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Abstract

Grant Number: 1R41HL084795-01
Project Title: Persistent Contrast Agent for Percent Infarct Map in MRI
PI Information:NameEmailTitle
SURANYI, PAL psuranyi@uab.edu

Abstract: DESCRIPTION (provided by applicant): The long term goal of this project is to establish the usefulness of a new infarct-avid, persistent contrast agent (PCA), Gd(ABE-DTTA), which due to its long lifetime in tissue allows construction of accurate relaxation-rate-enhancement(AR1)-based voxel-by-voxel viability maps of the acutely infarcted heart. Assisted by the slow tissue kinetics and infarct-specificity of Gd(ABE-DTTA), elaborate, voxel-by-voxel Percent-lnfarct-Maps (PIM) can be constructed using a method developed recently in our laboratory. PIM determines the per voxel percentage of infarcted tissue, essentially generating an in-vivo, clinically applicable equivalent for the post-mortem method of Triphenyl Tetrazolium Chloride (TTC) staining. Based on our preliminary data, the Gd(ABE-DTTA)-based PIMs are highly accurate, judged by their tight agreement with the results of the histochemical gold-standard, TTC-staining. This agent allows the obtaining of PIMs that are highly reproducible, timing-independent, and standardizable across different MRI equipments and imaging sequences in use. The Phase I project, the subject of this application, is designed to test the feasibility of the combination of this PCA and the PIM method to obtain statistically significant infarct distribution data validated by TTC data. The Specific Aim in the present Phase I application is to validate the PCA-enhanced PIM by MRI experiments comparing the in-vivo-obtained PIM with the corresponding TTC staining gold standard map. This will be done on a group of 6 dogs prepared with a reperfused infarct and administered PCA, post-infarct. To allow better coregistration between MRI and histochemistry, at the end of the in vivo MRI session, following in vivo TTC staining, a 3D high resolution ex vivo PIM will be also generated. Hearts will then be frozen, sliced with the same slice thickness as used for generating the ex vivo PIM, and color-photographed. A Phase II proposal that will encompass further objectives will be submitted once the results from Phase I proved, with statistical significance, the reliability of Gd(ABE-DTTA) to determine infarct size accurately and reproducibly. The long term objectives that will be then pursued: 1) Using the PCA-PIM combination in the acute phase of infarction, its ability for early prediction of myocardial recovery following reperfusion (long-term functional recovery and left ventricular remodeling) will be investigated. 2) PCA-PIM will be compared head-to-head with the Delayed Enhancement (DE) method, the present MRI gold standard for MRI determination of myocardial viability. Following Phase II, which will pursue the long term objective described above, steps will be taken towards Phase III commercialization.

Thesaurus Terms:
contrast media, diagnosis design /evaluation, heart disorder diagnosis, myocardial infarct sizing
evaluation /testing, heart function, heart imaging /visualization /scanning, myocardial infarction, noninvasive diagnosis, staining, three dimensional imaging /topography
bioimaging /biomedical imaging, dog, histochemistry /cytochemistry, magnetic resonance imaging

Institution: ELGAVISH PARAMAGNETICS, INC.
1737 VALPAR DR
BIRMINGHAM, AL 352262343
Fiscal Year: 2006
Department:
Project Start: 15-MAY-2006
Project End: 31-OCT-2007
ICD: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
IRG: ZRG1


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