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Lucas W. Remedios

Publications and source records attributed to Lucas W. Remedios.

25 records · Page 2Linked to original sources

Cell Spatial Analysis in Crohn's Disease: Unveiling Local Cell Arrangement Pattern with Graph-based Signatures

Crohn's disease (CD) is a chronic and relapsing inflammatory condition that affects segments of the gastrointestinal tract. CD activity is determined by histological findings, particularly the density of neutrophils observed on Hematoxylin and Eosin stains (H&E) imaging. However, understanding the broader morphometry and local cell arrangement beyond cell counting and tissue morphology remains challenging. To address this, we characterize six distinct cell types from H&E images and develop a novel approach for the local spatial signature of each cell. Specifically, we create a 10-cell neighborhood matrix, representing neighboring cell arrangements for each individual cell. Utilizing t-SNE for non-linear spatial projection in scatter-plot and Kernel Density Estimation contour-plot formats, our study examines patterns of differences in the cellular environment associated with the odds ratio of spatial patterns between active CD and control groups. This analysis is based on data collected at the two research institutes. The findings reveal heterogeneous nearest-neighbor patterns, signifying distinct tendencies of cell clustering, with a particular focus on the rectum region. These variations underscore the impact of data heterogeneity on cell spatial arrangements in CD patients. Moreover, the spatial distribution disparities between the two research sites highlight the significance of collaborative efforts among healthcare organizations. All research analysis pipeline tools are available at https://github.com/MASILab/cellNN.

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Feasibility of Universal Anomaly Detection without Knowing the Abnormality in Medical Images

Many anomaly detection approaches, especially deep learning methods, have been recently developed to identify abnormal image morphology by only employing normal images during training. Unfortunately, many prior anomaly detection methods were optimized for a specific "known" abnormality (e.g., brain tumor, bone fraction, cell types). Moreover, even though only the normal images were used in the training process, the abnormal images were often employed during the validation process (e.g., epoch selection, hyper-parameter tuning), which might leak the supposed ``unknown" abnormality unintentionally. In this study, we investigated these two essential aspects regarding universal anomaly detection in medical images by (1) comparing various anomaly detection methods across four medical datasets, (2) investigating the inevitable but often neglected issues on how to unbiasedly select the optimal anomaly detection model during the validation phase using only normal images, and (3) proposing a simple decision-level ensemble method to leverage the advantage of different kinds of anomaly detection without knowing the abnormality. The results of our experiments indicate that none of the evaluated methods consistently achieved the best performance across all datasets. Our proposed method enhanced the robustness of performance in general (average AUC 0.956).

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Democratizing Pathological Image Segmentation with Lay Annotators via Molecular-empowered Learning

Multi-class cell segmentation in high-resolution Giga-pixel whole slide images (WSI) is critical for various clinical applications. Training such an AI model typically requires labor-intensive pixel-wise manual annotation from experienced domain experts (e.g., pathologists). Moreover, such annotation is error-prone when differentiating fine-grained cell types (e.g., podocyte and mesangial cells) via the naked human eye. In this study, we assess the feasibility of democratizing pathological AI deployment by only using lay annotators (annotators without medical domain knowledge). The contribution of this paper is threefold: (1) We proposed a molecular-empowered learning scheme for multi-class cell segmentation using partial labels from lay annotators; (2) The proposed method integrated Giga-pixel level molecular-morphology cross-modality registration, molecular-informed annotation, and molecular-oriented segmentation model, so as to achieve significantly superior performance via 3 lay annotators as compared with 2 experienced pathologists; (3) A deep corrective learning (learning with imperfect label) method is proposed to further improve the segmentation performance using partially annotated noisy data. From the experimental results, our learning method achieved F1 = 0.8496 using molecular-informed annotations from lay annotators, which is better than conventional morphology-based annotations (F1 = 0.7015) from experienced pathologists. Our method democratizes the development of a pathological segmentation deep model to the lay annotator level, which consequently scales up the learning process similar to a non-medical computer vision task. The official implementation and cell annotations are publicly available at https://github.com/hrlblab/MolecularEL.

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Exploring shared memory architectures for end-to-end gigapixel deep learning

Deep learning has made great strides in medical imaging, enabled by hardware advances in GPUs. One major constraint for the development of new models has been the saturation of GPU memory resources during training. This is especially true in computational pathology, where images regularly contain more than 1 billion pixels. These pathological images are traditionally divided into small patches to enable deep learning due to hardware limitations. In this work, we explore whether the shared GPU/CPU memory architecture on the M1 Ultra systems-on-a-chip (SoCs) recently released by Apple, Inc. may provide a solution. These affordable systems (less than \$5000) provide access to 128 GB of unified memory (Mac Studio with M1 Ultra SoC). As a proof of concept for gigapixel deep learning, we identified tissue from background on gigapixel areas from whole slide images (WSIs). The model was a modified U-Net (4492 parameters) leveraging large kernels and high stride. The M1 Ultra SoC was able to train the model directly on gigapixel images (16000$\times$64000 pixels, 1.024 billion pixels) with a batch size of 1 using over 100 GB of unified memory for the process at an average speed of 1 minute and 21 seconds per batch with Tensorflow 2/Keras. As expected, the model converged with a high Dice score of 0.989 $\pm$ 0.005. Training up until this point took 111 hours and 24 minutes over 4940 steps. Other high RAM GPUs like the NVIDIA A100 (largest commercially accessible at 80 GB, $\sim$\$15000) are not yet widely available (in preview for select regions on Amazon Web Services at \$40.96/hour as a group of 8). This study is a promising step towards WSI-wise end-to-end deep learning with prevalent network architectures.

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Segment Anything Model (SAM) for Digital Pathology: Assess Zero-shot Segmentation on Whole Slide Imaging

The segment anything model (SAM) was released as a foundation model for image segmentation. The promptable segmentation model was trained by over 1 billion masks on 11M licensed and privacy-respecting images. The model supports zero-shot image segmentation with various segmentation prompts (e.g., points, boxes, masks). It makes the SAM attractive for medical image analysis, especially for digital pathology where the training data are rare. In this study, we evaluate the zero-shot segmentation performance of SAM model on representative segmentation tasks on whole slide imaging (WSI), including (1) tumor segmentation, (2) non-tumor tissue segmentation, (3) cell nuclei segmentation. Core Results: The results suggest that the zero-shot SAM model achieves remarkable segmentation performance for large connected objects. However, it does not consistently achieve satisfying performance for dense instance object segmentation, even with 20 prompts (clicks/boxes) on each image. We also summarized the identified limitations for digital pathology: (1) image resolution, (2) multiple scales, (3) prompt selection, and (4) model fine-tuning. In the future, the few-shot fine-tuning with images from downstream pathological segmentation tasks might help the model to achieve better performance in dense object segmentation.

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Cross-scale Attention Guided Multi-instance Learning for Crohn's Disease Diagnosis with Pathological Images

Multi-instance learning (MIL) is widely used in the computer-aided interpretation of pathological Whole Slide Images (WSIs) to solve the lack of pixel-wise or patch-wise annotations. Often, this approach directly applies "natural image driven" MIL algorithms which overlook the multi-scale (i.e. pyramidal) nature of WSIs. Off-the-shelf MIL algorithms are typically deployed on a single-scale of WSIs (e.g., 20x magnification), while human pathologists usually aggregate the global and local patterns in a multi-scale manner (e.g., by zooming in and out between different magnifications). In this study, we propose a novel cross-scale attention mechanism to explicitly aggregate inter-scale interactions into a single MIL network for Crohn's Disease (CD), which is a form of inflammatory bowel disease. The contribution of this paper is two-fold: (1) a cross-scale attention mechanism is proposed to aggregate features from different resolutions with multi-scale interaction; and (2) differential multi-scale attention visualizations are generated to localize explainable lesion patterns. By training ~250,000 H&E-stained Ascending Colon (AC) patches from 20 CD patient and 30 healthy control samples at different scales, our approach achieved a superior Area under the Curve (AUC) score of 0.8924 compared with baseline models. The official implementation is publicly available at https://github.com/hrlblab/CS-MIL.

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Semantic-Aware Contrastive Learning for Multi-object Medical Image Segmentation

Medical image segmentation, or computing voxelwise semantic masks, is a fundamental yet challenging task to compute a voxel-level semantic mask. To increase the ability of encoder-decoder neural networks to perform this task across large clinical cohorts, contrastive learning provides an opportunity to stabilize model initialization and enhance encoders without labels. However, multiple target objects (with different semantic meanings) may exist in a single image, which poses a problem for adapting traditional contrastive learning methods from prevalent 'image-level classification' to 'pixel-level segmentation'. In this paper, we propose a simple semantic-aware contrastive learning approach leveraging attention masks to advance multi-object semantic segmentation. Briefly, we embed different semantic objects to different clusters rather than the traditional image-level embeddings. We evaluate our proposed method on a multi-organ medical image segmentation task with both in-house data and MICCAI Challenge 2015 BTCV datasets. Compared with current state-of-the-art training strategies, our proposed pipeline yields a substantial improvement of 5.53% and 6.09% on Dice score for both medical image segmentation cohorts respectively (p-value<0.01). The performance of the proposed method is further assessed on natural images via the PASCAL VOC 2012 dataset, and achieves a substantial improvement of 2.75% on mIoU (p-value<0.01).

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