Robert J. Tamburo

Default-mode network connectivity and white matter burden in late-life depression

The brains default-mode network has been the focus of intense research. This study characterizes the default-mode network activity in late-life depression and the correlation of the default-mode network activity changes with the white-matter hyperintensities burden. We hypothesized that elderly depressed subjects would have altered default-mode network activity, which would correlate with the increased white-matter hyperintensities burden. Twelve depressed subjects (mean Hamilton Depression Rating Scale 19.8±4.1, mean age 70.5±4.9) and 12 non-depressed, comparison subjects (mean age 69±6.5) were included. Functional magnetic resonance imaging (fMRI) data were collected while subjects performed a low cognitive load, event-related task. We compared the default-mode network activity in these groups (including depressed subjects pre- and post-antidepressant treatment). We analyzed the resting connectivity patterns of the posterior cingulate cortex. Deconvolution was used to evaluate the correlation of resting-state connectivity scores with the white-matter hyperintensities burden. Compared with non-depressed elderly, depressed subjects pretreatment had decreased connectivity in the subgenual anterior cingulate cortex and increased connectivity in the dorsomedial prefrontal cortex and the orbito-frontal cortex. The abnormal connectivity was significantly correlated with the white-matter hyperintensities burden. Remitted elderly depressed subjects had improved functional connectivity compared to pretreatment, although alterations persisted in the anterior cingulate and the prefrontal cortex when remitted elderly depressed subjects were compared with non-depressed elderly. Our study provides evidence for altered default-mode network connectivity in late-life depression. The correlation between white-matter hyperintensities burden and default-mode network connectivity emphasizes the role of vascular changes in late-life depression etiopathogenesis.

Multivariate tensor-based morphometry on surfaces: application to mapping ventricular abnormalities in HIV/AIDS.

Here we developed a new method, called multivariate tensor-based surface morphometry (TBM), and applied it to study lateral ventricular surface differences associated with HIV/AIDS. Using concepts from differential geometry and the theory of differential forms, we created mathematical structures known as holomorphic one-forms, to obtain an efficient and accurate conformal parameterization of the lateral ventricular surfaces in the brain. The new meshing approach also provides a natural way to register anatomical surfaces across subjects, and improves on prior methods as it handles surfaces that branch and join at complex 3D junctions. To analyze anatomical differences, we computed new statistics from the Riemannian surface metrics-these retain multivariate information on local surface geometry. We applied this framework to analyze lateral ventricular surface morphometry in 3D MRI data from 11 subjects with HIV/AIDS and 8 healthy controls. Our method detected a 3D profile of surface abnormalities even in this small sample. Multivariate statistics on the local tensors gave better effect sizes for detecting group differences, relative to other TBM-based methods including analysis of the Jacobian determinant, the largest and smallest eigenvalues of the surface metric, and the pair of eigenvalues of the Jacobian matrix. The resulting analysis pipeline may improve the power of surface-based morphometry studies of the brain.

Amygdalae morphometry in late-life depression

The amygdalae have been a focus of mood disorder research due to their key role in processing emotional information. It has been long known that depressed individuals demonstrate impaired functional performance while engaged in emotional tasks. The structural basis for these functional differences has been investigated via volumetric analysis with mixed findings. In this study, we examined the morphometric basis for these functional changes in late‐life depression (LLD) by analyzing both the size and shape of the amygdalae with the hypothesis that shape differences may be apparent even when overall volume differences are inconsistent.

Guidance of Retrobulbar Injection With Real-time Tomographic Reflection

Objective. Retrobulbar and peribulbar injections are common ophthalmologic procedures used to deliver anesthetics and other medications for ophthalmic therapy and surgery. These injections, typically performed without any type of guidance, can lead to complications that are rare but visually devastating. The needle may penetrate the optic nerve, perforate the globe, or disperse toxic quantities of drugs intraocularly, causing major visual loss. Sonographic guidance may increase the accuracy of the needle placement, thereby decreasing the incidence of complications. However, difficulties arise in coordinating the relative location of the image, the needle, and the patient. Real‐time tomographic reflection is a new method for in situ visualization of sonographic images, permitting direct hand‐eye coordination to guide invasive instruments beneath the surface of the skin. Methods. In this preliminary study, real‐time tomographic reflection was used to visualize the eye and surrounding anatomic structures in a cadaver during a simulated retrobulbar injection. Results. The needle tip was easily followed as it was advanced into the retrobulbar space. Conclusions. The images presented in this preliminary study show the use of real‐time tomographic reflection to visualize insertion of an invasive instrument into the human body.

Tomographic reflection to merge ultrasound images with direct vision

Tomographic reflection is a method that may be used to merge the visual outer surface of a patient with a simultaneous ultrasound scan of the patients interior. The technique combines a flat-panel monitor with a half-silvered mirror such that the image on the monitor is reflected precisely at the proper location within the patient. In this way, the ultrasound image is superimposed in real time on the view of the patient along with the operators hands and any invasive tools in the field of view. Instead of looking away at an ultrasound monitor, the operator can manipulate needles and scalpels with direct hand-eye coordination. Invasive tools are visible up to where they enter the skin, permitting natural visual extrapolation to targets in the ultrasound slice. Tomographic reflection is independent of viewer location, requires no special apparatus to be worn by the operator, nor any registration of the patient.

AUTOMATED SEGMENTATION OF THE RIGHT HEART USING AN OPTIMIZED SHELLS AND SPHERES ALGORITHM

We have developed a novel framework for medical image analysis, known as shells and spheres. This framework utilizes spherical operators of variable radius centered at each image pixel and sized to reach, but not cross, the nearest object boundary. Statistical population tests are performed on adjacent spheres to compare image regions across boundaries. Previously, our framework was applied to segmentation of cardiac CT data with promising results. In this paper, we present a more accurate and versatile system by optimizing algorithm parameters for a particular data set to maximize agreement to manual segmentations. We perform parameter optimization on a selected 2D slice from a 3D image data set, generating effective parameters for 3D segmentation in practical computational time. Details of this approach are given, along with a validated application to cardiac MR data.

Shells and spheres: an n -dimensional framework for medial-based image segmentation

We have developed a method for extracting anatomical shape models from n-dimensional images using an image analysis framework we call Shells and Spheres. This framework utilizes a set of spherical operators centered at each image pixel, grown to reach, but not cross, the nearest object boundary by incorporating “shells” of pixel intensity values while analyzing intensity mean, variance, and first-order moment. Pairs of spheres on opposite sides of putative boundaries are then analyzed to determine boundary reflectance which is used to further constrain sphere size, establishing a consensus as to boundary location. The centers of a subset of spheres identified as medial (touching at least two boundaries) are connected to identify the interior of a particular anatomical structure. For the automated 3D algorithm, the only manual interaction consists of tracing a single contour on a 2D slice to optimize parameters, and identifying an initial point within the target structure.

LOCALIZING AMYGDALA STRUCTURE DIFFERENCES IN LATE-LIFE DEPRESSION

The amygdala is critical for processing emotional information and plays an important role in late-life depression (LLD). Volumetric studies of the amygdala have been inconclusive with reports of increased, decreased, and no volume changes. This study investigates amygdala shape morphometry to test the hypothesis that if structural changes are specific to certain nuclei, then shape changes may be apparent even when overall volume changes are inconsistent. We have developed a method of shape morphometry based on the work of to localize regions of structural differences. The method relies on generating surface meshes for segmented amygdalae, calculating distances from surface points to the medial manifold, and comparing the distance measures at corresponding surface points between groups. Resulting statistical maps revealed significant structural differences in multiple regions of both amygdalae. Shape morphometry can potentially relate local structure variation to underlying neuroanatomy for a better understanding of LLD neuropathology

Towards a clinically useful sonic flashlight

We have previously shown a new method of merging a direct view of the patient with an ultrasound image displayed in situ within the patient, using a half-silvered mirror. We call this method Real Time Tomographic Reflection (RTTR). This paper reviews our progress to date in developing an embodiment of RTTR that we call the sonic flashlight/spl trade/. The clinical utility of the sonic flashlight for guiding invasive procedures will depend on a number of factors, and we have explored these factors through a series of prototypes. Responding to feedback from our clinical collaborators, we have upgraded various elements of our original apparatus and implemented a new generation of the system that is smaller, lighter, and more easily manipulated. We have improved performance as we gain a better understanding of the optical parameters of the system. Our results demonstrate in situ visualization of vasculature of the neck in a human volunteer and the anatomy of the eye in a cadaver.

Novel method to automatically identify medial node correspondences between two images

Many modern forms of segmentation and registration require manual input, making them tedious and time-consuming processes. There have been some successes with automating these methods, but these tend to be unreliable due to inherent variations in anatomical shapes and image quality. It is toward this goal that we have developed methods of identifying correspondences in two images between medial nodes; image features related to anatomical structures. Medial based image features are used because they have proven robust against image noise and shape variation, and provide rotationally invariant properties of dimensionality and scale, while preserving orientation information independently. We have introduced several novel metrics for comparing the medial and geometric relationships between medial nodes and different cliques of medial nodes (a clique is a set of multiple medial nodes). These metrics overcome problems introduced by symmetry between cliques and provide increasing discriminability with the size of the clique. In this paper, we demonstrate medial-based correspondences and validate their specificity with standard Receiver Operator Characteristic (ROC) analysis. It is believed that our method of locating corresponding medial features may be useful for automatically locating anatomical structures or generating landmarks for registration.