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

The brain's 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.

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.

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.

OBJECTIVE: 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. METHODS: Magnetic resonance imaging data were acquired from 11 healthy, elderly individuals and 14 depressed, elderly individuals. Amygdalar size was quantified by computing total volume and amygdalar shape was quantified with a shape analysis method that we have developed. RESULTS: No significant volumetric differences were found for either amygdala. Nevertheless, localized regions of significant shape variation were detected for the left and right amygdalae. The most significant difference was contraction (LLD subjects as compared to control subjects) in a region typically associated with the basolateral nucleus, which plays a key role in emotion recognition in neurobiologic models of depression. CONCLUSIONS: In this LLD study, we have shown that, despite insignificant amygdalar volumetric findings, variations of amygdalar shape can be detected and localized. With further investigation, morphometric analysis of various brain structures may help elucidate the neurobiology associated with LLD and other mood disorders.

C-mode real-time tomographic reflection for a matrix array ultrasound sonic flashlight.

RATIONALE AND OBJECTIVES: Real-time tomographic reflection (RTTR) permits in situ visualization of tomographic images so that natural hand-eye coordination can be used directly during invasive procedures. The method uses a half-silvered mirror to merge the visual outer surface of the patient with a simultaneous scan of the patient's interior without requiring a head-mounted display or tracking. A viewpoint-independent virtual image is reflected precisely into its actual location. When applied to ultrasound, we call the resulting RTTR device the sonic flashlight. We previously implemented the sonic flashlight using conventional two-dimensional ultrasound scanners that produce B-mode slices. Real-time three-dimensional (RT3D) ultrasound scanners recently have been developed that permit RTTR to be applied to slices with other orientations, including C-mode (parallel to the face of the transducer). Such slice orientation may offer advantages for image-guided intervention. MATERIALS AND METHODS: Using a prototype scanner developed at Duke University (Durham, NC) with a matrix array that electronically steers an ultrasound beam at high speed in 3D, we implemented a sonic flashlight capable of displaying C-mode images in situ in real time. RESULTS: We present the first images from the C-mode sonic flashlight, showing bones in the hand and the cardiac ventricles. CONCLUSION: The extension of RTTR to matrix array RT3D ultrasound offers the ability to visualize in situ slices other than the conventional B-mode slice, including C-mode slices parallel to the face of the transducer. This orientation may provide a broader target, facilitating certain interventional procedures. Future work is discussed, including display of slices with arbitrary orientation and use of a holographic optical element instead of a mirror.

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. METHOD: 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. RESULT: 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.