Role of intestinal ultrasound in ulcerative colitis: A systematic review

Table 1 Summary of studies evaluating intestinal ultrasound for diagnosis of inflammatory bowel disease/ulcerative colitis and differentiating inflammatory bowel disease mimics

Ref.	Study type	Number of patients	Equipment	Criteria for abnormal findings	Reference	Sensitivity	Specificity	PPV	NPV
Hollerbach et al[5]	Prospective	227 suspected IBD patients	5 MHz curved array probe	BWT > 4 mm, target sign, lumen < 4 mm, ascites, abscess, reduced compressibility, conglomerate tumor (any 2 of the above)	Colonoscopy, enteroclysis, enema, CT scan, surgery	76% (84% CD, 66% UC) (10%-20% in jejunum, duodenum, rectum)	95%	98%	58%
Astegiano et al[1]	Prospective	313 (abdominal pain and altered bowel habits ≥ 3 mo)	7.5-10 MHz linear probe and 3.5 MHz convex probe	BWT ≥ 7 mm, BWT between 5-6 needs follow-up	Radiology and endoscopy	74% (84% CD, 38% UC)	98%	92%	92%
Chavannes et al[72]	Cross-sectional, single centre	33 children with suspected IBD (11 UC)	3-12 MHz linear probe and 3-10 MHz convex probe	BWT > 1.9 mm cut-off for inflamed bowel	Colonoscopy	64%	76%	-	-
Rossaint et al[3]	Prospective	487 suspected IBD patients	7.5 MHz linear, 3.5 MHz convex	BWT > 4 mm	Endoscopy, small bowel enteroclysis, CT	85% Rectum: 14% Duodenum/jejunum: 29%	95%	98%	75%
Dell'Era et al[7]	Retrospective	113 suspected pediatric IBD patients	3.5-5 MHz curvilinear probe, 4-8 MHz microconvex probe	BWT, BWS, lymph nodes, i-fat	Ileo-colonoscopy	BWS: 78.3% i-fat: 65.2%; BWT > 3: 69.6%. All 3: 56.5%. Any of 3: 82.6%	BWS: 93.3. i-fat: 92.2%; BWT > 3: 96.7%. All 3: 100%; Any of 3: 86.7%	BWS: 75% i-fat: 68.2%; BWT > 3: 84.2%; All 3: 100%. Any of 3: 61.3%	BWS: 94.4% i-fat: 91.2%; BWT > 3: 92.6%; All 3: 90%. Any of 3: 95.1%
Ziech et al[8]	Prospective	28 children with suspected IBD	Linear probe 5-12 MHz	BWT, BWS, lymph nodes, Doppler of mesenteric arteries	Ileo-colonoscopy and endoscopy	55% (improved with combination of MRI 83%-87%)	100%	-	-
White et al[9]	Prospective	37 patients with low-risk GI symptoms, FCP < 150 µg/g, CRP < 10 g/d	5-8 MHz curvilinear probe, 18 MHz linear probe	BWT > 3 mm, increased CDS, loss of BWS, inflammatory fat, lymph nodes	NA	-	-	-	-
Jeffrey et al[10]	Retrospective	32 patients with focal GI lesions, 20 controls	5 MHz linear array transducer	≥ 4 blood vessels measuring 3 mm or more over 5 cm segment/extending into mesentery	Surgery, biopsy, endoscopy	-	-	-	-
Zhang et al[11]	Retrospective	13 IBD, 38 colon cancer	Curvilinear probe 2-5 MHZ (for CEUS, MI 0.07-0.10, dynamic range 50 dB), linear probe 3-9 MHz, SonoVue contrast	Increased BWT, loss of BWS, “comb-teeth like” vessels on color Doppler, disordered enhancement, heterogeneous enhancement	Histology for colon cancer, clinical/pathologic and endoscopic exams for IBD	Colon cancer BWS: 97.4%; Disordered enhancement: 94.7%. Heterogeneous enhancement: 78.9%	Colon cancer BWS: 69.2%; Disordered enhancement: 92.3%. Heterogeneous enhancement: 100%	-	-
Kapoor et al[12]	Retrospective, single centre	76 patients with chronic diarrhoea and abdominal pain	Convex probe: 3.5-8 MHz, linear probe: 8-14 MHz	Abnormal bowel wall stiffness (> 12 kPa) and abnormal inflammation (> 14 m/s/kHz); wall thickening (> 3 and > 4 for small and large bowel), stratification, node, fluid, fat, and fistula	Contrast enhanced CT, endoscopic and surgical biopsy	100%	99%	-	-

IBD: Inflammatory bowel disease; BWT: Bowel wall thickness; CD: Crohn’s disease; UC: Ulcerative colitis; CT: Computed tomography; IBS: Irritable bowel syndrome; PPV: Positive predictive value; NPV: Negative predictive value.

Table 2 Studies evaluating scoring systems to assess disease activity in ulcerative colitis based on intestinal ultrasound

Ref.	Study type	Follow-up duration	IUS activity	Comparator	Number of patients	Results
Allocca et al[16]	Prospective	6 mo	BWT, CDS, BWS, lymph nodes	Colonoscopy	53 UC patients	BWT and CDS were independent predictors of colonoscopic activity; Humanitus ultrasound criteria: (1) BWT > 3 mm with CDS; and (2) BWT > 4.43 and absence of CDS. MUC > 6.2: Sensitivity 71%, specificity: 100%, AUC: 0.891. Addition of FCP increased sensitivity to 100%
Allocca et al[17]	Prospective	6 mo	BWT, CDS	Colonoscopy	43 UC patients	MUC score > 6.2 discriminated active UC (sensitivity 85%, specificity 94%, AUC 0.902); external validation study
Allocca et al[18]	Prospective	1.6 years (median)	MUC	-	98 UC patients	Milan ultrasound criteria > 6.2 at baseline was statistically significantly associated with adverse disease outcomes (treatment escalation, steroid use, hospitalization, and colectomy) (HR: 3.87)
Allocca et al[19]	Prospective	1 year	MUC	Colonoscopy	49 UC patients	MUC ≤ 6.2 at wk 12 is independent predictor of MES ≤ 1 at 1 year (OR: 5.8)
Maeda et al[20]	Retrospective	1 year	Milan criteria	Endoscopic Mayo score, fecal calprotectin	58 UC patients	MUC > 6.2 predicted 1 year relapse (HR: 3.22)
Goodsall et al[4]	Prospective cohort	8 wk	Milan criteria, BWT	NHI, colonoscopy (UCEIS score)	29 UC patients	IUS + FC accurately predicted histological activity in 88% of cases (sensitivity 88%, specificity 80%, positive predictive valve 95%, and negative predictive valve 57%)
Piazza et al[21]	Prospective, multi centre	11.5-31.9 mo	MUC, BWT	MES, FCP, CRP	141 UC patients	MUC > 7.7 was better in predicting colectomy (AUC: 0.83) risk than MES
Rispo et al[22]	Prospective	Cross-sectional	MUC	Colonoscopy (MES)	86 UC patients	Conventional and hand-held ultrasound had excellent agreement for MUC (kappa = 0.86). No difference in diagnostic accuracy (0.87 IUS vs 0.84 hand-held IUS)
Bots et al[23]	Prospective	3 wk	BWT, vascularity, haustrations, fat wrapping	Colonoscopy	60 UCpatients	UC-IUS score was developed which has strong correlation with endoscopic disease activity (ρ = 0.83 for Mayo score, ρ = 0.76 for UCEIS score)
Komatsu et al[24]	Retrospective validation	-	BWT, submucosal index	Colonoscopy	44 UC patients	High PPV (95%) and NPV (80%) to predict endoscopic improvement

CD: Crohn’s disease; IUS: Intestinal ultrasound; FC: Faecal calprotectin; UC: Ulcerative colitis; MUC: Milan ultrasound criteria; CI: Confidence interval; HUS: Humanitas ultrasound criteria; CWF: Colon wall flow; CWT: Colon wall thickness; SUS-CD: Simple ultrasound score-Crohn’s disease; IBUS-SAS: International bowel ultrasound-segmental activity score; BWT: Bowel wall thickness; CDAI: Crohn’s disease activity index; DBE: Double balloon enteroscopy; US-CD: US scoring system for Crohn’s disease; UC-IUS: Ulcerative colitis intestinal ultrasound; ρ: Spearman’s rho; UCEIS: Ulcerative colitis endoscopic index of severity; PPV: Positive predictive value; NPV: Negative predictive value.

Table 3 Role of intestinal ultrasound in predicting response to therapy in ulcerative colitis

Ref.	Study type	Number of patients	Treatment agent(s)	IUS predictor(s)	Follow-up duration	Time points of IUS	Therapeutic outcomes
Dubbins[25]	Retrospective	9 UC (19 CD)	Steroid ± immunosuppressive therapy	BWT	2-4 mo	Baseline, 2-4 mo	No significant change in BWT in UC but there was significant response in CD
Maconi et al[38]	Prospective	30 active UC	Steroids	BWT	2 mo	Baseline and 2 mo	Significant reduction in BWT in clinical responders; IUS response significantly correlated with clinical biochemical and endoscopic activity
Yoshida et al[26]	Prospective	26 UC	Cytaphresis + conventional therapy	BWT	1 year	Baseline and 2-3 wk	Early IUS response (decrease in BWT by 2.5 mm at 2-3 wk) predicted 1 year response (91% vs 40%) lower relapse (9% vs 47%)
Goertz et al[27]	Prospective	7 UC	Vedolizumab	BWT, CDS, CEUS- amplitude and time derived parameters	14 wk	Baseline, 14 wk	Decrease in CDS intensity. Decrease in amplitude dependent CEUS parameters (peak enhancement and wash in rates)
Maaser et al[28]	Prospective, multi centre	224 UC	Steroid, anti-TNF, anti-integrin, AZA/6-MP	BWT, BWS, CDS, haustration, lymph nodes, inflammatory fat, ascites	16 wk	Baseline, 2, 6, and 12 wk	Significant improvement in IUS parameters was seen as early as 2 wk. Significant correlation of normalisation of BWT at 12 wk with clinical improvement and biomarkers
Les et al[29]	Prospective	28 UC (89 CD)	5-ASA, budesonide, AZA, anti-TNF	BWT, BWS, CDS, i-fat, lymph nodes	6 mo	Baseline	Predictors (overall IBD); immediate treatment escalation (31.7%) Score = 1/[1 + Exp (-XB)] where XB = 0.75 × [BWT (mm)] + 3.5 × (CDS = 1) – 7.31; AUC: 0.94, score > 0.5 100% sensitivity, 83% specificity; subsequent treatment escalation (17.9%), AUC: 0.92; Score = 1/[1 + Exp (-XB)] where XB = 0.8X [bowel wall thickness (mm)] - 1.3X (Presence of wall stratification =1) – 3.82 Score > 0.6 has 90% sensitivity, 86.4% specificity
Smith et al[30]	Retrospective	23 CD, 8 UC (22 CD and 7 UC on biologics)	Anti-TNF, ustekinumab, vedolizumab	BWT, CDS	46 wk	2, 6, and 14 wk	16% improvement in BWT at 6 wk and 10% improvement at wk 14 predicted treatment persistence/response at 46 wk
Vaughan et al[31]	Prospective	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
Helwig et al[32]	Post-hoc analysis of prospective, multi centre studies	131 UC (118 CD)	Standard of care	BWT, CDS, BWS, i-fat, transmural healing, transmural response	52 wk	0, 12, 52 wk	76.6% TR and 45%-61.4% TH at 12 wk after treatment intensification
de Voogd et al[33]	Longitudinal, prospective	30 UC on tofacinib	Tofacitinib	BWT	8 wk	Baseline and 8 wk	Most accurate BWT cut-off for endoscopic remission was 2.8 mm; for endoscopic response: 3.9 mm and > 32% decrease in BWT
Ilvemark et al[34]	Blinded, prospective multi centre, observational	56 acute severe UC	IV steroid	BWT	48 h and 6 d	Baseline, 48 ± 24 h and 6 ± 1 d	≤ 20% reduction in BWT has 84.2% sensitivity and 78.4% specificity for determining non-response (AUC: 0.85)
Allocca et al[19]	Prospective	49 UC	Infliximab, adalimumab, vedolizumab, ustekinumab	Milan ultrasound criteria based on BWT and CDS intensity	1 year	Baseline, week 12, and 1 year	MUC ≤ 6.2 at week 12 independent predictor of MES ≤ 1; A ≥ 2 reduction in MUC predicted MES = 0
de Voogd et al[33]	Prospective, single center	51 UC patients	Steroids, 5-ASA, thiopurines, biologics, tofacitinib, cyclosporin	BWT, CDS, haustrations, BWS, fat wrapping, lymph nodes	26 wk	Baseline, week 2, week 6, weeks 8-26	BWT and CDS at weeks 2 and 6 predicted endoscopic remission and response at 8-26 wk

CD: Crohn’s disease; TNF: Tumor necrosis factor; TH: Transmural healing; BWT: Bowel wall thickness; CDS: Color doppler signal; IUS: Intestinal ultrasound; CEUS: Contrast enhanced ultrasound; TI: Terminal ileum; RCT: Randomized controlled trial; IFX: Infliximab; SWE: Shear wave elastography; SUS-CD: Simple Ultrasound Activity Score for CD; IBUS-SAS: International Bowel Ultrasound Segmental Activity Score; BUSS: Bowel Ultra-Sound Score; SICUS: Sall Intestine Contrast Ultrasonography.

Table 4 Summary of studies on superior mesenteric artery/inferior mesenteric artery artery flow in evaluating inflammatory bowel disease activity

Ref.	Study type	Number of patients	Parameters studied
Ahmed et al[41]	Prospective	84 UC (16 CD, 50 normal)	SMA and IMA PSV and EDV significantly higher in UC compared to controls; pulsatility index significantly higher in control group than UC
Maconi et al[38]	Prospective	24 UC (31 CD, 10 IBS)	Higher portal and mesenteric blood flow with lower RI of SMA was noted in active UC as compared to quiescent UC
Mirk et al[39]	Prospective	22 UC, 24 CD	IBD with active disease in left colon presented increases in flow velocity and flow volume with decrease in pulsatility index
Siğirci et al[40]	Prospective	44 (25 active, 19 inactive, 22 healthy)	IMA blood flow volume, mean PSV, ESV, mean velocity, and vessel diameter were higher and pulsatility index lower in active disease compared to quiescent disease; active disease in left colon had high higher mean PSV and velocity in IMA; mean EDV higher with lower mean PI and RI in SMA for those with pancolonic involvement

SMA: Superior mesenteric artery; CD: Crohn’s disease; IMA: Inferior mesenteric artery; PSV: Peak systolic velocity; EDV: End diastolic velocity; UC: Ulcerative colitis; ESV: End systolic velocity; RI: Resistive index; PI: Pulsatility index; IBS: Irritable bowel syndrome; IBD: Inflammatory bowel disease.

Table 5 Summary of studies on contrast enhanced ultrasound in ulcerative colitis

Ref.	Study type	Number of patients	Parameters studied
Romanini et al[42]	Prospective	18 UC, 15 CD	High vascular density (CD34+; > 265 vessels per high power field, 40 ×) correlated with CEUS (higher and early peak, higher blood flow and volume)
Goertz et al[27]	Prospective	7 UC, 11 CD	Decrease in amplitude dependent CEUS parameters (peak enhancement and wash in rates). Time dependent parameters (e.g., time to peak) remained stable
Zhang et al[11]	Retrospective	13 IBD, 38 colon cancer	Disordered and heterogeneous enhancement in colon cancer (95% and 79%) compared to IBD (9% and 0%). Colon cancer: Later enhancement, slower washout with lower speed to peak intensity

CD: Crohn’s disease; IBD: Inflammatory bowel disease.

Table 6 Summary of studies correlating clinical activity with intestinal ultrasound

Ref.	Study type	Number of patients	IUS predictors	Clinical score	Parameters studied
Goodsall et al[4]	Prospective	19 UC (29 paired data)	MUC	SCCAI, Mayo score	Mayo score: r = 0.307; 95%CI, 0.020-0.595; P = 0.036; SCCAI score: r = 0.04; 95%CI, −0.21 to 0.28; P = 0.768
Kinoshita et al[54]	Prospective, multi-centre	156 UC	Ultrasound severity score based on BWT, BWS, hypoechoic/hyperechoic changes in submucosa/mucosa	Rachmilewitz clinical activity index	r = 0.40, P < 0.001
Lim et al[63]	Prospective cross-sectional	29 UC, 22 CD	BWT, CDS, BWS, i-fat	Partial Mayo score	r = 0.192, P = 0.317
Maaser et al[28]	Prospective, multi-center	224 UC	BWT	SCCAI	Sigmoid colon: Baseline: r = 0.187; 12 wk: r = 0.547; descending colon: Baseline: r = 0.262; 12 wk: r = 0.5
Saleh et al[89]	Retrospective	39 UC, 108 DC	BWT, CDS, i-fat, BWS, lymph node, free fluid, haustartion, motility	Mayo score, UCAI	r = 0.016 Mayo score (P = 0.002); UCAI (P = 0.014)
de Voogd et al[2]	Prospective, single centre	16 UC, 22 CD	BWT, CDS, haustrations, BWS, fatty wrapping	SCCAI, Lichtiger index	SCCAI and BWT in the SC (r = 0.65, P < 0.0001) and DC (r = 0.59, P < 0.002). Lichtiger score and BWT SC (r = 0.65, P = 0.001) and DC (r =0.63, P = 0.001)
Yamada et al[62]	Prospective	26	SWE, SWD	UCEIS	Negative correlation with SWE (r = -0.505, P = 0.008); no correlation with (r = 0.001, P = 0.998)

CD: Crohn’s disease; UC: Ulcerative Colitis; SWE: Shear wave elastography; UCEIS: Ulcerative colitis endoscopic activity index; CDAI: Crohn’s disease activity index; BWT: Bowel wall thickness; UCAI: Ulcerative colitis activity index; MUC: Mayo ultrasound score.

Table 7 Summary of studies correlating blood (C-reactive protein/erythrocyte sedimentation rate) or fecal biomarkers (fecal calprotectin) with intestinal ultrasound in ulcerative colitis

Ref.	Study type	Number of patients	IUS comparator	Biomarker(s)	Time between IUS and biomarker testing	Conclusion
Bots et al[23]	Retrospective, single centre	65 UC (280 CD)	BWT, CDS, BWS, i-fat, haustrations, lymph nodes, motility	FCP, CRP	Within 1 wk	Higher FCP and CRP in IUS active disease Median FCP Active disease: 1720 µg/g; Inactive disease: 75 µg/g (P < 0.001); Median CRP Active disease: 3.6 mg/L; Inactive disease: 1.8 mg/L (P < 0.076)
Goodsall et al[4]	Prospective	19 severe UC (29 paired data)	BWT, CDI, BWS	FCP	Baseline	Log converted FCP had significant correlation with NHI (r = 0.027, 0 = 0.044), but not with MUC (r = 0.01, P = 0.064); Composite of MUC and FCP has 88% sensitivity, 80% specificity, 95% PPV, and 57% NPV (P = 0.007)
Ilvemark et al[34]	Blinded, prospective multi centre, observational	56 acute severe UC	BWT	CRP	Baseline	FCP is not a predictor of IV steroid response; BWT has significant association with CRP at 48 ± 24 h, r = 0.47, P < 0.005
Les et al[29]	Prospective	28 UC, 89 CD	BWT, loss of stratification, CD, mesenteric hypertrophy, lymph nodes	CRP, FCP	Baseline	FCP predicted immediate (AUC 0.86) and subsequent treatment intensification (AUC 0.81); CRP predicted immediate (AUC 0.81) and subsequent treatment intensification (AUC 0.55)
Lim et al[63]	Prospective cross-sectional	29 UC, 22 CD	BWT, BWS, vascularity, mesenteric fat, complications	FCP, CRP	Baseline	IUS parameters have good correlation with FCP (r = 0.489, P < 0.01) and CRP (r = 0.604, P < 0.01) significant
Maaser et al[28]	Prospective, multicentre	224 UC	BWT	FCP	Baseline, 2, 6, 12 wk	At 12 wk, 16% with increased BWT had FCP < 250 µg/g and 44.4% with normal BWT had FCP ≥ 250 µg/g
Sagami et al[57]	Single centre, prospective, cross-sectional	53 UC	BWT, CDS (rectum)	FCP	Baseline	BWT better than FCP (> 50 µg/g) for predicting histologic and endoscopic activity (MES > 1) in rectum by trans-perineal ultrasound; CDS not better than FCP
Sagami et al[78]	Prospective, single centre	100 UC	BWT, CDS (rectum)	FCP, CRP	Baseline 1, 8 wk	FCP and CRP were not independent predictors of remission at 8 wk; BWT and CDS were independent predictors of remission at 8 wk
Saleh et al[89]	Retrospective	39UC, 108 CD	BWT, BWS, CDS, mesenteric fat, complications	FCP, CRP	Baseline	54% of those with combined clinical and biochemical remission (ESR ≤ 40 mm/h and CRP ≤ 10 mg/L and FCP ≤ 50 µg/mg and fecal lactoferrin ≤ 30 µg/mL) had active IUS findings; 67% without combined remission had active IUS findings
de Voogd et al[2]	Prospective, single centre	16 UC, 22 CD	BWT, CDS, loss of haustration, bowel wall stratification, fatty wrapping	FCP	Baseline	Addition of FCP, decrease of FCP, or cutoff values for FCP did not improve the multivariate model (BWT, haustrations) to detect endoscopic remission, improvement, or response
St-Pierre et al[90]	Prospective, multicenter, observational cohort	18 UC, 123 CD	BWT, CDS	FCP	Baseline	Median FCP: IUS inactive inflammation: 50 µg/g, active inflammation 270 µg/g
Castellano et al[44]	Retrospective	44 pediatric IBD	CDS	FCP	Baseline	Median FCP low (median 92 µg/g) for low Doppler flow (≤ 2 /cm2) and high (median 2286 µg/g) for high Doppler flow (≥ 3 /cm2)

FCP: Fecal calprotectin; CDS: Color Doppler Signal; IBD: Inflammatory bowel disease; UC: Ulcerative colitis; CD: Crohn’ disease; IUS: Intestinal ultrasound; BWT: Bowel wall thickness; NPV: Negative predictive value; CRP: C-reactive protein.

Table 8 Summary of studies evaluating correlation of colonoscopy and intestinal ultrasound in ulcerative colitis

Ref.	Study type	Number of patients	Treatment	IUS predictors	Colonoscopy score	Follow-up duration	Time points of IUS	Correlation with colonoscopy
Borthne et al[48]	Prospective	UC 4, CD 17 (pediatric)	NA	BWT, length, CDS, lymph nodes	-	Cross-sectional	Baseline	Sensitivity and diagnostic accuracy of IUS as compared to endoscopy: 93.3%
Bremner et al[49]	Prospective	12 UC (25 CD, 1 in determinate colitis, 6 normal	NA	BWT	Subjective assessment	Cross-sectional	Baseline	Colonic BWT > 2.9: Sensitivity for moderate/severe disease: 48%, specificity: 93%, PPV: 83%; ileal BWT > 2.5 mm: Sensitivity for moderate/severe disease: 75%, specificity: 92%, PPV: 88%
Chavannes et al[72]	Cross-sectional, single centre	33 children with suspected IBD (11 UC)	NA	Ileo-colonoscopy	UCEIS	Cross-sectional	Baseline	Colonic BWT > 1.9 mm: AUC: 0.743, sensitivity: 64%, specificity: 76% to detect inflamed bowel; agreement with colonoscopy: Prediction of IBD: 69.7%, kappa = 0.52; distribution of disease: 45.5%, kappa = 0.48
Haber et al[47]	Prospective	21 UC pediatrics (26 CD, controls)	NA	BWT, BWS, wall echo pattern	No, mild, severe	Cross-sectional	Baseline	AUC: 0.743, sensitivity: 64%, specificity: 76% to detect inflamed bowel
Parente et al[50]	Prospective	83 moderate to severe UC	High dose systemic steroids	BWT, CDS	Baron score	15 mo	Baseline, 3, 9, and 15 mo	Agreement with colonoscopy: Prediction of IBD: 69.7%, kappa = 0.52; distribution of disease: 45.5%, kappa = 0.48
Parente et al[51]	Prospective	83 moderate to severe UC	Same as above	BWT, CDS	Baron score	15 mo	Baseline, 3, 9, and 15 mo	Similar result as the study above
Yamada et al[62]	Prospective	26 UC	NA	SWE, SWD	UCEIS	Cross-sectional	-	SWE and UCEIS correlation: r = -0.404, P = 0.041. No significant correlation between SWD & UCEIS
Carter et al[53]	Retrospective	11 UC (167 CD)	NA	BWT, BWS, CDS, wall echogenicity, i-fat	NA	Cross-sectional	Baseline	Sensitivity 90%, specificity: 23% as compared to colonoscopy/MRE (combined CD and UC)
Antonelli et al[52]	Retrospective	51 moderate to severe UC	NA	BWT > 4 mm	Mayo score	Cross-sectional	-	BWT strongly correlated with CRP and endoscopic score
Allocca et al[16]	Prospective	53 UC	NA	BWT > 3 + CDS; BWT > 4.43 + no CDS	Mayo endoscopic score	Cross-sectional	Baseline	Sensitivity: 68%, specificity: 100%, accuracy: 83%, PPV: 100%, NPV: 73%
Kinoshita et al[54]	Prospective, multi centre (n = 5)	156 UC	NA	BWT, BWS, wall echogenicity	Matt’s endoscopic classification	Cross-sectional	Baseline	Significant concordance between maximum grades (kappa = 0.47) and grades among all colonic segments (kappa = 0.55)
Luo et al[14]	Retrospective	50 UC, 50 CD, and 50 controls	NA	CDS	Active vs remission	Cross-sectional	Baseline	Higher Limberg’s score in active disease (odds ratio: 26.325, P < 0.05)
Sathananthan et al[58]	Prospective, single centre	39 UC (35 CD)	5-ASA, immunomodulator, biologics, steriods	BWT, CDS	MES	Cross-sectional	Same day or within 30 d	Same day colonoscopy (sensitivity 100%, specificity 100%, PPV 100%, NPV 100%, kappa = 1); colonoscopy within 30 d (sensitivity 92%, specificity 86%, PPV 92%, NPV 86%, kappa = 0.77 (MES ≥ 1). Extent: Sensitivity 92%, specificity 80%, PPV 88%, NPV 86%, kappa = 0.7
Sagami et al[57]	Single centre, prospective, cross-sectional	53 UC	5-ASA, immunomodulators, budesonide, anti-TNF	BWT, BWS, CDS	MES	Cross-sectional	Baseline	BWT > 4 mm trans-perineal USG (sensitivity: 100%, specificity: 45.8%, AUC: 0.904) to predict MES, better than trans-abdominal ultrasound (sensitivity: 96.3%, specificity: 12.5%, AUC: 0.667). Correlation of MES with rectal BWT (trans-perineal US): BWT and MES: r = 0.7204, P < 0.0001; CDS and MES: r = 0.6619, P < 0.0001
Kamel et al[56]	Prospective	14 UC (26 CD)	NA	BWT, CDS, BWS, i-fat, lymph nodes, stricture, abscess	NA	Cross-sectional	Baseline	100% agreement between colonoscopy and IUS
Allocca et al[17]	Prospective	43 UC	Details not available	BWT, CDS	Mayo endoscopic score	Cross-sectional	Baseline	MUC > 6.2 discriminated active UC (sensitivity 85%, specificity 94%, AUC 0.902); MUC > 8.2 100% specific; FCP no incremental value
Zhang et al[59]	Retrospective	103 UC	NA	BWT, CDS	Mayo endoscopic score	Cross-sectional	Baseline	Prediction of endoscopic activity: BWT: Not significant; CDS: OR = 2.492, P < 0.001
Bots et al[23]	Prospective	60 UC	Conventional therapy, biologic, tofacitinib, topical tacrolimus	BWT, vascularity, haustrations, fat wrapping	Mayo endoscopic score, UCEIS	Cross-sectional	Baseline	UC-IUS score has strong correlation with endoscopic disease activity (ρ = 0.83 for Mayo score, ρ = 0.76 for UCEIS score); BWT > 2.1 for Mayo 0 vs Mayo 1-3: Sensitivity: 82.6%, specificity: 93%, AUC: 0.91. BWT > 3.2 for Mayo 0-1 vs Mayo 2-3: Sensitivity: 89.1%, specificity: 92.3%, AUC: 0.946. BWT > 3.9 mm for Mayo 3 vs others: Sensitivity: 80.6%, specificity: 84.1, AUC: 0.909
Allocca et al[18]	Prospective	98 UC	NA	BWT, CDS	MES	Cross-sectional	Baseline	Significant correlation between MES and MUC (r = 0.653)
Bots et al[23]	Retrospective, single center	65 UC (280 CD)	Biologics, conventional therapy	BWT, CDS, BWS, i-fat, haustrations, lymph nodes, motility	MES	Cross-sectional	Baseline	Agreement with endoscopy: 86.3%. Correlation: 0.70. Kappa agreement: 0.61 (both UC and CD)
Miyoshi et al[61]	Retrospective	24 UC (31 CD, 10 IBS)	NA	BWT, BWS, CDS, modified Limberg’s score, SMI	MES	Cross-sectional	≤ 15 d between IUS and colonoscopy	BWT < 3.75 mm and SMI < 49.7: Sensitivity: 70%, specificity: 97.7%, PPV: 95.5%, NPV: 82.7%, accuracy: 86.5%
de Voogd et al[2]	Prospective	30 UC	Tofacitinib	BWT	MES and UCEIS	8 wk	Baseline and 8 wk	BWT correlated with MES and UCEIS. Cutoff values for BWT: (1) 2.8 mm for endoscopic remission (AUC: 0.87, 95%CI: 0.74-1.00, P = 0.006) (sensitivity 73%, specificity 100%); (2) 3.9 mm for improvement (AUC: 0.92, 95%CI: 0.82-1.00, P < 0.0001) (sensitivity 81%, specificity 100%); and (3) Decrease of 32% for response (AUC: 0.87, 95%CI: 0.74-1.00, P = 0.002) (sensitivity 71%, specificity 90%). Correlation: ΔBWT and ΔMES: 0.50, P = 0.009; ΔBWT and ΔUCEIS: 0.68, P < 0.0001 (sigmoid); ΔBWT and ΔMES: 0.67, P = 0.001; ΔBWT and ΔUCEIS: 0.50, P = 0.02 (descending colon)
van Wassenaer et al[64]	Prospective cross-sectional	35 UC (pediatric)	NA	UC-IUS score, Civitelli index	Mayo endoscopic score	Cross-sectional	Baseline	UC-IUS score better than Civitelli index for both sensitivity (88%-100% vs 65-80%) and specificity (84%-87% vs 89-93%) (MES ≥ 2). Higher AUC in ascending colon (0.82 vs 0.76) and transverse colon (0.88 vs 0.77). No difference in descending colon (both 0.84)
Goodsall et al[4]	Prospective	29 UC	NA	BWT, CDS, BWS, MUC	UCEIS	Cross-sectional	Baseline	MUC had significant correlation with UCEIS (r = 0.32; 95%CI: 0.14-0.49; P < 0.001)
Lim et al[63]	Prospective cross-sectional	29 UC (22CD)	NA	BWT, BWS, i-fat, CDS	UCEIS	Cross-sectional	Baseline	Sensitivity: 50%, specificity: 100%, PPV: 100%, NPV: 84%; 100% sensitivity/specificity in transverse colon; correlation with endoscopic activity index: 0.648 (P < 0.01)
Maeda et al[20]	Retrospective	58 UC	5-ASA, topical therapy, anti-TNF, vedolizumab	BWT, CDS, BWS, enlarged lymph nodes, MUC	MES	3 mo	Baseline, 3, 6, 12 mo	MUC and MES: 0.61 (entire colon). Most severely affected segment: BWT and MES: 0.88; CDS and MES: 0.98; MUC and MES: 0.88. Accuracy of MUC > 6.2 to differentiate MES ≥ 1 and 0 (sensitivity: 24%, specificity: 100%, PPV: 100%, NPV: 0.47, AUC: 0.67)
Rispo et al[22]	Prospective	86 UC	5-ASA, steroids, IMS, biologics	Milan ultrasound criteria	Mayo endoscopic score	Cross-sectional	-	HHIUS MUC > 6.2: Sensitivity: 80%, specificity: 88%, PPV: 83%, NPV: 86%, accuracy: 84%; highest in sigmoid colon; lowest in rectum

TNF: Tumor necrosis factor; BWT: Bowel wall thickness; CDS: Color Doppler signal; IUS: Intestinal ultrasound; IUS: Intestinal ultrasound; SWE: Shear wave elastography; HHIUS: Hand-held intestinal ultrasound; 5-ASA: 5-amino salicylic acid; UC: Ulcerative colitis; PPV: Positive predictive value; NPV: Negative predictive value; IMS: Immunosuppressant; MUC: Milan ultrasound score; MES: Mayo endoscopic score; BWS: Bowel wall stratification; UCEIS: Ulcerative colitis endoscopic activity index; i-fat: Inflammatory fat; CD: Crohn’s disease; CI: Confidence interval; AUC: Area under the curve; SMI: Submucosal index.

Table 9 Summary of studies comparing intestinal ultrasound and magnetic resonance enterography

Ref.	Study type	Number of patients	Follow-up duration	Comparator	IUS parameters	Gold standard	Results
Kamel et al[56]	Prospective	40 (14 UC, 26 CD)	Cross-sectional	Bowel ultrasound and MRE	BWT, CDS, mesenteric fat and lymph nodes, complications	MRE and colonoscopy	Accuracy of IUS (in IBD): 85% ileum, 70% large bowel, 100% correlation with MRI/colonoscopy with respect to active disease (in IBD) (no separate analysis for UC)
Ziech et al[8]	Prospective	28 suspected IBD pediatric	Cross-sectional	MR colonography	BWT, CDS, BWS, i-fat, haustrations, lymph nodes, motility	MR colonography	Sensitivity IUS: 55%; MR colonography: 57%; Specificity IUS: 100%; MR colonography: 75%; cannot effectively differentiate UC and CD unless terminal ileum is involved
Barber et al[71]	Retrospective	53 children	Cross-sectional	MRE	Scoring based on METRIC trial	Combined consensus score based imaging and clinical scores	Clinical correlation of IUS score (0.657) > MRE score (0.598). Agreement for IUS scoring: Lin coefficient 0.95 > MRE 0.60

CD: Crohn’s disease; UC: Ulcerative colitis; MRE: Magnetic resonance enterography; CTE: Computed tomography enterography; TI: Terminal ileum; BWT: Bowel wall thickness; BWS: Bowel wall stratification; AUC: Area under the curve; IBUS-SAS: International bowel ultrasound segmental activity score; HR-US: High resolution ultrasound.

Table 10 Summary of studies correlating histology with intestinal ultrasound

Ref.	Study type	Number of patients	Treatment	IUS predictors	Histologic score	Correlation
Scholbach et al[66]	Single center, cross-sectional	12 pediatric UC	NA	Dynamic tissue perfusion measurement (DTPM)	No score Parameters: crypt abscess, neutrophils and lymphocytic invasion, wall edema	Wall perfusion on DTPM positively correlated with crypt abscess, neutrophils, and lymphocytic invasion. Negative correlation with wall edema
Romanini et al[42]	Prospective	18 UC, 15 CD	NS	Peak intensity, time to peak, regional blood volume and flow	Vascular density	High vascular density (CD 34+; > 265 vessels per high power field, 40 ×) correlated with IUS and CEUS (higher and earlier peak, higher blood flow and volume)
Kinoshita et al[54]	Prospective	156 UC	NS	BWT, CDI, BWS, wall echogenicity	Matt’s histological grade (1-5)	r = 0.35, P < 0.001
Sagami et al[57]	Single center, prospective, cross-sectional	53 UC	5-ASA, immunomodulators, budesonide, anti-TNF	BWT, BWS	Robarts histopathology index and Nancy histological index	Only BWT independently predicted histological activity in rectum; BWT > 4 highest sensitivity (95.5%), specificity 41.6%, and AUC 0.869 to predict NHI >1; specificity (76.2%) higher and sensitivity (59.1%) lower with Limberg’s score ≥ 2 (AUC: 0.812)
Goodsall et al[4]	Prospective	19 UC (29 paired data)	NS	Milan ultrasound criteria (MUC), BWT, CDI, BWS	NHI	Coefficient: 0.14, P = 0.011; MUC > 6.3 and/or FCP ≥ 100 μg/g for NHI > 1 sensitivity 88%, specificity 90%, PPV 95%, NPV 57%

PPV: Positive predictive value; NPV: Negative predictive value; UC: Ulcerative Colitis; CD: Crohn’ disease; CDI: Color Doppler intensity; BWT: Bowel wall thickness; AUC: Area under the curve; NHI: Nancy histologic index; BWS: Bowel wall stratification; IUS: Intestinal ultrasound.

Table 11 Summary of studies on intestinal ultrasound in pediatric inflammatory bowel disease

Ref.	Study type	Number of patients	Follow-up duration	Gold standard	Comparator	Results
Borthne et al[48]	Prospective	43 children with suspected IBD	3 wk	Endoscopy	Endoscopy	Sensitivity and accuracy of IUS compared to endoscopy: 93.3%
Bremner et al[49]	Prospective	12 UC (25 CD, 1 indeterminate colitis, 6 normal)	Cross-sectional	ileo-colonoscopy	Ileo-colonoscopy	Colonic BWT > 2.9: Sensitivity for moderate/severe disease: 48%, specificity: 93%, PPV: 83%; ileal BWT > 2.5 mm: Sensitivity for moderate/severe disease: 75%, specificity: 92%, PPV: 88%
Haber et al[47]	Prospective	21 UC pediatrics (26 CD, controls)	Cross-sectional	Ileo-colonoscopy	Ileo-colonoscopy	Sensitivity and specificity of IUS as compared to endoscopy: 77% and 83%, respectively
Ziech et al[8]	Prospective	28 suspected IBD pediatrics	Cross-sectional	Ileocolonoscopy and endoscopy	MR colonography	Sensitivity IUS: 55%; MR colonography: 57%. Specificity IUS: 100%; MR colonography: 75%; cannot effectively differentiate UC and CD unless terminal ileum is involved
Barber et al[71]	Retrospective	53 children	Cross-sectional	Combined consensus score based imaging and clinical scores	MRE	Clinical correlation of IUS score (0.657) > MRE score (0.598); agreement for IUS scoring: Coefficient 0.95
Chavannes et al[72]	Cross-sectional, single centre	33 children with suspected IBD (1 UC)	Cross-sectional	Ileo-colonoscopy	Ileo-colonoscopy	Colonic BWT > 1.9 mm: AUC 0.743, sensitivity: 64%. specificity: 76% to detect inflamed bowel. Agreement with colonoscopy: Prediction of IBD: 69.7%, kappa = 0.52; distribution of disease: 45.5%, kappa = 0.48
Dell'Era et al[7]	Retrospective	113 suspected pediatric IBD	1 year	Ileo-colonoscopy and 1 year follow-up	Ileo-colonoscopy	IUS bowel pattern, mesenteric hypertrophy, and BWT > 3; all 3 sensitivity: 57.5%; specificity: 100%
Scarallo et al[35]	Single centre, retrospective	25 acute severe UC patients	Cross-sectional	NA	PUCAI > 45 at day 3; PUCAI > 65 day 5	At day 3 BWT > 3.4 mm and loss of BWS are independent predictors of steroid failure; BWT > 3.4 mm 92% sensitivity and 52% specificity for steroid resistance; PUCAI > 45 at day 3: 80.6% sensitivity and 45.5% specificity; PUCAI > 65 at day 5: 33.3% sensitivity and 90% specificity
van Wassenaer et al[68]	Prospective cross-sectional	22 UC	Cross-sectional	Ileo-colonoscopy	Physicians vs radiologists	Moderate inter-observer agreement for disease activity in terminal ileum (kappa = 0.58), descending colon (kappa = 0.52), and transverse colon (kappa = 0.49) between radiologists (AUC: 0.67-0.79) and gastroenterologists (AUC: 0.71-0.81)
Hudson et al[69]	Cross-sectional study	35 CD,15 UC,4 IBD	Cross-sectional	SES-CD, Mayo endoscopic score	MRE and endoscopy	High patient and caregiver satisfaction. Preferred over MRE and colonoscopy. No concern about IUS findings in those with co-existing anxiety
van Wassenaer et al[64]	Prospective cross-sectional	35 UC (pediatric)	Cross-sectional	Mayo endoscopic score	Endoscopy	UC-IUS score better than Civitelli index for both sensitivity (88-100% vs 65%-80%) and specificity (84%-87% vs 89%-93%) (MES ≥ 2); higher AUC in ascending colon (0.82 vs 0.76) and transverse colon (0.88 vs 0.77). No difference in descending colon (both 0.84)
Mohamed et al[74]	Prospective	40 IBD	Cross-sectional	Clinical and fecal calprotectin	Clinical activity	Combined gray scale ultrasound, color Doppler, and shear wave elastography increase accuracy (92%) with 100% accuracy
Otani et al[73]	Retrospective	40 UC	Cross-sectional	Colonoscopy and fecal calprotectin	Fecal calprotectin	Accuracy of sum of adjusted bowel wall thickness was higher than fecal calprotectin for detecting moderate colonic inflammation (Mayo endoscopic score 2)
Spyropoulou et al[70]	Prospective	32 UC	cross-sectional	Colonoscopy	Colon capsule endoscopy, fecal calprotectin	Sensitivity, specificity, PPV, and NPV of US are 85%, 92%, 94%, and 79%, respectively. Noninvasive approach combining CCE, FCP, and IUS better tolerated than colonoscopic monitoring

CD: Crohn’s disease; UC: Ulcerative colitis; TI: Terminal ileum; IUS: Intestinal ultrasound; HRUS: High resolution ultrasound; MRI: Magnetic resonance imaging; MRE: Magnetic resonance enterography; BWT: Bowel wall thickness; PCD: Pediatric Crohn’s disease; UC-IUS: Ulcerative colitis intestinal ultrasound score; PCDAI: Paediatric Crohn Disease Activity; CCE: Colon capsule endoscopy; FCP: Fecal calprotectin; AUC: Area under curve; IBD: Inflammatory bowel disease; PUCAI: Pediatric ulcerative colitis activity index, PPV: Positive predictive value; NPV: Negative predictive value.

Table 12 Summary of studies on transperianal ultrasound in ulcerative colitis

Ref.	Study type	Number of patients	Follow-up duration	Comparator	USG parameters	Results
Sagami et al[57]	Cross-sectional	55 UC	Cross-sectional	Endoscopy, Histopathology	BWT, CDS, BWS	BWT ≤ 4 MM predicts endoscopic healing (MES ≤ 1), AUC = 0.904. BWT ≤ 4 MM predicts rectal histologic mucosal healing, AUC = 0.869. Better than FCP
Sagami et al[78]	Prospective, single centre	100 UC	Cross-sectional	FCP, CRP	BWT, CDS	Rectal ΔBWT at 1 wk predicted remission at 8 wk (odds ratio for 1 mm increase is 1.9); FCP did not predict remission

MES: Mayo endoscopic score; UC: Ulcerative colitis; FCP: Fecal calprotectin; CRP: C- reactive protein; BWT: Bowel wall thickness; CDS: Color Doppler signal; AUC: Area under the curve; BWS: Bowel wall stratification.

Table 13 Summary of studies evaluating role of point-of-care ultrasound in inflammatory bowel disease

Ref.	Study type	Comparator	Follow-up duration	Number of patients	Impact on management
Bots et al[60]	Retrospective	MRI, colonoscopy	MRE within 8 wk of IUS	345 (280 CD and 65 UC)	POCUS changed management in 60%; change in medications 48%; correlation with IUS 86.3%; correlation with MRI 80%; reduced use of MRI with increased adoption of IUS
Sathananthan et al[58]	Prospective	Ileocolonoscopy	POCUS & ileocolonocscopy within 30 d of one another	74 (CD 35; UC 39)	Correlation with same day colonoscopy (sensitivity 100%, specificity 100%, PPV 100%, NPV 100%, kappa 1); correlation with colonoscopy within 30 d (sensitivity 92%, specificity 86%, PPV 92%, NPV 86%, kappa 0.77 (MES ≥ 1); extent: Sensitivity 92%, specificity 80%, PPV 88%, NPV 86%, kappa 0.7
Carter et al[53]	Retrospective	MRE	Cross-sectional	11 UC (167 CD)	Sensitivity 90%; specificity: 23% as compared to colonoscopy/MRE (combined CD and UC); impact on management not evaluated
de Voogd et al[2]	Prospective, single centre cohort	Clinical activity and FCP	Prospective, single centre cohort study	16 UC, 22 CD	Impact on management (56.25%); treatment escalation: n = 6 (UC); continue same treatment: n = 3 (UC)
Saleh et al[89]	Retrospective	Clinical (UCAI ≤ 5 and partial Mayo ≤ 2) and biomarker remission (ESR ≤ 40 mm/h and CRP ≤ 10 mg/L and fecal calprotectin ≤ 50 µg/mg and fecal lactoferrin ≤ 30 µg/mL)	Mean time between follow-up IUS 203 d	39 UC, 108 CD	25 active UC on IUS; change in plan: 13; continue therapy: 11; deescalate therapy: 1; 14 inactive UC; 80.7% continued therapy (overall IBD); 5.2% deescalated therapy; 14% change in therapy Treatment change more in those with higher BWT (≥ 5 mm, < 5 mm-> 3 mm, ≤ 3 mm); Treatment change did not differ by CDS (Limberg’s score 0, 1, ≥ 2)
Lu et al[77]	Prospective, observational	Sigmoidoscopy, FCP, CTE/MRE	1 year	UC-16 (CD-46)	Change in management in 80% with IUS only (all IBD); Sigmoidoscopy + IUS 83% change in management

CD: Crohn’s disease; MRE: Magnetic resonance enterography; IUS: Intestinal ultrasound; UC: Ulcerative colitis; MRI: Magnetic resonance imaging; BWT: Bowel wall thickness; POCUS: Point-of-care intestinal ultrasound; HHIUS: Hand-held intestinal ultrasound.

Table 14 Summary of studies on implementation of intestinal ultrasound services

Ref.	Year	Country	Survey participants	Main results
Maconi et al[96]	2011	Italy	12 sonographers	24% of ultrasound referrals were for bowel ultrasound; 78% referred by gastroenterologists; half for suspected bowel disease and half for follow-up
Hafeez et al[95]	2014	United Kingdom	63 radiology and 73 gastroenterology departments	Barium meal follow through and CT preferred for luminal and extraluminal complications; IUS mainly for young patients with low suspicion of Crohn’s disease; used in 44% of radiology departments
Rajagopalan et al[99]	2019	Australia	121 patients	IUS scored highest in the visual analogue scale as compared to colonoscopy, stool/blood sampling/imaging; IUS improved patient IBD specific knowledge of the need for medical therapy and disease extent
Radford et al[97]	2022	United Kingdom	103 IBD physicians	30% have IUS service (100% had MRI service); average time to reporting; USG (1-4 wk) (MRI: 4-6 wk); 59.6% confident in clinical decision-making using USG (MRI: 97%)
Radford et al[98]	2023	United Kingdom	14 stakeholders	Barriers to implement IUS service: (1) Reliance on existing imaging pathways; (2) Reluctance to change; (3) Perceived lack of precision; and (4) Initial financial and time outlay. Perceived benefits: (1) Reduced waiting time; (2) Earlier diagnosis and treatment allocation; (3) Reduced hospital appointments; and (4) Better understanding of disease

CT: Computed tomography; USG: Ultrasonography; IBD: Inflammatory bowel disease; MRI: Magnetic resonance imaging; IUS: Intestinal ultrasound.