Multi-arm U-Net with dense input and skip connectivity for T2 lesion segmentation in clinical trials of multiple sclerosis.

T2 lesion quantification plays a crucial role in monitoring disease progression and evaluating treatment response in multiple sclerosis (MS). We developed a 3D, multi-arm U-Net for T2 lesion segmentation, which was trained on a large, multicenter clinical trial dataset of relapsing MS. We investigated its generalization to other relapsing and primary progressive MS clinical trial datasets, and to an external dataset from the MICCAI 2016 MS lesion segmentation challenge. Additionally, we assessed the model's ability to reproduce the separation of T2 lesion volumes between treatment and control arms; and the association of baseline T2 lesion volumes with clinical disability scores compared with manual lesion annotations. The trained model achieved a mean dice coefficient of ≥ 0.66 and a lesion detection sensitivity of ≥ 0.72 across the internal test datasets. On the external test dataset, the model achieved a mean dice coefficient of 0.62, which is comparable to 0.59 from the best model in the challenge, and a lesion detection sensitivity of 0.68. Lesion detection performance was reduced for smaller lesions (≤ 30 μL, 3-10 voxels). The model successfully maintained the separation of the longitudinal changes in T2 lesion volumes between the treatment and control arms. Such tools could facilitate semi-automated MS lesion quantification; and reduce rater burden in clinical trials.