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Longitudinal Characterization of Cortical Lesion Development and Evolution in Multiple Sclerosis with 7.0-T MRI.

ABSTRACT: Background Cortical lesions develop early in multiple sclerosis (MS) and play a major role in disease progression. MRI at 7.0 T shows high sensitivity for detection of cortical lesions as well as better spatial resolution and signal-to-noise ratio compared with lower field strengths. Purpose To longitudinally characterize (a) the development and evolution of cortical lesions in multiple sclerosis across the cortical width, sulci, and gyri; (b) their relation with white matter lesion accrual; and (c) the contribution of 7.0-T cortical and white matter lesion load and cortical thickness to neurologic disability. Materials and Methods Twenty participants with relapsing-remitting MS and 13 with secondary progressive MS, along with 10 age-matched healthy controls, were prospectively recruited from 2010 to 2016 to acquire, in two imaging sessions (mean interval, 1.5 years), 7.0-T MRI T2*-weighted gradient-echo images (0.33 × 0.33 × 1.0 mm3) for cortical and white matter lesion segmentation and 3.0-T T1-weighted images for cortical surface reconstruction and cortical thickness estimation. Cortical lesions were sampled through the cortex to quantify cortical lesion distribution. The Expanded Disability Status Scale (EDSS) was used to assess neurologic disability. Nonparametric statistics assessed differences between and within groups in MRI metrics of cortical and white matter lesion burden; regression analysis explored associations of disability with MRI metrics. Results Twenty-five of 31 (81%) participants developed new cortical lesions per year (intracortical, 1.3 ± 1.7 vs leukocortical, 0.7 ± 1.9; P = .04), surpassing white matter lesion accrual (cortical, 2.0 ± 2.8 vs white matter, 0.7 ± 0.6; P = .01). In contrast to white matter lesions, cortical lesion accrual was greater in participants with secondary progressive MS than with relapsing-remitting MS (3.6 lesions/year ± 4.2 vs 1.1 lesions/year ± 0.9, respectively; P = .03) and preferentially localized in sulci. Total cortical lesion volume independently predicted baseline EDSS (? = 1.5, P < .001) and EDSS changes at follow-up (? = 0.5, P = .003). Conclusion Cortical lesions predominantly develop intracortically and within sulci, suggesting an inflammatory cerebrospinal fluid-mediated lesion pathogenesis. Cortical lesion accumulation was prominent at 7.0 T and independently predicted neurologic disability progression. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Filippi and Rocca in this issue.

SUBMITTER: Treaba CA

PROVIDER: S-EPMC6543899 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Longitudinal Characterization of Cortical Lesion Development and Evolution in Multiple Sclerosis with 7.0-T MRI.

Treaba Constantina A CA Granberg Tobias E TE Sormani Maria Pia MP Herranz Elena E Ouellette Russell A RA Louapre Céline C Sloane Jacob A JA Kinkel Revere P RP Mainero Caterina C

Radiology 20190409 3

Background Cortical lesions develop early in multiple sclerosis (MS) and play a major role in disease progression. MRI at 7.0 T shows high sensitivity for detection of cortical lesions as well as better spatial resolution and signal-to-noise ratio compared with lower field strengths. Purpose To longitudinally characterize <i>(a)</i> the development and evolution of cortical lesions in multiple sclerosis across the cortical width, sulci, and gyri; <i>(b)</i> their relation with white matter lesio ...[more]

PMID: 30964421

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Project description:Background and Objective: In multiple sclerosis (MS) patients, Double Inversion Recovery (DIR) magnetic resonance imaging (MRI) can be used to detect cortical lesions (CL). While the quantity and distribution of CLs seems to be associated with patients' disease course, literature lacks frequent assessments of CL volumes (CL-V) in this context. We investigated the reliability of DIR for the longitudinal assessment of CL-V development with frequent follow-up MRIs and examined the course of CL-V progressions in relation to white-matter lesions (WML), contrast enhancing lesions (CEL) and clinical parameters in patients with Relapsing-Remitting Multiple Sclerosis (RRMS). Methods: In this post-hoc analysis, image- and clinical data of a subset of 24 subjects that were part of a phase IIa clinical trial on the "Safety, Tolerability and Mechanisms of Action of Boswellic Acids in Multiple Sclerosis (SABA)" (ClinicalTrials.gov, NCT01450124) were included. The study was divided in three phases (screening, treatment, study-end). All patients received 12 MRI follow-up-examinations (including DIR) during a 16-months period. CL-Vs were assessed for each patient on each follow-up MRI separately by two experienced neuroradiologists. Results of neurological screening tests, as well as other MRI parameters (WML number and volume and CELs) were included from the SABA investigation data. Results: Inter-rater agreement regarding CL-V assessment over time was good-to-excellent (κ = 0.89). Mean intraobserver variability was 1.1%. In all patients, a total number of 218 CLs was found. Total CL-Vs of all patients increased during the 4 months of baseline screening followed by a continuous and significant decrease from month 5 until study-end (p < 0.001, Kendall'W = 0.413). A positive association between WML volumes and CL-Vs was observed during baseline screening. Decreased CL-V were associated with lower EDSS and also with improvements of SDMT- and SCRIPPS scores. Conclusion: DIR MRI seems to be a reliable tool for the frequent assessment of CL-Vs. Overall CL-Vs decreased during the follow-up period and were associated with improvements of cognitive and disability status scores. Our results suggest the presence of short-term CL-V dynamics in RRMS patients and we presume that the laborious evaluation of lesion volumes may be worthwhile for future investigations. Clinical Trial Numbers: www.ClinicalTrials.gov, "The SABA trial"; number: NCT01450124.

Project description:Quantitative MRI (qMRI) probes the microstructural properties of the central nervous system (CNS) by providing biophysical measures of tissue characteristics. In this work, we aimed to (i) identify qMRI measures that distinguish histological lesion types in postmortem multiple sclerosis (MS) brains, especially the remyelinated ones; and to (ii) investigate the relationship between those measures and quantitative histological markers of myelin, axons, and astrocytes in the same experimental setting. Three fixed MS whole brains were imaged with qMRI at 3T to obtain magnetization transfer ratio (MTR), myelin water fraction (MWF), quantitative T1 (qT1), quantitative susceptibility mapping (QSM), fractional anisotropy (FA) and radial diffusivity (RD) maps. The identification of lesion types (active, inactive, chronic active, or remyelinated) and quantification of tissue components were performed using histological staining methods as well as immunohistochemistry and immunofluorescence. Pairwise logistic and LASSO regression models were used to identify the best qMRI discriminators of lesion types. The association between qMRI and quantitative histological measures was performed using Spearman's correlations and linear mixed-effect models. We identified a total of 65 lesions. MTR and MWF best predicted the chance of a lesion to be remyelinated, whereas RD and QSM were useful in the discrimination of active lesions. The measurement of microstructural properties through qMRI did not show any difference between chronic active and inactive lesions. MWF and RD were associated with myelin content in both lesions and normal-appearing white matter (NAWM), FA was the measure most associated with axon content in both locations, while MWF was associated with astrocyte immunoreactivity only in lesions. Moreover, we provided evidence of extensive astrogliosis in remyelinated lesions. Our study provides new information on the discriminative power of qMRI in differentiating MS lesions -especially remyelinated ones- as well as on the relative association between multiple qMRI measures and myelin, axon and astrocytes.

Project description:Introduction: Changes in cortical and white matter lesion (CL, WML) load are pivotal metrics to diagnose and monitor multiple sclerosis patients. Yet, the relationship between (i) changes in CL/WML load and disease progression and between (ii) changes in CL/WML load and neurodegeneration at early MS stages is not yet established. In this work, we have assessed the hypothesis that the combined CL and WML load as well as their 2-years evolution are surrogate markers of neurodegeneration and clinical progression at early MS stages. To achieve this goal, we have studied a group of RRMS patients and have investigated the impact of both CL and WML load on neuroaxonal damage as measured by serum neurofilament light chain (sNfL). Next, we have explored whether changes in CL/WML load over 2 years in the same cohort of early-MS are related to motor and cognitive changes. Methods: Thirty-two RRMS patients (<5 years disease duration) underwent: (i) 3T MRI for CL/WML detection and clinical assessment at baseline and 2-years follow-up; and (ii) baseline blood test for sNfL. The correlation between the number and volume of CL/WML and sNfL was assessed by using the Spearman's rank correlation coefficient and a generalized linear model (GLM). A GLM was also used to assess the relationship between (i) the number/volume of new, enlarged, resolved, shrunken, stable lesions and (ii) the difference in clinical scores between two time-points. Results: At baseline, sNfL levels correlated with both total CL count/volume (ρ = 0.6/0.7, Corr-P <0.017/Corr-P < 0.001) and with total WML count/volume (ρ = 0.6/0.6, Corr-P < 0.01 for both). Baseline sNfL levels also correlated with new WML count/volume (ρ = 0.6/0.5, Corr-P < 0.01/Corr-P < 0.05) but not with new CL. Longitudinal changes in CL and WML count and volume were significantly associated with (i) sustained attention, auditory information, processing speed and flexibility (p < 0.01), (ii) verbal memory (p < 0.01); (iii) verbal fluency (p < 0.05); and (iv) hand-motor function (p < 0.05). Discussion: Changes in cortical and white matter focal damage in early MS patients correlate with global neuroaxonal damage and is associated to cognitive performances.

Dataset Information

Longitudinal Characterization of Cortical Lesion Development and Evolution in Multiple Sclerosis with 7.0-T MRI.

Publications

Longitudinal Characterization of Cortical Lesion Development and Evolution in Multiple Sclerosis with 7.0-T MRI.

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