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Absinta, M.

Publications and source records attributed to Absinta, M..

2 recordsLinked to original sources
bioRxiv2020

Fully Automated Detection of Paramagnetic Rims in Multiple Sclerosis Lesions on 3T Susceptibility-Based MR Imaging

Background and PurposeThe presence of a paramagnetic rim around a white matter lesion has recently been shown to be a hallmark of a particular pathological type of multiple sclerosis (MS) lesion. Increased prevalence of these paramagnetic rim lesions (PRLs) is associated with a more severe disease course in MS. The identification of these lesions is time-consuming to perform manually. We present a method to automatically detect PRLs on 3T T2*-phase images. MethodsT1-weighted, T2-FLAIR, and T2*-phase MRI of the brain were collected at 3T for 19 subjects with MS. The images were then processed with lesion segmentation, lesion center detection, lesion labelling, and lesion-level radiomic feature extraction. A total of 877 lesions were identified, 118 (13%) of which contained a paramagnetic rim. We divided our data into a training set (15 patients, 673 lesions) and a testing set (4 patients, 204 lesions). We fit a random forest classification model on the training set and assessed our ability to classify lesions as PRL on the test set. ResultsThe number of PRLs per subject identified via our automated lesion labelling method was highly correlated with the gold standard count of PRLs per subject, r = 0.91 (95% CI [0.79, 0.97]). The classification algorithm using radiomic features can classify a lesion as PRL or not with an area under the curve of 0.80 (95% CI [0.67, 0.86]). ConclusionThis study develops a fully automated technique for the detection of paramagnetic rim lesions using standard T1 and FLAIR sequences and a T2*phase sequence obtained on 3T MR images. HighlightsO_LIA fully automated method for both the identification and classification of paramagnetic rim lesions is proposed. C_LIO_LIRadiomic features in conjunction with machine learning algorithms can accurately classify paramagnetic rim lesions. C_LIO_LIChallenges for classification are largely driven by heterogeneity between lesions, including equivocal rim signatures and lesion location. C_LI

neuroscience↗
bioRxiv2020

Imaging meningeal inflammation in CNS autoimmunity identifies a therapeutic role for BTK inhibition

Leptomeningeal inflammation in multiple sclerosis is associated with worse clinical outcomes and greater cortical pathology. Despite progress in identification of this process in multiple sclerosis patients using post-contrast FLAIR imaging, early trials attempting to target meningeal inflammation have been unsuccessful. There is a lack of appropriate model systems to screen potential therapeutic agents targeting meningeal inflammation. We utilized ultra-high field (11.7 Tesla) MRI to perform post-contrast FLAIR imaging in SJL/J mice with experimental autoimmune encephalomyelitis induced using immunization with proteolipid protein peptide (PLP139-151) and complete Freunds adjuvant. Imaging was performed in both a cross-sectional and longitudinal fashion at time-points ranging from 2 to 14 weeks post-immunization. Following imaging, we euthanized animals and collected tissue for pathological evaluation, which identified dense cellular infiltrates corresponding to areas of contrast-enhancement involving the leptomeninges. These areas of meningeal inflammation contained B cells (B220+), T cells (CD3+) and myeloid cells (Mac2+). We also noted features consistent with tertiary lymphoid tissue within these areas - presence of peripheral node addressin (PNAd) positive structures, CXCL13 producing cells and FDC-M1+ follicular dendritic cells. In the cortex adjacent to areas of meningeal inflammation we identified astrocytosis, microgliosis, demyelination and evidence of axonal stress/damage. Since areas of meningeal contrast enhancement persisted over several weeks in longitudinal experiments, we utilized this model to test the effects of a therapeutic intervention on established meningeal inflammation. We randomized mice with evidence of meningeal contrast enhancement on MRI scans performed at 6 weeks post-immunization, to treatment with either vehicle or evobrutinib (a Brutons tyrosine kinase inhibitor) for a period of 4 weeks. These mice underwent serial imaging and we examined the effect of treatment on the areas of meningeal contrast enhancement and noted a significant reduction in the evobrutinib group compared to vehicle (30% reduction versus 5% increase; P = 0.003). We utilized ultra-high field MRI imaging to identify areas of meningeal inflammation and to track them over time in SJL/J mice with experimental autoimmune encephalomyelitis and then utilized this model to identify Brutons tyrosine kinase inhibition as a novel therapeutic approach to target meningeal inflammation. The results of this study provide support for future studies in multiple sclerosis patients with imaging evidence of meningeal inflammation.

neuroscience↗