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Quantifying the Effect of IV Contrast Media on Integrated PET/CT: Clinical Evaluation

¹ Department of Imaging Physics, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Box 56, Houston, TX 77030.
² Department of Diagnostic Radiology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030.

Received November 10, 2004; accepted after revision January 25, 2005.

 
Address correspondence to O. Mawlawi (Omawlawi{at}mdanderson.org).

Abstract

Top Abstract Introduction Materials and Methods Results Discussion References

 
OBJECTIVES. The use of IV contrast media in PET/CT can result in an overestimation of PET attenuation factors that potentially can affect interpretation. The objective of this study was to quantify the effect of IV contrast media in PET/CT and assess its impact on patients with intrathoracic malignancies.

MATERIALS AND METHODS. Nine patients had CTs performed with and without IV contrast media followed by ¹⁸F-FDG PET. PET images were reconstructed using contrast-enhanced and unenhanced CT. To quantify the effect of contrast media on standardized uptake values (SUV), similar regions of interest (ROIs) were drawn on the subclavian vein, heart, liver, spleen, and site of malignancy on both CT and corresponding reconstructed PET images, and the mean and maximum values were compared. In addition, two physicians blinded to the imaging parameters that were used evaluated the reconstructed PET images to assess whether IV contrast media had an effect on clinical interpretation.

RESULTS. For all patient studies, the subclavian vein region on the ipsilateral side of contrast media administration had the highest increase in CT numbers with a corresponding average SUV_max increase of 27.1%. Similarly, ROIs of the heart and at the site of malignancy showed an increase in the maximum attenuation value with a corresponding average SUV_max increase of 16.7% and 8.4%, respectively. Other locations had relatively small attenuation value differences with a correspondingly negligible SUV variation.

CONCLUSION. Although there is a significant increase in SUV in regions of high-contrast concentration when contrast-enhanced CT is used for attenuation correction, this increase is clinically insignificant. Accordingly, in PET/CT, IV contrast-enhanced CT can be used in combination with the PET to evaluate patients with cancer.

Keywords: artifact • attenuation • contrast media • PET/CT

Introduction

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PET with ¹⁸F-FDG and CT are often used in the initial determination of stage of the disease in patients with cancer. Traditionally, PET and CT are performed sequentially and interpretation is made by visual fusion of the physiologic and anatomic images. Recently, integrated PET/CT scanners have been introduced, allowing optimal temporal and spatial fusion of the two sets of images. This acquisition of spatially matched functional and morphologic data has been reported to allow more accurate localization of regions of increased ¹⁸F-FDG uptake and more accurate staging of cancer [1–3]. In addition, the use of the CT component for attenuation correction decreases image acquisition time. Besides these two advantages, the CT component of integrated PET/CT can also be used independently of the PET scan to improve the detection of metastases and the accuracy of staging in oncologic patients. However, for the CT component of the integrated PET/CT scan to replace the diagnostic CT, detection and characterization of lesions must be similar. Although CT protocols vary between institutions and the optimal imaging parameters have not been rigorously established, most diagnostic CT scans are performed after administration of contrast media. CT contrast media, whether IV or oral, are used to improve the delineation of vessels and bowel and to increase the sensitivity and accuracy of lesion detection and characterization [4–6].

In contradistinction to diagnostic CT scans, CT scans used for attenuation correction in whole-body integrated PET/CT are usually performed without the use of IV contrast media. The reluctance to administer IV contrast media is because the PET images are affected quantitatively when contrast-enhanced CT is used to attenuate correct the PET emission data [7, 8]. Specifically, during the transformation of the contrast-enhanced CT images to PET attenuation maps [9], the Hounsfield units corresponding to contrast-enhanced CT pixels are higher and hence result in an overestimation of PET attenuation factors. This can affect the standardized uptake value (SUV), the most commonly used parameter to quantify the intensity of ¹⁸F-FDG uptake in attenuation-corrected PET images. In this regard, several authors have studied the relationship between IV contrast media concentration, elevated CT Hounsfield units, and the impact on PET [7, 8]. However, these were either based on phantom studies or compared contrast-enhanced CT attenuation-corrected PET images with non–attenuation-corrected images [7, 8]. To our knowledge, there are no published data on the direct comparison of PET images corrected for attenuation using IV contrast-enhanced and unenhanced CT images. In this article, we report on the performance of such a comparison and assess the potential clinical impact this effect could have on the interpretation of the PET scan.

Materials and Methods

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Integrated PET/CT Scanner
Data acquisition for this study was performed on a Discovery ST integrated PET/CT scanner (GE Healthcare). The CT component of this scanner has a 50-cm transaxial field of view and can acquire eight slices per X-ray tube rotation. The CT slice thickness can range from 1.25 to 10 mm. The X-ray tube current can vary between 10 and 440 mA, and the tube voltage setting can be 80, 100, 120, or 140 kVp. The table feed rate of the CT scanner ranges from 1.25 to 30 mm per 360° rotation of the X-ray tube. The minimum and maximum scanning times per gantry rotation are 0.5 and 4 sec, respectively, with 0.32 mm as the highest in-plane spatial resolution.

The PET component of the Discovery ST scanner is composed of 24 rings of bismuth germanate oxide (BGO) detectors. The dimensions of each detector element are 6.3 x 6.3 x 30 mm in the tangential, axial, and radial directions, respectively. The scanner has a transaxial field of view of 70 cm and an axial field of view of 15.7 cm and can generate 47 slices per bed position. The scanner is also capable of acquiring data in 2D and 3D mode by retracting tungsten septa (54-mm long and 0.8-mm thick) from the field of view. The performance characterization of this scanner has been described [10].

Materials
Patient inclusion criteria required a history of an intrathoracic malignancy and performance of an integrated PET/CT scan and contrast-enhanced CT scan within a 1-day period. Nine oncologic patients (four men, five women; mean age, 62 ± 10 years [SD]) underwent staging evaluation and met these criteria. All patients fasted for at least 6 hr before the IV injection of approximately 555 MBq of ¹⁸F-FDG and were scanned 75 ± 10 min after injection. All patients had a whole body PET/CT performed without IV contrast media followed by a contrast-enhanced CT on the Discovery ST PET/CT scanner (Table 1).

The imaging protocol consisted of acquiring the unenhanced PET/CT scan followed by retracting the patient couch back to its initial position before injecting the contrast medium (Leibel-Flarsheim Angiomat Illumena, Mallinckrodt) and acquiring the second CT scan. The type of contrast medium, volume, injection rate, and delay time were the same as those routinely used in our institution when an enhanced chest, abdomen, and pelvis CT is performed (e.g., 100 mL of ioversol [Optiray 320, Mallinckrodt], 2.5 mL/sec, 20-sec delay). The imaging parameters for both CTs were 120 kVp, 300 mA, 1.35:1 pitch, 0.5-sec rotation, and an 8 x 1.25-mm detector configuration. During both CT scans, the patients were instructed to hold their breath at midexpiration to ensure similar chest geometry between the two scans. The PET acquisition parameters were 3 min/bed, 2D mode, and use of CT for attenuation correction. PET data were then reconstructed using the CT with and without contrast media using attentuation-weighted ordered subset expectation maximization (AW OSEM) [11] with two iterations and 30 subsets using a post and loop filters of 6 and 5.47 mm, respectively.

To quantify the effect of contrast on attenuation and SUV measurements, similar regions of interest (ROIs) were drawn on the enhanced and nonenhanced CTs and reconstructed PET scans corresponding to the subclavian vein, heart, liver, spleen, and sites of primary malignancy and metastases. The subclavian vein, heart, liver, and spleen were chosen based on the variation of their accumulation of IV contrast concentration at the time of the CT scan. For each patient study, the ROIs were originally drawn on the enhanced CT scan and then copied to the other image sets to maintain consistency in drawing and evaluation. In some cases, the ROIs were repositioned by relying on the patient's anatomic structures to account for slight differences in slice-plane acquisition resulting from patient respiration. In addition, two physicians experienced in CT and PET interpretation and blinded to the imaging parameters used randomly interpreted all the reconstructed PET images and evaluated whether IV contrast media had an effect on the clinical interpretation of the studies. A paired Student's t test of these results was also performed to assess the significance of the difference between the SUV obtained from the two reconstructed PET images.

Results

Top Abstract Introduction Materials and Methods Results Discussion References

 
As expected, our study confirmed that the use of IV contrast media increases the CT Hounsfield units in areas where contrast is present. These areas in turn were transformed to artifactually high PET attenuation factors and ultimately led to an overestimation of PET activity concentration. The mean and maximum ROI measurements of all locations and in each image set averaged over all nine patient studies are shown in Table 2. The highest Hounsfield measurements were in the subclavian vein region of the contrast-enhanced CT on the side of the contrast administration, with average mean and maximum values of 1,739 and 2,602 H. In five of the nine patients, the maximum Hounsfield value in this region reached the saturation limit of the Hounsfield scale. Accordingly, this region had the highest increase in SUV (mean, 27.1%; range, 8% to 60%) on the contrast-enhanced CT attenuation-corrected PET scans. Table 2 shows that the heart and the sites of malignancy on the contrast-enhanced CT had a moderate increase in Hounsfield units, with average mean (maximum) ROI values of 260 (278) and 52 (87), respectively. These regions had a corresponding SUV_max increase of 16.7% and 8.4%, respectively. Although the remaining locations (liver and spleen) had a moderate increase in Hounsfield values on the contrast-enhanced CT images, these regions had negligible increases in SUV on the corresponding PET images. The p value for each of these regions is shown in Table 2.

Examination of the PET images by two physicians blinded to the CT attenuation correction maps used to reconstruct the PET images revealed no differences in the clinical interpretations of the PET scans of all nine patients. However, there were differences in reported maximum SUVs of the malignancies on PET images reconstructed with the contrast-enhanced CT scans compared with the same PET images reconstructed with the unenhanced CT scans (Table 3) (Figs. 1A, 1B, 1C, 1D, 1E, 1F, 1G, 1H, 1I, 1J, 1K, 1L, 2A, 2B, 2C, 2D, 2E, 2F, 2G, 2H, 2I, 2J, 2K, 2L, 3A, 3B, 3C, 3D, 3E, and 3F). The measured SUVs of the primary malignancies and metastases showed that the largest increase in SUV_max was 18.6% when using the contrast-enhanced CT scans for attenuation correction. Importantly, the PET scans reconstructed with contrast-enhanced CT data showed no additional focal regions of increased ¹⁸F-FDG uptake due to the presence of the IV contrast media.

View larger version (85K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1A —60-year-old man with esophageal cancer and lung metastasis. Attenuation correction performed using unenhanced CT (A–C), (G–I) and IV contrast-enhanced CT (D–F), (J–L). Coronal images at level of subclavian vein and heart. Mean (maximum) region of interest (ROI) values for subclavian vein (short arrows) and left atrium (long arrows) were 36 (49) H and 35 (40) H, respectively, on unenhanced CT scan. Corresponding PET standardized uptake values (SUV) were 0.97 (1.0) and 1.88 (2.1), respectively. A, Unenhanced CT.

View larger version (68K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1B —60-year-old man with esophageal cancer and lung metastasis. Attenuation correction performed using unenhanced CT (A–C), (G–I) and IV contrast-enhanced CT (D–F), (J–L). Coronal images at level of subclavian vein and heart. Mean (maximum) region of interest (ROI) values for subclavian vein (short arrows) and left atrium (long arrows) were 36 (49) H and 35 (40) H, respectively, on unenhanced CT scan. Corresponding PET standardized uptake values (SUV) were 0.97 (1.0) and 1.88 (2.1), respectively. B, Attentuation-corrected PET with unenhanced CT.

View larger version (85K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1C —60-year-old man with esophageal cancer and lung metastasis. Attenuation correction performed using unenhanced CT (A–C), (G–I) and IV contrast-enhanced CT (D–F), (J–L). Coronal images at level of subclavian vein and heart. Mean (maximum) region of interest (ROI) values for subclavian vein (short arrows) and left atrium (long arrows) were 36 (49) H and 35 (40) H, respectively, on unenhanced CT scan. Corresponding PET standardized uptake values (SUV) were 0.97 (1.0) and 1.88 (2.1), respectively. C, Coregistered PET/CT.

View larger version (87K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1D —60-year-old man with esophageal cancer and lung metastasis. Attenuation correction performed using unenhanced CT (A–C), (G–I) and IV contrast-enhanced CT (D–F), (J–L). Coronal images at level of subclavian vein (short arrows) and left atrium (long arrows) show visual quality of PET image is not compromised when IV contrast CT is used for attenuation correction. However, mean (maximum) ROI values of subclavian vein and left atrium increased to 1,962 (3,070) and 260 (283) on contrast-enhanced CT images compared with A–C, respectively. Corresponding PET SUV values were 1.3 (1.6) and 2.45 (3.0), an increase in SUVmax of 60% and 43%, respectively. D, IV contrast-enhanced CT.

View larger version (70K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1E —60-year-old man with esophageal cancer and lung metastasis. Attenuation correction performed using unenhanced CT (A–C), (G–I) and IV contrast-enhanced CT (D–F), (J–L). Coronal images at level of subclavian vein (short arrows) and left atrium (long arrows) show visual quality of PET image is not compromised when IV contrast CT is used for attenuation correction. However, mean (maximum) ROI values of subclavian vein and left atrium increased to 1,962 (3,070) and 260 (283) on contrast-enhanced CT images compared with A–C, respectively. Corresponding PET SUV values were 1.3 (1.6) and 2.45 (3.0), an increase in SUVmax of 60% and 43%, respectively. E, Attenuation-corrected PET with unenhanced CT.

View larger version (86K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1F —60-year-old man with esophageal cancer and lung metastasis. Attenuation correction performed using unenhanced CT (A–C), (G–I) and IV contrast-enhanced CT (D–F), (J–L). Coronal images at level of subclavian vein (short arrows) and left atrium (long arrows) show visual quality of PET image is not compromised when IV contrast CT is used for attenuation correction. However, mean (maximum) ROI values of subclavian vein and left atrium increased to 1,962 (3,070) and 260 (283) on contrast-enhanced CT images compared with A–C, respectively. Corresponding PET SUV values were 1.3 (1.6) and 2.45 (3.0), an increase in SUVmax of 60% and 43%, respectively. F, Coregistered PET/CT.

View larger version (95K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1G —60-year-old man with esophageal cancer and lung metastasis. Attenuation correction performed using unenhanced CT (A–C), (G–I) and IV contrast-enhanced CT (D–F), (J–L). Axial images show 18F-FDG-avid small right upper lobe nodule (arrows). Mean (maximum) SUV values of nodule were 2.6 (3.9). Note slight misregistration of CT and PET images resulting from respiration. G, Unenhanced chest CT.

View larger version (64K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1H —60-year-old man with esophageal cancer and lung metastasis. Attenuation correction performed using unenhanced CT (A–C), (G–I) and IV contrast-enhanced CT (D–F), (J–L). Axial images show 18F-FDG-avid small right upper lobe nodule (arrows). Mean (maximum) SUV values of nodule were 2.6 (3.9). Note slight misregistration of CT and PET images resulting from respiration. H, Attenuation-corrected PET with unenhanced CT.

View larger version (90K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1I —60-year-old man with esophageal cancer and lung metastasis. Attenuation correction performed using unenhanced CT (A–C), (G–I) and IV contrast-enhanced CT (D–F), (J–L). Axial images show 18F-FDG-avid small right upper lobe nodule (arrows). Mean (maximum) SUV values of nodule were 2.6 (3.9). Note slight misregistration of CT and PET images resulting from respiration. I, Coregistered PET/CT.

View larger version (95K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1J —60-year-old man with esophageal cancer and lung metastasis. Attenuation correction performed using unenhanced CT (A–C), (G–I) and IV contrast-enhanced CT (D–F), (J–L). Axial images show minimal perceived difference in visual uptake of 18F-FDG in nodule (arrows) compared with G–I, Mean (maximum) SUV values of nodule increased to 2.8 (4.2) compared with G–I, an increase of 8%. Note slight misregistration of CT and PET images resulting from respiration. J, IV contrast-enhanced chest CT.

View larger version (67K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1K —60-year-old man with esophageal cancer and lung metastasis. Attenuation correction performed using unenhanced CT (A–C), (G–I) and IV contrast-enhanced CT (D–F), (J–L). Axial images show minimal perceived difference in visual uptake of 18F-FDG in nodule (arrows) compared with G–I, Mean (maximum) SUV values of nodule increased to 2.8 (4.2) compared with G–I, an increase of 8%. Note slight misregistration of CT and PET images resulting from respiration. K, Attenuation-corrected PET with enhanced CT.

View larger version (91K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1L —60-year-old man with esophageal cancer and lung metastasis. Attenuation correction performed using unenhanced CT (A–C), (G–I) and IV contrast-enhanced CT (D–F), (J–L). Axial images show minimal perceived difference in visual uptake of 18F-FDG in nodule (arrows) compared with G–I, Mean (maximum) SUV values of nodule increased to 2.8 (4.2) compared with G–I, an increase of 8%. Note slight misregistration of CT and PET images resulting from respiration. L, Coregistered PET/CT.

View larger version (83K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2A —71-year-old man with non–small cell lung cancer after pneumonectomy presenting with nodal and hepatic metastases. Attenuation correction performed using unenhanced CT (A–C), (G–I) and IV contrast-enhanced CT (D–F), (J–L). Axial images show 18F-FDG-avid mediastinal nodal metastasis (arrows). Mean (maximum) standardized uptake values (SUV) values of lymph node were 3.2 (4.3). A, Unenhanced chest CT.

View larger version (81K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2B —71-year-old man with non–small cell lung cancer after pneumonectomy presenting with nodal and hepatic metastases. Attenuation correction performed using unenhanced CT (A–C), (G–I) and IV contrast-enhanced CT (D–F), (J–L). Axial images show 18F-FDG-avid mediastinal nodal metastasis (arrows). Mean (maximum) standardized uptake values (SUV) values of lymph node were 3.2 (4.3). B, Attenuation-corrected PET with enhanced CT.

View larger version (95K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2C —71-year-old man with non–small cell lung cancer after pneumonectomy presenting with nodal and hepatic metastases. Attenuation correction performed using unenhanced CT (A–C), (G–I) and IV contrast-enhanced CT (D–F), (J–L). Axial images show 18F-FDG-avid mediastinal nodal metastasis (arrows). Mean (maximum) standardized uptake values (SUV) values of lymph node were 3.2 (4.3). C, Coregistered PET/CT.

View larger version (84K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2D —71-year-old man with non–small cell lung cancer after pneumonectomy presenting with nodal and hepatic metastases. Attenuation correction performed using unenhanced CT (A–C), (G–I) and IV contrast-enhanced CT (D–F), (J–L). Axial images show slight perceived visual increase in 18F-FDG in node (arrows) when images are reconstructed with IV contrast-enhanced CT. Mean (maximum) SUV values of lymph node were 3.75 (5.1), an increase of 5% compared with A–C. Note mediastinal background 18F-FDG activity is similar compared with A–C and quality of PET image is not compromised when IV contrast-enhanced CT is used for attenuation correction. D, IV contrast-enhanced chest CT.

View larger version (82K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2E —71-year-old man with non–small cell lung cancer after pneumonectomy presenting with nodal and hepatic metastases. Attenuation correction performed using unenhanced CT (A–C), (G–I) and IV contrast-enhanced CT (D–F), (J–L). Axial images show slight perceived visual increase in 18F-FDG in node (arrows) when images are reconstructed with IV contrast-enhanced CT. Mean (maximum) SUV values of lymph node were 3.75 (5.1), an increase of 5% compared with A–C. Note mediastinal background 18F-FDG activity is similar compared with A–C and quality of PET image is not compromised when IV contrast-enhanced CT is used for attenuation correction. E, Attenuation-corrected PET with unenhanced CT.

View larger version (96K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2F —71-year-old man with non–small cell lung cancer after pneumonectomy presenting with nodal and hepatic metastases. Attenuation correction performed using unenhanced CT (A–C), (G–I) and IV contrast-enhanced CT (D–F), (J–L). Axial images show slight perceived visual increase in 18F-FDG in node (arrows) when images are reconstructed with IV contrast-enhanced CT. Mean (maximum) SUV values of lymph node were 3.75 (5.1), an increase of 5% compared with A–C. Note mediastinal background 18F-FDG activity is similar compared with A–C and quality of PET image is not compromised when IV contrast-enhanced CT is used for attenuation correction. F, Coregistered PET/CT.

View larger version (114K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2G —71-year-old man with non–small cell lung cancer after pneumonectomy presenting with nodal and hepatic metastases. Attenuation correction performed using unenhanced CT (A–C), (G–I) and IV contrast-enhanced CT (D–F), (J–L). Axial images show 18F-FDG-avid hepatic metastasis (arrows). Mean (maximum) SUV values of metastasis were 6.3 (7). G, Unenhanced abdomen CT.

View larger version (99K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2H —71-year-old man with non–small cell lung cancer after pneumonectomy presenting with nodal and hepatic metastases. Attenuation correction performed using unenhanced CT (A–C), (G–I) and IV contrast-enhanced CT (D–F), (J–L). Axial images show 18F-FDG-avid hepatic metastasis (arrows). Mean (maximum) SUV values of metastasis were 6.3 (7). H, Attenuation-corrected PET with enhanced CT.

View larger version (103K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2I —71-year-old man with non–small cell lung cancer after pneumonectomy presenting with nodal and hepatic metastases. Attenuation correction performed using unenhanced CT (A–C), (G–I) and IV contrast-enhanced CT (D–F), (J–L). Axial images show 18F-FDG-avid hepatic metastasis (arrows). Mean (maximum) SUV values of metastasis were 6.3 (7). I, Coregistered PET/CT.

View larger version (120K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2J —71-year-old man with non–small cell lung cancer after pneumonectomy presenting with nodal and hepatic metastases. Attenuation correction performed using unenhanced CT (A–C), (G–I) and IV contrast-enhanced CT (D–F), (J–L). Axial images show slight visual increase in 18F-FDG activity in hepatic metastasis (arrows). Mean (maximum) SUV values of hepatic metastasis were 7.2 (8.1), an increase of 16% compared with G–I. Note 18F-FDG activity in contrast-enhanced liver is similar to G–I when unenhanced CT is used for attenuation correction. J, IV contrast-enhanced abdomen CT.

View larger version (96K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2K —71-year-old man with non–small cell lung cancer after pneumonectomy presenting with nodal and hepatic metastases. Attenuation correction performed using unenhanced CT (A–C), (G–I) and IV contrast-enhanced CT (D–F), (J–L). Axial images show slight visual increase in 18F-FDG activity in hepatic metastasis (arrows). Mean (maximum) SUV values of hepatic metastasis were 7.2 (8.1), an increase of 16% compared with G–I. Note 18F-FDG activity in contrast-enhanced liver is similar to G–I when unenhanced CT is used for attenuation correction. K, Attenuation-corrected PET with enhanced CT.

View larger version (102K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2L —71-year-old man with non–small cell lung cancer after pneumonectomy presenting with nodal and hepatic metastases. Attenuation correction performed using unenhanced CT (A–C), (G–I) and IV contrast-enhanced CT (D–F), (J–L). Axial images show slight visual increase in 18F-FDG activity in hepatic metastasis (arrows). Mean (maximum) SUV values of hepatic metastasis were 7.2 (8.1), an increase of 16% compared with G–I. Note 18F-FDG activity in contrast-enhanced liver is similar to G–I when unenhanced CT is used for attenuation correction. L, Coregistered PET/CT.

View larger version (81K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 3A —56-year-old man with non–small cell lung cancer manifesting as left upper lobe mass. Attenuation correction performed using unenhanced CT (A–C) and IV contrast-enhanced CT (D–F). Coronal images show 18F-FDG-avid mass (arrows). Mean (maximum) standardized uptake values (SUV) values of mass were 15.3 (21.4). A, Unenhanced chest CT.

View larger version (82K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 3B —56-year-old man with non–small cell lung cancer manifesting as left upper lobe mass. Attenuation correction performed using unenhanced CT (A–C) and IV contrast-enhanced CT (D–F). Coronal images show 18F-FDG-avid mass (arrows). Mean (maximum) standardized uptake values (SUV) values of mass were 15.3 (21.4). B, Attenuation-corrected PET with unenhanced CT.

View larger version (90K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 3C —56-year-old man with non–small cell lung cancer manifesting as left upper lobe mass. Attenuation correction performed using unenhanced CT (A–C) and IV contrast-enhanced CT (D–F). Coronal images show 18F-FDG-avid mass (arrows). Mean (maximum) standardized uptake values (SUV) values of mass were 15.3 (21.4). C, Coregistered PET/CT.

View larger version (84K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 3D —56-year-old man with non–small cell lung cancer manifesting as left upper lobe mass. Attenuation correction performed using unenhanced CT (A–C) and IV contrast-enhanced CT (D–F). Coronal images show no perceived visual increase in 18F-FDG activity in mass (arrows) compared with A–C. Mean (maximum) SUV values of mass were 17.3 (24.6), an increase of 14.9% compared with A–C. Note 18F-FDG activity in contrast-enhanced right subclavian vein and heart is similar to A–C when unenhanced CT is used for attenuation correction. D, IV contrast-enhanced chest CT.

View larger version (85K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 3E —56-year-old man with non–small cell lung cancer manifesting as left upper lobe mass. Attenuation correction performed using unenhanced CT (A–C) and IV contrast-enhanced CT (D–F). Coronal images show no perceived visual increase in 18F-FDG activity in mass (arrows) compared with A–C. Mean (maximum) SUV values of mass were 17.3 (24.6), an increase of 14.9% compared with A–C. Note 18F-FDG activity in contrast-enhanced right subclavian vein and heart is similar to A–C when unenhanced CT is used for attenuation correction. E, Attenuation-corrected PET with enhanced CT.

View larger version (86K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 3F —56-year-old man with non–small cell lung cancer manifesting as left upper lobe mass. Attenuation correction performed using unenhanced CT (A–C) and IV contrast-enhanced CT (D–F). Coronal images show no perceived visual increase in 18F-FDG activity in mass (arrows) compared with A–C. Mean (maximum) SUV values of mass were 17.3 (24.6), an increase of 14.9% compared with A–C. Note 18F-FDG activity in contrast-enhanced right subclavian vein and heart is similar to A–C when unenhanced CT is used for attenuation correction. F, Coregistered PET/CT.

Discussion

Top Abstract Introduction Materials and Methods Results Discussion References

 
Integrated PET/CT with coregistration of anatomic and functional imaging data overcomes inherent limitations of these techniques when performed separately and, in oncology patients, has been shown to improve tumor localization and the accuracy of staging [3, 12–16]. Typically, the CT component of this study is performed without the use of IV contrast media because of the overestimation of the PET attenuation factors when a contrast-enhanced CT is used for attenuation correction. Although it has been recently reported that PET scan quality is not compromised when oral and IV contrast media are used in integrated PET/CT performed to evaluate oncologic patients [14], no direct patient comparison between PET images corrected for attenuation using contrast-enhanced and unenhanced CT images has been reported. Our study shows that IV contrast-enhanced CT scans can be used for attenuation correction in oncologic patients with minimal effect on SUV in areas corresponding to low IV contrast media concentration. In regions of high contrast concentration, there is a significant increase in SUV; however, this increase is clinically insignificant in oncologic staging when these regions have background ¹⁸F-FDG uptake. Importantly, the increase in SUV measurement in these areas would not have been misinterpreted as sites of metastases.

The overestimation of the PET attenuation factors when an IV contrast-enhanced CT scan is used for attenuation correction is, in fact, a result of the difference in the attenuation properties of the contrast media when imaged using CT (70 keV effective energy) and PET energies (511 keV). At CT energies, tissue attenuation increases with contrast concentration but is negligibly affected at corresponding PET energies. It has thus been suggested that if the use of IV contrast media is considered essential for diagnostic interpretation of the CT scan, then this study should be performed separately after the unenhanced integrated PET/CT so that interpretation of the PET scan is not compromised [17, 18]. However, it would be beneficial if a contrast-enhanced CT could be obtained routinely in integrated PET/CT because as this has been shown to improve the localization and differentiation of a lesion identified with PET when compared with integrated PET/CT performed without the use of IV contrast media [15]. Our study shows that the change in SUV measurements caused by using an IV contrast-enhanced CT for attenuation correction in integrated PET/CT does not alter the clinical interpretation of the PET scan. This finding is similar to data published by Antoch et al. [14]. Specifically, there were no differences in clinical interpretation of the PET scans of all nine patients. In addition, the PET scans reconstructed with contrast-enhanced CT data showed no additional focal uptake because of the presence of the IV contrast media that could have been misinterpreted as malignancy. Accordingly, we recommend that a separate, contrast-enhanced diagnostic CT not be performed and advocate that IV contrast media could be used routinely when integrated PET/CT is performed to evaluate oncologic patients. However, an issue that may need to be addressed is the potential limitation of a CT performed in expiration, in terms of diagnostic quality. In this regard, our CT images are obtained in midexpiration, as this allows for optimal fusion of CT and PET images. However, acquisition of the CT in midexpiration rather than full inspiration (as is typically performed for diagnostic purposes) may potentially compromise detection of subtle pulmonary abnormalities.

The importance of confirming that IV contrast media use does not significantly alter the PET scan when a contrast-enhanced CT is used for attenuation correction is not limited to the detection and accurate staging of cancer. The use of PET in the clinical evaluation of therapeutic response and prognosis in oncologic patients is largely dependent on an accurate measurement of tumor SUV [19–31]. It has been reported that changes in ¹⁸F-FDG uptake after chemotherapy or radiation therapy correlate well with histopathologic tumor regression [19, 22–24, 26, 31–33]. The recommendation of the European Organization for Research and Treatment of Cancer on the measurement of ¹⁸F-FDG uptake for tumor response monitoring is that progressive disease be classified as a 25% increase in SUV compared with the baseline scan and partial response as a reduction of 15–25% in tumor SUV after one cycle of chemotherapy and greater than 25% after more than one treatment cycle [34]. However, SUV measurements are affected by the applied methods for image reconstruction and attenuation correction and could be compromised by using a contrast-enhanced CT for attenuation correction with integrated PET/CT [17, 35, 36]. In this regard, the effect on SUV measurements that occurs when a contrast-enhanced CT is used for attenuation correction could potentially have significant clinical ramifications because the percentage change in SUV that can determine or modify clinical management of oncology patients is small.

In our study, the measured SUVs of the primary malignancies and metastases showed that the largest increase in SUV_max was 18.6% when using contrast-enhanced CT for attenuation correction. This measured increase is larger than we would have anticipated when considering the bilinear graphic curve relationship of change in CT Hounsfield units and corresponding PET attenuation correction factors. Although the very large increase in the CT Hounsfield units in the region of the subclavian vein was expected to result in a large percentage increase in SUV (although visually and clinically insignificant), the increase in measured SUVs in malignancies that enhanced considerably less cannot be explained on the basis of the change in CT Hounsfield units. We postulate that the differences in the SUVs were to a large extent due to the slight misregistration of the PET and CT data when using the contrast-enhanced and unenhanced CT scans for PET attenuation correction. Misregistration of the CT and PET images results in the lesion not having the proper attenuation coefficients applied to the PET data; this may partially account for the discrepancy between the PET reconstructed with contrast-enhanced and unenhanced CT scans. This unexpected increase in measured SUVs was highest with the lung nodules analyzed and was most likely caused by the small size of the nodules and greater potential for misregistration compared with malignancies located in the mediastinum and bones.

One potential limitation of our study is the small number of patients evaluated. However, four anatomic areas were evaluated in each patient and the effect of contrast administration on the SUV was calculated in 12 tumor regions in the nine patients. In these 48 measurements, there was a significant statistical difference between the SUVs obtained from the PET scans reconstructed with contrast-enhanced CT scans versus the unenhanced CT scans. However, this statistical difference did not affect the clinical interpretation of the PET scan. Because of this, we believe that IV contrast-enhanced CT scans can be used for the attenuation correction of PET images. This conclusion was supported by provisional data presented by Graham et al. [37] at the 2004 annual meeting of the Radiological Society of North America. Other potential limitations of our study are the applicability of our results to other IV contrast-enhanced imaging protocols [37, 38] and nonmalignant etiologies such as infection.

In summary, although there is a significant increase in SUV in regions of high-contrast concentration when IV contrast-enhanced CT is used for attenuation correction, this increase is clinically insignificant in the evaluation of patients with cancer. Because the use of IV contrast media improves diagnostic interpretation and accuracy of staging in oncologic patients, the CT component of integrated PET/CT could be performed after IV contrast administration.

References

Top Abstract Introduction Materials and Methods Results Discussion References

 

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