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

ACCESS DATA

Publications

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

Similar Datasets

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:BACKGROUND:Autonomic nervous system dysfunction has been previously observed in multiple sclerosis (MS) patients. OBJECTIVE:To assess associations between magnetic resonance imaging-detected neuroinflammatory and neurodegenerative pathology and postural venous flow changes indicative of autonomic nervous system function. METHODS:We used a standardized 3T magnetic resonance imaging protocol to scan 138 patients with MS and 49 healthy controls. Lesion volume and brain volumes were assessed. The cerebral venous flow (CVF) was examined by color-Doppler sonography in supine and upright positions and the difference was calculated as ?CVF. Based on ?CVF, subjects were split into absolute or quartile groups. Student's t test, ?2-test, and analysis of covariance adjusted for age and sex were used accordingly. Benjamini-Hochberg procedure corrected the p-values for multiple comparisons. RESULTS:No differences were found between healthy controls and patients with MS in both supine and upright Doppler-derived CVF, nor in prevalence of abnormal postural venous control. Patients with absolute negative ?CVF had higher disability scores (p?=?0.013), lower gray matter (p?=?0.039) and cortical (p?=?0.044) volumes. The negative ?CVF MS group also showed numerically worse bladder/bowel function when compared to the positive ?CVF (2.3 vs. 1.5, p?=?0.052). Similarly, the lowest quartile ?CVF MS group had higher T1-lesion volumes (p?=?0.033), T2-lesion volumes (p?=?0.032), and lower deep gray matter (p?=?0.043) and thalamus (p?=?0.033) volumes when compared to those with higher ?CVF quartiles. CONCLUSION:No difference in postural venous outflow between patients with MS and healthy controls was found. However, when the abnormal ?CVF is present within the MS population, it may be associated with more inflammatory and neurodegenerative pathology. Further studies should explore whether the orthostatic venous changes are an aging or an MS-related phenomenon and if the etiology is due to impaired autonomic nervous system functioning.

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.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure