Institution:

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

Thomas Jefferson University 1020 Walnut St Philadelphia, PA 19107 1999 Radiation Oncology 23-APR-93 31-JAN-02 National Cancer Institute NCI )ROJECT TITLE

~ROJECT TITLE

BREAST CANCER DETECTION USING ULTRASOUND CONTRAST

Grant Number: 5R01CA60854-04 PI Name: Goldberg, Barry B.

Abstract: The effectiveness of an intravenously injected ultra- sound contrast agent (Levovist) to enhance Doppler signals from within and around breast masses will be evaluated. The procedure will be videotaped using a standard protocol, allow- ing for independent reading as well as intra- and inter-observer reliability measurements. Doppler pulsatility and resistive indi- ces will be recorded as well as the peak systolic frequency and the minimum end diastolic frequency. The region of the breast mass will be examined with color and pulsed Doppler ultra- sound, recording arc of vascularity within and around the visualiied mass. A dose of the ultrasound contrast agent will then be injected intravenously as a series of Doppler ultrasound recordings are taken from the mass and/or the adjacent normal portion of the breast. Since the agent lasts for up to six minutes, it will be possible to obtain information in both color and pulsed form, in both the normal and tumor regions. Contrast enhanced color harmonic imaging will also be performed. Specifically, the differences between the time of peak contrast enhancement and the washout of the contrast agent in benign and malignant masses will be measured. The hypothesis is that an ultrasound contrast agent wilt improve the ability to detect and differentiate tumors compared to images by x-ray mammography, conven- tional ultrasound and non-enhanced color Doppler. Surgical and pathological results will be used as a gold standard.

Thesaurus Terms: breast neoplasm/cancer diagnosis, diagnosis design/evaluation, ultrasonography breast surgery, contrast me- dia, dosage, female, intravenous administration, neoplasm/can- cer classification/staging, ultrasound scanning, videotape/video- disc biopsy, clinical research, colorimetry, histopathology, hu- man subject, mammography

Institution: Thomas Jefferson University 1020 Walnut St Philadelphia, PA 19107

Fiscal Year: 1999 Department: Radiology Project Start: 01-APR-96 Project End: 31-JAN-01 ICD: National Cancer Institute IRG: RNM

PROTON RELAXATION AND CONTRAST MECHANISMS IN MRI

Grant Number: 2R01CA40675-10A1 PI Name: Gore, John C.

Abstract: This proposal aims to continue studies to better un- derstand the physical factors that affect the NMR relaxation properties of protons in tissues and which determine contrast in MR images. We aim to better understand what influences the fundamental processes involved in relaxation in tissues at the molecular level. We have provided evidence of the role of mag- netization transfer (MT) in tissue-like model systems, and have shown how this depends on both chemical exchange and cross- relaxation, physico-chemical effects and macromolecular struc- ture. This evidence has been derived by developing new and im- proved methods of measuring MT. We aim to extend these stud- ies to other systems and tissues, and to more fully explore the molecular structural factors that influence MT and spin diffu- sion, and their roles in relaxation. This will include studies of the effects of surface groups, pH, and matrix rigidity. We will use novel quantitative methods of characterizing MT in media with different degrees of deuteration, along with new methods sensitive to Tlrho, to derive measures of the sizes and motional characteristics of proton pools within samples. We wilt use these measurements to examine the number of compartments required to fully explain MT data. We will also directly address questions of the importance of MT versus spin locking and direct satura- tion effects. We will investigate the degree to which MT in tis- sues and model systems is limited by rates of water diffusion, by studying the effects of diffusion on displacement profiles of wa- ter using novel pulse gradient spin echo methods. Finally, we will try to detect and investigate the influence of water that is preferentially oriented and rotating anisotropically, using magic angle radiofrequency field techniques. We will explore the use of stimulated echo measurements of dipolar correlation effects and multiple quantum filter techniques that are sensitive to mac- roscopic order and relatively long time-scale residual dipolar couplings that are not motionally averaged and which may ac- count for the shortening of T2 in tissues. We will study a se- lected group of tissues, biopolymers and gels, in different condi- tions and of varied composition. Overall this project should pro- vide many new insights into tissue relaxation phenomena to aid in the better understanding of the origin of contrast in NMR im- ages. This should in turn provide guidance on the interpretation

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of signals in conventional MR images and will motivate new approaches to tissue characterization.

Thesaurus Terms: magnetic resonance imaging, physical/ chemical interaction, structural biology biophysics, diffusion, magnetic field, quantum chemistry, technology/technique de- velopment bioimagingfoiomedical imaging, laboratory rat

Institution:

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

Yale University New Haven, CT 06520 1999 Diagnostic Radiology 01-JUL-85 28-FEB-03 National Cancer Institute ZRG1

ever, h is not adequate for assessing change in uptake as a mea- sure of response to therapy and frequently is inadequate for dif- ferentiating tumor from metabolically active normal tissue. For these reasons we intend to evaluate and compare 4 different ap- proaches for quantitating FDG uptake: standardized uptake value (SUV) and graphical analysis (Patlack method), along with glucose metabolic rate and k3 (hexokinase rate constant) using compartmental analysis with the Sokoloff/Phelps model. Sites of tumor and normal tissue will be confirmed with biopsy or appropriate follow-up. The accuracy of FDG PET imaging for predictin response to therapy after one cycle of chemo- therapy will be tested by correlating change in FDG parameters with response or lack of response, and length of survival fol- lowing 3-6 months of therapy.

Thesaurus Terms: carcinoma, colorectal neoplasm, diagnosis design/evaluation, liver neoplasm, metastasis, neoplasm/cancer diagnosis deoxyglucose, glucose metabolism clinical research, human subject, positron emission tomography ~ROJECT TITL!

FDG PET IMAGING OF COLON CARCINOMA RESPONSE TO THERAPY

Grant Number: 5R01CA74959-02 PI Name: Graham, Michael M.

Abstract: The underlying hypothesis for this project is that quantitative FDG PET imaging of tumors is a far more sensitive approach for determining response to therapy than the conven- tional approach of using an anatomic measure of change in size. Our specific goals are to determine the optimum time for FDG PET imaging in patients with metastatic colon carcinoma fol- lowing chemotherapy and the optimum data analysis strategy. All patients identified with metastatic colon cancer who are to receive 5-FU or irinotecan chemotherapy will undergo an FDG PET scan prior to the first cycle of chemotherapy. The quantita- tive measures of FDG uptake and the changes in FDG uptake at specific times after chemotherapy will be correlated with changes in CEA levels and in tumor size by CT following a full course of chemotherapy lasting 3-6 months. We will also evalu- ate the utility of FDG PET imaging for defining the response of metastatic colorectal or primary liver tumors to non-resectional forms of therapy, including trans-hepatic artery embolization (TAE), cryosurgical ablation, ethanol injection, and TAE fol- lowed by ethanol injection. These treatments usually leave a scar in the liver that cannot be distinguished from recurrent can- cer by conventional imaging tests (CT, MRI, or ultrasound). Pa- tients will have follow up FDG PET imaging at 3-4 weeks and at 6 months. At the same time as the PET study, all patients will undergo helical CT and, when appropriate, ultrasound or CT guided biopsy of the lesion. Long term follow up will be corre- lated with PET, biopsy, CT, and tumor markers. A significant part of this project will be to evaluate quantitative FDG PET imaging in these patients. Simple visual examination of FDG PET images is often sufficient to identify sites of tumor. How-

Institution:

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

University of Washington 3935 University Way NE Seattle, WA 98195 1998 Radiology 01-SEP-97 30-JUN-02 National Cancer Institute RNM

)ROJECT TITLE

DEVELOPMENT OF AN MR-PET TOMOGRAPHIC SCANNER

Grant Number: 5R29CA65523-05 PI Name: Hammer, Bruce E.

Abstract: An MR-PET scanner has the potential of acquiring anatomical, functional and gross metabolic tissue status through MRI/MRS and metabolic activity through PET. The ultimate goal of a hybrid scanner is to yield temporal and spatial coregistration of MR and PET data. The objective of this re- search is to demonstrate the feasibility of developing a hybrid MR-PET scanner that performs MR and PET tomography on bioreactors or small animals. To achieve this goal a section of a magnetic field tolerant PET ring will function in the center of a 5.0 T/40cm MR magnet. This is a continuation of the work done through Small Grant for Innovative Technology, NIH/I- R03-RR07042-01, that experimentally showed positron range squeezing in a magnetic field. This proposal should lay the foundation for engineering a hybrid MR-PET. scanner that si- multaneously performs MR and PET tomography.

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