Multimodality ultrasound in Crohn’s disease strictures

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.