Insufficiently precise diagnosis of clinical disease is likely responsible for many treatment failures, even for common conditions and treatments. With a large enough dataset, it may be possible to use unsupervised machine learning to define clinical disease patterns more precisely. We present an approach to learning these patterns by using probabilistic independence to disentangle the imprint on the medical record of causal latent sources of disease. We inferred a broad set of 2000 clinical signatures of latent sources from 9195 variables in 269,099 Electronic Health Records. The learned signatures produced better discrimination than the original variables in a lung cancer prediction task unknown to the inference algorithm, predicting 3-year malignancy in patients with no history of cancer before a solitary lung nodule was discovered. More importantly, the signatures' greater explanatory power identified pre-nodule signatures of apparently undiagnosed cancer in many of those patients.

The accuracy of predictive models for solitary pulmonary nodule (SPN) diagnosis can be greatly increased by incorporating repeat imaging and medical context, such as electronic health records (EHRs). However, clinically routine modalities such as imaging and diagnostic codes can be asynchronous and irregularly sampled over different time scales which are obstacles to longitudinal multimodal learning. In this work, we propose a transformer-based multimodal strategy to integrate repeat imaging with longitudinal clinical signatures from routinely collected EHRs for SPN classification. We perform unsupervised disentanglement of latent clinical signatures and leverage time-distance scaled self-attention to jointly learn from clinical signatures expressions and chest computed tomography (CT) scans. Our classifier is pretrained on 2,668 scans from a public dataset and 1,149 subjects with longitudinal chest CTs, billing codes, medications, and laboratory tests from EHRs of our home institution. Evaluation on 227 subjects with challenging SPNs revealed a significant AUC improvement over a longitudinal multimodal baseline (0.824 vs 0.752 AUC), as well as improvements over a single cross-section multimodal scenario (0.809 AUC) and a longitudinal imaging-only scenario (0.741 AUC). This work demonstrates significant advantages with a novel approach for co-learning longitudinal imaging and non-imaging phenotypes with transformers. Code available at https://github.com/MASILab/lmsignatures.

The use of needles to access sites within organs is fundamental to many interventional medical procedures both for diagnosis and treatment. Safe and accurate navigation of a needle through living tissue to an intra-tissue target is currently often challenging or infeasible due to the presence of anatomical obstacles in the tissue, high levels of uncertainty, and natural tissue motion (e.g., due to breathing). Medical robots capable of automating needle-based procedures in vivo have the potential to overcome these challenges and enable an enhanced level of patient care and safety. In this paper, we show the first medical robot that autonomously navigates a needle inside living tissue around anatomical obstacles to an intra-tissue target. Our system leverages an aiming device and a laser-patterned highly flexible steerable needle, a type of needle capable of maneuvering along curvilinear trajectories to avoid obstacles. The autonomous robot accounts for anatomical obstacles and uncertainty in living tissue/needle interaction with replanning and control and accounts for respiratory motion by defining safe insertion time windows during the breathing cycle. We apply the system to lung biopsy, which is critical in the diagnosis of lung cancer, the leading cause of cancer-related death in the United States. We demonstrate successful performance of our system in multiple in vivo porcine studies and also demonstrate that our approach leveraging autonomous needle steering outperforms a standard manual clinical technique for lung nodule access.