Clinical Observations
Nuclear Medicine
August 2007

Anterior Layering of Excreted 18F-FDG in the Bladder on PET/CT: Frequency and Cause

Abstract

OBJECTIVE. The objective of our study was to determine the frequency and cause of anterior layering of excreted 18F-FDG in the bladder on PET/CT.
CONCLUSION. Anterior layering of excreted FDG in the bladder is commonly seen on PET/CT scans obtained with IV iodinated contrast material and is due to displacement of FDG by excreted iodinated contrast material; this phenomenon may unmask FDG-avid bladder disease.

Introduction

Combined PET/CT with 18F-FDG is increasingly used for the diagnosis, staging, and surveillance of malignancy. The role of PET/CT in urothelial malignancies is limited in part by the normal concentration and accumulation of FDG in the renal collecting system that may mask hypermetabolic lesions within and adjacent to the ureters and urinary bladder [1-3]. Different protocols have been proposed to minimize bladder activity from excreted FDG, including instructing the patient to void immediately before imaging, scanning caudad to craniad, and performing bladder lavage [4]. Conversely, excreted iodinated contrast material may appear in the bladder as ureteral jets or as a dependent high-attenuation layer, and the utility of IV contrast material for whole-body PET/CT and the potential artifacts related to its use have been reported [5, 6].
To our knowledge, the potential for any imaging interaction between excreted FDG and excreted iodinated contrast material in the bladder has not been described. At our institution, IV iodinated contrast material is routinely administered for the CT component of the examination because we believe that contrast-enhanced PET/CT provides diagnostic morphologic and functional data in a single study, rendering additional diagnostic CT examinations unnecessary. In our experience, attenuation-correction errors related to IV contrast material are not clinically significant. In addition, we have anecdotally noted anterior layering of FDG in the urinary bladder on PET/CT examinations (Fig. 1). We therefore undertook this study to determine the frequency and cause of anterior layering of excreted FDG in the bladder on PET/CT performed with IV iodinated contrast material and to investigate any potential effect on the diagnosis of urinary tract disease.

Materials and Methods

Subjects

This retrospective single-institution study was approved by the Committee on Human Research at the University of California, San Francisco, and was compliant with the Health Insurance Portability and Accountability Act. Informed consent was waived. We performed a computerized search of our radiology information system (IDXrad software, version 9.7.1, IDX Systems) to identify the first 100 consecutive patients who had undergone PET/CT at our institution during March 2006. Each patient underwent one study, for a total of 100 PET/CT examinations.
The study population consisted of 58 women and 42 men with a mean age of 55 years (range, 18-84 years). The indications for PET/CT were staging or surveillance of breast cancer (n = 29), lymphoma (n = 15), lung cancer (n = 14), melanoma (n =12), head and neck cancer (n = 8), ovarian cancer (n =7), colorectal cancer (n = 6), sarcoma (n = 2), pheochromocytoma (n = 3), esophageal cancer (n =2), bladder cancer (n = 1), and nerve sheath tumor (n =1).

PET/CT Technique

All studies were performed on a PET/CT scanner (Biograph 16, Siemens Medical Solutions) that is a hybrid PET and 16-MDCT unit. CT was performed first at 152 mAs, 120 kV, and 0.75-mm collimation. Images were obtained from the top of the patient's head to the feet and were reconstructed as contiguous 5-mm slices. In 86 patients, 150 mL of IV iohexol (Omnipaque 350, Nycomed Amersham) was administered 70-80 seconds before CT. The contrast material was injected at a rate of 3 mL/s and followed by a 50-mL saline flush. PET was performed immediately after CT without repositioning the patient, and imaging commenced 60 ± 15 minutes (mean ± SD) after the injection of 12.5 ± 2.5 mCi (462.5 ± 92.5 MBq) of FDG. PET images were obtained at 7-10 stations per patient, with an acquisition time of 4 minutes per station, from the top of the patient's head to the feet. In other words, the PET images of the pelvis were obtained approximately 25-40 minutes after the injection of IV CT contrast material. CT data were used for attenuation correction, and results were reconstructed into sagittal, coronal, and axial planes. In the other 14 patients, no iodinated contrast material was given because of renal insufficiency (n = 11) or suspected pheochromocytoma (n = 3). Patients were instructed to remain still throughout the entire examination.
Fig. 1 52-year-old woman with breast cancer. Coned-down transverse PET image of urinary bladder shows fluid-fluid level with anterior layering of 18F-FDG-impregnated urine.
Fig. 2A —75-year-old man with melanoma imaged without IV iodinated contrast material. CT (A) and PET (B) images of urinary bladder show homogeneous appearance of bladder contents without anterior layering of 18F-FDG.
Fig. 2B —75-year-old man with melanoma imaged without IV iodinated contrast material. CT (A) and PET (B) images of urinary bladder show homogeneous appearance of bladder contents without anterior layering of 18F-FDG.

Image Interpretation

A single observer who was unaware of whether IV contrast material had been administered reviewed only the PET images on a dedicated image-processing workstation (Leonardo, Siemens Medical Solutions) and recorded the presence or absence of anterior layering of excreted FDG in the bladder. All studies were viewed with and without attenuation correction. Anterior layering of FDG in the urinary bladder was considered to be present when a fluid-fluid level was seen in the expected position of the urinary bladder with relative photopenia in the posterior bladder. Similar assessment was made for the renal pelvises. Any abnormal focal uptake in the urinary tract was also noted. Each patient's medical records were reviewed for the presence or absence of bladder abnormalities, and these findings were later correlated with the PET findings.

PET/CT Phantom

To further elucidate the cause of anterior layering of excreted FDG in the bladder, we performed in vitro PET/CT of specially constructed phantoms designed to mimic the content of the bladder during a PET/CT examination. The first phantom consisted of a 1-L radiolucent bottle containing an agitated mixture of 400 mL of diluted iodinated contrast material and 200 mL of diluted FDG. The diluted solution of FDG consisted of 250-μCi (9,250 kBq) FDG in 200 mL of isotonic saline. The diluted solution of iodinated contrast material consisted of 360 mL of isotonic saline mixed with 40 mL of iohexol (Omnipaque 350).
For the second phantom, a separate 1,000-mL bottle was filled with 100 mL of 125-μCi (4,625 kBq) FDG diluted in saline and then 100 mL of the same diluted iodinated contrast material was manually injected, using a catheter-tip syringe, into the dependent portion of the bottle over a period of 1 minute. We chose to inject the iodinated contrast material into the dependent portion of the bottle because at our institution CT contrast material is given after FDG and because the ureters insert into the posterior (dependent) portion of the bladder. PET/CT images of both phantoms were obtained at 0, 5, and 10 minutes after agitation using the same imaging parameters as described for our clinical in vivo studies.

Results

In Vivo Studies

Anterior layering of excreted FDG in the bladder was seen on 61 of 86 studies (71%) performed with IV iodinated contrast material but was not seen on any of the 14 studies performed without IV contrast material (Fig. 2A, 2B). This difference was highly significant (p < 0.001). Attenuation correction did not affect the appearance of anterior layering of FDG in the urinary bladder in any patient. In one patient, FDG uptake in a malignant posteriorly located bladder mass was unmasked by the anterior layering phenomenon (Fig. 3A, 3B, 3C). This mass was later biopsied at cystoscopy, with a final pathologic diagnosis of intestinal-type adenocarcinoma.

In Vitro Phantom Study

Imaging of the agitated phantom containing diluted FDG and iodinated contrast material showed the gradual development of a separation gradient, with the FDG activity becoming gradually localized to the nondependent portion of the phantom (Fig. 4A, 4B). Images of the nonagitated phantom revealed a sharp fluid-fluid level with no evidence of mixing on delayed imaging (Fig. 5).
Fig. 3A —72-year-old man with colon cancer and new bladder metastasis. IV and oral contrast-enhanced CT image obtained through pelvis shows enhancing mass (arrow) arising from left posterior bladder wall.
Fig. 3B —72-year-old man with colon cancer and new bladder metastasis. PET image obtained at same level as A shows anterior layering of excreted 18F-FDG (arrow), thereby revealing FDG-avid mass in posterior bladder.
Fig. 3C —72-year-old man with colon cancer and new bladder metastasis. Fused PET/CT image. Note that some misregistration (arrow) occurred due to gradual filling of bladder with urine between time of CT and time of PET image acquisitions.
Fig. 4A —Agitated PET/CT phantom. Volume-rendered CT reconstruction of bottle containing 18F-FDG solution and dilute iodinated contrast material that was shaken 5 minutes before imaging. Note gradual CT attenuation gradient with increased CT attenuation fluid in dependent portion of bottle.
Fig. 4B —Agitated PET/CT phantom. Volume-rendered reconstruction of fused PET/CT scan corresponding to A shows higher FDG activity displaced in nondependent portion of bottle.
Fig. 5 Nonagitated PET/CT phantom. Volume-rendered reconstruction of fused PET/CT images shows well-defined fluid-fluid level (arrow) after slow, dependent injection of iodinated contrast material, which anteriorly displaced 18F-FDG solution.

Discussion

The results of the in vivo arm of our study indicate that anterior layering of excreted FDG in the bladder is seen exclusively on scans obtained with IV iodinated contrast material. This phenomenon was reproduced with in vitro imaging of a phantom containing diluted FDG and iodinated contrast material. These observations suggest the layering phenomenon is due to anterior displacement of excreted FDG by excreted iodinated contrast material. The disparity in physical density between normal urine (normal range of specific gravity, 1.005-1.030) and iohexol (range, 1.16-1.41 for CT) [7] presumably allows this separation.
The clinical utility of this finding might seem limited, but in one case the anterior displacement of FDG did help unmask an FDG-avid posteriorly located bladder malignancy. Bladder activity merits close scrutiny on PET/CT studies, particularly if performed with iodinated IV contrast material, and should not be perfunctorily dismissed as always representing only excreted FDG. A more speculative interpretation of this finding is that it suggests the displacement phenomenon could potentially be exploited for improving bladder imaging at PET by imaging the patient in the supine or prone position or in both positions depending on the location of the lesion in question. This would avoid other burdensome and cumbersome techniques that have been suggested to assist evaluation of bladder abnormalities at PET, such as bladder lavage. However, the value of this potential application remains to be tested and may be limited by the fact that separation of the excreted FDG and iodinated contrast material is not observed in all studies performed with IV iodinated contrast material (71%).
It should be noted that our protocol was to acquire the contrast-enhanced CT images after administration of FDG but before acquisition of the PET images. Presumably at the time of PET image acquisition, iodinated contrast material had accumulated in the bladder in sufficient quantity to cause anterior layering of FDG, although we did not directly confirm this by performing delayed CT of the bladder at the exact same time as PET. Further study is needed to determine contributing factors to anterior layering, possibly with delayed CT and correlation with additional clinical information (including renal function). Another limitation of this study is that images were interpreted by a single observer. However, the appearance of anterior layering of FDG in the bladder is distinctive at PET and is unlikely to be misinterpreted.
In conclusion, anterior layering of excreted FDG in the bladder is commonly seen on PET/CT scans obtained with IV iodinated contrast material and is due to displacement of FDG by excreted iodinated contrast material; this phenomenon may unmask FDG-avid bladder disease.

Footnotes

Address correspondence to B. M. Yeh.
WEB This is a Web exclusive article.

References

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Deserno WM, Harisinghani MG, Taupitz M, et al. Urinary bladder cancer: preoperative nodal staging with ferumoxtran-10-enhanced MR imaging. Radiology 2004; 233:449-456
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Subhas N, Patel P, Pannu H, Jacene H, Fishman E, Wahl R. Imaging of pelvic malignancies with inline FDG PET-CT: case examples and pitfalls of FDG PET. RadioGraphics 2005; 25:1031-1043
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Schoder H, Larson SM. Positron emission tomography for prostate, bladder, and renal cancer. Semin Nucl Med 2004; 34:274-292
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Koyama K, Okamura T, Kawabe J, et al. Evaluation of 18F-FDG PET with bladder irrigation in patients with uterine and ovarian tumors. J Nucl Med 2003; 44:353-358
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Beyer T, Antoch G, Bockisch A, Stattaus J. Optimized intravenous contrast administration for diagnostic whole-body 18F-FDG PET/CT. J Nucl Med 2005; 46:429-435
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Yau YY, Chan WS, Tam YM, et al. Application of intravenous contrast in PET/CT: does it really introduce significant attenuation correction error? J Nucl Med 2005; 46:283-291
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Amersham Health Web page. Omnipaque product information: prescribing information sheet. Available at: www.amershamhealth-us.com/shared/pdfs/pi/Omnipaque.pdf. Accessed April 19, 2007

Information & Authors

Information

Published In

American Journal of Roentgenology
Pages: W96 - W99
PubMed: 17646448

History

Submitted: December 5, 2006
Accepted: March 28, 2007

Keywords

  1. bladder cancer
  2. bladder neoplasm
  3. contrast media
  4. FDG PET
  5. image artifacts
  6. oncologic imaging
  7. PET/CT

Authors

Affiliations

Derk D. Purcell
All authors: Department of Radiology, University of California, San Francisco, Box 0628, M-392, 505 Parnassus Ave., San Francisco, CA 94143-0628.
Fergus V. Coakley
All authors: Department of Radiology, University of California, San Francisco, Box 0628, M-392, 505 Parnassus Ave., San Francisco, CA 94143-0628.
Benjamin L. Franc
All authors: Department of Radiology, University of California, San Francisco, Box 0628, M-392, 505 Parnassus Ave., San Francisco, CA 94143-0628.
Randall A. Hawkins
All authors: Department of Radiology, University of California, San Francisco, Box 0628, M-392, 505 Parnassus Ave., San Francisco, CA 94143-0628.
Sophie E. Boddington
All authors: Department of Radiology, University of California, San Francisco, Box 0628, M-392, 505 Parnassus Ave., San Francisco, CA 94143-0628.
Benjamin M. Yeh
All authors: Department of Radiology, University of California, San Francisco, Box 0628, M-392, 505 Parnassus Ave., San Francisco, CA 94143-0628.

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