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1 Department of Diagnostic and Interventional Radiology, University Hospital
Essen, Hufelandstr. 55, 45122 Essen, Germany.
2 Department of Nuclear Medicine, University Hospital Essen, 45122 Essen,
Germany.
Received March 15, 2002; accepted after revision May 30, 2002.
Address correspondence to G. Antoch.
OBJECTIVE. Our objective was to show that oral and IV contrast materials improve CT image quality in dual-modality positron emission tomography (PET) and CT, resulting in an increase in diagnostic capacity. We also present a standardized scanning protocol for whole-body PET—CT with oral and IV contrast materials.
SUBJECTS AND METHODS. To evaluate the use of whole-body PET—CT in clinical practice, we examined 30 patients according to the protocol. The CT images were evaluated quantitatively by signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) analyses and qualitatively by two radiologists in consensus. PET quality was assessed quantitatively by measurements of standard uptake values that were compared with standard uptake values in 10 PET—CT examinations without contrast agents.
RESULTS. The application of oral and IV contrast materials led to a highly sufficient delineation of vascular and intestinal structures in 26 of 30 patients. Quantitative analysis revealed a mean vascular SNR of 15.8 ± 7.71 for the 30 patients who received contrast materials compared with 4.79 ± 1.45 for the 10 control group patients (p < 0.001). Similarly, the mean intestinal SNR of 17.06 ± 7.96 far exceeded that seen in the control group of 3.83 ± 1.16 (p < 0.001). Analyses led to a vessel-to-muscle CNR of 10.78 ± 5.89 (control group, -1.21 ± 0.89; p < 0.001) and an intestine-to-muscle CNR of 12.04 ± 6.07 (control group, -2.17 ± 1.22; p = 0.001) in the 30 patients. An evaluation of PET quality in patients who received contrast materials showed a mean standard uptake value of 2.09 ± 1.16 compared with 2.04 ± 0.83 in the control group (p = 0.702).
CONCLUSION. Our whole-body PET—CT protocol provided good vascular and intestinal enhancement without compromising PET quality, leading to a potential improvement in the diagnostic capacity of the combined PET—CT examination.
Recent technical advances have led to the development of combined positron emission tomography (PET) and CT scanners. Beyond the vast diagnostic poential associated with the ability to fuse morphologic and functional data, the availability of the CT data enhances the quality and speed of the required attenuation correction for PET. Thus, PET—CT systems are being installed at a rapid rate, emphasizing the need for standardized scanning protocols.
Although there is general agreement that both IV and oral contrast materials enhance the diagnostic value of CT [1,2,3], their use in combined PET—CT systems has not been established. Challenges include the requirement for whole-body coverage and the possibility of adverse effects on the CT-based attenuation correction for PET.
In our study, we present an optimized CT examination protocol with oral and IV contrast materials for whole-body FDG PET—CT. We assessed the ability of whole-body FDG PET—CT to delineate vessels and bowel on CT. We also determined the effects of oral and IV contrast materials on PET image quality by comparing contrast-enhanced PET—CT scans with those obtained in the absence of oral and IV contrast materials.
Subjects and Methods
Patients
Our study was based on 30 patients who were referred for whole-body
PET—CT for a variety of oncologic indications. The examinations were
carried out for reasons of tumor staging (n = 21), identifying cancer
of unknown primary origin (n = 5), and therapy monitoring (n
= 4). Written informed consent was obtained from all patients regarding the
simultaneous administration of oral and IV contrast materials, as well as FDG
for PET imaging, in full accordance with the approving institutional review
board.
Sixty minutes before the injection of the radiotracer, patients were given 750 mL of glucose-free barium for oral contrast of the small bowel at a concentration of 1.5 g of barium sulfate/100 mL (Micropaque CT; Guerbet, Sulzbach, Germany). Immediately before undergoing PET—CT, patients drank another 250 mL of the barium solution. Patients had been fasting for a minimum of 4 hr. The findings of the blood glucose levels were within the normal range (70-120 mg/dL), as determined by capillary blood samples obtained immediately preceding the IV administration of 350 MBq of FDG via an 18-gauge cannula into the right-sided antecubital vein. In three patients, the IV contrast material was administered via a port catheter. After the injection, the patients rested comfortably without speaking for 60 min to avoid muscular radiotracer enhancement. After voiding, the patients were transferred to the PET—CT examination table onto which their heads were fixed to prevent inadvertent motion. The patients' arms were placed on both sides of their bodies.
PET—CT
Dual-modality PET—CT (Biograph; Siemens Medical Solutions, Hoffman
Estates, IL) contains a single examination table serving both the CT and PET
components, which are installed in series
[4]. The CT component
represents a single-detector helical CT scanner (Somatom Emotion; Siemens
Medical Systems, Erlangen, Germany) with a minimal gantry rotation time of 800
msec and a maximal scanning time of 100 sec. Hence, it permits 125 full gantry
rotations in a series. The PET component (ECAT HR+; Siemens Medical Systems)
provides an in-plane spatial resolution of 4.6 mm and an axial field of view
of 15.5 cm for one bed position. PET images are acquired in a
three-dimensional mode. The maximal axial field of view for combined
PET—CT is 140 cm. Attenuation correction for the PET component is based
on the CT data [5], and
iterative algorithms are performed for reconstruction. Therefore, no
additional sources for transmission scans are required.
The scanning area for CT and PET was defined on a CT topogram. Whole-body CT was carried out first in a single spiral commencing at the head and subsequently covering the neck, thorax, abdomen, and pelvis. When scanning the head and neck regions, we instructed the patient to breathe freely, avoiding maximal inspiration and expiration to minimize breathing artifacts. Once the mid thorax at the height of the pulmonary trunk was reached, the patient was asked to exhale and maintain expiration for artifact-free imaging of the chest and liver. Once the liver was covered, the patient resumed breathing. Depending on the patient's size, the time required for coverage of the lower chest and the liver was 15-20 sec. In all patients, slice width was set to 5 mm with a table feed of 8 mm, resulting in a pitch of 1.6. Images were reconstructed at 2.5-mm increments, generating overlapping slices. Table 1 summarizes the CT parameters used for patients of normal weight, which were adjusted for patients who were overweight.
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To optimize vascular and parenchymal enhancement, we administered contrast material containing 300 mg I/mL (Xenetix 300; Guerbet) with an automated injector. First, 80 mL of contrast material was administered with a flow rate of 3 mL/sec for arterial enhancement of the head and neck. CT was started with a delay of 30 sec. Immediately after the first charge of contrast material, another 60 mL was administered at a flow rate of 2 mL/sec. On completion of the whole-body helical PET scan, we acquired data at the first bed position beginning in a caudocranial direction with the patient's upper thigh. The time to scan a single bed position was set to 5 min.
Image Analysis
CT and PET data sets were assessed both qualitatively and quantitatively.
Quantitative analyses consisted of signal-to-noise ratio (SNR) for vessels and
intestine, contrast-to-noise ratio (CNR) of vessel-to-muscle
(CNRVM), and intestine-to-muscle CNR (CNRIM)
determinations for the CT component. The vascular SNR (SNRV) was
defined as the mean signal intensity of all blood vessels measured divided by
the standard deviation (SD) of the background noise. Intestinal SNR
(SNRI) was calculated in the same way for mean signal intensity
within bowel structures. The CNRVM was defined as the difference in
signal intensity between the vascular system and the gluteal muscles divided
by the SD of the background noise. The CNRIM was calculated
accordingly. For SNR and CNR determinations, density measurements were
performed in regions of interest (ROIs) placed in the vessels under
consideration, the gluteal muscles, and the outside of the body. Intravascular
ROIs were placed in the carotid arteries, the thoracic and abdominal aorta,
the femoral arteries, and the internal jugular and portal veins. To
quantitatively assess the benefit of oral contrast material, we performed
density measurements in ROIs placed in the stomach, the duodenum, the mid
jejunum, and the ileum. The SNR and CNR of patients who underwent CT—PET
with IV and oral contrast materials were compared with the SNR and CNR in the
10 patients who underwent native CT scans as part of their PET—CT
examinations. Reproducibility of SNR and CNR values was tested by
determination of SNR and CNR in 10 patients. To test for interobserver
variability, three independent observers evaluated the images and determined
the SNR and CNR for 10 patients. Vascular and intestinal SNR and CNR SDs were
calculated to compare the findings determined by the different observers.
Intraobserver variability was determined by comparing SNR and CNR attained
from the same 10 patients by the same observer on three different days.
Standard deviations were determined to test for intraobserver variability.
Quantitative assessment of the PET component was based on standard uptake
values (SUV) that were calculated as follows:
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The activity concentration was based on ROI measurements from the liver (one in the center and three in the periphery). Mean values and SDs for all SNRs, CNRs, and standard uptake values were calculated. Differences between the 30 patients and the control group (which included 10 patients who underwent native CT) were evaluated for significance by applying the Student's unpaired t test. A test p value of 0.05 was considered to be statistically significant.
For qualitative evaluation, two radiologists in consensus rated vascular and bowel contrast on CT as good (IV and oral contrast materials were sufficient for delineation of vessels and bowel), suboptimal (reduced IV and oral contrast materials permit partial delineation of vessels and bowel), and poor (IV and oral contrast materials were insufficient for delineation and vessels or bowel). The PET scan was qualitatively evaluated by two nuclear medicine physicians. The quality of the PET scans was classified as good (regular parenchymal radiotracer uptake as expected in a PET scan with normal findings), suboptimal (decreased or increased parenchymal radiotracer uptake compared with uptake expected in a PET scan with normal findings), and poor (weak radiotracer uptake).
Image fusion was accomplished with syngo software (Siemens Medical Solutions), and fused images were again evaluated in consensus.
Results
Depending on the size of the patient, six to eight table positions were scanned, resulting in a PET examination time of 30-40 min. The mean overall examination time from positioning of the patient to completion of the PET scan was 46 min (range, 38-51 min).
CT image quality was considered good, with ample intravascular and oral contrast in 26 of the 30 patients when analyzed qualitatively by the two radiologists. Findings in one patient provided good intravascular enhancement, but small-bowel contrast was poor because of the inability of the patient to swallow the contrast material as a result of gastric discomfort. In three patients, intravascular enhancement was considered suboptimal, whereas bowel contrast was good. In all three patients, the IV contrast material had been administered via a port catheter. Quantitative analysis revealed a mean SNRV of 15.8 ± 7.71 for the 30 patients who underwent PET—CT with contrast material compared with 4.79 ± 1.45 in the 10 control group patients (p < 0.001). Similarly, the mean SNRI of 17.06 ± 7.96 far exceeded that seen in the control group of 3.83 ± 1.16 (p < 0.001). In the 30 patients, the CNRVM was 10.78 ± 5.89 (control group, -1.21 ± 0.89; p < 0.001) and the CNRIM was 12.04 ± 6.07 (control group, -2.17 ± 1.22; p = 0.001). Interobserver variability ranged from 5.71% to 6.11% (SNRV, 5.75%; SNRI, 5.86%; CNRVM, 6.11%; CNRIM, 5.71%), whereas intraobserver variability ranged between 6.46% and 7.77% (SNRV, 6.59%; SNRI, 7.68%; CNRVM, 6.46%; CNRIM, 7.77%). Typical enhancement patterns after the administration of oral and IV contrast materials are shown in Figure 1.
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The PET scan quality was considered good in 29 examinations (Fig. 2A,2B,2C) and was comparable to the quality of PET—CT scans acquired without contrast agents (Fig. 3A,3B,3C). Findings in one patient revealed suboptimal radiotracer uptake that was caused by partial paravasation of the radiotracer during injection. The mean standard uptake value in the 30 patients who received oral and IV contrast materials was 2.09 ± 1.16, whereas the control group showed a mean standard uptake value of 2.04 ± 0.83. Correlation of standard uptake values in the two groups did not reveal a statistically significant difference (p = 0.702).
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Discussion
The presented scanning protocol rendered diagnostic whole-body PET—CT examinations in all 30 patients. Both the PET and CT components of the examination were deemed of diagnostic quality. The administration of oral and IV contrast materials enhanced CT image quality by permitting delineation of vascular and intestinal structures without compromising PET image quality. Hence, the described contrast administration protocol fulfils the requirements for optimized PET—CT.
Although the true diagnostic benefit of dual-modality PET—CT will need to be determined in larger patient cohorts, the presented experience already highlights several advantages of a combined approach. Because of the CT-based attenuation correction, PET scanning times were reduced. Thus, whole-body examinations were completed in less than 1 hr. In addition, the simultaneous availability of spatially matched functional and morphologic data represents a potential advantage [4]. This power can be exploited only, however, if the CT examination is performed according to the highest quality standards. Regions of increased radiotracer uptake must be unequivocally matched with morphologic structures of the smallest size. Because not all tumors are characterized by increased FDG uptake [6], and some metastases have radiotracer uptake kinetics that differ from those of the primary malignancy, the CT data serve a distinct diagnostic purpose independent of morphologic correlation with PET. This finding mandates the administration of intravascular and intestinal contrast materials [1,2,3]. The presented scanning protocol permits whole-body PET—CT without compromising either the PET or the CT component.
Applying a dual-phase protocol of contrast material injection resulted in good intravascular enhancement in all body regions in 27 of the 30 patients. In all three patients in whom contrast material was administered via a port catheter, intravascular enhancement was deemed suboptimal. This finding was attributed to the small diameter of the port catheter, which prevented the contrast flow from reaching a rate of 3 mL/sec. Other causes may have been related to the timing of contrast material administration. Because no such problems were encountered in any of the other patients, the use of a sufficiently large peripheral venous cannula (18-gauge) is recommended. The quantitative data strongly support the qualitative analysis. Differences in the calculation of SNRV and CNRVM proved to be highly significant when compared with those of the control PET—CT scans featuring unenhanced CT.
Qualitative analysis revealed adequate bowel opacification in 29 of the 30 patients after the administration of the oral contrast agent. Because of nausea, one patient had difficulty ingesting the barium suspension, which resulted in suboptimal bowel contrast. Placement of a nasogastric tube could have eliminated this problem. Good delineation of intestinal structures could also be verified by quantitative analysis. The comparison of SNRI and CNRIM in patients who underwent imaging with and without oral administration of contrast material revealed a highly significant difference for both values. Analyses of SNRI and CNRIM were limited to the small bowel because the presented protocol ensures good small-bowel enhancement while the colon is not yet completely enhanced by the time of the examination. Because of the presence of air contrast in the colon, enhancement is generally considered less crucial than that in the small bowel.
In patients undergoing preoperative staging or suspected of harboring a gastrointestinal leak, the barium suspension should be substituted by water-soluble iodinated agents. It is unlikely that these agents would have a detrimental effect on PET image quality. Ongoing in vitro experiments are addressing this issue.
Dual-modality PET—CT attenuation correction for PET is based on the CT data [5]. In tissues (e.g., bone) containing elements of high atomic numbers and in structures containing contrast agents, photoelectric absorption dominates at 70-140 keV, which results in significant attenuation of the CT X-rays. At 511 keV (for PET), Compton scattering effects dominate, even in tissues containing elements of high atomic values, and lead to only minor attenuation of PET annihilation quanta [7]. CT X-rays, on the other hand, are attenuated more significantly. Hence, the CT-based attenuation correction for PET may be somewhat overestimated in the presence of CT contrast agents.
These theoretic considerations were not ruled out by analysis of the PET data, and further studies are required to address this subject. Qualitative analysis, however, revealed the quality of 29 of the 30 PET scans to be good, whereas only one PET scan showed decreased parenchymal radiotracer uptake related to extravasation of the injected FDG. Evaluation of the quantitative data supports the qualitative analysis: comparison of standard uptake values for the liver in PET—CT scans obtained using oral and IV contrast material with those that did not fail to reveal a statistically significant difference. The liver was chosen for its ease of comparability as well as its proximity to both vessels and intestines. Although contrast-induced standard uptake value measurement errors in other parts of the body cannot be totally excluded, such errors seem rather unlikely.
Based on a pitch of 1.6, CT data acquisition for a whole-body scan can be accomplished in 70-80 sec. Although the examination time is short, scanning during a single breath-hold is not feasible. It has been shown that the correlation of CT with PET images is improved if CT is acquired during expiration or free breathing rather than during maximal inspiration [8]. The patients were therefore scanned breathing freely during the acquisition of CT images of the head, neck, and upper thorax. Because motion artifacts are most dominant in the region of the diaphragm, patients were instructed to exhale as the CT scanner reached the mid thorax and to hold their breaths in expiration until coverage of the liver was complete. All patients tolerated this procedure well. Because motion artifacts from breathing are minimal in the upper parts of the lungs, the quality of the CT scans did not decrease in this region. Although it is likely that CT scanning in combined PET—CT examinations will benefit from further advances in multidetector CT technology, the use of a single-detector scanner was not considered a handicap in the examinations performed.
The presented protocol is applicable to tumor staging, follow-up examinations, or finding the primary tumor in cancer of unknown primary origin. Evaluation of benign diseases with whole-body coverage is limited by radiation exposure, which accounts for an overall dose of 21-25 mSv, with approximately 7 mSv from the PET component and 14-18 mSv from the CT component. Because vascular enhancement is limited to a single phase, CT images from the whole-body protocol will not answer dedicated questions related to the characterization of hepatic or pancreatic lesions. In these cases, classic three-phase contrast-enhanced CT of the ROI is recommended.
In conclusion, the presented whole-body PET—CT protocol with IV and oral contrast materials provides good intravascular and gastrointestinal enhancement without compromising PET quality.
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