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Application of Oral Contrast Media in Coregistered Positron Emission Tomography—CT

¹ All authors: Department of Medical Radiology, Division of Nuclear Medicine, University Hospital Zurich, Raemistr. 100, CH-8091 Zurich, Switzerland.

Received January 7, 2002; accepted after revision February 11, 2002.

Supported in part by General Electric Medical Systems, Buc, France, and the Radium Foundation, University of Zurich, Zurich, Switzerland.

Address correspondence to T. F. Hany.

Abstract

OBJECTIVE. Coregistration of positron emission tomography (PET) and CT images results in significantly improved localization of abnormal FDG uptake compared with PET images alone. For delineation of intestinal structures, application of oral contrast media is a standard procedure in CT. The influence of oral contrast agents in PET imaging using CT data for attenuation correction was evaluated in a comparative study on an in-line PET—CT system.

SUBJECTS AND METHODS. Sixty patients referred for PET—CT were evaluated in two groups. One group of 30 patients received oral Gastrografin 45 min before data acquisition. The second group received no contrast medium. PET images were reconstructed, using CT data for attenuation correction. Image analysis was performed by two reviewers in consensus, using a 4-point scale comparing FDG-uptake in the gastrointestinal tract in PET images of both groups. Furthermore, correlation of FDG uptake and localization of contrast media in the intestinal tract in CT images were determined.

RESULTS. No significant difference in FDG uptake in PET images in all regions of the gastrointestinal tract except the ascending colon was seen in both groups. No correlation was found in the location of increased FDG uptake and contrast media in the CT images.

CONCLUSION. An oral contrast agent can be used for coregistered PET—CT without the introduction of artifacts in PET.

Positron emission tomography (PET) and CT combined into a single scanner using low-dose CT providing hardware coregistered images significantly increase diagnostic accuracy of lesion type and location compared with PET alone [1, 2]. In addition, CT data can be used for attenuation correction to determine quantified uptake values, which are in agreement with the germanium-based technique [3]. This procedure results in a significant reduction of PET data acquisition time because data acquisition of attenuation scans with standard techniques in PET is a lengthy procedure. Image analysis of CT data in the abdomen is hampered by the similarity of CT densities of the bowel loops and other abdominal organs. Therefore, application of oral contrast media is a standard procedure to delineate intestinal structures from other retro- and intraperitoneal organs on CT.

Barium sulfate and meglumine diatrizoate (Gastrografin; Bracco Diagnostics, Princeton, NJ) are widely used as orally administered dilute contrast materials in CT imaging. Gastrografin contains 660 mg/mL of diatrizoate meglumine and 100 mg/mL of diatrizoate sodium. It is a water-soluble neutral iodinated contrast medium. The dose of nondiluted Gastrografin used for oral administration in clinical practice is usually 20-30 mL [4,5,6]. Sufficient luminal opacification of small bowel and parts of the colon is typically achieved 45 min after oral administration of 500-1000 mL of diluted contrast solutions.

In PET imaging, diffuse nonspecific intestinal FDG uptake of moderate degree is commonly seen and may interfere with the diagnosis of abnormal lesions [7]. The underlying causes are not well understood but do not seem to be related to peristalsis. Some authors postulate the cause to be increased FDG uptake into mucosal structures [8]. Attenuation correction may induce reconstruction artifacts around hyperdense structures such as metallic prostheses, which manifest themselves as low-uptake regions [3]. Administration of oral CT contrast agents improves the diagnostic value of CT images in PET-CT imaging. On the other hand, oral CT contrast agents could induce increased physiologic FDG uptake or reconstruction artifacts when CT data is used for PET attenuation correction.

The aim of our study was to determine the effect of an orally administered diluted Gastrografin solution in a patient population without clinical history of gastrointestinal disease. We compared the degree of FDG uptake in the gastrointestinal tract in two separate groups.

Subjects and Methods

Patient Selection
From June to September 2001, 60 consecutive patients who had a diagnosis or high suspicion for malignancy but no clinical history of intestinal disease and who gave written informed consent to participate in the study in accordance with regulations set forth by the institutional review board underwent combined whole-body PET—CT. One group (30 patients; 16 men, 14 women; age range, 23-76 years; mean age, 54.6 years) received 1000 mL of a 3% diluted diatrizoate meglumine and diatrizoate sodium solution (Gastrografin) before the FDG injection. The second group (control group; 30 patients; age range, 26-75 years; mean age, 54.3 years) received no contrast agent. The diagnoses in both groups are summarized in Table 1.

Data Acquisition
All imaging and data acquisition were performed on a novel combined PET—CT in-line system, combining an Advance NXi PET scanner and a multislice helical CT scanner (LightSpeed Plus; General Electric Medical Systems, Waukesha, WI) in one system (Discovery LS; General Electric Medical Systems). The axes of both systems were mechanically aligned to coincide perfectly. The offset between the CT and PET scanner-sensitive fields of view along the table axis was 60 cm. The same table was used to acquire PET and CT images. Because of mechanical limitations of the prototypical table version of the system, the table excursion was limited to six contiguous PET sections, covering 867 mm. This amount gave adequate coverage from head to pelvic floor in all patients examined. The PET and CT data sets were acquired on two independent computer consoles that were connected by an interface to transfer CT data to the PET scanner. Both machines could be used independently or as a combined system. PET and CT data sets were transferred to an independent, PC-based computer workstation (viewing station, version 1.2; General Electric Medical Systems) by Digital Imaging and COmmunications in Medicine transfer, on which viewing of all PET images was performed. PET—CT images were viewed using a dedicated software, again running on a PC-based workstation with viewing software (eNTEGRA; ELGEMS, Haifa, Israel). Although PET images were acquired during free breathing and all images were acquired over multiple respiratory cycles, CT scans were acquired during shallow breathing.

Before the examination, patients fasted for at least 4 hr before the IV administration of 10 mCi (370 MBq) of FDG. The examination was started 45 min after the injection. CT data were acquired first. The patient was positioned on the table in a headfirst supine position. Because the acquisition was limited to six contiguous volumes with an axial extent of 14.6 cm each, start and end locations were chosen carefully to ensure coverage of the region of interest of entire body from the level of the cerebellum to the pelvic floor. The arms of the patients were placed in an elevated position above the abdomen to reduce beam-hardening artifacts at the level of the liver. For the CT scan, the following parameters were used: tube rotation time, 0.5 sec/evolution; 140 kVp; 80 mA; reconstructed slice-thickness, 5 mm; scan length, 867 mm; acquisition time, 22.5 sec.

After the CT data acquisition was completed, the tabletop with the patient was automatically advanced into the PET-sensitive field of view, and acquisition of PET emission data was started at the level of the pelvic floor. Six incremental table positions, each 146 mm wide, were acquired with minimal overlap, thereby covering 867 mm of table travel. For each position, 35 two-dimensional non-attenuation-corrected scans were obtained simultaneously over a 4-min period. For attenuation correction, the CT scans were first reduced to the PET resolution by smoothing with a gaussian filter of 8 mm full-width, half-maximum. Next, the CT pixel values in Housfield units were transformed into linear attenuation coefficients in cm^-1 at 511 keV by a bilinear function defined by the three coordinates [-1000 H, 0 cm^-1], [0 H, 0.0933 cm^-1], and [1326 H, 0.172 cm^-1]. Axial attenuation-corrected slices were reconstructed using iterative reconstruction.

Image Analysis
PET images of both groups were randomized and analyzed by two reviewers in consensus. The reviewers were blinded to the diagnoses and had no access to the CT images. The gastrointestinal system was divided into the following seven regions: stomach, duodenum, small bowel, ascending colon, transversal colon, descending colon, and rectosigmoid. Each segment was graded on a 4-point scale: 1, uptake equals air; 2, uptake equals liver; 3, uptake is more than liver but less than brain; 4, uptake equals brain. Grades of 1 and 2 were qualified as low-intensity uptake; grades of 3 and 4 were qualified as high-intensity uptake.

In the group with administration of oral contrast agent, CT images were analyzed for the presence of opacification due to contrast agent (1, contrast present; 0, no contrast agent present).

Statistical Analysis
A chi-square test was applied to determine statistical differences of increased FDG uptake in both groups. To determine the correlation of contrast agent location and FDG uptake in the contrast agent group, a Spearman's rank correlation coefficient was calculated.

Results

All data were obtained without technical problems and with no claustrophobia in either group. All patients in the contrast agent group ingested the total amount of 1000 mL before FDG injection. No side effects were encountered within 24 hr after administration of Gastrografin.

The results of the analysis of high-intensity FDG uptake in patients who were administered Gastrografin were as follows: in 32 (15.2%) of 210 regions, high-intensity FDG uptake was seen (Table 2). The region most affected was the ascending colon including the cecum (16 [50%] of the 32 regions showing FDG uptake). The data concerning the FDG uptake in patients of the control group are listed in Table 2.

In the ascending colon, significantly more segments in the contrast group showed increased FDG uptake compared with the group not receiving oral contrast [X²(df = 1) = 13.02; p < 0.001] (Figs. 1A,1B and 2A,2B). However, comparison of both groups did not show a significant difference of distribution in high-intensity FDG uptake in the following intestinal regions: stomach, duodenum, small bowel, transversal colon, descending colon, and rectosigmoid [X²(df = 1) = 0.03; p > 0.05] (Figs. 3A,3B and 4A,4B).

View larger version (76K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1A. —68-year-old man with head and neck tumor of unknown primary origin detected after neck dissection on right side. Positron emission tomography (PET)—CT was performed without oral contrast media. Coronal PET image shows high-intensity FDG uptake in ascending colon.

View larger version (68K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1B. —68-year-old man with head and neck tumor of unknown primary origin detected after neck dissection on right side. Positron emission tomography (PET)—CT was performed without oral contrast media. Fused coronal PET-CT image at same location as A shows no opacification of intestinal structures in CT image.

View larger version (84K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2A. —53-year-old woman with history of breast cancer on left side. Positron emission tomography (PET)—CT was performed with oral contrast media. Coronal PET image shows high-intensity FDG uptake in ascending colon.

View larger version (70K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2B. —53-year-old woman with history of breast cancer on left side. Positron emission tomography (PET)—CT was performed with oral contrast media. Fused coronal PET—CT image at same location as A shows opacification of intestinal structures in ascending colon while high-intensity FDG uptake is present in ascending colon.

View larger version (88K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 3A. —65-year-old man with vocal cord carcinoma. Positron emission tomography (PET)—CT was performed without oral contrast media. Coronal PET image shows only low-intensity FDG uptake in intestinal structures.

View larger version (73K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 3B. —65-year-old man with vocal cord carcinoma. Positron emission tomography (PET)—CT was performed without oral contrast media. Fused coronal PET—CT image was obtained at same location as A.

View larger version (67K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 4A. —57-year-old man with hypopharyngeal carcinoma. Positron emission tomography (PET)—CT was performed with oral contrast media. PET image shows only low-intensity FDG uptake in intestinal structures.

View larger version (73K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 4B. —57-year-old man with hypopharyngeal carcinoma. Positron emission tomography (PET)—CT was performed with oral contrast media. Fused coronal PET—CT image was obtained at same coronal slice location as A. Note opacification of ascending and descending colon in CT images.

In the patient group receiving oral contrast material, no correlation was found between the location of increased FDG uptake and the presence of contrast media in the CT images using a Spearman's rank correlation coefficient (r < 0.36 for all segments) (Fig. 5).

View larger version (12K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 5. —Graph shows distribution of low- and high-intensity FDG uptake in contrast agent—containing regions in contrast group. Black bars = high-intensity FDG uptake, gray bars = low-intensity FDG uptake.

Discussion

An oral contrast agent can be used in combined PET—CT imaging because its effect on the PET images is minimal. Only a slight increase of FDG uptake was observed in the ascending colon. All other gastrointestinal structures showed no significant difference in FDG uptake using Gastrografin.

Imaging with FDG PET for tumor staging provides physiologic information on glucose uptake and metabolism. The main drawback of PET in tumor imaging is the virtual absence of anatomic landmarks, which impedes precise lesion localization. The potential of multimodality image fusion has been recognized early because CT, MR imaging, and PET yield complementary information in many diagnostic settings. Townsend and Cherry [9] introduced a combined PET—CT scanner, using a helical CT and a PET scanner, which permits the acquisition of hardware coregistered PET and CT images in the same imaging session. Analysis of the results showed an improvement in lesion localization and classification.

CT can depict abnormal anatomy and contrast enhancement due to disease. The use of oral contrast media is crucial in diagnostic imaging of the abdomen on CT. Oral contrast agents like Gastrografin are an effective method for opacifying the gastrointestinal tract, which is necessary to achieve optimal delineation of abdominal organs [10]. Opacifying the gastrointestinal tract also definitively aids in diagnosis of enteric perforation and in the depiction of small-bowel wall thickening and free intraabdominal fluid [11].

A major technical advantage in PET—CT is the use of CT data for attenuation correction in image reconstruction of PET emission data. Imaging time using the conventional germanium-based attenuation correction is lengthy compared with the 30 or less seconds using multidetector CT. However, using CT data for attenuation correction may interfere with PET image reconstruction. Kinahan et al. [3] have proven that CT data for attenuation correction is accurate. However, no data on the extent to which an oral contrast agent with rather high densities influences attenuation correction are available. We used a group of patients with unenhanced PET—CT as a control group because there is no substantial difference between germanium and CT data—corrected PET images.

No significant difference was seen in FDG uptake in PET images of all regions of the gastrointestinal tract except the ascending colon when we compared the patient groups with and without oral contrast material. No correlation was found in the location of increased FDG uptake and contrast media in the CT images for all regions. This lack of correlation can be explained by the data acquisition. CT data is acquired initially, whereas the emission data are acquired between 2 and 10 min later. In the meantime, contrast agent is traveling farther through the gastrointestinal system. Therefore, CT data do not exactly represent the distribution of contrast agent present during abdominal PET scanning. In principle, a mismatch of low CT density at the time of CT data acquisition and high CT contrast density at the time of emission data collection could occur. This situation would result in an artificially reduced FDG uptake.

Physiologic rather than technical effects may cause increased FDG uptake in the ascending colon. Gastrografin itself stimulates peristalsis, which could result in muscular uptake. However, no increased uptake in PET—CT using Gastrografin was observed in any region except the ascending colon. Our data, therefore, also suggest that increased FDG uptake observed in standard PET scans is most likely due to peristalsis-induced increased muscular uptake because in this case, all regions would be affected. This conclusion is also in accordance with the results of Nakada et al. [8], which suggest that increased FDG uptake is due to uptake into mucosal structures because in their experiments, muscular activity was eliminated. A difference existed in the histology of the intestinal glands in the ascending colon, the descending colon, the rectum, and the small intestine. Cormack [12] reported that glands in the ascending colon consist of small columnar cells, and glands in the descending colon and rectum contain vacuolated cells. The secretion of these vacuolated cells is more sulfated than that of small columnar cells [13]. Therefore, specific increased activation of glandular structures in the ascending colon compared with other regions could induce increased FDG uptake or even excretion into lumen.

Severe respiratory distress, toxic epidermal necrolysis, narcotizing enterocolitis, small-bowel angioedema, and anaphylactoid purpura reactions related to oral administration of diatrizoate meglumine and diatrizoate sodium are known to occur [14,15,16,17,18,19]. The possible cause of anaphylaxis is an absorption of iodine contained in Gastrografin [5]. However, several investigators have reported that severe reactions to oral contrast media are rare [15, 18, 20]. The hypertonicity of Gastrografin can cause pulmonary edema if the agent is aspirated [5, 21]. Recent publications reported that oral contrast administration does not substantially increase the risk of aspiration [11, 22, 23]. We did not observe any side effects in the 30 patients in our study.

Because PET—CT data can be used for radiation-treatment planning, the use of oral Gastrografin is contraindicated in patients who will undergo radiation treatment. Radiation doses are calculated using density maps from CT data. Artificially increased densities induced by contrast media will corrupt dose calculations for radiation-treatment planning.

A limitation of our study is the missing comparison of different oral contrast agents like barium sulfate, which is widely used for intestinal opacification on CT. Because barium sulfate has a higher attenuation coefficient, it may be expected to lead to increased attenuation on PET imaging. However, higher diluted barium sulfate solutions might also be suitable for combined PET—CT imaging; however, this option should be established in further studies.

We conclude that oral contrast agents like Gastrografin can be used for coregistered PET—CT imaging without the introduction of artifacts in PET imaging. We believe that slightly increased FDG uptake in the ascending colon is due to physiologic causes induced by administration of Gastrografin but does not interfere with diagnosis. The advantages of using oral contrast media in PET-CT imaging are evident because their benefits in diagnosis have been documented in the CT literature.

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This Article Abstract Figures Only Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dizendorf, E. V. Articles by Hany, T. F. Search for Related Content PubMed PubMed Citation Articles by Dizendorf, E. V. Articles by Hany, T. F. Social Bookmarking                      What's this?