Data-driven machine learning has made significant strides in medical image analysis. However, most existing methods are tailored to specific modalities and assume a particular resolution (often isotropic). This limits their generalizability in clinical settings, where variations in scan appearance arise from differences in sequence parameters, resolution, and orientation. Furthermore, most general-purpose models are designed for healthy subjects and suffer from performance degradation when pathology is present. We introduce UNA (Unraveling Normal Anatomy), the first modality-agnostic learning approach for normal brain anatomy reconstruction that can handle both healthy scans and cases with pathology. We propose a fluid-driven anomaly randomization method that generates an unlimited number of realistic pathology profiles on-the-fly. UNA is trained on a combination of synthetic and real data, and can be applied directly to real images with potential pathology without the need for fine-tuning. We demonstrate UNA's effectiveness in reconstructing healthy brain anatomy and showcase its direct application to anomaly detection, using both simulated and real images from 3D healthy and stroke datasets, including CT and MRI scans. By bridging the gap between healthy and diseased images, UNA enables the use of general-purpose models on diseased images, opening up new opportunities for large-scale analysis of uncurated clinical images in the presence of pathology. Code is available at https://github.com/peirong26/UNA.

Over recent years, deep learning based image registration has achieved impressive accuracy in many domains, including medical imaging and, specifically, human neuroimaging with magnetic resonance imaging (MRI). However, the uncertainty estimation associated with these methods has been largely limited to the application of generic techniques (e.g., Monte Carlo dropout) that do not exploit the peculiarities of the problem domain, particularly spatial modeling. Here, we propose a principled way to propagate uncertainties (epistemic or aleatoric) estimated at the level of spatial location by these methods, to the level of global transformation models, and further to downstream tasks. Specifically, we justify the choice of a Gaussian distribution for the local uncertainty modeling, and then propose a framework where uncertainties spread across hierarchical levels, depending on the choice of transformation model. Experiments on publicly available data sets show that Monte Carlo dropout correlates very poorly with the reference registration error, whereas our uncertainty estimates correlate much better. Crucially, the results also show that uncertainty-aware fitting of transformations improves the registration accuracy of brain MRI scans. Finally, we illustrate how sampling from the posterior distribution of the transformations can be used to propagate uncertainties to downstream neuroimaging tasks. Code is available at: https://github.com/HuXiaoling/Regre4Regis.

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, D2-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 normalabnormal decomposition can be used, for example, to quantify pathologies. Specifically, our model identifies the advection and diffusion contributions from the transport timeseries 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 anomalyencoded 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.

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.

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 postprocessing 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.

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.

Perfusion imaging is of great clinical importance and is used to assess a wide range of diseases including strokes and brain tumors. Commonly used approaches for the quantitative analysis of perfusion images are based on measuring the effect of a contrast agent moving through blood vessels and into tissue. Contrast-agent free approaches, for example, based on intravoxel incoherent motion and arterial spin labeling, also exist, but are so far not routinely used clinically. Existing contrast-agent-dependent methods typically rely on the estimation of the arterial input function (AIF) to approximately model tissue perfusion. These approaches neglect spatial dependencies. Further, as reliably estimating the AIF is non-trivial, different AIF estimates may lead to different perfusion measures. In this work we therefore propose PIANO, an approach that provides additional insights into the perfusion process. PIANO estimates the velocity and diffusion fields of an advection-diffusion model best explaining the contrast dynamics without using an AIF. 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. Simulation experiments show the robustness and effectiveness of PIANO, along with its ability to distinguish between advection and diffusion. We further apply PIANO on a public brain magnetic resonance (MR) perfusion dataset of acute stroke patients, and 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.