MRS and MRI of breast cancer at very high magnetic field

ABSTRACTS OF NIH GRANTS

Thesaurus Terms: drug design/synthesis/production, dye, neoplasm/cancer photoradiation therapy, photosensitizing agent analog, cytochrome, dosage, drug screening/evaluation, enzyme mechanism, hemoglobin, neoplasm/cancer pharmacology, nonvisual photosensitivity, oxygen consumption, oxygen tension, photochemistry, porphyrin, pulmonary diffusion, respiratory oxygenation, selenium, sulfur athymic mouse, fluorescence microscopy, laboratory rat, microelectrode, spectrometry

Institution:

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

University Of Rochester ORPA - RC Box 270140 Rochester, NY 14627 2002 Radiology 01-Jul-1995 28-Feb-2003 National Cancer Institute RAD

MECHANISMS OF DIFFUSION MRI WITH CHEMOTHERAPY Grant Number: PI Name:

5R01CA088285-02 Galons, Jean-Philippe

Abstract: Description (Verbatim from Applicant’s Abstract): A challenge to oncologists in the future is to individualize each and every tumor by tailoring treatments to those which are the most effective. Ideally, these choices must be made at the earliest point possible following the beginning of therapy. Monitoring therapeutic response is best done non-invasively, and can include molecular biological assays as well as radiological methods. A potentially powerful method to non-invasively monitor treatment response is Diffusion Magnetic Resonance Imaging (DWI). Diffusion MRI can accurately and quantitatively determine the apparent diffusion coefficient of tissue water (ADCW). Studies in experimental animals have shown that ADCW in tumors increases in cells undergoing successful chemotherapy. The observation of an increase in ADCW is potentially useful for clinical evaluation of chemotherapeutic response and this will be investigated in a companion R2 I proposal. However, a deeper understanding of the relationship between the diffusion properties of tumor water and the metabolic state of cells would increase its utility in assessing the state of tumor tissue, predicting outcome and designing therapies. In this proposal, we will examine the mechanisms underlining the ADCW changes using well-defined in vitro and in vivo systems. The two main hypotheses behind the proposed research plan are that 1) The ADCW in tumors is a surrogate measure of cell volume, and 2) The changes in ADCW in response to chemotherapy are a marker for apoptosis. This proposal represents a thorough evaluation of the relationship between

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ADCW, cell volume and response to chemotherapy. A wellcharacterized in vitro bioreactor system will provide the necessary control over system parameters to understand the basic mechanisms responsible for the observed changes in vivo. Thesaurus Terms: breast neoplasm, breast neoplasm/cancer diagnosis, diagnosis design/evaluation, magnetic resonance imaging, noninvasive diagnosis apoptosis, cell morphology, etoposide, necrosis, neoplasm/cancer chemotherapy, paclitaxel, tumor necrosis factor alpha, MCF7 cell, SCID mouse, bioreactor, flow cytometry, nuclear magnetic resonance spectroscopy

Institution:

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

University Of Arizona P O Box 3308 Tucson, AZ 857223308 2002 Radiology 01-Jun-2001 31-May-2006 National Cancer Institute ZRG1

MRS AND MRI OF BREAST CANCER AT VERY HIGH MAGNETIC FIELD Grant Number: PI Name:

1R01CA092004-01A1 Garwood, Michael G.

Abstract: Currently no diagnostic imaging method offers sufficient specificity to reliably differentiate between benign and malignant breast lesions in patients. Pathologic evaluation is presently the only way to obtain a definitive diagnosis. This research will use new methods in magnetic resonance spectroscopy (MRS) and a very high magnetic field (4 Tesla) to distinguish malignant from benign breast lesions. The required specificity will be gained from biochemical properties measured non- invasively with proton (1H) MRS. This work will further investigate the earlier finding that the presence of choline- containing compounds (Cho) at 3.2 ppm in 1H spectra may be a marker for malignancy in breast lesions. It is hypothesized that false-positive diagnoses can result from a resonance at 3.2 ppm that does not arise from Cho, but instead originates from lipids or other macromolecules with reduced mobility and short transverse relaxation time (T2). A macromolecular resonance at 3.2 ppm has been shown to occur in 1H spectra of brain. In the present project, the measured difference in intrinsic T2 should permit macromolecular and lipid resonances at 3.2 ppm to be distinguished from free Cho, thus eliminating false-positives. The improved SNR offered by the proposed MRS methods and the 4 Tesla magnetic field will significantly reduce the incidence of false-negative diagnoses. As an alternative means to characterize breast lesions, the ability of MRS to measure

ABSTRACTS OF NIH GRANTS

Academic Radiology, Vol 10, No 9, September 2003

glucose metabolism in breast lesions will also be investigated, by detecting 13C-labeled lactate following an intravenous injection of glucose enriched with the stable 13C isotope. Breast lesions will be visualized by dynamic contrastenhanced two-dimensional MRI and high resolution threedimensional MRI. MRI and MRS scans will be performed on clinically identified suspicious breast lesions prior to biopsy or surgical removal. Correlation with pathologic findings will reveal whether the proposed MRS measurements provide the additional specificity needed to accurately identify and characterize malignant lesions in breast patients. Thesaurus Terms: breast neoplasm, breast neoplasm/cancer diagnosis, diagnosis design/evaluation, magnetic field, magnetic resonance imaging, neoplasm/cancer classification/ staging, neoplastic growth, noninvasive diagnosis, nuclear magnetic resonance spectroscopy, carcinogenesis, choline, glucose metabolism, histopathology, lactate, method development, phosphorylcholine bioimaging/biomedical imaging, carbon, clinical research, human subject, mammography, stable isotope, ultrasonography

Institution:

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

University Of Minnesota Twin Cities Suite 450 Mcnamara Alumni Center Minneapolis, MN 554552070 2002 Radiology 01-May-2002 30-Apr-2007 National Cancer Institute RNM

PROGRAM IN CANCER OUTCOMES RESEARCH TRAINING (PCORT) Grant Number: PI Name:

1R25CA092203-01A1 Gazelle, Scott G.

Abstract: Description (provided by applicant): We propose to establish a Program in Cancer Outcomes Research Training (PCORT) within the Dana-Farber/Harvard Cancer Center (DF/HCC). The Program will be curriculum-based, highly interdisciplinary and involve collaboration across the entire Cancer Center and affiliated institutions. The goal of the Program will be to train pre- and post-doctoral candidates who will become leaders in cancer outcomes research. We request funding to support 4 M.D. and/or Ph.D. trainees and 2 predoctoral trainees per year, all of whom will spend at least two years in the Program. We will seek to recruit individuals with diverse prior research experience and training, and will integrate all trainees into a highly collaborative research environment. We will also actively recruit highly qualified minority and women applicants to the program. The Program will involve 3 components: 1) a specialized curriculum; 2) other didactic experiences; and 3) mentored, multidisci-

plinary cancer-related outcomes research. The specialized curriculum will involve weekly seminars alternating between didactic lectures and “research-in-progress” presentations by trainees and faculty. Appropriately qualified trainees will also attend the Harvard Program in Clinical Effectiveness, an intensive, seven-week, 15 credit classroom-based program that includes required courses in epidemiology and biostatistics, as well as a variety of electives. Qualified trainees may continue to take courses at HSPH, leading to a Master’s degree. Trainees will also be permitted to attend additional courses throughout Harvard University and its affiliated schools. Trainees will spend the largest part of their time participating in mentored cancer outcomes research under the direct supervision of PCORT faculty. All research projects undertaken by trainees will be multidisciplinary and highly collaborative. Trainees will be exposed to a broad range of cancer outcomes research. Trainees will be evaluated throughout and upon completion of the Program. After successful completion of the training program, they will be well prepared to conduct independent, externally funded, cancer outcomes research, and to do so effectively as part of a multidisciplinary research team. Thesaurus Terms: education evaluation/planning, health care personnel education, neoplasm/cancer education, outcomes research, training program/project curriculum, health science research, health science research support, postdoctoral investigator, predoctoral investigator, clinical research

Institution:

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

Massachusetts General Hospital 55 Fruit St Boston, MA 02114 2002 Radiology 01-SEP-2002 31-AUG-2007 National Cancer Institute NCI

COMPUTER AIDED DIAGNOSIS IN BREAST IMAGING Grant Number: PI Name:

5R01CA089452-02 Giger, Maryellen L.

Abstract: DESCRIPTION (Verbatim from Applicant’s Abstract): While screening mammography has been shown to be an effective method for the early detection of breast cancer, currently, 5-30 percent of women with breast cancer have a mammogram that is interpreted as normal. It has been reported that interpretation errors (when the radiologist sees the cancer but reports it as benign) are the cause of 54 percent of missed cancers. In addition, only 10-40 percent of women who have a biopsy actually have breast cancer, with biopsies being expensive, invasive and traumatic to the pa-

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