Technological innovation is generally thought of as the creation of something new — a faster or more powerful way of accomplishing a task, or a capability to achieve more complex tasks than was previously possible. In reality, however, the true innovations are often the combining — or fusion — of existing technologies to create more efficient and accurate approaches to solving a given problem.
Dual-modality imaging systems are one such example of this approach to innovation. Combining or fusing high-resolution anatomical imaging such as x-ray, CT, and MRI with functional or physiological imaging from nuclear medicine techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT), dual-modality imaging offers great promise in the detection, staging, and treatment of numerous diseases.
At the forefront of dual-modality imaging technology development is the University of California at San Francisco (UCSF) Radiology Department, specifically its nuclear medicine section and Physics Research Laboratory. Working in close collaboration, these two subdivisions of radiology are helping merge the research and clinical components of dual-modality imaging in order to bring its benefits into greater use in everyday practice.
As one of the forerunners in dual-modality imaging technology, the Physics Research Laboratory (PRL) has a history that in many ways parallels the development of the technology itself. The PRL was founded in the early 1980s by UCSF researcher Douglas Boyd, who also founded a company that now markets electron-beam CT scanners. When Boyd founded that company to develop electron-beam CT technology, his remaining research was retained as academic projects in what is now the PRL.
The key function of this laboratory is to develop new x-ray and radionuclide imaging techniques. Researchers at the laboratory are involved in a spectrum of activities from the development of instrumentation, to fundamental work in modeling the transport of electrons and radiation in detectors, to computer programming, and algorithm development. Recently, the laboratory has initiated animal and human studies using its dual-modality imaging prototypes.
Within this broad mission, the technology focus of the PRL has evolved over time. When the laboratory started research in dual-modality imaging in 1988, its initial goal was to build a multimodality imaging system that would combine the anatomical imaging from CT with the functional imaging from SPECT — all in one device. With funding support from the National Institutes of Health, the laboratory built a prototype system with a detector that performs both x-ray and radionuclide imaging. The laboratory devoted approximately 6 years to working on this system, doing everything from designing mechanical and control systems, and implementing detectors and electronics for recording the radiation signals, to developing computer software for image reconstruction, image display, and data analysis.
Around 1994, however, the laboratory began taking a different approach to the dual-modality imaging question. Bruce Hasegawa, PhD, director of the PRL, explains: “A product manager from [a vendor] heard one of my talks on dual-modality imaging; this started a fruitful relationship with [that vendor] in which they provided us with equipment to build a more clinically usable system.”
The equipment that was provided has enabled the PRL to tackle dual-modality imaging from a slightly different angle. Rather than combining the anatomical and radionuclide processes in one detector, the current system has two separate detectors, one for each function, which are used to image the patient sequentially rather than simultaneously. Hasegawa continues, “In current medical practice, a patient might receive a CT or MRI scan on one day, and a nuclear medicine study on a different day. Even if the images are obtained on the same day, the patient often is imaged with different body positions, at different states of respiration or on patient tables having different contours — all of which will change the body shape and the relative locations of internal organs and structures, making it difficult to match features in the two images.
“We’re trying to develop systems that can perform both anatomical and functional imaging without removing the patient from the system. By developing a dual-modality imaging system, we can facilitate image fusion to improve the diagnosis of disease in the patient.”
PET vs SPECT
While the equipment at the PRL utilizes the technologies of CT for anatomical and SPECT for functional imaging, other combinations are possible. In fact, research being pursued at the University of Pittsburgh aims at combining (PET) with CT.
PET imaging’s power derives from the radiopharmaceutical it employs: fluorine 18-labeled deoxyglucose (FDG). Tumors have a particularly high affinity for FDG, allowing for greater accuracy of detection. In addition, PET provides better spatial resolution and better detection sensitivity than other nuclear medicine techniques.
On the economic side, PET’s current popularity has been significantly enhanced by recent Health Care Financing Administration (HCFA) indications providing reimbursement for PET imaging. With reimbursement in place, sales of PET scanners have practically doubled for each of the past few years, as FDG is now easily obtained almost anywhere in the country.
Given the interest in PET, why has the PRL chosen to focus on SPECT? Hasegawa explains, “Our laboratory has experience in specific detectors and methods that are more appropriate for SPECT than for PET. In addition, SPECT is less complex technically than PET, and when we started this project 10 years ago, PET was a clinical research tool that had not yet developed into a routine diagnostic technique. Finally, although it is impractical to image FDG with SPECT, there are tumor agents for SPECT that now are growing in number and in importance.”
Integration with Other Disciplines
As part of the larger field of nuclear medicine, dual-modality imaging has evolved from techniques already in place as part of that discipline. Although nuclear medicine developed originally as a branch of internal medicine, its focus on imaging has led it in the recent past to be much more highly integrated into environments such as radiology. As Randall Hawkins, MD, PhD, professor of radiology and chief of nuclear medicine at UCSF, notes, “In general, the integration of nuclear medicine with radiology is a good idea, because there’s an overall fundamental relationship among different kinds of imaging technologies. For example, virtually every patient we see has had other imaging procedures done, whether PET, CT, or MRI scans. Part of the clinical challenge is to correlate the patient’s clinical information as well as imaging information; this can be facilitated by employing radiology equipment.”
For patients, the combining of anatomical and radionuclide images can lead to earlier and more accurate detection and staging of disease. As Hawkins explains it, anatomical imaging shows structure, while nuclear medicine imaging shows function — physiological processes such as blood flow, or biochemical processes such as glucose metabolism and drug binding. Key to dual-modality imaging’s benefit is the fact that many disease states, particularly various cancers, start out as an abnormality of function, whether biochemical or physiological, before they produce an anatomic abnormality. Thus, use of PET or SPECT in combination with an anatomical image can frequently show evidence of disease that may not be visible through anatomic imaging alone.
Patients benefit in terms of more accurate diagnosis as well, as Hawkins explains: “Humans have superb visual perception skills and can look at images and determine what the relationship is among many structures. But one of the advantages of using a formal fusion technique is that the observer can be very certain that a given biochemical signal is actually coming from a specific anatomical structure, with a level of precision that may not be possible by just looking at the procedures alone if they’re not formally fused.”
This precision also allows for growth in an area that has so far eluded observers: quantification. With a fused image set, more accurate quantification of signals is possible, enabling clinicians to monitor treatment more accurately using numerical or computer-processing techniques applied to medical image data. By combining more information about anatomical and functional relationships in the body with better information about the quantification of the function, it becomes possible to make more accurate estimates of the biochemical and physiological processes involved in a given disease state for a given patient.
Funding and Reimbursement
Perhaps unsurprisingly, Hasegawa describes his role in securing funding for the ongoing activities of the PRL as “more than a full-time job.” Funding for the laboratory’s research in dual-modality imaging is supported primarily by the federal government, specifically from NIH grants. Additional research for diagnosis of specific diseases has also been underwritten by organizations such as the American Heart Association and the Department of Defense Breast Cancer Research Program.
When asked about the role of vendors in providing resources, Hasegawa replies, “We frequently talk to and interact with vendors and manufacturers. Resources are stretched in the private sector just as they are in the public sector. Therefore, we do not get large amounts of funding from industry; instead, it is usually equipment, software, and things like that. Also, if we have questions that have to be solved, we often can get specific answers from experts who work in the private sector.”
While Hasegawa has seen the amount of direct corporate funding decline during his years at the PRL, the opposite has taken place in terms of federal dollars. “When I got into this field in the late seventies/early eighties, the level of available government funding was reasonably good,” he recalls. “Then it took a dip, and it became very difficult to get grant funding. Now it’s starting to go up again. In fact, the NIH’s annual research budget just went up another billion dollars or so.” Make no mistake though, he cautions. “It’s still difficult overall. We all work hard to keep the laboratory financially afloat.”
Complementing the budget increase have been the federal HCFA reimbursements, which have led to a dramatic growth in the number of PET scans performed both at UCSF and across the country, particularly in the area of cancer. Although Hawkins explains that many centers have been doing PET scans for years and have been getting reimbursed by private insurers, he states that the major payment breakthrough over the past year is Medicare reimbursement for some indications for PET, which has had tremendous impact on the overall dissemination of the technology. What is more, he believes, the level of reimbursement from Medicare is usually commensurate to the cost of actually performing a given study, which allows institutions to at least recover their costs and makes continued research activities feasible.
Today and Tomorrow
The three words most commonly used in conjunction with the application of dual-modality imaging are “diagnosis,” “staging” and “cancer.” As Hawkins describes it, “So far, the primary general impact on patients across the country has been to improve diagnosis and staging in selective cancers, and also to help in identifying disease recurrence.”
Hasegawa expands on this idea: “We are focusing on cancer because cancer treatment is becoming much more localized in nature. People have developed techniques where they can deliver radiation dose to treat cancer very precisely. Therefore, you need to use imaging techniques to identify the specific location of a tumor so you can deliver the radiation dose appropriately. Using conventional imaging techniques, you either get an anatomical image, where it’s often difficult to detect a tumor, or a functional image, where you can detect the tumor but have little information about its location. If you’re going to treat the a patient, you need to know first that the tumor/disease exists; second, where it’s located; and third, how extensive it is. These dual-modality imaging systems can help to provide you with this complementary information.”
Currently, the PRL has funding to look at breast cancer, prostate cancer, and the childhood cancer neuroblastoma. The laboratory also is working to improve the diagnosis of heart disease, using a method in which a radiopharmaceutical is administered to the patient to map myocardial perfusion.
A key goal of the department’s dual-modality imaging efforts is to expand the use of the technology in treatment planning and treatment monitoring. This is done by following serial changes in quantitative estimates of blood flow or tissue metabolism, and monitoring the efficacy of different interventions, whether they be from molecularly targeted drugs, different forms of radiation therapy, or even surgery. This is a long-term process, as Hawkins explains: “It understandably takes a longer amount of time and more clinical experience to actually develop the kind of database one needs to make clinical decisions based on numerical changes alone. It has been predictable that the initial impact of this technology has been primarily in terms of the presence or absence of disease, which does not rely on quantification. This kind of data can be determined a little earlier in the process than other, more outcome-focused endpoints such as magnitudes of change.”
On the technical side, Hasegawa points to three key goals for dual-modality imaging in the future: first, to continually improve the ability to determine the extent of disease; second, to improve image quality by using a priori information from the structural image to correct perturbations in the nuclear medicine image; and third, to improve the quantitative accuracy of the measurement, enabling observers to actually quantify radiopharmaceutical uptake by the target tissue and by surrounding tissues in a way that provides more specific and reliable information about the disease.
Beyond that, Hasegawa mentions that there is still much work to be done. “We have to find out exactly what kinds of diseases, what types of cancers and so forth, can be assessed with this technique,” he says. “We are just starting to do that, and we have not pushed it very far. There will have to be new display techniques, new algorithms written, new ways of interpreting the data, and then ways of actually using the data that can help to guide surgery and radiation therapy in a more localized, specific way. We should be able to use the technology very specifically in planning treatment; however, that goal has not yet been achieved in a direct way.”
However much work lies ahead, both Hawkins and Hasegawa feel confident that they are in a world-class setting that can meet the challenge. As Hasegawa says, “We have great people here — the students, postdoctoral fellows, and other faculty members are all very bright and very qualified. All of the activity provides an environment that allows this kind of research to progress. It is hard to imagine doing this kind of research if I were working by myself in an isolated setting; the university provides a wonderful environment for pursuing developments of this type.”
Joe Sadusky is a contributing writer for Decisions in Axis Imaging News.