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The histopathological distinction of lung adenocarcinoma (LADC) subtypes is subject to high inter-observer variability, which can compromise the optimal assessment of the patient prognosis. Therefore, this study developed convolutional neural networks (CNNs) capable of distinguishing LADC subtypes and predicting disease-specific survival, according to the LADC tumour grades established recently by the International Association for the Study of Lung Cancer pathology committee. Consensus LADC ground truth histopathological images were obtained from seventeen expert pulmonary pathologists and one pathologist in training. Two deep learning models (AI-1 and AI-2) were trained with EfficientNet b3 architecture to predict eight different LADC classes (lepidic, acinar, papillary, micropapillary, solid, invasive mucinous adenocarcinoma, other carcinoma types, and no carcinoma cells). Furthermore, the trained models were tested on an independent cohort of 133 patients. The models achieved high precision, recall, and F1-scores exceeding 0.90 for most of the LADC classes. Clear stratification of the three LADC grades was reached in predicting the disease-specific survival by the two models. Moreover, the grading prediction of one of the trained models was more accurate than those of 14 out of 15 pulmonary pathologists involved in the study (p=0.0003). Both trained models showed high stability in the segmentation of each pair of predicted grades with low variation in the hazard ratio across 200 bootstrapped samples. These findings indicate that the trained CNNs improve the diagnostic accuracy of the pathologist, standardise LADC subtype recognition, and refine LADC grade assessment. Thus, the trained models are promising tools that may assist in the routine evaluation of LADC subtypes and grades in clinical practice.

Colorectal cancer (CRC) is a heterogenous disease, and patients have differences in therapeutic response. However, the mechanisms underlying interpatient heterogeneity in the response to chemotherapeutic agents remain to be elucidated, and molecular tumor characteristics are required to select patients for specific therapies. Patient-derived organoids (PDOs) established from CRCs recapitulate various biological characteristics of tumor tissues, including cellular heterogeneity and the response to chemotherapy. Patient-derived organoids established from CRCs show various morphologies, but there are no criteria for defining these morphologies, which hampers the analysis of their biological significance. Here, we developed an artificial intelligence (AI)-based classifier to categorize PDOs based on microscopic images according to their similarity in appearance and classified tubular adenocarcinoma-derived PDOs into six types. Transcriptome analysis identified differential expression of genes related to cell adhesion in some of the morphological types. Genes involved in ribosome biogenesis were also differentially expressed and were most highly expressed in morphological types showing CRC stem cell properties. We identified an RNA polymerase I inhibitor, CX-5641, to be an upstream regulator of these type-specific gene sets. Notably, PDO types with increased expression of genes involved in ribosome biogenesis were resistant to CX-5461 treatment. Taken together, these results uncover the biological significance of the morphology of PDOs and provide novel indicators by which to categorize CRCs. Therefore, the AI-based classifier is a useful tool to support PDO-based cancer research.

Interstitial pneumonia is a heterogeneous disease with a progressive course and poor prognosis, at times even worse than those in the main cancer types. Histopathological examination is crucial for its diagnosis and estimation of prognosis. However, the evaluation strongly depends on the experience of pathologists, and the reproducibility of diagnosis is low.Herein, we propose MIXTURE (huMan-In-the-loop eXplainable artificial intelligence Through the Use of REcurrent training), a method to develop deep learning models for extracting pathologically significant findings based on an expert pathologist’s perspective with a small annotation effort. The procedure of MIXTURE consists of three steps as follows. First, we created feature extractors for tiles from whole slide images using self-supervised learning. The similar looking tiles were clustered based on the output features and then pathologists integrated the pathologically synonymous clusters. Using the integrated clusters as labeled data, deep learning models to classify the tiles into pathological findings were created by transfer-learning the feature extractors. We developed three models for different magnifications.Using these extracted findings, our model was able to predict the diagnosis of usual interstitial pneumonia, a finding suggestive of progressive disease, with high accuracy (AUC 0.90). This high accuracy could not be achieved without the integration of findings by pathologists. The patients predicted as UIP had significantly poorer prognosis (five-year overall survival [OS]: 55.4%) than those predicted as non-UIP (OS: 95.2%). The Cox proportional hazards model for each microscopic finding and prognosis pointed out dense fibrosis, fibroblastic foci, elastosis, and lymphocyte aggregation as independent risk factors. We suggest that MIXTURE may serve as a model approach to different diseases evaluated by medical imaging, including pathology and radiology, and be the prototype for artificial intelligence that can collaborate with humans.

An automatic object-detection method is necessary to facilitate the efficient analysis of satellite images consisting of multispectral images. Considering that the relationship between spectrums is...

Transfer learning is a machine learning technique designed to improve generalization performance by using pre-trained parameters obtained from other learning tasks. For image recognition tasks, many previous studies have reported that, when transfer learning is applied to deep neural networks, performance improves, despite having limited training data. This paper proposes a two-stage feature transfer learning method focusing on the recognition of textural medical images. During the proposed method, a model is successively trained with massive amounts of natural images, some textural images, and the target images. We applied this method to the classification task of textural X-ray computed tomography images of diffuse lung diseases. In our experiment, the two-stage feature transfer achieves the best performance compared to a from-scratch learning and a conventional single-stage feature transfer. We also investigated the robustness of the target dataset, based on size. Two-stage feature transfer shows better robustness than the other two learning methods. Moreover, we analyzed the feature representations obtained from DLDs imagery inputs for each feature transfer models using a visualization method. We showed that the two-stage feature transfer obtains both edge and textural features of DLDs, which does not occur in conventional single-stage feature transfer models.

The development of computer-assisted diagnosis (CAD) algorithms for pathological image analysis is an important research topic. Recently, convolutional neural networks (CNNs) have been used in several studies for the development of CAD algorithms. Such systems are required to be not only accurate but also explainable for their decisions, to ensure reliability. However, a limitation of using CNNs is that the basis of the decisions made by them are hardly interpretable by humans. Thus, in this paper, we present an explainable diagnosis method comprising two CNNs playing different roles. This method allows us to interpret the basis of the decisions made by the CNN from two perspectives: statistics and visualization. For the statistical explanation, the method constructs a dictionary of representative pathological features. It performs diagnoses based on the occurrence and importance of learned features referred from its dictionary. To construct the dictionary, we introduce a vector quantization scheme for CNN. For the visual interpretation, the method provides images of learned features embedded in a feature space as an index of the dictionary by generating them using a conditional autoregressive model. The experimental results showed that the proposed network learned pathological features that contributed to the diagnosis and yielded an area under the receiver operating curve (AUC) of approximately 0.93 for detecting atypical tissues in pathological images of the uterine cervix. Moreover, the proposed method demonstrated that it could provide visually interpretable images to show the rationales behind its decisions. Thus, the proposed method can serve as a valuable tool for pathological image analysis in terms of both its accuracy and explainability.