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FY 2010 OSEL Annual Report

Table of Contents

Preface

The Office of Science and Engineering Laboratories (OSEL), one of seven Offices within CDRH, contributes to the Center’s mission by providing laboratory data and consults. OSEL serves as the laboratory science nucleus for the Center. Specifically, OSEL supports the scientific basis for the Agency’s regulatory decision- making by developing independent laboratory information for regulatory and other public health activities of CDRH. In addition to providing consultation to the Center’s regulatory experts, OSEL researchers are involved in mission-oriented science activities including test methods development, risk assessments, forensic investigations, product evaluations, and technology assessment.

From a science breadth standpoint, OSEL conducts laboratory research in the areas of physical, life, and engineering sciences as related to the effects of medical devices on human health. CDRH relies upon this work to support its efforts ensuring public safety in areas as varied as medical imaging, medical device software, breast implants, and drug eluting stents.

OSEL laboratory science serves as an important foundation for the regulatory mission of the Center and the Agency. For example, OSEL scientists have developed a draft guidance document to assist industry, systems and service providers, consultants, FDA staff, and others in designing, developing, and evaluating radio frequency (RF) wireless technology in medical devices. Some of the scientific questions raised with real-life impact concern issues such as electromagnetic interference (EMI) where the performance of a device can be degraded by an electromagnetic disturbance, RF wireless medical devices (devices incorporating at least one function that is implemented using RF wireless communications), and specific absorption rate (SAR), which measures the rate at which energy is absorbed by the body when exposed to an RF electromagnetic field (such as with the ubiquitous cell phone). This guidance will reference national and international standards and also discuss some of FDA’s regulatory requirements for medical devices including pre-market and post-market requirements under the Quality System regulation (QS regulation) (21 CFR Part 820).1

Another OSEL initiative implemented in 2010 was developing “science-sharing seminars.” With the need for CDRH to respond with greater speed and accuracy to new emerging threats to the public health, it has become more important than ever for components within the Agency to work together seamlessly and productively. To that end, in 2010 OSEL began developing and offering to its colleagues in other CDRH Offices monthly scientific seminars to share information about current research and relevant projects critical to the Agency mission. A listing of these seminars can be found in appendix F.

OSEL continues to reach out to others in the scientific and regulatory community. Eight years ago in 2003, the first student intern science poster exhibit was held, and this event has since become an annual phenomenon. What began as an in-house event to provide a forum for scientists in OSEL to discuss their work with one another has now become a large annual event (held in the summer) that has been attended by the FDA Commissioner’s Office, as well as academics and industry professionals. Participation has been expanded to include interns from across FDA and also students from area colleges and universities. This event has yielded increased interest in collaboration from non-FDA entities.

The OSEL Annual Report offers current information about the Office’s organization and intramural science activities; provides a summary of the Office’s direct laboratory support for pre-market review and post-market evaluation; and provides a bibliography of scientific publications, presentations, and research seminars for the fiscal year. The report is presented along the line of OSEL organization structure: divisions are described, followed by descriptions of the research laboratories. The section on 2010 highlights describes examples of research projects and various laboratory accomplishments. This report also cites a few examples of the regulatory support work that OSEL provides to the Center’s post-and pre-market offices.

We hope you find this document useful and informative. We welcome your comments on the programs described in this report.

For additional information, please visit htm the OSEL web site or contact us at 301-796-2530.

Steven K. Pollack, Ph.D.
Director
Office of Science and Engineering Laboratories
Center for Devices and Radiological Health, FDA

Disclaimer: Please note that the mention of commercial products, their sources, or their use in connection with material reported herein is not to be construed as either an actual or implied endorsement of such products by the Department of Health and Human Services.

Regulatory Support Activities

Research conducted in the OSEL supports the regulatory activities of the Agency as follows:

  • Strategically manage research with the aim of providing a scientifically sound basis for responding to current needs and anticipating future regulatory challenges; and
  • Provide technical consults in support of the Center’s pre-market, post-market, and compliance activities.

Both activities are coordinated within OSEL in an effective manner so as to best meet Center’s regulatory science needs. Laboratory research is the cornerstone upon which the Office provides the regulatory support function. (The research is described in subsequent sections.) It is largely based on investigations related to the mechanistic understanding of device performance or test procedures, enabling the Center and device manufacturers to gain an improved understanding of issues related to safety and efficacy. In general, although the research is directed toward issues identified at the pre-market approval level, the reality is that the research has the largest impact on the post-market end of the Center’s business because most often the research is anticipatory in terms of potential issues of medical devices identified at the pre-market level.

The regulatory support function of the Office is provided through consults supporting both pre-market decisions and post-market actions using expertise developed in the laboratory. A consult is a request for expert advice or information of a specific nature, and provides information that contribute to sound regulatory decisions. Consults are often based on acknowledged scientific/engineering principles or on independent data generated in OSEL laboratories.

In 2010 OSEL provided the following:

Number of consults on pre-market issues 1585
Number of consults on post-market issues 124

The information provided by a consult is used in some of the following ways:

  • Evaluate a pre-market submission (IDE, HDE, PMA, 510(k));
  • Support a compliance action (regulatory case support/development, Health Hazard Evaluation, Health Risk Assessments, etc.);
  • Assist scientific collaboration;
  • Respond to a consumer inquiry;
  • Provide feedback on guidance documents;
  • Provide revisions to one-pagers for the new device approval page; and support health hazard evaluation/health risk assessments in device determinations/classifications.

For many post-market as well as pre-market regulatory issues, the consults/reviews and investigations conducted by OSEL independently assess the claims made by manufacturers or other parties concerning safety or effectiveness. In other cases, OSEL reviews may assess the adequacy of a design, a failure investigation, a production process, or a quality process employed by the manufacturer. These reviews and analyses rely on in-house expertise and are often augmented by expertise solicited from colleagues in academia, other government laboratories, or even other industry sectors. OSEL laboratory investigations may be undertaken in instances where the veracity of a performance claim needs to be independently verified by testing or when the claimant lacks the resources to conduct the investigation.

OSEL also provides analytical support to post-market regulatory activities in a variety of ways:

  • Provide scientific and engineering reviews and analyses;
  • Conduct laboratory investigations of product performance;
  • Participate in inspections of medical device establishments;
  • Conduct forensic reviews and investigations;
  • Identify device safety and performance issues;
  • Provide training to FDA and industry; and
  • Contribute to Center-wide Matrix teams on issues identification as well as science-based analysis of post-market device performance.

Finally, developing standards and measurements methods is a significant activity of this office. OSEL continues to provide innovative solutions to public health problems by constructing generic techniques that lead to the creation of national and international standards that will enhance product safety and effectiveness. OSEL staff actively participate in developing standards at the national and international levels by performing research to establish standard procedures, and by shouldering standards committees responsibilities to manage, develop and support standards development.

Office of Science and Engineering Laboratories 2010 Highlights

Biomarkers MAQC-II (Division of Imaging and Applied Mathematics)

The promise of biomarkers for use in the personalized medicine of the future will only be realized with a mature understanding of the complex issues surrounding biomarker evaluation and validation. OSEL/DIAM scientists are contributing to that knowledge through directed research efforts and associated publications. In particular, scientists are active participants in the Microarray Quality Control Consortium, whose phase two project was published in Nature Biotechnology (Nat Biotechnol 28(8), 827, 2010). MAQC-II aimed to assess the performance of a predictive genomic signature in predicting disease status and/or response to therapy in terms of reliability, cross-platform consistency and reproducibility, and to identify “best practices” in developing and validating predictive genomic classifiers. Over the 3 years of research collaborating with scientists from other Offices/Centers or academia and industry, scientists at CDRH/OSEL/DIAM made significant contributions to the project. Other MAQC-II papers authored or co-authored by DIAM scientists are also published or accepted for publication (Popovici et al. Breast Cancer Research 2010, 12:R5; Chen et al. Computational Statistics & Data Analysis, accepted).

Brain CT Overexposure (Division of Imaging and Applied Mathematics)

Brain perfusion computed tomography (CT) is among the highest of radiation dose diagnostic imaging procedures, but the relationship between the dose indicated by the scanner and actual dose to patient (skin and organ dose) can be particularly problematic for a brain perfusion study. Since October 2009, the FDA has received reports of more than 350 patients who were overexposed to radiation during brain perfusion computed tomography (CT) studies, with some patients receiving up to 8 times more than the typical radiation dose for the procedure. Such doses can cause acute radiation damage that includes skin burns and reddening, hair loss, an increased risk of radiation-induced cataracts, and an increased lifetime attributable risk (LAR) for developing cancer.

To address this serious public health concern, CDRH’s pre-market applied research has developed computer models that simulate brain perfusion CT exams. These models allow CDRH to estimate the average dose to specific organs as well as maximum organ doses (metrics that are better indicators of risk) and connect them to the CT scanner-reported CTDI (CT dose index) values. CDRH’s pre-market applied research is now making use of these software models to evaluate methods for reducing the radiation and iodine contrast dose for brain perfusion CT and to develop supportive software and database tools. These developments will enable radiology professionals to estimate and compare the dose to radiosensitive organs, such as the skin, and the eye lens during the brain perfusion CT scans, facilitating the safe use of this important radiological tool to enhance public health.

Control Contact Lens Solutions Give Inadequate Kill Results (Division of Biology)

The Laboratory of Infection Control in the Division of Biology has been conducting research involving contact lenses and contact lens solutions after recent outbreaks of infections and recalls of solutions led OSEL and, in collaboration, the Division of Ophthalmic, Neurological, and Ear, Nose and Throat Devices (DONED) in the Office of Device Evaluation (ODE), to believe that there was a need for additional scientific research in this area. During our research, we found that our control solution was giving us inadequate kill results, even under less stringent testing parameters. After additional testing using the protocols companies are required to use to show their products are effective (ISO 14729) and being unable to get positive results, we reported our findings to the Office of Compliance. The Office of Compliance determined that our findings constituted a possible major violation and proceeded to begin the process for an expedited directed inspection of the company’s manufacturing facilities in Spain, which took place in the beginning of March 2011.

Data sharing (Division of Imaging and Applied Mathematics)

The Division of Imaging and Applied Mathematics (DIAM) has been conducting research sponsored in part by the FDA Critical Path initiative related to improving the quantitative information that can be extracted from CT images. The goal is to facilitate the development of imaging-based methods for assessing new drug therapies for lung cancer. As part of this effort, DIAM scientists have systematically collected thousands of CT datasets from an anatomically accurate chest phantom containing simulated lung nodules. This data is being used internally to assess how differences in CT acquisition parameters (e.g., CT dose and slice thickness) impact the ability to accurately and precisely estimate lung nodule volume. DIAM has announced the public release of thousands of phantom data sets at annual meetings of the Radiological Society of North America (RSNA) and the SPIE Medical Imaging Symposium. This publicly available data serves as a resource to industry, academia, and government agencies as they investigate and evaluate medical imaging systems, imaging techniques, and analysis software. Outside groups such as the Quantitative Imaging Biomarker Alliance (QIBA) are already taking advantage of this public resource for intercomparisons of image analysis tools.

Display standard (Division of Imaging and Applied Mathematics)

A new international standard providing evaluation methodologies for testing image display systems in medical diagnostic imaging equipment was made available in late 2009 by IEC (62563-1). This document provides the first standardized set of test methods for assessing display image quality in the area of diagnostic imaging as well as the specifications for the instrumentation required to perform the tests. This standard will allow sponsors to describe the properties of display devices associated with imaging equipment with consistent and well-defined methodologies. The lead scientist of DIAM’s Imaging Physics Laboratory designed and wrote several of the test methods in the standard, contributed the section related to instrumentation required to test displays, and evaluated most of the proposed test methods in his laboratory as part of the consensus development effort. The scope of this document is restricted to display systems for grayscale images. An amendment for the display of color images is being formulated under his leadership. Those interested in learning more about this standard effort should contact Dr. Aldo Badano (aldo.badano@fda.hhs.gov).

Electrocardiographic Analysis to Improve Patient Selection for ICD and CRT Devices (Division of Physics)

One of the major problems facing the cardiac electrophysiology community is patient selection for implantable cardioverter defibrillators (ICD) and Cardiac Resynchronization Therapy (CRT). Both of these therapies are beneficial for some patients but offer few benefits (along with increased risks) for others. This research in the Division of Physics is employing a simple electrocardiographic (ECG) index to predict myocardial scar formation and therapy outcome for ICD and CRT devices. For ICDs, the issue of patient selection remains important because many implanted patients do not experience shockable rhythms, and some receive inappropriate shocks. This problem was recently discussed in the January 5, 2011, edition of the Journal of the American Medical Association. The analysis was done in 797 patients from the implantable defibrillator arm of the Sudden Cardiac Death in Heart Failure Trial. The study found that patients with no myocardial scar by the ECG index had a significantly reduced rate of appropriate defibrillator shocks. The results suggest that the ECG scar index might be an attractive non-invasive risk-stratification tool to help determine which patients are most likely to benefit from implantable defibrillators. ICDs are already FDA-approved for the patient population in this study; however this tool could help physicians better choose appropriate therapy for individual patients and reduce adverse events. Similar work is evaluating the utility of ECG indices for clinical success for CRT. Both of these uses of the ECG index will be published in 2011 in major cardiology journals.

Strauss DG, Selvester RH, Wagner GS. Defining left bundle branch block in the era of cardiac resynchronization therapy. American Journal of Cardiology. 2011; (in press March 2011).

Strauss DG, Poole JE, Wagner GS, Selvester RH, Miller JM, Anderson J, Johnson G, McNulty SE, Mark DB, Lee KL, Bardy GH, Wu KC. An ECG index of myocardial scar enhances prediction of defibrillator shocks: an analysis of the Sudden Cardiac Death in Heart Failure Trial. Heart Rhythm. 8:38-45, 2011.

Evaluation of Defibrillator Device Waveforms in Cardiac Electrophysiology Laboratory (Division of Physics)

Automatic external cardiac defibrillators are evolving in technology. New and proposed systems include less-expensive designs for public and over-the-counter use. These new designs involve components that produce longer-duration electrical shocks at lower voltages. Scientists at OSEL laboratories tested clinically relevant long-duration waveforms for safety by examining their ability to defibrillate without causing secondary arrhythmias including refibrillation. These studies were done in isolated and perfused rabbit hearts with a combination of electrical and optical recording. The results indicate potential danger from certain waveforms. This research is being applied to the evaluation of new defibrillators. The approach and laboratory capabilities are valuable for the evaluation of other forms of new defibrillation technology, including the simultaneous application of chest compressions and electrical shock.

Fetal Heart Rate Monitors (Division of Imaging and Applied Mathematics)

In response to elevated complaints regarding inaccurate readings by fetal heart rate monitors, FDA issued a safety alert and a “Dear Healthcare Provider” letter in 2009. Inaccurate readings by fetal heart rate monitors can lead to serious consequences, including inappropriate emergency Cesarean sections or failure to detect fetal abnormalities. The Office of Compliance within FDA’s Center for Devices and Radiological Health (CDRH) made a post-market request to the manufacturer to submit a 510(k) for a new, more accurate version of the fetal heart rate monitor. In response, the sponsor submitted a pre-IDE (investigational device exemption) and two supplements in 2010 to propose a testing protocol to validate device modifications. A DIAM scientist worked with reviewers in the CDRH Office of Device Evaluation to review the testing protocol and offer suggestions to ensure that it would be rigorous enough to facilitate FDA clearance of the modified device. Subsequently, the sponsor submitted a 510(k) that is currently being reviewed by a DIAM scientist and ODE reviewers. The OSEL research enterprise was a key element in determining the reason for this device performance concern and the subsequent approach to the validation of proposed device modifications.

Generic Infusion Pump (Division of Electrical and Software Engineering)

The Generic Infusion Pump (GIP) project investigates the use of model-based techniques for the engineering of infusion pump software. The project aims to develop a fully verifiable base (generic) model for infusion pumps that can be extended to produce concrete implementations for specific pumps. The model for the GIP is derived from an exhaustive hazard analysis of real-life pump implementations and implemented using a hierarchical state machine notation.

Regulators benefit from this research because it provides an unambiguous safety reference standard; academics benefit because the works provides an “open source” medical device model for refining high confidence (medical) software development ideas; and manufacturers benefit because the research provides a safety reference standard that can be used to verify their designs.

DESE researchers based their investigation on a safety analysis process wherein potential hazards common to infusion pumps are identified, and a baseline of safety properties for infusion pumps is established. This baseline of safety properties provides a foundation for constructing generic executable models for infusion pump software. The resulting model was published on an academic website (http://rtg.cis.upenn.edu/gip.php3) for public use.

In addition to the model, DESE scientists are developing a formalism to extend this generic model to more concrete implementations. Researchers will demonstrate this approach by deriving models for a patient-controlled analgesia pump and an insulin pump from the base model.

Glistenings in Intraocular Lenses (Division of Chemistry and Materials Sciences)

Intraocular lenses (IOLs) are medical devices used to replace the function of the natural crystalline lens after the onset of a cataract or other medical condition that renders the natural lens opaque. These devices have a tendency to form “glistenings,” which are fluid-filled cavities that form within the IOL optic, and their presence may impact the visual acuity of the patient. Research conducted within the Division of Chemistry of Material Science has, for the first time, identified a mechanism for formation and growth of these cavities that is consistent with clinical observations. As part of this effort, an analytical model was devised that links IOL material selection and manufacturing considerations to the propensity for glistening formation. By using the model, IOL manufacturers can quickly identify materials that will be resistant to cavitation. Although very recent, the potential impact of this work is already apparent. The research was highlighted in a review article only months after its publication, and the authors were invited to participate in an American Academy of Ophthalmology event dedicated to exploring the current knowledge of the glistening phenomenon.

Huber Needles (Division of Solid and Fluid Mechanics)

Huber needles are used to administer fluids and drugs, as well as to sample blood through a surgically implanted port. The needle is expected to perforate the port septum without removing material, known as a core, from the septum. When the Office of Surveillance and Biometrics became aware that some Huber needles created cores, they contacted OSEL/DSFM and the Office of Compliance. DSFM investigations of the properties of non-coring Huber needles contributed to the decision to issue a Class I recall of millions of Huber needles. DSFM worked with FDA Office of Regulatory Affairs field investigators on inspections of the major Huber needle manufacturers, investigating their manufacturing processes and sharing the results of DSFM investigations. The work has prompted at least two needle manufacturers to change their manufacturing process. DSFM is now working to develop a standardized coring test that can be used to ensure that marketed Huber needles do not core.

Intraocular Lens (IOL) Preclinical Evaluation Methods (Division of Physics)

The Division of Physics has also been working on intraocular lenses (IOLs).They developed precise preclinical testing and evaluation methods for optical characteristics, performance of IOL implants, including dioptric power, glare, scattering and imaging quality. The new methods ensure higher measurement accuracy and repeatability, and provide CDRH and the scientific community with an effective tool to evaluate IOL parameters more precisely, quickly and accurately, thereby enhancing the quality and speed for approvals of IOL implants. FDA is proposing that these test methods be incorporated into national and international standards for the optical quality of IOLs [Patent No. 7,719,668; May 18, 2010].

MRI Safety of Cardiac Pacemakers and Implanted Defibrillators (Division of Physics)

Patients with implanted cardiac pacemakers and defibrillators are generally excluded from magnetic resonance imaging (MRI) because of the possibility of dangerous heating of heart tissue near the tip of the electrode. However, magnetic resonance imaging has become a highly used diagnostic modality, and it is often needed for patients with implanted cardiac devices. The assessment of potential risks in animal studies is limited by differences in tissue properties and geometry compared to humans. Human trials are limited by the need to avoid configurations that could endanger study subjects. A complimentary solution developed by scientists in OSEL was the validation needed for a human computational model that permitted assessment of worst-case MRI-device interactions that could cause dangerous tissue heating. This model has been applied to the first approval of a pacemaker being labeled for use in a MRI. The model, in addition to animal and human trials, is to assess the general safety of human subjects with any metallic implants undergoing MRI. This research helped support the approval of the first MRI-conditional cardiac pacemaker device.

Patent Awarded (Division of Solid and Fluid Mechanics)

OSEL has been notified that their patent titled “Particle Image Velocimetry System Having an Improved Hollow-Waveguide-Based Laser Illumination System” has been granted and was issued as U.S. Patent No. 7,787,106 on August 31, 2010. This invention was a collaboration between the Division of Physics and the Division of Solid and Fluid Mechanics and relates to the development of a novel method for effective and safe digital particle image velocimetry (DPIV) using a simple all-hollow-waveguide laser delivery approach. It incorporates two key optical hollow waveguide based laser delivery techniques: an uncoated funnel-shaped hollow glass taper for a direct lens-free laser-to-taper coupling and a flexible hollow core waveguide for precise laser power delivery. The method provides the scientific community with an effective DPIV tool that ensures some essential advanced features over conventional DPIV techniques in terms of formatting thin, wide and uniform laser illumination sheet; high-peak-power laser delivery without damaging effects; flexibility; miniaturization; immunity to external influence; and safe and confined laser delivery.

Process Modeling of Controlled Drug Release Coatings (Division of Chemistry and Materials Science)

Drug eluting coatings represent a relatively new class of combination medical products that incorporate controlled release technologies with more traditional devices to improve functionality and performance. The primary example is the drug eluting stent (DES), which has demonstrated a significant reduction in the rate of restenosis after angioplasty compared to bare metal stents. Scientists in DCMS have developed a model to predict the impact of material chemistry and manufacturing on drug release from these products. Thus, calculations based on the model can provide guidance in materials selection and process design, thereby reducing empiricism and facilitating the development of more robust combination medical products. Further, the model can also be used to identify and assess the potential of new approaches to coating fabrication. After receiving inquires from major DES manufacturers regarding the model, OSEL/DCMS scientists have made the source code for the model publicly available at http://matforge.org/redmine/projects/therapy/wiki and held a workshop to educate device manufacturers on the theory underlying the model and how to utilize the source code. Once integrated into the research and development process, the model will facilitate the development of higher quality drug-device combination products and allow them to reach the market more readily.

Semantic Text Mining (Division of Electrical and Software Engineering)

The Software research group in the Division of Electrical and Software Engineering in OSEL has developed SARF – a semantic text mining framework. The framework is being used to analyze narrative text contained in the Center’s various document repositories, including adverse event reports and pre-market submissions.

Currently available data mining tools are based on traditional data mining and useful for analyzing structured data. However, specific details and contextual information often found only in the narratives is generally missed by these tools. As a result, analysis of narrative text is mostly carried out manually by analysts and subject matter experts. The semantic Search and Retrieval Framework (SARF) provides a narrative text query, analysis and signal prediction tool as an aid to CDRH analysts. Though still in development, SARF has proved very useful to analysts at CDRH, particularly in cases where an ad-hoc search is to be performed among large adverse event reports, incorporating text found within the narrative. With existing tools, this effort is entirely manual. The analysts download all reports for the device in question for the specific time period. After that, the analyst has to read through each of the narrative to arrive at specific conclusions.

Public health and safety-related decisions, including recalls, are made by analyzing regulatory documents submitted to the agency. SARF minimizes the time spent by the analyst in locating a small percentage of relevant documents amongst a very large number. This enables the analyst to spend quality time on limited relevant documents rather than identifying them manually. In one recent case, CDRH analysts needed to look for the presence of a few specified keywords for a set of product codes and over specific time period among Medical Device Adverse Event Reports (MDR). Doing this manually, the analysts found about 2500 MDRs for those product codes and time period. They then manually analyzed these 2500 reports to search for the specific keywords and terms indicating a problem. It took a considerable amount of time before the relevant reports could be identified.

The issue was brought to the attention of the SARF team to see if the tool could help. A query was performed using SARF to search for the list of keywords for the specific product codes within the given time constraints. SARF returned about 200 matching reports, in approximately one second. Not surprisingly, all 200 matching reports were relevant and when cross-checked against the entire 2500 reports, there was no other relevant report that SARF did not find! Thus, the analyst had the advantage of looking at just one-tenth of the reports with SARF. By providing only relevant documents to look at, within minutes of the requirement arising, the decision-making process gets much faster. Further, analysts would be able to make a larger number of decisions by using SARF. Faster signal detection and evaluation results in enhanced public health.

As we move forward, SARF will also provide the ability to search across document repositories from within, as well as across, different Centers of the Agency.

Software and Data Sharing in Toxicology (Division of Biology)

CDRH is evaluating the feasibility of implementing a Threshold of Toxicological Concern (TTC) approach for evaluating the potential for a compounds released from device materials to have adverse toxicological effects. This approach can be used to estimate the potency of compounds in lieu of conducting toxicity testing, if its structure is known. Toxtree software is being evaluated by staff in the Division of Biology to categorize compounds into various toxicity classes. In the absence of toxicity data from experimental studies, these software-predicted toxicity values can be used to develop safe levels of exposures for compounds released from medical devices. The Division of Biology has developed a searchable database of these provisional safety values that will help reviewers in the Office of Device Evaluation and OSEL implement this new evaluation approach.

Division Descriptions

DIVISION OF BIOLOGY (DB)

DB participates in the Center's mission by conducting research, participating in device review activities, developing consensus standards both domestic and international, developing regulatory guidance, testing forensic and regulatory samples, and providing educational programs in the area of biological sciences. Specifically, DB conducts research to support the Center’s mission to assure the safety and effectiveness and promote the improvement of medical devices in the areas of biological risk assessment, biosensors/nanotechnology, genomic and genetic technologies, infection control and sterility, tissue-device interactions, toxicity/biocompatibility, and radiation bioeffects.  Through laboratory studies, researchers evaluate the potential adverse effects of medical devices on host biological systems and, in collaboration with engineering divisions, identify the source and impact of product degradation on organ systems both under acute and chronic conditions. The Division staff develops measurements methods and analytical procedures to characterize and evaluate devices and products, studies molecular and cellular mechanisms and bioeffects of biomaterials, and supports the Center’s enforcement and product testing activities.  

The DB staff members are primarily biologists, chemists, and biomaterials scientists.

Laboratories

  • Biomechanisms
  • Cardiovascular and Interventional Therapies
  • Emerging Biosensors and Biotechnologies
  • Infection Control
  • Toxicology and Biocompatibility

DIVISION OF CHEMISTRY AND MATERIALS SCIENCES (DCMS)

DCMS participates in the Center's mission by conducting research, participating in device review activities, developing consensus standards both domestic and international, developing regulatory guidance, testing forensic and regulatory samples, and providing educational programs in the area of chemistry and materials sciences. Specifically, the DCMS focus is on developing experimental data, test methods and protocols for regulatory and scientific activities involving multicomponent mass transfer, reaction kinetics, absorption and swelling of network polymers, polymer processing, modeling of physiological processes, and materials degradation. Research activities in the division include synthesis and characterization of polymeric and nanocomposite materials; computational modeling of microstructures and microstructure development; evaluating drug and small-molecule elution, diffusion, and leaching from device materials; developing sensor evaluation protocols; measuring and modeling structural transitions and phase stability; hydrogel and biopolymer synthesis and characterization; and shelf-life and service life prediction. DCMS tests the performance of chemical processes of importance to medical devices, such as mass transfer through membranes used in dialysis and blood oxygenation, and manufacturing processes used to fabricate materials and evaluate tools and protocols for device performance.

The technical disciplines of the DCMS staff include physical chemistry, analytical chemistry, polymer science, pharmacology, materials science, materials engineering, biomedical engineering, and chemical engineering.

Laboratories

  • Active Materials
  • Materials Performance

DIVISION OF ELECTRICAL AND SOFTWARE ENGINEERING (DESE)

DESE participates in the Center's mission by conducting research, participating in device review activities, developing consensus standards both domestic and international, developing regulatory guidance, testing forensic and regulatory samples, and providing educational programs in the area of electrical engineering and software. Specifically, the DESE works in the application of electronics, software engineering, and systems engineering body of knowledge to the regulation of medical devices and electronic products that emit radiation. The Division addresses the cutting edge of medical devices through all phases of the product life cycle and all aspects of the product manufacturer’s business, from research and development through procurement, production, and ongoing customer support. DCMS hosts the following resources and capabilities: analog and digital circuit design, data acquisition and display, embedded microprocessor and PC-based systems, software-based virtual instruments, quality management and risk management as applicable to electronics and software, testing for hazards arising from the use of electrical and electronic technology in medical products, and electronic design including components, circuits, and analytical techniques for controlling high voltages and/or currents.

DESE staff members are primarily electronics and electrical engineers, physicists, biomedical engineers, and general engineers.

Laboratories

  • Medical Electronics
  • Software (Regulatory Support and Research)

DIVISION OF IMAGING AND APPLIED MATHEMATICS (DIAM)

DIAM participates in the Center's mission by conducting research, participating in device review activities, developing consensus standards both domestic and international, developing regulatory guidance, testing forensic and regulatory samples, and providing educational programs in the area of medical imaging and applied mathematics. Specifically, DIAM provides scientific expertise and carries out a program of applied research in support of CDRH regulation of radiation-emitting products, medical imaging systems, and other devices utilizing computer-assisted diagnostic technologies. Medical imaging research encompasses ionizing and non-ionizing radiation from data capture through image display and observer performance. The computer-assisted diagnostics work of DIAM is focused on the appropriate mathematical evaluation methodologies for sophisticated computational algorithms used to aid medical practitioners interpret diagnostic device results. The Division is charged with developing and disseminating performance assessment methodology appropriate to these modalities. DIAM operates a calibration laboratory for ionizing radiation detection instruments and participates in a full range of programs in support of the Public Law 90-602 mission of the Center.

DIAM staff members are primarily physicists, mathematicians, and physical science technicians.

Laboratories

  • Image Analysis
  • Imaging Physics
  • Ionizing Radiation Metrology

DIVISION OF PHYSICS (DP)

DP participates in the Center's mission by conducting research, participating in device review activities, developing consensus standards both domestic and international, developing regulatory guidance, testing forensic and regulatory samples, and providing educational programs in the area of physics. Specifically, DP conducts research and engineering studies to support the Center’s mission to assure the safety and effectiveness of medical devices and electronic products, and to promote their improvement. Scientific and technical specialties in the division include optical physics and metrology, sensors, fiber optics, electromagnetics, electromagnetic compatibility and electromagnetic interference, biophysics, functional imaging, cardiac, electrophysiology, neuroscience, and minimally invasive optical and electromagnetic technologies. The Division develops measurement methods, instrument calibration capabilities and analytical procedures to characterize and evaluate devices and products, and supports the Center’s enforcement and product testing activities. DP evaluates interactions of electromagnetic and optical energy with matter, analyzes implications for the safety and effectiveness of devices and products, and develops and evaluates procedures for minimizing or optimizing human exposure from such devices.

The technical disciplines of DP staff include physics, mathematics, biophysics, biomedical engineering, electronics, neuroscience, and general engineering. A newly formed laboratory is in human-device interfaces. The Human-Device Interface Laboratory is designed to support research in human factors and medical device use. The facility will examine the people who interact with medical devices, the ways they use devices, and the environments or settings in which they use them.

Laboratories

  • Biophysics
  • Electromagnetic and Wireless Technologies
  • Optical Diagnostic Devices
  • Optical Therapeutics and Medical Nanobiophotonics
  • Human-Device Interface

DIVISION OF SOLID AND FLUID MECHANICS (DSFM)

DSFM participates in the Center's mission by conducting research, participating in device review activities, developing consensus standards both domestic and international, developing regulatory guidance, testing forensic and regulatory samples, and providing educational programs in the area of solid and fluid mechanics. Specifically, the core responsibilities of this division involve issues for which mechanical interactions or transport are of primary concern, such as those involving motion; structural support, stabilization, or vibrations; device and material mechanical integrity; materials durability; and biologically relevant parameters of device and materials. The Division has expertise in the areas of fluid dynamics, solid mechanics and materials, acoustics and ultrasonics. DSFM develops measurement methods, instrument calibration capabilities, and analytical procedures to characterize and evaluate devices, device materials, and products, and supports the Center's enforcement and product testing activities. DSFM staff also evaluate interactions of ultrasound energy with matter and the implications of these interactions on the safety and effectiveness of devices and products.

Technical disciplines of the DSFM staff include mechanical engineering, materials science, biomedical engineering, general engineering, and physics.

Laboratories

  • Fluid Dynamics
  • Solid Mechanics
  • Ultrasonics

MANAGEMENT SUPPORT STAFF (MSS)

MSS provides leadership and support to the Office of the Director, Division Directors, and laboratory professionals on all administrative, general management, and knowledge management issues. MSS is responsible for planning, developing, and implementing Center and OSEL programmatic matters concerning financial management, personnel, procurement, contracts, inter-agency agreements, employee training, and facilities.

MSS is also tasked with managing and administering OSEL resources designed to support on-going programs. The staff ensures the proper distribution of operating and payroll dollars, facility plans, procurement and property, travel requests and ADP needs. MSS advises the Office of the Director on potential issues that may affect resources, staffing, and management issues to comply with policies and avoid potential conflicts. In addition, MSS directs and conducts special assignments or projects for the Center as well as the Office Director.

Office of Science and Engineering Laboratories - Research Laboratories and Selected 2010 Accomplishments

Active Materials (Division of Chemistry and Materials Sciences)

Scientists in the Active Materials Laboratory investigate materials used in devices in which the time dependence of materials properties is a key component of how the device's mode of action is provided. This includes combination products in which medical devices incorporate some material-based mechanism for drug delivery, such as drug eluting stents. It also includes nano-materials, in which the properties of the nano-particles are critical to delivery of expected results.

Accomplishments

Nanoparticles on Medical Devices

Studies were initiated on the behavior of silver nanoparticles due to the growing number of nano-silver containing devices submitted to FDA recently and of the need to better understand this new technology for medical device applications. Scientists in the Active Materials Laboratory use both experimental and computational approaches to access the ability of silver nanoparticles to release silver ions to reduce infections on implants. The experimental work involves the production of silver nanoparticles with controlled surface chemistry. An analytical model was also developed to account for the electrochemical processes responsible for the dissolution of the silver nanoparticles.

An important result of this research for the medical device industry is that the release rate of silver from the nanoparticles is strongly affected by the chemistry of the medical device surface on which the nanoparticles are deposited on. In addition, nanoparticles below 20nm in size release silver ions at a much accelerated rate. Both of these results have a critical impact on the concentration of ions at the implant-tissue interface and hence, their effectiveness at infection control.

Drug Deposition in Tissue

Drug-eluting stents (DES) are the treatment of choice for reducing restenosis rates after plaque removal. Successful innovation of new DES products continues to depend critically on advances in the understanding of key relationships between geometry, flow, drug physicochemical properties and the resulting deposition patterns. FDA is charged with evaluating how the drug is released and is developing test methods to evaluate both the design and manufacture of new drug releasing medical devices to address whether they release the optimum amount of drug.

To improve insight into DES performance and to facilitate future innovations, scientists in the Active Materials Laboratory developed a computational model of drug eluting stents deployed into a diseased blood vessel. These results were then used to analyze drug elution from the stent into the tissue and to analyze the impact of drug diffusivity and solubility. This tool is useful for studying the effect of drug physicochemical properties and local transport factors on drug distribution and retention in the vessel wall. In this way, investigators may determine if a medical device design releases the right amount of drug to be effective vs. toxic. The results of this work will be made available to the DES design community to facilitate future DES development.

Manufacturing Effects on Drug Release

Researchers in the Active Materials Laboratory have developed methods to improve manufacturing quality control to reduce failures of medical devices post-implantation. This work is providing industry and FDA regulators the tools needed to improve manufacturing quality and methods of testing the final product to provide optimum drug release from implants so they function properly and do not injure the patient. This involves a multi-billion per year industry and life saving implant devices crucial to the survival of the patient.

The investigators have designed computational and laboratory bench methods to predict the effects of manufacturing variations and design on the controlled delivery of drugs from cardiovascular stents and other products. These new methods clarify relationships between drug structure, processing, and performance in quantitatively consistent ways. They have been shared with manufacturers of drug eluting stents to promote the innovation of new, reliable products.

Gender Differences in Drug Release

Researchers in the Active Materials Laboratory are examining the potential for gender-based differences in the efficacy of drug eluting stents. On-going investigations are targeting possible effects of gender differences in atherosclerotic plaque. Current results suggest possible variations in drug release rate and distribution depends on the composition and morphology of the diseased vasculature. Such information is expected to illuminate clinical experience with existing devices and to open the door to new domains of product innovation.

Biomechanisms (Division of Biology)

The continued advancement in genomic and genetic technologies impact CDRH in major ways. The Center receives submissions of genomic and genetic diagnostic microarray devices and expects to receive more--some in co-development with drug or biological therapeutics manufacturers. Additionally, these technologies will be used to evaluate the safety of products such as implants and materials (toxico-genomics).

Accomplishments

Custom Immunoassay Arrays for Renal Biomarkers Developed: DB scientists have had initial success developing a competitive immunoassay for NGAL detection: A) Microscope slides are arrayed with multiple proteins. Here, three different concentrations of NGAL protein were arrayed along with chicken IgG (positive control) and clusterin, another biomarker (used here as a negative control and screen for cross-reactivity); and B) GenePix image of an arrayed slide exposed to a competitive immunoassay for NGAL. Both patterned regions were exposed to Cy5-goat-anti-NGAL and Cy5-rabbit-anti-chicken IgG, either in the absence or presence of 50 µg/ml NGAL solution. When no NGAL is present, the Cy5-labeled anti-NGAL antibody binds to the NGAL immobilized on the slide, generating fluorescence spots (white represents a extremely high intensity). However, when NGAL is present, it competes with the surface immobilized NGAL for binding sites on the Cy5-labeled NGAL antibody, causing a significant decrease in fluorescence intensity for the surface NGAL specific regions. The Cy5-rabbit-anti chicken IgG binds to the chicken IgG spots, while clusterin spots show little fluorescence intensity suggesting no cross reactivity.

Polymer Project: The studies demonstrate that bio-degradable polymers have a significant inflammatory potential that may counter the beneficial effects of drug eluting stents in managing coronary artery disease.

Early Detection of Renal Injuries: OSEL/DB researchers are developing a new method using RT-PCR and gene chip techniques for early detection of renal injuries caused by toxicities from drugs and medical devices as well as other pathological disorders in urine samples. The research is conducted in both human and animal subjects.

  • Human. So far, a total 18 patient urine samples were collected from clinical sources and tested with the gene chips the laboratory designed and prepared. As compared with the results in control samples (from normal people), 13 of these samples showed positive results, presenting genomic biomarkers Kim-1, NGAL, alpha-GST, m-GST, clusterin, and even pododin, respectively. Each of these genomic biomarkers has been recognized as renal injury-associated in different kidney segments. More samples will be collected and tested, and a paper will be written about the results.
  • Animal. The urine samples from the rats treated with different doses of gentamicin and lithium have been tested on laboratory-designed gene chips with the similar techniques mentioned above. Genomic biomarkers of kim-1, osteoponin, clusterin, RPA-1, HSP73, NGAL have been found in these samples. The method developed may potentially supply a more sensitive tool for CDRH in consideration of reviewing renal toxicities caused by medical devices in the future. A paper describing the study and results is being written.

Biophysics (Division of Physics)

Accomplishment

Computer Models for Body Heating from MRI

The review of MRI scanner submissions (Class II devices) is complicated by the fact that the applications and technology have been advancing rapidly. One of the developments has been in the area of radio-frequency (RF) resonator technology used in MRI scanners. The high power RF resonators are used during MR scanning to transmit high power pulses into the body, which raises a risk of local heating (due to local specific absorption rate (SAR) effects) in the body of the patient being scanned. As there are no accepted real time methods of studying heating (in humans), ensuring safety of these devices poses a challenge for both the sponsors and the reviewers. The MRI researchers at OSEL have been investigating the use of computer modeling to assess relative local SAR. These techniques are being proposed to ensure the initial adequacy of the methods used for the performance of MR systems for local SAR control. In the absence of clear special controls for this technology/device, the expertise and knowledge in this area is providing clear recommendations to the sponsors in terms of the necessary documentation to ensure safety.

Electromagnetic and Wireless Technologies (Division of Physics)

Accomplishment

Electromagnetic Compatibility (EMC) and Radio Frequency Identification (RFID)

The Division of Physics in OSEL in collaboration with device manufacturers tested the effects of radio frequency identification (RFID) readers on implantable pacemakers and implantable cardiac defibrillators (ICDs). The effects ranged from inducing negative events (potentially harmful inappropriate tachyarrhythmia detection and delivery of inappropriate therapy or complete inhibition of cardiac pacing) to inducing no clinically significant events. The research conducted is entirely proactive, as there have been no incident reports of pacemakers or ICDs being adversely affected by RFID to this date. FDA and industry are using the information collected in the study to improve the current EMC review process for pacemakers and ICDs. The information learned and experiences gained from RFID technology have given CDRH unique expertise in rapid decision-making for pre-market approval of RFID-enabled medical devices. The results of the study were published in the HeartRhythm Journal (January 2010 edition) and were covered.

Emerging Biosensors and Biotechnology (Division of Biology)

Accomplishments

Emerging Biosensors and Lab-on-a-chip Platforms

The research projects focus on assessing many aspects of the emerging technologies incorporated into IVD devices, including signal generation and transduction mechanisms, bioconjugation and labeling techniques, microfluidic generation, nanotechnology, systems integration and automation. Biomarker detection, through the use of multiplexed antibody and/or DNA arrays, is being studied and research results can be applied to a number of biomarkers associated with disease diagnosis and personalized medicine. Understanding the design and production of such multiplexed IVD systems will form the scientific basis upon which the FDA can define regulatory approaches and requirements for reviewing future diagnostic-based and biomarker monitoring submissions.

Nanoparticle Characterization and Application to Diagnostic Devices

Nanotechnology offers great potential in developing a vast array of new products to advance public health. And while in vivo nanoparticle applications are currently hampered by cytotoxicity concerns (an area the laboratory is working on in collaboration with other scientific staff within the Division of Biology), the market for in vitro tests using nanoparticles is rapidly expanding, as evident from the published literature. The resulting new technologies and devices are likely to come to fruition, and therefore, FDA approval will be sought much sooner than for their in vivo-based counterparts.

Fluid Dynamics (Division of Solid and Fluid Mechanics)

Fluid dynamics, as it applies to medical devices, can be broadly defined as the interaction of moving fluids with medical devices: both as the device affects the moving fluid and as the moving fluid affects the device. Often the moving fluid is blood, as in the flow of blood through a heart valve or through the filters and pumps of a renal dialysis apparatus. Damage to the flowing blood can result in serious clinical consequences, up to and including death. Damage to a device, such as might be caused by cavitation in a heart valve, can lead to catastrophic device failure causing death. Accordingly, the Laboratory of Fluid Dynamics, located in the Division of Solid and Fluid Mechanics, maintains a research program focused on the fundamental factors governing the interaction of flowing fluids with medical devices and the development of test methodologies to objectively characterize such interactions and their consequences.

Accomplishments

Computational Studies of Fluid Blood Transport in Vascular Devices

Computational fluid dynamics (CFD) is a subset of computer modeling used to simulate the flow of fluids and the physical forces acting on the fluid. CFD is already being used to develop and prototype blood-contacting medical devices, such as prosthetic heart valves and ventricular assist devices (VADs). However, the use of CFD to demonstrate product safety in FDA pre-market device applications and post-market investigations raises concerns about validation. This is especially true in the final step of predicting biological responses (e.g., blood damage, thrombus formation) from the purely physical results (e.g., pressures, velocities, shear stresses) of the simulations. To understand factors affecting accuracy of CFD in predicting flow, we conducted a study open to all comers of a benchmark nozzle model.

Results from an interlaboratory computational study performed by 28 groups were compared to velocity data from particle imaging velocimetry experiments performed at three independent laboratories in a nozzle model in which the throat Reynolds number (Re) was varied from 500 to 6500. At all Re's, the largest discrepancies appeared downstream of the throat. At Re=500, laminar simulations agreed well with experimental data. As the Re was increased, agreement between the measured results and those predicted by the participants became much more variable. While choice of turbulent model is one factor of many that affect simulation accuracy, analysis of results has helped us develop a suite of best practices (e.g., appropriate flow model, inlet/outlet length, maintaining mass conservation) for using CFD in medical device evaluations.

In a companion study, OSEL scientists collaborated with scientists at Penn State University and the Rochester Institute of Technology by conducting an interlaboratory comparison of fluid velocities and pressures were measured in a nozzle model to provide experimental validation for the companion round-robin CFD study. The simple benchmark nozzle model, which mimicked the flow fields in several medical devices, consisted of a gradual flow constriction, a narrow throat region, and a sudden expansion region where a fluid jet exited the center of the nozzle with recirculation zones near the model walls.

Measurements of mean velocity and turbulent flow quantities were made in the benchmark device using particle image velocimetry (PIV). Flow measurements were performed over a range of nozzle throat Reynolds numbers (Re throat) from 500 to 6500, covering the laminar, transitional, and turbulent flow regimes. A standard operating procedure was developed for performing experiments under controlled temperature and flow conditions, and for minimizing systematic errors during PIV image acquisition and processing.

For laminar and turbulent flow conditions, the velocities measured by the three laboratories were similar with an interlaboratory uncertainty of ~10% at most of the locations. However, for the transitional flow case (Re throat=2000), the uncertainty in the size and the velocity of the jet at the nozzle exit increased to ~60% and was very sensitive to the flow conditions. An error analysis showed that by minimizing the variability in the experimental parameters, such as flow rate and fluid viscosity, to less than 5% and by matching the inlet turbulence level between the labs, the uncertainties in the velocity field for the transitional flow case could be reduced to ~15%. The experimental procedure and flow results from this interlaboratory study, now available in a journal publication, will be useful for validating CFD simulations of the benchmark nozzle model and for performing PIV studies on other medical device models.

The project descriptions, raw data, and reports are being made available at a data repository website hosted by the National Cancer Institute, at https://fdacfd.nci.nih.gov.

Evaluation of Blood Damage Caused by Medical Materials and Devices

Although hemolysis testing provides a valuable and easily obtainable surrogate measure of damage to blood elements, it does not provide information about localized platelet activation and thrombus formation, which may occur in devices and lead to device malfunction and/or serious embolic complications. While several techniques are currently available for quantifying platelet activation and aggregation, no standardized methods have been established for the in vitro testing of medical devices, especially when performing tests with bovine blood. Hence, it is extremely difficult to determine the safety of a medical device based on platelet data provided in a company’s pre-market submission.

To evaluate thrombogenicity of biomaterials used in blood-contacting medical devices, current FDA/CDRH policy recommends an in vivo test involving a non-heparinized canine venous implant model. However, it has been suggested that this canine model may not be predictive of human clinical use because canine blood is more susceptible to thrombus formation than human blood. In addition, this model may not capture some potential thrombogenic events if formed thrombi are easily detached from the material surfaces. The widely referenced hemocompatibility standard ISO 10993-4 suggests a list of in vitro tests to assess thrombogenicity, but there are no detailed protocols to perform these tests, and their usefulness has not been established.

This year OSEL scientists studied two commonly used platelet activation marker antibodies, CD62P (platelet surface P-selectin) and PAC1 (activated GP IIb/IIIa), using flow cytometry. ACDA (Anticoagulant Citrate Dextrose Solution A) and heparin anticoagulated human blood from healthy donors were separately exposed to varying shear stresses using a cone-plate rheometer model, and immediately mixed with the platelet marker antibodies for analysis.  Following ADP stimulation, the percentage of both CD62P and PAC1 positive platelets increased in a dose-dependent fashion, even 8 hours after the blood was collected. After shear stress stimulation, both CD62P and PAC1 positive platelets increased significantly with shear stress levels when ACDA was used as the anticoagulant. However, for heparinized blood, the PAC1 positive platelets decreased with increasing shear stress, while the CD62P positive platelets increased. Besides the anticoagulant effect, the platelet staining buffer also impacted PAC1 response, but had little effect on CD62P positive platelets. These data suggest that CD62P is a more reliable marker compared to PAC1 for measuring shear-dependent platelet activation and it has the potential for use during in vitro medical device testing.

Image Analysis (Division of Imaging and Applied Mathematics)

A wide variety of new digital imaging and display devices is under development by academia and industry, with a broad range of performance characteristics. The Center requires augmented support for the evaluation of such devices. To this end, OSEL scientists in this laboratory are developing a fundamental understanding of how these new devices operate and are developing a unified methodological approach for validating the applicability of these new diagnostic medical systems. The emphasis of the Image Analysis Laboratory is to understand the building block of computer software tools and develop assessment methodologies that appropriately estimate performance and improve clinical and non-clinical trial designs. Application areas include mammography, optical imaging, computed tomography, nuclear medicine, immunohistochemistry, computer-aided diagnosis, and gene expression. This program is located within the Division of Imaging and Applied Mathematics (DIAM).

Identifying Sources of Volume Estimation Error in 1D, 2D, and 3D Measurement Methods in Lung Imaging.

The goal of a current important project is to identify and quantify the sources of volume estimation error in 1D, 2D, and 3D measurement methods used in lung imaging through carefully controlled, realistic phantom studies. These new and continuing studies will allow quantification of the variability of these measurement methods for all relevant imaging parameters, including patient exposure, x-ray beam parameters, slice thickness, table pitch, and image reconstruction algorithm. Knowing the degree to which the variability in measures of tumor size is due to the multi-detector CT (MDCT) image acquisition process, the software tool used to assess the tumor size estimate, or aspects of the patient (patient size, tumor size, density, shape, etc.) is the first step toward developing standards for imaging protocols and image analysis tools that allow drug trialists, medical device companies, and patient care clinicians to make optimal use of MDCT in the evaluation and treatment of lung cancer patients. This project is aligned with several specific areas in the FDA Critical Path Opportunities List (23-29) related to the importance of imaging in the evaluation of products that treat disease.

Accomplishments

DIAM scientists have completed collection of over 5400 CT datasets of an anthropomorphic thorax phantom containing simple and complex synthetic lung nodules with 1200 datasets currently available for public download and use (https://imaging.nci.nih.gov). They have completed a QIBA 1A reader study which compared the bias and variability of 1D, 2D and 3D size measurement techniques in measuring phantom nodules. Results were presented at the SPIE Medical Imaging Conference in early 2011. They have also concluded a simulation study looking at the noise properties of helical MSCT images and have submitted the result for publication in Physics in Medicine and Biology. DIAM researchers have developed a low-bias, low-variance lesion volume estimator based on matched-filter approach which has been published in IEEE Transaction on Medical Imaging.

Staff scientists also designed and finished data collection for a multi-site phantom study known as the QIBA 1C project. This is a collaborative study with NIST, UCLA, University of Maryland, Duke University and QIBA to develop standardized protocols across scanners from all major vendors, and make quantitative measurements of volume estimates as well as noise measures. As part of this effort, the anthropomorphic phantom and the synthetic nodules that DIAM researchers designed were scanned in each of six different sites around the country.

Design and Assessment of CAD

Developing a computer-aided diagnosis (CAD) system is often an iterative process. The developers may update their CAD algorithm multiple times after the original design due to a number of factors that make the update necessary or desirable. Although much research has been devoted to how an original CAD system should be assessed, there is currently little consensus about how updated CAD systems might be assessed. Conducting a multi-reader, multi-case observer study each time the CAD system is updated may provide the data required to assess the effectiveness of the updated system.

However, such an approach may not be the most optimal in terms of saving resources, and it certainly does not make use of all the knowledge and information that have been collected on the original system.

In the past year, DIAM has conducted a number of studies that may lead to a methodology for how the information already collected with the original system may be combined with the standalone performance of the updated system for assessment. DIAM researchers have authored three papers for the SPIE Medical Imaging 2011 symposium that concentrate on this topic. Additionally, they are working with a Commissioner’s Fellow to design an observer performance study that will analyze some of the issues related to the assessment of updated CAD systems. This is a unique research area that the FDA is best suited to lead, and DIAM’s research performance in the past year indicates that very good progress has been made on this difficult and important problem.

The general goals of this project are to lead or anticipate new methodology for the design and assessment of computer-assisted diagnosis (CAD), and to help FDA better understand and evaluate CAD. Three main sub-projects are (1) estimate the effect of an updated CAD system on radiologists without requiring new observer studies, (2) investigate the added value of commercial CT colonography CAD systems when they are used by radiologists, and (3) expand methods for computer-aided analysis of digital pathology data. In 2010, DIAM scientists conducted three studies to establish the underlying methodology for the first sub-project, all of which were submitted for presentation and publication. Researchers finalized the study design and reading protocol for the second sub-project. They have also begun in the third sub-project the design of a new CAD method that will be readily retrainable for use on different datasets. There were several technical accomplishments in 2010:

Accomplishments

IHC sub-project: Published article on the quantification of the benefit of computer-aided digital microscopy in reducing intra- and inter-observer variability in Archives of Pathology and Laboratory Medicine.

Colon CAD sub-project: Published article on optimization of a polyp detection algorithm using a pareto front approach in Pattern Recognition Letters.

Mammographic CAD sub-project: Published article in Medical Physics in collaboration with our academic partners on a CAD system for lesion classification on tomosynthesis images.

IHC: Researchers have laid the groundwork for a new algorithm for the computer-aided assessment of the biomarker HER2 for breast cancer, based on histogram analysis. The new algorithm will be readily re-trainable for use on different datasets, and is part of efforts to develop tools for reducing the inter-reader variability in the interpretation of IHC slides.

Colon CAD: The protocol has been finalized for the assessment of the role of CAD in improving observer performance of CT colonography. The design includes selection of cases for the reader study, sample size estimation, reader eligibility, reader training, reading protocol, and statistical endpoints.

Assessment of CAD update: DIAM scientists investigated how the calibration of a CADx system may affect user performance. Results indicate that in addition to standalone performance, CAD calibration may also have an impact on with-CAD performance of users. The study was submitted to the SPIE 2011 Medical Imaging Conference.

Assessment of CAD update: DIAM researchers investigated how a CAD update may affect the agreement between the updated and original systems. Although most investigators are focused on standalone CAD performance, the agreement between the two systems is likely to have implications for the effect of the CAD system on users. The study was submitted to the SPIE 2011 Medical Imaging Conference.

Assessment of CAD updates: DIAM scientists investigated the relationship between the number of distinct findings on thoracic CT images and the number of radiologists reading a dataset to identify lung nodules. This study is intended to determine whether a finite number of readers can detect almost all findings on an image dataset, and is part of DIAM’s investigation of how an updated CAD system can be assessed without a new observer study. The study was submitted to the SPIE 2011 Medical Imaging Conference.

Imaging Physics (Division of Imaging and Applied Mathematics)

A wide variety of advanced imaging systems with solid state detectors and digital display devices are under development by academia and industry, with a broad range of performance characteristics. To support the Center’s need for assistance evaluating such devices, OSEL scientists are developing evaluation methodologies for diagnostic medical imaging systems such as mammography and fluoroscopy, computed tomography, nuclear medicine, diagnostic ultrasound, and magnetic resonance imaging, as well as for novel soft-copy display devices for viewing medical images. This program is located within the Division of Imaging and Applied Mathematics (DIAM).

Accomplishments

Image Display

Performed study on visual tests for mobile displays and submitted a paper (accepted) to the SID conference on “Estimating the perceptual limits of mobile displays.”

Designed an experimental station to measure veiling glare in the human eye and in the display device and submitted a paper (accepted) to the SID conference on “Experimental methodology to measure veiling glare.”

Performed work on color displays and characterization. Gave lecture on tissue imaging and color aspects for CDRH Staff College. Submitted a paper (accepted) to the SID conference on “Virtual display,” a concept that will allow researchers to perform color studies of different display devices in pathology.

Dose and Image Quality in Cardiovascular Imaging: Applications to CT and Cine Angiography

Developed a number of high-resolution digital cardiac phantoms: developed two male, one female, and two pediatric whole body phantoms. These phantoms are currently being used with our Monte Carlo simulation software for imaging and dosimetry.

Developed models of CT and angiography imaging systems and the experimental methodology for CT system evaluation and have applied in clinical systems.

Developed methods for evaluating dose-to-patient organ (a paper is being written) and maximum skin dose for CT and angiography. Also developed methods for evaluating image quality for Ct and angiography.

Developed and published software for imaging and dosimetry simulations.

Breast Imaging

Presented a paper at the SPIE Medical Imaging Conference on direct detector simulation.

Published a paper on the analytical model for CsI screens in Medical Physics.

Infection Control (Division of Biology)

The Infection Control Laboratory is an interconnected program of laboratory research that provides consults addressing medical device-associated infections in areas such as pre-market submissions, public health notifications, safety alerts, and recalls; also develop guidance, and national and international standards designed to promote a scientific basis for regulatory decision making at CDRH/FDA.

Major research areas:

  1. Methods for detecting and identifying contaminants and emerging disease, assuring the safety of ophthalmic medical devices. The ophthalmic devices project had four major experiments:
    • Study the role of different soft contact lens on the biocidal efficacy in multipurpose contact lens solutions (MPS) against S. aureus;
    • Study the role of different soft contact lens on the biocidal efficacy in MPS against Fusarium solani (in collaboration with WEAC);
    • Develop protocol for efficacy testing of MPS against Acanthamoeba; and
    • The etiology of contaminants such as bacterial endotoxin in ophthalmic viscous materials used in cataract surgery to cause Toxic Anterior Segment Syndrome (TASS).
  2. The influence of device design and infection control.

Accomplishments

Developed a clinically relevant test soil for devices that are used in arthroscopic surgeries (e.g., arthroscopic shaver handles) and a method to quantify residual particulates on “cleaned” devices to determine if cleaning methods are effective.

Materials Performance Laboratory (Division of Chemistry and Materials Science)

Scientists in the Materials Performance Laboratory investigate materials used in devices in which the physico/chemical properties of a material impact its performance and the long-term behavior of these properties affect the device's safety or effectiveness. The goal of these efforts is to improve the review of pre-market submissions, establish materials test method and standards, assess post-market issues in light of materials performance or failure, and communicate information through publications and presentations regarding the public health impact of device materials selection, design, and processing.

Accomplishments

Wetting and Dewetting of Hydrogels

The adhesive and lubricating properties of hydrogels are critical to the performance of tissue sealants and adhesion barriers used in obstetrics-gynecology, cardiovascular, neurological, and cosmetic dermatological applications, as well as in mucosal drug delivery media. A limiting aspect to the performance of these device groups is the ability of a hydrogel to wet a surface and/or disrupt an interface, and then persist for the duration of its use.

In response to regulatory questions that arose from the increasing number of submissions that use hydrogel-based technologies, DCMS researchers aimed to improve the Agency’s understanding of how viscoelastic hydrogels stick to, detach from, and slide between surfaces, both tissue and artificial. They have explored the wetting and dewetting properties of hydrogels and are building a quasi-universal landscape of wetting/dewetting behavior. Using this information, there is the potential to build a better definition of hydrogel-based products, create a first-pass test for effectiveness, or develop a standard outlining the characteristics necessary for effectiveness in different applications. The results were presented to Office and Center senior management for review this year, as well as to an audience at an invited lecture at the University of Akron. The researchers are preparing a paper for publication.

Continuous Glucose Monitors

Diabetes affects more than 23 million people in the Unites States and contributes to approximately 170 billion dollars in health-care costs every year. Having accurate and reliable glucose monitoring devices on the market is crucial for improved diabetes management and prevention of diabetes-related complications. Additionally, accurate sensing of glucose is critical for developing a “Closed Loop” Artificial Pancreas to ensure that the pancreas will deliver the appropriate amount of insulin.

DCMS scientists tested the interference of select sugar substitutes, and pharmacological agents with the performance of continous glucose monitors (CGM) using known concentrations of glucose and potential interfering substances in blood, and they found that some of these substances may affect the accuracy of the readings. This results in the potential for incorrect administration of insulin. Researchers are developing an in vitro testing method that will provide basis for standardized CGM performance testing prior to clinical studies. OSEL/DCMS scientists, along with other experts within the Center, contributed to a public health notification addressing the margin of error in glucose monitors.

This research accomplishes the following: provides CDRH with scientific tools to evaluate the safety and effectiveness of glucometers, continuous glucose monitor (CGM) devices and electrochemical enzymatic biosensors; improve pre-market evaluation of CGM product manufacturing, product characterization, and relevant quality issues; establish tighter review criteria for glucose monitoring devices; and has a direct impact on the development of CGMs and a “Closed Loop” Artificial Pancreas by developing criteria for the sensor component of the Artificial Pancreas. This will enhance the lives of the growing number of diabetes patients by enabling effective management of blood glucose levels.

Hermeticity of Implantable Devices

In recent years, several regulatory issues have surfaced that directly or peripherally involve the transport of liquids and small molecules through polymeric materials. This project aims to apply state-of-the-art approaches to investigate the fundamental transport properties and interactions between polymeric materials in devices and certain liquids and small molecules. Of particular concern are moisture barriers for active implantable electronic devices (AIMDs). AIMDs require a hermetic seal between the electronic components and the moist environment inside the human body. DCMS researchers are currently exploring the influences of materials chemistry and manufacturing on the water transport properties of Poly(paraxylylene) (parylene) materials, which have emerged in new applications as robust, flexible, moisture barriers for AIMDs.

In the materials performance laboratory, scientists have prepared parylene films in house and studied the diffusion kinetics and mechanism of water transport in films with different chemistries and manufacturing history using Time-resolved Fourier transform infrared-attenuated total reflectance (FTIR-ATR) spectroscopy. In conjunction with in situ temperature-dependent X-ray scattering to study the polymer structure, they have achieved a new level of rigor in the characterization of parylene coatings. This work provides the most rigorous determination of diffusion coefficients in parylene to date, and we have identified unique structural effects that play a significant role in defining physical and transport properties. These efforts have provided key insights toward unraveling the complex structure-processing-transport relationships in PPX.

Medical Electronics Laboratory (Division of Electrical and Software Engineering)

The focus of the Medical Electronics Laboratory is on product realization — the engineering processes by which scientific advances are transformed into successful products that consistently perform as intended and satisfy user needs. Sound engineering underlies every successful medical device; poor engineering underlies many adverse events and recalls. While it is widely recognized that FDA is a science-based agency, the goal is to ensure that regulatory decisions are also based on sound engineering principles when electronics are incorporated in medical devices.2 Toward that end, OSEL/DESE staff bring the resources of a modern electronics laboratory to bear on a wide range of pre- and post-market regulatory issues.

The laboratory is often called upon to conduct independent investigations of the root cause of adverse events involving medical devices. In many of these cases, the root cause has been reported by device manufacturers as “use error” or “random component failure.” OSEL/DESE independent failure investigations repeatedly tell a different story: deficient designs (i.e., poor engineering) cause or contribute to many adverse events.3

In a few of these cases, the deficiency was not reasonably foreseeable. There are inherent risks in applying cutting-edge electronics to medical uses; such risks are balanced by the considerable benefits afforded by the technology. Part of OSEL’s role is illuminating the performance limitations of the electronics in cases where risk/benefit judgments need to be made.

Accomplishments

The documented findings of OSEL researchers helped establish the basis for FDA’s infusion pump initiative4, announced in March 2010. (DESE engineers determined thatthe pattern of poor engineering identified in the laboratory extends to defibrillators, infant incubators, ventilators, and many other device types also.)

The Medical Electronics Laboratory contributed substantially to a new guidance document for external infusion pumps that was published in draft form in 2010 as a part of the infusion pump initiative. The new guidance asks manufacturers to submit more engineering information than has customarily been provided in the past. This will afford CDRH engineers the opportunity to substantially see the same information that a manufacturer examines when conducting their own design review.5

The traditional engineering curriculum is largely silent with regard to product development methodology and quality management. The Medical Electronics Laboratory has engaged in an initiative with several biomedical schools to integrate this body of knowledge into the engineering curriculum. That effort has borne considerable fruit at Drexel University, where a three-credit course in medical device development, created by DESE laboratory staff, is now in its fifth year and has been well received by students and faculty. In 2010, the Drexel School of Biomedical Engineering received university approval to expand this single course offering into a course concentration at the masters’ degree level, and OSEL/DESE is working closely with them to achieve this.

As other universities have expressed an interest in replicating this success at Drexel, OSEL/DESE has proposed to expand the prototype curriculum using an open-source development methodology. In addition, DESE staff is planning a workshop to bring together interested educators to share best practices for teaching product development at the undergraduate and graduate levels. A key focus of this effort is to integrate product development concepts into existing courses whenever possible in lieu of creating new courses.

Optical Diagnostic Devices Laboratory (Division of Physics)

The rapid proliferation of novel diagnostic medical devices employing minimally or noninvasive optical technology is revolutionizing modern health care. These devices now perform a variety of critical in vivo tasks in the clinic, such as oximetry monitoring, atherosclerotic plaque assessment, high resolution retinal imaging, and early detection of lung, cervical and gastrointestinal cancers. These systems are based on a variety of optical mechanisms including fluorescence, reflectance and coherence-domain imaging. Furthermore, next-generation technologies currently in advanced stages of development hold promise for applications such as early breast cancer detection and noninvasive glucose sensing.

Given their increasing complexity, optical technologies represent a significant new regulatory challenge to FDA. There are distinct gaps in understanding the biophysical mechanisms of action, device- and tissue-specific light propagation effects, and tissue damage by ultraviolet, visible and infrared radiation. As a result, guidance documents and standardized test methods are currently not available for most optical diagnostic device classes. Basic mechanism studies are needed to facilitate the development of relevant evaluation criteria early in the regulatory process, thus enabling thorough and swift reviews of cutting edge optical technologies. The Optical Diagnostic Devices laboratory works to generate fundamental data through studies of light-tissue interaction mechanisms, device performance and tissue safety for a variety of optical technologies. Furthermore, the laboratory is developing bench-top performance test methods and advanced computational models of light propagation in tissue to elucidate device working mechanisms and facilitate the device review process. This program is located within the Division of Physics (DP).

Accomplishments

Test Phantoms for Optical Coherence Tomography (OCT) Imaging Devices

OCT is perhaps the fastest-growing medical imaging modality, from its invention 15 years ago to now being used at least 37,000 times per day to scan for eye diseases. The technology behind OCT has also been rapidly developing, whereupon scan rates and image resolution have increased by orders of magnitude over the past 15 years. In spite of all this growth and development, methods to validate and verify image quality and other device performance parameters have not been established. Having standardized test methods, such as the use of phantoms as test objects, would enhance both the regulatory vetting process as well as academic/industry research and development efforts. The Optical Diagnostic Devices Laboratory within the Division of Physics has been studying materials and methods for phantom development and has recently produced its first phantoms for rapidly assessing OCT image quality. DP researchers have described these phantoms in a peer-reviewed journal article, and have shared them with academic and government OCT researchers to initiate the endeavor of controlled performance comparison of various OCT device configurations.

Optical Therapeutics and Medical Nanophotonics Laboratory (Division of Physics)

Minimally invasive biophotonics techniques and devices have been recently developed as potential alternatives to conventional medical methods for diagnostics, monitoring and treatment of a variety of diseases, drug discovery, proteomics, and environmental detection of biological agents. These technologies offer a non-contact, effective, fast and painless way for sensing and monitoring various biomedical quantities. Medical devices utilizing minimally invasive biophotonics technology are rapidly finding their way into the mainstream for early disease diagnosis and improved patient acceptance and comfort. Optical therapeutics approaches are being proposed that use high-intensity ultra-short laser radiation, precise delivery fiber optics and near/mid-infrared biosensing and monitoring. CDRH recognizes the need to prepare for evaluating devices being developed to optically diagnose and treat various diseases, including pre-cancerous and cancerous conditions.

The Optical Therapeutics and Medical Nanophotonics Laboratory of CDRH/OSEL’s Division of Physics is responsible for providing and maintaining state-of-the-art knowledge and expertise in the biophotonics, nanobiophotonics, biomedical optics and medical laser field to assist the Center and Agency in the evaluation of new medical therapeutics devices that employ the latest minimally invasive optical technologies. The OTMN Laboratory also assists with the regulation of hazardous optical and laser radiation emissions potentially harmful to the general population, and with the latest measurement devices to evaluate new optical therapeutics products.

Accomplishments

Developed innovative approaches in the following:

  • Testing fundamental characteristics of intraocular lens (IOL) implants(P)
  • Ultrahigh-resolution confocal nanoscopy(P)
  • Effective and safe fiber laser delivery in particle image velocimetry(P)
  • Light therapy: fundamental mechanisms and applications(P)
  • Multimodal OCT and confocal microscopy for sensing and imaging
  • Biosensors using smart, tissue-activated fiber probes

(P) OTMN Lab patented innovations

Software Laboratory (Division of Electrical and Software Engineering)

The scope of this laboratory’s activities is to support CDRH pre-market and post-market software evaluation activities by establishing relevant in-house expertise and identifying, qualifying, quantifying, and communicating conformity assessment techniques and criteria which the Center can use to fulfill its mission.

Software is one of the most ubiquitous enabling technologies for many, if not most, classes of medical devices. Devices that incorporate this technology are inherently extremely complex and require that engineers must be able to skillfully peel back many layers of abstraction from the underlying mathematical, behavioral and physical models that govern device operation, to their hardware and software realizations, and down to the physical characteristics of component parts.

Accomplishments

Static Analysis of Medical Device Software

  • Deployed a static analysis capability for C# and Java
  • Performed a case study for a candidate application for architecture extraction
  • Deployed a capability to analyze software architecture

Semantic Data Mining

  • Implemented a preliminary design for the semantic mining framework, SARF
  • Set up the computing framework for SARF
  • Indexed all documents in the IMAGE repository
  • Indexed all documents the MAUDE repository for the last five years
  • Implemented a basic search utility
  • Extended the basic search utility to include sorting and filtering
  • Extended indexing and search utilities for repositories in CDER and CTP
    • Includes narrative text for all AERS reports (~7.8 million reports)
  • Provided support for three dictionaries
  • Implemented a rudimentary multi-corpus search feature
  • Implemented a web-based application for searching the indexed repositories

Solid Mechanics Laboratory (Division of Solid and Fluid Mechanics)

Activities in this program may be triggered within any phase of the product life cycle. In general, the activities of this group are directed not only toward resolving the specific issue that provided the trigger, but also in finding ways to apply the knowledge gained to future device problems. Since the inception of the FDA Medical Device program, this group has been heavily involved with voluntary device standards organizations, such as ASTM International. Staff participation in these standards activities continues to leverage the Agency’s resources with industry and academia to create lasting consensus solutions to regulatory issues once the laboratory studies have been completed. 

Accomplishments

Centrifugation Cell Adhesion Assay for Characterizing the Phenotype of Chondrocytes used for the Production of TEMPs

Current methods of cartilage repair are limited by the use of cadaveric sources, which can lead to complications such as infection, rejection and disease transmission. TEMPs are complex products that are composed of combinations of cells, soluble factors and material scaffolds, and are an attractive alternative for cartilage repair. EMPs promise increased clinical benefits for cartilage repair and comprise an increasing proportion of submissions to FDA. A major obstacle in chondrocyte-based TEMPs is the limited availability of cells that maintain their original phenotype. Propagation and amplification of chondrocytes in monolayer on two-dimensional polystyrene surfaces can result in de-differentiation of the chondrocytes to a fibroblastic phenotype. These phenotypic changes to the chondrocyte are sensitive to environmental factors, including culture conditions and physical stimulation. TEMP strategies for cartilage repair do not use either standardized culture methods or definitions of chondrocyte phenotype. Therefore, a critical need exists for methods that can define and monitor the biological and physical phenotype of chondrocytes. Initial results demonstrated that increasing passage number of bovine cells resulted in a shift from the chondrocyte to the fibroblastic phenotype between passage numbers three and four (Kaplan, D., Trans. Soc. Biomaterials, 2007).

This year DSFM scientists studied the effects of mechanical stimulation on maintenance of the chondrocyte phenotype by evaluating phenotypic markers including cell adhesive properties to a 2D substrate, chondrocytic gene expression, protein markers and quantitative histomorphometry. The findings demonstrated that the mechanical shear stress cell adhesion assay using a flow cell is extremely difficult to implement, and attempts to characterize the adhesive properties of chondrocytes as a function of passage number produced highly variable results. After a great deal of development, researchers concluded that the flow-cell based shear stress assay does not produce results that are sufficiently reproducible and repeatable. Instead OSEL/DSFM scientists have developed a new cell adhesion assay that involves cell centrifugation. Experiments using the new method have demonstrated that it is much simpler to perform and that results are replicable.

Preclinical Test Methods for Bioabsorbable Polymer Strength Retention

Bioabsorbable polymers are increasingly being used as raw materials in emerging medical devices including cardiovascular stents and scaffolds for tissue engineering, while their use in orthopaedic applications has a significant history. Bioabsorbable polymers have advantages over traditional metals and synthetic materials due to their similar mechanical properties to native tissues and generation of byproducts with low toxicity. However, despite the numerous benefits of these materials, their degradation characteristics and physical properties are not well understood in a physiologically relevant environment. For example, a lack of substantial information is available on polymer degradation rate and strength when the material is subjected to mechanical loading. This is significant because many currently approved and emerging pre-market devices fabricated from bioabsorbable polymers are implanted into anatomic sites with complex mechanical loading or into an environment where the device is expected to perform a structural role. In order to evaluate the safety and efficacy of these degradable devices, it is imperative to characterize them in a mechanically dynamic environment. Therefore, the overall goal of this proposal is to determine the effect of mechanical loading on the degradation and strength retention of bioabsorbable polymers. In this project DSFM scientists aim to establish new recommendations and protocols for testing absorbable devices exposed to mechanical loading. These recommendations and protocols will guide medical device manufacturers in developing future bioabsorbable implants and evaluating their long-term mechanical safety.

Effects of Vertebroplasty on Adjacent Level Fracture in Elderly Women

Vertebral compression fractures are a significant health issue for post-menopausal women. The primary surgical treatment for these procedures is vertebroplasty, which consists of injecting bone cement into the fractured vertebral body. While vertebroplasty procedures are relatively successful in relieving pain, approximately 25% of patients experience additional fractures within one year. It is unclear if these fractures are a result of altered spinal loading, a consequence of osteoporosis, or their combination. Prior investigations of additional fracture risk have been primarily limited to retrospective analyses of clinical data after secondary fractures have occurred. Thus, limited information exists on damage caused to spinal tissues by the vertebroplasty itself. The objective of this project is to distinguish between the contributions of vertebroplasty and osteopenia to pre-fracture damage in the spine. Specifically, OSEL/DSFM scientists hypothesize that vertebroplasty leads to increased damage in adjacent vertebral bodies and intervertebral discs as compared to pre-existing levels; and secondly, this effect is enhanced in patients with reduced bone mineral density. Researchers are testing hypotheses with an in vitro study of pre- and post-menopausal female cadaver spines subjected to vertebroplasty and simulated physiologic loading. Damage is being assessed through histology and compared against specimens without vertebroplasty. The results will allow scientists to discern the contributions of vertebroplasty and osteopenia to the degree of damage in the spine and, therefore, provide critical information to patients, surgeons, and FDA personnel on the risk-benefit ratio of vertebroplasty.

Preclinical Test Methods for Bioprosthetic Heart Valves: Effects of Non-Circular Configurations on Valve Leaflet Fatigue

The artificial heart valve market is fast becoming one dominated by minimally invasive technology. The fundamental design of this generation of heart valves involves a marriage of soft tissue valves, cardiovascular stent frame, and percutaneously delivered or other minimally invasive technology. The unique technology presents challenges in preclinical testing particularly in the area of long-term durability, which ideally depends on the deformed shape of the implanted valve in the annulus. Traditionally this type of testing is done in accelerated wear tester (AWT) systems with the manufactured valve (in “as is” state, which is commonly circular and symmetrical in shape). The purpose of this project is to develop a greater understanding of the non-uniform loading conditions on percutaneous heart valves and how to achieve such loading for long-term durability evaluation. Any increases in stresses and strains in the leaflets observed in finite element analysis (FEA) of pericardial tissue valves in the deformed annulus will be correlated with results from long term durability evaluation of non-uniformly loaded tissue valve configurations.

Toxicology and Biocompatibility Laboratory (Division of Biology)

This is an interconnected program of laboratory research, risk assessment, and standards development activities designed to provide a scientific basis for regulatory decision making in CDRH. Researchers evaluate the potential adverse effects of medical device materials and chemicals, including nano-sized particles, using in vivo and in vitro experimental models and approaches. Scientists use data to reduce uncertainties in assessing risks to patients exposed to physical and chemical exposures, and ultimately protect their health.

Accomplishments

Software Tools

New international consensus standards for conducting biocompatibility assessments of medical devices emphasize a chemical characterization-risk assessment approach to assess the biological safety of the device. A practical limitation to the implementation of this approach is the lack of toxicity data for many compounds released from device materials. To address this data gap, staff in the Division of Biology are using computational toxicology methods to predict the toxicity of these compounds. Specifically, they are determining the ability of Quantitative Structure Activity Relationship (QSAR) models to estimate the toxicity and carcinogenicity of compounds released from devices. CDRH scientists are collaborating closely with staff in CDER to develop and refine QSAR models on the CDRH “supercomputer.” The Division also serves as a Center-wide resource on computational toxicology issues for CDRH reviewers.

Ultrasound Laboratory (Division of Solid and Fluid Mechanics)

The Ultrasonics Laboratory continues to develop test methods and computational techniques for analyzing the safety and effectiveness of ultrasound ablation devices known as high intensity focused ultrasound (HIFU). Current accomplishments include developing a method for computing the intensity field at the focus of a HIFU transducer from IR thermographic measurements; adding the capability for measuring the phase response of ultrasonic hydrophones used in biomedical ultrasound exposimetry; characterizing egg white as a blood mimicking material for use in HIFU in vitro phantoms and comparing its coagulation behavior to pig, cow, and human blood; comparing thermocouple-based temperature rise measurements in a tissue mimicking material vs. those in ex vivo tissue; updating the capabilities of the HIFU beam simulator; and establishing a procedure for assessing when nonlinear rather than linear beam propagation modeling should be employed for accurate calculation of acoustic and thermal properties of HIFU beams. Further, the laboratory continues to study the neurological effects of pressure waves.

Accomplishments

Characterization of Ultrasonic Intensity Output of HIFU Transducers

A technique was developed for quantitatively characterizing HIFU transducers using infrared (IR) thermography. The method allows for the intensity distribution of a HIFU beam to be determined from the temperature measured at the boundary of a tissue phantom by an IR camera. When tested using IR data from numerical simulations, the technique produced the known intensity distribution to within 10% accuracy at the focus of the HIFU beam as well as pre-focal and post-focal locations. The technique is currently being applied to experimental IR data.

For accurate pressure and intensity field measurements using hydrophones, current measurement standards call for de-convolution of the hydrophone’s transfer function response, which requires that the phase as well as the magnitude response of the hydrophone be known. Therefore, the laboratory’s time delay spectrometry (TDS) system was expanded to enable calibration of both hydrophone magnitude and phase.

Development and Use of Tissue Mimicking Materials (Tmms) for Assessment of HIFU Devices

Egg white, a protein-containing solution, was characterized as a blood coagulation surrogate for the acoustical and thermal evaluation of therapeutic ultrasound, especially HIFU devices. Its physical properties, including coagulation temperature, frequency-dependent attenuation, sound speed, viscosity, and thermal properties, were measured as a function of temperature (20 - 95 oC) and found to be similar to reported values for blood. Also, the thermal coagulation behavior of egg white was characterized along with that of cow blood, pig blood, and human blood and the results compared well, making egg white a potentially useful bench testing tool for the safety and efficacy evaluation of therapeutic ultrasound systems.

When tissue mimicking materials (TMMs) containing thermal sensors are used to measure ultrasound-induced temperature rise during pre-clinical testing of HIFU devices, it is important that measurement results reasonably represent those that occur in biological tissue. To compare TMM- and tissue-based temperature measurements, both a previously developed TMM and fresh ex-vivo swine muscle were instrumented with bare wire thermocouples, a HIFU beam was focused at the thermocouple junction, and the temperature profile during and after sonication was recorded. Temperature traces obtained at various pressure levels demonstrated similar types of heating profiles in both the tissue and TMM, the exact nature of which depended on whether bubbles formed during the HIFU exposure.

Computational Techniques for Evaluating HIFU Safety and Effectiveness

Improvements were made to the HIFU simulation program previously developed and made available for public distribution. This user-friendly software package calculates the pressure and intensity fields, temperature rise, and thermal dose distributions for HIFU transducers. Enhancements include provisions for annular transducers, augmented heating due to shocks, improved plotting, and other algorithm refinements. The list of users now includes at least 8 companies, 12 universities, and 3 government research laboratories.

Previously, laboratory staff has developed an analytic temperature-mode model for computing the temperature rise in tissue under conditions when nonlinear propagation generates significant higher harmonics. They now have used this model to determine the conditions under which assumptions of linear acoustic propagation are insufficient to accurately model several physical and derived quantities, such as compressional pressure, rarefactional pressure, intensity, heat rate, temperature rise, and thermal lesion volume. The relative differences between linear and nonlinear predictions have been presented as a series of contours, enabling practitioners to locate their system in parameter space and determine whether nonlinearity significantly affects the quantities of interest.

Neurological Effects of Pressure Waves

Work continued into the study of the bioeffects of pressure waves on the brain. This project is a collaboration with the Uniformed Services University of Health Sciences (USUHS), Center for Neuroscience and Regenerative Medicine. Applications of this research include treatment of traumatic brain injury and the safety assessment of procedures such as HIFU brain tumor ablation, ultrasonic clot lysis, and ultrasonic neuromodulation. An amplitude-modulated pressure train possessing a pressure envelope similar to that of a blast wave was produced using a transducer driving voltage controlled by software. Evidence of mild-to-moderate traumatic brain injury was observed in mice, including swelling and disruption of the blood/brain barrier. Another aspect of the project was the investigation of the function of individual neurons that were exposed to high-intensity ultrasound. The function of the neuron was measured in terms of the action potential conducted along the axon in an earthworm. The amplitude and conduction velocity of the action potential were measured as the strength of the wave sonicating the nerve was varied. The strength of the waveform was quantified by various metrics, including both the acoustic impulse (pressure times the exposure time) for the most recent exposure, as well as the cumulative impulse for all exposures. It was found that conduction velocity as a function of cumulative impulse was the best predictor of nerve function for all the experiments performed. This parameter combination may be useful for predicting bioeffects of pressure waves.


APPENDIX A – OSEL Publications

January 1, 2010 – December 31, 2010

Abboud S, Badal A, Stern SH, Kyprianou IS. Designing a phantom for dose evaluation in multi-slice CT. Proceedings of SPIE, 7622:762232, 2010.

Abi-Jaoudeh N, Glossop N, Dake M, Pritchard WF, Chiesa A, Dreher MR, Tang T, Karanian JW, Wood BJ. Electromagnetic navigation for thoracic aortic stent-graft deployment: a pilot study in swine. J Vasc Interv Radiol, 21(6):888-95, June 2010.

Agrawal A, Gallas BD, Parker C, Agrawal KM, Pfefer TJ. Sensitivity of time-resolved fluorescence analysis methods for disease detection. IEEE J Sel Top Quantum Electron, 16(4):877-85, July-August 2010.

Agrawal A, Pfefer TJ, Gilani N, Drezek R. Three-dimensional characterization of optical coherence tomography point spread functions with a nanoparticle-embedded phantom. Opt Lett, 1:35(13):2269-71, July 2010.

Angelone LM, Ahveninen J, Belliveau JW, Bonmassar G. Analysis of the role of lead resistivity in specific absorption rate for deep brain stimulator leads at 3T MRI. IEEE Trans Med Imaging, 29(4):1029-38, April 2010.

Angelone LM, Bit-Babik G, Chou CK. Computational electromagnetic analysis in a human head model with EEG electrodes and leads exposed to RF-field sources at 915 MHz and 1748 MHz. Radiation Research, 174(1):91-100, July 2010.

Antonucci JM, Regnault WF, Skrtic D. Polymerization shrinkage and stress development in amorphous calcium phosphate/urethane dimethacrylate polymeric composites. J Compos Mater, 44(3):355-67, February 2010.

Badal A, Kyprianou IS, Sharma D, Badano A. Fast cardiac CT simulation using a graphics processing unit-accelerated Monte Carlo code. Proceedings of SPIE, 7622:762231, 2010.

Bonmassara G, Iwakib S, Goldmakherc G, Angelone LM, Belliveaua JW, Levc MH. On the measurement of electrical impedance spectroscopy (EIS) of the human head. Int J Bioelectromagn,12(1):32-46, January 2010.

Buckler AJ, Mozley PD, Schwartz L, Petrick N, McNitt-Gray M, Fenimore C, O'Donnell K, Hayes W, Kim HJ, Clarke L, Sullivan D. Volumetric CT in lung cancer: an example for the qualification of imaging as a biomarker. Academic Radiology, 17(1):107-15, January 2010.

Buckler AJ, Schwartz LH, Petrick N, McNitt-Gray M, Zhao B, Fenimore C, Reeves AP, Mozley PD, Avila RS. Data sets for the qualification of volumetric CT as a quantitative imaging biomarker in lung cancer. Opt Express, 18(14):15267-82, July 5, 2010.

Burvall A, Barrett HH, Myers KJ, Dainty C. Singular-value decomposition of a tomosynthesis system. Opt Express, 18(20):20699-711, September 27. 2010.

Chang IA. Considerations for thermal injury analysis for RF ablation devices. Open Biomedical Engineering J, 4:3-12, February 4, 2010.

Chen W, Giger ML, Newstead GM, Bick U, Jansen SA, Li H, Lan L. Computerized assessment of breast lesion malignancy using DCE-MRI robustness study on two independent clinical datasets from two manufacturers. Academic Radiology, 17(7):822-829, July 2010.

Chen W, Metz CE, Giger ML, Drukker K. A novel hybrid linear/nonlinear classifier for two-class classification: theory, algorithm, and applications. IEEE Transactions in Medical Imaging, 29(2):428-41, February 2010.

Christ A, Kainz W, Hahn EG, Honegger K, Zefferer M, Neufeld E, Rascher W, Janka R, Bautz W, Chen J, Kiefer B, Schmitt P, Hollenbach HP, Shen J, Oberle M, Szczerba D, Kam A, Guag JW, Kuster N. The Virtual Family--development of surface-based anatomical models of two adults and two children for dosimetric simulations. Phys Med Biol, 55(2):N23-38, January 2010.

Civelek M, Grant GR, Irolla CR, Shi C, Riley RJ, Chiesa OA, Stoeckert CJ Jr, Karanian JW, Pritchard WF, Davies PF. Prelesional arterial endothelial phenotypes in hypercholesterolemia: universal ABCA1 upregulation contrasts with region-specific gene expression in vivo. Am J Physiol Heart Circ Physiol, 298(1):H163-70, January 2010.

Dair BJ, Saylor DM, Cargal TE, French GR, Kennedy KM, Casas RS, Guyer JE, Warren JA, Kim CS, Pollack SK. The effect of substrate material on silver nanoparticle antimicrobial efficacy. Journal of Nanoscience and Nanotechnology10(12):8456-62, December 2010.

Dasgupta S, Wansapura J, Hariharan P, Pratt R, Witte D, Myers MR, Banerjee RK. HIFU lesion volume as a function of sonication time, as determined by MRI, histology, and computations. J Biomech Eng, 132(8):081005, August 2010.

Espandiari P, Rosenzweig B, Zhang J, Zhou Y, Schnackenberg L, Vaidya VS, Goering PL, Brown RP, Bonventre JV, Mahjoob K, Holland RD, Beger RD, Thompson K, Hanig J, Sadrieh N. Age-related differences in susceptibility to cisplatin-induced renal toxicity. Journal of Applied Toxicology30(2):172-82, March 2010.

Fohlmeister JF, Cohen ED, Newman EA. Mechanisms and distribution of ion channels in retinal ganglion cells: using temperature as an independent variable. J Neurophysiology, 103(3):1357-74, March 2010.

Freed M, Park S, Badano A. A fast, angle-dependent, analytical model of CsI detector response for optimization of 3D x-ray breast imaging systems. Medical Physics, 37(6):2593-605, June 2010.

Gammell PM, Maruvada S, Liu Y, Harris GR. A pre-emphasis technique to broaden the usable frequency range in time delay spectrometry systems. Review of Progress in Quantitative Nondestructive Evaluation, vol. 29, eds. DO Thompson and DE Chimenti (American Institute of Physics, New York) pp. 670-676, 2010.

Gavrielides MA, Kinnard LM, Myers KJ, Peregoy J, Pritchard WF, Zeng R, Esparza J, Karanian J, Petrick N. A resource for the assessment of lung nodule size estimation methods: database of thoracic CT scans of an anthropomorphic phantom. Opt Express,18(14):15244-55, July 5, 2010.

Gavrielides MA, Myers KJ, Petrick N. Three-dimensional volumetric assessment with thoracic CT: A reliable approach for noncalcified lung nodules? Response. Radiology, 254(2):635, February 2010.

Gavrielides MA , Zeng R, Kinnard LM, Myers KJ, Petrick N. Information-theoretic approach for analyzing bias and variance in lung nodule size estimation with CT: a phantom study. IEEE Trans Medical Imaging, 29(10):1795-807, October 2010.

Guerraty MA, Grant GR, Karanian JW, Chiesa OA, Pritchard WF, Davies PF. Hypercholesterolemia induces side-specific phenotypic changes and peroxisome proliferator-activated receptor-gamma pathway activation in swine aortic valve endothelium. Arterioscler Thromb Vasc Biol, 30(2):225-31, February 2010.

Han JH, Ilev IK, Kim DH, Song CG, Kang JU. Investigation of gold-coated bare fiber probe for in situ intra-vitreous coherence domain optical imaging and sensing. Appl Phys B, 2010 Jun 1;99(4):741-746.

He X, Gallas BD, Frey EC. Three-class ROC analysis--toward a general decision theoretic solution. IEEE Transactions in Medical Imaging, 29(1):206-15, January 2010.

Horner M, Joshi S, Dhruva V, Sett S, Stewart SFC. A two-species drug delivery model is required to predict deposition from drug-eluting stents. Cardiovasc Engr Tech. 1:225-234, 2010.

Huang A, Li J, Summers RM, Petrick N, Hara AK. Improving polyp detection algorithms for CT Colonography: Pareto Front Approach. Pattern Recognition Letters, 31(11):1461-1469, August 1, 2010.

Ilev IK , Wang LHV, Boppart SA, Andersson-Engels S, Kim BM. Introduction to the Special Issue on Biophotonics-Part 1. IEEE J Sel Top Quantum Electron, 16(3):475-7, May-June 2010.

Ilev IK , Wang LV, Boppart SA, Andersson-Engels S, Kim BM. Introduction to the Special Issue on Biophotonics - Part 2. IEEE J Sel Top Quantum Electron, 16(4):703-5, July-August 2010.

Isayeva I , Sarkar Das S, Chang A, Defoe J, Luu HM, Vorvolakos K, Patwardhan D, Whang J, Pollack S. pH effect on the synthesis, shear properties, and homogeneity of iron-crosslinked hyaluronic acid-based gel/adhesion barrier. J Biomed Mater Res B Applied Biomaterials,95(1):9-18, October 2010.

Kainz W , Guag J, Benkler S, Szczerba D, Neufeld E, Krauthamer V, Myklebust J, Bassen H, Chang I, Chavannes N, Kim JH, Sarntinoranont M, Kuster N. Development and validation of a magneto-hydrodynamic solver for blood flow analysis. Phys Med Biol, 55(23):7253-61, December 7, 2010.

Karanian JW , Peregoy JA, Chiesa OA, Murray TL, Ahn C, Pritchard WF. Efficiency of drug delivery to the coronary arteries in swine is dependent on the route of administration: assessment of luminal, intimal, and adventitial coronary artery and venous delivery methods. J Vasc Interv Radiol, 21(10):1555-64, October 2010.

Katz EJ, Ilev IK, Krauthamer V, Kim DH, Weinreich D. Excitation of primary afferent neurons by near-infrared light in vitro. Neuroreport, 21(9):662-6, June 23, 2010.

Kim DH, Ilev IK. Simple confocal thickness gauge based on fibre-optic confocal sensor for non-contact measurement. Electronics Letters46(24):1594-5, November 25, 2010.

Krauthamer V , Gomatam S, Tovar O. Performance aspects of automated rhythm detection capabilities for AEDs, EP Lab Digest 10:38-40, 2010.

Liu Y, Maruvada S, Herman BA, Harris GR. Egg white as a blood coagulation surrogate. J Acoust Soc Am, 128(1):480-9, July 2010.

Lyle DB , Breger JC, Baeva LF, Shallcross JC, Durfor CN, Wang NS, Langone JJ. Low molecular weight hyaluronic acid effects on murine macrophage nitric oxide production. J Biomed Mater Res A, 94(3):893-904, September 1, 2010.

Lyle DB , Bushar GS, Langone JJ. Screening biomaterials for functional complement activation in serum. J Biomed Mater Res A, 92(1):205-13, January 2010.

MAQC Consortium, Shi L, Campbell G, Jones WD, Campagne F, Wen Z, Walker SJ, Su Z, Chu TM, Goodsaid FM, Pusztai L, Shaughnessy JD Jr, Oberthuer A, Thomas RS, Paules RS, Fielden M, Barlogie B, Chen W, Du P, Fischer M, Furlanello C, Gallas BD, Ge X, Megherbi DB, Symmans WF, Wang MD, Zhang J, Bitter H, Brors B, Bushel PR, Bylesjo M, Chen M, Cheng J, Cheng J, Chou J, Davison TS, Delorenzi M, Deng Y, Devanarayan V, Dix DJ, Dopazo J, Dorff KC, Elloumi F, Fan J, Fan S, Fan X, Fang H, Gonzaludo N, Hess KR, Hong H, Huan J, Irizarry RA, Judson R, Juraeva D, Lababidi S, Lambert CG, Li L, Li Y, Li Z, Lin SM, Liu G, Lobenhofer EK, Luo J, Luo W, McCall MN, Nikolsky Y, Pennello GA, Perkins RG, Philip R, Popovici V, Price ND, Qian F, Scherer A, Shi T, Shi W, Sung J, Thierry-Mieg D, Thierry-Mieg J, Thodima V, Trygg J, Vishnuvajjala L, Wang SJ, Wu J, Wu Y, Xie Q, Yousef WA, Zhang L, Zhang X, Zhong S, Zhou Y, Zhu S, Arasappan D, Bao W, Lucas AB, Berthold F, Brennan RJ, Buness A, Catalano JG, Chang C, Chen R, Cheng Y, Cui J, Czika W, Demichelis F, Deng X, Dosymbekov D, Eils R, Feng Y, Fostel J, Fulmer-Smentek S, Fuscoe JC, Gatto L, Ge W, Goldstein DR, Guo L, Halbert DN, Han J, Harris SC, Hatzis C, Herman D, Huang J, Jensen RV, Jiang R, Johnson CD, Jurman G, Kahlert Y, Khuder SA, Kohl M, Li J, Li L, Li M, Li QZ, Li S, Li Z, Liu J, Liu Y, Liu Z, Meng L, Madera M, Martinez-Murillo F, Medina I, Meehan J, Miclaus K, Moffitt RA, Montaner D, Mukherjee P, Mulligan GJ, Neville P, Nikolskaya T, Ning B, Page GP, Parker J, Parry RM, Peng X, Peterson RL, Phan JH, Quanz B, Ren Y, Riccadonna S, Roter AH, Samuelson FW, Schumacher MM, Shambaugh JD, Shi Q, Shippy R, Si S, Smalter A, Sotiriou C, Soukup M, Staedtler F, Steiner G, Stokes TH, Sun Q, Tan PY, Tang R, Tezak Z, Thorn B, Tsyganova M, Turpaz Y, Vega SC, Visintainer R, von Frese J, Wang C, Wang E, Wang J, Wang W, Westermann F, Willey JC, Woods M, Wu S, Xiao N, Xu J, Xu L, Yang L, Zeng X, Zhang J, Zhang L, Zhang M, Zhao C, Puri RK, Scherf U, Tong W, Wolfinger RD. The MicroArray Quality Control (MAQC)-II study of common practices for the development and validation of microarray-based predictive models. Nat Biotechnol, 28(8):827-38, August 2010.

McDermott MK , Saylor DM, Casas R, Dair BJ, Guo J, Kim CS, Mahoney CM, Ng K, Pollack SK, Patwardhan DV, Sweigart DA, Thomas T, Toy J, Williams CM, Witkowski CN. Microstructure and elution of tetracycline from block copolymer coatings. J Pharm Sci,99(6):2777-85, June 2010.

Nell DM, Myers MR. Thermal effects generated by high-intensity focused ultrasound beams at normal incidence to a bone surface. Journal of the Acoustical Society of America, 127(1):549-59, January 2010.

Paquerault S , Hardy PT, Wersto N, Chen J, Smith RC. Investigation of optimal use of computer-aided detection systems: the role of the "machine" in decision making process. Academic Radiololgy, 17(9):1112-21, September 2010.

Park S , Jennings R, Liu H, Badano A, Myers K. A statistical, task-based evaluation method for three-dimensional x-ray breast imaging systems using variable-background phantoms. Medical Physics, 37(12):6253-70, December 2010.

Pfefer TJ , Wang Q, Drezek RA. Monte Carlo modeling of time-resolved fluorescence for depth-selective interrogation of layered tissue. Comput Methods Programs Biomed, November 24, 2010 [Epub ahead of print].

Phillips RA, Stratmeyer ME, Harris GR. Safety and U.S. Regulatory considerations in the nonclinical use of medical ultrasound devices. Ultrasound Med Biol, 36(8):1224-8, August 2010.

Pope SJ, Godar DE. Solar UV Geometric Conversion Factors: Horizontal Plane to Cylinder Model. Photochemistry and Photobiology, 86(2):457-66, March-April 2010.

Popovici V, Chen W, Gallas BG, Hatzis C, Shi W, Samuelson FW, Nikolsky Y, Tsyganova M, Ishkin A, Nikolskaya T, Hess KR, Valero V, Booser D, Delorenzi M, Hortobagyi GN, Shi L, Symmans WF, Pusztai L. Effect of training-sample size and classification difficulty on the accuracy of genomic predictors. Breast Cancer Research, 12(1):R5, January 11, 2010.

Ravenscroft-Chang MS, Stohlman JM, Molnar P, Natarajan A, Canavan HE, Teliska M, Stancescu M, Krauthamer V, Hickman JJ. Altered calcium dynamics in cardiac cells grown on silane-modified surfaces. Biomaterials, 31(4):602-7, February 2010.

Ray A, Jetley R. Model-Based Development: A new approach to engineering medical software. Biomed Instrum Technol, 44(1):51-3, January 2010.

Resnik L, Klinger S, Krauthamer V, Barnabe K. FDA regulation of prosthetic research, development and testing. Journal of Prosthetics and Orthotics, 22:121-126, 2010.

Saha A, Kelley EF, Badano A. Accurate color measurement methods for medical displays. Medical Physics37(1):74-81, January 2010.

Sapsford KE , Blanco-Canosa JB, Dawson PE, Medintz IL. Detection of HIV-1 specific monoclonal antibodies using enhancement of dye-labeled antigenic peptides. Bioconjug Chem, 21(2):393-8, February 17, 2010.

Saylor DM , Richardson DC, Dair BJ, Pollack SK. Osmotic cavitation of elastomeric intraocular lenses. Acta Biomaterialia, 6(3):1090-8, 2010.

Seidman SJ , Brockman R, Lewis BM, Guag J, Shein MJ, Clement WJ, Kippola J, Digby D, Barber C, Huntwork D. In vitro tests reveal sample radiofrequency identification readers inducing clinically significant electromagnetic interference to implantable pacemakers and implantable cardioverter-defibrillators. Heart Rhythm, 7(1):99-107, January 2010.

Seidman SJ , Kainz W, Casamento J, Witters D. Electromagnetic compatibility testing of implantable neurostimulators exposed to metal detectors. J Open Biomed Eng, 4:63-70, March 9, 2010.

Sharma KV, Dreher MR, Tang Y, Pritchard W, Chiesa OA, Karanian J, Peregoy J, Orandi B, Woods D, Donahue D, Esparza J, Jones G, Willis SL, Lewis AL, Wood BJ. Development of "imageable" beads for transcatheter embolotherapy. J Vasc Interv Radiol, 21(6):865-76, June 2010.

Shin YJ, Tata DB, Waynant RE, Gehlbach PL, Chuck RS. Fluorometric determination of the redox state and distribution of mitochondria in human malignant glioblastoma cells grown on different culturing substrates. Photomed Laser Surg, 28 Suppl 1:S105-10, August 2010.

Sistare FD, Dieterle F, Troth S, Holder DJ, Gerhold D, Andrews-Cleavenger D, Baer W, Betton G, Bounous D, Carl K, Collins N, Goering P, Goodsaid F, Gu YZ, Guilpin V, Harpur E, Hassan A, Jacobson-Kram D, Kasper P, Laurie D, Lima BS, Maciulaitis R, Mattes W, Maurer G, Obert LA, Ozer J, Papaluca-Amati M, Phillips JA, Pinches M, Schipper MJ, Thompson KL, Vamvakas S, Vidal JM, Vonderscher J, Walker E, Webb C, Yu Y. Towards consensus practices to qualify safety biomarkers for use in early drug development. Nat Biotechnol, 28(5):446-54, May 2010.

Soneson JE , Myers MR. Thresholds for nonlinear effects in high- intensity focused ultrasound propagation and tissue heating. IEEE Trans Ultrason Ferroelectr, 57(11):2450-9, November 2010.

Stratmeyer ME , Goering PL, Hitchins VM, Umbreit TH. What we know and don't know about the bioeffects of nanoparticles: developing experimental approaches for safety assessment. Biomed Microdevices, 12(4):569-73, August 2010.

Summers RM, Liu J, Rehani B, Stafford P, Brown L, Louie A, Barlow DS, Jensen DW, Cash B, Choi JR, Pickhardt PJ, Petrick N. CT colonography computer-aided polyp detection: Effect on radiologist observers of polyp identification by CAD on both the supine and prone scans. Academic Radiology17(8):948-59, August 2010.

Sun S, Francis J, Sapsford KE, Kostov Y, Rasooly A. Multi-wavelength Spatial LED illumination based detector for in vitro detection of Botulinum Neurotoxin A Activity. Sensors Actuators B Chem, 146(1-8):297-306, April 8, 2010.

Sun S, Yang M, Kostov Y, Rasooly A. ELISA-LOC: lab-on-a-chip for enzyme-linked immunodetection. Lab Chip, 10(16):2093-100, August 21, 2010.

Tu EY, Joslin CE, Shoff ME. Successful treatment of chronic stromal acanthamoeba keratitis with oral voriconazole monotherapy. Cornea, 29(9):1066-8, September 2010.

Tu EY, Joslin CE, Shoff ME, Lee JA, Fuerst PE. Sequential corneal infection with two genotypically distinct Acanthamoebae associated with renewed contact lens wear. Eye, 24(6):1119-21, June 2010.

Vaidya VS, Ozer JS, Dieterle F, Collings FB, Ramirez V, Troth S, Muniappa N, Thudium D, Gerhold D, Holder DJ, Bobadilla NA, Marrer E, Perentes E, Cordier A, Vonderscher J, Maurer G, Goering PL, Sistare FD, Bonventre JV. Kidney injury molecule-1 outperforms traditional biomarkers of kidney injury in preclinical biomarker qualification studies. Nat Biotechnol, 2010 28(5):478-85, May 2010.

Vecchiarelli AG, Han YW, Tan X, Mizuuchi M, Ghirlando R, Biert¸mpfel C, Funnell BE, Mizuuchi K. ATP control of dynamic P1 ParA-DNA interactions: a key role for the nucleoid in plasmid partition. Mol Microbiol, 78(1):78-9, October 2010.

Venkatasubramanian KK, Gupta SKS, Jetley RP, Jones PL. Interoperable Medical Devices. IEEE Pulse, 1(2):16-27, September-October 2010.

Vesnovsky O, Casamento JP, Brooks ME, Schwerin MR, Herman WA, Pollack SK, Flack MN, Collins BW, Grossman LW. Performance testing of Huber Needles for coring of Port Septa. Journal of Medical Devices, 4(3):031008, September 2010.

Vesnovsky O , Demian HW, Woods TO , Topoleski LDT. A method for reducing variability in bending strength. Transactions of the 34th Annual Meeting SFB, p. 762, 2010.

Vorvolakos K , Isayeva IS, Luu HMD, Patwardhan DV, Pollack SK. Ionically cross-linked hyaluronic acid: wetting, lubrication, and viscoelasticity of a modified adhesion barrier gel. Medical Devices: Evidence and Research2011(4):1–10, 2010.

Wang Q , Agrawal A, Wang NS, Pfefer TJ. Condensed Monte Carlo modeling of reflectance from biological tissue with a single illumination-detection fiber. IEEE J Sel Top Quantum Electron, 16(3):627-34, May-June 2010.

Wang Q , Shastri K, Pfefer TJ. Experimental and theoretical evaluation of a fiber-optic approach for optical property measurement in layered epithelial tissue. Appl Opt, 49(28):5309-20, October 1, 2010.

Wang S, Yao J, Petrick N, Summers RM. Combining statistical and geometric features for colonic polyp detection in CTC based on multiple kernel learning. Int J Comput Intell Appl, 9(1):1-15, January 1, 2010.

Wanner T, Fuller ER, Saylor DM. Homology metrics for microstructure response fields in polycrystals. Acta Materialia, 58(1):102-10, January 2010.

Wear K . Robert F. Wagner 1938-2008 In memoriam. Ultrason Imaging, 32(3):129-30, July 2010.

Wear KA . Decomposition of two-component ultrasound pulses in cancellous bone using modified least squares prony method--phantom experiment and simulation. Ultrasound Med Biol, 36(2):276-87, February 2010.

Wear KA . Cancellous bone analysis with modified least squares Prony's method and chirp filter: Phantom experiments and simulation. Journal of the Acoustic Society of America, 128(4):2191-203, October 2010.

Weininger S , Kapur KC, Pecht M. Exploring medical device reliability and its relationship to safety and effectiveness. IEEE Trans Components Packaging Techn, 33(1):240-5, March 2010.

Witten J , Park S, Myers K. Partial least squares: a method to estimate efficient channels for the ideal observers. IEEE Transactions in Medical Imaging, 29(4):1050-8, April 2010.

Wood SC , Tang X, Tesfamariam B. Paclitaxel potentiates inflammatory cytokine-induced prothrombotic molecules in endothelial cells. J Cardiovasc Pharmacol, 55(3):276-85, March 2010.

Yang M, Bruck HA, Kostov Y, Rasooly A. Biological semiconductor based on electrical percolation. Anal Chem, 82(9):3567-72, May 1, 2010.

Yang M, Sun S, Bruck HA, Kostov Y, Rasooly A. Electrical percolation-based biosensor for real-time direct detection of staphylococcal enterotoxin B (SEB). Biosens Bioelectron, 25(12):2573-8, August 15, 2010.

Yang M, Sun S, Bruck HA, Kostov Y, Rasooly A. Lab-on-a-chip for label free biological semiconductor analysis of Staphylococcal Enterotoxin B. Lab Chip, 10(19):2534-40, October 7, 2010.

Yang M, Sun S, Kostov Y, Rasooly A. Lab-on-a-chip for carbon nanotubes based immunoassay detection of Staphylococcal Enterotoxin B (SEB). Lab Chip , 10(8):1011-7, April 21, 2010.

Zhang K, Akpek EK, Weiblinger RP, Kim DH, Kang JU, Ilev IK. Noninvasive volumetric quality evaluation of post-surgical clear corneal incision via high-resolution Fourier-domain optical coherence tomography. Electronics Lett , 46(22):1482-3, October 28, 2010.

Zhang K, Katz E, Kim DH, Kang JU, Ilev IK. Common-path optical coherence tomography guided fibre probe for spatially precise optical nerve stimulation. Electronics Lett, 46(2):118-9, January 21, 2010.

Zhang Q, Hitchins VM, Schrand AM, Hussain SM, Goering PL. Uptake of gold nanoparticles in murine macrophage cells without cytotoxicity or production of pro-inflammatory mediators. Nanotoxicology, September 17, 2010 [Epub ahead of print].

Zhang Y, Jones PL, Jetley R. A hazard analysis for a generic insulin infusion pump. J Diabetes Sci Technol, 4(2):263-283, March 1, 2010.

Zhang Y, Jones PL, Klonoff DC. Second Insulin Pump Safety Meeting: Summary Report. J Diabetes Sci Technol, 4(2):488-493, March 1, 2010.


APPENDIX B – OSEL Presentations

January 1, 2010 – December 31, 2010

Abboud S , Badal A, Stern SH, Kyprianou IS. Designing a phantom for dose evaluation in multi-slice CT. Medical Imaging 2010, San Diego, CA, February 13-18, 2010.

Abi-Jaoudeh N, Pritchard W, Adams JD, Chiesa OA, Amalou H, Esparza JA, Hancock HA, Karanian JW, Wood BJ. Pulsed high intensity focused ultrasound (pHIFU) for thrombolysis of occluded bypass grafts in swine. Society of Interventional Radiology 35th Annual Scientific Meeting, Tampa, FL, March 13-18, 2010.

Badal A , Kyprianou IS, Sharma D, Badano A. Fast cardiac CT simulation using a graphics processing unit-accelerated Monte Carlo code. Medical Imaging 2010, San Diego, CA, February 13-18, 2010.

Badano A . Overview of women's imaging physics research (funded by OWH) at DIAM. FDA Office of Women's Health Science Day 2010, Silver Spring, MD, September 14, 2010.

Badano AG . In silico imaging: possibilities and challenges. Imaging 2010 (Royal Institute of Technology), Stockholm, Sweden, June 8-11, 2010.

Badano AG . The promise of 3D displays in medical imaging. Frontiers of Multi-Core Computing, 2nd Workshop on, Baltimore, MD, September 22-23, 2010.

Breger J , Isayeva I, Fisher B, Pollack SK, Lightfoote M, Wang NS. Comparison of select material properties for ionic or covalent crosslinked hydrogels for therapeutic cell encapsulation. University of Maryland Bioscience Research and Technology Review Day 2011, College Park, MD, November 9, 2010.

Brothers K , Guo J, Saylor D, Patwardhan D. Effect of sex-based differences in atherosclerotic plaque on the safety and efficacy of drug-eluting stents (oral presentation). Case Study: Sex & Gender Differences in Medical Devices – FDA Commissioner’s Fellowship Program, Silver Spring, MD, July 2010.

Brothers K , Guo J, Kim C, Saylor D, Patwardhan D. Effect of sex-based differences in atherosclerotic plaque on the safety and efficacy of drug-eluting stents containing bioabsorbable materials (poster). Office of Women’s Health Science Day, Silver Spring, MD, September 2010.

Brown R . Evaluation of new biomarkers of kidney injury. United States Environmental Protection Agency Seminar, Research Triangle Park, NC, April 13, 2010.

Brunner CC, Hurowitz SA, Abboud SF, Hoeschen C, Kyprianou IS. Noise characterization of computed tomography using the covariance matrix. Medical Imaging 2010, San Diego, CA, February 13-18, 2010.

Bryans et al. Abstract and poster presentation. Sterility assurance levels for termination sterilization of new/emerging healthcare products. Changing paradigms in infection prevention towards elimination of adverse events. International Conference on Healthcare-Associated Infections 2010 Fifth Decennial Meeting, Atlanta, GA, March 18-22, 2010.

Carey CC, Zhang YT. Developing IEEE medical device standards: A case study, wearable cuffless blood pressure measuring devices. IEEE Engineering in Medicine and Biology Society Annual International Conference, 32nd, Buenos Aires, Argentina, August 31-September 4, 2010.

Chan D , Aguel F. Conduction properties of cultured neonatal rat ventricular cardiac myocytes in response to uniaxial mechanical stress. Southern Biomedical Engineering Conference, 26th, College Park, MD, April 30 - May 2, 2010.

Chan HP, Sahiner B, Wei J, Hadjiiski LM, Zhou C, Helvie MA. Digital breast tomosynthesis: computerized detection of microcalcifications in reconstructed breast volume using a 3D approach. Medical Imaging 2010, San Diego, CA, February 13-18, 2010.

Chen W , Gallas BD. Training variability in the evaluation of automated classifiers. Medical Imaging 2010, San Diego, CA, February 13-18, 2010.

Cheng WC . A reconfigurable stereomicroscopic imaging system for digital pathology. Society for Information Display 2010 International Symposium, Seattle, Washington, May 23-28, 2010.

Cheng WC , Badano A. A gaze-contingent high-dynamic range display for medical imaging applications. Medical Imaging 2010, San Diego, CA, February 13-18, 2010.

Cohen ED , Minnikanti S, Huang B, Peixoto N. Measurement, impedance analysis, and modeling of the electric fields developed in rabbit retina by retinal prosthesis electrodes. Association for Research in Vision and Ophthalmology 2010, Ft. Lauderdale, FL, May 2-6, 2010.

Cotton LM, Burgess S, Crenshaw S, Stitcher B, Fisher BR. The effects of ifosfamide and cypermethrin on the male reproductive systems of New Zealand White (NZW) and Dutch Belted (DB) Rabbits. American College of Toxicology 31st Annual Meeting, Baltimore, MD, November 7-10, 2010.

Das SS , Lucas AD, Johns DE, Casas RS, McDermott MK, Patwardhan DV, Saylor DM. Elution of tetracycline from drug-plga coated surfaces. Society for Biomaterials 2010 Annual Meeting and Exposition, Seattle, WA, April 21-24, 2010.

Das SS , McDermott MK, Lucas AD, Cargal TE, Patel L, Saylor DM, Patwardhan DV. Absorbable coatings: structure and drug elution. Southern Biomedical Engineering Conference, 26th, College Park, MD, April 30 - May 2, 2010.

Das SS , McDermott MK, Lucas AD, Cargal TE, Patel L, Saylor DM, Patwardhan DV. Drug elution kinetics and structure of absorbable matrix coatings. American Chemical Society Mid-Atlantic Regional Meeting 2010, Wilmington, DE, April 10-13, 2010.

Das SS , Schwerin M, Walsh D, Tack C, Coleman Richardson D. Changes in viscoelastic properties of latex condoms due to personal lubricants. Southern Biomedical Engineering Conference, 26th, College Park, MD, April 30 - May 2, 2010.

Dasgupta S, Hariharan P, Myers M, Banerjee R. Reduction in beam positioning error during HIFU ablation studies in tissue phantoms. American Society of Mechanical Engineers Summer Bioengineering Conference 2010, Naples, FL, June 16-19, 2010.

Davis EM, Elabd YA, Winey KI, Regnault WF, Benetatos NM. New characterization techniques for assessing the structure and water transport properties of parylene coatings. American Chemical Society National Meeting, 239th, Anaheim, California, March 21-25, 2010.

Dreher M . Medical device regulation in the U.S. and protecting the public health. George Washington University, Washington DC, November 4, 2010.

Dreher M . Tissue engineered medical products at FDA. 12th Annual Conference of the North Carolina Tissue Engineering and Regenerative Medicine Society, Durham, NC, November 12, 2010.

Elespuru RK . Regulatory issues related to genotoxicity safety assessment of nanomaterials. Environmental Mutagen Society 41st Annual Meeting, Fort Worth, Texas, October 23-27, 2010.

Elespuru RK . Birth defects and new sentinels for heritable genetic effects in an era of personalized medicine. Environmental Mutagen Society 41st Annual Meeting, Fort Worth, Texas, October 23-27, 2010.

Fang Y , Badal A, Allec N, Karim KS, Badano A. Detection statistics in amorphous selenium using Monte Carlo simulation of X-ray, electron, and electron hole pair transport. RSNA 2010, Chicago IL, November 28-December 3, 2010.

Fang Y , Badal A, Allec N, Karim KS, Badano A, Myers KJ. Monte Carlo simulation of amorphous selenium imaging detectors. Medical Imaging 2010, San Diego, CA, February 13-18, 2010.

Fisher B . An evaluation of developmental landmark assessment in DART rodent testing. Middle Atlantic Reproduction and Teratology Association Fall Meeting 2010, Lahaska, PA, October 21-22, 2010.

Forrey C , Yager KG. Molecular dynamics study of block copolymer thin film morphology: Effect of substrate and free surface. American Chemical Society National Meeting, 240th, Boston, MA, August 22-26, 2010.

Fowlkes JB, Lewin PA, O'Brien WD Jr, Vaezy S, Wear KA. Regulatory and safety issues in medical ultrasound. IEEE International Ultrasonics Symposium 2010, San Diego, CA, October 11-14, 2010.

Freed M , de Awart JA, Duyn JH, Loud JT, Greene MH, El Khouli RH, Bluemke DA, Gallas BD, Myers KJ, Badano A. Development of a tissue-mimicking physical phantom for quantitative evaluation of breast MRI. University of Maryland/National Cancer Institute NIH Systems Biology Collaboration Workshop 2010, College Park, MD, January 26, 2010.

Freeman A , Zhang Q, Goering P, Brown R, Tang X. Development of a customized DNA microchip for the detection of changes in gene expression associated with renal injury. University of Maryland Bioscience Research and Technology Review Day 2011, College Park, MD, November 9, 2010.

Gallas BD . Agreement by concordance and reader studies. FDA/Industry Statistics Workshop 2010, Washington, DC, September 19-21, 2010.

Gavrielides MA , Kinnard LM, Myers KJ, Zheng R, Petrick N. FDA phantom CT database: a resource for the assessment of lung nodule size estimation methodologies and software development. Medical Imaging 2010, San Diego, CA, February 13-18, 2010.

Goering P . What we know and don't know about the bioeffects of nanomaterials: developing experimental approaches for safety assessment. Manchester College Science Department Seminar, Manchester, IN, April 19, 2010.

Goering PL . What we know and don't know about the bioeffects of nanomaterials: developing experimental approaches for safety assessment. Purdue University Seminar, West Lafayette, IN, September 29, 2010.

Guo J . The impact of sex-based differences in atherosclerotic plaque on the response to drug eluting stent (DES) implantation. Transactions of the 34th annual Meeting of The Society For Biomaterials, Seattle, WA, April, 22, 2010.

Hajiiski LM, Chan HP, Wei J, Sahiner B, Zhou, Helvie MA. Digital breast tomosynthesis: feasibility of automated detection of microcalcification clusters on projections views. Medical Imaging 2010, San Diego, CA, February 13-18, 2010.

Hariharan P . Interlaboratory measurements of flow parameters for comparison to CFD simulations of FDA’s nozzle model. American Society of Internal Artificial Organs 56th Annual Conference, Baltimore, MD, May 27-29, 2010.

Haugen S, Hitchins V. Cleaning and testing for debris in reusable medical devices. American Society for Testing and Materials November 2010 Committee Week, San Antonio, TX, November 14-19, 2010.

Herbertson L . A single-pass orifice system to assess red blood cell fragility. American Society of Internal Artificial Organs 56th Annual Conference, Baltimore, MD, May 27-29, 2010.

Herbertson L . Medical Devices: A regulatory perspective. Pennsylvania State University Seminar, University Park, PA, April 8, 2010.

Huang Y , Xu Y. A case study of issues with subgroup analysis for medical devices. Joint Statistical Meetings 2010, Vancouver, British Columbia, Canada, July 31 - August 5, 2010.

Ilev I . Innovative combined sensing and imaging approaches in biophotonics. Conference on Lasers and Electro-Optics (CLEO) 2010, San Jose, CA, May 16-21, 2010.

Karanian JW . The pharmacokinetics of anti-proliferative drug delivery from catheter based local drug delivery systems. Transcatheter Cardiovascular Therapeutics 22nd Annual Scientific Symposium, Washington, DC, September 21-25, 2010.

Karanian JW , Chiesa OA, Desai P, Seward K, Kreitz M, Lopez O, Virmani R, Pritchard WF. Drug retention in the coronary and femoral arteries is dependent on the route of administration in swine: assessment of intimal and adventitial endovascular and systemic pharmacokinetics and toxicology with nanoparticle albumin bound-paclitaxel. Cardiovascular Research Technology 2010, Washington, DC, February 21-23, 2010.

Karanian JW , Esparza J, Pritchard WF. Pilot animal studies: Proof of concept, non-GLP studies, and beyond. Transcatheter Cardiovascular Therapeutics 22nd Annual Scientific Symposium, Washington, DC, September 21-25, 2010.

Karanian JW , Lopez O, Chiesa OA, Pritchard WF. What do preclinical models tell us about the efficiency of various drug delivery methods in peripheral vessels? Transcatheter Cardiovascular Therapeutics 22nd Annual Scientific Symposium, Washington, DC, September 21-25, 2010.

Karanian JW , Nagaraja S, Dreher M, Constante E, McDowell B, Rad D, Lopez O, Kreitz M, Chiesa OA, Pritchard WF. Predictors of stent failure in a swine model: role of implant site, implant material and musculoskeletal motion. Cardiovascular Research Technology 2010, Washington, DC, February 21-23, 2010.

Kettermann A, Gallas B, Sahiner B, Paquerault S, Hadjiiski L, Chan HP. Interobserver variability in characterization of breast masses: impact of adding ultrasound examination and CADx to mammography. RSNA 2010, Chicago IL, November 28-December 3, 2010.

Khokhlova VA , Bessonova OV, Averiyanov MV, Soneson JE, Cleveland RO. Modeling of nonlinear shock wave propagation and thermal effects in high-intensity focused ultrasound fields. Acoustical Society of America Meeting and Noise-Con 2010, Joint 159th, Baltimore, MD, April 19-23, 2010.

Kim D, Ilev IK. Analysis of some substantial collimating lens functions in fiber optic confocal microscopy. SPIE Photonics West BiOS 2010, San Francisco, CA, January 23-28, 2010.

Kim D, Ilev IK, Klein K. Suppression of modal noise in a multimode fiber-optic delivery output from an ultra-broadband supercontinuum light source. SPIE Photonics West BiOS 2010, San Francisco, CA, January 23-28, 2010.

Kim D, Zhang K, Kang J, Ilev I. A confocal thickness gauge based on reference comparison method for noncontact thickness measurement. Conference on Lasers and Electro-Optics (CLEO) 2010, San Jose, CA, May 16-21, 2010.

Kinnard LM, Gavrielides MA, Myers KJ, Zeng R, Whiting B,Lin-Gibson S, Petrick N. Micro CT based truth estimation of nodule volume. Medical Imaging 2010, San Diego, CA, February 13-18, 2010.

Liu H , Badano AG, Chakrabarti K, Kaczmarek RV, Iyprianou I. Task specific evaluation of clinical full field digital mammography systems using the Fourier definition of the Hotelling observer SNR. Medical Imaging 2010, San Diego, CA, February 13-18, 2010.

Lu Q , Hofferbert BV, Koo G, Malinauskas RA. Assessing shear-induced platelet activation: In vitro comparison between human and bovine blood. American Society of Internal Artificial Organs 56th Annual Conference, Baltimore, MD, May 27-29, 2010.

Lucas AD . The U.S. FDA's current perspective on the regulations, standards, and guidances for natural rubber latex in medical devices. Rubber Glove Conference and Exhibition, 5th International, Kuala Lampur, Malaysia, September 28-30, 2010.

Lucas AD , Gordon EA. Analysis of polyhexamethylene biguanide in multipurpose contact lens solutions. American Chemical Society Mid-Atlantic Regional Meeting 2010, Wilmington, DE, April 10-13, 2010.

Mahoney CM, Staymates M, McDermott MK, Patwardhan D. Surface and in-depth characterization of polymer-based drug delivery devices with cluster secondary ion mass spectrometry. Practical Surface Analysis, 5th International Symposium on, Gyeongju, Korea, October 3-7, 2010.

Maruvada S , Liu Y, Herman BA, Harris GR. Evaluation of a tissue mimicking material during HIFU exposure, International Conference on Advanced Metrology for Ultrasound in Medicine, Teddington, Middlesex, UK, May 2010.

McCabe J, Moratz C, Liu Y, Egan R, Chen H, Liu J, Budinich C, Burton E, Danquah J, Myers M. Animal models for the study of military-related, blast-induced traumatic brain injury. Biomedical Sciences and Engineering Conference, Oak Ridge, TN, 2010.

McCabe J, Moratz C, Liu Y, Egan R, Chen H, Liu J, Budinich C, Burton E, Danquah J, Myers M. Technical refinements in the development of high intensity focused ultrasound exposure as a model for blast-induced brain injury in rodents. National Neurotrauma Symposium, Las Vegas, NV, 2010.

McKeon M, Fisher B, Latimer K, Suttie A, Makle B, Williams C. The effects of continuous infusion rates on pre- and postnatal development, including maternal function in rats. American College of Toxicology 31st Annual Meeting, Baltimore, MD, November 7-10, 2010.

Miller J, Hudson A, Bhattaram A, Jetley R, Nallani S. An open-source model of propofol uptake, distribution and elimination for collaborative research. American Society of Anesthesiologists Annual Meeting 2010, San Diego, CA, October 16-20, 2010.

Minnikanti S, Cohen E, Peixoto N. Quasi static analysis of electric field distributions by disc electrodes in a rabbit eye model. Southern Biomedical Engineering Conference, 26th, College Park, MD, April 30 - May 2, 2010.

Moratz C, Burton E, Woodard G, Danq J, Chen H, Liu J, Budinich C, Egan R, Liu Y, Myers M, Mccabe JT. Blood brain barrier integrity and neuro-immune sequale after mild non-impact blast brain injury utilizing a new high-intensity focused ultrasound model. Society for Neuroscience 40th Annual Meeting, San Diego, CA, November 13-17, 2010.

Myers KJ . Principles of Imaging Science: Is there a science of imaging?. National Academies Keck Futures Initiative 2010 Conference on Imaging Science, Irvine, CA, November 17-19, 2010.

Myers KJ . From Roentgen to virtual reality: The past and future of radiological imaging. Distinctive Voices@The Beckman Center, Irvine, CA, November 16, 2010.

Nagaraja S , Dreher M. The effects of vertebroplasty devices on adjacent level fracture in elderly women. Medical Device Technology Innovative Partnership (MD-TIP) Project Workshop, White Oak, MD, October 26, 2010.

Nagaraja S . Fretting, corrosion, and fracture of overlapped cardiovascular stents in-vivo. George Washington University, Department of Mechanical Engineering, Washington, DC, December 3, 2010.

Neufeld E, Szczerba D, Benkler S, Kyriakou A, Guag J, Kainz W, Krauthamer V, Bassen H, Kozerke S, Kuster N. Simulation of the magneto-hemodynamic effect for aortic flow. Bioelectromagnetics Society 32nd Annual Meeting, Seoul, Korea, June 13-18, 2010.

Park S , Clarkson E. An efficient method of estimating the Bayesian Classifier in signal detection tasks involving complex high-dimensional data. Joint Statistical Meetings 2010, Vancouver, British Columbia, Canada, July 31 - August 5, 2010.

Park S , Zeng R, Myers KJ. Singular system analysis of breast tomosynthesis systems for choosing projection angles. Medical Imaging 2010, San Diego, CA, February 13-18, 2010.

Petrick N , Gavrielides MA, Zeng RP, Kinnard LM, Myers KJ. Update on FDA Center for Devices and Radiological Health investigation of quantitative CT through anthropomorphic phantom studies. Lung Cancer Workshop VII Proceedings, Bethesda, MD, May 13-14, 2010.

Petrick N , Kim HJ, Clunie D, Borradaile K, Ford R, Zeng R, McNitt-Gray MF, Fenimore C, Lu J, Buckler, AJ. Evaluation of 1D, 2D and 3D nodule size estimation by radiologists for simple and complex shaped nodules through CT thoracic phantom imaging. RSNA 2010, Chicago IL, November 28 - December 3, 2010.

Petrick NA . Evaluation of current and emerging technologies in breast imaging. RSNA 2010, Chicago IL, November 28 - December 3, 2010.

Petrick NA , Wang S, Yao J. Matching colonic polyps using correlation optimized warping. Medical Imaging 2010, San Diego, CA, February 13-18, 2010.

Platisa L, Boossens B, Vansteenkiste E, Badano A, Philips W. Using channelized Hotelling observers to quantify temporal effects of medical liquid crystal displays on detection performance. Medical Imaging 2010, San Diego, CA, February 13-18, 2010.

Popescu LM . Image quality evaluation using automatic image scanning and a novel nonparametric free-response data analysis method. Application to PET Energy-Based Scatter Correction Evaluation. IEEE Nuclear Science Symposium, 2010, Knoxville, TN, October 30-November 6, 2010.

Qiang R, Chen J, Min S, Viohl I, Keef A, Cox T, Kainz W. An efficient estimation of electric field at leads tip using the reciprocity theorem. Bioelectromagnetics Society 32nd Annual Meeting, Seoul, Korea, June 13-18, 2010.

Qiang R, Shen J, Chen J, Min S, Viohl I, Keef A, Cox T, Kainz W. An efficient estimation of electric field variation due to tissue parameter uncertainty using a stochastic collocation method. Bioelectromagnetics Society 32nd Annual Meeting, Seoul, Korea, June 13-18, 2010.

Rajan SS , Bernardo M, Herbertson L, Shah V, Choyke PL. Construction and testing of a flow phantom for the validation of dynamic contrast-enhanced MRI (DCE-MRI). RSNA 2010, Chicago, IL, November 28 - December 3, 2010.

Rajan SS , Bernardo M, Herbertson L, Shah V, Choyke PL. Diffusion-weighted imaging (DWI) of adenomyosis and fibroids of the uterus. RSNA 2010, Chicago, IL, November 28-December 3, 2010.

Rao N, Freed M, Badano A. Comparing experimental measurements of indirect x-ray
detector responses with Monte Carlo predictions: figures of merit and model development. Medical Imaging 2010, San Diego, CA, February 13-18, 2010.

Razjouyan F, Kapoor A, Glossop N, Kruecker J, Xu S, Viswanathan A, Chiesa OA, Karanian JW, Pritchard W, Levy E, Venkatesan A, Solbiati L, Wood BJ. A comparison of methods for tracking RFA probes and sensitivity to RF field and temperature. Society of Interventional Radiology 35th Annual Scientific Meeting, Tampa, FL, March 13-18, 2010.

Reddy G, Sharma KV, Dreher M, Woods DL, Donahue D, Karanian JW, Chiesa OA, Pritchard W, Tang Y, Forster R, Willis S, Lewis A, Wood BJ. Tissue penetration of drug from Doxorubicin eluting radiopaque embolization beads. Society of Interventional Radiology 35th Annual Scientific Meeting, Tampa, FL, March 13-18, 2010.

Sahiner B . Computer-assisted decision systems in radiology - the hope, the hype, and the hard truth: CAD applications in colon imaging and beyond. RSNA 2010, Chicago IL, November 28-December 3, 2010.

Sapsford KE . Energy transfer-based biosensing of protease activity: potential use in portable screening applications. University of Maryland, Department of Bioengineering Seminar, College Park, MD, February 12, 2010.

Saylor D . Predicting microstructure evolution in drug eluting coatings. Materials Science and Technology 2010 Conference & Exhibition, Houston, TX, October 17-21, 2010.

Saylor D . Predicting microstructure evolution in controlled drug release coatings. FDA / NHLBI / NSF Workshop on Computer Methods for Cardiovascular Devices, Rockville, MD, June 2010.

Saylor D . Microstructure modeling of controlled drug release coatings. ISCST 2010, St. Paul, MN, September 2010 (invited).

Saylor D . Microstructure modeling of controlled drug release coatings. The University of Minnesota, Minneapolis, MN, September 2010 (invited).

Schlichting A, Waynant RW, Tata DB. In-vitro suppression of metabolic activity in malignant human glioblastomas due to pulsed - low frequency electric potential exposures. Mechanisms for Low-Light Therapy V, San Francisco, CA, January 23, 2010.

Shoff ME , Brown JN, Lucas AD, Hitchins VM. The effects of contact lens and lens cases on disinfection activity in multipurpose contact lens solution against S. aureus. Abstract and poster presentation (#I-1736; p. 133). American Society for Microbiology, 110th General Meeting, San Diego, CA, May 22-27, 2010.

Soneson JE . A parallel algorithm for high-intensity focused ultrasound simulation. Acoustical Society of America Meeting and Noise-Con 2010, Joint 159th, Baltimore, MD, April 19-23, 2010.

Spees B , Berndt DC. Introducing state machines in everyday devices. Washington Academy of Sciences: Science 2010, Arlington, VA, March 27-28, 2010.

Stewart S . Turbulence modeling as a source of error in FDA's “Critical Path” interlaboratory computational study of flow in a nozzle model. American Society of Internal Artificial Organs 56th Annual Conference, Baltimore, MD, May 27-29, 2010.

Stewart SFC , Hariharan P, Burgreen GW, Paterson EG, Reddy V, Day SW, Giarra M, Manning KB, Deutsch S, Myers MR, Berman MR, Malinauskas RA. FDA’s interlaboratory computational study of flow in a nozzle model: using experimental results to refine simulations. FDA & NHLBI Third Annual Workshop on Cardiovascular Device Modeling, Rockville, MD, June 10-11, 2010.

Szczerba D, Christ A, Neufeld E, Kainz W, Kuster N. Whole body human models for biomedical simulations. Virtual Physiological Human 2010, Brussels, Belgium, September 30 - October 1, 2010.

Tan X , Ilev I . Advanced laser spectroscopy approaches for sensing surface contaminants on medical devices. SPIE Photonics West BiOS 2010, San Francisco, CA, January 23-28, 2010.

Tata D , Abliz E, Waynant R, Collins J, Friedberg J, Kumar A, Bell H. Novel application of rare-earth particles in activating Photofrin II through X-ray induced visible luminescence: an in vitro study. American Society for Laser Medicine and Surgery 30th Annual Conference, Phoenix, Arizona, April 16-18, 2010.

Tata DB , Schlichting A, Waynant RW. In vitro suppression of metabolic activity in malignant human brain cancer and normal human fi broblast due to extremely low frequency pulsed electric potential exposures. SPIE Photonics West BiOS 2010, San Francisco, CA, January 23-28, 2010.

Tata DB , Waynant RW, Collins JE, Friedberg JS, Kumar A, Bell H. Novel applications of diagnostic x-rays in activating photo-agents through x-ray induced visible fl uorescence from rare-earth particles: an in-vitro study. SPIE Photonics West BiOS 2010, San Francisco, CA, January 23-28, 2010.

Tock CL, Altiner A, Turner LR, Batra P, Warner JA, Therrien J, Turner ML, Miller SA, Beer JZ, Kraemer KH, Udey MC, Vogel JC, Terunuma A. A typical daily close of ultraviolet radiation on human skin treated with an FDA-standardized sunscreen leaves a unique “UVA signature” on the transcriptome. Society for Investigative Dermatology 2010 Annual Meeting, Atlanta, Georgia, May 5-8, 2010.

Vesnovsky O, Demian HW, Woods TO, Topoleski LDT. A method for reducing variability in Bending Strength. Society for Biomaterials 2010 Annual Meeting and Exposition, Seattle, WA, April 21-24, 2010.

Vorvolakos K . Dynamic wetting and dewetting of viscoelastic hyaluronic acid solutions (invited). University of Akron's Department of Polymer Science, Akron, OH, July 30, 2010.

Wahab R, Liu Y, Krauthamer V, McCabe J, Moratz C, Egan R, Zderic V, Myers M. Effects of a simulated blast pulse train on a simple neural model. Acoustical Society of America Meeting and Noise-Con 2010, Joint 159th, Baltimore, MD, April 19-23, 2010.

Wang M, Shen J, Chen J, Kainz W, Mendoza G, Bit Babik G. Electromagnetic compatibility issues between vehicular mounted antennas and implantable medical devices. Asia-Pacific Electromagnetic Compatibility Symposium and Technical Exhibition 2010, Beijing, China, April 12-16, 2010.

Wang Q , Shastri K, Agrawal A, Pfefer J. In situ optical property measurement in layered tissue: theoretical and experimental assessment of an unconstrained approach. SPIE Photonics West BiOS 2010, San Francisco, CA, January 23-28, 2010.

Wear KA . Frequency dependence of phase shifts in human calcaneus in vitro. Acoustical Society of America Meeting and Noise-Con 2010, Joint 159th, Baltimore, MD, April 19-23, 2010.

Wear KA . Decomposition of two-component pulses: Simulation and phantom experiment. Acoustical Society of America Meeting and Noise-Con 2010, Joint 159th, Baltimore, MD, April 19-23, 2010.

Wear KA . Decomposition of two-component pulses in bone: phantom experiment and simulation. IEEE International Ultrasonics Symposium 2010, San Diego, CA, October 11-14, 2010.

Wear KA , Harris GR. FDA regulation of medical ultrasound devices. Short course: Regulatory and Safety Issues in Medical Ultrasound (Invited). IEEE International Ultrasonics Symposium, San Diego, CA, October 2010.

Weaver EV, McDowell E, Fisher B, Latimer KS, Suttie AW. Comparison of toxicology parameters in pregnant and nonpregnant rats. American College of Toxicology 31st Annual Meeting, Baltimore, MD, November 7-10, 2010.

Wei J, Chan HP, Zhou C, Helvie MA, Hadjiiski LM, Sahiner B. Association of a mammographic parenchymal pattern (MPP) descriptor with breast cancer risk: a case-control study. Medical Imaging 2010, San Diego, CA, February 13-18, 2010.

Witters D , Seidman S, Bassen H. EMC and wireless healthcare. Asia-Pacific Electromagnetic Compatibility Symposium and Technical Exhibition 2010, Beijing, China, April 12-16, 2010.

Woods TO . Regulation of tissue engineered medical products. Roundtable on Biomedical Engineering Materials and Applications. National Academies, Woods Hole, Massachusetts, July 8, 2010.

Woods TO . Current status of FDA safety guidelines for medical devices in the MR environment. ISMRM Workshop on MR Safety: RF Heating of the Human in MRI Stillwater, Minnesota, October 2010.

Zeng R , Petrick NA, Gavrielides MA, Myers KJ. Approximations of noise structures in helical multi-detector CT scans: application to lung nodule volume estimation. Medical Imaging 2010, San Diego, CA, February 13-18, 2010.

Zhang K, Akpek E, Weiblinger RP, Kim DH, Kang JU, Ilev I. Post-surgical volumetric evaluation of clear corneal incision quality using a high-resolution 3-D spectral-domain optical coherence tomography. Conference on Lasers and Electro-Optics (CLEO) 2010, San Jose, CA, May 16-21, 2010.

Zhang K, Katz E, Kim DH, Kang JU, Ilev I. A fiber-optic nerve stimulation probe integrated with a precise common-path optical coherence tomography distance sensor. Conference on Lasers and Electro-Optics (CLEO) 2010, San Jose, CA, May 16-21, 2010.

Zhang Q , Hitchins VM, Schrand AM, Hussain SM, Goering PL. Uptake of gold nanoparticles in murine macrophage cells without cytotoxicity or production of pro-inflammatory mediators. Society of Toxicology 49th Annual Meeting, Salt Lake City, Utah, March 7-11, 2010.

Zhou C, Chan HP, Chughtai A, Patel S, Hadjiiski LM, Sahiner B, Wei J, Kazerooni EA. Automated segmentation and tracking of coronary arteries in cardiac CT scans: comparison of performance with a clinically used commercial software. Medical Imaging 2010, San Diego, CA, February 13-18, 2010.


APPENDIX C – OSEL Academic Affiliations

January 1, 2010 – December 31, 2010

Agrawal, Anant
Virginia State University
Department of Mathematics and Computer Science
Member, Master’s thesis committee

Badano, Aldo, Ph.D.
University of Maryland, College Park
Adjunct Prof
Fischell Department of Bioengineering

Bassen, Howard I.
University of Maryland
College of Engineering
Lecturer

Chang, Isaac A, Ph.D.
Catholic University of America
Department of Biomedical Engineering
Assistant Professor

George Washington University
Department of Electrical and Computer Engineering
Research Advisor, Ph.D. Student

Dair, Benita J., Ph.D.
University of Maryland
Fischell Department of Bioengineering
Adjunct Professor

Di Prima, Matthew, Ph.D.
University of Texas at Dallas
School of Engineering and Computer Science
Visiting Researcher

Dreher, Maureen, Ph.D.
University of Maryland
Fischell Department of Bioengineering
Adjunct Professor

Goering, Peter L., Ph.D.
University of Maryland
School of Medicine
Baltimore, MD
Adjunct Professor

The George Washington University
Department of Biological Sciences
Washington, DC
Adjunct Associate Professor

Gray, Richard, Ph.D.
University of Alabama at Birmingham
Department of Biomedical Engineering
Associate Professor

University of Alabama at Birmingham
Center for Glial Biology in Medicine
Scientist

Vanderbilt University
Department of Biomedical Engineering
Adjunct Associate Professor

Vanderbilt University
Vanderbilt Institute for Integrative Biosystems
Research and Education
External Associate

Jetley, Raoul, Ph.D.
University of Arkansas at Little Rock
Department of Computer Science
Adjunct Faculty Member, and
Member, Doctoral Dissertation Committee

Kainz Wolfgang, Ph.D.
University of Houston
Department of Electrical and Computer Engineering
Member, Doctoral thesis committee

Mehrabi, Ali , Ph.D.
Strayer University
Adjunct professor
Undergraduate Math

Stratford University
Adjunct professor
Graduate and Undergraduate courses in Networking, CIS, MIS, and Telecommunications
Department of Electrical and Computer Engineering

Pfefer, T. Josh, Ph.D.
University of Maryland
Department of Chemical and Biomolecular Engineering
Doctoral thesis committee

Waynant, Ronald W. , Ph.D.
Catholic University of America
Electrical Engineering Department
Adjunct Associate Professor
Uniformed Services University of the Health Sciences
Adjunct Professor

Wear, Keith A., Ph.D.
Georgetown University
Radiology Department
Adjunct Professor

Henry M. Jackson Foundation for the Advancement of Military Medicine
Guest Scientist

Weininger, Sandy, Ph.D.
Drexel University
Lecturer and course/program developer


APPENDIX D – OSEL Patents

January 1, 2010 – December 31, 2010

Anders J, Ilev I, Waynant R, Byrnes K. Method for regeneration and functional recovery after spinal cord injury using phototherapy. Patent No. 7,695,504 (April 13, 2010).

Ilev I . Confocal fiber-optic laser device and method for intraocular lens power measurements. Patent No. 7,719,668 (May 18, 2010).

Ilev I , Robinson R, Waynant R. Particle image velocimetry system having an improved hollow-waveguide-based laser illumination system. Patent No. 7,787,106 (August 31, 2010).


APPENDIX E – OSEL-Sponsored Seminars

January 1, 2010 – December 31, 2010

Cherkassky V, University of Minnesota. Statistical considerations related to analyzing learning machine algorithms. June 3, 2010.

Dong M, Rice University. Chameleon: energy-efficient color-adaptive web browser for mobile OLED displays. October 27, 2010. 

James RH . CDRH Staff College. Characteristics of UV radiation-OCER training course on tanning. Silver Spring, MD, September 8, 2010.

Kang R. Air Force Medical Service Corps. Air Force human research protection program and ethics of military supported basic research. September 8, 2010.

Kimpe T and A. Xthona, Barco. Features and clinical performance of the next generation mammography display. November 8, 2010.

Koay C, National Institutes of Health. Construction of a DT-MRI data-processing pipeline: theory and practice. Bethesda, MD, February 22, 2010.

LiKamWa R , Rice University . Mobile display content stabilization. October 27, 2010. 

MariniBettolo C, KTH. Performance studies and star tracking for PoGOLite. Sweden. September 15, 2010.

Nehrt N, Indiana University. Testing the ‘ortholog conjecture’ with functional genomic data from mammals. February 25, 2010.

Peng R, University of North Carolina at Chapel Hill. Carbon nanotube field emission x-ray technology. May 26, 2010.

Siewerdsen J, Johns Hopkins University. From image science to image-guided interventions. Baltimore, MD, May 20, 2010.

Toth T, GE Healthcare (retired) and D. Rohler, Plexar Associates, Inc. CT image quality metric proposition. March 4, 2010.

Yousef W, Helwan University. Detecting abnormalities in digital mammography. October 7, 2010.


APPENDIX F – OSEL Science Sharing Seminars

June 28, 2010 – December 13, 2010

June 28

Bassen H , Seidman S, Witters D (Division of Physcis). Testing for electromagnetic effects on devices: iPods, cell phones, metal detectors, and MRIs – innocuous or not?

July 12

Benetatos N , Regnault W. (Division of Chemistry). From stents and catheters to bionic eyes: the expanding role of polymeric coatings in devices.

July 26

Myers MR , Soneson J. (Division of Solid and Fluid Mechanics). Computer simulations of focused-ultrasound surgical procedures: a tool for reducing dependence upon animal studies and clinical trials.

August 9

Rajan S . (Division of Physics). New applications of MRI: beyond routine anatomical imaging.

August 23

Wear K . (Division of Imaging and Applied Mathematics). Medical ultrasound: tissue-mimicking phantoms, 3d breast imaging, osteoporosis detection, and safety considerations.

September 20

Sapsford K . (Division of Biology). Rapid screening assays for diagnostic device and import safety applications.

October 4

Stewart S , Malinauskas R. (Division of Solid and Fluid Mechanics). Can computer simulations predict fluid flow and blood damage in medical devices?

October 18

Sudarsan S , Jetley R. (Division of Electrical and Software Engineering). Semantic text mining: a new approach to searching CDRH’s regulatory documents.

November 1

Saylor D , Guo J. (Division of Chemistry and Materials Science). Microstructure in controlled drug release: how manufacturing affects performance.

November 15

Shoff M . (Division of Biology). Contact lens-related eye infections: how we got here, where we are going.

November 29

Midgette W . (Division of Electrical and Software Engineering). Why is risk management the way to evaluate device safety?

December 13

Petrick N . (Division of Imaging and Applied Mathematics). Quantitative CT imaging: can it be a biomarker for the success of cancer treatment?


APPENDIX G – Interagency Agreements/CRADAs

January 1, 2010 – December 31, 2010

New Reimbursable IAGs:

Safety and Reliability of Neurological Devices Implanted in the Nervous System
DARPA/MTO: Defense Advanced Research Projects Agency, Microsystems Technology Office
PI: Victor Krauthamer (Division of Physics)

Subject Matter Expert Support by the U.S. Food and Drug Administration
NRL: Naval Research Laboratory
PI: Kim Sapsford (Division of Biology)

Development of Anti-Ebola MHC Tetramers
NIH/NIAID: National Institutes of Health/National Institute of Allergy and Infectious Diseases
PI: Steven Wood (Division of Biology)

Renewed Reimbursable IAGs (2010):

Assistance in Test Bed Development for Deep Bleeder Acoustic Coagulation Program
DARPA: Defense Advanced Research Projects Agency,
PI: Gerald Harris, Larry Grossman (Division of Solid and Fluid Mechanics)

Image-Guided Interventional Therapeutics
NIH/CC: National Institutes of Health/Clinical Center
PI: William Pritchard, John Karanian (Division of Biology)

Special Safety Analysis and Measurement Related to Advanced Passenger Screening Technology
DHS/S&T: Department of Homeland Security/Science and Technology Directorate
PI: Donald Witters, Howard Bassen (Division of Physics)

New CRADAs (2010)

Imricor Medical Systems, Inc
PI: Leonardo Angelone (DP)


APPENDIX H - OSEL Laboratory Leaders

Updated June 2, 2011
Primary contacts for new technical support requests

DIVISION OF BIOLOGY

Division Director: Marilyn Lightfoote (301) 796-0235

Deputy Director: Ben Fisher (301) 796-0245

  • Toxicology and Biocompatibility: Peter Goering (301) 796-0253
  • Biomolecular Mechanisms (molecular biology, immunology, allergy, cell biology, genomics/genetics): Steve Wood* (301) 796-0243
  • Cardiovascular & Interventional Therapeutics: John W. Karanian (301) 210-4247
  • Emerging Biosensors and Biotechnologies: Kim Sapsford (301) 796-0311
  • Infection Control: Vicki Hitchins (301) 796-0258

DIVISION OF CHEMISTRY AND MATERIALS SCIENCE

Division Director: Dinesh Patwardhan (301) 796-2622

Deputy Director: Benita Dair (301) 796-2614

  • Active Materials: Martin (Ken) McDermott (301) 796-2621
  • Materials Performance: Benita Dair (301) 796-2614

DIVISION OF ELECTRICAL AND SOFTWARE ENGINEERING

Division Director: Al Taylor (301) 796-2583

Deputy Director: Brian Fitzgerald (301) 796-2579

  • Electrical Engineering: vacant
  • Software (Research): Raoul Jetley (301) 796-2547
    Software (Regulatory Support): Joseph Jorgens (301) 796-2588

DIVISION OF IMAGING AND APPLIED MATHEMATICS

Division Director: Kyle J. Myers (301) 796-2562

Deputy Director: Nicholas Petrick (301) 796-2563

  • Image Analysis: Nicholas Petrick (301) 796-2563
  • Imaging Physics: Aldo Badano (301) 796-2534
  • Ionizing Radiation Metrology: Mary Walker (301) 796-2558

DIVISION OF PHYSICS

Division Director: Victor Krauthamer (301) 796-2474

Deputy Director: Brian Beard (301) 796-2469

  • Biophysics: Sunder Rajan (301) 796-4194
  • Electromagnetic and Wireless Technologies: Howard Bassen (301) 796-2472
  • Optical Diagnostic Devices: Joshua Pfefer (301) 796-2494
  • Optical Therapeutics and Medical Nanophotonics: Ilko Ilev (301) 796-2489
  • Functional Performance and Device Use Laboratory: Karen Siegel (301) 796-0653

DIVISION OF SOLID AND FLUID MECHANICS

Division Director: Laurence Grossman (301) 796-2502

Deputy Director: Jon Casamento (301) 796-2499

  • Fluid Dynamics: Laurence Grossman (301) 796-2502
  • Solid Mechanics: Terry Woods (301) 796-2503
  • Ultrasonics: Gerald Harris (301) 796-2508

* denotes Acting


1 The QS regulation is applicable to any finished device (21 CFR 820.1). The regulation for design controls, 21 CFR 820.30, applies to class III, class II, and specific class I devices, including devices automated with computer software.

2 Science and engineering are popularly conflated in the public mind, but they are very different disciplines. cf. Petroski, Henry, “Engineering Is Not Science,” IEEE Spectrum, December 2010.

3 For example, a “random component failure” turned out, under closer scrutiny, to have been caused by overstress due to the fact that the circuit in which the component was used violated a condition that was expressly stated in the component’s data sheet.

4 www.fda.gov/infusionpumps

5 This more comprehensive engineering review need not be time-consuming. In fact, in many cases the total review time will be less because the need for rounds of additional questions is eliminated.