Manbir Singh - US grants

A rapid and quantitative metod of imaging the three-dimensional in vivo distribution of radionuclides provides unique and valuable biochemical functional information. The proposed research is a collaborative effort among physicists, chemists, engineers, computer scientists and physicians to achieve a fundamental improvement in radionuclide imaging instrumentation. Focusing on radiolabelled monoclonal antibody imaging as a promising modality, the ultimate objective of the proposed research is to increase the sensitivity and quantitation accuracy of tumor imaging. Unlike conventional scintillation cameras which use mechanical collimation for imaging single photon emitting radionuclides and consequently suffer from an inherently low sensitivity since a large portion of the emitted radiation is absorbed by the lead septa, our proposed instrument provides more than an order of magnitude increase in sensitivity by using an electronic method of collimation. A sequential interaction of the emitted gamma rays with two position and energy sensitive detectors is used to localize activity upon conical surfaces within the body wherefrom the three-dimensional distribution can be reconstructed. The system design is based on an array of germanium detectors to serve as the first detector and a scintillation camera without its collimator as the second detector. Having successfully fabricated a unique 4x4 germanium detector for a prototype subsystem, we now propose to fabricate a 16x16 germanium detector and incorporate it into an instrument for preclinical evaluation studies of tumor imaging with radionuclides covering a wide range of energies. (Unlike mechanical collimation, electronic collimation is well suited to a wide energy range, from 100 keV to several MeV). Also, we propose to use modular scintillation cameras, instead of the conventional large-area scintillation camera, as the second detector. Modular cameras are essential to our design because the "singles" count rates are very high. Eventually, a clinical system comprising two orthogonal 32x32 germanium detectors and 16 scintillation camera modules will be implemented. A microcomputer based data acquisition circuit will be developed to record coincident counts between the germanium and the scintillation cameras. Computer simulation studies and experiments with various test objects and radionuclides will continue for developing appropriate algorithms to reconstruct three-dimensional emission images from the coincident counts.

The central mission of the neuroimaging core is to develop and implement state-of-the-art functional and anatomical brain imaging techniques for use by ADRC investigators at participating sites. Particular emphasis will be placed on developing strategies and computer programs to improve the data acquisition, processing and image display aspects of functional Magnetic Resonance Imaging (fMRI) to study brain function related to sensory and cognitive stimulation. Common fMRI protocols will be implemented on MRI systems at USC Hospital, LAC/USC Imaging Center and Ranchos Amigos Medical Center and resources will be developed to support research and pilot projects leading to R01 submissions. As an example, the core enabled pilot studies leading to submission of a working memory related fMRI RO1 project within this ADRC and the core will continue to provide resources including access to an MRI system, fMRI paradigm development, data acquisition, processing and analysis in support of this project. A second area of emphasis is the development of technology to combine fMRI, electroencephalography (EEG) and evoke potential (EP) measurements to produce brain images depicting regions involved in the generation of either spontaneous brain activity, such as the alpha rhythm, or activity evoked in response to specific stimuli. It is well known that significant changes in the EEG, particularly the alpha rhythm, occur at an early stage in Alzheimer's Disease (AD). The capability of combining fMRI with EEG is expected to provide unique insights into the origin and characteristics of EEG slowing and incoherency observed in AD, leading to new research projects to study electrophysiological changes in AD. Similarly, the capability of combining EP measurements with fMRI data is expected to yield unique tools and resources for investigating the spatiotemporal relationships among different regions of the brain activated during specific tasks. In addition to fMRI, the core will facilitate the development of image- guided proton magnetic resonance spectroscopy, positron emission tomography (PET) and single photon emission computed tomography (SPECT) for used by ADRC investigators. Also with the goal of developing techniques that are transportable to a clinical setting and can be used at different sites, image processing routines will be developed to segment the brain and obtain volumetric measurements of regions of interests within anatomical or functional images.

White matter integrity is critical to cognitive functions. Using diffusion-tensor imaging (DTI), it is now possible to directly assess the pattern and severity of white matter disruption in the early stages of dementia. This proposal considers the role of white matter tracts in AD and in subcortical vascular dementia (SVD). The hypotheses will examine whether: a) SVD initially disrupts frontal-subcortical loops, whereas in AD long cortical-cortical connections incur damage later and in addition to damage to the perforant pathway, b) fronto-occipital connectivity and thalamo-frontal connectivity correlate with MRI determined volumes of hippocampii, frontal cortical gray matter, and white matter hyperintensities (WMH), and c) fronto-occipital connectivity and thalamo-frontal connectivity correlate with severity of cognitive impairment (as assessed by global cognitive ability, memory, and executive function) using hippocampal volume and apoE as covariates. A cohort of 60 subjects divided into three groups, normal controls (NC), AD and SVD will be studied. The AD group will include persons with mild amnestic-type cognitive impairment (MCI) as well as probable AD. The SVD group will include persons with vascular cognitive impairment (VCI), as well as dementia meeting criteria for probable or possible VD (vascular dementia) or mixed AD/VD. Recruitment and follow-up of subjects and quantitative MRI will use resources from the ADRC Clinical and Imaging Cores, as well as the ischemic vascular dementia (IVD) Program Project Stet. Subjects will undergo MRI and neuropsychological testing at baseline and again after an interval of two years. Structural images will be segmented for volumetric analyses of selected regions. Diffusion weighted images will be converted into fractional anisotropy maps for DTI-Tractography. Connectivity will be quantified through metrics representing a normalized count of tracts between selected regions and the distribution of fractional anisotropy along these tracts.The connectivity metrics, volumetric analyses and neuropsychological scores will be used to test the hypotheses.

The Neuroimaging Core develops and implements state-of-the-art functional and structural brain imaging techniques for use by ADRC and other investigators pursuing AD-related brain imaging projects at USC and neighboring Institutes, to educate these investigators on the potential of structural/functional brain imaging, and to facilitate use of imaging resources at USC for AD and related projects. The specific aims are to: (1) Provide technical support to investigators to conduct functonal MRI (fMRI) or diffusion tensor imaging (DTI) pilots and other imaging studies for testing their hypotheses in AD and related areas, including technical support to Project 1 "Diffusion tensor tractography in AD and SVD" (2) Develop techniques to improve methodology for structural/functional neuroimaging including functional fMRI, functional connectivity, DTI-based white-matter tractography, and MRI volumetric measurements. Implement fMRI protocols on MRI systems at USC University Hospital, USC Imaging Science Center, and Rancho Los Amigos. Conduct pilot studies to validate technological developments. (3) Continue to refine methodology to combine fMRI with electroencephalography (EEG and magneto-encephalography (MEG) to enable fundamental improvements in the spatiotemporal resolution of functional brain imaging, and (4) Archive MRIs acquired for Projects 1, 2, and the Clinical Core. The core has developed key technology in IMRI, functional connectivity, EEG source localization, DTI-tractography and quantification of tractography based connectivity. During the past five years, the core supported approximately 20 projects including several RO 1s and pilots through design of preliminary fMRI studies and actually performing pilot experiments for these projects. In the proposed period, the core will support Project 1 (Diffusion tensor tractography AD and SVD) by providing data and image processing resources, and by adapting core-developed DTI and volumetric analysis methodology. The Core will also archive MRI data for the Clinical Core, Satellite, Project 1, and Project 2.

Abstract

Program: NSF 04-588 CISE Computing Research Infrastructure
Title: CRI: Reconfigurable computing infrastructure for high end and embedded computing applications
Proposal: CNS 0454407
PI: Prasanna, Viktor K.
Institution: University of Southern California

The investigators will acquire a reconfigurable computer comprised of general purpose processors, field programmable gate arrays (FPGAs), a common memory, and an interconnect fabric joined under a programming model that works with all the parts. The acquisition of this machine will enable research at a realistic scale on actual reconfigurable machines for performance testing, validation, and applications demonstrations. This infrastructure will be robust enough to implement application "kernels" such as (e,g, an LU implementation or n-body simulation) that give realistic scale experimental results. Applications that will be explored include matrix operations, computational genomics, molecular dynamics, density functional theory, and finite element methods. The team will also be able to work on energy efficiency for embedded FPGAs. Broader impacts of this project include the potential impact on reconfigurable systems, use of FPGAs for applications, and discoveries in the applications areas. The investigators participate in USC's Minority Opportunities in Research (MORE) program.

Adult; Alzheimer's Disease; Archives; Arteriogram; Arts; base; Blood flow; Brain; Brain imaging; Cerebrovascular Disorders; Chinese American; cognitive change; Communities; data acquisition; Data Analyses; Databases; design; Diffusion; Diffusion Magnetic Resonance Imaging; Early Diagnosis; Elderly; Functional Imaging; Functional Magnetic Resonance Imaging; Funding; Grant; Image; Image Analysis; image processing; Impaired cognition; Institutes; instrumentation; Magnetic Resonance Imaging; mild cognitive impairment; Mission; multimodality; National Center for Research Resources; neuroimaging; Online Systems; Perfusion; Persons; Pilot Projects; Play; Process; Protocols documentation; Radiology Specialty; Research; Research Personnel; Resources; Retinal; Retrieval; Role; Screening procedure; Site; spatiotemporal; Spin Labels; Technology; tool; United States National Institutes of Health; white matter