Paramagnetic rim lesions are associated with choroid plexus inflammation and expansion over 5 years in people with multiple sclerosis.

Background: Chronic active white matter inflammation is linked with multiple sclerosis (MS) clinical severity and is likely integral in MS progression. It has also been associated with choroid plexus (CP) inflammation in vivo, pointing to a potential pathophysiological link between the two phenomena. However, how these aspects of the disease co-evolve over time remains poorly understood nor has their relationship been specifically assessed in people with progressive MS (pwPMS).

Evaluating the role of anti-EBV antibodies as biomarkers for the evolution of multiple sclerosis: A longitudinal study.

Background: Epstein-Barr virus seropositivity has been strongly associated with the onset of multiple sclerosis (MS); however, the utility of measuring EBV-antibodies as biomarkers for MS progression remains uncertain.

Objectives: To determine if baseline anti-EBV antibody titer levels are associated with mid-term evolution of MS.

Methods: A total of 237 participants (187 MS patients and 50 healthy controls, HC) were tested for anti-EBNA1 and anti-VCA IgG levels, whose relative concentrations were categorized into lower and highest quartiles.

IRONMAP: Iron network mapping and analysis protocol for detecting over-time brain iron abnormalities in neurological disease.

Altered iron levels, detected using iron-sensitive MRI techniques such as quantitative susceptibility mapping (QSM), are observed in neurological disorders and may play a crucial role in disease pathophysiology. However, brain iron changes occur slowly, even in neurological diseases, and can be influenced by physiological or environmental factors that are difficult to quantify in the research or clinical settings. Therefore, novel analysis methods are needed to improve sensitivity to disease-related iron changes beyond conventional region-based approaches.

Sensitivity of Quantitative Susceptibility Mapping for Clinical Research in Deep Gray Matter.

Quantitative susceptibility mapping (QSM) is an advanced MRI technique for assessing iron, calcium, and myelin tissue levels based on magnetic susceptibility. QSM consists of multiple processing steps, with various choices for each step. While QSM is increasingly applied in neurodegenerative disease research, its reproducibility and sensitivity in detecting susceptibility changes across groups or over time, which underpin the interpretation of clinical outcomes, have not been thoroughly quantified.

Thalamic iron in multiple sclerosis: Waning support for the early-rise late-decline hypothesis.

Background: Studies of thalamic iron levels in multiple sclerosis (MS) have yielded variable findings, potentially due to differences in study cohorts. For example, studies in relatively young cohorts (average ages below 40 years) have reported elevated susceptibility in people with MS (pwMS), whereas studies in older cohorts (above 40 years) found decreased susceptibility.

Objective: To test the "early-rise late-decline" hypothesis, which posits that age differences in study cohorts are responsible for conflicting findings regarding thalamic susceptibility in MS.

Diffusion- and Tractography-Based Characterization of Tissue Damage Within and Surrounding Paramagnetic Rim Lesions in Multiple Sclerosis.

Background And Purpose: Paramagnetic rim lesions (PRLs) are an imaging biomarker of chronic inflammation in MS that are associated with more aggressive disease. However, the precise tissue characteristics and extent of their damage, particularly with regard to connected axonal tracts, are incompletely understood. Quantitative diffusion tissue measurements and fiber tractography can provide a more complete picture of these phenomena.

Sensitivity of Quantitative Susceptibility Mapping in Clinical Brain Research.

Background: Quantitative susceptibility mapping (QSM) of the brain is an advanced MRI technique for assessing tissue characteristics based on magnetic susceptibility, which varies with the composition of the tissue, such as iron, calcium, and myelin levels. QSM consists of multiple processing steps, with various choices for each step. Despite its increasing application in detecting and monitoring neurodegenerative diseases, the impact of algorithmic choices in QSM's workflow on clinical outcomes has not been thoroughly quantified.

IRONMAP: Iron Network Mapping and Analysis Protocol for Detecting Over-Time Brain Iron Abnormalities in Neurological Disease.

Pathologically altered iron levels, detected using iron-sensitive MRI techniques such as quantitative susceptibility mapping (QSM), are observed in neurological disorders such as multiple sclerosis (MS) and may play a crucial role in disease pathophysiology. However, brain iron changes occur slowly, even in neurological diseases, and can be influenced by physiological factors such as diet. Therefore, novel analysis methods are needed to improve sensitivity to disease-related iron changes as compared to conventional region-based analysis methods.

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).

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.

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.

Reliability of paramagnetic rim lesion classification on quantitative susceptibility mapping (QSM) in people with multiple sclerosis: Single-site experience and systematic review.

Background: Recent developments in iron-sensitive MRI techniques have enabled visualization of chronic active lesions as paramagnetic rim lesions (PRLs) in vivo. Although PRLs have potential as a diagnostic and prognostic tool for multiple sclerosis (MS), limited studies have reported the reliability of PRL assessment. Further evaluation of PRL reliability, through original investigations and review of PRL literature, are warranted.

Paramagnetic rim lesions are associated with greater incidence of relapse and worse cognitive recovery following relapse.

Background: Paramagnetic rim lesions (PRL) may be linked to relapse risk of people with relapsing-remitting multiple sclerosis (pwRRMS).

Objective: To determine the relationship between presence of PRL lesions and cognitive recovery after relapse.

Methods: PRL load was compared between acutely relapsing pwRRMS and matched stable pwRRMS controls (each group  = 21).

Susceptibility networks reveal independent patterns of brain iron abnormalities in multiple sclerosis.

Brain iron homeostasis is necessary for healthy brain function. MRI and histological studies have shown altered brain iron levels in the brains of patients with multiple sclerosis (MS), particularly in the deep gray matter (DGM). Previous studies were able to only partially separate iron-modifying effects because of incomplete knowledge of iron-modifying processes and influencing factors.

A direct test of competitive versus cooperative episodic-procedural network dynamics in human memory.

Classical lesion studies led to a consensus that episodic and procedural memory arises from segregated networks identified with the hippocampus and the caudate nucleus, respectively. Neuroimaging studies, however, show that competitive and cooperative interactions occur between networks during memory tasks. Furthermore, causal experiments to manipulate connectivity between these networks have not been performed in humans.

Reproducing the effect of hippocampal network-targeted transcranial magnetic stimulation on episodic memory.

Repetitive transcranial magnetic stimulation (rTMS) targeted to the hippocampal network via the inferior parietal cortex (HN-Stim) can strengthen hippocampal-cortical connectivity and improve episodic memory, offering a potential clinical intervention. However, acceptance of this technique has been tempered by the infrequent reproduction of findings in rTMS research on cognitive processes. We tested the reproducibility of the HN-Stim effect on episodic memory in our laboratory using different procedures from those previously published.

Multiple parietal pathways are associated with rTMS-induced hippocampal network enhancement and episodic memory changes.

Repetitive transcranial magnetic stimulation (rTMS) of the inferior parietal cortex (IPC) increases resting-state functional connectivity (rsFC) of the hippocampus with the precuneus and other posterior cortical areas and causes proportional improvement of episodic memory. The anatomical pathway(s) responsible for the propagation of these effects from the IPC is unknown and may not be direct. In order to assess the relative contributions of candidate pathways from the IPC to the MTL via the parahippocampal cortex and precuneus, to the effects of rTMS on rsFC and memory improvement, we used diffusion tensor imaging to measure the extent to which individual differences in fractional anisotropy (FA) in these pathways accounted for individual differences in response.

Identifying site- and stimulation-specific TMS-evoked EEG potentials using a quantitative cosine similarity metric.

The ability to interpret transcranial magnetic stimulation (TMS)-evoked electroencephalography (EEG) potentials (TEPs) is limited by artifacts, such as auditory evoked responses produced by discharge of the TMS coil. TEPs generated from direct cortical stimulation should vary in their topographical activity pattern according to stimulation site and differ from responses to sham stimulation. Responses that do not show these effects are likely to be artifactual.

Optimizing Hippocampal-Cortical Network Modulation via Repetitive Transcranial Magnetic Stimulation: A Dose-Finding Study Using the Continual Reassessment Method.

Objective: Repetitive transcranial magnetic stimulation (rTMS) can cause potentially useful changes in brain functional connectivity (FC), but the number of treatment sessions required is unknown. We applied the continual reassessment method (CRM), a Bayesian, adaptive, dose-finding procedure to a rTMS paradigm in an attempt to answer this question.

Materials And Methods: The sample size was predetermined at 15 subjects and the cohort size was set with three individuals (i.

Persistent Enhancement of Hippocampal Network Connectivity by Parietal rTMS Is Reproducible.

Wang et al. (2014) found that that five daily sessions of repetitive transcranial magnetic stimulation (rTMS) of the posterior parietal cortex (PPC) significantly increased functional connectivity (FC) in a network centered on the hippocampus, and caused a correlated increase in memory performance. However, this finding has not been reproduced independently and the requirement for five sessions has not been validated.

Microfluidic Genipin Deposition Technique for Extended Culture of Micropatterned Vascular Muscular Thin Films.

The chronic nature of vascular disease progression requires the development of experimental techniques that simulate physiologic and pathologic vascular behaviors on disease-relevant time scales. Previously, microcontact printing has been used to fabricate two-dimensional functional arterial mimics through patterning of extracellular matrix protein as guidance cues for tissue organization. Vascular muscular thin films utilized these mimics to assess functional contractility.

Long-term vascular contractility assay using genipin-modified muscular thin films.

Vascular disease is a leading cause of death globally and typically manifests chronically due to long-term maladaptive arterial growth and remodeling. To date, there is no in vitro technique for studying vascular function over relevant disease time courses that both mimics in vivo-like tissue structure and provides a simple readout of tissue stress. We aimed to extend tissue viability in our muscular thin film contractility assay by modifying the polydimethylsiloxane (PDMS) substrate with micropatterned genipin, allowing extracellular matrix turnover without cell loss.