Advances in molecular imaging are yielding a new generation of single-photon-emission-computed- tomography (SPECT) brain-imaging agents that will lead the way in understanding the human brain by enabling the development of biomarkers with unprecedented specificity for mapping neuroreceptors and proteinopathies associated with disease and dementia. SPECT is an ideal tracer-imaging tool for investigating the underlying mechanisms in brain disorders, their differential diagnoses, and monitoring their treatment because of its lower cost and radiation dose relative to PET, longer half-lives of the radionuclides imaged, and ability to simultaneously image multiple imaging agents labeled with different radionuclides. However, most clinical brain SPECT is still being performed by 2-headed systems with collimators designed for planar scintigraphy. To meet the potential for better patient care offered by these new imaging agents, and vastly improve the utility of existing agents, a revolution in SPECT brain-imaging system design is required. In Phase 1 of this Biomedical Research Partnership (BRP) application we propose to meet this requirement by creating a multi-detector-module multi-pinhole (MPH) SPECT brain-imaging system ideally suited for quantitative dynamic and high-spatial-resolution static SPECT imaging. Based on its heritage and intent for clinical imaging, we have named this proposed system AdaptiSPECT-C. Dynamic imaging will be enabled by obtaining sufficient angular sampling without the need for rotation. The system will automatically adapt its imaging characteristics (aperture size and number of pinholes open for imaging) in response to the imaging tasks and individual patients. It will thereby optimize lesion detection and quantification, as well as provide optimal data for pharmacokinetic analysis within structures throughout the brain. Automatic alignment to existent CT diagnostic studies of the patient for use in providing anatomical correlation, formation of attenuation maps, and templates for PVE correction will be enabled through usage of depth- sensing cameras, which will also be used for correction for head motion. Comparison of AdaptiSPECT-C to clinical systems will be conducted through inviCRO, one of the nation's top contract research organizations (CROs) serving the pharmaceutical industry. These studies will provide the documentation of system performance necessary to enable ?Big-Pharma? companies to use the system to gather the clinical data necessary for FDA approval of new pharmaceuticals.
Our Specific Aims are: 1. Construct an adaptable brain-SPECT system and test performance versus design specifications; 2. Develop reconstruction software for optimal image quality and activity quantification; 3.Integrate depth-sensing camera imaging to correct patient motion and align existent CT slices; and 4. Incorporate analysis software, and validate system through prototype human imaging.

Public Health Relevance

In Phase 1 (years 1-5) of this Biomedical Research Partnership (BRP) application we are proposing to develop an innovative multi-detector-module multi-pinhole single-photon-emission computed tomography (SPECT) brain-imaging system to be called AdaptiSPECT-C. We envision that this system will lead the way in advancing the understanding of the human brain by enabling the development of biomarkers that supersede current options for mapping neuroreceptors and proteinopathies associated with disease and dementia (e.g., inflammation imaging), as well as doing unprecedented clinical imaging with already FDA approved radiopharmaceuticals. AdaptiSPECT-C will be designed to have better combined sensitivity and resolution than any existing SPECT brain-imaging system, will be able to track the kinetics of biomarkers in the whole brain in three-dimensions, and will adapt during imaging to deliver the best compromise between sensitivity and spatial resolution for a given imaging task and individual patient. AdaptiSPECT-C thus simultaneously enhances the support of continued new drug discovery trials while introducing a next-generation improved clinical camera for patient diagnosis and therapy evaluation. Automatic alignment to existent CT diagnostic studies of the patient for use in providing anatomical correlation, formation of attenuation maps, and templates for PVE correction as well as correction for head motion will be enabled through usage of depth-sensing cameras. AdaptiSPECT-C is the outgrowth of years of tremendous accomplishments in SPECT design, fabrication, reconstruction, and task-based image quality assessment, mostly at the pre-clinical level, at the Center for Gamma Ray Imaging (CGRI) at the University of Arizona, and correction for image degradations which occur in clinical SPECT imaging at the University of Massachusetts (UMass). Joining this unique partnership will be Dr Zubal of Z-Concepts, LLC who will lead the development of kinetic modeling and quantitative image analysis with the assistance of inviCRO. In the last quarter of the project period exploration of new clinical applications afforded by AdaptiSPECT-C in comparison to existing SPECT systems will be conducted at the two institutions under contract studies through inviCRO.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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Sastre, Antonio
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University of Massachusetts Medical School Worcester
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