Dataset Information

Multiple sclerosis-related white matter microstructural change alters the BOLD hemodynamic response.

ABSTRACT: Multiple sclerosis (MS) results in inflammatory damage to white matter microstructure. Prior research using blood-oxygen-level dependent (BOLD) imaging indicates MS-related alterations to brain function. What is currently unknown is the extent to which white matter microstructural damage influences BOLD signal in MS. Here we assessed changes in parameters of the BOLD hemodynamic response function (HRF) in patients with relapsing-remitting MS compared to healthy controls. We also used diffusion tensor imaging to assess whether MS-related changes to the BOLD-HRF were affected by changes in white matter microstructural integrity. Our results showed MS-related reductions in BOLD-HRF peak amplitude. These MS-related amplitude decreases were influenced by individual differences in white matter microstructural integrity. Other MS-related factors including altered reaction time, limited spatial extent of BOLD activity, elevated lesion burden, or lesion proximity to regions of interest were not mediators of group differences in BOLD-HRF amplitude. Results are discussed in terms of functional hyperemic mechanisms and implications for analysis of BOLD signal differences.

SUBMITTER: Hubbard NA

PROVIDER: S-EPMC5094308 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Multiple sclerosis-related white matter microstructural change alters the BOLD hemodynamic response.

Hubbard Nicholas A NA Turner Monroe M Hutchison Joanna L JL Ouyang Austin A Strain Jeremy J Oasay Larry L Sundaram Saranya S Davis Scott S Remington Gina G Brigante Ryan R Huang Hao H Hart John J Frohman Teresa T Frohman Elliot E Biswal Bharat B BB Rypma Bart B

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20151109 11

Multiple sclerosis (MS) results in inflammatory damage to white matter microstructure. Prior research using blood-oxygen-level dependent (BOLD) imaging indicates MS-related alterations to brain function. What is currently unknown is the extent to which white matter microstructural damage influences BOLD signal in MS. Here we assessed changes in parameters of the BOLD hemodynamic response function (HRF) in patients with relapsing-remitting MS compared to healthy controls. We also used diffusion t ...[more]

PMID: 26661225

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Project description:Irreversible white matter (WM) damage, including severe demyelination and axonal loss, is a main determinant of long-term disability in multiple sclerosis (MS). Non-invasive detection of changes in microstructural WM integrity in the disease is challenging since commonly used imaging metrics lack the necessary sensitivity, especially in the early phase of the disease. This study aims at assessing microstructural WM abnormalities in early-stage MS by using ultra-high gradient strength multi-shell diffusion MRI and the restricted signal fraction (FR) from the Composite Hindered and Restricted Model of Diffusion (CHARMED), a metric sensitive to the volume fraction of axons. In 22 early MS subjects (disease duration ?5?years) and 15 age-matched healthy controls, restricted fraction estimates were obtained through the CHARMED model along with conventional Diffusion Tensor Imaging (DTI) metrics. All imaging parameters were compared cross-sectionally between the MS subjects and controls both in WM lesions and normal-appearing white matter (NAWM). We found a significant reduction in FR focally in WM lesions and widespread in the NAWM in MS patients relative to controls (corrected p?<?.05). Signal fraction changes in NAWM were not driven by perilesional tissue, nor were they influenced by proximity to the ventricles, challenging the hypothesis of an outside-in pathological process driven by CSF-mediated immune cytotoxic factors. No significant differences were found in conventional DTI parameters. In a cross-validated classification task, FR showed the largest effect size and outperformed all other diffusion imaging metrics in discerning lesions from contralateral NAWM. Taken together, our data provide evidence for the presence of widespread microstructural changes in the NAWM in early MS stages that are, at least in part, unrelated to focal demyelinating lesions. Interestingly, these pathological changes were not yet detectable by conventional diffusion imaging at this early disease stage, highlighting the sensitivity and value of multi-shell diffusion imaging for better characterizing axonal microstructure in MS.

Project description:Multiple sclerosis features complex pathological changes in grey matter that begin early and eventually lead to diffuse atrophy. Novel approaches to image grey-matter microstructural alterations in vivo are highly sought after and would enable more sensitive monitoring of disease activity and progression. This cross-sectional study aimed to assess the sensitivity of high-gradient diffusion MRI for microstructural tissue damage in cortical and deep grey matter in people with multiple sclerosis and test the hypothesis that reduced cortical cell body density is associated with cortical and deep grey-matter volume loss. Forty-one people with multiple sclerosis (age 24-72, 14 females) and 37 age- and sex-matched healthy controls were scanned on a 3 T Connectom MRI scanner equipped with 300 mT/m gradients using a multi-shell diffusion MRI protocol. The soma and neurite density imaging model was fitted to high-gradient diffusion MRI data to obtain estimates of intra-neurite, intra-cellular and extra-cellular signal fractions and apparent soma radius. Cortical and deep grey-matter microstructural imaging metrics were compared between multiple sclerosis and healthy controls and correlated with grey-matter volume, clinical disability and cognitive outcomes. People with multiple sclerosis showed significant cortical and deep grey-matter volume loss compared with healthy controls. People with multiple sclerosis showed trends towards lower cortical intra-cellular signal fraction and significantly lower intra-cellular and higher extra-cellular signal fractions in deep grey matter, especially the thalamus and caudate, compared with healthy controls. Changes were most pronounced in progressive disease and correlated with the Expanded Disability Status Scale, but not the Symbol Digit Modalities Test. In multiple sclerosis, normalized thalamic volume was associated with thalamic microstructural imaging metrics. Whereas thalamic volume loss did not correlate with cortical volume loss, cortical microstructural imaging metrics were significantly associated with thalamic volume, and not with cortical volume. Compared with the short diffusion time (Δ = 19 ms) achievable on the Connectom scanner, at the longer diffusion time of Δ = 49 ms attainable on clinical scanners, multiple sclerosis-related changes in imaging metrics were generally less apparent with lower effect sizes in cortical and deep grey matter. Soma and neurite density imaging metrics obtained from high-gradient diffusion MRI data provide detailed grey-matter characterization beyond cortical and thalamic volumes and distinguish multiple sclerosis-related microstructural pathology from healthy controls. Cortical cell body density correlates with thalamic volume, appears sensitive to the microstructural substrate of neurodegeneration and reflects disability status in people with multiple sclerosis, becoming more pronounced as disability worsens.

Dataset Information

Multiple sclerosis-related white matter microstructural change alters the BOLD hemodynamic response.

Publications

Multiple sclerosis-related white matter microstructural change alters the BOLD hemodynamic response.

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