No Arabic abstract
The emergence of digital pathology has opened new horizons for histopathology and cytology. Artificial-intelligence algorithms are able to operate on digitized slides to assist pathologists with diagnostic tasks. Whereas machine learning involving classification and segmentation methods have obvious benefits for image analysis in pathology, image search represents a fundamental shift in computational pathology. Matching the pathology of new patients with already diagnosed and curated cases offers pathologist a novel approach to improve diagnostic accuracy through visual inspection of similar cases and computational majority vote for consensus building. In this study, we report the results from searching the largest public repository (The Cancer Genome Atlas [TCGA] program by National Cancer Institute, USA) of whole slide images from almost 11,000 patients depicting different types of malignancies. For the first time, we successfully indexed and searched almost 30,000 high-resolution digitized slides constituting 16 terabytes of data comprised of 20 million 1000x1000 pixels image patches. The TCGA image database covers 25 anatomic sites and contains 32 cancer subtypes. High-performance storage and GPU power were employed for experimentation. The results were assessed with conservative majority voting to build consensus for subtype diagnosis through vertical search and demonstrated high accuracy values for both frozen sections slides (e.g., bladder urothelial carcinoma 93%, kidney renal clear cell carcinoma 97%, and ovarian serous cystadenocarcinoma 99%) and permanent histopathology slides (e.g., prostate adenocarcinoma 98%, skin cutaneous melanoma 99%, and thymoma 100%). The key finding of this validation study was that computational consensus appears to be possible for rendering diagnoses if a sufficiently large number of searchable cases are available for each cancer subtype.
The vast majority of semantic segmentation approaches rely on pixel-level annotations that are tedious and time consuming to obtain and suffer from significant inter and intra-expert variability. To address these issues, recent approaches have leveraged categorical annotations at the slide-level, that in general suffer from robustness and generalization. In this paper, we propose a novel weakly supervised multi-instance learning approach that deciphers quantitative slide-level annotations which are fast to obtain and regularly present in clinical routine. The extreme potentials of the proposed approach are demonstrated for tumor segmentation of solid cancer subtypes. The proposed approach achieves superior performance in out-of-distribution, out-of-location, and out-of-domain testing sets.
Breast density is an important risk factor for breast cancer that also affects the specificity and sensitivity of screening mammography. Current federal legislation mandates reporting of breast density for all women undergoing breast screening. Clinically, breast density is assessed visually using the American College of Radiology Breast Imaging Reporting And Data System (BI-RADS) scale. Here, we introduce an artificial intelligence (AI) method to estimate breast percentage density (PD) from digital mammograms. Our method leverages deep learning (DL) using two convolutional neural network architectures to accurately segment the breast area. A machine-learning algorithm combining superpixel generation, texture feature analysis, and support vector machine is then applied to differentiate dense from non-dense tissue regions, from which PD is estimated. Our method has been trained and validated on a multi-ethnic, multi-institutional dataset of 15,661 images (4,437 women), and then tested on an independent dataset of 6,368 digital mammograms (1,702 women; cases=414) for both PD estimation and discrimination of breast cancer. On the independent dataset, PD estimates from Deep-LIBRA and an expert reader were strongly correlated (Spearman correlation coefficient = 0.90). Moreover, Deep-LIBRA yielded a higher breast cancer discrimination performance (area under the ROC curve, AUC = 0.611 [95% confidence interval (CI): 0.583, 0.639]) compared to four other widely-used research and commercial PD assessment methods (AUCs = 0.528 to 0.588). Our results suggest a strong agreement of PD estimates between Deep-LIBRA and gold-standard assessment by an expert reader, as well as improved performance in breast cancer risk assessment over state-of-the-art open-source and commercial methods.
The distribution and appearance of nuclei are essential markers for the diagnosis and study of cancer. Despite the importance of nuclear morphology, there is a lack of large scale, accurate, publicly accessible nucleus segmentation data. To address this, we developed an analysis pipeline that segments nuclei in whole slide tissue images from multiple cancer types with a quality control process. We have generated nucleus segmentation results in 5,060 Whole Slide Tissue images from 10 cancer types in The Cancer Genome Atlas. One key component of our work is that we carried out a multi-level quality control process (WSI-level and image patch-level), to evaluate the quality of our segmentation results. The image patch-level quality control used manual segmentation ground truth data from 1,356 sampled image patches. The datasets we publish in this work consist of roughly 5 billion quality controlled nuclei from more than 5,060 TCGA WSIs from 10 different TCGA cancer types and 1,356 manually segmented TCGA image patches from the same 10 cancer types plus additional 4 cancer types. Data is available at https://doi.org/10.7937/tcia.2019.4a4dkp9u
The optic nerve head (ONH) typically experiences complex neural- and connective-tissue structural changes with the development and progression of glaucoma, and monitoring these changes could be critical for improved diagnosis and prognosis in the glaucoma clinic. The gold-standard technique to assess structural changes of the ONH clinically is optical coherence tomography (OCT). However, OCT is limited to the measurement of a few hand-engineered parameters, such as the thickness of the retinal nerve fiber layer (RNFL), and has not yet been qualified as a stand-alone device for glaucoma diagnosis and prognosis applications. We argue this is because the vast amount of information available in a 3D OCT scan of the ONH has not been fully exploited. In this study we propose a deep learning approach that can: textbf{(1)} fully exploit information from an OCT scan of the ONH; textbf{(2)} describe the structural phenotype of the glaucomatous ONH; and that can textbf{(3)} be used as a robust glaucoma diagnosis tool. Specifically, the structural features identified by our algorithm were found to be related to clinical observations of glaucoma. The diagnostic accuracy from these structural features was $92.0 pm 2.3 %$ with a sensitivity of $90.0 pm 2.4 % $ (at $95 %$ specificity). By changing their magnitudes in steps, we were able to reveal how the morphology of the ONH changes as one transitions from a `non-glaucoma to a `glaucoma condition. We believe our work may have strong clinical implication for our understanding of glaucoma pathogenesis, and could be improved in the future to also predict future loss of vision.
Accurate segmentation of lung cancer in pathology slides is a critical step in improving patient care. We proposed the ACDC@LungHP (Automatic Cancer Detection and Classification in Whole-slide Lung Histopathology) challenge for evaluating different computer-aided diagnosis (CADs) methods on the automatic diagnosis of lung cancer. The ACDC@LungHP 2019 focused on segmentation (pixel-wise detection) of cancer tissue in whole slide imaging (WSI), using an annotated dataset of 150 training images and 50 test images from 200 patients. This paper reviews this challenge and summarizes the top 10 submitted methods for lung cancer segmentation. All methods were evaluated using the false positive rate, false negative rate, and DICE coefficient (DC). The DC ranged from 0.7354$pm$0.1149 to 0.8372$pm$0.0858. The DC of the best method was close to the inter-observer agreement (0.8398$pm$0.0890). All methods were based on deep learning and categorized into two groups: multi-model method and single model method. In general, multi-model methods were significantly better ($textit{p}$<$0.01$) than single model methods, with mean DC of 0.7966 and 0.7544, respectively. Deep learning based methods could potentially help pathologists find suspicious regions for further analysis of lung cancer in WSI.