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Register a new userUsing deep learning to detect patients at risk for prostate cancer despite benign biopsies
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Background: Transrectal ultrasound guided systematic biopsies of the prostate is a routine procedure to establish a prostate cancer diagnosis. However, the 10-12 prostate core biopsies only sample a relatively small volume of the prostate, and tumour lesions in regions between biopsy cores can be missed, leading to a well-known low sensitivity to detect clinically relevant cancer. As a proof-of-principle, we developed and validated a deep convolutional neural network model to distinguish between morphological patterns in benign prostate biopsy whole slide images from men with and without established cancer. Methods: This study included 14,354 hematoxylin and eosin stained whole slide images from benign prostate biopsies from 1,508 men in two groups: men without an established prostate cancer (PCa) diagnosis and men with at least one core biopsy diagnosed with PCa. 80% of the participants were assigned as training data and used for model optimization (1,211 men), and the remaining 20% (297 men) as a held-out test set used to evaluate model performance. An ensemble of 10 deep convolutional neural network models was optimized for classification of biopsies from men with and without established cancer. Hyperparameter optimization and model selection was performed by cross-validation in the training data . Results: Area under the receiver operating characteristic curve (ROC-AUC) was estimated as 0.727 (bootstrap 95% CI: 0.708-0.745) on biopsy level and 0.738 (bootstrap 95% CI: 0.682 - 0.796) on man level. At a specificity of 0.9 the model had an estimated sensitivity of 0.348. Conclusion: The developed model has the ability to detect men with risk of missed PCa due to under-sampling of the prostate. The proposed model has the potential to reduce the number of false negative cases in routine systematic prostate biopsies and to indicate men who could benefit from MRI-guided re-biopsy.
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The Gleason score is the most important prognostic marker for prostate cancer patients but suffers from significant inter-observer variability. We developed a fully automated deep learning system to grade prostate biopsies. The system was developed using 5834 biopsies from 1243 patients. A semi-automatic labeling technique was used to circumvent the need for full manual annotation by pathologists. The developed system achieved a high agreement with the reference standard. In a separate observer experiment, the deep learning system outperformed 10 out of 15 pathologists. The system has the potential to improve prostate cancer prognostics by acting as a first or second reader.
We investigated the ability of deep learning models for imaging based HPV status detection. To overcome the problem of small medical datasets we used a transfer learning approach. A 3D convolutional network pre-trained on sports video clips was fine tuned such that full 3D information in the CT images could be exploited. The video pre-trained model was able to differentiate HPV-positive from HPV-negative cases with an area under the receiver operating characteristic curve (AUC) of 0.81 for an external test set. In comparison to a 3D convolutional neural network (CNN) trained from scratch and a 2D architecture pre-trained on ImageNet the video pre-trained model performed best.
The diagnosis of prostate cancer faces a problem with overdiagnosis that leads to damaging side effects due to unnecessary treatment. Research has shown that the use of multi-parametric magnetic resonance images to conduct biopsies can drastically help to mitigate the overdiagnosis, thus reducing the side effects on healthy patients. This study aims to investigate the use of deep learning techniques to explore computer-aid diagnosis based on MRI as input. Several diagnosis problems ranging from classification of lesions as being clinically significant or not to the detection and segmentation of lesions are addressed with deep learning based approaches. This thesis tackled two main problems regarding the diagnosis of prostate cancer. Firstly, XmasNet was used to conduct two large experiments on the classification of lesions. Secondly, detection and segmentation experiments were conducted, first on the prostate and afterward on the prostate cancer lesions. The former experiments explored the lesions through a two-dimensional space, while the latter explored models to work with three-dimensional inputs. For this task, the 3D models explored were the 3D U-Net and a pretrained 3D ResNet-18. A rigorous analysis of all these problems was conducted with a total of two networks, two cropping techniques, two resampling techniques, two crop sizes, five input sizes and data augmentations experimented for lesion classification. While for segmentation two models, two input sizes and data augmentations were experimented. However, while the binary classification of the clinical significance of lesions and the detection and segmentation of the prostate already achieve the desired results (0.870 AUC and 0.915 dice score respectively), the classification of the PIRADS score and the segmentation of lesions still have a large margin to improve (0.664 accuracy and 0.690 dice score respectively).
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.
Background: The detection of perineural invasion (PNI) by carcinoma in prostate biopsies has been shown to be associated with poor prognosis. The assessment and quantification of PNI is; however, labor intensive. In the study we aimed to develop an algorithm based on deep neural networks to aid pathologists in this task. Methods: We collected, digitized and pixel-wise annotated the PNI findings in each of the approximately 80,000 biopsy cores from the 7,406 men who underwent biopsy in the prospective and diagnostic STHLM3 trial between 2012 and 2014. In total, 485 biopsy cores showed PNI. We also digitized more than 10% (n=8,318) of the PNI negative biopsy cores. Digitized biopsies from a random selection of 80% of the men were used to build deep neural networks, and the remaining 20% were used to evaluate the performance of the algorithm. Results: For the detection of PNI in prostate biopsy cores the network had an estimated area under the receiver operating characteristics curve of 0.98 (95% CI 0.97-0.99) based on 106 PNI positive cores and 1,652 PNI negative cores in the independent test set. For the pre-specified operating point this translates to sensitivity of 0.87 and specificity of 0.97. The corresponding positive and negative predictive values were 0.67 and 0.99, respectively. For localizing the regions of PNI within a slide we estimated an average intersection over union of 0.50 (CI: 0.46-0.55). Conclusion: We have developed an algorithm based on deep neural networks for detecting PNI in prostate biopsies with apparently acceptable diagnostic properties. These algorithms have the potential to aid pathologists in the day-to-day work by drastically reducing the number of biopsy cores that need to be assessed for PNI and by highlighting regions of diagnostic interest.
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