Introduction
Introduction
Colorectal cancer (CRC) remains the second leading cause of cancer mortality in western
countries. Approximately 6 % of the population will develop CRC during their lifetime
[1]. The majority of colon cancers develop from non-malignant adenomas or polyps [2]. Thus, cancer screening programs targeting precancerous polyps with subsequent endoscopic
polypectomy could potentially reduce the incidence and thus the mortality of colorectal
cancer significantly.
Insufficient diagnostic accuracy and/or poor patient acceptance characterise most
available colorectal screening modalities, including testing for occult fecal blood,
conventional colonoscopy, or double-contrast barium enema [3]
[4]. Recently virtual colonography (VC), based on 3D CT or MR data sets has been propagated
for colorectal screening. VC has been found to be highly sensitive for detecting colorectal
polyps exceeding 8 mm in size [5]
[6]. Despite high diagnostic accuracy, the considerable exposure to ionising radiation
casts a shadow over the future of CT colonography as a screening exam for colorectal
cancer [7]. Hence, efforts have been focussed on MR colonography (MRC).
To date, MRC has been based upon the administration of a rectal enema containing paramagnetic
contrast. On 3D gradient echo data sets only the contrast-containing colonic lumen
is bright whereas the surrounding tissues including colonic wall and polyps remain
low in signal intensity. Hence the technique has been referred to as ‘bright lumen’
MRC. Polypoid colonic masses appear as dark filling defects within the bright colonic
lumen - an appearance which is difficult to differentiate from residual fecal material
and/or small pockets of air. To avoid false positive findings induced by residual
stool, patients are required to rigorously cleanse their colon prior to the exam.
To compensate for the presence of residual air, the 3D acquisition is performed in
both the prone and supine positions.
In this communication we describe our initial experience with a simplified, less costly
variation on MR-colonography - MRI of the contrast-enhanced colonic wall. The technique
is based on the acquisition of a 3D gradient echo sequence collected after administration
of a rectal water-enema and an intravenous injection of paramagnetic contrast. The
colonic wall as well as masses arising from it brightly enhance and are thus easily
delineated against the background of dark surrounding tissues and a dark colonic lumen
- hence ‘dark lumen’ MRC.
Materials and methods
Materials and methods
‘Dark lumen’ MRC: technique
Following standard preparation for bowel cleansing (oral ingestion of 4 L Golytely,
Braintree Laboratories, Braintree, Massachusetts) MR examinations were performed on
a 1.5 T MR system (Magnetom Sonata, Siemens Medical Systems, Erlangen, Germany). A
combination of two surface coils were used in conjunction with the built-in spine
array coil for signal reception to permit coverage of the entire colon. To minimize
bowel peristalsis, 40 mg of scopolamine (Buscopan; Boehringer Ingelheim, Germany)
were injected intravenously. Following placement of a rectal enema tube (E-Z-Em, Westbury,
NY), the colon was filled with 3000 ml of warm tap water. To ensure safe and complete
filling, the administration of the enema was monitored using a fast 2D TrueFISP sequence
(TR/TE/flip 3.2/1.6/70°; slice thickness 5mm) which allowed for the acquisition of
one image every three seconds. Once complete filling and distension of the colon was
assured, a first ‘pre-contrast’ T1w 3D gradient echo data set was collected. Data
acquisition was performed with the patient in the prone position, only. For the 3D
sequence the following parameters were used: TR/TE 1.64/0.6 ms, flip angle 15°, field
of view (FOV) 450 x 450 mm, matrix 512 × 460, effective slice thickness 1.57 mm. Subsequently
paramagnetic contrast (gadobenate dimeglumine, Gd-BOPTA, Multihance, Bracco, Italy)
was administered i. v. at a dosage of 0.2 mmol/kg and a flow rate of 3.5 ml/s. After
a delay of 75 s, the ‘pre-contrast’ 3D acquisition was repeated with identical imaging
parameters. The 3D data set was collected breahthheld in 23 s.
Patients
MRI of the colonic wall was performed on 12 subjects (8 men, 4 women, age range 44
- 76 years, mean age 60.2 years) in whom a colorectal mass was suspected due to positive
family history (n = 3) or a positive fecal occult blood test (n = 9). The study was
performed in accordance with all guidelines set forth by the local ethical committee
and all patients signed informed consent.
In addition to MRI of the colonic wall all patients underwent conventional colonoscopy
performed within five to fourteen days following the MR exam. Besides, three subjects
agreed to undergo MR-colonography based on the published ‘bright lumen’ protocol [8]. These exams were performed seven days following the ‘dark lumen’ MRC, on the same
MR system, using identical patient and coil positioning, as well as the same 3D gradient
echo sequence for display of the colon. In contrast to the ‘dark lumen’ MRC protocol,
Gd-DTPA was added to the rectal water enema (1 : 100) and no intravenous contrast
agent was applied.
Data Analysis
All MRI exams were evaluated by two experienced radiologists. Analysis was based on
individual source images, multiplanar reformations and virtual endoscopic renderings.
Signal intensities were measured in Regions-of-interest (ROI) positioned within the
walls of the ascending, transverse, descending and sigmoid colon as well as within
all mass lesions on both unenhanced and enhanced 3D GRE images. Signal-to-Noise Ratios
(SNR) were calculated in the usual manner using the following formula: SNR = SI (colonic
wall)/noise defined as the standard deviation of an ROI measurement outside the subject.
All MR findings were compared to those obtained with conventional endoscopy.
Results
Results
‘Dark lumen’ MRC, including placement of the rectal tube and colonic filling with
warm tap water was well-tolerated by all twelve subjects. All twelve exams were considered
diagnostic. The in-room time ranged between 10 and 15 minutes (mean 12 minutes). Image
analysis time amounted to 10 ± 4 minutes.
Five polyps ranging in diameter between 7 and 12 mm were detected with ‘dark lumen’
MRC (Fig. 1). All five lesions were confirmed by conventional colonoscopy and subsequent polypectomy
was performed. There were no false negative findings.
Fig. 1 49-year-old woman referred for MRC and conventional colonoscopy due to positive occult
fecal blood test. 10 mm polyp could be detected in the ascending colon based on the
contrast uptake in (b) (arrow) compared to the corresponding native sequence show in (a) (arrow). Diagnosis was confirmed by virtual endoscopic rendering (c) as well as by conventional colonoscopy.
On ‘bright lumen’ MRC, performed in addition in only three patients, three polyps
were seen in two patients. One lesion corresponded to a polyp seen on ‘dark lumen’
MRC as well as at colonoscopy. Two lesions identified in one patient did not have
a correlate on either ‘dark lumen’ MRC or conventional colonoscopy. The two false
positive findings were retrospectively interpreted as either residual air bubbles
or residual stool adherent to the colonic wall .
The intravenous administration of paramagnetic contrast resulted in an average SNR
increase within the colonic wall of 170 % from 9.2 to 24.8 ± 2.6. This difference
was statistically significant (p< 0.001). Polyps revealed even more enhancement with
signal intensities increasing by 306 % from 8.9 ± 1.6 to 36.1 ± 3.9. Lack of contrast
enhancement correctly identified three bright “lesions“ as residual stool (Fig. 2).
Fig. 2 61-year-old female patient undergoing MRC for colorectal cancer screening. Polyp-simulating
protrusion in the sigmoid colon (b, arrow) turned out to be residual stool because of the same signal intensity compared
to native scan (a, arrow). Subsequent conventional colonoscopy confirmed absence of colorectal pathologies.
In addition, ‘dark lumen’ contrast-enhanced MRC revealed four extra-intestinal lesions:
two renal cysts in two patients, a single hepatic hemangioma in one patient, and an
aortic abdominal aneurysm measuring 4 cm in diameter in another patient.
Discussion
Discussion
The preliminary experience documented in this communication suggests that ‘dark lumen’
MRC works well. The technique is well tolerated and appears highly accurate regarding
the detection of colorectal masses - all 5 polyps were readily identified. Compared
to ‘bright lumen’ MRC which has been extensively evaluated in the past, ‘dark lumen’
MRC harbors considerable advantages including reduced cost, reduced examination and
post-processing times, as well as potentially higher diagnostic accuracy and confidence.
‘Bright lumen’ MRC, which has been shown to be accurate in detecting colorectal polyps
larger than 8 mm in size, requires the administration of a gadolinium-containing rectal
enema [6]
[8]
[9]. Although most authors suggest a mixture of 1 : 100 [6], some studies recommend the use of a 1 : 50 Gd/water dilution [8]. Assuming a colonic volume of 3000 ml, between 30 and 60 ml of costly paramagnetic
contrast are needed for the rectal enema alone. In addition, most ‘bright lumen’ MRC
protocols call for the additional administration of paramagnetic contrast in a dose
of 0.1 mmol/kg for better assessment of surrounding organs such as the liver. The
‘dark lumen’ MR-colonography approach on the other hand requires merely a single intravenous
injection of less than 30 ml of paramagnetic contrast for a subject weighing 70 kg.
No additional injection of contrast is required for concomitant assessment of parenchymal
organs.
To compensate for residual air pockets, which obscure the outline of the colonic wall,
‘bright lumen’ MRC requires the collection of two data sets: one obtained in the prone
and a second obtained in the supine patient position. Turning the patient during the
exam is cumbersome and can be associated with considerable time delays. Occasionally
the patient moves so much that a new landmark is required. In any case, a new localizing
sequence is required to assure full coverage of the colon in the subsequent 3D acquisition.
During this delay, contrast frequently escapes from the colon into the small bowel.
As a result the colon looses distension and the resultant data set is of reduced diagnostic
quality. ‘Dark blood’ MRC obviates the need for a 3D acquisition in a second patient
position. Since air is signalless on all sequences, its appearance on heavily T1-weighted
3D GRE images is identical to water, which is used to distend the colon. The enhancing
colonic wall and mass lesions arising from it are easily differentiated. Thus the
time for both the actual exam as well as image interpretation is considerably reduced
amounting to less than 30 minutes.
The detection of colorectal lesions with ‘bright lumen’ MRC relies on the visualization
of filling defects. Differential considerations for such a filling defect include
air bubbles as well as residual fecal material. Collecting two data sets in the prone
and supine patient position allows the use of ‘motion’ as a differentiating criterion.
Only those lesions that remain in the same position are considered a true polyp. Unfortunately
this differentiating criteria can introduce severe errors, both regarding false negatives
and false positives. Thus polyps with a long stalk may move sufficiently to impress
as a moving air bubble or more likely residual stool, while stool adherent to the
colonic wall may not move at all and thus falsely impress as a polyp. This was the
case in one patient examined in the current collective - based on the ‘bright lumen’
technique two small polyps were identified, which had no correlate on either ‘dark
lumen’ MRC or conventional colonoscopy.
All techniques for virtual colonography, regardless whether based on CT or MRI are
handicapped by residual stool. The proposed ‘dark lumen’ technique copes with this
problem in a simple manner: if the lesion enhances it is a polyp, if it does not enhance
it represents stool. Suspicious appearing lesions are analyzed by comparing signal
intensities on the pre- and post-contrast images. Lesions identified in this limited
number of patients enhanced in average by more than 300 %. Comparing post- to pre-contrast
data sets is crucial, as stool can be quite bright on T1-weighted images. The presence
of iron and manganese is implicated as the cause for the bright signal within stool.
If analysis were limited to the post-contrast data set, bright stool could be misinterpreted
as a polyp. Comparison with the pre-contrast images documents the lack of contrast
enhancement which assures the correct diagnosis. In the current study, several patients
exhibited bright stool which was readily identified as such based on assessment of
the pre-contrast images (Fig. 2).
Enhancement of colorectal masses following the intravenous administration of contrast
has been documented before in conjunction with MR-colonography [10] and CT colonography [11]. The use of intravenously administered contrast material had significantly improved
reader confidence in the assessment of bowel wall conspicuity and the ability of CT
colonography to depict medium polyps in suboptimally prepared colons. Interestingly,
the enhancement observed within polyps exceeded the increase determined within the
colonic wall. In view of the very limited number of lesions, the reliability of this
observation remains unclear. If proven true, this difference may aid in differentiating
even very small polyps from thickened haustral folds.
A further advantage of ‘dark lumen’ MRC relates to the fact that it permits direct
analysis of the bowel wall. This might facilitate the evaluation of inflammatory changes
in patients with Crohn¿s disease. Increased contrast uptake and bowel wall thickening,
as documented on contrast-enhanced T1-weighted images has already been shown to correlate
well with the degree of inflammation in the small bowel [12]. Hence, the ‘dark lumen’ approach may indeed amplify the list of indications for
MRC in the future to also encompass inflammatory bowel disease.
Finally, the intravenous application of paramagnetic contrast permits a more comprehensive
assessment of parenchymal abdominal organs contained within the field of view. By
combining pre- and post-contrast T1-weighted imaging, the liver can be accurately
evaluated regarding the presence and type of concomitant disease. Accordingly, a hepatic
hemangioma was not merely detected but immediately characterized as such on the contrast-enhanced
scan. Not only hepatic lesions, but also vascular structures can be interpreted with
more confidence. Thus one patient with an abdominal aortic aneurysm was readily identified.
‘Dark blood’ MRC also offers new perspectives regarding optimization of bowel distention.
Although the administration of water as a rectal enema does not adversely effect patient
comfort in most cases, a modified strategy could be based on the application of gas
like CO2
[13]. The gas is signalless and would thus easily permit delineation of the contrast-enhanced
colonic wall and masses. Eventually, the technique may also offer new perspectives
for ‘fecal tagging’ [14]. If the signal of stool could be reliably nulled, cleansing of the colon prior to
the exam would no longer be necessary. Preliminary experiments using various orally
applied contrast agents appear promising [15].
Conclusion
Conclusion
‘Dark lumen’ MR colonography is based on the contrast enhancement of the colonic wall
and masses arising from it. Compared to ‘bright lumen’ MRC, the technique appears
to enhance diagnostic accuracy and confidence, while at the same time reducing cost
and shortening exam as well as post-processing times.