"ischemic penumbra." Its ischemic condition has the potential for reversal and is the targe[~of all therapies aimed at reversing the progress of an ischemic event. The hypothesis that will be tested is that in vivo Magnetic Resonance (MR) maps of cerebral oxygen consumption can unequivocally distinguish penumbral regions from infarcted regions during episodes of focal ischemia. In order to test this hypothesis, it is proposed to develop a novel MR method that can provide high resolution noninvasive maps of cerebral oxygen consumption and blood flow. This method, which is based on indirect detection of oxygen-17 using proton MR, has already been demonstrated as a sensitive technique for detecting small differences in oxygen concentration in tissue phantoms. The applicants proposed to further evaluate this tech- nique in normal rat models and validate it against existing meth- ods of measuring cerebral oxygen consumption. Following the validation in healthy rats this method will be evaluated by study- ing reversible stroke models of varying duration in a second set of rats. These data will be correlated with histological evaluation of the region of reversible ischemia. These results will be com- bined with other MR methods, which provide complementary information, to provide improved diagnostic sensitivity and specificity in addition to allowing for the evaluation of therapeu- tic efficacy for the reversal of cerebral ischemia. Once developed in animal models, these methods can be rapidly and easily adopted for human studies due to the noninvasive nature of the technique and the ready availability of clinical MRI scanners.

Thesaurus Terms: brain metabolism, cerebral ischemia / hypoxia, diagnosis design/evaluation, magnetic resonance imaging, oxygen consumption blood flow measurement, cere- brovascular visualization, disease model, noninvasive diagnosis, stroke bioimaging/biomedical imaging, laboratory rat

Institution: University Of Pennsylvania Philadelphia, PA 19104-6380

Fiscal Year: 1999 .Department: Radiology Project Start: 05-Aug-96 Project End: 30-Jun-01 ICD: National Inst Of Neurological

Disordersand Stroke IRG: ZRG7

)ROJECT TITLE

QUANTATIVE HIGH FIELD CLINICAL 1H MR NEUROSPECTROSCOPY

Grant Number: 5R29NS34899-04 PI Name: Shungu, Dikoma C.

Abstract: DESCRII:q'ION (Adapted from Applicant's Abstract): "Whole-body" magnetic resonance (MR) scanners operating with main fields that are 2-3 times stronger than those of most existing human instruments (1.5-2.0T) have recently become available for clinical investigations; this laboratory has completed installation

of a 4.23 T clinical spectrometer/imager, current the highest field whole-body MR in the U.S. Due to the novelty of these high- field human instruments, a great deal of technological develop- ment is still required to fully harness and realize their potential. Therefore, the applicants proposed: (a) To develop and optimize volume selection pulse sequences suitable for high-field 1H spec- troscopic imaging (SI) studies of the human brain, with emphasis on overcoming spatial localization errors due to increased spec- tral dispersion, and (b) to develop efficient methods for automati- cally processing, analyzing and converting recorded SI spectral amplitudes to absolute metabolite concentrations on a voxel-by- voxel basis. All pulse sequences will employ spatially tailored outer volume suppression (OVS) pulses to achieve 2-D confor- real localization of the brain that will eliminate the thin rim of pericranial lipids and tissues, without affecting spins in the region of interest. Full volume localization and spin excitation will then be achieved with a single echo sequence utilizing an orthogonal slice-selective 90 degree and spectrally-selective 180 degree refo- cusing pulse. Multi-echo and multi-slice version of this sequence will be developed to maximize the efficiency of SI data acquisi- tion. Metabolite relaxation times will be measured and entered into databases, which will subsequently be utilized to efficiently convert SI spectral amplitudes to absolute concentrations, voxel- by-voxel, using cerebral tissue water as an internal concentration standard. Computer software will be developed to automate this conversion of peak amplitudes to molar concentrations. Through the development and optimization of pulse sequences, the appli- cants proposed to preserve the inherent signal-to-noise advantage of a high field magnet, which can then be exchanges (a) for smaller voxel sizes to allow the study of smaller lesions, rumors or infarcts, or (b) for shorter scan times to minimize cost and pa- tient discomfort. Absolute quantitation of SI data will yield me- tabolite maps or images in which pixel intensities will represent actual metabolite concentrations. This will standardize results, facilitating comparisons with biochemical data or with results ob- tained at different sites using different localization sequences or instruments. Finally, automation of metabolite quantitation will make quantitative SI practical for routine clinical use.

Thesaurus Terms: biomedical equipment development, brain visualization, clinical biomedical equipment, magnetic reso- nance imaging body water, brain metabolism, computer assisted diagnosis, diagnosis design/evaluation, image processing bio- imaging/biomedical imaging, clinical research, human subject

Institution: Columbia University Health Sciences

New York, NY 10032 Fiscal Year: 1999 Department: Radiology Project Start: 17-Jul-96 Project End: 30-Apr-01 ICD: National Inst Of Neurological

Disorders And Stroke IRG: ZRG7

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