RealKeyMorph: Keypoints in Real-world Coordinates for Resolution-agnostic Image Registration

Many real-world settings require registration of a pair of medical images that differ in spatial resolution, which may arise from differences in image acquisition parameters like pixel spacing, slice thickness, and field-of-view. However, all previous machine learning-based registration techniques resample images onto a fixed resolution. This is suboptimal because resampling can introduce artifacts due to interpolation. To address this, we present RealKeyMorph (RKM), a resolution-agnostic method for image registration. RKM is an extension of KeyMorph, a registration framework which works by training a network to learn corresponding keypoints for a given pair of images, after which a closed-form keypoint matching step is used to derive the transformation that aligns them. To avoid resampling and enable operating on the raw data, RKM outputs keypoints in real-world coordinates of the scanner. To do this, we leverage the affine matrix produced by the scanner (e.g., MRI machine) that encodes the mapping from voxel coordinates to real world coordinates. By transforming keypoints into real-world space and integrating this into the training process, RKM effectively enables the extracted keypoints to be resolution-agnostic. In our experiments, we demonstrate the advantages of RKM on the registration task for orthogonal 2D stacks of abdominal MRIs, as well as 3D volumes with varying resolutions in brain datasets.

IRS: Incremental Relationship-guided Segmentation for Digital Pathology

Continual learning is rapidly emerging as a key focus in computer vision, aiming to develop AI systems capable of continuous improvement, thereby enhancing their value and practicality in diverse real-world applications. In healthcare, continual learning holds great promise for continuously acquired digital pathology data, which is collected in hospitals on a daily basis. However, panoramic segmentation on digital whole slide images (WSIs) presents significant challenges, as it is often infeasible to obtain comprehensive annotations for all potential objects, spanning from coarse structures (e.g., regions and unit objects) to fine structures (e.g., cells). This results in temporally and partially annotated data, posing a major challenge in developing a holistic segmentation framework. Moreover, an ideal segmentation model should incorporate new phenotypes, unseen diseases, and diverse populations, making this task even more complex. In this paper, we introduce a novel and unified Incremental Relationship-guided Segmentation (IRS) learning scheme to address temporally acquired, partially annotated data while maintaining out-of-distribution (OOD) continual learning capacity in digital pathology. The key innovation of IRS lies in its ability to realize a new spatial-temporal OOD continual learning paradigm by mathematically modeling anatomical relationships between existing and newly introduced classes through a simple incremental universal proposition matrix. Experimental results demonstrate that the IRS method effectively handles the multi-scale nature of pathological segmentation, enabling precise kidney segmentation across various structures (regions, units, and cells) as well as OOD disease lesions at multiple magnifications. This capability significantly enhances domain generalization, making IRS a robust approach for real-world digital pathology applications.

Fine-tuning Vision Language Models with Graph-based Knowledge for Explainable Medical Image Analysis

Accurate staging of Diabetic Retinopathy (DR) is essential for guiding timely interventions and preventing vision loss. However, current staging models are hardly interpretable, and most public datasets contain no clinical reasoning or interpretation beyond image-level labels. In this paper, we present a novel method that integrates graph representation learning with vision-language models (VLMs) to deliver explainable DR diagnosis. Our approach leverages optical coherence tomography angiography (OCTA) images by constructing biologically informed graphs that encode key retinal vascular features such as vessel morphology and spatial connectivity. A graph neural network (GNN) then performs DR staging while integrated gradients highlight critical nodes and edges and their individual features that drive the classification decisions. We collect this graph-based knowledge which attributes the model's prediction to physiological structures and their characteristics. We then transform it into textual descriptions for VLMs. We perform instruction-tuning with these textual descriptions and the corresponding image to train a student VLM. This final agent can classify the disease and explain its decision in a human interpretable way solely based on a single image input. Experimental evaluations on both proprietary and public datasets demonstrate that our method not only improves classification accuracy but also offers more clinically interpretable results. An expert study further demonstrates that our method provides more accurate diagnostic explanations and paves the way for precise localization of pathologies in OCTA images.

Cancer Type, Stage and Prognosis Assessment from Pathology Reports using LLMs

Large Language Models (LLMs) have shown significant promise across various natural language processing tasks. However, their application in the field of pathology, particularly for extracting meaningful insights from unstructured medical texts such as pathology reports, remains underexplored and not well quantified. In this project, we leverage state-of-the-art language models, including the GPT family, Mistral models, and the open-source Llama models, to evaluate their performance in comprehensively analyzing pathology reports. Specifically, we assess their performance in cancer type identification, AJCC stage determination, and prognosis assessment, encompassing both information extraction and higher-order reasoning tasks. Based on a detailed analysis of their performance metrics in a zero-shot setting, we developed two instruction-tuned models: Path-llama3.1-8B and Path-GPT-4o-mini-FT. These models demonstrated superior performance in zero-shot cancer type identification, staging, and prognosis assessment compared to the other models evaluated.

CASC-AI: Consensus-aware Self-corrective AI Agents for Noise Cell Segmentation

Multi-class cell segmentation in high-resolution gigapixel whole slide images (WSI) is crucial for various clinical applications. However, training such models typically requires labor-intensive, pixel-wise annotations by domain experts. Recent efforts have democratized this process by involving lay annotators without medical expertise. However, conventional non-agent-based approaches struggle to handle annotation noise adaptively, as they lack mechanisms to mitigate false positives (FP) and false negatives (FN) at both the image-feature and pixel levels. In this paper, we propose a consensus-aware self-corrective AI agent that leverages the Consensus Matrix to guide its learning process. The Consensus Matrix defines regions where both the AI and annotators agree on cell and non-cell annotations, which are prioritized with stronger supervision. Conversely, areas of disagreement are adaptively weighted based on their feature similarity to high-confidence agreement regions, with more similar regions receiving greater attention. Additionally, contrastive learning is employed to separate features of noisy regions from those of reliable agreement regions by maximizing their dissimilarity. This paradigm enables the AI to iteratively refine noisy labels, enhancing its robustness. Validated on one real-world lay-annotated cell dataset and two simulated noisy datasets, our method demonstrates improved segmentation performance, effectively correcting FP and FN errors and showcasing its potential for training robust models on noisy datasets. The official implementation and cell annotations are publicly available at https://github.com/ddrrnn123/CASC-AI.

POROver: Improving Safety and Reducing Overrefusal in Large Language Models with Overgeneration and Preference Optimization

Balancing safety and usefulness in large language models has become a critical challenge in recent years. Models often exhibit unsafe behavior or adopt an overly cautious approach, leading to frequent overrefusal of benign prompts, which reduces their usefulness. Addressing these issues requires methods that maintain safety while avoiding overrefusal. In this work, we examine how the overgeneration of training data using advanced teacher models (e.g., GPT-4o), including responses to both general-purpose and toxic prompts, influences the safety and overrefusal balance of instruction-following language models. Additionally, we present POROver, a strategy to use preference optimization methods in order to reduce overrefusal, via employing a superior teacher model's completions. Our results show that overgenerating completions for general-purpose prompts significantly improves the balance between safety and usefulness. Specifically, the F1 score calculated between safety and usefulness increases from 70.8% to 88.3%. Moreover, overgeneration for toxic prompts substantially reduces overrefusal, decreasing it from 94.4% to 45.2%. Furthermore, preference optimization algorithms, when applied with carefully curated preference data, can effectively reduce a model's overrefusal from 45.2% to 15.0% while maintaining comparable safety levels. Our code and data are available at https://github.com/batuhankmkaraman/POROver.

Adapting to Shifting Correlations with Unlabeled Data Calibration

Distribution shifts between sites can seriously degrade model performance since models are prone to exploiting unstable correlations. Thus, many methods try to find features that are stable across sites and discard unstable features. However, unstable features might have complementary information that, if used appropriately, could increase accuracy. More recent methods try to adapt to unstable features at the new sites to achieve higher accuracy. However, they make unrealistic assumptions or fail to scale to multiple confounding features. We propose Generalized Prevalence Adjustment (GPA for short), a flexible method that adjusts model predictions to the shifting correlations between prediction target and confounders to safely exploit unstable features. GPA can infer the interaction between target and confounders in new sites using unlabeled samples from those sites. We evaluate GPA on several real and synthetic datasets, and show that it outperforms competitive baselines.

Knockout: A simple way to handle missing inputs

Deep learning models can extract predictive and actionable information from complex inputs. The richer the inputs, the better these models usually perform. However, models that leverage rich inputs (e.g., multi-modality) can be difficult to deploy widely, because some inputs may be missing at inference. Current popular solutions to this problem include marginalization, imputation, and training multiple models. Marginalization can obtain calibrated predictions but it is computationally costly and therefore only feasible for low dimensional inputs. Imputation may result in inaccurate predictions because it employs point estimates for missing variables and does not work well for high dimensional inputs (e.g., images). Training multiple models whereby each model takes different subsets of inputs can work well but requires knowing missing input patterns in advance. Furthermore, training and retaining multiple models can be costly. We propose an efficient way to learn both the conditional distribution using full inputs and the marginal distributions. Our method, Knockout, randomly replaces input features with appropriate placeholder values during training. We provide a theoretical justification of Knockout and show that it can be viewed as an implicit marginalization strategy. We evaluate Knockout in a wide range of simulations and real-world datasets and show that it can offer strong empirical performance.

The 2024 Brain Tumor Segmentation (BraTS) Challenge: Glioma Segmentation on Post-treatment MRI

Gliomas are the most common malignant primary brain tumors in adults and one of the deadliest types of cancer. There are many challenges in treatment and monitoring due to the genetic diversity and high intrinsic heterogeneity in appearance, shape, histology, and treatment response. Treatments include surgery, radiation, and systemic therapies, with magnetic resonance imaging (MRI) playing a key role in treatment planning and post-treatment longitudinal assessment. The 2024 Brain Tumor Segmentation (BraTS) challenge on post-treatment glioma MRI will provide a community standard and benchmark for state-of-the-art automated segmentation models based on the largest expert-annotated post-treatment glioma MRI dataset. Challenge competitors will develop automated segmentation models to predict four distinct tumor sub-regions consisting of enhancing tissue (ET), surrounding non-enhancing T2/fluid-attenuated inversion recovery (FLAIR) hyperintensity (SNFH), non-enhancing tumor core (NETC), and resection cavity (RC). Models will be evaluated on separate validation and test datasets using standardized performance metrics utilized across the BraTS 2024 cluster of challenges, including lesion-wise Dice Similarity Coefficient and Hausdorff Distance. Models developed during this challenge will advance the field of automated MRI segmentation and contribute to their integration into clinical practice, ultimately enhancing patient care.

Assessing the significance of longitudinal data in Alzheimer's Disease forecasting

In this study, we employ a transformer encoder model to characterize the significance of longitudinal patient data for forecasting the progression of Alzheimer's Disease (AD). Our model, Longitudinal Forecasting Model for Alzheimer's Disease (LongForMAD), harnesses the comprehensive temporal information embedded in sequences of patient visits that incorporate multimodal data, providing a deeper understanding of disease progression than can be drawn from single-visit data alone. We present an empirical analysis across two patient groups-Cognitively Normal (CN) and Mild Cognitive Impairment (MCI)-over a span of five follow-up years. Our findings reveal that models incorporating more extended patient histories can outperform those relying solely on present information, suggesting a deeper historical context is critical in enhancing predictive accuracy for future AD progression. Our results support the incorporation of longitudinal data in clinical settings to enhance the early detection and monitoring of AD. Our code is available at \url{https://github.com/batuhankmkaraman/LongForMAD}.