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Keywords:

  • inflammatory bowel disease;
  • Crohn's disease;
  • children;
  • magnetic resonance imaging;
  • small intestine

Abstract

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. CONCLUSION
  7. REFERENCES

Background:

We report the manifestations of Crohn's disease (CD) observed on magnetic resonance enterography (MRE) in a pediatric population at the time of CD diagnosis.

Methods:

MRE of 95 consecutive pediatric patients with inflammatory bowel disease (IBD) examined in 2006–2009 were retrospectively analyzed, with documentation of findings based on type and location of the small bowel (SB) disease.

Results:

In all, 51 were boys and 44 girls. 54 had CD, 31 non-CD IBD, and 10 no IBD. The most common site of SB involvement in CD was the terminal ileum seen in 29 (53.7%) patients, followed by ileum in 10 (18.5%) and jejunum in 9 (16.7%) patients. Solitary jejunal inflammation (3.7%), SB stenoses (1.9%), fistula formation (0.95%), and abscess (0.95%) were much less common. Perienteric lymphadenopathy was seen in 30 (55.6%) patients and fatty proliferation in 9 (16.7%). The most common manifestation of SB inflammation was increased contrast enhancement of bowel wall (93.5%), thickening of the bowel wall (90.3%), and derangement of bowel shape with saccular formations (25.8%).

Conclusions:

MRE in the pediatric population often demonstrates increased contrast uptake, bowel wall thickening, and perienteral lymphadenopathy in CD. More chronic small bowel changes seen commonly in adults and solitary jejunal involvements are less commonly seen. (Inflamm Bowel Dis 2012;)

Magnetic resonance enterography (MRE) has gained popularity for imaging of the small bowel in patients with Crohn's disease (CD).1–3 Computed tomography enterography (CTE),4 small bowel follow-through, and conventional enteroclysis are associated with high doses of ionizing radiation,5, 6 while MRE involves no radiation. Although both conventional enteroclysis and capsule endoscopy can visualize small mucosal lesions, there are other advantages of cross-sectional imaging with MRE, since the aforementioned methods are virtually unable to visualize findings beyond the luminal side of the bowel wall.7 Conventional enteroclysis has also been questioned even from a cost/benefit perspective.8, 9 This method involves ionizing radiation, and it is very unpleasant to the patient. Moreover it only demonstrates mucosal changes. Additionally, it suffers from lower accuracy for detection of CD lesions in the small bowel compared to MRE.10 Capsule endoscopy suffers from lower specificity11 and does not seem to be a cost-effective method in CD.12 There are also fears that it might lead to obstruction in patients with strictures. In fact, capsule endoscopy and MRE seem to be complementary.13

MRE is based on patients receiving an oral contrast agent for adequate distension of the small bowel. Different oral agents can be used, but most institutions use an agent with nonabsorbable inert material dissolved in water.14, 15 The presence of sufficient amounts of water leads to increased signal intensity on T2-weighted imaging (T2WI) and low intensity on T1-weighted images (T1WI), both of which are employed in MRE. Briefly, T1WI is used mainly with intravenous contrast enhancement for looking at blood supply of the intestines and other organs and structures. Marked increased contrast enhancement is associated with increased blood flow and thus a sign of inflammation.16 These changes are similarly seen on contrast-enhanced CT. T1WI is also used with thin sections and with fat signal suppression, which help detect inflammation. T2WI is used mostly for signs associated with edema and fluid collections.

CD can affect the small intestine in many ways, although some manifestations are more common. Some early signs of disease of the small intestine could be missed on MRE (Fig. 1).17 Manifestations of CD are varied, and there seems to be an influence based on age and duration of the disease.18, 19 Knowledge of different locations of the disease at the time of initial imaging cannot be overemphasized. The Vienna Classification initially classified disease based on several simple factors, among them location, into terminal ileum (L1), colon (L2), ileocolon (L3), and upper gastrointestinal (L4).20 Later, the Montreal Classification modified L4 into a modifier that could be added to L1-3 groups.21 Recently, this classification was modified specifically for children. The Paris Classification, first, distinguishes disease above the distal ileum as L4a (proximal to ligament of Treitz) and L4b (distal to ligament of Treitz to above distal 1/3 of ileum), and allowing both stenosing and penetrating disease to be classified in the same patient (B2B3). In addition, the Paris Classification exchanges terminal ileum for distal one-third of the small intestine.22 Our aim was therefore to look into the location and extent of small intestine involvement in pediatric cases presenting with IBD. We were unable to find a description of imaging findings at the time of diagnosis in the pediatric population with MRE. Therefore, we studied the manifestations and extension of CD as observed at MRE in a pediatric population with MRE imaging for the first time in their lives.

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Figure 1. Trauma CT (a,b) performed at the time of traffic accident, June 2005, almost 7 PM (box in a). The reformatted coronal image (a) shows marked increased contrast enhancement of the terminal ileum (white arrow). Semisagittal reformatted image (b) shows increased bowel wall enhancement in a nondistended terminal ileum (white arrows), increased vascularity (short black arrows), and increased number and size of regional lymph nodes (long thin black arrows). The trauma CT is reported uneventful. August 2008 the patient was examined for the suspicion of debut of IBD. Coronal SSH image (c) demonstrates increased wall thickness of the terminal ileum (long white arrow), increased mesenteric fat (black arrow), loss of haustrations, and presence of edema in the wall of transverse colon (dotted arrows) and increased abdominal free fluid (white arrows). This case illustrates the virtually universal delay in diagnosis of CD.

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MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. CONCLUSION
  7. REFERENCES

Between 2006 and 2009, 95 consecutive pediatric patients (age less than 18 years) imaged with MRE with onset of suspected or confirmed IBD were retrieved from the database of our radiology departments at Astrid Lindgren Children's Hospital and Uppsala University Hospital. The manifestations of their disease on MRE were documented according to a protocol. The study was approved by the local Ethical Committees at Uppsala University Hospital and Karolinska Institute.

MRE

First an intravenous line was inserted after the patient had been offered application of topical anesthetic gel. This was offered to patients and guardians of patients. The patients began drinking the oral contrast agent distributed in cups of ≈150 mL with specific instructions that each cup should be finished during 5–10 minutes. The total amount of orally administered contrast agent was based on the patient's height according to the following formula: Minimum amount = 6 mL × (patient's height in cm − 100) + 1 L. Maximum 1.5 L.

However, the radiology nurse was instructed that the amount should be tailored to the patient's compliance, stopping when risk of vomiting was considered eminent as expressed by the patient. The contrast agent was administered during 60 minutes evenly unless the patient was unable. In patients with a nutritional nasogastric catheter, the catheter was used for administration of the same amount of oral agent.

During the first 10–15 minutes and while the oral agent was being taken/administered a small dose of erythromycin (50 mg) was administered intravenously in order to promote emptying of the stomach. This policy was discontinued in 2008 when the oral contrast agent was changed.

The first oral contrast was an in-house product based on a combination of methyl-cellulose (Guaran, Apoteket, Stockholm, Sweden) and a sugar-free commercial drink (Funlight) in concentrated form with different flavors. The flavor could be chosen by the patient. Since 2008 VoLumen (E-Z-EM and later Bracco Diagnostics, Princeton, NJ) has been used.

After oral administration of contrast agent, patients were imaged in the prone position in a 1.5 T Philips Intera system (Best, Netherlands). The imaging began with steady-state free precession sequence (BFFE-balanced fast field echo, Philips, or True-FISP) images in the coronal plane. With the in-house oral contrast agent, if the jejunal loops were not adequately distended or if the contrast column had not reached the terminal ileum, 25 mg erythromycine was administered again. After switching the oral agent, this part of monitoring with True-FISP as well as administration of erythromycine was abandoned.

T2WI (Half Fourier single shot; Fig. 2a) in the coronal and axial planes were performed. The next phases included dynamic cine images with True-FISP (Fig. 2b–d), and a 3D, T1W-prepared gradient echo sequence with fat saturation (THRIVE, Philips) before and after intravenous (IV) gadolinium contrast agent (Fig. 2e). As the IV contrast agent, gadodiamide (Omniscan 0.5 mmol/mL, GE Healthcare, Milwaukee, WI) was administered as a bolus slowly (≈1 min) in a peripheral vein at a dose of 0.2 mL/kg body weight or 0.1 mmol/kg body weight. Before T1WI, an antiperistaltic agent (Glucagon, IV) was administered. The sequence parameters are summarized in Table 1. Cine-imaging was also performed in a predefined fashion.23

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Figure 2. Patient 1 with CD and inflammation of the terminal ileum. Single shot image is T2W and shows high signal of the free abdominal fluid (white arrows) around the urinary bladder. The patient has thickened terminal ileum (black arrows) marked by variable bowel wall thickness, ulcers, and layered bowel wall. A specific type of intestinal dilatation (black star) is seen, characterized by mesenteric shortening and antimesenteric sacculation. True-FISP image (b) of patient 1 shows the same findings in addition to better depiction of mesenteric changes, in this case increased vascularity. Two of the cine True-FISP images from patient 2 (c,d) show two separate areas of bowel pathology (white arrows). These images are useful for monitoring bowel kinetic. Bowel loops not distended at one moment in time, may become distended the next moment (hatched arrows). Also note the pseudopolyp (white circles). Gadolinium-enhanced 3D FSPGR image of patient 1 is marked by increased contrast enhancement of the area with pathology (black arrow) compared to normal bowel loops (white arrows).

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Table 1. Sequence Characteristics Used for MR Enterography
SequenceCoronal SSHSteady-state Free Precession Sequence3D, T1W-prepared Gradient Echo Sequence with Fat Saturation
FOV (mm)485485445
Matrix256x204 (512)256x256 (512)192x115 (256)
Slice thickness (mm)461.8
No. slices202470
NSA111
TR (ms)17006.34.1
TE (ms)1003.21.93

Acute inflammation was diagnosed in the presence of bowel wall edema on T2WI, hyperperfusion of all bowel wall layers on T1WI. In contrast, sacculations, perienteric fatty proliferation, bowel wall stiffness on dynamic True-FISP, and irregular lymph nodes were considered signs of chronicity.

Imaging was performed within 2 months from the referral from the pediatricians specialized in pediatric gastroenterology. The IBD diagnosis was based on the final diagnosis with 1–4 years follow-up based on clinical assessment, endoscopic results, radiological (current MRE as well other follow-up imaging), and surgery (whenever applied). At our centers we do not perform any other elective radiological examination of the small intestine routinely due to unethically high doses of ionizing radiation in children. Other radiological methods have not demonstrated a higher accuracy in CD compared to MRE. However, all patients undergo upper gastrointestinal endoscopy and colonoscopy. The results of MRE were interpreted by one or two radiologists in consensus (M.R.T., U.U.), with special interest in gastrointestinal radiology.

Statistics

Tabulation of results was done using Microsoft Excel 2007. Comparison between patients was done using Fisher's exact test for analysis of contingency tables whenever applicable. The odds ratio (OR) was calculated for measuring effect size for binary data whenever applicable.

RESULTS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. CONCLUSION
  7. REFERENCES

MRE of 95 consecutive patients (boys n = 51, girls n = 44) were included. The patients had a median age of 14 years (range 7–18) at the time of investigation. Nine of these patients were 17 to 18 years old. The reason for outlining patients age 17–18 separately is because the Montreal schema includes patients age 17–18 as part of group A2.24 Based on final medical diagnoses, 54 of these patients were diagnosed as having CD, 31 other forms of IBD (UC or indeterminate colitis), and 10 as no IBD. All patients had undergone endoscopy (colonoscopy as well upper endoscopy). In all 4, (7.4%) of CD patients demonstrated upper gastrointestinal findings consistent with CD, and 41 (75.9%) had colonic findings consistent with CD.

The most common site of involvement was the terminal ileum (defined as the last 10 cm of the ileum) seen in 29 patients (30.5% of all and 53.7% of CD patients) patients (Fig. 3), followed by more proximal ileum (Fig. 4) in 10 (10.5% of all and 18.5% of patients with CD) and jejunum (Fig. 5) in 9 (9.5% of all and 16.7% of patients with CD) patients. All but two patients with small bowel CD had inflammation of the terminal ileum. Five cases had involvement of ileum, terminal ileum, and jejunum. Involvement of terminal ileum and ileum was seen in three cases. Simultaneous involvement of jejunum and terminal ileum was seen in two patients. There were no cases of involvement of ileum without coexisting involvement of the terminal ileum. Solitary jejunal inflammation was seen alone only in two patients.

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Figure 3. Patient with CD and inflammation of the terminal ileum manifested at layered bowel wall thickness (arrow) on this True-FISP image (a), and as thickened bowel loop with increased contrast enhancement (b). No other intestinal inflammatory signs were observed in this patient.

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Figure 4. Patient with inflammation of ileum. Coronal SSH image (a) shows thickening of ileocecal valve (black hatched arrow), terminal ileum (black arrow), and higher up in ileum (white arrow). Axial True-FISP image (b) shows edematous ileal loops with thickened walls (arrows) surrounded by increased vascularity. Semicoronal image gadolinium-enhanced 3D FSPGR (c) image aligned along the course of inflammation shows inflammatory changes in terminal ileum and ileum (black arrows). Note also the pseudopolyps (hatched arrows).

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Figure 5. Two nonconsecutive axial SSH images in a patient with involvement of jejunum. Image at a lower level (a) demonstrates the bow-formed jejunal loop (white arrows). There are areas of swollen mucosa bulging intraluminally, otherwise known as pseudopolyps (dotted arrows). Note also the presence of creeping fat (star). SSH are known for blurring of mesenteric structures, especially vessels. The high signal of the fat can also obscure edema. Smaller lymph nodes can also be missed; however, larger lymph nodes (dashed arrows) can be seen a level higher up (b) closer to mesenterial root. At this level the jejunum is imaged perpendicular to its axis, thus bowel wall edema and layered bowel wall pattern (white arrows) can be seen clearly. Presence of enlarged lymph nodes, bow-formation of bowel loop (shortening of mesenterial side with antimesenteric sacculation), and creeping fat are attributed to the chronic nature of the disease.

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Perienteric lymphadenopathy could be seen in 30 (31.6%) patients and fatty proliferation in 9 (9.5%). Perienteric lymphadenopathy and fatty proliferation were not seen in the absence of small bowel inflammation. Fistula formation and abscess/phlegmonous tissue were seen only in one patient each.

The most common manifestation of small bowel inflammation was increased contrast enhancement of bowel wall and comb sign, each seen in 29/31 (93.5%), thickening of the bowel wall in 28/31 (90.3%), and derangement of bowel shape with saccular formations in 8/31 (25.8%). Ulcers were also seen; however, deep ulcers are seen more easily detected with MRE than superficial ulcerations (Fig. 6). Interestingly, five of nine patients with jejunal involvement also had sacculations, while only three patients with sacculation did not have any jejunal involvement. Comparison between patients with or without jejunal inflammation with Fisher's exact test revealed a 2-tailed P-value of 0.0002 (statistically significant) for harboring sacculations, and also an OR of 32.1 (95% confidence interval [CI] 5.6–184.4). In other words, patients with jejunal inflammation have a much higher likelihood of having sacculations (Fig. 7). Other imaging findings (increased contrast enhancement of the bowel wall, comb sign, bowel wall thickening, and perienteral lymphadenopathy) did not show any statistically significant differences (P > 0.05) regarding location of the disease.

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Figure 6. Tiny aphthous ulceration seen in patient with limited disease. Ulcerations shown by white signal (white arrows) are seen as high signal in the bowel wall and capped by thin layer of mucosa.

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Figure 7. A 16-year-old female treated for 1 year for anorexia nervosa until she was suspected of having CD as a cause of stunted growth. Coronal image shows several bowel loops showing sacculation of the antimesenteric side (white arrows) with more marked thickening of the mesenteric side (black arrows).

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Most patients had signs of acute inflammatory disease (93%), while only a few demonstrated manifestation of chronic disease (26.7%), with some having both manifestations (20%).

As additional findings, colonic inflammation could be diagnosed in 26 (27.3%) of cases. Appendiceal inflammation, annular pancreas, superior mesenteric artery syndrome (Fig. 8), and Ladd's bands in malrotation could be seen in one patient each.

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Figure 8. Patient with UC suspected of having CD due to postprandial pain. Retrograde ileoscopy and conventional endoscopy had been negative. Coronal SSH image (a) shows clearly distended stomach with food residue (star) and proximal portion of the duodenum (not shown). This is pathologic, as elective examinations with fasting food residue should not be seen. Also note that the normal terminal ileum (white arrow), which does not demonstrate the same high signal of luminal content as the rest of small intestine due to prolonged passage time. Axial SSH image (b) shows distended duodenum (star) tapering acutely (black arrow) when passing between aorta and superior mesenteric artery. This pattern was confirmed on all other imaging sequences including cine imaging (not shown). This coupled with short distance between the two vessels and narrow angle between the origin of mesenteric artery and aorta confirmed the diagnosis. Methods based on enteroclysis will miss this diagnosis, as the tube is placed distal to the area of pathology.

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DISCUSSION

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. CONCLUSION
  7. REFERENCES

IBD and especially CD are very heterogeneous diseases,25 with increasing incidence and prevalence.26, 27 The disease heterogeneity is manifested in several ways. First, different parts of the gastrointestinal tract can be affected.28, 29

When involving the small bowel, we encounter a second form of heterogeneity, namely, that different segments of the small bowel segments can be involved. Our study demonstrates that involvement of the terminal ileum is more than three times more common than involvement of the jejunum and rest of the ileum. This is in accordance with previous studies which always show frequent involvement of the terminal ileum, especially at the time of diagnosis.30 This has also been seen in the pediatric population.31 This probably explains why ultrasound of the right lower quadrant has been shown to have relatively high sensitivity for detection of CD.32

Interestingly, involvement of jejunum alone is uncommon. This is most probably due to several factors, one being that there is a genuinely lower incidence of jejunal involvement, but also that jejunal involvement is almost invariably milder than involvement of the terminal ileum, and jejunum with its tendency to stay nondistended is the most difficult segment of small bowel to diagnose adequately. This is not only related to radiological studies, but even endoscopy has problems reaching this area. This is the reason some radiologists advocate enteroclysis while others believe that the gain does not justify the morbidity and radiation dose.33 Despite this, we found a much higher incidence of jejunal involvement than previously reported based on endoscopy and x-ray.34 This could be due to the fact that older studies used only conventional enteroclysis and small bowel follow-through, while with newer techniques we can detect more discrete changes. Also, the radiologists involved in this study have an established profile in small bowel imaging, a factor that has been shown to be relevant for more accurate diagnosis of small bowel MRI.35

The third and fourth points of heterogeneity in CD are that the disease manifestations in any particular segment vary in severity and chronicity. Abscesses, fistula, and sinus formations are known complications of intestinal inflammation. We had few cases with penetrating type (fistula, abscess, etc.) or stricture type; the probable reason is that our patients were imaged at a relatively earlier stage of their disease. The natural history of the disease starts out as mural inflammation and then becomes stricturing and penetrating over time, as demonstrated by longitudinal studies by Cosnes et al and Cosnes37, 38 (as shown in the patient in Fig. 1). Also, abscesses and other acute complications usually lead to emergency imaging and therapy. It is therefore not surprising that our patients who were imaged on a more elective basis did not have abscess formation.

Changes such as sacculation and stenoses are usually encountered in chronic stages of the disease, and therefore more commonly in higher age groups. We noted chronic and diffuse changes much more commonly in patients with jejunal involvement. The reason for this cannot be explained with certainty, but one reason can be delay in diagnosis for these patients.36 Another suggested reason could be that this disease site constitutes a separate entity with more aggressive behavior.39, 40

CTE indeed has higher spatial resolution and is much faster and much more convenient. However, in our experience of more than 1000 cases of CTE, CTE has several disadvantages: a large dose of ionizing radiation, which is important even in adults since even adults with CD will be imaged several times during their lifetime; CTE does not have the high soft tissue contrast enabling us to see bowel wall edema, probably the most important radiological sign for distinguishing active from chronic disease; and absence of cine images that are invaluable when some bowel loops are temporarily not distended (Fig. 2c,d) or when bowel motility and adhesions are studied.

Regarding compliance, we have not had any more problems with children compared to adults. One has to note that our youngest patient in this study was 7 years old, and the youngest we have performed MRE on was 6. It was impossible for us to study much younger children, as general anesthesia might be needed, but at the same time we cannot distend the bowel with fluids while undergoing anesthesia.

We have not experienced any tolerance problems in children. In our experience with adults and children, children seem to complain less often. This could be due to several factors: children are smaller than adults and therefore not as claustrophobic perhaps; their parents are present in the MRI unit with them; and children are probably less vocal in their complaints. At our hospitals children can visit the MRI room prior to the examination date to have the examination explained to them and the MRI unit is shown.

Although there have been some concerns recently regarding the use of gadolinium-containing contrast agents, we have not observed any case of nephrogenic systemic fibrosis due to our policy of not including patients with low renal function.

CONCLUSION

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. CONCLUSION
  7. REFERENCES

MRE is an excellent and feasible method for demonstrating involvement of the small bowel in a pediatric population with clinically suspected or confirmed IBD, and usually showing involvement of ileum with acute changes such as increased contrast uptake, bowel wall thickening, and mesenterial lymphadenopathy. More chronic and longstanding pathologic changes of the disease and/or jejunal involvements, especially solitary, are less commonly seen in the pediatric patients at the time of diagnosis.

REFERENCES

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. CONCLUSION
  7. REFERENCES