Role of MR enterography versus ileo-colonoscopy in the assessment of inflammatory bowel diseases

Inflammatory bowel disease (IBD) is widespread and rapidly rising in developing countries. It remains a significant issue in Western culture with a prevalence of more than 0.3%. Symptom control has been the only focus of treatment before the discovery that many individuals with IBD continue to have disease activity even in the absence of clinical symptoms. Therefore, treatment goals now include establishing clinical remission, steroid-free remission, and mucosal healing, which may eventually be complemented by transmural healing in cross-sectional imaging modalities. Magnetic resonance enterography (MRE), computed tomography enterography, and small-bowel ultrasound are now reliable methods for staging intramural lesions and extramural consequences in CD and for determining disease activity and severity. Recently literature suggests the incorporation of (MRE) for periodic reevaluation of IBD patients, as it offers small-bowel, colonic, and extra-enteric assessment as well as monitors the response to the anti-inflammatory therapy. The purpose of the current study was to compare MRE with ileo-colonoscopy findings in the diagnosis of IBD features, specifically Crohn's disease, and ulcerative colitis, as well as in the detection of disease exacerbation (Activity). This study used MRE and ileo-colonoscopy to assess chronic inflammatory bowel disease patients; the patient population (n = 30) was made up of (14/30, 46.7%) females and (16/30, 53.3%) males, with a mean age of 32 ± SD 13 years. MRE alone detected lymphadenopathy in 73.3% of patients, and mural thickening with a mean of 4.1 ± SD 5.1 mm. It has detected mucosal enhancement with 80% sensitivity and 60% specificity. However, it was unable to detect mucosal erosions or ulceration. MRE is sensitive, inexpensive, noninvasive, and radiation-free for inflammatory bowel disease detection, with 86.7% diagnostic accuracy for affected areas. Unlike ileo-colonoscopy, it could examine the entire small intestine, precisely measure the affected loop, and detect activity signs such as mural thickening and lymphadenopathy. Only ileo-colonoscopy could detect mucosal degradation and superficial ulcers. IBD treatment protocols should incorporate MRE for small-bowel, colonic, and extra-enteric assessment, monitoring of disease activity, and anti-inflammatory therapy response.


Background
Inflammatory bowel diseases (IBDs) are characterized by chronic idiopathic inflammation of the gastrointestinal (GI) tract. IBD patients most commonly experience Crohn's disease (CD) or ulcerative colitis (UC). Transmural inflammation, a hallmark of IBD, particularly CD, causes the GI wall to thicken and narrow, eventually resulting in the disabling development of deep lacerations, fistulae, strictures, and abscesses. Additionally, persistent deep transmural inflammation increases the likelihood of colitis-associated neoplasia and causes irreparable structural damage [1].
IBD is now a worldwide problem with a fast-increasing prevalence in poorer nations, and it is still a major problem in Western civilization, with a prevalence of above 0.3% [2].
Small-bowel imaging with magnetic resonance enterography (MRE), computed tomography enterography, and ultrasound has been shown to accurately measure disease activity and severity, as well as the staging of transmural lesions and extramural consequences in Crohn's disease (CD) [3].
Due to the failure of previous therapeutic techniques to change the course of CD, innovative treatment aims such as early intervention with effective treatment, treat to target, tight disease control, and surveillance can help patients have better results. These goals necessitate regular and timely patient assessments to track clinical (patient-reported outcomes, PRO), endoscopic (mucosal healing), and radiographic outcomes so that management can be optimized proactively [4].
Before it was realized that many individuals with IBD have ongoing disease activity even in the absence of clinical symptoms, the entire focus of treatment has always been on symptom control. Thus, instead of just treating clinical symptoms, treatment goals now include establishing clinical remission, steroid-free remission, and finally mucosal healing, which may eventually be supplemented by transmural healing in cross-sectional imaging modalities [5].
Resolution of stomach discomfort and normalization of bowel habits, as well as the absence of ulceration on ileocolonoscopy, is the goal of the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) program in the treatment of CD. During the active period of the disease, clinical results were to be monitored every three months, whereas endoscopic outcomes were to be measured every six to nine months [1].
The rationale for this shift in treatment objectives is based on data that mucosal healing is linked to a better long-term patient outcome, as measured by a lower chance of relapse, decreased hospitalization rates, steroid-free remission in the follow-up examination, and resection-free intervals [6]. In terms of direct clinical usefulness, it has been demonstrated that individuals with CD who have mucosal healing have a lower risk of penetrating problems and surgery as compared with patients with severe ulcerations [7].
Costs, potential hazards (perforation, hemorrhage, and cardiovascular issues related to anesthesia), and lack of patient cooperation impede routine endoscopic evaluation. Nonetheless, more than two-thirds of CD patients experience inflammation of the small intestine. Unfortunately, some inflamed bowel segments may be inaccessible through endoscopy (e.g., strictures, adhesions, and proximal small bowel) [8].
MR enterography (MRE) is a sensitive imaging method that does not require ionizing radiation, which can be a significant concern in young patients with IBD. MR enterography is also useful for helping to classify newly diagnosed IBD in patients who have isolated colon disease or an indeterminate form of colitis. The detection of clinically unexpected small-bowel inflammation by MR enterography could become a crucial step in diagnosing CD and subsequently guiding therapy [9].
Endoscopy and imaging are crucial to the diagnosis and treatment of IBD. In addition to allowing the assessment of disease type and distribution, endoscopic evaluation permits the histopathological investigation required for establishing the diagnosis and separating IBD subtypes [10].
With the growing availability and experience of MRI (magnetic resonance imaging) techniques, treating physicians now have more diagnostic options for monitoring patients with CD and UC [11].

Aim of work
-Comparison between MRE and ileo-colonoscopy findings in the detection of IBD features, and the evaluation role of MRE in the assessment of IBD patients, namely Crohn's disease and ulcerative colitis. -Comparison of MRE versus ileo-colonoscopy in the detection of disease exacerbation (Activity).

Methods
This study is an observational cross-sectional analytic study. Data were collected prospectively after getting ethical approval from the institutional review board (IRB) of the faculty of medicine, in our university, Code: (MS-456-2020).

Study population
The sample size was 30 adult patients who were diagnosed and on the treatment of IBD, referred from the IBD clinic, (ICRID clinic) of our institution, within the period from December 2020 to September 2021. This number was adopted by using MedCalc 19 program by setting alpha error significance of 0.05%, 95% confidence level, and 80% power sample. This study's sample size was determined by using the previous study of Alexander et al. [12] value for the Spearman correlation between the Crohn's Disease Endoscopic Index of Severity (CDEIS) and the Magnetic Resonance Index of Activity (MaRIA), which was calculated as 0.49. Informed consent was taken from all patients before the study. The patient population (n = 30) consisted of 30 adult patients, 16 (53.3%) males and 14 (46.7%) females, with a mean age of 32 ± 13 years (range 18-81 years). This study included eligible adult males and females with evidence of IBD as diagnosed by clinical, laboratory, imaging, and endoscopic criteria. We excluded children less than 18 years, low kidney functions patients (eGFR < 30 ml/min), pregnant and lactating women as well as contraindicated patients to MRI as patients with cardiac pacemakers or claustrophobia. Besides we have excluded patients who had intervals between ileo-colonoscopy and MRE of more than 2 weeks.

Clinical and laboratory assessment
An expert gastroenterologist has documented the symptoms, physical, and laboratory findings of the patients as part of their assessment in the IBD clinic.

Endoscopic protocol
Pre-procedural oral preparation (such as laxatives, enema, and prevention of dairy products, carbonated beverages, and red-colored liquids) was used for bowel cleansing, which is essential for adequate mucosal examination. Variable types of sedation (such as propofol) with cardiac and oxygen monitoring were introduced for patient comfort, depending upon the predicted difficulty of the procedure. Bowel distention by Polyethelene Glycol was preferred for adequate mucosal examination. A full clinical examination was done, and a digital rectal examination was conducted by an expert gastroenterologist to check for skin tags, polyps, and fistulas.
A gastroenterologist with ten years of experience in colonoscopy has employed a flexible colonoscopy tube that is passed through the anus and into the colon.
A multichannel system for air insufflation, water suction, video, and power supply was attached to the colonoscope: "Olympus video-scope was used in this study, " which is supported by the magnification available with narrow-band imaging (NBI). The ileo-colonoscopy protocol is in agreement with Somwaru et al. [13]. Ileo-colonoscopy findings have represented the standard reference for the evaluation of the role of MRE.

MRI acquisition
Within 2 weeks intervals maximum after ileo-colonoscopy; patients underwent MR enterography using a 1.5 T MR scanner: "Philips Achieva 1.5 T device" using a phased array body coil. Patients were prepared before the examination with a low-residue diet for 24 h and 8 h of fasting before imaging and rectal enema before the examination procedure. Mannitol-water contrast solution was administered using 350 ml mannitol 20% over 1150 ml water. Patients were advised to start drinking one hour prior to the examination one cup (250 ml/10 min). They were asked to lie in the supine position. Three-plane localizer: from the xiphisternum to Symphysis Pubis, was done followed by the standard MR protocol for enterography in our institution as follows: • Axial and coronal: T2-weighted single-shot fast spin echo sequences (SSFSE) and diffusion-weighted sequences. • Injection of I.V. antiperistaltic agent (20 mg Buscopan) and 10 ml Magnevist I.V (0.1 mmol/kg BW), followed by dynamic coronal 3D T1-weighted gradient echo sequences with fat suppression, obtained in time intervals of 45-55, 70, and 180 s. • Post-contrast axial 3D T1-weighted gradient echo sequences with fat suppression is obtained between the coronal portal and delayed phases. • Coronal post-contrast axial 2D or 3D T1-weighted sequences with fat suppression are acquired. Coronal cuts should be at least 6 mm slice thickness and 0.5 mm gaps. • Our institutional protocol has been found to be in agreement with that of Yoon et al. [14].
The MRE images were interpreted by a radiologist with 12 years of experience in GIT sub-specialty, who was blinded to the ileo-colonoscopy findings.

Statistical analysis
Data were described in the form of frequencies (number of patients) and percentages using the "Microsoft Office Excel Software" application for Windows (2010).
• Statistical analysis for the data was conducted using SPSS 22nd edition, numeric variables were presented in mean and standard deviation, and paired comparison was done using Wilcoxon sign rank test

Demographic data
• This prospective study involved thirty IBD patients who were referred from our IBD clinic. Age range 18-81 years old. The patient population (n = 30) included 16 (53.3%) males and 14 (46.7%) females with a mean age of 32 SD 13 years of age (Table 1).
A. Analysis of the ileo-colonoscopy data.

Comparison of MRE versus ileo-colonoscopy in the detection of disease exacerbation
I. Mucosal hyperemia/edema by ileo-colonoscopy versus mucosal/mural enhancement by MRE (Table 6).
Paired comparison of mucosal enhancement by MRE and mucosal hyperemia by ileo-colonoscopy showed that there is a moderate concordance between results of MRE and ileo-colonoscopy regarding mucosal hyperemia/ enhancement between both modalities with p value 0.50 (Table 6); however, the diagnostic indices of MRE versus colonoscopy in terms of mucosal affection showed that MRE had a sensitivity 80% and specificity 60% in detecting mucosal affection (Table 7).

II. Mural thickening
Ileo-colonoscopy was not able to estimate mural thickening at all, while MRE could estimate the mural thickening with a mean of 4.1 ± 5.1 mm SD.

III. Mucosal erosions and ulcerations
Mucosal erosions and ulcerations could not be detected by MRE at all, while ileo-colonoscopy could detect 18/30 cases (60%) with mucosal erosions and ulcerations.

Discussion
Inflammatory bowel disease (IBD) includes both Crohn's disease (CD) and ulcerative colitis (UC). In comparison with the general population, it primarily affects young people, significantly affecting their quality of life and raising morbidity [15].
MRE is useful to assess bowel inflammation and complications such as perforation, fibrosis, and stenosis during the disease course [16].
The current study had a mean patient age of 32 years, which agrees with most of the evidence published in the literature that IBD had a peak incidence during the second and third decades of life with a rare incidence in the 6th decade of life [17].
These findings are agreeing with Esmat et al. [18], who found that the most commonly affected part of the colon in patients diagnosed with UC is mainly the left-sided colon (65%) followed by the recto-sigmoid area (18.5%) and finally whole colon (16.3%) as reported by Egyptian gastroenterologists. Also, Petagna et al. [19] have stated that CD mainly affects the ileocecal junction followed by the distal ilium, and this agrees with many authors who correlated the extent of affection of ileum with CD as a part of its pathogenesis where it affects the Peyer's patches which defined as a group of lymphoid follicles in the mucous membrane that lines the small intestine.
In the present study, MRE showed advancement in the assessment of the length of the affected loop of the intestine which was significantly higher in colonoscopy with a mean of 48 ± SD 44 cm versus 15.8 ± SD 19.7 cm, with a p value of 0.0001. We assume that the higher length of ileo-colonoscopy is not as accurate as MRE.
There was a concordance of findings between both imaging modalities in terms of: mural enhancement/hyperemia, loss of haustral/vascular pattern, Fig. 9 A 41-year-old female patient, known ulcerative colitis disease for 5 years on mesalazine (Pentasa) and steroids, presented with bleeding per rectum and tenesmus for follow-up. Axial T2-w SPAIR A shows mild circumferential uniform rectal mural thickening, axial post-contrast THRIVE image B shows corresponding rectal mural thickening and hyperenhancement, and coronal post-contrast THRIVE image C shows corresponding rectal mural thickening and hyperenhancement with a small polyp seen (arrow). Ileo-colonoscopy showed mild ulcerative proctosigmoiditis with 2 small polyps and granular mucosa of the rectum     this difference was not statistically significant with P value 0.50. Loss of vascular and haustral pattern was reported in (6/30, 20%) of cases by ileo-colonoscopy, while it was only detected in (5/30, 16.7%) of cases by MRE with one false-negative case; however, this difference was not statistically significant with P value 1.0.
In the present study, MRE was defective in the detection of mucosal lesions, such as pseudo-polyps and polyps as MRE only reported (1/30, 3.3%) cases with pseudo-polyps, while ileo-colonoscopy was positive in (5/30, 16.7%) cases; however, this difference was not statistically significant with p value 0.12.
In the present study, extraluminal affection such as fat smudging, abscess formation, related vascular congestion, and regional lymphadenopathy was only detected by MRE in (4/30, 13.3%), (1/30, 3.3%), (2/30, 6.7%), and (22/30, 73.3%) of cases, respectively, versus no cases by colonoscopy with p value 0.0001 for the abscess formation and the regional lymphadenopathy, and P value 0.12 and 0.50 for fat smudging and related vascular congestion, respectively. Agreeing with Kim et al. [20] as they have mentioned that MRE is a noninvasive diagnostic tool that assesses both small and large bowel affection in IBD, as well as, can identify intraluminal and extraluminal adverse events. And with Langan et al. [21], who have stated that although endoscopy has distinct advantages, it cannot be used to assess extraintestinal abnormalities and can be limited when strictures impede the passage of the endoscope and thus prevent completion of the examination.
According to Neumann et al. [22] who had added that in addition to the lack of extraintestinal visualization using ileo-colonoscopy, as it is mainly limited to the luminal visualization, standard endoscopy may have technical restrictions that hinder the examination of all colon hidden parts. This is because traditional endoscopes only have a 170° field of view due to the use of a complementary metal oxide semiconductor (CMOS) or charge-coupled device (CCD) optics. New developments have been made to improve visualization using seven light-emitting diodes. Particularly, the FUSE colonoscopy's multiple CCD chips, which enable a field of view of up to 330°.
In the present study, paired comparison of both modalities showed that ileo-colonoscopy had a higher detection rate of diseased areas than detected by MRE; however, this difference was not significant with a p value of 0.12. MRE showed a sensitivity of 88.5%, a specificity of 75%, a negative predictive value of 95.8%, a positive predictive value of 50%, and overall diagnostic accuracy of 86.7% in detecting diseased areas within the intestine.
These results are confirmed by a large prospective study conducted by Taylor et al. [23] in the UK where they included all patients diagnosed with IBD and they were assessed using conventional ileo-colonoscopy, MRE, and ultrasound. Results showed that the sensitivity of MRE in the detection of IBD is 97% and for detection of the extent of the disease is 80%; however, specificity in the detection of disease extent was 95% which was higher than reported in our study.
Monitoring the patient's reaction to anti-inflammatory treatment is another possible application for MRE, which would allow for more accurate and less invasive ways of surveillance [24].
Due to the failure of prior therapeutic methods to alter the course of CD, novel therapeutic objectives such as early intervention with effective treatment, treat to target, tight disease control, and surveillance can help patients achieve improved outcomes. These objectives involve regular and timely patient evaluations to monitor clinical (Patient Reported Outcomes, PRO), endoscopic (mucosal healing), and radiographic outcomes so that proactive therapy can be optimized [4].
There was a progression in radiologic evaluation from barium enema investigations to advanced cross-sectional imaging procedures like MR enterography. Endoscopy and magnetic resonance (MR) enterography are complementing diagnostic procedures for the evaluation of inflammatory bowel disease (IBD), as stated by Sahi et al. [25], and Gallego et al. [26]. It has been demonstrated that MR enterography correlates well with endoscopy in predicting disease activity, particularly in Crohn's disease.
Importantly, a higher risk of complications may exist even with lower cumulative radiation exposures [27]. Therefore, imaging techniques that are not using ionizing radiation, such as MRE, are especially appealing in a population of young patients who are susceptible to recurrent imaging [28].
According to Lanier et al. [16], magnetic resonance enterography (MRE) has become the imaging modality of choice for the assessment of IBD activity in both adults and children. A systematic review and meta-analysis on the role of MRI in the detection of Crohn's disease activity concluded its effectiveness as an alternative to CT enterography as it has good diagnostic accuracy without radiation exposure [29].
Mucosal hyperemia/enhancement was detected by MRE with a sensitivity of 80% and specificity of 60%. MRE could estimate the mural thickening with a mean of 4.1 ± SD 5.1 mm. Yet, mural thickening could not be detected by ileo-colonoscopy at all, with a significant difference; the p value was 0.001.
In the current study, MRE could detect related lymphadenopathy in (22/30, 73.3%) cases versus (0/30, 0%) cases by ileo-colonoscopy with a significant difference of P value of 0.0001. DWI was useful in the detection of lymphadenopathy, which is an important marker of disease exacerbation; lymph nodes with restricted DWI were of good value in the detection of the active inflammatory process. According to the literature, DWI with parallel imaging permits the detection of inflammation in Crohn's disease patients, and the lower ADC values in the inflamed bowel segments indicate restricted diffusion [34].
However, mucosal erosions and ulcerations could not be detected by MRE in this study, while using ileocolonoscopy could detect (18/30, 60%) of cases, with mucosal erosions and ulcerations, versus (0/30, 0%) of cases by MRE, with a significant difference P value 0.0001. According to Sinha et al. [35], superficial aphthous ulcers might appear on T2WI when there is good distention of the lumen. It appears as an intermediate signal on T2WI, surrounded by a focal area of bright T2WI signal. This might have been apparent in UC cases with a lack of proper colonic distension in the MRE. They have also stated that deep ulcers would appear as thin lines penetrating the bowel wall that appears bright in T2 W sequences with fat suppression. These deep ulcers might complicate to become penetrating fistulae [36]. The current study included (2/30, 6.7%) cases with fistulae/sinus tracts that were detected equally by MRE and ileo-colonoscopy.
On the other hand, Dulai et al. [37] have stated that MRE has a low negative predictive value for the detection of mucosal pathology because it may exclude the presence of active inflammation or ulceration when it is present, and further endoscopic assessment may still be necessary for patients with persistent symptoms despite the appearance of normal mucosa on MRE.
Related vascular congestion of the mesenteric arteries (vasa recta) was detected by MRE in (2/30, 6.7%) of cases, while it was not detected by ileo-colonoscopy. With a P value of 0.50, this was described by Tolan et al. [33] as a sign of active illness when combined with intestinal wall edema and enhancement.

Limitations
In the present study, we were limited by the lack of longterm follow-up of patients to assess the patterns of disease activities. Also, we only assessed patients with CD and UC and disregarded patients with idiopathic inflammatory bowel disease, so our results cannot be generalized over all types of IBD.
Our study showed some MRE examination difficulties that include prolonged examination time and patients with associated spine and sacroiliac joint inflammation who have found difficulty in the prolonged supine position during examination.
Although the MRE was reported by an expert radiologist with 12 years of experience in GIT sub-specialty who was blinded to the ileo-colonoscopy results, it would have been better if it was reported by two radiologists.

Recommendations
The use of 3 T MR operators will provide a more reasonable evaluation for dynamic contrast-enhanced and diffusion-weighted MR images to better detect active versus chronic stages of the disease. It will also allow a faster scanning time about 15-20 min rather than the standard 30-60 min while utilizing a 1.5 T MR operator.

Conclusions
MRE is sensitive, inexpensive, noninvasive, and radiation-free for inflammatory bowel disease detection, with 86.7% diagnostic accuracy for affected areas. Unlike ileocolonoscopy, it could examine the entire small intestine, precisely measure the affected loop, and detect activity signs such as mural thickening and lymphadenopathy. However, ileo-colonoscopy is useful in assessing the large intestine and terminal ileum in IBD patients, and it was superior in detecting mucosal erosions and superficial ulcers. IBD treatment protocols should incorporate MRE for small-bowel, colonic, and extra-enteric assessment, monitoring of disease activity, and anti-inflammatory therapy response.

IBD
Inflammatory bowel disease GI Gastrointestinal CD Crohn's disease