. Automated organ segmentation on CT images can enable the clinical use of advanced quantitative software devices, but model performance sensitivities must be understood before widespread adoption can occur. The goal of this study was to investigate performance differences between Convolutional Neural Networks (CNNs) trained to segment one (single-class) versus multiple (multi-class) organs, and between CNNs trained on scans from a single manufacturer versus multiple manufacturers.. The multi-class CNN was trained on CT images obtained from 455 whole-body PET/CT scans (413 for training, 42 for testing) taken with Siemens, GE, and Phillips PET/CT scanners where 16 organs were segmented. The multi-class CNN was compared to 16 smaller single-class CNNs trained using the same data, but with segmentations of only one organ per model. In addition, CNNs trained on Siemens-only (N = 186) and GE-only (N = 219) scans (manufacturer-specific) were compared with CNNs trained on data from both Siemens and GE scanners (manufacturer-mixed). Segmentation performance was quantified using five performance metrics, including the Dice Similarity Coefficient (DSC).. The multi-class CNN performed well compared to previous studies, even in organs usually considered difficult auto-segmentation targets (e.g., pancreas, bowel). Segmentations from the multi-class CNN were significantly superior to those from smaller single-class CNNs in most organs, and the 16 single-class models took, on average, six times longer to segment all 16 organs compared to the single multi-class model. The manufacturer-mixed approach achieved minimally higher performance over the manufacturer-specific approach.. A CNN trained on contours of multiple organs and CT data from multiple manufacturers yielded high-quality segmentations. Such a model is an essential enabler of image processing in a software device that quantifies and analyzes such data to determine a patient's treatment response. To date, this activity of whole organ segmentation has not been adopted due to the intense manual workload and time required.

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