3D delineation of anatomical structures is a cardinal goal in medical imaging analysis. Prior to deep learning, statistical shape models (SSMs) that imposed anatomical constraints and produced high quality surfaces were a core technology. Today’s fully-convolutional networks (FCNs), while dominant, do not offer these capabilities. We present deep implicit statistical shape models (DISSMs), a new approach that marries the representation power of deep networks with the benefits of SSMs. DISSMs use an implicit representation to produce compact and descriptive deep surface embeddings that permit statistical models of anatomical variance. To reliably fit anatomically plausible shapes to an image, we introduce a novel rigid and non-rigid pose estimation pipeline that is modelled as a Markov decision process (MDP). Intra-dataset experiments on the task of pathological liver segmentation demonstrate that DISSMs can perform more robustly than four leading FCN models, including nnU-Net + an adversarial prior: reducing the mean Hausdorff distance (HD) by 7.5-14.3 mm and improving the worst case Dice-Sørensen coefficient (DSC) by 1.2-2.3%. More critically, cross-dataset experiments on an external and highly challenging clinical dataset demonstrate that DISSMs improve the mean DSC and HD by 2.1-5.9% and 9.9-24.5 mm, respectively, and the worst-case DSC by 5.4-7.3%. Supplemental validation on a highly challenging and low-contrast larynx dataset further demonstrate DISSM’s improvements. These improvements are over and above any benefits from representing delineations with high-quality surfaces.

Deep learning methods can struggle to handle domain shifts not seen in training data, which can cause them to not generalize well to unseen domains. This has led to research attention on domain generalization (DG), which aims to the model's generalization ability to out-of-distribution. Adversarial domain generalization is a popular approach to DG, but conventional approaches (1) struggle to sufficiently align features so that local neighborhoods are mixed across domains; and (2) can suffer from feature space over collapse which can threaten generalization performance. To address these limitations, we propose localized adversarial domain generalization with space compactness maintenance (LADG) which constitutes two major contributions. First, we propose an adversarial localized classifier as the domain discriminator, along with a principled primary branch. This constructs a min-max game whereby the aim of the featurizer is to produce locally mixed domains. Second, we propose to use a coding-rate loss to alleviate feature space over collapse. We conduct comprehensive experiments on the Wilds DG benchmark to validate our approach, where LADG outperforms leading competitors on most datasets.

Radiological images such as computed tomography (CT) and X-rays render anatomy with intrinsic structures. Being able to reliably locate the same anatomical structure across varying images is a fundamental task in medical image analysis. In principle it is possible to use landmark detection or semantic segmentation for this task, but to work well these require large numbers of labeled data for each anatomical structure and sub-structure of interest. A more universal approach would learn the intrinsic structure from unlabeled images. We introduce such an approach, called Self-supervised Anatomical eMbedding (SAM). SAM generates semantic embeddings for each image pixel that describes its anatomical location or body part. To produce such embeddings, we propose a pixel-level contrastive learning framework. A coarse-to-fine strategy ensures both global and local anatomical information are encoded. Negative sample selection strategies are designed to enhance the embedding's discriminability. Using SAM, one can label any point of interest on a template image and then locate the same body part in other images by simple nearest neighbor searching. We demonstrate the effectiveness of SAM in multiple tasks with 2D and 3D image modalities. On a chest CT dataset with 19 landmarks, SAM outperforms widely-used registration algorithms while only taking 0.23 seconds for inference. On two X-ray datasets, SAM, with only one labeled template image, surpasses supervised methods trained on 50 labeled images. We also apply SAM on whole-body follow-up lesion matching in CT and obtain an accuracy of 91%. SAM can also be applied for improving image registration and initializing CNN weights.

Object detection methods are widely adopted for computer-aided diagnosis using medical images. Anomalous findings are usually treated as objects that are described by bounding boxes. Yet, many pathological findings, e.g., bone fractures, cannot be clearly defined by bounding boxes, owing to considerable instance, shape and boundary ambiguities. This makes bounding box annotations, and their associated losses, highly ill-suited. In this work, we propose a new bone fracture detection method for X-ray images, based on a labor effective and flexible annotation scheme suitable for abnormal findings with no clear object-level spatial extents or boundaries. Our method employs a simple, intuitive, and informative point-based annotation protocol to mark localized pathology information. To address the uncertainty in the fracture scales annotated via point(s), we convert the annotations into pixel-wise supervision that uses lower and upper bounds with positive, negative, and uncertain regions. A novel Window Loss is subsequently proposed to only penalize the predictions outside of the uncertain regions. Our method has been extensively evaluated on 4410 pelvic X-ray images of unique patients. Experiments demonstrate that our method outperforms previous state-of-the-art image classification and object detection baselines by healthy margins, with an AUROC of 0.983 and FROC score of 89.6%.

Monitoring treatment response in longitudinal studies plays an important role in clinical practice. Accurately identifying lesions across serial imaging follow-up is the core to the monitoring procedure. Typically this incorporates both image and anatomical considerations. However, matching lesions manually is labor-intensive and time-consuming. In this work, we present deep lesion tracker (DLT), a deep learning approach that uses both appearance- and anatomical-based signals. To incorporate anatomical constraints, we propose an anatomical signal encoder, which prevents lesions being matched with visually similar but spurious regions. In addition, we present a new formulation for Siamese networks that avoids the heavy computational loads of 3D cross-correlation. To present our network with greater varieties of images, we also propose a self-supervised learning (SSL) strategy to train trackers with unpaired images, overcoming barriers to data collection. To train and evaluate our tracker, we introduce and release the first lesion tracking benchmark, consisting of 3891 lesion pairs from the public DeepLesion database. The proposed method, DLT, locates lesion centers with a mean error distance of 7mm. This is 5% better than a leading registration algorithm while running 14 times faster on whole CT volumes. We demonstrate even greater improvements over detector or similarity-learning alternatives. DLT also generalizes well on an external clinical test set of 100 longitudinal studies, achieving 88% accuracy. Finally, we plug DLT into an automatic tumor monitoring workflow where it leads to an accuracy of 85% in assessing lesion treatment responses, which is only 0.46% lower than the accuracy of manual inputs.

The acquisition of large-scale medical image data, necessary for training machine learning algorithms, is hampered by associated expert-driven annotation costs. Mining hospital archives can address this problem, but labels often incomplete or noisy, e.g., 50% of the lesions in DeepLesion are left unlabeled. Thus, effective label harvesting methods are critical. This is the goal of our work, where we introduce Lesion-Harvester-a powerful system to harvest missing annotations from lesion datasets at high precision. Accepting the need for some degree of expert labor, we use a small fully-labeled image subset to intelligently mine annotations from the remainder. To do this, we chain together a highly sensitive lesion proposal generator (LPG) and a very selective lesion proposal classifier (LPC). Using a new hard negative suppression loss, the resulting harvested and hard-negative proposals are then employed to iteratively finetune our LPG. While our framework is generic, we optimize our performance by proposing a new 3D contextual LPG and by using a global-local multi-view LPC. Experiments on DeepLesion demonstrate that Lesion-Harvester can discover an additional 9,805 lesions at a precision of 90%. We publicly release the harvested lesions, along with a new test set of completely annotated DeepLesion volumes. We also present a pseudo 3D IoU evaluation metric that corresponds much better to the real 3D IoU than current DeepLesion evaluation metrics. To quantify the downstream benefits of Lesion-Harvester we show that augmenting the DeepLesion annotations with our harvested lesions allows state-of-the-art detectors to boost their average precision by 7 to 10%.

Accurate segmentation of anatomical structures is vital for medical image analysis. The state-of-the-art accuracy is typically achieved by supervised learning methods, where gathering the requisite expert-labeled image annotations in a scalable manner remains a main obstacle. Therefore, annotation-efficient methods that permit to produce accurate anatomical structure segmentation are highly desirable. In this work, we present Contour Transformer Network (CTN), a one-shot anatomy segmentation method with a naturally built-in human-in-the-loop mechanism. We formulate anatomy segmentation as a contour evolution process and model the evolution behavior by graph convolutional networks (GCNs). Training the CTN model requires only one labeled image exemplar and leverages additional unlabeled data through newly introduced loss functions that measure the global shape and appearance consistency of contours. On segmentation tasks of four different anatomies, we demonstrate that our one-shot learning method significantly outperforms non-learning-based methods and performs competitively to the state-of-the-art fully supervised deep learning methods. With minimal human-in-the-loop editing feedback, the segmentation performance can be further improved to surpass the fully supervised methods.

Large-scale datasets with high-quality labels are desired for training accurate deep learning models. However, due to the annotation cost, datasets in medical imaging are often either partially-labeled or small. For example, DeepLesion is such a large-scale CT image dataset with lesions of various types, but it also has many unlabeled lesions (missing annotations). When training a lesion detector on a partially-labeled dataset, the missing annotations will generate incorrect negative signals and degrade the performance. Besides DeepLesion, there are several small single-type datasets, such as LUNA for lung nodules and LiTS for liver tumors. These datasets have heterogeneous label scopes, i.e., different lesion types are labeled in different datasets with other types ignored. In this work, we aim to develop a universal lesion detection algorithm to detect a variety of lesions. The problem of heterogeneous and partial labels is tackled. First, we build a simple yet effective lesion detection framework named Lesion ENSemble (LENS). LENS can efficiently learn from multiple heterogeneous lesion datasets in a multi-task fashion and leverage their synergy by proposal fusion. Next, we propose strategies to mine missing annotations from partially-labeled datasets by exploiting clinical prior knowledge and cross-dataset knowledge transfer. Finally, we train our framework on four public lesion datasets and evaluate it on 800 manually-labeled sub-volumes in DeepLesion. Our method brings a relative improvement of 49% compared to the current state-of-the-art approach in the metric of average sensitivity. We have publicly released our manual 3D annotations of DeepLesion online.11https://github.com/viggin/DeepLesion_manual_test_set

OAR segmentation is a critical step in radiotherapy of head and neck (H&N) cancer, where inconsistencies across radiation oncologists and prohibitive labor costs motivate automated approaches. However, leading methods using standard fully convolutional network workflows that are challenged when the number of OARs becomes large, e.g. > 40. For such scenarios, insights can be gained from the stratification approaches seen in manual clinical OAR delineation. This is the goal of our work, where we introduce stratified organ at risk segmentation (SOARS), an approach that stratifies OARs into anchor, mid-level, and small & hard (S&H) categories. SOARS stratifies across two dimensions. The first dimension is that distinct processing pipelines are used for each OAR category. In particular, inspired by clinical practices, anchor OARs are used to guide the mid-level and S&H categories. The second dimension is that distinct network architectures are used to manage the significant contrast, size, and anatomy variations between different OARs. We use differentiable neural architecture search (NAS), allowing the network to choose among 2D, 3D or Pseudo-3D convolutions. Extensive 4-fold cross-validation on 142 H&N cancer patients with 42 manually labeled OARs, the most comprehensive OAR dataset to date, demonstrates that both pipeline- and NAS-stratification significantly improves quantitative performance over the state-of-the-art (from 69.52% to 73.68% in absolute Dice scores). Thus, SOARS provides a powerful and principled means to manage the highly complex segmentation space of OARs.

Radiologists in their daily work routinely find and annotate significant abnormalities on a large number of radiology images. Such abnormalities, or lesions, have collected over years and stored in hospitals' picture archiving and communication systems. However, they are basically unsorted and lack semantic annotations like type and location. In this paper, we aim to organize and explore them by learning a deep feature representation for each lesion. A large-scale and comprehensive dataset, DeepLesion, is introduced for this task. DeepLesion contains bounding boxes and size measurements of over 32K lesions. To model their similarity relationship, we leverage multiple supervision information including types, self-supervised location coordinates, and sizes. They require little manual annotation effort but describe useful attributes of the lesions. Then, a triplet network is utilized to learn lesion embeddings with a sequential sampling strategy to depict their hierarchical similarity structure. Experiments show promising qualitative and quantitative results on lesion retrieval, clustering, and classification. The learned embeddings can be further employed to build a lesion graph for various clinically useful applications. An algorithm for intra-patient lesion matching is proposed and validated with experiments.

Photometric stereo and depth-map estimation provide a way to construct a depth map from images of an object under one viewpoint but with varying illumination directions. While estimating surface normals using the Lambertian model of reflectance is well established, depth-map estimation is an ongoing field of research and dealing with image noise is an active topic. Using the zero-mean Gaussian model of image noise, this paper introduces a method for maximum likelihood depth-map estimation that accounts for the propagation of noise through all steps of the estimation process. Solving for maximum likelihood depth-map estimates involves an independent sequence of nonlinear regression estimates, one for each pixel, followed by a single large and sparse linear regression estimate. The linear system employs anisotropic weights, which arise naturally and differ in value to related work. The new depth-map estimation method remains efficient and fast, making it practical for realistic image sizes. Experiments using synthetic images demonstrate the method's ability to robustly estimate depth maps under the noise model. Practical benefits of the method on challenging imaging scenarios are illustrated by experiments using the Extended Yale Face Database B and an extensive data set of 500 reflected light microscopy image sequences.