Diagnostic accuracy of simple magnetic resonance imaging markers for detection of treatment response compared to complex disease activity scores in patients with active Crohn's disease

Abstract

Background

Magnetic resonance imaging (MRI) scores have been validated for monitoring Crohn’s disease (CD) but are not widely used in clinical practice.

Purpose

To evaluate treatment response in patients with active CD using simple imaging markers compared to complex multifactorial scores.

Material and Methods

This was a post-hoc analysis of MRI-enterocolonographies performed in a prospective, blinded, multicenter study. Patients with endoscopically active CD completed ileocolonoscopy and MRI with intravenous contrast and diffusion-weighted sequences before and after medical treatment. Response was defined as ≥50% reduction of the Simple Endoscopic Score for Crohn’s Disease. Changes in bowel wall thickness (BWT) and apparent diffusion coefficient (ADC) were compared to the magnetic resonance index of activity (MaRIA), simplified MaRIA, and Clermont score.

Results

A total of 42 patients entered the analysis, and endoscopic response was achieved in 19 (45.2%). All activity scores improved in patients with endoscopic response compared to non-responders (P <0.05). The relative reduction of BWT for the most severely affected bowel segment (area under the curve [AUC]=0.76, 95% confidence interval [CI]=0.61–0.91) trended towards a higher diagnostic accuracy compared to the global MaRIA score (AUC=0.63, 95% CI=0.45–0.81; P = 0.1). The per-segment response was more accurately evaluated with BWT compared to the segmental MaRIA score (AUC=0.82 and 0.67, respectively; P = 0.05). A 17% decrease in BWT resulted in an optimal sensitivity and specificity of 78.9% (95% CI=54.4–93.9) and 85.2% (95% CI=66.3–95.8), respectively.

Conclusion

BWT is not inferior to MaRIA when determining treatment response in CD. This measure is simple to perform and does not require intravenous contrast.

Keywords

Crohn's disease inflammatory bowel disease magnetic resonance imaging

Introduction

Crohn's disease (CD) falls under the umbrella of inflammatory bowel diseases (IBD), which requires lifelong monitoring due to its progressive and destructive nature (1). The clinical presentation is weakly correlated to endoscopic disease activity; thus, endoscopic assessment is often required (2,3). However, endoscopy presents several significant disadvantages, e.g. the examination is physically taxing, time-consuming, and disruptive for the patient (4,5). Furthermore, there is a risk of perforation, bleeding, and not catching transmural disease activity (6,7).

Minimally invasive modalities have shown significant potential for monitoring disease severity and treatment response in CD (8,9). Several magnetic resonance imaging (MRI) scoring systems have been validated in research settings. These calculations are time-consuming, which limits their widespread adoption in clinical practice (10).

Studies have shown that measurement of bowel wall thickness (BWT) with intestinal ultrasound (IUS) and MRI correlate with disease activity and response to treatment in patients experiencing CD (3,10,11). Furthermore, it has been suggested that it may be just as clinically useful as composite scores, but this has yet to be explored.

In STRIDE-II, the treat-to-target goals are symptomatic remission, normalization of C-reactive protein, decrease in fecal calprotectin, and eventually endoscopic healing (12). Transmural and histological healing are long-term considerations but not formal targets. However, growing evidence suggests that achieving these goals improves patient outcomes (13,14). Different definitions of transmural healing have been proposed, but there is no validated and globally accepted definition (15).

A post-hoc analysis was conducted to further examine the validity and usefulness of MRI-enterocolonography (MREC) for disease monitoring. The aim of the present study was to evaluate treatment response in patients with active CD using simple imaging markers and complex multifactorial scores compared to the preferred standard of care (endoscopy). We hypothesized that simple imaging scores such as apparent diffusion coefficient (ADC) and BWT could potentially be an effective, simple, and minimally invasive method for monitoring treatment response in patients with CD.

Material and Methods

This post-hoc analysis was conducted using data from a prospective, blinded, multicenter study (16). Patients were recruited from three centers in the southern Denmark managing adult patients with IBD. Eligible participants were newly diagnosed or had a pre-existing diagnosis of CD, a pre-treatment ileocolonoscopy (IC) with a Simple Endoscopic Score for Crohn's Disease (SES-CD) of ≥3, and a clinical indication for medical treatment. Exclusion criteria were acute bowel obstruction, use of non-steroidal anti-inflammatory drugs, pregnancy, alcohol or drug abuse, a known gastrointestinal disorder other than IBD, renal failure, claustrophobia, cardiac pacemaker, or implanted magnetic foreign bodies.

All patients were scheduled for a standardized work-up, including IC and MREC with intravenous contrast and diffusion-weighted imaging (DWI) sequences before and 12 weeks after medical treatment. The protocol also included the collection of calprotectin, IUS, and capsule endoscopy; these results have been published elsewhere (16). All data for this study were collected prospectively.

Ileocolonoscopy

IC served as the gold standard. The patients were prepared according to standard clinical practice with a preceding bowel preparation with sodium picosulfate (Picoprep; Ferring Pharmaceuticals, Saint-Prex, Switzerland). A complete IC included intubation of the terminal ileum, and the length of terminal ileum intubation was assessed visually. Endoscopic disease activity was evaluated with SES-CD. Endoscopic response was defined as a reduction of the total SES-CD score ≥50% (12). Segmental response was defined as a reduction of the segmental SES-CD score ≥50%. Segments not visualized with IC were excluded from the analysis.

MRI-enterocolonography

MREC was performed after overnight fasting with a 3-T MRI unit (Intera; Philips, Eindhoven, the Netherlands) with a Syn-body coil apart from nine patients who were examined with a 1.5-T MRI unit at baseline. Patients ingested 1 L of Mannitol 7.5% solution 1.5 h before the examination. Hyoscine butylbromide 20 mg was administered intravenously to reduce artefacts from bowel peristalsis. Furthermore, 15 mL gadoterate meglumine (0.5 mmol/mL) (Dotarem; Guerbet, Raleigh, NC, USA) was administered intravenously for post-contrast assessment. Images were recorded with cor T2, B-FFE, T1, SPIR, axial T1-weighted, and DWI sequences. MREC was analyzed using a single dedicated abdominal MRI specialist with more than 20 years of experience (SRR). The small intestine was divided into thirds, and the colon was divided into six segments: cecum; ascending; transverse; descending; sigmoid colon; and rectum.

Simple markers evaluated were BWT and ADC. Measurements were performed on the most severely affected ileocolonic segment, and the maximum value was recorded. A BWT >3.0 mm was considered pathological. Magnetic resonance index of activity (MaRIA), simplified MaRIA (sMaRIA), and the Clermont score were calculated as described as previously described (17 –20). Active disease was defined as MaRIA segmental score ≥7, sMaRIA ≥1, or Clermont score >8.4 (10,19). A MaRIA segmental score <11 or < 7 in abnormal segments with an index score <11 defined response to treatment (10). Similarly, a Clermont score <12.5 or <8.5 in segments with a baseline score 8.5–12.5 was consistent with treatment response (19).

Statistics

Patients included in the study had endoscopically active CD in at least one ileocolonic segment. A baseline MREC that was inconsistent with active CD resulted in exclusion from the analysis. Continuous data were summarized using descriptive statistics. Data that are not normally distributed are reported as the median and interquartile range (interquartile range [IQR] = p25–p75). A receiver operating characteristic (ROC) analysis was conducted to compare the diagnostic accuracy of the absolute or relative reduction of BWT, ADC, MaRIA, sMaRIA, and Clermont score compared to IC. Diagnostic accuracy was compared with area under the ROC curve (AUC), and the P value was Bonferroni adjusted.

P <0.05 was considered statistically significant. Optimal cutoffs were determined with the Youden index (21). The sensitivity and specificity of specific MRI cutoffs for the detection of endoscopic response were calculated on 2 × 2 tables. The relationship among paired measures assessed on two occasions was evaluated with repeated measures correlation (RMC) (22). Correlation coefficients were interpreted as follows: 0 = none; 0.01–0.19 = negligible; 0.20–0.29 = weak; 0.30–0.39 = moderate; 0.40–0.69 = strong; 0.70–0.99 = very strong; and 1 = perfect. All analyses were done in StataBE 17 (Stata Statistical Software: Release 17; StataCorp LLC, College Station, TX, USA).

Ethics, approvals, and registration

The study was approved by the Local Ethics Committee of Southern Denmark (S-20170188) and the Region of Southern Denmark (journal number 18/11210) and conducted in accordance with the principles of the Helsinki Declaration. All patients gave informed consent before inclusion in the study, which was registered at ClinicalTrials.gov (NCT03435016).

Results

A total of 62 patients with endoscopically active CD were enrolled in the study between May 2018 and January 2023. In total, 42 patients with a complete ileocolonoscopy and MREC performed before and after medical treatment were included in this analysis. CD was newly diagnosed in 21 (50.0%) patients. Patient characteristics and medical treatments administered between evaluations are shown in Table 1.

Table 1.

Characteristics of the 42 patients with known Crohn's disease included in the study.

Characteristics	Value
Sex
Female	20 (48)
Male	22 (52)
Age (years)	36 (17–74)
Crohn's disease
Newly diagnosed	21 (50)
Known	21 (50)
Disease duration (years)	4 (0–48)
The Montreal Classification
A1 = <17 years	3 (7)
A2 = 17–40 years	32 (76)
A3 = >40 years	7 (17)
L1 = ileal	17 (40)
L2 = colonic	12 (29)
L3 = ileocolonic	13 (31)
B1 = luminal	28 (67)
B2 = stricturing	12 (29)
B3 = penetrating	2 (5)
p = perianal disease	7 (17)
Medical treatment	Before inclusion	After inclusion
None	21 (50)	0 (0)
Glucocorticoids	20 (48)	9 (21)
Thiopurines	18 (43)	11 (26)
Methotrexate	1 (2)	0 (0)
5-ASA	1 (2)	0 (0)
Infliximab	12 (29)	18 (43)
Adalimumab	6 (14)	11 (26)
Vedolizumab	2 (5)	2 (5)
Ustekinumab	2 (5)	7 (17)
Previous bowel resection
None	32 (76)
Small intestine	3 (7)
Appendix	1 (2)
Colon	1 (2)
Stoma	1 (2)
BMI (kg/m²)	24 (17–36)
HBI	7 (0–21)
CRP (mg/L)	18 (0.6–62)
Fecal calprotectin (mg/kg)	1921 (203–6000)

Values are given as n (%) or median (range).

BMI, body mass index; CRP, C-reactive protein; HBI, Harvey–Bradshaw Index.

Endoscopic activity vs. MREC

A total of 210 ileocolonic bowel segments were assessed with MREC and IC. IC identified 96 (45.7%) segments with active CD (SES-CD ≥1) at baseline: terminal ileum = 30; right colon = 18; transverse colon = 16; left colon = 20; and rectum = 12. Ulcers were present in 92 (43.8%) segments. MREC identified 46 (21.9%) segments at baseline with a MaRIA ≥7, sMaRIA ≥1, and Clermont score >8.4: terminal ileum = 27; right colon = 6; transverse colon = 2; left colon = 8; and rectum = 3. The per-segment sensitivity, specificity, and AUC of MREC for detection of endoscopically active ileocolonic CD was 45.8% (95% confidence interval [CI] = 35.6–56.3), 98.2% (95% CI = 93.4–99.8), and 0.72 (95% CI = 0.67–0.77), respectively. For detection of segments with ulcerations, MREC had a sensitivity of 47.8% (95% CI = 37.3–58.5).

Dynamics of MRI parameters

The median total SES-CD decreased from 11.5 (IQR 9–17) before medical treatment to 7.0 (IQR 0–13) after treatment; P <0.001. Endoscopic response was achieved in 19 (45.2%) patients. ADC, BWT, Clermont score, MaRIA, and sMaRIA improved in patients with endoscopic response compared to non-responders (P <0.05). Data are shown in Fig. 1 and Table 2.

Fig. 1.

Box plots comparing BWT, ADC, Clermont score, sMaRIA, and MaRIA before and after medical treatment. ADC and BWT were measured on the most severely affected bowel segment. Patients were divided into responders and non-responders, as determined by the post-treatment ileocolonoscopy. The response is defined as a reduction in the total SES-CD score of ≥50%. All measures improved in patients with endoscopic response compared to non-responders (P <0.05). ADC, apparent diffusion coefficient; BWT, bowel wall thickness; SES-CD, Simple Endoscopic Score for Crohn's Disease; sMaRIA, simplified magnetic resonance index of activity.

Table 2.

ADC, BWT, and global disease activity scores (MaRIA, sMaRIA, and Clermont score) in 42 patients with active Crohn's disease before and after treatment according to endoscopic response.

			Median (IQR)	P value
ADC	Before		1.24 (0.96–1.35)	–
	After	Non-responder	1.15 (0.90–1.40)	0.01
	After	Responder	1.62 (1.20–1.88)	0.01
BWT	Before		7 (5–8)	–
	After	Non-responder	6 (5–7)	0.03
	After	Responder	3 (3–7)	0.03
Clermont	Before		22.12 (17.18–28.55)	–
	After	Non-responder	19.57 (14.12–27.34)	0.02
	After	Responder	8.40 (7.49–18.00)	0.02
MaRIA	Before		36.01 (29.76–42.80)	–
	After	Non-responder	33.00 (24.52–40.58)	0.02
	After	Responder	22.60 (18.00–36.72)	0.02
sMaRIA	Before		2 (2–3)	–
	After	Non-responder	2 (1–4)	0.01
	After	Responder	1 (0–2)	0.01

Values are given as median (IQR). Response was defined as a reduction of the total SES-CD score of ≥50%. ADC and BWT were measured on the most severely affected bowel segment. The P values were calculated using the Wilcoxon rank-sum test for non-responders vs. responders.

ADC, apparent diffusion coefficient; BWT, bowel wall thickness; sMaRIA, simplified magnetic resonance index of activity.

The RMC between global MRI activity indexes were very strong: MaRIA vs. sMaRIA (r = 0.92, 95% CI = 0.85–0.94), MaRIA vs. Clermont score (r = 0.90, 95% CI = 0.84–0.93), and sMaRIA vs. Clermont score (r = 0.75, 95% CI = 0.65–0.84). The RMC between segmental MRI measurements are shown in Table 3. Correlations between multifactorial indices and BWT were strong but were weak to moderate compared to ADC.

Table 3.

Repeated measurement correlations for MRI activity scores on a segmental level.

	sMaRIA	Clermont	ADC	BWT
MaRIA	0.71 (0.58–0.80)	0.92 (0.88–0.95)	0.38 (0.18–0.54)	0.62 (0.47–0.73)
sMaRIA	–	0.71 (0.59–0.80)	0.20 (−0.01–0.39)	0.42 (0.23–0.57)
Clermont	–	–	0.41 (0.23–0.57)	0.74 (0.63–0.82)
ADC	–	–	–	0.34 (0.14–0.51)

Values are given as correlation coefficients with 95% CIs for 46 bowel segments with active Crohn's disease at baseline.

ADC, apparent diffusion coefficient; BWT, bowel wall thickness; sMaRIA, simplified magnetic resonance index of activity.

Global disease activity

A ROC analysis assessed global MaRIA, global sMaRIA, and global Clermont score compared to endoscopic response on a per-patient level. Changes in BWT and ADC for the most severely affected segment were included in the analysis (Fig. 2). The diagnostic accuracy for the absolute difference in BWT (AUC = 0.74, 95% CI = 0.58–0.89) and ADC (AUC = 0.75, 95% CI = 0.60–0.90) was higher when compared to MaRIA, but was not statistically significant (AUC = 0.60, 95% CI = 0.42–0.78; P = 0.12 and P = 0.13, respectively). Furthermore, the relative reduction of BWT (AUC = 0.76, 95% CI = 0.61–0.91) trended towards a higher diagnostic accuracy compared to MaRIA (AUC = 0.63, 95% CI = 0.45–0.81; P = 0.098). AUCs for the global MaRIA, global sMaRIA, and global Clermont score were equal (P >0.50). A relative reduction in BWT exceeding 17% was associated with an optimal AUC of 0.82 (95% CI = 0.70–0.94) and a >0.16 absolute increase of ADC yielded an optimal AUC of 0.71 (95% CI = 0.57–0.85).

Fig. 2.

ROC analysis for changes in BWT, ADC, MaRIA, sMaRIA, and Clermont score compared to the endoscopic response in 42 patients treated for active Crohn's disease. Endoscopic response was defined as a reduction of the total SES-CD of ≥50%. ADC and BWT were measured in the most severely affected bowel segment. Results are displayed as (a) the absolute difference and (b) the relative reduction of MRI measurements. ADC, apparent diffusion coefficient; BWT, bowel wall thickness; MRI, magnetic resonance imaging; ROC, receiver operating characteristic; SES-CD, Simple Endoscopic Score for Crohn's Disease; sMaRIA, simplified magnetic resonance index of activity.

Per-segment diagnostic accuracy

The per-segment diagnostic accuracy of MREC for the assessment of treatment response was evaluated in 46 matched ileocolonic segments with active CD at baseline. Established definitions for MaRIA and Clermont score were compared to the optimal cutoffs for BWT and ADC demonstrated in this study (Table 4). Treatment response was more accurately evaluated with BWT compared to the segmental MaRIA score: AUC = 0.82 (95% CI = 0.70–0.94) and 0.67 (95% CI = 0.53–0.81), respectively (P = 0.05). A 17% decrease in BWT had a sensitivity and specificity of 78.9% (95% CI = 54.4–93.9) and 85.2% (95% CI = 66.3–95.8), respectively.

Table 4.

Diagnostic accuracy of MRI disease activity scores for the assessment of treatment response in 46 matched ileocolonic segments with active Crohn's disease at baseline.

Endoscopic response	MRI definition of response	Sensitivity (%)	Specificity (%)	AUC
≥50% reduction of segmental SES-CD	MaRIA <11 or <7 in segments with a score 7–11	63.2 (38.4–83.7)	70.4 (49.8–86.2)	0.67* (0.53–0.81)
	Clermont <12.5 or <8.5 in segments with a score 8.5–12.5	63.2 (38.4–83.7)	85.2 (66.3–95.8)	0.74 (0.61–0.87)
	≥17% relative reduction of BWT	78.9 (54.4–93.9)	85.2 (66.3–95.8)	0.82* (0.70–0.94)
	≥0.16 absolute increase of ADC	63.2 (38.4–83.7)	74.1 (53.7–88.9)	0.69 (0.55–0.83)

Values in parentheses are 95% CI. Ileocolonoscopy served as the gold standard.

*P = 0.05.

AUC, area under the receiver operating characteristic curve; CI, confidence interval; SES-CD, SES-CD, Simple Endoscopic Score for Crohn's Disease.

Discussion

In this post-hoc analysis of treatment responses in patients with known CD, we evaluated the performance of simple MRI markers compared to complex multifactorial scores. BWT demonstrated comparable accuracy in evaluating treatment response, particularly at the segmental level, compared to MaRIA, sMaRIA, and the Clermont score. These findings suggest that BWT could serve as a straightforward alternative to complex imaging scores for monitoring therapeutic response in CD.

As the number of tools available to clinicians grows, accurately assessing treatment response in CD with minimally invasive methods becomes more challenging; MRI encompasses multiple methods for assessing disease activity and treatment response.

The MaRIA scoring system is a complex, multifactorial score that assesses CD activity with gadolinium contrast-enhanced MRI enterography (17,20). It consists of the global MaRIA score, which is calculated with the segmental index score for six predefined anatomical segments of the bowel. The score needs multiple assessments: thickness; edema; ulceration; and the relative contrast enhancement (RCE) to be calculated accurately. RCE itself requires a separate calculation including standard deviation. Due to the complexity of the original scoring system and the need for contrast-enhanced sequences, a simplified system, sMaRIA was developed that foregoes intravenous contrast (18). The Clermont score is also based on the principles of the established MaRIA scoring system (19). Similarly to the sMaRIA, the Clermont score does not require contrast-enhanced sequences; ADC values are used in the place of RCE in the formula. ADC is a measure of the magnitude of diffusion of water molecules within tissue, where a high ADC indicates healthy bowel tissue and low score indicates disease activity (23).

Growing evidence shows that gadolinium-enhanced MRI examinations may not be required for the majority of patients with CD, as studies have found that ADC in the absence of gadolinium was non-inferior to gadolinium-enhanced MRE for detecting disease activity (9). However, gadolinium is still useful for monitoring patients with penetrating disease (24). Furthermore, the side effects associated with gadolinium exposure—such as nephrogenic systemic fibrosis, deposition of gadolinium in the brain, hypersensitivity reactions, and gadolinium toxicity—make the systematic use of contrast less appealing (25).

We observed a significant improvement in all MRI markers among endoscopic responders compared to non-responders. MRI demonstrated low per-segment sensitivity in detecting endoscopically active CD. By contrast, the diagnostic accuracy of BWT for the detection of response to medical treatment was favorable. There was no advantage in using complex multifactorial scores over simple imaging markers. Measuring BWT for the most severely affected ileocolonic segment seems to be equivalent or better than MaRIA. In addition, this measure is simple to perform and does not require intravenous contrast.

In the RMC analysis, we found very strong correlation between MaRIA vs. Clermont, MaRIA vs. sMaRIA, and sMaRIA vs. Clermont. This was expected as both the Clermont score and the sMaRIA are derived from the MaRIA score. Among the simple measurements, BWT showed the strongest correlation with the Clermont score, suggesting that MRI scores that prioritizing BWT over contrast enhancement may be more reliable. ADC showed the weakest correlation and was most strongly correlated with the Clermont score, which includes ADC.

A systematic review and expert consensus statement from 2022 by Ilvemark et al. sought to define IUS response, transmural healing, and transmural remission in inflammatory bowel disease (11). They defined treatment response in patients with CD in terms of BWT as either >25%, >2.0 mm, or >1.0 mm and a reduction of the Doppler signal by one color. In our study, we found that a reduction of BWT by 17% resulted in an optimal sensitivity and specificity, which is comparable to what is defined as treatment response when assessing with IUS (16). This 17% threshold is derived from this cohort alone and should be validated in a larger, prospective study in the future.

Few studies have evaluated changes in various MRI scoring systems during treatment; one such study found that the Clermont score and MaRIA, along with other MRI scoring systems, are comparable in terms of inter-observer agreement, correlation with endoscopic and histopathologic reference standards, and diagnostic accuracy for active and ulcerating endoscopic disease (26). The same study also found that ulcers are the most common factor causing discrepancies between MRI evaluations and scores that do not account for ulcers.

MREC excels at evaluating the transmural component of CD because it produces cross-sectional images of the bowels, but as it stands, transmural healing is not a formal target in STRIDE-II (12,27).

Likewise, limited research exists concerning the value of ADC as a tool for determining treatment response in CD. BWT and ADC performed the best in the present study, while MaRIA had the lowest predictive power. A recent paper by Rimola et al. evaluated ADC's ability to identify bowel inflammation and therapeutic response in patients with CD being treated with biological therapy (28). They found that AUC for detecting healing based on ileocolonoscopy was significantly higher for MaRIA compared to ADC. They concluded that ADC may have an adjunct role in assessing bowel inflammation in CD but showed limited performance in detecting therapy response. Conversely, a meta-analysis from 2023 supported the utility of ADC values for assessment of disease activity in patients with CD (29).

MaRIA relies on two distinct parameters that may explain why the diagnostic accuracy was inadequate in this study. First, identifying ulcers with MRI is challenging and can be affected by factors such as shape, orientation, severity, and observer experience (30). Second, MaRIA, which relies on RCE, can be confounded by fibrosis, as both inflammation and fibrosis can affect contrast enhancement, making it challenging to distinguish between the two (31). Distinguishing between fibrosis and inflammation represents a confounding factor in all MRI evaluations that are not supported by supplementary modalities to verify findings, and multiple parameters are affected (BWT, RCE, and ADC).

Simple MRI assessments show potential as a minimally invasive and patient-friendly alternative to IC for evaluating disease severity and monitoring response to medical treatment in patients. Furthermore, they may find use in clinical practice, as they are relatively easy and quick compared to the validated disease activity scores that struggle to find a foothold outside research settings.

Strengths and Limitations

This post-hoc analysis study included patients with active CD requiring medical treatment with steroids or biological therapy. IC and MREC were performed by specialists blinded to the other imaging modalities. Endoscopic examinations, serving as the reference standard, were performed by experienced gastroenterologists at each participating center, while MREC analysis was conducted by a single radiologist with extensive expertise in abdominal MRI. Variations between multiple observers were not accounted for in this study.

The present study has some limitations. Results should be interpreted with caution because of the limited sample size and uneven distribution of analyzable segments, reducing both statistical power and generalizability. Most affected segments are in the ileum and right colon, which limits their applicability to left-sided or rectal disease. BWT was superior to MaRIA for assessment of treatment response on a segmental level. However, the sample size was not sufficient to determine superiority when comparing disease activity scores on a patient level.

Enrolling patients in the study and completing examinations according to the study protocol was challenging due to the extensive diagnostic workup within a small window of time (16). Not all patients entering the study had a complete diagnostic workup and were thus excluded from the analysis of treatment response. IC served as the gold standard for treatment response, due to its role in STRIDE-II. This puts MRI at a disadvantage to some degree, as IC more accurately diagnoses mucosal inflammation than MRI (32,33).

The study is based on prospectively collected data, but the comparison of simple MRI markers to composite scores was planned post-hoc. This presents an increased risk of bias and overfitting to the specific dataset. Conversely, it has previously been demonstrated that simple imaging markers can act as trustworthy measures of disease activity in comparable imaging modalities (11).

It should be noted that a single radiologist assessed the MRI findings, which could limit external reproducibility. Inter-observer agreement between radiologists assessing MRECs was examined in a study by Ding et al. from 2022, which found moderate consistency of BWT between radiologists (ICC = 0.638) (34).

Conclusion

In conclusion, our findings suggest that in patients with active CD repeated measurements of BWT or ADC in the most diseased ileocolonic segment demonstrate comparable performance to validated scoring systems, such as MaRIA, sMaRIA, and the Clermont score, for assessing response to medical treatment. These findings are hypothesis-generating and should be validated in a larger, prospective study in the future.

Footnotes

Data availability

The trial protocol and data underlying this article will be shared upon reasonable request to the corresponding author.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by public grants from the Region of Southern Denmark (grant no. 17/33843) and Lillebaelt Hospital – University Hospital of Southern Denmark (grant no. 17/33843).

ORCID iDs

Emilia Nejatbakhsh

Soeren R Rafaelsen

Jacob B Brodersen

Torben Knudsen

Jens Kjeldsen

Michael D Jensen

References

Dolinger

Torres

Vermeire

. Crohn's disease. Lancet 2024;403:1177–1191.

Cellier

Sahmoud

Froguel

, et al. Correlations between clinical activity, endoscopic severity, and biological parameters in colonic or ileocolonic Crohn’s disease. A prospective multicentre study of 121 cases. The Groupe d’Etudes Therapeutiques des Affections Inflammatoires Digestives. Gut 1994;35:231–235.

Maaser

Sturm

Vavricka

, et al. ECCO-ESGAR guideline for diagnostic assessment in IBD part 1: initial diagnosis, monitoring of known IBD, detection of complications. J Crohns Colitis 2019;13:144–164.

Denters

Schreuder

Depla

, et al. Patients’ perception of colonoscopy: patients with inflammatory bowel disease and irritable bowel syndrome experience the largest burden. Eur J Gastroenterol Hepatol 2013;25:964–972.

Holt

Yimam

, et al. Patient tolerability of bowel preparation is associated with polyp detection rate during colonoscopy. J Gastrointestin Liver Dis 2014;23:135–140.

Kim

Park

. Adverse events related to colonoscopy: global trends and future challenges. World J Gastroenterol 2019;25:190–204.

Wilkens

Novak

Maaser

, et al. Relevance of monitoring transmural disease activity in patients with Crohn’s disease: current status and future perspectives. Therap Adv Gastroenterol 2021;14:17562848211006672.

Rosentreter

Parker

, et al. International expert guidance for defining and monitoring small bowel strictures in Crohn’s disease on intestinal ultrasound: a consensus statement. Lancet Gastroenterol Hepatol 2024;9:1101–1110.

Kumar

De Kock

Blad

, et al. Magnetic resonance enterography and intestinal ultrasound for the assessment and monitoring of Crohn’s disease. J Crohns Colitis 2024;18:1450–1463.

10.

Caron

Jairath

Laurent

, et al. Defining magnetic resonance imaging treatment response and remission in Crohn’s disease: a systematic review. J Crohns Colitis 2024;18:162–170.

11.

Ilvemark

Hansen

Goodsall

, et al. Defining transabdominal intestinal ultrasound treatment response and remission in inflammatory bowel disease: systematic review and expert consensus statement. J Crohns Colitis 2022;16:554–580.

12.

Turner

Ricciuto

Lewis

, et al. STRIDE-II: an update on the selecting therapeutic targets in inflammatory bowel disease (STRIDE) initiative of the international organization for the study of IBD (IOIBD): determining therapeutic goals for treat-to-target strategies in IBD. Gastroenterology 2021;160:1570–1583.

13.

Gupta

Peyrin-Biroulet

, et al. Treat to target: the role of histologic healing in inflammatory bowel diseases: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 2021;19:1800–13 e4.

14.

Geyl

Guillo

Laurent

, et al. Transmural healing as a therapeutic goal in Crohn’s disease: a systematic review. Lancet Gastroenterol Hepatol 2021;6:659–667.

15.

Castiglione

Mainenti

Testa

, et al. Cross-sectional evaluation of transmural healing in patients with Crohn’s disease on maintenance treatment with anti-TNF alpha agents. Dig Liver Dis 2017;49:484–489.

16.

Brodersen

Rafaelsen

Juel

, et al. Assessment of treatment response in known Crohn’s disease-a prospective blinded study comparing the diagnostic accuracy of intestinal ultrasound, magnetic resonance enterocolonography, panenteric capsule endoscopy, and fecal calprotectin. Inflamm Bowel Dis 2025; 31: 1891–1901.

17.

Rimola

Ordas

Rodriguez

, et al. Magnetic resonance imaging for evaluation of Crohn’s disease: validation of parameters of severity and quantitative index of activity. Inflamm Bowel Dis 2011;17:1759–1768.

18.

Ordas

Rimola

Alfaro

, et al. Development and validation of a simplified magnetic resonance Index of activity for Crohn’s disease. Gastroenterology 2019;157:432–439 e1.

19.

Buisson

Joubert

Montoriol

, et al. Diffusion-weighted magnetic resonance imaging for detecting and assessing ileal inflammation in Crohn’s disease. Aliment Pharmacol Ther 2013;37:537–545.

20.

Rimola

Rodriguez

Garcia-Bosch

, et al. Magnetic resonance for assessment of disease activity and severity in ileocolonic Crohn’s disease. Gut 2009;58:1113–1120.

21.

Youden

. Index for rating diagnostic tests. Cancer 1950;3:32–35.

22.

Bakdash

Marusich

. Repeated measures correlation. Front Psychol 2017;8:456.

23.

Zhu

Zhang

Liu

, et al. Identifying the inflammatory and fibrotic bowel stricture: MRI diffusion-weighted imaging in Crohn’s disease. Radiology of Infectious Diseases 2015;2:128–133.

24.

Rao

Kumar

Taylor

, et al. Diagnostic pathways in Crohn’s disease. Clin Radiol 2019;74:578–591.

25.

Starekova

Pirasteh

Reeder

. Update on gadolinium-based contrast agent safety, from the AJR special series on contrast Media. AJR Am J Roentgenol 2024;223:e2330036.

26.

Puylaert

CAJ

Nolthenius

CJT

Tielbeek

JAW

, et al. Comparison of MRI activity scoring systems and features for the terminal ileum in patients with Crohn disease. AJR Am J Roentgenol 2019;212:W25–W31.

27.

Kucharzik

Tielbeek

Carter

, et al. ECCO-ESGAR topical review on optimizing reporting for cross-sectional imaging in inflammatory bowel disease. J Crohns Colitis 2022;16:523–543.

28.

Rimola

Fernandez-Clotet

Capozzi

, et al. ADC values for detecting bowel inflammation and biologic therapy response in patients with Crohn disease: a post hoc prospective trial analysis. AJR Am J Roentgenol 2024;222:e2329639.

29.

Thormann

Melekh

Bar

, et al. Apparent diffusion coefficient for assessing Crohn’s disease activity: a meta-analysis. Eur Radiol 2023;33:1677–1686.

30.

Kim

Jang

Park

, et al. MR enterography assessment of bowel inflammation severity in Crohn disease using the MR Index of Activity Score: modifying roles of DWI and effects of contrast phases. AJR Am J Roentgenol 2017;208:1022–1029.

31.

Wilkens

Hagemann-Madsen

Peters

, et al. Validity of contrast-enhanced ultrasonography and dynamic contrast-enhanced MR enterography in the assessment of transmural activity and fibrosis in Crohn’s disease. J Crohns Colitis 2018;12:48–56.

32.

Taylor

Mallett

Bhatnagar

, et al. Diagnostic accuracy of magnetic resonance enterography and small bowel ultrasound for the extent and activity of newly diagnosed and relapsed Crohn’s disease (METRIC): a multicentre trial. Lancet Gastroenterol Hepatol 2018;3:548–558.

33.

Brodersen

Knudsen

Kjeldsen

, et al. Diagnostic accuracy of pan-enteric capsule endoscopy and magnetic resonance enterocolonography in suspected Crohn’s disease. United European Gastroenterol J 2022;10:973–982.

34.

Ding

Jiang

, et al. Assessing the inflammatory severity of the terminal ileum in Crohn disease using radiomics based on MRI. BMC Med Imaging 2022;22:118.