Elazer R. Edelman

Karim Kadry, Abhishek Karmakar, Andreas Schuh et al.

Coronary computed tomography angiography (CCTA) provides 3D information on obstructive coronary artery disease, but cannot fully visualize high-resolution features within the vessel wall. Intravascular imaging, in contrast, can spatially resolve atherosclerotic in cross sectional slices, but is limited in capturing 3D relationships between each slice. Co-registering CCTA and intravascular images enables a variety of clinical research applications but is time consuming and user-dependent. This is due to intravascular images suffering from non-rigid distortions arising from irregularities in the imaging catheter path. To address these issues, we present a morphology-based framework for the rigid and non-rigid matching of intravascular images to CCTA images. To do this, we find the optimal virtual catheter path that samples the coronary artery in CCTA image space to recapitulate the coronary artery morphology observed in the intravascular image. We validate our framework on a multi-center cohort of 40 patients using bifurcation landmarks as ground truth for longitudinal and rotational registration. Our registration approach significantly outperforms other approaches for bifurcation alignment. By providing a differentiable framework for multi-modal vascular co-registration, our framework reduces the manual effort required to conduct large-scale multi-modal clinical studies and enables the development of machine learning-based co-registration approaches.

Karim Kadry, Shreya Gupta, Jonas Sogbadji et al.

Virtual interventions enable the physics-based simulation of device deployment within coronary arteries. This framework allows for counterfactual reasoning by deploying the same device in different arterial anatomies. However, current methods to create such counterfactual arteries face a trade-off between controllability and realism. In this study, we investigate how Latent Diffusion Models (LDMs) can custom synthesize coronary anatomy for virtual intervention studies based on mid-level anatomic constraints such as topological validity, local morphological shape, and global skeletal structure. We also extend diffusion model guidance strategies to the context of morpho-skeletal conditioning and propose a novel guidance method for continuous attributes that adaptively updates the negative guiding condition throughout sampling. Our framework enables the generation and editing of coronary anatomy in a controllable manner, allowing device designers to derive mechanistic insights regarding anatomic variation and simulated device deployment.

Vitor Martins, Sara M. Cerqueira, Mercedes Balcells et al.

Work-Related Musculoskeletal Disorders continue to be a major challenge in industrial environments, leading to reduced workforce participation, increased healthcare costs, and long-term disability. This study introduces a human-sensitive robotic system aimed at reintegrating individuals with a history of musculoskeletal disorders into standard job roles, while simultaneously optimizing ergonomic conditions for the broader workforce. This research leverages reinforcement learning (RL) to develop a human-aware control strategy for collaborative robots, focusing on optimizing ergonomic conditions and preventing pain during task execution. Two RL approaches, Q-Learning and Deep Q-Network (DQN), were implemented and tested to personalize control strategies based on individual user characteristics. Although experimental results revealed a simulation-to-real gap, a fine-tuning phase successfully adapted the policies to real-world conditions. DQN outperformed Q-Learning by completing tasks faster while maintaining zero pain risk and safe ergonomic levels, achieving on average 38% shorter task completion times across all tested anthropometries. The structured testing protocol confirmed the system's adaptability to diverse human anthropometries, underscoring the potential of RL-driven cobots to enable safer, more inclusive workplaces.

Karim Kadry, Shreya Gupta, Farhad R. Nezami et al.

Numerical simulations can model the physical processes that govern cardiovascular device deployment. When such simulations incorporate digital twins; computational models of patient-specific anatomy, they can expedite and de-risk the device design process. Nonetheless, the exclusive use of patient-specific data constrains the anatomic variability which can be precisely or fully explored. In this study, we investigate the capacity of Latent Diffusion Models (LDMs) to edit digital twins to create anatomic variants, which we term digital siblings. Digital twins and their corresponding siblings can serve as the basis for comparative simulations, enabling the study of how subtle anatomic variations impact the simulated deployment of cardiovascular devices, as well as the augmentation of virtual cohorts for device assessment. However, while diffusion models have been characterized in their ability to edit natural images, their capacity to anatomically edit digital twins has yet to be studied. Using a case example centered on 3D digital twins of cardiac anatomy, we implement various methods for generating digital siblings and characterize them through morphological and topological analyses. We specifically edit digital twins to introduce anatomic variation at different spatial scales and within localized regions, demonstrating the existence of bias towards common anatomic features. We further show that such anatomic bias can be leveraged for virtual cohort augmentation through selective editing, partially alleviating issues related to dataset imbalance and lack of diversity. Our experimental framework thus delineates the limits and capabilities of using latent diffusion models in synthesizing anatomic variation for in silico trials.

Karim Kadry, Shoaib Goraya, Ajay Manicka et al.

Generative models of 3D anatomy, when integrated with biophysical simulators, enable the study of structure-function relationships for clinical research and medical device design. However, current models face a trade-off between controllability and anatomical realism. We propose a programmable and compositional framework for guiding unconditional diffusion models of human anatomy using interpretable ellipsoidal primitives embedded in 3D space. Our method involves the selection of certain tissues within multi-tissue segmentation maps, upon which we apply geometric moment losses to guide the reverse diffusion process. This framework supports the independent control over size, shape, and position, as well as the composition of multi-component constraints during inference.

Farhan Khodaee, Rohola Zandie, Yufan Xia et al.

We propose a new theory for aging based on dynamical systems and provide a data-driven computational method to quantify the changes at the cellular level. We use ergodic theory to decompose the dynamics of changes during aging and show that aging is fundamentally a dissipative process within biological systems, akin to dynamical systems where dissipation occurs due to non-conservative forces. To quantify the dissipation dynamics, we employ a transformer-based machine learning algorithm to analyze gene expression data, incorporating age as a token to assess how age-related dissipation is reflected in the embedding space. By evaluating the dynamics of gene and age embeddings, we provide a cellular aging map (CAM) and identify patterns indicative of divergence in gene embedding space, nonlinear transitions, and entropy variations during aging for various tissues and cell types. Our results provide a novel perspective on aging as a dissipative process and introduce a computational framework that enables measuring age-related changes with molecular resolution.