Image Analysis

The quantitative characterization of surface structures captured in scanning electron microscopy (SEM) images has proven to be effective for discerning provenance of an unknown nuclear material. Recently, many works have taken advantage of the powerful performance of convolutional neural networks (CNNs) to provide faster and more consistent characterization of surface structures. However, one inherent limitation of CNNs is their degradation in performance when encountering discrepancy between training and test datasets, which limits their use widely.The common discrepancy in an SEM image dataset occurs at low-level image information due to user-bias in selecting acquisition parameters and microscopes from different manufacturers.Therefore, in this study, we present a domain adaptation framework to improve robustness of CNNs against the discrepancy in low-level image information. Furthermore, our proposed approach makes use of only unlabeled test samples to adapt a pretrained model, which is more suitable for nuclear forensics application for which obtaining both training and test datasets simultaneously is a challenge due to data sensitivity. Through extensive experiments, we demonstrate that our proposed approach effectively improves the performance of a model by at least 18% when encountering domain discrepancy, and can be deployed in many CNN architectures.

We present MedShapeNet, a large collection of anatomical shapes (e.g., bones, organs, vessels) and 3D surgical instrument models. Prior to the deep learning era, the broad application of statistical shape models (SSMs) in medical image analysis is evidence that shapes have been commonly used to describe medical data. Nowadays, however, state-of-the-art (SOTA) deep learning algorithms in medical imaging are predominantly voxel-based. In computer vision, on the contrary, shapes (including, voxel occupancy grids, meshes, point clouds and implicit surface models) are preferred data representations in 3D, as seen from the numerous shape-related publications in premier vision conferences, such as the IEEE/CVF Conference on Computer Vision and Pattern Recognition (CVPR), as well as the increasing popularity of ShapeNet (about 51,300 models) and Princeton ModelNet (127,915 models) in computer vision research. MedShapeNet is created as an alternative to these commonly used shape benchmarks to facilitate the translation of data-driven vision algorithms to medical applications, and it extends the opportunities to adapt SOTA vision algorithms to solve critical medical problems. Besides, the majority of the medical shapes in MedShapeNet are modeled directly on the imaging data of real patients, and therefore it complements well existing shape benchmarks consisting of computer-aided design (CAD) models. MedShapeNet currently includes more than 100,000 medical shapes, and provides annotations in the form of paired data. It is therefore also a freely available repository of 3D models for extended reality (virtual reality - VR, augmented reality - AR, mixed reality - MR) and medical 3D printing. This white paper describes in detail the motivations behind MedShapeNet, the shape acquisition procedures, the use cases, as well as the usage of the online shape search portal: https://medshapenet.ikim.nrw/

With the advent of digital scanners and deep learning, diagnostic operations may move from a microscope to a desktop. Hematoxylin and Eosin (H&E) staining is one of the most frequently used stains for disease analysis, diagnosis, and grading, but pathologists do need different immunohistochemical (IHC) stains to analyze specific structures or cells. Obtaining all of these stains (H&E and different IHCs) on a single specimen is a tedious and time-consuming task. Consequently, virtual staining has emerged as an essential research direction. Here, we propose a novel generative model, Structural Cycle-GAN (SC-GAN), for synthesizing IHC stains from H&E images, and vice versa. Our method expressly incorporates structural information in the form of edges (in addition to color data) and employs attention modules exclusively in the decoder of the proposed generator model. This integration enhances feature localization and preserves contextual information during the generation process. In addition, a structural loss is incorporated to ensure accurate structure alignment between the generated and input markers. To demonstrate the efficacy of the proposed model, experiments are conducted with two IHC markers emphasizing distinct structures of glands in the colon: the nucleus of epithelial cells (CDX2) and the cytoplasm (CK818). Quantitative metrics such as FID and SSIM are frequently used for the analysis of generative models, but they do not correlate explicitly with higher-quality virtual staining results. Therefore, we propose two new quantitative metrics that correlate directly with the virtual staining specificity of IHC markers.

Deep learning based methods for automatic organ segmentation have shown promise in aiding diagnosis and treatment planning. However, quantifying and understanding the uncertainty associated with model predictions is crucial in critical clinical applications. While many techniques have been proposed for epistemic or model-based uncertainty estimation, it is unclear which method is preferred in the medical image analysis setting. This paper presents a comprehensive benchmarking study that evaluates epistemic uncertainty quantification methods in organ segmentation in terms of accuracy, uncertainty calibration, and scalability. We provide a comprehensive discussion of the strengths, weaknesses, and out-of-distribution detection capabilities of each method as well as recommendations for future improvements. These findings contribute to the development of reliable and robust models that yield accurate segmentations while effectively quantifying epistemic uncertainty.

Objective: We present the development of a non-contrast multi-parametric magnetic resonance (MPMR) imaging biomarker to assess treatment outcomes for magnetic resonance-guided focused ultrasound (MRgFUS) ablations of localized tumors. Images obtained immediately following MRgFUS ablation were inputs for voxel- wise supervised learning classifiers, trained using registered histology as a label for thermal necrosis. Methods: VX2 tumors in New Zealand white rabbits quadriceps were thermally ablated using an MRgFUS system under 3 T MRI guidance. Animals were re-imaged three days post-ablation and euthanized. Histological necrosis labels were created by 3D registration between MR images and digitized H&E segmentations of thermal necrosis to enable voxel- wise classification of necrosis. Supervised MPMR classifier inputs included maximum temperature rise, cumulative thermal dose (CTD), post-FUS differences in T2-weighted images, and apparent diffusion coefficient, or ADC, maps. A logistic regression, support vector machine, and random forest classifier were trained in red a leave-one-out strategy in test data from four subjects. Results: In the validation dataset, the MPMR classifiers achieved higher recall and Dice than than a clinically adopted 240 cumulative equivalent minutes at 43^∘ C (CEM ₄₃ ) threshold (0.43) in all subjects.redThe average Dice scores of overlap with the registered histological label for the logistic regression (0.63) and support vector machine (0.63) MPMR classifiers were within 6% of the acute contrast-enhanced non-perfused volume (0.67). Conclusions: Voxel- wise registration of MPMR data to histological outcomes facilitated supervised learning of an accurate non-contrast MR biomarker for MRgFUS ablations in a rabbit VX2 tumor model.

Annotating medical imaging datasets is costly, so fine-tuning (or transfer learning) is the most effective method for digital pathology vision applications such as disease classification and semantic segmentation. However, due to texture bias in models trained on real-world images, transfer learning for histopathology applications might result in underperforming models, which necessitates the need for using unlabeled histopathology data and self-supervised methods to discover domain-specific characteristics. Here, we tested the premise that histopathology-specific pretrained models provide better initializations for pathology vision tasks, i.e., gland and cell segmentation. In this study, we compare the performance of gland and cell segmentation tasks with domain-specific and non-domain-specific pretrained weights. Moreover, we investigate the data size at which domain-specific pretraining produces a statistically significant difference in performance. In addition, we investigated whether domain-specific initialization improves the effectiveness of out-of-domain testing on distinct datasets but the same task. The results indicate that performance gain using domain-specific pretraining depends on both the task and the size of the training dataset. In instances with limited dataset sizes, a significant improvement in gland segmentation performance was also observed, whereas models trained on cell segmentation datasets exhibit no improvement.

Statistical shape models (SSM) have been well-established as an excellent tool for identifying variations in the morphology of anatomy across the underlying population. Shape models use consistent shape representation across all the samples in a given cohort, which helps to compare shapes and identify the variations that can detect pathologies and help in formulating treatment plans. In medical imaging, computing these shape representations from CT/MRI scans requires time-intensive preprocessing operations, including but not limited to anatomy segmentation annotations, registration, and texture denoising. Deep learning models have demonstrated exceptional capabilities in learning shape representations directly from volumetric images, giving rise to highly effective and efficient Image-to-SSM. Nevertheless, these models are data-hungry and due to the limited availability of medical data, deep learning models tend to overfit. Offline data augmentation techniques, that use kernel density estimation based (KDE) methods for generating shape-augmented samples, have successfully aided Image-to-SSM networks in achieving comparable accuracy to traditional SSM methods. However, these augmentation methods focus on shape augmentation, whereas deep learning models exhibit image-based texture bias results in sub-optimal models. This paper introduces a novel strategy for on-the-fly data augmentation for the Image-to-SSM framework by leveraging data-dependent noise generation or texture augmentation. The proposed framework is trained as an adversary to the Image-to-SSM network, augmenting diverse and challenging noisy samples. Our approach achieves improved accuracy by encouraging the model to focus on the underlying geometry rather than relying solely on pixel values.

The goal of diffusion-weighted magnetic resonance imaging (DWI) is to infer the structural connectivity of an individual subject's brain in vivo. To statistically study the variability and differences between normal and abnormal brain connectomes, a mathematical model of the neural connections is required. In this paper, we represent the brain connectome as a Riemannian manifold, which allows us to model neural connections as geodesics. This leads to the challenging problem of estimating a Riemannian metric that is compatible with the DWI data, i.e., a metric such that the geodesic curves represent individual fiber tracts of the connectomics. We reduce this problem to that of solving a highly nonlinear set of partial differential equations (PDEs) and study the applicability of convolutional encoder-decoder neural networks (CEDNNs) for solving this geometrically motivated PDE. Our method achieves excellent performance in the alignment of geodesics with white matter pathways and tackles a long-standing issue in previous geodesic tractography methods: the inability to recover crossing fibers with high fidelity. Code is available at https://github.com/aarentai/Metric-Cnn-3D-IPMI.

We introduce Point2SSM, a novel unsupervised learning approach that can accurately construct correspondence-based statistical shape models (SSMs) of anatomy directly from point clouds. SSMs are crucial in clinical research for analyzing the population-level morphological variation in bones and organs. However, traditional methods for creating SSMs have limitations that hinder their widespread adoption, such as the need for noise-free surface meshes or binary volumes, reliance on assumptions or predefined templates, and simultaneous optimization of the entire cohort leading to lengthy inference times given new data. Point2SSM overcomes these barriers by providing a data-driven solution that infers SSMs directly from raw point clouds, reducing inference burdens and increasing applicability as point clouds are more easily acquired. Deep learning on 3D point clouds has seen recent success in unsupervised representation learning, point-to-point matching, and shape correspondence; however, their application to constructing SSMs of anatomies is largely unexplored. In this work, we benchmark state-of-the-art point cloud deep networks on the task of SSM and demonstrate that they are not robust to the challenges of anatomical SSM, such as noisy, sparse, or incomplete input and significantly limited training data. Point2SSM addresses these challenges via an attention-based module that provides correspondence mappings from learned point features. We demonstrate that the proposed method significantly outperforms existing networks in terms of both accurate surface sampling and correspondence, better capturing population-level statistics.

Statistical shape modeling (SSM) is an essential tool for analyzing variations in anatomical morphology. In a typical SSM pipeline, 3D anatomical images, gone through segmentation and rigid registration, are represented using lower-dimensional shape features, on which statistical analysis can be performed. Various methods for constructing compact shape representations have been proposed, but they involve laborious and costly steps. We propose Image2SSM, a novel deep-learning-based approach for SSM that leverages image-segmentation pairs to learn a radial-basis-function (RBF)-based representation of shapes directly from images. This RBF-based shape representation offers a rich self-supervised signal for the network to estimate a continuous, yet compact representation of the underlying surface that can adapt to complex geometries in a data-driven manner. Image2SSM can characterize populations of biological structures of interest by constructing statistical landmark-based shape models of ensembles of anatomical shapes while requiring minimal parameter tuning and no user assistance. Once trained, Image2SSM can be used to infer low-dimensional shape representations from new unsegmented images, paving the way toward scalable approaches for SSM, especially when dealing with large cohorts. Experiments on synthetic and real datasets show the efficacy of the proposed method compared to the state-of-art correspondence-based method for SSM.

Statistical shape modeling is the computational process of discovering significant shape parameters from segmented anatomies captured by medical images (such as MRI and CT scans), which can fully describe subject-specific anatomy in the context of a population. The presence of substantial non-linear variability in human anatomy often makes the traditional shape modeling process challenging. Deep learning techniques can learn complex non-linear representations of shapes and generate statistical shape models that are more faithful to the underlying population-level variability. However, existing deep learning models still have limitations and require established/optimized shape models for training. We propose Mesh2SSM, a new approach that leverages unsupervised, permutation-invariant representation learning to estimate how to deform a template point cloud to subject-specific meshes, forming a correspondence-based shape model. Mesh2SSM can also learn a population-specific template, reducing any bias due to template selection. The proposed method operates directly on meshes and is computationally efficient, making it an attractive alternative to traditional and deep learning-based SSM approaches.

Statistical Shape Modeling (SSM) is a valuable tool for investigating and quantifying anatomical variations within populations of anatomies. However, traditional correspondence-based SSM generation methods require a time-consuming re-optimization process each time a new subject is added to the cohort, making the inference process prohibitive for clinical research. Additionally, they require complete geometric proxies (e.g., high-resolution binary volumes or surface meshes) as input shapes to construct the SSM. Unordered 3D point cloud representations of shapes are more easily acquired from various medical imaging practices (e.g., thresholded images and surface scanning). Point cloud deep networks have recently achieved remarkable success in learning permutation-invariant features for different point cloud tasks (e.g., completion, semantic segmentation, classification). However, their application to learning SSM from point clouds is to-date unexplored. In this work, we demonstrate that existing point cloud encoder-decoder-based completion networks can provide an untapped potential for SSM, capturing population-level statistical representations of shapes while reducing the inference burden and relaxing the input requirement. We discuss the limitations of these techniques to the SSM application and suggest future improvements. Our work paves the way for further exploration of point cloud deep learning for SSM, a promising avenue for advancing shape analysis literature and broadening SSM to diverse use cases.

Semantic segmentation is a critical step in automated image interpretation and analysis where pixels are classified into one or more predefined semantically meaningful classes. Deep learning approaches for semantic segmentation rely on harnessing the power of annotated images to learn features indicative of these semantic classes. Nonetheless, they often fail to generalize when there is a significant domain (i.e., distributional) shift between the training (i.e., source) data and the dataset(s) encountered when deployed (i.e., target), necessitating manual annotations for the target data to achieve acceptable performance. This is especially important in medical imaging because different image modalities have significant intra- and inter-site variations due to protocol and vendor variability. Current techniques are sensitive to hyperparameter tuning and target dataset size. This paper presents an unsupervised domain adaptation approach for semantic segmentation that alleviates the need for annotating target data. Using kernel density estimation, we match the target data distribution to the source data in the feature space. We demonstrate that our results are comparable or superior on multiple-site prostate MRI and histopathology images, which mitigates the need for annotating target data.

Homography estimation is a basic image-alignment method in many applications. Recently, with the development of convolutional neural networks (CNNs), some learning based approaches have shown great success in this task. However, the performance across different domains has never been researched. Unlike other common tasks (e.g., classification, detection, segmentation), CNN based homography estimation models show a domain shift immunity, which means a model can be trained on one dataset and tested on another without any transfer learning. To explain this unusual performance, we need to determine how CNNs estimate homography. In this study, we first show the domain shift immunity of different deep homography estimation models. We then use a shallow network with a specially designed dataset to analyze the features used for estimation. The results show that networks use low-level texture information to estimate homography. We also design some experiments to compare the performance between different texture densities and image features distorted on some common datasets to demonstrate our findings. Based on these findings, we provide an explanation of the domain shift immunity of deep homography estimation.

Neural operator learning as a means of mapping between complex function spaces has garnered significant attention in the field of computational science and engineering (CS&E). In this paper, we apply Neural operator learning to the time-of-flight ultrasound computed tomography (USCT) problem. We learn the mapping between time-of-flight (TOF) data and the heterogeneous sound speed field using a full-wave solver to generate the training data. This novel application of operator learning circumnavigates the need to solve the computationally intensive iterative inverse problem. The operator learns the non-linear mapping offline and predicts the heterogeneous sound field with a single forward pass through the model. This is the first time operator learning has been used for ultrasound tomography and is the first step in potential real-time predictions of soft tissue distribution for tumor identification in beast imaging.

Introduction:
The diagnosis and management of metopic craniosynostosis involves subjective decision-making at the point of care. The purpose of this work is to describe a quantitative severity metric and point-of-care user interface to aid clinicians in the management of metopic craniosynostosis and to provide a platform for future research through deep phenotyping.

Methods:
Two machine-learning algorithms were developed that quantify the severity of craniosynostosis – a supervised model specific to metopic craniosynostosis (Metopic Severity Score) and an unsupervised model used for cranial morphology in general (Cranial Morphology Deviation). CT imaging from multiple institutions were compiled to establish the spectrum of severity and a point-of-care tool was developed and validated.

Results:
Over the study period (2019-2021), 254 patients with metopic craniosynostosis and 92 control patients who underwent CT scan between the ages of 6 and 18 months were included. Scans were processed using an unsupervised machine-learning based dysmorphology quantification tool, CranioRate TM. The average Metopic severity score (MSS) for normal controls was 0.0±1.0 and for metopic synostosis was 4.9±2.3 (p<0.001). The average Cranial Morphology Deviation (CMD) for normal controls was 85.2±19.2 and for metopic synostosis was 189.9±43.4 (p<0.001). A point-of-care user interface (craniorate.org) has processed 46 CT images from 10 institutions.

The microscopic evaluation of glands in the colon is of utmost importance in the diagnosis of inflammatory bowel disease (IBD) and cancer. When properly trained, deep learning pipelines can provide a systematic, reproducible, and quantitative assessment of disease-related changes in glandular tissue architecture. The training and testing of deep learning models require large amounts of manual annotations, which are difficult, time-consuming, and expensive to obtain. Here, we propose a method for the automated generation of ground truth in digital H&E slides using immunohistochemistry (IHC) labels. The image processing pipeline generates annotations of glands in H&E histopathology images from colon biopsies by transfer of gland masks from CK8/18, CDX2, or EpCAM IHC. The IHC gland outlines are transferred to co-registered H&E images for the training of deep learning models. We compare the performance of the deep learning models to manual annotations using an internal held-out set of biopsies as well as two public data sets. Our results show that EpCAM IHC provides gland outlines that closely match manual gland annotations (DICE = 0.89) and are robust to damage by inflammation. In addition, we propose a simple data sampling technique that allows models trained on data from several sources to be adapted to a new data source using just a few newly annotated samples. The best-performing models achieved average DICE scores of 0.902 and 0.89, respectively, on GLAS and CRAG colon cancer public datasets when trained with only 10% of annotated cases from either public cohort. Altogether, the performances of our models indicate that automated annotations using cell type-specific IHC markers can safely replace manual annotations. The automated IHC labels from single institution cohorts can be combined with small numbers of hand-annotated cases from multi-institutional cohorts to train models that generalize well to diverse data sources.

Traditionally, two-dimensional conventional radiographs have been the primary tool to measure the complex morphology of the foot and ankle. However, the subtalar, talonavicular, and calcaneocuboid joints are challenging to assess due to their bone morphology and locations within the ankle. Weightbearing computed tomography is a novel high-resolution volumetric imaging mechanism that allows detailed generation of 3D bone reconstructions. This study aimed to develop a multi-domain statistical shape model to assess morphologic and alignment variation of the subtalar, talonavicular, and calcaneocuboid joints across an asymptomatic population and calculate 3D joint measurements in a consistent weightbearing position. Specific joint measurements included joint space distance, congruence, and coverage. Noteworthy anatomical variation predominantly included the talus and calcaneus, specifically an inverse relationship regarding talar dome heightening and calcaneal shortening. While there was minimal navicular and cuboid shape variation, there were alignment variations within these joints; the most notable is the rotational aspect about the anterior-posterior axis. This study also found that multi-domain modeling may be able to predict joint space distance measurements within a population. Additionally, variation across a population of these four bones may be driven far more by morphology than by alignment variation based on all three joint measurements. These data are beneficial in furthering our understanding of joint-level morphology and alignment variants to guide advancements in ankle joint pathological care and operative treatments.

Large-scale three-dimensional (3D) microscopy acquisitions fre-quently create terabytes of image data at high resolution and magni-fication. Imaging large specimens at high magnifications requires acquiring 3D overlapping image stacks as tiles arranged on a two-dimensional (2D) grid that must subsequently be aligned and fused into a single 3D volume. Due to their sheer size, aligning many overlapping gigabyte-sized 3D tiles in parallel and at full resolution is memory intensive and often I/O bound. Current techniques trade accuracy for scalability, perform alignment on subsampled images, and require additional postprocess algorithms to refine the alignment quality, usually with high computational requirements. One common solution to the memory problem is to subdivide the overlap region into smaller chunks (sub-blocks) and align the sub-block pairs in parallel, choosing the pair with the most reliable alignment to determine the global transformation. Yet aligning all sub-block pairs at full resolution remains computationally expensive. The key to quickly developing a fast, high-quality, low-memory solution is to identify a single or a small set of sub-blocks that give good alignment at full resolution without touching all the overlapping data. In this paper, we present a new iterative approach that leverages coarse resolution alignments to progressively refine and align only the promising candidates at finer resolutions, thereby aligning only a small user-defined number of sub-blocks at full resolution to determine the lowest error transformation between pairwise overlapping tiles. Our progressive approach is 2.6x faster than the state of the art, requires less than 450MB of peak RAM (per parallel thread), and offers a higher quality alignment without the need for additional postprocessing refinement steps to correct for alignment errors.