Thesaurus Terms: drug design/synthesis/production, dye,neoplasm/cancer photoradiation therapy, photosensitizingagent analog, cytochrome, dosage, drug screening/evaluation,enzyme mechanism, hemoglobin, neoplasm/cancer pharma-cology, nonvisual photosensitivity, oxygen consumption, ox-ygen tension, photochemistry, porphyrin, pulmonary diffu-sion, respiratory oxygenation, selenium, sulfur athymicmouse, fluorescence microscopy, laboratory rat, microelec-trode, spectrometry

Institution: University Of RochesterORPA - RC Box 270140Rochester, NY 14627

Fiscal Year: 2002Department: RadiologyProject Start: 01-Jul-1995Project End: 28-Feb-2003ICD: National Cancer InstituteIRG: RAD

MECHANISMS OF DIFFUSION MRI WITHCHEMOTHERAPY

Grant Number: 5R01CA088285-02PI Name: Galons, Jean-Philippe

Abstract: Description (Verbatim from Applicant’s Abstract):A challenge to oncologists in the future is to individualizeeach and every tumor by tailoring treatments to those whichare the most effective. Ideally, these choices must be madeat the earliest point possible following the beginning of ther-apy. Monitoring therapeutic response is best done non-inva-sively, and can include molecular biological assays as wellas radiological methods. A potentially powerful method tonon-invasively monitor treatment response is Diffusion Mag-netic Resonance Imaging (DWI). Diffusion MRI can accu-rately and quantitatively determine the apparent diffusioncoefficient of tissue water (ADCW). Studies in experimentalanimals have shown that ADCW in tumors increases in cellsundergoing successful chemotherapy. The observation of anincrease in ADCW is potentially useful for clinical evalua-tion of chemotherapeutic response and this will be investi-gated in a companion R2 I proposal. However, a deeper un-derstanding of the relationship between the diffusion proper-ties of tumor water and the metabolic state of cells wouldincrease its utility in assessing the state of tumor tissue, pre-dicting outcome and designing therapies. In this proposal, wewill examine the mechanisms underlining the ADCWchanges using well-defined in vitro and in vivo systems. Thetwo main hypotheses behind the proposed research plan arethat 1) The ADCW in tumors is a surrogate measure of cellvolume, and 2) The changes in ADCW in response to che-motherapy are a marker for apoptosis. This proposal repre-sents a thorough evaluation of the relationship between

ADCW, cell volume and response to chemotherapy. A well-characterized in vitro bioreactor system will provide the nec-essary control over system parameters to understand the ba-sic mechanisms responsible for the observed changes invivo.

Thesaurus Terms: breast neoplasm, breast neoplasm/cancerdiagnosis, diagnosis design/evaluation, magnetic resonanceimaging, noninvasive diagnosis apoptosis, cell morphology,etoposide, necrosis, neoplasm/cancer chemotherapy, pacli-taxel, tumor necrosis factor alpha, MCF7 cell, SCID mouse,bioreactor, flow cytometry, nuclear magnetic resonance spec-troscopy

Institution: University Of ArizonaP O Box 3308Tucson, AZ 857223308

Fiscal Year: 2002Department: RadiologyProject Start: 01-Jun-2001Project End: 31-May-2006ICD: National Cancer InstituteIRG: ZRG1

MRS AND MRI OF BREAST CANCER ATVERY HIGH MAGNETIC FIELD

Grant Number: 1R01CA092004-01A1PI Name: Garwood, Michael G.

Abstract: Currently no diagnostic imaging method offerssufficient specificity to reliably differentiate between benignand malignant breast lesions in patients. Pathologic evalua-tion is presently the only way to obtain a definitive diagno-sis. This research will use new methods in magnetic reso-nance spectroscopy (MRS) and a very high magnetic field (4Tesla) to distinguish malignant from benign breast lesions.The required specificity will be gained from biochemicalproperties measured non- invasively with proton (1H) MRS.This work will further investigate the earlier finding that thepresence of choline- containing compounds (Cho) at 3.2 ppmin 1H spectra may be a marker for malignancy in breast le-sions. It is hypothesized that false-positive diagnoses canresult from a resonance at 3.2 ppm that does not arise fromCho, but instead originates from lipids or other macromole-cules with reduced mobility and short transverse relaxationtime (T2). A macromolecular resonance at 3.2 ppm has beenshown to occur in 1H spectra of brain. In the present project,the measured difference in intrinsic T2 should permit macro-molecular and lipid resonances at 3.2 ppm to be distin-guished from free Cho, thus eliminating false-positives. Theimproved SNR offered by the proposed MRS methods andthe 4 Tesla magnetic field will significantly reduce the inci-dence of false-negative diagnoses. As an alternative means tocharacterize breast lesions, the ability of MRS to measure

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glucose metabolism in breast lesions will also be investigated,by detecting 13C-labeled lactate following an intravenousinjection of glucose enriched with the stable 13C isotope.Breast lesions will be visualized by dynamic contrast-enhanced two-dimensional MRI and high resolution three-dimensional MRI. MRI and MRS scans will be performedon clinically identified suspicious breast lesions prior to bi-opsy or surgical removal. Correlation with pathologic find-ings will reveal whether the proposed MRS measurementsprovide the additional specificity needed to accurately iden-tify and characterize malignant lesions in breast patients.

Thesaurus Terms: breast neoplasm, breast neoplasm/cancerdiagnosis, diagnosis design/evaluation, magnetic field, mag-netic resonance imaging, neoplasm/cancer classification/staging, neoplastic growth, noninvasive diagnosis, nuclearmagnetic resonance spectroscopy, carcinogenesis, choline,glucose metabolism, histopathology, lactate, method develop-ment, phosphorylcholine bioimaging/biomedical imaging,carbon, clinical research, human subject, mammography, sta-ble isotope, ultrasonography

Institution: University Of Minnesota Twin CitiesSuite 450 Mcnamara Alumni CenterMinneapolis, MN 554552070

Fiscal Year: 2002Department: RadiologyProject Start: 01-May-2002Project End: 30-Apr-2007ICD: National Cancer InstituteIRG: RNM

PROGRAM IN CANCER OUTCOMESRESEARCH TRAINING (PCORT)

Grant Number: 1R25CA092203-01A1PI Name: Gazelle, Scott G.

Abstract: Description (provided by applicant): We proposeto establish a Program in Cancer Outcomes Research Train-ing (PCORT) within the Dana-Farber/Harvard Cancer Center(DF/HCC). The Program will be curriculum-based, highlyinterdisciplinary and involve collaboration across the entireCancer Center and affiliated institutions. The goal of the Pro-gram will be to train pre- and post-doctoral candidates whowill become leaders in cancer outcomes research. We requestfunding to support 4 M.D. and/or Ph.D. trainees and 2 pre-doctoral trainees per year, all of whom will spend at leasttwo years in the Program. We will seek to recruit individualswith diverse prior research experience and training, and willintegrate all trainees into a highly collaborative research en-vironment. We will also actively recruit highly qualified mi-nority and women applicants to the program. The Programwill involve 3 components: 1) a specialized curriculum; 2)other didactic experiences; and 3) mentored, multidisci-

plinary cancer-related outcomes research. The specializedcurriculum will involve weekly seminars alternating betweendidactic lectures and “research-in-progress” presentations bytrainees and faculty. Appropriately qualified trainees willalso attend the Harvard Program in Clinical Effectiveness, anintensive, seven-week, 15 credit classroom-based programthat includes required courses in epidemiology and biostatis-tics, as well as a variety of electives. Qualified trainees maycontinue to take courses at HSPH, leading to a Master’s de-gree. Trainees will also be permitted to attend additionalcourses throughout Harvard University and its affiliatedschools. Trainees will spend the largest part of their timeparticipating in mentored cancer outcomes research under thedirect supervision of PCORT faculty. All research projectsundertaken by trainees will be multidisciplinary and highlycollaborative. Trainees will be exposed to a broad range ofcancer outcomes research. Trainees will be evaluatedthroughout and upon completion of the Program. After suc-cessful completion of the training program, they will be wellprepared to conduct independent, externally funded, canceroutcomes research, and to do so effectively as part of a mul-tidisciplinary research team.

Thesaurus Terms: education evaluation/planning, healthcare personnel education, neoplasm/cancer education, out-comes research, training program/project curriculum, healthscience research, health science research support, postdoc-toral investigator, predoctoral investigator, clinical research

Institution: Massachusetts General Hospital55 Fruit StBoston, MA 02114

Fiscal Year: 2002Department: RadiologyProject Start: 01-SEP-2002Project End: 31-AUG-2007ICD: National Cancer InstituteIRG: NCI

COMPUTER AIDED DIAGNOSIS INBREAST IMAGING

Grant Number: 5R01CA089452-02PI Name: Giger, Maryellen L.

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

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