Search

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.

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.

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.

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.

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

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.

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

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.