Knockout: A simple way to handle missing inputs

Deep learning models can extract predictive and actionable information from complex inputs. The richer the inputs, the better these models usually perform. However, models that leverage rich inputs (e.g., multi-modality) can be difficult to deploy widely, because some inputs may be missing at inference. Current popular solutions to this problem include marginalization, imputation, and training multiple models. Marginalization can obtain calibrated predictions but it is computationally costly and therefore only feasible for low dimensional inputs. Imputation may result in inaccurate predictions because it employs point estimates for missing variables and does not work well for high dimensional inputs (e.g., images). Training multiple models whereby each model takes different subsets of inputs can work well but requires knowing missing input patterns in advance. Furthermore, training and retaining multiple models can be costly. We propose an efficient way to learn both the conditional distribution using full inputs and the marginal distributions. Our method, Knockout, randomly replaces input features with appropriate placeholder values during training. We provide a theoretical justification of Knockout and show that it can be viewed as an implicit marginalization strategy. We evaluate Knockout in a wide range of simulations and real-world datasets and show that it can offer strong empirical performance.

BrainMorph: A Foundational Keypoint Model for Robust and Flexible Brain MRI Registration

We present a keypoint-based foundation model for general purpose brain MRI registration, based on the recently-proposed KeyMorph framework. Our model, called BrainMorph, serves as a tool that supports multi-modal, pairwise, and scalable groupwise registration. BrainMorph is trained on a massive dataset of over 100,000 3D volumes, skull-stripped and non-skull-stripped, from nearly 16,000 unique healthy and diseased subjects. BrainMorph is robust to large misalignments, interpretable via interrogating automatically-extracted keypoints, and enables rapid and controllable generation of many plausible transformations with different alignment types and different degrees of nonlinearity at test-time. We demonstrate the superiority of BrainMorph in solving 3D rigid, affine, and nonlinear registration on a variety of multi-modal brain MRI scans of healthy and diseased subjects, in both the pairwise and groupwise setting. In particular, we show registration accuracy and speeds that surpass current state-of-the-art methods, especially in the context of large initial misalignments and large group settings. All code and models are available at https://github.com/alanqrwang/brainmorph.

Robust Learning via Conditional Prevalence Adjustment

Healthcare data often come from multiple sites in which the correlations between confounding variables can vary widely. If deep learning models exploit these unstable correlations, they might fail catastrophically in unseen sites. Although many methods have been proposed to tackle unstable correlations, each has its limitations. For example, adversarial training forces models to completely ignore unstable correlations, but doing so may lead to poor predictive performance. Other methods (e.g. Invariant risk minimization [4]) try to learn domain-invariant representations that rely only on stable associations by assuming a causal data-generating process (input X causes class label Y ). Thus, they may be ineffective for anti-causal tasks (Y causes X), which are common in computer vision. We propose a method called CoPA (Conditional Prevalence-Adjustment) for anti-causal tasks. CoPA assumes that (1) generation mechanism is stable, i.e. label Y and confounding variable(s) Z generate X, and (2) the unstable conditional prevalence in each site E fully accounts for the unstable correlations between X and Y . Our crucial observation is that confounding variables are routinely recorded in healthcare settings and the prevalence can be readily estimated, for example, from a set of (Y, Z) samples (no need for corresponding samples of X). CoPA can work even if there is a single training site, a scenario which is often overlooked by existing methods. Our experiments on synthetic and real data show CoPA beating competitive baselines.

A Framework for Interpretability in Machine Learning for Medical Imaging

Interpretability for machine learning models in medical imaging (MLMI) is an important direction of research. However, there is a general sense of murkiness in what interpretability means. Why does the need for interpretability in MLMI arise? What goals does one actually seek to address when interpretability is needed? To answer these questions, we identify a need to formalize the goals and elements of interpretability in MLMI. By reasoning about real-world tasks and goals common in both medical image analysis and its intersection with machine learning, we identify four core elements of interpretability: localization, visual recognizability, physical attribution, and transparency. Overall, this paper formalizes interpretability needs in the context of medical imaging, and our applied perspective clarifies concrete MLMI-specific goals and considerations in order to guide method design and improve real-world usage. Our goal is to provide practical and didactic information for model designers and practitioners, inspire developers of models in the medical imaging field to reason more deeply about what interpretability is achieving, and suggest future directions of interpretability research.

Empirical Analysis of a Segmentation Foundation Model in Prostate Imaging

Most state-of-the-art techniques for medical image segmentation rely on deep-learning models. These models, however, are often trained on narrowly-defined tasks in a supervised fashion, which requires expensive labeled datasets. Recent advances in several machine learning domains, such as natural language generation have demonstrated the feasibility and utility of building foundation models that can be customized for various downstream tasks with little to no labeled data. This likely represents a paradigm shift for medical imaging, where we expect that foundation models may shape the future of the field. In this paper, we consider a recently developed foundation model for medical image segmentation, UniverSeg. We conduct an empirical evaluation study in the context of prostate imaging and compare it against the conventional approach of training a task-specific segmentation model. Our results and discussion highlight several important factors that will likely be important in the development and adoption of foundation models for medical image segmentation.

Learning to Compare Longitudinal Images

Longitudinal studies, where a series of images from the same set of individuals are acquired at different time-points, represent a popular technique for studying and characterizing temporal dynamics in biomedical applications. The classical approach for longitudinal comparison involves normalizing for nuisance variations, such as image orientation or contrast differences, via pre-processing. Statistical analysis is, in turn, conducted to detect changes of interest, either at the individual or population level. This classical approach can suffer from pre-processing issues and limitations of the statistical modeling. For example, normalizing for nuisance variation might be hard in settings where there are a lot of idiosyncratic changes. In this paper, we present a simple machine learning-based approach that can alleviate these issues. In our approach, we train a deep learning model (called PaIRNet, for Pairwise Image Ranking Network) to compare pairs of longitudinal images, with or without supervision. In the self-supervised setup, for instance, the model is trained to temporally order the images, which requires learning to recognize time-irreversible changes. Our results from four datasets demonstrate that PaIRNet can be very effective in localizing and quantifying meaningful longitudinal changes while discounting nuisance variation. Our code is available at \url{https://github.com/heejong-kim/learning-to-compare-longitudinal-images.git}

Q-space Conditioned Translation Networks for Directional Synthesis of Diffusion Weighted Images from Multi-modal Structural MRI

Current deep learning approaches for diffusion MRI modeling circumvent the need for densely-sampled diffusion-weighted images (DWIs) by directly predicting microstructural indices from sparsely-sampled DWIs. However, they implicitly make unrealistic assumptions of static $q$-space sampling during training and reconstruction. Further, such approaches can restrict downstream usage of variably sampled DWIs for usages including the estimation of microstructural indices or tractography. We propose a generative adversarial translation framework for high-quality DWI synthesis with arbitrary $q$-space sampling given commonly acquired structural images (e.g., B0, T1, T2). Our translation network linearly modulates its internal representations conditioned on continuous $q$-space information, thus removing the need for fixed sampling schemes. Moreover, this approach enables downstream estimation of high-quality microstructural maps from arbitrarily subsampled DWIs, which may be particularly important in cases with sparsely sampled DWIs. Across several recent methodologies, the proposed approach yields improved DWI synthesis accuracy and fidelity with enhanced downstream utility as quantified by the accuracy of scalar microstructure indices estimated from the synthesized images. Code is available at https://github.com/mengweiren/q-space-conditioned-dwi-synthesis.

Equivariant Spherical Deconvolution: Learning Sparse Orientation Distribution Functions from Spherical Data

We present a rotation-equivariant unsupervised learning framework for the sparse deconvolution of non-negative scalar fields defined on the unit sphere. Spherical signals with multiple peaks naturally arise in Diffusion MRI (dMRI), where each voxel consists of one or more signal sources corresponding to anisotropic tissue structure such as white matter. Due to spatial and spectral partial voluming, clinically-feasible dMRI struggles to resolve crossing-fiber white matter configurations, leading to extensive development in spherical deconvolution methodology to recover underlying fiber directions. However, these methods are typically linear and struggle with small crossing-angles and partial volume fraction estimation. In this work, we improve on current methodologies by nonlinearly estimating fiber structures via unsupervised spherical convolutional networks with guaranteed equivariance to spherical rotation. Experimentally, we first validate our proposition via extensive single and multi-shell synthetic benchmarks demonstrating competitive performance against common baselines. We then show improved downstream performance on fiber tractography measures on the Tractometer benchmark dataset. Finally, we show downstream improvements in terms of tractography and partial volume estimation on a multi-shell dataset of human subjects.