Beyond focal cortical lesions in MS: An in vivo quantitative and spatial imaging study at 7T

Abstract

Objectives: Using quantitative T2* 7-tesla (7T) MRI as a marker of demyelination and iron loss, we investigated, in patients with relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS), spatial and tissue intrinsic characteristics of cortical lesion(s) (CL) types, and structural integrity of perilesional normal-appearing cortical gray matter (NACGM) as a function of distance from lesions.

Methods: Patients with MS (18 RRMS, 11 SPMS), showing at least 2 CL, underwent 7T T2* imaging to obtain (1) magnitude images for segmenting focal intracortical lesion(s) (ICL) and leukocortical lesion(s) (LCL), and (2) cortical T2* maps. Anatomical scans were collected at 3T for cortical surface reconstruction using FreeSurfer. Seventeen age-matched healthy participants served as controls.

Results: ICL were predominantly located in sulci of frontal, parietal, and cingulate cortex; LCL distribution was more random. In MS, T2* was higher in both ICL and LCL, indicating myelin and iron loss, than in NACGM (p < 0.00003) irrespective of CL subtype and MS phenotype. T2* was increased in perilesional cortex, tapering away from CL toward NACGM, the wider changes being for LCL in SPMS. NACGM T2* was higher in SPMS relative to RRMS (p = 0.006) and healthy cortex (p = 0.02).

Conclusions: CL had the same degree of demyelination and iron loss regardless of lesion subtype and disease stage. Cortical damage expanded beyond visible CL, close to lesions in RRMS, and more diffusely in SPMS. Evaluation of NACGM integrity, beyond focal CL, could represent a surrogate marker of MS progression.

© 2015 American Academy of Neurology.

Figures

Figure 1. Overlay on “fsaverage” template of cortical lesion probability maps in patients with multiple sclerosis

The color overlay represents the vertex-wise frequency of cortical lesion occurrence. ICL = intracortical lesion(s); lat. = lateral; LCL = leukocortical lesion(s); LH = left hemisphere; med. = medial; RH = right hemisphere.

Figure 2. Boxplots of T2* relaxation time (ms) in cortical tissue compartments in controls (green), RRMS (pink), and SPMS (red)

SPMS showed higher NACGM T2* relative to cortical T2* in controls (p = 0.01) and NACGM T2* in RRMS (p = 0.005), by linear regression including age and cortical thickness as nuisance factors. In RRMS and SPMS, T2* within cortical lesions (ICL and LCL) was higher than NACGM T2* and than control cortex T2*. aStatistical significance (p value) of T2* difference between lesional and NACGM within each MS group, by paired t test. bStatistical significance (p value) of T2* difference between lesional cortex from patients with MS and cortex from controls, by linear regression including age and cortical thickness as nuisance factor. All p values are corrected for multiple comparisons using false discovery rate. ICL = intracortical lesion(s); LCL = leukocortical lesion(s); MS = multiple sclerosis; NACGM = normal-appearing cortical gray matter; RRMS = relapsing-remitting multiple sclerosis; SPMS = secondary progressive multiple sclerosis.

Figure 3. T2* in cortical lesions and perilesional cortex

(A) Example of the geodesic distance contour surrounding lesional cortex overlaid on the left hemisphere cortical surface of a patient with RRMS. Binary mask of ICL was projected on the cortical surface, providing a 2-dimensional ICL mask (in red). Perilesional vertices were identified using their geodesic distance from the lesions, each value (1–20) being assigned a different color for visualization purposes. Each cortical lesion mask was analyzed as a whole for each participant, implying that there was no ambiguity when calculating the geodesic distance to lesions that were close to each other as figured in this example. (B) Boxplots of T2* relaxation time (ms) as a function of the geodesic distance from the lesions in all patients with MS, patients with RRMS, and patients with SPMS. T2* is expressed relative to its baseline value in each participant (see methods section). Boxplots in red indicate that there is a difference between mean T2* of the given geodesic distance and mean T2* far from the lesions (geodesic distance of 20) for the specified group of participants. ***p < 0.001, **p < 0.01, *p < 0.05. ICL = intracortical lesion(s); MS = multiple sclerosis; RRMS = relapsing-remitting multiple sclerosis; SPMS = secondary progressive multiple sclerosis.