Institution: University Of Chicago5801 S Ellis AveChicago, IL 60637

Fiscal Year: 2002Department: RadiologyProject 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 fiberop-tics. The proposed prototype using an array of seamlesslytiled CCDs coupled to a structured CsI:TI scintillator by anon-tapering fiberoptic 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, au-toradiography, iodine, radionuclide

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

Fiscal Year: 2002Department: RadiologyProject Start: 01-Jan-2001Project End: 31-Dec-2004ICD: National Cancer InstituteIRG: RAD

THERAPEUTIC/TOXIC EFFECTS OFELECTRON EMITTING NUCLIDES

Grant Number: 5R01CA015523-28PI Name: Kassis, Amin I.

Abstract: The objective of the proposed research is to un-derstand the implications of densely ionizing radiations emit-ted by diagnostic and therapeutic radionuclides (Auger elec-trons and alpha particles) for both radiation protection andcancer therapy. We plan to elucidate the radiation biophysicsof these short-range, high-LET particles and to use the infor-mation in studies of various radiobiologic effects and in ex-perimental therapeutics. To this end, we propose to examinethe microscopic distribution of damage in well-characterizedand relatively simple systems (e.g. oligonucleotides, plas-mids) in response to spatial positioning of the decaying nu-clide and to changes in the surrounding environment. Inaddition, we will utilize individual cells as test systems fordetermining the quantitative relationships between micro-scopic dose and detrimental biologic effects by (i) exploringthe molecular consequences of noncovalent DNA binding ofAuger-electron emitting radiohalides as expressed by DNAstrand breaks; and (ii) determining the radiotoxicity and mu-tagenic effects of the diagnostic radionuclides 99mTC and111In when they are concentrated by cells and relating theresults to the microscopic distribution of their conversionelectrons. Studies will be repeated in the presence of radicalscavengers to explore the role of hydroxyl radicals in theseprocesses. In addition, we plan to continue our studies ofcytotoxicity mutagenesis, and cellular transformation follow-ing the decay of the alpha particle emitters 211At and 212Biwhen localized extra-cellularly, on plasma membranes, andintranuclearly. We will also exploit animal tumor models aspre-clinical systems for determining the utility of theseagents in therapy and for establishing preliminary time-doserelationships. These models will include closed systems(brain, spinal cord, peritoneum) for the introduction of radio-pharmaceuticals and one system accessible by differentialperfusion (liver). Finally, in an attempt to extend the utilityof radionuclide particle therapy, we plan to initiate combinedmodality experiments with photons plus alpha particle orAuger electron emitters.

Thesaurus Terms: electron radiation, neoplasm/cancer ra-dionuclide therapy, nuclear medicine, radiation sensitivity,radiobiology DNA damage, cell transformation, chromatin,cytotoxicity, free radical scavenger, ionizing radiation, radia-tion dosage, radiation genetics, radiation hazard, radionuclidediagnosis, radionuclide imaging/scanning, radiopharmacol-ogy, relative biological effectiveness, autoradiography, bio-logical model, laboratory mouse, laboratory rat, magneticresonance imaging

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

Fiscal Year: 2002Department: RadiologyProject Start: 01-May-1977Project End: 31-Dec-2002ICD: National Cancer InstituteIRG: RNM

DIGITAL RESTORATION OF SPECTIMAGES FOR TUMOR DETECTION

Grant Number: 5R01CA042165-13PI Name: King, Michael A.

Abstract: Our goal is to determine the extent to which state-of-the-art acquisition and reconstruction strategies can over-come the factors that limit the detection of, and estimation ofactivity within, tumors in gamma-camera-based emission-computed-tomographic imaging of tumor-avid imagingagents. Altering acquisition and reconstruction strategies toaccount for a source of degradation is costly in terms of pro-cessing time, added complexity in imaging and processing,and/or enhancement of other sources of degradation. There-fore, it is essential to establish the degree to which degrada-tions are detrimental, and to determine the extent to whichtheir impact can be mitigated. Thus far, we have determinedusing human-observer LROC studies employing simulatedGa-67 citrate images that noise regularization, nonuniformattenuation compensation (AC), and detector resolution com-pensation (DRC) significantly increase the detection accuracyof small, low-contrast lesions. We propose to proceed byinvestigating scatter compensation (SC), and the explicit in-clusion of noise regularization in iterative reconstruction(IR). We also propose to investigate the impact of respira-tory motion on tumor detection. These studies will be con-ducted with simulations where imaging can be accuratelymodeled and upper limits of improvement assessed. How-ever, simulated images do not fully reflect the structuredbackground present in clinical images, and are created withsystem models that only approximate actual systems. There-fore, we propose to investigate noise regularization, AC,DRC, and SC through hybrid images, which are actual clini-

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