Critical Path—Noninvasive Imaging – NCTR scientists have completed trial experiments in the new NCTR MicroPET Imaging Center investigating whether, early in development, anesthetic exposures alter patterns of normal programmed cell death. PET, or Positron Emission Tomography, is most commonly known for its use in oncology clinics to detect tumor masses and follow the time-course of disease and treatment effects. However, PET also is highly versatile in monitoring changes in body metabolism in health and disease through use of a variety of positron-emitting radiochemicals. Utilization of the NCTR facility is enhanced through cooperation with the nearby University of Arkansas for Medical Sciences cyclotron facilities that provide the short half-life radiochemicals required for this work. Use of MicroPET, which is configured specifically for very high quality imagery in small animals and other imaging techniques, will provide the FDA with noninvasive procedures for repeatedly monitoring and detecting the time-course of rarer toxicological events that may have direct applications in clinical settings. The MicroPET will provide the opportunity to follow such events noninvasively in longitudinal fashion, providing time-course information on lesion development, severity, and recovery. In like fashion, although using different technology, NCTR will also employ Magnetic Resonance Imaging and Spectroscopy (MRI/MRS) approaches with its new high power (7 tesla) magnet system. Imaging at such high power provides outstanding structural resolution in relatively short scan times and allows for the quantitataion of metabolic changes in living tissue over time. The ability to repeatedly image the same subjects provides the opportunity to gather information on the life cycle of chemically-induced lesions, disease progression and the effectives of interventions.
Electronic Imaging as a Tool for Pathology Review – There has been an ongoing need for a cost-effective method to archive images of pathology data with the concurrent ability to review. Methods for electronic imaging have been developed and now validated by scientists at the National Center for Toxicological Research (NCTR). This new state-of-the-art technology allows pathologists at remote sites to observe slide images for review and/or comment. A program has been created that allows multiple users to review the same image from off-site locations using identical PC/notebooks, monitors, and software specifically designed for this purpose. The identity of slides is protected by the addition of unique bar codes. Slides are converted to electronic images using the Aperio ScanScope XT at 40X magnification, and the images are then stored on a secure server at NCTR. A copy of each image can be transferred to a Pathology Data Images remote and secure server using a unique file-transfer protocol. The images then become available for review through the Spectrum Web Viewer. Because an important requirement for the system was that users see the same image at the same resolution, this became an integral part of the validation process. Validation also included a side-by-side comparison of traditional techniques with the new system. This is a technological advance that will allow for multiple participants to review slides in real time while providing consultative expertise from remote sites. In addition, there will be significant savings of time and resources while security and integrity of the study material is maintained.
The Virtual Pathology Environment – NCTR has established a secure digital-imaging and software system to be used by Pathology Working Groups (PWGs) in the formal peer review of GLP studies. Although digital imaging has been used informally by pathologists to share information for a long time, advances in technology have allowed these applications to be incorporated into the formal pathology peer-review environment. This virtual-pathology environment significantly reduces procedural costs and facilitates the organization of global professionals producing the most expert and timely reviews possible.
PET Imaging at NCTR – PET (or positron emission tomography) is an established clinical imaging tool used to detect and follow the biological course of several diseases at the molecular level before anatomical changes may be apparent; e.g., several cancers, heart disease including coronary artery disease, neurological disorders including Alzheimer’s, Parkinson’s, and epilepsy.
NCTR’s high-resolution MicroPET installation has been completed and is being used in preclinical studies to evaluate the emergence and development of toxicity. The first NCTR protocol, “Methods Development for High Resolution Micro-Positron Emission Tomography (MicroPET) to Assess Rodent Neuroplasticity and Toxicity during Development,” was used to evaluate system performance and demonstrate utility. High-resolution MicroPET will dramatically increase the level and sophistication of data that can be obtained from animal models of toxicity and disease and provide direct links to clinical applications. Recent studies indicate that this approach will be invaluable in studies on the developmental neurotoxicity associated with exposure to general anesthetics used in the pediatric setting.