Imaging the Choroid Plexus.

The choroid plexus (CP), a highly vascularized structure within the ventricles of the brain, has come under increased scrutiny over the last several years as potentially having a role in the pathophysiology of multiple sclerosis (MS). Originally consider as being only responsible for the production of cerebrospinal fluid, it is now widely recognized that the CP is also involved in immunosurveillance and immune cell trafficking. Histopathology studies have found several immunological changes in donor tissue, including the accumulation of inflammatory cells.

Association between paramagnetic rim lesions and pulvinar iron depletion in persons with multiple sclerosis.

Background: The deep gray matter (DGM), especially the pulvinar, and the white matter surrounding chronic active lesions have demonstrated depleted iron levels, indicating a possible mechanistic link. However, no studies have investigated the potential relationship between these phenomena.

Objectives: The study aimed to determine whether PRLs were associated with pulvinar iron depletion and, if so, whether this relationship was spatially mediated.

Determinants of long-term paramagnetic rim lesion evolution in people with multiple sclerosis.

Objective: Baseline paramagnetic rim lesion (PRL) load predicts disease progression in people with multiple sclerosis (pwMS). Understanding how PRLs relate to other known MS-related factors, and the practical utility of PRLs in clinical trials, is crucial for informing clinical decision-making and guiding development of novel disease-modifying treatments (DMTs).

Methods: This study included 152 pwMS enrolled in a larger prospective, longitudinal cohort study who had 3T MRI scans and clinical assessments at baseline and 5- or 10-year follow-ups.

Associations Between Paramagnetic Rim Lesion Evolution and Clinical and Radiologic Disease Progression in Persons With Multiple Sclerosis.

Background And Objectives: Recent technological advances have enabled visualizing in vivo a subset of chronic active brain lesions in persons with multiple sclerosis (pwMS), referred to as "paramagnetic rim lesions" (PRLs), with iron-sensitive MRI. PRLs predict future clinical disease progression, making them a promising clinical and translational imaging marker. However, it is unknown how disease progression is modified by PRL evolution (PRL disappearance, new PRL appearance).

Greater humoral EBV response may be associated with choroid plexus inflammation in progressive MS.

Choroid plexus (CP) inflammation can be quantified in vivo with MRI in people with multiple sclerosis (pwMS). It remains unknown whether Epstein Barr Virus (EBV) is related to CP changes. Total of 170 pwMS (116 relapsing-remitting; RRMS and 54 progressive MS; PMS) underwent MRI examination and measurement of humoral anti-EBV response.

Brain atrophy assessment in multiple sclerosis: technical- and subject-related barriers for translation to real-world application in individual subjects.

Introduction: Brain atrophy is a well-established MRI outcome for predicting clinical progression and monitoring treatment response in persons with multiple sclerosis (pwMS) at the group level. Despite the important progress made, the translation of brain atrophy assessment into clinical practice faces several challenges.

Areas Covered: In this review, the authors discuss technical- and subject-related barriers for implementing brain atrophy assessment as part of the clinical routine at the individual level.

Cognitive progression independent of relapse in multiple sclerosis.

Background: Substantial physical-disability worsening in relapsing-remitting multiple sclerosis (RRMS) occurs outside of clinically recorded relapse. This phenomenon, termed progression independent of relapse activity (PIRA), is yet to be established for cognitive decline.

Methods: Retrospective analysis of RRMS patients.

Comorbid onset of cardiovascular diagnosis and long-term confirmed disability progression in multiple sclerosis: A 15-year follow-up study.

Background: People with multiple sclerosis (pwMS) have greater prevalence of comorbid cardiovascular diseases (CVD) when compared to the general population despite similar frequency of CV risk factors.

Objective: Determine the impact of comorbid-onset of CVD diagnosis on long-term confirmed disability progression (CDP).

Methods: 276 pwMS (29 clinically isolated syndrome, 130 relapsing-remitting and 117 progressive) were clinically followed an average of 14.

Serum Biomarker Signatures of Choroid Plexus Volume Changes in Multiple Sclerosis.

Increased choroid plexus (CP) volume has been recently implicated as a potential predictor of worse multiple sclerosis (MS) outcomes. The biomarker signature of CP changes in MS are currently unknown. To determine the blood-based biomarker characteristics of the cross-sectional and longitudinal MRI-based CP changes in a heterogeneous group of people with MS (pwMS), a total of 202 pwMS (148 pwRRMS and 54 pwPMS) underwent MRI examination at baseline and at a 5-year follow-up.

Clinical risk stratification: Development and validation of the DAAE score, a tool for estimating patient risk of transition to secondary progressive multiple sclerosis.

Background: Because secondary progressive multiple sclerosis (SPMS) is associated with worse prognosis, early predictive tools are needed. We aimed to use systematic literature review and advanced methods to create and validate a clinical tool for estimating individual patient risk of transition to SPMS over five years.

Methods: Data from the Jacobs Multiple Sclerosis Center (JMSC) and the Multiple Sclerosis Center Amsterdam (MSCA) was collected between 1994 and 2022.

Cognitive function in severe progressive multiple sclerosis.

Cognitive impairment is common in multiple sclerosis and negatively impacts quality of life. Cognitive status has yet to be described in people with severe progressive multiple sclerosis, in whom conventional neuropsychological testing is exceptionally difficult. The objective for the study was to characterize cognitive performance in severe progressive multiple sclerosis and compare them with age-, sex- and disease duration-matched less disabled people with multiple sclerosis using a specifically developed auditory, non-motor test of attention/cognitive processing speed-Auditory Test of Processing Speed.

Decoding Gray Matter Involvement in Multiple Sclerosis via Imaging.

Multiple sclerosis (MS) is increasingly understood not only as a white matter disease but also involving both the deep and cortical gray matter (GM). GM pathology in people with MS (pwMS) includes the presence of lesions, leptomeningeal inflammation, atrophy, altered iron concentration, and microstructural changes. Studies using 7T and 3T MR imaging with optimized protocols established that GM damage is a principal driver of disease progression in pwMS.

Lower arterial cerebral blood flow is associated with worse neuroinflammation and immunomodulation composite proteomic scores.

Background: Brain hypoperfusion is linked with worse physical, cognitive and MRI outcomes in multiple sclerosis (MS). Understanding the proteomic signatures related to hypoperfusion could provide insights into the pathophysiological mechanism.

Methods: 140 people with MS (pwMS; 86 clinically isolated syndrome (CIS)/relapsing-remitting (RRMS) and 54 progressive (PMS)) were included.

MRIO: the Magnetic Resonance Imaging Acquisition and Analysis Ontology.

Magnetic resonance imaging of the brain is a useful tool in both the clinic and research settings, aiding in the diagnosis and treatments of neurological disease and expanding our knowledge of the brain. However, there are many challenges inherent in managing and analyzing MRI data, due in large part to the heterogeneity of data acquisition. To address this, we have developed MRIO, the Magnetic Resonance Imaging Acquisition and Analysis Ontology.

Glial cell injury and atrophied lesion volume as measures of chronic multiple sclerosis inflammation.

Background: Atrophied lesion volume (aLV), a proposed biomarker of disability progression in multiple sclerosis (MS) and transition into progressive MS (PMS), depicts chronic periventricular white matter (WM) pathology. Meningeal infiltrates, imaged as leptomeningeal contrast enhancement (LMCE), are linked with greater cortical pathology.

Objectives: To determine the relationship between serum-derived proteomic data with the development of aLV and LMCE in a heterogeneous group of people with MS (pwMS).

Neuroimaging assessment of facility-bound severely-affected MS reveals the critical role of cortical gray matter pathology: results from the CASA-MS case-controlled study.

Background: A subgroup of people with multiple sclerosis (pwMS) will develop severe disability. The pathophysiology underlying severe MS is unknown. The comprehensive assessment of severely affected MS (CASA-MS) was a case-controlled study that compared severely disabled in skilled nursing (SD/SN) (EDSS ≥ 7.

Choroid plexus enlargement is associated with future periventricular neurodegeneration in multiple sclerosis.

Background: The choroid plexus (CP), located within the ventricles of the brain and the primary producer of cerebrospinal fluid, has been shown to be enlarged in patients with multiple sclerosis (MS) and linked to periventricular remyelination failure. Atrophied T2-lesion volume (aT2-LV), a promising neurodegenerative imaging marker in progressive MS (PMS), reflects the volume of periventricular lesions subsumed into cerebrospinal fluid over the follow-up.

Methods: In a cohort of 143 people with relapsing-remitting MS (RRMS) and 53 with PMS, we used 3T magnetic resonance imaging (MRI) to quantify CP volume (CPV) at baseline and aT2-LV over an average of 5.

Thalamic atrophy and dysconnectivity are associated with cognitive impairment in a multi-center, clinical routine, real-word study of people with relapsing-remitting multiple sclerosis.

Background: Prior research has established a link between thalamic pathology and cognitive impairment (CI) in people with multiple sclerosis (pwMS). However, the translation of these findings to pwMS in everyday clinical settings has been insufficient.

Objective: To assess which global and/or thalamic imaging biomarkers can be used to identify pwMS at risk for CI and cognitive worsening (CW) in a real-world setting.

Dynamic disability measures decrease the clinico-radiological gap in people with severely affected multiple sclerosis.

Background: Expanded Disability Status Scale (EDSS) is limited when utilized in highly disabled people with multiple sclerosis (pwMS).

Objetive: To explore the relationship between disability measures and MRI outcomes in severely-affected pwMS.

Methods: PwMS recruited from The Boston Home (TBH), a specialized residential facility for severly-affected pwMS and University at Buffalo (UB) MS Center were assessed using EDSS, MS Severity Scale, age-related MSS, Scripps Neurological Rating Scale (SNRS) and Combinatorial Weight-Adjusted Disability Score (CombiWISE).

An Automated Tool to Classify and Transform Unstructured MRI Data into BIDS Datasets.

The increasing use of neuroimaging in clinical research has driven the creation of many large imaging datasets. However, these datasets often rely on inconsistent naming conventions in image file headers to describe acquisition, and time-consuming manual curation is necessary. Therefore, we sought to automate the process of classifying and organizing magnetic resonance imaging (MRI) data according to acquisition types common to the clinical routine, as well as automate the transformation of raw, unstructured images into Brain Imaging Data Structure (BIDS) datasets.

Paramagnetic rim lesions predict greater long-term relapse rates and clinical progression over 10 years.

Background: Paramagnetic rim lesions (PRLs) have been linked to higher clinical disease severity and relapse frequency. However, it remains unclear whether PRLs predict future, long-term disease progression.

Objectives: The study aimed to assess whether baseline PRLs were associated with subsequent long-term (10 years) Expanded Disability Status Scale (EDSS) increase and relapse frequency and, if so, whether PRL-associated EDSS increase was mediated by relapse.

Proteomic signatures of physical, cognitive, and imaging outcomes in multiple sclerosis.

Background: A quantitative measurement of serum proteome biomarkers that would associate with disease progression endpoints can provide risk stratification for persons with multiple sclerosis (PwMS) and supplement the clinical decision-making process.

Materials And Methods: In total, 202 PwMS were enrolled in a longitudinal study with measurements at two time points with an average follow-up time of 5.4 years.