Initial Meeting of the
NCI Imaging Sciences Working Group
July 17-18, 1997Introduction and purpose of meeting:
Dr. Richard Klausner introduced the "Working Group concept," noting that the role of these "think tanks" is to identify an intellectually robust vision for new investment in particular areas of cancer (identified in the NCI Bypass Budget for fiscal years 1997-1998). It is expected that the Working Groups will make recommendations for actions that the NCI can take to advance research opportunities in these areas. An important element of the Working Groups is that they bring together diverse communities that often do not interact with each other. Therefore, as this group explores ways to enhance the contribution of imaging sciences to the understanding of cancer, Dr. Klausner encouraged them to consider the relationships between traditional imaging and the concepts of the molecular basis of cancer, including the detection of subtle genomic and molecular changes.
Dr. Klausner used the activities of the Developmental Diagnostics Working Group to illustrate how a Working Group has functioned and how the NCI has utilized Working Group Recommendations. The Developmental Diagnostic Working Group identified the need for the molecular characterization of normal, precancerous and malignant cells. The NCI responded to this need by developing the Cancer Genome Anatomy Project (CGAP), which includes the Tumor Gene Index (TGI) project, and several related Requests for Applications and Program Announcements.
Ms. Susan Waldrop provided guidance about Working Group meetings and interactions. Working Group participants will engage in discussions of the issues and needs related to high priority "investment opportunities." Participants were reminded that these discussions may include unpublished data and sensitive information that needed to remain confidential. Working Group recommendations are used by the NCI to develop and prioritize Institute goals and objectives, and serve as a platform for the development of operational plans by the NCI Divisions. The NCI staff develops specific requirements for any new initiatives or programs, which are reviewed by the appropriate NCI advisory committees. The activities of the Working Group are conducted under the auspices of the Advisory Committee to the Director, NCI.
Dr. David Bragg noted that the anticipated outcome of the meeting was to create a vision for the role of imaging sciences in the diagnosis, treatment and prevention of cancer.
Outcome of group discussion:
Ideally, an imaging device or technique will assist the oncologist with the following:
- Neoplasm Detection. The image should provide data about the biological significance of a given lesion (e.g., compute the numerical likelihood of malignancy) and monitor the transition of cells from a preneoplastic to neoplastic state. A combination of several technologies may be required to image the molecular and genetic characterization of tumors.
- Determine the Extent of Malignant Progression. The image should indicate the tumor phenotype, progression and heterogeneity of this progression, invasiveness, virulence, metastagenicity, angiogenesis, apoptotic mechanism, and microvessel density. The image should indicate the presence and location of metastases and the similarities to and differences from the primary tumor and each other in terms of genotype, phenotype, and physiology.
- Determining Anatomic Location of the Tumor (to the cellular level). The location of all cancer cells and concentration of tumor cells, as well as the tumor margins, should be determined at the molecular level. To increase the effectiveness of treatment modalities - surgery, radiation, and chemotherapy, which generally affect normal tissue as well as malignant tissue - and decrease associated morbidity, the size of the area treated must be made more precise.
- Understanding Tumor Physiology. The image should enable the oncologist to determine, for example, the metabolic activity of the tumor, observe such separate phenomena as scar tissue, necrosis, and host reaction (all in anatomic format), and track physiologic variations during treatment. Functional, structural, and physiological imaging resolution should be at the cellular level.
- Determine Relation of the Tumor to Normal Tissues. The image should aid the oncologist in mapping the tissues surrounding the tumor.
- Monitor Tumors. The ability to monitor tumors and their responses (e.g., to treatment) in real time is a priority. Monitoring may include defining angiogenesis, proliferation kinetics, metastatic potential, microvessel density, and genotype.
Issues and Barriers:
- The development of new imaging techniques should be driven by the needs and priorities of the biomedical community.
- The development of imaging technology should emphasize the detection of the dynamics of cell metabolism and function, rather than anatomic resolution. This will require the development of new instrumentation, and new types of contrast media and radiopharmaceuticals. It was noted that parallel advances in MR spectroscopy, new imaging techniques (e.g., optical imaging), and the exploitation of single photon and PET imaging, combined with opportunities in ultrasound, would likely be needed.
- The development of amplification techniques to visualize cellular metabolic activities is needed to image gene expression and to move toward in vivo molecular imaging.
- Improvements in imaging-related informatics to permit better and more cost effective techniques for the management, manipulation, storage and transmission of the complex images and large amounts of data generated from images in the clinical are needed. Such improvements are currently impeded by an inadequate infrastructure, lack of standard formats for image manipulation and interpretation, non-standard terminology and lack of guidelines for data interchange, and inconsistent guidelines for the use of informatics tools in medical practice. An interest was expressed in software and other tools that would enable the oncologist to efficiently compare images over time.
- Partnerships between government, academia, and industry are a critical part of produce development and should be actively pursued. The NIH can facilitate technology transfer by: helping to support clinical evaluation of new diagnostic imaging techniques; assessing the clinical value of new technologies; supporting new innovations through the start-up phase; and sponsoring workshops for industry/academia/clinicians/government to learn about opportunities to collaborate on new technologies (the NCI Digital Mammography Initiative was cited as an example of a successful collaboration between government/industry for technology development). A streamlined, responsive federal approval process for new medical devices is fundamental to the advancement of the imaging sciences field.
- Although images are collected and interpreted by people, there has been little study of human factors in image analysis. It was noted that the military has compiled an extensive body of information on the man-machine interface.
- The training of professionals in imaging sciences research, whether new scientists or experienced researchers/clinicians who wish to become proficient in imaging sciences research, is problematic because of the inadequacies of training programs in this area, including the limited laboratory time for trainees to conduct imaging sciences research. The group felt strongly that this issue needs to be addressed, perhaps through the creation of federally-supported training centers and/or programs.
Recommendations and Action
Seven task forces were established to address the above issues and challenges.
- Technology Assessment: Chair - William Hendee, Ph.D. This group will develop methods to evaluate the impact of new technologies and imaging agents and recommend a more efficient and less costly federal approval process for imaging devices.
- Training: Chair - Stanley Baum, M.D. This group will define a tailored, multidisciplinary research training program for both new and practicing imaging personnel. The group will consider the reasons why past training programs have not been successful to help ensure that future efforts are successful.
- In Vivo Molecular Imaging Development: Chair - Elias Zerhouni, M.D., This group is charged with identifying ways to understand and track genetic, molecular, biological physiological, and metabolic events in vivo, with the ultimate goal of tracking gene function in vivo. The group will discuss the concept of improved imaging based in radioactive tracer kinetic analysis of specifically altered biochemical processes that characterize the phenotype of human genes that predispose to cancer.
- Match Clinical and Biological Needs with Emerging Technologies: Chair - Michael Vannier, M.D. This group will identify ways to stimulate the development of emerging technologies (including optical imaging, MRS, fusion techniques, ultrasound, improved image analysis, image display, and data management), and will discuss ways to coordinate the development of these technologies with the priorities of the clinical and biological sciences, including partnerships between industry, academia/clinicians, and government.
- Screening and Early Detection: Chair - Charles Putman, M.D. The charge to this group is to identify tumor targets for which better detection approaches have the potential to improve disease management and survival. This group will initially address lung and ovarian cancer, and screening for individuals at high risk for cancer due to environmental exposures, genetics, or other factors.
- Technology Development: Mark Henkelman, Ph.D. This group will consider the history of the development of imaging technology as it formulates recommendations for encouraging the future development of instrument technology and pharmaceuticals (e.g., tracers, probes, and contrast materials). The group will also make recommendations about ways the NCI can bridge the gap between the discovery, development and application of new technologies, including the role of industry and the relationships between industry, biotech, academia, and government. Drs. Dahl, Hendee and Strausberg will assist with this effort.
- Image-Guided Treatment: Chair: Ferenc Jolesz, M.D. This group will define clinical problems appropriate for minimally invasive image-guided interventions, including refinement of techniques and the biological evaluation of therapeutic agents.
The task forces were given the following general charges:
- The Chairs were asked to think very broadly about participants for each task force to ensure that each group has the optimal representation to develop forward-thinking recommendations.
- The Chairs were reminded to consider industry in their discussion. "Industry" may include manufacturers of devices or software, as well as others, such as the movie or defense industries, who may be developing or using technologies that could be applied to imaging sciences problems.