Introduction
In clinical practice, imaging techniques are used at the initial presentation to establish a diagnosis and to assess the exact location, extent, and severity of dis- ease [1]. These modalities are also used as follow-up, during and after treatment, to determine the optimal choice and dose of medication (e.g., systemically or topically active) [2, 3]. With the advent of new med- ication such as infliximab, an immunomodulatory drug with considerable side effects, follow-up to determine if medication is becoming increasingly important.
In Crohn’s disease, formation of perianal fistulas and/or abscesses can be seen in a large percentage of patients. Nowadays, there is a tendency towards imaging of these fistulae, given that in Crohn’s disease fistulae can be very extensive and complex, rendering the conventional gold standard (i.e., examination under anesthesia) not wholly accurate [4]. As misclas- sification of fistulae can lead to severe, irreversible complications (e.g., fecal incontinence) or recurrent disease, the American Gastroenterology Association (AGA) has recently stated the importance of preoper- ative imaging. Another reason for performing imag- ing studies is the increasing use of infliximab, which has been associated not only with external closure of perianal fistulae but also with the persistence of tracks as can be visualized with MRI [5, 6].
The earliest change caused by the disease occurs in the submucosa and consists of lymphoid hyperplasia and lymphedema. Radiologic findings at this (early) stage include subtle elevations and aphthoid ulcers.
As the disease progresses, it extends transmurally to the serosa (transmural stage) and beyond to the mesentery and adjacent organs (extramural stage).
Aphthoid ulcers develop into linear ulcers and fis- sures to produce an ulcero-nodular or “cobblestone”
appearance. The bowel wall is thickened by a combi- nation of fibrosis and inflammatory infiltrates. Bowel obstruction, strictures, abscesses or phlegmon, fistu- lae, and sinus tracts are common complications of advanced disease [1, 2].
Abdominal MRI
The diagnosis of Crohn’s disease should include assessment of the presence, severity, and extent of disease, inflammatory lesion activity, and the pres- ence of extra-intestinal complications to aid in treat- ment planning, which largely depends on imaging findings, particularly those of cross-sectional imag- ing. Endoscopy and barium studies are the principal tools for diagnosis and evaluation of Crohn’s disease;
however, they are limited in their capability to demonstrate the transmural or extramural extent of disease or extra-intestinal complications.
With MRI, both inflammatory changes of the bowel wall and the extramural complications of Crohn’s disease can be assessed. The non-invasive- ness of this technique, as well as its lack of ionizing radiation, has prompted many groups to perform systematic studies of MRI for evaluation of Crohn’s disease.
Computed tomography (CT) is currently the cross-sectional imaging modality of choice at most institutions; however, magnetic resonance (MR) imaging has also proved highly effective in this set- ting. The role of cross-sectional imaging in the diag- nosis of Crohn’s disease has expanded with recent advances in CT and MR imaging technology, which allow rapid acquisition of high-resolution images of the intestines during a breath-hold examination.
Both imaging modalities provide information that is crucial in the diagnosis of Crohn’s disease and in treatment planning [7–16].
Intraluminal Contrast Media
Adequate distension of the bowel lumen is mandato- ry in MRI, as it facilitates demonstration of morpho- logical changes caused by Crohn’s disease and allows identification of subtle abnormalities. Collapsed bowel loops can hide lesions or mimic disease by mimicking pathologically thickened bowel wall in
MRI in Inflammatory Small-Bowel Diseases
Riccardo Manfredi, Roberto Malagò, Marco Testoni, Veronica Girardi, Roberto Pozzi Mucelli
collapsed segments [17]. Moreover, collapsed normal bowel loops can exhibit enhancement that is similar to diseased segments, after administration of an intravenous contrast medium [18].
Various kinds of intraluminal contrast agents have been proposed for MR imaging [7, 18–26] and are classified as positive, negative, or biphasic. Posi- tive agents produce high intraluminal signal, and negative agents produce little or no intraluminal sig- nal regardless of the applied pulse sequence. Biphasic contrast agents may produce either a high or low sig- nal depending on the pulse sequence used, usually demonstrating low signal intensity on T1-weighted MR images and high signal intensity on T2-weighted images. Negative or biphasic contrast agents seem to be more suitable for assessing the small bowel [7, 19].
Polyethylene glycol has been proposed by several authors as a suitable biphasic contrast medium; it is not absorbable, remains unmodified in the small bowel, is easily prepared and administered, and pro- vides adequate bowel distension. Furthermore, tran- sit time is fast, allowing for small-bowel distension
within 30 min. However, undesirable side effects (e.g., motion artifacts or severe diarrhea) can occur due to the prokinetic action of the solution. Theoret- ically, water would be a perfect biphasic contrast medium, but in many patients, the water is reab- sorbed before it has reached the terminal ileum.
Moreover, it does not optimally distend the bowel (Fig. 1).
An anti-peristaltic agent is injected to minimize potential artifacts caused by bowel movement or contraction. Although many authors reporting on MR enteroclysis administer anti-peristaltic drugs to reduce motion artifacts, reflex atony is induced by high flow rates, theoretically allowing images (almost) to be free of motion artifacts.
Sequences
Technological advances, including the use of respira- tion-suspended sequences, improved coils, fat sup- pressions, and intravenous gadolinium, have extend-
a
d e
b c
Fig. 1.Coronal T2W Hal Fourier RARE image (a) and fat-suppressed true-FISP images along the coronal (b), sagittal (c), and axial (d, e) planes show good distension of bowel loops after oral administration of biphasic contrast media (PEG), thus permitting the distinguishing of the jejunal and ileal loops
ed the role of MRI in the evaluation of the gastroin- testinal tract. Various MR sequences for evaluating the gastrointestinal tract have been advocated by dif- ferent authors. However, no sole sequence can be used for comprehensive imaging of Crohn’s disease, as each sequence has its specific advantages and lim- itations. Therefore, it is essential to use a compre- hensive examination protocol in which disadvan- tages of one sequence can be compensated by the advantages of the others.
Fast Spin Echo T2-Weighted Sequence
Half-Fourier acquisition single shot turbo spin echo (HASTE) demonstrate lack of magnetic susceptibil- ity artifacts and lack of artifacts from bowel peri- stalsis theoretically making the HASTE sequence ideal for imaging bowel. A limitation of HASTE is its sensitivity to intraluminal flow voids, while another disadvantage is that no information on mesenteries can be obtained due to K-space filtering effects (Fig. 1).
True-FISP Sequence
Another sequence promoted for the evaluation of Crohn’s disease is the true fast imaging with steady- state precession (true-FISP) sequence, which is a completely refocused steady-state gradient echo sequence (also called balanced fast-field echo (Fig. 1).
Motion-related artifacts are minimal due to the short acquisition time, while at the same time insensitivity to intraluminal flow voids is observed due to the bal- anced and symmetric gradient design. The bowel wall is well visualized due to good differentiation in contrast (via positive or biphasic contrast agent) between the hypointense bowel wall and the hyperin- tense bowel lumen (Fig. 1). The true-FISP sequence is particularly good for obtaining information about extra-intestinal complications; the mesenteries are very well visualized and lymph nodes are very con- spicuous with this technique. The black boundary artifact encountered with the true-FISP sequence, at fat-water interfaces, may hamper the perception of subtle thickening of the bowel wall.
Gadolinium-Enhanced T1-Weighted Sequence
Many study groups have focused on gadolinium- enhanced T1-weighted images for assessment of dis- ease [27-30], as both localization and severity of inflammation can be appraised with this sequence.
Inflamed bowel segments show pathological enhancement after administration of intravenous gadolinium. When combining T1-weighted sequences with fat suppression and use of intravenous gadolin- ium-chelates, very good differentiation in contrast is obtained between the pathologically enhancing bowel wall and the dark bowel lumen and suppressed perivisceral fat (Fig. 2). The marked increase in signal intensity of inflamed bowel after administration of
Fig. 2.Coronal fat suppressed T1-weighted spoiled gradient echo sequence acquired before (a) and 30 s following intra- venous administration of gadolinium chelate (b), demonstrating marked parietal enhancement of the distal ileal loop (arrow)
a b
intravenous gadolinium is due to increased tissue perfusion and vascular permeability (Fig. 2).
MR Enteroclisis Findings
Early lesions of Crohn’s disease such as blunting, flattening, thickening, distortion and straightening of the valvulae conniventes and tiny aphthae were clearly shown at conventional enteroclysis, but they were not consistently depicted with MR enteroclysis due to its inadequate spatial resolution. The valvulae conniventes were shown to their best advantage and distortion of the mucosal folds was easily detected with MR enteroclysis.
The characteristic discrete longitudinal or trans- verse ulcers of Crohn’s disease could be shown at MR enteroclysis, provided there was satisfactory disten- tion of the bowel. MR enteroclysis was less sensitive than conventional enteroclysis in the detection of lin- ear ulcers due to low spatial resolution and lack of compression techniques. Thin high-signal-intensity
lines within the bowel wall on true FISP MR images represented linear ulcers. Cobblestoning was caused mostly by a combination of longitudinal and trans- verse ulceration and was easily shown with MR ente- roclysis. The true FISP sequence was superior to HASTE in showing linear ulcers, cobblestoning, and intramural tracts, while the three-dimensional gradi- ent echo sequence was less satisfactory in depicting such lesions smaller than 3 mm in diameter.
Bowel-wall thickening was clearly shown with all MR enteroclysis sequences (Figs. 2, 3). The thickened wall had moderate signal intensity on true FISP images and could be easily differentiated from the black boundary artifact. Bowel-wall thickness and length of small-bowel involvement could be meas- ured on MR enteroclysis images. Narrowing of the lumen and associated prestenotic dilatation were easily recognized on MR enteroclysis images obtained with all sequences (Figs. 2, 3). Asymmetric involvement, pseudo-diverticula formation, and skip or multiple lesions were easily depicted via MR ente- roclysis.
Fig. 3.A 57-year-old female with active Crohn’s disease. a, b Axial fat-suppressed true-FISP images show severe thickening of the terminal ileum with luminal stenosis and fibro-fatty proliferation. c, d After Gadolinium administration fat sup- pressed T1-weighted spoiled gradient echo images show enhancement of the bowel wall due to Crohn’s disease activity
a
c
b
d
Quantification of Dynamic Contrast-Enhanced MRI (DCE)
DCE-MRI imaging techniques are still evolving and methods of image analysis remain mostly qualitative, variable, and nonstandard, making these techniques unsuitable for comparisons between different insti- tutions or different study protocols. In the attempt to standardize and make this analysis quantitative, a number of pharmacokinetic multicompartment models have been proposed that would serve to infer
“absolute” physiological quantities from the data gathered with the dynamic scan.
When the contrast agent is injected, it equilibrates with the blood plasma and is rapidly delivered to the different tissues. The blood plasma (the central com- partment) and the extra-vascular, extra-cellular space of the inflamed tissue lesion (the peripheral compartment) are connected by linear exchange processes in both directions. The measurement of microvessel permeability is possible by assessment of the rate at which a contrast agent transfers from the blood pool to the extra-vascular extra-cellular space.
Similarly, the transfer of the contrast agent back to the blood can be expressed as the reflux coefficient.
In addition, the measurement of increased blood vol- ume is possible by permitting calculation of fraction- al plasma volume [31]. This method offers the great advantage of being quantitative, i.e., not measure- ment-dependent but pathology-dependent, so that the results from different studies/sites can be direct- ly compared.
Clinical scoring (such as the Crohn’s disease activ- ity index [32], biologic indexes [33], endoscopy, and imaging studies have all been used to monitor activi- ty, but no established gold standard exists. Assess- ment of activity is usually made using a combination of clinical symptoms, physical findings, laboratory investigations, endoscopy, and imaging tests. The assessment of biologic activity, based on the positiv- ity for three of four acute phase reactants (WBC, ery- throcyte sedimentation rate, and C-reactive protein), has been found to be a sensitive determinant of activ- ity, especially when supported by endoscopic or imaging findings.
Extra-Mural Manifestations and Complications
MR enteroclysis had a clear advantage over conven- tional enteroclysis in the demonstration of extramu- ral manifestations or complications of Crohn’s dis- ease. The extent of fibro-fatty proliferation and its composition, mostly fatty or mostly fibrotic, could be assessed with MR enteroclysis, especially when true FISP images were obtained (Fig. 3). The so-called
comb sign (Fig. 4), corresponding to increased mesenteric vascularity, could be ideally seen on true FISP images close to the mesenteric border of a small-bowel segment in the form of short, parallel, low-signal-intensity linear structures perpendicular to the intestinal long axis. The comb sign could be seen on three-dimensional FLASH images as high- signal-intensity linear elements.
Small mesenteric lymph nodes were easily detect- ed by their low signal intensity within the high-sig- nal-intensity mesenteric fat on true FISP images (Fig. 5). Their presence was not as obvious with other MR enteroclysis sequences due to short T2 filtering effects on HASTE images and to saturation of mesen- teric fat signal on three-dimensional FLASH images.
Sinus tracts and fistulae were disclosed by the high- signal intensity of their fluid content on true FISP and HASTE images, but they could be missed on the three-dimensional FLASH images due to limited con- trast with surrounding tissues. All fistulae shown at conventional enteroclysis were also depicted at MR enteroclysis, while only half of the sinus tracts were detected at MR enteroclysis, even in retrospect in our series. Abscesses could be recognized by their fluid content and contrast enhancement of the wall. There were strong indications that disease activity can be appreciated with MR enteroclysis (Fig. 6) [34, 35].
Conclusions
MR imaging is an emerging technique in this field and is expected to play a role similar to that of CT.
The clinical efficacy of MR imaging has been investi- gated, and favorable results have been reported as described in this article. High soft-tissue contrast, static and dynamic imaging capabilities, and the absence of ionizing radiation exposure represent the advantages of MR imaging over CT. On the other hand, MR imaging is more time consuming, less readily available, and more expensive [36–39].
Advantages of CT over MR imaging include greater availability, shorter examination times, flexibility in choosing imaging thickness and planes after data acquisition with multidetector row CT, and higher spatial resolution. Precise indications for MR imag- ing in the diagnosis of Crohn’s disease and its use as a complement to CT or other imaging procedures need further investigation. Clinical management decisions might be influenced by the presence of unsuspected additional lesions that were seen only on CT or MR imaging, as reported by Fishman et al.
and Turetschek et al., with management changes
occurring in 28 and 62% of cases, respectively. Cross-
sectional imaging should be included or even per-
formed as a primary examination in the clinical eval-
uation of Crohn’s disease, along with conventional imaging and clinical and laboratory tests. Cross-sec- tional imaging should be used to evaluate for the presence of entities that indicate elective gastroin-
testinal surgery–e.g., marked prestenotic dilatation (severe stenosis), skip lesions, fistulae, perforations, abscesses.
Fig. 4.A 27-year-old man with active Crohn’s disease. a, b On coronal true FISP images Mesenteric vessels (vasa resta) are clearly detectable depicting the so-called “comb sign” which corresponds to hypertrophied mesenteric vascularisation perpendicular to the axis of the affected bowel loop (arrow). c, d Contrast enhanced T1-weighted gradient echo images, confirm disease activity (arrows)
a
c
b
d
Fig. 5.Coronal (a, b) and sagittal (c) fat-suppressed true- FISP images show thickening of the bowel wall (short arrows) of the terminal ileum. Small mesenteric lymph nodes (arrowhead) are also depicted along the vessels a
c
b
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