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Ann Thorac Surg 2002;74:160-163
© 2002 The Society of Thoracic Surgeons

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Original article: general thoracic

Impact of computed tomography-positron emission tomography fusion in staging patients with thoracic malignancies

^a Division of Cardiothoracic Surgery, Duke University Medical Center, Durham, North Carolina, USA
^b division of Nuclear Medicine, Duke University Medical Center, Durham, North Carolina, USA

* Address reprint requests to Dr D’Amico, Duke University Medical Center, Box 3496, Durham, NC 27710, USA
e-mail: damic001{at}mc.duke.edu

Presented at the Forty-eighth Annual Meeting of the Southern Thoracic Surgical Association, San Antonio, TX, Nov 8–10, 2001.

	Abstract

Top Abstract Introduction Patients and methods Results Comment Discussion References

 
Background. Positron emission tomography (PET) has been demonstrated to improve staging in patients with thoracic malignancies. This study evaluates the ability of a new imaging technique to improve the spatial resolution and accuracy of PET.

Methods. Patients with known or suspected malignancy (n = 21) who were referred for a dedicated PET scan were also evaluated with a new camera-based PET system, which uniquely allows simultaneous computed tomography (CT) and fusion of the camera-based PET images with the CT images. The dedicated PET scan was obtained 1 hour after intravenous injection of fluorodeoxyglucose. The camera-based PET imaging was fused with the CT images at approximately 2 hours after injection. The camera-based PET and CT-PET fusion images were read independently and blindly by 2 experienced observers and the presence and location of abnormalities was compared with dedicated PET scans.

Results. Dedicated PET identified 18 sites in the chest as abnormal. The CT-PET fusion was superior to the camera-based PET alone, concordant with the dedicated PET in 16 of 21 patients compared with 13 of 21 by camera-based PET. The lesions missed by the camera-based PET were less than 1 cm in diameter. Fused CT-PET images provided superior anatomic localization and spatial resolution compared with dedicated PET and camera-based PET.

Conclusions. CT-PET fusion images were more accurate than camera-based PET alone. CT-PET fusion improves the spatial resolution compared with dedicated PET and may improve the availability and efficacy of staging of patients with thoracic malignancies.

	Introduction

Top Abstract Introduction Patients and methods Results Comment Discussion References

 
The management of lung cancer, the most common cause of death by malignancy in both men and women in the United States [1], is dictated by the stage of disease. In the current staging system for nonsmall cell lung cancer (NSCLC), which considers the size and location of the primary tumor (T), the involvement of regional lymph nodes (N), and the presence of distant metastases (M), pathologic staging is considered more accurate than clinical or radiographic staging [2]. Although radiographic staging frequently understages patients, positron emission tomography (PET) has been shown to improve the detection of nodal and distant metastases in patients with lung cancer [3–8] and other thoracic malignancies [9–13].

There are several important limitations of PET in the staging of thoracic malignancies, including spatial resolution, false-positive scans, and limited availability. The use of PET in combination with other imaging modalities may improve the spatial resolution, sensitivity, and specificity [14]. Because of the improvements in electronics, gamma cameras are being used for PET as opposed to dedicated PET systems. The intrinsic resolution of these camera-based PET systems is comparable with that of dedicated PET scanners but the systems are less sensitive owing to the thin sodium iodide detector and the limitations of imaging with two cameras instead of with the thousands of independent detectors typical of dedicated PET scanners [15]. Camera-based PET has been developed as a less expensive alternative to dedicated PET and thus is more widely available; however, the spatial resolution, sensitivity, and specificity of camera-based PET is inferior to that of dedicated PET [16].

A novel imaging system is under development in which the images from camera-based PET are registered and fused with a simultaneously obtained CT scan. In this pilot study fused CT-PET imaging is compared with standard dedicated PET and camera-based PET in a group of patients with thoracic malignancies.

	Patients and methods

Top Abstract Introduction Patients and methods Results Comment Discussion References

 
Patients with suspected or proven malignancy who were referred for PET scan at Duke University Medical Center were considered eligible for this protocol, which was approved by the Institutional Review Board. All patients were injected with 18F-fluorodeoxyglucose (FDG) intravenously (0.14 mCi/kg) and whole-body scanning was performed as per protocol. Dedicated PET scans were obtained (approximately 60 minutes) followed by CT-PET fusion imaging (approximately 120 minutes). CT scans were obtained of the thorax (including adrenals) without contrast as per protocol [17].

Dedicated PET, camera-based PET, and CT-PET fusion scans were independently interpreted by two nuclear medicine physicians and suspicious foci graded on a scale from 1 (normal) to 5 (malignant). Discrepancies were resolved by consensus.

Dedicated PET scans were performed on the Advance system (GE Medical Systems, Milwaukee, WI). Two-dimension emission scans (4 minutes per bed position) and transmission scans (3 minutes per bed position) were obtained. Images underwent segmented attenuation-correction and were reformatted in axial, sagittal, and coronal planes [16].

CT-PET fusion scans were performed on the Millennium VG Hawkeye system (GE Medical Systems). The CT scans (10 minutes per bed position) and two-dimensional emission scans (24 minutes per bed position) were obtained. Images underwent segmented attenuation-correction and were reformatted in axial, sagittal, and coronal planes (Figs 1, 2, and 3).

View larger version (73K): [in this window] [in a new window]   Fig 1. Transaxial view of imaged left upper lung nodule. (Left) Computed tomography. (Middle) Camera-based positron emission tomography. (Right) Fused image.

View larger version (83K): [in this window] [in a new window]   Fig 2. Coronal view (reconstructed) of imaged left upper lung nodule. (Left) Computed tomography. (Middle) Camera-based positron emission tomography. (Right) Fused image.

View larger version (81K): [in this window] [in a new window]   Fig 3. Sagittal view (reconstructed) of imaged left upper lung nodule. (Left) Computed tomography. (Middle) Camera-based positron emission tomography. (Right) Fused image.

	Results

Top Abstract Introduction Patients and methods Results Comment Discussion References

Fusion of the CT images altered the sensitivity of the camera-based PET scans. Of the 23 lesions that were identified by the CT-PET fusion system the CT fusion showed the lesions to be less suspicious in 4 (17%) and more suspicious in 3 (13%). In particular CT precisely identified the source of positive foci, including normal thyroid, normal small intestine, arthritis, and a lung nodule. Furthermore, CT-PET fusion supported malignancy in 2 patients with false negative camera-based PET scans who were later found to have lymphoma and sarcoma.

	Comment

Top Abstract Introduction Patients and methods Results Comment Discussion References

 
The efficacy of dedicated PET systems in staging patients with thoracic malignancies is well recognized [3–15]. Until recently only dedicated PET scanners were being used for FDG imaging. The cost and availability of dedicated PET systems has limited its utility and has stimulated the development of PET imaging using gamma cameras [14–16]. It is estimated that there are approximately twice as many camera-based PET scanners than dedicated PET scanners [3]. The implementation of more generalized indications for PET has increased the use of this technology, especially the use of camera-based systems, which are neither as sensitive nor as specific as dedicated systems [3, 14].

Camera-based PET scanners initially used crystals that were three-eighths-inch thick but the low sensitivity of this crystal thickness limited its utility. Crystals with thicknesses of five-eighths’ inch and three-quarters’ inch are now being used, dramatically improving single photon sensitivity. Even with the thicker crystal the system sensitivity of the camera-based system is much less than that of the dedicated PET scanner. In a phantom study the sensitivity of camera-based PET was 10,000 counts per image whereas that for dedicated PET was 200,000 counts per image [14].

FDG PET imaging with dedicated PET scanners is very sensitive and accurate for evaluating focal pulmonary lesions that are indeterminate at computed tomography [18]. However, even using dedicated PET systems the specificity is lower than the sensitivity because some inflammatory processes such as granulomatous inflammation may accumulate FDG to the same degree as malignant lesions. Low-grade malignant lesions such as carcinoid tumors [19] and bronchoalveolar cell carcinoma [20] may not appear abnormal on dedicated PET scans. The use of standardized uptake values and lesion-to-background ratios has permitted semiquantitative analysis of the attenuation-corrected images but semiquantitative analysis has not been demonstrated to be better than experienced qualitative (visual) analysis [21]. Improving the spatial resolution of camera-based PET using CT fusion may improve the sensitivity and specificity, making it comparable to dedicated PET systems.

The spatial resolution of PET is suboptimal. In some patients hypermetabolic foci can not be clearly distinguished as the primary tumor or involved adenopathy in patients with lung cancer and esophageal cancer. In patients with lymphoma undetected asymmetric malignant involvement of mediastinal masses may make biopsies challenging. The improvement of the spatial resolution using CT-PET fused images may improve the staging and management in selected patients with thoracic malignancies.

In this study the detection of suspicious lesions was comparable using the two systems. Dedicated PET and CT-PET fusion were concordant for 76% of the lesions. Due to the nature of this study not all of the lesions have been documented as malignant, and at this point the false-positive rates of the two systems can not be compared without longer clinical follow-up. At this point, however, it seems reasonable to conclude that the CT-PET fusion appears comparable to dedicated PET in sensitivity.

Fusion of the CT images improved the sensitivity and specificity of the camera-based PET scans in this study, demonstrating foci to be less suspicious in 17% and more suspicious in 13%. The addition of CT-fusion also identified the source of several false positive foci and supported malignancy in 2 patients with false negative camera-based PET scans who were later found to have lymphoma and sarcoma.

CT fusion of camera-based PET images appears to improve the sensitivity, specificity, false negative rate, and false positive rate associated with camera-based PET alone. In addition CT-PET fusion appears to be as efficacious as dedicated PET systems although final assessment awaits longer clinical follow-up. This study supports further investigation of this technique, which may provide improved access to this otherwise limited and valuable resource. The expanding indications for PET in the diagnosis and staging of patients with thoracic malignancies, including patients with lung cancer, esophageal cancer, pulmonary metastases, and mediastinal malignancies, support the need for improved availability.

In the future CT-PET fusion may have other indications in the staging and management of patients with thoracic malignancies. The use of fused CT-PET images may improve radiation therapy treatment planning especially in patients with recurrences. The addition of PET to spiral CT images may improve the specificity of lung cancer screening. The utility of CT-PET fusion as compared with dedicated PET must be determined by the results of larger, ongoing studies.

	Discussion

Top Abstract Introduction Patients and methods Results Comment Discussion References

 
DR GARRETT L. WALSH (Houston, TX): I would like to thank Dr. D’Amico for allowing me to review this paper. It is promising technology that will hopefully improve the sensitivity and specificity of camera-based PET scans that are presently used in the community, often with poor resolution. A few questions. In your study, the dedicated PET was performed 1 hour after the FDG administration, with the camera-based PETs delayed an additional hour. Do you think you would have actually improved the sensitivity of your camera-based PETs if you could have reversed the order of the imaging tests in some of the patients?

Newer software in dedicated PETs is now improving the spatial resolution and localization of hot spots by our ability to rotate the images in three dimensions. I anticipate that it is a desired outcome for this fusion imaging system to drive down the cost of PET imaging (through the use of cheaper camera-based PETS) with comparable sensitivity and specificity to the dedicated PETS. What is the price of a CT-PET scanner versus a dedicated PET scanner? What is your present workup at Duke for a patient with resectable lung cancer? Are you still using bone scans or are you exclusively using PETs? What is your experience at Duke with PET imaging of the mediastinal nodes? And finally, how would you manage the not uncommon clinical scenario of a patient with lung cancer who demonstrates an "extrathoracic" hot spot on PET imaging but has no obvious target lesion to biopsy to refute or confirm stage IV disease? Would you go ahead and resect the primary lesion in these patients? How would you follow up with them?

DR D’AMICO: Thank you, Dr. Walsh, for your critical review of our paper. In terms of the time of injection, patients have approximately a 4-hour window after injection for a standard dedicated PET in terms of the ability to obtain a sensitive and specific scan. So the 3-hour window that we use should be adequate but your point is certainly germane. If we wanted to actually evaluate one versus the other we should randomly obtain either the camera-based PET first or the dedicated PET first. What we did in this study was to take patients who were referred for a dedicated PET and then have them consent to have the second study to follow up, because we did not know what the sensitivity would be. But you are absolutely right, although I think within our window we are within an acceptable time period.

In terms of the price of a dedicated PET, I do not know the exact figure but the dedicated PET scanners are certainly more expensive than the camera-based systems. And the purpose of this study was to try to develop a camera-based system that was superior to what is being used in the community because so many patients get referred to our institutions with SPECT scans that are unreliable and have to be repeated.

The workup of patients with apparent stage I lung cancer at Duke includes the following: all of the patients will eventually undergo mediastinoscopy; most of the patients will have obtained a PET scan. Although I personally do not order a PET scan on every single patient, I may order some on a patient based on advanced age or other factors. But often before the patient even sees me, a PET scan has already been obtained. Our experience with PET at Duke is that it is superior to bone scans for bony lesions and it is inferior to mediastinoscopy in the mediastinum. And finally, for false-positive PETs, we are obligated to pursue the area of interest to the degree that it is possible but we will not turn a patient down based on a positive PET scan result if there is no anatomic correlation and no biopsy has been performed.

	References

Top Abstract Introduction Patients and methods Results Comment Discussion References

 

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