Multimodality ultrasound in Crohn’s disease strictures

Abstract

BACKGROUND

Stricture formation in Crohn’s disease (CD) poses a significant clinical challenge, often requiring differentiation between inflammatory and fibrotic components to guide appropriate therapy.

AIM

To evaluate the utility of multimodal intestinal ultrasound - including small intestine contrast ultrasonography (SICUS), contrast-enhanced ultrasound (CEUS), and ultrasound-based elastography - in detecting and characterizing CD-related small bowel strictures.

METHODS

A review was conducted in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. A comprehensive search of PubMed and EMBASE databases from inception to June 2025 yielded 697 records, respectively. After screening and full-text assessment, 43 studies were included. Eligible studies reported on the use of SICUS, CEUS, and elastography for detecting or phenotyping CD strictures, with comparisons to cross-sectional imaging, histopathology, endoscopy, or surgical findings.

RESULTS

Across heterogeneous study designs, SICUS demonstrated high sensitivity for stricture detection (typically approximately 88%-98%) with specificity that varied by cohort and criteria. Common thresholds included bowel wall thickness > 3 mm, luminal narrowing < 1 cm, and/or prestenotic dilation > 2.5 cm. CEUS effectively distinguished fibrotic from inflammatory strictures using time-intensity curve metrics: Fibrotic strictures showed reduced peak enhancement (e.g., 25 dB vs 38 dB), and lower perfusion area under the curve (AUC) values (e.g., 570 intensity time units vs 1168 intensity time units), reflecting diminished vascularity. Cutoffs such as peak enhancement < 30 dB and AUC < 700 units were associated with fibrosis. Elastography - particularly shear wave elastography achieved AUCs of 0.88-0.91 for fibrosis detection using cutoffs of 2.5-2.9 m/second (sensitivity 80%-88%, specificity 85%-100%). Strain ratio thresholds between 2.2 and 3.0 also differentiated fibrotic from inflammatory lesions with diagnostic AUCs up to 0.91. Among elastography modalities, shear wave elastography consistently outperformed strain elastography and acoustic radiation force impulse in accuracy and reproducibility.

CONCLUSION

Multimodal intestinal ultrasound - including SICUS, CEUS, and elastography - offers a comprehensive, radiation-free framework to detect, localize, and phenotype CD strictures. While performance is promising, variability in thresholds and reference standards limits generalizability. Standardized acquisition, predefined cut-offs, and multicenter validation are priorities before widespread adoption in treatment algorithms.

Key Words: Crohn’s disease; Intestinal ultrasound; Small intestine contrast ultrasonography; Contrast-enhanced ultrasound; Elastography

Core Tip: Multimodal intestinal ultrasound - including contrast-enhanced ultrasound, small intestine contrast ultrasonography, and ultrasound-based elastography - offers a noninvasive, radiation-free, and accurate approach to characterize Crohn’s disease strictures. Small intestine contrast ultrasonography reliably detects strictures and disease extent with performance comparable to cross-sectional imaging. Contrast-enhanced ultrasound perfusion parameters such as peak enhancement and AUC help differentiate inflammation from fibrosis, especially when combined with elastography. Shear wave elastography provides quantitative stiffness assessment, with velocities > 2.5 m/second indicating fibrosis. These tools support precise stricture phenotyping and may guide tailored therapy and surgical decision-making.

INTRODUCTION

Stricture formation is a common and clinically significant complication of Crohn’s disease (CD), affecting up to 30%-50% of patients within 10 years of diagnosis. These strictures often lead to obstructive symptoms, reduced quality of life, and surgical interventions. However, not all strictures behave the same: While inflammatory strictures may respond to medical therapy, fibrotic strictures typically require endoscopic or surgical intervention. Accurately distinguishing between these phenotypes is essential to avoid overtreatment, delay in surgery, or ineffective biologic therapy. As transmural disease involvement cannot be fully captured by endoscopy alone, imaging plays a central role in stricture assessment[1].

Despite the widespread use of cross-sectional imaging modalities like magnetic resonance enterography (MRE) and computed tomography (CT) enterography, their ability to distinguish inflammation from fibrosis remains limited, with variability in both interpretation and correlation with histology. Endoscopy provides mucosal views but fails to assess mural or extramural features such as prestenotic dilation, fistulae, or mesenteric changes. Moreover, repeated use of radiation-based techniques is undesirable, particularly in younger or treatment-naïve patients. A reliable, accessible, and reproducible bedside tool for noninvasive stricture characterization - especially for routine monitoring and postoperative assessment - remains an important clinical gap[2].

This review explores the role of multimodal intestinal ultrasound (IUS), including small intestine contrast ultrasonography (SICUS), contrast-enhanced ultrasound (CEUS), and ultrasound elastography, in the detection and phenotyping of CD strictures. By synthesizing evidence across studies, it attempts to highlight diagnostic thresholds, comparative accuracy with gold standards, and emerging biomarkers such as perfusion kinetics and stiffness metrics. The review aims to support clinicians in adopting validated ultrasound techniques for individualized, radiation-free, and cost-effective assessment of CD strictures across diverse clinical scenarios.

MATERIALS AND METHODS

This scoping review was conducted in accordance with the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews 2020 guidelines. No protocol was registered a priori. Eligibility criteria included adults or children with CD undergoing IUS for suspected or known strictures. Concept included advanced ultrasound modalities - SICUS, CEUS, and ultrasound-based elastography - used to detect, characterize, or phenotype small-bowel strictures. Context was any clinical care or research setting. Prospective/retrospective cohorts, cross-sectional studies, surgical validation studies, and ex vivo validations were included. Case reports, non-human studies, conference abstracts, reviews, and non-English studies were excluded. A comprehensive literature search of PubMed and EMBASE was performed from inception to June 2025 using the following search strategy: “Crohn Disease” OR “Crohn’s disease” OR “inflammatory bowel disease” OR “IBD”) AND (“Ultrasonography” OR “Intestinal Ultrasound” OR “Bowel Ultrasound” OR “IUS” OR “Transabdominal Ultrasound” OR “Contrast-Enhanced Ultrasound” OR “CEUS” OR “Contrast Enhanced Ultrasonography” OR “Small Intestine Contrast Ultrasonography” OR “SICUS” OR “Ultrasound Elastography” OR “Sonoelastography”) AND (“Stricture” OR “Strictures” OR “Stenosis” OR “Fibrostenotic” OR “Fibrosis” OR “Bowel Narrowing” OR “Stricture Evaluation” OR “Fibrotic Stricture” OR “Inflammatory Stricture”). Two reviewers independently screened titles/abstracts and full texts (Pal P and Kata P); disagreements were resolved by a third reviewer (Mateen MA). We extracted: Study design, setting/centers, sample size, reference standard(s), ultrasound modality and parameters (including cut-offs), index definition of stricture, accuracy metrics (sensitivity/specificity), and key findings. Given thresholds, reference standards, and outcomes varied substantially across studies, meta-analysis and formal forest plots were not appropriate; we instead present study-level accuracy in structured tables and depict ranges in a narrative summary. Where possible, we report commonly used cut-offs and the range of diagnostic performance across studies.

RESULTS

Study selection and characteristics

From 697 records, 43 studies met the inclusion criteria (Figure 1). Study designs included prospective/retrospective cohorts, surgical validation, and ex vivo analyses. Reference standards comprised surgery/histology, MRE/CT enterography (CTE), endoscopy, and clinical follow-up. Tables 1, 2, and 3 summarize key characteristics (design, setting/centers, sample size), index test definitions and cut-offs, reference standards, and diagnostic accuracy.

Figure 1 Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 checklist.

Table 1 Diagnostic accuracy of small intestine contrast ultrasonography for detecting Crohn’s disease strictures across key validation studies.

Ref.	Design	Number	Reference standard	Sensitivity (%)	Specificity (%)	Definition (if stated)	Comparator modality (if any)	Kappa (if any)	Comments/additional findings
Calabrese et al[7], 2013	Prospective comparative study	38	Surgical and histopathological findings	95.5	80	Lumen < 1 cm or upstream dilation > 2.5 cm with wall thickening	CT-enteroclysis	Not reported	High correlation with surgical lesion extent (ρ = 0.83)
Onali et al[8], 2012	Prospective validation	13	Surgical and histological findings	92	Not separately stated	Wall thickening + lumen narrowing ± prestenotic dilation	CT-enteroclysis	Not reported	Feasible in all patients; comparable to CTE for all complications
Parente et al[4], 2004	Prospective cohort	102	Barium enteroclysis, ileocolonoscopy	89	93	Stiff wall, lumen narrowing + upstream dilation	Conventional US, BE	0.95 (for expert vs reference)	PEG-enhanced US improved sensitivity, reduced interobserver variability
Calabrese et al[14], 2009	Prospective postoperative study	72	Ileocolonoscopy (Rutgeerts’ score)	92.5	20	BWT > 3 mm, lumen < 1 cm ± dilation > 2.5 cm	None	Not stated	BWT correlated with endoscopic recurrence (r = 0.67)
Calabrese et al[5], 2005	Prospective comparative study	38	Surgical/histological findings	95	80	Wall thickening, lumen < 1 cm, ± dilation > 2.5 cm	CT-enteroclysis	Not reported	High correlation with extent of disease (ρ = 0.83)
Pallotta et al[13], 2012	Prospective study vs surgical findings	49	Surgical/pathology	97.5	100	Lumen < 1 cm, wall thickening, ± dilation > 2.5 cm	IUS	0.93	Also reported fistula (96%) and abscess (100%) accuracy
Kumar et al[10], 2014	Retrospective comparative study	25	Intraoperative findings	88	88	Wall thickening + fixed loop or absence of peristalsis	MRE	0.73	Substantial agreement with MRE and surgery
Chatu et al[6], 2012	Retrospective	52	Multimodal including surgery	88	Not stated	Wall thickening + narrowed lumen	CT/MRE	Not reported	SICUS helped define disease extent and complications
Aloi et al[11], 2015	Pediatric prospective cohort	26	MRE	85.7	100	Not precisely defined	MRE	0.82	High agreement between modalities

CD: Crohn’s disease; SICUS: Small intestine contrast ultrasonography; CT: Computed tomographic; CTE: Computed tomographic enteroclysis; MRE: Magnetic resonance enterography; BE: Barium enteroclysis; BWT: Bowel wall thickness; IUS: Intestinal ultrasound.

Table 2 Summary of studies evaluating contrast-enhanced ultrasound for characterization of Crohn’s disease strictures, with emphasis on fibrosis detection and correlation with histological or imaging reference standards.

Ref.	Study design	n (CD strictures)	CEUS modality	Reference standard	Key findings
Goertz et al[25], 2018	Prospective cohort	30	Quantitative CEUS (peak enhancement, AUC, TTP)	Surgery or clinical follow-up	CEUS correlated well with histological fibrosis; peak enhancement and AUC were lower in fibrotic vs inflammatory strictures
Horjus Talabur Horje et al[21], 2015	Prospective observational	30	CEUS with dynamic perfusion analysis	Surgical pathology	CEUS showed correlation with fibrosis; fibrotic strictures had lower contrast uptake
Servais et al[22], 2021	Prospective cohort	34	Qualitative CEUS, quantitative (AUC, TTP, PI)	Histopathology	Combined CEUS + elastography improved diagnostic accuracy for fibrostenotic vs inflammatory
Wilkens et al[20], 2018	Prospective diagnostic accuracy study	25	Quantitative CEUS	Surgery	Moderate accuracy in distinguishing fibrosis; combined CEUS + DCE-MRE showed complementary roles
Lu et al[2], 2022	Prospective study	40	CEUS and SWE	Histology	CEUS parameters and shear wave velocity discriminated fibrosis; AUC and PE were reduced in fibrotic strictures
Ma et al[16], 2020	Prospective study	20	Quantitative CEUS + elastography	CT and endoscopy	CEUS differentiated inflammatory vs fibrotic stenosis; AUC and PE were higher in the inflammatory group
Nylund et al[24], 2013	Pilot feasibility study	15	Quantitative CEUS	Endoscopy	CEUS is feasible and safe; potential for stricture characterization; inflammation showed higher perfusion
Quaia et al[17], 2018	Prospective pilot study	20	Visual CEUS + strain elastography	Histopathology	Combined CEUS + elastography improved accuracy (AUC up to 0.95); good inter-reader agreement
Serra et al[18], 2017	Prospective study	29	CEUS + strain elastography	Histology	No correlation between CEUS parameters and histologic fibrosis; overlap of inflammation and fibrosis
Sidhu et al[19], 2023	Prospective pediatric study	25 (11 surgical)	CEUS + SWE	Surgical pathology	CEUS AUC correlated with fibrosis and muscular hypertrophy; it helped identify candidates for surgery
Ripollés et al[26], 2013	Prospective observational	28	B-mode, CDI, CEUS with PME and TTP analysis	Surgical specimens	PME correlated with inflammatory activity; CEUS showed low PME in fibrotic strictures
Schirin-Sokhan et al[29], 2011	Pilot prospective	18	Quantitative CEUS with QONTRAST software	Endoscopy + histology + follow-up	No significant correlation between quantitative CEUS and histologic fibrosis; Limberg score and CDAI better correlated with inflammation
Wilkens et al[28], 2022	Prospective cohort	18	CEUS + DCE-MRE + elastography	Biomechanical stiffness ex vivo	CEUS perfusion did not correlate with stricture stiffness; DCE-MRE slope correlated better with mechanical stiffness
Ponorac et al[27], 2021	Prospective single-center	24	Quantitative CEUS (PI, TTP, AUC)	Surgical pathology	Lower AUC and TTP values in fibrotic strictures; CEUS is useful in stricture phenotype classification
Quaia et al[23], 2012	Prospective pilot	28	CEUS with PME, wash-in slope	Endoscopy + MRE	PME is significantly lower in fibrostenotic than in inflammatory strictures; good intraobserver reproducibility

CEUS: Contrast-enhanced ultrasound; CD: Crohn’s disease; AUC: Area under the curve; TTP: Time to peak; PI: Peak intensity; PME: Percentage of maximal enhancement; SWE: Shear wave elastography; DCE-MRE: Dynamic contrast-enhanced magnetic resonance enterography; CDI: Color Doppler imaging; CT: Computed tomography; MRE: Magnetic resonance enterography; CDAI: Crohn’s disease activity index; PE: Peak enhancement.

Table 3 Table summarizing key prospective, ex vivo, and pilot studies evaluating various ultrasound elastography modalities for characterizing Crohn’s disease strictures, with comparison to histological, surgical, or clinical reference standards.

Ref.	Study design	n (CD strictures)	Elastography modality	Reference standard	Key findings
Abu-Ata et al[37], 2023	Prospective	33	SWE	Histology	SWE cut-off > 2.5 m/second had 80% sensitivity, 85% specificity; good fibrosis correlation
Baumgart et al[30], 2015	Ex vivo study	16	Strain elastography	Histology, tensiometry	Strain 1.56 (fibrotic) vs 3.74 (non-fibrotic), P < 0.0001; correlated with collagen
Chen et al[31], 2023	Prospective	52	SWE	Histology	ρ = 0.74 with fibrosis; SWE differentiated fibrosis with high accuracy
Dillman et al[41], 2014	Ex vivo	12	Strain elastography	Histology	Inverse correlation with fibrosis grade (ρ = -0.66), hydroxyproline (ρ = -0.72)
Ding et al[39], 2019	Prospective	25	SE, ARFI, pSWE	Histology	pSWE AUC = 0.833; SWE superior to SE/ARFI in fibrosis detection
Fraquelli et al[33], 2015	Prospective	47	Strain elastography	Histology	SR: 2.64 (severe) vs 1.16 (mild/no fibrosis), AUC = 0.91
Fufezan et al[38], 2015	Pilot pediatric	24	SWE	Clinical indices	Higher SWE values with more active disease; a scoring system proposed
Lu et al[2], 2022	Prospective	40	SWE + CEUS	Histology	SWE + CEUS showed distinct profiles for fibrosis vs inflammation
Ma et al[16], 2020	Prospective	20	SWE + CEUS	CT/endoscopy	SWE and CEUS parameters significantly differed in fibrotic vs inflammatory groups
Matsumoto et al[36], 2023	Prospective	21	SWE	IUS + clinical	SWE decreased only in ustekinumab group (P = 0.028); tracked stiffness after biologics
Mazza et al[34], 2022	Prospective	31	RTE	Histology + MRE	SR AUC = 0.88 for fibrosis; RTE outperformed MRE delayed enhancement (AUC = 0.61)
Orlando et al[35], 2018	Prospective	34	Strain elastography	Histology	SR > 2.52 predicted fibrosis with 90% sensitivity, 88% specificity
Sconfienza et al[32], 2016	Prospective	18	Axial strain sonoelastography	Histology	Improved fibrosis detection vs MRE; better visual pattern recognition
Serra et al[18], 2017	Prospective	29	Strain elastography	Histology	No correlation between SR and fibrosis; overlapping inflammation/fibrosis
Sidhu et al[19], 2023	Prospective pediatric	25	SWE + CEUS	Surgery	SWE + CEUS identified fibrosis/muscular hypertrophy; helpful for surgical planning
Stidham et al[40], 2011	Animal + ex vivo	31	Strain UEI	Histology, tensiometry	UEI strain -2.07 (inflamed) vs -1.10 (fibrotic), Young’s modulus 2.75 kPa vs 0.3 kPa
Zhang et al[42], 2023	Retrospective	37	SWE	Histology	Emean > 21.3 kPa AUC = 0.877 for fibrosis; SWE stronger fibrosis correlation vs CTE

CD: Crohn’s disease; SWE: Shear wave elastography; CEUS: Contrast-enhanced ultrasound; SR: Strain ratio; RTE: Real-time elastography; ARFI: Acoustic radiation force impulse; pSWE: Point shear wave elastography; UEI: Ultrasound elasticity imaging; CT: Computed tomography; MRE: Magnetic resonance enterography; IUS: Intestinal ultrasound; AUC: Area under the curve; ρ: Spearman correlation coefficient.

Overview of findings by modality

SICUS consistently detected strictures and disease extent with high sensitivity (typically approximately 88%-98%) and context-dependent specificity, with commonly used definitions including bowel wall thickness (BWT) > 3 mm, luminal diameter < 1 cm, and/or prestenotic dilation > 2.5 cm. CEUS differentiated perfusion profiles of inflammatory vs fibrotic strictures using time-intensity curve (TIC) metrics [e.g., peak enhancement (PE) and area under the curve (AUC)], and complemented B (Brightness)-mode. Elastography - particularly shear wave elastography (SWE) - quantified stiffness and correlated with histologic fibrosis in several surgical validation cohorts; commonly reported thresholds for fibrosis ranged around shearwave velocity approximately 2.5-2.9 m/second or strain-ratio approximately > 2.2-3.0.

SICUS

SICUS is a non-invasive, radiation-free imaging modality developed to overcome the limitations of conventional transabdominal ultrasound (TAS) in evaluating small bowel lesions, particularly in CD (Table 1). By administering an oral anechoic contrast solution (typically 30 minutes after injection of polyethylene glycol 500 mL), SICUS achieves uniform small bowel distension, improving loop separation and wall visibility from the duodenojejunal flexure to the ileocecal valve. This enables better delineation of disease extent, mural abnormalities, and complications such as strictures, prestenotic dilation, fistulas, and abscesses.

In a pivotal pediatric study by Pallotta et al[3], SICUS demonstrated superior diagnostic accuracy compared to TAS and comparable performance to radiological standards [small bowel follow-through (SBFT)]. SICUS achieved 100% sensitivity and specificity for detecting small bowel CD in undiagnosed patients and 96% sensitivity and 100% specificity in those with established disease. It also outperformed IUS in identifying both proximal (93% vs 50%) and distal (97% vs 83%) small bowel involvement, with almost perfect agreement with SBFT (κ = 0.93). Additionally, SICUS accurately assessed the length of lesions (mean 23 cm), with a strong correlation to radiology (r = 0.86), while TUS significantly underestimated disease extent. Notably, SICUS identified small bowel strictures with 94% sensitivity, compared to 70% with TUS, and detected strictures missed by both TUS and SBFT, including jejunal lesions confirmed at surgery[3]. These findings establish SICUS as a first-line tool in the evaluation and follow-up of CD, especially in pediatric populations where radiation exposure is a significant concern.

Comparison of SICUS with SBFT, small bowel enema, and ileocolonoscopy

Several prospective studies (Table 1) have compared SICUS to traditional modalities such as SBFT, small bowel enema (SBE), and ileocolonoscopy (IC), particularly for evaluating small bowel strictures in CD. In a pivotal prospective study involving 102 patients, Parente et al[4] demonstrated that SICUS achieved higher sensitivity for detecting strictures (89%) compared to conventional ultrasound (74%) and showed excellent correlation with barium enteroclysis for assessing disease extent (r = 0.94). Importantly, SICUS also improved interobserver agreement and significantly reduced variability in BWT and lesion localization[4]. The study concluded that SICUS was comparable to barium enteroclysis in characterizing lesion location and extent, while offering the added advantages of reduced cost, improved tolerability, and no radiation exposure.

In another prospective head-to-head comparison, Calabrese et al[5] evaluated SICUS against conventional TAS and SBE in 40 patients with CD. SICUS had a sensitivity of 94% for detecting strictures compared to 78% with SBE, and it provided more accurate estimates of disease extent (mean stricture length 15.7 cm vs 12.4 cm with SBE, P < 0.05). SICUS also performed better in detecting multiple strictures and assessing bowel elasticity, which could help distinguish fibrotic from inflammatory stenosis. The overall agreement for stricture detection between SICUS and intraoperative findings was stronger than with SBE, confirming its clinical reliability.

Chatu et al[6] conducted a large retrospective United Kingdom study including 143 patients who underwent SICUS and were compared against SBFT, CT, histology, and IC. SICUS demonstrated 93% sensitivity and 99% specificity for detecting small bowel CD, with kappa agreement coefficients of 0.88 with SBFT and 0.91 with CT. Among patients with strictures, SICUS identified all cases confirmed by SBFT or CT, and in two cases, it revealed additional pathology missed by SBFT. The agreement between SICUS and histology (k = 0.62) was also notable, outperforming C-reactive protein (k = 0.07) as a surrogate of disease activity. Additionally, SICUS provided valuable data in patients with prior resections and helped in surgical decision-making when IC was incomplete or inconclusive[6]. Collectively, these studies underscore SICUS as a highly accurate, non-invasive alternative to SBFT and SBE, with better tolerability, no radiation, and the added benefit of detecting both mural and transmural disease characteristics. While IC remains essential for mucosal evaluation and histology, SICUS offers critical complementary information, particularly for detecting fibrostenotic disease and proximal small bowel involvement that may be inaccessible to endoscopy.

Comparison of SICUS and CTE

Several studies (Table 1) have directly compared SICUS with CTE for the characterization of strictures in CD, consistently demonstrating comparable diagnostic performance. In a prospective study of 59 patients, Calabrese et al[7] reported that SICUS identified ileal strictures with 95.5% sensitivity, 80% specificity, and 91.5% diagnostic accuracy, with strong correlation to CTE in assessing both BWT (ρ = 0.79) and disease extent (ρ = 0.89). Notably, the correlation between SICUS and surgical measurements of disease length (ρ = 0.83) was higher than that of CTE (ρ = 0.68), suggesting better surgical concordance[7]. Similarly, in a surgical validation study, Onali et al[8] found that both SICUS and CTE detected strictures in nearly all patients, with SICUS slightly outperforming CTE for identifying prestenotic dilation (85% vs 82%) and achieving equivalent accuracy for detecting fistulas and abscesses. Chatu et al[6] supported these findings in a real-world UK cohort, reporting strong agreement between SICUS and CT (κ = 0.91) for detecting small bowel CD and strictures, with SICUS identifying all strictures that were also detected by CT and proving useful even when CT was inconclusive. These data collectively affirm that SICUS matches CTE in stricture detection and extent characterization, with the additional advantages of no radiation exposure, repeatability, and superior surgical correlation, supporting its role as a frontline imaging modality in experienced centers.

Comparison of SICUS and MRE

Multiple studies (Table 1) have demonstrated that SICUS performs comparably to MRE in detecting and characterizing strictures in CD. In a prospective pediatric study, Hakim et al[9] reported substantial agreement between SICUS and MRE in identifying strictures (κ = 0.77), proximal and distal disease location (κ = 0.78-0.87), and upstream dilatation (κ = 0.68), with SICUS detecting some dilatations missed by MRE. Kumar et al[10], in a surgical validation study, showed that SICUS achieved a sensitivity of 87.5% and κ = 0.73 for strictures compared to surgical findings, while MRE demonstrated slightly higher sensitivity (100%) and κ = 0.88. However, SICUS had superior sensitivity for detecting fistulae (88% vs 67%), bowel wall thickening (95% vs 82%), and dilatation (100% vs 67%) compared to MRE. Notably, the concordance between SICUS and MRE was almost perfect for identifying strictures and their number/Location (κ = 0.84-0.85), and substantial for mucosal thickening and fistulae (κ = 0.61-0.65)[10]. In a pediatric comparison by Aloi et al[11], SICUS and MRE were both effective in detecting ileal and colonic involvement, with SICUS demonstrating higher sensitivity for jejunal disease (92% vs 75%), while MRE was slightly more sensitive in the mid and proximal ileum. Collectively, these findings suggest that SICUS is a valid, accurate, and radiation-free alternative to MRE for stricture characterization in both children and adults, particularly advantageous in routine and repeated assessments where patient tolerance or access to MRE may be limiting.

Comparison of SICUS and small bowel capsule endoscopy

SICUS and small bowel capsule endoscopy (SBCE) offer complementary strengths in the assessment of CD, with SICUS excelling in transmural and stricturing disease, and SBCE in mucosal lesion detection. In a prospective multicenter pediatric study, Aloi et al[11] found comparable diagnostic yields between SICUS and SBCE for detecting ileal involvement, with both modalities identifying disease in 88% of patients with histologically confirmed CD. However, SBCE provided superior sensitivity for identifying jejunal lesions (92% vs 69% for SICUS), while SICUS was more effective in detecting wall thickening and strictures[11]. In contrast, Petruzziello et al[12] evaluated 30 adults with symptoms highly compatible with CD and inconclusive findings from conventional tests (including SICUS), and showed that SBCE identified lesions compatible with CD in 40% of cases that were not diagnosed by SICUS. Concordance between SBCE and SICUS was low (κ = 0.13), suggesting that SBCE may detect superficial mucosal lesions missed by SICUS, particularly in early or limited disease. Notably, SICUS detected a clinically relevant stricture in one patient where SBCE retention occurred, requiring surgical removal - highlighting SICUS's critical role in pre-SBCE screening to avoid complications[12]. Together, these studies demonstrate that while SBCE is valuable for visualizing mucosal ulcers and erosions, especially in the proximal small bowel, SICUS remains essential for assessing transmural disease, strictures, and for safely triaging patients before capsule endoscopy.

Comparison of SICUS and intraoperative findings

Both Pallotta et al[13] and Kumar et al[10] evaluated the diagnostic accuracy of SICUS against intraoperative findings in CD. In Pallotta’s prospective study of 49 surgical CD patients, SICUS demonstrated excellent sensitivity and specificity for detecting strictures (97.5%, 100%; κ = 0.93), fistulas (96%, 90.5%; κ = 0.88), and abscesses (100%, 95%; κ = 0.89), with strong agreement in stricture location and number. The extension of strictures measured by SICUS closely matched surgical values (6.6 cm vs 6.8 cm, not significant)[13]. Kumar et al’s retrospective study[10] (n = 25) yielded similarly high concordance: Sensitivity/specificity of 88% each for strictures (κ = 0.73), 86%/94% for fistulas (κ = 0.82), and 100%/95% for abscesses (κ = 0.87). Both studies confirm that SICUS reliably identifies and localizes CD-related complications - comparable to intraoperative assessment - supporting its use as a noninvasive, radiation-free, and accurate modality in the preoperative evaluation of complicated small bowel CD.

SICUS in detecting stricture due to postoperative recurrence of CD

SICUS has demonstrated high diagnostic accuracy in detecting postoperative recurrence (POR) of CD when compared with IC, the current gold standard. In a prospective study of 72 patients, Calabrese et al[14] reported that SICUS had a sensitivity of 92.5%, positive predictive value of 94%, and accuracy of 87.5% for detecting POR. Importantly, SICUS findings such as increased BWT > 3 mm, stricture, and prestenotic dilation significantly correlated with Rutgeerts’ endoscopic scores (r = 0.67, P < 0.0001), with greater BWT and lesion extent observed in patients with advanced recurrence (scores ≥ 3). SICUS was especially valuable in patients with anastomotic stenosis, where it enabled visualization of the neoterminal ileum that was inaccessible to endoscopy[14]. Similarly, Castiglione et al[15] showed that oral contrast-enhanced sonography - a variant of SICUS - achieved 82% sensitivity and 94% specificity, with a BWT threshold ≥ 4 mm accurately distinguishing severe recurrence (grades 3-4) from mild or no recurrence. Both studies underscore SICUS’s ability to detect transmural and stenosing disease recurrence with high correlation to endoscopic severity grading, supporting its utility as a noninvasive, repeatable modality for postoperative surveillance, especially in patients who are asymptomatic, at high risk, or unwilling to undergo endoscopy.

Overall diagnostic performance of SICUS

Common SICUS criteria included BWT > 3 mm, luminal diameter < 1 cm, and/or prestenotic dilation > 2.5 cm; across surgical and radiologic validation cohorts, these definitions yielded sensitivity typically approximately 88%-98% with context-dependent specificity.

CEUS

Several prospective studies (Table 2) have explored the role of CEUS in distinguishing inflammatory from fibrotic strictures in CD, with mixed results. Lu et al[2] demonstrated that CEUS parameters - particularly PE and AUC - were significantly reduced in fibrotic compared to inflammatory strictures, aligning well with histologic fibrosis scores. Similarly, Ma et al[16] found that CEUS combined with SWE could differentiate stricture phenotypes, with inflammatory lesions showing higher AUC and PE values. Quaia et al[17] also found that CEUS, especially when integrated with elastography, offered high diagnostic accuracy (AUC up to 0.95) in characterizing strictures, showing good interobserver agreement. In contrast, Serra et al[18] reported no significant correlation between CEUS enhancement patterns and histologic fibrosis grades; most strictures exhibited mixed inflammatory and fibrotic features, potentially confounding perfusion-based discrimination. Notably, in pediatric CD, Sidhu et al[19] observed significantly elevated AUC values on CEUS in patients requiring surgical resection, with strong correlation to muscularis propria hypertrophy and histologic fibrosis. Adding to this body of evidence, de Voogd et al[1] developed the Stricture Score Amsterdam by integrating B-mode ultrasound and CEUS parameters, including wash-in AUC and wall stratification loss, to accurately differentiate inflammatory and chronic strictures. The Stricture Score Amsterdam achieved an area under the receiver operating curve values of 0.88 and 0.90 for inflammatory and chronic phenotypes, respectively, with good interobserver agreement, underscoring CEUS’s reproducibility and added value beyond Doppler alone[1]. Together, these studies suggest that CEUS, particularly when integrated with structural and perfusion metrics, offers a valuable non-invasive tool in the multimodal assessment of stricture phenotype in CD.

CEUS vs MRE

CEUS and MRE are increasingly employed to assess transmural disease in CD. Comparative studies show key distinctions in their diagnostic capabilities. In a prospective study, Wilkens et al[20] found that neither CEUS nor dynamic contrast-enhanced MRE (DCE-MRE) showed significant correlation with histological scores of fibrosis or inflammation, although BWT measured on ultrasound correlated moderately with both inflammation (r = 0.61) and fibrosis (r = 0.40), while DCE-MRE tended to overestimate wall thickness with weaker correlations[20]. Horjus Talabur Horje et al[21] evaluated patients with active ileal CD - half of whom had strictures - and reported that CEUS was feasible even in the presence of strictures, showing higher concordance with endoscopic inflammation scores than MRE and greater sensitivity for detecting mucosal hyperemia. Although strictures were not quantitatively analyzed, their presence did not impair CEUS performance, suggesting its utility in evaluating inflammation within strictured segments[21]. Servais et al[22] further demonstrated that CEUS, particularly when combined with elastography, improved the ability to distinguish inflammatory from fibrotic strictures, with diagnostic performance comparable to MRE. Collectively, these findings support CEUS as a high-resolution, radiation-free tool for assessing Crohn’s strictures, particularly when paired with elastographic techniques, though standalone perfusion imaging alone may be insufficient to reliably separate fibrosis from inflammation.

Role of TIC parameters in CEUS for differentiating Crohn’s strictures

Quantitative analysis of CEUS using TICs offers valuable insight into the differentiation of inflammatory vs fibrotic Crohn’s strictures. Two key studies - Quaia et al[23] and Nylund et al[24] - demonstrate the diagnostic relevance of TIC-derived perfusion metrics. Quaia et al[23] found that inflammatory strictures showed significantly higher percentage of maximal enhancement and area under the enhancement curve (AUC) compared to fibrotic strictures (45.9% vs 37.3%, and 1168 vs 570, respectively; both P < 0.05), while time to PE was not significantly different[23]. Similarly, Nylund et al[24] used a pharmacokinetic modeling approach and reported that fibrotic segments had substantially lower absolute blood volume (0.9 mL/100 mL vs 3.4 mL/100 mL) and blood flow (22.6 mL/minute/100 mL vs 45.3 mL/minute/100 mL) than inflamed tissue, with no significant difference in mean transit time. These findings suggest that perfusion magnitude parameters (e.g., peak intensity, AUC, and flow) are more reliable than kinetic parameters [e.g., time to peak (TTP)] for fibrosis discrimination, and support the clinical utility of TIC-based CEUS quantification in evaluating Crohn’s strictures.

Role of CEUS parameters in monitoring biologic therapy response

Quantitative CEUS offers valuable insight into treatment monitoring in CD, particularly through software-generated TIC analysis. Goertz et al[25] evaluated CEUS-derived parameters in patients undergoing vedolizumab therapy and found that amplitude-based parameters, such as PE and wash-in AUC, significantly decreased in clinical responders over 14 weeks, while remaining stable or increased in non-responders. Notably, the wash-in rate was the only parameter to show a statistically significant decline across all responders (P = 0.016), indicating its potential as a robust early biomarker of therapeutic efficacy. In contrast, time-derived parameters such as TTP, rise time, and fall time did not consistently correlate with clinical response[25]. These findings align with earlier studies demonstrating that amplitude-related perfusion metrics outperform timing parameters in differentiating inflammatory activity. Thus, CEUS TIC analysis - particularly focused on PE, wash-in rate, and AUC - provides a promising noninvasive tool for tracking early biological response in stricturing CD, especially when conventional endoscopy is not feasible.

CEUS and Histology Correlation in CD

Several studies (Table 2) have investigated the relationship between CEUS parameters and histologic features of CD strictures, aiming to differentiate between inflammation and fibrosis. In a prospective surgical validation study, Serra et al[18] assessed CEUS, color Doppler, and real-time elastography (RTE) in resected bowel segments but found no significant correlation between CEUS perfusion patterns and histological scores of inflammation or fibrosis. Vascular signal intensity on CEUS also did not correlate with histologic vessel density, highlighting the limitations of qualitative CEUS for distinguishing fibrotic from inflammatory strictures in mixed lesions[18]. In contrast, Servais et al[22] applied TIC analysis and found that time-based CEUS parameters - specifically TTP and rise time - correlated well with histologic inflammation severity, achieving area under the receiver operating curves of 0.88 and 0.86, respectively. Although fibrosis was less consistently assessed due to the underrepresentation of low-fibrosis cases, the study demonstrated CEUS’s utility in identifying active inflammatory processes[22]. Ripollés et al[26] also observed that percentage enhancement increase was associated with histologic inflammation, while TTP inversely correlated with fibrosis, suggesting that perfusion delay may reflect transmural fibrotic remodeling. Additionally, Ponorac et al[27] reported a moderate correlation between quantitative CEUS perfusion metrics and histologic inflammation grades, although findings were tempered by variability in histologic scoring and sample size. Together, these studies suggest that while qualitative CEUS alone may have limited histologic concordance, quantitative TIC-derived parameters - especially time-based indices - offer meaningful correlation with inflammatory activity and may assist in the noninvasive characterization of CD strictures.

Experimental correlation between CEUS and biomechanical properties of CD strictures

In a unique prospective ex vivo study, Wilkens et al[28] investigated whether CEUS and DCE-MRE could predict the biomechanical stiffness of CD strictures by comparing imaging features with direct mechanical testing on surgically resected intestinal specimens. The stiffness of the stricture, quantified as circumferential Young’s modulus, was significantly associated with the initial slope of enhancement on DCE-MRE (ρ = 0.63, P = 0.007), indicating that increased perfusion on MRE may correspond to more active or stiffer lesions. In contrast, CEUS perfusion parameters, including peak intensity and wash-in slope, showed no significant correlation with biomechanical stiffness, highlighting limitations in CEUS alone for quantifying fibrotic remodeling. However, structural features on preoperative ultrasound, particularly the degree of prestenotic dilatation, were positively associated with stiffness (τb = 0.43, P = 0.02), suggesting a potential surrogate marker for fibrotic strictures. Furthermore, BWT measured on ultrasound (ρ = 0.48, P = 0.045) and MRE global activity score (MEGS, ρ = 0.55, P = 0.018) were moderately correlated with stiffness, whereas elastography did not reliably reflect biomechanical properties. These findings underscore the complexity of transmural remodeling in Crohn’s strictures and suggest that while CEUS may not directly quantify stiffness, its utility may increase when combined with structural markers or elastography within a multimodal framework[28].

CEUS-based perfusion quantification and stenosis scoring

In a prospective pilot study, Schirin-Sokhan et al[29] investigated the ability of CEUS to differentiate inflammatory from fibrostenotic small bowel strictures in CD using a novel computerized algorithm. Eighteen patients with significant small bowel strictures underwent standardized CEUS with time-intensity curve analysis using QONTRAST software, alongside color Doppler and clinical evaluation. Despite reliable quantification of vascularity parameters - PE, TTP, and rise rate - none of these quantitative CEUS metrics showed significant correlation with the histologic or clinical classification of strictures. Instead, a composite “stenosis score” incorporating histology, Rutgeerts score, and therapeutic response was more reflective of stricture phenotype. Interestingly, semiquantitative measures such as the Limberg score and Crohn’s disease Activity Index were significantly associated with inflammatory stenosis, and a high CEUS rise rate was associated with earlier need for surgery in inflammatory cases[29]. This suggests that while CEUS-based perfusion metrics may not reliably distinguish fibrosis from inflammation at a single time point, they may hold prognostic value, particularly in stratifying patients for early surgical intervention.

Overall results of CEUS in phenotype differentiation

Across studies using TIC analysis, lower PE (e.g., approximately ≤ 30 dB) and reduced perfusion AUC (e.g., approximately ≤ 700 intensity time units) were associated with fibrosis, whereas higher values suggested inflammatory activity.

Elastography for characterizing CD strictures

Ultrasound-based elastography has been increasingly explored for differentiating fibrotic from inflammatory strictures in CD (Table 3). In a landmark study, Baumgart et al[30] demonstrated that RTE could detect increased stiffness in fibrotic bowel segments compared to unaffected tissue, showing a good correlation with surgical histology. Similarly, Chen et al[31] employed SWE and found that shear wave speed was significantly higher in fibrotic vs inflammatory strictures (2.78 m/second vs 1.59 m/second, P < 0.001), with a high AUC (AUC = 0.902) for fibrosis detection. Sconfienza et al[32] applied axial strain sonoelastography to classify strictures into elastic, intermediate, and stiff categories and observed a strong correlation with histologic fibrosis, highlighting its potential for preoperative stricture characterization. However, findings from Serra et al[18] were more cautious - while they attempted to correlate strain ratios (SRs) from RTE with histologic scores, no significant association was found, possibly due to high coexisting inflammation within fibrotic segments. Taken together, these studies suggest that while elastography - especially SWE and axial strain methods - holds promise for noninvasive fibrosis detection in CD strictures, results may vary by technique, operator, and disease phenotype, and standardized protocols with histologic validation remain essential.

SR in differentiating fibrosis in CD strictures

SR from RTE provides a semi-quantitative assessment of bowel wall stiffness and has been evaluated as a marker to differentiate fibrotic from inflammatory strictures in CD. In a prospective surgical validation study, Fraquelli et al[33] reported that SR values were significantly higher in patients with severe histologic fibrosis (median SR: 2.64) compared to those with mild or no fibrosis (median SR: 1.16), with an AUC of 0.91 for detecting high-grade fibrosis. Mazza et al[34] also demonstrated a strong correlation between SR and histological fibrosis score (r = 0.76), with mean SR values of 3.0 ± 0.5 in fibrotic segments vs 1.7 ± 0.4 in non-fibrotic ones, and found SR to outperform MRE-based fibrosis indices. In the study by Orlando et al[35], SR values were significantly higher in fibrostenotic strictures (mean SR: 3.18 ± 1.07) compared to predominantly inflammatory lesions (mean SR: 1.45 ± 0.58), with an optimal cut-off SR > 2.2 yielding a sensitivity of 83% and specificity of 88%. There was no improvement in strain ratio after anti-TNF therapy. Another study by Matsumoto et al[36], showed SWE indices did not change in the infliximab or bio-switch groups, while only the ustekinumab group showed a significant shear wave speed reduction. This likely reflects longstanding fibrosis in bio-switch patients and suggests that early ustekinumab may better suppress fibrotic progression, pending histological confirmation. In contrast, Serra et al[18] reported no statistically significant difference in SR across fibrosis grades, with overlapping values and poor correlation with histologic scores, possibly due to high coexisting inflammation and technical variability in strain measurement. Taken together, these findings suggest that SR thresholds between 2.2 and 3.0 may help discriminate fibrotic strictures in selected settings, but variability across studies underscores the need for technical standardization and multi-institutional validation before clinical adoption.

SWE in CD stricture characterization

SWE has emerged as a promising quantitative tool to differentiate fibrotic from inflammatory strictures in CD. In a prospective study, Chen et al[31] demonstrated that fibrotic strictures exhibited significantly higher shear wave velocities (2.78 ± 0.53 m/second) than inflammatory ones (1.59 ± 0.41 m/second), with an AUC of 0.902 for fibrosis detection. Similarly, Lu et al[2] reported velocities of 3.43 ± 0.70 m/second in fibrotic segments vs 2.13 ± 0.60 m/second in inflammatory ones, alongside significantly higher Young’s modulus values (40.2 ± 7.3 kPa vs 22.2 ± 6.7 kPa), correlating well with histology[2]. Ma et al[16] supported these findings, showing shear wave speeds of 3.63 ± 0.86 m/second in fibrotic strictures and 2.51 ± 0.66 m/second in inflammatory ones, with parallel differences in elasticity modulus (42.1 ± 14.5 kPa vs 21.4 ± 8.8 kPa). Abu-Ata et al[37] also found SWE effective, distinguishing fibrotic (2.9 ± 0.6 m/second) from inflammatory strictures (1.7 ± 0.5 m/second) with strong histologic correlation. In pediatric CD, Fufezan et al[38] reported slightly elevated velocities in active disease (1.59 ± 0.27 m/second) compared to inactive (1.39 ± 0.24 m/second), suggesting SWE’s potential in pediatric monitoring. However, Sidhu et al[19] noted minimal SWE differences between fibrotic and inflammatory groups (1.26 m/second vs 1.23 m/second), though CEUS in the same study performed better. Based on current evidence, a shear wave velocity cut-off of approximately 2.5 m/second appears to distinguish fibrotic from inflammatory strictures in most adult studies, though variability across patient populations, techniques, and equipment underscores the need for further standardization before clinical adoption.

Comparative performance of strain elastography, acoustic radiation force impulse imaging, and point SWE in CD stricture assessment

Ding et al[39] conducted a prospective study comparing three ultrasound elastography techniques - strain elastography (SE), acoustic radiation force impulse (ARFI) imaging, and point SWE (p-SWE) - in 25 patients with suspected CD strictures. Histopathology was used as the reference standard. The results showed that p-SWE outperformed both SE and ARFI in distinguishing fibrotic from inflammatory strictures. Specifically, a shear wave velocity cut-off of 2.73 m/second yielded a sensitivity of 75%, specificity of 100%, accuracy of 96%, and an AUC of 0.833 (P < 0.05). In contrast, SE and ARFI - both semi-quantitative methods - had lower diagnostic performance: For SE (cut-off score ≥ 4), sensitivity was 75%, specificity 66.7%, accuracy 68%, and AUC 0.708 (P = 0.195); while ARFI imaging (cut-off score ≥ 4) had sensitivity 50%, specificity 81%, accuracy 76%, and AUC 0.696 (P = 0.221)[39]. These findings highlight the superior reproducibility and diagnostic accuracy of p-SWE over qualitative or semi-quantitative techniques, reinforcing its potential as a reliable tool for non-invasive fibrosis detection in Crohn’s strictures.

Preclinical and ex vivo studies

Several preclinical and ex vivo studies (Table 3) have validated ultrasound-based elastography for distinguishing fibrotic from inflammatory CD strictures. In a TNBS-induced rat colitis model, Stidham et al[40] demonstrated that TAS elasticity imaging could differentiate stricture phenotype, with significantly lower normalized strain in inflamed segments (-2.07 ± 0.71) compared to fibrotic segments (-1.10 ± 0.40, P < 0.05). These values correlated with ex vivo tensiometry: Fibrotic colon showed a Young’s modulus of 2.75 kPa vs 0.30 kPa in healthy control tissue (P < 0.01)[40]. Using ex vivo human ileal specimens, Baumgart et al[30] applied RTE and reported median strain values of 1.56 in fibrotic bowel vs 3.74 in non-fibrotic regions (P < 0.0001), correlating strongly with histological collagen deposition. Dillman et al[41] further confirmed this relationship in a blinded study using resected ileal specimens, showing that strain values from ultrasound elastography inversely correlated with histologic fibrosis grade (ρ = -0.66, P < 0.001) and hydroxyproline content (ρ = -0.72,P < 0.001), a marker of collagen load. These models underscore the mechanistic validity of elastographic parameters and support their translational role as biomechanical biomarkers for fibrotic stricture assessment in CD.

Elastography and histology correlation in CD strictures

Multiple studies (Table 3) have explored the correlation between elastographic findings and histological measures of fibrosis and inflammation in CD strictures. Chen et al[31] demonstrated that SWE significantly differentiated fibrotic from inflammatory strictures, with higher mean shear wave velocities in fibrotic segments and a strong correlation with histologic fibrosis scores (ρ = 0.74, P < 0.001). Similarly, Abu-Ata et al[36] found that SWE velocity values correlated well with histological fibrosis grade, reporting a sensitivity of 80% and specificity of 85% using a 2.5 m/second cut-off. Lu et al[2] further corroborated this association by integrating CEUS with SWE, noting that fibrotic segments had significantly higher stiffness values and lower enhancement, both of which aligned with histological scoring. On the SE side, Fraquelli et al[33] showed that the mean SR correlated inversely with fibrosis severity (SR: 2.3 ± 1.0 in mild vs 4.5 ± 1.4 in severe fibrosis, P < 0.01). However, Serra et al[18] reported no significant correlation between SR and histologic fibrosis (P = 0.877), possibly due to overlapping inflammation and fibrosis in many segments. In experimental validation, Stidham et al[39] used ex vivo tissue and rat models to confirm that ultrasound-based elasticity imaging could accurately differentiate inflammatory from fibrotic tissue, with strain values of -0.87 in fibrotic vs -1.99 in normal bowel (P = 0.0008), and strong inverse correlation with Young’s modulus (r = -0.81). Collectively, these findings suggest that while not universally consistent across all techniques, elastography - particularly SWE - demonstrates promising correlation with histologic fibrosis and may serve as a valuable non-invasive biomarker in CD stricture phenotyping.

Comparison of elastography with cross-sectional imaging for CD stricture assessment

Recent studies (Table 3) have highlighted that ultrasound elastography - particularly SWE - may provide greater specificity for detecting fibrosis compared to MRE or CTE. In a prospective study, Mazza et al[34] found that RTE SRs significantly correlated with histologic fibrosis (ρ = 0.63, P < 0.01), whereas delayed enhancement on MRE showed weaker correlation (ρ = 0.32, P = 0.09), suggesting RTE may outperform MRE in fibrosis detection. Similarly, Sconfienza et al[32] observed that axial strain sonoelastography could distinguish inflammatory from fibrotic strictures with greater clarity than MR findings, which were often limited by overlapping features. Zhang et al[42] directly compared SWE and CTE in 37 surgical CD cases: SWE showed strong correlation with fibrosis (r = 0.653), using a cut-off of 21.3 kPa (AUC: 0.877; sensitivity 88.9%, specificity 89.5%), while CTE correlated better with inflammation (r = 0.479), using a 4.5-point score (AUC: 0.766). When combined, SWE and CTE improved diagnostic accuracy (AUC: 0.918; specificity: 94.7%)[41]. These findings suggest that while CTE and MRE are valuable for detecting inflammation and complications, elastography - especially SWE - offers a more targeted and quantitative approach for fibrosis evaluation in CD strictures.

Role of elastography in differentiating CD strictures among chronic diarrhea patients

In a large retrospective cohort of 225 patients presenting with chronic diarrhea, Kapoor et al[43] evaluated the utility of combining SWE and shear wave dispersion (SWD) with IUS for characterizing bowel wall abnormalities. Among 76 patients with thickened bowel walls, 33 had fibrotic strictures - 11 of which were due to CD. These fibrotic CD strictures demonstrated a mean Young’s modulus (E) of 33 kPa and SWD of 9 m/second/kHz, indicating stiff yet non-viscous bowel wall changes. This contrasted with inflammatory CD cases, which had high SWD (mean 19.5 m/second/kHz) and normal stiffness (E approximately 6.5 kPa), reflecting increased tissue viscosity without fibrosis. Mixed phenotype strictures showed intermediate values. Notably, the presence of stricture length > 5 cm, SBWT > 5.8 mm, fistula formation, and Limberg grade 2 on IUS were distinguishing features in fibrotic CD. With an E cutoff > 22 kPa, SWE showed 100% sensitivity and 94% specificity for fibrosis detection. This two-step SWE + IUS approach outperformed contrast-enhanced CT, which had only 27% sensitivity for inflammatory changes. These findings highlight the emerging role of multiparametric ultrasound - including SWE and SWD - in identifying fibrotic Crohn’s strictures in patients with chronic diarrhea.

Overall results of elastography in fibrosis quantification

Most adult cohorts reported shearwave velocity thresholds around 2.5-2.9 m/second indicating fibrosis, with sensitivities approximately 80%-88% and specificities ≈85%-100%; reported strainratio thresholds ranged approximately 2.2-3.0 in surgical validation studies.

DISCUSSION

This scoping review demonstrates that multimodal IUS, including SICUS, CEUS, and elastography, offers high diagnostic accuracy for detecting and characterizing CD strictures. SICUS consistently identified strictures and assessed disease extent with sensitivity ranging from 88% to 98%. CEUS provided valuable perfusion-based differentiation between inflammatory and fibrotic lesions, with PE < 30 dB and AUC < 700 units correlating with fibrosis. Elastographic modalities, particularly SWE, showed strong correlation with histology, using cutoffs of 2.5-2.9 m/second and SR thresholds between 2.2 and 3.0 to differentiate fibrosis (Figure 2). SICUS demonstrated diagnostic performance comparable to cross-sectional imaging while offering the advantages of safety, repeatability, and high sensitivity for strictures. It reliably identified proximal disease and POR, with good agreement with surgical and histologic findings. Compared to MRE and CTE, SICUS showed superior correlation with surgical disease length and stricture detection, especially in pediatric and postoperative cohorts[9,11].

Figure 2 B-mode intestinal ultrasound. A: Terminal ileal stricture; B: Prestenotic dilation; C: Dual mode scanning before injecting intravenous contrast for contrast enhanced ultrasound; D: Peak enhancement after contrast injection; E: Wash out during contrast enhanced ultrasound; F: Shear wave elastography showing stiffness of 42.1 kPa; G: Colonoscopic view of stricture; H: Real time elastography showing a soft stricture showing predominantly red and green areas; I: Small intestinal contrast ultrasound showing mid ileal stricture with enteroliths; J: Ileal stricture with prestenotic dilation on small intestinal contrast ultrasound seen using curvilinear probe (1-7 MHz); K: Same stricture seen with linear probe (2-9 MHz).

CEUS effectively identified perfusion differences between inflammatory and fibrotic strictures using TIC-derived parameters. While some studies showed conflicting histologic correlations, the integration of CEUS with elastography enhanced diagnostic accuracy. CEUS was particularly useful for therapy monitoring, with amplitude-based parameters (e.g., PE and wash-in AUC) reflecting biologic response[25]. Its role is complementary to MRE, offering bedside feasibility and radiation-free monitoring[20]. Among elastographic techniques, SWE emerged as the most reproducible and quantitatively robust modality, with strong correlation to histologic fibrosis and defined velocity thresholds[38]. SR also performed well in surgical validation studies but showed variability across operators and equipment[33]. Ex vivo and preclinical models supported the mechanistic basis of elastographic stiffness metrics, reinforcing their translational value[30,39].

The review included heterogeneous study designs, varied reference standards, and different ultrasound platforms, which may affect generalizability. Few studies employed standardized acquisition protocols or centralized image analysis. Histologic correlation, while strong in some studies, was not universally available or uniformly scored. Pediatric data were limited, and there is a lack of large, multicenter validation studies comparing all modalities head-to-head. Additionally, elastography techniques remain operator-dependent and technically challenging in deep or obese abdomens.

Future research should focus on multicenter prospective trials with histologic validation to standardize cutoff values and optimize acquisition protocols. Development of composite sonographic scores integrating B-mode, SICUS, CEUS, and elastographic features may enhance diagnostic precision. Training programs and certification in advanced IUS techniques should be promoted to improve operator consistency. With increasing evidence, multimodal IUS could become the frontline tool for stricture evaluation, replacing radiation-based imaging in selected scenarios. Technological advancements in artificial intelligence assisted analysis may further enhance its diagnostic capability. Included studies varied in patient selection, index definitions and thresholds, image acquisition platforms, and reference standards (surgery, histology, cross-sectional imaging, endoscopy, or clinical follow-up). Pediatric data were sparse, and few multicenter validations were available. These factors limit cross-study comparability and precluded metaanalysis.

Implications and research agenda

Standardize CEUS TIC acquisition and reporting (PE, AUC) and define modality-specific cut-offs for fibrosis vs inflammation. Validate shear-wave elastography thresholds across vendors and body habitus; establish reference phantoms and quality metrics. Develop composite IUS scores integrating B-mode, SICUS, CEUS, and elastography, with surgical/histologic validation. Prioritize multicenter prospective cohorts with prespecified outcomes, blinded reads, and core lab analysis.

CONCLUSION

In conclusion, multimodal IUS, including SICUS, CEUS, and elastography, offers a comprehensive, radiation-free strategy for the detection and phenotyping of CD strictures. Each modality contributes unique diagnostic insights - from mural visualization and perfusion assessment to tissue stiffness quantification. With high accuracy, histologic correlation, and potential for real-time decision-making, these techniques support individualized management and improved outcomes in CD. Ongoing efforts toward standardization, validation, and dissemination are critical for widespread clinical adoption.