An Intrinsically Explainable Approach to Detecting Vertebral Compression Fractures in CT Scans via Neurosymbolic Modeling

Vertebral compression fractures (VCFs) are a common and potentially serious consequence of osteoporosis. Yet, they often remain undiagnosed. Opportunistic screening, which involves automated analysis of medical imaging data acquired primarily for other purposes, is a cost-effective method to identify undiagnosed VCFs. In high-stakes scenarios like opportunistic medical diagnosis, model interpretability is a key factor for the adoption of AI recommendations. Rule-based methods are inherently explainable and closely align with clinical guidelines, but they are not immediately applicable to high-dimensional data such as CT scans. To address this gap, we introduce a neurosymbolic approach for VCF detection in CT volumes. The proposed model combines deep learning (DL) for vertebral segmentation with a shape-based algorithm (SBA) that analyzes vertebral height distributions in salient anatomical regions. This allows for the definition of a rule set over the height distributions to detect VCFs. Evaluation of VerSe19 dataset shows that our method achieves an accuracy of 96% and a sensitivity of 91% in VCF detection. In comparison, a black box model, DenseNet, achieved an accuracy of 95% and sensitivity of 91% in the same dataset. Our results demonstrate that our intrinsically explainable approach can match or surpass the performance of black box deep neural networks while providing additional insights into why a prediction was made. This transparency can enhance clinician's trust thus, supporting more informed decision-making in VCF diagnosis and treatment planning.

Memorizing SAM: 3D Medical Segment Anything Model with Memorizing Transformer

Segment Anything Models (SAMs) have gained increasing attention in medical image analysis due to their zero-shot generalization capability in segmenting objects of unseen classes and domains when provided with appropriate user prompts. Addressing this performance gap is important to fully leverage the pre-trained weights of SAMs, particularly in the domain of volumetric medical image segmentation, where accuracy is important but well-annotated 3D medical data for fine-tuning is limited. In this work, we investigate whether introducing the memory mechanism as a plug-in, specifically the ability to memorize and recall internal representations of past inputs, can improve the performance of SAM with limited computation cost. To this end, we propose Memorizing SAM, a novel 3D SAM architecture incorporating a memory Transformer as a plug-in. Unlike conventional memorizing Transformers that save the internal representation during training or inference, our Memorizing SAM utilizes existing highly accurate internal representation as the memory source to ensure the quality of memory. We evaluate the performance of Memorizing SAM in 33 categories from the TotalSegmentator dataset, which indicates that Memorizing SAM can outperform state-of-the-art 3D SAM variant i.e., FastSAM3D with an average Dice increase of 11.36% at the cost of only 4.38 millisecond increase in inference time. The source code is publicly available at https://github.com/swedfr/memorizingSAM

DiffuseReg: Denoising Diffusion Model for Obtaining Deformation Fields in Unsupervised Deformable Image Registration

Deformable image registration aims to precisely align medical images from different modalities or times. Traditional deep learning methods, while effective, often lack interpretability, real-time observability and adjustment capacity during registration inference. Denoising diffusion models present an alternative by reformulating registration as iterative image denoising. However, existing diffusion registration approaches do not fully harness capabilities, neglecting the critical sampling phase that enables continuous observability during the inference. Hence, we introduce DiffuseReg, an innovative diffusion-based method that denoises deformation fields instead of images for improved transparency. We also propose a novel denoising network upon Swin Transformer, which better integrates moving and fixed images with diffusion time step throughout the denoising process. Furthermore, we enhance control over the denoising registration process with a novel similarity consistency regularization. Experiments on ACDC datasets demonstrate DiffuseReg outperforms existing diffusion registration methods by 1.32 in Dice score. The sampling process in DiffuseReg enables real-time output observability and adjustment unmatched by previous deep models.

A Survey for Large Language Models in Biomedicine

Recent breakthroughs in large language models (LLMs) offer unprecedented natural language understanding and generation capabilities. However, existing surveys on LLMs in biomedicine often focus on specific applications or model architectures, lacking a comprehensive analysis that integrates the latest advancements across various biomedical domains. This review, based on an analysis of 484 publications sourced from databases including PubMed, Web of Science, and arXiv, provides an in-depth examination of the current landscape, applications, challenges, and prospects of LLMs in biomedicine, distinguishing itself by focusing on the practical implications of these models in real-world biomedical contexts. Firstly, we explore the capabilities of LLMs in zero-shot learning across a broad spectrum of biomedical tasks, including diagnostic assistance, drug discovery, and personalized medicine, among others, with insights drawn from 137 key studies. Then, we discuss adaptation strategies of LLMs, including fine-tuning methods for both uni-modal and multi-modal LLMs to enhance their performance in specialized biomedical contexts where zero-shot fails to achieve, such as medical question answering and efficient processing of biomedical literature. Finally, we discuss the challenges that LLMs face in the biomedicine domain including data privacy concerns, limited model interpretability, issues with dataset quality, and ethics due to the sensitive nature of biomedical data, the need for highly reliable model outputs, and the ethical implications of deploying AI in healthcare. To address these challenges, we also identify future research directions of LLM in biomedicine including federated learning methods to preserve data privacy and integrating explainable AI methodologies to enhance the transparency of LLMs.

TourSynbio: A Multi-Modal Large Model and Agent Framework to Bridge Text and Protein Sequences for Protein Engineering

The structural similarities between protein sequences and natural languages have led to parallel advancements in deep learning across both domains. While large language models (LLMs) have achieved much progress in the domain of natural language processing, their potential in protein engineering remains largely unexplored. Previous approaches have equipped LLMs with protein understanding capabilities by incorporating external protein encoders, but this fails to fully leverage the inherent similarities between protein sequences and natural languages, resulting in sub-optimal performance and increased model complexity. To address this gap, we present TourSynbio-7B, the first multi-modal large model specifically designed for protein engineering tasks without external protein encoders. TourSynbio-7B demonstrates that LLMs can inherently learn to understand proteins as language. The model is post-trained and instruction fine-tuned on InternLM2-7B using ProteinLMDataset, a dataset comprising 17.46 billion tokens of text and protein sequence for self-supervised pretraining and 893K instructions for supervised fine-tuning. TourSynbio-7B outperforms GPT-4 on the ProteinLMBench, a benchmark of 944 manually verified multiple-choice questions, with 62.18% accuracy. Leveraging TourSynbio-7B's enhanced protein sequence understanding capability, we introduce TourSynbio-Agent, an innovative framework capable of performing various protein engineering tasks, including mutation analysis, inverse folding, protein folding, and visualization. TourSynbio-Agent integrates previously disconnected deep learning models in the protein engineering domain, offering a unified conversational user interface for improved usability. Finally, we demonstrate the efficacy of TourSynbio-7B and TourSynbio-Agent through two wet lab case studies on vanilla key enzyme modification and steroid compound catalysis.

Performance and Non-adversarial Robustness of the Segment Anything Model 2 in Surgical Video Segmentation

Fully supervised deep learning (DL) models for surgical video segmentation have been shown to struggle with non-adversarial, real-world corruptions of image quality including smoke, bleeding, and low illumination. Foundation models for image segmentation, such as the segment anything model (SAM) that focuses on interactive prompt-based segmentation, move away from semantic classes and thus can be trained on larger and more diverse data, which offers outstanding zero-shot generalization with appropriate user prompts. Recently, building upon this success, SAM-2 has been proposed to further extend the zero-shot interactive segmentation capabilities from independent frame-by-frame to video segmentation. In this paper, we present a first experimental study evaluating SAM-2's performance on surgical video data. Leveraging the SegSTRONG-C MICCAI EndoVIS 2024 sub-challenge dataset, we assess SAM-2's effectiveness on uncorrupted endoscopic sequences and evaluate its non-adversarial robustness on videos with corrupted image quality simulating smoke, bleeding, and low brightness conditions under various prompt strategies. Our experiments demonstrate that SAM-2, in zero-shot manner, can achieve competitive or even superior performance compared to fully-supervised deep learning models on surgical video data, including under non-adversarial corruptions of image quality. Additionally, SAM-2 consistently outperforms the original SAM and its medical variants across all conditions. Finally, frame-sparse prompting can consistently outperform frame-wise prompting for SAM-2, suggesting that allowing SAM-2 to leverage its temporal modeling capabilities leads to more coherent and accurate segmentation compared to frequent prompting.

AutoM3L: An Automated Multimodal Machine Learning Framework with Large Language Models

Automated Machine Learning (AutoML) offers a promising approach to streamline the training of machine learning models. However, existing AutoML frameworks are often limited to unimodal scenarios and require extensive manual configuration. Recent advancements in Large Language Models (LLMs) have showcased their exceptional abilities in reasoning, interaction, and code generation, presenting an opportunity to develop a more automated and user-friendly framework. To this end, we introduce AutoM3L, an innovative Automated Multimodal Machine Learning framework that leverages LLMs as controllers to automatically construct multimodal training pipelines. AutoM3L comprehends data modalities and selects appropriate models based on user requirements, providing automation and interactivity. By eliminating the need for manual feature engineering and hyperparameter optimization, our framework simplifies user engagement and enables customization through directives, addressing the limitations of previous rule-based AutoML approaches. We evaluate the performance of AutoM3L on six diverse multimodal datasets spanning classification, regression, and retrieval tasks, as well as a comprehensive set of unimodal datasets. The results demonstrate that AutoM3L achieves competitive or superior performance compared to traditional rule-based AutoML methods. Furthermore, a user study highlights the user-friendliness and usability of our framework, compared to the rule-based AutoML methods.

FastSAM-3DSlicer: A 3D-Slicer Extension for 3D Volumetric Segment Anything Model with Uncertainty Quantification

Accurate segmentation of anatomical structures and pathological regions in medical images is crucial for diagnosis, treatment planning, and disease monitoring. While the Segment Anything Model (SAM) and its variants have demonstrated impressive interactive segmentation capabilities on image types not seen during training without the need for domain adaptation or retraining, their practical application in volumetric 3D medical imaging workflows has been hindered by the lack of a user-friendly interface. To address this challenge, we introduce FastSAM-3DSlicer, a 3D Slicer extension that integrates both 2D and 3D SAM models, including SAM-Med2D, MedSAM, SAM-Med3D, and FastSAM-3D. Building on the well-established open-source 3D Slicer platform, our extension enables efficient, real-time segmentation of 3D volumetric medical images, with seamless interaction and visualization. By automating the handling of raw image data, user prompts, and segmented masks, FastSAM-3DSlicer provides a streamlined, user-friendly interface that can be easily incorporated into medical image analysis workflows. Performance evaluations reveal that the FastSAM-3DSlicer extension running FastSAM-3D achieves low inference times of only 1.09 seconds per volume on CPU and 0.73 seconds per volume on GPU, making it well-suited for real-time interactive segmentation. Moreover, we introduce an uncertainty quantification scheme that leverages the rapid inference capabilities of FastSAM-3D for practical implementation, further enhancing its reliability and applicability in medical settings. FastSAM-3DSlicer offers an interactive platform and user interface for 2D and 3D interactive volumetric medical image segmentation, offering a powerful combination of efficiency, precision, and ease of use with SAMs. The source code and a video demonstration are publicly available at https://github.com/arcadelab/FastSAM3D_slicer.

Promptable Counterfactual Diffusion Model for Unified Brain Tumor Segmentation and Generation with MRIs

Brain tumor analysis in Magnetic Resonance Imaging (MRI) is crucial for accurate diagnosis and treatment planning. However, the task remains challenging due to the complexity and variability of tumor appearances, as well as the scarcity of labeled data. Traditional approaches often address tumor segmentation and image generation separately, limiting their effectiveness in capturing the intricate relationships between healthy and pathological tissue structures. We introduce a novel promptable counterfactual diffusion model as a unified solution for brain tumor segmentation and generation in MRI. The key innovation lies in our mask-level prompting mechanism at the sampling stage, which enables guided generation and manipulation of specific healthy or unhealthy regions in MRI images. Specifically, the model's architecture allows for bidirectional inference, which can segment tumors in existing images and generate realistic tumor structures in healthy brain scans. Furthermore, we present a two-step approach for tumor generation and position transfer, showcasing the model's versatility in synthesizing realistic tumor structures. Experiments on the BRATS2021 dataset demonstrate that our method outperforms traditional counterfactual diffusion approaches, achieving a mean IoU of 0.653 and mean Dice score of 0.785 for tumor segmentation, outperforming the 0.344 and 0.475 of conventional counterfactual diffusion model. Our work contributes to improving brain tumor detection and segmentation accuracy, with potential implications for data augmentation and clinical decision support in neuro-oncology. The code is available at https://github.com/arcadelab/counterfactual_diffusion.

A Fine-tuning Dataset and Benchmark for Large Language Models for Protein Understanding

The parallels between protein sequences and natural language in their sequential structures have inspired the application of large language models (LLMs) to protein understanding. Despite the success of LLMs in NLP, their effectiveness in comprehending protein sequences remains an open question, largely due to the absence of datasets linking protein sequences to descriptive text. Researchers have then attempted to adapt LLMs for protein understanding by integrating a protein sequence encoder with a pre-trained LLM. However, this adaptation raises a fundamental question: "Can LLMs, originally designed for NLP, effectively comprehend protein sequences as a form of language?" Current datasets fall short in addressing this question due to the lack of a direct correlation between protein sequences and corresponding text descriptions, limiting the ability to train and evaluate LLMs for protein understanding effectively. To bridge this gap, we introduce ProteinLMDataset, a dataset specifically designed for further self-supervised pretraining and supervised fine-tuning (SFT) of LLMs to enhance their capability for protein sequence comprehension. Specifically, ProteinLMDataset includes 17.46 billion tokens for pretraining and 893,000 instructions for SFT. Additionally, we present ProteinLMBench, the first benchmark dataset consisting of 944 manually verified multiple-choice questions for assessing the protein understanding capabilities of LLMs. ProteinLMBench incorporates protein-related details and sequences in multiple languages, establishing a new standard for evaluating LLMs' abilities in protein comprehension. The large language model InternLM2-7B, pretrained and fine-tuned on the ProteinLMDataset, outperforms GPT-4 on ProteinLMBench, achieving the highest accuracy score. The dataset and the benchmark are available at https://huggingface.co/datasets/tsynbio/ProteinLMBench.