Multiple sclerosis (MS) is the most common neurological disease of young adults in the United States, with a prevalence estimated to be 400,000 and with annual medical expenses and lost productivity costs of approximately $9.5 billion. We hypothesize (Central Hypothesis) that microvascular abnormalities (a consequence of the perivenous inflammation known to occur in MS) are a final common pathway leading to injury of the central nervous system. This hypothesis is based upon preliminary data we have gathered and is supported by pathological evidence of such injury. Ensuing microvascular ischemic damage to axons/neurons interferes with normal iron homeostasis, resulting in accumulation of excess iron in the deep gray matter. Neurocognitive deficits and fatigue experienced by MS patients are consequences of oxidative injury by iron accretion in the basal ganglia and thalamus. To test this hypothesis, we propose four Specific Aims:
Specific Aim 1 defines baseline perfusion (cerebral blood flow;cerebral blood volume;mean transit time), magnetic resonance (MR) spectroscopy (N-acetyl aspartate), and quantitative MR metrics (diffusion tensor;diffusion kurtosis;magnetic field correlation;structural volume) at high-field (3 Tesla) in 30 early relapsing remitting MS patients and age/sex matched controls.
Specific Aim 2 measures baseline cognitive impairment and fatigue and associates these results with quantitative MR metrics of the deep gray matter.
Specific Aim 3 associates, over a 4 year duration, deep gray matter iron accumulation with both damage to these structures and progressive brain parenchymal loss.
Specific Aim 4 associates, over a 4 year duration, the decline in neurocognitive function and fatigue with deep gray matter injury. This research will provide new insights into the pathophysiology of Multiple Sclerosis and common morbidities (cognitive decline and fatigue) experienced by MS patients. It will result in more appropriate measures to detect and quantitate the effect of the disease and will provide a rationale for innovative treatment regimes.
|Zhou, Yongxia (2016) Quantitative PET/MRI Evaluation and Application in Dementia. Jacobs J Med Diagn Med Imaging 1:|
|Chawla, S; Kister, I; Wuerfel, J et al. (2016) Iron and Non-Iron-Related Characteristics of Multiple Sclerosis and Neuromyelitis Optica Lesions at 7T MRI. AJNR Am J Neuroradiol 37:1223-30|
|Chawla, S; Ge, Y; Lu, H et al. (2015) Whole-Brain N-Acetylaspartate Concentration Is Preserved during Mild Hypercapnia Challenge. AJNR Am J Neuroradiol 36:2055-61|
|Raz, Eytan; Branson, Brittany; Jensen, Jens H et al. (2015) Relationship between iron accumulation and white matter injury in multiple sclerosis: a case-control study. J Neurol 262:402-9|
|Jonkman, Laura E; Rosenthal, Diana M; Sormani, Maria Pia et al. (2015) Gray Matter Correlates of Cognitive Performance Differ between Relapsing-Remitting and Primary-Progressive Multiple Sclerosis. PLoS One 10:e0129380|
|Bester, M; Jensen, J H; Babb, J S et al. (2015) Non-Gaussian diffusion MRI of gray matter is associated with cognitive impairment in multiple sclerosis. Mult Scler 21:935-44|
|Marshall, Olga; Lu, Hanzhang; Brisset, Jean-Christophe et al. (2014) Impaired cerebrovascular reactivity in multiple sclerosis. JAMA Neurol 71:1275-81|
|Chang, K; Barnes, S; Haacke, E M et al. (2014) Imaging the effects of oxygen saturation changes in voluntary apnea and hyperventilation on susceptibility-weighted imaging. AJNR Am J Neuroradiol 35:1091-5|
|Lu, Hanzhang; Liu, Peiying; Yezhuvath, Uma et al. (2014) MRI mapping of cerebrovascular reactivity via gas inhalation challenges. J Vis Exp :|
|Zhou, Yongxia; Lui, Yvonne W; Zuo, Xi-Nian et al. (2014) Characterization of thalamo-cortical association using amplitude and connectivity of functional MRI in mild traumatic brain injury. J Magn Reson Imaging 39:1558-68|
Showing the most recent 10 out of 102 publications