Stephen C. Moore - US grants

DESCRIPTION (Adapted from Applicant's Abstract): The goal of the proposed research is to improve the acquisition, reconstruction, and extraction of quantitative information from Ga-67 SPECT data, and to assess these improvements to the imaging system using task-dependent criteria. Gallium has proven to be a useful nuclear medicine tracer for imaging certain tumors, and it is known that gallium avidity is correlated with histopathologic tumor grade. Imaging Ga-67, however, is challenging because it emits many high-energy photons. Quantitative estimates of Ga-67 tumor uptake are degraded by three principal sources of error: a location-dependent bias caused by imperfect correction for photon scatter and nonuniform attenuation, a size-dependent bias due to blurring by the nonstationary detector response function, and stochastic variability arising from Poisson noise in the acquired data. The proposed research will address these challenges by (1) optimizing for Ga-67 imaging several methods of correcting images for the effects of scatter and attenuation in the patient, (2) modifying for Ga-67 SPECT methods that have previously been developed for estimating activity within volumes of interest using a priori boundary information from registered CT images, and (3) designing a new collimator, tailored for Ga-67 quantitation in body imaging. These aspects of the imaging system will be optimized and evaluated on the basis of performance in several quantitative imaging tasks. The tasks to be considered, prototypes of tumor quantitation in the chest and abdomen, will involve estimation of activity concentration and size of lesions located in anatomically realistic backgrounds. For each of these tasks, Cramer-Rao lower bounds on variance or mean-squared error will be computed to determine the best possible performance for different correction methods, while maximum-likelihood or Bayesian parameter estimation will be used to measure best realized performance. Volume-of-interest activity estimation with resolution recovery will be used to assess clinically realizable performance. The investigators will measure, by simulation and phantom experiment, the improvements in performance in these tasks, and compare the results with theoretical bounds on performance. They will also consider clinical classification tasks related to non-Hodgkin s lymphoma. It is expect that the proposed imaging system improvements will lead to more accurate staging of lymphoma patients and, consequently, improved patient care due to enhanced capability to follow the progression of disease, choose the best treatment, and monitor the response to therapy.

DESCRIPTION (provided by applicant): We propose to purchase a high performance, multiscale, single-photon emission computed tomographic (SPECT) scanner to be used by researchers at Harvard Medical School (HMS), the Harvard School of Public Health (HSPH), and the adjacent HMS-affiliated teaching hospitals to image animals ranging in size from transgenic mice to large primates, as well as phantoms for physics research on new imaging techniques. The system will consist of a large field-of-view triple-head SPECT instrument with enhanced capability, through the addition of multiple pinhole collimators, for high-resolution (1-2 mm FWHM) imaging of rodents. This instrument will provide HMS researchers with the ability to image three-dimensional distributions of long-half-life radionuclides, as well as the capability, unique to SPECT, for simultaneous imaging of dual isotopes. The HMS campus is an ideal environment for optimal use of this instrument. The proposed location is adjacent to a 4.7T research MR animal imager, facilitating fusion of the SPECT images and MR images, and in close proximity to the Rodent Histopathology Core Facility of the Dana-Farber/Harvard Cancer Center. Also adjoining the proposed SPECT facility are the radiobiology and radiopharmaceutical chemistry groups, comprised of researchers who can radiolabel ligands with the required single-photon emitters, as well as a SPECT physics research group who will ensure state-of-the art quantitative SPECT imaging, customized for the users, by developing application-specific reconstruction algorithms, new correction methods, and new collimation tailored to certain biomedical imaging applications. The users of our research SPECT facility will pursue basic studies of molecular biology and genetics, development of new techniques for diagnosis and treatment of cancer, research on new radiopharmaceuticals for SPECT and positron emission tomographic (PET) imaging, basic studies of pulmonary physiology, research on Parkinson's disease and neurotransmission disorders, and development and testing of new techniques of correcting for systematic effects that can adversely affect the clarity and quantitative accuracy of SPECT images. The instrument will initially be used by 11 research groups, including 15 principal investigators, all of whom have their own external grant funding, primarily from the National Institutes of Health, but also from the Department of Energy, the US. Army, the Massachusetts Department of Public Health, the American Cancer Society, and the Dana Foundation.

[unreadable] DESCRIPTION (provided by applicant): [unreadable] The long-term goals of the proposed research are to improve the acquisition, reconstruction, and extraction of quantitative information from SPECT images of medium-energy radionuclides, and to assess these improvements to the imaging system using task-dependent criteria. Medium-energy radionuclides are becoming increasingly important for the diagnosis, staging, and treatment of cancer. During the first project period, we focused our attention on improving collimation and corrections for scatter and nonuniform attenuation for Ga-67 SPECT imaging, as well as on enhancing our techniques for Monte Carlo simulation of medium-energy photons. In this renewal application, we turn our attention to similar improvements to SPECT imaging of other medium-energy radionuclides, such as In-111, Lu-177, and Cu-67, that are playing an increasing role in cancer diagnosis and therapy. We will construct and evaluate new collimators, designed for Ga-67 during the previous funding period, and design, construct, and evaluate new collimation for In-111. Our experience in simultaneous dual-isotope SPECT imaging will be extended to radionuclide pairs that include medium-energy photon emitters. We will develop a new joint iterative algorithm, based on very rapid Monte Carlo simulation of scatter, crosstalk, and lead x-rays in several energy windows, to correct simultaneously for these phenomena on SPECT images of isotopes emitting multiple decay photons, as well as to accomplish simultaneous imaging of dual-isotope pairs. We will measure, using simulated data, as well as phantom and patient data, the improvements in activity and size estimation due to improved imaging procedures, and compare the performance achieved to theoretical bounds. We will also compare the utility of several gamma/beta-emitting nuclides (or nuclide pairs) on the basis of the accuracy with which radioimmunotherapy dosimetry can be accomplished. The feasibility of our simultaneous dual-isotope procedures will be evaluated on the basis of performance in two clinical tasks using patient images. The first is prediction of progression from low-grade to higher-grade NHL using simultaneous imaging of Ga-67 and TI-201, and the second is diagnosis of vertebral osteomyelitis based on simultaneous imaging of Ga-67 and Tc-99m-MDP. We expect that the imaging system improvements that will be accomplished during the proposed project period will lead to more accurate diagnosis, staging, and/or treatment of patients and, consequently, improved patient care. [unreadable] [unreadable]

DESCRIPTION (provided by applicant): The long-term goals of the proposed research are to improve the acquisition, reconstruction, and extraction of quantitative information from emission tomographic images of challenging radionuclides and to assess these improvements using task-dependent criteria. During the current project period, we have concentrated our efforts on complex radionuclides, e.g., 111In and 67Cu, as well as on simultaneous dual- radionuclide imaging of 111In and 99mTc. During the next project period, we will refine our research with these radionuclides;however, we will also extend the work in three new directions in order to address important technical challenges in pre-clinical emission tomographic imaging of mice, bremsstrahlung imaging of beta emitters used for radionuclide therapy, and reduction of systematic errors due to physical factors that currently limit the accuracy and precision of treatment planning in targeted radionuclide therapy. The imaging tasks that we will consider involve estimation of activity concentration in tumors or in regions of infection. We will measure, using simulated data as well as phantom, animal, and/or patient data, the improvements in task performance resulting from our new methodologies, and compare the performance achieved to theoretical bounds. We will consider clinical tasks related to treatment planning for radiotherapy of tumors expressing somatostatin receptors, as well as to treatment of hepatic tumors and metastases with 90Y- labeled microspheres, and to the diagnosis of osteomyelitis. We will extend our SPECT collimator design work to the case of simultaneous dual-radionuclide imaging, and to address the unresolved issue of whether collimator optimization on the basis of projection datasets is sufficient, or whether the collimator should be jointly optimized with the reconstruction algorithm. We will also develop and assess a reconstruction technique for bremsstrahlung SPECT, as well as a model- based procedure for correcting SPECT-CT and PET-CT images for the "partial volume effect." Finally, we will compare the performance of a Monte-Carlo based iterative reconstruction algorithm to that of a quantitative planar imaging approach for the diagnosis of osteomyelitis using dual-tracer data. PUBLIC HEALTH RELEVANCE: The proposed research will address technical challenges which complicate emission tomographic imaging of several radionuclides which are of value for diagnosis, treatment planning, and therapy of cancer, as well as for diagnosis of bone infection. The insights and improved imaging techniques which will emerge from this research will lead to better diagnosis and management of these diseases.