Dr. Bakshi is an assistant professor of neurology at Buffalo. During 1991 to 1996, he completed an internship at Massachusetts General Hospital, followed by neurology residency at UCLA and neuroimaging fellowship at Buffalo. His immediate goal is to .perform clinical-neuroimaging correlation research concentrating on multiple sclerosis (MS). His long- term career goal is to obtain the skills and experience necessary to develop into a funded independent clinical investigator using neuroimaging to study the pathophysiology of MS. The proposed three- year research training will provide skills for him in important aspects of patient-oriented research in MS. He will deepen his knowledge of biostatistics and epidemiology through formal coursework and supervision. He will learn a variety of computer-assisted MRI analysis methods under the teaching of Dr. Jack Simon that are critical in assessing MS. He will learn how to correlate these data with clinical and neuropathologic findings under the guidance of Dr. Lawrence Jacobs. Dr. Bakshi proposes to study MRI T2 shortening - """"""""Black T2"""""""" (BT2) - as a surrogate marker of brain injury in MS. He will extend and attempt to confirm his preliminary observations that BT2 is present commonly in deep central gray matter as compared to normal controls by measuring tissue intensities and T2 relaxation times. He will determine if BT2 varies over time in parallel with other MRI changes (plaques/atrophy), clinical evolution, and therapeutic effects by analyzing 2-year longitudinal data of interferon-beta vs. placebo treated MS patients. To evaluate the hypothesis that BT2 represents pathologic iron deposition, Dr. Bakshi will examine autopsied MS brains in collaboration with Dr. Peter Ostrow for microscopic iron deposition. If the current study is fruitful, BT2 could become a useful laboratory marker of disease burden to assess the course of disease, select patients for therapies, or measure immunotherapeutic effects. In future studies, BT2 can be correlated with metabolism and MR spectroscopic evidence of neuronal injury in deep gray matter. If iron plays a pathophysiologic role in MS, this could offer a novel therapeutic opportunity. Alternatively, if iron accumulation is a disease epiphenomenon, then BT2 could be used as a noninvasive marker of brain degeneration.

Project Start
2001-01-25
Project End
2004-12-31
Budget Start
2004-07-01
Budget End
2004-12-31
Support Year
4
Fiscal Year
2003
Total Cost
$27,607
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
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Neema, Mohit; Goldberg-Zimring, Daniel; Guss, Zachary D et al. (2009) 3 T MRI relaxometry detects T2 prolongation in the cerebral normal-appearing white matter in multiple sclerosis. Neuroimage 46:633-41
Stankiewicz, James; Panter, S Scott; Neema, Mohit et al. (2007) Iron in chronic brain disorders: imaging and neurotherapeutic implications. Neurotherapeutics 4:371-86
Neema, Mohit; Stankiewicz, James; Arora, Ashish et al. (2007) MRI in multiple sclerosis: what's inside the toolbox? Neurotherapeutics 4:602-17
Houtchens, M K; Benedict, R H B; Killiany, R et al. (2007) Thalamic atrophy and cognition in multiple sclerosis. Neurology 69:1213-23
Janardhan, Vallabh; Suri, Sonu; Bakshi, Rohit (2007) Multiple sclerosis: hyperintense lesions in the brain on nonenhanced T1-weighted MR images evidenced as areas of T1 shortening. Radiology 244:823-31
Neema, Mohit; Stankiewicz, James; Arora, Ashish et al. (2007) T1- and T2-based MRI measures of diffuse gray matter and white matter damage in patients with multiple sclerosis. J Neuroimaging 17 Suppl 1:16S-21S
Sharma, Jitendra; Zivadinov, Robert; Jaisani, Zeenat et al. (2006) A magnetization transfer MRI study of deep gray matter involvement in multiple sclerosis. J Neuroimaging 16:302-10
Sanfilipo, Michael P; Benedict, Ralph H B; Weinstock-Guttman, Bianca et al. (2006) Gray and white matter brain atrophy and neuropsychological impairment in multiple sclerosis. Neurology 66:685-92
Brass, S D; Benedict, R H B; Weinstock-Guttman, B et al. (2006) Cognitive impairment is associated with subcortical magnetic resonance imaging grey matter T2 hypointensity in multiple sclerosis. Mult Scler 12:437-44

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