OBJECTIVES: To address the need for interactive visualization tools and databases in characterizing multimorbidity patterns across different populations, we developed the Phenome-wide Multi-Institutional Multimorbidity Explorer (PheMIME). This tool leverages three large-scale EHR systems to facilitate efficient analysis and visualization of disease multimorbidity, aiming to reveal both robust and novel disease associations that are consistent across different systems and to provide insight for enhancing personalized healthcare strategies. MATERIALS AND METHODS: PheMIME integrates summary statistics from phenome-wide analyses of disease multimorbidities, utilizing data from Vanderbilt University Medical Center, Mass General Brigham, and the UK Biobank. It offers interactive and multifaceted visualizations for exploring multimorbidity. Incorporating an enhanced version of associationSubgraphs, PheMIME also enables dynamic analysis and inference of disease clusters, promoting the discovery of complex multimorbidity patterns. A case study on schizophrenia demonstrates its capability for generating interactive visualizations of multimorbidity networks within and across multiple systems. Additionally, PheMIME supports diverse multimorbidity-based discoveries, detailed further in online case studies. RESULTS: The PheMIME is accessible at https://prod.tbilab.org/PheMIME/. A comprehensive tutorial and multiple case studies for demonstration are available at https://prod.tbilab.org/PheMIME_supplementary_materials/. The source code can be downloaded from https://github.com/tbilab/PheMIME. DISCUSSION: PheMIME represents a significant advancement in medical informatics, offering an efficient solution for accessing, analyzing, and interpreting the complex and noisy real-world patient data in electronic health records. CONCLUSION: PheMIME provides an extensive multimorbidity knowledge base that consolidates data from three EHR systems, and it is a novel interactive tool designed to analyze and visualize multimorbidities across multiple EHR datasets. It stands out as the first of its kind to offer extensive multimorbidity knowledge integration with substantial support for efficient online analysis and interactive visualization.

MOTIVATION: Making sense of networked multivariate association patterns is vitally important to many areas of high-dimensional analysis. Unfortunately, as the data-space dimensions grow, the number of association pairs increases in O(n2); this means that traditional visualizations such as heatmaps quickly become too complicated to parse effectively. RESULTS: Here, we present associationSubgraphs: a new interactive visualization method to quickly and intuitively explore high-dimensional association datasets using network percolation and clustering. The goal is to provide an efficient investigation of association subgraphs, each containing a subset of variables with stronger and more frequent associations among themselves than the remaining variables outside the subset, by showing the entire clustering dynamics and providing subgraphs under all possible cutoff values at once. Particularly, we apply associationSubgraphs to a phenome-wide multimorbidity association matrix generated from an electronic health record and provide an online, interactive demonstration for exploring multimorbidity subgraphs. AVAILABILITY AND IMPLEMENTATION: An R package implementing both the algorithm and visualization components of associationSubgraphs is available at https://github.com/tbilab/associationsubgraphs. Online documentation is available at https://prod.tbilab.org/associationsubgraphs_info/. A demo using a multimorbidity association matrix is available at https://prod.tbilab.org/associationsubgraphs-example/.

Body part regression is a promising new technique that enables content navigation through self-supervised learning. Using this technique, the global quantitative spatial location for each axial view slice is obtained from computed tomography (CT). However, it is challenging to define a unified global coordinate system for body CT scans due to the large variabilities in image resolution, contrasts, sequences, and patient anatomy. Therefore, the widely used supervised learning approach cannot be easily deployed. To address these concerns, we propose an annotation-free method named blind-unsupervised-supervision network (BUSN). The contributions of the work are in four folds: (1) 1030 multi-center CT scans are used in developing BUSN without any manual annotation. (2) the proposed BUSN corrects the predictions from unsupervised learning and uses the corrected results as the new supervision; (3) to improve the consistency of predictions, we propose a novel neighbor message passing (NMP) scheme that is integrated with BUSN as a statistical learning based correction; and (4) we introduce a new pre-processing pipeline with inclusion of the BUSN, which is validated on 3D multi-organ segmentation. The proposed method is trained on 1,030 whole body CT scans (230,650 slices) from five datasets, as well as an independent external validation cohort with 100 scans. From the body part regression results, the proposed BUSN achieved significantly higher median R-squared score (=0.9089) than the state-of-the-art unsupervised method (=0.7153). When introducing BUSN as a preprocessing stage in volumetric segmentation, the proposed pre-processing pipeline using BUSN approach increases the total mean Dice score of the 3D abdominal multi-organ segmentation from 0.7991 to 0.8145.

The findings of splenomegaly, abnormal enlargement of the spleen, is a non-invasive clinical biomarker for liver and spleen diseases. Automated segmentation methods are essential to efficiently quantify splenomegaly from clinically acquired abdominal magnetic resonance imaging (MRI) scans. However, the task is challenging due to: 1) large anatomical and spatial variations of splenomegaly; 2) large inter- and intra-scan intensity variations on multi-modal MRI; and 3) limited numbers of labeled splenomegaly scans. In this paper, we propose the Splenomegaly Segmentation Network (SS-Net) to introduce the deep convolutional neural network (DCNN) approaches in multi-modal MRI splenomegaly segmentation. Large convolutional kernel layers were used to address the spatial and anatomical variations, while the conditional generative adversarial networks were employed to leverage the segmentation performance of SS-Net in an end-to-end manner. A clinically acquired cohort containing both T1-weighted (T1w) and T2-weighted (T2w) MRI splenomegaly scans was used to train and evaluate the performance of multi-atlas segmentation (MAS), 2D DCNN networks, and a 3-D DCNN network. From the experimental results, the DCNN methods achieved superior performance to the state-of-the-art MAS method. The proposed SS-Net method has achieved the highest median and mean Dice scores among the investigated baseline DCNN methods.

A key limitation of deep convolutional neural networks (DCNN) based image segmentation methods is the lack of generalizability. Manually traced training images are typically required when segmenting organs in a new imaging modality or from distinct disease cohort. The manual efforts can be alleviated if the manually traced images in one imaging modality (e.g., MRI) are able to train a segmentation network for another imaging modality (e.g., CT). In this paper, we propose an end-to-end synthetic segmentation network (SynSeg-Net) to train a segmentation network for a target imaging modality without having manual labels. SynSeg-Net is trained by using (1) unpaired intensity images from source and target modalities, and (2) manual labels only from source modality. SynSeg-Net is enabled by the recent advances of cycle generative adversarial networks (CycleGAN) and DCNN. We evaluate the performance of the SynSeg-Net on two experiments: (1) MRI to CT splenomegaly synthetic segmentation for abdominal images, and (2) CT to MRI total intracranial volume synthetic segmentation (TICV) for brain images. The proposed end-to-end approach achieved superior performance to two stage methods. Moreover, the SynSeg-Net achieved comparable performance to the traditional segmentation network using target modality labels in certain scenarios. The source code of SynSeg-Net is publicly available 2.