Ultrasound and MRI for Pediatric Crohn's Disease Assessment: Correlations of the MaRIA Score and IBUS-SAS with Endoscopic Disease Activity and Optimal Cutoff Values

Ultrasound and MRI for Pediatric Crohn's Disease Assessment: Correlations of the MaRIA Score and IBUS-SAS with Endoscopic Disease Activity and Optimal Cutoff Values | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Ultrasound and MRI for Pediatric Crohn's Disease Assessment: Correlations of the MaRIA Score and IBUS-SAS with Endoscopic Disease Activity and Optimal Cutoff Values yu yu, Bing Xu, Jie Chen, Hong Zhao, Kerong Peng, Lujing Tang, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7224257/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 21 Nov, 2025 Read the published version in Abdominal Radiology → Version 1 posted 9 You are reading this latest preprint version Abstract Objectives To assess transmural damage in patients with Crohn's disease (CD), imaging techniques such as magnetic resonance enterography (MRE) and intestinal ultrasound (IUS) are used. The Magnetic Resonance Index of Activity (MaRIA) and the International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) are scoring systems for MRE and IUS, respectively. This study examined their correlation with the Crohn's Disease Endoscopic Index of Severity (CDEIS) in children with CD. Methods This was a retrospective analysis of children with new-onset CD who were treated from 2017–2022 at Zhejiang University Children's Hospital. Patients underwent IUS examination and IBUS-SAS scoring, MRE examination and MaRIA evaluation, colonoscopy and CDEIS calculation, and in addition, the PCDAI value was calculated. Blood samples were also collected for analysis. Nonnormally distributed data were analysed using Spearman's rank correlation coefficient. Results Forty-eight children were included in this study. The MaRIA and IBUS-SAS scores were positively correlated with the CDEIS value (r = 0.334 and r = 0.328, both p < 0.05). In the colon, the Spearman's rank correlation coefficient between the MaRIA score and the CDEIS value was 0.345 (P < 0.05), and that between the IBUS-SAS score and the CDEIS value was 0.501 (P < 0.05). The IBUS-SAS had an AUC of 0.655 for the prediction of moderate active disease (CDEIS ≥ 9), with a cut-off of 55.5. Conclusions Both the MaRIA and the IBUS-SAS scores are correlated with the CDEIS score in children with newly diagnosed CD. An IBUS-SAS score above 55.5 suggests moderate disease activity. IUS can serve as an alternative to MRE for disease activity assessment when MRE is not viable. Crohn’s disease Paediatric MaRIA IBUS-SAS CDEIS Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Crohn's disease (CD) is a chronic inflammatory disorder that affects the entire thickness of the gastrointestinal tract. This disease most frequently involves the terminal ileum but can affect any GI segment from the mouth to the anus. In recent years, CD has emerged as a significant global health burden. This is due to its high prevalence in developed nations and a marked increase in incidence rates within developing countries 1 . Notably, approximately 20–30% of individuals with CD are diagnosed during childhood 2 . Assessment of CD activity presents a clinical challenge and typically relies on a combination of methodologies. These include evaluations of clinical symptoms, measurement of inflammatory biomarkers, endoscopic examination, radiographic imaging, and histopathological analysis. Among these methods, direct endoscopic visualization of mucosal lesions is widely recognized as the gold standard for assessing mucosal inflammation 3, 4 . However, endoscopy also has limitations due to its invasive nature, the need for anaesthesia, and potential complications such as perforation and patient discomfort. Imaging modalities, including computed tomography enterography (CTE), MRE, and intestinal ultrasound (IUS), serve as pivotal tools for the comprehensive evaluation of CD activity and its associated complications. These techniques not only identify the extent of disease and related complications, but they also effectively gauge the severity of CD. The European Crohn's and Colitis Organization (ECCO) and the European Society of Gastrointestinal and Abdominal Radiology (ESGAR) guidelines state that CTE/MRE/IUS are the most precise imaging methods for the diagnosis of intestinal lesions in patients with CD 5 . Considering the inherent radiation exposure associated with CTE, MRI and IUS offer greater advantages in the diagnosis and follow-up of paediatric patients with CD. Accurate disease severity grading is crucial for determining the optimal CD treatment and for monitoring treatment efficacy. Many studies have revealed a variety of MRI features that are instrumental in the evaluation of the disease activity level 6, 7 . Multiple activity scoring systems have been crafted and validated on the basis of these findings 8–12 . Among them, the Magnetic Resonance Index of Activity (MaRIA) is striking as it is the sole MR scoring system that has been validated for use 11 . Moreover, recent studies have demonstrated that the MaRIA scoring system is capable of not only assessing treatment response but also predicting mucosal healing in patients with CD 13, 14 . Although the use of IUS for monitoring the disease activity of CD is becoming increasingly common, especially since it requires no special bowel preparation or sedation and is cost-effective, no widely accepted, reproducible IUS activity-scoring system has been established to assess the severity of CD inflammation. This is primarily because the development methods of scoring systems in most studies are inadequate, and no scoring system has been sufficiently validated. 15 The International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) includes assessments of bowel wall thickness (BWT), bowel wall stratification (BWS), colour Doppler signals (CDSs), and inflammatory mesenteric adipose tissue (i-FAT). However, since the development of the IBUS-SAS did not involve the use of ileocolonoscopy as a reference standard, the score lacks well-defined cut-off values for remission and activity 16 . This study aimed to assess the correlation between the MaRIA score and the CDEIS value, as well as that between the IBUS-SAS score and the CDEIS value, to identify predictive cut-off values for endoscopic activity. We also evaluated the correlation between the MaRIA score and the IBUS-SAS score and between these two scoring systems and the Paediatric Crohn's Disease Activity Index (PCDAI) value and routine laboratory indicators. Methods Patients : The picture archiving and communication system (PACS) and medical records of our hospital were accessed according to the ethical standards of the Retrospective Clinical Research Institution Protocol. From April 2017 to April 2022, consecutive patients diagnosed with CD were enrolled according to clinical, endoscopic, and histological criteria, and these patients underwent at least one contrast-enhanced MRE at the time of disease diagnosis. The inclusion criteria were as follows: (1) diagnosis of CD; (2) underwent ileocolonoscopy, IUS (each patient underwent B-IUS and PCDAI) and MRE; and (3) underwent endoscopy, IUS and MRE within 7 days. The exclusion criteria were as follows: (1) history of bowel resection; (2) allergy to contrast media; and (3) gastrointestinal perforation or bleeding. This study was approved by the Ethics Committee of the Children’s Hospital of Zhejiang University School of Medicine (2022-IRB-270). Data collection : We retrospectively collected clinical, anthropometric, and routine laboratory data (CRP levels, the ESR, serum ALB levels, haemoglobin levels, haematocrit and platelet count) from the electronic database and clinical records at the time of diagnosis. Clinical disease activity was assessed according to the PCDAI. We performed endoscopic, MRE and IUS evaluations, the specific procedures of which are discussed below. Enteroscopic procedures and evaluation A team of trained gastroenterologists at our centre performed colonoscopies on patients with CD. Two gastroenterologists were randomly selected to participate in the endoscopic scoring of the terminal ileum to the rectum, and of these, one was responsible for scoring using the CDEIS and the other was responsible for auditing. The CDEIS score ranges from 0 to 44 and is used to categorize patients into 4 disease levels: < 3, remission; 3 to < 9, mild disease; 9 to < 12, moderate disease; and ≥ 12, severe disease. MR procedure and evaluation For the present study, an extended MRI protocol involving specialized sequences and additional bowel preparation for colonic distention was performed. Before the examination, all patients fasted and were deprived of water for 4–6 hours, and 2.5% isotonic mannitol solution was administered in fractions starting 1 hour before the scan (to fill the bowel). An intravenous injection of 0.3 mg/kg of ethanolamine was administered before the scan to inhibit intestinal peristalsis, and 0.5 ml/kg of 10% chloral hydrate solution was orally administered 30 min before the examination to sedate uncooperative children. MRI scans were performed on a 1.5-T scanner (Avanto; Siemens Medical Solutions, Erlangen, Germany) with various sequences, including TrueFisp, T1, T2, and VIBE. A gadolinium contrast agent was used, and enhanced images were acquired postinjection. All MRE images were evaluated by a radiologist. The MaRIA scoring system is a validated method used to assess activity in the ileocolonic region in patients with CD via contrast-enhanced MRI enterography. The score is calculated on the basis of endoscopic signs of intestinal inflammation and includes parameters such as bowel wall thickness, oedema, ulceration, and relative contrast enhancement (RCE). The MaRIA score was used to assess six different segments: 1. The terminal ileum (10 cm extension from the ileocecal valve or anastomotic site to the ileum); 2. Ascending colon; 3. Transverse colon; 4. Descending colon 5. Sigmoid colon; 6. Rectum. The MaRIA score of each segment was calculated according to the following formula: MaRIA = 1.5×wall thickness (mm) + 0.02×relative contrast enhancement (RCE) + 5× oedema + 10 ×ulcers. where the relative contrast enhancement (RCE) was calculated via the pre- and postcontrast T1-weighted images: In addition, MR-active lesions were defined as follows: active disease (MaRIA ≥ 7) and severe disease (MaRIA ≥ 11). IUS assessment and evaluation Patients did not require special bowel preparation. All the examinations were performed by radiologists with extensive ultrasound experience, and the relevant data were recorded. The radiologists performed all examination andevaluated six different segments: 1) terminal ileum, 2) ascending colon in the caecum, 3) transverse colon, 4) descending colon, 5) sigmoid colon, and 6) rectum. Each involved bowel segment, echo characteristics, and bowel wall stratification (BWS) were recorded. The Limberg scoring system of the CDAI was used to observe the vascularization of the thickest part of the bowel wall. Grades 0, I, and II indicate remission, whereas grades III and IV indicate the active phase. We performed IBUS-SAS scoring on the segment with the most severe transmural damage among the 6 intestinal segments. In this scoring system, the area of the bowel most affected by inflammatory disease activity was scored according to four parameters: I. BWT: The average of four precisely measured values, two cross-sectional and two longitudinal, each to the nearest millimetre, was calculated; II. BWS is scored from 0 to 3 (full-length clear mucosal layers are graded as 0, indeterminate layers are scored as 1, and layers with bowel wall destruction are scored as 2 (focal, ≤ 3 cm) or 3 (extensive, > 3 cm)). "; III. The colour Doppler signal (CDS) was scored from 0 to 3 (0: no persistent detectable blood flow signals in the bowel wall; 1: scattered punctate blood flow signals (< 5); 2: linear signals without perienteric signals; 3: linear signals with perienteric signals); IV. Inflammatory mesenteric fat (i-fat) was scored from 0 to 2 (0: absent; 1: indeterminate; 2: present). All scores were calculated according to the following formula: IBUS-SAS (0–100) = 4 × BWT + 15 × i-fat + 7 × CDS + 4 × BWS. Statistical analysis All the statistical analyses were performed using the Statistical Package for the Social Sciences version 23.0 (IBM Corporation, New York, NY, USA). Descriptive variables are presented as the means and standard deviations (SDs) with 95% confidence intervals (CIs) or as medians and ranges. Categorical variables are presented as frequencies and percentages. Correlations among the clinical, laboratory, and endoscopic variables and between MRE and IUS were estimated via the two-tailed Spearman’s rank‒order correlation coefficient (r). The cut-off values for the IBUS-SAS and MaRIA scoring systems were obtained using receiver operating characteristic (ROC) curve analysis using Youden’s index. A p value less than 0.05 indicated statistical significance. Results Clinical and demographic characteristics In all, 48 patients (27 males and 21 females, median age 13 years; Table 1) were ultimately enrolled in this study. All 48 patients underwent both MRE and B-IUS examinations, and damage to their bowel wall was scored separately according to the MaRIA and IBUS-SAS scoring systems. Forty-five patients underwent endoscopy at our hospital (three of them underwent endoscopy at other hospitals and were diagnosed with CD by the pathology department of our hospital). Table 1. Clinical and demographic characteristics at baseline of patients with Crohn’s disease Parameters Number of patients Included patients 48 Sex Male, n (%) 27（56.25%） Female, n (%) 21（43.75%） Age, median (IQR), years 13（3） Disease location (Montreal classification), n (%) (L1) 8(16.67%) (L2) 3(6.25%) (L3) 31(64.58%) (L4a) 17(35.42%) (L4b) 41(85.42%) CDEIS, mean ± SD 9.57±7.49 PCDAI, mean ± SD 27.63±12.95 C-reactive protein, mean ± SD, mg/L 30.37±30.28 Erythrocyte sedimentation rate, mean ± SD, mm 42.92±28.71 Platelet, mean ± SD, mg/L 417.57±130.36 Serum albumin, mean ± SD, g/L 35.36±7.90 hemoglobin, mean ± SD, g/L 105.68±17.09 hematocrit , mean ± SD, % 43.40±4.61 IQR indicates interquartile range, SD standard deviation, CDEIS Crohn’s Disease Endoscopic Index of Severity, PCDAI pediatric Crohn’s disease activity index Correlation analysis of the MaRIA and IBUS-SAS scores with the CDEIS score We evaluated the correlation of the MaRIA score or the IBUS-SAS score of all intestinal segments (from the terminal ileum to the rectum) with the CDEIS values. The Spearman's rank correlation coefficient between the total MaRIA score and the CDEIS value was 0.334 (P<0.05; Figure 1), and that between the IBUS-SAS score and the CDEIS value was 0.328 (P < 0.05; Figure 1). In the colon, the Spearman's rank correlation coefficient between the MaRIA score and the CDEIS value was 0.345 (P < 0.05; Figure 2), and that between the IBUS-SAS score and the CDEIS value was 0.501 (P<0.05; Figure 2). However, in the terminal ileum, both the MaRIA score and the IBUS-SAS were poorly correlated with the CDEIS value (Spearman's r=0.190, p=0.211 and r=0.175, p=0.250). Prediction of endoscopically active disease Using a cut-off point of 16.6, the sensitivity and specificity for the prediction of endoscopically active disease in patients with a CDEIS value ≥3 were 100% and 40%, respectively, with an AUC of 0.670 (95% CI 0.453–0.887). In the colonic segment, the IBUS-SAS scoring system demonstrated superior predictive efficacy. IBUS-SAS for the prediction of endoscopically active disease in the colon had an AUC of 0.736 (95% CI 0.539–0.933), with a sensitivity of 83% and a specificity of 70% for a cut-off value of 16.0. Using a cut-off point of 7.86, the total MaRIA score showed a high accuracy for the prediction of disease activity (CDEIS value ≥3), with an AUC of 0.600 (95% CI 0.392–0.807), a sensitivity of 66% and a specificity of 70%. ROC analysis of the colonic MaRIA score for the prediction of disease activity revealed an AUC of 0.597 (95% CI 0.407–0.788), with a sensitivity of 49% and a specificity of 80% for a cut-off value of 8.46. The sensitivity and specificity for the prediction of endoscopically active disease in patients with a CDEIS value ≥9 were 85% and 48%, respectively, with an AUC of 0.655 (95% CI 0.496–0.814) when the cut-off point was 55.5. In the same cohort, the colonic IBUS-SAS score for the prediction of endoscopically active disease had an AUC of 0.770 (95% CI 0.627–0.913), with a sensitivity of 95% and a specificity of 60% for a cut-off value of 41.0. ROC analysis of the total MaRIA score for the prediction of endoscopically moderate active disease revealed an AUC of 0.758 (95% CI 0.614–0.902), with a sensitivity of 75% and a specificity of 72% for a cut-off value of 8.6. ROC analysis of the colonic MaRIA score for the prediction of endoscopically moderate active disease revealed an AUC of 0.750 (95% CI 0.599–0.901), with a sensitivity of 70% and a specificity of 84% for a cut-off value of 10.5. Table 2.Sensitivity, Specifcity and Youden index of IBUS-SAS and MaRIA at predicting endoscopically active disease cut-off sensitivity specificity Youden index CDEIS≥3 total_IBUS-SAS 16.60 100% 40% 0.40 colon_IBUS-SAS 16.00 83% 70% 0.53 total_MaRIA* 7.86 66% 70% 0.36 colon_MaRIA ▲ 8.46 49% 80% 0.29 CDEIS≥9 total_IBUS-SAS 55.50 85% 48% 0.33 colon_IBUS-SAS 41.00 95% 60% 0.55 total_MaRIA* 8.60 75% 72% 0.47 colon_MaRIA ▲ 10.46 70% 84% 0.54 CDEIS Crohn’s Disease Endoscopic Index of Severity, PCDAI pediatric Crohn’s disease activity index, total_IBUS-SAS the maximum value of IBUS-SAS scores for six intestinal segments from terminal ileum to rectum, colon_IBUS-SAS the maximum value of IBUS-SAS scores for five intestinal segments from the ascending colon to the rectum, total_MaRIA* The mean of MaRIA score of the six intestinal segments from the terminal ileum to the rectum , colon_MaRIA ▲ The mean of MaRIA score of the five intestinal segments from the ascending colon to the rectum Comparison of the MaRIA and the IBUS-SAS scores A moderate positive correlation was observed between the colonic MaRIA score and the colonic IBUS-SAS score (r = 0.489, p < 0.001), while a weak correlation was observed between the MaRIA score and the IBUS-SAS score in the terminal ileum (r = 0.377, p < 0.05). Spearman correlation analysis between the MaRIA/IBUS-SAS scores and the PCDAI score and laboratory measurements Both the MaRIA score and the IBUS-SAS score were positively correlated with the PCDAI score (r = 0.357, p < 0.001 and r = 0.348, p < 0.001). The MaRIA score and the IBUS-SAS score were negatively correlated with haemoglobin, haematocrit, and albumin levels (r = -0.515, p < 0.001; r = -0.461, p < 0.001; r = -0.377, p < 0.001 for the MaRIA score; r = -0.534, p < 0.001, r = -0.480, p < 0.001, r = -0.455, p < 0.001 for the IBUS-SAS score). The IBUS-SAS score was also positively correlated with the CRP level and the erythrocyte sedimentation rate (r = 0.412, p < 0.001 and r = 0.327, p < 0.001, respectively). Discussion CD, which is characterized by transmural involvement and complications due to recurrent aggressive inflammation, necessitates laborious diagnosis and therapeutic efficacy assessment to ensure timely treatment, as these evaluations are crucial for disease prognosis and the selection of an optimal treatment strategy. Endoscopy is the best diagnostic technique, but its invasiveness and associated risks hinder its application in the diagnosis and follow-up of paediatric patients. Considerable controversy exists regarding the diagnostic accuracy of alternative methods for the detection of CD, such as IUS and MRE. Our study utilized the MaRIA and IBUS-SAS systems to assess the degree of transmural damage in CD via MRE and IUS, which allowed us to explore the relationships of these scores with endoscopic activity, clinical disease severity, and routine laboratory indicators in newly diagnosed paediatric CD patients. The METRIC trial compared the diagnostic accuracy of MRE and IUS for CD and supported their competitiveness and feasibility as alternative diagnostic imaging modalities to invasive ileocolonoscopy 17 . This study revealed that in the group of newly diagnosed patients, the sensitivity of ultrasound (67% [95% CI 49–81]) for the presence of colonic disease was significantly greater than that of MRE (47% [31-64]), with a difference of 20% (1-39). No significant difference was observed in sensitivity or specificity between MRE and IUS in terms of the extent and presence of colonic disease. Xu et al. reached the same conclusion that B-IUS has the highest accuracy for the detection of CD in patients with terminal ileum involvement. 18 Various MRE scoring systems for disease activity have been developed and validated. The first and best validated index is the MaRIA, the scores for which are calculated on the basis of endoscopic signs of intestinal inflammation 11 . Our study revealed that a MaRIA cut-off value of 7.86 predicts endoscopic disease activity (CDEIS value ≥3), which is consistent with the currently accepted threshold for transmural active disease (MaRIA score ≥ 7). Furthermore, we also found that a MaRIA cut-off value of 8.60 can predict moderate disease activity on endoscopy (CDEIS value ≥ 9), with increased sensitivity and specificity. During the development phase of the IBUS-SAS, the sample size was adequate, the method was dependent on the opinions of experts, and both quantitative and semiquantitative parameters were considered. However, when these parameters are selected now, endoscopic scores are not utilized, and the cut-off values for endoscopic scoring are unknown 16 . In our study, the IBUS-SAS cut-off value for the prediction of endoscopic disease activity was 16.6. An IBUS-SAS value of 55.5 or higher suggests the presence of moderate endoscopic activity. Currently, only a few studies on the optimal cut-off value of the IBUS-SAS score have been published, but the values reported are inconsistent. In a prospective study of 93 patients, Allocca et al. selected endoscopic remission (SES-CD ≤ 2) and calculated the cut-off value to be an IBUS-SAS score ≤ 22.8. The sensitivity and specificity were 95% (95% CI: 77–99) and 83% (72–91), respectively [AUROC: 0.906, 95% CI: 0.827–0.957] 19 . However, a study conducted by Xu et al. integrated endoscopic activity scores from both colonoscopy and balloon-assisted enteroscopy and reported that a cut-off value of 46.7 for the IBUS-SAS could predict mucosal activity on endoscopy (SES-CD > 2) 18 . Another study used the Harvey‒Bradshaw Index (HBI) and biomarkers (CRP and FC) as indicators of disease activity, after which an optimal cut-off of 42.9 was determined for the IBUS-SAS. 20 However, in our study, when the CDEIS value was used as the gold standard, the conclusions differed. Our study has several limitations. This was a retrospective validation study, and prospective studies are needed to confirm our findings. Moreover, the patients with CD who were included in this study were primarily newly diagnosed with CD; in later studies, we may include more patients with CD who have a history of follow-up visits to assess the sensitivity and specificity of future imaging examination methods. Since the included patients mainly underwent imaging examinations for disease assessment and efficacy monitoring, most patients were in the active phase of the disease; therefore, the small number of patients in remission may have affected the statistical results. In summary, MRE and B-IUS are more sensitive for the detection of CD lesions in the colon and rectum than in the terminal ileum. When the disease is active on MRE (MaRIA score > 7), this status can in turn be used to predict disease activity on endoscopy. We also propose that an IBUS-SAS score above 16 indicates endoscopically active disease and that a score of 55.5 indicates endoscopically moderate active disease. Both the IBUS-SAS score and the MaRIA score are correlated with the PCDAI value, the CDEIS value, and the levels of albumin, haemoglobin, haematocrit, and serum inflammatory markers. When MRE is not feasible or is contraindicated, IUS can serve as an alternative imaging method for repeated follow-up and assessment of disease activity. Declarations Author Contribution Y.L.and C. wrote the main manuscript text. X. performed the ultrasonography and scoring. M. conducted the MRE reading and scoring. Z.P.andT. carried out the enteroscopy and scoring. All authors reviewed the manuscript. References Kaplan GG and Windsor JW. The four epidemiological stages in the global evolution of inflammatory bowel disease. 2021; 18: 56-66. Conrad MA and Rosh JR. Pediatric Inflammatory Bowel Disease. Pediatr Clin North Am . 2017; 64: 577-91. 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EClinicalMedicine . 2024; 71: 102559. Dragoni G, Innocenti T, Lynch EN, et al. P141 IBUS-SAS for Crohn’s disease ultrasound activity: initial validation and research of the optimal cut-off score. Journal of Crohn's and Colitis . 2021; 15: S226-S7. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 21 Nov, 2025 Read the published version in Abdominal Radiology → Version 1 posted Editorial decision: Revision requested 25 Aug, 2025 Reviews received at journal 25 Aug, 2025 Reviews received at journal 19 Aug, 2025 Reviewers agreed at journal 08 Aug, 2025 Reviewers agreed at journal 31 Jul, 2025 Reviewers invited by journal 28 Jul, 2025 Editor assigned by journal 28 Jul, 2025 Submission checks completed at journal 28 Jul, 2025 First submitted to journal 27 Jul, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7224257","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":492352828,"identity":"fb05174e-08f2-4b7d-b9ca-e691262e201b","order_by":0,"name":"yu yu","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"yu","middleName":"","lastName":"yu","suffix":""},{"id":492352829,"identity":"f111250a-160e-4460-988b-97da542a960e","order_by":1,"name":"Bing 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Tang","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Lujing","middleName":"","lastName":"Tang","suffix":""},{"id":492352834,"identity":"cd579c5a-d357-467a-8bf9-a39836a0c481","order_by":6,"name":"Youyou Luo","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAyklEQVRIie3RsQrCMBCA4StCs5x2jaDvUCgUoYOvkiK0izh3cAgUunb1ca4EOkVcHRycOvcJxFoXp5hugvnhhoP7hhAAl+sHWwB4BEAYAIhhn30n/jAjWcqpBEIadxvCSqK+uK2iC3UciiSV7Exmgq1oTrrDmCjjoPNU4kGYCd+Hal4pjBuZca9SqeQY2pGohIE8ppDQfxFpQ95vUcg17DaizaMK92YSsLK594XaBrVOr/0xWddMm8lHKMbP9G3vhxhNOHa5XK5/6glb5EQWiDvCcwAAAABJRU5ErkJggg==","orcid":"","institution":"","correspondingAuthor":true,"prefix":"","firstName":"Youyou","middleName":"","lastName":"Luo","suffix":""},{"id":492352835,"identity":"dd305d39-9154-455a-aed5-f27d218bc833","order_by":7,"name":"Xiaohui Ma","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Xiaohui","middleName":"","lastName":"Ma","suffix":""}],"badges":[],"createdAt":"2025-07-27 05:38:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7224257/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7224257/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00261-025-05274-3","type":"published","date":"2025-11-21T15:59:06+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":88003321,"identity":"fc4d8413-0a7f-4c31-a571-d3dc3435d5bd","added_by":"auto","created_at":"2025-07-31 10:31:57","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":271902,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe correlation between the CDEIS and total MaRIA(A) and The correlation between the CDEIS and total IBUS-SAS(B).\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7224257/v1/06b3b09cd0800ac90514f56b.png"},{"id":88005333,"identity":"7e3f61c4-3891-4caf-a404-2ee2bf317274","added_by":"auto","created_at":"2025-07-31 10:39:57","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":183667,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe correlation between the CDEIS and MaRIA(A) and The correlation between the CDEIS and IBUS-SAS(B) in colon.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-7224257/v1/365f0aecc1c1b2d06f0fc81c.png"},{"id":88005332,"identity":"c5c7674d-1f28-4b88-9c0d-6728a44c3103","added_by":"auto","created_at":"2025-07-31 10:39:57","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":45188,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eROC curve analysis to predict endoscopically active disease (CDEIS ≥ 3)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure Legends：MARIA(T) The total value of MaRIA score of the six intestinal segments from the terminal ileum to the rectum, MARIA(C) The total value of MaRIA score of the five intestinal segments from the ascending colon to the rectum, IBUS-SAS(T) the maximum value of IBUS-SAS scores for six intestinal segments from terminal ileum to rectum, IBUS-SAS(C) the maximum value of IBUS-SAS scores for five intestinal segments from the ascending colon to the rectum.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-7224257/v1/7c67c9d7b097e9efae035d26.png"},{"id":88003320,"identity":"7b757bdb-b1e4-40ac-a611-2ce60a00616e","added_by":"auto","created_at":"2025-07-31 10:31:57","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":39664,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eROC curve analysis to predict endoscopically moderate active disease (CDEIS ≥ 9)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure Legends：MARIA(T) The total value of MaRIA score of the six intestinal segments from the terminal ileum to the rectum, MARIA(C) The total value of MaRIA score of the five intestinal segments from the ascending colon to the rectum, IBUS-SAS(T) the maximum value of IBUS-SAS scores for six intestinal segments from terminal ileum to rectum, IBUS-SAS(C) the maximum value of IBUS-SAS scores for five intestinal segments from the ascending colon to the rectum.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-7224257/v1/1e2b5e264838ae087409e6b5.png"},{"id":96650964,"identity":"74570993-ce60-4d5d-afff-7afcea12a367","added_by":"auto","created_at":"2025-11-24 16:13:07","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1771295,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7224257/v1/cc236439-cc7a-4298-9d84-c7301a286c08.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Ultrasound and MRI for Pediatric Crohn's Disease Assessment: Correlations of the MaRIA Score and IBUS-SAS with Endoscopic Disease Activity and Optimal Cutoff Values","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCrohn's disease (CD) is a chronic inflammatory disorder that affects the entire thickness of the gastrointestinal tract. This disease most frequently involves the terminal ileum but can affect any GI segment from the mouth to the anus. In recent years, CD has emerged as a significant global health burden. This is due to its high prevalence in developed nations and a marked increase in incidence rates within developing countries \u003csup\u003e1\u003c/sup\u003e. Notably, approximately 20–30% of individuals with CD are diagnosed during childhood \u003csup\u003e2\u003c/sup\u003e. Assessment of CD activity presents a clinical challenge and typically relies on a combination of methodologies. These include evaluations of clinical symptoms, measurement of inflammatory biomarkers, endoscopic examination, radiographic imaging, and histopathological analysis. Among these methods, direct endoscopic visualization of mucosal lesions is widely recognized as the gold standard for assessing mucosal inflammation\u003csup\u003e3, 4\u003c/sup\u003e. However, endoscopy also has limitations due to its invasive nature, the need for anaesthesia, and potential complications such as perforation and patient discomfort.\u003c/p\u003e\u003cp\u003eImaging modalities, including computed tomography enterography (CTE), MRE, and intestinal ultrasound (IUS), serve as pivotal tools for the comprehensive evaluation of CD activity and its associated complications. These techniques not only identify the extent of disease and related complications, but they also effectively gauge the severity of CD. The European Crohn's and Colitis Organization (ECCO) and the European Society of Gastrointestinal and Abdominal Radiology (ESGAR) guidelines state that CTE/MRE/IUS are the most precise imaging methods for the diagnosis of intestinal lesions in patients with CD\u003csup\u003e5\u003c/sup\u003e. Considering the inherent radiation exposure associated with CTE, MRI and IUS offer greater advantages in the diagnosis and follow-up of paediatric patients with CD.\u003c/p\u003e\u003cp\u003eAccurate disease severity grading is crucial for determining the optimal CD treatment and for monitoring treatment efficacy. Many studies have revealed a variety of MRI features that are instrumental in the evaluation of the disease activity level \u003csup\u003e6, 7\u003c/sup\u003e. Multiple activity scoring systems have been crafted and validated on the basis of these findings \u003csup\u003e8–12\u003c/sup\u003e. Among them, the Magnetic Resonance Index of Activity (MaRIA) is striking as it is the sole MR scoring system that has been validated for use \u003csup\u003e11\u003c/sup\u003e. Moreover, recent studies have demonstrated that the MaRIA scoring system is capable of not only assessing treatment response but also predicting mucosal healing in patients with CD \u003csup\u003e13, 14\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eAlthough the use of IUS for monitoring the disease activity of CD is becoming increasingly common, especially since it requires no special bowel preparation or sedation and is cost-effective, no widely accepted, reproducible IUS activity-scoring system has been established to assess the severity of CD inflammation. This is primarily because the development methods of scoring systems in most studies are inadequate, and no scoring system has been sufficiently validated.\u003csup\u003e15\u003c/sup\u003e The International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) includes assessments of bowel wall thickness (BWT), bowel wall stratification (BWS), colour Doppler signals (CDSs), and inflammatory mesenteric adipose tissue (i-FAT). However, since the development of the IBUS-SAS did not involve the use of ileocolonoscopy as a reference standard, the score lacks well-defined cut-off values for remission and activity\u003csup\u003e16\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThis study aimed to assess the correlation between the MaRIA score and the CDEIS value, as well as that between the IBUS-SAS score and the CDEIS value, to identify predictive cut-off values for endoscopic activity. We also evaluated the correlation between the MaRIA score and the IBUS-SAS score and between these two scoring systems and the Paediatric Crohn's Disease Activity Index (PCDAI) value and routine laboratory indicators.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003ePatients\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eThe picture archiving and communication system (PACS) and medical records of our hospital were accessed according to the ethical standards of the Retrospective Clinical Research Institution Protocol. From April 2017 to April 2022, consecutive patients diagnosed with CD were enrolled according to clinical, endoscopic, and histological criteria, and these patients underwent at least one contrast-enhanced MRE at the time of disease diagnosis. The inclusion criteria were as follows: (1) diagnosis of CD; (2) underwent ileocolonoscopy, IUS (each patient underwent B-IUS and PCDAI) and MRE; and (3) underwent endoscopy, IUS and MRE within 7 days. The exclusion criteria were as follows: (1) history of bowel resection; (2) allergy to contrast media; and (3) gastrointestinal perforation or bleeding.\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Ethics Committee of the Children\u0026rsquo;s Hospital of Zhejiang University School of Medicine (2022-IRB-270).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData collection\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eWe retrospectively collected clinical, anthropometric, and routine laboratory data (CRP levels, the ESR, serum ALB levels, haemoglobin levels, haematocrit and platelet count) from the electronic database and clinical records at the time of diagnosis. Clinical disease activity was assessed according to the PCDAI. We performed endoscopic, MRE and IUS evaluations, the specific procedures of which are discussed below.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEnteroscopic procedures and evaluation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA team of trained gastroenterologists at our centre performed colonoscopies on patients with CD. Two gastroenterologists were randomly selected to participate in the endoscopic scoring of the terminal ileum to the rectum, and of these, one was responsible for scoring using the CDEIS and the other was responsible for auditing. The CDEIS score ranges from 0 to 44 and is used to categorize patients into 4 disease levels: \u0026lt; 3, remission; 3 to \u0026lt;\u0026thinsp;9, mild disease; 9 to \u0026lt;\u0026thinsp;12, moderate disease; and \u0026ge;\u0026thinsp;12, severe disease.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMR procedure and evaluation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFor the present study, an extended MRI protocol involving specialized sequences and additional bowel preparation for colonic distention was performed. Before the examination, all patients fasted and were deprived of water for 4\u0026ndash;6 hours, and 2.5% isotonic mannitol solution was administered in fractions starting 1 hour before the scan (to fill the bowel). An intravenous injection of 0.3 mg/kg of ethanolamine was administered before the scan to inhibit intestinal peristalsis, and 0.5 ml/kg of 10% chloral hydrate solution was orally administered 30 min before the examination to sedate uncooperative children. MRI scans were performed on a 1.5-T scanner (Avanto; Siemens Medical Solutions, Erlangen, Germany) with various sequences, including TrueFisp, T1, T2, and VIBE. A gadolinium contrast agent was used, and enhanced images were acquired postinjection. All MRE images were evaluated by a radiologist.\u003c/p\u003e\n\u003cp\u003eThe MaRIA scoring system is a validated method used to assess activity in the ileocolonic region in patients with CD via contrast-enhanced MRI enterography. The score is calculated on the basis of endoscopic signs of intestinal inflammation and includes parameters such as bowel wall thickness, oedema, ulceration, and relative contrast enhancement (RCE). The MaRIA score was used to assess six different segments: 1. The terminal ileum (10 cm extension from the ileocecal valve or anastomotic site to the ileum); 2. Ascending colon; 3. Transverse colon; 4. Descending colon 5. Sigmoid colon; 6. Rectum. The MaRIA score of each segment was calculated according to the following formula: MaRIA\u0026thinsp;=\u0026thinsp;1.5\u0026times;wall thickness (mm)\u0026thinsp;+\u0026thinsp;0.02\u0026times;relative contrast enhancement (RCE)\u0026thinsp;+\u0026thinsp;5\u0026times; oedema\u0026thinsp;+\u0026thinsp;10 \u0026times;ulcers.\u003c/p\u003e\n\u003cp\u003ewhere the relative contrast enhancement (RCE) was calculated via the pre- and postcontrast T1-weighted images:\u003c/p\u003e\n\u003cp\u003e\u003cimg 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\" width=\"758\" height=\"75\"\u003e\u003c/p\u003e\n\u003cp\u003eIn addition, MR-active lesions were defined as follows: active disease (MaRIA\u0026thinsp;\u0026ge;\u0026thinsp;7) and severe disease (MaRIA\u0026thinsp;\u0026ge;\u0026thinsp;11).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIUS assessment and evaluation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients did not require special bowel preparation. All the examinations were performed by radiologists with extensive ultrasound experience, and the relevant data were recorded. The radiologists performed all examination andevaluated six different segments: 1) terminal ileum, 2) ascending colon in the caecum, 3) transverse colon, 4) descending colon, 5) sigmoid colon, and 6) rectum. Each involved bowel segment, echo characteristics, and bowel wall stratification (BWS) were recorded. The Limberg scoring system of the CDAI was used to observe the vascularization of the thickest part of the bowel wall. Grades 0, I, and II indicate remission, whereas grades III and IV indicate the active phase.\u003c/p\u003e\n\u003cp\u003eWe performed IBUS-SAS scoring on the segment with the most severe transmural damage among the 6 intestinal segments. In this scoring system, the area of the bowel most affected by inflammatory disease activity was scored according to four parameters: I. BWT: The average of four precisely measured values, two cross-sectional and two longitudinal, each to the nearest millimetre, was calculated; II. BWS is scored from 0 to 3 (full-length clear mucosal layers are graded as 0, indeterminate layers are scored as 1, and layers with bowel wall destruction are scored as 2 (focal, \u0026le;\u0026thinsp;3 cm) or 3 (extensive, \u0026gt;\u0026thinsp;3 cm)). \u0026quot;; III. The colour Doppler signal (CDS) was scored from 0 to 3 (0: no persistent detectable blood flow signals in the bowel wall; 1: scattered punctate blood flow signals (\u0026lt;\u0026thinsp;5); 2: linear signals without perienteric signals; 3: linear signals with perienteric signals); IV. Inflammatory mesenteric fat (i-fat) was scored from 0 to 2 (0: absent; 1: indeterminate; 2: present). All scores were calculated according to the following formula: IBUS-SAS (0\u0026ndash;100)\u0026thinsp;=\u0026thinsp;4 \u0026times; BWT\u0026thinsp;+\u0026thinsp;15 \u0026times; i-fat\u0026thinsp;+\u0026thinsp;7 \u0026times; CDS\u0026thinsp;+\u0026thinsp;4 \u0026times; BWS.\u003c/p\u003e\n\u003ch2\u003eStatistical analysis\u003c/h2\u003e\n\u003cp\u003eAll the statistical analyses were performed using the Statistical Package for the Social Sciences version 23.0 (IBM Corporation, New York, NY, USA). Descriptive variables are presented as the means and standard deviations (SDs) with 95% confidence intervals (CIs) or as medians and ranges. Categorical variables are presented as frequencies and percentages. Correlations among the clinical, laboratory, and endoscopic variables and between MRE and IUS were estimated via the two-tailed Spearman\u0026rsquo;s rank‒order correlation coefficient (r). The cut-off values for the IBUS-SAS and MaRIA scoring systems were obtained using receiver operating characteristic (ROC) curve analysis using Youden\u0026rsquo;s index. A p value less than 0.05 indicated statistical significance.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eClinical and demographic characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn all, 48 patients (27 males and 21 females, median age 13 years; Table 1) were ultimately enrolled in this study. All 48 patients underwent both MRE and B-IUS examinations, and damage to their bowel wall was scored separately according to the MaRIA and IBUS-SAS scoring systems. Forty-five patients underwent endoscopy at our hospital (three of them underwent endoscopy at other hospitals and were diagnosed with CD by the pathology department of our hospital).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1. Clinical and demographic characteristics at baseline of patients with Crohn\u0026rsquo;s disease\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 350px;\"\u003e\n \u003cp\u003eParameters\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003eNumber of patients\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 350px;\"\u003e\n \u003cp\u003eIncluded patients\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 493px;\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 350px;\"\u003e\n \u003cp\u003e\u0026nbsp;Male, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e27（56.25%）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 350px;\"\u003e\n \u003cp\u003e\u0026nbsp;Female, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e21（43.75%）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 350px;\"\u003e\n \u003cp\u003eAge, median (IQR), years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e13（3）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 493px;\"\u003e\n \u003cp\u003eDisease location (Montreal classification),\u0026nbsp;n\u0026nbsp;(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 350px;\"\u003e\n \u003cp\u003e(L1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp\u003e8(16.67%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 350px;\"\u003e\n \u003cp\u003e(L2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp\u003e3(6.25%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 350px;\"\u003e\n \u003cp\u003e(L3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp\u003e31(64.58%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 350px;\"\u003e\n \u003cp\u003e(L4a)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp\u003e17(35.42%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 350px;\"\u003e\n \u003cp\u003e(L4b)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp\u003e41(85.42%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 350px;\"\u003e\n \u003cp\u003eCDEIS, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp\u003e9.57\u0026plusmn;7.49\u0026thinsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 350px;\"\u003e\n \u003cp\u003ePCDAI, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp\u003e27.63\u0026plusmn;12.95\u0026thinsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 350px;\"\u003e\n \u003cp\u003eC-reactive protein, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, mg/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp\u003e30.37\u0026plusmn;30.28\u0026thinsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 350px;\"\u003e\n \u003cp\u003eErythrocyte sedimentation rate, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp\u003e42.92\u0026plusmn;28.71\u0026thinsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 350px;\"\u003e\n \u003cp\u003ePlatelet, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, mg/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp\u003e417.57\u0026plusmn;130.36\u0026thinsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 350px;\"\u003e\n \u003cp\u003eSerum albumin, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, g/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp\u003e35.36\u0026plusmn;7.90\u0026thinsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 350px;\"\u003e\n \u003cp\u003ehemoglobin, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, g/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp\u003e105.68\u0026plusmn;17.09\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 350px;\"\u003e\n \u003cp\u003ehematocrit , mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 143px;\"\u003e\n \u003cp\u003e43.40\u0026plusmn;4.61\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 493px;\"\u003e\n \u003cp\u003eIQR\u0026nbsp;indicates interquartile range,\u0026nbsp;SD\u0026nbsp;standard deviation,\u0026nbsp;CDEIS\u0026nbsp;Crohn\u0026rsquo;s Disease Endoscopic Index of Severity,\u0026nbsp;PCDAI\u0026nbsp;pediatric Crohn\u0026rsquo;s disease activity index\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCorrelation analysis of the MaRIA and IBUS-SAS\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003escores\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003ewith the CDEIS\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003escore\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe evaluated the correlation of the MaRIA score or the IBUS-SAS score of all intestinal segments (from the terminal ileum to the rectum) with the CDEIS values. The Spearman\u0026apos;s rank correlation coefficient between the total MaRIA score and the CDEIS value was 0.334 (P\u0026lt;0.05; Figure 1), and that between the IBUS-SAS score and the CDEIS value was 0.328 (P \u0026lt; 0.05; Figure 1). In the colon, the Spearman\u0026apos;s rank correlation coefficient between the MaRIA score and the CDEIS value was 0.345 (P \u0026lt; 0.05; Figure 2), and that between the IBUS-SAS score and the CDEIS value was 0.501 (P\u0026lt;0.05; Figure 2). However, in the terminal ileum, both the MaRIA score and the IBUS-SAS were poorly correlated with the CDEIS value (Spearman\u0026apos;s r=0.190, p=0.211 and r=0.175, p=0.250).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePrediction of endoscopically active disease\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eUsing a cut-off point of 16.6, the sensitivity and specificity\u0026nbsp;for the prediction of endoscopically active disease in patients with a CDEIS value \u0026ge;3 were 100% and 40%, respectively, with an AUC of 0.670 (95% CI 0.453\u0026ndash;0.887). In the colonic segment, the IBUS-SAS scoring system demonstrated superior predictive efficacy. IBUS-SAS for the prediction of endoscopically active disease in the colon\u0026nbsp;had\u0026nbsp;an AUC of 0.736 (95% CI 0.539\u0026ndash;0.933), with a sensitivity of 83% and a specificity of 70% for a cut-off value of 16.0.\u003c/p\u003e\n\u003cp\u003eUsing a cut-off point of 7.86, the total MaRIA score showed a high accuracy for the\u0026nbsp;prediction of disease activity (CDEIS value \u0026ge;3),\u0026nbsp;with an AUC of 0.600\u0026nbsp;(95% CI 0.392\u0026ndash;0.807),\u0026nbsp;a\u0026nbsp;sensitivity of 66% and\u0026nbsp;a\u0026nbsp;specificity of 70%. ROC analysis of the colonic MaRIA score for the prediction of disease activity revealed an AUC of 0.597 (95% CI 0.407\u0026ndash;0.788), with a sensitivity of 49% and a specificity of 80% for a cut-off value of 8.46.\u003c/p\u003e\n\u003cp\u003eThe sensitivity and specificity for the prediction of endoscopically active disease in patients with a CDEIS value \u0026ge;9 were 85% and 48%, respectively, with an AUC of 0.655 (95% CI 0.496\u0026ndash;0.814) when the cut-off point was 55.5. In the same cohort, the colonic IBUS-SAS score for the prediction of endoscopically active disease had an AUC of 0.770 (95% CI 0.627\u0026ndash;0.913), with a sensitivity of 95% and a specificity of 60% for a cut-off value of 41.0.\u003c/p\u003e\n\u003cp\u003eROC analysis of the total MaRIA score for the prediction of endoscopically moderate active disease revealed an AUC of 0.758 (95% CI 0.614\u0026ndash;0.902), with a sensitivity of 75% and a specificity of 72% for a cut-off value of 8.6. ROC analysis of the colonic MaRIA score for the prediction of endoscopically moderate active disease revealed an AUC of 0.750 (95% CI 0.599\u0026ndash;0.901), with a sensitivity of 70% and a specificity of 84% for a cut-off value of 10.5.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2.Sensitivity, Specifcity and Youden index of IBUS-SAS and MaRIA at predicting endoscopically active disease\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003ecut-off\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003esensitivity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003especificity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eYouden index\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" valign=\"bottom\"\u003e\n \u003cp\u003eCDEIS\u0026ge;3\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003etotal_IBUS-SAS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e16.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e100%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e40%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e0.40\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003ecolon_IBUS-SAS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e16.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e83%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e70%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e0.53\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003etotal_MaRIA*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e7.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e66%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e70%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e0.36\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003ecolon_MaRIA\u003csup\u003e▲\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e8.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e49%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e80%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e0.29\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" valign=\"bottom\"\u003e\n \u003cp\u003eCDEIS\u0026ge;9\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003etotal_IBUS-SAS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e55.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e85%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e48%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e0.33\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003ecolon_IBUS-SAS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e41.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e95%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e60%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e0.55\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003etotal_MaRIA*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e8.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e75%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e72%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e0.47\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003ecolon_MaRIA\u003csup\u003e▲\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e10.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e70%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e84%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e0.54\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" valign=\"top\"\u003e\n \u003cp\u003eCDEIS Crohn\u0026rsquo;s Disease Endoscopic Index of Severity, PCDAI pediatric Crohn\u0026rsquo;s disease activity index, total_IBUS-SAS\u0026nbsp;the\u0026nbsp;maximum value of IBUS-SAS scores for six intestinal segments from terminal ileum to rectum, colon_IBUS-SAS the maximum value of IBUS-SAS scores for five intestinal segments from the ascending colon to the rectum, total_MaRIA* The mean of MaRIA score of the six intestinal segments from the terminal ileum to the rectum , colon_MaRIA\u003csup\u003e▲\u003c/sup\u003e The mean of MaRIA score of the five intestinal segments from the ascending colon to the rectum\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eComparison of the MaRIA and the IBUS-SAS scores\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA moderate positive correlation was observed between the colonic MaRIA score and the colonic IBUS-SAS score (r = 0.489, p \u0026lt; 0.001), while a weak correlation was observed between the MaRIA score and the IBUS-SAS score in the terminal ileum (r = 0.377, p \u0026lt; 0.05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSpearman correlation analysis between the MaRIA/IBUS-SAS\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003escores\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eand the PCDAI\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003escore\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eand laboratory measurements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBoth the MaRIA score and the IBUS-SAS score were positively correlated with the PCDAI score (r = 0.357, p \u0026lt; 0.001 and r = 0.348, p \u0026lt; 0.001). The MaRIA score and the IBUS-SAS score were negatively correlated with haemoglobin, haematocrit, and albumin levels (r = -0.515, p \u0026lt; 0.001; r = -0.461, p \u0026lt; 0.001; r = -0.377, p \u0026lt; 0.001 for the MaRIA score; r = -0.534, p \u0026lt; 0.001, r = -0.480, p \u0026lt; 0.001, r = -0.455, p \u0026lt; 0.001 for the IBUS-SAS score). The IBUS-SAS score was also positively correlated with the CRP level and the erythrocyte sedimentation rate (r = 0.412, p \u0026lt; 0.001 and r = 0.327, p \u0026lt; 0.001, respectively).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eCD, which is characterized by transmural involvement and complications due to recurrent aggressive inflammation, necessitates laborious diagnosis and therapeutic efficacy assessment to ensure timely treatment, as these evaluations are crucial for disease prognosis and the selection of an optimal treatment strategy. Endoscopy is the best diagnostic technique, but its invasiveness and associated risks hinder its application in the diagnosis and follow-up of paediatric patients.\u003c/p\u003e\n\u003cp\u003eConsiderable controversy exists regarding the diagnostic accuracy of alternative methods for the detection of CD, such as IUS and MRE. Our study utilized the MaRIA and IBUS-SAS systems to assess the degree of transmural damage in CD via MRE and IUS, which allowed us to explore the relationships of these scores with endoscopic activity, clinical disease severity, and routine laboratory indicators in newly diagnosed paediatric CD patients.\u003c/p\u003e\n\u003cp\u003eThe METRIC trial compared the diagnostic accuracy of MRE and IUS for CD and supported their competitiveness and feasibility as alternative diagnostic imaging modalities to invasive ileocolonoscopy \u003csup\u003e17\u003c/sup\u003e. This study revealed that in the group of newly diagnosed patients, the sensitivity of ultrasound (67% [95% CI 49\u0026ndash;81]) for the presence of colonic disease was significantly greater than that of MRE (47% [31-64]), with a difference of 20% (1-39). No significant difference was observed in sensitivity or specificity between MRE and IUS in terms of the extent and presence of colonic disease. Xu et al. reached the same conclusion that B-IUS has the highest accuracy for the detection of CD in patients with terminal ileum involvement.\u003csup\u003e18\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eVarious MRE scoring systems for disease activity have been developed and validated. The first and best validated index is the MaRIA, the scores for which are calculated on the basis of endoscopic signs of intestinal inflammation\u003csup\u003e11\u003c/sup\u003e.\u0026nbsp;Our study revealed that a MaRIA cut-off value of 7.86 predicts endoscopic disease activity (CDEIS value \u0026ge;3), which is consistent with the currently accepted threshold for transmural active disease (MaRIA score \u0026ge; 7). Furthermore, we also found that a MaRIA cut-off value of 8.60 can predict moderate disease activity on endoscopy (CDEIS value \u0026ge; 9), with increased sensitivity and specificity.\u003c/p\u003e\n\u003cp\u003eDuring the development phase of the IBUS-SAS, the sample size was adequate, the method was dependent on the opinions of experts, and both quantitative and semiquantitative parameters were considered. However, when these parameters are selected now, endoscopic scores are not utilized, and the cut-off values for endoscopic scoring are unknown\u003csup\u003e16\u003c/sup\u003e.\u0026nbsp;In our study, the IBUS-SAS cut-off value for the prediction of endoscopic disease activity was 16.6. An IBUS-SAS value of 55.5 or higher suggests the presence of moderate endoscopic activity.\u003c/p\u003e\n\u003cp\u003eCurrently, only a few studies on the optimal cut-off value of the IBUS-SAS score have been published, but the values reported are inconsistent. In a prospective study of 93 patients, Allocca et al. selected endoscopic remission (SES-CD \u0026le; 2) and calculated the cut-off value to be an IBUS-SAS score \u0026le; 22.8. The sensitivity and specificity were 95% (95% CI: 77\u0026ndash;99) and 83% (72\u0026ndash;91), respectively [AUROC: 0.906, 95% CI: 0.827\u0026ndash;0.957] \u003csup\u003e19\u003c/sup\u003e. However, a study conducted by Xu et al. integrated endoscopic activity scores from both colonoscopy and balloon-assisted enteroscopy and reported that a cut-off value of 46.7 for the IBUS-SAS could predict mucosal activity on endoscopy (SES-CD \u0026gt; 2)\u003csup\u003e18\u003c/sup\u003e. Another study used the Harvey‒Bradshaw Index (HBI) and biomarkers (CRP and FC) as indicators of disease activity, after which an optimal cut-off of 42.9 was determined for the IBUS-SAS. \u003csup\u003e20\u003c/sup\u003eHowever, in our study, when the CDEIS value was used as the gold standard, the conclusions differed.\u003c/p\u003e\n\u003cp\u003eOur study has several limitations. This was a retrospective validation study, and prospective studies are needed to confirm our findings. Moreover, the patients with CD who were included in this study were primarily newly diagnosed with CD; in later studies, we may include more patients with CD who have a history of follow-up visits to assess the sensitivity and specificity of future imaging examination methods. Since the included patients mainly underwent imaging examinations for disease assessment and efficacy monitoring, most patients were in the active phase of the disease; therefore, the small number of patients in remission may have affected the statistical results.\u003c/p\u003e\n\u003cp\u003eIn summary, MRE and B-IUS are more sensitive for the detection of CD lesions in the colon and rectum than in the terminal ileum. When the disease is active on MRE (MaRIA score \u0026gt; 7), this status can in turn be used to predict disease activity on endoscopy. We also propose that an IBUS-SAS score above 16 indicates endoscopically active disease and that a score of 55.5 indicates endoscopically moderate active disease. Both the IBUS-SAS score and the MaRIA score are correlated with the PCDAI value, the CDEIS value, and the levels of albumin, haemoglobin, haematocrit, and serum inflammatory markers. When MRE is not feasible or is contraindicated, IUS can serve as an alternative imaging method for repeated follow-up and assessment of disease activity.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eY.L.and C. wrote the main manuscript text. X. performed the ultrasonography and scoring. M. conducted the MRE reading and scoring. Z.P.andT. carried out the enteroscopy and scoring. All authors reviewed the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eKaplan GG and Windsor JW. The four epidemiological stages in the global evolution of inflammatory bowel disease. 2021; 18: 56-66.\u003c/li\u003e\n\u003cli\u003eConrad MA and Rosh JR. Pediatric Inflammatory Bowel Disease. \u003cem\u003ePediatr Clin North Am\u003c/em\u003e. 2017; 64: 577-91.\u003c/li\u003e\n\u003cli\u003eMary JY and Modigliani R. Development and validation of an endoscopic index of the severity for Crohn\u0026apos;s disease: a prospective multicentre study. Groupe d\u0026apos;Etudes Th\u0026eacute;rapeutiques des Affections Inflammatoires du Tube Digestif (GETAID). \u003cem\u003eGut\u003c/em\u003e. 1989; 30: 983-9.\u003c/li\u003e\n\u003cli\u003eNikolaus S and Schreiber S. Diagnostics of inflammatory bowel disease. \u003cem\u003eGastroenterology\u003c/em\u003e. 2007; 133: 1670-89.\u003c/li\u003e\n\u003cli\u003eMaaser C, Sturm A, Vavricka SR, et al. ECCO-ESGAR Guideline for Diagnostic Assessment in IBD Part 1: Initial diagnosis, monitoring of known IBD, detection of complications. \u003cem\u003eJ Crohns Colitis\u003c/em\u003e. 2019; 13: 144-64.\u003c/li\u003e\n\u003cli\u003eTielbeek JA, Makanyanga JC, Bipat S, et al. Grading Crohn disease activity with MRI: interobserver variability of MRI features, MRI scoring of severity, and correlation with Crohn disease endoscopic index of severity. \u003cem\u003eAJR Am J Roentgenol\u003c/em\u003e. 2013; 201: 1220-8.\u003c/li\u003e\n\u003cli\u003eRozendorn N, Amitai MM, Eliakim RA and Kopylov U. A review of magnetic resonance enterography-based indices for quantification of Crohn\u0026apos;s disease inflammation. 2018; 11: 1756284818765956.\u003c/li\u003e\n\u003cli\u003eZheng X, Li M, Wu Y, et al. Assessment of pediatric Crohn\u0026apos;s disease activity: validation of the magnetic resonance enterography global score (MEGS) against endoscopic activity score (SES-CD). \u003cem\u003eAbdom Radiol (NY)\u003c/em\u003e. 2020; 45: 3653-61.\u003c/li\u003e\n\u003cli\u003ePuylaert CAJ, Nolthenius CJT, Tielbeek JAW, et al. Comparison of MRI Activity Scoring Systems and Features for the Terminal Ileum in Patients With Crohn Disease. \u003cem\u003eAJR Am J Roentgenol\u003c/em\u003e. 2019; 212: W25-w31.\u003c/li\u003e\n\u003cli\u003ePariente B, Mary JY, Danese S, et al. Development of the L\u0026eacute;mann index to assess digestive tract damage in patients with Crohn\u0026apos;s disease. \u003cem\u003eGastroenterology\u003c/em\u003e. 2015; 148: 52-63.e3.\u003c/li\u003e\n\u003cli\u003eRimola J, Rodriguez S, Garc\u0026iacute;a-Bosch O, et al. Magnetic resonance for assessment of disease activity and severity in ileocolonic Crohn\u0026apos;s disease. \u003cem\u003eGut\u003c/em\u003e. 2009; 58: 1113-20.\u003c/li\u003e\n\u003cli\u003eChurch PC, Greer MC, Cytter-Kuint R, et al. Magnetic resonance enterography has good inter-rater agreement and diagnostic accuracy for detecting inflammation in pediatric Crohn disease. \u003cem\u003ePediatr Radiol\u003c/em\u003e. 2017; 47: 565-75.\u003c/li\u003e\n\u003cli\u003eRimola J, Ord\u0026aacute;s I, Rodriguez S, et al. Magnetic resonance imaging for evaluation of Crohn\u0026apos;s disease: validation of parameters of severity and quantitative index of activity. \u003cem\u003eInflamm Bowel Dis\u003c/em\u003e. 2011; 17: 1759-68.\u003c/li\u003e\n\u003cli\u003eTakenaka K, Ohtsuka K, Kitazume Y, et al. Utility of Magnetic Resonance Enterography For Small Bowel Endoscopic Healing in Patients With Crohn\u0026apos;s Disease. \u003cem\u003eAm J Gastroenterol\u003c/em\u003e. 2018; 113: 283-94.\u003c/li\u003e\n\u003cli\u003eBots S, Nylund K, L\u0026ouml;wenberg M, Gecse K, Gilja OH and D\u0026apos;Haens G. Ultrasound for Assessing Disease Activity in IBD Patients: A Systematic Review of Activity Scores. \u003cem\u003eJ Crohns Colitis\u003c/em\u003e. 2018; 12: 920-9.\u003c/li\u003e\n\u003cli\u003eNovak KL, Nylund K, Maaser C, et al. Expert Consensus on Optimal Acquisition and Development of the International Bowel Ultrasound Segmental Activity Score [IBUS-SAS]: A Reliability and Inter-rater Variability Study on Intestinal Ultrasonography in Crohn\u0026apos;s Disease. \u003cem\u003eJ Crohns Colitis\u003c/em\u003e. 2021; 15: 609-16.\u003c/li\u003e\n\u003cli\u003eTaylor SA, Mallett S, Bhatnagar G, et al. Diagnostic accuracy of magnetic resonance enterography and small bowel ultrasound for the extent and activity of newly diagnosed and relapsed Crohn\u0026apos;s disease (METRIC): a multicentre trial. \u003cem\u003eLancet Gastroenterol Hepatol\u003c/em\u003e. 2018; 3: 548-58.\u003c/li\u003e\n\u003cli\u003eXu C, Li L, Zhang Y, Wang R and Zhang H. Diagnostic accuracy of different cross-sectional imaging techniques for disease location and activity in Crohn\u0026apos;s disease and external validation and comparison of MARIAs and IBUS-SAS. \u003cem\u003eAbdom Radiol (NY)\u003c/em\u003e. 2023; 48: 821-32.\u003c/li\u003e\n\u003cli\u003eAllocca M, Dell\u0026apos;Avalle C, Zilli A, et al. Ultrasound remission after biologic induction and long-term endoscopic remission in Crohn\u0026apos;s disease: a prospective cohort study. \u003cem\u003eEClinicalMedicine\u003c/em\u003e. 2024; 71: 102559.\u003c/li\u003e\n\u003cli\u003eDragoni G, Innocenti T, Lynch EN, et al. P141 IBUS-SAS for Crohn\u0026rsquo;s disease ultrasound activity: initial validation and research of the optimal cut-off score. \u003cem\u003eJournal of Crohn\u0026apos;s and Colitis\u003c/em\u003e. 2021; 15: S226-S7.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"abdominal-radiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"aima","sideBox":"Learn more about [Abdominal Radiology](http://link.springer.com/journal/261)","snPcode":"261","submissionUrl":"https://submission.springernature.com/new-submission/261/3","title":"Abdominal Radiology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Crohn’s disease, Paediatric, MaRIA, IBUS-SAS, CDEIS","lastPublishedDoi":"10.21203/rs.3.rs-7224257/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7224257/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjectives\u003c/h2\u003e\u003cp\u003eTo assess transmural damage in patients with Crohn's disease (CD), imaging techniques such as magnetic resonance enterography (MRE) and intestinal ultrasound (IUS) are used. The Magnetic Resonance Index of Activity (MaRIA) and the International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) are scoring systems for MRE and IUS, respectively. This study examined their correlation with the Crohn's Disease Endoscopic Index of Severity (CDEIS) in children with CD.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThis was a retrospective analysis of children with new-onset CD who were treated from 2017\u0026ndash;2022 at Zhejiang University Children's Hospital. Patients underwent IUS examination and IBUS-SAS scoring, MRE examination and MaRIA evaluation, colonoscopy and CDEIS calculation, and in addition, the PCDAI value was calculated. Blood samples were also collected for analysis. Nonnormally distributed data were analysed using Spearman's rank correlation coefficient.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eForty-eight children were included in this study. The MaRIA and IBUS-SAS scores were positively correlated with the CDEIS value (r\u0026thinsp;=\u0026thinsp;0.334 and r\u0026thinsp;=\u0026thinsp;0.328, both p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). In the colon, the Spearman's rank correlation coefficient between the MaRIA score and the CDEIS value was 0.345 (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), and that between the IBUS-SAS score and the CDEIS value was 0.501 (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The IBUS-SAS had an AUC of 0.655 for the prediction of moderate active disease (CDEIS\u0026thinsp;\u0026ge;\u0026thinsp;9), with a cut-off of 55.5.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eBoth the MaRIA and the IBUS-SAS scores are correlated with the CDEIS score in children with newly diagnosed CD. An IBUS-SAS score above 55.5 suggests moderate disease activity. IUS can serve as an alternative to MRE for disease activity assessment when MRE is not viable.\u003c/p\u003e","manuscriptTitle":"Ultrasound and MRI for Pediatric Crohn's Disease Assessment: Correlations of the MaRIA Score and IBUS-SAS with Endoscopic Disease Activity and Optimal Cutoff Values","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-31 10:31:52","doi":"10.21203/rs.3.rs-7224257/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-08-26T00:35:31+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-25T15:47:49+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-20T02:43:23+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"34451082574210494491078448248222844808","date":"2025-08-09T02:16:44+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"170509637536163452336503063500407054908","date":"2025-07-31T13:21:25+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-29T00:56:08+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-28T07:35:36+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-07-28T07:33:10+00:00","index":"","fulltext":""},{"type":"submitted","content":"Abdominal Radiology","date":"2025-07-27T05:24:22+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"abdominal-radiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"aima","sideBox":"Learn more about [Abdominal Radiology](http://link.springer.com/journal/261)","snPcode":"261","submissionUrl":"https://submission.springernature.com/new-submission/261/3","title":"Abdominal Radiology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"7c3523e7-4042-48cd-aea7-ec3736b8c735","owner":[],"postedDate":"July 31st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-11-24T16:10:04+00:00","versionOfRecord":{"articleIdentity":"rs-7224257","link":"https://doi.org/10.1007/s00261-025-05274-3","journal":{"identity":"abdominal-radiology","isVorOnly":false,"title":"Abdominal Radiology"},"publishedOn":"2025-11-21 15:59:06","publishedOnDateReadable":"November 21st, 2025"},"versionCreatedAt":"2025-07-31 10:31:52","video":"","vorDoi":"10.1007/s00261-025-05274-3","vorDoiUrl":"https://doi.org/10.1007/s00261-025-05274-3","workflowStages":[]},"version":"v1","identity":"rs-7224257","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7224257","identity":"rs-7224257","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}