DOI:10.2214/AJR.04.1337
AJR 2005; 185:1045-1047
© American Roentgen Ray Society
Contrast-Enhanced Dark Lumen PET/CT and MR Colonography in a Rodent Polyp Model: Initial Results with Histopathologic Correlation
Christiane A. Kuehle1,
Patrick Veit1,
Gerald Antoch1,
Florian Grabellus2,
Philippe Robert3,
Thomas Beyer1 and
Christoph U. Herborn1
1 Department of Diagnostic and Interventional Radiology, University Hospital
Essen, Hufelandstrasse 55, 45122 Essen, Germany.
2 Institute of Pathology, University Hospital Essen, Essen, Germany.
3 Guerbet Group, Aulnay-sous-Bois, France.
Received September 9, 2004;
accepted after revision November 23, 2004.
Address correspondence to C. U. Herborn.
Abstract
OBJECTIVE. The objective of this study was to assess the feasibility
of PET/CT for the detection of colorectal masses in a rodent polyp model in an
intraindividual comparison with dark-lumen MR colonography.
CONCLUSION. Detection of small tumors with PET/CT and MR
colonography is possible in a rodent model. The technique thus warrants
further evaluation in animal studies as well as in patients with suspected
colorectal disease.
Introduction
Although precursors of colorectal cancer are detectable with endoscopic
colonography, colorectal carcinoma is still the second most frequent malignant
tumor in Western countries [1].
In part, this is due to the lack of acceptance for endoscopy because of
procedural discomfort and the risk of complications. Thus, alternative imaging
strategies are mandatory. Cross-sectional imaging techniques such as CT and
MRI have been clinically introduced successfully for detection of colorectal
polyps
[2-3].
Clinical benefits of cross-sectional over fiberoptic imaging include
noninvasiveness, complete coverage of the colon, and detection of extraluminal
findings, to mention only a few
[4-5].
MRI offers excellent soft-tissue contrast without the risk of ionizing
radiation, and the contrast agents lack nephrotoxicity. On the other hand, CT
provides high spatial resolution, fast data acquisition, and wide clinical
availability. However, both CT and MRI are based on anatomic morphology rather
than on functional information.
18F-FDG PET provides functional data because of its ability to
detect elevated glucose metabolism, but it suffers from low spatial
resolution. Most recently, dual-technique PET/CT has been clinically
introduced [6]. This approach
provides accurately fused functional PET and morphologic CT data in a single
examination. Current knowledge regarding the role and clinical impact of
PET/CT in diagnosing cancer of the large bowel is limited, making evaluation
of the technique in an animal model attractive. The aim of this study was to
assess the feasibility of PET/CT for the detection of colorectal masses in a
rodent polyp model.
Materials and Methods
Animal Model
All animal experiments were performed in full accordance with regulations
set forth by our institutional animal care and use committee. At the age of 4
months, four male Wistar rats received a total of four colon enemas of
carcinogenic N-methyl-N-nitro-N-nitrosoguanidine
solution (MNNG, 5 mg/mL; 0.5 mL per injection) to induce polyps
[7]. PET/CT and MRI were
performed after a time interval of 8 months.
Animal Preparation
The animals were deprived of food and allowed to drink only 5% glucose
saline 24 hr before the diagnostic experiments to clean the gastrointestinal
tract. Before imaging, the animals were fully anesthetized with an
intraperitoneal injection of pentobarbital (30 mg/kg body weight). All animals
were examined in a supine position. For colon distention, a small rectal tube
(diameter, 0.4 cm; length, 2.0 cm) was carefully inserted. A 22-gauge plastic
venous cannula was placed in the tail vein. To minimize bowel peristalsis, a
body-weight-adjusted dose (0.5 mg/kg) of scopolamine (Buscopan, Boehringer
Ingelheim) was administered IV before filling the colon with a saline enema
(20 mL, 37°C, manual application). The rectal tube was locked with a
rubber seal to prevent leakage during the examination.
PET/CT Colonography
Dual-technique PET/CT was performed on a Biograph System (Siemens Medical
Solutions) based on a dual-slice CT scanner (Somatom Emotion, Siemens) and a
full-ring PET scanner (ECAT HR+, Siemens). In this scanner the respective
field of view is 15.5 cm per bed position, and all animals matched into one of
those. CT data were used for attenuation correction. Parameters were as
follows: 120 mAs; 130 kV; 1-mm slice thickness with a 0.5 incremental
reconstruction; 8-mm table feed. The in-plane spatial resolution was 4.6 mm.
Images were acquired 60 min after administration of 25-30 MBq of
18F-FDG; blood glucose levels were measured before administration
of 18F-FDG to ensure normal range. Manual injection of 1 mL of
iodinated contrast agent (iobitridole, Xenetix 300; Guerbet) directly before
the CT examination was followed by a bolus of 2 of mL of saline both at a rate
of approximately 0.5 mL/sec. Scanning was performed in caudocranial direction
after a delay of 20 sec.
MR Colonography
Image acquisition was performed directly after the PET/CT examination on a
clinical 1.5-T whole-body MRI system (Magnetom Sonata, Siemens) using the knee
coil. Unenhanced and 0.3 mmol/kg contrast-enhanced (gadoterate meglumine,
Dotarem; Guerbet) 3D T1-weighted gradient echo scans were acquired in the
coronal plane with the following parameters: field of view, 7.5 x 5 cm;
TR/TE, 6.11/2.02; flip angle, 12°, fat saturation; matrix size, 144
x 256; spatial resolution (zero interpolation), 0.6 x 0.5 x
1.2 mm; four averages; acquisition time, 4:06 min. Manual contrast agent
injection was followed by a bolus of 2 of mL of saline both at a rate of
approximately 0.5 mL/sec. The unenhanced scan was later subtracted from the
contrast-enhanced scan.
Image Analysis
The Biograph provides separate CT and PET data sets that can be accurately
coregistered on a workstation. PET/CT data were evaluated for lesion detection
by two radiologists in consensus. On CT images, the radiologists considered
masses or thickening of the bowel indicative for polyps, on PET images, an SUV
of more than 2.5 was considered indicative.
For MRI, commercially available postprocessing software (Leonardo, Siemens)
provided interactive multiplanar viewing and rendered 3D displays of the
colorectal structures. Lesions were defined as intraluminal soft-tissue masses
with enhancement after MRI contrast administration. Two radiologists analyzed
the MRI data sets in consensus for lesion detection. All reviewers were
unaware of postmortem results.
Histopathologic Analysis
After the imaging procedures, all animals were sacrificed by an IV overdose
of pentobarbital. Histopathologic analysis of the colon was the standard of
reference. Location and size of colonic masses were recorded. The attending
pathologist was unaware of the PET/CT and MRI findings.
Results
Postmortem macroscopic and histologic evaluation revealed two dysplastic
polyps (7 and 9 mm in diameter, respectively) in two of four rodents. PET/CT
colonography proved feasible in all animals without any periprocedural
complications and allowed for prospective detection of one of two polyps with
an overestimated size of 1.1 cm (Figs.
1A,
1B, and
1C). The SUV of the tumor was
1.7. The second polyp was only found retrospectively due to its location
behind the bladder, demanding special windowing and reconstruction. The
diameter was also slightly overestimated at 9 mm. SUV of the second lesion was
1.5. The bladder in this particular case had an SUV of 5.1. There were no
false-positive PET/CT findings.
With MRI, both polyps were correctly detected prospectively (Figs.
2A,
2B,
2C,
2D, and
2E) and lesion diameters were
correctly identified. However, MRI interpretation identified one
false-positive lesion because residual stool was misjudged as a polyp.
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Fig. 2A —Same rodent as in Figures
1A,
1B, and
1C with distal colon polyp. All
images are anterior coronal views of MR colonography data sets (T1-weighted
gradient-recalled echo sequence). Polyp (arrow) is difficult to
detect on unenhanced image.
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Fig. 2B —Same rodent as in Figures
1A,
1B, and
1C with distal colon polyp. All
images are anterior coronal views of MR colonography data sets (T1-weighted
gradient-recalled echo sequence). Polyp is detectable after contrast agent
administration (0.3 mmol/kg gadoterate meglumine) as lesion with focal
enhancement (arrow).
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Fig. 2C —Same rodent as in Figures
1A,
1B, and
1C with distal colon polyp. All
images are anterior coronal views of MR colonography data sets (T1-weighted
gradient-recalled echo sequence). Subtraction of unenhanced image from
contrast-enhanced image delineates polyp (arrow).
|
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Fig. 2D —Same rodent as in Figures
1A,
1B, and
1C with distal colon polyp. All
images are anterior coronal views of MR colonography data sets (T1-weighted
gradient-recalled echo sequence). Macroscopic view of opened colon shows polyp
(arrow).
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Fig. 2E —Same rodent as in Figures
1A,
1B, and
1C with distal colon polyp. All
images are anterior coronal views of MR colonography data sets (T1-weighted
gradient-recalled echo sequence). Histologic section of tubular polyp
(arrowheads) arising from regular colonic wall (arrows)
shows minimal branching, hyperchromatic nuclei, and decreased mucin.
|
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Discussion
In this article, we present preliminary results of a PET/CT colonography
examination that proves feasible for visualization of large bowel polyps in
rodents. Polyps show up with high glucose uptake, which makes them easily
detectable on PET and anatomic localization can be achieved through CT. This
combination might translate into increased sensitivity and specificity over
single PET and MRI for colorectal lesions in humans because PET/CT can connect
functional information with excellent anatomic correlation. However,
particular consideration has to be placed on the colon segments behind the
bladder to differentiate between renal excretion and 18F-FDG
accumulation in the bladder and enhancement of bordering colon polyps.
Also MRI has been shown to accurately detect polyps and inflammatory
lesions within the large bowel
[8]. Nevertheless, the high
signal of residual stool and bowel peristalsis during measurements for later
data subtraction might impair diagnostic quality. This was shown in one
false-positive lesion in this study.
The polyps in this animal model are relatively small, not exceeding 9 mm in
diameter. By human standards, polyps measuring 1 cm or larger are considered
clinically significant [1].
18F-FDG is physiologically taken up in the bowel wall,
especially when peristalsis is present. This might obscure subtle parietal
lesions, or it could cause false-positive findings. However, this risk can be
minimized by effective suppression of peristalsis with a precedent scopolamine
injection [9].
Our study shows that detection of small tumors with PET/CT is possible in a
rodent model. The technique thus warrants further evaluation in animal studies
and in clinical studies in patients with suspected colorectal disease.
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Abstract
Introduction
