Retinitis pigmentosa (RP) is a group of inherited diseases marked by progressive photoreceptor degeneration, affecting 1.5 million people worldwide. The vascular (choroidal and retinal) layers located on either side of the retina and other (bipolar and ganglion) cell layers are also affected. Current clinical assessment of RP relies heavily on visual testing. Non-invasive imaging technologies capable of detecting layer-specific cellular and vascular changes would enable objective early detection, longitudinal disease staging, monitoring of therapeutic intervention, and improved understanding of the underlying pathophysiology. Optical-based retinal imaging techniques can be limited by media opacity (i.e., cataracts and vitreous hemorrhages) which precludes visualization of deep retinal layers and vessels. In contrast, magnetic resonance imaging (MRI) provides non-invasive images of anatomy, physiology and function without depth limitation. Achieving sufficient spatial resolution for retinal MRI, however, remains challenging. In this proposal, we will develop novel anatomical, physiologic and functional MRI to resolve various layers of the retina at 60x60x500 5m, and vigorously test this capability by longitudinally investigating progressive, layer-specific retinal degeneration in the Royal-College-of-Surgeon (RCS) rat retinas, an established model of human RP.
This proposal outlines the development, cross-validation and application of novel MRI approaches to resolve structural, physiological and functional laminar specificity of the retina at very high spatial resolution. It has strong clinical significance and potential impact to the field in that it can provide 1) an early marker of retinal degeneration and for monitoring therapeutic intervention and 2) powerful insights into how retinal and choroidal blood flow and oxygenation are regulated and how retinal degeneration affects the two vasculatures and the neural tissues they subserve. Data from these animal studies should advance these areas of research, open up new avenues for retinal research, and lay the foundation for future human studies.
|Bresnen, Andrew; Duong, Timothy Q (2015) Brain high-energy phosphates and creatine kinase synthesis rate under graded isoflurane anesthesia: An in vivo (31) P magnetization transfer study at 11.7 tesla. Magn Reson Med 73:726-30|
|Muir, Eric R; Chandra, Saurav B; De La Garza, Bryan H et al. (2015) Layer-Specific Manganese-Enhanced MRI of the Diabetic Rat Retina in Light and Dark Adaptation at 11.7 Tesla. Invest Ophthalmol Vis Sci 56:4006-12|
|Emeterio Nateras, Oscar San; Harrison, Joseph M; Muir, Eric R et al. (2014) Choroidal blood flow decreases with age: an MRI study. Curr Eye Res 39:1059-67|
|Shih, Yen-Yu I; De La Garza, Bryan H; Huang, Shiliang et al. (2014) Comparison of retinal and cerebral blood flow between continuous arterial spin labeling MRI and fluorescent microsphere techniques. J Magn Reson Imaging 40:609-15|
|Muir, Eric R; Cardenas, Damon; Huang, Shiliang et al. (2014) MRI under hyperbaric air and oxygen: effects on local magnetic field and relaxation times. Magn Reson Med 72:1176-81|
|Duong, Timothy Q (2014) Magnetic resonance imaging of the retina: from mice to men. Magn Reson Med 71:1526-30|
|Li, Guang; Shih, Yen-Yu Ian; Kiel, Jeffrey W et al. (2013) MRI study of cerebral, retinal and choroidal blood flow responses to acute hypertension. Exp Eye Res 112:118-24|
|Muir, Eric R; Zhang, Yi; San Emeterio Nateras, Oscar et al. (2013) Human vitreous: MR imaging of oxygen partial pressure. Radiology 266:905-11|
|Park, Sung-Hong; Wang, Danny J J; Duong, Timothy Q (2013) Balanced steady state free precession for arterial spin labeling MRI: Initial experience for blood flow mapping in human brain, retina, and kidney. Magn Reson Imaging 31:1044-50|
|Shih, Yen-Yu I; Wang, Lin; De La Garza, Bryan H et al. (2013) Quantitative retinal and choroidal blood flow during light, dark adaptation and flicker light stimulation in rats using fluorescent microspheres. Curr Eye Res 38:292-8|
Showing the most recent 10 out of 49 publications