ABSTRACTS OF NIH GRANTS
Academic Radiology, Vol 10, No 9, September 2003
Abstract: The central hypothesis of this proposal is that H1 and 15C MRS can predict and detect response to radiation therapy. The long-term goal is to develop in magnetic resonance spectroscopy (MRS) methods for the clinical management of radiation therapy and for experimental cancer research. Availability of such methods would facilitate optimization of radiation treatment schedules to the needs of the individual patient. Sophisticated 1H and 13C MRS methods developed during the previous funding period will be used to test this hypothesis on two well-defined tumor models RIF-l and EMT6 - which have significantly different hypoxic fractions. The ability of these methods to predict radiosensitivity and to detect tumor response to radiation therapy will be evaluated. The mechanisms underlying spectral changes during untreated growth and following radiation therapy will be investigated in perfused cells. Diffusion spectroscopy will be employed to measure changes in intracellular volumes, cellular concentrations of metabolites and transmembrane distribution of key metabolites such as lactate, in a perfused cell system, following irradiation. In viva magnetic resonance measurements will be related to tumor histology radiosensitivity, tumor perfusion and oxygenation. Studies during the previous funding period have already demonstrated that 1H MRS methods with imaging resolution as low as 2 ul at 4.7 T can detect tumor response to radiation doses as low as 2 Gy, the dose employed in clinical fractionated therapy schedules Response to radiation results in a significant decrease in lactate concentration. We have also found that the (rate of glycolysis of RIF-l (a radiation responsive tumor) is about twice that of EMT6 (a radiation-resistant tumor) for volume matched tumors. The possibility that glycolytic rate is predictive for solid tumor radiosensitivity for different tumor cell lines and steady state lactate concentration is predictive within a cell line will be examined. Thesaurus Terms: cellular oncology, neoplasm/cancer radiation therapy, nonhuman therapy evaluation, nuclear magnetic resonance spectroscopy, patient-monitoring device, prognosis, radiobiology bioenergetics, cell morphology, choline, disease/disorder model, glycolysis, lactate, radiation sensitivity, radiation therapy dosage, respiratory oxygenation, tumor progression, autoradiography, histology, laboratory mouse, perfusion
Institution:
Fiscal Year: Department: Project Start: Project End: ICD: IRG:
University Of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 2002 Radiology 09-Aug-1991 30-Jun-2003 National Cancer Institute RNM
SMALL ANIMAL MULTI-MODALITY IMAGING CENTER (SAMMIC) Grant Number: PI Name:
5R24CA083105-04 Glickson, Jerry D.
Abstract: Creation of a Small Animal Imaging Resource Program (SAIRP) at the University of Pennsylvania supporting research by investigators at this institution and also at the Fox Chase Cancer Center and Thomas Jefferson University is proposed. This SAIRP will provide three imaging modalities – 1) Magnetic Resonance Imaging and Spectroscopy (MRI/S). 2) Optical imaging covering the ultraviolet through near infrared (UV-NIR), and positron emission tomography (PET). The MRI/S facilities are now in place; the UV-NIR and PET facilities are now operational on the scale of human patients and will be adapted to studies of small animals (mice and rats) by the end of the first year. The SAIRP will support the research of 13 NIH funded projects dealing with 1) modification of tumor response to radiation and hyperthermia, 2) methods of monitoring tumor hypoxia, 3) gene therapy of brain tumors, 4) immunotherapy of tumors, 5) detection of breast cancer and 6) detection of tumor response to chemotherapy and radiation therapy. Ancillary facilities for redox scanning, NIR time resolved spectroscopy, electronics, animal management, synthesis of contrast agent and physiological probes, histology, computer resources, biostatistics and MR of perfused cells will be provided. Research and development and D) projects will be directed towards the development of novel NMR capabilities that will enhance the research capabilities of the base projects. These R and D projects are: A. MRI of Small Animal Tumors, including: A1. Small Animal Microimaging. A2. Functional Imaging of Tumors, B. Multinuclear Spectroscopy, including: B1. Chemical Shift Selective MR Imaging of 31P in Animal Tumors, B2. 1H{17O} MRI of Tumors, B3. In Vivo Imaging of Intra- and Extracellular Na⫹ and pH in Tumors, and C. NMR Techniques for Monitoring Gene Therapy of Brain Tumors. Thesaurus Terms: bioimaging/biomedical imaging, biomedical resource, magnetic resonance imaging, positron emission tomography
Institution:
Fiscal Year: Department: Project Start: Project End: ICD: IRG:
University Of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 2002 Radiology 01-Sep-1999 31-Jul-2004 National Cancer Institute ZCA1
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