Choroid Plexus Enlargement in Multiple Sclerosis Correlates with Cortical and Phase Rim lesions on 7-T MRI and Predicts Progression Independent of Relapse Activity.

Background And Purpose: In multiple sclerosis (MS), the choroid plexus is thought to promote and sustain the disease immunopathological inflammatory process. However, its association with cortical pathology and disease progression is still uncertain. We aim to characterize choroid plexus enlargement and evolution in MS, its relationship with imaging markers of compartmentalized inflammation and clinical outcome.

Monitoring morphometric drift in lifelong learning segmentation of the spinal cord.

Morphometric measures derived from spinal cord segmentations can serve as diagnostic and prognostic biomarkers in neurological diseases and injuries affecting the spinal cord. For instance, the spinal cord cross-sectional area can be used to monitor cord atrophy in multiple sclerosis and to characterize compression in degenerative cervical myelopathy. While robust, automatic segmentation methods to a wide variety of contrasts and pathologies have been developed over the past few years, whether their predictions are stable as the model is updated using new datasets has not been assessed.

Spinal Cord Versus Brain Imaging Biomarkers of Multiple Sclerosis Trajectory Combining 7T and 3T MRI.

Background: In multiple sclerosis (MS), 7 Tesla (7T) MRI improves the visualization of cortical (CLs) and white matter (WM) lesions with a paramagnetic rim (PRLs), associated with smoldering inflammation. Spinal cord (SC) atrophy is a critical determinant of clinical disability in MS, but its importance relative to PRLs and CLs in predicting neurological disability remains unclear.

Purpose: To identify the most relevant predictors for baseline neurological disability and 4-year disease progression independent of relapse activity (PIRA) in a heterogeneous MS cohort.

The association between white matter chronic inflammation and degeneration in multiple sclerosis: A combined C-PBR28 PET-MRI study.

In multiple sclerosis (MS), the interplay between white matter (WM) microglia mediated inflammation and degeneration is still unclear. Using positron emission tomography and diffusion tensor imaging, we assessed the association between WM chronic inflammation and damage in different regions including periventricular, deep, and subcortical WM and their association with clinical measures. Twenty-three people with MS (PwMS) and 13 healthy subjects underwent C-PBR28 imaging on an integrated 3T MR-Positron Emission Tomography system.

Development of a fibrin-targeted theranostic for gastric cancer.

Patients with advanced gastric cancer (GCa) have limited treatment options, and alternative treatment approaches are necessary to improve their clinical outcomes. Because fibrin is abundant in gastric tumors but not in healthy tissues, we hypothesized that fibrin could be used as a high-concentration depot for a high-energy beta-emitting cytotoxic radiopharmaceutical delivered to tumor cells. We showed that fibrin is present in 64 to 75% of primary gastric tumors and 50 to 100% of metastatic gastric adenocarcinoma cores.

The contribution of paramagnetic rim and cortical lesions to physical and cognitive disability at multiple sclerosis clinical onset: evaluating the power of MRI and OCT biomarkers.

Background: In multiple sclerosis (MS), imaging biomarkers play a crucial role in characterizing the disease at the time of diagnosis. MRI and optical coherence tomography (OCT) provide readily available biomarkers that may help to define the patient's clinical profile. However, the evaluation of cortical and paramagnetic rim lesions (CL, PRL), as well as retinal atrophy, is not routinely performed in clinic.

Characterization of cortico-meningeal translocator protein expression in multiple sclerosis.

Compartmentalized meningeal inflammation is thought to represent one of the key players in the pathogenesis of cortical demyelination in multiple sclerosis. PET targeting the 18 kDa mitochondrial translocator protein (TSPO) is a molecular-specific approach to quantifying immune cell-mediated density in the cortico-meningeal tissue compartment in vivo. This study aimed to characterize cortical and meningeal TSPO expression in a heterogeneous cohort of multiple sclerosis cases using in vivo simultaneous MR-PET with 11C-PBR28, a second-generation TSPO radioligand, and ex vivo immunohistochemistry.

White matter paramagnetic rim and non-rim lesions share a periventricular gradient in multiple sclerosis: A 7-T imaging study.

Background: Paramagnetic rim white matter (WM) lesions (PRL) are thought to be a main driver of non-relapsing multiple sclerosis (MS) progression. It is unknown whether cerebrospinal fluid (CSF)-soluble factors diffusing from the ventricles contribute to PRL formation.

Objective: To investigate the distribution of PRL and non-rim brain WM lesions as a function of distance from ventricular CSF, their relationship with cortical lesions, the contribution of lesion phenotype, and localization to neurological disability.

A translational MRI approach to validate acute axonal damage detection as an early event in multiple sclerosis.

Axonal degeneration is a central pathological feature of multiple sclerosis and is closely associated with irreversible clinical disability. Current noninvasive methods to detect axonal damage in vivo are limited in their specificity and clinical applicability, and by the lack of proper validation. We aimed to validate an MRI framework based on multicompartment modeling of the diffusion signal (AxCaliber) in rats in the presence of axonal pathology, achieved through injection of a neurotoxin damaging the neuronal terminal of axons.

Imaging cortical lesions in multiple sclerosis.

Purpose Of Review: Cortical lesions are an established pathological feature of multiple sclerosis, develop from the earliest disease stages and contribute to disease progression. Here, we discuss current imaging approaches for detecting cortical lesions in vivo and their contribution for improving our understanding of cortical lesion pathogenesis as well as their clinical significance.

Recent Findings: Although a variable portion of cortical lesions goes undetected at clinical field strength and even at ultra-high field MRI, their evaluation is still clinically relevant.

In vivo characterization of microglia and myelin relation in multiple sclerosis by combined C-PBR28 PET and synthetic MRI.

Background: The in vivo relation between microglia activation and demyelination in multiple sclerosis is still unclear.

Objective: We combined C-PBR28 positron emission tomography and rapid estimation of myelin for diagnostic imaging (REMyDI) to characterize the relation between these pathological processes in a heterogeneous MS cohort.

Methods: C-PBR28 standardized uptake values normalized by a pseudo-reference region (SUVR) were used to measure activated microglia.

An Interpretable Machine Learning Model to Predict Cortical Atrophy in Multiple Sclerosis.

To date, the relationship between central hallmarks of multiple sclerosis (MS), such as white matter (WM)/cortical demyelinated lesions and cortical gray matter atrophy, remains unclear. We investigated the interplay between cortical atrophy and individual lesion-type patterns that have recently emerged as new radiological markers of MS disease progression. We employed a machine learning model to predict mean cortical thinning in whole-brain and single hemispheres in 150 cortical regions using demographic and lesion-related characteristics, evaluated via an ultrahigh field (7 Tesla) MRI.

Cortical and white matter lesion topology influences focal corpus callosum atrophy in multiple sclerosis.

Background And Purpose: Corpus callosum (CC) atrophy is a strong predictor of multiple sclerosis (MS) disability but the contributing pathological mechanisms remain uncertain. We aimed to apply advanced MRI to explore what drives the often nonuniform callosal atrophy.

Methods: Prospective brain 7 Tesla and 3 Tesla Human Connectom Scanner MRI were performed in 92 MS patients.

Cortical and phase rim lesions on 7 T MRI as markers of multiple sclerosis disease progression.

In multiple sclerosis, individual lesion-type patterns on magnetic resonance imaging might be valuable for predicting clinical outcome and monitoring treatment effects. Neuropathological and imaging studies consistently show that cortical lesions contribute to disease progression. The presence of chronic active white matter lesions harbouring a paramagnetic rim on susceptibility-weighted magnetic resonance imaging has also been associated with an aggressive form of multiple sclerosis.

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.

Hemostatic factors in the pathogenesis of neuroinflammation in multiple sclerosis.

Background: A growing body of evidence has shed light on the role of the hemostatic pathway and its components in the pathogenesis of multiple sclerosis (MS), particularly in enhancing and sustaining neuroinflammation.

Objective: To review the clinical, experimental, and neuroimaging evidence supporting the role of different components of the hemostatic pathway in the pathogenesis of neuroinflammation in MS and discuss their translational potential as disease biomarkers and therapeutic targets.

Methods: A literature search for most relevant articles from 1956 to 2020 was conducted in PubMed and Scopus.

The relevance of multiple sclerosis cortical lesions on cortical thinning and their clinical impact as assessed by 7.0-T MRI.

Objective: This study aimed to investigate at 7.0-T MRI a) the role of multiple sclerosis (MS) cortical lesions in cortical tissue loss b) their relation to neurological disability.

Methods: In 76 relapsing remitting and 26 secondary progressive MS patients (N = 102) and 56 healthy subjects 7.

7 T imaging reveals a gradient in spinal cord lesion distribution in multiple sclerosis.

We used 7 T MRI to: (i) characterize the grey and white matter pathology in the cervical spinal cord of patients with early relapsing-remitting and secondary progressive multiple sclerosis; (ii) assess the spinal cord lesion spatial distribution and the hypothesis of an outside-in pathological process possibly driven by CSF-mediated immune cytotoxic factors; and (iii) evaluate the association of spinal cord pathology with brain burden and its contribution to neurological disability. We prospectively recruited 20 relapsing-remitting, 15 secondary progressive multiple sclerosis participants and 11 age-matched healthy control subjects to undergo 7 T imaging of the cervical spinal cord and brain as well as conventional 3 T brain acquisition. Cervical spinal cord imaging at 7 T was used to segment grey and white matter, including lesions therein.

Ultra-high field 7 T imaging in multiple sclerosis.

Purpose Of Review: Ultra-high field 7 T MRI has multiple applications for the in vivo characterization of the heterogeneous aspects underlying multiple sclerosis including the identification of cortical lesions, characterization of the different types of white matter plaques, evaluation of structures difficult to assess with conventional MRI (thalamus, cerebellum, spinal cord, meninges).

Recent Findings: The sensitivity of cortical lesion detection at 7 T is twice than at lower field MRI, especially for subpial lesions, the most common cortical lesion type in multiple sclerosis. Cortical lesion load accrual is independent of that in the white matter and predicts disability progression.

Characterization of thalamic lesions and their correlates in multiple sclerosis by ultra-high-field MRI.

Background: Thalamic pathology is a marker for neurodegeneration and multiple sclerosis (MS) disease progression.

Objective: To characterize (1) the morphology of thalamic lesions, (2) their relation to cortical and white matter (WM) lesions, and (3) clinical measures, and to assess (4) the imaging correlates of thalamic atrophy.

Methods: A total of 90 MS patients and 44 healthy controls underwent acquisition of 7 Tesla images for lesion segmentation and 3 Tesla scans for atrophy evaluation.

Validation of Rapid Magnetic Resonance Myelin Imaging in Multiple Sclerosis.

Objective: Magnetic resonance imaging (MRI) is essential for multiple sclerosis diagnostics but is conventionally not specific to demyelination. Myelin imaging is often hampered by long scanning times, complex postprocessing, or lack of clinical approval. This study aimed to assess the specificity, robustness, and clinical value of Rapid Estimation of Myelin for Diagnostic Imaging, a new myelin imaging technique based on time-efficient simultaneous T /T relaxometry and proton density mapping in multiple sclerosis.

Whole brain in vivo axonal diameter mapping in multiple sclerosis.

Traditional techniques based on diffusion MR imaging suffer from extremely low specificity in separating disease-related alterations in white matter microstructure, which can involve multiple phenomena including axonal loss, demyelination and changes in axonal size. Multi-shell diffusion MRI is able to greatly increase specificity by concomitantly exploring multiple diffusion timescales. If multi-shell acquisition is combined with an exploration of different diffusion times, diffusion data allows the estimation of sophisticated compartmental models, which provide greatly enhanced specificity to the presence of different tissue sub-compartments, as well as estimates of intra-voxel axonal diameter distributions.