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There is a lack of benchmarks for evaluating large language models (LLMs) in long-form medical question answering (QA). Most existing medical QA evaluation benchmarks focus on automatic metrics and multiple-choice questions. While valuable, these benchmarks fail to fully capture or assess the complexities of real-world clinical applications where LLMs are being deployed. Furthermore, existing studies on evaluating long-form answer generation in medical QA are primarily closed-source, lacking access to human medical expert annotations, which makes it difficult to reproduce results and enhance existing baselines. In this work, we introduce a new publicly available benchmark featuring real-world consumer medical questions with long-form answer evaluations annotated by medical doctors. We performed pairwise comparisons of responses from various open and closed-source medical and general-purpose LLMs based on criteria such as correctness, helpfulness, harmfulness, and bias. Additionally, we performed a comprehensive LLM-as-a-judge analysis to study the alignment between human judgments and LLMs. Our preliminary results highlight the strong potential of open LLMs in medical QA compared to leading closed models. Code & Data: https://github.com/lavita-ai/medical-eval-sphere, Comment: AIM-FM: Advancements in Medical Foundation Models Workshop, 38th Conference on Neural Information Processing Systems (NeurIPS 2024)

Handling implicit language is essential for natural language processing systems to achieve precise text understanding and facilitate natural interactions with users. Despite its importance, the absence of a robust metric for accurately measuring the implicitness of language significantly constrains the depth of analysis possible in evaluating models' comprehension capabilities. This paper addresses this gap by developing a scalar metric that quantifies the implicitness level of language without relying on external references. Drawing on principles from traditional linguistics, we define ''implicitness'' as the divergence between semantic meaning and pragmatic interpretation. To operationalize this definition, we introduce ImpScore, a novel, reference-free metric formulated through an interpretable regression model. This model is trained using pairwise contrastive learning on a specially curated dataset comprising $112,580$ (implicit sentence, explicit sentence) pairs. We validate ImpScore through a user study that compares its assessments with human evaluations on out-of-distribution data, demonstrating its accuracy and strong correlation with human judgments. Additionally, we apply ImpScore to hate speech detection datasets, illustrating its utility and highlighting significant limitations in current large language models' ability to understand highly implicit content. The metric model and its training data are available at https://github.com/audreycs/ImpScore.

Grading inflammatory bowel disease (IBD) activity using standardized histopathological scoring systems remains challenging due to resource constraints and inter-observer variability. In this study, we developed a deep learning model to classify activity grades in hematoxylin and eosin-stained whole slide images (WSIs) from patients with IBD, offering a robust approach for general pathologists. We utilized 2,077 WSIs from 636 patients treated at Dartmouth-Hitchcock Medical Center in 2018 and 2019, scanned at 40x magnification (0.25 micron/pixel). Board-certified gastrointestinal pathologists categorized the WSIs into four activity classes: inactive, mildly active, moderately active, and severely active. A transformer-based model was developed and validated using five-fold cross-validation to classify IBD activity. Using HoVerNet, we examined neutrophil distribution across activity grades. Attention maps from our model highlighted areas contributing to its prediction. The model classified IBD activity with weighted averages of 0.871 [95% Confidence Interval (CI): 0.860-0.883] for the area under the curve, 0.695 [95% CI: 0.674-0.715] for precision, 0.697 [95% CI: 0.678-0.716] for recall, and 0.695 [95% CI: 0.674-0.714] for F1-score. Neutrophil distribution was significantly different across activity classes. Qualitative evaluation of attention maps by a gastrointestinal pathologist suggested their potential for improved interpretability. Our model demonstrates robust diagnostic performance and could enhance consistency and efficiency in IBD activity assessment.

Colonoscopy screening is an effective method to find and remove colon polyps before they can develop into colorectal cancer (CRC). Current follow-up recommendations, as outlined by the U.S. Multi-Society Task Force for individuals found to have polyps, primarily rely on histopathological characteristics, neglecting other significant CRC risk factors. Moreover, the considerable variability in colorectal polyp characterization among pathologists poses challenges in effective colonoscopy follow-up or surveillance. The evolution of digital pathology and recent advancements in deep learning provide a unique opportunity to investigate the added benefits of including the additional medical record information and automatic processing of pathology slides using computer vision techniques in the calculation of future CRC risk. Leveraging the New Hampshire Colonoscopy Registry's extensive dataset, many with longitudinal colonoscopy follow-up information, we adapted our recently developed transformer-based model for histopathology image analysis in 5-year CRC risk prediction. Additionally, we investigated various multimodal fusion techniques, combining medical record information with deep learning derived risk estimates. Our findings reveal that training a transformer model to predict intermediate clinical variables contributes to enhancing 5-year CRC risk prediction performance, with an AUC of 0.630 comparing to direct prediction. Furthermore, the fusion of imaging and non-imaging features, while not requiring manual inspection of microscopy images, demonstrates improved predictive capabilities for 5-year CRC risk comparing to variables extracted from colonoscopy procedure and microscopy findings. This study signifies the potential of integrating diverse data sources and advanced computational techniques in transforming the accuracy and effectiveness of future CRC risk assessments.

This study introduces a new framework for the artificial intelligence-assisted characterization of Gram-stained whole-slide images (WSIs). As a test for the diagnosis of bloodstream infections, Gram stains provide critical early data to inform patient treatment. Rapid and reliable analysis of Gram stains has been shown to be positively associated with better clinical outcomes, underscoring the need for improved tools to automate Gram stain analysis. In this work, we developed a novel transformer-based model for Gram-stained WSI classification, which is more scalable to large datasets than previous convolutional neural network (CNN) -based methods as it does not require patch-level manual annotations. We also introduce a large Gram stain dataset from Dartmouth-Hitchcock Medical Center (Lebanon, New Hampshire, USA) to evaluate our model, exploring the classification of five major categories of Gram-stained WSIs: Gram-positive cocci in clusters, Gram-positive cocci in pairs/chains, Gram-positive rods, Gram-negative rods, and slides with no bacteria. Our model achieves a classification accuracy of 0.858 (95% CI: 0.805, 0.905) and an AUC of 0.952 (95% CI: 0.922, 0.976) using five-fold nested cross-validation on our 475-slide dataset, demonstrating the potential of large-scale transformer models for Gram stain classification. We further demonstrate the generalizability of our trained model, which achieves strong performance on external datasets without additional fine-tuning.

Mental manipulation, a significant form of abuse in interpersonal conversations, presents a challenge to identify due to its context-dependent and often subtle nature. The detection of manipulative language is essential for protecting potential victims, yet the field of Natural Language Processing (NLP) currently faces a scarcity of resources and research on this topic. Our study addresses this gap by introducing a new dataset, named ${\rm M{\small ental}M{\small anip}}$, which consists of $4,000$ annotated movie dialogues. This dataset enables a comprehensive analysis of mental manipulation, pinpointing both the techniques utilized for manipulation and the vulnerabilities targeted in victims. Our research further explores the effectiveness of leading-edge models in recognizing manipulative dialogue and its components through a series of experiments with various configurations. The results demonstrate that these models inadequately identify and categorize manipulative content. Attempts to improve their performance by fine-tuning with existing datasets on mental health and toxicity have not overcome these limitations. We anticipate that ${\rm M{\small ental}M{\small anip}}$ will stimulate further research, leading to progress in both understanding and mitigating the impact of mental manipulation in conversations., Comment: Accepted at ACL 2024

Breast cancer is the most common malignancy affecting women worldwide and is notable for its morphologic and biologic diversity, with varying risks of recurrence following treatment. The Oncotype DX Breast Recurrence Score test is an important predictive and prognostic genomic assay for estrogen receptor-positive breast cancer that guides therapeutic strategies; however, such tests can be expensive, delay care, and are not widely available. The aim of this study was to develop a multi-model approach integrating the analysis of whole slide images and clinicopathologic data to predict their associated breast cancer recurrence risks and categorize these patients into two risk groups according to the predicted score: low and high risk. The proposed novel methodology uses convolutional neural networks for feature extraction and vision transformers for contextual aggregation, complemented by a logistic regression model that analyzes clinicopathologic data for classification into two risk categories. This method was trained and tested on 993 hematoxylin and eosin-stained whole-slide images of breast cancers with corresponding clinicopathological features that had prior Oncotype DX testing. The model's performance was evaluated using an internal test set of 198 patients from Dartmouth Health and an external test set of 418 patients from the University of Chicago. The multi-model approach achieved an AUC of 0.92 (95 percent CI: 0.88-0.96) on the internal set and an AUC of 0.85 (95 percent CI: 0.79-0.90) on the external cohort. These results suggest that with further validation, the proposed methodology could provide an alternative to assist clinicians in personalizing treatment for breast cancer patients and potentially improving their outcomes., Comment: 16 pages, 4 figures and 4 tables

Endometrial cancer, the fourth most common cancer in females in the United States, with the lifetime risk for developing this disease is approximately 2.8% in women. Precise histologic evaluation and molecular classification of endometrial cancer is important for effective patient management and determining the best treatment modalities. This study introduces EndoNet, which uses convolutional neural networks for extracting histologic features and a vision transformer for aggregating these features and classifying slides based on their visual characteristics into high- and low- grade. The model was trained on 929 digitized hematoxylin and eosin-stained whole-slide images of endometrial cancer from hysterectomy cases at Dartmouth-Health. It classifies these slides into low-grade (Endometroid Grades 1 and 2) and high-grade (endometroid carcinoma FIGO grade 3, uterine serous carcinoma, carcinosarcoma) categories. EndoNet was evaluated on an internal test set of 110 patients and an external test set of 100 patients from the public TCGA database. The model achieved a weighted average F1-score of 0.91 (95% CI: 0.86-0.95) and an AUC of 0.95 (95% CI: 0.89-0.99) on the internal test, and 0.86 (95% CI: 0.80-0.94) for F1-score and 0.86 (95% CI: 0.75-0.93) for AUC on the external test. Pending further validation, EndoNet has the potential to support pathologists without the need of manual annotations in classifying the grades of gynecologic pathology tumors., Comment: 4 Tables and 3 Figures

Large Language Models (LLMs) have significantly advanced the field of Natural Language Processing (NLP), but their lack of interpretability has been a major concern. Current methods for interpreting LLMs are post hoc, applied after inference time, and have limitations such as their focus on low-level features and lack of explainability at higher level text units. In this work, we introduce proto-lm, a prototypical network-based white-box framework that allows LLMs to learn immediately interpretable embeddings during the fine-tuning stage while maintaining competitive performance. Our method's applicability and interpretability are demonstrated through experiments on a wide range of NLP tasks, and our results indicate a new possibility of creating interpretable models without sacrificing performance. This novel approach to interpretability in LLMs can pave the way for more interpretable models without the need to sacrifice performance., Comment: Accepted to the Findings of EMNLP 2023

Recent advances in whole-slide image (WSI) scanners and computational capabilities have significantly propelled the application of artificial intelligence in histopathology slide analysis. While these strides are promising, current supervised learning approaches for WSI analysis come with the challenge of exhaustively labeling high-resolution slides - a process that is both labor-intensive and time-consuming. In contrast, self-supervised learning (SSL) pretraining strategies are emerging as a viable alternative, given that they don't rely on explicit data annotations. These SSL strategies are quickly bridging the performance disparity with their supervised counterparts. In this context, we introduce an SSL framework. This framework aims for transferable representation learning and semantically meaningful clustering by synergizing invariance loss and clustering loss in WSI analysis. Notably, our approach outperforms common SSL methods in downstream classification and clustering tasks, as evidenced by tests on the Camelyon16 and a pancreatic cancer dataset., Comment: Accepted by ICCV2023

In digital pathology, whole slide images (WSIs) are widely used for applications such as cancer diagnosis and prognosis prediction. Visual transformer models have recently emerged as a promising method for encoding large regions of WSIs while preserving spatial relationships among patches. However, due to the large number of model parameters and limited labeled data, applying transformer models to WSIs remains challenging. Inspired by masked language models, we propose a pretext task for training the transformer model without labeled data to address this problem. Our model, MaskHIT, uses the transformer output to reconstruct masked patches and learn representative histological features based on their positions and visual features. The experimental results demonstrate that MaskHIT surpasses various multiple instance learning approaches by 3% and 2% on survival prediction and cancer subtype classification tasks, respectively. Furthermore, MaskHIT also outperforms two of the most recent state-of-the-art transformer-based methods. Finally, a comparison between the attention maps generated by the MaskHIT model with pathologist's annotations indicates that the model can accurately identify clinically relevant histological structures in each task.

Deep learning has been effective for histology image analysis in digital pathology. However, many current deep learning approaches require large, strongly- or weakly-labeled images and regions of interest, which can be time-consuming and resource-intensive to obtain. To address this challenge, we present HistoPerm, a view generation method for representation learning using joint embedding architectures that enhances representation learning for histology images. HistoPerm permutes augmented views of patches extracted from whole-slide histology images to improve classification performance. We evaluated the effectiveness of HistoPerm on two histology image datasets for Celiac disease and Renal Cell Carcinoma, using three widely used joint embedding architecture-based representation learning methods: BYOL, SimCLR, and VICReg. Our results show that HistoPerm consistently improves patch- and slide-level classification performance in terms of accuracy, F1-score, and AUC. Specifically, for patch-level classification accuracy on the Celiac disease dataset, HistoPerm boosts BYOL and VICReg by 8% and SimCLR by 3%. On the Renal Cell Carcinoma dataset, patch-level classification accuracy is increased by 2% for BYOL and VICReg, and by 1% for SimCLR. In addition, on the Celiac disease dataset, models with HistoPerm outperform the fully-supervised baseline model by 6%, 5%, and 2% for BYOL, SimCLR, and VICReg, respectively. For the Renal Cell Carcinoma dataset, HistoPerm lowers the classification accuracy gap for the models up to 10% relative to the fully-supervised baseline. These findings suggest that HistoPerm can be a valuable tool for improving representation learning of histopathology features when access to labeled data is limited and can lead to whole-slide classification results that are comparable to or superior to fully-supervised methods.

Machine learning (ML) models have been applied to a wide range of natural language processing (NLP) tasks in recent years. In addition to making accurate decisions, the necessity of understanding how models make their decisions has become apparent in many applications. To that end, many interpretability methods that help explain the decision processes of ML models have been developed. Yet, there currently exists no widely-accepted metric to evaluate the quality of explanations generated by these methods. As a result, there currently is no standard way of measuring to what degree an interpretability method achieves an intended objective. Moreover, there is no accepted standard of performance by which we can compare and rank the current existing interpretability methods. In this paper, we propose a novel metric for quantifying the quality of explanations generated by interpretability methods. We compute the metric on three NLP tasks using six interpretability methods and present our results.

Artificial intelligence, particularly through recent advancements in deep learning, has achieved exceptional performances in many tasks in fields such as natural language processing and computer vision. In addition to desirable evaluation metrics, a high level of interpretability is often required for these models to be reliably utilized. Therefore, explanations that offer insight into the process by which a model maps its inputs onto its outputs are much sought-after. Unfortunately, the current black box nature of machine learning models is still an unresolved issue and this very nature prevents researchers from learning and providing explicative descriptions for a model's behavior and final predictions. In this work, we propose a novel framework utilizing Adversarial Inverse Reinforcement Learning that can provide global explanations for decisions made by a Reinforcement Learning model and capture intuitive tendencies that the model follows by summarizing the model's decision-making process., Comment: Paper accepted to ICPR 2022

The classification of histopathology images fundamentally differs from traditional image classification tasks because histopathology images naturally exhibit a range of diagnostic features, resulting in a diverse range of annotator agreement levels. However, examples with high annotator disagreement are often either assigned the majority label or discarded entirely when training histopathology image classifiers. This widespread practice often yields classifiers that do not account for example difficulty and exhibit poor model calibration. In this paper, we ask: can we improve model calibration by endowing histopathology image classifiers with inductive biases about example difficulty? We propose several label smoothing methods that utilize per-image annotator agreement. Though our methods are simple, we find that they substantially improve model calibration, while maintaining (or even improving) accuracy. For colorectal polyp classification, a common yet challenging task in gastrointestinal pathology, we find that our proposed agreement-aware label smoothing methods reduce calibration error by almost 70%. Moreover, we find that using model confidence as a proxy for annotator agreement also improves calibration and accuracy, suggesting that datasets without multiple annotators can still benefit from our proposed label smoothing methods via our proposed confidence-aware label smoothing methods. Given the importance of calibration (especially in histopathology image analysis), the improvements from our proposed techniques merit further exploration and potential implementation in other histopathology image classification tasks.

In pathology, whole-slide images (WSI) based survival prediction has attracted increasing interest. However, given the large size of WSIs and the lack of pathologist annotations, extracting the prognostic information from WSIs remains a challenging task. Previous studies have used multiple instance learning approaches to combine the information from multiple randomly sampled patches, but different visual patterns may contribute differently to prognosis prediction. In this study, we developed a multi-head attention approach to focus on various parts of a tumor slide, for more comprehensive information extraction from WSIs. We evaluated our approach on four cancer types from The Cancer Genome Atlas database. Our model achieved an average c-index of 0.640, outperforming two existing state-of-the-art approaches for WSI-based survival prediction, which have an average c-index of 0.603 and 0.619 on these datasets. Visualization of our attention maps reveals each attention head focuses synergistically on different morphological patterns.

With the rise of deep learning, there has been increased interest in using neural networks for histopathology image analysis, a field that investigates the properties of biopsy or resected specimens traditionally manually examined under a microscope by pathologists. However, challenges such as limited data, costly annotation, and processing high-resolution and variable-size images make it difficult to quickly iterate over model designs. Throughout scientific history, many significant research directions have leveraged small-scale experimental setups as petri dishes to efficiently evaluate exploratory ideas. In this paper, we introduce a minimalist histopathology image analysis dataset (MHIST), an analogous petri dish for histopathology image analysis. MHIST is a binary classification dataset of 3,152 fixed-size images of colorectal polyps, each with a gold-standard label determined by the majority vote of seven board-certified gastrointestinal pathologists and annotator agreement level. MHIST occupies less than 400 MB of disk space, and a ResNet-18 baseline can be trained to convergence on MHIST in just 6 minutes using 3.5 GB of memory on a NVIDIA RTX 3090. As example use cases, we use MHIST to study natural questions such as how dataset size, network depth, transfer learning, and high-disagreement examples affect model performance. By introducing MHIST, we hope to not only help facilitate the work of current histopathology imaging researchers, but also make the field more-accessible to the general community. Our dataset is available at https://bmirds.github.io/MHIST., Comment: In proceedings of Artificial Intelligence in Medicine (AIME) 2021

Developing deep learning models to analyze histology images has been computationally challenging, as the massive size of the images causes excessive strain on all parts of the computing pipeline. This paper proposes a novel deep learning-based methodology for improving the computational efficiency of histology image classification. The proposed approach is robust when used with images that have reduced input resolution and can be trained effectively with limited labeled data. Pre-trained on the original high-resolution (HR) images, our method uses knowledge distillation (KD) to transfer learned knowledge from a teacher model to a student model trained on the same images at a much lower resolution. To address the lack of large-scale labeled histology image datasets, we perform KD in a self-supervised manner. We evaluate our approach on two histology image datasets associated with celiac disease (CD) and lung adenocarcinoma (LUAD). Our results show that a combination of KD and self-supervision allows the student model to approach, and in some cases, surpass the classification accuracy of the teacher, while being much more efficient. Additionally, we observe an increase in student classification performance as the size of the unlabeled dataset increases, indicating that there is potential to scale further. For the CD data, our model outperforms the HR teacher model, while needing 4 times fewer computations. For the LUAD data, our student model results at 1.25x magnification are within 3% of the teacher model at 10x magnification, with a 64 times computational cost reduction. Moreover, our CD outcomes benefit from performance scaling with the use of more unlabeled data. For 0.625x magnification, using unlabeled data improves accuracy by 4% over the baseline. Thus, our method can improve the feasibility of deep learning solutions for digital pathology with standard computational hardware.

Renal cell carcinoma (RCC) is the most common renal cancer in adults. The histopathologic classification of RCC is essential for diagnosis, prognosis, and management of patients. Reorganization and classification of complex histologic patterns of RCC on biopsy and surgical resection slides under a microscope remains a heavily specialized, error-prone, and time-consuming task for pathologists. In this study, we developed a deep neural network model that can accurately classify digitized surgical resection slides and biopsy slides into five related classes: clear cell RCC, papillary RCC, chromophobe RCC, renal oncocytoma, and normal. In addition to the whole-slide classification pipeline, we visualized the identified indicative regions and features on slides for classification by reprocessing patch-level classification results to ensure the explainability of our diagnostic model. We evaluated our model on independent test sets of 78 surgical resection whole slides and 79 biopsy slides from our tertiary medical institution, and 69 randomly selected surgical resection slides from The Cancer Genome Atlas (TCGA) database. The average area under the curve (AUC) of our classifier on the internal resection slides, internal biopsy slides, and external TCGA slides is 0.98, 0.98 and 0.99, respectively. Our results suggest that the high generalizability of our approach across different data sources and specimen types. More importantly, our model has the potential to assist pathologists by (1) automatically pre-screening slides to reduce false-negative cases, (2) highlighting regions of importance on digitized slides to accelerate diagnosis, and (3) providing objective and accurate diagnosis as the second opinion.

Background: Deep learning has great potential to assist with detecting and triaging critical findings such as pneumoperitoneum on medical images. To be clinically useful, the performance of this technology still needs to be validated for generalizability across different types of imaging systems. Materials and Methods: This retrospective study included 1,287 chest X-ray images of patients who underwent initial chest radiography at 13 different hospitals between 2011 and 2019. The chest X-ray images were labelled independently by four radiologist experts as positive or negative for pneumoperitoneum. State-of-the-art deep learning models (ResNet101, InceptionV3, DenseNet161, and ResNeXt101) were trained on a subset of this dataset, and the automated classification performance was evaluated on the rest of the dataset by measuring the AUC, sensitivity, and specificity for each model. Furthermore, the generalizability of these deep learning models was assessed by stratifying the test dataset according to the type of the utilized imaging systems. Results: All deep learning models performed well for identifying radiographs with pneumoperitoneum, while DenseNet161 achieved the highest AUC of 95.7%, Specificity of 89.9%, and Sensitivity of 91.6%. DenseNet161 model was able to accurately classify radiographs from different imaging systems (Accuracy: 90.8%), while it was trained on images captured from a specific imaging system from a single institution. This result suggests the generalizability of our model for learning salient features in chest X-ray images to detect pneumoperitoneum, independent of the imaging system., Comment: 21 Pages, 4 Tables and 6 Figures

There has been a substantial amount of research involving computer methods and technology for the detection and recognition of diabetic foot ulcers (DFUs), but there is a lack of systematic comparisons of state-of-the-art deep learning object detection frameworks applied to this problem. DFUC2020 provided participants with a comprehensive dataset consisting of 2,000 images for training and 2,000 images for testing. This paper summarises the results of DFUC2020 by comparing the deep learning-based algorithms proposed by the winning teams: Faster R-CNN, three variants of Faster R-CNN and an ensemble method; YOLOv3; YOLOv5; EfficientDet; and a new Cascade Attention Network. For each deep learning method, we provide a detailed description of model architecture, parameter settings for training and additional stages including pre-processing, data augmentation and post-processing. We provide a comprehensive evaluation for each method. All the methods required a data augmentation stage to increase the number of images available for training and a post-processing stage to remove false positives. The best performance was obtained from Deformable Convolution, a variant of Faster R-CNN, with a mean average precision (mAP) of 0.6940 and an F1-Score of 0.7434. Finally, we demonstrate that the ensemble method based on different deep learning methods can enhanced the F1-Score but not the mAP., Comment: 19 pages, 18 figures, 10 tables

Applying curriculum learning requires both a range of difficulty in data and a method for determining the difficulty of examples. In many tasks, however, satisfying these requirements can be a formidable challenge. In this paper, we contend that histopathology image classification is a compelling use case for curriculum learning. Based on the nature of histopathology images, a range of difficulty inherently exists among examples, and, since medical datasets are often labeled by multiple annotators, annotator agreement can be used as a natural proxy for the difficulty of a given example. Hence, we propose a simple curriculum learning method that trains on progressively-harder images as determined by annotator agreement. We evaluate our hypothesis on the challenging and clinically-important task of colorectal polyp classification. Whereas vanilla training achieves an AUC of 83.7% for this task, a model trained with our proposed curriculum learning approach achieves an AUC of 88.2%, an improvement of 4.5%. Our work aims to inspire researchers to think more creatively and rigorously when choosing contexts for applying curriculum learning.

Diabetic Foot Ulcers (DFU) that affect the lower extremities are a major complication of diabetes. Each year, more than 1 million diabetic patients undergo amputation due to failure to recognize DFU and get the proper treatment from clinicians. There is an urgent need to use a CAD system for the detection of DFU. In this paper, we propose using deep learning methods (EfficientDet Architectures) for the detection of DFU in the DFUC2020 challenge dataset, which consists of 4,500 DFU images. We further refined the EfficientDet architecture to avoid false negative and false positive predictions. The code for this method is available at https://github.com/Manugoyal12345/Yet-Another-EfficientDet-Pytorch., Comment: 8 Pages and DFUC Challenge

The unique nature of histopathology images opens the door to domain-specific formulations of image translation models. We propose a difficulty translation model that modifies colorectal histopathology images to be more challenging to classify. Our model comprises a scorer, which provides an output confidence to measure the difficulty of images, and an image translator, which learns to translate images from easy-to-classify to hard-to-classify using a training set defined by the scorer. We present three findings. First, generated images were indeed harder to classify for both human pathologists and machine learning classifiers than their corresponding source images. Second, image classifiers trained with generated images as augmented data performed better on both easy and hard images from an independent test set. Finally, human annotator agreement and our model's measure of difficulty correlated strongly, implying that for future work requiring human annotator agreement, the confidence score of a machine learning classifier could be used as a proxy., Comment: Accepted to 2020 Artificial Intelligence in Medicine (AIME) conference. Invited for long oral presentation

Objective: Currently, a major limitation for natural language processing (NLP) analyses in clinical applications is that a concept can be referenced in various forms across different texts. This paper introduces Multi-Ontology Refined Embeddings (MORE), a novel hybrid framework for incorporating domain knowledge from multiple ontologies into a distributional semantic model, learned from a corpus of clinical text. Materials and Methods: We use the RadCore and MIMIC-III free-text datasets for the corpus-based component of MORE. For the ontology-based part, we use the Medical Subject Headings (MeSH) ontology and three state-of-the-art ontology-based similarity measures. In our approach, we propose a new learning objective, modified from the Sigmoid cross-entropy objective function. Results and Discussion: We evaluate the quality of the generated word embeddings using two established datasets of semantic similarities among biomedical concept pairs. On the first dataset with 29 concept pairs, with the similarity scores established by physicians and medical coders, MORE's similarity scores have the highest combined correlation (0.633), which is 5.0% higher than that of the baseline model and 12.4% higher than that of the best ontology-based similarity measure.On the second dataset with 449 concept pairs, MORE's similarity scores have a correlation of 0.481, with the average of four medical residents' similarity ratings, and that outperforms the skip-gram model by 8.1% and the best ontology measure by 6.9%.

Machine learning methods have recently achieved high-performance in biomedical text analysis. However, a major bottleneck in the widespread application of these methods is obtaining the required large amounts of annotated training data, which is resource intensive and time consuming. Recent progress in self-supervised learning has shown promise in leveraging large text corpora without explicit annotations. In this work, we built a self-supervised contextual language representation model using BERT, a deep bidirectional transformer architecture, to identify radiology reports requiring prompt communication to the referring physicians. We pre-trained the BERT model on a large unlabeled corpus of radiology reports and used the resulting contextual representations in a final text classifier for communication urgency. Our model achieved a precision of 97.0%, recall of 93.3%, and F-measure of 95.1% on an independent test set in identifying radiology reports for prompt communication, and significantly outperformed the previous state-of-the-art model based on word2vec representations., Comment: Accepted in AMIA 2020 Informatics Summit

Recently, there has been great interest in developing Artificial Intelligence (AI) enabled computer-aided diagnostics solutions for the diagnosis of skin cancer. With the increasing incidence of skin cancers, low awareness among a growing population, and a lack of adequate clinical expertise and services, there is an immediate need for AI systems to assist clinicians in this domain. A large number of skin lesion datasets are available publicly, and researchers have developed AI-based image classification solutions, particularly deep learning algorithms, to distinguish malignant skin lesions from benign lesions in different image modalities such as dermoscopic, clinical, and histopathology images. Despite the various claims of AI systems achieving higher accuracy than dermatologists in the classification of different skin lesions, these AI systems are still in the very early stages of clinical application in terms of being ready to aid clinicians in the diagnosis of skin cancers. In this review, we discuss advancements in the digital image-based AI solutions for the diagnosis of skin cancer, along with some challenges and future opportunities to improve these AI systems to support dermatologists and enhance their ability to diagnose skin cancer., Comment: AI Skin Cancer

In this paper, we demonstrate the feasibility and performance of deep residual neural networks for volumetric segmentation of irreversibly damaged brain tissue lesions on T1-weighted MRI scans for chronic stroke patients. A total of 239 T1-weighted MRI scans of chronic ischemic stroke patients from a public dataset were retrospectively analyzed by 3D deep convolutional segmentation models with residual learning, using a novel zoom-in&out strategy. Dice similarity coefficient (DSC), Average symmetric surface distance (ASSD), and Hausdorff distance (HD) of the identified lesions were measured by using the manual tracing of lesions as the reference standard. Bootstrapping was employed for all metrics to estimate 95% confidence intervals. The models were assessed on the test set of 31 scans. The average DSC was 0.64 (0.51-0.76) with a median of 0.78. ASSD and HD were 3.6 mm (1.7-6.2 mm) and 20.4 mm (10.0-33.3 mm), respectively. To the best of our knowledge, this performance is the highest achieved on this public dataset. The latest deep learning architecture and techniques were applied for 3D segmentation on MRI scans and demonstrated to be effective for volumetric segmentation of chronic ischemic stroke lesions.

Identifying patient characteristics that influence the rate of colorectal polyp recurrence can provide important insights into which patients are at higher risk for recurrence. We used natural language processing to extract polyp morphological characteristics from 953 polyp-presenting patients' electronic medical records. We used subsequent colonoscopy reports to examine how the time to polyp recurrence (731 patients experienced recurrence) is influenced by these characteristics as well as anthropometric features using Kaplan-Meier curves, Cox proportional hazards modeling, and random survival forest models. We found that the rate of recurrence differed significantly by polyp size, number, and location and patient smoking status. Additionally, right-sided colon polyps increased recurrence risk by 30% compared to left-sided polyps. History of tobacco use increased polyp recurrence risk by 20% compared to never-users. A random survival forest model showed an AUC of 0.65 and identified several other predictive variables, which can inform development of personalized polyp surveillance plans., Comment: Accepted in AMIA 2020 Informatics Summit

We present an image translation approach to generate augmented data for mitigating data imbalances in a dataset of histopathology images of colorectal polyps, adenomatous tumors that can lead to colorectal cancer if left untreated. By applying cycle-consistent generative adversarial networks (CycleGANs) to a source domain of normal colonic mucosa images, we generate synthetic colorectal polyp images that belong to diagnostically less common polyp classes. Generated images maintain the general structure of their source image but exhibit adenomatous features that can be enhanced with our proposed filtration module, called Path-Rank-Filter. We evaluate the quality of generated images through Turing tests with four gastrointestinal pathologists, finding that at least two of the four pathologists could not identify generated images at a statistically significant level. Finally, we demonstrate that using CycleGAN-generated images to augment training data improves the AUC of a convolutional neural network for detecting sessile serrated adenomas by over 10%, suggesting that our approach might warrant further research for other histopathology image classification tasks., Comment: NeurIPS 2019 Machine Learning for Health Workshop Full Paper (19/111 accepted papers = 17% acceptance rate)

Histological classification of colorectal polyps plays a critical role in both screening for colorectal cancer and care of affected patients. An accurate and automated algorithm for the classification of colorectal polyps on digitized histopathology slides could benefit clinicians and patients. Evaluate the performance and assess the generalizability of a deep neural network for colorectal polyp classification on histopathology slide images using a multi-institutional dataset. In this study, we developed a deep neural network for classification of four major colorectal polyp types, tubular adenoma, tubulovillous/villous adenoma, hyperplastic polyp, and sessile serrated adenoma, based on digitized histopathology slides from our institution, Dartmouth-Hitchcock Medical Center (DHMC), in New Hampshire. We evaluated the deep neural network on an internal dataset of 157 histopathology slide images from DHMC, as well as on an external dataset of 238 histopathology slide images from 24 different institutions spanning 13 states in the United States. We measured accuracy, sensitivity, and specificity of our model in this evaluation and compared its performance to local pathologists' diagnoses at the point-of-care retrieved from corresponding pathology laboratories. For the internal evaluation, the deep neural network had a mean accuracy of 93.5% (95% CI 89.6%-97.4%), compared with local pathologists' accuracy of 91.4% (95% CI 87.0%-95.8%). On the external test set, the deep neural network achieved an accuracy of 87.0% (95% CI 82.7%-91.3%), comparable with local pathologists' accuracy of 86.6% (95% CI 82.3%-90.9%). If confirmed in clinical settings, our model could assist pathologists by improving the diagnostic efficiency, reproducibility, and accuracy of colorectal cancer screenings.

Classification of histologic patterns in lung adenocarcinoma is critical for determining tumor grade and treatment for patients. However, this task is often challenging due to the heterogeneous nature of lung adenocarcinoma and the subjective criteria for evaluation. In this study, we propose a deep learning model that automatically classifies the histologic patterns of lung adenocarcinoma on surgical resection slides. Our model uses a convolutional neural network to identify regions of neoplastic cells, then aggregates those classifications to infer predominant and minor histologic patterns for any given whole-slide image. We evaluated our model on an independent set of 143 whole-slide images. It achieved a kappa score of 0.525 and an agreement of 66.6% with three pathologists for classifying the predominant patterns, slightly higher than the inter-pathologist kappa score of 0.485 and agreement of 62.7% on this test set. All evaluation metrics for our model and the three pathologists were within 95% confidence intervals of agreement. If confirmed in clinical practice, our model can assist pathologists in improving classification of lung adenocarcinoma patterns by automatically pre-screening and highlighting cancerous regions prior to review. Our approach can be generalized to any whole-slide image classification task, and code is made publicly available at https://github.com/BMIRDS/deepslide.

Celiac disease prevalence and diagnosis have increased substantially in recent years. The current gold standard for celiac disease confirmation is visual examination of duodenal mucosal biopsies. An accurate computer-aided biopsy analysis system using deep learning can help pathologists diagnose celiac disease more efficiently. In this study, we trained a deep learning model to detect celiac disease on duodenal biopsy images. Our model uses a state-of-the-art residual convolutional neural network to evaluate patches of duodenal tissue and then aggregates those predictions for whole-slide classification. We tested the model on an independent set of 212 images and evaluated its classification results against reference standards established by pathologists. Our model identified celiac disease, normal tissue, and nonspecific duodenitis with accuracies of 95.3%, 91.0%, and 89.2%, respectively. The area under the receiver operating characteristic curve was greater than 0.95 for all classes. We have developed an automated biopsy analysis system that achieves high performance in detecting celiac disease on biopsy slides. Our system can highlight areas of interest and provide preliminary classification of duodenal biopsies prior to review by pathologists. This technology has great potential for improving the accuracy and efficiency of celiac disease diagnosis., Comment: Accepted in Journal of Pathology Informatics

Deep learning-based methods, such as the sliding window approach for cropped-image classification and heuristic aggregation for whole-slide inference, for analyzing histological patterns in high-resolution microscopy images have shown promising results. These approaches, however, require a laborious annotation process and are fragmented. This diagnostic study collected deidentified high-resolution histological images (N = 379) for training a new model composed of a convolutional neural network and a grid-based attention network, trainable without region-of-interest annotations. Histological images of patients who underwent endoscopic esophagus and gastroesophageal junction mucosal biopsy between January 1, 2016, and December 31, 2018, at Dartmouth-Hitchcock Medical Center (Lebanon, New Hampshire) were collected. The method achieved a mean accuracy of 0.83 in classifying 123 test images. These results were comparable with or better than the performance from the current state-of-the-art sliding window approach, which was trained with regions of interest. Results of this study suggest that the proposed attention-based deep neural network framework for Barrett esophagus and esophageal adenocarcinoma detection is important because it is based solely on tissue-level annotations, unlike existing methods that are based on regions of interest. This new model is expected to open avenues for applying deep learning to digital pathology., Comment: Accepted for publication at the Journal of JAMA Network Open

Rapid growth in the development of medical imaging analysis technology has been propelled by the great interest in improving computer-aided diagnosis and detection (CAD) systems for three popular image visualization tasks: classification, segmentation, and Region of Interest (ROI) detection. However, a limited number of datasets with ground truth annotations are available for developing segmentation and ROI detection of lesions, as expert annotations are laborious and expensive. Detecting the ROI is vital to locate lesions accurately. In this paper, we propose the use of two deep object detection meta-architectures (Faster R-CNN Inception-V2 and SSD Inception-V2) to develop robust ROI detection of skin lesions in dermoscopic datasets (2017 ISIC Challenge, PH2, and HAM10000), and compared the performance with state-of-the-art segmentation algorithm (DeeplabV3+). To further demonstrate the potential of our work, we built a smartphone application for real-time automated detection of skin lesions based on this methodology. In addition, we developed an automated natural data-augmentation method from ROI detection to produce augmented copies of dermoscopic images, as a pre-processing step in the segmentation of skin lesions to further improve the performance of the current state-of-the-art deep learning algorithm. Our proposed ROI detection has the potential to more appropriately streamline dermatology referrals and reduce unnecessary biopsies in the diagnosis of skin cancer., Comment: Natural Augmentation

Melanoma is clinically difficult to distinguish from common benign skin lesions, particularly melanocytic naevus and seborrhoeic keratosis. The dermoscopic appearance of these lesions has huge intra-class variations and high inter-class visual similarities. Most current research is focusing on single-class segmentation irrespective of classes of skin lesions. In this work, we evaluate the performance of deep learning on multi-class segmentation of ISIC-2017 challenge dataset, which consists of 2,750 dermoscopic images. We propose an end-to-end solution using fully convolutional networks (FCNs) for multi-class semantic segmentation to automatically segment the melanoma, seborrhoeic keratosis and naevus. To improve the performance of FCNs, transfer learning and a hybrid loss function are used. We evaluate the performance of the deep learning segmentation methods for multi-class segmentation and lesion diagnosis (with post-processing method) on the testing set of the ISIC-2017 challenge dataset. The results showed that the two-tier level transfer learning FCN-8s achieved the overall best result with \textit{Dice} score of 78.5% in a naevus category, 65.3% in melanoma, and 55.7% in seborrhoeic keratosis in multi-class segmentation and Accuracy of 84.62% for recognition of melanoma in lesion diagnosis., Comment: Comp2clinic workshop at Biostec 2020

Histopathological characterization of colorectal polyps is an important principle for determining the risk of colorectal cancer and future rates of surveillance for patients. This characterization is time-intensive, requires years of specialized training, and suffers from significant inter-observer and intra-observer variability. In this work, we built an automatic image-understanding method that can accurately classify different types of colorectal polyps in whole-slide histology images to help pathologists with histopathological characterization and diagnosis of colorectal polyps. The proposed image-understanding method is based on deep-learning techniques, which rely on numerous levels of abstraction for data representation and have shown state-of-the-art results for various image analysis tasks. Our image-understanding method covers all five polyp types (hyperplastic polyp, sessile serrated polyp, traditional serrated adenoma, tubular adenoma, and tubulovillous/villous adenoma) that are included in the US multi-society task force guidelines for colorectal cancer risk assessment and surveillance, and encompasses the most common occurrences of colorectal polyps. Our evaluation on 239 independent test samples shows our proposed method can identify the types of colorectal polyps in whole-slide images with a high efficacy (accuracy: 93.0%, precision: 89.7%, recall: 88.3%, F1 score: 88.8%). The presented method in this paper can reduce the cognitive burden on pathologists and improve their accuracy and efficiency in histopathological characterization of colorectal polyps, and in subsequent risk assessment and follow-up recommendations.