phantom model bioimaging/biomedical imaging, clinical re- search, human subject

Institution:

Fiscal Year: Department: Project Start: Project End: ICD:

IRG:

University Of Virginia Charlottesville

Charlottesville, VA 22903 1999 Radiology 01-May-96 29-Feb-00 National Inst Of Neurological

Disorders And Stroke ZRG7

)ROJECT TITLE

SERIAL MAGNETIC RESONANCE IN MULTIPLE SCLEROSIS

Grant Number: 3R01NS31499-07S1 PI Name: Narayana, Ponnada A.

Abstract: Magnetic resonance imaging (MRI) is the most sensitive radiologic modality in visualizing multiple sclerosis (MS) plaques. However, the monotonous appearance of many lesions limits the usefulness of a single MR/in distinguishing active lesions from inactive ones. The proposed longitudinal studies are designed to utilize state-of-the-art volumetric image analysis and image-guided in vivo proton magnetic resonance spectroscopy (MRS) in combination with the paramagnetic contrast agent gadolinium diethylentriaminepentaacetic acid (GdDTPA) for distinguishing different stages of MR/-defined and clinically correlated disease activity. Volumetric image analysis performed on dual echo thin slices (3rnm) with no interslice gap will allow quantitation of total lesion burden as well as volumes of individual plaques independent of small unavoidable errors in repositioning the patients on serial scans. The number and degree of enhancement of plaques will also be quantified using the image analysis. Multivoxel proton MRS will be performed at short-echo times to visualize lipids and other membrane breakdown products from the plaque-contain- ing as well as adjacent-tissue with a volume resolution on the order of 2 cc. MRS data will be quantitatively analyzed to critically assess the role of lipids, N-acetyl aspartate (NAA) and other MR-visible neurochemicals in the characterization of MS plaques. Linked GdDTPA MRI and MRS should allow us to determine the MRS-defined changes in the neurochemicals in relation to acute changes in regional vascular permeability. Computed Relaxation images should allow the detection of plaques even when they are too small to be resolved on MRI or prior to GdDTPA enhancement. Many of the patients will be scanned at intervals of four weeks up to a period of six months. Magnetic resonance results will be correlated with clinical sta- tus. These multi-pronged MA studies should allow us to char-

acterize and follow the evolution of MS plaques and improve our understanding of the pathophysiology of MS. A further significance of these studies is that they may enable us to fol- low objectively and quantitatively the efficacy of drugs in the treatment of MS.

Thesaurus Terms: brain disorder diagnosis, magnetic reso- nance imaging, multiple sclerosis, nuclear magnetic reso- nance spectroscopy blood brain barrier, brain metabolism, brain visualization, lipid metabolism, longitudinal human study, myelin, pathologic process bioimaging/biomedical imaging, clinical research, human subject

Institution: University Of Texas Hlth Sci Ctr Houston

Box 20036 Houston, TX 77225

Fiscal Year: 1999 Department: Radiology Project Start: 01-Apr-93 Project End: 31-Mar-02 ICD: National Inst Of Neurological

Disorders And Stroke IRG: NEUA

)ROJECT TITLE

MAGNETIC RESONANCE OF SPINAL CORD INJURY

Grant Number: 5R01NS30821- PI Name: Narayana, Ponnada A.

Abstract: Every year in the United States 10,000 to 20,000 young adults suffer permanent disability as a result of spinal cord injury. However, a proper evaluation and characterization of spinal cord injury is hindered by lack of a non-invasive ra- diologic modality. In these studies we propose to critically as- sess the role of magnetic resonance (MR), which includes both magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS), in the non-invasive diagnosis and prog- nosis of spinal cord injury. The proposed studies will be per- formed on three types of injuries with different severity in a ro- dent model with histopathological profiles similar to those seen in humans. The MRI-inferred extent and location of hemor- rhage, edema and residual cord tissue (based on fast spin echo volume imaging and three-dimensional image analysis) will be validated with quantitative histology performed on the same animals. The MRS-determined changes in the concentration of N-acetyl aspartate (NAA) and lactate as a result of injury to the spinal cord will be compared with those determined using stan- dard biochemical techniques. Both these studies will be per- formed at seven time points following the cord injury. In addi- tion, MR results will be compared and correlated with func- tional (behavioral and electrophysiological) studies performed

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longitudinally. These studies could provide non-invasively additional and important infofi'nation for predicting neurologic outcome following spinal cord injury and help customizing treatment on an individual basis in humans.

Thesaurus Terms: magnetic resonance imaging, nervous system disorder diagnosis, spinal cord injury, spinal cord vi- sualization biological model biochemistry, bioimaging/bio- medical imaging, histology, laboratory rat

Institution: University Of Texas Health Science Center Houston

Box 20036 Houston, TX 77225 1999 Radiology 01-Jul-92 30-Jun-01 National Inst Of Neurological

Disorders And Stroke IRG: NEUA

Fiscal Year: Department: Project Start: Project End: ICD:

PROJECT TITL[

CNS INJURYmMECHANISM(S) OF DWI CONTRAST

Grant Number: 5R01NS35912-03 PI Name: Neil, Jeffrey J.

Abstract: DESCRIPTION (Adapted from Applicant's Ab- stract): Diffusion-weighted imaging (DWI) is a magnetic resonance imaging method that shows great promise for e~ly detection of a number of forms of central nervous system (CNS) injury, including stroke, trauma, and status epilepticus. At the present time, the mechanism(s) underlying the rapid change in contrast in diffusion-weighted images after CNS injury is poorly understood. As a first step to understanding these mechanisms, two classes of experiments are proposed to evaluate changes in water apparent diffusion coefficient (ADC) in the intra-and extracellular spaces in association with rat models of stroke or status epilepticus. The first utilizes NMR-detectable, compartment-specific probes to indirectly de- tect changes in motion in either the intra- or extracellular space in association with CNS injury. Probes of the intracellular space will be 133Cs+, in situ generated 2-fluorodeoxyglucose- 6-phosphate (with 19F detection), 23Na+, and endogenous 1H metabolites. Probes of the extracellular space will be 3-aminopropylphosphonate (with 31P detection), 2-fluoro- deoxyglucose-6-phosphate (with 19F detection), and 23Na+. The second class of experiments will involve infusion of re- laxation contrast agent (gadoteridol) into the lateral cerebral ventricle of rats, from which it spreads throughout the extra- cellular space and greatly reduces the T1 relaxation time con- stant of extracellular water. Once this is accomplished, it is

possible to design NMR pulse sequences which permit ac- quisition of ADC data which is heavily weighted to signal from either intra- or extracellular compartment. For these studies, compartment-specific changes in water ADC will be correlated with histologic assessment of infarct severity. In a third class of experiments, the possibility that some of the ADC decrease associated with stroke is due to underestimates of ADC caused by paramagnetic effects of deoxyhemoglobin will be examined. Taken together, these studies are designed to begin unraveling the compartment-specific ADC changes responsible for DWI contrast in an effort to permit more pre- cise use of this promising imaging modality.

Thesaurus Terms: brain disorder diagnosis, brain visualiza- tion, central nervous system, diagnosis design/evaluation, magnetic resonance imaging, method development, nerve injury brain injury, cell water, cerebral ischemia/hypoxia, cerebral ventricle, disease model, early diagnosis, extracel- lular matrix, generalized seizure, intracellular, stroke bio- imaging/biomedical imaging, injection/infusion, laboratory rat, radiofluorescent probe

Institution:

Fiscal Year: Department: Project Start: Project End: ICD:

IRG:

Washington University Lindell And Skinker Blvd St. Louis, MO 63130 1999 Radiology 15-May-97 28-Feb-01 National Inst Of Neurological

Disorders And Stroke RNM

~ROJECT TITLE

POSITRON EMISSION TOMOGRAPHY INVESTIGATIONS OF DYSTONIA

Grant Number: • 5R01NS31001-05 PI Name: Perlmutter, Joel S.

Abstract: DESCRIPTION: Dystonia is a syndrome of inter- mittent or sustained involuntary muscle contractions that frequently causes twisting and repetitive movements pro- ducing abnormal postures. These involuntary movements can affect many parts of the body (generalized) or affect more limited areas such as the focal dystonias. The patho- physiology of these syndromes remains unclear but a vari- ety of clues suggest abnormalities of central dopaminergic pathways. We now have evidence that there is an abnormality of [18F]spiperone ([18F]SP) binding in the putamen, one of the key basal ganglia nuclei involved in motor control.

[18F]SP, however, binds to both D2-1ike dopaminergic re- ceptors and to $2 receptors in primate striatum. The objec- tive of this research proposal is to determine whether pa- tients with idiopathic focal dystonias have alterations in

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