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BACKGROUND: Contrast-enhancing (CE) lesions are an important finding on brain magnetic resonance imaging (MRI) in patients with multiple sclerosis (MS) but can be missed easily. Automated solutions for reliable CE lesion detection are emerging; however, independent validation of artificial intelligence (AI) tools in the clinical routine is still rare. METHODS: A three-dimensional convolutional neural network for CE lesion segmentation was trained externally on 1488 datasets of 934 MS patients from 81 scanners using concatenated information from FLAIR and T1-weighted post-contrast imaging. This externally trained model was tested on an independent dataset comprising 504 T1-weighted post-contrast and FLAIR image datasets of MS patients from clinical routine. Two neuroradiologists (R1, R2) labeled CE lesions for gold standard definition in the clinical test dataset. The algorithmic output was evaluated on both patient- and lesion-level. RESULTS: On a patient-level, recall, specificity, precision, and accuracy of the AI tool to predict patients with CE lesions were 0.75, 0.99, 0.91, and 0.96. The agreement between the AI tool and both readers was within the range of inter-rater agreement (Cohen's kappa; AI vs. R1: 0.69; AI vs. R2: 0.76; R1 vs. R2: 0.76). On a lesion-level, false negative lesions were predominately found in infratentorial location, significantly smaller, and at lower contrast than true positive lesions (p < 0.05). CONCLUSIONS: AI-based identification of CE lesions on brain MRI is feasible, approaching human reader performance in independent clinical data and might be of help as a second reader in the neuroradiological assessment of active inflammation in MS patients. CRITICAL RELEVANCE STATEMENT: Al-based detection of contrast-enhancing multiple sclerosis lesions approaches human reader performance, but careful visual inspection is still needed, especially for infratentorial, small and low-contrast lesions.
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INTRODUCTION: Several recent studies indicate that deep gray matter or thalamic volume loss (VL) might be promising surrogate markers of disease activity in multiple sclerosis (MS) patients. To allow applying these markers to individual MS patients in clinical routine, age-dependent cut-offs distinguishing physiological from pathological VL and an estimation of the measurement error, which provides the confidence of the result, are to be defined. METHODS: Longitudinal MRI scans of the following cohorts were analyzed in this study: 189 healthy controls (HC) (mean age 54 years, 22% female), 98 MS patients from Zurich university hospital (mean age 34 years, 62% female), 33 MS patients from Dresden university hospital (mean age 38 years, 60% female), and publicly available reliability data sets consisting of 162 short-term MRI scan-rescan pairs with scan intervals of days or few weeks. Percentage annualized whole brain volume loss (BVL), gray matter (GM) volume loss (GMVL), deep gray matter volume loss (deep GMVL), and thalamic volume loss (ThalaVL) were computed deploying the Jacobian integration (JI) method. BVL was additionally computed using Siena, an established method used in many Phase III drug trials. A linear mixed effect model was used to estimate the measurement error as the standard deviation (SD) of model residuals of all 162 scan-rescan pairs For estimation of age-dependent cut-offs, a quadratic regression function between age and the corresponding annualized VL values of the HC was computed. The 5th percentile was defined as the threshold for pathological VL per year since 95% of HC subjects exhibit a less pronounced VL for a given age. For the MS patients BVL, GMVL, deep GMVL, and ThalaVL were mutually compared and a paired t-test was used to test whether there are systematic differences in VL between these brain regions. RESULTS: Siena and JI showed a high agreement for BVL measures, with a median absolute difference of 0.1% and a correlation coefficient of r = 0.78. Siena and GMVL showed a similar standard deviation (SD) of the scan-rescan error of 0.28% and 0.29%, respectively. For deep GMVL, ThalaVL the SD of the scan-rescan error was slightly higher (0.43% and 0.5%, respectively). Among the HC the thalamus showed the highest mean VL (-0.16%, -0.39%, and -0.59% at ages 35, 55, and 75, respectively). Corresponding cut-offs for a pathological VL/year were -0.68%, -0.91%, and -1.11%. The MS cohorts did not differ in BVL and GMVL. However, both MS cohorts showed a significantly (p = 0.05) stronger deep GMVL than BVL per year. CONCLUSION: It might be methodologically feasible to assess deep GMVL using JI in individual MS patients. However, age and the measurement error need to be taken into account. Furthermore, deep GMVL may be used as a complementary marker to BVL since MS patients exhibit a significantly stronger deep GMVL than BVL.