Publications by Year: 2009

Diffusion tensor imaging (DTI) and fiber tractography are useful tools for reconstructing white matter tracts (WMT) in the brain. Previous tractography studies have sought to segment reconstructed WMT into anatomical structures using several approaches, but quantification has been limited to extracting mean values of diffusion indices. Delineating WMT in schizophrenia is of particular interest because schizophrenia has been hypothesized to be a disorder of disrupted connectivity, especially between frontal and temporal regions of the brain. In this study, we aim to differentiate diffusion properties of thalamo-frontal pathways in schizophrenia from normal controls. We present a quantitative group comparison method, which combines the strengths of both tractography-based and voxel-based studies. Our algorithm extracts white matter pathways using whole brain tractography. Functionally relevant bundles are selected and parsed from the resulting set of tracts, using an internal capsule (IC) region of interest (ROI) as "source", and different Brodmann area (BA) ROIs as "targets". The resulting bundles are then longitudinally parameterized so that diffusion properties can be measured and compared along the WMT. Using this processing pipeline, we were able to find altered diffusion properties in male patients with chronic schizophrenia in terms of fractional anisotropy (FA) decreases and mean diffusivity (MD) increases in precise and functionally relevant locations. These findings suggest that our method can enhance the regional and functional specificity of DTI group studies, thus improving our understanding of brain function.

Two of the most frequently investigated regions in diffusion tensor imaging studies in chronic schizophrenia are the uncinate fasciculus (UF) and cingulum bundle (CB). The purpose of the present study was to determine whether UF and CB white matter integrity were altered at the early stage of illness and specific to schizophrenia. Fifteen schizophrenia subjects and 15 affective psychosis within 4 years of first hospitalization (12 patients with schizophrenia and 12 patients with affective psychosis during their first hospitalization), and 15 psychiatrically healthy controls underwent line-scan diffusion tensor imaging. Fractional anisotropy (FA) and mean diffusivity (D(m)) were used to quantify water diffusion, and cross-sectional area was defined with a directional threshold method. Bilaterally reduced FA, but not D(m), was present in the UF of schizophrenia compared with healthy controls. Affective psychosis was intermediate between schizophrenia subjects and healthy controls, but not significantly different from either. For CB, there was no significant group difference for FA or D(m). These findings suggest that UF, but not CB, white matter integrity is altered at the early stage of illness in schizophrenia although it may not be specific to schizophrenia. The CB abnormalities reported in chronic schizophrenia may develop during the later course of the disease.

We introduce a framework for computing geometrical properties of white matter fibres directly from diffusion tensor fields. The key idea is to isolate the portion of the gradient of the tensor field corresponding to local variation in tensor orientation, and to project it onto a coordinate frame of tensor eigenvectors. The resulting eigenframe-centered representation makes it possible to define scalar geometrical measures that describe the underlying white matter fibres, directly from the diffusion tensor field and its gradient, without requiring prior tractography. We define two new scalar measures of (1) fibre dispersion and (2) fibre curving, and we demonstrate them on synthetic and in-vivo datasets. Finally, we illustrate their applicability in a group study on schizophrenia.

BACKGROUND: Previously, we reported abnormal volume and global shape in the caudate nucleus in schizotypal personality disorder (SPD). Here, we use a new shape measure which importantly permits local in addition to global shape analysis, as well as local correlations with behavioral measures. METHODS: Thirty-two female and 15 male SPDs, and 29 female and 14 male normal controls (NCLs), underwent brain magnetic resonance imaging (MRI). We assessed caudate shape measures using spherical harmonic-point distribution model (SPHARM-PDM) methodology. RESULTS: We found more pronounced global shape differences in the right caudate in male and female SPD, compared with NCLs. Local shape differences, principally in the caudate head, survived statistical correction on the right. Also, we performed correlations between local surface deformations with clinical measures and found significant correlations between local shape deflated deformations in the anterior medial surface of the caudate with verbal learning capacity in female SPD. CONCLUSIONS: Using SPHARM-PDM methodology, we found both global and local caudate shape abnormalities in male and female SPD, particularly right-sided, and largely restricted to limbic and cognitive anterior caudate. The most important and novel findings were bilateral statistically significant correlations between local surface deflations in the anterior medial surface of the head of the caudate and verbal learning capacity in female SPD. By extension, these local caudate correlation findings implicate the ventromedial prefrontal cortex (vmPFC), which innervates that area of the caudate, and demonstrate the utility of local shape analysis to investigate the relationship between specific subcortical and cortical brain structures in neuropsychiatric conditions.

A progressive post-onset decrease in gray matter volume 1.5 years after first hospitalization in schizophrenia has been shown in superior temporal gyrus (STG). However, it is still controversial whether progressive volume reduction occurs in chronic schizophrenia in the STG and amygdala-hippocampal complex (AHC), structures found to be abnormal in chronic schizophrenia. These structures were measured at two time points in 16 chronic schizophrenia patients and 20 normal comparison subjects using manual tracing with high spatial resolution magnetic resonance imaging (MRI). Average interscan interval was 3.1 years for schizophrenia patients and 1.4 years for healthy comparison subjects. Cross-sectional comparisons showed smaller relative volumes in schizophrenia compared with controls in posterior STG and AHC. An ANCOVA with interscan interval as a covariate showed there was no statistically significant progression of volume reduction in either the STG or AHC in the schizophrenia group compared with normal subjects. In the schizophrenia group, volume change in the left anterior AHC significantly correlated with PANSS negative symptoms. These data, and separately reported first episode data from our laboratory, suggest marked progression at the initial stage of schizophrenia, but less in chronic schizophrenia.

Attention and memory deficits are among the most prominent cognitive disturbances observed in schizophrenia. It has been suggested that a disruption in anatomical connectivity between areas involved in attentional control might be responsible for these abnormalities. We used Diffusion Tensor Tractography and Color Stroop/Negative Priming(NP) paradigm to investigate integrity of Cingulum Bundle(CB), the main white matter tract interconnecting these regions, and its relationship with executive functions in patients with schizophrenia and matched controls. The Fractional Anisotropy(FA), was calculated along the CB pathways, and correlated with reaction times for each Stroop item, and both Stroop, and NP effects. Patients with schizophrenia demonstrated decreased CB integrity and diminished NP effect, compared with controls, but both groups showed Stroop effect. For patients only, reaction times for every item, as well as for Stroop effect, correlated with left CB FA. These findings suggest that CB integrity disruptions might compromise the executive processes in schizophrenia.

An inherent drawback of the traditional diffusion tensor model is its limited ability to provide detailed information about multidirectional fiber architecture within a voxel. This leads to erroneous fiber tractography results in locations where fiber bundles cross each other. This may lead to the inability to visualize clinically important tracts such as the lateral projections of the corticospinal tract. In this report, we present a deterministic two-tensor eXtended Streamline Tractography (XST) technique, which successfully traces through regions of crossing fibers. We evaluated the method on simulated and in vivo human brain data, comparing the results with the traditional single-tensor and with a probabilistic tractography technique. By tracing the corticospinal tract and correlating with fMRI-determined motor cortex in both healthy subjects and patients with brain tumors, we demonstrate that two-tensor deterministic streamline tractography can accurately identify fiber bundles consistent with anatomy and previously not detected by conventional single-tensor tractography. When compared to the dense connectivity maps generated by probabilistic tractography, the method is computationally efficient and generates discrete geometric pathways that are simple to visualize and clinically useful. Detection of crossing white matter pathways can improve neurosurgical visualization of functionally relevant white matter areas.

We introduce an automatic method that we call tract-based morphometry, or TBM, for measurement and analysis of diffusion MRI data along white matter fiber tracts. Using subject-specific tractography bundle segmentations, we generate an arc length parameterization of the bundle with point correspondences across all fibers and all subjects, allowing tract-based measurement and analysis. In this paper we present a quantitative comparison of fiber coordinate systems from the literature and we introduce an improved optimal match method that reduces spatial distortion and improves intra- and inter-subject variability of FA measurements. We propose a method for generating arc length correspondences across hemispheres, enabling a TBM study of interhemispheric diffusion asymmetries in the arcuate fasciculus (AF) and cingulum bundle (CB). The results of this study demonstrate that TBM can detect differences that may not be found by measuring means of scalar invariants in entire tracts, such as the mean diffusivity (MD) differences found in AF. We report TBM results of higher fractional anisotropy (FA) in the left hemisphere in AF (caused primarily by lower lambda(3), the smallest eigenvalue of the diffusion tensor, in the left AF), and higher left hemisphere FA in CB (related to higher lambda(1), the largest eigenvalue of the diffusion tensor, in the left CB). By mapping the significance levels onto the tractography trajectories for each structure, we demonstrate the anatomical locations of the interhemispheric differences. The TBM approach brings analysis of DTI data into the clinically and neuroanatomically relevant framework of the tract anatomy.

Computing the orientation distribution function (ODF) from high angular resolution diffusion imaging (HARDI) signals makes it possible to determine the orientation of fiber bundles of the brain. The HARDI signals are samples measured from a spherical shell and thus require processing on the sphere. Past work on ODF estimation involved using the spherical harmonics or spherical radial basis functions. In this work, we propose three novel directional functions able to represent the measured signals in a very compact manner, i.e., they require very few parameters to completely describe the measured signal. Analytical expressions are derived for computing the corresponding ODF. The directional functions can represent diffusion in a particular direction and mixture models can be used to represent multi-fiber orientations. We show how to estimate the parameters of this mixture model and elaborate on the differences between these functions. We also compare this general framework with estimation of ODF using spherical harmonics on some real and synthetic data. The proposed method could be particularly useful in applications such as tractography and segmentation. Details are also given on different ways in which interpolation can be performed using directional functions. In particular, we discuss a complete Euclidean as well as a "hybrid" framework, comprising of the Riemannian as well as Euclidean spaces, to perform interpolation and compute geodesic distances between two ODF’s.

BACKGROUND: Superior temporal gyrus (STG) volume reduction is one of the most consistent findings in schizophrenia. The goal of this study was to conduct the first Diffusion Tensor Imaging (DTI) study to investigate altered structural integrity in STG gray and white matter in patients with chronic schizophrenia compared with healthy controls. METHODS: Magnetic resonance imaging (MRI) and DTI were acquired in 21 male patients with schizophrenia and 22 age-, handedness-, and parental social economic status-matched male comparison subjects. After manual segmentation of gray and white matter, mean diffusivity and fractional anisotropy were measured within STG. Correlational analyses were also conducted to test possible associations between DTI and clinical measures, including positive and negative symptoms of schizophrenia. RESULTS: Compared with controls, patients demonstrated reduced volume, bilaterally, in STG gray matter but not in white matter. For DTI measures, patients showed increased mean diffusivity, bilaterally, in STG gray matter, and in left STG white matter. In addition, mean diffusivity in left STG white matter showed statistically significant correlations with auditory hallucinations and attentional impairments in patients. CONCLUSIONS: These findings suggest a disruption of tissue integrity in STG gray and white matter in schizophrenia. In addition, increased water diffusivity in left-side STG, which was associated with auditory hallucinations and attentional impairments, suggests the possibility of a disconnection among auditory/language processing regions in schizophrenia.