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Evaluation of the 3D bone morphology of the glenohumeral joint is necessary for pre-surgical planning. Zero echo time (ZTE) magnetic resonance imaging (MRI) provides excellent bone contrast and can potentially be used in the place of computed tomography. Segmentation of the shoulder anatomy, particularly the humeral head and the acetabulum, is needed for the detailed assessment of each anatomy and for pre-surgical preparation. In this study, we compared the performance of two popular deep learning models based on Google’s DeepLab and U-Net to perform automated segmentation on ZTE MRI of human shoulders. Axial ZTE images of normal shoulders (n = 31) acquired at 3-Tesla were annotated for training with DeepLab and 2D U-Net, and the trained model was validated with testing data (n = 13). While both models showed visually satisfactory results for segmenting the humeral bone, U-Net slightly over-estimated while DeepLab under-estimated the segmented area compared to the ground truth. Testing accuracy quantified by Dice score was significantly higher (p < 0.05) for U-Net (88%) than DeepLab (81%) for the humeral segmentation. We have also implemented the U-Net model onto an MRI console for push-button DL segmentation processing. Although this is an early work with limitations, our approach has the potential to improve shoulder MR evaluation hindered by manual post-processing and may provide clinical benefit for quickly visualizing bones of the glenohumeral joint.

The multispecific organic anion transporters, OAT1 (SLC22A6) and OAT3 (SLC22A8), the main kidney elimination pathways for many common drugs, are often considered to have largely-redundant roles. However, whereas examination of metabolomics data from Oat-knockout mice (Oat1 and Oat3KO) revealed considerable overlap, over a hundred metabolites were increased in the plasma of one or the other of these knockout mice. Many of these relatively unique metabolites are components of distinct biochemical and signaling pathways, including those involving amino acids, lipids, bile acids, and uremic toxins. Cheminformatics, together with a "logical" statistical and machine learning-based approach, identified a number of molecular features distinguishing these unique endogenous substrates. Compared with OAT1, OAT3 tends to interact with more complex substrates possessing more rings and chiral centers. An independent "brute force" approach, analyzing all possible combinations of molecular features, supported the logical approach. Together, the results suggest the potential molecular basis by which OAT1 and OAT3 modulate distinct metabolic and signaling pathways in vivo As suggested by the Remote Sensing and Signaling Theory, the analysis provides a potential mechanism by which "multispecific" kidney proximal tubule transporters exert distinct physiological effects. Furthermore, a strong metabolite-based machine-learning classifier was able to successfully predict unique OAT1 versus OAT3 drugs; this suggests the feasibility of drug design based on knockout metabolomics of drug transporters. The approach can be applied to other SLC and ATP-binding cassette drug transporters to define their nonredundant physiological roles and for analyzing the potential impact of drug-metabolite interactions.