National Cancer Institute

HIGH SPECTRAL & SPATIALRESOLUTION MRI OF RODENT TUMORS

Grant Number: 1R21CA089408-01A1PI Name: Karczmar, Groegory S.

Abstract: Description (provided by applicant): Because ofits excellent soft tissue contrast, Magnetic Resonance Imag-ing (MRI) may aid early detection and staging of breast andprostate cancer. MRI has high sensitivity but its specificityhas been disappointing. New methods that improve identifi-cation of metastatic lesions by MRI would have a significantimpact on early detection and treatment of cancer. Previouswork in this laboratory showed that high spectral and spatialresolution (HiSS) MRI improves image quality and detectionof the effects of contrast agents. HiSS images can be ac-quired with clinically acceptable run times by using fre-quency resolved echo planar methods to obtain detailedspectra of the water and fat resonances associated with eachimage voxel. The proposed research tests the hypothesis thatcontrast enhanced HiSS MRI can distinguish metastatic tu-mors from non-metastatic tumors based on measures of im-age texture and edge delineation. We will develop methodsfor acquiring and processing HiSS datasets to maximize con-trast, edge delineation and signal-to-noise ratio. Contrast me-dia will be used to enhance contrast, improve depiction oftumor boundaries, and detect tumor vascular structure. Wewill test these experimental MRI methods using the well-characterized Dunning system of prostatic cancers. We pro-pose to use four cell lines that vary in metastatic ability.

HiSS MRI data will be correlated with tumor growth rateand size, microvessel density, degree and spatial distributionof necrosis, and number of overt metastases. This will im-prove our understanding of the biological processes that de-termine contrast in HiSS images and optimize HiSS MRI todetect features that differentiate metastatic and non-meta-static cancers. We will determine whether properties of theprimary tumor measured by MRI can predict the behavior ofmetastases. The specific areas of innovation are: 1) Use ofHiSS for anatomic and functional imaging 2) Application ofHiSS to differentiate between metastatic and non-metastaticcancers 3) Application of CAD (computer aided diagnosis)methods developed by Dr. Giger and coworkers to analyzeHiSS data 4) Use of molecular biologic methods to producemodel tumors that guide the development of new imagingmethods. The proposed research brings together a strong in-terdisciplinary team including Dr. Giger (image analysis,CAD), Dr. Rinker-Schaeffer (molecular biology, cancer biol-ogy), and Dr. Karczmar (MRI, tumor physiology). This workwould have a significant and rapid impact on clinical prac-tice.

Thesaurus Terms: diagnosis design/evaluation, magneticresonance imaging, neoplasm/cancer diagnosis, prostate neo-plasm computer assisted diagnosis, computer system design/evaluation, metastasis bioimaging/biomedical imaging, labo-ratory mouse

Institution: University Of Chicago5801 S Ellis AveChicago, IL 60637

Fiscal Year: 2002Department: Radiology

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Research Corner

Abstracts of Funded NationalInstitutes of Health Grants

The following abstracts of diagnostic radiology research and training grants funded by the National Institutes of Health (NIH)were awarded to principal investigators (PIs) whose primary appointments are in medical school departments of radiology.These abstracts are listed on the NIH Web page (http://www-commons.cit.nih.gov/crisp/) and are printed here verbatim.

The grant identification number (eg, 1RO1AI12345-01) contains a three-digit activity code (in the previous example, RO1)that identifies a specific category of extramural activity. All current NIH activity code titles and definitions can be ob-tained at the NIH Web page http://silk.nih.gov/silk/brownbooks/actcod.

IRG (Internal Review Group) refers to the study section that reviewed the application. ICD (Institute, Center, Division) re-fers to the NIH funding source.

The abstracts of the funded grants are printed alphabetically by author according to the funding institute or center.

Project Start: 01-Apr-2002Project End: 31-Mar-2004ICD: National Cancer InstituteIRG: RNM

DIGITAL MAMMOGRAPHY HIGHRESOLUTION FLAT PANEL IMAGER

Grant Number: 5R01CA088792-02PI Name: Karellas, Andrew

Abstract: Description (Adapted from Applicant’s Abstract):This is a Bioengineering Research Partnership betweenUMass Medical School and Lockheed-Martin Corporation. Itis aimed at developing and evaluating a new high resolutionflat panel mammographic imager with a variable pixel size(40 microns and 80 microns) using tiled charged-coupleddevices (CCD). The detector will cover an area essentiallythe same as the sensitive area of a conventional mammo-graphic cassette. The specific hypotheses are: (a) the newimager will exhibit better detective quantum efficiency(DQE) than current screen-film technology. (b) Unlike cur-rent screen-film, the system will exhibit higher dynamicrange. (c) The spatial resolution will be higher than currentflat-panel imaging systems due to the smaller pixel size and100 percent fill factor. (d) The contrast will be significantlybetter than existing screen-film systems resulting in bettervisualization of breast anatomy at a reduced radiation doseto the patient due to the improved DQE. (e) A well-designedmammographic system driven in an optimized acquisitionmode will replace screen-film systems for full-breast mam-mographic imaging. Preliminary computational and experi-mental studies suggest that a CCD flat panel detector of thistype is feasible. The experimental plan calls for comprehen-sive evaluation of the characteristics of the detector andevaluation of the system though objective and universallyaccepted metrics such as the spatially dependent modulationtransfer function and DQE. The applicants report experiencewith the 100 micron pixel GE clinical evaluation prototypein a screening population, which appears to demonstrateequivalency for cancer detection with similar sensitivities.However, there are concerns about of the more subtle formsof calcifications such as punctate and amorphous. When cal-cium is seen the edge sharpness does not appear to have thesame sharpness as that of spot film views. These problemsmay be related to the relatively large pixel size (100 mi-crons) of the detector. The applicants propose to develop andevaluate the next generation of high resolution digital mam-mography with high spatial resolution and without the detri-mental loss in the signal-to-noise ratio, which is commonwith the older generation, which uses demagnifying fiberoptics. The proposed prototype using an array of seamlesslytiled CCDs coupled to a structured CsI:TI scintillator by anon-tapering fiber optic plate will deliver the highest resolu-tion than any other flat panel mammographic detector.

Thesaurus Terms: biomedical equipment development,charge coupled device camera, digital imaging, fiber optics,mammography, calcification, human data

Institution: Univ Of Massachusetts Med SchWorcester

Office of Research FundingWorcester, MA 01655

Fiscal Year: 2002Department: RadiologyProject Start: 01-Jul-2001Project End: 30-Jun-2004ICD: National Cancer InstituteIRG: ZRG1

RADIODIAGNOSIS & RADIOTHERAPY OFLUNG CANCER METASTASES

Grant Number: 5R01CA089648-02PI Name: Kassis, Amin I.

Abstract: Lung cancer claims approximately 150,000 liveseach year in the USA and its incidence is increasing glo-bally. Early diagnosis of this disease is difficult to obtain.The five-year survival rate of patients with lung cancer isapproximately 14 percent and has not changed over the pastseveral decades. The purpose of the proposed research is toestablish the potential of the thymidine analog 5-iodo-2�-deoxyuridine (IUdR) radiolabeled with the gamma-emittingisotope iodine-123 (I-123) for the scintigraphic detection oflung cancer and radiolabeled with either the Auger electron-emitting isotope iodine-125 or the beta-emitting isotope io-dine-131 for the therapy of lung cancer. To this end, experi-ments have been designed to examine the specific uptake ofradiolabeled IUdR in nude mice bearing cancer cells grow-ing within the lungs. The approaches described should pro-vide an opportunity for the selective targeting of dividingcancerous cells within the lungs and lead to methods forscintigraphic detection of lung cancer as well as develop-ment of an effective/adjuvant therapeutic approach.

Thesaurus Terms: lung neoplasm, metastasis, neoplasm/cancer radionuclide diagnosis, neoplasm/cancer radionuclidetherapy, nonhuman therapy evaluation drug administrationrate/duration, idoxuridine, intravenous administration, metho-trexate, neoplasm/cancer pharmacology athymic mouse, auto-radiography, iodine, radionuclide

Institution: Harvard University (Medical School)Medical School CampusBoston, MA 02115

Fiscal Year: 2002Department: RadiologyProject Start: 01-Jan-2001

NCI Academic Radiology, Vol 10, No 10, October 2003

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