Crohn's disease (CD) is a chronic inflammatory bowel disorder characterized by remittent and relapsing episodes.1 Assessment of inflammatory activity is crucial to decide optimal treatment: patients with severe inflammatory lesions receive medical therapy, while patients without or with moderate inflammatory lesions associated with obstructive symptoms undergo surgery.2, 3
Numerous criteria are used to assess disease activity including clinical symptoms, physical findings, laboratory parameters, and endoscopic results.4 However, clinical and biological criteria must be supported by results of other diagnostic techniques because these scores are unreliable4, 5; moreover, clinical activity seems to be independent of the severity of mucosal lesions and biological activity.5, 6
Conventional and/or wireless capsule endoscopies only provide information about the intestinal mucosa, while conventional small bowel contrast studies only provide indirect information about the intestinal wall. These limitations are important because inflammation in CD is commonly transmural.1, 7
New imaging tools such as computed tomography (CT) and magnetic resonance imaging (MRI) provide information about the mucosa, the intestinal wall, and adjacent structure abnormalities, including complications such as fistula or abscesses.8, 9
The accuracy of CT enteroclysis seems to be good for evaluating CD. Chiorean et al10 correlated CT findings with surgical pathology to assess the accuracy of CT enteroclysis in differentiating inflammatory from fibrostenotic lesions. A scoring system was defined to reliably differentiate these lesions. However, because of the radiation doses of CT scan and the increased risk of radiation-induced cancers,11, 12 especially in young people, reliable nonradiation diagnostic techniques must be developed to follow these patients who require regular evaluations.13
Because of its excellent soft-tissue contrast, multiplanar images, the absence of exposure to radiation, safe contrast agents, and ability to show mural and extramural abnormalities,14 MRI is becoming the standard imaging technique for CD.3 Several studies have shown that MRI plays a role in the assessment of CD activity, using different variables.9, 15–17 These variables have only been correlated with clinical and biological scores (e.g., the Crohn's Disease Activity Index [CDAI]) or with endoscopic findings, which all have certain limits because CD is a mural and transmural disease.
To our knowledge, only one study has compared MRI findings with the pathological analysis of surgical specimens, but with a small number of patients.18 The aim of our study was to determine the diagnostic value of MRI findings in CD in correlation with inflammatory activity with surgical pathological analysis as a reference method.
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- PATIENTS AND METHODS
Our study permitted us to identify MRI signs significantly associated with pathological inflammation. The ability to recognize inflammation is of major interest in the management of patients in the clinical setting, as this condition is potentially reversible using medical therapy, and its absence usually leads to surgical therapy. Two analytical methods (MRI and pathological analysis of resected specimens) were selected that evaluate both mural and extramural components. Indeed, histological analysis of intestinal resection is essential to determine CD activity because active lesions are often transmural, enclosing fissures or fistula mixed with edema and neutrophil infiltration if the disease is still active.
Certain mural MRI findings were found to be associated with our CD pathological inflammatory score of the disease. Wall thickness on either T1- or T2-weighted sequences as well as wall thickness on whole-mount slides were shown to be significantly increased with disease activity. Our results show that a threshold of 6 mm can be used to distinguish between patients with inactive disease (grade 0) and active disease (grade 1 or 2) (sensitivity and specificity, 63.6% and 92.9%, respectively). This value agrees with other studies which suggest that a normal bowel wall is between 1 and 3 mm thick, and the minimal value for wall thickness in CD is 4 mm22 or 5 mm.16, 23 Furthermore, a threshold of 11 mm provides a distinction between severe active CD patients (grade 2) and others (grade 0 or 1) (sensitivity and specificity, 40.7% and 92.3%, respectively). Although this measurement may be obtained on T1- or T2-weighted sequences, it was easier on T2 sequences. This finding was found to be significantly associated in most CT or MRI studies.10, 15–17, 24
Bowel wall enhancement has also been extensively investigated in CD patients. However, results from the literature are confusing because various acquisition times, different enhancement patterns (homogeneous, layered, mucosal), and various estimations of the degree of wall enhancement10, 15–17 have been used. Interestingly, all the enhancement criteria evaluated in this study were significantly related to the CD pathological inflammatory score in the different grades, except the degree of wall enhancement at the parenchymatous phase. The most striking finding to differentiate inactive CD (grade 0) from moderately active (grade 1) and severely active (grade 2) CD patients was the degree of wall enhancement on delayed T1-weighted sequences. Therefore, delayed T1-weighted sequences seem to play an important role in assessing disease activity.
As reported by others,17 wall signal intensity in T2-weighted sequences was associated with disease activity in this series. We also found that a blurred enhancement pattern in delayed phase imaging was well correlated with activity grading, and was essentially observed in severely active CD patients. This probably corresponds to transmural inflammation extending to adjacent mesentery fat, described by Colombel et al5 as perienteric inflammation, which correlated well with increased CRP, as in our study.
Certain extramural MRI findings were significantly associated with disease activity: the presence of the comb sign, fistula, and abscesses, findings which were mostly observed in active CD patients. Despite one negative study,16 the comb sign has mostly been reported in active CD patients.10, 15, 17 Diagnosis of abscesses is a major issue in clinical practice because it changes the course and management of the disease and usually requires interventional treatment.17
Conversely, no relationship was found between the presence of lymph nodes or fatty proliferation and disease activity. Chiorean et al and Gourtsoyiannis et al observed a significant number of lymph nodes in active CD patients.10, 15–17, 24 This discrepancy could be explained because we considered all lymph nodes whatever the size, number, or enhancement.
To our knowledge, only two studies compared MRI and surgical pathological findings, including 18 and 17 patients, respectively.18, 25 One of these studies did not mention pathological classification reference and used MRI-determined categories.25
Most of the findings that were significant in our study were also described in the study of Punwani et al.18 Wall thickness, T2 hypersignal, and pattern of enhancement are associated with histologic markers of acute inflammation, whereas degree of enhancement at parenchymatous time (70 seconds for this study) and lymph nodes are not associated.18 Moreover, we think our study brings additional information. We used a pathological score for acute inflammation and fibrosis which was, as in their study, adapted from the classification of Borley et al.21 However, we simplified this score, which makes it easier for daily practice. Our data were qualitative and not quantitative, contrary to their study, as it has been suggested that quantitative measurements are less reliable than visual estimates for identifying active CD.5 Last, we also studied all the findings at a very delayed time (8 minutes), and we have shown that this timing is very important in distinguishing moderately active CD patients (grade 1) from severely active CD patients (grade 2).
Compared with the study which evaluated CT scan imaging and surgical pathological findings,10 our pathological score has the two major advantages of not mixing chronic (lymphoid infiltrates) and acute (neutrophil infiltrates) inflammation and distinguishing perforating and nonperforating phenotypes.
In our study, fibrosis was evaluated and found to be well correlated with inflammation. The relationship between transmural fibrosis and the severity of acute inflammation (deep fissures and fistula) is consistent with previous pathological studies, showing the correlation between fistula formation and strictures with massive mural fibrosis.26, 27 This correlation between acute inflammation and fibrosis is an important and innovative point, suggesting that it may not be relevant to make an exclusive distinction, as is usually done, between inflammatory patients and fibrotic patients. Moreover, we did not find any correlation between the fibrosis score and MRI pattern or degree of enhancement wall.
The present study has certain limitations. First, it is a retrospective study. Second, we deliberately chose oral administration of contrast medium and therefore did not investigate certain mural criteria such as superficial ulcers, fold thickening, and nodularity. As shown previously by Gourtsoyiannis et al,16 MRI enteroclysis provides better results for these subtle abnormalities than MRI without enteroclysis. Nevertheless, although these are early CD findings, the relationship between their presence and disease activity is questionable.16 Moreover, naso-jejunal tube placement is uncomfortable, making movement artifacts more frequent, and it has clearly been shown that small bowel MRI with oral administration is much more acceptable to patients than MRI enteroclysis.28
In conclusion, this study identified several MRI findings that were significantly associated with inflammatory activity in CD using surgical pathological examination as the reference method. Demonstration of the high accuracy of MRI for detecting the presence of inflammatory activity is of significant clinical relevance because of its therapeutic implications as patients with severe inflammatory lesions will receive medical therapy, while those without or with only moderate inflammatory lesions will preferably undergo surgery. Altogether, these results could help us to select patients for medical or surgical therapy and also be used to monitor responses to therapeutic interventions both in the clinical setting and in therapeutic trials.