In vivo detection of damage in multiple sclerosis cortex and cortical lesions using NODDI

ObjectiveTo characterise in vivo the microstructural abnormalities of multiple sclerosis (MS) normal-appearing (NA) cortex and cortical lesions (CLs) and their relations with clinical phenotypes and disability using neurite orientation dispersion and density imaging (NODDI).MethodsOne hundred and seventy-two patients with MS (101 relapsing–remitting multiple sclerosis (RRMS), 71 progressive multiple sclerosis (PMS)) and 62 healthy controls (HCs) underwent a brain 3T MRI. Brain cortex and CLs were segmented from three-dimensional T1-weighted and double inversion recovery sequences. Using NODDI on diffusion-weighted sequence, intracellular volume fraction (ICV_f) and Orientation Dispersion Index (ODI) were assessed in NA cortex and CLs with default or optimised parallel diffusivity for the cortex (D//=1.7 or 1.2 µm2/ms, respectively).ResultsThe NA cortex of patients with MS had significantly lower ICV_f versus HCs’ cortex with both D// values (false discovery rate (FDR)-p <0.001). CLs showed significantly decreased ICV_f and ODI versus NA cortex of both HCs and patients with MS with both D// values (FDR-p ≤0.008). Patients with PMS versus RRMS had significantly decreased NA cortex ICV_f and ODI (FDR-p=0.050 and FDR-p=0.032) with only D//=1.7 µm2/ms. No CL microstructural differences were found between MS clinical phenotypes. MS NA cortex ICV_f and ODI were significantly correlated with disease duration, clinical disability, lesion burden and global and regional brain atrophy (r from −0.51 to 0.71, FDR-p from <0.001 to 0.045).ConclusionsA significant neurite loss occurs in MS NA cortex. CLs show a further neurite density reduction and a reduced ODI suggesting a simplification of neurite complexity. NODDI is relevant to investigate in vivo the heterogeneous pathology affecting the MS cortex.

FLAIR2 post-processing: improving MS lesion detection in standard MS imaging protocols

Background Technical improvements in magnetic resonance imaging (MRI) acquisition, such as higher field strength and optimized sequences, lead to better multiple sclerosis (MS) lesion detection and characterization. Multiplication of 3D-FLAIR with 3D-T2 sequences (FLAIR2) results in isovoxel images with increased contrast-to-noise ratio, increased white–gray-matter contrast, and improved MS lesion visualization without increasing MRI acquisition time. The current study aims to assess the potential of 3D-FLAIR2 in detecting cortical/leucocortical (LC), juxtacortical (JC), and white matter (WM) lesions. Objective To compare lesion detection of 3D-FLAIR2 with state-of-the-art 3D-T2-FLAIR and 3D-T2-weighted images. Methods We retrospectively analyzed MRI scans of thirteen MS patients, showing previously noted high cortical lesion load. Scans were acquired using a 3 T MRI scanner. WM, JC, and LC lesions were manually labeled and manually counted after randomization of 3D-T2, 3D-FLAIR, and 3D-FLAIR2 scans using the ITK-SNAP tool. Results LC lesion visibility was significantly improved by 3D-FLAIR2 in comparison to 3D-FLAIR (4 vs 1; p = 0.018) and 3D-T2 (4 vs 1; p = 0.007). Comparing LC lesion detection in 3D-FLAIR2 vs. 3D-FLAIR, 3D-FLAIR2 detected on average 3.2 more cortical lesions (95% CI − 9.1 to 2.8). Comparing against 3D-T2, 3D-FLAIR2 detected on average 3.7 more LC lesions (95% CI 3.3–10.7). Conclusions 3D-FLAIR2 is an easily applicable time-sparing MR post-processing method to improve cortical lesion detection. Larger sampled studies are warranted to validate the sensitivity and specificity of 3D-FLAIR2.

Attack Interval Is the Key to the Likely Pathogenesis of Multiple Transient Ischemic Attacks

<b><i>Introduction:</i></b> The aim of this study was to test the hypothesis that the attack interval of multiple transient ischemic attacks (TIAs) is correlated with the underlying pathogenesis of ischemia. <b><i>Methods:</i></b> Patients with multiple TIAs, defined as 2 or more motor deficits within 7 days, were studied. The attack interval between the last 2 episodes was classified into 3 groups: 2 episodes within an hour (Hour group), over hours within a day (Day group), and over days within a week (Week group). Patients with a lacunar syndrome, no cortical lesions, and no embolic sources were recognized as having a small vessel disease (SVD) etiology for their multiple events. <b><i>Results:</i></b> Of 312 TIA patients admitted over a 9-year period, 50 (37 males, 13 females, mean 67.6 years) had multiple TIAs. Twelve patients were classified as being within the Hour group, 23 within the Day group, and 15 within the Week group. Lacunar syndromes were observed in 30 (75%, 35%, and 67%), embolic sources were detected in 28 (25%, 65%, and 67%), and a high signal lesion on diffusion-weighted imaging was depicted in 30 (75%, 48%, and 67%) patients (18 cortical, 11 subcortical, and one cerebellar). Patients in the Hour group had a significantly higher prevalence of SVD etiology (75%) than those in the Day and Week groups (30%, <i>p</i> = 0.0165; 27%, <i>p</i> = 0.0213, respectively). Four patients had a subsequent stroke within 7 days. <b><i>Conclusion:</i></b> Attack intervals of multiple TIAs may be correlated with the underlying pathogenesis of ischemia. Two motor deficits within an hour are more likely to suggest a SVD etiology.

Comparison of Phase-Sensitive Inversion Recovery and Conventional Magnetic Resonance Imaging for Detection of Cortical Plaques in MS Patients

Background: Precise detection and classification of intracortical (IC) lesions in multiple sclerosis (MS) patients are very important for understanding their role in disease progression and determining their effects on the clinical presentations of the disease. Objectives: This study aimed to evaluate the efficacy of phase-sensitive inversion recovery (PSIR) in delineation of cortical lesions in MS patients. Patients and Methods: This cross-sectional, single-center study was performed among 38 patients with the mean age of 31 years, who were recruited from December 2018 to August 2020. All MS patients underwent magnetic resonance imaging (MRI), using a 1.5-Tesla scanner. Two expert neuroradiologists interpreted the fluid-attenuated inversion recovery (FLAIR), T2-weighted turbo spin echo (T2W-TSE), and PSIR images. The lesions were classified as purely IC, mixed gray/white matter (WM) [leukocortical (LC)], and juxtacortical (JC). The number of lesions in each region was compared between the FLAIR, T2W-TSE, and PSIR sequences. Results: The number of cortical lesions (IC and LC) was significantly higher in PSIR compared to T2W-TSE and Fluid attenuated inversion recovery (FLAIR) (P < 0.001), while the number of JC lesions was lower; in other words, the mean number of plaques was higher in T2W-TSE and FLAIR as compared to PSIR. Conclusion: The PSIR sequence significantly improved the delineation of cortical lesions and could be useful in monitoring cortical injuries and disease progression in MS patients.

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

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.

A toolbox for studying cortical physiology in primates

Lesioning and neurophysiological studies have facilitated the elucidation of cortical functions and mechanisms of functional recovery following injury. Clinical translation of such studies is contingent on their employment in non-human primates (NHPs), yet tools for monitoring and modulating cortical physiology are incompatible with conventional NHP lesioning techniques. To address these challenges, we developed a toolbox demonstrated in seven macaques. We introduce the photothrombotic method to induce focal cortical lesions alongside a quantitative model for the design of lesion profiles based on experimental needs. Large-scale (~5 cm2) vascular and neural dynamics can be monitored and lesion induction can be validated in vivo with optical coherence tomography angiography and our electrocorticographic array, the latter of which also enables testing stimulation-based interventions. By combining optical and electrophysiological techniques in NHPs, we can enhance our understanding of cortical functions, investigate functional recovery mechanisms, integrate physiological and behavioral findings, and develop treatments for neurological disorders.

Migraine-Like Positive Visual Phenomena Related to Focal Cortical Lesions with Undetectable Visual Field Defects

Migraines are commonly associated with a visual aura that has a characteristic clinical presentation. Cortical lesions within or in close proximity to the retrochiasmal visual pathways may also present in a manner that mimics migrainous visual phenomena and, in some cases, may be too small to manifest with a visual field defect on formal testing. We present 4 patients (3 females and 1 male) with an average age of 48.5 (range 28–67) years who had migraine-like visual disturbances related to a right temporal meningioma, occipital cavernoma, occipital lobe infarction, and demyelination in the optic radiations, which was the presenting sign of multiple sclerosis. No patient underwent neurosurgical intervention, and 1 patient (occipital lobe infarct) had complete resolution of the symptom after initial presentation. All patients had normal visual fields at follow-up and no thinning evident on optical coherence tomography. Our cases emphasize the importance of a history in assessing patients with transient positive visual phenomena and identify pathology that may present without visual field defects. Clinical features that should raise a doubt about a diagnosis of migraine visual aura include the absence of headache, brief visual disturbance lasting &#x3c;5 min or those lasting &#x3e;60 min, and age &#x3e;40, especially with no past medical history of migraine.