Treat to transmural healing: how to incorporate intestinal ultrasound into the treatment of inflammatory bowel disease

Intestinal ultrasound (IUS) is emerging as a key tool to achieving the therapeutic target of transmural healing in inflammatory bowel disease (IBD). IUS is a non-invasive, radiation-free, imaging modality comparable to MRI, CT and ileocolonoscopy (IC). With the appropriate training and equipment, IUS can be an easily repeatable bedside test for IBD diagnosis and disease monitoring, including treatment response. Core to successful high quality IUS employment are appropriate training and expert techniques; however, the training pathway will not be explored in this review. Given the increasing shift towards objective assessment for tight disease control, gastroenterologist-led IUS should be incorporated into the armamentarium of imaging modalities alongside radiologists, to enhance our diagnostic and monitoring toolbox. This comprehensive review aims to outline the current literature around IUS and propose the placement of IUS in a treat-to-target algorithm in IBD. Ultimately, IUS facilitates timely management decisions to optimise patient care with potential to revolutionise patient outcomes, moving towards transmural healing as the holy grail of therapy in IBD.


INTRODUCTION
Inflammatory bowel diseases (IBD), comprised of Crohn's disease (CD) and ulcerative colitis (UC), are chronic immune-mediated gastrointestinal disorders characterised by periods of activity and remission.[4] The updated Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE II) guidelines raise treatment expectations.Therapeutic targets focus on clinical and endoscopic healing (EH), however, aspirational targets include histologic and transmural healing (TH) which reduce relapse rates, hospitalisation and need for surgery. 1 Although ileocolonoscopy (IC) is the gold-standard for disease assessment, 5 myriad limitations include need for anaesthesia/sedation, invasiveness, high costs with challenging access.Cross-sectional imaging has limitations: CT imparts radiation and requires iodine-based intravenous (i.v.) contrast, thus is not recommended for surveillance 5,6 ; magnetic resonance enterography (MRE) involves long image acquisition times and often requires contrast. 6,7IUS presents a safe, accurate, cost-effective alternative for transmural assessment.Cost comparison of these modalities is however needed.][10] This review aims to summarise how IUS is gaining recognition in IBD practice and illustrate IUS as an indispensable objective tool to guide therapy and limit disease progression and complications. 4RE MRE is preferred over CT without significant difference in disease localisation (p = 1.0), bowel wall thickening (BWT) (p = 1.0), wall enhancement (p = 1.0) or detection of fistulae (p = 0.08), lymphadenopathy (p = 1.0) and perivisceral fat enhancement (p = 0.31).Additionally, MRI is superior in per segment analysis in detecting ileal wall enhancement (p = 0.02) and strictures (p = 0.04). 22Ample literature supports high correlation between MRE and endoscopy in assessment of inflammatory IBD activity. 20,24,25RE is however time-consuming and costly, somewhat limited by breath-holding ability and claustrophobia. 26Risks of contrast agents when employed, such as nephrogenic systemic fibrosis and substance accumulation within the basal ganglia have been documented, however, the former is usually minimised through routine renal function testing and appropriate patient selection, and the clinical significance of the latter remains unclear. 27

IUS
A landmark prospective multicentre trial comparing the diagnostic accuracy of MRE and IUS for the extent and activity of newly-diagnosed and relapsed CD (METRIC) confirmed both are accurate with high sensitivity for detecting small intestinal disease. 21MRE sensitivity was 97% (95% CI 91-99) for detecting terminal ileal disease with IUS sensitivity 91% (95% CI 79-97). 21olonic disease is universally more challenging: MRE sensitivity was 41% [26-58] while IUS was 49% [33-65], not statistically significant. 21Unlike IUS, the accuracy of MR for distal colonic disease is enhanced with rectal contrast. 28Literature demonstrates comparable agreement between IUS and MRE in detecting IBD location and activity, 19,29 although MRE is more sensitive in assessing disease extent. 19

STANDARD MONITORING IN IBD
Clinical, biochemical and endoscopic parameters are used to assess IBD activity and therapeutic response with a shift towards objective improvement to guide therapy. 1,5,30Notably, imaging cannot replace endoscopy and biopsies for dysplasia surveillance and tissue diagnosis. 5ochemical markers C-reactive protein (CRP) >5 mg l −1 has high specificity for detecting endoscopic IBD activity but low sensitivity in excluding a flare. 31Faecal calprotectin (fcal), a neutrophil-derived protein with high sensitivity and low specificity for intestinal inflammation, correlates with endoscopic disease in IBD diagnosis, relapse and treatment response, particularly in the colon 5,[32][33][34] with values <150 μg/g suggesting endoscopic healing (EH). 1 It is more specific and sensitive than CRP, unaffected by extraintestinal pathology. 35Abnormal CRP and fcal should prompt exclusion of infection and confirmation with endoscopy or imaging. 5Whilst blood and stool biomarkers are compositely used to predict disease activity and therapeutic response, they cannot predict disease location nor extent, and can be falsely negative. 1,36doscopy EH in CD is associated with improved long-term outcomes, reduction in bowel damage, relapse, surgery risk and complications even in clinical remission. 37,38IC or flexible sigmoidoscopy ± biopsies remain the reference standard for disease activity assessment. 5Mucosal healing (MH) is associated with long-term corticosteroid-free clinical remission, reduced risk of colectomy and inflammation at 5 years. 39,40Histologic healing is associated with reduced complications including hospitalisation, corticosteroid use 41 and cancer prevention. 42However, histological targets are tempered by lack of established incremental gain over MH alone. 43deo capsule endoscopy (VCE) is an adjunctive modality for small bowel evaluation.VCE is well-tolerated, minimally invasive, without sedation requirement; 44,45 however, access is not ubiquitous due to cost and local expertise. 46Patency capsule clearance may be necessary 5,45 as VCE retention occurs in 2-13% due to stenoses/strictures. 47 It is considered safe to proceed to VCE if the patency capsule is passed after 30 h or confirmed radiologically. 48

ADVANTAGES OF IUS COMPARED TO OTHER MONITORING TECHNIQUES
Transmural healing (TH) is an aspirational target for CD beyond endoscopic MH, imparting further beneficial outcomes 49 with IUS well-placed to assess TH (Figure 1).Patient experience and preference are increasingly recognised in monitoring strategies, given the potential impact on adherence and outcome, yet have not directed algorithms nor guidelines to date. 5 IUS is well-tolerated, easily repeatable with opportunity to engage patients in real-time. 50Otherwise, patients need to return to their provider for information. 35,51Bedside IUS facilitates timely medical decision-making 35,51 a distinct advantages over MR/CT. 50Patients report enhanced disease understanding and confidence in making informed treatment decisions. 51Nearly all (99%) patients in the METRIC trial rated IUS as acceptable compared to 88% for MRE. 21IUS also exhibits high interobserver agreement; 51,52 in the METRIC cohort, κ coefficient (k) was 0.64 for small bowel disease diagnosis and 0.63 for relapsing disease. 53In UC, interobserver agreement for BWT is almost perfect with intraclass correlation coefficient (ICC) of 0.96, with substantial agreement for colour Doppler imaging (CDI) k = 0.63, disease activity k = 0.77 and ICC of 0.93 for disease severity emphasising IUS reliability. 54Real-time interobserver agreement is also demonstrated in CD: six blinded operators exhibited moderate agreement on BWT and stratification, vascularisation, and lymphadenopathy and substantial agreement on lesion location, and presence of fistula, phlegmon and abscess.Not so for mesenteric adiposity changes, lesion extent, narrowing and prestenotic dilatation with poor agreement demonstrated. 55In certain populations, IUS may be less prone to technical difficulties compared with MRE, without motion artifact causing image degradation 29 or bowel preparation. 50There are recognised challenges in performance of IUS, such as increased abdominal adiposity limiting resolution of bowel loops in addition to limitations in anatomic resolution.

IUS FINDINGS Bowel wall thickness (BWT)
BWT is the most reliable and important measure of IBD activity with good interobserver agreement (k 0.72-1). 3,18,56BWT is measured perpendicular to the wall in axial and longitudinal axes, from the mucosal interface to the serosa, avoiding mucosal folds and haustra 3,4,57 (Figure 1).A threshold value of >3 mm is agreed to be pathological, with a sensitivity of 88% and specificity of 93%, more accurate compared to a cut-off of 4 mm (75 and 97% respectively). 57,58While some advocate for a continuous scoring of BWT, others categorise, e.g.Ultrasound Global Assessment of Disease Activity Score, BWT of 4.0-6.0 is mild inflammation; 6.1-8.0 moderate; and >8.0 severe. 57BWT is considered a surrogate marker of transmural inflammation with thickening predictive of disease recurrence and surgery risk. 59,60wel wall stratification (BWS) IUS is the only modality that clearly depicts wall layering 4,57 (Figure 2).Interreader variability for detecting BWS is fairly reliable with k −0.22-0.85. 56Focal and/or extensive disruption in BWS correlates with active disease. 3Chronic inflammatory changes often lead to architectural alterations involving the intestinal submucosa, characterised by increased BWT and echogenicity. 57peraemia Increased vascularity of the bowel wall due to inflammation is assessed by colour Doppler imaging (CDI), set to detect low flow, small calibre vessels. 57Normal bowel has minimal vascularity on CDI; however, increased intramural and extramural flow strongly correlates with histologic inflammation 61 (Figure 3a and b) with grading as suggested (Table 2) .There is variable interobserver agreement with k 0.53-0.89, 56likely due to its semi-quantitative and subjective assessment, contingent upon machine settings and physiologic variability. 4Reliable depiction of CDI requires careful, consistent machine calibration, breath-holding, and standard machine settings. 63It is predominantly qualitative thus should be interpreted with some caution.Deep bowel loops may reveal falsely low signal, and inflamed bowel may not have detectable flow.However, CDI remains one of the most important parameters contributing to inflammatory activity.

Lymphadenopathy
Mesenteric lymph nodes (LN) are common yet non-specific, often present in healthy individuals, especially children. 4,64,65LNs > 10 mm (short axis) are more likely to be pathologic. 3,65Interobserver LN assessment is reproducible (k 0.56-0.90). 56However, the lack of association with clinical or biochemical activity and poor specificity excludes LNs from most activity indices. 63

Mesenteric fat hypertrophy (MFH)
Creeping fat or MFH due to fibro-fatty proliferation is important pathophysiologically, 66 appearing as hyperechoic, homogeneous  tissue on the mesenteric aspect of diseased bowel. 3,64,67Although it has poor interobserver agreement (k 0.14-0.69), 56MFH is associated most strongly with histological grade of inflammation compared with focal hyperechogenicity without fat wrapping or stratified pattern. 68tramural complications: strictures, fistulae, abscesses Strictures are common in CD, leading to clinical and subclinical obstruction (Figure 4a, b and c).Defined as luminal narrowing, strictures exhibit increased BWT, pre-stenotic dilatation, with luminal diameter greater than 25-30 mm often associated with hyperperistalsis of the prestenotic segment. 3,69Early strictures may not exhibit proximal dilatation.Discerning the relative contribution of inflammatory vs fibrotic components (potentially reversible vs irreversible) remains challenging, impacting optimal medical vs surgical/endoscopic dilation intervention. 70US techniques are rapidly evolving to address this conundrum: CDI, elastography, echostratification and contrast-enhanced ultrasound (CEUS) may provide valuable insight. 3,71Strictures associated with inflammation may exhibit BWS loss and hyperaemia.Stratification loss may also signify smooth muscle hypertrophy, refractory to medical therapy (CDI may help to discern the two); fibrotic strictures can exhibit echogenicity and hypovascularity portending need for endoscopic dilatation or surgery. 3,64,72,73IUS detection is highly accurate compared to CT/MRI and gross pathology: pooled sensitivity of 79% (95% CI 71-84%) and specificity 92% (95% CI 87-96%). 9,74IUS also affords real-time assessment of intestinal motility, distinguishing collapsed bowel or functional contractions in strictures and dysmotility associated with obstruction. 64S can detect fistulae, sinus tracts and fissures 3,57,64 with similar accuracy to CT and MRI 22,75 (Figure 5a).Fistulae result from extramural fissures arising from deep intestinal ulcerations communicating with other tissues, whereas sinus tracts are linear extensions/blind-ends. 3,64Both sinus tracts and fistulae are hypoechoic irregularities arising from thickened bowel with or without gas, with a diameter <2 cm. 3,19,76In one systematic review, IUS had a pooled sensitivity of 74% (95% CI 67-79%) in detection of enteric fistulae compared with surgery. 16mpared with surgery, IUS has a pooled sensitivity of 84% (95% CI 79-88%) and specificity 93% (95% CI 89-95%) for abscess detection. 16Microperforations may appear as inflammatory perienteric masses without extraluminal air (phlegmon).Spiculation or hypoechoic stranding from the outer serosa 57,77 are harbingers of penetrating complications: abscesses (Figure 5b) or poorly defined inflammatory masses (Figure 5c): hypoechoic masses with or without echogenic gas. 57An inflammatory mass can be differentiated from abscess with CDI or CEUS. 3,57,64nterobserver agreement is excellent for detection of stenosis in IBD using IUS (k 0.81-1), whereas for fistulae it varies. 56S can characterise small bowel motility in real-time although standardisation is needed.Peristalsis is non-specific, however, can be reduced or absent in diseased bowel.Free intra-abdominal fluid juxtaposed to diseased bowel is non-specific but can reflect disease severity. 3,64

UTILITY OF IUS IN CD Diagnosis, disease extent and activity
Although important for quality of life, clinical symptoms correlate poorly with objective inflammation.In the CALM trial, use of symptoms to guide treatment in CD resulted in lower rates of EH compared to patients with composite clinical and biomarker assessments. 36IUS is comparable in diagnosing CD compared to MRE and IC 19,21 with diagnostic sensitivity of 94%, specificity of 97%, a positive-predictive value of 97% and negativepredictive value of 94%. 19 Allocca et al 52 showed IUS had 92% sensitivity and 100% specificity for presence of ulcers at colonoscopy, with high diagnostic accuracy compared to MRE and IC: 91% for disease localisation,  96% for ulceration. 52Repeatability during follow up and timely therapeutic response measurement is key: Kucharzik et al. 67 conducted the multicentre TRUST study, serially following CD patients over 12 months demonstrating IUS changes in response to therapy. 79st-operative recurrence IUS confers high accuracy in detecting recurrence compared to IC, 64,80 whereas clinical and biomarkers correlate poorly with IC. 81 Although fcal is accurate, a moderate false-positive rate in discerning post-operative recurrence exits 82 which may improve when combined with IUS. 64BWT correlates with endoscopic recurrence and lack of therapeutic response signifying surgical risk. 59,83,84BWT > 3 mm had 79% sensitivity and 95% specificity for post-surgical endoscopic recurrence (Rutgeerts' score ≥i2): sensitivity 93% for detecting severe post-surgical recurrence (Rutgeerts' score ≥i3). 60

UTILITY OF IUS IN UC Diagnosis, disease extent and activity
Evidence for IUS in UC is evolving with IC and biopsies the mainstay of UC diagnosis. 3,5,20,85In UC, symptom correlation is still imperfect. 1,86Persistent, low-grade inflammation portends worse outcomes, including hospitalisation and corticosteroid need. 41IUS can be used to detect BWT in active UC 3 although absence of BWT does not exclude active inflammation, and CDI is an important tool to detect mild to moderate inflammation limited to the mucosa.It is accurate in detecting inflammation and defining extent proximal to the rectum. 3,87TRUST&UC, a multicentre prospective observational study demonstrated IUS as a sensitive tool detecting disease activity with increased BWT in 88.5% of those flaring with left-sided or pancolitis. 35Whilst rectal assessment can be challenging, a transperineal approach is promising 88 and IUS remains valuable conferring more than 70% sensitivity in detecting disease proximal to the rectum, with up to 97% sensitivity in the sigmoid and descending colon. 10oss of BWS, increased hyperaemia and MFH are also features of greater disease activity. 4,10,35e TRUST group demonstrated BWT and CDI mirrored improvements in clinical scores and fcal at 3 months, with changes seen as early as 2 weeks. 35This rapid IUS response to intensified therapy with subsequent response on clinical indices cements the role of IUS in UC monitoring. 35Early evidence also predicts corticosteroid response in guiding salvage therapy timing in acute severe UC. 89

ADJUNCTIVE TECHNIQUES IN IUS Small intestine contrast ultrasonography (SICUS)
Ingestion of a neutral oral contrast agent, (500-800 ml polyethylene-glcyol/PEG) 30 min pre-examination increases sensitivity for detection of proximal small bowel disease, strictures and penetrating complications. 3,64,76Pallota et al showed SICUS had 97.5% sensitivity and 100% specificity in identifying at least one stricture (k = 0.93) and sensitivity of 75 and 100% specificity for at least two or more strictures (k = 0.78). 76Additionally, SICUS had 96% sensitivity and 90.5% specificity (k = 0.88) in identifying fistulae in 27/28 patients as well as 100% sensitivity and 95% specificity (k = 0.89) in detecting intraabdominal abscesses in 10 patients undergoing bowel surgery. 76espite this, oral contrast is not commonly employed clinically, as it prolongs exam time and is not preferred by patients.

Transperineal ultrasound (TPUS)
A small high frequency curvilinear or linear transducer on the perineum can visualise the anal canal and surrounding soft tissues to characterise penetrating, perianal disease. 57,64Presence of internal and external fistulae, location within the anal canal and clock-face representation can be accurately documented. 57PUS has high diagnostic accuracy compared with both endoanal ultrasound: sensitivity of 84.9% for fistulae detection 90 ; and MRI, with a sensitivity of 90.6%, with excellent agreement between TPUS and MRI (k = 0.783).91 The accuracy in detecting abscesses has pooled sensitivity of 86% (95% CI 67-99%) and positive-predictive value of 90% (95% CI 76-99) in a metaanalysis.92 Whilst TPUS is currently useful in screening for perianal disease, its role in assessing disease severity and monitoring response remains to be clarified, and operator expertise must be acknowledged.92

Contrast-enhanced ultrasound (CEUS)
Although CEUS utility with standard greyscale B mode IUS for luminal assessment of disease activity is limited globally, it can aid in differentiation between an inflammatory mass vs abscess.IUS with microbubble contrast, comprised of 2-6 μm lipid-coated gas particles 57 is used to augment perfusion assessment.A retrospective review demonstrated 100% specificity for abscess detection among 71 inflammatory masses in 50 patients, resulting in k = 0.972 for differentiating abscess vs phlegmon. 93he role of CEUS in activity assessment is contentious, with lack of agreement on peak enhancement or area under the curve thresholds, adding significant complexity to standard examination, limiting uptake.

Shear wave elastography (SWE)
SWE is an exciting IUS application measuring shear wave speed generated by an acoustic pressure wave through bowel as a marker of tissue density and stiffness in real-time, 57,64,94 reflecting fibrosis vs inflammation in strictures.SWE is higher in fibrosis with AUC of 0.822 when using cut-off 22.55 kPa as a discriminator between mild-moderate and severe fibrosis. 95ombined with CEUS, SWE can accurately identify inflammation and smooth-muscle hypertrophy. 95However, its application is limited as standardisation of measures across machines is lacking.

IUS ACTIVITY SCORES: UTILITY AND LIMITATIONS
There is no consensus on an optimal IUS scoring index. 96The recently derived International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) uses reliable sonographic components including BWT, BWS, CDS and inflammatory fat. 63The Simple Sonographic Score comprises BWT and Doppler, 97 developed using statistically significant parameters in a retrospective then prospective evaluation of IUS with endoscopy with an AUROC of 0.836 when applied to a prospective cohort for external validation. 97Due to lack of prospective validation, widespread use of scores is limited.Currently, a large international multicentre trial is in progress to establish this. 98

TARGETING TRANSMURAL REMISSION (TR): IUS IN CLINICAL PRACTICE
Transmural remission (TR), defined as the resolution of mucosal ulcerations, transmural disease and extramural disease 99 is associated with sustained clinical remission, reduced need for medical escalation, surgery and prevention of bowel disease progression with better outcomes than endoscopic remission 49,100,101 (Figure 1).We propose an algorithm for timing IUS at index, followed by routine surveillance 36 (Figure 6).IUS performed at baseline for those with suspected IBD or symptoms, as recommended by ECCO-ESGAR, to ensure exclusion of complications and proximal disease in IBD. 5 In established IBD, serial exam intervals are contingent upon treatment trajectory: to evaluate therapeutic response, after drug initiation, evaluation at 12 weeks is ideal.Earlier evaluation may be important as the TRUST UC showed changes at 2 weeks. 35Post-operative IUS should occur within 3-6 months with fcal, which may obviate endoscopic confirmation and optimise resource use.Use of MRE/ CTE is important where IUS is limited or for complex perianal disease, complex post-operative anatomy or need for exclusion of extraintestinal manifestations, such as sacroiliitis.IUS should be correlated with biomarkers to objectively guide timely clinical decisions.Presence of complications may necessitate additional imaging such as MRE prior to endoscopic or surgical intervention.

What is the treatment target in IUS and is it achievable?
A recent systematic review established much needed expert consensus on IUS treatment response and transmural remission. 102The presence of complications including stenoses portends poorer response and clinical outcomes compared to uncomplicated luminal inflammatory disease, likely related to the reversibility of disease and respective damage. 102High quality, large population studies are needed regarding monitoring and resolution of CD-related intestinal complications.Colonic disease tends to respond faster than ileal disease. 102nother important reportable aspect of response is reduction in length of disease, in addition to improvement in BWT (>25%), BWS, hyperaemia, mesenteric inflammatory fat proliferation, and lymphadenopathy. 35Incremental levels of healing offer superior outcomes in IBD, although a minority of patients will achieve deeper TH (~25%) and histological healing (~10%) with conventional therapy (Figure 7).

FUTURE DIRECTIONS
Despite its paradigm-changing potential, widespread uptake of IUS remains challenging. 64,103Incorporation of IUS into routine IBD practice requires specialised training, service delivery adaptation, with investment into ultrasound technology and funding model evolution. 103Current funding models favour MRE or CTE.Coordinated efforts between national and international groups beyond Europe are needed to encourage IUS in guidelines for IBD monitoring and must include patient experience and preference in their consensus. 64,103Broadening IUS applicability to other intestinal disorders has been suggested given its timely nature including functional motility gastrointestinal disorders and visualisation of faecal loading, 64 however further prospective studies are warranted to validate such use.

CONCLUSION
IUS is integral to future patient-centred, innovative models of IBD care.Monitoring strategies should align with patient preferences and foster patient engagement.Multidisciplinary care is the foundation of excellence in care, combining expertise in imaging from both specialist gastroenterologists coordinating medical care with experts in diagnostic imaging, to leverage the benefits of all dedicated small bowel imaging modalities.Integration of IUS into clinical practice will facilitate early and accurate IBD disease assessment to enable objective monitoring and expedited therapeutic decision-making, improving patient experience, outcomes and quality of life.

CONFLICTS OF INTEREST
AA has no conflicts; RV has no conflicts; BC received consulting fees/speaker's honoraria from Janssen, AbbVie, Takeda, Gilead and Novartis and research grants from Pfizer, Ferring and Janssen; RVB has received Grant/Research support/Speaker fees (all paid to employer for research support): AbbVie, Ferring, Janssen, Shire, Takeda, Emerge Health; shareholder in Biomebank; KN reports advisory board fees from AbbVie, Janssen, Pfizer, Ferring and Takeda; speaker's fees from AbbVie, Janssen and Pfizer; and research support from AbbVie, Janssen FUNDING Open access publishing facilitated by The University of Melbourne, as part of the Wiley -The University of Melbourne agreement via the Council of Australian University Librarians

Figure 1 .
Figure 1.Normal BWT seen in longitudinal view of the sigmoid colon.BWT, bowel wall thickening

Figure 2 .
Figure 2. Complete loss of bowel wall stratification.

Figure 3 .
Figure 3. (a) Increased signal on colour Doppler imaging of the terminal ileum.(b) Grade 4 hyperaemia on Doppler with extension into mesentery.

Figure 4 .
Figure 4. (a) Stricture with pre-stenotic features of hyperaemia, loss of wall stratification and marked mesenteric inflammatory fat (b).Dilated small bowel segment with stagnant fluid contents suggestive of bowel obstruction (c).Luminal narrowing with per-stenotic dilation and loss of wall stratification within a stricture.

Figure 5 .
Figure 5. (a) Enterovesical fistula with echogenic inflammatory fat.(b) Penetrating terminal ileal disease with hypoechoic area (6*4.1 mm) suspicious for abscess with marked inflammatory for echo.(c) Severs increase in BWT in the terminal ileum hypoechoic area deep to inflamed loop suggestive of phlegmon.BWT, bowel wall thickening.

ACKNOWLEDGEMENTS
AA is supported by scholarships and grants from Crohn's and Colitis Australia, the Australian Commonwealth Government Research Training Program (University of Melbourne), the Gastroenterogical Society of Australia and Celltrion Healthcare.KN is supported by the Helmsley Trust CONTRIBUTORS AA, BC, RB and KN developed the manuscript outline.AA, KN drafted the manuscript.All authors edited and approved the final review prior to its publication.

Table 1 .
Advantages of IUS as point-of-care tool