SPECT/CT settles into variety of clinical practice settings

Contributions to cardiology, oncology, and infection imaging continue, while potential applications emerge from unexpected directions

SPECT/CT has been tagged, rather unkindly, as a modality solution looking for a problem. But as early adopters are showing, it has considerable potential as an all-rounder in busy nuclear medicine departments.

Nuclear cardiology is a prime example. All SPECT images are subject to a certain degree of spatial distortion, caused by differing scatter and absorption of emitted photons before they reach the detector. Correction for this likely attenuation is especially important in cardiac SPECT, where soft-tissue attenuation artifacts can become confused with perfusion defects. Such artifacts can also mask signs of coronary artery disease.

Attenuation correction can be performed relatively easily on hybrid scanners, using anatomic maps derived from CT. The results are impressive, according to Dr. Robert Iwanochko, an assistant professor of medicine at Toronto Western Hospital in Canada, who started using SPECT/CT in the hospital's cardiac center this spring.

"We look at all the information, both corrected and uncorrected, so we can see a clear advantage using CT for attenuation correction," he said. "Transmission-based correction is dying. That technology will probably not even be available in two or three more years."

Approximately 30 patients a day undergo SPECT at Toronto Western's cardiac center. One-third of these will be directed onto the hybrid scanner. Patients with a high body mass index are usually directed to the SPECT/CT system, given that attenuation artifacts are theoretically worse in obese subjects.

Iwanochko is keen to test how SPECT/CT fares against a top-class rival. The gold standard for attenuation correction in perfusion imaging at present is rubidium-82 PET, he said. A head-to-head comparison between the two techniques is likely once the planned installation of a new PET scanner at the cardiac center has been completed.

For now, however, Iwanochko is concentrating on building experience with SPECT/CT. Time will tell whether the hybrid scanner lives up to its promise of improving diagnostic confidence.

"The 'equivocal/probable' category tends to shrink when you have good attenuation correction, and that's what we are hoping for," he said. "Patients are either assigned a defect on the basis of SPECT imaging, or they are assigned to be normal."

The 16-slice SPECT/CT system up and running since July 2005 at Baptist Hospital in Miami, Florida, was purchased primarily with cardiac applications in mind. Approximately 60% of the workload is now cardiac SPECT/CT, according to Dr. Jack Ziffer, chief of radiology. A second system is due to come online once room renovations are complete, which will ease demands for time on the hybrid scanner.

Attenuation correction for myocardial perfusion imaging has proven to be robust, Ziffer said. Prone scans are now unnecessary in nearly all cases, leading to faster examinations. Diagnostic-quality CT also permits coronary calcium scoring to be carried out while patients are still on the table. If calcium scores indicate a low risk of myocardial infarction, patients may then be triaged home without the need for stress testing.

Achieving a good match between the CT and SPECT images was not automatic, Ziffer said. CT data for attenuation correction had previously been acquired on a nondiagnostic scanner during respiration. The images may have been blurred, but at least they fit well with the cardiac SPECT data, which were also acquired during respiration. Moving to 16-slice CT raised the question of exactly when to image: during slow breathing, inspiration, or expiration?

"We have learned that end-tidal expiration is the best time to do the CT," Ziffer said. "We still use a software application to align the heart with the mediastinum, because sometimes the nuclear and CT images are not exact. That's an important piece for getting good cardiac attenuation correction."

The six-slice SPECT/CT system acquired by The Cleveland Clinic Foundation in Ohio is similarly being used for both attenuation correction and calcium scoring during cardiac examinations. Time for cardiac studies is limited, however, given competing demands on the system from other specialties, said Dr. Donald Neumann, director of molecular oncologic applications. The real advantages of hybrid imaging are crucial when it comes to scheduling.

"We have tended to focus on larger patients, with the hope of removing some of the problems associated with attenuation artifacts," he said. "But it is premature at this point to say which cardiac patient is going to benefit most from that unit."

LOCALIZING PATHOLOGY

Many neurologic applications are also likely to reap benefits from SPECT/CT through superior attenuation correction, according to Neumann. Where oncology can gain is through anatomic localization.

Nuclear medicine techniques are adept at seeking out areas of malignancy. The growing armamentarium of radioisotope tracers is also widening options for cancer diagnosis, staging, and follow-up far beyond FDG-PET. The poor spatial resolution of nuclear medicine images can make it difficult to pinpoint the exact location of pathology, however, with important implications for therapy planning and the use of imaging to monitor treatment efficacy.

Overlaying PET or SPECT images with CT data can provide the ideal combination of functional and anatomic information in a single view. If both sets of data have been collected in the same examination, making a good match is likely to be much easier.

Patients undergoing indium-111 octreotide studies, meta-iodobenzylguanidine (MIBG) studies for neuroblastoma, and In-111 Prostascint for prostate antibody imaging are all routinely scheduled onto the Cleveland Clinic's SPECT/CT unit. Cases of hyperparathyroid tumors and suspected hepatic hemangiomas are evaluated on the hybrid system as well.

"On occasion, we also get a call for evaluation of an abdominal mass, with the suspicion of a possible accessory spleen or splenic remnant, and those will definitely be performed on the SPECT/CT, too," Neumann said.

The improved capacity for anatomic localization has yielded additional benefits in lymphoscintigraphy.1 The lymphatic drainage pattern is often ambiguous in patients with head and/or neck melanomas, he said. Surgeons looking for help in localizing the sentinel lymph nodes have found that coregistered CT and SPECT images provide the information they require.

"I used to be able to say 'I think there's a sentinel lymph node in the right neck.' Now I can tell 'There are three sentinel lymph nodes: One is at right level Ib, the second one is at level Va, and the third is at level III on the right," Neumann said.

Sentinel lymph node mapping is also much quicker when using a single SPECT/CT unit, according to Dr. Shahid Mahmood, clinical director of Mount Elizabeth Hospital in Singapore. Mount Elizabeth's nuclear medicine and PET center receives patients from Malaysia, Indonesia, and Thailand as well as from Singapore itself. The new six-slice SPECT/CT unit, which came online in September 2005, is also being used in diagnostic oncology to improve the throughput and accuracy of octreotide studies and parathyroid imaging.

Dr. Homer Macapinlac, chair of nuclear medicine at M.D. Anderson Cancer Center in Houston, Texas, was so confident that SPECT/CT would benefit the center's oncology practice that he supported investment in five new multislice hybrid scanners. All systems came online together for clinical work at the start of this year. Now physicians are working to gain experience with the protocols they have instituted.

One prime area of use is likely to be screening for bone metastases in patients with breast or prostate cancer. Nuclear medicine bone scans, on their own, can often suggest that patients are getting worse, Macapinlac said. So-called flare phenomena can be misinterpreted as metastatic progression when, in fact, patients are responding to treatment. Performing CT with SPECT could confirm this by showing whether lesions are becoming more calcified. This finding would then remove the need for a follow-up bone scan in three to six months and reduce unnecessary patient anxiety.

"This could make us more efficient and effective, in diminishing the number of times we scan to try and evaluate whether these patients are getting better or worse," Macapinlac said. "Having CT together with SPECT should make this a stronger modality for evaluating metastatic disease."

Other diagnostic oncology applications at M.D. Anderson include In-111 octreotide for neuroendocrine tumors, I-123 MIBG imaging of neuroblastomas in pediatric patients, and presurgical localization of parathyroid adenomas using technetium-99m 2-methoxy isobutyl isonitrile (MIBI).

"I now ask myself why we never had these machines before," Macapinlac said. "The additive information from the SPECT and CT together make them potentially more powerful and accurate than the separate studies. SPECT contributes to the interpretation of the CT study, and vice versa."

Another issue physicians must grapple with is how to deal with patients whose scans may have been misdiagnosed in the past, Macapinlac said. Previous reports based on separate SPECT and CT scans may have failed to identify true malignancies and/or benign lesions because findings appeared ambiguous.

"With the better imaging we now have, we are trying to update the status of our patients in the best way that we can," he said. "It's not just identification of disease but also the identification of what is benign. That can be more important than the identification of the cancer itself."

Most SPECT/CT studies performed at Maasland Hospital in Sittard, the Netherlands, are likewise related to oncology applications. The hybrid system, which has an integrated dual-slice CT scanner, came online for clinical work in August 2005.

All patients suspected of having bone metastases are now scheduled for a SPECT/CT scan. This helps differentiate true metastases from, for instance, signs of trauma or degenerative joint disease, said Dr. Paul Thimister, a nuclear physician at Maasland. Meanwhile, sentinel lymph node imaging for breast cancer patients and imaging of patients with parathyroid tumors are proving to be of considerable use to the surgical team.

"We have seen some very small parathyroid tumors, and with the combined SPECT/CT, we were able to locate the node exactly. We had two patients in which this was in the mediastinal region, so it was very important for the surgeon to know whether he had to perform a sternotomy to reach the node," Thimister said.

Upgrading to SPECT/CT has made presurgical assessment of parathyroid adenomas a great deal easier, according to Ziffer. Prior to installation of the hybrid scanner, patients first underwent planar imaging and SPECT with Tc-99m MIBI. Adorned with appropriately placed radiopaque markers, they would then be moved to a separate unit for neck CT.

The strategy provided surgeons with sufficient anatomic detail that they could perform accurate parathyroid adenoma surgery extremely quickly, Ziffer said. But nuclear physicians and patients had to cope with a relatively cumbersome procedure. Now all imaging can be performed on a single machine, removing the need for markers and movement between scanners.

"This has streamlined things and made image registration much more exact," Ziffer said.

At New York City's Lenox Hill Hospital, oncology applications have taken a back seat to other uses. Here the year-old 16-slice SPECT/CT system is more often used to seek out signs of infection, using the radioisotopes In-111 and gallium-67. As with oncology, infection imaging is another area of nuclear medicine that can benefit from the greater anatomic localization provided by SPECT/CT. More accurate identification of infection sites can assist considerably with treatment planning.

ORTHOPEDIC OPTIONS

The biggest impact of SPECT/CT at Lenox Hill, however, has been in orthopedics, according to Dr. Stephen Scharf, chief of nuclear medicine. Scharf is using the hybrid system to improve presurgical evaluation of the large number of patients referred to nuclear medicine with chronic foot pain. Surgery is generally regarded as a last resort for these patients. Bone scans are typically performed prior to intervention, so surgeons can double-check that their planned strategy is targeting the correct area.

"When we moved to doing this patient group on SPECT/CT, we found that the detail we could give the surgeons was in some cases sufficient to change their mind about whether to do surgery," Scharf said. "It gives us tremendous anatomic detail and allows us to characterize pathology in a way that we have never been able to do before."

A considerable number of arthritic patients with chronic pain in the arches of the foot, or the midfoot, will benefit from drastic surgical intervention such as bone fusion, Scharf said. But intervention may not be the best option for patients whose pain is actually due to an occult fracture or past traumatic episode. SPECT/CT helps differentiate between these two patient groups by distinguishing focal activity along a joint line from activity within the bone itself.

SPECT/CT changed the management of one of the first foot pain patients scanned with it, he said. Imaging sowed sufficient doubts about the wisdom of bone fusion that the surgeon opted instead to administer a local anesthetic and steroids under fluoroscopy guidance. One year later, the patient has yet to experience any recurrence of pain.

The combination of functional and anatomic data may also aid assessment of patients scheduled for spinal surgery, Scharf said. Experience from a handful of patients scheduled for vertebroplasty has highlighted the significance of seeing anatomy in more detail. Vertebroplasty can be an extremely effective way of alleviating pain caused by disc degeneration. But surgeons are unlikely to cement all abnormal discs lest procedures become too long, too expensive, and subject to greater risks. Morphing CT and SPECT data can indicate exactly where the needle should be placed.

"We had one dramatic case in which it was clear that if we had left the surgeon to his own devices, he would have chosen the wrong one," Scharf said. "The abnormality on the bone scan was right at the junction of two vertebrae. The one that was collapsed turned out not to be the one that was abnormal."

He acknowledges that orthopedic imaging is somewhat of a bonus area for SPECT/CT. Little if anything had been said on this topic when the hybrid systems were launched. One reason is likely to be the rise of MRI for musculoskeletal imaging, especially in the U.S. In the face of such competition, many orthopedists have abandoned bone scanning for all but a few specialized areas, Scharf said.

"Around here, I've got 10 MR scanners within 10 blocks," he said. "But now the foot surgeons have started to come back and look at this as an interesting technology, and we are starting to do all of our vertebroplasty patients on SPECT/CT."

Dr. Paul Shreve, a radiologist with PET Medical Imaging Center and Advanced Radiology Services in Grand Rapids, Michigan, has similarly identified vertebroplasty as an important application for SPECT/CT. He hopes to start working with a hybrid scanner later this year.

"Sometimes it is hard to figure out which vertebral body is hot on the bone scan, and what it corresponds to on the CT scan. With SPECT/CT, we will be able do both examinations at once, and everything will be aligned correctly," he said.

In Europe, where MRI has yet to exert as strong a grip on musculoskeletal imaging, early adopters of SPECT/CT have been quick to spot potential benefits in this area. The first patient imaged with SPECT/CT at Maasland Hospital demonstrated the potential of hybrid scanning to orthopedic applications. The patient was suffering from low back pain, and after bone scintigraphy, clinicians suspected osteomyelitis. But CT data from the region of interest identified on SPECT revealed a fracture in the lower spine and spinal compression. Instead of receiving antibiotics, as had been planned, the patient was scheduled for corrective surgery.

Orthopedic problems make up a significant proportion of cases evaluated on the dual-slice SPECT/CT system at the University of Erlangen in Germany. Clearly, no one would recommend that every patient with low back pain receive a SPECT/CT examination, said Prof. Torsten Kuwert, chair of nuclear medicine. But in certain cases, the hybrid scanner can resolve difficult differential diagnoses.

Kuwert is especially interested in the use of SPECT/CT to distinguish degenerative skeletal disease from bone metastases. An investigation is currently under way to assess the value of SPECT/CT in clarifying ambiguous findings from bone scans. Cancer patients undergoing whole-body planar scintigraphy with Tc-99m-labeled diphosphonates would traditionally have been scheduled for additional tests, including MRI, if the radiographs proved inconclusive.

Access to the hybrid scanner should permit necessary follow-up to be performed while the patient is still in situ, while also improving diagnostic accuracy. Early results from a group of 40 cancer patients suggest that the combined imaging approach does indeed yield considerable gain in specificity. Out of 31 lesions identified by enhanced tracer uptake on planar imaging, CT showed 11 to be osteolyses. A further 16 hot spots could be linked to degenerative changes, while only four remained ambiguous and warranted additional follow-up.2

EMERGING APPLICATIONS

Evaluation of SPECT/CT's clinical value has just begun. One niche application for SPECT/CT could be the evaluation of patients with renal colic, according to Ziffer. The warm climate and hard water in south Florida send more than the usual number of patients with kidney stones to Miami's Baptist Hospital. The standard workup for renal colic is an unenhanced CT scan of the abdomen and pelvis. While this is usually sufficient for diagnosis, it can sometimes be difficult to differentiate phleboleths from renal stones.

It can also be hard to glean prognostic information from the unenhanced scans. Administration of radiographic contrast to provide information on the degree of obstruction could easily mask a calcified stone, Ziffer said. He instead plans to administer Tc-99m mercaptoacetylglycine (MAG3) and the diuretic furosemide, then use SPECT/CT to gain an overview of kinetic and anatomic information.

"We do around 10 to 20 CT scans every day for renal colic," he said. "When patients come in, doctors want to know whether there is a stone, where it is, how big it is, and the degree of obstruction. With SPECT/CT, we could do this in one very quick study."

A number of other sites are investigating how SPECT/CT could improve applications where quantification is desirable. At M.D. Anderson, for example, researchers are using the dual modality to look at the distribution of therapeutic tracers. Candidates for investigation include I-131 for thyroid cancer and two treatments for non-Hodgkin's lymphoma: the monoclonal antibody Zevalin (administered first with In-111 and then yttrium-90) and Bexxar (administered as tositumomab and I-131 tositumomab).

Mahood is hopeful that SPECT/CT dosimetry studies may eventually lead to a more accurate measure of radiation delivery. Figures used currently in clinical practice are based on assumptions of organ mass. A low-dose CT scan should provide a better estimation of mass, volume, and radioisotope distribution, he said.

Kuwert is also subjecting the hybrid system to a trial for therapeutic oncology applications. Patients scheduled for Y-90 therapy for hepatocellular carcinoma are first injected with Tc-99m-labeled albumin to assess vascularity. CT data are acquired at the same time to determine the mass and volume of the liver and gain additional anatomic information on the target tumor.

"Before we got the SPECT/CT, we did this manually, and it was a very laborious process. It has become much easier to do the therapy planning with this system," he said.

Another area where SPECT/CT may aid quantification of functional information is ventilation-perfusion scanning. A combined imaging examination that includes a SPECT perfusion scan and also CT pulmonary angiography should provide a better assessment of residual lung function in acute patients with suspected pulmonary embolism, Mahmood said.

"If you do CT pulmonary angiography on its own, it is sometimes very difficult to see peripheral defects. But if you combine it with perfusion, it becomes easy to pick up where there is a perfusion defect," he said.

References

1. Lerman H, Metser U, Lievshitz G, et al. Lymphoscintigraphic sentinal node identification in patients with breast cancer: the role of SPECT-CT. EJNM 2005;33(3):329-337.

2. Romer W, Noemayr A, Uder M, et al. The value of SPECT/spiral-CT hybrid imaging in unclear foci of increased bone metabolism: first clinical results. Presented at annual RSNA meeting, Chicago, November 2005.

Ms. Gould is a contributing editor of Diagnostic Imaging.