Intestinal ultrasound in Crohn’s disease: A systematic review of its role in diagnosis, monitoring, and treatment response

Table 1 Summary of studies evaluating impact of intestinal ultrasound in the management of Crohn’s disease

Ref.	Study type	Number of patients	Impact on management
Novak et al[18], 2015	Prospective	49 CD	Clinical decisions changed in up to 60% of cases post-IUS compared to before IUS. Half of the patients with clinically asymptomatic disease had active disease on IUS
Wilkens et al[19], 2015	Retrospective	115 CD	70% with mild or no endoscopic inflammation on ileo-colonoscopy had moderate to severe disease on IUS. 75% of the above group had significant management changes
Kakkadasam Ramaswamy et al[27], 2020	Prospective	35 CD	IUS findings of BWT, BWS, and CDS activity correlate with endoscopic and clinical indices. Sensitivity (MRE gold standard): Transverse colon (100%) > ileum (93.7%) > left colon (89%) > right colon (80%). Specificity: 100% (all segments)
Freitas et al[39], 2022	Retrospective	50 CD	SUS-CD and IBUS-SAS scores in IUS were not different between active and inactive disease. Peak intensity in contrast-enhanced IUS correlated well with endoscopic activity (AUC: 0.80)
Bots et al[20], 2022	Retrospective	280 CD	60% had an impact on disease management and predicted preclinical relapse. Good correlation with MRI (86.3%) and endoscopy (80%). Use of MRI reduced after IUS
Allocca et al[64], 2022	Prospective	225 ileal and/or colonic disease	Bowel ultrasound score > 3.52, complications (stricture, fistula, abscess), fecal calprotectin ≥ 250 µg/g, and male sex predicted the 12-month course in CD
Esteban et al[23], 2001	Prospective	79	Color Doppler ultrasound showed increased vascularity in active CD. RI was lower in active vs inactive cases, correlating with clinical and histological activity
Goertz et al[26], 2021	Retrospective	221	Bowel wall thickening (> 3 mm) and hypervascularization strongly correlated with histological inflammation in Crohn’s ileitis. Limberg score had significant correlation with histopathology
Pedersen et al[22], 1986	Prospective	30 CD, 27 controls	Dynamic ultrasound detected bowel wall thickening (target lesions) in 67% of radiologically confirmed CD. Found useful for follow-up to reduce repeated radiographic exams

CD: Crohn’s disease; UC: Ulcerative colitis; IUS: Intestinal ultrasound; SUS-CD: Simple ultrasound activity score for Crohn’s disease; IBUS-SAS: International bowel ultrasound segmental activity score; AUC: Area under the curve; BWT: Bowel wall thickness; BWS: Bowel wall stratification; CDS: Colour doppler signal; MRI: Magnetic resonance imaging; MRE: Magnetic resonance enterography; RI: Resistive index.

Table 2 Studies summarizing utility of contrast-enhanced ultrasound in Crohn’s disease activity assessment

Ref.	Study type	Number of patients	Utility of CEUS in CD
Sidhu et al[50], 2023	Retrospective	25 pediatric	CEUS with shear wave elastography differentiated inflammatory from fibrotic strictures, correlating with histopathology
Wang et al[36], 2024	Retrospective	52	CEUS detected active inflammation using dynamic perfusion parameters with high sensitivity (97.4%) and specificity (100%)
Cheng et al[33], 2016	Retrospective	77	CEUS quantified intestinal wall perfusion and identified influencing factors like depth, pressure, and intraluminal gas
Giangregorio et al[29], 2009	Prospective	30	CEUS predicted clinical activity and follow-up outcomes using time-intensity curves and vascularization analysis
Girlich et al[30], 2009	Retrospective	20 CD, 4 controls	Quantified bowel wall vascularity and inflammation with CEUS, showing significant differences compared to controls
Horjus Talabur Horje et al[32], 2015	Prospective	105	CEUS matched MRE accuracy (99%) for active ileitis, with high sensitivity (100%) and specificity (92%)
Kratzer et al[28], 2005	Prospective	21	CEUS quantified vascularity and differentiated active from inactive CD and other complications like abscesses
Laterza et al[102], 2020	Prospective	54	CEUS perfusion parameters predicted response to anti-TNF therapy and identified patients at risk of clinical relapse
Białecki et al[34], 2014	Prospective	42	CEUS correlated with endoscopic activity and fecal calprotectin. Higher vascularity and peak enhancement indicated active CD
Ding et al[149], 2022	Prospective	76	CEUS showed similar diagnostic accuracy to CTE for active inflammation. CEUS was better at detecting mural vascularization
Guidi et al[113], 2006	Prospective	25	CEUS predicted response to infliximab in active CD by assessing vascularization and bowel wall enhancement
Malagò et al[47], 2012	Prospective	30	CEUS findings showed good correlation with MRI in lesion length, wall thickness, and inflammatory activity assessment
Nylund et al[44], 2013	Retrospective	37	Quantitative CEUS differentiated inflammatory from fibrotic strictures based on blood flow and volume
Paredes et al[45], 2013	Prospective	60	CEUS demonstrated high accuracy (98.3%) for postoperative recurrence in CD, correlating well with endoscopy
Pauls et al[46], 2006	Prospective	21	CEUS and MRI were comparable in evaluating vascularity and bowel wall inflammation in active CD
Ponorac et al[48], 2023	Prospective	36 pediatric	CEUS showed high specificity (100%) for assessing pediatric CD activity, correlating well with endoscopy and PCDAI scores
Ripollés et al[93], 2013	Retrospective	50	CEUS differentiated phlegmon from abscess with 100% specificity, aiding in treatment planning for CD complications
Ripollés et al[31], 2013	Prospective	25	CEUS differentiated inflammatory from fibrostenotic lesions with good correlation to histopathology, aiding in therapy decisions
Mao et al[49], 2018	Prospective	31	CEUS detected fistulous tracts associated with abscesses, with high sensitivity (86.7%) and specificity (100%), improving diagnostic precision
Schirin-Sokhan et al[42], 2011	Prospective	18	CEUS demonstrated partial agreement with CDS and was superior for therapy response assessment in active CD
Wilkens et al[38], 2018	Retrospective	50	High peak CEUS enhancement with minimal decline suggested severe CD due to prolonged microbubble retention in inflamed bowel walls
Wilkens et al[87], 2018	Prospective	20	CEUS and dynamic CE-MRE provided complementary insights into stricture stiffness, with CEUS emphasizing inflammatory characteristics

CD: Crohn’s disease; CEUS: Contrast-enhanced ultrasound; CDS: Colour doppler signal; MRI: Magnetic resonance imaging; MRE: Magnetic resonance enterography; TNF: Tumor necrosis factor; PCDAI: Pediatric Crohn’s Disease Activity Index.

Table 3 Studies summarizing utility of small intestinal contrast ultrasound in Crohn’s disease

Ref.	Study type	Number of patients	Impact on management
Hakim et al[54], 2019	Retrospective	93 pediatric	Sensitivity of 98.7% and specificity of 100% for small bowel lesions; substantial agreement with MRE (κ = 0.77)
Pallotta et al[55], 2013	Prospective	51 pediatric	Sensitivity of 96% in proven CD, superior to conventional ultrasound for jejunal and ileal lesions, with excellent lesion localization
Parente et al[56], 2004	Prospective	102 adults	Comparable to barium studies for disease extent; improved interobserver agreement after contrast ingestion
Onali et al[60], 2012	Prospective	15 adults	Sensitivity of 92% for strictures; comparable to CTE for lesions and luminal complications

CD: Crohn’s disease; MRE: Magnetic resonance enterography; CTE: Computed tomography enterography.

Table 4 Studies evaluating scoring systems to assess disease activity in inflammatory bowel diseases based on intestinal ultrasound

Ref.	Study type	Follow up	IUS activity	Comparator	Number of patients	Result
Liu et al[60], 2020	Retrospective	8 weeks	UCS	SES-CD	66 CD	UCS > 6 had 92.3% accuracy to identify endoscopically active disease
Allocca et al[64], 2022	Prospective, observational	6 months	BUSS	SES-CD	49 CD	BUSS determined endoscopic response with 80% accuracy and endoscopic remission with 78%
Wang et al[66], 2023	Retrospective	14 months (median)	IBUS-SAS, SUS-CD	SES-CD	140 CD	IBUS-SAS > 48.7 (AUC: 0.895) and SUS-CD > 2.5 (AUC: 0.835) correlated with SES-CD
Kumar et al[67], 2024	Retrospective	6 months	SUS-CD	SES-CD	98 CD	SUS-CD > 3.4 had sensitivity of 82.5% and specificity of 89.2% for active disease
Wang et al[69], 2024	Retrospective	12 weeks	IBUS-SAS	SES-CD	60 pediatric CD	IBUS-SAS showed sensitivity of 87% and specificity of 85% for infliximab response
Xu et al[68], 2023	Prospective	NA	IBUS-SAS	MARIA and SES-CD	100 CD	IBUS-SAS > 47.5 (AUC: 0.91) correlated with MARIA and SES-CD for assessing mucosal activity
Novak et al[59], 2017	Retrospective	NA	SUS-CD	SES-CD, Rutgeerts	160 CD	SUS-CD based on wall thickness and Doppler correlated with endoscopy (AUC: 0.8658)
Ripollés et al[61], 2021	Prospective	NA	Wall thickness, Doppler, and contrast parameters	SES-CD	72 CD	Combined parameters showed AUC: 0.972 for active disease; simpler score AUC: 0.923
Sævik et al[62], 2020	Prospective	NA	Simple ultrasound activity score	SES-CD	40 development, 124 validation	Ultrasound activity index based on wall thickness and Doppler correlated well with SES-CD (AUC: 0.92)

CD: Crohn’s disease; IUS: Intestinal ultrasound; UCS: Ultrasound consolidated score; SES-CD: Simple endoscopic score for Crohn’s disease; BUSS: Bowel ultrasound score; IBUS-SAS: International bowel ultrasound segmental activity score; SUS-CD: Simple ultrasound score for Crohn’s disease; AUC: Area under the curve; FC: Fecal calprotectin; MARIA: Magnetic resonance index of activity.

Table 5 Summary of studies evaluating role of intestinal ultrasound elastography in characterizing strictures in Crohn’s disease

Ref.	Study type	Number of patients	IUS parameter	Follow up	Results
Maconi et al[72], 2003	Retrospective	43 (with single ileal stenosis undergoing surgery)	Echo pattern at stenosis site	Cross sectional	Stratified echo pattern: Fibrotic stricture; Hypoechoic pattern: Inflammatory stricture; Mixed echo pattern: Mixed stricture
Fraquelli et al[76], 2015	Prospective	23 ileal or ileocolonic CD for surgery (20 inflammatory CD as controls)	Quantitative strain ratio in ileum	Cross sectional	Higher strain ratio indicated higher ileal fibrosis based on semiquantitative and quantitative analysis (Masson’s trichrome staining). Excellent inter-rater agreement for assessing strain ratio
Serra et al[77], 2017	Prospective	26 symptomatic stricturing CD	MSR	Cross sectional	No significant correlation was found between MSR and fibrosis score (P = 0.877). MSR could not distinguish fibrotic from inflammatory stricture
Chen et al[73], 2018	Prospective	35 with ileal/ileocolonic stricture enrolled	SWE, Vascularization	Cross sectional	22.55 KPa was the cut-off in discriminating mild-moderate vs severe fibrosis (AUC 0.822). Vascularization (Limberg III/IV) predicted severe inflammation vs mild-moderate inflammation (AUC 0.811)
Orlando et al[78], 2018	Prospective	30 ileal/ileocolonic CD	Strain ratio	20 months (median)	Inverse correlation between strain ratio at baseline and thickness variations on anti-TNF therapy at 12 and 52 weeks. Baseline strain ratio lower in patients with transmural healing
Ding et al[85], 2018	Prospective	25 strictures	Strain elastography, ARFI, and SWE	Cross sectional	Shear wave velocity > 2.73 m/s had the highest accuracy (96%) compared to ARFI (accuracy 76%) and strain elastography (accuracy 68%)
Wilkens et al[87], 2018	Prospective	25 CD	Contrast enhancement	Cross sectional	No correlation between inflammation and fibrosis on histology with contrast-enhanced ultrasound (r = 0.16, P = 0.45 for inflammation and r = -0.28, P = 0.19 for fibrosis)
Ueno et al[84], 2022	Retrospective	36 CD	ARFI	30 months	Strong correlation noted between fibrocyte numbers and ARFI on IUS (R = 0.8383). High fibrocyte number associated with escalation of medical therapy and endoscopic/surgical treatment at 30 months follow-up
Zhang et al[81], 2022	Retrospective	37 CD	Shear wave elastography and CT enterography	30 months	The cut-off value for fibrotic lesions stiffness > 21.30 KPa (AUC: 0.877, sensitivity: 88.90%, specificity: 89.50%, 95%CI: 0.755–0.999, P < 0.001)
Sidhu et al[50], 2023	Retrospective	25 Pediatric	Shear wave elastography	Cross-sectional	SWE differentiated fibrotic from inflammatory strictures with good accuracy
Chen et al[73], 2024	Retrospective	130	SWE and stiffness thresholds	33 months	SWE (> 12.75 kPa) predicted progression to stricturing/penetrating disease with AUC: 0.792
Zhao et al[82], 2021	Retrospective	19	Histologic correlation with stiffness	Cross-sectional	Bowel stiffness correlated strongly with histopathology, including fibrosis and chronic inflammation (r > 0.69, P < 0.001)

IUS: Intestinal ultrasound; CD: Crohn's disease; AUC: Area under the curve; ARFI: Acoustic radiation force impulse; TNF: Tumor necrosis factor; SWE: Shear wave elastography; MSR: Mean strain ratio; CT: Computed tomography.

Table 6 Summary of studies evaluating role of contrast enhanced ultrasound in characterizing strictures in Crohn’s disease

Ref.	Study type	Number of patients	IUS parameter	Follow-up	Results
Białecki et al[34], 2014	Prospective	42 (Adult CD)	CEUS	Cross-Sectional	CEUS correlated with endoscopic activity and fecal calprotectin; higher vascularity and peak enhancement indicated active CD
Ding et al[149], 2022	Prospective	76 (Adult CD)	CEUS vs CTE	Cross-Sectional	CEUS showed similar diagnostic accuracy to CTE for active inflammation; CEUS was better at detecting mural vascularization
Guidi et al[113], 2006	Prospective	25 (Adult CD)	CEUS	Cross-Sectional	CEUS predicted response to infliximab in active CD by assessing vascularization and bowel wall enhancement
Malagò et al[47], 2012	Prospective	30 (Adult CD)	CEUS vs MRI	Cross-Sectional	CEUS findings correlated well with MRI in lesion length, wall thickness, and inflammatory activity assessment
Nylund et al[44], 2013	Retrospective	37 (Adult CD)	Quantitative CEUS	Cross-Sectional	Quantitative CEUS differentiated inflammatory from fibrotic strictures based on blood flow and volume
Paredes et al[45], 2013	Prospective	60 (Adult CD Post-Surgery)	CEUS Parameters	Cross-Sectional	Sonographic score using CEUS achieved 98% sensitivity and 100% specificity for detecting postoperative recurrence; kappa = 0.946
Pauls et al[46], 2006	Prospective	21 (Adult CD)	CEUS vs Dynamic MRI	Cross-Sectional	High correlation between CEUS and MRI in assessing bowel wall vascularity; CEUS showed 217.5% enhancement compared to MRI's 262%, r = 0.623
Ponorac et al[48], 2023	Prospective	36 (Pediatric CD)	Quantitative CEUS, PCDAI, and fecal calprotectin	Cross-Sectional	Quantitative CEUS demonstrated 78.57% sensitivity and 100% specificity compared to endoscopy; substantial agreement with PCDAI (kappa = 0.62)
Wang et al[36], 2024	Retrospective	52	Dynamic CEUS parameters	12 months	CEUS showed high sensitivity (97.4%) and specificity (100%) for active CD
Ripollés et al[93], 2013	Retrospective	50 (Adult CD)	CEUS (Phlegmon vs Abscess)	Cross-Sectional	CEUS showed 100% specificity for distinguishing abscess from phlegmon, with excellent interobserver agreement (kappa = 0.953)
Ripollés et al[31], 2013	Prospective	25 (Adult CD undergoing surgery)	CEUS vs histopathology	Cross-Sectional	CEUS correctly classified 23/28 segments based on histopathological inflammation or fibrostenosis with substantial agreement (kappa = 0.632)

CD: Crohn’s disease; CEUS: Contrast-enhanced ultrasound; IUS: Intestinal ultrasound; CTE: Computed tomography enterography; MRI: Magnetic resonance imaging; PCDAI: Pediatric Crohn’s Disease Activity Index.

Table 7 Role of intestinal ultrasound in predicting response to biologic therapy

Ref.	Study type	Number of patients	Biologic agent	IUS predictors	Follow up	Time points of IUS	Therapeutic outcomes
Moreno et al[96], 2014	Prospective	34 CD	Anti-TNF and/or immunomodulators	Wall thickness, CDS, wall enhancement	1 year	Baseline and 1 year	Good correlation between endoscopic remission and sonographic normalization (κ = 0.73, P < 0.001), highest correlation with wall thickness
Orlando et al[78], 2018	Prospective	30 CD	Anti-TNF	Strain ratio ≥ 2; BWT ≤ 3 mm	52 weeks	Baseline, week 14 and 52	Surgery higher with strain ratio ≥ 2. Lower strain ratio in those with transmural healing
Paredes et al[98], 2019	Prospective	36 CD	Anti-TNF	Transmural healing	48.5 months	Baseline, 12 weeks, 1 year	TH related to steroid free remission, less need for treatment escalation and surgery
Ungar et al[100], 2020	Prospective, observational	44 CD (50 IUS)	Adalimumab	BWT (TI and colon)	1 year	Within 30 days of trough level measurement	Trough level < 3 µg/mL higher BWT in TI and colon. Adalimumab retention higher with TI BWT < 4 mm
Albshesh et al[99], 2020	Retrospective	60 CD	IFX	BWT	16 months	Baseline	Small bowel BWT ≥ 4 mm associated with treatment failure
de Voogd et al[105], 2022	Prospective	40 CD	Anti-TNF	BWT, color doppler signals, CEUS	32 weeks	Baseline, 4-8 weeks (T1), 12-34 weeks (T2)	18% and 28% decrease in BWT predicted endoscopic response at T1 and T2 respectively. Absence of CDS and CEUS washout rate improved prediction
Chen et al[4], 2022	Prospective pilot study	30 CD	Anti-TNF	BWT, CDS, SWE	14 weeks	Week 2, 6 and 14	Changes in BWT, CDS and SWE occurred as early as week 2 in responders Baseline SWE and BWT were higher in non-responders
Kucharzik et al[109], 2023	Post hoc analysis of RCT	77 CD	Ustekinumab	TH, BWT, CDS, mesenteric fat, stratification	48 weeks	4 weeks, 48 weeks	IUS response, TH, BWT, CDS normalization highest in colon and biologic-naive patients. Week 4 IUS predicted week 48 endoscopic response. IUS endoscopy agreement > 90% (TI)
Vaughan et al[107], 2022	Prospective study	79 UC and 24 CD	Maintenance Infliximab	BWT, CDS	Cross sectional (median disease duration 8 years)	Cross sectional data	Lower infliximab trough level was associated with higher CDS in both UC and CD. Transmural healing in CD was associated with higher infliximab trough levels
Han et al[103], 2022	Retrospective	92 CD	IFX, ADA	BWT, ultrasonographic response	14 weeks	Week 0, week 14	Higher trough levels correlated with significant ultrasonographic response
Hoffmann et al[108], 2020	Prospective	23 CD	Ustekinumab	BWT reduction ≥ 1 mm	8 weeks	Week 0, week 8	Reduction in BWT predicted clinical and biochemical response
Calabrese et al[111], 2021	Prospective	40 CD	Anti-TNF	BWT, CDS	12 months	Baseline, interim, 12 months	Tight-control monitoring improved endoscopic remission and reduced disease activity
Guidi et al[113], 2006	Prospective	20 CD	Infliximab	CEUS enhancement, wall thickness	6 weeks	Baseline, after induction	CEUS changes correlated strongly with inflammatory markers and therapy response
Dolinger et al[112], 2021	Prospective pediatric	15 CD	Infliximab	SWE elasticity changes	1 year	Baseline, Week 14	SWE accurately predicted treatment response in pediatric CD patients
Dolinger et al[163], 2024	Prospective pediatric	30 CD	Infliximab	SWE, CEUS	Cross-sectional	Baseline	Differentiated inflammatory activity from fibrosis, enabling tailored therapies
Ainora et al[115], 2024	Prospective	40 CD	Anti-TNF	Combined IUS parameters with biomarkers	6 months	Baseline, interim, endpoint	Multimodal assessment improved precision in therapeutic adjustments
Allocca et al[110], 2023	Prospective	93 CD	Adalimumab, Ustekinumab, Vedolizumab	BUSS ≤ 3.52, IBUS-SAS ≤ 22.8	12 months	Baseline, Week 12	Week 12 BUSS ≤ 3.52 strongly predicted long-term endoscopic remission (OR 9.93, P < 0.001)

CD: Crohn’s disease; CEUS: Contrast-enhanced ultrasound; IUS: Intestinal ultrasound; BUSS: Bowel ultrasound score; IBUS-SAS: International bowel ultrasound segmental activity score; SWE: Shear wave elastography; BWT: Bowel wall thickness: TNF: Tumor necrosis factor; OR: Odds ratio; IFX: Infliximab; ADA: Adalimumab; CDS: Color doppler signal; TH: Transmural healing; RCT: Randomized controlled trial; UC: Ulcerative colitis.

Table 8 Summary of studies evaluating correlation intestinal ultrasound and fecal calprotectin

Ref.	Study type	Biomarkers	IUS comparators	Number of patients	Conclusion
Paredes et al[116], 2022	Prospective	FCP, CRP	BWT, CDS, presence of complications	105 CD	FCP of 100 µg/g reflected IUS activity with sensitivity of 73%, specificity of 71.4%, and PPV of 79.3%
Prentice et al[121], 2022	Case report	FCP		Case-based	Highlighted FCP utility in stricturing CD during pregnancy, complementing IUS findings
Fang et al[117], 2023	Retrospective	ESR, CRP, PLR, MLR, NLR	IBUS-SAS, BWT, CDS, BWS, I-Fat, SES-CD	40 CD	Combining IBUS-SAS with ESR/CRP had the highest AUC (0.912) for active disease detection, with sensitivity of 88% and specificity of 80%
Yzet et al[120], 2024	Prospective	FCP	BWT, CDS	153 CD	FCP < 92.9 µg/g and BWT < 3 mm had high predictive values for mucosal healing (PPV: 96%, specificity: 89%, sensitivity: 77%)

IUS: Intestinal ultrasound; CD: Crohn’s disease; ESR: Erythrocyte sedimentation rate; NLR: Neutrophil-to-lymphocytes ratio; PLR: Platelet-to-lymphocyte ratio; IBUS-SAS: International bowel ultrasound segmental activity score; MLR: Monocyte-to-lymphocyte ratio; CDS: Color doppler signal; BWT: Bowel wall thickness; BWS: Bowel wall stratification; FCP: Fecal calprotectin; PPV: Positive predictive valve; SES-CD: Simple endoscopic score for Crohn’s disease; CRP: C-reactive protein.

Table 9 Summary of studies evaluating transmural healing in Crohn’s disease with intestinal ultrasound

Ref.	Study type	Number of patients	Follow-up	Definition of healing	Outcomes of TH or TR
Vaughan et al[127], 2022	Retrospective	202 CD	19 months	Normal BWT, no CDS, no inflammatory fat, no loss of wall stratification	TH associated with steroid-free and treatment escalation-free survival but not hospitalization or surgery
Helwig et al[123], 2022	Post hoc analysis (TRUST)	351 CD and UC	52 weeks	Simplified TH: Normal BWT, no CDS; Extended TH: Normal BWT + 2 of 3 (normal CDS, no loss of stratification, no inflammatory fat); Complete TH: Normal BWT + all 3	TH at week 12 associated with clinical remission and no escalation of therapy at 52 weeks
Ma et al[128], 2021	Prospective	77 CD	12 months	Normal BWT, no hypervascularization, no inflammatory fat, no loss of stratification	TH predicted steroid-free clinical remission, lower need for drug escalation, and hospitalization; TH showed better predictive value than mucosal healing
Castiglione et al[124], 2013	Observational longitudinal	133 CD	2 years	TH: Normalization of BWT ≤ 3 mm on bowel sonography	25% achieved TH on anti-TNF, correlating with mucosal healing; TH as an indicator of deeper remission and improved outcomes
Castiglione et al[125], 2022	Observational longitudinal	118 CD	2 years	TH: Normal BWT ≤ 3 mm; correlation with fecal calprotectin and CRP	TH achieved in 32.2%, associated with improved long-term outcomes, including relapse reduction
Ferrer et al[122], 2021	Retrospective	277 CD	24 months	Parietal healing: Normal BWT, no hyperemia, and absence of complications	PH associated with better outcomes, including relapse-free survival and reduced disease activity

CD: Crohn’s disease; TH: Transmural healing; TR: Transmural response; BWT: Bowel wall thickness, CDS: Colour Doppler signal; TNF: Tumor necrosis factor; CRP: C-reactive protein.

Table 10 Summary of studies evaluating correlation of endoscopy and intestinal ultrasound

Ref.	Study type	Number of patients	Treatment	IUS predictors	Colonoscopy score	Follow up	Time points of IUS	Therapeutic outcomes
Sævik et al[133], 2022	Prospective	145 CD	5-ASA, azathioprine, methotrexate, steroids, biologics	BWT, CDS	SES-CD	Cross sectional		BWT sensitivity and specificity 92.2 % and 86 % CDS sensitivity and specificity 66.7 % and 97.7%
Dragoni et al[65], 2023	Prospective	73 CD	5-ASA, IMS, anti-TNF, ustekinumab, vedolizumab	IBUS-SAS, BUSS, Simple-US, SUS-CD	SES-CD Rutgreets score	Cross sectional	Within 6 weeks	IUS scores showed significant correlation with endoscopy (IBUS-SAS highest) (AUC 0.95, sensitivity 82%, specificity 100% for cut off 25.2)
Lim et al[134], 2023	Prospective, cross sectional	51 IBD	Not mentioned specifically	BWT, BWS, vascularity, mesenteric fat, complications	SES-CD, UCEIS	Cross sectional		IUS sensitivity 67%, specificity 97% foe endoscopically active disease. Highest sensitivity (100%) ans specificity (95%) in transverse colon

ASA: Amino salicylic acid; CD: Crohn’s disease; TNF: Tumor necrosis factor; BWT: Bowel wall thickness; CDS: Colour doppler signal; IUS: Intestinal ultrasound; SES-CD: Simple endoscopic score Crohn’s disease; BWS: Bowel wall stratification; UCEIS: Ulcerative colitis endoscopic index of severity; IMS: Immunosuppressants; AUC: Area under the curve; IBUS-SAS: International bowel ultrasound segmental activity score; SUS-CD: Simple ultrasound score- Crohn’s disease; IBD: Inflammatory bowel diseases.

Table 11 Summary of studies comparing intestinal ultrasound and magnetic resonance enterography or computed tomography enterography

Ref.	Study type	Number of patients	Follow up	Comparator	IUS parameter	Gold standard	Result
Miao et al[135], 2002	Prospective, single center	30 CD	15 months (median)	Ultrasound and MRI	BWT and contrast enhancement	Clinical + endoscopy/barium/surgery	Sensitivity: MRI (100%)> IUS (87%). Specificity: IUS (87%)> MRI (71%)
Schmidt et al[136], 2003	Prospective	48 CD	Three investigations done within 16 months	MRE, CT enteroclysis	Length of inflamed bowel, wall thickness, stenosis, fistula, abscess		MRE and IUS could predict all the parameters accurately except fistula where CT Enteroclysis was highly sensitive
Maccioni et al[145], 2014	Prospective	50 known pediatric CD	MRE done within 15 days	MRE	High resolution ultrasound	Capsule endoscopy, barium study	MRE identified jejunal lesions not detected in high resolution ultrasound (n = 2). False positive MRE findings in proximal to mid ileum (n = 1). 100% sensitivity and specificity of MRE in terminal ileum
Allocca et al[141], 2018	Prospective	60 ileo-colonic CD	20 Months	CS + MRE and MRE alone	Localisation, bowel wall flow, active disease, structure, fistula and abscess	MRE and colonoscopy	IUS highly specific (> 85%), sensitive (> 85%), accurate (about 90%) with high negative predictive value (> 85%) except for stricture (75% sensitivity). Excellent positive predictive value except for CD complications Concordance in CD management in about 80%
Taylor et al[1], 2018	Prospective, multi center	284 (newly diagnosed and relapsed CD)	6 months	MRE + IUS	Presence and extent of small, bowel disease	MRE	Extent of SB disease. Sensitivity: MRE (80%) > IUS (70%). Specificity: MRE (95%) > IUS (81%). Presence of SB disease. Sensitivity: MRE (97%) > IUS (92%). Specificity: MRE (94%) > IUS (84%)
Yuksel et al[142], 2019	Prospective, observational	71 known CD	1 Month	MRE, ileocolonoscopy	BWT, CDS, BWS, mesenteric fat, stenosis, dilation, rigidity	Ileocolonoscopy	Sensitivity to identify loss of stratification and stenosis was better with MRE Specificity for BWT, BWS and stenosis better with IUS
Hakim et al[54], 2020	Retrospective	93 CD (pediatric) (known, suspected)	Cross-sectional	MRE	Presence of lesion, stricture and dilation	MRE	Substantial agreement for presence of lesions (κ = 0.63), stricture (κ = 0.77) and dilation (κ = 0.68)
Bhatnagar et al[147], 2020	Prospective	38 (11 new, 27 relapsing)	2 IUS examinations done within 7 days	IUS	Mural and extra-mural features	MRE	Agreement for presence of Small bowel disease (MRI): 82% (new diagnosis). 81% (relapsing cohort). Colonic disease 64% (new diagnosis) 78% (relapsing cohort)
Kamel et al[138], 2020	Prospective	40 (14 UC, 26 CD)	Cross-sectional	Bowel ultrasound and MRE	BWT, CDS, mesenteric fat and lymph nodes, complication	MRE and colonoscopy	Accuracy of IUS: 85% ileum, 70% large bowel, 95% for fistula, strictures and proximal dilatation and 100% for abscess
Livne et al[139], 2020	Retrospective	42 CD	< 3 months between IUS and MRE	MRE	BWT, CDS, BWS, mesenteric fat, complications	MRE	Terminal ileum thickness and mesenteric fat proliferation are useful to build a stepwise regression model which can predict MARIA score in terminal ileum on MRE
Calavrezos et al[137], 2022	Retrospective	54 IBD (44 CD)	< 3 months between IUS and MRE	MRE	BWT, CDS, BWS	MRE	MRE and IUS were comparable in detecting active inflammation and complications. There was concordance in therapeutic decisions
Xu et al[68], 2023	Retrospective	115 CD	Investigations done within 7 days of each other	CTE, MRE	IBUS-SAS	MRE, IBUS	Sensitivitysmall bowel: MRE > IUS. Terminal ileum: IUS > MRE. Colon: IUS, CTE, MRE similar. IBUS-SAS ≥ 46.7 predicted active disease with AUC of 0.86
Ahmad et al[143], 2022	Correlation study	376	Not specified	MRE	Bowel wall enhancement and thickness	Clinical evaluation	Strong positive correlation (r = 0.83) between IUS and MRE findings for disease activity
Castiglione et al[140], 2013	Prospective	234	Not specified	MRE	BWT, disease extension	Ileocolonoscopy	Comparable sensitivity for IUS (94%) and MRE (96%); MRE superior in defining disease extension
Dillman et al[144], 2015	Prospective	29 pediatric CD	Multiple assessments	MRE	Bowel wall thickness, strictures, abscesses	MRE	Moderate to substantial agreement for BWT and complications (κ = 0.61–0.96)
Hakim et al[54], 2020	Retrospective	93 pediatric CD	Cross-sectional	MRE	Lesions, strictures, dilatation	Ileocolonoscopy, MRE	Substantial agreement for strictures (κ = 0.77) and lesions (κ = 0.63)
Malagò et al[47], 2012	Prospective	30	Not specified	MRE	Vascularity, lesion length, wall thickness	Clinical and imaging correlation	High correlation between CEUS and MRE for bowel wall vascularity and thickness; CEUS is a low-cost alternative
Onali et al[57], 2012	Prospective	15	≤ 3 months pre-surgery	CT Enteroclysis	Strictures, fistulas, abscesses	Surgical findings	SICUS and CT enteroclysis had comparable sensitivity and specificity for lesions; SICUS is non-invasive and radiation-free
Pauls et al[46], 2006	Prospective	21	21 months	Dynamic MRI	Bowel wall vascularity, segment length	MRI and histology	Significant correlation between CEUS and MRI for disease activity; CEUS effective in differentiating inflammatory vs fibrostenotic processes
Statie et al[151], 2023	Prospective	44	27 months	MRE	BWT, Limberg score	Clinical severity (CDAI, HBI)	Limberg score sensitivity of 93.33% and specificity of 71.43% for active disease; MRE better correlated with fecal calprotectin
Xu et al[68], 2023	Retrospective	115	7 days (comparison)	MRE, CT enterography	IBUS-SAS	Endoscopy	IBUS-SAS cutoff ≥ 46.7 predicted active disease (AUC = 0.86); MRE more sensitive for small bowel disease, IUS better for terminal ileum lesions

IUS: Intestinal ultrasound; CD: Crohn’s disease; UC: Ulcerative colitis; MRE: Magnetic resonance enterography; CTE: Computed tomography enterography; BWT: Bowel wall thickness; BWS: Bowel wall stratification; AUC: Area under curve; IBUS-SAS: International bowel ultrasound segmental activity score; MRI: Magnetic resonance imaging; CS: Colonoscopy; CDS: Color doppler signal; MARIA: Magnetic resonance index of activity; CEUS: Contrast-enhanced ultrasound; SICUS: Small intestinal contrast ultrasound; CDAI: Crohn’s disease activity index; HBI: Harvey Bradshaw Index.

Table 12 Summary of studies on intestinal ultrasound in pediatric inflammatory bowel disease

Ref.	Study type	Number of patients	Follow up	Gold standard	Com parator	Results
Borthne et al[158], 2006	Prospective	43 children	3 weeks	Endoscopy	MRI	MRI with 300 mL mannitol and IUS both had good correlation with colonoscopy for terminal ileum
Maccioni et al[145], 2014	Prospective	50 known pediatric CD	MRE done within 15 days	Capsule endoscopy barium study	MRE	MRE identified jejunal lesions not detected in HRUS (n = 2), False positive MRE findings in proximal to mid ileum (n = 1) 100% sensitivity and specificity of MRE in terminal ileum
Rosenbaum et al[132], 2017	Retrospective	98 Pediatric CD	2 months of each other	Surgical biopsy	MRE	Increased BWT, loss of BWS and fibrofatty proliferation on IUS in surgical vs non-surgical patients
Barber et al[159], 2017	Retrospective	49 IBD	30 days	MRE	Endoscopy and histology	Good correlation between MRE and IUS on the location and severity of disease
Dillman et al[162], 2017	Prospective cross-sectional study	28 pediatrics	2 weeks, 1 month, 3 months and 6 months on infliximab			BWT, length of bowel involved, bowel and mesenteric colour doppler signal changes as early as 2 weeks of infliximab therapy. Storing correlation between CDS intensity and fecal calprotectin
van Wassenaer et al[164], 2023	Prospective	74 CD	Cross-sectional	SES-CD score	Ileo-colonoscopy	PCD-US score. Based on BWT in TI. And BWT + mesenteric fat infiltration in colon. Cut-off 1: Sensitivity 82% (TI), 85% (colon). Cut-off 3: Specificity: 88% (TI), 92% colon. External validation required
Dolinger et al[163], 2023	Prospective longitudinal	44 children	1 year	Endoscopy (SES-CD)	PCDAI, CRP	≥ 18% decrease in BWT at week 8 predicted endoscopic remission with AUROC 0.99
Dolinger et al[112], 2021	Prospective cohort	13 children	14 weeks	Clinical remission	SBUS	Bowel wall hyperemia decreased post-induction (P = 0.01). No correlation was seen with changes in BWT
Okuhira et al[166], 2022	Retrospective	22 procedures	Not specified	SBCE	IUS, biomarkers	SBWT and mesenteric lymph node size correlated with Lewis Score (r = 0.52 and r = 0.45, respectively)
Pallotta et al[155], 2013	Prospective cohort	51 pediatric patients	Cross-sectional	Small bowel follow-through	SICUS	SICUS sensitivity and specificity for CD lesions were 96% and 100%, superior to TUS (sensitivity 76%)
Ponorac et al[48], 2023	Prospective cohort	36 children	30 days	Endoscopy (SES-CD)	CEUS, PCDAI, FC	CEUS sensitivity 78.57%, specificity 100%. Concordance with endoscopy was substantial (κ = 0.62)

CD: Crohn’s disease; TI: Terminal ileum; IUS: Intestinal ultrasound; MRE: Magnetic resonance enterography; BWT: Bowel wall thickness; PCD: Pediatric Crohn’s disease; BWS: Bowel wall stratification; CDS: Colour doppler signal; MRI: Magnetic resonance imaging; HRUS: High-resolution ultrasonography; IBD: Inflammatory bowel disease; SES-CD: Simple endoscopic score for Crohn’s disease; PCD-US: Pediatric Crohn’s disease intestinal ultrasound score; PCDAI: CRP: C-reactive protein; AUROC: SBUS: Small bowel ultrasound; SBCE: Small bowel capsule endoscopy; SICUS: Small intestinal contrast ultrasound; CEUS: Contrast enhanced ultrasound; FC: Fecal calprotectin; TUS: Traditional ultrasound.

Table 13 Summary of studies evaluating role of intestinal ultrasound in post-operative Crohn’s disease

Ref.	Study type	Follow up	Number of patients	Results
Maconi et al[168], 2001	Prospective	6 months	85 CD	BWT after surgery was unchanged or worsened in 43.3% of patients. Patients with unchanged/worsened BWT had a higher risk of clinical and surgical recurrence compared with those with normalized/improved BWT
Parente et al[167], 2004	Prospective	41 months (median)	127 CD	BWT > 6 mm at 12 months after surgery was associated with a six-fold higher hazard of CD recurrence
Paredes et al[45], 2013	Prospective	Within 3 days of colonoscopy	60 CD	Sonographic Score 2 (BWT > 5 mm or contrast enhancement > 46%) showed sensitivity (98%), specificity (100%), and accuracy (98.3%) for detecting endoscopic recurrence. Sonographic Score 3 was effective in identifying severe recurrence
Cammarota et al[169], 2013	Retrospective	12 months (mean)	196 ileal/ileocolonic CD	Incremental risk of re-operation with increasing BWT: 13% with 3 mm, 40% with > 6 mm
Carmona et al[170], 2021	Retrospective	-	31 CD	Significant association between endoscopic recurrence and BWT/colour Doppler signal intensity. BWT > 3.4 mm had sensitivity (100%) and specificity (86%)
Macedo et al[172], 2022	Cross-sectional	14 months	39 CD	Diagnostic accuracy of IUS was superior to CRP, fecal calprotectin, and clinical parameters
Furfaro et al[5], 2023	Prospective	3 months	91 CD	BWT ≥ 3 mm plus FCP > 50 μg/g identified 75% of patients with endoscopic recurrence (false positives 5%). Presence of mesenteric lymph nodes identified 56% of endoscopic recurrence

CD: Crohn’s disease; IUS: Intestinal ultrasound; BWT: Bowel wall thickness; FCP: Faecal calprotectin; CRP: C-reactive protein.

Table 14 Role of trans-perineal ultrasound in Crohn’s disease

Ref.	Design	No. of patients (CD)	Gold standard	Aim	Key results
Terracciano et al[178], 2016	Prospective	28	MRI	Fistula detection and classification, abscess detection	TPUS demonstrated strong correlation with MRI in detecting perianal fistulas, offering a non-invasive, patient-friendly approach for fistula detection with high diagnostic accuracy. TPUS was effective in identifying superficial and intersphincteric tracts, complementing MRI for complex disease
Mallohui et al[181], 2004	Prospective	19	EUA/MRI/FUP	Fistula and abscess detection	TPUS showed excellent concordance with MRI and EUA for detecting superficial abscesses and fistulas, providing real-time visualization. While MRI excelled in deep-seated abscesses, TPUS was invaluable in mapping superficial tracts and guiding management
Maconi et al[179], 2013	Prospective	59	MRI	Fistula detection and classification, abscess detection	TPUS demonstrated diagnostic accuracy comparable to MRI in detecting fistulas and abscesses. Its real-time imaging capability made it a suitable alternative in cases where MRI was contraindicated or unavailable
Maconi et al[180], 2007	Prospective	44	TRUS	Fistula detection and classification, abscess detection and classification	TPUS effectively identified internal openings and perianal abscesses, particularly in superficial fistulas. Its ease of use and non-invasive nature highlighted its utility in outpatient settings and as a complement to TRUS
Wedemeyer et al[183], 2004	Prospective	25	MRI	Fistula detection and classification, abscess detection and classification	TPUS demonstrated utility in identifying perianal fistulas and abscesses, though MRI provided additional details for complex and deep-seated lesions. TPUS was particularly effective in identifying inflammation and monitoring post-treatment changes
Stewart et al[182], 2001	Prospective	28/26	EUA/FUP	Fistula detection and classification, internal opening and abscess detection	TPUS was a valuable tool for detecting superficial fistulas and internal openings. Its real-time imaging capability complemented EUA by providing an additional, less invasive option for follow-up assessments

CD: Crohn’s disease; EUA: Examination under anesthesia; TPUS: Transperineal ultrasound; MRI: Magnetic resonance imaging.

Table 15 Summary of studies evaluating role of point of care ultrasound in inflammatory bowel disease

Ref.	Study type	Comparator	Follow up	Number of patients	Impact on management
Novak et al[18], 2015	Prospective	CRP, Harvey Bradshaw Index	2 years	49 CD	POCUS changed management (escalation, de-escalation, surgery referral) in nearly 60% of cases. Half of the patients with clinically inactive disease had IUS activity
Wright et al[186], 2020	Prospective cross-sectional	MRE and ileo-colonoscopy	POCUS done within 3 months of MRE	42 CD	Compared to MRE, POCUS was accurate in assessing disease activity, extent, and complications. POCUS had moderate agreement with MRE (κ = 0.50) and ileo-colonoscopy (κ = 0.55)
Gonen et al[193], 2021	Prospective	Colonoscopy	3 months	117 CD	POCUS changed management in 40% of cases. Accuracy of decision improved from 63% to 90%. Surgical decisions were taken in 11% of cases. Colonoscopy and POCUS assessments were comparable
Bots et al[20], 2022	Retrospective	MRI, Colonoscopy	MRE within 8 weeks of IUS	345 (280 CD and 65 UC)	POCUS changed management in 60% of cases, leading to a 48% change in medications. Correlation with IUS was 86.3%, and correlation with MRI was 80%. Adoption of IUS reduced the reliance on MRI
Rispo et al[173], 2023	Prospective	Ileo-colonoscopy, IUS	Cross-sectional	86 UC	Hand-held IUS and standard IUS were comparable in terms of BWT and BWS Excellent agreement between HHIUS and IUS (κ= 0.86)
St-Pierre et al[196], 2023	Multicenter observational	N/A	Cross-sectional	158 IBD	POCUS detected active inflammation in 65% of cases, leading to changes in IBD-specific medications in 57%. Avoided or delayed urgent endoscopy in 85%, significantly improving resource utilization and reducing procedural burden

CD: Crohn’s disease; MRE: Magnetic resonance enterography; IUS-Intestinal ultrasound; UC: Ulcerative colitis; MRI: Imagnetic resonance imaging; BWT: Bowel wall thickness; POCUS: Point of care intestinal ultrasound; IBD: Inflammatory bowel diseases; CRP: C-reactive protein; BWS: Bowel wall stratification.