HELM: Hierarchical Encoding for mRNA Language Modeling

Messenger RNA (mRNA) plays a crucial role in protein synthesis, with its codon structure directly impacting biological properties. While Language Models (LMs) have shown promise in analyzing biological sequences, existing approaches fail to account for the hierarchical nature of mRNA's codon structure. We introduce Hierarchical Encoding for mRNA Language Modeling (HELM), a novel pre-training strategy that incorporates codon-level hierarchical structure into language model training. HELM modulates the loss function based on codon synonymity, aligning the model's learning process with the biological reality of mRNA sequences. We evaluate HELM on diverse mRNA datasets and tasks, demonstrating that HELM outperforms standard language model pre-training as well as existing foundation model baselines on six diverse downstream property prediction tasks and an antibody region annotation tasks on average by around 8\%. Additionally, HELM enhances the generative capabilities of language model, producing diverse mRNA sequences that better align with the underlying true data distribution compared to non-hierarchical baselines.

Beyond Sequence: Impact of Geometric Context for RNA Property Prediction

Accurate prediction of RNA properties, such as stability and interactions, is crucial for advancing our understanding of biological processes and developing RNA-based therapeutics. RNA structures can be represented as 1D sequences, 2D topological graphs, or 3D all-atom models, each offering different insights into its function. Existing works predominantly focus on 1D sequence-based models, which overlook the geometric context provided by 2D and 3D geometries. This study presents the first systematic evaluation of incorporating explicit 2D and 3D geometric information into RNA property prediction, considering not only performance but also real-world challenges such as limited data availability, partial labeling, sequencing noise, and computational efficiency. To this end, we introduce a newly curated set of RNA datasets with enhanced 2D and 3D structural annotations, providing a resource for model evaluation on RNA data. Our findings reveal that models with explicit geometry encoding generally outperform sequence-based models, with an average prediction RMSE reduction of around 12% across all various RNA tasks and excelling in low-data and partial labeling regimes, underscoring the value of explicitly incorporating geometric context. On the other hand, geometry-unaware sequence-based models are more robust under sequencing noise but often require around 2-5x training data to match the performance of geometry-aware models. Our study offers further insights into the trade-offs between different RNA representations in practical applications and addresses a significant gap in evaluating deep learning models for RNA tasks.

Arges: Spatio-Temporal Transformer for Ulcerative Colitis Severity Assessment in Endoscopy Videos

Accurate assessment of disease severity from endoscopy videos in ulcerative colitis (UC) is crucial for evaluating drug efficacy in clinical trials. Severity is often measured by the Mayo Endoscopic Subscore (MES) and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score. However, expert MES/UCEIS annotation is time-consuming and susceptible to inter-rater variability, factors addressable by automation. Automation attempts with frame-level labels face challenges in fully-supervised solutions due to the prevalence of video-level labels in clinical trials. CNN-based weakly-supervised models (WSL) with end-to-end (e2e) training lack generalization to new disease scores and ignore spatio-temporal information crucial for accurate scoring. To address these limitations, we propose "Arges", a deep learning framework that utilizes a transformer with positional encoding to incorporate spatio-temporal information from frame features to estimate disease severity scores in endoscopy video. Extracted features are derived from a foundation model (ArgesFM), pre-trained on a large diverse dataset from multiple clinical trials (61M frames, 3927 videos). We evaluate four UC disease severity scores, including MES and three UCEIS component scores. Test set evaluation indicates significant improvements, with F1 scores increasing by 4.1% for MES and 18.8%, 6.6%, 3.8% for the three UCEIS component scores compared to state-of-the-art methods. Prospective validation on previously unseen clinical trial data further demonstrates the model's successful generalization.

SE(3)-Hyena Operator for Scalable Equivariant Learning

Modeling global geometric context while maintaining equivariance is crucial for accurate predictions in many fields such as biology, chemistry, or vision. Yet, this is challenging due to the computational demands of processing high-dimensional data at scale. Existing approaches such as equivariant self-attention or distance-based message passing, suffer from quadratic complexity with respect to sequence length, while localized methods sacrifice global information. Inspired by the recent success of state-space and long-convolutional models, in this work, we introduce SE(3)-Hyena operator, an equivariant long-convolutional model based on the Hyena operator. The SE(3)-Hyena captures global geometric context at sub-quadratic complexity while maintaining equivariance to rotations and translations. Evaluated on equivariant associative recall and n-body modeling, SE(3)-Hyena matches or outperforms equivariant self-attention while requiring significantly less memory and computational resources for long sequences. Our model processes the geometric context of 20k tokens x3.5 times faster than the equivariant transformer and allows x175 longer a context within the same memory budget.

Cardiac ultrasound simulation for autonomous ultrasound navigation

Ultrasound is well-established as an imaging modality for diagnostic and interventional purposes. However, the image quality varies with operator skills as acquiring and interpreting ultrasound images requires extensive training due to the imaging artefacts, the range of acquisition parameters and the variability of patient anatomies. Automating the image acquisition task could improve acquisition reproducibility and quality but training such an algorithm requires large amounts of navigation data, not saved in routine examinations. Thus, we propose a method to generate large amounts of ultrasound images from other modalities and from arbitrary positions, such that this pipeline can later be used by learning algorithms for navigation. We present a novel simulation pipeline which uses segmentations from other modalities, an optimized volumetric data representation and GPU-accelerated Monte Carlo path tracing to generate view-dependent and patient-specific ultrasound images. We extensively validate the correctness of our pipeline with a phantom experiment, where structures' sizes, contrast and speckle noise properties are assessed. Furthermore, we demonstrate its usability to train neural networks for navigation in an echocardiography view classification experiment by generating synthetic images from more than 1000 patients. Networks pre-trained with our simulations achieve significantly superior performance in settings where large real datasets are not available, especially for under-represented classes. The proposed approach allows for fast and accurate patient-specific ultrasound image generation, and its usability for training networks for navigation-related tasks is demonstrated.

A multi-organ point cloud registration algorithm for abdominal CT registration

Registering CT images of the chest is a crucial step for several tasks such as disease progression tracking or surgical planning. It is also a challenging step because of the heterogeneous content of the human abdomen which implies complex deformations. In this work, we focus on accurately registering a subset of organs of interest. We register organ surface point clouds, as may typically be extracted from an automatic segmentation pipeline, by expanding the Bayesian Coherent Point Drift algorithm (BCPD). We introduce MO-BCPD, a multi-organ version of the BCPD algorithm which explicitly models three important aspects of this task: organ individual elastic properties, inter-organ motion coherence and segmentation inaccuracy. This model also provides an interpolation framework to estimate the deformation of the entire volume. We demonstrate the efficiency of our method by registering different patients from the LITS challenge dataset. The target registration error on anatomical landmarks is almost twice as small for MO-BCPD compared to standard BCPD while imposing the same constraints on individual organs deformation.

Automated Catheter Tip Repositioning for Intra-cardiac Echocardiography

Purpose: Intra-Cardiac Echocardiography (ICE) is a powerful imaging modality for guiding cardiac electrophysiology and structural heart interventions. ICE provides real-time observation of anatomy and devices, while enabling direct monitoring of potential complications. In single operator settings, the physician needs to switch back-and-forth between the ICE catheter and therapy device, making continuous ICE support impossible. Two operators setup are therefore sometimes implemented, with the challenge of increase room occupation and cost. Two operator setups are sometimes implemented, but increase procedural costs and room occupation. Methods: ICE catheter robotic control system is developed with automated catheter tip repositioning (i.e. view recovery) method, which can reproduce important views previously navigated to and saved by the user. The performance of the proposed method is demonstrated and evaluated in a combination of heart phantom and animal experiments. Results: Automated ICE view recovery achieved catheter tip position accuracy of 2.09 +/-0.90 mm and catheter image orientation accuracy of 3.93 +/- 2.07 degree in animal studies, and 0.67 +/- 0.79 mm and 0.37 +/- 0.19 degree in heart phantom studies, respectively. Our proposed method is also successfully used during transeptal puncture in animals without complications, showing the possibility for fluoro-less transeptal puncture with ICE catheter robot. Conclusion: Robotic ICE imaging has the potential to provide precise and reproducible anatomical views, which can reduce overall execution time, labor burden of procedures, and x-ray usage for a range of cardiac procedures. Keywords: Automated View Recovery, Path Planning, Intra-cardiac echocardiography (ICE), Catheter, Tendon-driven manipulator, Cardiac Imaging

A Wide-area, Low-latency, and Power-efficient 6-DoF Pose Tracking System for Rigid Objects

Position sensitive detectors (PSDs) offer possibility to track single active marker's two (or three) degrees of freedom (DoF) position with a high accuracy, while having a fast response time with high update frequency and low latency, all using a very simple signal processing circuit. However they are not particularly suitable for 6-DoF object pose tracking system due to lack of orientation measurement, limited tracking range, and sensitivity to environmental variation. We propose a novel 6-DoF pose tracking system for a rigid object tracking requiring a single active marker. The proposed system uses a stereo-based PSD pair and multiple Inertial Measurement Units (IMUs). This is done based on a practical approach to identify and control the power of Infrared-Light Emitting Diode (IR-LED) active markers, with an aim to increase the tracking work space and reduce the power consumption. Our proposed tracking system is validated with three different work space sizes and for static and dynamic positional accuracy using robotic arm manipulator with three different dynamic motion patterns. The results show that the static position root-mean-square (RMS) error is 0.6mm. The dynamic position RMS error is 0.7-0.9mm. The orientation RMS error is between 0.04 and 0.9 degree at varied dynamic motion. Overall, our proposed tracking system is capable of tracking a rigid object pose with sub-millimeter accuracy at the mid range of the work space and sub-degree accuracy for all work space under a lab setting.

Shape-adaptive Hysteresis Compensation for Tendon-driven Continuum Manipulators

Tendon-driven continuum manipulators (TDCM) are commonly used in minimally invasive surgical systems due to their long, thin, flexible structure that is compliant in narrow or tortuous environments. There exist many researches for precise tip control of the articulating section. However, these models do not account for the proximal shaft shape of TDCM, affecting the tip controls in practical settings. In this paper, we propose a gradient-based shift detection method based on motor current that can easily find the offset of task space models (i.e., hysteresis). We analyze our proposed methods with multiple Intra-cardiac Echocardiography catheters, which are typical commercial example of TDCM. Our results show that the errors from varied proximal shape are considerably reduced, and the accuracy of the tip manipulation is improved when changing external environmental structures.

Non-linear Hysteresis Compensation of a Tendon-sheath-driven Robotic Manipulator using Motor Current

Tendon-sheath-driven manipulators (TSM) are widely used in minimally invasive surgical systems due to their long, thin shape, flexibility, and compliance making them easily steerable in narrow or tortuous environments. Many commercial TSM-based medical devices have non-linear phenomena resulting from their composition such as backlash and dead zone hysteresis, which lead to a considerable challenge for achieving precise control of the end effector pose. However, many recent works in the literature do not consider the combined effects and compensation of these phenomena, and less focus on practical ways to identify model parameters in real field. In this paper, we propose a simplified piece-wise linear model to compensate both backlash and dead zone hysteresis together. Further, we introduce a practical method to identify model parameters using motor current from a robotic controller for the TSM. We analyze our proposed methods with multiple Intra-cardiac Echocardiography catheters, which are typical commercial example of TSM. Our results show that the errors from backlash and dead zone hysteresis are considerably reduced and therefore the accuracy of robotic control is improved when applying the presented methods.