Dataset Information

Lipid biochemical changes detected in normal appearing white matter of chronic multiple sclerosis by spectral coherent Raman imaging.

ABSTRACT: Multiple sclerosis (MS) exhibits demyelination, inflammatory infiltration, axonal degeneration, and gliosis, affecting widespread regions of the central nervous system (CNS). While white matter MS lesions have been well characterized pathologically, evidence indicates that the MS brain may be globally altered, with subtle abnormalities found in grossly normal appearing white matter (NAWM). These subtle changes are difficult to investigate by common methods such as histochemical stains and conventional magnetic resonance imaging. Thus, the prototypical inflammatory lesion likely represents the most obvious manifestation of a more widespread involvement of the CNS. We describe the application of spectral coherent anti-Stokes Raman Scattering (sCARS) microscopy to study such changes in chronic MS tissue particularly in NAWM. Subtle changes in myelin lipid biochemical signatures and intra-molecular disorder of fatty acid acyl chains of otherwise normal-appearing myelin were detected, supporting the notion that the biochemical involvement of the MS brain is far more extensive than conventional methods would suggest.

SUBMITTER: Poon KWC

PROVIDER: S-EPMC5890326 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Lipid biochemical changes detected in normal appearing white matter of chronic multiple sclerosis by spectral coherent Raman imaging.

Poon K W C KWC Brideau C C Klaver R R Schenk G J GJ Geurts J J JJ Stys P K PK

Chemical science 20180102 6

Multiple sclerosis (MS) exhibits demyelination, inflammatory infiltration, axonal degeneration, and gliosis, affecting widespread regions of the central nervous system (CNS). While white matter MS lesions have been well characterized pathologically, evidence indicates that the MS brain may be globally altered, with subtle abnormalities found in grossly normal appearing white matter (NAWM). These subtle changes are difficult to investigate by common methods such as histochemical stains and conven ...[more]

PMID: 29675203

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Project description:Normal-appearing white matter is far from normal in multiple sclerosis; little is known about the precise pathology or spatial pattern of this alteration and its relation to subsequent lesion formation. This study was undertaken to evaluate normal-appearing white matter abnormalities in brain areas where multiple sclerosis lesions subsequently form, and to investigate the spatial distribution of normal-appearing white matter abnormalities in persons with multiple sclerosis. Brain MRIs of pre-lesion normal-appearing white matter were analysed in participants with new T2 lesions, pooled from three clinical trials: SYNERGY (NCT01864148; n = 85 with relapsing multiple sclerosis) was the test data set; ASCEND (NCT01416181; n = 154 with secondary progressive multiple sclerosis) and ADVANCE (NCT00906399; n = 261 with relapsing-remitting multiple sclerosis) were used as validation data sets. Focal normal-appearing white matter tissue state was analysed prior to lesion formation in areas where new T2 lesions later formed (pre-lesion normal-appearing white matter) using normalized magnetization transfer ratio and T2-weighted (nT2) intensities, and compared with overall normal-appearing white matter and spatially matched contralateral normal-appearing white matter. Each outcome was analysed using linear mixed-effects models. Follow-up time (as a categorical variable), patient-level characteristics (including treatment group) and other baseline variables were treated as fixed effects. In SYNERGY, nT2 intensity was significantly higher, and normalized magnetization transfer ratio was lower in pre-lesion normal-appearing white matter versus overall and contralateral normal-appearing white matter at all time points up to 24 weeks before new T2 lesion onset. In ASCEND and ADVANCE (for which normalized magnetization transfer ratio was not available), nT2 intensity in pre-lesion normal-appearing white matter was significantly higher compared to both overall and contralateral normal-appearing white matter at all pre-lesion time points extending up to 2 years prior to lesion formation. In all trials, nT2 intensity in the contralateral normal-appearing white matter was also significantly higher at all pre-lesion time points compared to overall normal-appearing white matter. Brain atlases of normal-appearing white matter abnormalities were generated using measures of voxel-wise differences in normalized magnetization transfer ratio of normal-appearing white matter in persons with multiple sclerosis compared to scanner-matched healthy controls. We observed that overall spatial distribution of normal-appearing white matter abnormalities in persons with multiple sclerosis largely recapitulated the anatomical distribution of probabilities of T2 hyperintense lesions. Overall, these findings suggest that intrinsic spatial properties and/or longstanding precursory abnormalities of normal-appearing white matter tissue may contribute to the risk of autoimmune acute demyelination in multiple sclerosis.

Dataset Information

Lipid biochemical changes detected in normal appearing white matter of chronic multiple sclerosis by spectral coherent Raman imaging.

Publications

Lipid biochemical changes detected in normal appearing white matter of chronic multiple sclerosis by spectral coherent Raman imaging.

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