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 < 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 < 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.

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.

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 Thalamic lesions in multiple sclerosis by 7T MRI: Clinical implications and relationship to cortical pathology

2015 ◽  
Vol 21 (9) ◽  
pp. 1139-1150 ◽  
Author(s):  
Daniel M Harrison ◽  
Jiwon Oh ◽  
Snehashis Roy ◽  
Emily T Wood ◽  
Anna Whetstone ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Gray Matter ◽  
Demographic Data ◽  
Clinical Information ◽  
7 Tesla ◽  
Cortical Lesion ◽  
Thalamic Lesion ◽  
Cortical Lesions ◽  
Thalamic Lesions

Objective: Pathology in both cortex and deep gray matter contribute to disability in multiple sclerosis (MS). We used the increased signal-to-noise ratio of 7-tesla (7T) MRI to visualize small lesions within the thalamus and to relate this to clinical information and cortical lesions. Methods: We obtained 7T MRI scans on 34 MS cases and 15 healthy volunteers. Thalamic lesion number and volume were related to demographic data, clinical disability measures, and lesions in cortical gray matter. Results: Thalamic lesions were found in 24/34 of MS cases. Two lesion subtypes were noted: discrete, ovoid lesions, and more diffuse lesional areas lining the periventricular surface. The number of thalamic lesions was greater in progressive MS compared to relapsing–remitting (mean ±SD, 10.7 ±0.7 vs. 3.0 ±0.7, respectively, p < 0.001). Thalamic lesion burden (count and volume) correlated with EDSS score and measures of cortical lesion burden, but not with white matter lesion burden or white matter volume. Conclusions: Using 7T MRI allows identification of thalamic lesions in MS, which are associated with disability, progressive disease, and cortical lesions. Thalamic lesion analysis may be a simpler, more rapid estimate of overall gray matter lesion burden in MS.

Torticollis as an Initial Manifestation of a Seronegative Demyelinating Disorder in a Child: A Case Report

2021 ◽  
Author(s):  
Sandesh Kini ◽  
Yellanthoor Ramesh Bhat ◽  
Lakshmikanth Halegubbi Karegowda
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Case Report ◽  
Demyelinating Disease ◽  
Oligoclonal Bands ◽  
Initial Manifestation ◽  
Demyelinating Disorder ◽  
The Brain

AbstractTorticollis refers to a condition in which the head is persistently tilted to one side, sometimes associated with pain. Torticollis in a child can be congenital or acquired. Torticollis as an initial manifestation of an underlying demyelinating syndrome is quite rare in children. Here, we report a 7-year-old girl who presented with persistent torticollis. Neuroimaging of the brain revealed features of a demyelinating disease. Further studies did not show any evidence of multiple sclerosis. Cerebrospinal fluid was negative for antiaquaporin-4 antibodies, antimyelin oligodendrocyte glycoprotein antibodies, and oligoclonal bands. A seronegative demyelinating disorder was considered. She was treated with pulsed methylprednisolone therapy. She responded well to steroids with no progression of illness during follow-up. Torticollis was partially improved.

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

2020 ◽  
Vol 30 (8) ◽  
pp. 4586-4594 ◽  
Author(s):  
Sirio Cocozza ◽  
Mirco Cosottini ◽  
Alessio Signori ◽  
Lazar Fleysher ◽  
Mohamed Mounir El Mendili ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
7 Tesla ◽  
Cortical Lesions

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.

Biochemical changes in the brain of hemiplegic migraine patients measured with 7 tesla 1H-MRS

Cephalalgia ◽  
2014 ◽  
Vol 34 (12) ◽  
pp. 959-967 ◽  
Author(s):  
R Zielman ◽  
WM Teeuwisse ◽  
F Bakels ◽  
J Van der Grond ◽  
A Webb ◽  
...  
Keyword(s):  
Occipital Lobe ◽  
Brain Regions ◽  
Biochemical Changes ◽  
High Spectral Resolution ◽  
7 Tesla ◽  
Healthy Controls ◽  
Hemiplegic Migraine ◽  
1H Mrs ◽  
Total N ◽  
The Brain

Aim The aim of this study was to assess biochemical changes in the brain of patients with hemiplegic migraine in between attacks. Methods Eighteen patients with hemiplegic migraine (M:F, 7:11; age 38 ± 14 years) of whom eight had a known familial hemiplegic migraine (FHM) mutation (five in the CACNA1A gene (FHM1), three in the ATP1A2 gene (FHM2)) and 19 age- and sex-matched healthy controls (M:F, 7:12; mean age 38 ±  12 years) were studied. We used single-voxel 7 tesla 1H-MRS (STEAM, TR/TM/TE = 2000/19/21 ms) to investigate four brain regions in between attacks: cerebellum, hypothalamus, occipital lobe, and pons. Results Patients with hemiplegic migraine showed a significantly lower total N-acetylaspartate/total creatine ratio (tNAA/tCre) in the cerebellum (median 0.73, range 0.59–1.03) than healthy controls (median 0.79, range (0.67–0.95); p = 0.02). In FHM1 patients with a CACNA1A mutation, the tNAA/tCre was lowest. Discussion We found a decreased cerebellar tNAA/tCre ratio that might serve as an early biomarker for neuronal dysfunction and/or loss. This is the first high-spectral resolution 7 tesla 1H-MRS study of interictal biochemical brain changes in hemiplegic migraine patients.

scholarly journals Temporal Lobe Epilepsy as a Unique Manifestation of Multiple Sclerosis

2003 ◽  
Vol 30 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Antonio Gambardella ◽  
Paola Valentino ◽  
Angelo Labate ◽  
Grazia Sibilia ◽  
Francesca Ruscica ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Brain Mri ◽  
Epileptic Seizures ◽  
Cortical Lesion ◽  
Temporal Region ◽  
Antiepileptic Medication ◽  
Long Term Follow Up

Objective:To report on five patients with temporal lobe epilepsy (TLE) as the unique manifestation of multiple sclerosis (MS).Methods:Among 350 consecutive MS patients, we identified 16/350 (4.6%) who also had epileptic seizures. Here, we review their electrophysiological and clinical features.Results:Five of these 16 patients (four female, one male; mean age 34.2 years; range 31 to 38) with MS and epileptic seizures had an extremely homogeneous clinical picture characterized by TLE as the unique manifestation of MS, even at long follow-up (mean: five years; range 4 to 10). In all patients, seizures started in the second or third decade. Brain MRI revealed at least one juxta-cortical lesion within the temporal region. Antiepileptic medication was always effective.Conclusions:The present study provides the first evidence of a peculiar form of MS characterized by TLE as the unique manifestation of the disease with no disability or MS relapses at long-term follow-up.

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.

scholarly journals Multiple sclerosis lesions in motor tracts from brain to cervical cord: spatial distribution and correlation with disability

Brain ◽  
2020 ◽  
Vol 143 (7) ◽  
pp. 2089-2105 ◽  
Author(s):  
Anne Kerbrat ◽  
Charley Gros ◽  
Atef Badji ◽  
Elise Bannier ◽  
Francesca Galassi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Volume Fraction ◽  
Lesion Volume ◽  
Corticospinal Tracts ◽  
Disability Status ◽  
Relapsing Remitting ◽  
The Brain ◽  
Lesion Frequency

Abstract Despite important efforts to solve the clinico-radiological paradox, correlation between lesion load and physical disability in patients with multiple sclerosis remains modest. One hypothesis could be that lesion location in corticospinal tracts plays a key role in explaining motor impairment. In this study, we describe the distribution of lesions along the corticospinal tracts from the cortex to the cervical spinal cord in patients with various disease phenotypes and disability status. We also assess the link between lesion load and location within corticospinal tracts, and disability at baseline and 2-year follow-up. We retrospectively included 290 patients (22 clinically isolated syndrome, 198 relapsing remitting, 39 secondary progressive, 31 primary progressive multiple sclerosis) from eight sites. Lesions were segmented on both brain (T2-FLAIR or T2-weighted) and cervical (axial T2- or T2*-weighted) MRI scans. Data were processed using an automated and publicly available pipeline. Brain, brainstem and spinal cord portions of the corticospinal tracts were identified using probabilistic atlases to measure the lesion volume fraction. Lesion frequency maps were produced for each phenotype and disability scores assessed with Expanded Disability Status Scale score and pyramidal functional system score. Results show that lesions were not homogeneously distributed along the corticospinal tracts, with the highest lesion frequency in the corona radiata and between C2 and C4 vertebral levels. The lesion volume fraction in the corticospinal tracts was higher in secondary and primary progressive patients (mean = 3.6 ± 2.7% and 2.9 ± 2.4%), compared to relapsing-remitting patients (1.6 ± 2.1%, both P &lt; 0.0001). Voxel-wise analyses confirmed that lesion frequency was higher in progressive compared to relapsing-remitting patients, with significant bilateral clusters in the spinal cord corticospinal tracts (P &lt; 0.01). The baseline Expanded Disability Status Scale score was associated with lesion volume fraction within the brain (r = 0.31, P &lt; 0.0001), brainstem (r = 0.45, P &lt; 0.0001) and spinal cord (r = 0.57, P &lt; 0.0001) corticospinal tracts. The spinal cord corticospinal tracts lesion volume fraction remained the strongest factor in the multiple linear regression model, independently from cord atrophy. Baseline spinal cord corticospinal tracts lesion volume fraction was also associated with disability progression at 2-year follow-up (P = 0.003). Our results suggest a cumulative effect of lesions within the corticospinal tracts along the brain, brainstem and spinal cord portions to explain physical disability in multiple sclerosis patients, with a predominant impact of intramedullary lesions.

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