Multi-Cohort Framework with Cohort-Aware Attention and Adversarial Mutual-Information Minimization for Whole Slide Image Classification

Whole Slide Images (WSIs) are critical for various clinical applications, including histopathological analysis. However, current deep learning approaches in this field predominantly focus on individual tumor types, limiting model generalization and scalability. This relatively narrow focus ultimately stems from the inherent heterogeneity in histopathology and the diverse morphological and molecular characteristics of different tumors. To this end, we propose a novel approach for multi-cohort WSI analysis, designed to leverage the diversity of different tumor types. We introduce a Cohort-Aware Attention module, enabling the capture of both shared and tumor-specific pathological patterns, enhancing cross-tumor generalization. Furthermore, we construct an adversarial cohort regularization mechanism to minimize cohort-specific biases through mutual information minimization. Additionally, we develop a hierarchical sample balancing strategy to mitigate cohort imbalances and promote unbiased learning. Together, these form a cohesive framework for unbiased multi-cohort WSI analysis. Extensive experiments on a uniquely constructed multi-cancer dataset demonstrate significant improvements in generalization, providing a scalable solution for WSI classification across diverse cancer types. Our code for the experiments is publicly available at <link>.

SIMPLE: Simultaneous Multi-Plane Self-Supervised Learning for Isotropic MRI Restoration from Anisotropic Data

Magnetic resonance imaging (MRI) is crucial in diagnosing various abdominal conditions and anomalies. Traditional MRI scans often yield anisotropic data due to technical constraints, resulting in varying resolutions across spatial dimensions, which limits diagnostic accuracy and volumetric analysis. Super-resolution (SR) techniques aim to address these limitations by reconstructing isotropic high-resolution images from anisotropic data. However, current SR methods often rely on indirect mappings and limited training data, focusing mainly on two-dimensional improvements rather than achieving true three-dimensional isotropy. We introduce SIMPLE, a Simultaneous Multi-Plane Self-Supervised Learning approach for isotropic MRI restoration from anisotropic data. Our method leverages existing anisotropic clinical data acquired in different planes, bypassing the need for simulated downsampling processes. By considering the inherent three-dimensional nature of MRI data, SIMPLE ensures realistic isotropic data generation rather than solely improving through-plane slices. This approach flexibility allows it to be extended to multiple contrast types and acquisition methods commonly used in clinical settings. Our experiments show that SIMPLE outperforms state-of-the-art methods both quantitatively using the Kernel Inception Distance (KID) and semi-quantitatively through radiologist evaluations. The generated isotropic volume facilitates more accurate volumetric analysis and 3D reconstructions, promising significant improvements in clinical diagnostic capabilities.

MBSS-T1: Model-Based Self-Supervised Motion Correction for Robust Cardiac T1 Mapping

T1 mapping is a valuable quantitative MRI technique for diagnosing diffuse myocardial diseases. Traditional methods, relying on breath-hold sequences and echo triggering, face challenges with patient compliance and arrhythmias, limiting their effectiveness. Image registration can enable motion-robust T1 mapping, but inherent intensity differences between time points pose a challenge. We introduce MBSS-T1, a self-supervised model for motion correction in cardiac T1 mapping, constrained by physical and anatomical principles. The physical constraints ensure expected signal decay behavior, while the anatomical constraints maintain realistic deformations. The unique combination of these constraints ensures accurate T1 mapping along the longitudinal relaxation axis. MBSS-T1 outperformed baseline deep-learning-based image registration approaches in a 5-fold experiment on a public dataset of 210 patients (STONE sequence) and an internal dataset of 19 patients (MOLLI sequence). MBSS-T1 excelled in model fitting quality (R2: 0.974 vs. 0.941, 0.946), anatomical alignment (Dice score: 0.921 vs. 0.984, 0.988), and expert visual quality assessment for the presence of visible motion artifacts (4.33 vs. 3.34, 3.62). MBSS-T1 has the potential to enable motion-robust T1 mapping for a broader range of patients, overcoming challenges such as arrhythmias, and suboptimal compliance, and allowing for free-breathing T1 mapping without requiring large training datasets.

Leveraging Prompt-Learning for Structured Information Extraction from Crohn's Disease Radiology Reports in a Low-Resource Language

Automatic conversion of free-text radiology reports into structured data using Natural Language Processing (NLP) techniques is crucial for analyzing diseases on a large scale. While effective for tasks in widely spoken languages like English, generative large language models (LLMs) typically underperform with less common languages and can pose potential risks to patient privacy. Fine-tuning local NLP models is hindered by the skewed nature of real-world medical datasets, where rare findings represent a significant data imbalance. We introduce SMP-BERT, a novel prompt learning method that leverages the structured nature of reports to overcome these challenges. In our studies involving a substantial collection of Crohn's disease radiology reports in Hebrew (over 8,000 patients and 10,000 reports), SMP-BERT greatly surpassed traditional fine-tuning methods in performance, notably in detecting infrequent conditions (AUC: 0.99 vs 0.94, F1: 0.84 vs 0.34). SMP-BERT empowers more accurate AI diagnostics available for low-resource languages.

Automated Prediction of Breast Cancer Response to Neoadjuvant Chemotherapy from DWI Data

Effective surgical planning for breast cancer hinges on accurately predicting pathological complete response (pCR) to neoadjuvant chemotherapy (NAC). Diffusion-weighted MRI (DWI) and machine learning offer a non-invasive approach for early pCR assessment. However, most machine-learning models require manual tumor segmentation, a cumbersome and error-prone task. We propose a deep learning model employing "Size-Adaptive Lesion Weighting" for automatic DWI tumor segmentation to enhance pCR prediction accuracy. Despite histopathological changes during NAC complicating DWI image segmentation, our model demonstrates robust performance. Utilizing the BMMR2 challenge dataset, it matches human experts in pCR prediction pre-NAC with an area under the curve (AUC) of 0.76 vs. 0.796, and surpasses standard automated methods mid-NAC, with an AUC of 0.729 vs. 0.654 and 0.576. Our approach represents a significant advancement in automating breast cancer treatment planning, enabling more reliable pCR predictions without manual segmentation.

NPB-REC: A Non-parametric Bayesian Deep-learning Approach for Undersampled MRI Reconstruction with Uncertainty Estimation

The ability to reconstruct high-quality images from undersampled MRI data is vital in improving MRI temporal resolution and reducing acquisition times. Deep learning methods have been proposed for this task, but the lack of verified methods to quantify the uncertainty in the reconstructed images hampered clinical applicability. We introduce "NPB-REC", a non-parametric fully Bayesian framework, for MRI reconstruction from undersampled data with uncertainty estimation. We use Stochastic Gradient Langevin Dynamics during training to characterize the posterior distribution of the network parameters. This enables us to both improve the quality of the reconstructed images and quantify the uncertainty in the reconstructed images. We demonstrate the efficacy of our approach on a multi-coil MRI dataset from the fastMRI challenge and compare it to the baseline End-to-End Variational Network (E2E-VarNet). Our approach outperforms the baseline in terms of reconstruction accuracy by means of PSNR and SSIM ($34.55$, $0.908$ vs. $33.08$, $0.897$, $p<0.01$, acceleration rate $R=8$) and provides uncertainty measures that correlate better with the reconstruction error (Pearson correlation, $R=0.94$ vs. $R=0.91$). Additionally, our approach exhibits better generalization capabilities against anatomical distribution shifts (PSNR and SSIM of $32.38$, $0.849$ vs. $31.63$, $0.836$, $p<0.01$, training on brain data, inference on knee data, acceleration rate $R=8$). NPB-REC has the potential to facilitate the safe utilization of deep learning-based methods for MRI reconstruction from undersampled data. Code and trained models are available at \url{https://github.com/samahkh/NPB-REC}.

A self-attention model for robust rigid slice-to-volume registration of functional MRI

Functional Magnetic Resonance Imaging (fMRI) is vital in neuroscience, enabling investigations into brain disorders, treatment monitoring, and brain function mapping. However, head motion during fMRI scans, occurring between shots of slice acquisition, can result in distortion, biased analyses, and increased costs due to the need for scan repetitions. Therefore, retrospective slice-level motion correction through slice-to-volume registration (SVR) is crucial. Previous studies have utilized deep learning (DL) based models to address the SVR task; however, they overlooked the uncertainty stemming from the input stack of slices and did not assign weighting or scoring to each slice. In this work, we introduce an end-to-end SVR model for aligning 2D fMRI slices with a 3D reference volume, incorporating a self-attention mechanism to enhance robustness against input data variations and uncertainties. It utilizes independent slice and volume encoders and a self-attention module to assign pixel-wise scores for each slice. We conducted evaluation experiments on 200 images involving synthetic rigid motion generated from 27 subjects belonging to the test set, from the publicly available Healthy Brain Network (HBN) dataset. Our experimental results demonstrate that our model achieves competitive performance in terms of alignment accuracy compared to state-of-the-art deep learning-based methods (Euclidean distance of $0.93$ [mm] vs. $1.86$ [mm]). Furthermore, our approach exhibits significantly faster registration speed compared to conventional iterative methods ($0.096$ sec. vs. $1.17$ sec.). Our end-to-end SVR model facilitates real-time head motion tracking during fMRI acquisition, ensuring reliability and robustness against uncertainties in inputs. source code, which includes the training and evaluations, will be available soon.

CIMIL-CRC: a clinically-informed multiple instance learning framework for patient-level colorectal cancer molecular subtypes classification from H\&E stained images

Treatment approaches for colorectal cancer (CRC) are highly dependent on the molecular subtype, as immunotherapy has shown efficacy in cases with microsatellite instability (MSI) but is ineffective for the microsatellite stable (MSS) subtype. There is promising potential in utilizing deep neural networks (DNNs) to automate the differentiation of CRC subtypes by analyzing Hematoxylin and Eosin (H\&E) stained whole-slide images (WSIs). Due to the extensive size of WSIs, Multiple Instance Learning (MIL) techniques are typically explored. However, existing MIL methods focus on identifying the most representative image patches for classification, which may result in the loss of critical information. Additionally, these methods often overlook clinically relevant information, like the tendency for MSI class tumors to predominantly occur on the proximal (right side) colon. We introduce `CIMIL-CRC', a DNN framework that: 1) solves the MSI/MSS MIL problem by efficiently combining a pre-trained feature extraction model with principal component analysis (PCA) to aggregate information from all patches, and 2) integrates clinical priors, particularly the tumor location within the colon, into the model to enhance patient-level classification accuracy. We assessed our CIMIL-CRC method using the average area under the curve (AUC) from a 5-fold cross-validation experimental setup for model development on the TCGA-CRC-DX cohort, contrasting it with a baseline patch-level classification, MIL-only approach, and Clinically-informed patch-level classification approach. Our CIMIL-CRC outperformed all methods (AUROC: $0.92\pm0.002$ (95\% CI 0.91-0.92), vs. $0.79\pm0.02$ (95\% CI 0.76-0.82), $0.86\pm0.01$ (95\% CI 0.85-0.88), and $0.87\pm0.01$ (95\% CI 0.86-0.88), respectively). The improvement was statistically significant.

IVIM-Morph: Motion-compensated quantitative Intra-voxel Incoherent Motion (IVIM) analysis for functional fetal lung maturity assessment from diffusion-weighted MRI data

Quantitative analysis of pseudo-diffusion in diffusion-weighted magnetic resonance imaging (DWI) data shows potential for assessing fetal lung maturation and generating valuable imaging biomarkers. Yet, the clinical utility of DWI data is hindered by unavoidable fetal motion during acquisition. We present IVIM-morph, a self-supervised deep neural network model for motion-corrected quantitative analysis of DWI data using the Intra-voxel Incoherent Motion (IVIM) model. IVIM-morph combines two sub-networks, a registration sub-network, and an IVIM model fitting sub-network, enabling simultaneous estimation of IVIM model parameters and motion. To promote physically plausible image registration, we introduce a biophysically informed loss function that effectively balances registration and model-fitting quality. We validated the efficacy of IVIM-morph by establishing a correlation between the predicted IVIM model parameters of the lung and gestational age (GA) using fetal DWI data of 39 subjects. IVIM-morph exhibited a notably improved correlation with gestational age (GA) when performing in-vivo quantitative analysis of fetal lung DWI data during the canalicular phase. IVIM-morph shows potential in developing valuable biomarkers for non-invasive assessment of fetal lung maturity with DWI data. Moreover, its adaptability opens the door to potential applications in other clinical contexts where motion compensation is essential for quantitative DWI analysis. The IVIM-morph code is readily available at: https://github.com/TechnionComputationalMRILab/qDWI-Morph.

LUNet: Deep Learning for the Segmentation of Arterioles and Venules in High Resolution Fundus Images

The retina is the only part of the human body in which blood vessels can be accessed non-invasively using imaging techniques such as digital fundus images (DFI). The spatial distribution of the retinal microvasculature may change with cardiovascular diseases and thus the eyes may be regarded as a window to our hearts. Computerized segmentation of the retinal arterioles and venules (A/V) is essential for automated microvasculature analysis. Using active learning, we created a new DFI dataset containing 240 crowd-sourced manual A/V segmentations performed by fifteen medical students and reviewed by an ophthalmologist, and developed LUNet, a novel deep learning architecture for high resolution A/V segmentation. LUNet architecture includes a double dilated convolutional block that aims to enhance the receptive field of the model and reduce its parameter count. Furthermore, LUNet has a long tail that operates at high resolution to refine the segmentation. The custom loss function emphasizes the continuity of the blood vessels. LUNet is shown to significantly outperform two state-of-the-art segmentation algorithms on the local test set as well as on four external test sets simulating distribution shifts across ethnicity, comorbidities, and annotators. We make the newly created dataset open access (upon publication).