About

Research Statement

My long-term goals are to further develop my research programs in developing and applying MRI methods to investigate physiology in neurovascular diseases of the retina and brain. A major focus of my work has been to i) develop high-resolution MRI to image different layers of the retina in animal models and humans ii) to develop and apply sophisticated MRI techniques to investigate neurological disease pathophysiology in rodent models and humans. These developments include: a) methods to measure layer-specific blood flow of the retina and choroid, b) high-resolution functional MRI to detect physiologically induced changes in the retina and choroid, c) methods to directly image water exchange using deuterium oxide MRI, and d) measurement of ocular oxygen tension in the vitreous and the brain. I have experience developing and applying these sophisticated MRI techniques to investigate vascular dysfunction and pathophysiology of retinal disease in rodent models of numerous diseases, including diabetic retinopathy, glaucoma, and retinal degeneration. I have also used similar methods translated to human studies of aging, diabetic retinopathy, and age-related macular degeneration. In recognition of my contributions to advancing ocular and retinal MRI, I have been selected as a Junior Fellow by the International Society for Magnetic Resonance in Medicine.

I further have experience developing and applying sophisticated MRI techniques to investigate neurological and neurovascular disease pathophysiology in rodent models of numerous diseases, including Alzheimer’s disease, Parkinson’s disease, diabetes, hypertension, stroke, and traumatic brain injury. I have developed novel MRI methods, including novel MRI techniques for measuring blood flow in mice and a method to measure changes in brain oxygen tension. In humans I have also used MRI to investigate functional, anatomical, and diffusion changes in the brain in normal aging and in glaucoma. Details of these studies include:

1. Layer-specific blood flow of the retina in animal models:A major focus of my research has been to investigate physiology, particularly blood flow (BF), in the retina with MRI. The retina is nourished by two separate circulations, the retinal and the choroidal vessels, located on either side of the retina. The two circulations have substantially different physiology from each other and likely have different susceptibilities in retinal diseases, so it is important to be able to distinguish the two. The spatial resolutions that had previously been achieved with BF MRI were too low to distinguish the retinal and choroidal BF. I implemented BF MRI at higher resolution (42µm) than had ever previously been reported and demonstrated for the first time that BF MRI can separate the retinal and choroidal BF layers in mice. I have recently developed the curved object imaging MRI acquisition method for imaging of curved objects with improved laminar resolution and SNR, which now allows for 3D retinal blood flow MRI with vascular laminar resolution for the first time.
2. Pathophysiology of retinal blood flow in and vascular damage in retinal disease:I have applied the blood flow (BF) MRI, as well as other MRI methods, to investigate retinal pathophysiology in various rodent models of disease, including retinitis pigmentosa, glaucoma, diabetic retinopathy, hypertensive retinopathy, and retinal ischemia. In both mouse and rat models of retinitis pigmentosa, retinal BF is reduced at later stages of degeneration, while choroidal BF is unaffected. In a glaucoma model, both retinal and choroidal BF are progressively reduced with age, likely as a result of the increased intraocular pressure associated with glaucoma compressing the ocular vessels. I have also studied ocular blood flow and visual function in rodent models of diabetic retinopathy. Subtle loss of contrast sensitivity is reported in diabetic retinopathy prior to clinical symptoms. In rodents, soon after onset of diabetes, I found that choroidal BF is significantly reduced, while retinal BF and contrast sensitivity are normal. This suggests that reduced choroidal BF may be an early sign of pathology, but the choroid has rarely been studied in diabetic retinopathy previously due to the lack of suitable techniques.
3. Physiology of the human eye and retina:We have translated many of the MRI methodologies I developed for imaging the rodent eye to study the human eye and retinal disease on clinical scanners. We have found that retinal-choroidal BF is reduced in human is progressively reduced with age. I have also been developing and optimizing a new method to image intraocular oxygenation with MRI, including studies to develop calibration and correction schemes to improve quantification of physiological parameters from MRI scans of the eye. I have also begun to investigate ocular blood flow in patients with age-related macular degeneration and with diabetic retinopathy, with preliminary findings showing that reduced choroidal blood flow correlates with thinner choroids in AMD patients.
4. Physiological MRI of the rodent brain:Quantitative cerebral blood flow can be measured with MRI by many different methods. One particular method, known two-coil continuous arterial spin labeling, provides excellent blood flow contrast compared to other MRI blood flow methods. This method has been employed in various species from rats to humans, but it had not yet been used in mice. I was able to successfully implement this method in mice for the first time, overcoming artifacts that occur in mice due to their small size but do not happen in other species. I have also developed a novel method to measure changes in brain tissue pO2 modeled from T1 MRI, which provides brain pO2 estimates in good agreement with electrode values. I have since used this method in studies to investigate regulation of brain physiology and metabolism in rodents, such as studying the role of oxygen on brain physiology by performing MRI studies under hyperbaric oxygen.
5. MRI of neurological and neurovascular disease:I have used my expertise and experience in MRI to investigate cerebral pathophysiology in numerous neurodegenerative diseases, as well as other systemic disease which can affect the brain in animal and humans. In a mouse model of Alzheimer’s disease, we have shown that rapamycin treatment improves cerebral vascular integrity along with mitigating memory deficits. Our recent studies have shown the efficacy of hydrogen-enriched water is protective in ischemic stroke in a rat model. We have also investigated cerebrovascular dysfunction in the brain in rodent models of hypertension and of diabetes, and shown that cerebrovascular dysfunction in the brain in diabetes is mitigated by over-expression endothelial nitric oxide synthase. In glaucoma patients we have found wide-spread neurodegenerative changes in the visual pathway of the brain, including using functional MRI of visual stimuli to retinotopically map the visual cortex in human subjects, having found that function and organization of the visual cortex declines with normal aging and in glaucoma. We have also shown that in glaucoma, the visual cortex atrophies using structural MRI and that the white mater tracts of the visual system have axonal abnormalities using diffusion tensor MRI.

Service and Engagement Statement

I have for a long time contributed my expertise to the scholarly community by peer-reviewing for many well-established journals in the field of MRI and medical imaging. Many of these the same journals that I submit my manuscripts too, so it has been a rewarding experience to review for these. In the past several years, I have also reviewed for several NIH review panels as ad-hoc and mail reviewer. My unique research area of developing and applying neuroimaging techniques to the retina has allowed me to provide my expertise in review to both ophthalmic disease and MRI development.

In addition to my contributions to the research field, I also have experience providing service for my department / university. I was the Director of the Preclinical MRI Center at Stony Brook University which provides a core service of MRI of small animal imaging both for Stony Brook investigators and external investigators in the Long Island region. My responsibilities as director included managing the facilities (equipment upkeep, fire system and IACUC inspections), discussing MRI studies with investigators to help them to design and implement protocols for their experiments, providing information for grant submissions that will utilize the center, helping to manage scheduling and billing, assisting the centers technician to setup new imaging protocols when needed. I also undertook activities to promote the Preclinical MRI Center to investigators by giving several presentations on the capabilities of the center to other centers/departments at the university. I also took the initiative to design a website for the center to provide detailed information on the facilities and example research studies to give greater visibility. At UNC I will have the appointment of Human MR Imaging Technical Director at the Biomedical Research Imaging Center, in which I plan to provide similar services.

Honors and Awards

• Junior Fellow of the International Society for Magnetic Resonance in Medicine
• International Society for Magnetic Resonance in Medicine Magna Cum Laude Merit Award
• Postdoctoral trainee on NIH Institutional Training Grant (NHLBI T32HL007446, PI Linda McManus)
• Educational stipends for International Society for Magnetic Resonance in Medicine annual scientific meetings (Honolulu 2009, Stockholm 2010, Montreal 2011, Melbourne 2012, Salt Lake City 2013)
• Predoctoral trainee on NIH Institutional Training Grant (NIBIB T32EB005969, PI Xiaoping Hu)
• BS awarded with highest honors, Georgia Institute of Technology