Slide Images Research Articles

Whole slide image based prognosis prediction in rectal cancer using unsupervised artificial intelligence

BackgroundRectal cancer is a common cancer worldwide and lacks effective prognostic markers. The development of prognostic markers by computational pathology methods has attracted increasing attention. This paper aims to construct a prognostic signature from whole slide images for predicting progression-free survival (PFS) of rectal cancer through an unsupervised artificial intelligence algorithm.MethodsA total of 238 patients with rectal cancer from two datasets were collected for the development and validation of the prognostic signature. A tumor detection model was built by transfer learning. Then, on the basis of the tumor patches recognized by the tumor detection model, a convolutional autoencoder model was built for decoding the tumor patches into deep latent features. Next, on the basis of the deep latent features, the tumor patches were divided into different clusters. The cluster number and other hyperparameters were optimized by a nested cross-validation method. The percentage of each cluster from the patient’s tumor patches, which is hereafter called PCF, was calculated for prognostic signature construction. The prognostic signature was constructed by Cox proportional hazard regression with L2 regularization. Finally, bioinformatic analysis was performed to explore the underlying biological mechanisms of the PCFs.ResultsThe accuracy of the tumor detection model in distinguishing tumor patches from non-tumor patches achieved 99.3%. The optimal cluster number was determined to be 9. Therfore, 9 PCFs were calculated to construct the prognostic signature. The prognostic signature achieved a concordance index of 0.701 in the validation cohort. The Kaplan-Meier survival curves showed the prognostic signature had good risk stratification ability. Through the bioinformatic analysis, several PCF-associated genes were identified. These genes were enriched in various gene ontology terms.ConclusionThe developed prognostic signature can effectively predict PFS in patients with rectal cancer and exploration of the underlying biological mechanisms may help to promote its clinical translation.

Deployment of a Machine Learning Algorithm in a Real-World Cohort for Quality Control Monitoring of Human Epidermal Growth Factor-2-Stained Clinical Specimens in Breast Cancer.

Precise determination of biomarker status is necessary for clinical trial enrollment and endpoint analyses, as well as for optimal treatment determination in real-world practice. However, variabilities may be introduced into this process due to the processing of clinical specimens by different laboratories and assessment by distinct pathologists. Machine learning tools have the potential to minimize inconsistencies, although their use is not presently widespread. To assess the applicability of machine learning to the quality control process for biomarker scoring in oncology, we developed and validated an automated machine learning model to be applied as a quality control tool for monitoring the assessment of human epidermal growth factor-2 (HER2). The model was trained using whole slide images from multiple sources to quantify HER2 expression and measure immunohistochemistry stain intensity, tumor area, and the presence of artifacts or ductal carcinoma in situ across breast cancer phenotypes. The quality control tool was deployed in a real-world cohort of HER2-stained breast cancer sample images collected from routine diagnostic practice to evaluate trends in HER2 testing quality indicators and between pathology laboratories. Automated image analysis for HER2 scoring is consistent and reliable using this algorithm. Deployment of the HER2 quality control tool across 3 clinical laboratories revealed interlaboratory variability in HER2 scoring and inconsistencies in data reporting. These results support the future incorporation of quality control algorithms for real-time monitoring of clinical laboratories contributing to clinical trials in oncology and in the real-world setting of HER2 immunohistochemistry testing in local clinical laboratories and hospitals.

Nuclear morphological characterisation of lobular carcinoma variants: a morphometric study.

Lobular carcinoma (LC) of the breast exhibits diverse morphology and clinical behaviour. The pleomorphic variant (pLC) displays distinct cytonuclear features and aggressiveness compared to the classic variant (cLC). However, diagnosing pLC remains subjective. This study aims to refine LC's cytonuclear features, focusing on pLC. Whole slide images of 59 LCs, including both in situ (LCIS) and invasive (ILC) lesions, were analysed. Nuclear measurements, including nuclear size and variability, were scored using QuPath imageanalysis software. For comparison, selected features were scored in normal cells (n = 10) and pleomorphism score-matched invasive breast carcinoma (IBC) of NST type (n = 33). Additional visual assessment of the pleomorphic ILC (pILC) cohort (n = 90) was conducted for cytomorphological features characterisation. pILC demonstrated larger nuclear area and higher nuclear variability with abundance of cytoplasm than cILC. Compared to lymphocytes, pILC demonstrated a median area ranging from 2.7 to 4.7 times larger. Cut-off values for differentiating pILC from other ILC subtypes included median nuclear area > 48.2 μm2 and interquartile range (IQR) > 19.4, nuclear perimeter median > 25.2 μm and IQR > 5.3 and maximum diameter > 9.1 μm and IQR > 2.2. Multivariable logistic regression confirmed these parameters as independent predictors of pILC, with the maximum diameter being the most significant (P < 0.001). Visual assessment recognised two pILC subtypes: apocrine and non-apocrine. Apocrine variant showed nuclear roundness, pale vesicular chromatin patterns and prominent nucleoli, while non-apocrine variant exhibited greater nuclear size and shape variation. Objective nuclear measurements, combined with cytoplasmic and architectural features, provide a robust framework for diagnosing LC subtypes, improving diagnostic accuracy and reproducibility.

Mesothelin expression prediction in pancreatic cancer based on multimodal stochastic configuration networks.

Predicting tumor biomarkers with high precision is essential for improving the diagnostic accuracy and developing more effective treatment strategies. This paper proposes a machine learning model that utilizes CT images and biopsy whole slide images (WSI) to classify mesothelin expression levels in pancreatic cancer. By combining multimodal learning and stochastic configuration networks, a radiopathomics mesothelin-prediction system named RPMSNet is developed. The system extracts radiomic and pathomic features from CT images and WSI, respectively, and sends them into stochastic configuration networks for the final prediction. Compared to traditional radiomics or pathomics, this system has the capability to capture more comprehensive image features, providing a multidimensional insight into tissue characteristics. The experiments and analyses demonstrate the accuracy and effectiveness of the system, with an area under the curve of 81.03%, an accuracy of 73.67%, a sensitivity of 71.54%, a precision of 76.78%, and a F1-score of 72.61%, surpassing both single-modality and dual-modality models. RPMSNet highlights its potential for early diagnosis and personalized treatment in precision medicine.

Deep Learning for Automated Segmentation of Basal Cell Carcinoma on Mohs Micrographic Surgery Frozen Section Slides.

Deep learning has been used to classify basal cell carcinoma (BCC) on histopathologic images. Segmentation models, required for localization of tumor on Mohs surgery (MMS) frozen section slides, have yet to reach clinical utility. To train a segmentation model to localize BCC on MMS frozen section slides and to evaluate performance by BCC subtype. The study included 348 fresh frozen tissue slides, scanned as whole slide images, from patients treated with MMS for BCC. BCC foci were manually outlined using the Grand Challenge annotation platform. The data set was divided into 80% for training, 10% for validation, and 10% for the test data set. Segmentation was performed using the Ultralytics YOLOv8 model. Sensitivity was .71 for all tumors, .87 for nodular BCC, .79 for superficial BCC, .74 for micronodular BCC, and .51 for morpheaform and infiltrative BCC. Specificity was .75 for all tumors, .59 for nodular BCC, .58 for superficial BCC, .83 for micronodular BCC, and .74 for morpheaform and infiltrative BCC. This study trained a segmentation model to localize BCC on MMS frozen section slides with reasonably high sensitivity and specificity, and this varied by BCC subtype. More accurate and clinically relevant performance metrics for segmentation studies are needed.

Auxiliary diagnosis of primary bone tumors based on Machine learning model

ObjectiveResearch on auxiliary diagnosis of primary bone tumors can enhance diagnostic accuracy, facilitate early detection, and enable personalized treatment, thereby reducing misdiagnosis and missed cases, ultimately leading to improved patient prognosis and survival rates. In this study, we established a whole slide imaging (WSI) database comprising histopathological samples from all categories of bone tumors and integrated multiple neural network architectures for machine learning models. We then evaluated the accuracy of these models in diagnosing primary bone tumors. MethodsIn this paper, the machine learning model based on the deep convolutional neural network (DC-NN) method was combined with imaging omics analysis to analyze and discuss its clinical value in diagnosing primary bone tumors. In addition, this paper proposed a screening method for differentially expressed genes. Based on the paired T-test method, the process first estimated the tumor purity in the experimental data of each sample case, then assessed the actual gene expression value of the experimental data of each sample case, and finally calculated the optimized paired T-test statistics, and screened differentially expressed genes according to the threshold value. ResultsThe selected model demonstrated excellent diagnostic accuracy in distinguishing between normal and tumor images, with overall accuracy of (99.8 ± 0.4) % for five rounds of testing using the DCNN model and positive and negative predictive values of (100.0 ± 0.0) % and (99.6 ± 0.8) %, respectively. The mean area under each dataset’s curve (AUC) was (0.998 ± 0.004). Further, ten rounds of testing using the DCNN model showed an overall accuracy of (71.2 ± 1.6) % and a substantial positive predictive value of (91.9 ± 8.5) % in distinguishing benign from malignant bone tumors, with an average AUC of (0.62 ± 0.06) across datasets. ConclusionThe deep learning model accurately classifies bone tumor histopathology based on the degree of infiltration, achieving diagnostic performance comparable to that of senior pathologists. These findings affirm the feasibility and effectiveness of histopathological diagnosis in bone tumors, providing a theoretical foundation for the application and advancement of machine learning-assisted histopathological diagnosis in this field.

Exploring the Efficacy of Various CNN Architectures in Diagnosing Oral Cancer from Squamous Cell Carcinoma

Oral cancer can result from mutations in cells located in the lips or mouth. Diagnosing oral cavity squamous cell carcinoma (OCSCC) is particularly challenging, often occurring at advanced stages. To address this, computer-aided diagnosis methods are increasingly being used. In this work, a deep learning-based approach utilizing models such as VGG16, ResNet50, LeNet-5, MobileNetV2, and Inception V3 is presented. NEOR and OCSCC datasets were used for feature extraction, with virtual slide images divided into tiles and classified as normal or squamous cell cancer. Performance metrics like accuracy, F1-score, AUC, precision, and recall were analyzed to determine the prerequisites for optimal CNN performance. The proposed CNN approaches were effective for classifying OCSCC and oral dysplasia, with the highest accuracy of 95.41% achieved using MobileNetV2. Key findingsDeep learning models, particularly MobileNetV2, achieved high classification accuracy (95.41%) for OCSCC.CNN-based methods show promise for early-stage OCSCC and oral dysplasia diagnosis. Performance parameters like precision, recall, and F1-score help optimize CNN model selection for this task.

PHIM-MIL: Multiple instance learning with prototype similarity-guided feature fusion and hard instance mining for whole slide image classification

PHIM-MIL: Multiple instance learning with prototype similarity-guided feature fusion and hard instance mining for whole slide image classification

Breast histopathological imaging using ultra-fast fluorescence confocal microscopy to identify cancer lesions at early stage.

Ultrafast fluorescent confocal microscopy is a hypothetical approach for breast cancer detection because of its potential to achieve instantaneous, high-resolution images of cellular-level tissue features. Traditional approaches such as mammography and biopsy are laborious, invasive, and inefficient; confocal microscopy offers many benefits over these approaches. However, confocal microscopy enables the exact differentiation of malignant cells, the expeditious examination of extensive tissue sections, and the optical sectioning of tissue samples into tiny slices. The primary goal should be to prevent cancer altogether, although detecting it early can help achieve that objective. This research presents a novel Breast Histopathology Convolutional Neural Network (BHCNN) for feature extraction and recursive feature elimination method for selecting the most significant features. The proposed approach utilizes full slide images to identify tissue in regions affected by invasive ductal carcinoma. In addition, a transfer learning approach is employed to enhance the performance and accuracy of the models in detecting breast cancer, while also reducing computation time by modifying the final layer of the proposed model. The results showed that the BHCNN model outperformed other models in terms of accuracy, achieving a testing accuracy of 98.42% and a training accuracy of 99.94%. The confusion matrix results show that the IDC positive (+) class achieved 97.44% accuracy and 2.56% inaccurate results, while the IDC negative (-) class achieved 98.73% accuracy and 1.27% inaccurate results. Furthermore, the model achieved less than 0.05 validation loss. RESEARCH HIGHLIGHTS: The objective is to develop an innovative framework using ultra-fast fluorescence confocal microscopy, particularly for the challenging problem of breast cancer diagnosis. This framework will extract essential features from microscopy and employ a gradient recurrent unit for detection. The proposed research offers significant potential in enhancing medical imaging through the provision of a reliable and resilient system for precise diagnosis of breast cancer, thereby propelling the progression of state-of-the-art medical technology. The most suitable feature was determined using BHRFE optimization techniques after retrieving the features by proposed model. Finally, the features chosen are integrated into a proposed methodology, which is then classified using a GRU deep model. The aforementioned research has significant potential to improve medical imaging by providing a complex and reliable system for precise evaluation of breast cancer, hence advancing the development of cutting-edge medical technology.

A novel AI-based score for assessing the prognostic value of intra-epithelial lymphocytes in oral epithelial dysplasia.

Oral epithelial dysplasia (OED) poses a significant clinical challenge due to its potential for malignant transformation and the lack of reliable prognostic markers. Current OED grading systems do not reliably predict transformation and suffer from considerable observer variability. Recent studies have highlighted that peri-epithelial lymphocytes may play an important role in OED malignant transformation, with indication that intra-epithelial lymphocytes (IELs) may also be important. We propose a novel artificial intelligence (AI) based IEL score from Haematoxylin and Eosin (H&E) stained Whole Slide Images (WSIs) of OED tissue slides. We determine the prognostic value of our IEL score on a digital dataset of 219 OED WSIs (acquired using three different scanners), compared to pathologist-led clinical grading. Our IEL scores demonstrated significant prognostic value (C-index = 0.67, p < 0.001) and were shown to improve both the binary/WHO grading systems in multivariate analyses (p < 0.001). Nuclear analyses confirmed the positive association between higher IEL scores, more severe OED and malignant transformation (p < 0.05). This underscores the potential importance of IELs, and by extension our IEL score, as prognostic indicators in OED. Further validation through prospective multi-centric studies is warranted to confirm the clinical utility of IELs.

Multiple-Instance Learning for thyroid gland disease classification: A hands-on experience

The morphological diagnosis of thyroid gland neoplasms presents a dual challenge: it requires the expertise of highly trained specialists and considerable time, particularly when evaluating multiple whole slide images (WSIs) from a single patient. The integration of artificial intelligence (AI) techniques into the diagnostic workflow is a hot area of research. However, most studies rely on meticulously curated datasets, the preparation of which is both costly and fraught with complexities. This paper investigates the development of machine learning models using weakly-annotated “real-world” data, devoid of the selective preprocessing typical in common research datasets. Our study demonstrates that a Multiple-Instance Learning (MIL) model, trained on a weak patient-level annotations of 1102 patients encompassing 5104 WSIs, successfully discriminates between benign and malignant conditions at the patient level, achieving an average test set F1-Score of 0.85 with a standard deviation of 0.05. This study is, to our knowledge, the first to report findings from an AI model trained on patient-level data without prior labeling refinement. Additionally, we identify potential pitfalls in data quality that could induce model overfitting, such as the inadvertent inclusion of dye used to highlight resection margins, which correlates with the target variable. We also assessed the impact of detailed slide-level versus coarse patient-level annotations on classification accuracy using a smaller, more precisely annotated dataset of 36 laboratory cases (91 WSIs). The results indicate that detailed annotations substantially enhance classification performance in smaller datasets.

Deep learning algorithm on H&E whole slide images to characterize TP53 alterations frequency and spatial distribution in breast cancer

The tumor suppressor TP53 is frequently mutated in hormone receptor-negative, HER2-positive breast cancer (BC), contributing to tumor aggressiveness. Traditional ancillary methods like immunohistochemistry (IHC) to assess TP53 functionality face pre- and post-analytical challenges. This proof-of-concept study employed a deep learning (DL) algorithm to predict TP53 mutational status from H&E-stained whole slide images (WSIs) of BC tissue. Using a pre-trained convolutional neural network, the model identified tumor areas and predicted TP53 mutations with a Dice coefficient score of 0.82. Predictions were validated through IHC and next-generation sequencing (NGS), confirming TP53 aberrant expression in 92 % of the tumor area, closely matching IHC findings (90 %). The DL model exhibited high accuracy in tissue quantification and TP53 status prediction, outperforming traditional methods in terms of precision and efficiency. DL-based approaches offer significant promise for enhancing biomarker testing and precision oncology by reducing intra- and inter-observer variability, but further validation is required to optimize their integration into real-world clinical workflows. This study underscores the potential of DL algorithms to predict key genetic alterations, such as TP53 mutations, in BC. DL-based histopathological analysis represents a valuable tool for improving patient management and tailoring treatment approaches based on molecular biomarker status.

Unveiling the biological side of PET-derived biomarkers: a simulation-based approach applied to PDAC assessment.

Radiomics has revolutionized clinical research by enabling objective measurements of imaging-derived biomarkers. However, the true potential of radiomics necessitates a comprehensive understanding of the biological basis of extracted features to serve as a clinical decision support. In this work, we propose an end-to-end framework for the in silico simulation of [18F]FLT PET imaging process in Pancreatic Ductal Adenocarcinoma, accounting for the biological characterization of tissues (including perfusion and fibrosis) on tracer delivery. We thus establish a direct association between radiomics features and the underlying biological properties of tissues. We considered 4 immunohistochemically stained Whole Slide Images of pancreatic tissue of one healthy control and three patients with PDAC and/or precursor lesions. From marker-specific images, tissue-depending diffusivity properties were estimated and computational domains were built to simulate the [18F]FLT spatial-temporal uptake exploiting Partial Differential Equations and Finite Elements Method. Consequently, we simulated the imaging process obtaining surrogated PET images for the considered patients, and we performed image-derived features extraction from PET images to be mapped with biological properties via correlation estimation. The framework captured the phenotypic differences and generated Time Activity Curves reflecting the underlying tissue composition. Image-derived biomarkers were ranked in view of their association with biological characteristics of the tissue, unveiling their molecular correlative. Moreover, we showed that the proposed pipeline could serve as a digital phantom to optimize the image acquisition for lesion detection. This innovative framework holds the potential to enhance interpretability and reliability of radiomics, fostering the adoption in personalized nuclear medicine and patient care.

Prognostic and predictive value of pathohistological features in gastric cancer and identification of SLITRK4 as a potential biomarker for gastric cancer

The aim of this study was to develop a quantitative feature-based model from histopathologic images to assess the prognosis of patients with gastric cancer. Whole slide image (WSI) images of H&E-stained histologic specimens of gastric cancer patients from The Cancer Genome Atlas were included and randomly assigned to training and test groups in a 7:3 ratio. A systematic preprocessing approach was employed as well as a non-overlapping segmentation method that combined patch-level prediction with a multi-instance learning approach to integrate features across the slide images. Subjects were categorized into high- or low-risk groups based on the median risk score derived from the model, and the significance of this stratification was assessed using a log-rank test. In addition, combining transcriptomic data from patients and data from other large cohort studies, we further searched for genes associated with pathological features and their prognostic value. A total of 165 gastric cancer patients were included for model training, and a total of 26 features were integrated through multi-instance learning, with each process generating 11 probabilistic features and 2 predictive labeling features. We applied a 10-fold Lasso-Cox regression model to achieve dimensionality reduction of these features. The predictive accuracy of the model was verified using Kaplan-Meyer (KM) curves for stratification with a consistency index of 0.741 for the training set and 0.585 for the test set. Deep learning-based resultant supervised pathohistological features have the potential for superior prognostic stratification of gastric cancer patients, transforming image pixels into an effective and labor-saving tool to optimize the clinical management of gastric cancer patients. Also, SLITRK4 was identified as a prognostic marker for gastric cancer.

Multiple Instance Bagging and Risk Histogram for Survival Time Analysis Based on Whole Slide Images of Brain Cancer Patients

This study tackles the challenges in computer-aided prognosis for glioblastoma multiforme, a highly aggressive brain cancer, using only whole slide images (WSIs) as input. Unlike traditional methods that rely on random selection or region-of-interest (ROI) extraction to choose meaningful subsets of patches representing the whole slide, we propose a multiple instance bagging approach. This method utilizes all patches extracted from the whole slide, employing different subsets in each training epoch, thereby leveraging information from the entire slide while keeping the training computationally feasible. Additionally, we developed a two-stage framework based on the ResNet-CBAM model which estimates not just the usual survival risk, but also predicts the actual survival time. Using risk scores of patches estimated from the risk estimation stage, a risk histogram can be constructed and used as input to train a survival time prediction model. A censor hinge loss based on root mean square error was also developed to handle censored data when training the regression model. Tests using the Cancer Genome Atlas Program’s glioblastoma public database yielded a concordance index of 73.16±2.15%, surpassing existing models. Log-rank testing on predicted high- and low-risk groups using the Kaplan–Meier method revealed a p-value of 3.88×10−9, well below the usual threshold of 0.005, indicating the model’s ability to significantly differentiate between the two groups. We also implemented a heatmap visualization method that provides interpretable risk assessments at the patch level, potentially aiding clinicians in identifying high-risk regions within WSIs. Notably, these results were achieved using 98% fewer parameters compared to state-of-the-art models.

PROSurvival: A Technical Case Report on Creating and Publishing a Dataset for Federated Learning on Survival Prediction of Prostate Cancer Patients.

The PROSurvival project aims to improve the prediction of recurrence-free survival in prostate cancer by applying federated machine learning to whole slide images combined with selected clinical data. Both the image and clinical data will be aggregated into an anonymized dataset compliant with the General Data Protection Regulation and published under the principles of findable, accessible, interoperable, and reusable data. The DICOM standard will be used for the image data. For the accompanying clinical data, a human-readable, compact and flexible standard is yet to be defined. From the set of existing standards, mostly extendable with varying degrees of modifications, we chose oBDS as a starting point and modified it to include missing data points and to remove mandatory items not applicable to our dataset. Clinical and survival data from clinic-specific spreadsheets were converted into this modified standard, ensuring on-site data privacy during processing. For publication of the dataset, both image and clinical data are anonymized using established methods. The key challenges arose during the clinical data anonymization and in identifying research repositories meeting all of our requirements. Each clinic had to coordinate the publication with their responsible data protection officers, requiring different approval processes due to the individual states' differing interpretations of the legal regulations. The newly established German Health Data Utilization Act is expected to simplify future data sharing in a responsible and powerful way.

Dual attention model with reinforcement learning for classification of histology whole-slide images

Digital whole slide images (WSIs) are generally captured at microscopic resolution and encompass extensive spatial data (several billions of pixels per image). Directly feeding these images to deep learning models is computationally intractable due to memory constraints, while downsampling the WSIs risks incurring information loss. Alternatively, splitting the WSIs into smaller patches (or tiles) may result in a loss of important contextual information. In this paper, we propose a novel dual attention approach, consisting of two main components, both inspired by the visual examination process of a pathologist: The first soft attention model processes a low magnification view of the WSI to identify relevant regions of interest (ROIs), followed by a custom sampling method to extract diverse and spatially distinct image tiles from the selected ROIs. The second component, the hard attention classification model further extracts a sequence of multi-resolution glimpses from each tile for classification. Since hard attention is non-differentiable, we train this component using reinforcement learning to predict the location of the glimpses. This approach allows the model to focus on essential regions instead of processing the entire tile, thereby aligning with a pathologist’s way of diagnosis. The two components are trained in an end-to-end fashion using a joint loss function to demonstrate the efficacy of the model. The proposed model was evaluated on two WSI-level classification problems: Human epidermal growth factor receptor 2 (HER2) scoring on breast cancer histology images and prediction of Intact/Loss status of two Mismatch Repair (MMR) biomarkers from colorectal cancer histology images. We show that the proposed model achieves performance better than or comparable to the state-of-the-art methods while processing less than 10% of the WSI at the highest magnification and reducing the time required to infer the WSI-level label by more than 75%. The code is available at github.

Whole Slide Imaging, Artificial Intelligence, and Machine Learning in Pediatric and Perinatal Pathology: Current Status and Future Directions

The integration of artificial intelligence (AI) into healthcare is becoming increasingly mainstream. Leveraging digital technologies, such as AI and deep learning, impacts researchers, clinicians, and industry due to promising performance and clinical potential. Digital pathology is now a proven technology, enabling generation of high-resolution digital images from glass slides (whole slide images; WSI). WSIs facilitates AI-based image analysis to aid pathologists in diagnostic tasks, improve workflow efficiency, and address workforce shortages. Example applications include tumor segmentation, disease classification, detection, quantitation and grading, rare object identification, and outcome prediction. While advancements have occurred, integration of WSI-AI into clinical laboratories faces challenges, including concerns regarding evidence quality, regulatory adaptations, clinical evaluation, and safety considerations. In pediatric and developmental histopathology, adoption of AI could improve diagnostic efficiency, automate routine tasks, and address specific diagnostic challenges unique to the specialty, such as standardizing placental pathology and developmental autopsy findings, as well as mitigating staffing shortages in the subspeciality. Additionally, AI-based tools have potential to mitigate medicolegal implications by enhancing reproducibility and objectivity in diagnostic evaluations. An overview of recent developments and challenges in applying AI to pediatric and developmental pathology, focusing on machine learning methods applied to WSIs of pediatric pathology specimens is presented.

Generating and evaluating synthetic data in digital pathology through diffusion models

Synthetic data is becoming a valuable tool for computational pathologists, aiding in tasks like data augmentation and addressing data scarcity and privacy. However, its use necessitates careful planning and evaluation to prevent the creation of clinically irrelevant artifacts.This manuscript introduces a comprehensive pipeline for generating and evaluating synthetic pathology data using a diffusion model. The pipeline features a multifaceted evaluation strategy with an integrated explainability procedure, addressing two key aspects of synthetic data use in the medical domain.The evaluation of the generated data employs an ensemble-like approach. The first step includes assessing the similarity between real and synthetic data using established metrics. The second step involves evaluating the usability of the generated images in deep learning models accompanied with explainable AI methods. The final step entails verifying their histopathological realism through questionnaires answered by professional pathologists. We show that each of these evaluation steps are necessary as they provide complementary information on the generated data’s quality.The pipeline is demonstrated on the public GTEx dataset of 650 Whole Slide Images (WSIs), including five different tissues. An equal number of tiles from each tissue are generated and their reliability is assessed using the proposed evaluation pipeline, yielding promising results.In summary, the proposed workflow offers a comprehensive solution for generative AI in digital pathology, potentially aiding the community in their transition towards digitalization and data-driven modeling.

NACNet: A histology context-aware transformer graph convolution network for predicting treatment response to neoadjuvant chemotherapy in Triple Negative Breast Cancer

Neoadjuvant chemotherapy (NAC) response prediction for triple negative breast cancer (TNBC) patients is a challenging task clinically as it requires understanding complex histology interactions within the tumor microenvironment (TME). Digital whole slide images (WSIs) capture detailed tissue information, but their giga-pixel size necessitates computational methods based on multiple instance learning, which typically analyze small, isolated image tiles without the spatial context of the TME. To address this limitation and incorporate TME spatial histology interactions in predicting NAC response for TNBC patients, we developed a histology context-aware transformer graph convolution network (NACNet). Our deep learning method identifies the histopathological labels on individual image tiles from WSIs, constructs a spatial TME graph, and represents each node with features derived from tissue texture and social network analysis. It predicts NAC response using a transformer graph convolution network model enhanced with graph isomorphism network layers. We evaluate our method with WSIs of a cohort of TNBC patient (N=105) and compared its performance with multiple state-of-the-art machine learning and deep learning models, including both graph and non-graph approaches. Our NACNet achieves 90.0% accuracy, 96.0% sensitivity, 88.0% specificity, and an AUC of 0.82, through eight-fold cross-validation, outperforming baseline models. These comprehensive experimental results suggest that NACNet holds strong potential for stratifying TNBC patients by NAC response, thereby helping to prevent overtreatment, improve patient quality of life, reduce treatment cost, and enhance clinical outcomes, marking an important advancement toward personalized breast cancer treatment.