Automated Differentiation of Atypical Parkinsonian Syndromes Using Brain Iron Patterns in Susceptibility Weighted Imaging.

In recent studies, iron overload has been reported in atypical parkinsonian syndromes. The topographic patterns of iron distribution in deep brain nuclei vary by each subtype of parkinsonian syndrome, which is affected by underlying disease pathologies. In this study, we developed a novel framework that automatically analyzes the disease-specific patterns of iron accumulation using susceptibility weighted imaging (SWI). We constructed various machine learning models that can classify diseases using radiomic features extracted from SWI, representing distinctive iron distribution patterns for each disorder. Since radiomic features are sensitive to the region of interest, we used a combination of T1-weighted MRI and SWI to improve the segmentation of deep brain nuclei. Radiomics was applied to SWI from 34 patients with a parkinsonian variant of multiple system atrophy, 21 patients with cerebellar variant multiple system atrophy, 17 patients with progressive supranuclear palsy, and 56 patients with Parkinson's disease. The machine learning classifiers that learn the radiomic features extracted from iron-reflected segmentation results produced an average area under receiver operating characteristic curve (AUC) of 0.8607 on the training data and 0.8489 on the testing data, which is superior to the conventional classifier with segmentation using only T1-weighted images. Our radiomic model based on the hybrid images is a promising tool for automatically differentiating atypical parkinsonian syndromes.

G-RMOS: GPU-accelerated Riemannian Metric Optimization on Surfaces.

Surface mapping is used in various brain imaging studies, such as for mapping gray matter atrophy patterns in Alzheimer's disease. Riemannian metrics on surface (RMOS) is a state-of-the-art surface mapping algorithm that optimizes Riemannian metrics to establish one-to-one correspondences between surfaces in the Laplace-Beltrami embedding space. However, owing to the complex calculation with accurate one-to-one correspondences, RMOS registration takes a long time. In this study, we propose G-RMOS, a graphics processing unit (GPU)-accelerated RMOS registration pipeline that uses three GPU kernel design strategies: 1. using GPU computing capability with a batch scheme; 2. using the cache in the GPU block to minimize memory latency in register and shared memory; and 3. maximizing the effective number of instructions per GPU cycle using instruction level parallelism. Using the experimental results, we compare the acceleration speed of the G-RMOS framework with that of RMOS using hippocampus and cortical surfaces, and show that G-RMOS achieves a significant speedup in surface mapping. We also compare the memory requirements for cortical surface mapping and show that G-RMOS uses less memory than RMOS.

3D Retinal Vessel Density Mapping With OCT-Angiography.

Optical Coherence Tomography Angiography (OCTA) is a novel, non-invasive imaging modality of retinal capillaries at micron resolution. Recent studies have correlated macular OCTA vascular measures with retinal disease severity and supported their use as a diagnostic tool. However, these measurements mostly rely on a few summary statistics in retinal layers or regions of interest in the two-dimensional (2D) en face projection images. To enable 3D and localized comparisons of retinal vasculature between longitudinal scans and across populations, we develop a novel approach for mapping retinal vessel density from OCTA images. We first obtain a high-quality 3D representation of OCTA-based vessel networks via curvelet-based denoising and optimally oriented flux (OOF). Then, an effective 3D retinal vessel density mapping method is proposed. In this framework, a vessel density image (VDI) is constructed by diffusing the vessel mask derived from OOF-based analysis to the entire image volume. Subsequently, we utilize a non-linear, 3D OCT image registration method to provide localized comparisons of retinal vasculature across subjects. In our experimental results, we demonstrate an application of our method for longitudinal qualitative analysis of two pathological subjects with edema during the course of clinical care. Additionally, we quantitatively validate our method on synthetic data with simulated capillary dropout, a dataset obtained from a normal control (NC) population divided into two age groups and a dataset obtained from patients with diabetic retinopathy (DR). Our results show that we can successfully detect localized vascular changes caused by simulated capillary loss, normal aging, and DR pathology even in presence of edema. These results demonstrate the potential of the proposed framework in localized detection of microvascular changes and monitoring retinal disease progression.

Automated Deformation-Based Analysis of 3D Optical Coherence Tomography in Diabetic Retinopathy.

Diabetic retinopathy (DR) is a significant microvascular complication of diabetes mellitus and a leading cause of vision impairment in working age adults. Optical coherence tomography (OCT) is a routinely used clinical tool to observe retinal structural and thickness alterations in DR. Pathological changes that alter the normal anatomy of the retina, such as intraretinal edema, pose great challenges for conventional layer-based analysis of OCT images. We present an alternative approach for the automated analysis of OCT volumes in DR research based on nonlinear registration. In this paper, we first obtain an anatomically consistent volume of interest (VOI) in different OCT images via carefully designed masking and affine registration. After that, efficient B-spline transformations are computed using stochastic gradient descent optimization. Using the OCT volumes of normal controls, for which layer-based segmentation works well, we demonstrate the accuracy of our registration-based analysis in aligning layer boundaries. By nonlinearly registering the OCT volumes of DR subjects to an atlas constructed from normal controls and measuring the Jacobian determinant of the deformation, we can simultaneously visualize tissue contraction and expansion due to DR pathology. Tensor-based morphometry (TBM) can also be performed for quantitative analysis of local structural changes. In our experimental results, we apply our method to a dataset of 105 subjects and demonstrate that volumetric OCT registration and TBM analysis can successfully detect local retinal structural alterations due to DR.

Surface-based Tracking of U-fibers in the Superficial White Matter.

The superficial white matter (SWM) lies directly underneath the cortical ribbon and contains the short association fibers, or U-fibers, that connect neighboring gyri. Connectivity of these U-fibers is important for various neuroscientific research from the development to the aging of the brain. Nonetheless, conventional tractography methods can only provide a partial representation of these connections. Moreover, previous studies on U-fibers mainly extract tracts based on their shape characteristics without imposing the biologically critical condition that they should tightly follow the cortical surface. In this work we leverage the high resolution diffusion imaging data from the Human Connectome Project (HCP), and develop a novel surface-based framework for reconstructing the U-fibers. Guided by the projected fiber orientation distributions (FODs) on cortical surfaces, our method tracks the U-fibers from sulcal seed regions to neighboring gyrus on the triangular mesh representation of the cortex. Compared to volume-based tractography, the main advantage of our method is that it is intrinsic to the cortical geometry. More specifically, we define a novel approach for measuring the change of angles on the tangent space of the surface and use them to determine the U-fiber passing through a sulcal seed point. In experimental results, we compare our surface-based method with state-of-the-art FOD-based tractography from MRtrix on a large-scale dataset of 484 HCP subjects, and demonstrate that our method clearly achieves superior performance on the reconstruction of U-fibers between the precentral and postcentral gyrus.

Riemannian metric optimization on surfaces (RMOS) for intrinsic brain mapping in the Laplace-Beltrami embedding space.

Surface mapping methods play an important role in various brain imaging studies from tracking the maturation of adolescent brains to mapping gray matter atrophy patterns in Alzheimer's disease. Popular surface mapping approaches based on spherical registration, however, have inherent numerical limitations when severe metric distortions are present during the spherical parameterization step. In this paper, we propose a novel computational framework for intrinsic surface mapping in the Laplace-Beltrami (LB) embedding space based on Riemannian metric optimization on surfaces (RMOS). Given a diffeomorphism between two surfaces, an isometry can be defined using the pullback metric, which in turn results in identical LB embeddings from the two surfaces. The proposed RMOS approach builds upon this mathematical foundation and achieves general feature-driven surface mapping in the LB embedding space by iteratively optimizing the Riemannian metric defined on the edges of triangular meshes. At the core of our framework is an optimization engine that converts an energy function for surface mapping into a distance measure in the LB embedding space, which can be effectively optimized using gradients of the LB eigen-system with respect to the Riemannian metrics. In the experimental results, we compare the RMOS algorithm with spherical registration using large-scale brain imaging data, and show that RMOS achieves superior performance in the prediction of hippocampal subfields and cortical gyral labels, and the holistic mapping of striatal surfaces for the construction of a striatal connectivity atlas from substantia nigra.

Patch-based Mapping of Transentorhinal Cortex with a Distributed Atlas.

The significance of the transentorhinal (TE) cortex has been well known for the early diagnosis of Alzheimer's disease (AD). However, precise mapping of the TE cortex for the detection of local changes in the region was not well established mostly due to significant geometric variations around TE. In this paper, we propose a novel framework for automated patch generation of the TE cortex, patch-based mapping, and construction of an atlas with a distributed network. We locate the TE cortex and extract a small patch surrounding the TE cortex from a cortical surface using a coarse map by FreeSurfer. We apply a recently developed intrinsic surface mapping algorithm based on Riemannian metric optimization on surfaces (RMOS) in the Laplace-Beltrami embedding space to compute fine maps between the small patches. We also develop a distributed atlas of the TE cortex, formed by a shortest path tree whose nodes are atlas subjects, to reduce anatomical misalignments by mapping only between similar patches. In our experimental results, we construct the distributed atlas of the TE cortex using 50 subjects from the Human Connectome Project (HCP), and show that detailed correspondences within the distributed network are established. Using a large-scale dataset of 380 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we demonstrate that our patch-based mapping with the distribute atlas outperforms the conventional centralized mapping (direct mapping to a single atlas) for detecting atrophy of the TE cortex in the early stage of AD.

Topological false discovery rates for brain mapping based on signal height.

Correcting the effect of multiple testing is important in statistical parametric mapping. If the threshold is too liberal, then spurious claims may flood in; if it is too conservative, then true hints may be overlooked. It is highly desirable to combine random field theory and the false discovery rate (FDR) to achieve more powerful detection under gauged topological errors. However, the current FDR method based on peak height does not fully meet this expectation, and sometimes is more conservative than the traditional family-wise error rate method, for unexplained reasons. In this paper, we introduce a new topological FDR method based on signal height. As analyzed in theory and validated with extensive experiments, it controls error rates much more accurately than the peak FDR method does, and substantially gains detection power. In addition, we discover reasons behind the peak FDR method's under-performance, and formulate equations to predict the two methods' behavior.

Holistic Mapping of Striatum Surfaces in the Laplace-Beltrami Embedding Space.

In brain shape analysis, the striatum is typically divided into three parts: the caudate, putamen, and accumbens nuclei for its analysis. Recent connectivity and animal studies, however, indicate striatum-cortical inter-connections do not always follow such subdivisions. For the holistic mapping of striatum surfaces, conventional spherical registration techniques are not suitable due to the large metric distortions in spherical parameterization of striatal surfaces. To overcome this difficulty, we develop a novel striatal surface mapping method using the recently proposed Riemannian metric optimization techniques in the Laplace-Beltrami (LB) embedding space. For the robust resolution of sign ambiguities in the LB spectrum, we also devise novel anatomical contextual features to guide the surface mapping in the embedding space. In our experimental results, we compare with spherical registration tools from FreeSurfer and FSL to demonstrate that our novel method provides a superior solution to the striatal mapping problem. We also apply our method to map the striatal surfaces from 211 subjects of the Human Connectome Project (HCP), and use the surface maps to construct a cortical connectivity atlas. Our atlas results show that the striato-cortical connectivity is not distinctive according to traditional structural subdivision of the striatum, and further confirms the holistic approach for mapping striatal surfaces.

Riemannian Metric Optimization for Connectivity-driven Surface Mapping.

With the advance of human connectome research, there are great interests in computing diffeomorphic maps of brain surfaces with rich connectivity features. In this paper, we propose a novel framework for connectivity-driven surface mapping based on Riemannian metric optimization on surfaces (RMOS) in the Laplace-Beltrami (LB) embedding space. The mathematical foundation of our method is that we can use the pullback metric to define an isometry between surfaces for an arbitrary diffeomorphism, which in turn results in identical LB embeddings from the two surfaces. For connectivity-driven surface mapping, our goal is to compute a diffeomorphism that can match a set of connectivity features defined over anatomical surfaces. The proposed RMOS approach achieves this goal by iteratively optimizing the Riemannian metric on surfaces to match the connectivity features in the LB embedding space. At the core of our framework is an optimization approach that converts the cost function of connectivity features into a distance measure in the LB embedding space, and optimizes it using gradients of the LB eigen-system with respect to the Riemannian metric. We demonstrate our method on the mapping of thalamic surfaces according to connectivity to ten cortical regions, which we compute with the multi-shell diffusion imaging data from the Human Connectome Project (HCP). Comparisons with a state-of-the-art method show that the RMOS method can more effectively match anatomical features and detect thalamic atrophy due to normal aging.

The effects of noise over the complete space of diffusion tensor shape.

Diffusion tensor magnetic resonance imaging (DT-MRI) is a technique used to quantify the microstructural organization of biological tissues. Multiple images are necessary to reconstruct the tensor data and each acquisition is subject to complex thermal noise. As such, measures of tensor invariants, which characterize components of tensor shape, derived from the tensor data will be biased from their true values. Previous work has examined this bias, but over a narrow range of tensor shape. Herein, we define the mathematics for constructing a tensor from tensor invariants, which permits an intuitive and principled means for building tensors with a complete range of tensor shape and salient microstructural properties. Thereafter, we use this development to evaluate by simulation the effects of noise on characterizing tensor shape over the complete space of tensor shape for three encoding schemes with different SNR and gradient directions. We also define a new framework for determining the distribution of the true values of tensor invariants given their measures, which provides guidance about the confidence the observer should have in the measures. Finally, we present the statistics of tensor invariant estimates over the complete space of tensor shape to demonstrate how the noise sensitivity of tensor invariants varies across the space of tensor shape as well as how the imaging protocol impacts measures of tensor invariants.

Linear invariant tensor interpolation applied to cardiac diffusion tensor MRI.

PURPOSE: Various methods exist for interpolating diffusion tensor fields, but none of them linearly interpolate tensor shape attributes. Linear interpolation is expected not to introduce spurious changes in tensor shape. METHODS: Herein we define a new linear invariant (LI) tensor interpolation method that linearly interpolates components of tensor shape (tensor invariants) and recapitulates the interpolated tensor from the linearly interpolated tensor invariants and the eigenvectors of a linearly interpolated tensor. The LI tensor interpolation method is compared to the Euclidean (EU), affine-invariant Riemannian (AI), log-Euclidean (LE) and geodesic-loxodrome (GL) interpolation methods using both a synthetic tensor field and three experimentally measured cardiac DT-MRI datasets. RESULTS: EU, AI, and LE introduce significant microstructural bias, which can be avoided through the use of GL or LI. CONCLUSION: GL introduces the least microstructural bias, but LI tensor interpolation performs very similarly and at substantially reduced computational cost.