Contrastive learning has shown superior performance in embedding global and spatial invariant features in computer vision (e.g., image classification). However, its overall success of embedding local and spatial variant features is still limited, especially for semantic segmentation. In a per-pixel prediction task, more than one label can exist in a single image for segmentation (e.g., an image contains both cat, dog, and grass), thereby it is difficult to define 'positive' or 'negative' pairs in a canonical contrastive learning setting. In this paper, we propose an attention-guided supervised contrastive learning approach to highlight a single semantic object every time as the target. With our design, the same image can be embedded to different semantic clusters with semantic attention (i.e., coerce semantic masks) as an additional input channel. To achieve such attention, a novel two-stage training strategy is presented. We evaluate the proposed method on multi-organ medical image segmentation task, as our major task, with both in-house data and BTCV 2015 datasets. Comparing with the supervised and semi-supervised training state-of-the-art in the backbone of ResNet-50, our proposed pipeline yields substantial improvement of 5.53% and 6.09% in Dice score for both medical image segmentation cohorts respectively. The performance of the proposed method on natural images is assessed via PASCAL VOC 2012 dataset, and achieves 2.75% substantial improvement.
The construction of three-dimensional multi-modal tissue maps provides an opportunity to spur interdisciplinary innovations across temporal and spatial scales through information integration. While the preponderance of effort is allocated to the cellular level and explore the changes in cell interactions and organizations, contextualizing findings within organs and systems is essential to visualize and interpret higher resolution linkage across scales. There is a substantial normal variation of kidney morphometry and appearance across body size, sex, and imaging protocols in abdominal computed tomography (CT). A volumetric atlas framework is needed to integrate and visualize the variability across scales. However, there is no abdominal and retroperitoneal organs atlas framework for multi-contrast CT. Hence, we proposed a high-resolution CT retroperitoneal atlas specifically optimized for the kidney across non-contrast CT and early arterial, late arterial, venous and delayed contrast enhanced CT. Briefly, we introduce a deep learning-based volume of interest extraction method and an automated two-stage hierarchal registration pipeline to register abdominal volumes to a high-resolution CT atlas template. To generate and evaluate the atlas, multi-contrast modality CT scans of 500 subjects (without reported history of renal disease, age: 15-50 years, 250 males & 250 females) were processed. We demonstrate a stable generalizability of the atlas template for integrating the normal kidney variation from small to large, across contrast modalities and populations with great variability of demographics. The linkage of atlas and demographics provided a better understanding of the variation of kidney anatomy across populations.
Performing coarse-to-fine abdominal multi-organ segmentation facilitates to extract high-resolution segmentation minimizing the lost of spatial contextual information. However, current coarse-to-refine approaches require a significant number of models to perform single organ refine segmentation corresponding to the extracted organ region of interest (ROI). We propose a coarse-to-fine pipeline, which starts from the extraction of the global prior context of multiple organs from 3D volumes using a low-resolution coarse network, followed by a fine phase that uses a single refined model to segment all abdominal organs instead of multiple organ corresponding models. We combine the anatomical prior with corresponding extracted patches to preserve the anatomical locations and boundary information for performing high-resolution segmentation across all organs in a single model. To train and evaluate our method, a clinical research cohort consisting of 100 patient volumes with 13 organs well-annotated is used. We tested our algorithms with 4-fold cross-validation and computed the Dice score for evaluating the segmentation performance of the 13 organs. Our proposed method using single auto-context outperforms the state-of-the-art on 13 models with an average Dice score 84.58% versus 81.69% (p<0.0001).
A major goal of lung cancer screening is to identify individuals with particular phenotypes that are associated with high risk of cancer. Identifying relevant phenotypes is complicated by the variation in body position and body composition. In the brain, standardized coordinate systems (e.g., atlases) have enabled separate consideration of local features from gross/global structure. To date, no analogous standard atlas has been presented to enable spatial mapping and harmonization in chest computational tomography (CT). In this paper, we propose a thoracic atlas built upon a large low dose CT (LDCT) database of lung cancer screening program. The study cohort includes 466 male and 387 female subjects with no screening detected malignancy (age 46-79 years, mean 64.9 years). To provide spatial mapping, we optimize a multi-stage inter-subject non-rigid registration pipeline for the entire thoracic space. We evaluate the optimized pipeline relative to two baselines with alternative non-rigid registration module: the same software with default parameters and an alternative software. We achieve a significant improvement in terms of registration success rate based on manual QA. For the entire study cohort, the optimized pipeline achieves a registration success rate of 91.7%. The application validity of the developed atlas is evaluated in terms of discriminative capability for different anatomic phenotypes, including body mass index (BMI), chronic obstructive pulmonary disease (COPD), and coronary artery calcification (CAC).
Clinical data elements (CDEs) (e.g., age, smoking history), blood markers and chest computed tomography (CT) structural features have been regarded as effective means for assessing lung cancer risk. These independent variables can provide complementary information and we hypothesize that combining them will improve the prediction accuracy. In practice, not all patients have all these variables available. In this paper, we propose a new network design, termed as multi-path multi-modal missing network (M3Net), to integrate the multi-modal data (i.e., CDEs, biomarker and CT image) considering missing modality with multiple paths neural network. Each path learns discriminative features of one modality, and different modalities are fused in a second stage for an integrated prediction. The network can be trained end-to-end with both medical image features and CDEs/biomarkers, or make a prediction with single modality. We evaluate M3Net with datasets including three sites from the Consortium for Molecular and Cellular Characterization of Screen-Detected Lesions (MCL) project. Our method is cross validated within a cohort of 1291 subjects (383 subjects with complete CDEs/biomarkers and CT images), and externally validated with a cohort of 99 subjects (99 with complete CDEs/biomarkers and CT images). Both cross-validation and external-validation results show that combining multiple modality significantly improves the predicting performance of single modality. The results suggest that integrating subjects with missing either CDEs/biomarker or CT imaging features can contribute to the discriminatory power of our model (p < 0.05, bootstrap two-tailed test). In summary, the proposed M3Net framework provides an effective way to integrate image and non-image data in the context of missing information.
Segmentation of abdominal computed tomography(CT) provides spatial context, morphological properties, and a framework for tissue-specific radiomics to guide quantitative Radiological assessment. A 2015 MICCAI challenge spurred substantial innovation in multi-organ abdominal CT segmentation with both traditional and deep learning methods. Recent innovations in deep methods have driven performance toward levels for which clinical translation is appealing. However, continued cross-validation on open datasets presents the risk of indirect knowledge contamination and could result in circular reasoning. Moreover, 'real world' segmentations can be challenging due to the wide variability of abdomen physiology within patients. Herein, we perform two data retrievals to capture clinically acquired deidentified abdominal CT cohorts with respect to a recently published variation on 3D U-Net (baseline algorithm). First, we retrieved 2004 deidentified studies on 476 patients with diagnosis codes involving spleen abnormalities (cohort A). Second, we retrieved 4313 deidentified studies on 1754 patients without diagnosis codes involving spleen abnormalities (cohort B). We perform prospective evaluation of the existing algorithm on both cohorts, yielding 13% and 8% failure rate, respectively. Then, we identified 51 subjects in cohort A with segmentation failures and manually corrected the liver and gallbladder labels. We re-trained the model adding the manual labels, resulting in performance improvement of 9% and 6% failure rate for the A and B cohorts, respectively. In summary, the performance of the baseline on the prospective cohorts was similar to that on previously published datasets. Moreover, adding data from the first cohort substantively improved performance when evaluated on the second withheld validation cohort.
Abdominal multi-organ segmentation of computed tomography (CT) images has been the subject of extensive research interest. It presents a substantial challenge in medical image processing, as the shape and distribution of abdominal organs can vary greatly among the population and within an individual over time. While continuous integration of novel datasets into the training set provides potential for better segmentation performance, collection of data at scale is not only costly, but also impractical in some contexts. Moreover, it remains unclear what marginal value additional data have to offer. Herein, we propose a single-pass active learning method through human quality assurance (QA). We built on a pre-trained 3D U-Net model for abdominal multi-organ segmentation and augmented the dataset either with outlier data (e.g., exemplars for which the baseline algorithm failed) or inliers (e.g., exemplars for which the baseline algorithm worked). The new models were trained using the augmented datasets with 5-fold cross-validation (for outlier data) and withheld outlier samples (for inlier data). Manual labeling of outliers increased Dice scores with outliers by 0.130, compared to an increase of 0.067 with inliers (p<0.001, two-tailed paired t-test). By adding 5 to 37 inliers or outliers to training, we find that the marginal value of adding outliers is higher than that of adding inliers. In summary, improvement on single-organ performance was obtained without diminishing multi-organ performance or significantly increasing training time. Hence, identification and correction of baseline failure cases present an effective and efficient method of selecting training data to improve algorithm performance.
Recently, multi-task networks have shown to both offer additional estimation capabilities, and, perhaps more importantly, increased performance over single-task networks on a "main/primary" task. However, balancing the optimization criteria of multi-task networks across different tasks is an area of active exploration. Here, we extend a previously proposed 3D attention-based network with four additional multi-task subnetworks for the detection of lung cancer and four auxiliary tasks (diagnosis of asthma, chronic bronchitis, chronic obstructive pulmonary disease, and emphysema). We introduce and evaluate a learning policy, Periodic Focusing Learning Policy (PFLP), that alternates the dominance of tasks throughout the training. To improve performance on the primary task, we propose an Internal-Transfer Weighting (ITW) strategy to suppress the loss functions on auxiliary tasks for the final stages of training. To evaluate this approach, we examined 3386 patients (single scan per patient) from the National Lung Screening Trial (NLST) and de-identified data from the Vanderbilt Lung Screening Program, with a 2517/277/592 (scans) split for training, validation, and testing. Baseline networks include a single-task strategy and a multi-task strategy without adaptive weights (PFLP/ITW), while primary experiments are multi-task trials with either PFLP or ITW or both. On the test set for lung cancer prediction, the baseline single-task network achieved prediction AUC of 0.8080 and the multi-task baseline failed to converge (AUC 0.6720). However, applying PFLP helped multi-task network clarify and achieved test set lung cancer prediction AUC of 0.8402. Furthermore, our ITW technique boosted the PFLP enabled multi-task network and achieved an AUC of 0.8462 (McNemar test, p < 0.01).
Tissue window filtering has been widely used in deep learning for computed tomography (CT) image analyses to improve training performance (e.g., soft tissue windows for abdominal CT). However, the effectiveness of tissue window normalization is questionable since the generalizability of the trained model might be further harmed, especially when such models are applied to new cohorts with different CT reconstruction kernels, contrast mechanisms, dynamic variations in the acquisition, and physiological changes. We evaluate the effectiveness of both with and without using soft tissue window normalization on multisite CT cohorts. Moreover, we propose a stochastic tissue window normalization (SWN) method to improve the generalizability of tissue window normalization. Different from the random sampling, the SWN method centers the randomization around the soft tissue window to maintain the specificity for abdominal organs. To evaluate the performance of different strategies, 80 training and 453 validation and testing scans from six datasets are employed to perform multi-organ segmentation using standard 2D U-Net. The six datasets cover the scenarios, where the training and testing scans are from (1) same scanner and same population, (2) same CT contrast but different pathology, and (3) different CT contrast and pathology. The traditional soft tissue window and nonwindowed approaches achieved better performance on (1). The proposed SWN achieved general superior performance on (2) and (3) with statistical analyses, which offers better generalizability for a trained model.
Dynamic contrast enhanced computed tomography (CT) is an imaging technique that provides critical information on the relationship of vascular structure and dynamics in the context of underlying anatomy. A key challenge for image processing with contrast enhanced CT is that phase discrepancies are latent in different tissues due to contrast protocols, vascular dynamics, and metabolism variance. Previous studies with deep learning frameworks have been proposed for classifying contrast enhancement with networks inspired by computer vision. Here, we revisit the challenge in the context of whole abdomen contrast enhanced CTs. To capture and compensate for the complex contrast changes, we propose a novel discriminator in the form of a multi-domain disentangled representation learning network. The goal of this network is to learn an intermediate representation that separates contrast enhancement from anatomy and enables classification of images with varying contrast time. Briefly, our unpaired contrast disentangling GAN(CD-GAN) Discriminator follows the ResNet architecture to classify a CT scan from different enhancement phases. To evaluate the approach, we trained the enhancement phase classifier on 21060 slices from two clinical cohorts of 230 subjects. Testing was performed on 9100 slices from 30 independent subjects who had been imaged with CT scans from all contrast phases. Performance was quantified in terms of the multi-class normalized confusion matrix. The proposed network significantly improved correspondence over baseline UNet, ResNet50 and StarGAN performance of accuracy scores 0.54. 0.55, 0.62 and 0.91, respectively. The proposed discriminator from the disentangled network presents a promising technique that may allow deeper modeling of dynamic imaging against patient specific anatomies.