The goals of this review paper on deep learning (DL) in medical imaging and radiation therapy are to (a) summarize what has been achieved to date; (b) identify common and unique challenges, and strategies that researchers have taken to address these challenges; and (c) identify some of the promising avenues for the future both in terms of applications as well as technical innovations. We introduce the general principles of DL and convolutional neural networks, survey five major areas of application of DL in medical imaging and radiation therapy, identify common themes, discuss methods for dataset expansion, and conclude by summarizing lessons learned, remaining challenges, and future directions.

Purpose: The authors are developing a computerized system for bladder segmentation in CT urography (CTU) as a critical component for computer-aided detection of bladder cancer. Methods: A deep-learning convolutional neural network (DL-CNN) was trained to distinguish between the inside and the outside of the bladder using 160 000 regions of interest (ROI) from CTU images. The trained DL-CNN was used to estimate the likelihood of an ROI being inside the bladder for ROIs centered at each voxel in a CTU case, resulting in a likelihood map. Thresholding and hole-filling were applied to the map to generate the initial contour for the bladder, which was then refined by 3D and 2D level sets. The segmentation performance was evaluated using 173 cases: 81 cases in the training set (42 lesions, 21 wall thickenings, and 18 normal bladders) and 92 cases in the test set (43 lesions, 36 wall thickenings, and 13 normal bladders). The computerized segmentation accuracy using the DL likelihood map was compared to that using a likelihood map generated by Haar features and a random forest classifier, and that using our previous conjoint level set analysis and segmentation system (CLASS) without using a likelihood map. All methods were evaluated relative to the 3D hand-segmented reference contours. Results: With DL-CNN-based likelihood map and level sets, the average volume intersection ratio, average percent volume error, average absolute volume error, average minimum distance, and the Jaccard index for the test set were 81.9% ± 12.1%, 10.2% ± 16.2%, 14.0% ± 13.0%, 3.6 ± 2.0 mm, and 76.2% ± 11.8%, respectively. With the Haar-feature-based likelihood map and level sets, the corresponding values were 74.3% ± 12.7%, 13.0% ± 22.3%, 20.5% ± 15.7%, 5.7 ± 2.6 mm, and 66.7% ± 12.6%, respectively. With our previous CLASS with local contour refinement (LCR) method, the corresponding values were 78.0% ± 14.7%, 16.5% ± 16.8%, 18.2% ± 15.0%, 3.8 ± 2.3 mm, and 73.9% ± 13.5%, respectively. Conclusions: The authors demonstrated that the DL-CNN can overcome the strong boundary between two regions that have large difference in gray levels and provides a seamless mask to guide level set segmentation, which has been a problem for many gradient-based segmentation methods. Compared to our previous CLASS with LCR method, which required two user inputs to initialize the segmentation, DL-CNN with level sets achieved better segmentation performance while using a single user input. Compared to the Haar-feature-based likelihood map, the DL-CNN-based likelihood map could guide the level sets to achieve better segmentation. The results demonstrate the feasibility of our new approach of using DL-CNN in combination with level sets for segmentation of the bladder. C 2016 American Association of Physicists in Medicine. [http://dx

Cross-sectional X-ray imaging has become the standard for staging most solid organ malignancies. However, for some malignancies such as urinary bladder cancer, the ability to accurately assess local extent of the disease and understand response to systemic chemotherapy is limited with current imaging approaches. In this study, we explored the feasibility that radiomics-based predictive models using pre- and post-treatment computed tomography (CT) images might be able to distinguish between bladder cancers with and without complete chemotherapy responses. We assessed three unique radiomics-based predictive models, each of which employed different fundamental design principles ranging from a pattern recognition method via deep-learning convolution neural network (DL-CNN), to a more deterministic radiomics feature-based approach and then a bridging method between the two, utilizing a system which extracts radiomics features from the image patterns. Our study indicates that the computerized assessment using radiomics information from the pre- and post-treatment CT of bladder cancer patients has the potential to assist in assessment of treatment response.

Transfer learning in deep convolutional neural networks (DCNNs) is an important step in its application to medical imaging tasks. We propose a multi-task transfer learning DCNN with the aims of translating the ‘knowledge’ learned from non-medical images to medical diagnostic tasks through supervised training and increasing the generalization capabilities of DCNNs by simultaneously learning auxiliary tasks. We studied this approach in an important application: classification of malignant and benign breast masses. With IRB approval, digitized screen-film mammograms (SFMs) and digital mammograms (DMs) were collected from our patient files and additional SFMs were obtained from the Digital Database for Screening Mammography. The data set consisted of 2,242 views with 2,454 masses (1,057 malignant, 1,397 benign). In single-task transfer learning, the DCNN was trained and tested on SFMs. In multi-task transfer learning, SFMs and DMs were used to train the DCNN, which was then tested on SFMs. N-fold cross-validation with the training set was used for training and parameter optimization. On the independent test set, the multitask transfer learning DCNN was found to have significantly (p=0.007) higher performance compared to the single-task transfer learning DCNN. This study demonstrates that multitask transfer learning may be an effective approach for training DCNN in medical imaging applications when training samples from a single modality are limited.

In this work we developed a deep convolutional neural network (CNN) for classification of malignant and benign masses in digital breast tomosynthesis (DBT) using a multi-stage transfer learning approach that utilized data from similar auxiliary domains for intermediate-stage finetuning. Breast imaging data from DBT and digitized screen-film mammography (SFM), digital mammography (DM) totaling 4,039 unique ROIs (1,797 malignant and 2,242 benign) were collected. Using cross-validation, we selected the best transfer network from six transfer networks by varying the level up to which the convolutional layers were frozen. In a single-stage transfer learning approach, knowledge from CNN trained on ImageNet data was fine-tuned directly with DBT data. In a multi-stage transfer learning approach, knowledge learned from ImageNet was first fine-tuned with the mammography data and then fine-tuned with the DBT data. Two transfer networks were compared for the second-stage transfer learning by freezing most of the CNN structure versus freezing only the first convolutional layer. We studied the dependence of the classification performance on training sample size for various transfer learning and fine-tuning schemes by varying the training data from 1% to 100% of the available sets. The area under the receiver operating characteristic curve (AUC) was used as a performance measure. The view-based AUC on the test set for single-stage transfer learning was 0.85±0.05 and improved significantly (p<0.05) to 0.91±0.03 for multi-stage learning. This study demonstrated that, when the training sample size from the target domain is limited, an additional stage of transfer-learning using data from a similar auxiliary domain is advantageous.