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Modern medical image registration approaches predict deformations using deep networks. These approaches achieve state-of-the-art (SOTA) registration accuracy and are generally fast. However, deep learning (DL) approaches are, in contrast to conventional non-deep-learning-based approaches, anatomy-specific. Recently, a universal deep registration approach, uniGradICON, has been proposed. However, uniGradICON focuses on monomodal image registration. In this work, we therefore develop multiGradICON as a first step towards universal *multimodal* medical image registration. Specifically, we show that 1) we can train a DL registration model that is suitable for monomodal *and* multimodal registration; 2) loss function randomization can increase multimodal registration accuracy; and 3) training a model with multimodal data helps multimodal generalization. Our code and the multiGradICON model are available at https://github.com/uncbiag/uniGradICON.

Artificial intelligence has significantly impacted medical applications, particularly with the advent of Medical Large Vision Language Models (Med-LVLMs), sparking optimism for the future of automated and personalized healthcare. However, the trustworthiness of Med-LVLMs remains unverified, posing significant risks for future model deployment. In this paper, we introduce CARES and aim to comprehensively evaluate the Trustworthiness of Med-LVLMs across the medical domain. We assess the trustworthiness of Med-LVLMs across five dimensions, including trustfulness, fairness, safety, privacy, and robustness. CARES comprises about 41K question-answer pairs in both closed and open-ended formats, covering 16 medical image modalities and 27 anatomical regions. Our analysis reveals that the models consistently exhibit concerns regarding trustworthiness, often displaying factual inaccuracies and failing to maintain fairness across different demographic groups. Furthermore, they are vulnerable to attacks and demonstrate a lack of privacy awareness. We publicly release our benchmark and code in https://github.com/richard-peng-xia/CARES.

Image registration estimates spatial correspondences between a pair of images. These estimates are typically obtained via numerical optimization or regression by a deep network. A desirable property of such estimators is that a correspondence estimate (e.g., the true oracle correspondence) for an image pair is maintained under deformations of the input images. Formally, the estimator should be equivariant to a desired class of image transformations. In this work, we present careful analyses of the desired equivariance properties in the context of multi-step deep registration networks. Based on these analyses we 1) introduce the notions of $[U,U]$ equivariance (network equivariance to the same deformations of the input images) and $[W,U]$ equivariance (where input images can undergo different deformations); we 2) show that in a suitable multi-step registration setup it is sufficient for overall $[W,U]$ equivariance if the first step has $[W,U]$ equivariance and all others have $[U,U]$ equivariance; we 3) show that common displacement-predicting networks only exhibit $[U,U]$ equivariance to translations instead of the more powerful $[W,U]$ equivariance; and we 4) show how to achieve multi-step $[W,U]$ equivariance via a coordinate-attention mechanism combined with displacement-predicting refinement layers (CARL). Overall, our approach obtains excellent practical registration performance on several 3D medical image registration tasks and outperforms existing unsupervised approaches for the challenging problem of abdomen registration.

The goal of interactive image segmentation is to delineate specific regions within an image via visual or language prompts. Low-latency and high-quality interactive segmentation with diverse prompts remain challenging for existing specialist and generalist models. Specialist models, with their limited prompts and task-specific designs, experience high latency because the image must be recomputed every time the prompt is updated, due to the joint encoding of image and visual prompts. Generalist models, exemplified by the Segment Anything Model (SAM), have recently excelled in prompt diversity and efficiency, lifting image segmentation to the foundation model era. However, for high-quality segmentations, SAM still lags behind state-of-the-art specialist models despite SAM being trained with x100 more segmentation masks. In this work, we delve deep into the architectural differences between the two types of models. We observe that dense representation and fusion of visual prompts are the key design choices contributing to the high segmentation quality of specialist models. In light of this, we reintroduce this dense design into the generalist models, to facilitate the development of generalist models with high segmentation quality. To densely represent diverse visual prompts, we propose to use a dense map to capture five types: clicks, boxes, polygons, scribbles, and masks. Thus, we propose SegNext, a next-generation interactive segmentation approach offering low latency, high quality, and diverse prompt support. Our method outperforms current state-of-the-art methods on HQSeg-44K and DAVIS, both quantitatively and qualitatively., Comment: CVPR 2024 https://github.com/uncbiag/SegNext

Monocular depth estimation in endoscopy videos can enable assistive and robotic surgery to obtain better coverage of the organ and detection of various health issues. Despite promising progress on mainstream, natural image depth estimation, techniques perform poorly on endoscopy images due to a lack of strong geometric features and challenging illumination effects. In this paper, we utilize the photometric cues, i.e., the light emitted from an endoscope and reflected by the surface, to improve monocular depth estimation. We first create two novel loss functions with supervised and self-supervised variants that utilize a per-pixel shading representation. We then propose a novel depth refinement network (PPSNet) that leverages the same per-pixel shading representation. Finally, we introduce teacher-student transfer learning to produce better depth maps from both synthetic data with supervision and clinical data with self-supervision. We achieve state-of-the-art results on the C3VD dataset while estimating high-quality depth maps from clinical data. Our code, pre-trained models, and supplementary materials can be found on our project page: https://ppsnet.github.io/, Comment: Accepted to ECCV 2024. 27 pages, 8 tables, 8 figures. Updated to include reference to clinical dataset

Medical records often consist of different modalities, such as images, text, and tabular information. Integrating all modalities offers a holistic view of a patient's condition, while analyzing them longitudinally provides a better understanding of disease progression. However, real-world longitudinal medical records present challenges: 1) patients may lack some or all of the data for a specific timepoint, and 2) certain modalities or views might be absent for all patients during a particular period. In this work, we introduce a unified model for longitudinal multi-modal multi-view prediction with missingness. Our method allows as many timepoints as desired for input, and aims to leverage all available data, regardless of their availability. We conduct extensive experiments on the knee osteoarthritis dataset from the Osteoarthritis Initiative for pain and Kellgren-Lawrence grade prediction at a future timepoint. We demonstrate the effectiveness of our method by comparing results from our unified model to specific models that use the same modality and view combinations during training and evaluation. We also show the benefit of having extended temporal data and provide post-hoc analysis for a deeper understanding of each modality/view's importance for different tasks.

Optical coherence tomography (OCT) is a popular modality in ophthalmology and is also used intravascularly. Our interest in this work is OCT in the context of airway abnormalities in infants and children where the high resolution of OCT and the fact that it is radiation-free is important. The goal of airway OCT is to provide accurate estimates of airway geometry (in 2D and 3D) to assess airway abnormalities such as subglottic stenosis. We propose $\texttt{NeuralOCT}$, a learning-based approach to process airway OCT images. Specifically, $\texttt{NeuralOCT}$ extracts 3D geometries from OCT scans by robustly bridging two steps: point cloud extraction via 2D segmentation and 3D reconstruction from point clouds via neural fields. Our experiments show that $\texttt{NeuralOCT}$ produces accurate and robust 3D airway reconstructions with an average A-line error smaller than 70 micrometer. Our code will cbe available on GitHub.

Conventional medical image registration approaches directly optimize over the parameters of a transformation model. These approaches have been highly successful and are used generically for registrations of different anatomical regions. Recent deep registration networks are incredibly fast and accurate but are only trained for specific tasks. Hence, they are no longer generic registration approaches. We therefore propose uniGradICON, a first step toward a foundation model for registration providing 1) great performance \emph{across} multiple datasets which is not feasible for current learning-based registration methods, 2) zero-shot capabilities for new registration tasks suitable for different acquisitions, anatomical regions, and modalities compared to the training dataset, and 3) a strong initialization for finetuning on out-of-distribution registration tasks. UniGradICON unifies the speed and accuracy benefits of learning-based registration algorithms with the generic applicability of conventional non-deep-learning approaches. We extensively trained and evaluated uniGradICON on twelve different public datasets. Our code and the uniGradICON model are available at https://github.com/uncbiag/uniGradICON.

Image registration is a fundamental medical image analysis task. Ideally, registration should focus on aligning semantically corresponding voxels, i.e., the same anatomical locations. However, existing methods often optimize similarity measures computed directly on intensities or on hand-crafted features, which lack anatomical semantic information. These similarity measures may lead to sub-optimal solutions where large deformations, complex anatomical differences, or cross-modality imagery exist. In this work, we introduce a fast and accurate method for unsupervised 3D medical image registration building on top of a Self-supervised Anatomical eMbedding (SAM) algorithm, which is capable of computing dense anatomical correspondences between two images at the voxel level. We name our approach SAM-Enhanced registration (SAME++), which decomposes image registration into four steps: affine transformation, coarse deformation, deep non-parametric transformation, and instance optimization. Using SAM embeddings, we enhance these steps by finding more coherent correspondence and providing features with better semantic guidance. We extensively evaluated SAME++ using more than 50 labeled organs on three challenging inter-subject registration tasks of different body parts. As a complete registration framework, SAME++ markedly outperforms leading methods by $4.2\%$ - $8.2\%$ in terms of Dice score while being orders of magnitude faster than numerical optimization-based methods. Code is available at \url{https://github.com/alibaba-damo-academy/same}.

Multi-task approaches to joint depth and segmentation prediction are well-studied for monocular images. Yet, predictions from a single-view are inherently limited, while multiple views are available in many robotics applications. On the other end of the spectrum, video-based and full 3D methods require numerous frames to perform reconstruction and segmentation. With this work we propose a Multi-View Stereo (MVS) technique for depth prediction that benefits from rich semantic features of the Segment Anything Model (SAM). This enhanced depth prediction, in turn, serves as a prompt to our Transformer-based semantic segmentation decoder. We report the mutual benefit that both tasks enjoy in our quantitative and qualitative studies on the ScanNet dataset. Our approach consistently outperforms single-task MVS and segmentation models, along with multi-task monocular methods., Comment: To appear in the 2024 IEEE/CVF Winter Conference on Applications of Computer Vision

This work proposes NePhi, a generalizable neural deformation model which results in approximately diffeomorphic transformations. In contrast to the predominant voxel-based transformation fields used in learning-based registration approaches, NePhi represents deformations functionally, leading to great flexibility within the design space of memory consumption during training and inference, inference time, registration accuracy, as well as transformation regularity. Specifically, NePhi 1) requires less memory compared to voxel-based learning approaches, 2) improves inference speed by predicting latent codes, compared to current existing neural deformation based registration approaches that \emph{only} rely on optimization, 3) improves accuracy via instance optimization, and 4) shows excellent deformation regularity which is highly desirable for medical image registration. We demonstrate the performance of NePhi on a 2D synthetic dataset as well as for real 3D lung registration. Our results show that NePhi can match the accuracy of voxel-based representations in a single-resolution registration setting. For multi-resolution registration, our method matches the accuracy of current SOTA learning-based registration approaches with instance optimization while reducing memory requirements by a factor of five.

A Point Distribution Model (PDM) is the basis of a Statistical Shape Model (SSM) that relies on a set of landmark points to represent a shape and characterize the shape variation. In this work, we present a self-supervised approach to extract landmark points from a given registration model for the PDMs. Based on the assumption that the landmarks are the points that have the most influence on registration, existing works learn a point-based registration model with a small number of points to estimate the landmark points that influence the deformation the most. However, such approaches assume that the deformation can be captured by point-based registration and quality landmarks can be learned solely with the deformation capturing objective. We argue that data with complicated deformations can not easily be modeled with point-based registration when only a limited number of points is used to extract influential landmark points. Further, landmark consistency is not assured in existing approaches In contrast, we propose to extract landmarks based on a given registration model, which is tailored for the target data, so we can obtain more accurate correspondences. Secondly, to establish the anatomical consistency of the predicted landmarks, we introduce a landmark discovery loss to explicitly encourage the model to predict the landmarks that are anatomically consistent across subjects. We conduct experiments on an osteoarthritis progression prediction task and show our method outperforms existing image-based and point-based approaches.

Multimodal learning has mainly focused on learning large models on, and fusing feature representations from, different modalities for better performances on downstream tasks. In this work, we take a detour from this trend and study the intrinsic nature of multimodal data by asking the following questions: 1) Can we learn more structured latent representations of general multimodal data?; and 2) can we intuitively understand, both mathematically and visually, what the latent representations capture? To answer 1), we propose a general and lightweight framework, Multimodal Understanding Through Correlation Maximization and Minimization (MUCMM), that can be incorporated into any large pre-trained network. MUCMM learns both the common and individual representations. The common representations capture what is common between the modalities; the individual representations capture the unique aspect of the modalities. To answer 2), we propose novel scores that summarize the learned common and individual structures and visualize the score gradients with respect to the input, visually discerning what the different representations capture. We further provide mathematical intuitions of the computed gradients in a linear setting, and demonstrate the effectiveness of our approach through a variety of experiments., Comment: 15 pages

Inverse consistency is a desirable property for image registration. We propose a simple technique to make a neural registration network inverse consistent by construction, as a consequence of its structure, as long as it parameterizes its output transform by a Lie group. We extend this technique to multi-step neural registration by composing many such networks in a way that preserves inverse consistency. This multi-step approach also allows for inverse-consistent coarse to fine registration. We evaluate our technique on synthetic 2-D data and four 3-D medical image registration tasks and obtain excellent registration accuracy while assuring inverse consistency.

Inspired by recent findings that generative diffusion models learn semantically meaningful representations, we use them to discover the intrinsic hierarchical structure in biomedical 3D images using unsupervised segmentation. We show that features of diffusion models from different stages of a U-Net-based ladder-like architecture capture different hierarchy levels in 3D biomedical images. We design three losses to train a predictive unsupervised segmentation network that encourages the decomposition of 3D volumes into meaningful nested subvolumes that represent a hierarchy. First, we pretrain 3D diffusion models and use the consistency of their features across subvolumes. Second, we use the visual consistency between subvolumes. Third, we use the invariance to photometric augmentations as a regularizer. Our models achieve better performance than prior unsupervised structure discovery approaches on challenging biologically-inspired synthetic datasets and on a real-world brain tumor MRI dataset., Comment: MICCAI 2023

Multiple imaging modalities are often used for disease diagnosis, prediction, or population-based analyses. However, not all modalities might be available due to cost, different study designs, or changes in imaging technology. If the differences between the types of imaging are small, data harmonization approaches can be used; for larger changes, direct image synthesis approaches have been explored. In this paper, we develop an approach based on multi-modal metric learning to synthesize images of diverse modalities. We use metric learning via multi-modal image retrieval, resulting in embeddings that can relate images of different modalities. Given a large image database, the learned image embeddings allow us to use k-nearest neighbor (k-NN) regression for image synthesis. Our driving medical problem is knee osteoarthritis (KOA), but our developed method is general after proper image alignment. We test our approach by synthesizing cartilage thickness maps obtained from 3D magnetic resonance (MR) images using 2D radiographs. Our experiments show that the proposed method outperforms direct image synthesis and that the synthesized thickness maps retain information relevant to downstream tasks such as progression prediction and Kellgren-Lawrence grading (KLG). Our results suggest that retrieval approaches can be used to obtain high-quality and meaningful image synthesis results given large image databases.

Deep implicit functions (DIFs) have emerged as a powerful paradigm for many computer vision tasks such as 3D shape reconstruction, generation, registration, completion, editing, and understanding. However, given a set of 3D shapes with associated covariates there is at present no shape representation method which allows to precisely represent the shapes while capturing the individual dependencies on each covariate. Such a method would be of high utility to researchers to discover knowledge hidden in a population of shapes. For scientific shape discovery, we propose a 3D Neural Additive Model for Interpretable Shape Representation ($\texttt{NAISR}$) which describes individual shapes by deforming a shape atlas in accordance to the effect of disentangled covariates. Our approach captures shape population trends and allows for patient-specific predictions through shape transfer. $\texttt{NAISR}$ is the first approach to combine the benefits of deep implicit shape representations with an atlas deforming according to specified covariates. We evaluate $\texttt{NAISR}$ with respect to shape reconstruction, shape disentanglement, shape evolution, and shape transfer on three datasets: 1) $\textit{Starman}$, a simulated 2D shape dataset; 2) the ADNI hippocampus 3D shape dataset; and 3) a pediatric airway 3D shape dataset. Our experiments demonstrate that $\textit{Starman}$ achieves excellent shape reconstruction performance while retaining interpretability. Our code is available at $\href{https://github.com/uncbiag/NAISR}{https://github.com/uncbiag/NAISR}$., Comment: 33 pages

Automatic medical volume segmentation often lacks clinical accuracy, necessitating further refinement. In this work, we interactively approach medical volume segmentation via two decoupled modules: interaction-to-segmentation and segmentation propagation. Given a medical volume, a user first segments a slice (or several slices) via the interaction module and then propagates the segmentation(s) to the remaining slices. The user may repeat this process multiple times until a sufficiently high volume segmentation quality is achieved. However, due to the lack of human correction during propagation, segmentation errors are prone to accumulate in the intermediate slices and may lead to sub-optimal performance. To alleviate this issue, we propose a simple yet effective cycle consistency loss that regularizes an intermediate segmentation by referencing the accurate segmentation in the starting slice. To this end, we introduce a backward segmentation path that propagates the intermediate segmentation back to the starting slice using the same propagation network. With cycle consistency training, the propagation network is better regularized than in standard forward-only training approaches. Evaluation results on challenging AbdomenCT-1K and OAI-ZIB datasets demonstrate the effectiveness of our method., Comment: Major revision of tech report. Code: https://github.com/uncbiag/iSegFormer/tree/v2.0

A major data pre-processing step for large, multi-site studies is to handle site effects by harmonizing data, generating a dataset that enables more powerful analyses and more robust algorithms. There is a wide variety of data harmonization techniques, but there are few tools that streamline the process of harmonizing data, comparing across techniques, and benchmarking new techniques. In this paper, we introduce HArmonization BEnchmarking Tool (HABET), an open source tool for generating harmonized images and evaluating the performance of different harmonization algorithms. To demonstrate the capabilities of HABET, we harmonize diffusion MRI images from the Adolescent Brain and Cognitive Development (ABCD) study using two different approaches, and we compare their performance., Comment: This work has been submitted to the IEEE for possible publication. Copyright may be transferred without notice, after which this version may no longer be accessible

Click-based interactive image segmentation aims at extracting objects with a limited user clicking. A hierarchical backbone is the de-facto architecture for current methods. Recently, the plain, non-hierarchical Vision Transformer (ViT) has emerged as a competitive backbone for dense prediction tasks. This design allows the original ViT to be a foundation model that can be finetuned for downstream tasks without redesigning a hierarchical backbone for pretraining. Although this design is simple and has been proven effective, it has not yet been explored for interactive image segmentation. To fill this gap, we propose SimpleClick, the first interactive segmentation method that leverages a plain backbone. Based on the plain backbone, we introduce a symmetric patch embedding layer that encodes clicks into the backbone with minor modifications to the backbone itself. With the plain backbone pretrained as a masked autoencoder (MAE), SimpleClick achieves state-of-the-art performance. Remarkably, our method achieves 4.15 NoC@90 on SBD, improving 21.8% over the previous best result. Extensive evaluation on medical images demonstrates the generalizability of our method. We further develop an extremely tiny ViT backbone for SimpleClick and provide a detailed computational analysis, highlighting its suitability as a practical annotation tool., Comment: Tech report. Update 03/11/2023: Add results on a tiny model and append supplementary materials

Deep learning models struggle with compositional generalization, i.e. the ability to recognize or generate novel combinations of observed elementary concepts. In hopes of enabling compositional generalization, various unsupervised learning algorithms have been proposed with inductive biases that aim to induce compositional structure in learned representations (e.g. disentangled representation and emergent language learning). In this work, we evaluate these unsupervised learning algorithms in terms of how well they enable compositional generalization. Specifically, our evaluation protocol focuses on whether or not it is easy to train a simple model on top of the learned representation that generalizes to new combinations of compositional factors. We systematically study three unsupervised representation learning algorithms - $\beta$-VAE, $\beta$-TCVAE, and emergent language (EL) autoencoders - on two datasets that allow directly testing compositional generalization. We find that directly using the bottleneck representation with simple models and few labels may lead to worse generalization than using representations from layers before or after the learned representation itself. In addition, we find that the previously proposed metrics for evaluating the levels of compositionality are not correlated with actual compositional generalization in our framework. Surprisingly, we find that increasing pressure to produce a disentangled representation produces representations with worse generalization, while representations from EL models show strong compositional generalization. Taken together, our results shed new light on the compositional generalization behavior of different unsupervised learning algorithms with a new setting to rigorously test this behavior, and suggest the potential benefits of delevoping EL learning algorithms for more generalizable representations., Comment: NeurIPS 2022

Brain pathologies often manifest as partial or complete loss of tissue. The goal of many neuroimaging studies is to capture the location and amount of tissue changes with respect to a clinical variable of interest, such as disease progression. Morphometric analysis approaches capture local differences in the distribution of tissue or other quantities of interest in relation to a clinical variable. We propose to augment morphometric analysis with an additional feature extraction step based on unbalanced optimal transport. The optimal transport feature extraction step increases statistical power for pathologies that cause spatially dispersed tissue loss, minimizes sensitivity to shifts due to spatial misalignment or differences in brain topology, and separates changes due to volume differences from changes due to tissue location. We demonstrate the proposed optimal transport feature extraction step in the context of a volumetric morphometric analysis of the OASIS-1 study for Alzheimer's disease. The results demonstrate that the proposed approach can identify tissue changes and differences that are not otherwise measurable., Comment: submitted to Medical Image Analysis

The goal of click-based interactive image segmentation is to obtain precise object segmentation masks with limited user interaction, i.e., by a minimal number of user clicks. Existing methods require users to provide all the clicks: by first inspecting the segmentation mask and then providing points on mislabeled regions, iteratively. We ask the question: can our model directly predict where to click, so as to further reduce the user interaction cost? To this end, we propose {\PseudoClick}, a generic framework that enables existing segmentation networks to propose candidate next clicks. These automatically generated clicks, termed pseudo clicks in this work, serve as an imitation of human clicks to refine the segmentation mask., Comment: 18 pages, 6 figures, 7 tables. ECCV 2022

We present an approach to learning regular spatial transformations between image pairs in the context of medical image registration. Contrary to optimization-based registration techniques and many modern learning-based methods, we do not directly penalize transformation irregularities but instead promote transformation regularity via an inverse consistency penalty. We use a neural network to predict a map between a source and a target image as well as the map when swapping the source and target images. Different from existing approaches, we compose these two resulting maps and regularize deviations of the $\bf{Jacobian}$ of this composition from the identity matrix. This regularizer -- $\texttt{GradICON}$ -- results in much better convergence when training registration models compared to promoting inverse consistency of the composition of maps directly while retaining the desirable implicit regularization effects of the latter. We achieve state-of-the-art registration performance on a variety of real-world medical image datasets using a single set of hyperparameters and a single non-dataset-specific training protocol., Comment: 29 pages, 16 figures, CVPR 2023

We propose LiftReg, a 2D/3D deformable registration approach. LiftReg is a deep registration framework which is trained using sets of digitally reconstructed radiographs (DRR) and computed tomography (CT) image pairs. By using simulated training data, LiftReg can use a high-quality CT-CT image similarity measure, which helps the network to learn a high-quality deformation space. To further improve registration quality and to address the inherent depth ambiguities of very limited angle acquisitions, we propose to use features extracted from the backprojected 2D images and a statistical deformation model. We test our approach on the DirLab lung registration dataset and show that it outperforms an existing learning-based pairwise registration approach., Comment: MICCAI 2022

Registration is widely used in image-guided therapy and image-guided surgery to estimate spatial correspondences between organs of interest between planning and treatment images. However, while high-quality computed tomography (CT) images are often available at planning time, limited angle acquisitions are frequently used during treatment because of radiation concerns or imaging time constraints. This requires algorithms to register CT images based on limited angle acquisitions. We, therefore, formulate a 3D/2D registration approach which infers a 3D deformation based on measured projections and digitally reconstructed radiographs of the CT. Most 3D/2D registration approaches use simple transformation models or require complex mathematical derivations to formulate the underlying optimization problem. Instead, our approach entirely relies on differentiable operations which can be combined with modern computational toolboxes supporting automatic differentiation. This then allows for rapid prototyping, integration with deep neural networks, and to support a variety of transformation models including fluid flow models. We demonstrate our approach for the registration between CT and stationary chest tomosynthesis (sDCT) images and show how it naturally leads to an iterative image reconstruction approach.

We study the excess capacity of deep networks in the context of supervised classification. That is, given a capacity measure of the underlying hypothesis class - in our case, empirical Rademacher complexity - to what extent can we (a priori) constrain this class while retaining an empirical error on a par with the unconstrained regime? To assess excess capacity in modern architectures (such as residual networks), we extend and unify prior Rademacher complexity bounds to accommodate function composition and addition, as well as the structure of convolutions. The capacity-driving terms in our bounds are the Lipschitz constants of the layers and an (2, 1) group norm distance to the initializations of the convolution weights. Experiments on benchmark datasets of varying task difficulty indicate that (1) there is a substantial amount of excess capacity per task, and (2) capacity can be kept at a surprisingly similar level across tasks. Overall, this suggests a notion of compressibility with respect to weight norms, complementary to classic compression via weight pruning. Source code is available at https://github.com/rkwitt/excess_capacity., Comment: Updated to Neurips 2022 camera-ready version

Atlas building and image registration are important tasks for medical image analysis. Once one or multiple atlases from an image population have been constructed, commonly (1) images are warped into an atlas space to study intra-subject or inter-subject variations or (2) a possibly probabilistic atlas is warped into image space to assign anatomical labels. Atlas estimation and nonparametric transformations are computationally expensive as they usually require numerical optimization. Additionally, previous approaches for atlas building often define similarity measures between a fuzzy atlas and each individual image, which may cause alignment difficulties because a fuzzy atlas does not exhibit clear anatomical structures in contrast to the individual images. This work explores using a convolutional neural network (CNN) to jointly predict the atlas and a stationary velocity field (SVF) parameterization for diffeomorphic image registration with respect to the atlas. Our approach does not require affine pre-registrations and utilizes pairwise image alignment losses to increase registration accuracy. We evaluate our model on 3D knee magnetic resonance images (MRI) from the OAI-ZIB dataset. Our results show that the proposed framework achieves better performance than other state-of-the-art image registration algorithms, allows for end-to-end training, and for fast inference at test time., Comment: Accepted by CVPR-2022

We propose iSegFormer, a memory-efficient transformer that combines a Swin transformer with a lightweight multilayer perceptron (MLP) decoder. With the efficient Swin transformer blocks for hierarchical self-attention and the simple MLP decoder for aggregating both local and global attention, iSegFormer learns powerful representations while achieving high computational efficiencies. Specifically, we apply iSegFormer to interactive 3D medical image segmentation., Comment: MICCAI'22 camera-ready

Registration of longitudinal brain MRI scans containing pathologies is challenging due to dramatic changes in tissue appearance. Although there has been progress in developing general-purpose medical image registration techniques, they have not yet attained the requisite precision and reliability for this task, highlighting its inherent complexity. Here we describe the Brain Tumor Sequence Registration (BraTS-Reg) challenge, as the first public benchmark environment for deformable registration algorithms focusing on estimating correspondences between pre-operative and follow-up scans of the same patient diagnosed with a diffuse brain glioma. The BraTS-Reg data comprise de-identified multi-institutional multi-parametric MRI (mpMRI) scans, curated for size and resolution according to a canonical anatomical template, and divided into training, validation, and testing sets. Clinical experts annotated ground truth (GT) landmark points of anatomical locations distinct across the temporal domain. Quantitative evaluation and ranking were based on the Median Euclidean Error (MEE), Robustness, and the determinant of the Jacobian of the displacement field. The top-ranked methodologies yielded similar performance across all evaluation metrics and shared several methodological commonalities, including pre-alignment, deep neural networks, inverse consistency analysis, and test-time instance optimization per-case basis as a post-processing step. The top-ranked method attained the MEE at or below that of the inter-rater variability for approximately 60% of the evaluated landmarks, underscoring the scope for further accuracy and robustness improvements, especially relative to human experts. The aim of BraTS-Reg is to continue to serve as an active resource for research, with the data and online evaluation tools accessible at https://bratsreg.github.io/.

Advection-diffusion equations describe a large family of natural transport processes, e.g., fluid flow, heat transfer, and wind transport. They are also used for optical flow and perfusion imaging computations. We develop a machine learning model, D^2-SONATA, built upon a stochastic advection-diffusion equation, which predicts the velocity and diffusion fields that drive 2D/3D image time-series of transport. In particular, our proposed model incorporates a model of transport atypicality, which isolates abnormal differences between expected normal transport behavior and the observed transport. In a medical context such a normal-abnormal decomposition can be used, for example, to quantify pathologies. Specifically, our model identifies the advection and diffusion contributions from the transport time-series and simultaneously predicts an anomaly value field to provide a decomposition into normal and abnormal advection and diffusion behavior. To achieve improved estimation performance for the velocity and diffusion-tensor fields underlying the advection-diffusion process and for the estimation of the anomaly fields, we create a 2D/3D anomaly-encoded advection-diffusion simulator, which allows for supervised learning. We further apply our model on a brain perfusion dataset from ischemic stroke patients via transfer learning. Extensive comparisons demonstrate that our model successfully distinguishes stroke lesions (abnormal) from normal brain regions, while reconstructing the underlying velocity and diffusion tensor fields., Comment: Accepted as ORAL to CVPR 2022 (15 pages, 5 figures)

This work investigates the use of robust optimal transport (OT) for shape matching. Specifically, we show that recent OT solvers improve both optimization-based and deep learning methods for point cloud registration, boosting accuracy at an affordable computational cost. This manuscript starts with a practical overview of modern OT theory. We then provide solutions to the main difficulties in using this framework for shape matching. Finally, we showcase the performance of transport-enhanced registration models on a wide range of challenging tasks: rigid registration for partial shapes; scene flow estimation on the Kitti dataset; and nonparametric registration of lung vascular trees between inspiration and expiration. Our OT-based methods achieve state-of-the-art results on Kitti and for the challenging lung registration task, both in terms of accuracy and scalability. We also release PVT1010, a new public dataset of 1,010 pairs of lung vascular trees with densely sampled points. This dataset provides a challenging use case for point cloud registration algorithms with highly complex shapes and deformations. Our work demonstrates that robust OT enables fast pre-alignment and fine-tuning for a wide range of registration models, thereby providing a new key method for the computer vision toolbox. Our code and dataset are available online at: https://github.com/uncbiag/robot., Comment: Accepted in NeurIPS 2021

Learning maps between data samples is fundamental. Applications range from representation learning, image translation and generative modeling, to the estimation of spatial deformations. Such maps relate feature vectors, or map between feature spaces. Well-behaved maps should be regular, which can be imposed explicitly or may emanate from the data itself. We explore what induces regularity for spatial transformations, e.g., when computing image registrations. Classical optimization-based models compute maps between pairs of samples and rely on an appropriate regularizer for well-posedness. Recent deep learning approaches have attempted to avoid using such regularizers altogether by relying on the sample population instead. We explore if it is possible to obtain spatial regularity using an inverse consistency loss only and elucidate what explains map regularity in such a context. We find that deep networks combined with an inverse consistency loss and randomized off-grid interpolation yield well behaved, approximately diffeomorphic, spatial transformations. Despite the simplicity of this approach, our experiments present compelling evidence, on both synthetic and real data, that regular maps can be obtained without carefully tuned explicit regularizers, while achieving competitive registration performance.

Minimizing cross-entropy over the softmax scores of a linear map composed with a high-capacity encoder is arguably the most popular choice for training neural networks on supervised learning tasks. However, recent works show that one can directly optimize the encoder instead, to obtain equally (or even more) discriminative representations via a supervised variant of a contrastive objective. In this work, we address the question whether there are fundamental differences in the sought-for representation geometry in the output space of the encoder at minimal loss. Specifically, we prove, under mild assumptions, that both losses attain their minimum once the representations of each class collapse to the vertices of a regular simplex, inscribed in a hypersphere. We provide empirical evidence that this configuration is attained in practice and that reaching a close-to-optimal state typically indicates good generalization performance. Yet, the two losses show remarkably different optimization behavior. The number of iterations required to perfectly fit to data scales superlinearly with the amount of randomly flipped labels for the supervised contrastive loss. This is in contrast to the approximately linear scaling previously reported for networks trained with cross-entropy., Comment: v4 updates: - updated appendix section S1.3 - this includes fixing an oversight in the proofs (Lemma 1 missed an equality condition, which now appears in Lemma 2) - improved figure quality

Transport processes are ubiquitous. They are, for example, at the heart of optical flow approaches; or of perfusion imaging, where blood transport is assessed, most commonly by injecting a tracer. An advection-diffusion equation is widely used to describe these transport phenomena. Our goal is estimating the underlying physics of advection-diffusion equations, expressed as velocity and diffusion tensor fields. We propose a learning framework (YETI) building on an auto-encoder structure between 2D and 3D image time-series, which incorporates the advection-diffusion model. To help with identifiability, we develop an advection-diffusion simulator which allows pre-training of our model by supervised learning using the velocity and diffusion tensor fields. Instead of directly learning these velocity and diffusion tensor fields, we introduce representations that assure incompressible flow and symmetric positive semi-definite diffusion fields and demonstrate the additional benefits of these representations on improving estimation accuracy. We further use transfer learning to apply YETI on a public brain magnetic resonance (MR) perfusion dataset of stroke patients and show its ability to successfully distinguish stroke lesions from normal brain regions via the estimated velocity and diffusion tensor fields., Comment: Accepted as ORAL at CVPR 2021 (20 pages, 13 figures)

Multi-atlas segmentation (MAS) is a popular image segmentation technique for medical images. In this work, we improve the performance of MAS by correcting registration errors before label fusion. Specifically, we use a volumetric displacement field to refine registrations based on image anatomical appearance and predicted labels. We show the influence of the initial spatial alignment as well as the beneficial effect of using label information for MAS performance. Experiments demonstrate that the proposed refinement approach improves MAS performance on a 3D magnetic resonance dataset of the knee.

Perfusion imaging (PI) is clinically used to assess strokes and brain tumors. Commonly used PI approaches based on magnetic resonance imaging (MRI) or computed tomography (CT) measure the effect of a contrast agent moving through blood vessels and into tissue. Contrast-agent free approaches, for example, based on intravoxel incoherent motion, also exist, but are so far not routinely used clinically. These methods rely on estimating on the arterial input function (AIF) to approximately model tissue perfusion, neglecting spatial dependencies, and reliably estimating the AIF is also non-trivial, leading to difficulties with standardizing perfusion measures. In this work we therefore propose a data-assimilation approach (PIANO) which estimates the velocity and diffusion fields of an advection-diffusion model that best explains the contrast dynamics. PIANO accounts for spatial dependencies and neither requires estimating the AIF nor relies on a particular contrast agent bolus shape. Specifically, we propose a convenient parameterization of the estimation problem, a numerical estimation approach, and extensively evaluate PIANO. We demonstrate that PIANO can successfully resolve velocity and diffusion field ambiguities and results in sensitive measures for the assessment of stroke, comparing favorably to conventional measures of perfusion., Comment: Submitted to IEEE-TMI 2020

Algorithmic fairness seeks to identify and correct sources of bias in machine learning algorithms. Confoundingly, ensuring fairness often comes at the cost of accuracy. We provide formal tools in this work for reconciling this fundamental tension in algorithm fairness. Specifically, we put to use the concept of Pareto optimality from multi-objective optimization and seek the fairness-accuracy Pareto front of a neural network classifier. We demonstrate that many existing algorithmic fairness methods are performing the so-called linear scalarization scheme which has severe limitations in recovering Pareto optimal solutions. We instead apply the Chebyshev scalarization scheme which is provably superior theoretically and no more computationally burdensome at recovering Pareto optimal solutions compared to the linear scheme., Comment: added toy figs to illustrate pareto optimality, some re-organization for clarity following reviewer comments

Registration of images with pathologies is challenging due to tissue appearance changes and missing correspondences caused by the pathologies. Moreover, mass effects as observed for brain tumors may displace tissue, creating larger deformations over time than what is observed in a healthy brain. Deep learning models have successfully been applied to image registration to offer dramatic speed up and to use surrogate information (e.g., segmentations) during training. However, existing approaches focus on learning registration models using images from healthy patients. They are therefore not designed for the registration of images with strong pathologies for example in the context of brain tumors, and traumatic brain injuries. In this work, we explore a deep learning approach to register images with brain tumors to an atlas. Our model learns an appearance mapping from images with tumors to the atlas, while simultaneously predicting the transformation to atlas space. Using separate decoders, the network disentangles the tumor mass effect from the reconstruction of quasi-normal images. Results on both synthetic and real brain tumor scans show that our approach outperforms cost function masking for registration to the atlas and that reconstructed quasi-normal images can be used for better longitudinal registrations.

For semantic segmentation, label probabilities are often uncalibrated as they are typically only the by-product of a segmentation task. Intersection over Union (IoU) and Dice score are often used as criteria for segmentation success, while metrics related to label probabilities are not often explored. However, probability calibration approaches have been studied, which match probability outputs with experimentally observed errors. These approaches mainly focus on classification tasks, but not on semantic segmentation. Thus, we propose a learning-based calibration method that focuses on multi-label semantic segmentation. Specifically, we adopt a convolutional neural network to predict local temperature values for probability calibration. One advantage of our approach is that it does not change prediction accuracy, hence allowing for calibration as a post-processing step. Experiments on the COCO, CamVid, and LPBA40 datasets demonstrate improved calibration performance for a range of different metrics. We also demonstrate the good performance of our method for multi-atlas brain segmentation from magnetic resonance images., Comment: Accepted by ICCV-2021

While successful for various computer vision tasks, deep neural networks have shown to be vulnerable to texture style shifts and small perturbations to which humans are robust. In this work, we show that the robustness of neural networks can be greatly improved through the use of random convolutions as data augmentation. Random convolutions are approximately shape-preserving and may distort local textures. Intuitively, randomized convolutions create an infinite number of new domains with similar global shapes but random local textures. Therefore, we explore using outputs of multi-scale random convolutions as new images or mixing them with the original images during training. When applying a network trained with our approach to unseen domains, our method consistently improves the performance on domain generalization benchmarks and is scalable to ImageNet. In particular, in the challenging scenario of generalizing to the sketch domain in PACS and to ImageNet-Sketch, our method outperforms state-of-art methods by a large margin. More interestingly, our method can benefit downstream tasks by providing a more robust pretrained visual representation., Comment: ICLR 2021. Code is available at https://github.com/wildphoton/RandConv

We introduce a fluid-based image augmentation method for medical image analysis. In contrast to existing methods, our framework generates anatomically meaningful images via interpolation from the geodesic subspace underlying given samples. Our approach consists of three steps: 1) given a source image and a set of target images, we construct a geodesic subspace using the Large Deformation Diffeomorphic Metric Mapping (LDDMM) model; 2) we sample transformations from the resulting geodesic subspace; 3) we obtain deformed images and segmentations via interpolation. Experiments on brain (LPBA) and knee (OAI) data illustrate the performance of our approach on two tasks: 1) data augmentation during training and testing for image segmentation; 2) one-shot learning for single atlas image segmentation. We demonstrate that our approach generates anatomically meaningful data and improves performance on these tasks over competing approaches. Code is available at https://github.com/uncbiag/easyreg., Comment: MICCAI 2020

Continuous-depth neural networks can be viewed as deep limits of discrete neural networks whose dynamics resemble a discretization of an ordinary differential equation (ODE). Although important steps have been taken to realize the advantages of such continuous formulations, most current techniques are not truly continuous-depth as they assume \textit{identical} layers. Indeed, existing works throw into relief the myriad difficulties presented by an infinite-dimensional parameter space in learning a continuous-depth neural ODE. To this end, we introduce a shooting formulation which shifts the perspective from parameterizing a network layer-by-layer to parameterizing over optimal networks described only by a set of initial conditions. For scalability, we propose a novel particle-ensemble parametrization which fully specifies the optimal weight trajectory of the continuous-depth neural network. Our experiments show that our particle-ensemble shooting formulation can achieve competitive performance, especially on long-range forecasting tasks. Finally, though the current work is inspired by continuous-depth neural networks, the particle-ensemble shooting formulation also applies to discrete-time networks and may lead to a new fertile area of research in deep learning parametrization.

Clustering and prediction are two primary tasks in the fields of unsupervised and supervised learning, respectively. Although much of the recent advances in machine learning have been centered around those two tasks, the interdependent, mutually beneficial relationship between them is rarely explored. One could reasonably expect appropriately clustering the data would aid the downstream prediction task and, conversely, a better prediction performance for the downstream task could potentially inform a more appropriate clustering strategy. In this work, we focus on the latter part of this mutually beneficial relationship. To this end, we introduce Deep Goal-Oriented Clustering (DGC), a probabilistic framework that clusters the data by jointly using supervision via side-information and unsupervised modeling of the inherent data structure in an end-to-end fashion. We show the effectiveness of our model on a range of datasets by achieving prediction accuracies comparable to the state-of-the-art, while, more importantly in our setting, simultaneously learning congruent clustering strategies., Comment: 15 pages

We study regularization in the context of small sample-size learning with over-parameterized neural networks. Specifically, we shift focus from architectural properties, such as norms on the network weights, to properties of the internal representations before a linear classifier. Specifically, we impose a topological constraint on samples drawn from the probability measure induced in that space. This provably leads to mass concentration effects around the representations of training instances, i.e., a property beneficial for generalization. By leveraging previous work to impose topological constraints in a neural network setting, we provide empirical evidence (across various vision benchmarks) to support our claim for better generalization.

A key challenge in modern data analysis is understanding connections between complex and differing modalities of data. For example, two of the main approaches to the study of breast cancer are histopathology (analyzing visual characteristics of tumors) and genetics. While histopathology is the gold standard for diagnostics and there have been many recent breakthroughs in genetics, there is little overlap between these two fields. We aim to bridge this gap by developing methods based on Angle-based Joint and Individual Variation Explained (AJIVE) to directly explore similarities and differences between these two modalities. Our approach exploits Convolutional Neural Networks (CNNs) as a powerful, automatic method for image feature extraction to address some of the challenges presented by statistical analysis of histopathology image data. CNNs raise issues of interpretability that we address by developing novel methods to explore visual modes of variation captured by statistical algorithms (e.g. PCA or AJIVE) applied to CNN features. Our results provide many interpretable connections and contrasts between histopathology and genetics.

In this work, we improve the performance of multi-atlas segmentation (MAS) by integrating the recently proposed VoteNet model with the joint label fusion (JLF) approach. Specifically, we first illustrate that using a deep convolutional neural network to predict atlas probabilities can better distinguish correct atlas labels from incorrect ones than relying on image intensity difference as is typical in JLF. Motivated by this finding, we propose VoteNet+, an improved deep network to locally predict the probability of an atlas label to differs from the label of the target image. Furthermore, we show that JLF is more suitable for the VoteNet framework as a label fusion method than plurality voting. Lastly, we use Platt scaling to calibrate the probabilities of our new model. Results on LPBA40 3D MR brain images show that our proposed method can achieve better performance than VoteNet., Comment: Accepted by ISBI-2020