Cortical Lesions In Multiple Sclerosis Research Articles

Quantifying Remyelination Using χ-Separation in White Matter and Cortical Multiple Sclerosis Lesions.

Myelin and iron play essential roles in remyelination processes of multiple sclerosis (MS) lesions. χ-separation, a novel biophysical model applied to multiecho T2*-data and T2-data, estimates the contribution of myelin and iron to the obtained susceptibility signal. We used this method to investigate myelin and iron levels in lesion and nonlesion brain areas in patients with MS and healthy individuals. This prospective MS cohort study included patients with MS fulfilling the McDonald Criteria 2017 and healthy individuals, aged 18 years or older, with no other neurologic comorbidities. Participants underwent MRI at baseline and after 2 years, including multiecho GRE-(T2*) and FAST-(T2) sequences. Using χ-separation, we generated myelin-sensitive and iron-sensitive susceptibility maps. White matter lesions (WMLs), cortical lesions (CLs), surrounding normal-appearing white matter (NAWM), and normal-appearing gray matter were segmented on fluid-attenuated inversion recovery and magnetization-prepared 2 rapid gradient echo images, respectively. Cross-sectional group comparisons used Wilcoxon rank-sum tests, longitudinal analyses applied Wilcoxon signed-rank tests. Associations with clinical outcomes (disease phenotype, age, sex, disease duration, disability measured by Expanded Disability Status Scale [EDSS], neurofilament light chain levels, and T2-lesion number and volume) were assessed using linear regression models. Of 168 patients with MS (median [interquartile range (IQR)] age 47.0 [21.7] years; 101 women; 6,898 WMLs, 775 CLs) and 103 healthy individuals (age 33.0 [10.5] years, 57 women), 108 and 62 were followed for a median of 2 years, respectively (IQR 0.1; 5,030 WMLs, 485 CLs). At baseline, WMLs had lower myelin (median 0.025 [IQR 0.015] parts per million [ppm]) and iron (0.017 [0.015] ppm) than the corresponding NAWM (myelin 0.030 [0.012]; iron 0.019 [0.011] ppm; both p < 0.001). After 2 years, both myelin (0.027 [0.014] ppm) and iron had increased (0.018 [0.015] ppm; both p < 0.001). Younger age (p < 0.001, b = -5.111 × 10-5), lower disability (p = 0.04, b = -2.352 × 10-5), and relapsing-remitting phenotype (RRMS, 0.003 [0.01] vs primary progressive 0.002 [IQR 0.01], p < 0.001; vs secondary progressive 0.0004 [IQR 0.01], p < 0.001) at baseline were associated with remyelination. Increment of myelin correlated with clinical improvement measured by EDSS (p = 0.015, b = -6.686 × 10-4). χ-separation, a novel mathematical model applied to multiecho T2*-images and T2-images shows that young RRMS patients with low disability exhibit higher remyelination capacity, which correlated with clinical disability over a 2-year follow-up.

Central Vein Sign, Cortical Lesions, and Paramagnetic Rim Lesions for the Diagnostic and Prognostic Workup of Multiple Sclerosis.

The diagnosis of multiple sclerosis (MS) can be challenging in clinical practice because MS presentation can be atypical and mimicked by other diseases. We evaluated the diagnostic performance, alone or in combination, of the central vein sign (CVS), paramagnetic rim lesion (PRL), and cortical lesion (CL), as well as their association with clinical outcomes. In this multicenter observational study, we first conducted a cross-sectional analysis of the CVS (proportion of CVS-positive lesions or simplified determination of CVS in 3/6 lesions-Select3*/Select6*), PRL, and CL in MS and non-MS cases on 3T-MRI brain images, including 3D T2-FLAIR, T2*-echo-planar imaging magnitude and phase, double inversion recovery, and magnetization prepared rapid gradient echo image sequences. Then, we longitudinally analyzed the progression independent of relapse and MRI activity (PIRA) in MS cases over the 2 years after study entry. Receiver operating characteristic curves were used to test diagnostic performance and regression models to predict diagnosis and clinical outcomes. The presence of ≥41% CVS-positive lesions/≥1 CL/≥1 PRL (optimal cutoffs) had 96%/90%/93% specificity, 97%/84%/60% sensitivity, and 0.99/0.90/0.77 area under the curve (AUC), respectively, to distinguish MS (n = 185) from non-MS (n = 100) cases. The Select3*/Select6* algorithms showed 93%/95% specificity, 97%/89% sensitivity, and 0.95/0.92 AUC. The combination of CVS, CL, and PRL improved the diagnostic performance, especially when Select3*/Select6* were used (93%/94% specificity, 98%/96% sensitivity, 0.99/0.98 AUC; p = 0.002/p < 0.001). In MS cases (n = 185), both CL and PRL were associated with higher MS disability and severity. Longitudinal analysis (n = 61) showed that MS cases with >4 PRL at baseline were more likely to experience PIRA at 2-year follow-up (odds ratio 17.0, 95% confidence interval: 2.1-138.5; p = 0.008), whereas no association was observed between other baseline MRI measures and PIRA, including the number of CL. The combination of CVS, CL, and PRL can improve MS differential diagnosis. CL and PRL also correlated with clinical measures of poor prognosis, with PRL being a predictor of disability accrual independent of clinical/MRI activity.

Usefulness of Phase Sensitive Inversion Recovery MRI Sequence in the Detection of Cortical Lesions in Multiple Sclerosis

Usefulness of Phase Sensitive Inversion Recovery MRI Sequence in the Detection of Cortical Lesions in Multiple Sclerosis

Location and morphology of cortical lesions in multiple sclerosis

Location and morphology of cortical lesions in multiple sclerosis

Multifaceted Evaluation of Double Inversion Recovery Brain MRI in Detection of Cervical Spine Multiple Sclerosis Lesions (P11-3.002)

<h3>Objective:</h3> To quantitatively study the efficacy of Brain Double Inversion Recovery (DIR) MRI for the detection of cervical spinal cord lesions in Multiple Sclerosis (MS) patients using blinded readings as well as contrast to noise ratios (C/N). <h3>Background:</h3> DIR is a well-established MRI pulse sequence for detection of cerebral cortical and juxtacortical MS lesions. Since the superior half of the cervical cord is visible on sagittally acquired volumetric DIR of the brain, we investigated the efficacy of Brain MRI for detecting upper spinal cord of MS patients. <h3>Design/Methods:</h3> We retrospectively examined the MRI of the brain of 64 patients with established MS, who had also undergone cervical spine MRI. Two blinded MS expert readers, who assessed the scans for lesion numbers and rated lesion visibility and overall image quality, reviewed brain 3D DIR sagittal and coronal images. Official cervical spine study reports were used as the “gold standard” in this analysis. Additionally, standardized Mean contrast-to-noise ratios (C/N) and standard deviation (S.D.) were calculated in representative lesions for each patient and compared to those of 3D brain FLAIR images. <h3>Results:</h3> The sensitivity of brain DIR was found to be 87% and specificity was found to 61% when all “definite” lesions were included. When considering both “probable” and “definite” lesions, the sensitivity increased to 91% and specificity decreased to 54%. Contrast to noise ratio of brain DIR lesions was significantly higher compared to brain FLAIR lesions (7.56 +/−1.77 vs. 0.67+/−1.27). <h3>Conclusions:</h3> Sagittally acquired volumetric Brain DIR can provide useful information on cervical spinal cord lesions, with high C/N. In some cases, this should facilitate the attainment of the MRI components of McDonald’s diagnostic criteria without a dedicated cervical spine study. <b>Disclosure:</b> Mr. Patel has nothing to disclose. Marina Creed has nothing to disclose. Dr. Gershon has nothing to disclose. The institution of Dr. Wolansky has received research support from Guerbet. Dr. Imitola has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis . The institution of Dr. Imitola has received research support from biogen. Dr. Imitola has a non-compensated relationship as a Board Member with National MS Society that is relevant to AAN interests or activities. Dr. Imitola has a non-compensated relationship as a Committee Member with International Society for Stem Cell Research that is relevant to AAN interests or activities.

The ipsilateral silent period and its link to cortical lesions in multiple sclerosis

The ipsilateral silent period and its link to cortical lesions in multiple sclerosis

Accurate Diagnosis of Cortical and Infratentorial Lesions in Multiple Sclerosis Using Accelerated Fluid and White Matter Suppression Imaging.

The precise location of multiple sclerosis (MS) cortical lesions can be very challenging at 3 T, yet distinguishing them from subcortical lesions is essential for the diagnosis and prognosis of the disease. Compressed sensing-accelerated fluid and white matter suppression imaging (CS-FLAWS) is a new magnetic resonance imaging sequence derived from magnetization-prepared 2 rapid acquisition gradient echo with promising features for the detection and classification of MS lesions. The objective of this study was to compare the diagnostic performances of CS-FLAWS (evaluated imaging) and phase sensitive inversion recovery (PSIR; reference imaging) for classification of cortical lesions (primary objective) and infratentorial lesions (secondary objective) in MS, in combination with 3-dimensional (3D) double inversion recovery (DIR). Prospective 3 T scans (MS first diagnosis or follow-up) acquired between March and August 2021 were retrospectively analyzed. All underwent 3D CS-FLAWS, axial 2D PSIR, and 3D DIR. Double-blinded reading sessions exclusively in axial plane and final consensual reading were performed to assess the number of cortical and infratentorial lesions. Wilcoxon test was used to compare the 2 imaging datasets (FLAWS + DIR and PSIR + DIR), and intraobserver and interobserver agreement was assessed using the intraclass correlation coefficient. Forty-two patients were analyzed (38 with relapsing-remitting MS, 29 women, 42.7 ± 12.6 years old). Compressed sensing-accelerated FLAWS allowed the identification of 263 cortical lesions versus 251 with PSIR ( P = 0.74) and 123 infratentorial lesions versus 109 with PSIR ( P = 0.63), corresponding to a nonsignificant difference between the 2 sequences. Compressed sensing-accelerated FLAWS exhibited fewer false-negative findings than PSIR either for cortical lesions (1 vs 13; P < 0.01) or infratentorial lesions (1 vs 15; P < 0.01). No false-positive findings were found with any of the 2 sequences. Diagnostic confidence was high for each contrast. Three-dimensional CS-FLAWS is as accurate as 2D PSIR imaging for classification of cortical and infratentorial MS lesions, with fewer false-negative findings, opening the way to a reliable full brain MS exploration in a clinically acceptable duration (5 minutes 15 seconds).

Whole-Brain Water Content Mapping Using Super-Resolution Reconstruction with MRI Acquisitionin3Orthogonal Orientations.

Brain water content provides rich tissue contrast comparable to that of longitudinal relaxation time T1 , but mapping is usually performed at modest resolution. In particular, the slice thickness in 2D mapping methods is limited. Here, we combine super-resolution reconstruction techniques with a fast water content mapping method to acquire high and isotropic resolution (0.75 mm) water content maps at 3Tesla. A high-resolution multi-echo gradient echo image is super-resolution-reconstructed from 3 low-resolution, orthogonal multi-echo gradient echo image acquisitions, followed by water content mapping. The mapping accuracy and SNR of the proposed method are assessed using numerical simulations, phantom studies, and in vivo data acquired from 6 healthy volunteers at 3Tesla. A high-resolution acquisition with an established mapping method is used as a reference. Whole-brain water content maps with 0.75 mm isotropic resolution are demonstrated. No bias in the water content values was seen following super-resolution reconstruction. In the in vivo experiments, a lower SD of the mean water content values was observed with the proposed method compared to the reference method. Super-resolution reconstruction of multi-echo gradient echo data is demonstrated, enabling whole-brain water content mapping with high and isotropic resolution. The accuracy of the proposed method is shown using phantoms and 6 healthy volunteers and was found to be unchanged compared to the conventional acquisition. The proposed method could increase the sensitivity of water content mapping sufficiently to enable the detection of very small lesions, such as cortical lesions in multiple sclerosis.

Multiple sclerosis cortical lesion detection with deep learning at ultra-high-field MRI.

Manually segmenting multiple sclerosis (MS) cortical lesions (CLs) is extremely time consuming, and past studies have shown only moderate inter‐rater reliability. To accelerate this task, we developed a deep‐learning‐based framework (CLAIMS: Cortical Lesion AI‐Based Assessment in Multiple Sclerosis) for the automated detection and classification of MS CLs with 7 T MRI. Two 7 T datasets, acquired at different sites, were considered. The first consisted of 60 scans that include 0.5 mm isotropic MP2RAGE acquired four times (MP2RAGE×4), 0.7 mm MP2RAGE, 0.5 mm T 2*‐weighted GRE, and 0.5 mm T 2*‐weighted EPI. The second dataset consisted of 20 scans including only 0.75 × 0.75 × 0.9 mm3 MP2RAGE. CLAIMS was first evaluated using sixfold cross‐validation with single and multi‐contrast 0.5 mm MRI input. Second, the performance of the model was tested on 0.7 mm MP2RAGE images after training with either 0.5 mm MP2RAGE×4, 0.7 mm MP2RAGE, or alternating the two. Third, its generalizability was evaluated on the second external dataset and compared with a state‐of‐the‐art technique based on partial volume estimation and topological constraints (MSLAST). CLAIMS trained only with MP2RAGE×4 achieved results comparable to those of the multi‐contrast model, reaching a CL true positive rate of 74% with a false positive rate of 30%. Detection rate was excellent for leukocortical and subpial lesions (83%, and 70%, respectively), whereas it reached 53% for intracortical lesions. The correlation between disability measures and CL count was similar for manual and CLAIMS lesion counts. Applying a domain‐scanner adaptation approach and testing CLAIMS on the second dataset, the performance was superior to MSLAST when considering a minimum lesion volume of 6 μL (lesion‐wise detection rate of 71% versus 48%). The proposed framework outperforms previous state‐of‐the‐art methods for automated CL detection across scanners and protocols. In the future, CLAIMS may be useful to support clinical decisions at 7 T MRI, especially in the field of diagnosis and differential diagnosis of MS patients.

Artificial double inversion recovery images can substitute conventionally acquired images: an MRI-histology study

Cortical multiple sclerosis lesions are disease-specific, yet inconspicuous on magnetic resonance images (MRI). Double inversion recovery (DIR) images are sensitive, but often unavailable in clinical routine and clinical trials. Artificially generated images can mitigate this issue, but lack histopathological validation. In this work, artificial DIR images were generated from postmortem 3D-T1 and proton-density (PD)/T2 or 3D-T1 and 3D fluid-inversion recovery (FLAIR) images, using a generative adversarial network. All sequences were scored for cortical lesions, blinded to histopathology. Subsequently, tissue samples were stained for proteolipid protein (myelin) and scored for cortical lesions type I-IV (leukocortical, intracortical, subpial and cortex-spanning, respectively). Histopathological scorings were then (unblinded) compared to MRI using linear mixed models. Images from 38 patients (26 female, mean age 64.3 ± 10.7) were included. A total of 142 cortical lesions were detected, predominantly subpial. Histopathology-blinded/unblinded sensitivity was 13.4/35.2% for artificial DIR generated from T1-PD/T2, 14.1/41.5% for artificial DIR from T1-FLAIR, 17.6/49.3% for conventional DIR and 10.6/34.5% for 3D-T1. When blinded to histopathology, there were no differences; with histopathological feedback at hand, conventional DIR and artificial DIR from T1-FLAIR outperformed the other sequences. Differences between histopathology-blinded/unblinded sensitivity could be minified through adjustment of the scoring criteria. In conclusion, artificial DIR images, particularly generated from T1-FLAIR could potentially substitute conventional DIR images when these are unavailable.

Neurophysiological changes associated with cortical lesions in multiple sclerosis.

Neurophysiological changes associated with cortical lesions in multiple sclerosis.

Association of retinal atrophy with cortical lesions and leptomeningeal enhancement in multiple sclerosis on 7T MRI

Background: Retinal atrophy in multiple sclerosis (MS) as measured by optical coherence tomography (OCT) correlates with demyelinating lesions and brain atrophy, but its relationship with cortical lesions (CLs) and meningeal inflammation is not well known. Objectives: To evaluate the relationship of retinal layer atrophy with leptomeningeal enhancement (LME) and CLs in MS as visualized on 7 Tesla (7T) magnetic resonance imaging (MRI). Methods: Forty participants with MS underwent 7T MRI of the brain and OCT. Partial correlation and mixed-effects regression evaluated relationships between MRI and OCT findings. Results: All participants had CLs and 32 (80%) participants had LME on post-contrast MRI. Ganglion cell/inner plexiform layer (GCIPL) thickness correlated with total CL volume (r =−0.45, p < 0.01). Participants with LME at baseline had thinner macular retinal nerve fiber layer (mRNFL; p = 0.01) and GCIPL (p < 0.01). Atrophy in various retinal layers was faster in those with certain patterns of LME. For example, mRNFL declined –1.113 (–1.974, –0.252) μm/year faster in those with spread/fill-pattern LME foci at baseline compared with those without (p = 0.01). Conclusion: This study associates MRI findings of LME and cortical pathology with thinning of retinal layers as measured by OCT, suggesting a common link between meningeal inflammation, CLs, and retinal atrophy in MS.

Imaging cortical multiple sclerosis lesions with ultra-high field MRI

BackgroundCortical lesions are abundant in multiple sclerosis (MS), yet difficult to visualize in vivo. Ultra-high field (UHF) MRI at 7 T and above provides technological advances suited to optimize the detection of cortical lesions in MS. PurposeTo provide a narrative and quantitative systematic review of the literature on UHF MRI of cortical lesions in MS. MethodsA systematic search of all literature on UHF MRI of cortical lesions in MS published before September 2020. Quantitative outcome measures included cortical lesion numbers reported using 3 T and 7 T MRI and between 7 T MRI sequences, along with sensitivity of UHF MRI towards cortical lesions verified by histopathology. Results7 T MRI detected on average 52 ± 26% (mean ± 95% confidence interval) more cortical lesions than the best performing image contrast at 3 T, with the largest increase in type II-IV intracortical lesion detection. Across all studies, the mean cortical lesion number was 17 ± 6 per patient. In progressive MS cohorts, approximately four times more cortical lesions were reported than in CIS/early RRMS, and RRMS. Yet, there was no difference in lesion type ratio between these MS subtypes. Furthermore, superiority of one MRI sequence over another could not be established from available data. Post-mortem lesion detection with UHF MRI agreed only modestly with pathological examinations. Mean pro- and retrospective sensitivity was 33 ± 6% and 71 ± 10%, respectively, with the highest sensitivity towards type I and type IV lesions. ConclusionUHF MRI improves cortical lesion detection in MS considerably compared to 3 T MRI, particularly for type II-IV lesions. Despite modest sensitivity, 7 T MRI is still capable of visualizing all aspects of cortical lesion pathology and could potentially aid clinicians in diagnosing and monitoring MS, and progressive MS in particular. However, standardization of acquisition and segmentation protocols is needed.

Detection of Cortical and Deep Gray Matter Lesions in Multiple Sclerosis Using DIR and FLAIR at 3T.

The comparative detection rates of deep gray matter (GM) multiple sclerosis (MS) lesions using double inversion recovery (DIR) and fluid-attenuated inversion-recovery (FLAIR) on 3T MR imaging remain unknown. We aimed to assess the detectability of cortical and deep GM MS lesions using DIR and FLAIR on 3T clinical exams and evaluate the relationship between deep GM lesions and brain atrophy. One hundred fifty consecutive MS patients underwent routine brain MRI that included 3D DIR and 2D T2 FLAIR on the same 3T scanner. Three neuroradiologists independently reviewed all exams for cortical and deep GM lesions. Statistical parametric mapping (SPM) and FMRIB software library (FSL)-FIRST pipelines were used to determine normalized whole brain and deep GM volumes. A total of 65 cortical and 98 deep lesions were detected on DIR versus 24 and 20, respectively, on FLAIR. Among all 150 patients, the number and percentage of patients with GM lesions on DIR and FLAIR were as follows: cortical 43 (28.7%) versus 24 (16.0%) (P < .001), thalamus 47 (31.3%) versus 20 (13.3%) (P<.001), putamen 10 (6.7%) versus 3 (2.0%) (P = .02), globus pallidus 9 (6.0%) versus 3 (1.3%) (P = .02), and caudate 5 (3.3%) versus 1 (0.7%) (P = .125). Presence of deep GM lesions weakly correlated with deep GM volume fractions. Deep GM MS lesions can be detected using routine clinical brain MRI including DIR and FLAIR at 3T. Future studies to optimize these sequences may improve the detection rates of cortical and deep GM lesions. The presence of GM lesions showed weak correlation with GM atrophy.

Imaging Butyrylcholinesterase in Multiple Sclerosis.

Molecular imaging agents targeting butyrylcholinesterase (BChE) have shown promise in other neurodegenerative disorders and may have utility in detecting changes to normal appearing white matter in multiple sclerosis (MS). BChE activity is present in white matter and localizes to activated microglia associated with MS lesions. The purpose of this study was to further characterize changes in the cholinergic system in MS pathology, and to explore the utility of BChE radioligands as potential diagnostic and treatment monitoring agents in MS. Cortical and white matter lesions were identified using myelin staining, and lesions were classified based on microglial activation patterns. Adjacent brain sections were used for cholinesterase histochemistry and in vitro autoradiography using phenyl 4-[123I]-iodophenylcarbamate (123I-PIP), a previously described small-molecule cholinesterase-binding radioligand. BChE activity is positively correlated with microglial activation in white matter MS lesions. There is no alteration in cholinesterase activity in cortical MS lesions. 123I-PIP autoradiography revealed uptake of radioactivity in normal white matter, absence of radioactivity within demyelinated MS lesions, and variable uptake of radioactivity in adjacent normal-appearing white matter. BChE imaging agents have the potential to detect MS lesions and subtle pathology in normal-appearing white matter in postmortem MS brain tissue. The possibility of BChE imaging agents serving to supplement current diagnostic and treatment monitoring strategies should be evaluated.

Inversion Recovery Susceptibility Weighted Imaging With Enhanced T2 Weighting at 3 T Improves Visualization of Subpial Cortical Multiple Sclerosis Lesions.

Cortical demyelination is common in multiple sclerosis (MS) and can be extensive. Cortical lesions contribute to disability independently from white matter lesions and may form via a distinct mechanism. However, current magnetic resonance imaging methods at 3 T are insensitive to cortical, and especially subpial cortical, lesions. Subpial lesions are well seen on T2*-weighted imaging at 7 T, but T2*-weighted methods on 3 T scanners are limited by poor lesion-to-cortex and cerebrospinal fluid-to-lesion contrast. We aimed to develop and evaluate a cerebrospinal fluid-suppressed, T2*-weighted sequence optimized for subpial cortical lesion visualization. We developed a new magnetic resonance imaging sequence, inversion recovery susceptibility weighted imaging with enhanced T2 weighting (IR-SWIET; 0.8 mm × 0.8 mm in plane, 0.64 mm slice thickness with whole brain coverage, acquisition time ~5 minutes). We compared cortical lesion visualization independently on IR-SWIET (median signal from 4 acquisitions), magnetization-prepared 2 rapid acquisition gradient echoes (MP2RAGE), double inversion recovery (DIR), T2*-weighted segmented echo-planar imaging, and phase-sensitive inversion recovery images for 10 adults with MS. We also identified cortical lesions with a multicontrast reading of IR-SWIET (median of 2 acquisitions), MP2RAGE, and fluid-attenuated inversion recovery (FLAIR) images for each case. Lesions identified on 3 T images were verified on "gold standard" 7 T T2* and MP2RAGE images. Cortical, and particularly subpial, lesions appeared much more conspicuous on IR-SWIET compared with other 3 T methods. A total of 101 true-positive subpial lesions were identified on IR-SWIET (average per-participant sensitivity vs 7 T, 29% ± 8%) versus 36 on MP2RAGE (5% ± 2%; comparison to IR-SWIET sensitivity, P = 0.07), 17 on FLAIR (2% ± 1%; P < 0.05), 28 on DIR (6% ± 2%; P < 0.05), 42 on T2*-weighted segmented echo-planar imaging (11% ± 5%; P < 0.05), and 13 on phase-sensitive inversion recovery (4% ± 2%; P < 0.05). When a combination of IR-SWIET, MP2RAGE, and FLAIR images was used, a total of 147 subpial lesions (30% ± 5%) were identified versus 83 (16% ± 3%, P < 0.01) on a combination of DIR, MP2RAGE, and FLAIR. More cases had at least 1 subpial lesion on IR-SWIET, and IR-SWIET improved cortical lesion subtyping accuracy and correlation with 7 T subpial lesion number. Subpial lesions are better visualized on IR-SWIET compared with other 3 T methods. A 3 T protocol combining IR-SWIET with MP2RAGE, in which leukocortical lesions are well seen, improves cortical lesion visualization over existing approaches. Therefore, IR-SWIET may enable improved MS diagnostic specificity and a better understanding of the clinical implications of cortical demyelination.

A clinically feasible 7-Tesla protocol for the identification of cortical lesions in Multiple Sclerosis.

The aim of this study was to evaluate the capability of sequences acquired on a 7-T MRI scanner, within times and anatomical coverage appropriate for clinical studies, to identify cortical lesions (CLs) in patients with Multiple Sclerosis (MS). Furthermore, we aimed to confirm the clinical significance of CL, testing the correlations between gray matter (GM) lesions and clinical scores. A 7-T MRI protocol included 3D-T1-weighted and T2*-weighted sequences. Images were evaluated independently by three readers of different experience, and the number of CLs was recorded. Between-rater concordance was assessed calculating the intraclass correlation coefficient (ICC). Lin's concordance correlation coefficient was used to compare CL detection between sequences, while partial correlations and multivariable regression models were used to study the relationship between CL and clinical data. Forty MS patients (M/F, 17/23; 44.7 ± 12.6years) were enrolled in this study, and CLs were identified in 35/40 subjects (87.5%). CL detection rate on 3D-T1-weighted images was significantly correlated with the detection rate on T2*-weighted images (r = 0.99; p < 0.001), with high concordance between readers (ICC ≥ 0.995). CLs were significantly correlated with both motor and cognitive scores (all with p ≤ 0.04). CL can be identified over the whole brain at 7-T in MS using a 3D-T1-weighted volume, acquired in a clinically feasible time and with comparable performance to that achievable using the T2*-weighted sequence. Based on the central role of CL in the development of clinical disability, we suggest that 3D-T1-weighted volume may play a role in the evaluation of CL in MS undergoing MRI on ultra-high-field scanners. • Cortical lesions can be identified in a clinically feasible time with a 7-T protocol, which includes a 3D-T1-weighted volume. • Cortical lesions correlated significantly with both motor and cognitive disability in MS patients. • Given their correlation with clinical disability, evaluation of a cortical lesion on a 7-T clinical protocol could help in the management of MS patients.

Automated Detection and Segmentation of Multiple Sclerosis Lesions Using Ultra-High-Field MP2RAGE.

The aim of this study was to develop a new automated segmentation method of white matter (WM) and cortical multiple sclerosis (MS) lesions visible on magnetization-prepared 2 inversion-contrast rapid gradient echo (MP2RAGE) images acquired at 7 T MRI. The proposed prototype (MSLAST [Multiple Sclerosis Lesion Analysis at Seven Tesla]) takes as input a single image contrast derived from the 7T MP2RAGE prototype sequence and is based on partial volume estimation and topological constraints. First, MSLAST performs a skull-strip of MP2RAGE images and computes tissue concentration maps for WM, gray matter (GM), and cerebrospinal fluid (CSF) using a partial volume model of tissues within each voxel. Second, MSLAST performs (1) connected-component analysis to GM and CSF concentration maps to classify small isolated components as MS lesions; (2) hole-filling in the WM concentration map to classify areas with low WM concentration surrounded by WM (ie, MS lesions); and (3) outlier rejection to the WM mask to improve the classification of small WM lesions. Third, MSLAST unifies the 3 maps obtained from 1, 2, and 3 processing steps to generate a global lesion mask. Quantitative and qualitative assessments were performed using MSLAST in 25 MS patients from 2 research centers. Overall, MSLAST detected a median of 71% of MS lesions, specifically 74% of WM and 58% of cortical lesions, when a minimum lesion size of 6 μL was considered. The median false-positive rate was 40%. When a 15 μL minimal lesions size was applied, which is the approximation of the minimal size recommended for 1.5/3 T images, the median detection rate was 80% for WM and 63% for cortical lesions, respectively, and the median false-positive rate was 33%. We observed high correlation between MSLAST and manual segmentations (Spearman rank correlation coefficient, ρ = 0.91), although MSLAST underestimated the total lesion volume (average difference of 1.1 mL), especially in patients with high lesion loads. MSLAST also showed good scan-rescan repeatability within the same session with an average absolute volume difference and F1 score of 0.38 ± 0.32 mL and 84%, respectively. We propose a new methodology to facilitate the segmentation of WM and cortical MS lesions at 7 T MRI, our approach uses a single MP2RAGE scan and may be of special interest to clinicians and researchers.

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

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 (β = 1.5, P < .001) and EDSS changes at follow-up (β = 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.

Longitudinal analysis of white matter and cortical lesions in multiple sclerosis.

PurposeThe goals of this study were to assess the performance of a novel lesion segmentation tool for longitudinal analyses, as well as to validate the generated lesion progression map between two time points using conventional and non-conventional MR sequences.Material and methodsThe lesion segmentation approach was evaluated with (LeMan-PV) and without (LeMan) the partial volume framework using “conventional” and “non-conventional” MR imaging in a two-year follow-up prospective study of 32 early RRMS patients. Manual segmentations of new, enlarged, shrunken, and stable lesions were used to evaluate the performance of the method variants. The true positive rate was estimated for those lesion evolutions in both white matter and cortex. The number of false positives was compared with two strategies for longitudinal analyses. New lesion tissue volume estimation was evaluated using Bland-Altman plots. Wilcoxon signed-rank test was used to evaluate the different setups.ResultsThe best median of the true positive rate was obtained using LeMan-PV with non-conventional sequences (P < .05): 87%, 87%, 100%, 83%, for new, enlarged, shrunken, and stable WM lesions, and 50%, 60%, 50%, 80%, for new, enlarged, shrunken, and stable cortical lesions, respectively. Most of the missed lesions were below the mean lesion size in each category. Lesion progression maps presented a median of 0 false positives (range:0–9) and the partial volume framework improved the volume estimation of new lesion tissue.ConclusionLeMan-PV exhibited the best performance in the detection of new, enlarged, shrunken and stable WM lesions. The method showed lower performance in the detection of cortical lesions, likely due to their low occurrence, small size and low contrast with respect to surrounding tissues. The proposed lesion progression map might be useful in clinical trials or clinical routine.