Evaluation of the quality and the productivity of neuroradiological reading of multiple sclerosis follow-up MRI scans using an intelligent automation software.

PURPOSE: The assessment of multiple sclerosis (MS) lesions on follow-up magnetic resonance imaging (MRI) is tedious, time-consuming, and error-prone. Automation of low-level tasks could enhance the radiologist in this work. We evaluate the intelligent automation software Jazz in a blinded three centers study, for the assessment of new, slowly expanding, and contrast-enhancing MS lesions. METHODS: In three separate centers, 117 MS follow-up MRIs were blindly analyzed on fluid attenuated inversion recovery (FLAIR), pre- and post-gadolinium T1-weighted images using Jazz by 2 neuroradiologists in each center. The reading time was recorded. The ground truth was defined in a second reading by side-by-side comparison of both reports from Jazz and the standard clinical report. The number of described new, slowly expanding, and contrast-enhancing lesions described with Jazz was compared to the lesions described in the standard clinical report. RESULTS: A total of 96 new lesions from 41 patients and 162 slowly expanding lesions (SELs) from 61 patients were described in the ground truth reading. A significantly larger number of new lesions were described using Jazz compared to the standard clinical report (63 versus 24). No SELs were reported in the standard clinical report, while 95 SELs were reported on average using Jazz. A total of 4 new contrast-enhancing lesions were found in all reports. The reading with Jazz was very time efficient, taking on average 2min33s ± 1min0s per case. Overall inter-reader agreement for new lesions between the readers using Jazz was moderate for new lesions (Cohen kappa = 0.5) and slight for SELs (0.08). CONCLUSION: The quality and the productivity of neuroradiological reading of MS follow-up MRI scans can be significantly improved using the dedicated software Jazz.

Clinical features of neurotoxicity after CD19 CAR T-cell therapy in mantle cell lymphoma.

ABSTRACT: CD19 chimeric antigen receptor (CAR) T-cell therapy has proven highly effective for treating relapsed/refractory mantle cell lymphoma (MCL). However, immune effector cell-associated neurotoxicity syndrome (ICANS) remains a significant concern. This study aimed to evaluate the clinical, radiological, and laboratory correlatives associated with ICANS development after CD19 CAR T-cell therapy in patients with MCL. All patients (N = 26) who received standard-of-care brexucabtagene autoleucel until July 2022 at our institution were evaluated. Laboratory and radiographic correlatives including brain magnetic resonance imaging (MRI) and electroencephalogram (EEG) were evaluated to determine the clinical impact of ICANS. Seventeen (65%) patients experienced ICANS after treatment, with a median onset on day 6. Ten (38%) patients experienced severe (grade ≥3) ICANS. All patients with ICANS had antecedent cytokine release syndrome (CRS), but no correlation was observed between ICANS severity and CRS grade. Overall, 92% of EEGs revealed interictal changes; no patients experienced frank seizures because of ICANS. In total, 86% of patients with severe ICANS with postinfusion brain MRIs demonstrated acute neuroimaging findings not seen on pretreatment MRI. Severe ICANS was also associated with higher rates of cytopenia, coagulopathy, increased cumulative steroid exposure, and prolonged hospitalization. However, severe ICANS did not affect treatment outcomes of patients with MCL. Severe ICANS is frequently associated with a range of postinfusion brain MRI changes and abnormal EEG findings. Longer hospitalization was observed in patients with severe ICANS, especially those with abnormal acute MRI or EEG findings, but there was no discernible impact on overall treatment response and survival.

Single-cell peripheral immunoprofiling of lewy body and Parkinson's disease in a multi-site cohort.

BACKGROUND: Multiple lines of evidence support peripheral organs in the initiation or progression of Lewy body disease (LBD), a spectrum of neurodegenerative diagnoses that include Parkinson's Disease (PD) without or with dementia (PDD) and dementia with Lewy bodies (DLB). However, the potential contribution of the peripheral immune response to LBD remains unclear. This study aims to characterize peripheral immune responses unique to participants with LBD at single-cell resolution to highlight potential biomarkers and increase mechanistic understanding of LBD pathogenesis in humans. METHODS: In a case-control study, peripheral mononuclear cell (PBMC) samples from research participants were randomly sampled from multiple sites across the United States. The diagnosis groups comprise healthy controls (HC, n = 159), LBD (n = 110), Alzheimer's disease dementia (ADD, n = 97), other neurodegenerative disease controls (NDC, n = 19), and immune disease controls (IDC, n = 14). PBMCs were activated with three stimulants (LPS, IL-6, and IFNa) or remained at basal state, stained by 13 surface markers and 7 intracellular signal markers, and analyzed by flow cytometry, which generated 1,184 immune features after gating. RESULTS: The model classified LBD from HC with an AUROC of 0.87 ± 0.06 and AUPRC of 0.80 ± 0.06. Without retraining, the same model was able to distinguish LBD from ADD, NDC, and IDC. Model predictions were driven by pPLCγ2, p38, and pSTAT5 signals from specific cell populations under specific activation. The immune responses characteristic for LBD were not associated with other common medical conditions related to the risk of LBD or dementia, such as sleep disorders, hypertension, or diabetes. CONCLUSIONS AND RELEVANCE: Quantification of PBMC immune response from multisite research participants yielded a unique pattern for LBD compared to HC, multiple related neurodegenerative diseases, and autoimmune diseases thereby highlighting potential biomarkers and mechanisms of disease.