High Resolution Optical Imaging
Over the last several decades, a variety of high resolution in vivo optical imaging methods have emerged which enable visualization of biological structures and processes on the micrometer scale, near the diffraction limit of light. The concomitant rise in computational power has propelled the sophistication of these imaging techniques: from two dimensional slices to three dimensional volumes, from static to dynamic processes, from qualitative to quantitative information. Real-time analysis and display of these detailed optical images now empowers scientists and clinicians with unprecedented insights into previously unseen biological phenomena.
The overall vision of the High Resolution Optical Imaging (HROI) program has two components:
- To better understand the safety and effectiveness of HROI technologies integrated into medical devices
- To apply HROI methods in targeted regulatory science investigations of medical devices and biological tissue
OCT images of (a) retina phantom and (b) human retina. Scale bar is 100 µm optical depth.
Composite image showing optical coherence angiography (OCA, grayscale) of capillaries and two-photon fluorescence microscopy (TPFM, in green) of neurons (layer 5 pyramidal cells) in the mouse motor cortex. Both OCA and TPFM images are 100 µm thick maximum intensity projections below an implanted window. Scale bar is 100 µm.
The primary imaging methods under study in the HROI program include optical coherence tomography (OCT), adaptive optics (AO), two-photon fluorescence microscopy (TPFM), and photoacoustic microscopy (PAM). Because of its subsurface and 3D imaging capabilities, OCT is now widely used as a clinical tool to visualize and measure disease processes in ophthalmology, but it has also established its value in cardiovascular medicine and other areas of the body. Motivated by the first component of the HROI program vision, we have been developing physical models known as phantoms to characterize OCT medical device imaging performance through controlled bench testing (see OCT images). The second component of our program vision encompasses the application of HROI techniques (OCT and TPFM) to investigate the neurological system response to implanted electrodes under development for medical device applications such as a brain-computer interface (see composite image). Beyond these ongoing research projects, we are also exploring other novel in vivo and in vitro HROI modalities and applications aligned with regulatory and public health needs.
Current funding sources
Anant Agrawal, Ph.D.
Ethan Cohen, Ph.D.
Daniel X. Hammer, Ph.D.
Zhuolin Liu, Ph.D.
Joshua Pfefer, Ph.D.
University of Pittsburgh Medical Center
National Eye Institute
Johns Hopkins University
- Three spectral domain OCT systems with 850 nm, 1070 nm, and 1310 nm source wavelengths
- Adaptive optics ophthalmoscope with 780 nm source wavelength
- Two-photon fluorescence microscope with 690-1030 nm tunable laser source
- Photo-acoustic microscope with 550-700 nm tunable dye laser source
Relevant standards & guidances
International Standard ISO 16971, Ophthalmic instruments — Optical coherence tomograph for the posterior segment of the human eye
Selected peer-review publications
- Agrawal et al., Methods to assess sensitivity of optical coherence tomography systems. Biomedical Optics Express, 2017.
- Hammer et al., Acute insertion effects of penetrating cortical microelectrodes imaged with quantitative optical coherence angiography. Neurophotonics, 2016.
- Lozzi et al., Image quality metrics for optical coherence angiography, Biomedical Optics Express, 2015.
- Hammer et al., Longitudinal vascular dynamics following cranial window and electrode implantation measured with speckle variance optical coherence angiography, Biomedical Optics Express, 2014.
- Baxi et al., Retina-simulating phantom for optical coherence tomography, Journal of Biomedical Optics, 2014.
- Agrawal et al., Multilayer thin-film phantoms for axial contrast transfer function measurement in optical coherence tomography, Biomedical Optics Express, 2013
- Agrawal et al., Characterizing the point spread function of retinal OCT devices with a model eye-based phantom, Biomedical Optics Express, 2012.
- Cohen et al., Optical coherence tomography imaging of retinal damage in real time under a stimulus electrode, Journal of Neural Engineering, 2011.
- Agrawal et al., Three-dimensional characterization of optical coherence tomography point spread functions with a nanoparticle-embedded phantom, Optics Letters, 2010.
- Agrawal et al., Quantitative evaluation of optical coherence tomography signal enhancement with gold nanoshells. Journal of Biomedical Optics, 2006.