Recent advances in deep learning for medical image segmentation demonstrate expert-level accuracy. However, application of these models in clinically realistic environments can result in poor generalization and decreased accuracy, mainly due to the domain shift across different hospitals, scanner vendors, imaging protocols, and patient populations etc. Common transfer learning and domain adaptation techniques are proposed to address this bottleneck. However, these solutions require data (and annotations) from the target domain to retrain the model, and is therefore restrictive in practice for widespread model deployment. Ideally, we wish to have a trained (locked) model that can work uniformly well across unseen domains without further training. In this paper, we propose a deep stacked transformation approach for domain generalization. Specifically, a series of ${n}$ stacked transformations are applied to each image during network training. The underlying assumption is that the “expected” domain shift for a specific medical imaging modality could be simulated by applying extensive data augmentation on a single source domain, and consequently, a deep model trained on the augmented “big” data (BigAug) could generalize well on unseen domains. We exploit four surprisingly effective, but previously understudied, image-based characteristics for data augmentation to overcome the domain generalization problem. We train and evaluate the BigAug model (with ${n}={9}$ transformations) on three different 3D segmentation tasks (prostate gland, left atrial, left ventricle) covering two medical imaging modalities (MRI and ultrasound) involving eight publicly available challenge datasets. The results show that when training on relatively small dataset (n = 10~32 volumes, depending on the size of the available datasets) from a single source domain: (i) BigAug models degrade an average of 11%(Dice score change) from source to unseen domain, substantially better than conventional augmentation (degrading 39%) and CycleGAN-based domain adaptation method (degrading 25%), (ii) BigAug is better than “shallower” stacked transforms (i.e. those with fewer transforms) on unseen domains and demonstrates modest improvement to conventional augmentation on the source domain, (iii) after training with BigAug on one source domain, performance on an unseen domain is similar to training a model from scratch on that domain when using the same number of training samples. When training on large datasets (n = 465 volumes) with BigAug, (iv) application to unseen domains reaches the performance of state-of-the-art fully supervised models that are trained and tested on their source domains. These findings establish a strong benchmark for the study of domain generalization in medical imaging, and can be generalized to the design of highly robust deep segmentation models for clinical deployment.

Automation-assisted cervical screening via Pap smear or liquid-based cytology (LBC) is a highly effective cell imaging based cancer detection tool, where cells are partitioned into “abnormal” and “normal” categories. However, the success of most traditional classification methods relies on the presence of accurate cell segmentations. Despite sixty years of research in this field, accurate segmentation remains a challenge in the presence of cell clusters and pathologies. Moreover, previous classification methods are only built upon the extraction of hand-crafted features, such as morphology and texture. This paper addresses these limitations by proposing a method to directly classify cervical cells-without prior segmentation- based on deep features, using convolutional neural networks (ConvNets). First, the ConvNet is pretrained on a natural image dataset. It is subsequently fine-tuned on a cervical cell dataset consisting of adaptively resampled image patches coarsely centered on the nuclei. In the testing phase, aggregation is used to average the prediction scores of a similar set of image patches. The proposed method is evaluated on both Pap smear and LBC datasets. Results show that our method outperforms previous algorithms in classification accuracy (98.3%), area under the curve (0.99) values, and especially specificity (98.3%), when applied to the Herlev benchmark Pap smear dataset and evaluated using five-fold cross validation. Similar superior performances are also achieved on the HEMLBC (H&E stained manual LBC) dataset. Our method is promising for the development of automation-assisted reading systems in primary cervical screening.

Pancreatic ductal adenocarcinoma (PDAC), the most deadly solid malignancy, is typically detected late and at an inoperable stage. Early or incidental detection is associated with prolonged survival, but screening asymptomatic individuals for PDAC using a single test remains unfeasible due to the low prevalence and potential harms of false positives. Non-contrast computed tomography (CT), routinely performed for clinical indications, offers the potential for large-scale screening, however, identification of PDAC using non-contrast CT has long been considered impossible. Here, we develop a deep learning approach, pancreatic cancer detection with artificial intelligence (PANDA), that can detect and classify pancreatic lesions with high accuracy via non-contrast CT. PANDA is trained on a dataset of 3,208 patients from a single center. PANDA achieves an area under the receiver operating characteristic curve (AUC) of 0.986–0.996 for lesion detection in a multicenter validation involving 6,239 patients across 10 centers, outperforms the mean radiologist performance by 34.1% in sensitivity and 6.3% in specificity for PDAC identification, and achieves a sensitivity of 92.9% and specificity of 99.9% for lesion detection in a real-world multi-scenario validation consisting of 20,530 consecutive patients. Notably, PANDA utilized with non-contrast CT shows non-inferiority to radiology reports (using contrast-enhanced CT) in the differentiation of common pancreatic lesion subtypes. PANDA could potentially serve as a new tool for large-scale pancreatic cancer screening.

An artificial intelligence model outperformed radiologists and clinical and radiomics models for prediction of lymph node metastasis at CT in patients with pancreatic ductal adenocarcinoma. Background Although deep learning has brought revolutionary changes in health care, reliance on manually selected cross-sectional images and segmentation remain methodological barriers. Purpose To ...

Prognostic tumor growth modeling via volumetric medical imaging observations can potentially lead to better outcomes of tumor treatment management and surgical planning. Recent advances of convolutional networks (ConvNets) have demonstrated higher accuracy than traditional mathematical models can be achieved in predicting future tumor volumes. This indicates that deep learning based data-driven techniques may have great potentials on addressing such problem. However, current 2D image patch based modeling approaches can not make full use of the spatio-temporal imaging context of the tumor's longitudinal 4D (3D + time) patient data. Moreover, they are incapable to predict clinically-relevant tumor properties, other than the tumor volumes. In this paper, we exploit to formulate the tumor growth process through convolutional Long Short-Term Memory (ConvLSTM) that extract tumor's static imaging appearances and simultaneously capture its temporal dynamic changes within a single network. We extend ConvLSTM into the spatio-temporal domain (ST-ConvLSTM) by jointly learning the inter-slice 3D contexts and the longitudinal or temporal dynamics from multiple patient studies. Our approach can incorporate other non-imaging patient information in an end-to-end trainable manner. Experiments are conducted on the largest 4D longitudinal tumor dataset of 33 patients to date. Results validate that the proposed ST-ConvLSTM model produces a Dice score of 83.2%±5.1% and a RVD of 11.2%±10.8%, both statistically significantly outperforming (p <; 0.05) other compared methods of traditional linear model, ConvLSTM, and generative adversarial network (GAN) under the metric of predicting future tumor volumes. Additionally, our new method enables the prediction of both cell density and CT intensity numbers. Last, we demonstrate the generalizability of ST-ConvLSTM by employing it in 4D medical image segmentation task, which achieves an averaged Dice score of 86.3%±1.2% for left-ventricle segmentation in 4D ultrasound with 3 seconds per patient case.

Tumor growth is associated with cell invasion and mass-effect, which are traditionally formulated by mathematical models, namely reaction-diffusion equations and biomechanics. Such models can be personalized based on clinical measurements to build the predictive models for tumor growth. In this paper, we investigate the possibility of using deep convolutional neural networks to directly represent and learn the cell invasion and mass-effect, and to predict the subsequent involvement regions of a tumor. The invasion network learns the cell invasion from information related to metabolic rate, cell density, and tumor boundary derived from multimodal imaging data. The expansion network models the mass-effect from the growing motion of tumor mass. We also study different architectures that fuse the invasion and expansion networks, in order to exploit the inherent correlations among them. Our network can easily be trained on population data and personalized to a target patient, unlike most previous mathematical modeling methods that fail to incorporate population data. Quantitative experiments on a pancreatic tumor data set show that the proposed method substantially outperforms a state-of-the-art mathematical model-based approach in both accuracy and efficiency, and that the information captured by each of the two subnetworks is complementary.