Radiologists play a substantial role in the management of pediatric Crohn disease (CD). Diagnostic imaging helps the gastroenterologist make the initial diagnosis, monitor response to therapy, and plan operative management. Cross-sectional imaging is particularly helpful through its ability to delineate the extent and severity of bowel inflammation, assess for the presence of strictures, and diagnose extraluminal complications such as fistulae or abscesses (1–3).
Computed tomography (CT) has become the predominant cross-sectional imaging modality used in the evaluation of inflammatory bowel disease due to its accuracy, speed, and availability at most centers. The addition of enteric contrast either per os (CT enterography) or per nasojejunal tube (CT enteroclysis) has led to even better luminal distension and examination of the bowel wall. Unfortunately, the major limitation of CT scan, especially with regard to children is exposure to ionizing radiation. The US National Research Council has estimated that approximately 1 in 1000 individuals would develop cancer from a radiation exposure near that of 1 adult abdominal CT (4). Furthermore, cancer mortality from CT radiation appears to be age dependent with greater risk of death for younger patients (5,6).
In the past, magnetic resonance (MR) imaging of the bowel has been limited by motion artifact and poor resolution. Recent advances in MR technology have allowed for thinner cross-sectional images to be obtained more quickly with improved signal-to-noise ratio, thereby allowing better visualization of the gastrointestinal tract and particularly the small bowel. Similar to CT enterography, MR enterography (MRE) uses oral contrast to distend the small bowel, displace intraluminal air, and allow for more detailed evaluation of wall thickness. Intravenous administration of gadolinium can depict abnormal mucosal enhancement indicative of inflammation as well as delineate fistulae, phlegmons, and abscesses (1–3).
Although there are a number of studies evaluating MRE in the adult CD population (7–17), pediatric studies are more limited. Initial studies, predominantly from Europe, have demonstrated positive correlation between MR findings, disease distribution on endoscopy, and clinical markers of disease severity (18–21).
Although these findings are encouraging, they are difficult to extrapolate to all of the patient populations because there is no standardized MRE protocol between institutions. This is particularly true with regard to the choice of oral contrast agent, which can directly affect the degree of bowel distension and hence image quality (22). Thus, any results must be considered within the context of the specific agent used. Those used in previous studies include methylcellulose, mannitol, and polyethylene glycol (PEG). Volumen (EZ-EM Inc, Westbury, NY) is a low-concentration barium solution with sorbitol that has been commonly used for CT enterography. This has been shown to achieve similar bowel distension to mannitol and PEG in adults (23,24), has had superior patient acceptance in our hands, and therefore is the agent of choice at our institution.
This is a preliminary report to determine first whether we are able to evaluate the sensitivity and specificity of our specific MRE protocol for the diagnosis of terminal ileitis in children with known or suspected CD. A secondary goal is to determine the correlation between inflammatory activity on MRE and the Pediatric Crohn Disease Activity Index (PCDAI), a validated tool for determining disease severity in children with CD (25,26). Positive results will warrant a much more extensive, multicenter, prospective study.
The present study was performed with approval from the Lifespan/Rhode Island Hospital institutional review board. Waiver of informed consent was appropriately obtained.
The present study was performed as a retrospective chart review. To identify patients for the present study, we first searched the Picture Archiving and Communication System to identify all of the patients who had undergone MRI of the abdomen and pelvis at our institution as well as at local outpatient imaging centers between June 15, 2007 and April 1, 2010. From this list, we identified patients 18 years of age or younger who specifically underwent MRE for known or suspected CD.
MRE was performed with 900 mL of Volumen (EZ-EM Inc) and 450 mL of water as oral contrast and gadolinium-based intravenous (IV) contrast (0.1 mmol/kg). No antiperistaltic agent was used. MRE protocol consisted of multiplanar (axial and coronal) steady-state free-precision images, multiplanar fat-suppressed single-shot fast-spin-echo images, axial chemical-shift images, and multiplanar T1-weighted fat-suppressed spoiled gradient echo images before and after administration of IV contrast.
Assessment and Scoring of MRE
Each MRE was blindly assessed by the same attending radiologist, D.G., who is also 1 of the authors on the study. First, each image was graded as poor, adequate, or excellent based on bowel distension and motion artifact. Next, each MRE was assessed for inflammatory activity. A numeric score was assigned to each MRE based on the following 5 parameters: wall thickness of the most diseased segment (regardless of location), IV contrast enhancement, T2 signal, mesenteric engorgement, and lymphadenopathy. Wall thickness was directly measured in millimeters, whereas the other 4 parameters were assigned a score of 0 (none), 1 (mild), or 2 (severe). These 5 parameters were then totaled to determine the overall MR score. It should be noted that although there are presently no validated MRE scoring tools in the literature, the parameters we chose to include in our score are all of the known signs of CD activity (27,28).
After scoring each MRE, the medical record for each patient was reviewed. First, we reviewed all of the colonoscopy and pathology reports within 90 days of each MRE. A patient was defined as having terminal ileitis if signs of chronic inflammation were found on histology consistent with a diagnosis of CD. Our pathologists use standard criteria consistent with the National Institutes of Health guidelines for diagnosis found in the National Institute of Diabetes, Digestive, and Kidney Diseases inflammatory bowel disease genetics consortium phenotyping manual (29).
For those patients who underwent colonoscopy, we recorded all of the medications received between the date of colonoscopy and the date of MRE. Each of these MREs were then placed into one of the following categories based on the medications received by that particular patient: no medications, steroids alone, steroids plus 5-aminosalicylates (5-ASA) or antibiotics, steroids plus immunomodulators (IM), 5-ASA and/or antibiotics, IM alone, and IM plus antibiotics (Table 1).
We then recorded history, physical, and laboratory data for each patient using the clinical encounter closest in calendar days to the MRE. For outpatients, we obtained this information from our clinic notes, which are specifically designed to match the parameters on the PCDAI, enabling a score to be calculated. For inpatients, we used both the daily progress note and the nursing flow sheet to obtain the necessary information. In the case of inpatients, any abdominal pain was automatically assigned a value of 10 for “unable to ignore,” and activity level was automatically assigned a value of 10 for “frequent limitation of activities.”
Sensitivity and specificity of MRE for terminal ileitis were calculated using a standard 2 × 2 table (Table 2). Correlation coefficient was used to measure the relation between MRE score and PCDAI. P value was calculated using a 2-tailed t test.
Seventy-two patients underwent a total of 80 MREs during the study period. The age range was 6 to 18 years with a mean of age of 14. MRE was performed for suspected CD in 33 of 80 cases (41.3%) and for known CD in 47 of 80 cases (58.8%).
MRE was normal in 29 cases, with no evidence of inflammation. Among the remaining 51 MREs, terminal ileitis was found in 35, proximal ileitis in 4, jejunitis in 2, colitis in 19, and pouchitis in 2 (certain studies had >1 diseased segment). Signs of inflammatory activity included wall thickening, IV contrast enhancement, and T2 brightness (Figs. 1–3). Bowel distention was graded as excellent in 66 cases (82.5%), adequate in 12 (15%), and poor in only 2 (2.5%).
MRE Versus Ileocolonoscopy
Forty-two of the 72 patients (58.3%) underwent colonoscopy within 3 months of MRE. The terminal ileum was successfully intubated in 33 of these 42 patients. In the remaining 9 patients, reasons for the terminal ileum not being intubated included examiner choice (1 patient), narrowed ileocecal valve (3 patients), colonic stricture (1 patient), bleeding of the colon (3 patients), and presence of an ileal pouch (1 patient).
Among the 33 patients in whom the terminal ileum was intubated, 35 MREs were performed during the study period. Compared with histology, we found that MRE had a sensitivity of 71.4% and a specificity of 100% for terminal ileitis. The positive and negative predictive values were 100% and 70%, respectively (Table 2).
There were no falsely positive MREs, and only 6 of the 35 MREs were falsely negative. Four of the 6 false-negative MREs were in patients that were medically treated between the date of MRE and colonoscopy including 2 in patients on steroids plus 5-ASA, 1 in a patient taking antibiotics alone, and 1 in a patient taking IM alone (Table 1).
The average time between MRE and colonoscopy was 24 days. Four of the 6 false-negative MREs came within 14 days of colonoscopy, whereas the remaining 2 came within 30 to 60 days (Table 3).
MRE Score Versus PCDAI
We were able to calculate PCDAI in 39 of the 72 patients (54.2%). Among these, 28 had data collected from outpatient charts, and 11 had data collected from inpatient records. Average time between MRE and clinical encounter was 8.2 days. PCDAI could not be completed for the remaining 33 patients due to incomplete charting. PCDAI and MRE score were found to have a statistically significant positive correlation of 0.37 (P = 0.020426) (Fig. 4).
We determined that our specific MRE protocol had a sensitivity of 71.4% and a specificity of 100% for the detection of terminal ileitis using histology as the gold standard. The positive and negative predictive values were 100% and 70%, respectively. Our findings are similar to those from a previous report from Laghi et al (20), in which MRE using PEG as oral contrast was found to have a sensitivity of 84% and a specificity of 100% for erosive terminal ileitis when compared with ileocolonoscopy, and similar to the report from Pilleul et al (18), in which MRE using mannitol as oral contrast had a sensitivity of 83% and a specificity of 100% for the diagnosis of CD.
Our lower sensitivity in comparison with our specificity may have been due to several reasons. First, we found that a little more than half of our patients actually underwent colonoscopy within 90 days of MRE, and even fewer had successful intubation of the terminal ileum. As a result, the sample size ultimately available for determining the sensitivity of MRE was decreased. Next, the majority of our false-negative studies (4/6) were in patients treated with medications between the date of MRE and the date of colonoscopy. Although some of the medications received are not necessarily believed to induce mucosal healing, it is plausible that MRE would be less able to detect terminal ileitis in patients being medically treated at the time. Motion artifact diminished the accuracy of one of the MREs, which was performed in a patient in the pediatric intensive care unit with respiratory distress. Finally, MRE as a diagnostic modality may simply fail to capture patients with more subtle histologic findings of terminal ileitis, thereby leading to a greater proportion of false-negative tests. Interestingly, timing between MRE and colonoscopy did not appear to have much of an effect on our sensitivity because the majority of the false-negative studies were done within only 14 days of colonoscopy.
In the second part of our study, we found a statistically significant positive correlation between the degree of inflammatory activity on MRE and PCDAI. We consider this especially significant because this was a retrospective study in which PCDAI and MRE were not necessarily performed at the same time. Because PCDAI is a validated tool to assess disease severity, this suggests that MRE has a potential role in assessing clinically significant degrees of mucosal inflammation. What remains to be seen is whether MRE is sensitive enough to adequately predict complete mucosal healing. This will be an important question to answer because there is growing evidence that complete mucosal healing predicts sustained clinical remission in CD. Baert et al (30) reported that complete mucosal healing was the only factor that predicted sustained, steroid-free remission 3 and 4 years after the initiation of therapy for a group of patients with newly diagnosed CD. Nevertheless, if MRE can be used to accurately assess clinically significant mucosal disease activity, it can serve as an important adjunctive tool by tracking mucosal inflammation over time in a way that is safe and noninvasive.
In conclusion, our MRE protocol has a high specificity and positive predictive value for terminal ileal disease in children with known and suspected CD while providing excellent image quality. Our study also demonstrated a statistically significant positive correlation between severity of mucosal disease activity on MRE and PCDAI. MRE has great promise in the future of pediatric CD through its ability to image the gastrointestinal tract without exposure to radiation. Our promising results suggest that a large, prospective, multicenter study should be undertaken to further validate its use.
1. Lin MF, Narra V. Developing role of magnetic resonance imaging in Crohn's disease. Curr Opin Gastroenterol
2. Toma P, Granata C, Magnano G, et al. CT and MRI of paediatric Crohn disease
. Pediatr Radiol
3. Darge K, Anupindi SA, Jaramillo D. MR imaging of the bowel: pediatric applications. Magn Reson Imaging Clin N Am
4. Committee to Assess Health Risks from Exposure to Low Levels of Radiation
, National Research Council. Health Risks from Exposure to Low Levels of Radiation
: BEIR VII phase 2. http://dels.nas.edu/dels/rpt_briefs/beir_vii_final.pdf
5. Brenner DJ, Elliston CD, Hall EJ, et al. Estimated risks of radiation
-induced fatal cancer from pediatric CT. AJR
6. Brenner DJ, Hall EJ. Computed tomography—an increasing source of radiation
exposure. N Engl J Med
7. Riimola J, Rodriguez S, García-Bosch O, et al. Magnetic resonance for assessment of disease activity and severity in ileocolonic Crohn's disease. Gut
8. Koh DM, Miao Y, Chinn RJ, et al. MR imaging evaluation of the activity of Crohn's disease. AJR
9. Florie J, Horsthuis K, Hommes DW, et al. Magnetic resonance imaging compared with ileocolonoscopy in evaluating disease severity in Crohn's disease. Clin Gastroenterol Hepatol
10. Girometti R, Zuiani C, Toso F, et al. MRI scoring system including dynamic motility evaluation in assessing the activity of Crohn's disease of the terminal ileum. Acad Radiol
11. Del Vescovo R, Sansoni I, Caviglia R, et al. Dynamic contrast enhanced magnetic resonance imaging of the terminal ileum: differentiation of activity of Crohn's disease. Abdom Imaging
12. Florie J, Wasser MN, Arts-Cieslik K, et al. Dynamic contrast-enhanced MRI of the bowel wall for assessment of disease activity in Crohn's disease. AJR
13. Bernstein CN, Greenberg H, Boult I, et al. A prospective comparison study of MRI versus small bowel follow-through in recurrent Crohn's disease. Am J Gastroenterol
14. Siddiki HA, Fidler JL, Fletcher JG, et al. Prospective comparison of state-of-the-art MR enterography
and CT enterography in small-bowel Crohn's disease. AJR
15. Lee SS, Kim AY, Yang SK, et al. Crohn disease
of the small bowel: comparison of CT enterography, MR enterography
, and small-bowel follow-through as diagnostic techniques. Radiology
16. Punwani S, Rodriguez-Justo M, Bainbridge A, et al. Mural inflammation in Crohn disease
: location-matched histologic validation of MR imaging features. Radiology
17. Horsthuis K, Bipat S, Bennink R, et al. Inflammatory bowel disease diagnosed with US, MR, scintigraphy, and CT: meta-analysis of prospective studies. Radiology
18. Pilleul F, Godefroy C, Yzebe-Beziat D, et al. Magnetic resonance imaging in Crohn's disease. Gastroenterol Clin Biol
19. Magnano G, Granata C, Barabino A, et al. Polyethylene glycol and contrast-enhanced MRI of Crohn's disease in children: preliminary experience. Pediatr Radiol
20. Laghi A, Borrelli O, Paolantonio P, et al. Contrast enhanced magnetic resonance imaging of the terminal ileum in children with Crohn's disease. Gut
21. Laghi A, Paolantonio P, Iafrate F, et al. MR of the small bowel with a biphasic oral contrast agent (polyethylene glycol): technical aspects and findings in patients affected by Crohn's disease. Radiol Med
22. Young BM, Fletcher JG, Booya F, et al. Head-to-head comparison of oral contrast agents for cross-sectional enterography: small bowel distension, timing, and side effects. J Comput Assist Tomogr
23. Kuehle CA, Ajaj W, Ladd SC, et al. Hydro-MRI of the small bowel: effect of contrast volume, timing of contrast administration, and data acquisition on bowel distension. AJR
24. Young BM, Fletcher JG, Booya F, et al. Head-to-head comparison of oral contrast agents for cross-sectional enterography: small bowel distension, timing, and side effects. J Comput Assist Tomogr
25. Hyams JS, Ferry GD, Mandel FS, et al. Development and validation of a pediatric Crohn's disease activity index. J Pediatr Gastroenterol Nutr
26. Hyams J, Markowitz J, Otley A, et al. Evaluation of the Pediatric Crohn's Disease Activity Index: a prospective multicenter experience. J Pediatr Gastroenterol Nutr
27. Siddiki H, Fidler J. MR imaging of the small bowel in Crohn's disease. Eur J Radiol
28. Maccioni F, Bruni A, Viscido A, et al. MR imaging in patients with Crohn's disease: value of T2- versus T1-weighted gadolinium-enhanced mr sequences with use of an oral superparamagnetic contrast agent. Radiology
29. Inflammatory Bowel Disease Genetics Consortium. Phenotype Operating Manual: Guidelines for Recruiting Individuals to the IBD Genetics Consortium and Detailed Forms for Phenotyping Crohn's Disease, Ulcerative Colitis, Indeterminate Colitis, and Unaffected Controls. http://medicine.yale.edu/intmed/ibdgc/resources/81330_Phenotyping_Manual_2.9.11.pdf
30. Baert F, Moortgat L, Van Assche G, et al. Mucosal healing predicts sustained clinical remission in patients with early-stage Crohn's disease. Gastroenterology