A new method substantially improves the accuracy of mapped brain networks using anatomy and microstructure informed tractography.

In patients with multiple sclerosis (PwMS), thalamic atrophy occurs during the disease course. However, there is little understanding of the mechanisms leading to volume loss and of the relationship between microstructural thalamic pathology and disease progression. This cross-sectional and longitudinal study aimed to comprehensively characterize in vivo pathologic changes within thalamic microstructure in PwMS using advanced multiparametric quantitative MRI (qMRI). Thalamic microstructural integrity was evaluated using quantitative T1, magnetization transfer saturation, multishell diffusion, and quantitative susceptibility mapping (QSM) in 183 PwMS and 105 healthy controls (HCs). The same qMRI protocol was available for 127 PwMS and 73 HCs after a 2-year follow-up period. Inclusion criteria for PwMS encompassed either an active relapsing-remitting MS (RRMS) or inactive progressive MS (PMS) disease course. Thalamic alterations were compared between PwMS and HCs and among disease phenotypes. In addition, the study investigated the relationship between thalamic damage and clinical and conventional MRI measures of disease severity. Compared with HCs, PwMS exhibited substantial thalamic alterations, indicative of microstructural and macrostructural damage, demyelination, and disruption in iron homeostasis. These alterations extended beyond focal thalamic lesions, affecting normal-appearing thalamic tissue diffusely. Over the follow-up period, PwMS displayed an accelerated decrease in myelin volume fraction [mean difference in annualized percentage change (MD-ApC) = -1.50; p = 0.041] and increase in quantitative T1 (MD-ApC = 0.92; p < 0.0001) values, indicating heightened demyelinating and neurodegenerative processes. The observed differences between PwMS and HCs were substantially driven by the subgroup with PMS, wherein thalamic degeneration was significantly accelerated, even in comparison with patients with RRMS. Thalamic qMRI alterations showed extensive correlations with conventional MRI, clinical, and cognitive disease burden measures. Disability progression over follow-up was associated with accelerated thalamic degeneration, as reflected by enhanced diffusion (β = -0.067; p = 0.039) and QSM (β = -0.077; p = 0.027) changes. Thalamic qMRI metrics emerged as significant predictors of neurologic and cognitive disability even when accounting for other established markers including white matter lesion load and brain and thalamic atrophy. These findings offer deeper insights into thalamic pathology in PwMS, emphasizing the clinical relevance of thalamic damage and its link to disease progression. Advanced qMRI biomarkers show promising potential in guiding interventions aimed at mitigating thalamic neurodegenerative processes.

We present scilpy, an open-source Python library for diffusion magnetic resonance imaging (dMRI) and tractography. It provides a large collection of well-documented, user-friendly scripts that support nearly every stage of the dMRI processing pipeline, from preprocessing (such as denoising, registration, and local fiber reconstruction) to tractography and post-processing of tractograms, including connectivity and bundle analyses. Scilpy leverages the strength of DIPY, is well-tested through modern continuous integration practices, and is actively maintained.

Progression independent of relapse activity (PIRA) is associated with worse outcomes in people with multiple sclerosis (pwMS). Although previous research has linked PIRA to accelerated brain and spinal cord atrophy and compartmentalized chronic inflammation, the role of white matter (WM) tract degeneration remains unclear. This study aimed to explore the relationship between PIRA and the integrity of major WM tracts using diffusion tensor imaging (DTI). A cohort of 258 pwMS was stratified based on the presence or absence of PIRA over a 4-year follow-up period. At the end of follow-up, DTI metrics were compared between groups using propensity score-weighted linear regression models to account for potential confounders. PwMS with ≥1 PIRA event (n = 39) exhibited significant reductions in fractional anisotropy and increases in radial, axial, and mean diffusivity within the corpus callosum and motor tracts (false discovery rate-adjusted p ≤ 0.04) compared with those without PIRA, indicating more pronounced WM damage. Our findings highlight an association between PIRA and microstructural damage in key WM tracts. The observed DTI changes likely reflect processes such as Wallerian degeneration and contribute to the growing evidence linking PIRA to neurodegeneration.

Objective: The involvement of cortical inflammation in migraine, particularly migraine with aura, has been a subject of considerable interest, but has proved challenging to demonstrate. We aimed to detect and characterize signs of cortical inflammation in adults with migraine using a novel, multimodal magnetic resonance imaging (MRI) technique.Methods: We used T2 mapping to measure water content/cellularity, T1 mapping to measure tissue microstructure integrity, and apparent diffusion coefficient (ADC) mapping to measure intra‐ or extracellular edema. We compared these values between participants with migraine (with and without aura) and healthy controls using general linear models adjusted for age and sex.Result: Two hundred ninety‐six adult participants with migraine and 155 age‐ and sex‐matched healthy controls provided eligible imaging data. Among the participants with migraine, 103 had migraine with aura, 180 chronic migraine, and 88 were ictal during the scan. Participants with migraine had higher quantitative T2 (qT2) in the left occipital cortex than healthy controls (p < 0.0001). In migraine with aura, the higher qT2 was more widespread and located bilaterally in the occipital cortices, compared with controls (left, p < 0.0001; right p = 0.004). Post‐hoc analysis revealed overlapping ADC elevations in migraine with aura compared with controls (p = 0.0069).Interpretation: Quantitative MRI changes compatible with cortical inflammation were detected in participants with migraine, and appeared driven by the subgroup with aura. Higher occipital qT2 in migraine with aura might represent either extracellular edema or accumulation of inflammatory microglia or astrocytes. These results support the importance of cortical inflammation in migraine pathophysiology, particularly in migraine with aura. ANN NEUROL 2025;97:1168–1179