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Dealing with Label Scarcity in Computational Pathology: A Use Case in Prostate Cancer Classification

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 Added by Koen Dercksen
 Publication date 2019
and research's language is English




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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.



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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.
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.
84 - Zhihao Fang , Wanyi Zhang , He Ma 2019
Ultrasound image diagnosis of breast tumors has been widely used in recent years. However, there are some problems of it, for instance, poor quality, intense noise and uneven echo distribution, which has created a huge obstacle to diagnosis. To overcome these problems, we propose a novel method, a breast cancer classification with ultrasound images based on SLIC (BCCUI). We first utilize the Region of Interest (ROI) extraction based on Simple Linear Iterative Clustering (SLIC) algorithm and region growing algorithm to extract the ROI at the super-pixel level. Next, the features of ROI are extracted. Furthermore, the Support Vector Machine (SVM) classifier is applied. The calculation states that the accuracy of this segment algorithm is up to 88.00% and the sensitivity of the algorithm is up to 92.05%, which proves that the classifier presents in this paper has certain research meaning and applied worthiness.
Breast cancer is the malignant tumor that causes the highest number of cancer deaths in females. Digital mammograms (DM or 2D mammogram) and digital breast tomosynthesis (DBT or 3D mammogram) are the two types of mammography imagery that are used in clinical practice for breast cancer detection and diagnosis. Radiologists usually read both imaging modalities in combination; however, existing computer-aided diagnosis tools are designed using only one imaging modality. Inspired by clinical practice, we propose an innovative convolutional neural network (CNN) architecture for breast cancer classification, which uses both 2D and 3D mammograms, simultaneously. Our experiment shows that the proposed method significantly improves the performance of breast cancer classification. By assembling three CNN classifiers, the proposed model achieves 0.97 AUC, which is 34.72% higher than the methods using only one imaging modality.
Accurate delineation of the intraprostatic gross tumour volume (GTV) is a prerequisite for treatment approaches in patients with primary prostate cancer (PCa). Prostate-specific membrane antigen positron emission tomography (PSMA-PET) may outperform MRI in GTV detection. However, visual GTV delineation underlies interobserver heterogeneity and is time consuming. The aim of this study was to develop a convolutional neural network (CNN) for automated segmentation of intraprostatic tumour (GTV-CNN) in PSMA-PET. Methods: The CNN (3D U-Net) was trained on [68Ga]PSMA-PET images of 152 patients from two different institutions and the training labels were generated manually using a validated technique. The CNN was tested on two independent internal (cohort 1: [68Ga]PSMA-PET, n=18 and cohort 2: [18F]PSMA-PET, n=19) and one external (cohort 3: [68Ga]PSMA-PET, n=20) test-datasets. Accordance between manual contours and GTV-CNN was assessed with Dice-S{o}rensen coefficient (DSC). Sensitivity and specificity were calculated for the two internal test-datasets by using whole-mount histology. Results: Median DSCs for cohorts 1-3 were 0.84 (range: 0.32-0.95), 0.81 (range: 0.28-0.93) and 0.83 (range: 0.32-0.93), respectively. Sensitivities and specificities for GTV-CNN were comparable with manual expert contours: 0.98 and 0.76 (cohort 1) and 1 and 0.57 (cohort 2), respectively. Computation time was around 6 seconds for a standard dataset. Conclusion: The application of a CNN for automated contouring of intraprostatic GTV in [68Ga]PSMA- and [18F]PSMA-PET images resulted in a high concordance with expert contours and in high sensitivities and specificities in comparison with histology reference. This robust, accurate and fast technique may be implemented for treatment concepts in primary PCa. The trained model and the studys source code are available in an open source repository.
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