RESOLUTION AND CONTRAST ENHANCEMENT IN ULTRASONOGRAPHY

DESCRIPTION (Adapted from Applicant's Abstract): The applicants proposed to evaluate a new algorithm for ultrasound B-scan image formation. The algorithm is based on a hybrid continuous-discrete state imaging model that represents the effects of abrupt changes in attenuation and scatterer density as the transducer pulse propagates across tissue boundaries and through cystic and calcified structures. The applicants reported having tested the approach on phantom data and obtained substantial improvements in B-scan resolution and contrast. They expect the algorithm to result in improved imagery in a broad range of applications. The applicants proposed to focus evaluation on transrectal prostate imaging with the goal of demonstrating significantly improved prostate zonal differentiation. The resulting imagery could enable physicians to better estimate prostate volume and identify the zones in which lesions are located or hypertrophy is occurring, capabilities important in the diagnosis of prostate-related medical problems. The applicants proposed to evaluate the algorithm using synthetic, phantom, and canine prostate pulse echo characteristics and their relationship to histology. They would collect the pulse-echo data using three GE transducers, including a recently introduced Microslice probe, and will experimentally determine the improvement in the ability of clinicians to differentiate prostate anatomical structures. Following a successful evaluation in Phase I, they would develop the algorithm for real-time operation in Phase II. $ = TOTAL AWARD AMTS & NOT LIMITED TO PORTION OF PROJECT RELATED TO SUBJECT OF SEARCH SUBPROJECT $ = TOTAL AWARD AMOUNT DIVIDED BY NUMBER OF SUBPROJECTS SOURCE: CRISP FORMAT F FY 97 LAST UPDATE 04-07-98 1QUERY 1536 ID SEARCH 06/01/98 PAGE 219 --PROJECT NUMBER......1 R43 CA76855-01 INVESTIGATOR NAME/ADDRESS FY 97 KLEIN, JERRY L IRG/INTRAMURAL UNIT..ZRG2 PERIMMUNE INC AWARD AMOUNT......... $100,000 1330 PICCARD DRIVE ROCKVILLE, MD 20850-4396 PERFORMING ORGANIZATION: PERIMMUNE, INC. TITLE INTRATUMORAL RADIOLABELED ANTIBODY THERAPY--HEAD/NECK CANCER ABSTRACT: DESCRIPTION: The direct intratumoral injection of an yttrium-labeled monoclonal antibody has the potential to deliver radiation doses to the tumor and regional lymph nodes in the therapeutic range. The applicants will test this hypothesis in patients with primary and recurrent head and neck cancer. The long-term goal is to develop a treatment to increase local tumor control and to decrease the morbidity associated with therapy in this locally growing tumor. Patients will be injected intratumorally with both indium and yttrium (trace) labeled antibody and will be evaluated by nuclear scanning, surgery and pathology, and direct scintillation gamma counting of resected tissues. The specific aims of this study are to 1) Evaluate the biodistribution of a radiolabeled, totally human, monoclonal antibody (16.88) in patients with either primary or recurrent disease following an intratumoral injection, 2) compare the biodistribution of indium labeled antibody (scanning, dosimetry ) to yttrium labeled antibody (therapy) in the same patient to determine if indium is predictive of yttrium, 3) perform dosimetry calculations based on gamma camera imaging and direct tissue counting, 4) perform pathological evaluation of the primary tumor and regional lymph nodes, and 5) select the patient population(s) for phase I and II clinical therapy trials. $ = TOTAL AWARD AMTS & NOT LIMITED TO PORTION OF PROJECT RELATED TO SUBJECT OF SEARCH SUBPROJECT $ = TOTAL AWARD AMOUNT DIVIDED BY NUMBER OF SUBPROJECTS SOURCE: CRISP FORMAT F FY 97 LAST UPDATE 04-07-98 1QUERY 1536 ID SEARCH 06/01/98 PAGE 220 --PROJECT NUMBER......1 R43 CA76858-01 INVESTIGATOR NAME/ADDRESS FY 97 CLAUSER, JOHN F IRG/INTRAMURAL UNIT..ZRG7 JF CLAUSER & ASSOC AWARD AMOUNT......... $99,565 817 HAWTHORNE DRIVE WALNUT CREEK, CA 94596-6112 PERFORMING ORGANIZATION: J. F. CLAUSER AND ASSOCIATES TITLE X RAY REFRACTIVE INDEX AND ELEMENT SELECTIVE IMAGING ABSTRACT: The project demonstrates an ultra-high resolution x-ray imaging system. It provides high contrast images of the density structure of objects that are otherwise x-ray transparent, e.g. low-Z human soft-tissue, and obtains edge enhanced contrast from x-ray refractive-index gradients. In mammography the contrast of a microcalcification is increased typically by 4-fold, and cancerous masses by much more. The system can be tuned to obtain element selective contrast to image resonantly minute quantities of a tracer element with Z=35-56, and only that element. It virtually eliminates the blurring and contrast-reducing effects of x-ray scatter. It operates at 15-40keV average x-ray energy with 3-50- fold reduced patient dosage, and significantly reduces the scanning time for CT 3D-imaging. It uses physical optics principles to form a Talbot-Lau imaging x-ray interferometer. It uses a conventional x-ray tube and filter, two microfabricated x-ray diffraction gratings, a CCD detector (and/or film), and an in-situ laser interferometer for alignment. Phase-I demonstrates a scatter-free 3cmx3cm image at - 50micrometers resolution, with refractive-index and/or tracer imaging. Phase-II similarly obtains >10cmx10cm images with an engineering prototype for a marketable device. $ = TOTAL AWARD AMTS & NOT LIMITED TO PORTION OF PROJECT RELATED TO SUBJECT OF SEARCH SUBPROJECT $ = TOTAL AWARD AMOUNT DIVIDED BY NUMBER OF SUBPROJECTS SOURCE: CRISP FORMAT F FY 97 LAST UPDATE 04-07-98 1QUERY 1536 ID SEARCH 06/01/98 PAGE 221 --PROJECT NUMBER......1 R43 CA76860-01 INVESTIGATOR NAME/ADDRESS FY 97 PENG, YONGREN B IRG/INTRAMURAL UNIT..ZRG2 XL SCI-TECH INC AWARD AMOUNT......... $99,146 PO BOX 1726 RICHLAND, WA 99352 PERFORMING ORGANIZATION: XL SCI-TECH, INC. TITLE TIMED BIORESORBABLE Y 90 MICROSPHERES FOR RADIOTHERAPY ABSTRACT: DESCRIPTION: Leakage of radioactive material away from the injection site reduces therapeutic efficacy, induces undesirable damage to normal tissues, and increases the risk of side effects (dermitis, neuritis) and secondary neoplasia (leukemia and osteosarcoma). Insoluble glass or ceramic microspheres may contain radioactivity to the injection site and inhibit leakage, but may also later induce inflammation, deterioration of tissues, and fibrosis, or cause physical damage to healing/healed joints. These obstacles may be overcome with a new, timed- bioresorbable calcium phosphate microspheres. These microspheres can be made to maintain structural integrity for 30 days (11 physical half- lives for Y-90, i.e., decayed to negligible activity) before they begin to dissolve at a predetermined rate, leaving nothing in the patient to cause irritation, blockage or physical damage. The purpose of this project is to prepare and test Y-90-containing microspheres with pre- programmed bioresorption. Glass composition range and Y-90 solubility in glasses will be established. The in vitro properties of bioresorbable Y-90 calcium phosphate glass microspheres will be characterized so that follow-up tests can be conducted in laboratory animals. Applications of Y-90 microspheres include direct intratumoral injection (infusional brachytherapy) in treatment of cancers of liver, pancreas, brain, etc., and radiation synovectomy of rheumatoid arthritis. $ = TOTAL AWARD AMTS & NOT LIMITED TO PORTION OF PROJECT RELATED TO SUBJECT OF SEARCH SUBPROJECT $ = TOTAL AWARD AMOUNT DIVIDED BY NUMBER OF SUBPROJECTS SOURCE: CRISP FORMAT F FY 97 LAST UPDATE 04-07-98 1QUERY 1536 ID SEARCH 06/01/98 PAGE 222 --PROJECT NUMBER......1 R43 CA76900-01 INVESTIGATOR NAME/ADDRESS FY 97 WOODGATE, SANDRA R IRG/INTRAMURAL UNIT..ZRG2 ONCOR, INC AWARD AMOUNT......... $100,000 209 PERRY PARKWAY GAITHERSBURG, MD 20877 PERFORMING ORGANIZATION: ONCOR, INC. TITLE RARE TARGET SCREENING FOR EARLY DIAGNOSIS OF LUNG CANCER ABSTRACT: Lung cancer is the leading cause of cancer related deaths in American adults. Mutations in c-Kiras and p53 oncogenes occur early in tumor development and are retained as specific markers for lung cancer. Analysis of these genes in sputum samples revealed mutations in patients one year before clinical diagnosis. We aim to develop a method to simultaneously detect approximately 200 specific point mutations in these genes as an early detection test for lung cancer. The method is based on ligation and selective amplification of a single oligonucleotide probe designed to give base discrimination and detection of 1 rare target in 105 normal molecules. Unlike allele specific PCR and LCR, this method analyzes mutations in parallel without loss of discrimination or sensitivity. Commercial plans are to adapt the genetic screen to microfabricated arrays for automated analysis. The objectives of Phase I will determine: i) optimal oligonucleotide probe sequence for target discrimination and selective amplification; ii) optimal ligation conditions for target discrimination and probe circularization; iii) if DNA polymerase fidelity is required for additional discrimination; and iv) signal amplification and compatibility with immobilized probe. In Phase II we will assemble the mutation panel, identify test format, and assess clinical utility.