PET and SPECT nuclear imaging are emerging as preferred choices for detecting a broad range of cancers, often with superior accuracy than CT. But, what is the imaging specialist to do when a clear hot spot is seen on PET or SPECT scans but not clearly on CT or MRI? Computer fusion of images can be used but remains limited outside the brain. Fusing the form and function by acquiring both with a single device in a single imaging session, either SPECT/CT or PET/CT seems the answer. While such devices are still in evolution, both Dr. Hasegawa and Dr. Townsend have made such devices a reality. It is expected that such devices and their progeny will become increasingly common in imaging departments over the next few years. Form and function fused form the future of imaging.

Richard L. Wahl, MD
Director, Division of Nuclear Medicine
Johns Hopkins Medical Institutions
Baltimore, Md

Development of a combined PET/CT scanner

David W. Townsend, Ph.D.

Fusing technologies rather than images assures accurate spatial localization of functional abnormalities.

David W. Townsend, PhD

Multi-modality image fusion allows images from different modalities to be spatially registered and displayed as overlays, a powerful approach to the identification and localization of disease. When the modalities offer complementary information, such as anatomical and functional imaging, fused images can significantly enhance the diagnostic utility of the two modalities viewed separately. Image fusion is generally achieved through the use of software techniques that minimize the pixel-by-pixel differences between the two modalities. Such an approach works well for the brain, an organ fixed within the skull where sufficient common structures may be identified from both the anatomical and functional image sets. However, image fusion for other regions of the body is not as straightforward, owing to the lack of common anatomical details, the movement of internal organs, and differences in patient positioning and scanner bed profiles.

To address these difficulties, a prototype combined positron emission tomography (PET) and CT scanner has been developed, thereby fusing the technologies directly rather than the images postacquisition. In this design, a clinical, helical CT scanner images patient anatomy, while a clinical PET scanner images organ function. Both sets of images are acquired in a single scanning session so that they are intrinsically aligned. Accurate spatial localization of functional abnormalities, a unique feature of this approach, can then be achieved routinely for each patient study.

The PET/CT prototype is based on the combination of a third-generation, spiral CT scanner, with the PET components from a rotating partial ring tomograph. Both the PET and CT components are mounted on the same assembly, with the PET detectors on the reverse side of the rotating support of the CT scanner. The entire assembly rotates at 30 rpm and is housed inside a single gantry, with the centers of the two tomographs offset axially by 60 cm. The bed is installed at the front of the combined gantry and is used for both the PET and CT imaging. The bed travel allows dual-modality PET and CT images to be acquired for an axial extent of 100 cm, sufficient to cover a range from chin to lower thigh in most patients.

A typical PET/CT scan protocol consists of a 7-mCi injection of fluorine 18-labeled deoxyglucose (FDG) followed by a 60-minute uptake period, after which the patient is positioned in the scanner. A spiral CT scan is then performed covering an appropriate axial length of the patient. For head and neck cancers and some lung cancers, the CT scan is acquired with intravenous contrast, while for abdominal malignancy, the CT scan is acquired with oral contrast. The complete CT scan duration may be up to 5 minutes depending on the axial range covered. Following the CT scan, the patient bed is translated axially into the PET field of view and a multi-bed PET scan acquired over the same axial range as the CT. The PET scan may take up to 45 minutes with an acquisition time of 6-10 minutes at each bed position; the total PET/CT scan duration is less than 1 hour.

To date, more than 180 patients have been studied in the combined PET/CT scanner, covering a wide range of different cancers including head and neck, melanoma, lymphoma, lung, colorectal, and ovarian. The advantages of combined PET/CT imaging include accurate localization of functional abnormalities, distinction of pathology from normal physiological uptake, and improved accuracy in monitoring response to therapy. Other important potential applications that have yet to be explored include elimination of sampling errors in CT-guided biopsies, and reduction of the irradiated volume in radiation therapy treatment planning.

The studies performed with the prototype have demonstrated the importance of a detailed anatomical framework against which the functional images can be interpreted. The choice of clinical-quality CT images to provide that framework can potentially introduce functional imaging into application areas that are currently the exclusive domain of anatomical imaging. The clinical success of this prototype has stimulated the development of a PET/CT scanner that will become commercially available during the course of 2001. The commercial design is based on a high-end PET scanner and a state-of-the-art, mid-range CT scanner, and these dual-modality tomographs will enter into limited clinical trials at a number of key cancer centers in the United States and Europe beginning around mid-2001.

Case Study

Figure. A coronal section through the fused image showing a focus of FDG uptake in the left obturator lymph node area consistent with malignancy. The node was surgically removed and the pathology was positive for malignancy.

A 50-year-old woman was diagnosed with a primary adenocarcinoma of the left fallopian tube in 1996. The patient underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy. In early 1997 she presented with left inguinal lymphadenopathy, which was biopsied and confirmed to be metastatic adenocarcinoma. Five cycles of chemotherapy were completed. The patient did well until November 1998 when CT revealed left and right inguinal lymphadenopathy. Excisional biopsy confirmed recurrence of the adenocarcinoma. Pelvic and inguinal radiotherapy was undertaken and both nodules resolved. A follow-up CT scan of the abdomen and pelvis in December 1999 showed no evidence of disease. In response to a rising CA-125 marker, a clinical whole-body PET scan and a combined PET/CT scan were acquired in February 2000 to assess for recurrent disease. The clinical whole-body PET scan revealed a focus of moderate FDG elevation superolateral to the bladder on the left. This finding was equivocal from the clinical PET scan alone, as benign etiology such as ureteral diverticulum might also explain the finding. A PET/CT scan performed directly after the clinical study localized the lesion to the superolateral left pelvis, showing that this uptake was separate from, and lateral to, the ureter (see figure, page 14). A laparatomy was performed and, based on the PET/CT finding, a tissue mass was located in the left obturator lymph node area, consistent with the localization obtained from the combined PET/CT scan. The tumor was debulked and surgical pathology verified malignancy.

Using an emission-transmission system, dual-modality imaging methods utilize a priori structural information to improve accuracy of correlated physiological information

Fusion Imaging with CT/SPECT

Bruce Hasegawa PhD

Bruce Hasegawa PhD

Until recently, the complementary roles of structure and function in medical diagnosis had not been integrated in contemporary medical imaging systems. The gap between these resembles that separating anatomy and physiology; it can be bridged using dual-modality or emission-transmission systems, which perform both x-ray transmission imaging to obtain anatomical information and radionuclide emission imaging to extract functional information. These dual-modality imaging methods offer two features not available with conventional imaging: they facilitate coregistration of anatomical and physiological information and they use a priori structural information to improve the quantitative accuracy of correlated physiological information. One such dual-modality imaging system was reported in the Soviet patent literature in 1987,1 but apparently never was placed in clinical practice. A functional emission-transmission computed tomography (ETCT) system was implemented at the University of California San Francisco (UCSF) in 1990.2-4 The prototype system could perform CT and single-photon emission computed tomography (SPECT) simultaneously, but the radionuclide data were prone to contamination by x-rays produced at high rates by the x-ray tube.5 Clinical implementation of the ETCT system also was impeded by the cost of the large-area semiconductor detectors necessary for simultaneous emission-transmission imaging of humans.

For emission-transmission imaging in a clinical setting, the UCSF group configured a combined CT/SPECT system that incorporates a conventional x-ray CT scanner and a scintillation camera for dual-modality imaging.6,7 The system produces high-quality anatomical images with a conventional CT detector and a high-power x-ray tube, and it incorporates the large-area radionuclide detector needed to complete the nuclear medicine study in a practical scan time. The system has a common patient table so that sequential CT and SPECT images can be obtained without having the patient leave the table. The x-ray and radionuclide images from the CT/SPECT system are registered by applying rigid body rotation and translation of the data from the coordinate space of one imaging system to the other.6-8 This approach minimizes problems of patient motion, inconsistencies in patient position, or differences in functional status that can occur when two image sets are acquired on different machines at different times. The patient is asked to breathe quietly during both CT and SPECT scanning to minimize differences in respiratory state. Differences in cardiac motion are averaged by acquiring the CT and SPECT studies over more than one cardiac cycle, while peristalsis is minimized by acquiring the x-ray and radionuclide images in rapid succession.

CT (Top) and single-photon emission computed tomography (SPECT) (center) images acquired using CT/SPECT of a patient with prostate cancer who has been administered indium in 111 capromab pendetide. The CT/SPECT images (bottom) shows functional-anatomical correlation, which helps to delineate normal versus abnormal uptake of the radiopharmaceutical.

Image-warping methods have not been needed to correct for geometrical discrepancies between the two image data sets. At UCSF, the CT/SPECT methodology is being investigated to evaluate metastatic disease in patients with prostate cancer using indium In 111 capromab pendetide,9 and to evaluate axillary lymph node involvement using technetium Tc 99m sestamibi in breast-cancer patients.

The CT image can also be used to generate a patient-specific attenuation map to correct the emission data for photon-attenuation errors.6,7 The attenuation map is incorporated into a maximum-likelihood expectation-maximization (or other iterative algorithm) for reconstruction of the radionuclide images. In addition, quantitative errors in a radionuclide imaging system can be compensated for using a technique8,10,11 that defines objects in the CT image to model the acquisition of the radionuclide image. The correction factors obtained with this technique can be applied to the radionuclide image to compensate for photon attenuation, collimator response, scatter radiation, and other physical effects. Phantom studies of tumor imaging8,10 have demonstrated that this technique significantly improves quantification of the radionuclide uptake of simulated lesions in the phantom, in comparison with conventional techniques12,13 that quantify the radionuclide data without using correlated structural data from CT. Work at UCSF also has quantified the regional uptake of a myocardial perfusion agent (technetium Tc 99m sestamibi) in a porcine model.14 The CT/SPECT method reduced errors significantly, compared with myocardial perfusion measurements obtained using SPECT alone, either with or without attenuation correction. UCSF currently is using these techniques to perform accurate radiation dosimetry for patients undergoing radionuclide therapy for the treatment of neuroblastoma15 and other cancers.

UCSF is one site developing combined x-ray/radionuclide imaging systems, and dual-modality imaging now has progressed to a point at which it is becoming available for clinical studies. One commercial vendor has introduced a dual-headed scintillation camera that can perform planar scintigraphy or SPECT of conventional radiopharmaceuticals or coincidence imaging of positron emission tomography agents. The system16 also includes an x-ray tube and x-ray detector to generate transmission tomograms with 3-mm spatial resolution and a 10-mm slice width for attenuation compensation and for anatomical localization of the radionuclide data. The first systems have been installed and are now used clinically at several sites worldwide for both oncological imaging and myocardial perfusion assessments using radiopharmaceuticals. Dual-modality imaging systems at Vanderbilt University, Nashville, Tenn, and at Rambam Medical Center, Haifa, Israel, are being used to improve the diagnosis of endocrine neoplasms17,18 by enhancing lesion localization and by differentiating disease from normal radionuclide uptake16,19,20 with a variety of single-photon agents, including technetium Tc 99m sestamibi, iodine I 131, and iodine I 123 metaiodobenzylguanidine, as well as with positron agents such as fluorine F 18 labeled deoxyglucose (FDG). At Rambam Medical Center, researchers21 have evaluated lymphoma patients using dual-modality imaging of both FDG and gallium Ga 67. The Vanderbilt group22 has used dual-modality imaging to acquire FDG and medium-resolution (approximately 4-mm) CT images, which are registered with conventional high-resolution CT images for treatment planning for cancer patients undergoing external-beam radiation therapy. Researchers at Vanderbilt also performed a pilot study23 in which they concluded that attenuation correction by x-ray CT improves the diagnostic quality of myocardial SPECT images obtained with technetium Tc 99m sestamibi.

To date, most work with dual-modality imaging has focused on anatomical correlation of CT and radionuclide imaging of tumor-specific agents such as FDG.19,20,24 In this role, dual-modality imaging can help to differentiate tumor from normal tissue, which is important for staging the disease and for planning surgical or radiation treatment.22,25 Dual-modality imaging also improves radionuclide quantification (in comparison with conventional radionuclide imaging methods). These radionuclide quantification methods have a potential role in assessing tissue metabolism, in treatment planning for external-beam radiation therapy, in radiation dosimetry for patients undergoing radioimmunotherapy,15 and in myocardial perfusion measurements for patients with cardiovascular or coronary artery disease.11

David W. Townsend, PhD, is professor of radiology and acting co-director, University of Pittsburgh PET Facility, Pittsburgh PA.

Bruce Hasegawa, PhD, is a professor of radiology and bioengineering, University of California, San Francisco.


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