Human brain atlas-based multimodal MRI analysis of volumetry, diffusimetry, relaxometry and lesion distribution in multiple sclerosis patients and healthy adult controls: Implications for understanding the pathogenesis of multiple sclerosis and consolidation of quantitative MRI results in MS

Abstract

Multiple sclerosis (MS) is the most common immune-mediated disabling neurological disease of the central nervous system. The pathogenesis of MS is not fully understood. Histopathology implicates both demyelination and axonal degeneration as the major contributors to the accumulation of disability. The application of several in vivo quantitative magnetic resonance imaging (MRI) methods to both lesioned and normal-appearing brain tissue has not yet provided a solid conclusive support of the hypothesis that MS might be a diffuse disease. In this work, we adopted FreeSurfer to provide standardized macrostructure or volumetry of lesion free normal-appearing brain tissue in combination with multiple quantitative MRI metrics (T2 relaxation time, diffusion tensor anisotropy and diffusivities) that characterize tissue microstructural integrity. By incorporating a large number of healthy controls, we have attempted to separate the natural age-related change from the disease-induced effects. Our work shows elevation in diffusivity and relaxation times and reduction in volume in a number of normal-appearing white matter and gray matter structures in relapsing-remitting multiple sclerosis patients. These changes were related in part with the spatial distribution of lesions. The whole brain lesion load and age-adjusted expanded disability status score showed strongest correlations in regions such as corpus callosum with qMRI metrics that are believed to be specific markers of axonal dysfunction, consistent with histologic data of others indicating axonal loss that is independent of focal lesions. Our results support that MS at least in part has a neurodegenerative component.

Structural Image Analysis of the Brain in Neuropsychology Using Magnetic Resonance Imaging (MRI) Techniques

“…Excellent techniques for identifying size, thickness, surface area, shape and contour are available for the field of neuropsychology to explore anatomical and pathological relations. This review focused on just the structural side of neuroimaging analyses but contemporary neuroimaging yields numerous other methods that can be integrated with structural imaging for a multimodal MR approach to understanding brain-behavior relations (Goh et al 2014(Goh et al , 2015Hasan et al 2012;Sui et al 2015). The next few decades of basic and clinical research will likely provide a rich array of quantitative m e t h o d s f o r i m a g e a n a l y s i s f o r a l l a s p e c t s o f neuropsychology.…”

DTI microstructural abnormalities in adolescent siblings of patients with childhood-onset schizophrenia

“…Microstructural abnormalities may also play a role in the pathophysiology of schizophrenia and underlie some of the deficits experienced by relatives of schizophrenia patients as well. DTI is traditionally used for characterizing microstructural properties of white matter tracts, but has recently been employed in a novel way to detect microstructural abnormalities and overall cellular damage in subcortical gray matter regions as well (Bozzali et al, 2002;Cavallari et al, 2014;Caverzasi et al, 2014;Ciccarelli et al, 2001;Hannoun et al, 2012;Hasan et al, 2009Hasan et al, , 2012Hasan et al, , 2011Muller et al, 2007;Piras et al, 2010;Spoletini et al, 2011;Vrenken et al, 2006). DTI can capture subtle changes in structure even before clinically measureable changes become apparent (Hulst et al, 2013).…”

Quantitative MR Imaging of Brain Tissue and Brain Pathologies

“…However, with relaxation times of different pathologies overlapping considerably [3][4][5], more complex tissue characterization came into focus, for example, those based on water diffusion, magnetization transfer, and perfusion. It became obvious that the strengths of quantitative or semi-quantitative MR parameter maps lie in the detection of diffuse changes in brain tissues that appeared normal in conventional MRI [6][7][8], best demonstrated in multiple sclerosis patients [2,7,[9][10][11][12][13][14].…”