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Register a new userProstate cancer histopathology with label-free multispectral deep UV microscopy quantifies phenotypes of tumor grade and aggressiveness
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Identifying prostate cancer patients that are harboring aggressive forms of prostate cancer remains a significant clinical challenge. To shed light on this problem, we develop an approach based on multispectral deep-ultraviolet (UV) microscopy that provides novel quantitative insight into the aggressiveness and grade of this disease. First, we find that UV spectral signatures from endogenous molecules give rise to a phenotypical continuum that differentiates critical structures of thin tissue sections with subcellular spatial resolution, including nuclei, cytoplasm, stroma, basal cells, nerves, and inflammation. Further, we show that this phenotypical continuum can be applied as a surrogate biomarker of prostate cancer malignancy, where patients with the most aggressive tumors show a ubiquitous glandular phenotypical shift. Lastly, we adapt a two-part Cycle-consistent Generative Adversarial Network to translate the label-free deep-UV images into virtual hematoxylin and eosin (H&E) stained images. Agreement between the virtual H&E images and the gold standard H&E-stained tissue sections is evaluated by a panel of pathologists who find that the two modalities are in excellent agreement. This work has significant implications towards improving our ability to objectively quantify prostate cancer grade and aggressiveness, thus improving the management and clinical outcomes of prostate cancer patients. This same approach can also be applied broadly in other tumor types to achieve low-cost, stain-free, quantitative histopathological analysis.
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The emergence of multi-parametric magnetic resonance imaging (mpMRI) has had a profound impact on the diagnosis of prostate cancers (PCa), which is the most prevalent malignancy in males in the western world, enabling a better selection of patients for confirmation biopsy. However, analyzing these images is complex even for experts, hence opening an opportunity for computer-aided diagnosis systems to seize. This paper proposes a fully automatic system based on Deep Learning that takes a prostate mpMRI from a PCa-suspect patient and, by leveraging the Retina U-Net detection framework, locates PCa lesions, segments them, and predicts their most likely Gleason grade group (GGG). It uses 490 mpMRIs for training/validation, and 75 patients for testing from two different datasets: ProstateX and IVO (Valencia Oncology Institute Foundation). In the test set, it achieves an excellent lesion-level AUC/sensitivity/specificity for the GGG$geq$2 significance criterion of 0.96/1.00/0.79 for the ProstateX dataset, and 0.95/1.00/0.80 for the IVO dataset. Evaluated at a patient level, the results are 0.87/1.00/0.375 in ProstateX, and 0.91/1.00/0.762 in IVO. Furthermore, on the online ProstateX grand challenge, the model obtained an AUC of 0.85 (0.87 when trained only on the ProstateX data, tying up with the original winner of the challenge). For expert comparison, IVO radiologists PI-RADS 4 sensitivity/specificity were 0.88/0.56 at a lesion level, and 0.85/0.58 at a patient level. Additional subsystems for automatic prostate zonal segmentation and mpMRI non-rigid sequence registration were also employed to produce the final fully automated system. The code for the ProstateX-trained system has been made openly available at https://github.com/OscarPellicer/prostate_lesion_detection. We hope that this will represent a landmark for future research to use, compare and improve upon.
Large amounts of unlabelled data are commonplace for many applications in computational pathology, whereas labelled data is often expensive, both in time and cost, to acquire. We investigate the performance of unsupervised and supervised deep learning methods when few labelled data are available. Three methods are compared: clustering autoencoder latent vectors (unsupervised), a single layer classifier combined with a pre-trained autoencoder (semi-supervised), and a supervised CNN. We apply these methods on hematoxylin and eosin (H&E) stained prostatectomy images to classify tumour versus non-tumour tissue. Results show that semi-/unsupervised methods have an advantage over supervised learning when few labels are available. Additionally, we show that incorporating immunohistochemistry (IHC) stained data provides an increase in performance over only using H&E.
Prostate cancer is one of the most common forms of cancer and the third leading cause of cancer death in North America. As an integrated part of computer-aided detection (CAD) tools, diffusion-weighted magnetic resonance imaging (DWI) has been intensively studied for accurate detection of prostate cancer. With deep convolutional neural networks (CNNs) significant success in computer vision tasks such as object detection and segmentation, different CNNs architectures are increasingly investigated in medical imaging research community as promising solutions for designing more accurate CAD tools for cancer detection. In this work, we developed and implemented an automated CNNs-based pipeline for detection of clinically significant prostate cancer (PCa) for a given axial DWI image and for each patient. DWI images of 427 patients were used as the dataset, which contained 175 patients with PCa and 252 healthy patients. To measure the performance of the proposed pipeline, a test set of 108 (out of 427) patients were set aside and not used in the training phase. The proposed pipeline achieved area under the receiver operating characteristic curve (AUC) of 0.87 (95% Confidence Interval (CI): 0.84-0.90) and 0.84 (95% CI: 0.76-0.91) at slice level and patient level, respectively.
Label-free imaging approaches seek to simplify and augment histopathologic assessment by replacing the current practice of staining by dyes to visualize tissue morphology with quantitative optical measurements. Quantitative phase imaging (QPI) operates with visible/UV light and thus provides a resolution matched to current practice. Here we introduce and demonstrate confocal QPI for label-free imaging of tissue sections and assess its utility for manual histopathologic inspection. Imaging cancerous and normal adjacent human breast and prostate, we show that tissue structural organization can be resolved with high spatial detail comparable to conventional H&E stains. Our confocal QPI images are found to be free of halo, solving this common problem in QPI. We further describe and apply a virtual imaging system based on Finite-Difference Time-Domain (FDTD) calculations to quantitatively compare confocal with wide-field QPI methods and explore performance limits using numerical tissue phantoms.
$bf{Purpose:}$ The goal of this study was (i) to use artificial intelligence to automate the traditionally labor-intensive process of manual segmentation of tumor regions in pathology slides performed by a pathologist and (ii) to validate the use of a well-known and readily available deep learning architecture. Automation will reduce the human error involved in manual delineation, increase efficiency, and result in accurate and reproducible segmentation. This advancement will alleviate the bottleneck in the workflow in clinical and research applications due to a lack of pathologist time. Our application is patient-specific microdosimetry and radiobiological modeling, which builds on the contoured pathology slides. $bf{Methods:}$ A U-Net architecture was used to segment tumor regions in pathology core biopsies of lung tissue with adenocarcinoma stained using hematoxylin and eosin. A pathologist manually contoured the tumor regions in 56 images with binary masks for training. Overlapping patch extraction with various patch sizes and image downsampling were investigated individually. Data augmentation and 8-fold cross-validation were used. $bf{Results:}$ The U-Net achieved accuracy of 0.91$pm$0.06, specificity of 0.90$pm$0.08, sensitivity of 0.92$pm$0.07, and precision of 0.8$pm$0.1. The F1/DICE score was 0.85$pm$0.07, with a segmentation time of 3.24$pm$0.03 seconds per image, achieving a 370$pm$3 times increased efficiency over manual segmentation. In some cases, the U-Net correctly delineated the tumors stroma from its epithelial component in regions that were classified as tumor by the pathologist. $bf{Conclusion:}$ The U-Net architecture can segment images with a level of efficiency and accuracy that makes it suitable for tumor segmentation of histopathological images in fields such as radiotherapy dosimetry, specifically in the subfields of microdosimetry.
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