O. Al-LouziNational Institute of Neurological Disorders and Stroke Translational Neuroradiology Section
Dr. Omar Al-Louzi is a neuroimmunology and multiple sclerosis (MS) fellow at the translational neuroradiology section of the National Institute of Neurological Disorders and Stroke (NINDS). His research focuses on the use of imaging biomarkers and MRI analysis tools to better understand the pathobiology of MS and progressive multifocal leukoencephalopathy, and as outcome measures in clinical trials. He is particularly interested in the application of automated image analysis pipelines, and machine learning methodology in clinical research. Dr. Al-Louzi is supported by a Clinician Scientist Development Award from the National Multiple Sclerosis Society and American Brain Foundation (FAN-1807-32163).
Author Of 1 Presentation
FC03.02 - A step forward toward the fully automated assessment of the central vein sign
A deep-learning prototype method, called CVSNet, was recently introduced for the automated detection of the central vein sign (CVS) in brain lesions and demonstrated effective and accurate discrimination of multiple sclerosis (MS) from its mimics. However, this method solely considered focal lesions displaying the central vein sign (CVS+) or not (CVS−), therefore requiring a manual pre-selection of the lesions to be evaluated by eliminating the so-called excluded lesions (CVSe) as defined by the NAIMS criteria. CVSe lesions may however play an important role in differential diagnosis. Moreover, extending the automated CVS classification to these lesions would facilitate the integration of CVSNet with existing MS lesion segmentation algorithms in a fully automated pipeline.
To develop an improved version of the CVSNet prototype method able to classify all types of lesions (CVS+, CVS− and CVSe).
Patients with an established MS or CIS diagnosis (RRMS 29; SPMS 10; PPMS 10; CIS 1; mean ± SD age: 50 ± 11 years; male/female: 23/27), and healthy controls (n=8; mean ± SD age: 41 ± 9 years; male/female: 5/3), underwent 3T brain MRI (MAGNETOM Skyra and MAGNETOM Prisma, Siemens Healthcare, Erlangen, Germany, or Achieva, Philips Healthcare, Best, Netherlands). Brain lesions were automatically segmented and manually corrected by a single rater. CVS assessment was conducted on FLAIR* images by two raters, according to the NAIMS guidelines, yielding 1542 CVS+, 1004 CVS−, and 1131 CVSe lesions. A convolutional neural network (CNN) based on the CVSnet architecture was trained with different configurations using 3021 samples (1261 CVS+, 847 CVS−, and 913 CVSe) and evaluated in 656 unseen samples (281 CVS+, 157 CVS−, and 218 CVSe, from 13 patients) for final testing. The configurations relied on different combinations of the following channels as input: (i) FLAIR*, (ii) T2*, (iii) lesion mask, and (iv) CSF and brain tissue concentration maps obtained from a partial-volume estimation algorithm. Lesion-wise classification performance was evaluated for the different configurations by estimating the sensitivity, specificity, and accuracy for each lesion class.
The results were similar across the different configurations. The best performance in the unseen testing set was obtained when all channels were used as input (sensitivity: 0.71, 0.73; specificity: 0.71, 0.81; and accuracy: 0.71, 0.79 for CVS+, CVS−, respectively). For CVSe, this approach achieved 0.52 sensitivity, 0.94 specificity, and 0.80 accuracy.
We introduced a modified CVSNet prototype method that can analyze the presence of the central vein for all types of brain lesions, enabling its integration with current MS lesion segmentation algorithms. This new feature will allow a fully automated assessment of the CVS in patients’ brains, speeding up the evaluation of CVS as a diagnostic biomarker for differentiating MS from mimicking diseases.
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PS11.05 - Inclusion of small ovoid lesions in central vein sign assessment improves sensitivity for multiple sclerosis
The ‘central vein sign’ (CVS) is increasingly recognized as a valuable biomarker with high specificity and sensitivity for multiple sclerosis (MS) MRI lesions. Current consensus North American Imaging in Multiple Sclerosis (NAIMS) guidelines recommend excluding lesions <3mm in diameter in any plane for CVS assessment. However, different lesion-size exclusion cut-offs for CVS have not been systematically evaluated.
To evaluate the impact of different lesion size cut-offs and exclusion methodologies on CVS analysis and select3* criteria for MS diagnosis.
MS patients and non-MS controls were recruited as part of the National Institute of Neurological Disorders and Stroke MS natural history study and underwent 3T MRI on either Siemens Skyra or Philips Achieva scanners. MS lesions were segmented using a deep learning-based method and manually corrected by a single rater. Individual lesions were extracted as clusters of connected voxels, and their principal axes lengths (calculated as the lengths of the major axes of an ellipsoid with the same normalized second central moments) were used to measure lesion size in 3 dimensions. Ground truth CVS assessment was conducted by two raters on all lesions regardless of size. Two paradigms of lesion exclusion were compared: (1) excluding lesions if any dimension was less than threshold (ExcAny), or (2) if all dimensions were less than threshold (ExcAll).
A total of 3920 lesions from 71 subjects (8 healthy controls, 36 RRMS, 12 SPMS, 14 PPMS, 1 CIS) were included in the analysis. CVS+ lesions were more likely to be ovoid and less spherical compared to their CVS- counterparts, as measured by the fractional anisotropy of lesion dimensions (mean difference 0.02, p=0.001). Of the 1679 CVS+ lesions in the cohort, 82% met the ExcAny criteria to be excluded at a 3mm cut-off, which was reduced to 29% when ExcAll criteria were used (McNemar test, p < 0.001). At the subject-level, an increase in the sensitivity of select3* CVS criteria for MS diagnosis was noted at 3mm using the less strict ExcAll (95%) compared to the more conservative ExcAny criteria (61%), without impacting specificity (100% for both methods). There was a reduction in specificity for both ExcAny and ExcAll criteria when size cut-offs less than or equal to 2mm were used (88% for both).
Compared to the current NAIMS guidelines, ExcAll criteria for CVS lesion analysis allow the inclusion of a larger proportion of CVS+ lesions and improve the sensitivity of select3* criteria for MS diagnosis. These findings improve the applicability of the CVS as a diagnostic marker for MS in clinical practice and provide evidence for future modifications of CVS lesion exclusion guidelines.