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Joel Saltz

Publications and source records attributed to Joel Saltz.

At least 37 records · Page 2Linked to original sources

Learned representation-guided diffusion models for large-image generation

To synthesize high-fidelity samples, diffusion models typically require auxiliary data to guide the generation process. However, it is impractical to procure the painstaking patch-level annotation effort required in specialized domains like histopathology and satellite imagery; it is often performed by domain experts and involves hundreds of millions of patches. Modern-day self-supervised learning (SSL) representations encode rich semantic and visual information. In this paper, we posit that such representations are expressive enough to act as proxies to fine-grained human labels. We introduce a novel approach that trains diffusion models conditioned on embeddings from SSL. Our diffusion models successfully project these features back to high-quality histopathology and remote sensing images. In addition, we construct larger images by assembling spatially consistent patches inferred from SSL embeddings, preserving long-range dependencies. Augmenting real data by generating variations of real images improves downstream classifier accuracy for patch-level and larger, image-scale classification tasks. Our models are effective even on datasets not encountered during training, demonstrating their robustness and generalizability. Generating images from learned embeddings is agnostic to the source of the embeddings. The SSL embeddings used to generate a large image can either be extracted from a reference image, or sampled from an auxiliary model conditioned on any related modality (e.g. class labels, text, genomic data). As proof of concept, we introduce the text-to-large image synthesis paradigm where we successfully synthesize large pathology and satellite images out of text descriptions.

cs.CV↗

PathLDM: Text conditioned Latent Diffusion Model for Histopathology

To achieve high-quality results, diffusion models must be trained on large datasets. This can be notably prohibitive for models in specialized domains, such as computational pathology. Conditioning on labeled data is known to help in data-efficient model training. Therefore, histopathology reports, which are rich in valuable clinical information, are an ideal choice as guidance for a histopathology generative model. In this paper, we introduce PathLDM, the first text-conditioned Latent Diffusion Model tailored for generating high-quality histopathology images. Leveraging the rich contextual information provided by pathology text reports, our approach fuses image and textual data to enhance the generation process. By utilizing GPT's capabilities to distill and summarize complex text reports, we establish an effective conditioning mechanism. Through strategic conditioning and necessary architectural enhancements, we achieved a SoTA FID score of 7.64 for text-to-image generation on the TCGA-BRCA dataset, significantly outperforming the closest text-conditioned competitor with FID 30.1.

cs.CV↗

Prompt-MIL: Boosting Multi-Instance Learning Schemes via Task-specific Prompt Tuning

Whole slide image (WSI) classification is a critical task in computational pathology, requiring the processing of gigapixel-sized images, which is challenging for current deep-learning methods. Current state of the art methods are based on multi-instance learning schemes (MIL), which usually rely on pretrained features to represent the instances. Due to the lack of task-specific annotated data, these features are either obtained from well-established backbones on natural images, or, more recently from self-supervised models pretrained on histopathology. However, both approaches yield task-agnostic features, resulting in performance loss compared to the appropriate task-related supervision, if available. In this paper, we show that when task-specific annotations are limited, we can inject such supervision into downstream task training, to reduce the gap between fully task-tuned and task agnostic features. We propose Prompt-MIL, an MIL framework that integrates prompts into WSI classification. Prompt-MIL adopts a prompt tuning mechanism, where only a small fraction of parameters calibrates the pretrained features to encode task-specific information, rather than the conventional full fine-tuning approaches. Extensive experiments on three WSI datasets, TCGA-BRCA, TCGA-CRC, and BRIGHT, demonstrate the superiority of Prompt-MIL over conventional MIL methods, achieving a relative improvement of 1.49%-4.03% in accuracy and 0.25%-8.97% in AUROC while using fewer than 0.3% additional parameters. Compared to conventional full fine-tuning approaches, we fine-tune less than 1.3% of the parameters, yet achieve a relative improvement of 1.29%-13.61% in accuracy and 3.22%-27.18% in AUROC and reduce GPU memory consumption by 38%-45% while training 21%-27% faster. Our code is available at https://github.com/cvlab-stonybrook/PromptMIL.

cs.CV↗

Attention De-sparsification Matters: Inducing Diversity in Digital Pathology Representation Learning

We propose DiRL, a Diversity-inducing Representation Learning technique for histopathology imaging. Self-supervised learning techniques, such as contrastive and non-contrastive approaches, have been shown to learn rich and effective representations of digitized tissue samples with limited pathologist supervision. Our analysis of vanilla SSL-pretrained models' attention distribution reveals an insightful observation: sparsity in attention, i.e, models tends to localize most of their attention to some prominent patterns in the image. Although attention sparsity can be beneficial in natural images due to these prominent patterns being the object of interest itself, this can be sub-optimal in digital pathology; this is because, unlike natural images, digital pathology scans are not object-centric, but rather a complex phenotype of various spatially intermixed biological components. Inadequate diversification of attention in these complex images could result in crucial information loss. To address this, we leverage cell segmentation to densely extract multiple histopathology-specific representations, and then propose a prior-guided dense pretext task for SSL, designed to match the multiple corresponding representations between the views. Through this, the model learns to attend to various components more closely and evenly, thus inducing adequate diversification in attention for capturing context rich representations. Through quantitative and qualitative analysis on multiple tasks across cancer types, we demonstrate the efficacy of our method and observe that the attention is more globally distributed.

cs.CV↗

SAM-Path: A Segment Anything Model for Semantic Segmentation in Digital Pathology

Semantic segmentations of pathological entities have crucial clinical value in computational pathology workflows. Foundation models, such as the Segment Anything Model (SAM), have been recently proposed for universal use in segmentation tasks. SAM shows remarkable promise in instance segmentation on natural images. However, the applicability of SAM to computational pathology tasks is limited due to the following factors: (1) lack of comprehensive pathology datasets used in SAM training and (2) the design of SAM is not inherently optimized for semantic segmentation tasks. In this work, we adapt SAM for semantic segmentation by introducing trainable class prompts, followed by further enhancements through the incorporation of a pathology encoder, specifically a pathology foundation model. Our framework, SAM-Path enhances SAM's ability to conduct semantic segmentation in digital pathology without human input prompts. Through experiments on two public pathology datasets, the BCSS and the CRAG datasets, we demonstrate that the fine-tuning with trainable class prompts outperforms vanilla SAM with manual prompts and post-processing by 27.52% in Dice score and 71.63% in IOU. On these two datasets, the proposed additional pathology foundation model further achieves a relative improvement of 5.07% to 5.12% in Dice score and 4.50% to 8.48% in IOU.

eess.IV↗

Halcyon -- A Pathology Imaging and Feature analysis and Management System

Halcyon is a new pathology imaging analysis and feature management system based on W3C linked-data open standards and is designed to scale to support the needs for the voluminous production of features from deep-learning feature pipelines. Halcyon can support multiple users with a web-based UX with access to all user data over a standards-based web API allowing for integration with other processes and software systems. Identity management and data security is also provided.

cs.HC↗

Topology-Guided Multi-Class Cell Context Generation for Digital Pathology

In digital pathology, the spatial context of cells is important for cell classification, cancer diagnosis and prognosis. To model such complex cell context, however, is challenging. Cells form different mixtures, lineages, clusters and holes. To model such structural patterns in a learnable fashion, we introduce several mathematical tools from spatial statistics and topological data analysis. We incorporate such structural descriptors into a deep generative model as both conditional inputs and a differentiable loss. This way, we are able to generate high quality multi-class cell layouts for the first time. We show that the topology-rich cell layouts can be used for data augmentation and improve the performance of downstream tasks such as cell classification.

eess.IV↗

Precise Location Matching Improves Dense Contrastive Learning in Digital Pathology

Dense prediction tasks such as segmentation and detection of pathological entities hold crucial clinical value in computational pathology workflows. However, obtaining dense annotations on large cohorts is usually tedious and expensive. Contrastive learning (CL) is thus often employed to leverage large volumes of unlabeled data to pre-train the backbone network. To boost CL for dense prediction, some studies have proposed variations of dense matching objectives in pre-training. However, our analysis shows that employing existing dense matching strategies on histopathology images enforces invariance among incorrect pairs of dense features and, thus, is imprecise. To address this, we propose a precise location-based matching mechanism that utilizes the overlapping information between geometric transformations to precisely match regions in two augmentations. Extensive experiments on two pretraining datasets (TCGA-BRCA, NCT-CRC-HE) and three downstream datasets (GlaS, CRAG, BCSS) highlight the superiority of our method in semantic and instance segmentation tasks. Our method outperforms previous dense matching methods by up to 7.2% in average precision for detection and 5.6% in average precision for instance segmentation tasks. Additionally, by using our matching mechanism in the three popular contrastive learning frameworks, MoCo-v2, VICRegL, and ConCL, the average precision in detection is improved by 0.7% to 5.2%, and the average precision in segmentation is improved by 0.7% to 4.0%, demonstrating generalizability. Our code is available at https://github.com/cvlab-stonybrook/PLM_SSL.

cs.CV↗

Gigapixel Whole-Slide Images Classification using Locally Supervised Learning

Histopathology whole slide images (WSIs) play a very important role in clinical studies and serve as the gold standard for many cancer diagnoses. However, generating automatic tools for processing WSIs is challenging due to their enormous sizes. Currently, to deal with this issue, conventional methods rely on a multiple instance learning (MIL) strategy to process a WSI at patch level. Although effective, such methods are computationally expensive, because tiling a WSI into patches takes time and does not explore the spatial relations between these tiles. To tackle these limitations, we propose a locally supervised learning framework which processes the entire slide by exploring the entire local and global information that it contains. This framework divides a pre-trained network into several modules and optimizes each module locally using an auxiliary model. We also introduce a random feature reconstruction unit (RFR) to preserve distinguishing features during training and improve the performance of our method by 1% to 3%. Extensive experiments on three publicly available WSI datasets: TCGA-NSCLC, TCGA-RCC and LKS, highlight the superiority of our method on different classification tasks. Our method outperforms the state-of-the-art MIL methods by 2% to 5% in accuracy, while being 7 to 10 times faster. Additionally, when dividing it into eight modules, our method requires as little as 20% of the total gpu memory required by end-to-end training. Our code is available at https://github.com/cvlab-stonybrook/local_learning_wsi.

cs.CV↗

Learning Topological Interactions for Multi-Class Medical Image Segmentation

Deep learning methods have achieved impressive performance for multi-class medical image segmentation. However, they are limited in their ability to encode topological interactions among different classes (e.g., containment and exclusion). These constraints naturally arise in biomedical images and can be crucial in improving segmentation quality. In this paper, we introduce a novel topological interaction module to encode the topological interactions into a deep neural network. The implementation is completely convolution-based and thus can be very efficient. This empowers us to incorporate the constraints into end-to-end training and enrich the feature representation of neural networks. The efficacy of the proposed method is validated on different types of interactions. We also demonstrate the generalizability of the method on both proprietary and public challenge datasets, in both 2D and 3D settings, as well as across different modalities such as CT and Ultrasound. Code is available at: https://github.com/TopoXLab/TopoInteraction

cs.CV↗

ImageBox3: No-Server Tile Serving to Traverse Whole Slide Images on the Web

Whole slide imaging (WSI) has become the primary modality for digital pathology data. However, due to the size and high-resolution nature of these images, they are generally only accessed in smaller sections or tiles via specialized platforms, most of which require extensive setup and/or costly infrastructure. These platforms typically also need a copy of the images to be locally available to them, potentially causing issues with data governance and provenance. To address these concerns, we developed ImageBox3, an in-browser tiling mechanism to enable zero-footprint traversal of remote WSI data. All computation is performed client-side without compromising user governance, operating public and private images alike as long as the storage service supports HTTP range requests (standard in Cloud storage and most web servers). ImageBox3 thus removes significant hurdles to WSI operation and effective collaboration, allowing for the sort of democratized analytical tools needed to establish participative, FAIR digital pathology data commons. Availability: code - https://github.com/episphere/imagebox3; fig1 (live) - https://episphere.github.io/imagebox3/demo/scriptTag ; fig2 (live) - https://episphere.github.io/imagebox3/demo/serviceWorker ; fig 3 (live) - https://observablehq.com/@prafulb/imagebox3-in-observable .

q-bio.QM↗

AI and Pathology: Steering Treatment and Predicting Outcomes

The combination of data analysis methods, increasing computing capacity, and improved sensors enable quantitative granular, multi-scale, cell-based analyses. We describe the rich set of application challenges related to tissue interpretation and survey AI methods currently used to address these challenges. We focus on a particular class of targeted human tissue analysis - histopathology - aimed at quantitative characterization of disease state, patient outcome prediction and treatment steering.

cs.AI↗

Multi-Class Cell Detection Using Spatial Context Representation

In digital pathology, both detection and classification of cells are important for automatic diagnostic and prognostic tasks. Classifying cells into subtypes, such as tumor cells, lymphocytes or stromal cells is particularly challenging. Existing methods focus on morphological appearance of individual cells, whereas in practice pathologists often infer cell classes through their spatial context. In this paper, we propose a novel method for both detection and classification that explicitly incorporates spatial contextual information. We use the spatial statistical function to describe local density in both a multi-class and a multi-scale manner. Through representation learning and deep clustering techniques, we learn advanced cell representation with both appearance and spatial context. On various benchmarks, our method achieves better performance than state-of-the-arts, especially on the classification task. We also create a new dataset for multi-class cell detection and classification in breast cancer and we make both our code and data publicly available.

cs.CV↗

A Novel Framework for Characterization of Tumor-Immune Spatial Relationships in Tumor Microenvironment

Understanding the impact of tumor biology on the composition of nearby cells often requires characterizing the impact of biologically distinct tumor regions. Biomarkers have been developed to label biologically distinct tumor regions, but challenges arise because of differences in the spatial extent and distribution of differentially labeled regions. In this work, we present a framework for systematically investigating the impact of distinct tumor regions on cells near the tumor borders, accounting their cross spatial distributions. We apply the framework to multiplex immunohistochemistry (mIHC) studies of pancreatic cancer and show its efficacy in demonstrating how biologically different tumor regions impact the immune response in the tumor microenvironment. Furthermore, we show that the proposed framework can be extended to largescale whole slide image analysis.

q-bio.QM↗

A Pathologist-Annotated Dataset for Validating Artificial Intelligence: A Project Description and Pilot Study

Purpose: In this work, we present a collaboration to create a validation dataset of pathologist annotations for algorithms that process whole slide images (WSIs). We focus on data collection and evaluation of algorithm performance in the context of estimating the density of stromal tumor infiltrating lymphocytes (sTILs) in breast cancer. Methods: We digitized 64 glass slides of hematoxylin- and eosin-stained ductal carcinoma core biopsies prepared at a single clinical site. We created training materials and workflows to crowdsource pathologist image annotations on two modes: an optical microscope and two digital platforms. The workflows collect the ROI type, a decision on whether the ROI is appropriate for estimating the density of sTILs, and if appropriate, the sTIL density value for that ROI. Results: The pilot study yielded an abundant number of cases with nominal sTIL infiltration. Furthermore, we found that the sTIL densities are correlated within a case, and there is notable pathologist variability. Consequently, we outline plans to improve our ROI and case sampling methods. We also outline statistical methods to account for ROI correlations within a case and pathologist variability when validating an algorithm. Conclusion: We have built workflows for efficient data collection and tested them in a pilot study. As we prepare for pivotal studies, we will consider what it will take for the dataset to be fit for a regulatory purpose: study size, patient population, and pathologist training and qualifications. To this end, we will elicit feedback from the FDA via the Medical Device Development Tool program and from the broader digital pathology and AI community. Ultimately, we intend to share the dataset, statistical methods, and lessons learned.

q-bio.QM↗

Identifying Risk of Opioid Use Disorder for Patients Taking Opioid Medications with Deep Learning

The United States is experiencing an opioid epidemic, and there were more than 10 million opioid misusers aged 12 or older each year. Identifying patients at high risk of Opioid Use Disorder (OUD) can help to make early clinical interventions to reduce the risk of OUD. Our goal is to predict OUD patients among opioid prescription users through analyzing electronic health records with machine learning and deep learning methods. This will help us to better understand the diagnoses of OUD, providing new insights on opioid epidemic. Electronic health records of patients who have been prescribed with medications containing active opioid ingredients were extracted from Cerner Health Facts database between January 1, 2008 and December 31, 2017. Long Short-Term Memory (LSTM) models were applied to predict opioid use disorder risk in the future based on recent five encounters, and compared to Logistic Regression, Random Forest, Decision Tree and Dense Neural Network. Prediction performance was assessed using F-1 score, precision, recall, and AUROC. Our temporal deep learning model provided promising prediction results which outperformed other methods, with a F1 score of 0.8023 and AUCROC of 0.9369. The model can identify OUD related medications and vital signs as important features for the prediction. LSTM based temporal deep learning model is effective on predicting opioid use disorder using a patient past history of electronic health records, with minimal domain knowledge. It has potential to improve clinical decision support for early intervention and prevention to combat the opioid epidemic.

cs.LG↗

Representing Whole Slide Cancer Image Features with Hilbert Curves

Regions of Interest (ROI) contain morphological features in pathology whole slide images (WSI) are delimited with polygons[1]. These polygons are often represented in either a textual notation (with the array of edges) or in a binary mask form. Textual notations have an advantage of human readability and portability, whereas, binary mask representations are more useful as the input and output of feature-extraction pipelines that employ deep learning methodologies. For any given whole slide image, more than a million cellular features can be segmented generating a corresponding number of polygons. The corpus of these segmentations for all processed whole slide images creates various challenges for filtering specific areas of data for use in interactive real-time and multi-scale displays and analysis. Simple range queries of image locations do not scale and, instead, spatial indexing schemes are required. In this paper we propose using Hilbert Curves simultaneously for spatial indexing and as a polygonal ROI representation. This is achieved by using a series of Hilbert Curves[2] creating an efficient and inherently spatially-indexed machine-usable form. The distinctive property of Hilbert curves that enables both mask and polygon delimitation of ROIs is that the elements of the vector extracted ro describe morphological features maintain their relative positions for different scales of the same image.

cs.GR↗

Utilizing Automated Breast Cancer Detection to Identify Spatial Distributions of Tumor Infiltrating Lymphocytes in Invasive Breast Cancer

Quantitative assessment of Tumor-TIL spatial relationships is increasingly important in both basic science and clinical aspects of breast cancer research. We have developed and evaluated convolutional neural network (CNN) analysis pipelines to generate combined maps of cancer regions and tumor infiltrating lymphocytes (TILs) in routine diagnostic breast cancer whole slide tissue images (WSIs). We produce interactive whole slide maps that provide 1) insight about the structural patterns and spatial distribution of lymphocytic infiltrates and 2) facilitate improved quantification of TILs. We evaluated both tumor and TIL analyses using three CNN networks - Resnet-34, VGG16 and Inception v4, and demonstrated that the results compared favorably to those obtained by what believe are the best published methods. We have produced open-source tools and generated a public dataset consisting of tumor/TIL maps for 1,015 TCGA breast cancer images. We also present a customized web-based interface that enables easy visualization and interactive exploration of high-resolution combined Tumor-TIL maps for 1,015TCGA invasive breast cancer cases that can be downloaded for further downstream analyses.

eess.IV↗