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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY018855-04
Application #
8244510
Study Section
Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Shen, Grace L
Project Start
2009-04-01
Project End
2014-03-31
Budget Start
2012-04-01
Budget End
2014-03-31
Support Year
4
Fiscal Year
2012
Total Cost
$176,418
Indirect Cost
$57,618
Name
University of Texas Health Science Center San Antonio
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229
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
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
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
Duong, Timothy Q (2014) Magnetic resonance imaging of the retina: from mice to men. Magn Reson Med 71:1526-30
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
Huang, Shiliang; Du, Fang; Shih, Yen-Yu I et al. (2013) Methylene blue potentiates stimulus-evoked fMRI responses and cerebral oxygen consumption during normoxia and hypoxia. Neuroimage 72:237-42
Muir, Eric R; De La Garza, Bryan; Duong, Timothy Q (2013) Blood flow and anatomical MRI in a mouse model of retinitis pigmentosa. Magn Reson Med 69:221-8
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

Showing the most recent 10 out of 49 publications