Person:

Rathi, Yogesh

The main contribution of this work is the careful syntactical definition of major white matter tracts in the human brain based on a neuroanatomist’s expert knowledge. We present a technique to formally describe white matter tracts and to automatically extract them from diffusion MRI data. The framework is based on a novel query language with a near-to-English textual syntax. This query language allows us to construct a dictionary of anatomical definitions describing white matter tracts. The definitions include adjacent gray and white matter regions, and rules for spatial relations. This enables automated coherent labeling of white matter anatomy across subjects. We use our method to encode anatomical knowledge in human white matter describing 10 association and 8 projection tracts per hemisphere and 7 commissural tracts. The technique is shown to be comparable in accuracy to manual labeling. We present results applying this framework to create a white matter atlas from 77 healthy subjects, and we use this atlas in a proof-of-concept study to detect tract changes specific to schizophrenia.

A significant percentage of individuals diagnosed with mild traumatic brain injury (mTBI) experience persistent post-concussive symptoms (PPCS). Little is known about the pathology of these symptoms and there is often no radiological evidence based on conventional clinical imaging. We aimed to utilize methods to evaluate microstructural tissue changes and to determine whether or not a link with PPCS was present. A novel analysis method was developed to identify abnormalities in high-resolution diffusion tensor imaging (DTI) when the location of brain injury is heterogeneous across subjects. A normative atlas with 145 brain regions of interest (ROI) was built from 47 normal controls. Comparing each subject’s diffusion measures to the atlas generated subject-specific profiles of injury. Abnormal ROIs were defined by absolute z-score values above a given threshold. The method was applied to 11 PPCS patients following mTBI and 11 matched controls. Z-score information for each individual was summarized with two location-independent measures: “load” (number of abnormal regions) and “severity” (largest absolute z-score). Group differences were then computed using Wilcoxon rank sum tests. Results showed statistically significantly higher load (p = 0.018) and severity (p = 0.006) for fractional anisotropy (FA) in patients compared with controls. Subject-specific profiles of injury evinced abnormally high FA regions in gray matter (30 occurrences over 11 patients), and abnormally low FA in white matter (3 occurrences over 11 subjects). Subject-specific profiles provide important information regarding the pathology associated with PPCS. Increased gray matter (GM) anisotropy is a novel in-vivo finding, which is consistent with an animal model of brain trauma that associates increased FA in GM with pathologies such as gliosis. In addition, the individualized analysis shows promise for enhancing the clinical care of PPCS patients as it could play a role in the diagnosis of brain injury not revealed using conventional imaging.

Magnetic resonance spectroscopic imaging (MRSI) is often used to estimate the concentration of several brain metabolites. Abnormalities in these concentrations can indicate specific pathology, which can be quite useful in understanding the disease mechanism underlying those changes. Due to higher concentration, metabolites such as N-acetylaspartate (NAA), Creatine (Cr) and Choline (Cho) can be readily estimated using standard Fourier transform techniques. However, metabolites such as Glutamate (Glu) and Glutamine (Gln) occur in significantly lower concentrations and their resonance peaks are very close to each other making it di!cult to accurately estimate their concentrations (separately). In this work, we propose to use the theory of ‘Spectral Zooming’ or high-resolution spectral analysis to separate the Glutamate and Glutamine peaks and accurately estimate their concentrations. The method works by estimating a unique power spectral density, which corresponds to the maximum entropy solution of a zero-mean stationary Gaussian process. We demonstrate our estimation technique on several physical phantom data sets as well as on invivo brain spectroscopic imaging data. The proposed technique is quite general and can be used to estimate the concentration of any other metabolite of interest.

Richly labeled images representing several sub-structures of an organ occur quite frequently in medical images. For example, a typical brain image can be labeled into grey matter, white matter or cerebrospinal fluid, each of which may be subdivided further. Many manipulations such as interpolation, transformation, smoothing, or registration need to be performed on these images before they can be used in further analysis. In this work, we present a novel multi-shape representation and compare it with the existing representations to demonstrate certain advantages of using the proposed scheme. Specifically, we propose label space, a representation that is both flexible and well suited for coupled multi-shape analysis. Under this framework, object labels are mapped to vertices of a regular simplex, e.g the unit interval for two labels, a triangle for three labels, a tetrahedron for four labels, etc. This forms the basis of a convex linear structure with the property that all labels are equally spaced. We will demonstrate that this representation has several desirable properties: algebraic operations may be performed directly, label uncertainty is expressed equivalently as a weighted mixture of labels or in a probabilistic manner, and interpolation is unbiased toward any label or the background. In order to demonstrate these properties, we compare label space to signed distance maps as well as other implicit representations in tasks such as smoothing, interpolation, registration, and principal component analysis.

Background: Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a neurogenetic disorder that is associated with a 25-fold increase in schizophrenia. Both individuals with 22q11.2DS and those with schizophrenia present with social cognitive deficits, which are putatively subserved by a network of brain regions that are involved in the processing of social cognitive information. This study used two-tensor tractography to examine the white matter tracts believed to underlie the social brain network in a group of 57 young adults with 22q11.2DS compared to 30 unaffected controls. Results: Results indicated that relative to controls, participants with 22q11.2DS showed significant differences in several DTI metrics within the inferior fronto-occipital fasciculus, cingulum bundle, thalamo-frontal tract, and inferior longitudinal fasciculus. In addition, participants with 22q11.2DS showed significant differences in scores on measures of social cognition, including the Social Responsiveness Scale and Trait Emotional Intelligence Questionnaire. Further analyses among individuals with 22q11.2DS demonstrated an association between DTI metrics and positive and negative symptoms of psychosis, as well as differentiation between individuals with 22q11.2DS and overt psychosis, relative to those with positive prodromal symptoms or no psychosis. Conclusions: Findings suggest that white matter disruption, specifically disrupted axonal coherence in the right inferior fronto-occipital fasciculus, may be a biomarker for social cognitive difficulties and psychosis in individuals with 22q11.2DS. Electronic supplementary material The online version of this article (doi:10.1186/s12993-017-0122-7) contains supplementary material, which is available to authorized users.

Although diffusion tensor imaging (DTI) studies have reported fractional anisotropy (FA) abnormalities in multiple white matter (WM) regions in schizophrenia, relationship between abnormal FA and negative symptoms has not been fully explored. DTI data were acquired from twenty-four patients with chronic schizophrenia and twenty-five healthy controls. Regional brain abnormalities were evaluated by conducting FA comparisons in the cerebral and each lobar WMs between groups. Focal abnormalities were also evaluated with a voxel-wise tract specific method. Associations between structural WM changes and negative symptoms were assessed using the Scale for the Assessment of Negative Symptoms (SANS). The patient group showed decreased FA in the cerebrum, especially in the frontal lobe, compared with controls. A voxel wise analysis showed FA decreases in almost all WM tracts in schizophrenia. Correlation analyses demonstrated negative relationships between FA in the cerebrum, particularly in the left hemisphere, and SANS global and global rating scores (Anhedonia-Asociality, Attention, and Affective-Flattening), and also associations between FA of left frontal lobe and SANS global score, Anhedonia Asociality, and Attention. This study demonstrates that patients with chronic schizophrenia evince widespread cerebral FA abnormalities and that these abnormalities, especially in the left hemisphere, are associated with negative symptoms.

Diffusion magnetic resonance imaging (dMRI) is an important tool that allows non-invasive investigation of neural architecture of the brain. The data obtained from these in-vivo scans provides important information about the integrity and connectivity of neural fiber bundles in the brain. A multi-shell imaging (MSI) scan can be of great value in the study of several psychiatric and neurological disorders, yet its usability has been limited due to the long acquisition times required. A typical MSI scan involves acquiring a large number of gradient directions for the 2 (or more) spherical shells (several b-values), making the acquisition time significantly long for clinical application. In this work, we propose to use results from the theory of compressive sampling and determine the minimum number of gradient directions required to attain signal reconstruction similar to a traditional MSI scan. In particular, we propose a generalization of the single shell spherical ridgelets basis for sparse representation of multi shell signals. We demonstrate its efficacy on several synthetic and in-vivo data sets and perform quantitative comparisons with solid spherical harmonics based representation. Our preliminary results show that around 20–24 directions per shell are enough for robustly recovering the diffusion propagator.

This paper proposes a method for the registration of white matter tract bundles traced from diffusion images and its extension to atlas generation. Our framework is based on a Gaussian process representation of tract density maps. Such a representation avoids the need for point-to point correspondences, is robust to tract interruptions and reconnections and seamlessly handles the comparison and combination of white matter tract bundles. Moreover, being a parametric model, this approach has the potential to be defined in the Gaussian processes’ parameter space, without the need for resampling the fiber bundles during the registration process. We use the similarity measure of our Gaussian process framework, which is in fact an inner product, to drive a diffeomorphic registration algorithm between two sets of homologous bundles which is not biased by point-to-point correspondences or the parametrization of the tracts. We estimate a dense deformation of the underlying white matter using the bundles as anatomical landmarks and obtain a population atlas of those fiber bundles. Finally we test our results in several different bundles obtained from in-vivo data.

We describe a technique that uses tractography to drive the local fiber model estimation. Existing techniques use independent estimation at each voxel so there is no running knowledge of confidence in the estimated model fit. We formulate fiber tracking as recursive estimation: at each step of tracing the fiber, the current estimate is guided by those previous. To do this we perform tractography within a filter framework and use a discrete mixture of Gaussian tensors to model the signal. Starting from a seed point, each fiber is traced to its termination using an unscented Kalman filter to simultaneously fit the local model to the signal and propagate in the most consistent direction. Despite the presence of noise and uncertainty, this provides a causal estimate of the local structure at each point along the fiber. Using two- and three-fiber models we demonstrate in synthetic experiments that this approach significantly improves the angular resolution at crossings and branchings. In vivo experiments confirm the ability to trace through regions known to contain such crossing and branching while providing inherent path regularization.

We introduce a fibre tractography framework based on a particle filter which estimates a local geometrical model of the underlying white matter tract, formulated as a `streamline flow' using generalized helicoids. The method is not dependent on the diffusion model, and is applicable to diffusion tensor (DT) data as well as to high angular resolution reconstructions. The geometrical model allows for a robust inference of local tract geometry, which, in the context of the causal filter estimation, guides tractography through regions with partial volume effects. We validate the method on synthetic data and present results on two types in vivo data: diffusion tensors and a spherical harmonic reconstruction of the fibre orientation distribution function (fODF).