Fusion Imaging: Where Form Meets Function

With the sum being greater than it parts, fusion imaging - largely of PET-CT images - is having a growing impact on cancer diagnosis, staging, re-staging and therapy follow-up. And the technology is beginning to stretch its wings into assessing oncology drug therapy, cardiovascular and neurological imaging and targeted radiotherapy.

Multimodality or fusion imaging is making its mark in diagnosis and therapy of cancer thanks to boosts in physician confidence and improvements in patient care. And it is beginning to earn believers in cardiac and neurology imaging applications.

The leading hybrid modality today is PET-CT. A positron emission tomography scanner uses small concentrations of radioactive material injected into the blood to show concentrations of cancer cells in color spectrum, while computed tomography scanners produce cross sectional x-rays of the body. By combining the two modalities, radiologists and nuclear medicine physicians possess images that combine metabolic function and anatomic form. Tumors can be located more accurately and physicians can determine whether or not it has invaded other nearby structures or spread elsewhere in the body.

"This is a rapidly moving and evolving field," says Richard Wahl, MD, director of nuclear medicine/PET and vice chair of technology and business development at Johns Hopkins Medicine. "Virtually any study that has been looked at with PET-CT is at least as accurate as and generally more accurate than PET and CT done alone."

Embraced as a better diagnostic tool in the spectrum of cancer care, PET-CT has fueled market numbers, too. In 2002, Frost & Sullivan estimated that PET-CT garnered 45 percent of the overall PET market and within one to two years could surpass standalone PET systems in total sales. According to the American Society of Radiologic Technologists (ASRT), an estimated 150 PET-CT units were in operation in 2002 and 225 units by 2003. By the end of 2004, more than 400 units will have been sold to hospital-based nuclear medicine, CT or radiation therapy departments as well as outpatient center-based radiology and oncology departments.


PET-CT was developed jointly by David Townsend, PhD, senior PET physicist and professor of radiology at the University of Pittsburgh School of Medicine and Ronald Nutt, PhD, president of CPS Innovations, Knoxville, Tenn. The first prototype was tested at University Pittsburgh Medical Center (UPMC) from 1998 to 2001 and results from the trials led to the FDA approval of PET-CT as a diagnostic tool for cancer in October 2000.

Since 1998, UPMC has performed 8,000 PET-CT scans. The facility uses two Reveal-RTs (CPS Innovations), a dual-slice Lutetium oxyorthosilicate (LSO) PET-CT scanner and a Bismuth sermante (BGO) single slice PET-CT scanner. The systems, located in the PET center of the facility separate from both nuclear medicine and radiology, are used for the diagnosis, restaging and therapy planning for cancer. "Since 1998, many studies that we do have changed patient management solely because of the fusion scanner," says Todd Blodgett, MD, radiology resident at UPMC.

To date, fusion imaging is only reimbursed by insurance companies for a number of malignancies. The Centers for Medicare & Medicaid Services (CMS) offer Medicare coverage for non-small cell lung cancer, lymphoma, colorectal cancer, melanoma, head/neck cancer, esophageal cancer, breast cancer and thyroid cancer. Malignancies that will most likely benefit from hybrid imaging but are not yet covered by Medicare include small cell lung cancer, ovarian cancer, cervical cancer, testicular cancer, pancreatic cancer, multiple myeloma and soft-tissue sarcoma.

Reimbursement is hindering private practices and imaging centers from purchasing the expensive modality, with PET-CT systems ranging in cost from $1.5 million to $3 million. A 16-slice CT with high-resolution PET scanner is significantly more expensive than a dual-slice scanner and a regular PET system. No fixed CPT codes exist for PET-CT. "Basically, you have two options," explains Blodgett. "You can either charge for PET only or you can charge for PET and CT. At UPMC, we bill for both the CT and PET portion of the exam and that's because we are using contrast [agents]."


Many academic medicine centers administer contrast agents (oral or intravenous) for the CT portion of the PET-CT exam because they have a credentialed radiologist on board to interpret the diagnostic study. "A lot of community-based facilities only have a nuclear medicine physician reading the PET-CT because they do not have the experience to read a CT," notes Blodgett. "Those facilities are not doing diagnostic quality CT; they are just doing a low-dose CT for localization purposes."

PET-CT technology is wedged between radiology and nuclear medicine and who exactly should interpret the exams has sparked much debate in the imaging community. Like Blodgett says, academic centers have both a radiologist and a nuclear medicine physician to read each portion of the exam and generate a dual report. UPMC even has three dually trained physicians in radiology and PET who can read the fused studies themselves.

The University of Maryland Medical Center installed a Philips Medical Systems Gemini PET-CT six months ago "and are finding ourselves becoming more and more aware of the fact that our training has to expand," says Bruce Line, MD, professor of diagnostic radiology and director of the division of nuclear medicine.

"In an academic practice such as ours, there are specialists in various organ systems and body regions," continues Line. "For example, the neuroradiologist, thoracic radiologist and the abdominal radiologist partition the body according to their areas of expertise. That poses logistically a challenge for us when we read a patient with disseminated disease. We find commonly that we have to get multiple specialists to drop into nuclear medicine to finish a case."

What about the technologists? The ASRT reports that there are fewer than 5,000 technologists who are certified in both radiology and nuclear medicine and fewer than 200 technologists certified in both nuclear medicine and CT. The national numbers have a direct impact on the centers that own and operate PET-CT scanners. Right now the Stanford University Medical Center cannot perform CT studies with contrast. "Now a PET tech can still do the CT without CT certification, but they cannot inject contrast, which is important," says Andrew Quon, MD, assistant professor of radiology and nuclear medicine at Stanford. "Our strategy is to take one of our current CT techs and put them through a PET training course, which takes about four months."


The challenges of reimbursement, training and staffing aside, PET-CT is becoming a revered technology. Physicians not only gain the ability to localize tumors better, but the technology helps in determining whether or not a patient needs a biopsy or surgery. Physicians also can use the fused data sets to assess how well patients are responding to chemotherapy and other treatment regiments.

"Fusion imaging, and specifically PET/CT, has increased our sensitivity for detecting cancer and it's increased the specificity of the diagnosis and made our diagnosis more confident based on the higher quality information," says Edward Coleman, MD, professor of radiology and director of nuclear medicine at Duke University Medical Center. The facility images about 15 to 20 patients daily on GE Healthcare's Discovery ST PET-CT system. "At our institution, we also have a dedicated PET scanner," notes Coleman. "All of the whole-body oncology studies are done on our PET-CT and brain and research studies are performed on our PET device."

Since UPMC also has multiple scanners, the physicians developed a triage method for patients who should only be scanned with PET and patients who should get a PET-CT. "In general, it comes down to patient population - solitary pulmonary nodules and lymphoma patients in whom you have a low suspicion of residual disease - get PET," says Blodgett. "All other malignancies get PET-CT."

When performing the PET-CT exam, physicians hope for as little body movement as possible as to not cause distortions or artifacts to appear in the fused data sets. This is difficult because the CT scan can take anywhere from 25 to 90 seconds (depending on the number of slices) and the PET portion of the exam takes 10 to 30 minutes. There are ongoing efforts to figure out how to eliminate the distortions, which should improve the performance of the scanners and the quality of the fusion of the two studies.

The University of Maryland Medical Center images four to five patients daily on its PET-CT scanner and expects that number to "rise as new indications and expanded use pushes the envelope of PET-CT," says Line. About 95 percent of patient volume now is associated with oncology in the area of diagnosis, staging, re-staging and therapy follow up. "We are starting up a program with radiation oncology and we are seeing a number of patients coming from that source," adds Line. "We also are working on a nuclear cardiology side of PET-CT. So in addition to oncology patients, we will study patients for cardiac disease as well as radiation oncology treatment planning."


Multimodality imaging also is finding a niche in targeted radiotherapy. While more research is needed to suggest that the technology is decreasing the reoccurrence rate of patients treated for cancer, the combined anatomical and functional information is boosting the confidence of radiation oncologists in treating cancer. At the Florida Radiation Oncology Group in Jacksonville, radiation oncologists are using Siemens Medical Solutions' biograph PET-CT to identify targets for treatments in the beginning and targets for boosting in the end.

The system is situated on a medical coach that travels to multiple locations in Northern Florida. John Wells, MD, a radiation oncologist with the practice, says the PET and CT information is taken from the scanner in DICOM format and imported on a treatment planning computer, which is where the fusion occurs. "I think the way to look at it is that the rules that we defined for treatment are still the same," says Wells. "But you define the initial shape of your field better. Most importantly, when you go to boost therapy, you can identify sites that need boosting much better than you could before."

Wells notes that the PET-CT scanner also allows for tremendous throughput because a procedure that used to take 40 to 45 minutes now takes 20 minutes. The traveling component to the system helps reduce the expense because it serves many communities. "The system is excellent for us because we needed a high-resolution scanner to help us in the planning and then the PET comes in on top of that" says Wells. "Structure helps in identifying the areas of concern, but a lot of times you may just have some scar tissue or other tissue around the area that does not have anything to do with cancer and may be confusing. This lets you see better where you want to target."


The future of PET-CT, and fusion imaging in general, is promising. Many PET-CT systems now are sold as 4 and 8-slice systems. As the newer generation of CT scanners with higher resolution - such as 16, 32 and 40-slice systems - become more prevalent in the marketplace, imaging capabilities will expand.

"With a 16-slice CT scanner and PET system, you can start to do very sophisticated cardiac imaging that includes virtual angiography on the CT side," opines Stanford's Quon. "In the future, you will be able to actually overlay a PET cardiac perfusion and viability image with a cardiac CT angiogram and therefore in a single study assess how well the heart is being perfused, whether or not there is infarct or hibernating myocardium, and attribute these abnormalities to specific vessels seen on the CT angiogram."

The University of Maryland's Line is enthusiastic as to PET-CT applications in cardiac applications in the next several years. "There will be a lot of new exciting developments in cardiology as we get highly resolved anatomic images from the CT and correlate them with the PET images," Line says. "There also will be a lot of exciting new areas where therapy will be impacted from PET-CT, both from the standpoint of external radiation sources and internal radiation sources. A large fraction of what we do in nuclear medicine will be redefined from a hybrid or fused standpoint - from the standpoint of PET-CT and from the standpoint of SPECT/CT."

Johns Hopkins is very committed to using anatomical and fusion data, says Wahl. In addition to PET-CT, the facility owns four SPECT/CT scanners. "We have a higher confidence in our diagnosis," relays Wahl. "I think that with SPECT/CT and PET-CT we are achieving higher accuracy with less uncertainty in our diagnosis. In most cost/benefit schemes, the cheapest diagnosis is an early, accurate diagnosis. It is very helpful to get an early accurate diagnosis. I believe that by combining form and function we are achieving that."

The Cost-Effective Fusion Software Option

The versatility of fusion imaging software ranges from combining images captured on PET-CT and SPECT/CT systems to the merging of data sets acquired on different modalities, such as CT, MR, PET and SPECT - oftentimes acquired on different days and sometimes in different medical facilities. The technology is not only a lower-cost option used by private practices who cannot afford hybrid modalities. Duke University Medical Center and Johns Hopkins, two healthcare organizations that own hybrid scanners, use fusion software to combine images such as PET with MR or PET with CT acquired on different scanners. And the clinical applications of fusion software are expanding.

"The premise of PET-CT or SPECT/CT is you have a functional modality with an anatomical modality," says Joel Leong, MD, medical advisor at Mirada Solutions Ltd. (acquired by CTI Molecular Imaging Inc. in August 2003). "The clinical utility is providing an anatomical reference for functional imaging data. In the other instances when you are fusing CT/MR, sometimes your MR study does not provide you with adequate information or vice versa. With mono-modality fusion software where you are doing CT/CT or MR/MR, fusion coupled with quantification is quite a powerful tool in assessing the effectiveness of a therapy."

For example, fusing the pre- and post-chemotherapeutic CT scans of a patient gives physicians the opportunity to gain an accurate and objective understanding of what is happening within a tumor, says Leong. Mirada sells the Reveal MVS Workstation and package fusion technology as a plug-in for OEM vendors.

In addition to assessing a change in pathology, fusion software also is used by radiation oncologists in radiation treatment planning and surgeons who want to look at different studies taken over an extended period of time.

Software fusion takes place on a non-rigid and non-linear level. The latter, otherwise known as deformable fusion, can change the parameters of one image to match the other. "This software morphing technology may be useful as a supplement in our setting, where we already have hardware fusion, because there may be subtle shifts in anatomical structures between PET and CT portions of the exam," says Andrew Quon, MD, assistant professor of radiology and nuclear medicine at Stanford University Medical Center. "Software morphing can correct these shifts in location, particularly in the head and neck and around the diaphragm."

Fusion Diagnostic Group LLC. (FDG) in San Francisco is a PET imaging center specializing in inter-modality fusion imaging. The center uses Hermes Medical Solutions' Multimodality Fusion software to fuse PET/PET, PET/MR, PET-CT, PET/SPECT and MR/MR images. "The software does not care, it just wants to take imaging information that's in DICOM format and do a three-dimensional co-registration," says Steven Bunker, MD, medical director at FDG. In FDG's case, the software is an alternative to a hybrid scanner because of limited reimbursement and a small referral base.

"The monetary thing is not insignificant for anyone who is trying to make ends meet on a center in a competitive market," opines Bunker. "It is good for those facilities that want to get into fusion imaging without having to sink a million dollars into it until maybe after they have developed their market pretty well. The fusion software is really a good alternative."