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Divide-and-Rule: Self-Supervised Learning for Survival Analysis in Colorectal Cancer

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 Added by Christian Abbet
 Publication date 2020
and research's language is English




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With the long-term rapid increase in incidences of colorectal cancer (CRC), there is an urgent clinical need to improve risk stratification. The conventional pathology report is usually limited to only a few histopathological features. However, most of the tumor microenvironments used to describe patterns of aggressive tumor behavior are ignored. In this work, we aim to learn histopathological patterns within cancerous tissue regions that can be used to improve prognostic stratification for colorectal cancer. To do so, we propose a self-supervised learning method that jointly learns a representation of tissue regions as well as a metric of the clustering to obtain their underlying patterns. These histopathological patterns are then used to represent the interaction between complex tissues and predict clinical outcomes directly. We furthermore show that the proposed approach can benefit from linear predictors to avoid overfitting in patient outcomes predictions. To this end, we introduce a new well-characterized clinicopathological dataset, including a retrospective collective of 374 patients, with their survival time and treatment information. Histomorphological clusters obtained by our method are evaluated by training survival models. The experimental results demonstrate statistically significant patient stratification, and our approach outperformed the state-of-the-art deep clustering methods.



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Deriving interpretable prognostic features from deep-learning-based prognostic histopathology models remains a challenge. In this study, we developed a deep learning system (DLS) for predicting disease specific survival for stage II and III colorectal cancer using 3,652 cases (27,300 slides). When evaluated on two validation datasets containing 1,239 cases (9,340 slides) and 738 cases (7,140 slides) respectively, the DLS achieved a 5-year disease-specific survival AUC of 0.70 (95%CI 0.66-0.73) and 0.69 (95%CI 0.64-0.72), and added significant predictive value to a set of 9 clinicopathologic features. To interpret the DLS, we explored the ability of different human-interpretable features to explain the variance in DLS scores. We observed that clinicopathologic features such as T-category, N-category, and grade explained a small fraction of the variance in DLS scores (R2=18% in both validation sets). Next, we generated human-interpretable histologic features by clustering embeddings from a deep-learning based image-similarity model and showed that they explain the majority of the variance (R2 of 73% to 80%). Furthermore, the clustering-derived feature most strongly associated with high DLS scores was also highly prognostic in isolation. With a distinct visual appearance (poorly differentiated tumor cell clusters adjacent to adipose tissue), this feature was identified by annotators with 87.0-95.5% accuracy. Our approach can be used to explain predictions from a prognostic deep learning model and uncover potentially-novel prognostic features that can be reliably identified by people for future validation studies.
Microscopic examination of tissues or histopathology is one of the diagnostic procedures for detecting colorectal cancer. The pathologist involved in such an examination usually identifies tissue type based on texture analysis, especially focusing on tumour-stroma ratio. In this work, we automate the task of tissue classification within colorectal cancer histology samples using deep transfer learning. We use discriminative fine-tuning with one-cycle-policy and apply structure-preserving colour normalization to boost our results. We also provide visual explanations of the deep neural networks decision on texture classification. With achieving state-of-the-art test accuracy of 96.2% we also embark on using deployment friendly architecture called SqueezeNet for memory-limited hardware.
Colorectal cancer is a leading cause of death worldwide. However, early diagnosis dramatically increases the chances of survival, for which it is crucial to identify the tumor in the body. Since its imaging uses high-resolution techniques, annotating the tumor is time-consuming and requires particular expertise. Lately, methods built upon Convolutional Neural Networks(CNNs) have proven to be at par, if not better in many biomedical segmentation tasks. For the task at hand, we propose another CNN-based approach, which uses atrous convolutions and residual connections besides the conventional filters. The training and inference were made using an efficient patch-based approach, which significantly reduced unnecessary computations. The proposed AtResUNet was trained on the DigestPath 2019 Challenge dataset for colorectal cancer segmentation with results having a Dice Coefficient of 0.748.
Background and Objective: Early detection of lung cancer is crucial as it has high mortality rate with patients commonly present with the disease at stage 3 and above. There are only relatively few methods that simultaneously detect and classify nodules from computed tomography (CT) scans. Furthermore, very few studies have used semi-supervised learning for lung cancer prediction. This study presents a complete end-to-end scheme to detect and classify lung nodules using the state-of-the-art Self-training with Noisy Student method on a comprehensive CT lung screening dataset of around 4,000 CT scans. Methods: We used three datasets, namely LUNA16, LIDC and NLST, for this study. We first utilise a three-dimensional deep convolutional neural network model to detect lung nodules in the detection stage. The classification model known as Maxout Local-Global Network uses non-local networks to detect global features including shape features, residual blocks to detect local features including nodule texture, and a Maxout layer to detect nodule variations. We trained the first Self-training with Noisy Student model to predict lung cancer on the unlabelled NLST datasets. Then, we performed Mixup regularization to enhance our scheme and provide robustness to erroneous labels. Results and Conclusions: Our new Mixup Maxout Local-Global network achieves an AUC of 0.87 on 2,005 completely independent testing scans from the NLST dataset. Our new scheme significantly outperformed the next highest performing method at the 5% significance level using DeLongs test (p = 0.0001). This study presents a new complete end-to-end scheme to predict lung cancer using Self-training with Noisy Student combined with Mixup regularization. On a completely independent dataset of 2,005 scans, we achieved state-of-the-art performance even with more images as compared to other methods.
Deep learning (DL) has emerged as a powerful tool for accelerated MRI reconstruction, but these methods often necessitate a database of fully-sampled measurements for training. Recent self-supervised and unsupervised learning approaches enable training without fully-sampled data. However, a database of undersampled measurements may not be available in many scenarios, especially for scans involving contrast or recently developed translational acquisitions. Moreover, database-trained models may not generalize well when the unseen measurements differ in terms of sampling pattern, acceleration rate, SNR, image contrast, and anatomy. Such challenges necessitate a new methodology that can enable scan-specific DL MRI reconstruction without any external training datasets. In this work, we propose a zero-shot self-supervised learning approach to perform scan-specific accelerated MRI reconstruction to tackle these issues. The proposed approach splits available measurements for each scan into three disjoint sets. Two of these sets are used to enforce data consistency and define loss during training, while the last set is used to establish an early stopping criterion. In the presence of models pre-trained on a database with different image characteristics, we show that the proposed approach can be combined with transfer learning to further improve reconstruction quality.
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