Publications

The most rostral portion of the human temporal cortex, the temporal pole (TP), has been described as "enigmatic" because its functional neuroanatomy remains unclear. Comparative anatomy studies are only partially helpful, because the human TP is larger and cytoarchitectonically more complex than in nonhuman primates. Considered by Brodmann as a single area (BA 38), the human TP has been recently parceled into an array of cytoarchitectonic subfields. In order to clarify the functional connectivity of subregions of the TP, we undertook a study of 172 healthy adults using resting-state functional connectivity MRI. Remarkably, a hierarchical cluster analysis performed to group the seeds into distinct subsystems according to their large-scale functional connectivity grouped 87.5% of the seeds according to the recently described cytoarchitectonic subregions of the TP. Based on large-scale functional connectivity, there appear to be 4 major subregions of the TP: (1) dorsal, with predominant connectivity to auditory/somatosensory and language networks; (2) ventromedial, predominantly connected to visual networks; (3) medial, connected to paralimbic structures; and (4) anterolateral, connected to the default-semantic network. The functional connectivity of the human TP, far more complex than its known anatomic connectivity in monkey, is concordant with its hypothesized role as a cortical convergence zone.

Harmonizing diffusion MRI (dMRI) images across multiple sites is imperative for joint analysis of the data to significantly increase the sample size and statistical power of neuroimaging studies. In this work, we develop a method to harmonize diffusion MRI data across multiple sites and scanners that incorporates two main novelties: i) we take into account the spatial variability of the signal (for different sites) in different parts of the brain as opposed to existing methods, which consider one linear statistical covariate for the entire brain; ii) our method is model-free, in that no a-priori model of diffusion (e.g., tensor, compartmental models, etc.) is assumed and the signal itself is corrected for scanner related differences. We use spherical harmonic basis functions to represent the signal and compute several rotation invariant features, which are used to estimate a regionally specific linear mapping between signal from different sites (and scanners). We validate our method on diffusion data acquired from four different sites (including two GE and two Siemens scanners) on a group of healthy subjects. Diffusion measures such fractional anisotropy, mean diffusivity and generalized fractional anisotropy are compared across multiple sites before and after the mapping. Our experimental results demonstrate that, for identical acquisition protocol across sites, scanner-specific differences can be accurately removed using the proposed method.

Multimodal neuroimaging is increasingly used in neuroscience research, as it overcomes the limitations of individual modalities. One of the most important applications of multimodal neuroimaging is the provision of vital diagnostic data for neuropsychiatric disorders. Multimodal neuroimaging computing enables the visualization and quantitative analysis of the alterations in brain structure and function, and has reshaped how neuroscience research is carried out. Research in this area is growing exponentially, and so it is an appropriate time to review the current and future development of this emerging area. Hence, in this paper, we review the recent advances in multimodal neuroimaging (MRI, PET) and electrophysiological (EEG, MEG) technologies, and their applications to the neuropsychiatric disorders. We also outline some future directions for multimodal neuroimaging where researchers will design more advanced methods and models for neuropsychiatric research.

We present a novel approach to determine a local q-space metric that is optimal from an information theoreticperspective with respect to the expected signal statistics. It should be noted that the approach does not attempt to optimize the quality of a pre-defined mathematical representation, the estimator. In contrast, our suggestion aims at obtaining the maximum amount of information without enforcing a particular feature representation. Results for three significantly different average propagator distributions are presented. The results show that the optimal q-space metric has a strong dependence on the assumed distribution in the targeted tissue. In many practical cases educated guesses can be made regarding the average propagator distribution present. In such cases the presented analysis can produce a metric that is optimal with respect to this distribution. The metric will be different at different q-space locations and is defined by the amount of additional information that is obtained when adding a second sample at a given offset from a first sample. The intention is to use the obtained metric as a guide for the generation of specific efficient q-space sample distributions for the targeted tissue.

In traditional diffusion MRI, short pulsed field gradients (PFG) are used for the diffusion encoding. The standard Stejskal-Tanner sequence uses one single pair of such gradients, known as single-PFG (sPFG). In this work we describe how trajectories in q-space can be used for diffusion encoding. We discuss how such encoding enables the extension of the well-known scalar b-value to a tensor-valued entity we call the diffusion measurement tensor. The new measurements contain information about higher order diffusion propagator covariances not present in sPFG. As an example analysis, we use this new information to estimate a Gaussian distribution over diffusion tensors in each voxel, described by its mean (a diffusion tensor) and its covariance (a 4th order tensor).

Techniques in medical image analysis are many times used for the comparison or regression on the intensities of images. In general, the domain of the image is a given Cartesian grids. Shape analysis, on the other hand, studies the similarities and differences among spatial objects of arbitrary geometry and topology. Usually, there is no function defined on the domain of shapes. Recently, there has been a growing needs for defining and analyzing functions defined on the shape space, and a coupled analysis on both the shapes and the functions defined on them. Following this direction, in this work we present a coupled analysis for both images and shapes. As a result, the statistically significant discrepancies in both the image intensities as well as on the underlying shapes are detected. The method is applied on both brain images for the schizophrenia and heart images for atrial fibrillation patients.

Longitudinal analysis of medical imaging data has become central to the study of many disorders. Unfortunately, various constraints (study design, patient availability, technological limitations) restrict the acquisition of data to only a few time points, limiting the study of continuous disease/treatment progression. Having the ability to produce a sensible time interpolation of the data can lead to improved analysis, such as intuitive visualizations of anatomical changes, or the creation of more samples to improve statistical analysis. In this work, we model interpolation of medical image data, in particular shape data, using the theory of optimal mass transport (OMT), which can construct a continuous transition from two time points while preserving "mass" (e.g., image intensity, shape volume) during the transition. The theory even allows a short extrapolation in time and may help predict short-term treatment impact or disease progression on anatomical structure. We apply the proposed method to the hippocampus-amygdala complex in schizophrenia, the heart in atrial fibrillation, and full head MR images in traumatic brain injury.

The medial orbitofrontal cortex (mOFC) and rostral anterior cingulate cortex (rACC) are part of a wider neural network that plays an important role in general intelligence and executive function. We used structural brain imaging to quantify magnetic resonance gray matter volume and diffusion tensor white matter integrity of the mOFC-rACC network in 26 healthy participants who also completed neuropsychological tests of intellectual abilities and executive function. Stochastic tractography, the most effective Diffusion Tensor Imaging method for examining white matter connections between adjacent gray matter regions, was employed to assess the integrity of mOFC-rACC pathways. Fractional anisotropy (FA), which reflects the integrity of white matter connections, was calculated. Results indicated that higher intelligence correlated with greater gray matter volumes for both mOFC and rACC, as well as with increased FA for left posterior mOFC-rACC connectivity. Hierarchical regression analyses revealed that DTI-derived FA of left posterior mOFC-rACC uniquely accounted for 29%-34% of the variance in IQ, in comparison to 11%-16% uniquely explained by gray matter volume of the left rACC. Together, left rACC gray matter volume and white matter connectivity between left posterior mOFC and rACC accounted for up to 50% of the variance in general intelligence. This study is to our knowledge the first to examine white matter connectivity between OFC and ACC, two gray matter regions of interests that are very close in physical proximity, and underscores the important independent contributions of variations in rACC gray matter volume and mOFC-rACC white matter connectivity to individual differences in general intelligence.

Current neuroimaging investigation of the white matter typically focuses on measurements derived from diffusion tensor imaging, such as fractional anisotropy (FA). In contrast, imaging studies of the gray matter oftentimes focus on morphological features such as cortical thickness, folding and surface curvature. As a result, it is not clear how to combine findings from these two types of approaches in order to obtain a consistent picture of morphological changes in both gray and white matter. In this paper, we propose a joint investigation of gray and white matter morphology by combining geometrical information from white and the gray matter. To achieve this, we first introduce a novel method for computing multi-scale white matter tract geometry. Its formulation is based on the differential geometry of curve sets and is easily incorporated into a continuous scale-space framework. We then incorporate this method into a novel framework for "fusing" white and gray matter geometrical information. Given a set of fiber tracts originating in a particular cortical region, the key idea is to compute two scalar fields that represent geometrical characteristics of the white matter and of the surface of the cortical region. A quantitative marker is created by combining the distributions of these scalar values using Mutual Information. This marker can be then used in the study of normal and pathological brain structure and development. We apply this framework to a study on autism spectrum disorder in children. Our preliminary results support the view that autism may be characterized by early brain overgrowth, followed by reduced or arrested growth (Courchesne, 2004).

Sports-related concussions are one of the major causes of mild traumatic brain injury. Although most patients recover completely within days to weeks, those who experience repetitive brain trauma (RBT) may be at risk for developing a condition known as chronic traumatic encephalopathy (CTE). While this condition is most commonly observed in athletes who experience repetitive concussive and/or subconcussive blows to the head, such as boxers, football players, or hockey players, CTE may also affect soldiers on active duty. Currently, the only means by which to diagnose CTE is by the presence of phosphorylated tau aggregations post-mortem. Non-invasive neuroimaging, however, may allow early diagnosis as well as improve our understanding of the underlying pathophysiology of RBT. The purpose of this article is to review advanced neuroimaging methods used to investigate RBT, including diffusion tensor imaging, magnetic resonance spectroscopy, functional magnetic resonance imaging, susceptibility weighted imaging, and positron emission tomography. While there is a considerable literature using these methods in brain injury in general, the focus of this review is on RBT and those subject populations currently known to be susceptible to RBT, namely athletes and soldiers. Further, while direct detection of CTE in vivo has not yet been achieved, all of the methods described in this review provide insight into RBT and will likely lead to a better characterization (diagnosis), in vivo, of CTE than measures of self-report.