11Skull-stripping and region segmentation are fundamental steps in preclinical magnetic resonance imaging (MRI) studies, and these common procedures are usually performed manually. We present Multi-task U-Net (MU-Net), a convolutional neural network designed to accomplish both tasks simultaneously. MU-Net achieved higher segmentation accuracy than state-of-theart multi-atlas segmentation methods with an inference time of 0.35 seconds and no pre-processing requirements. We evaluated the performance of our network in the presence of skip connections and recently proposed framing connections, finding the simplest network to be the most effective. We tested MU-Net with an unusually large dataset combining several independent studies consisting of 1,782 mouse brain MRI volumes of both healthy and Huntington animals, and measured average Dice scores of 0.906 (striati), 0.937 (cortex), and 0.978 (brain mask). These high evaluation scores demonstrate that MU-Net is a powerful tool for segmentation and skull-stripping, decreasing inter and intra-rater variability of manual segmentation. The MU-Net code and the trained model are publicly available at https://github.com/Hierakonpolis/MU-Net. 12 1 Introduction 13 Preclinical imaging studies serve a fundamental role in biological and medical research, relating research results at the 14 molecular level to clinical application in diagnosis and therapy. Magnetic Resonance Imaging (MRI) represents about 23% of 15 all small-animal imaging studies providing the opportunity to monitor the development of pathological condition and response 16to treatment in a non-invasive way 1 . Its unique qualities also include the availability of different imaging contrasts, making MRI 17 especially useful in the context of preclinical neuroscience, from drug development 2 to structural, parametric and functional 18 studies 3 . 19 Skull-stripping and region segmentation represent an integral part of processing pipelines in both human and murine MR 20 imaging. Skull-stripping refers to the identification of the brain within the MRI volume and region segmentation refers to 21 the labeling of specific anatomical regions of interest (ROIs) within the brain. Especially in preclinical imaging, these tasks 22 are often performed manually. While manual segmentation represents the gold standard and is employed as the ground truth 23 when evaluating automated segmentation algorithms, it is a slow process that depends on the expertise of the individual expert. 24 Furthermore, manual segmentation suffers from both intra-and inter-rater variability. Dice scores are typically used to quantify 25 segmentation agreement 4 . Inter-and intra-rater Dice scores reported in literature range between 0.80 to 0.96 across different 26 segmentation tasks, and can be as low as 0.75 in the presence of pathological states 5-7 .
27In preclinical MRI, state-of-the-art automated region segmentation pipelines are based on atlas registration: individual MRI 28 volumes are aligned with a labeled template (atlas) to propagate...