scholarly journals Quantitative MRI phenotypes capture biological heterogeneity in multiple sclerosis patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ide Smets ◽  
An Goris ◽  
Marijne Vandebergh ◽  
Jelle Demeestere ◽  
Stefan Sunaert ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Risk Score ◽  
Grey Matter ◽  
Quantitative Mri ◽  
Grey Matter Volume ◽  
Magnetization Transfer Ratio ◽  
Lesion Volume ◽  
Total Brain ◽  
Multiple Sclerosis Patients

AbstractMagnetization transfer ratio (MTR) and brain volumetric imaging are (semi-)quantitative MRI markers capturing demyelination, axonal degeneration and/or inflammation. However, factors shaping variation in these traits are largely unknown. In this study, we collected a longitudinal cohort of 33 multiple sclerosis (MS) patients and extended it cross-sectionally to 213. We measured MTR in lesions, normal-appearing white matter (NAWM), normal-appearing grey matter (NAGM) and total brain, grey matter, white matter and lesion volume. We also calculated the polygenic MS risk score. Longitudinally, inter-patient differences at inclusion and intra-patient changes during follow-up together explained > 70% of variance in MRI, with inter-patient differences at inclusion being the predominant source of variance. Cross-sectionally, we observed a moderate correlation of MTR between NAGM and NAWM and, less pronounced, with lesions. Age and gender explained about 30% of variance in total brain and grey matter volume. However, they contributed less than 10% to variance in MTR measures. There were no significant associations between MRI traits and the genetic risk score. In conclusion, (semi-)quantitative MRI traits change with ongoing disease activity but this change is modest in comparison to pre-existing inter-patient differences. These traits reflect individual variation in biological processes, which appear different from those involved in genetic MS susceptibility.

Different white matter lesion characteristics correlate with distinct grey matter abnormalities on magnetic resonance imaging in secondary progressive multiple sclerosis

2009 ◽  
Vol 15 (6) ◽  
pp. 687-694 ◽  
Author(s):  
J Furby ◽  
T Hayton ◽  
D Altmann ◽  
R Brenner ◽  
J Chataway ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Grey Matter ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Lesion Volume ◽  
Secondary Degeneration ◽  
Secondary Progressive ◽  
Demyelinating Lesions ◽  
The Relationship

Background Although MRI measures of grey matter abnormality correlate with clinical disability in multiple sclerosis, it is uncertain whether grey matter abnormality measured on MRI is entirely due to a primary grey matter process or whether it is partly related to disease in the white matter. Methods To explore potential mechanisms of grey matter damage we assessed the relationship of white matter T2 lesion volume, T1 lesion volume, and mean lesion magnetisation transfer ratio (MTR), with MRI measures of tissue atrophy and MTR in the grey matter in 117 subjects with secondary progressive multiple sclerosis. Results Grey matter fraction and mean grey matter MTR were strongly associated with lesion volumes and lesion MTR mean ( r = ±0.63–0.72). In contrast, only weak to moderate correlations existed between white matter and lesion measures. In a stepwise regression model, T1 lesion volume was the only independent lesion correlate of grey matter fraction and accounted for 52% of the variance. Lesion MTR mean and T2 lesion volume were independent correlates of mean grey matter MTR, accounting for 57% of the variance. Conclusions Axonal transection within lesions with secondary degeneration into the grey matter may explain the relationship between T1 lesions and grey matter fraction. A parallel accumulation of demyelinating lesions in white and grey matter may contribute to the association of T2 lesion volume and lesion MTR with grey matter MTR.

T1 cortical hypointensities and their association with cognitive disability in multiple sclerosis

2010 ◽  
Vol 16 (10) ◽  
pp. 1203-1212 ◽  
Author(s):  
Francesca Bagnato ◽  
Zeena Salman ◽  
Robert Kane ◽  
Sungyoung Auh ◽  
Fredric K Cantor ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Impairment ◽  
White Matter ◽  
Statistical Significance ◽  
Verbal Learning ◽  
Lesion Volume ◽  
Cognitive Disability ◽  
3.0 Tesla ◽  
Multiple Sclerosis Patients ◽  
The Impact

Background: Neocortical lesions (NLs) largely contribute to the pathology of multiple sclerosis (MS), although their relevance in patients’ disability remains unknown. Objective: To assess the incidence of T1 hypointense NLs by 3.0-Tesla magnetic resonance imaging (MRI) in patients with MS and examine neocortical lesion association with cognitive impairment. Methods: In this case-control study, 21 MS patients and 21 age-, sex- and years of education-matched healthy volunteers underwent: (i) a neuropsychological examination rating cognitive impairment (Minimal Assessment of Cognitive Function in MS); (ii) a 3.0-Tesla MRI inclusive of an isotropic 1.0 mm3 three-dimensional inversion prepared spoiled gradient-recalled-echo (3D-IRSPGR) image and T1- and T2-weighted images. Hypointensities on 3D-IRSPGR lying in the cortex, either entirely or partially were counted and association between NLs and cognitive impairment investigated. Results: A total of 95 NLs were observed in 14 (66.7%) patients. NL+ patients performed poorer (p = 0.020) than NLpatients only on the delayed recall component of the California Verbal Learning Test. This difference lost statistical significance when a correction for white matter lesion volume was employed. Conclusions: Although T 1 hypointense NLs may be present in a relatively high proportion of multiple sclerosis patients, the impact that they have in cognitive impairment is not independent from white matter disease.

scholarly journals Age-specific adult rat brain MRI templates and tissue probability maps

2021 ◽  
Author(s):  
Eilidh MacNicol ◽  
Paul Wright ◽  
Eugene Kim ◽  
Irene Brusini ◽  
Oscar Esteban ◽  
...  
Keyword(s):  
White Matter ◽  
Rat Brain ◽  
Grey Matter ◽  
Brain Volume ◽  
Grey Matter Volume ◽  
Total Brain Volume ◽  
Adult Rat ◽  
Matter Volume ◽  
Probability Maps ◽  
Total Brain

Age-specific resources mitigate biases in human MRI processing arising from structural changes across the lifespan. There are fewer age-specific resources for preclinical imaging, and they only represent developmental periods rather than adulthood. Since rats recapitulate many facets of human aging, it was hypothesized that brain volume and each tissue’s relative contribution to total brain volume would change with age in the adult rat. However, the currently available tissue probability maps, which provide a priori information for tissue volume estimation, provide inaccurate grey matter probabilities in subcortical structures, particularly the thalamus. Consequently, age-specific templates and tissue probability maps were generated from a longitudinal study that scanned a cohort of rats at 3, 5, 11, and 17 months old. Mixed-effects models assessed the effect of age on brain, grey matter, white matter, and CSF volumes, and the relative tissue proportions. Grey and white matter volume increased with age, and the tissue proportions relative to total brain volume varied throughout adulthood. Furthermore, we present evidence of a systematic underestimation of thalamic grey matter volume with existing resources, which is mitigated with the use of age-specific tissue probability maps since the derived estimates better matched histological evidence. To reduce age-related biases in image pre-processing, a set of rat brain resources from across the adult lifespan is consequently released to expand the preclinical MRI community’s fundamental resources.

Surface-in pathology in multiple sclerosis: a new view on pathogenesis?

Brain ◽  
2021 ◽  
Author(s):  
Matteo Pardini ◽  
J William L Brown ◽  
Roberta Magliozzi ◽  
Richard Reynolds ◽  
Declan T Chard
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Grey Matter ◽  
Magnetization Transfer ◽  
Neuronal Loss ◽  
Magnetization Transfer Ratio ◽  
Supporting Evidence ◽  
Transfer Ratio ◽  
Meningeal Inflammation

Abstract While multiple sclerosis can affect any part of the CNS, it does not do so evenly. In white matter it has long been recognized that lesions tend to occur around the ventricles, and grey matter lesions mainly accrue in the outermost (subpial) cortex. In cortical grey matter, neuronal loss is greater in the outermost layers. This cortical gradient has been replicated in vivo with magnetization transfer ratio and similar gradients in grey and white matter magnetization transfer ratio are seen around the ventricles, with the most severe abnormalities abutting the ventricular surface. The cause of these gradients remains uncertain, though soluble factors released from meningeal inflammation into the CSF has the most supporting evidence. In this Update, we review this ‘surface-in’ spatial distribution of multiple sclerosis abnormalities and consider the implications for understanding pathogenic mechanisms and treatments designed to slow or stop them.

scholarly journals MRI of the corpus callosum in multiple sclerosis: association with disability

2010 ◽  
Vol 16 (2) ◽  
pp. 166-177 ◽  
Author(s):  
A. Ozturk ◽  
SA Smith ◽  
EM Gordon-Lipkin ◽  
DM Harrison ◽  
N. Shiee ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Corpus Callosum ◽  
Diffusion Tensor ◽  
Magnetization Transfer ◽  
Quantitative Mri ◽  
Magnetization Transfer Ratio ◽  
Lesion Volume ◽  
Impaired Performance ◽  
Disability Status ◽  
Axon Damage

Inflammatory demyelination and axon damage in the corpus callosum are prominent features of multiple sclerosis (MS) and may partially account for impaired performance on complex tasks. The objective of this article was to characterize quantitative callosal MRI abnormalities and their association with disability. In 69 participants with MS and 29 healthy volunteers, lesional and extralesional callosal MRI indices were estimated via diffusion tensor tractography. expanded disability status scale (EDSS) and MS functional composite (MSFC) scores were recorded in 53 of the participants with MS. All tested callosal MRI indices were diffusely abnormal in MS. EDSS score was correlated only with age (r = 0.51). Scores on the overall MSFC and its paced serial auditory addition test (PASAT) and 9-hole peg test components were correlated with callosal fractional anisotropy (r = 0.27, 0.35, and 0.31, respectively) and perpendicular diffusivity (r = —0.29, —0.30, and —0.31) but not with overall callosal volume or callosal lesion volume; the PASAT score was more weakly correlated with callosal magnetization-transfer ratio (r = 0.21). Anterior callosal abnormalities were associated with impaired PASAT performance and posterior abnormalities with slow performance on the 9-hole peg test. In conclusion, abnormalities in the corpus callosum can be assessed with quantitative MRI and are associated with cognitive and complex upper-extremity dysfunction in MS.

MRI characteristics of familial and sporadic multiple sclerosis patients

2012 ◽  
Vol 19 (9) ◽  
pp. 1145-1152 ◽  
Author(s):  
Anita Tipirneni ◽  
Bianca Weinstock-Guttman ◽  
Murali Ramanathan ◽  
Nadir Abdelrahman ◽  
Sara Hussein ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Family History ◽  
Clinical Status ◽  
Positive Family History ◽  
Magnetization Transfer Ratio ◽  
Lesion Volume ◽  
Sporadic Group ◽  
History Of ◽  
Multiple Sclerosis Patients ◽  
Mri Characteristics

Purpose: To investigate the MRI characteristics in a large cohort of multiple sclerosis (MS) patients with and without a family history of MS. Methods: Enrolled in this prospective study were 758 consecutive MS patients (mean age 46.2 ± 10.1 years, disease duration 13.6 ± 9.2 years and EDSS 3.4 ± 2.1), of whom 477 had relapsing–remitting, 222 secondary-progressive, and 30 primary-progressive disease courses and 29 had clinically isolated syndrome. One hundred and ninety-six patients (25.9%) had a positive family history of MS. Patients were assessed using measurements of lesions, brain atrophy, magnetization transfer ratio (MTR) and diffusion-weighted imaging. Results: The familial MS group had greater T1-lesion volume ( p=0.009) and a trend for lower MTR of T1-lesion volume ( p=0.047) than the sporadic MS group. No clinical differences were found between familial versus sporadic group, or by a degree of affected relative subgroups. Conclusions: While familial MS was associated with more severe T1-lesion volume and its MTR characteristics, there were no clinical status differences between familial and sporadic MS patients. Therefore, a better understanding of the genetic and/or epigenetic influences causing these differences can advance the understanding and management of MS.

scholarly journals Quantitative MRI Demonstrates Abnormality of the Fornix and Cingulum in Multiple Sclerosis

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Stephanie B. Syc ◽  
Daniel M. Harrison ◽  
Shiv Saidha ◽  
Michaela Seigo ◽  
Peter A. Calabresi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Healthy Volunteers ◽  
Cognitive Dysfunction ◽  
Diffusion Tensor ◽  
Magnetization Transfer ◽  
Mean Diffusivity ◽  
Brain Structures ◽  
Quantitative Mri ◽  
Magnetization Transfer Ratio

Objective. To characterize MR signal changes associated with tissue damage in the fornix and cingulum in multiple sclerosis (MS) using quantitative MRI measures and to determine associations with cognitive dysfunction.Background. The fornix and cingulum are white-matter bundles that carry information related to cognition. While cognitive dysfunction is reported in 40–60% of MS patients, the neuroanatomical correlates of cognitive impairment remain incompletely understood.Methods. The cingulum, pillars of the fornix, and corticospinal tract were segmented by fiber tracking via diffusion tensor imaging. Average tract-specific fractional anisotropy (FA), mean diffusivity (MD), and magnetization transfer ratio (MTR) were compared in MS cases and healthy volunteers. Associations with clinical measures and neuropsychological tests were derived by multivariate linear regression.Results. Fornix FA (P=0.004) and MTR (P=0.005) were decreased, and fornix MD (P<0.001) and cingulum MD (P<0.001) increased, in MS cases (n=101) relative to healthy volunteers (n=16) after adjustment for age and sex. Lower fornix FA and MTR, and higher fornix MD andλ∥, were correlated with lower PASAT-3 scores, but not with slower 25FTW times. Lower PASAT-3 scores were associated with lower cingulum FA and higher MD andλ⊥.Conclusions. Cognitive dysfunction in MS may involve damage to a widespread network of brain structures, including white-matter pathways within the limbic system.

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