Tizhoosh, Hamid R.

Steatohepatitis with diverse etiologies is the most common histological manifestation in patients with liver disease. However, there are currently no specific histopathological features pathognomonic for metabolic dysfunction–associated steatotic liver disease, alcohol-associated liver disease, or metabolic dysfunction–associated steatotic liver disease with increased alcohol intake. Digitizing traditional pathology slides has created an emerging field of digital pathology, allowing for easier access, storage, sharing, and analysis of whole-slide images. Artificial intelligence (AI) algorithms have been developed for whole-slide images to enhance the accuracy and speed of the histological interpretation of steatohepatitis and are currently employed in biomarker development. Spatial biology is a novel field that enables investigators to map gene and protein expression within a specific region of interest on liver histological sections, examine disease heterogeneity within tissues, and understand the relationship between molecular changes and distinct tissue morphology. Here, we review the utility of digital pathology (using linear and nonlinear microscopy) augmented with AI analysis to improve the accuracy of histological interpretation. We will also discuss the spatial omics landscape with special emphasis on the strengths and limitations of established spatial transcriptomics and proteomics technologies and their application in steatohepatitis. We then highlight the power of multimodal integration of digital pathology augmented by machine learning (ML)algorithms with spatial biology. The review concludes with a discussion of the current gaps in knowledge, the limitations and premises of these tools and technologies, and the areas of future research.

Abstract The exponential growth of data across various medical domains has generated a substantial demand for techniques to analyze multimodal big data. This demand is particularly pronounced in fields such as computational pathology due to the diverse nature of the tissue. Cross-modal retrieval aims to identify a common latent space where different modalities, such as image-text pairs, exhibit close alignment. The primary challenge, however, often lies in the representation of tissue features. While language models can be trained relatively easily, visual models frequently struggle due to the scarcity of labeled data. To address this issue, the innovative concept of harmonization has been introduced, extending the learning scheme distillation without supervision, known as DINO. The harmonization of scale refines the DINO paradigm through a novel patching approach, overcoming the complexities posed by gigapixel whole slide images in digital pathology. Experiments conducted on diverse datasets have demonstrated that the proposed approach significantly enhances cross-modal retrieval in tissue imaging. Moreover, it exhibits vast potential for other fields that rely on gigapixel imaging.

Abstract Patching whole slide images (WSIs) is an important task in computational pathology. While most of the are designed to classify or detect the presence of pathological lesions in a WSI, the confounding role and redundant nature of normal histology are generally overlooked. In this paper, we propose and validate the concept of an “atlas of normal tissue” solely using samples of WSIs obtained from normal biopsies. Such atlases can be employed to eliminate normal fragments of tissue samples and hence increase the representativeness the remaining patches. We tested our proposed method by establishing a normal atlas using 107 normal skin WSIs and demonstrated how established search engines like Yottixel can be improved. We used 553 WSIs of cutaneous squamous cell carcinoma to demonstrate the advantage. We also validated our method applied to an external dataset of 451 breast WSIs. The number of selected WSI patches was reduced by 30% to 50% after utilizing the proposed normal atlas while maintaining the same indexing and search performance in leave-one-patient-out validation for both datasets. We show that the proposed concept of establishing and using a normal atlas shows promise for unsupervised selection of the most representative patches of the abnormal WSI patches.

AbstractAn increasing number of machine learning applications are being developed and applied to digital pathology, including hematopathology. The goal of these modern computerized tools is often to support diagnostic workflows by extracting and summarizing information from multiple data sources, including digital images of human tissue. Hematopathology is inherently multimodal and can serve as an ideal case study for machine learning applications. However, hematopathology also poses unique challenges compared to other pathology subspecialities when applying machine learning approaches. By modeling the pathologist workflow and thinking process, machine learning algorithms may be designed to address practical and tangible problems in hematopathology. In this article, we discuss the current trends in machine learning in hematopathology. We review currently available machine learning enabled medical devices supporting hematopathology workflows. We then explore current machine learning research trends of the field with a focus on bone marrow cytology and histopathology, and how adoption of new machine learning tools may be enabled through the transition to digital pathology.

Abstract Appearing traces of bias in deep networks is a serious issue that can play a significant role in ethics and generalization. Recent studies report that the deep features extracted from the histopathology images of The Cancer Genome Atlas (TCGA), the largest publicly available archive of 11,000 patients covering 25 organs and 32 cancer subtypes, are surprisingly able to accurately classify the whole slide images (WSIs) based on their acquisition site. This is clear evidence that the utilized Deep Neural Networks (DNNs) unexpectedly detect the specific patterns of the source site rather than histomorphologic patterns, biased behaviour resulting in degraded generalization. This observation motivated us to propose a method to alleviate the destructive impact of hospital bias through a novel feature selection process. To this effect, we have proposed an evolutionary strategy select a small set of optimal features to not only accurately represent the histological patterns of tissue samples but also to eliminate the features leading to internal bias toward the institution. The performance of the proposed method has been assessed using the features extracted from TCGA images made available by NIH (National Institute of Health). The selected features extracted by a state-of-the-art network trained on TCGA images (i.e., the KimiaNet), considerably decreased the institutional bias. The proposed scheme is not limited to DNNs and/or specific types of biases; it can be employed to reduce various kinds of bias in a much more comprehensive range of data-driven feature extraction models. The conducted experiments, the external validation in specific, clearly demonstrate that the bias cannot be fully controlled just during training a model. Therefore, a feature selection for downstream tasks plays a crucial role in significantly reducing the bias.