Imaging the tip of the iceberg: visualization of cortical lesions in multiple sclerosis

2011 ◽  
Vol 17 (10) ◽  
pp. 1202-1210 ◽  
Author(s):  
Alexandra Seewann ◽  
Hugo Vrenken ◽  
Evert-Jan Kooi ◽  
Paul van der Valk ◽  
Dirk L Knol ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Brain Slice ◽  
Brain Slices ◽  
Region Of Interest ◽  
Lesion Size ◽  
Quantitative Mri ◽  
Cortical Lesion ◽  
Cortical Lesions ◽  
Conventional Mri ◽  
Magnetic Resonance Imaging Mri

Background: Cortical lesions (CLs) occur frequently in multiple sclerosis (MS), but only few CLs are observed on conventional magnetic resonance imaging (MRI). Why some CLs are visible and others are not is currently unknown. Here, we investigated whether CLs that are visible on conventional MRI differ from MRI-invisible CLs in terms of underlying histopathology and quantitative MRI (qMRI) measures. Methods: A total of 16 brain slices from 10 patients with chronic MS were analysed histopathologically and with conventional and qMRI. A region-of-interest approach was used to compare MRI-visible CLs with MRI-invisible CLs. Results: Although under-powering cannot be completely excluded in this study, MRI-visible CLs did not seem to differ from MRI-invisible CLs in terms of histopathology or qMRI measures. They were, however, significantly larger than their invisible counterparts (mean 13.3 ± 1.7 mm2 versus 6.9 ± 1.3 mm2; p = 0.001). Furthermore, the number of MRI-visible lesions correlated with the overall number of CLs in the brain slice ( r = 0.96, p < 0.01) and with the overall percentage of demyelination ( r = 0.78, p < 0.01) per hemispheric brain slice. Conclusion: MRI visibility of CLs is determined by lesion size, and not by any distinctive underlying pathology. Visible CLs are associated with a higher total cortical lesion load, which suggests that when CLs in patients with MS become detectable on MRI, they merely represent ‘the tip of the pathological iceberg’.

scholarly journals Quantitative 7-Tesla Imaging of Cortical Myelin Changes in Early Multiple Sclerosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Valeria Barletta ◽  
Elena Herranz ◽  
Constantina A. Treaba ◽  
Ambica Mehndiratta ◽  
Russell Ouellette ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Quantitative Mri ◽  
7 Tesla ◽  
Cortical Lesion ◽  
Healthy Controls ◽  
Cortical Lesions ◽  
Lesion Analysis ◽  
Cortical Map ◽  
The Brain

Cortical demyelination occurs early in multiple sclerosis (MS) and relates to disease outcome. The brain cortex has endogenous propensity for remyelination as proven from histopathology study. In this study, we aimed at characterizing cortical microstructural abnormalities related to myelin content by applying a novel quantitative MRI technique in early MS. A combined myelin estimation (CME) cortical map was obtained from quantitative 7-Tesla (7T) T2* and T1 acquisitions in 25 patients with early MS and 19 healthy volunteers. Cortical lesions in MS patients were classified based on their myelin content by comparison with CME values in healthy controls as demyelinated, partially demyelinated, or non-demyelinated. At follow-up, we registered changes in cortical lesions as increased, decreased, or stable CME. Vertex-wise analysis compared cortical CME in the normal-appearing cortex in 25 MS patients vs. 19 healthy controls at baseline and investigated longitudinal changes at 1 year in 10 MS patients. Measurements from the neurite orientation dispersion and density imaging (NODDI) diffusion model were obtained to account for cortical neurite/dendrite loss at baseline and follow-up. Finally, CME maps were correlated with clinical metrics. CME was overall low in cortical lesions (p = 0.03) and several normal-appearing cortical areas (p &lt; 0.05) in the absence of NODDI abnormalities. Individual cortical lesion analysis revealed, however, heterogeneous CME patterns from extensive to partial or absent demyelination. At follow-up, CME overall decreased in cortical lesions and non-lesioned cortex, with few areas showing an increase (p &lt; 0.05). Cortical CME maps correlated with processing speed in several areas across the cortex. In conclusion, CME allows detection of cortical microstructural changes related to coexisting demyelination and remyelination since the early phases of MS, and shows to be more sensitive than NODDI and relates to cognitive performance.

Heterogeneous pathological processes account for thalamic degeneration in multiple sclerosis: Insights from 7 T imaging

2017 ◽  
Vol 24 (11) ◽  
pp. 1433-1444 ◽  
Author(s):  
Céline Louapre ◽  
Sindhuja T Govindarajan ◽  
Costanza Giannì ◽  
Nancy Madigan ◽  
Jacob A Sloane ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Progressive Multiple Sclerosis ◽  
Lesion Volume ◽  
Thalamic Lesion ◽  
Cortical Lesions ◽  
Focal Lesions ◽  
Thalamic Degeneration ◽  
Relapsing Remitting ◽  
Thalamic Lesions ◽  
Magnetic Resonance Imaging Mri

Background: Thalamic degeneration impacts multiple sclerosis (MS) prognosis. Objective: To investigate heterogeneous thalamic pathology, its correlation with white matter (WM), cortical lesions and thickness, and as function of distance from cerebrospinal fluid (CSF). Methods: In 41 MS subjects and 17 controls, using 3 and 7 T imaging, we tested for (1) differences in thalamic volume and quantitative T2* (q-T2*) (2) globally and (3) within concentric bands originating from the CSF/thalamus interface; (4) the relation between thalamic, cortical, and WM metrics; and (5) the contribution of magnetic resonance imaging (MRI) metrics to clinical scores. We also assessed MS thalamic lesion distribution as a function of distance from CSF. Results: Thalamic lesions were mainly located next to the ventricles. Thalamic volume was decreased in MS versus controls ( p < 10−2); global q-T2* was longer in secondary progressive multiple sclerosis (SPMS) only ( p < 10−2), indicating myelin and/or iron loss. Thalamic atrophy and longer q-T2* correlated with WM lesion volume ( p < 0.01). In relapsing-remitting MS, q-T2* thalamic abnormalities were located next to the WM ( p < 0.01 (uncorrected), p = 0.09 (corrected)), while they were homogeneously distributed in SPMS. Cortical MRI metrics were the strongest predictors of clinical outcome. Conclusion: Heterogeneous pathological processes affect the thalamus in MS. While focal lesions are likely mainly driven by CSF-mediated factors, overall thalamic degeneration develops in association with WM lesions.

scholarly journals Brain and Spinal Cord MRI in Multiple Sclerosis: an Update

2017 ◽  
Vol 01 (04) ◽  
pp. E294-E306 ◽  
Author(s):  
Mike Wattjes ◽  
Peter Raab
Keyword(s):  
Multiple Sclerosis ◽  
Quantitative Mri ◽  
Central Vein ◽  
Resonance Imaging ◽  
Ultra High Field ◽  
Important Differential Diagnosis ◽  
Magnetic Resonance Imaging Mri ◽  
Near Future ◽  
Brain And Spinal Cord

AbstractMagnetic resonance imaging (MRI) plays an important role in the diagnosis of multiple sclerosis and has been incorporated into the McDonald diagnostic criteria for MS. In particular, for the exclusion of important differential diagnosis and comorbidities, new MRI markers have been established such as the “central vein sign”. In addition to diagnostic purposes, the role of MRI in MS monitoring is becoming increasingly important, particularly for pharmacovigilance. This includes treatment efficacy monitoring, prediction of treatment response and safety monitoring. Quantitative MRI methods and ultra-high-field MRI offer the opportunity for the quantitative assessment of damage in normal-appearing brain tissue. However, the standardization of these techniques with the goal of implementation in clinical routine will be one of the major challenges in the near future.

scholarly journals Profiles of cortical inflammation in multiple sclerosis by 11C-PBR28 MR-PET and 7 Tesla imaging

2019 ◽  
Vol 26 (12) ◽  
pp. 1497-1509 ◽  
Author(s):  
Elena Herranz ◽  
Céline Louapre ◽  
Constantina Andrada Treaba ◽  
Sindhuja T Govindarajan ◽  
Russell Ouellette ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Burden ◽  
Relative Difference ◽  
Tracer Uptake ◽  
Microglia Activation ◽  
Inactive Disease ◽  
7 Tesla ◽  
Cortical Lesion ◽  
Cortical Lesions ◽  
Cortical Areas

Background: Neuroinflammation with microglia activation is thought to be closely related to cortical multiple sclerosis (MS) lesion pathogenesis. Objective: Using 11C-PBR28 and 7 Tesla (7T) imaging, we assessed in 9 relapsing–remitting multiple sclerosis (RRMS) and 10 secondary progressive multiple sclerosis (SPMS) patients the following: (1) microglia activation in lesioned and normal-appearing cortex, (2) cortical lesion inflammatory profiles, and (3) the relationship between neuroinflammation and cortical integrity. Methods: Mean 11C-PBR28 uptake was measured in focal cortical lesions, cortical areas with 7T quantitative T2* (q-T2*) abnormalities, and normal-appearing cortex. The relative difference in cortical 11C-PBR28 uptake between patients and 14 controls was used to classify cortical lesions as either active or inactive. Disease burden was investigated according to cortical lesion inflammatory profiles. The relation between q-T2* and 11C-PBR28 uptake along the cortex was assessed. Results: 11C-PBR28 uptake was abnormally high in cortical lesions in RRMS and SPMS; in SPMS, tracer uptake was significantly increased also in normal-appearing cortex. 11C-PBR28 uptake and q-T2* correlated positively in many cortical areas, negatively in some regions. Patients with high cortical lesion inflammation had worse clinical outcome and higher intracortical lesion burden than patients with low inflammation. Conclusion: 11C-PBR28 and 7T imaging reveal distinct profiles of cortical inflammation in MS, which are related to disease burden.

scholarly journals Ultrahigh-resolution MRI Reveals Extensive Cortical Demyelination in a Nonhuman Primate Model of Multiple Sclerosis

2020 ◽  
Vol 31 (1) ◽  
pp. 439-447 ◽  
Author(s):  
Maxime Donadieu ◽  
Hannah Kelly ◽  
Diego Szczupak ◽  
Jing-Ping Lin ◽  
Yeajin Song ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Proteolipid Protein ◽  
Common Marmoset ◽  
Cortical Lesion ◽  
Tissue Preparation ◽  
Cortical Lesions ◽  
Primate Model ◽  
Relevant Animal Model ◽  
Primary Driver

Abstract Cortical lesions are a primary driver of disability in multiple sclerosis (MS). However, noninvasive detection of cortical lesions with in vivo magnetic resonance imaging (MRI) remains challenging. Experimental autoimmune encephalomyelitis (EAE) in the common marmoset is a relevant animal model of MS for investigating the pathophysiological mechanisms leading to brain damage. This study aimed to characterize cortical lesions in marmosets with EAE using ultrahigh-field (7 T) MRI and histological analysis. Tissue preparation was optimized to enable the acquisition of high-spatial resolution (50-μm isotropic) T2*-weighted images. A total of 14 animals were scanned in this study, and 70% of the diseased animals presented at least one cortical lesion on postmortem imaging. Cortical lesions identified on MRI were verified with myelin proteolipid protein immunostaining. An optimized T2*-weighted sequence was developed for in vivo imaging and shown to capture 65% of cortical lesions detected postmortem. Immunostaining confirmed extensive demyelination with preserved neuronal somata in several cortical areas of EAE animals. Overall, this study demonstrates the relevance and feasibility of the marmoset EAE model to study cortical lesions, among the most important yet least understood features of MS.

scholarly journals Exploratory Radiomic Analysis of Conventional vs. Quantitative Brain MRI: Toward Automatic Diagnosis of Early Multiple Sclerosis

2021 ◽  
Vol 15 ◽  
Author(s):  
Elizaveta Lavrova ◽  
Emilie Lommers ◽  
Henry C. Woodruff ◽  
Avishek Chatterjee ◽  
Pierre Maquet ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Magnetization Transfer ◽  
Medical Image Analysis ◽  
Brain Mri ◽  
External Validation ◽  
Region Of Interest ◽  
Quantitative Mri ◽  
Training Dataset ◽  
Image Type

Conventional magnetic resonance imaging (cMRI) is poorly sensitive to pathological changes related to multiple sclerosis (MS) in normal-appearing white matter (NAWM) and gray matter (GM), with the added difficulty of not being very reproducible. Quantitative MRI (qMRI), on the other hand, attempts to represent the physical properties of tissues, making it an ideal candidate for quantitative medical image analysis or radiomics. We therefore hypothesized that qMRI-based radiomic features have added diagnostic value in MS compared to cMRI. This study investigated the ability of cMRI (T1w) and qMRI features extracted from white matter (WM), NAWM, and GM to distinguish between MS patients (MSP) and healthy control subjects (HCS). We developed exploratory radiomic classification models on a dataset comprising 36 MSP and 36 HCS recruited in CHU Liege, Belgium, acquired with cMRI and qMRI. For each image type and region of interest, qMRI radiomic models for MS diagnosis were developed on a training subset and validated on a testing subset. Radiomic models based on cMRI were developed on the entire training dataset and externally validated on open-source datasets with 167 HCS and 10 MSP. Ranked by region of interest, the best diagnostic performance was achieved in the whole WM. Here the model based on magnetization transfer imaging (a type of qMRI) features yielded a median area under the receiver operating characteristic curve (AUC) of 1.00 in the testing sub-cohort. Ranked by image type, the best performance was achieved by the magnetization transfer models, with median AUCs of 0.79 (0.69–0.90, 90% CI) in NAWM and 0.81 (0.71–0.90) in GM. The external validation of the T1w models yielded an AUC of 0.78 (0.47–1.00) in the whole WM, demonstrating a large 95% CI and a low sensitivity of 0.30 (0.10–0.70). This exploratory study indicates that qMRI radiomics could provide efficient diagnostic information using NAWM and GM analysis in MSP. T1w radiomics could be useful for a fast and automated check of conventional MRI for WM abnormalities once acquisition and reconstruction heterogeneities have been overcome. Further prospective validation is needed, involving more data for better interpretation and generalization of the results.

scholarly journals Histopathology-validated recommendations for cortical lesion imaging in multiple sclerosis

Brain ◽  
2020 ◽  
Vol 143 (10) ◽  
pp. 2988-2997
Author(s):  
Piet M Bouman ◽  
Martijn D Steenwijk ◽  
Petra J W Pouwels ◽  
Menno M Schoonheim ◽  
Frederik Barkhof ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Sensitivity And Specificity ◽  
Inversion Recovery ◽  
Double Inversion Recovery ◽  
Cortical Lesion ◽  
Proton Density ◽  
Cortical Lesions ◽  
Phase Sensitive Inversion Recovery ◽  
Mri Sequences ◽  
Phase Sensitive

Abstract Cortical demyelinating lesions are clinically important in multiple sclerosis, but notoriously difficult to visualize with MRI. At clinical field strengths, double inversion recovery MRI is most sensitive, but still only detects 18% of all histopathologically validated cortical lesions. More recently, phase-sensitive inversion recovery was suggested to have a higher sensitivity than double inversion recovery, although this claim was not histopathologically validated. Therefore, this retrospective study aimed to provide clarity on this matter by identifying which MRI sequence best detects histopathologically-validated cortical lesions at clinical field strength, by comparing sensitivity and specificity of the thus far most commonly used MRI sequences, which are T2, fluid-attenuated inversion recovery (FLAIR), double inversion recovery and phase-sensitive inversion recovery. Post-mortem MRI was performed on non-fixed coronal hemispheric brain slices of 23 patients with progressive multiple sclerosis directly after autopsy, at 3 T, using T1 and proton-density/T2-weighted, as well as FLAIR, double inversion recovery and phase-sensitive inversion recovery sequences. A total of 93 cortical tissue blocks were sampled from these slices. Blinded to histopathology, all MRI sequences were consensus scored for cortical lesions. Subsequently, tissue samples were stained for proteolipid protein (myelin) and scored for cortical lesion types I–IV (mixed grey matter/white matter, intracortical, subpial and cortex-spanning lesions, respectively). MRI scores were compared to histopathological scores to calculate sensitivity and specificity per sequence. Next, a retrospective (unblinded) scoring was performed to explore maximum scoring potential per sequence. Histopathologically, 224 cortical lesions were detected, of which the majority were subpial. In a mixed model, sensitivity of T1, proton-density/T2, FLAIR, double inversion recovery and phase-sensitive inversion recovery was 8.9%, 5.4%, 5.4%, 22.8% and 23.7%, respectively (20, 12, 12, 51 and 53 cortical lesions). Specificity of the prospective scoring was 80.0%, 75.0%, 80.0%, 91.1% and 88.3%. Sensitivity and specificity did not significantly differ between double inversion recovery and phase-sensitive inversion recovery, while phase-sensitive inversion recovery identified more lesions than double inversion recovery upon retrospective analysis (126 versus 95; P &lt; 0.001). We conclude that, at 3 T, double inversion recovery and phase-sensitive inversion recovery sequences outperform conventional sequences T1, proton-density/T2 and FLAIR. While their overall sensitivity does not exceed 25%, double inversion recovery and phase-sensitive inversion recovery are highly pathologically specific when using existing scoring criteria and their use is recommended for optimal cortical lesion assessment in multiple sclerosis.

Natalizumab strongly suppresses cortical pathology in relapsing–remitting multiple sclerosis

2012 ◽  
Vol 18 (12) ◽  
pp. 1760-1767 ◽  
Author(s):  
F Rinaldi ◽  
M Calabrese ◽  
D Seppi ◽  
M Puthenparampil ◽  
P Perini ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Reference Population ◽  
Cortical Atrophy ◽  
Cortical Lesion ◽  
Cognitive Disability ◽  
Cortical Lesions ◽  
Immunomodulatory Agents ◽  
Relapsing Remitting ◽  
Relevant Role ◽  
Cortical Pathology

Background: Since cortical pathology has been indicated to play a relevant role in the physical and cognitive disability of multiple sclerosis (MS) patients, this study aims to analyze the efficacy of natalizumab in slowing down its progression. Methods: A total of 120 relapsing–remitting MS patients completed a 2-year prospective study: 35 received natalizumab, 50 received interferon beta-1a or glatiramer acetate (immunomodulatory agents - IMA) and 35 remained untreated. Forty healthy subjects constituted the reference population. Clinical and magnetic resonance imaging (MRI) evaluations (including cortical lesions and atrophy) were performed at baseline and after 2 years. Results: Natalizumab significantly reduced accumulation of new cortical lesions (0.2±0.6,range 0–3) compared to immunomodulatory agents (1.3±1.1 togli spazio, range 1–6, p=0.001) and no treatment (2.9±1.5, range 1–8, p<0.001). The percentage of patients with new cortical lesions was also lower in natalizumab-treated patients (20%) compared to IMA-treated and untreated patients (68.0% and 74.2%; p<0.001 for both comparisons). Furthermore, the progression of cortical atrophy was significantly reduced by natalizumab (% change=1.7%) compared to IMA (3.7%, p=0.003) and no therapy (4.6%, p<0.001). Finally, a greater percentage (51.4%) of natalizumab-treated patients remained disease-free (no clinical or MRI evidence of disease activity or progression) compared to IMA-treated (18%, p=0.001) and untreated patients (5.7%, p<0.001). Conclusions: Natalizumab treatment significantly decreases cortical lesion accumulation and cortical atrophy progression in severe relapsing–remitting MS. While supporting the inflammatory origin of cortical lesions, our results highlight the significant impact of natalizumab on cortical pathology.

scholarly journals Correlation of cortical lesions of multiple sclerosis at double inversion recovery with cognition screening scores

2021 ◽  
Vol 57 (1) ◽  
Author(s):  
Sally Mohamed Shaaban ◽  
Azza Elmongui Elmongui ◽  
Ahmed Abdel Khalek Abdel Razek ◽  
Tamer Mohamed Belal
Keyword(s):  
Multiple Sclerosis ◽  
Gray Matter ◽  
Inverse Correlation ◽  
Inversion Recovery ◽  
Double Inversion Recovery ◽  
Cortical Lesion ◽  
Cortical Lesions ◽  
Lesion Load ◽  
Significant Inverse Correlation ◽  
Lesion Number

Abstract Background Multiple sclerosis is a chronic inflammatory disease affecting both white and gray matters of the central nervous system. It has been approved that the degree of gray matter involvement is closely associated with the degree of physical disability and the extent of cognitive impairment. Thus, it is necessary to incorporate widely available simple methods for neurocognitive evaluation and gray matter detection in the periodic assessment of MS patients that will influence treatment decisions. Objectives To assess the correlation of cortical lesions of multiple sclerosis (MS) at double inversion recovery (DIR) with cognition screening scores Methods This study was conducted on 30 patients with MS with an average age of 31.3±13.6 years. All of them underwent MRI and clinical assessment with the calculation of Expanded Disability Status Scale (EDSS), Montreal Cognitive Assessment (MoCA), and Symbol Digit Modality Test (SDMT) scores. The image analysis was performed by 2 reviewers for cortical lesion number, shape, and subtypes, and total lesion load. Results Both MoCA and SDMT scales had a significant inverse correlation with cortical lesions number (r=− 0.68, − 0.72) respectively and total lesion load (r=− 0.53, − 0.65) respectively. Besides, there was a significant inverse correlation between the MoCA test, varied cortical subtypes: leukocortical, juxtacortical, and intracortical subtypes (r = − 0.63, − 0.56, − 0.52) respectively, and different cortical lesion shapes: oval, wedge, and curvilinear shaped (r = − 0.62, − 0.69, − 0.49) respectively. As well, the SDMT scale showed a significant inverse correlation with varied cortical subtypes: intracortical, leukocortical, and juxtacortical subtypes (r = − 0.63, − 0.61, − 0.57) respectively, and different cortical lesion shapes: oval, curvilinear, and wedge shaped (r = − 0.61, − 0.59, − 0.46) respectively. Interestingly, there was an excellent inter-observer correlation of cortical lesion number (r = 0.96), total lesion load (r = 0.95), subtypes of cortical lesion (r = 0.94), and cortical lesion shapes (r = 0.77). Conclusion We concluded that DIR can detect cortical lesions of MS, and MRI findings were well-correlated with cognitive dysfunction in these patients.

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