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The Next Frontiers of Intestinal Ultrasound for the Assessment of Inflammatory Bowel Disease (IBD): CEUS, SICUS, and Elastography

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In recent years, the utility of intestinal ultrasound (IUS) in diagnosing and managing inflammatory bowel disease (IBD) has gained substantial momentum. The Scan featured a blog post in June 2024 describing the features and uses of IUS for diagnosing and monitoring IBD. That previous article highlighted the many features that can be monitored to assess IBD disease activity and severity right at the bedside using B-mode ultrasound, highlighting that bowel wall thickness (BWT), Doppler signaling (hyperemia), loss of stratification of bowel wall layers (BWS), and peri-intestinal hyperechoic fat are important features of inflammatory on IUS.1 However, adjunct techniques, such as using contrast with ultrasound, may permit better detection of disease complications and activity, particularly in Crohn’s disease, where patients are at risk of developing intestinal strictures (narrowing), bowel perforation, and abscesses. Indeed, these advanced ultrasound techniques push the boundaries of what noninvasive imaging can offer. This blog post delves into three promising techniques—contrast-enhanced ultrasound (CEUS), small intestinal contrast-enhanced ultrasound (SICUS), and elastography—each providing new dimensions to our understanding of IBD and its management.

Contrast-Enhanced Ultrasound (CEUS): Adding Depth to Vascular Assessment

CEUS represents a significant advancement in IUS, particularly in assessing disease activity and vascularization. By injecting a contrast composed of gas-filled microbubbles stabilized by a lipid capsule into the bloodstream, CEUS enhances the visualization of bowel wall vascularity, which is a key indicator of inflammation in IBD. The evaluation relies on the dynamic assessment of the contrast uptake in areas with increased vascular activities, whose intensity can change over time.2 Although visual evaluation can demonstrate areas of activities on CEUS, advanced software is also used to generate time-intensity curves, which measure the signal intensity from the first bubble arrival in the bowel segment of interest and progressive decline in intensity (wash-out) usually over 2 minutes of image capture.3

CEUS can be used in various clinical contexts to monitor Crohn’s disease. The time-intensity curves generated by CEUS are used to calculate the signal’s peak intensity and area under the curve (AUC). Wilkens et al demonstrated that peak intensity and AUC are increased in patients with active disease as compared to controls.4 Further studies have demonstrated promising results in differentiating Crohn’s disease lesions with active inflammation instead of lesions composed predominantly of fibrostenotic tissue.5 Variations in outcomes may be related to the type of contrast used, the quantitative CEUS value of interest analyzed, and the variability in the ultrasound system and analysis software used, which are not standardized between systems.5 However, such findings may be important in predicting response to therapy instead of prioritizing surgical options, as limited data demonstrated higher inflammation quantified by CEUS had a higher response rate to therapies.6

CEUS has emerged as a valuable tool in monitoring complications of Crohn’s disease (CD), particularly in assessing the presence and extent of fistulas and abscesses. By enhancing the visibility of vascular structures and inflammatory activity, CEUS allows for the precise identification and measurement of these complications, which can be challenging to characterize with conventional imaging methods. This enhanced visualization is crucial for guiding clinical decisions, including the need for surgical intervention or adjustments in medical therapy.7

Small Intestinal Oral Contrast-Enhanced Ultrasound (SICUS): Expanding the Reach of IUS

While CEUS focuses on enhancing vascular imaging, SICUS takes a different approach by improving the visualization of the small intestine, an area notoriously difficult to image using traditional ultrasound techniques. SICUS is performed in the fasted state and involves the oral administration of a non-absorbable contrast medium, generally a polyethylene glycol solution, that distends the small bowel loops, allowing for better visualization of the bowel wall and lumen. The exam may last 30 to 45 minutes for the contrast to arrive at the areas of interest.8

This technique is particularly valuable in the assessment of small bowel CD, where skip lesions and strictures can be challenging to detect and characterize. SICUS enhances the delineation of these abnormalities, providing a clearer picture of the disease’s extent and severity. Moreover, SICUS can be employed alongside B-mode and CEUS to offer a comprehensive assessment of the small intestine. The combined use of these modalities allows for a more nuanced evaluation of both the inflammatory and structural components of the disease, leading to more informed treatment strategies.9

Elastography: A Noninvasive Window Into Fibrosis

One of the most challenging aspects of managing IBD is differentiating between inflammation and fibrosis, particularly in chronic CD, where long-standing inflammation can lead to fibrotic changes in the bowel wall. Elastography, a technique that measures tissue stiffness, is a promising solution to this issue. By applying mechanical waves to the tissue and measuring the speed at which they propagate, elastography can provide a quantitative assessment of bowel wall stiffness—a surrogate marker for fibrosis.5 Again, this is essential in predicting lesions that would be amendable to medical therapy as opposed to surgery. However, challenges exist in the assessment of the bowel using this technique, as measurements can be affected by peristalsis, and a large body habitus can impede the penetration of the sound waves. Values are not yet standardized between ultrasound systems, making the validation of specific thresholds difficult between centers.5 As research continues to validate its accuracy and reliability, elastography may become a standard tool in the long-term management of IBD.

The Future of IUS in IBD Management

The integration of CEUS, SICUS, and elastography into the IUS toolkit marks a significant step forward in the management of IBD. These advanced techniques not only enhance our ability to diagnose and monitor the disease but also provide critical insights that can tailor treatment strategies to the individual patient.

As we continue to refine these methods and validate their use in clinical practice, the future of IUS in IBD management looks promising. The ability to assess the disease’s inflammatory and fibrotic components in real-time, noninvasively, and with high accuracy will undoubtedly improve patient outcomes and quality of life. However, to move toward more widespread adoption, more training in these techniques will be necessary, and further validation of the data generated is warranted.

In conclusion, the advancements in IUS, particularly with the advent of CEUS, SICUS, and elastography, are poised to transform the landscape of IBD management. These techniques offer a more detailed and nuanced understanding of the disease, enabling us to make more informed decisions that ultimately benefit our patients. As we look to the future, the continued evolution of IUS will undoubtedly play a pivotal role in the quest for better outcomes in IBD care.

Mallory Chavannes, MD, MHSc, FRCPC, FAAP, is an Assistant Professor of Pediatrics in the Division of Gastroenterology, Hepatology, & Nutrition, and is Medical Director of the Inflammatory Bowel Disease Program, at Children’s Hospital Los Angeles.

References:

  1. Novak KL, Nylund K, Maaser C, et al. Expert consensus on optimal acquisition and development of the international bowel ultrasound segmental activity score [IBUS-SAS]: a reliability and inter-rater variability study on intestinal ultrasonography in Crohn’s disease. J Crohns Colitis 2021; 15:609–616. doi: 10.1093/ecco-jcc/jjaa216. PMID: 33098642; PMCID: PMC8023841.
  2. Pecere S, Holleran G, Ainora ME, et al. Usefulness of contrast-enhanced ultrasound (CEUS) in inflammatory bowel disease (IBD). Dig Liver Dis 2018; 50:761–767. doi: 10.1016/j.dld.2018.03.023. Epub 2018 Apr 3. PMID: 29705029.
  3. Merrill C, Wilson SR. Ultrasound of the bowel with a focus on IBD: the new best practice [published online ahead of print August 14, 2024]. Abdom Radiol (NY) doi: 10.1007/s00261-024-04496-1. PMID: 39141152.
  4. Wilkens R, Wilson A, Burns PN, Ghosh S, Wilson SR. Persistent enhancement on contrast-enhanced ultrasound studies of severe Crohn’s disease: stuck bubbles? Ultrasound Med Biol 2018; 44:2189–2198. doi: 10.1016/j.ultrasmedbio.2018.06.018. PMID: 30076030.
  5. Coelho R, Ribeiro H, Maconi G. Bowel thickening in Crohn’s disease: fibrosis or inflammation? Diagnostic ultrasound imaging tools. Inflamm Bowel Dis 2017; 23:23–34. doi: 10.1097/MIB.0000000000000997. PMID: 28002125.
  6. Quaia E, Gennari AG, Cova MA, van Beek EJR. Differentiation of inflammatory from fibrotic ileal strictures among patients with Crohn’s disease based on visual analysis: feasibility study combining conventional B-mode ultrasound, contrast-enhanced ultrasound and strain elastography. Ultrasound Med Biol 2018; 44:762–770. doi: 10.1016/j.ultrasmedbio.2017.11.015. PMID: 29331357.
  7. Pecere S, Holleran G, Ainora ME, et al. Usefulness of contrast-enhanced ultrasound (CEUS) in inflammatory bowel disease (IBD). Dig Liver Dis 2018; 50:761–767. doi: 10.1016/j.dld.2018.03.023. PMID: 29705029.
  8. Losurdo G, De Bellis M, Rima R, et al. Small intestinal contrast ultrasonography (SICUS) in Crohn’s disease: systematic review and meta-analysis. J Clin Med 2023; 12(24):7714. doi: 10.3390/jcm12247714. PMID: 38137782; PMCID: PMC10744114.

Mocci G, Migaleddu V, Cabras F, et al. SICUS and CEUS imaging in Crohn’s disease: an update. J Ultrasound 2017; 20:1–9. doi: 10.1007/s40477-016-0230-5. PMID: 28298939; PMCID: PMC5334271.

Advancing Inflammatory Bowel Disease Management: Harnessing Intestinal Ultrasound for Screening and Monitoring

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Inflammatory bowel disease (IBD) encompasses a group of chronic inflammatory conditions of the gastrointestinal tract, primarily including Crohn’s disease and ulcerative colitis. The rate of patients affected by these conditions has been growing in the last decades, with an estimated 2.39 million Americans living with this diagnosis in 2020.1 About 25% of those affected are children.2 Active inflammation in the context of IBD increases the risk of disease complications, such as requiring surgery and developing colon cancer. However, symptoms have been shown to not accurately correlate to intestinal inflammation and ongoing bowel damage.3,4 Therefore, the assessment of disease activity relies on invasive techniques, such as colonoscopy and cross-sectional imaging (ie, Computer Tomography Enterography and Magnetic Resonance Enterography), which are costly and laborious tests. Repeated imaging using these techniques is important to assess for the complete reversal of inflammation, termed mucosal healing, which was shown to lead to much better long-term outcomes.5

Intestinal ultrasound (IUS) has emerged as a valuable technique for screening patients with concerning symptoms of IBD and monitoring individuals with known disease. It has the advantages of being feasible at the bedside in the gastrointestinal clinic, noninvasive, painless, requiring no preparation from the patient, and not exposing the patient to ionizing radiation. IUS has been used for monitoring disease activity for many years in Europe and is now being rapidly adopted in the United States.

IUS Features of Intestinal Inflammation

IUS is generally performed using a high-frequency linear transducer to visualize the intestinal wall and surrounding structures in real-time and a curvilinear low-frequency transducer to assess for disease complications, often located in the pelvis. The thickness of the bowel wall, which comprises layers such as the mucosa, submucosa, and muscularis, measures under 3mm in healthy adults, but this measurement increases in the setting of inflammation.6 Bowel layers can be distinct or more disturbed depending on disease severity. Other important features include the presence of abnormal increased Doppler signals in and along the bowel wall, which are usually absent in healthy patients and progressively more prominent in diseased bowel. Furthermore, peri-intestinal fat can be increased in the presence of disease. Examples of these IUS features are illustrated in Figure 1.

Figure 1A
Figure 1B

Screening With IUS

One of the key advantages of IUS in IBD management is its ability to screen for the presence of disease in patients with nonspecific symptoms that could be due to IBD. By visualizing the thickness of the intestinal wall, the presence of bowel wall edema, and the extent of inflammation, ultrasound can help identify active disease and assess its severity. Indeed, a study demonstrated that IUS could distinguish between patients with Irritable Bowel Syndrome (IBS) or functional symptoms and patients with new or flaring IBD.7,8 The use of IUS by trained providers can help with resource allocation and expedite invasive testing in the right patient without delays, and avoid unnecessary invasive investigation in patients who do not require it.

Monitoring Disease Progression and Treatment Response

In addition to screening, IUS can have a central role in monitoring response to treatment. Although there is a growing armamentarium of treatments for IBD, no single treatment has led to endoscopic remission rates higher than about 40–50%.9 Repeat ultrasound examinations can track changes in the thickness of the intestinal wall and complications over time. This real-time feedback allows for the timely optimization of treatment strategies, with subsequent improvement in patient outcomes. This proactive approach to objective evaluation of disease activity and continuous optimization of therapies, named the treat-to-target approach, has been demonstrated to improve long-term complication-free remission.5,10 Moreover, ultrasound can detect complications such as strictures, abscesses, and fistulas, guiding treatment decisions and surgical planning.

Advantages of IUS

Several factors contribute to the growing popularity of IUS in IBD management:

  1. Noninvasive: IUS does not require the insertion of instruments into the body, minimizing patient discomfort and reducing the risk of complications.
  2. Radiation-free: Unlike CT scans, which involve ionizing radiation, ultrasound uses harmless sound waves, making it safe for repeated examinations by professionals, including in pregnant women and children.
  3. Real-time imaging: IUS provides immediate feedback, allowing healthcare providers to assess disease activity and complications on the spot.
  4. Cost-effective: Compared to other imaging modalities, IUS is relatively affordable, potentially increasing patient accessibility in various healthcare settings.

Conclusion

Intestinal ultrasound (IUS) has emerged as a valuable tool in the screening and monitoring of inflammatory bowel disease. Its noninvasive nature, lack of radiation exposure, real-time imaging capabilities, and cost-effectiveness make it an attractive option for healthcare providers and patients alike. By incorporating IUS into the diagnostic algorithm for IBD, clinicians can improve the accuracy of diagnosis, optimize treatment strategies, and enhance patient outcomes.

In the ever-evolving landscape of IBD management, IUS stands out as a versatile and effective imaging modality, offering valuable insights into disease activity and treatment response. As research continues to elucidate its utility and refine its techniques, IUS is poised to play an increasingly prominent role in the personalized care of individuals living with IBD.

References:

  1. Lewis JD, Parlett LE, Jonsson Funk ML, et al. Incidence, prevalence, and racial and ethnic distribution of inflammatory bowel disease in the United States. Gastroenterology 2023 Nov; 165(5):1197–1205.e2. doi: 10.1053/j.gastro.2023.07.003. Epub 2023 Jul 20. PMID: 37481117; PMCID: PMC10592313.
  2. Abraham BP, Mehta S, El-Serag HB. Natural history of pediatric-onset inflammatory bowel disease: a systematic review. J Clin Gastroenterol 2012; 46:581–589.
  3. Modigliani R, Mary JY, Simon JF, et al. Clinical, biological, and endoscopic picture of attacks of Crohn’s disease. Evolution on prednisolone. Groupe d’Etude Thérapeutique des Affections Inflammatoires Digestives. Gastroenterology 1990; 98:811–818. doi: 10.1016/0016-5085(90)90002-i. PMID: 2179031.
  4. Jharap B, Sandborn WJ, Reinisch W, et al. Randomised clinical study: discrepancies between patient-reported outcomes and endoscopic appearance in moderate to severe ulcerative colitis. Aliment Pharmacol Ther 2015; 42:1082–1092. doi: 10.1111/apt.13387
  5. Ungaro RC, Yzet C, Bossuyt P, et al. Deep remission at 1 year prevents progression of early Crohn’s disease. Gastroenterology 2020 Jul; 159(1):139–147. doi: 10.1053/j.gastro.2020.03.039. Epub 2020 Mar 26. PMID: 32224129; PMCID: PMC7751802.
  6. Novak KL, Nylund K, Maaser C, et al. Expert consensus on optimal acquisition and development of the international bowel ultrasound segmental activity score [IBUS-SAS]: a reliability and inter-rater variability study on intestinal ultrasonography in Crohn’s disease. J Crohns Colitis 2021; 15:609–616. doi: 10.1093/ecco-jcc/jjaa216. PMID: 33098642; PMCID: PMC8023841.
  7. Novak KL, Jacob D, Kaplan GG, et al. Point of care ultrasound accurately distinguishes inflammatory from noninflammatory disease in patients presenting with abdominal pain and diarrhea. Can J Gastroenterol Hepatol 2016; 2016:4023065. doi: 10.1155/2016/4023065. Epub 2016 Apr 20. PMID: 27446838; PMCID: PMC4904691.
  8. St-Pierre J, Delisle M, Kheirkhahrahimabadi H, et al. Bedside intestinal ultrasound performed in an inflammatory bowel disease urgent assessment clinic improves clinical decision-making and resource utilization. Crohns Colitis 360 2023 Sep 21; 5(4):otad050. doi: 10.1093/crocol/otad050. PMID: 37809033; PMCID: PMC10558199.
  9. Cholapranee A, Hazlewood GS, Kaplan GG, Peyrin-Biroulet L, Ananthakrishnan AN. Systematic review with meta-analysis: comparative efficacy of biologics for induction and maintenance of mucosal healing in Crohn’s disease and ulcerative colitis controlled trials. Aliment Pharmacol Ther 2017 May; 45(10):1291–1302. doi: 10.1111/apt.14030. Epub 2017 Mar 22. PMID: 28326566; PMCID: PMC5395316.
  10. Colombel JF, Panaccione R, Bossuyt P, et al. Effect of tight control management on Crohn’s disease (CALM): a multicentre, randomised, controlled phase 3 trial. Lancet 2017 Dec 23; 390(10114):2779–2789. doi: 10.1016/S0140-6736(17)32641-7. Epub 2017 Oct 31. Erratum in: Lancet 2018 Dec 23; 390(10114):2768. PMID: 29096949.

Mallory Chavannes, MD, MHSc, is an Assistant Professor of Pediatrics in the Division of Gastroenterology, Hepatology, & Nutrition, and is Medical Director of the Inflammatory Bowel Disease Program, at Children’s Hospital Los Angeles.