Recent self-supervised advances in medical computer vision exploit the global and local anatomical self-similarity for pretraining prior to downstream tasks such as segmentation. However, current methods assume i.i.d. image acquisition, which is invalid in clinical study designs where follow-up longitudinal scans track subject-specific temporal changes. Further, existing self-supervised methods for medically-relevant image-to-image architectures exploit only spatial or temporal self-similarity and do so via a loss applied only at a single image-scale, with naive multi-scale spatiotemporal extensions collapsing to degenerate solutions. To these ends, this paper makes two contributions: (1) It presents a local and multi-scale spatiotemporal representation learning method for image-to-image architectures trained on longitudinal images. It exploits the spatiotemporal self-similarity of learned multi-scale intra-subject image features for pretraining and develops several feature-wise regularizations that avoid degenerate representations; (2) During finetuning, it proposes a surprisingly simple self-supervised segmentation consistency regularization to exploit intra-subject correlation. Benchmarked across various segmentation tasks, the proposed framework outperforms both well-tuned randomly-initialized baselines and current self-supervised techniques designed for both i.i.d. and longitudinal datasets. These improvements are demonstrated across both longitudinal neurodegenerative adult MRI and developing infant brain MRI and yield both higher performance and longitudinal consistency.

Human brain is a complex yet economically organized system, where a small portion of critical hub regions support the majority of brain functions. The identification of common hub nodes in a population of networks is often simplified as a voting procedure on the set of identified hub nodes across individual brain networks, which ignores the intrinsic data geometry and partially lacks the reproducible findings in neuroscience. Hence, we propose a first-ever group-wise hub identification method to identify hub nodes that are common across a population of individual brain networks. Specifically, the backbone of our method is to learn common graph embedding that can represent the majority of local topological profiles. By requiring orthogonality among the graph embedding vectors, each graph embedding as a data element is residing on the Grassmannian manifold. We present a novel Grassmannian manifold optimization scheme that allows us to find the common graph embeddings, which not only identify the most reliable hub nodes in each network but also yield a population-based common hub node map. Results of the accuracy and replicability on both synthetic and real network data show that the proposed manifold learning approach outperforms all hub identification methods employed in this evaluation.

Converging evidence shows that disease-relevant brain alterations do not appear in random brain locations, instead, their spatial patterns follow large-scale brain networks. In this context, a powerful network analysis approach with a mathematical foundation is indispensable to understand the mechanisms of neuropathological events as they spread through the brain. Indeed, the topology of each brain network is governed by its native harmonic waves, which are a set of orthogonal bases derived from the Eigen-system of the underlying Laplacian matrix. To that end, we propose a novel connectome harmonic analysis framework that provides enhanced mathematical insights by detecting frequency-based alterations relevant to brain disorders. The backbone of our framework is a novel manifold algebra appropriate for inference across harmonic waves. This algebra overcomes the limitations of using classic Euclidean operations on irregular data structures. The individual harmonic differences are measured by a set of common harmonic waves learned from a population of individual Eigen-systems, where each native Eigen-system is regarded as a sample drawn from the Stiefel manifold. Specifically, a manifold optimization scheme is tailored to find the common harmonic waves, which reside at the center of the Stiefel manifold. To that end, the common harmonic waves constitute a new set of neurobiological bases to understand disease progression. Each harmonic wave exhibits a unique propagation pattern of neuropathological burden spreading across brain networks. The statistical power of our novel connectome harmonic analysis approach is evaluated by identifying frequency-based alterations relevant to Alzheimer's disease, where our learning-based manifold approach discovers more significant and reproducible network dysfunction patterns than Euclidean methods.

The plethora of data from neuroimaging studies provide a rich opportunity to discover effects and generate hypotheses through exploratory data analysis. Brain pathologies often manifest in changes in shape along with deterioration and alteration of brain matter, i.e., changes in mass. We propose a morphometry approach using unbalanced optimal transport that detects and localizes changes in mass and separates them from changes due to the location of mass. The approach generates images of mass allocation and mass transport cost for each subject in the population. Voxelwise correlations with clinical variables highlight regions of mass allocation or mass transfer related to the variables. We demonstrate the method on the white and gray matter segmentations from the OASIS brain MRI data set. The separation of white and gray matter ensures that optimal transport does not transfer mass between different tissues types and separates gray and white matter related changes. The OASIS data set includes subjects ranging from healthy to mild and moderate dementia, and the results corroborate known pathology changes related to dementia that are not discovered with traditional voxel-based morphometry. The transport-based morphometry increases the explanatory power of regression on clinical variables compared to traditional voxel-based morphometry, indicating that transport cost and mass allocation images capture a larger portion of pathology induced changes.

We present novel spherical deformation for a landmark-free shape correspondence in a group-wise manner. In this work, we aim at both addressing template selection bias and minimizing registration distortion in a single framework. The proposed spherical deformation yields a non-rigid deformation field without referring to any particular spherical coordinate system. Specifically, we extend a rigid rotation represented by well-known Euler angles to general non-rigid local deformation via spatial-varying Euler angles. The proposed method employs spherical harmonics interpolation of the local displacements to simultaneously solve rigid and non-rigid local deformation during the optimization. This consequently leads to a continuous, smooth, and hierarchical representation of the deformation field that minimizes registration distortion. In addition, the proposed method is group-wise registration that requires no specific template to establish a shape correspondence. In the experiments, we show an improved shape correspondence with high accuracy in cortical surface parcellation as well as significantly low registration distortion in surface area and edge length compared to the existing registration methods while achieving fast registration in 3 mins per subject.

A proper geometric representation of the cortical regions is a fundamental task for cortical shape analysis and landmark extraction. However, a significant challenge has arisen due to the highly variable, convoluted cortical folding patterns. In this paper, we propose a novel topological graph representation for automatic sulcal curve extraction (TRACE). In practice, the reconstructed surface suffers from noise influences introduced during image acquisition/surface reconstruction. In the presence of noise on the surface, TRACE determines stable sulcal fundic regions by employing the line simplification method that prevents the sulcal folding pattern from being significantly smoothed out. The sulcal curves are then traced over the connected graph in the determined regions by the Dijkstra's shortest path algorithm. For validation, we used the state-of-the-art surface reconstruction pipelines on a reproducibility data set. The experimental results showed higher reproducibility and robustness to noise in TRACE than the existing method (Li et al. 2010) with over 20% relative improvement in error for both surface reconstruction pipelines. In addition, the extracted sulcal curves by TRACE were well-aligned with manually delineated primary sulcal curves. We also provided a choice of parameters to control quality of the extracted sulcal curves and showed the influences of the parameter selection on the resulting curves.

We present a novel approach for improving the shape statistics of medical image objects by generating correspondence of skeletal points. Each object's interior is modeled by an s-rep, i.e., by a sampled, folded, two-sided skeletal sheet with spoke vectors proceeding from the skeletal sheet to the boundary. The skeleton is divided into three parts: the up side, the down side, and the fold curve. The spokes on each part are treated separately and, using spoke interpolation, are shifted along that skeleton in each training sample so as to tighten the probability distribution on those spokes' geometric properties while sampling the object interior regularly. As with the surface/boundary-based correspondence method of Cates et al., entropy is used to measure both the probability distribution tightness and the sampling regularity, here of the spokes' geometric properties. Evaluation on synthetic and real world lateral ventricle and hippocampus data sets demonstrate improvement in the performance of statistics using the resulting probability distributions. This improvement is greater than that achieved by an entropy-based correspondence method on the boundary points.

Trends in longitudinal or cross-sectional studies over time are often captured through regression models. In their simplest manifestation, these regression models are formulated in $R^n$. However, in the context of imaging studies, the objects of interest which are to be regressed are frequently best modeled as elements of a Riemannian manifold. Regression on such spaces can be accomplished through geodesic regression. This paper develops an approach to compute confidence intervals for geodesic regression models. The approach is general, but illustrated and specifically developed for the Grassmann manifold, which allows us, e.g., to regress shapes or linear dynamical systems. Extensions to other manifolds can be obtained in a similar manner. We demonstrate our approach for regression with 2D/3D shapes using synthetic and real data.

We present a scheme that propagates a reference skeletal model (s-rep) into a particular case of an object, thereby propagating the initial shape-related layout of the skeleton-to-boundary vectors, called spokes. The scheme represents the surfaces of the template as well as the target objects by spherical harmonics and computes a warp between these via a thin plate spline. To form the propagated s-rep, it applies the warp to the spokes of the template s-rep and then statistically refines. This automatic approach promises to make s-rep fitting robust for complicated objects, which allows s-rep based statistics to be available to all. The improvement in fitting and statistics is significant compared with the previous methods and in statistics compared with a state-of-the-art boundary based method.

Longitudinal imaging studies are frequently used to investigate temporal changes in brain morphology and often require spatial correspondence between images achieved through image registration. Beside morphological changes, image intensity may also change over time, for example when studying brain maturation. However, such intensity changes are not accounted for in image similarity measures for standard image registration methods. Hence, 1) local similarity measures, 2) methods estimating intensity transformations between images, and 3) metamorphosis approaches have been developed to either achieve robustness with respect to intensity changes or to simultaneously capture spatial and intensity changes. For these methods, longitudinal intensity changes are not explicitly modeled and images are treated as independent static samples. Here, we propose a model-based image similarity measure for longitudinal image registration that estimates a temporal model of intensity change using all available images simultaneously.

Twin imaging studies have been valuable for understanding the relative contribution of the environment and genes on brain structures and their functions. Conventional analyses of twin imaging data include three sequential steps: spatially smoothing imaging data, independently fitting a structural equation model at each voxel, and finally correcting for multiple comparisons. However, conventional analyses are limited due to the same amount of smoothing throughout the whole image, the arbitrary choice of smoothing extent, and the decreased power in detecting environmental and genetic effects introduced by smoothing raw images. The goal of this paper is to develop a two-stage multiscale adaptive regression method (TwinMARM) for spatial and adaptive analysis of twin neuroimaging and behavioral data. The first stage is to establish the relationship between twin imaging data and a set of covariates of interest, such as age and gender. The second stage is to disentangle the environmental and genetic influences on brain structures and their functions. In each stage, TwinMARM employs hierarchically nested spheres with increasing radii at each location and then captures spatial dependence among imaging observations via consecutively connected spheres across all voxels. Simulation studies show that our TwinMARM significantly outperforms conventional analyses of twin imaging data. Finally, we use our method to detect statistically significant effects of genetic and environmental variations on white matter structures in a neonatal twin study.

One goal of statistical shape analysis is the discrimination between two populations of objects. Whereas traditional shape analysis was mostly concerned with single objects, analysis of multi-object complexes presents new challenges related to alignment and pose. In this paper, we present a methodology for discriminant analysis of multiple objects represented by sampled medial manifolds. Non-euclidean metrics that describe geodesic distances between sets of sampled representations are used for alignment and discrimination. Our choice of discriminant method is the distance-weighted discriminant because of its generalization ability in high-dimensional, low sample size settings. Using an unbiased, soft discrimination score, we associate a statistical hypothesis test with the discrimination results. We explore the effectiveness of different choices of features as input to the discriminant analysis, using measures like volume, pose, shape, and the combination of pose and shape. Our method is applied to a longitudinal pediatric autism study with 10 subcortical brain structures in a population of 70 subjects. It is shown that the choices of type of global alignment and of intrinsic versus extrinsic shape features, the latter being sensitive to relative pose, are crucial factors for group discrimination and also for explaining the nature of shape change in terms of the application domain.

Diffusion tensor imaging (DTI) provides important information on the structure of white matter fiber bundles as well as detailed tissue properties along these fiber bundles in vivo. This paper presents a functional regression framework, called FRATS, for the analysis of multiple diffusion properties along fiber bundle as functions in an infinite dimensional space and their association with a set of covariates of interest, such as age, diagnostic status and gender, in real applications. The functional regression framework consists of four integrated components: the local polynomial kernel method for smoothing multiple diffusion properties along individual fiber bundles, a functional linear model for characterizing the association between fiber bundle diffusion properties and a set of covariates, a global test statistic for testing hypotheses of interest, and a resampling method for approximating the p-value of the global test statistic. The proposed methodology is applied to characterizing the development of five diffusion properties including fractional anisotropy, mean diffusivity, and the three eigenvalues of diffusion tensor along the splenium of the corpus callosum tract and the right internal capsule tract in a clinical study of neurodevelopment. Significant age and gestational age effects on the five diffusion properties were found in both tracts. The resulting analysis pipeline can be used for understanding normal brain development, the neural bases of neuropsychiatric disorders, and the joint effects of environmental and genetic factors on white matter fiber bundles.

This paper presents a comparison study between 10 automatic and six interactive methods for liver segmentation from contrast-enhanced CT images. It is based on results from the "MICCAI 2007 Grand Challenge" workshop, where 16 teams evaluated their algorithms on a common database. A collection of 20 clinical images with reference segmentations was provided to train and tune algorithms in advance. Participants were also allowed to use additional proprietary training data for that purpose. All teams then had to apply their methods to 10 test datasets and submit the obtained results. Employed algorithms include statistical shape models, atlas registration, level-sets, graph-cuts and rule-based systems. All results were compared to reference segmentations five error measures that highlight different aspects of segmentation accuracy. All measures were combined according to a specific scoring system relating the obtained values to human expert variability. In general, interactive methods reached higher average scores than automatic approaches and featured a better consistency of segmentation quality. However, the best automatic methods (mainly based on statistical shape models with some additional free deformation) could compete well on the majority of test images. The study provides an insight in performance of different segmentation approaches under real-world conditions and highlights achievements and limitations of current image analysis techniques.

An important goal of statistical shape analysis is the discrimination between populations of objects, exploring group differences in morphology not explained by standard volumetric analysis. Certain applications additionally require analysis of objects in their embedding context by joint statistical analysis of sets of interrelated objects. In this paper, we present a framework for discriminant analysis of populations of 3-D multi-object sets. In view of the driving medical applications, a skeletal object parametrization of shape is chosen since it naturally encodes thickening, bending and twisting. In a multi-object setting, we not only consider a joint analysis of sets of shapes but also must take into account differences in pose. Statistics on features of medial descriptions and pose parameters, which include rotational frames and distances, uses a Riemannian symmetric space instead of the standard Euclidean metric. Our choice of discriminant method is the distance weighted discriminant (DWD) because of its generalization ability in high dimensional, low sample size settings. Joint analysis of 10 subcortical brain structures in a pediatric autism study demonstrates that multi-object analysis of shape results in a better group discrimination than pose, and that the combination of pose and shape performs better than shape alone. Finally, given a discriminating axis of shape and pose, we can visualize the differences between the populations.

The paper presents a novel processing scheme for the automatic computation of a medial shape model which is representative for an object population with shape variability. The sensitivity of medial descriptions to object variations and small boundary perturbations are fundamental problems of any skeletonization technique. These problems are approached with the computation of a model with common medial branching topology and grid sampling. This model is then used for a medial shape description of individual objects via a constrained model fit. The process starts from parametric 3D boundary representations with existing point-to-point homology between objects. The Voronoi diagram of each sampled object boundary is grouped into medial sheets and simplified by a pruning algorithm using a volumetric contribution criterion. Medial sheets are combined to form a common medial branching topology. Finally, the medial sheets are sampled and represented as meshes of medial primitives. We present new results on populations of up to 184 biological objects. For these objects, the common medial branching topology is described by a small number of sheets. Despite the coarse medial sampling, a close approximation of individual objects is achieved.

This paper presents a new approach to the correction of intensity inhomogeneities in magnetic resonance imaging (MRI) that significantly improves intensity-based tissue segmentation. The distortion of the image brightness values by a low-frequency bias field impedes visual inspection and segmentation. The new correction method called parametric bias field correction (PABIC) is based on a simplified model of the imaging process, a parametric model of tissue class statistics, and a polynomial model of the inhomogeneity field. We assume that the image is composed of pixels assigned to a small number of categories with a priori known statistics. Further we assume that the image is corrupted by noise and a low-frequency inhomogeneity field. The estimation of the parametric bias field is formulated as a nonlinear energy minimization problem using an evolution strategy (ES). The resulting bias field is independent of the image region configurations and thus overcomes limitations of methods based on homomorphic filtering. Furthermore, PABIC can correct bias distortions much larger than the image contrast. Input parameters are the intensity statistics of the classes and the degree of the polynomial function. The polynomial approach combines bias correction with histogram adjustment, making it well suited for normalizing the intensity histogram of datasets from serial studies. We present simulations and a quantitative validation with phantom and test images. A large number of MR image data acquired with breast, surface, and head coils, both in two dimensions and three dimensions, have been processed and demonstrate the versatility and robustness of this new bias correction scheme.