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Calibrated imaging reveals altered grey matter metabolism related to white matter microstructure and symptom severity in multiple sclerosis.

ABSTRACT: Multiple sclerosis (MS) involves damage to white matter microstructures. This damage has been related to grey matter function as measured by standard, physiologically-nonspecific neuroimaging indices (i.e., blood-oxygen-level dependent signal [BOLD]). Here, we used calibrated functional magnetic resonance imaging and diffusion tensor imaging to examine the extent to which specific, evoked grey matter physiological processes were associated with white matter diffusion in MS. Evoked changes in BOLD, cerebral blood flow (CBF), and oxygen metabolism (CMRO₂ ) were measured in visual cortex. Individual differences in the diffusion tensor measure, radial diffusivity, within occipital tracts were strongly associated with MS patients' BOLD and CMRO₂ . However, these relationships were in opposite directions, complicating the interpretation of the relationship between BOLD and white matter microstructural damage in MS. CMRO₂ was strongly associated with individual differences in patients' fatigue and neurological disability, suggesting that alterations to evoked oxygen metabolic processes may be taken as a marker for primary symptoms of MS. This work demonstrates the first application of calibrated and diffusion imaging together and details the first application of calibrated functional MRI in a neurological population. Results lend support for neuroenergetic hypotheses of MS pathophysiology and provide an initial demonstration of the utility of evoked oxygen metabolism signals for neurology research. Hum Brain Mapp 38:5375-5390, 2017. © 2017 Wiley Periodicals, Inc.

SUBMITTER: Hubbard NA

PROVIDER: S-EPMC5877313 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionMild traumatic brain injury (TBI) is a global public health concern that affects millions of children annually. Mild TBI tends to result in subtle and diffuse alterations in brain tissue, which challenges accurate clinical detection and prognostication. Diffusion tensor imaging (DTI) holds promise as a diagnostic and prognostic tool, but little research has examined DTI in post-acute mild TBI. The current study compared post-acute white matter microstructure in children with mild TBI versus those with mild orthopedic injury (OI), and examined whether post-acute DTI metrics can predict post-acute and chronic post-concussive symptoms (PCS).Materials and methodsChildren aged 8-16.99 years with mild TBI (n = 132) or OI (n = 69) were recruited at emergency department visits to two children's hospitals, during which parents rated children's pre-injury symptoms retrospectively. Children completed a post-acute (<2 weeks post-injury) assessment, which included a 3T MRI, and 3- and 6-month post-injury assessments. Parents and children rated PCS at each assessment. Mean diffusivity (MD) and fractional anisotropy (FA) were derived from diffusion-weighted MRI using Automatic Fiber Quantification software. Multiple multivariable linear and negative binomial regression models were used to test study aims, with False Discovery Rate (FDR) correction for multiple comparisons.ResultsNo significant group differences were found in any of the 20 white matter tracts after FDR correction. DTI metrics varied by age and sex, and site was a significant covariate. No interactions involving group, age, and sex were significant. DTI metrics in several tracts robustly predicted PCS ratings at 3- and 6-months post-injury, but only corpus callosum genu MD was significantly associated with post-acute PCS after FDR correction. Significant group by DTI metric interactions on chronic PCS ratings indicated that left cingulum hippocampus and thalamic radiation MD was positively associated with 3-month PCS in the OI group, but not in the mild TBI group.ConclusionsPost-acute white matter microstructure did not differ for children with mild TBI versus OI after correcting for multiple comparisons, but was predictive of post-acute and chronic PCS in both injury groups. These findings support the potential prognostic utility of this advanced DTI technique.

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Calibrated imaging reveals altered grey matter metabolism related to white matter microstructure and symptom severity in multiple sclerosis.

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