Increased Intrathecal B and Plasma Cells in Patients With Anti-IgLON5 Disease

Background and ObjectivesDespite detection of autoantibodies, anti-IgLON5 disease was historically considered a tau-associated neurodegenerative disease, with limited treatment options and detrimental consequences for the patients. Observations in increasing case numbers hint toward underlying inflammatory mechanisms that, early detection provided, open a valuable window of opportunity for therapeutic intervention. We aimed to further substantiate this view by studying the CSF of patients with anti-IgLON5.MethodsWe identified 11 patients with anti-IgLON5 from our database and compared clinical, MRI, and CSF findings with a cohort of 20 patients with progressive supranuclear palsy (PSP) (as a noninflammatory tauopathy) and 22 patients with functional neurologic disorder.ResultsPatients with anti-IgLON5 show inflammatory changes in routine CSF analysis, an increase in B-lymphocyte frequency, and the presence of plasma cells in comparison to the PSP-control group and functional neurologic disease controls. Patients with intrathecal plasma cells showed a clinical response to rituximab.DiscussionOur findings indicate the importance of inflammatory mechanisms, in particular in early and acute anti-IgLON5 cases, which may support the use of immune-suppressive treatments in these cases. The main limitation of the study is the small number of cases due to the rarity of the disease.

Paramagnetic rim lesions are associated with pathogenic CSF profiles and worse clinical outcomes in multiple sclerosis: a retrospective cross-sectional study

Background and Objective: Paramagnetic rims have been observed as a feature of some MS lesions on susceptibility-sensitive MRI and indicate ongoing inflammation, principally consisting of compartmentalized activated microglia/macrophages. We investigated clinical, MRI, and intrathecal (cerebrospinal fluid, CSF) associations of paramagnetic rim lesions (PRL) using 3T MRI in MS. Methods: This is a retrospective, cross-sectional analysis of patients at a single neuroimmunology clinic. All patients had standardized 3T MRI using a multiecho T2*-weighted sequence with susceptibility postprocessing (SWAN protocol, GE) as part of the inclusion criteria. SWAN-derived filtered phase maps and corresponding T2-FLAIR images were manually reviewed by one expert rater blinded to clinical data, and PRL were determined based on qualitative assessment of hypointense paramagnetic edges on corresponding T2-hyperintense lesions. Descriptive statistics, t-tests, ANOVA, and linear regression determined demographic, clinical, MRI, and intrathecal profile associations with the presence of one or more PRL. Results: One hundred and forty-seven (147) MS patients were included in this analysis (2 clinically isolated syndrome, 118 relapsing-remitting, 14 secondary progressive, 13 primary progressive). Baseline mean age was 48.8 years, disease duration 12.8 years, and median EDSS 2, with 79% women. Seventy-five percent of patients were receiving a disease-modifying therapy, and 79 patients (54%) had available cerebrospinal fluid (CSF) analysis. Sixty-three patients (43%) had at least 1 PRL. PRL status (presence or absence) did not vary by sex or EDSS but was associated with younger age (51 vs 46 years; p=0.01) and shorter disease duration (14.5 vs 10.5 years; p=0.01). PRL status was also associated with worse disease (MS severity score: 2.8 vs 3.7; p=0.05) and blood-brain barrier disruption as determined by higher protein and pathologically elevated albumin quotient, as well as the presence of CSF oligoclonal bands (all p≤0.05); there was no association with immunoglobulin index or synthesis rate. PRL status was additionally associated with higher burden of T2-hyperintense cerebral lesion volume (T2LV), higher age-adjusted cerebral brain volume loss (especially of gray matter), and poorer performance on multiple clinical measures, including the 9-hole peg test and symbol digit modalities test (but not timed 25-foot walk speed). Clinical and intrathecal profiles remained associated with PRL after adjustment for age and in many cases T2LV as well. Sensitivity analyses limited to subgroups of patients without disease activity at the time of CSF sampling remained supportive of results. Patients with PRL were being treated with higher-efficacy disease-modifying therapies at the time of the data query. Conclusions: PRL, an emerging noninvasive biomarker of chronic cerebral neuroinflammation in MS, are confirmed to be associated with greater disease severity and newly shown to be associated with intrathecal inflammation and blood-brain-barrier disruption.

Vendor-neutral sequences (VENUS) and fully transparent workflows improve inter-vendor reproducibility of quantitative MRI

Purpose: We developed a transparent end-to-end qMRI workflow that starts with a vendor-neutral acquisition and tested the hypothesis that vendor-neutral sequences (VENUS) decrease inter-vendor variability of T1, MTR and MTsat measurements. Methods: We developed and deployed a vendor-neutral 3D spoiled gradient-echo (SPGR) sequence on three clinical scanners by two MRI vendors and acquired T1 maps on the NIST phantom, as well as T1, MTR and MTsat maps in three healthy participants. We performed hierarchical shift function analysis in vivo to characterize the differences between scanners when VENUS is used instead of commercial vendor implementations. Inter-vendor deviations were compared for statistical significance to test the hypothesis. Results: In the NIST phantom, VENUS reduced inter-vendor differences from 8 - 19.4% to 0.2 - 5% with an overall accuracy improvement, reducing ground truth T1 deviation from 7 - 11% to 0.2 - 4%. In vivo we found that the variability between vendors is significantly reduced (p = 0.015) for all maps (T1, MTR and MTsat) using VENUS. Conclusion: We conclude that vendor-neutral workflows are feasible and compatible with clinical MRI scanners. The significant reduction of inter-vendor variability using VENUS has important implications for qMRI research and for the reliability of multicenter clinical trials.

Synthesis of High-Resolution Research-Quality MRI Data from Clinical MRI Data in Patients with COVID-19

Pathophysiological mechanisms of neurological disorders in patients with coronavirus disease 2019 (COVID-19) are poorly understood, partly because of a lack of high-resolution neuroimaging data. We applied SynthSR, a convolutional neural network that synthesizes high-resolution isotropic research-quality data from thick-slice clinical MRI data, to a cohort of 11 patients with severe COVID-19. SynthSR successfully synthesized T1-weighted MPRAGE data at 1 mm spatial resolution for all 11 patients, each of whom had at least one brain lesion. Correlations between volumetric measures derived from synthesized and acquired MPRAGE data were strong for the cortical grey matter, subcortical grey matter, brainstem, hippocampus, and hemispheric white matter (r=0.84 to 0.96, p≤0.001), but absent for the cerebellar white matter and corpus callosum (r=0.04 to 0.17, p>0.61). SynthSR creates an opportunity to quantitatively study clinical MRI scans and elucidate the pathophysiology of neurological disorders in patients with COVID-19, including those with focal lesions.

P.127 Ultra-high field 7-Tesla magnetic resonance imaging and electroencephalography findings in epilepsy

Background: Assessment of patients for temporal lobe epilepsy (TLE) surgery requires multimodality input, including EEG to ensure optimal surgical planning. Often EEG demonstrates abnormal foci not detected on clinical MRI. 7T MRI provides improved resolution and we investigated its utility to detect potential abnormalities associated with EEG. Methods: Images were acquired on 7T MRI scanner (N=13) in oatients with TLE. Evaluation of 7T imaging for focal abnormalities was performed. Correlation of 7T MRI findings with EEG of focal slowing or interictal epileptic spikes (IEDs) and seizures was performed. Results: Assessment of 7T MRI demonstrated concordance with TLE in 8/13 cases. Three cases exhibited abnormal 7T MRI abnormalities not detected by 1.5 T MRI. Eleven out of 13 cases had EEG findings without anatomic correlates on MRI, with IEDs localizing to contralateral temporal, frontal, and parieto-occipital lobes. 7T images did not reveal focal anatomical abnormalities to account for the EEG findings in these patients. Conclusions: To our knowledge, this is the first study to investigate the role of 7T MRI in relation to EEG abnormalities. 7T RI findings show concordance with clinical data. 7T MRI did not reveal anatomical findings to account for EEG abnormalities, suggesting that such changes may be functional rather than anatomical.

Circularly polarized RF coil for energy harvesting in clinical MRI

Radiofrequency (RF) harvesting is a promising technology for the wireless power supply of various in-bore devices used in magnetic resonance imaging. However, current technical solutions in this area are based on the conversion of linearly polarized RF fields, and thus their efficiency is limited, as they interact only with a fraction of circularly polarized RF fields. In the present work, we introduce and experimentally realize a novel harvesting setup allowing for converting circularly polarized RF fields to direct current.

NEIM-01. PREDICTION OF RESPONSE TO COMBINATION OF NIVOLUMAB AND BEVACIZUMAB IN PATIENTS WITH RECURRENT GLIOBLASTOMA VIA RADIOMIC ANALYSIS ON CLINICAL MRI SCANS

PURPOSE The use of immunotherapy in glioblastoma management is under active investigation. Glioblastomas are “cold” tumors, meaning that they have inactivated or fewer tumor infiltrative lymphocytes in addition to substantial tumor necrosis, attributing to their poor response to immunotherapy. A significant challenge is the apriori identification of Glioblastoma patients who will respond favorably to immunotherapy. In this work, we evaluated the ability of computerized MRI-based quantitative features (radiomics) extracted from the lesion habitat (including enhancing lesion, necrosis, and peritumoral hyperintensities) to predict response and progression-free survival (PFS) in recurrent GBM patients treated with combination of Nivolumab and Bevacizumab. METHODS Immunotherapy response assessment in neuro-oncology (iRANO) criteria along with PFS were used to analyze n=50 patients enrolled in a randomized clinical trial where patients received Nivolumab with either standard or low dose Bevacizumab. These patients were assessed to see if they had complete response, partial response, stable disease (i.e. responders, n=31), or disease progression (i.e. non-responders, n=19). Lesion habitat constituting necrotic core, enhancing tumor, and edema were delineated by expert radiologist on Gd-T1w, T2w and FLAIR MRI scans. COLIAGE radiomic features from each of the delineated regions were selected using minimum redundancy maximum relevance (mRMR) via cross-validation, to segregate non-responder patients from responders. A multivariable cox proportional hazard model was used to predict survival (PFS). RESULTS CoLlAGe correlation, sum average, and sum variance features (capture local heterogeneity) from the lesion habitat, were found to segregate non-responder patients from responders with an accuracy of 86%, followed by 80% using features from peritumoral hyperintensities and 78% from enhancing tumor. In our survival analysis, C-index of 0.688 was obtained using features from the entire lesion habitat, followed by peritumoral hyperintensities (0.675) and enhancing tumor (0.656). CONCLUSION Radiomic features from the lesion habitat may predict response to combination of Nivolumab and Bevacizumab in recurrent Glioblastomas.