Toward confident prostate cancer detection using ultrasound: a multi-center study.

PURPOSE: Deep learning-based analysis of micro-ultrasound images to detect cancerous lesions is a promising tool for improving prostate cancer (PCa) diagnosis. An ideal model should confidently identify cancer while responding with appropriate uncertainty when presented with out-of-distribution inputs that arise during deployment due to imaging artifacts and the biological heterogeneity of patients and prostatic tissue. METHODS: Using micro-ultrasound data from 693 patients across 5 clinical centers who underwent micro-ultrasound guided prostate biopsy, we train and evaluate convolutional neural network models for PCa detection. To improve robustness to out-of-distribution inputs, we employ and comprehensively benchmark several state-of-the-art uncertainty estimation methods. RESULTS: PCa detection models achieve performance scores up to 76 % average AUROC with a 10-fold cross validation setup. Models with uncertainty estimation obtain expected calibration error scores as low as 2 % , indicating that confident predictions are very likely to be correct. Visualizations of the model output demonstrate that the model correctly identifies healthy versus malignant tissue. CONCLUSION: Deep learning models have been developed to confidently detect PCa lesions from micro-ultrasound. The performance of these models, determined from a large and diverse dataset, is competitive with visual analysis of magnetic resonance imaging, the clinical benchmark to identify PCa lesions for targeted biopsy. Deep learning with micro-ultrasound should be further studied as an avenue for targeted prostate biopsy.

LensePro: label noise-tolerant prototype-based network for improving cancer detection in prostate ultrasound with limited annotations.

PURPOSE: The standard of care for prostate cancer (PCa) diagnosis is the histopathological analysis of tissue samples obtained via transrectal ultrasound (TRUS) guided biopsy. Models built with deep neural networks (DNNs) hold the potential for direct PCa detection from TRUS, which allows targeted biopsy and subsequently enhances outcomes. Yet, there are ongoing challenges with training robust models, stemming from issues such as noisy labels, out-of-distribution (OOD) data, and limited labeled data. METHODS: This study presents LensePro, a unified method that not only excels in label efficiency but also demonstrates robustness against label noise and OOD data. LensePro comprises two key stages: first, self-supervised learning to extract high-quality feature representations from abundant unlabeled TRUS data and, second, label noise-tolerant prototype-based learning to classify the extracted features. RESULTS: Using data from 124 patients who underwent systematic prostate biopsy, LensePro achieves an AUROC, sensitivity, and specificity of 77.9%, 85.9%, and 57.5%, respectively, for detecting PCa in ultrasound. Our model shows it is effective for detecting OOD data in test time, critical for clinical deployment. Ablation studies demonstrate that each component of our method improves PCa detection by addressing one of the three challenges, reinforcing the benefits of a unified approach. CONCLUSION: Through comprehensive experiments, LensePro demonstrates its state-of-the-art performance for TRUS-based PCa detection. Although further research is necessary to confirm its clinical applicability, LensePro marks a notable advancement in enhancing automated computer-aided systems for detecting prostate cancer in ultrasound.

Self-Supervised Learning With Limited Labeled Data for Prostate Cancer Detection in High-Frequency Ultrasound.

Deep learning-based analysis of high-frequency, high-resolution micro-ultrasound data shows great promise for prostate cancer (PCa) detection. Previous approaches to analysis of ultrasound data largely follow a supervised learning (SL) paradigm. Ground truth labels for ultrasound images used for training deep networks often include coarse annotations generated from the histopathological analysis of tissue samples obtained via biopsy. This creates inherent limitations on the availability and quality of labeled data, posing major challenges to the success of SL methods. However, unlabeled prostate ultrasound data are more abundant. In this work, we successfully apply self-supervised representation learning to micro-ultrasound data. Using ultrasound data from 1028 biopsy cores of 391 subjects obtained in two clinical centers, we demonstrate that feature representations learned with this method can be used to classify cancer from noncancer tissue, obtaining an AUROC score of 91% on an independent test set. To the best of our knowledge, this is the first successful end-to-end self-SL (SSL) approach for PCa detection using ultrasound data. Our method outperforms baseline SL approaches, generalizes well between different data centers, and scales well in performance as more unlabeled data are added, making it a promising approach for future research using large volumes of unlabeled data. Our code is publicly available at https://www.github.com/MahdiGilany/SSL_micro_ultrasound.

TRUSformer: improving prostate cancer detection from micro-ultrasound using attention and self-supervision.

PURPOSE: A large body of previous machine learning methods for ultrasound-based prostate cancer detection classify small regions of interest (ROIs) of ultrasound signals that lie within a larger needle trace corresponding to a prostate tissue biopsy (called biopsy core). These ROI-scale models suffer from weak labeling as histopathology results available for biopsy cores only approximate the distribution of cancer in the ROIs. ROI-scale models do not take advantage of contextual information that are normally considered by pathologists, i.e., they do not consider information about surrounding tissue and larger-scale trends when identifying cancer. We aim to improve cancer detection by taking a multi-scale, i.e., ROI-scale and biopsy core-scale, approach. METHODS: Our multi-scale approach combines (i) an "ROI-scale" model trained using self-supervised learning to extract features from small ROIs and (ii) a "core-scale" transformer model that processes a collection of extracted features from multiple ROIs in the needle trace region to predict the tissue type of the corresponding core. Attention maps, as a by-product, allow us to localize cancer at the ROI scale. RESULTS: We analyze this method using a dataset of micro-ultrasound acquired from 578 patients who underwent prostate biopsy, and compare our model to baseline models and other large-scale studies in the literature. Our model shows consistent and substantial performance improvements compared to ROI-scale-only models. It achieves [Formula: see text] AUROC, a statistically significant improvement over ROI-scale classification. We also compare our method to large studies on prostate cancer detection, using other imaging modalities. CONCLUSIONS: Taking a multi-scale approach that leverages contextual information improves prostate cancer detection compared to ROI-scale-only models. The proposed model achieves a statistically significant improvement in performance and outperforms other large-scale studies in the literature. Our code is publicly available at www.github.com/med-i-lab/TRUSFormer .

Biparametric MR signal characteristics can predict histopathological measures of prostate cancer.

OBJECTIVES: The aim of this study was to establish a new data-driven metric from MRI signal intensity that can quantify histopathological characteristics of prostate cancer. METHODS: This retrospective study was conducted on 488 patients who underwent biparametric MRI (bp-MRI), including T2-weighted imaging (T2W) and apparent diffusion coefficient (ADC) of diffusion-weighted imaging, and having biopsy-proven prostate cancer between August 2011 and July 2015. Forty-two of the patients who underwent radical prostatectomy and the rest of 446 patients constitute the labeled and unlabeled datasets, respectively. A deep learning model was built to predict the density of epithelium, epithelial nuclei, stroma, and lumen from bp-MRI, called MR-driven tissue density. On both the labeled validation set and the whole unlabeled dataset, the quality of MR-driven tissue density and its relation to bp-MRI signal intensity were examined with respect to different histopathologic and radiologic conditions using different statistical analyses. RESULTS: MR-driven tissue density and bp-MRI of 446 patients were evaluated. MR-driven tissue density was significantly related to bp-MRI (p < 0.05). The relationship was generally stronger in cancer regions than in benign regions. Regarding cancer grades, significant differences were found in the intensity of bp-MRI and MR-driven tissue density of epithelium, epithelial nuclei, and stroma (p < 0.05). Comparing MR true-negative to MR false-positive regions, MR-driven lumen density was significantly different, similar to the intensity of bp-MRI (p < 0.001). CONCLUSIONS: MR-driven tissue density could serve as a reliable histopathological measure of the prostate on bp-MRI, leading to an improved understanding of prostate cancer and cancer progression. KEY POINTS: • Semi-supervised deep learning enables non-invasive and quantitative histopathology in the prostate from biparametric MRI. • Tissue density derived from biparametric MRI demonstrates similar characteristics to the direct estimation of tissue density from histopathology images. • The analysis of MR-driven tissue density reveals significantly different tissue compositions among different cancer grades as well as between MR-positive and MR-negative benign.

Coarse label refinement for improving prostate cancer detection in ultrasound imaging.

PURPOSE: Ultrasound-guided biopsy plays a major role in prostate cancer (PCa) detection, yet is limited by a high rate of false negatives and low diagnostic yield of the current systematic, non-targeted approaches. Developing machine learning models for accurately identifying cancerous tissue in ultrasound would help sample tissues from regions with higher cancer likelihood. A plausible approach for this purpose is to use individual ultrasound signals corresponding to a core as inputs and consider the histopathology diagnosis for the entire core as labels. However, this introduces significant amount of label noise to training and degrades the classification performance. Previously, we suggested that histopathology-reported cancer involvement can be a reasonable approximation for the label noise. METHODS: Here, we propose an involvement-based label refinement (iLR) method to correct corrupted labels and improve cancer classification. The difference between predicted and true cancer involvements is used to guide the label refinement process. We further incorporate iLR into state-of-the-art methods for learning with noisy labels and predicting cancer involvement. RESULTS: We use 258 biopsy cores from 70 patients and demonstrate that our proposed label refinement method improves the performance of multiple noise-tolerant approaches and achieves a balanced accuracy, correlation coefficient, and mean absolute error of 76.7%, 0.68, and 12.4, respectively. CONCLUSIONS: Our key contribution is to leverage a data-centric method to deal with noisy labels using histopathology reports, and improve the performance of prostate cancer diagnosis through a hierarchical training process with label refinement.

Deep regression neural networks for collateral imaging from dynamic susceptibility contrast-enhanced magnetic resonance perfusion in acute ischemic stroke.

PURPOSE: Acute ischemic stroke is one of the primary causes of death worldwide. Recent studies have shown that the assessment of collateral status could aid in improving the treatment for patients with acute ischemic stroke. We present a 3D deep regression neural network to automatically generate the collateral images from dynamic susceptibility contrast-enhanced magnetic resonance perfusion (DSC-MRP) in acute ischemic stroke. METHODS: This retrospective study includes 144 subjects with acute ischemic stroke (stroke cases) and 201 subjects without acute ischemic stroke (controls). DSC-MRP images of these subjects were manually inspected for collateral assessment in arterial, capillary, early and late venous, and delay phases. The proposed network was trained on 205 subjects, and the optimal model was chosen using the validation set of 64 subjects. The predictive power of the network was assessed on the test set of 76 subjects using the squared correlation coefficient (R-squared), mean absolute error (MAE), Tanimoto measure (TM), and structural similarity index (SSIM). RESULTS: The proposed network was able to predict the five phase maps with high accuracy. On average, 0.897 R-squared, 0.581 × 10-1 MAE, 0.946 TM, and 0.846 SSIM were achieved for the five phase maps. No statistically significant difference was, in general, found between controls and stroke cases. The performance of the proposed network was lower in the arterial and venous phases than the other three phases. CONCLUSION: The results suggested that the proposed network performs equally well for both control and acute ischemic stroke groups. The proposed network could help automate the assessment of collateral status in an efficient and effective manner and improve the quality and yield of diagnosis of acute ischemic stroke. The follow-up study will entail the clinical evaluation of the collateral images that are generated by the proposed network.

BACH: Grand challenge on breast cancer histology images.

Breast cancer is the most common invasive cancer in women, affecting more than 10% of women worldwide. Microscopic analysis of a biopsy remains one of the most important methods to diagnose the type of breast cancer. This requires specialized analysis by pathologists, in a task that i) is highly time- and cost-consuming and ii) often leads to nonconsensual results. The relevance and potential of automatic classification algorithms using hematoxylin-eosin stained histopathological images has already been demonstrated, but the reported results are still sub-optimal for clinical use. With the goal of advancing the state-of-the-art in automatic classification, the Grand Challenge on BreAst Cancer Histology images (BACH) was organized in conjunction with the 15th International Conference on Image Analysis and Recognition (ICIAR 2018). BACH aimed at the classification and localization of clinically relevant histopathological classes in microscopy and whole-slide images from a large annotated dataset, specifically compiled and made publicly available for the challenge. Following a positive response from the scientific community, a total of 64 submissions, out of 677 registrations, effectively entered the competition. The submitted algorithms improved the state-of-the-art in automatic classification of breast cancer with microscopy images to an accuracy of 87%. Convolutional neuronal networks were the most successful methodology in the BACH challenge. Detailed analysis of the collective results allowed the identification of remaining challenges in the field and recommendations for future developments. The BACH dataset remains publicly available as to promote further improvements to the field of automatic classification in digital pathology.

Methods for Segmentation and Classification of Digital Microscopy Tissue Images.

High-resolution microscopy images of tissue specimens provide detailed information about the morphology of normal and diseased tissue. Image analysis of tissue morphology can help cancer researchers develop a better understanding of cancer biology. Segmentation of nuclei and classification of tissue images are two common tasks in tissue image analysis. Development of accurate and efficient algorithms for these tasks is a challenging problem because of the complexity of tissue morphology and tumor heterogeneity. In this paper we present two computer algorithms; one designed for segmentation of nuclei and the other for classification of whole slide tissue images. The segmentation algorithm implements a multiscale deep residual aggregation network to accurately segment nuclear material and then separate clumped nuclei into individual nuclei. The classification algorithm initially carries out patch-level classification via a deep learning method, then patch-level statistical and morphological features are used as input to a random forest regression model for whole slide image classification. The segmentation and classification algorithms were evaluated in the MICCAI 2017 Digital Pathology challenge. The segmentation algorithm achieved an accuracy score of 0.78. The classification algorithm achieved an accuracy score of 0.81. These scores were the highest in the challenge.

Deep dense multi-path neural network for prostate segmentation in magnetic resonance imaging.

PURPOSE: We propose an approach of 3D convolutional neural network to segment the prostate in MR images. METHODS: A 3D deep dense multi-path convolutional neural network that follows the framework of the encoder-decoder design is proposed. The encoder is built based upon densely connected layers that learn the high-level feature representation of the prostate. The decoder interprets the features and predicts the whole prostate volume by utilizing a residual layout and grouped convolution. A set of sub-volumes of MR images, centered at the prostate, is generated and fed into the proposed network for training purpose. The performance of the proposed network is compared to previously reported approaches. RESULTS: Two independent datasets were employed to assess the proposed network. In quantitative evaluations, the proposed network achieved 95.11 and 89.01 Dice coefficients for the two datasets. The segmentation results were robust to variations in MR images. In comparison experiments, the segmentation performance of the proposed network was comparable to the previously reported approaches. In qualitative evaluations, the segmentation results by the proposed network were well matched to the ground truth provided by human experts. CONCLUSIONS: The proposed network is capable of segmenting the prostate in an accurate and robust manner. This approach can be applied to other types of medical images.