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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.

The Potential of Elastography in MSK Ultrasound

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Elastography is a method of imaging that detects the compressibility or stiffness of tissues in the imaging field and then overlays a false-color map upon the greyscale image to indicate which tissues are hard/stiff versus soft/compressible. The science behind the technique is beyond the scope of a blog post, particularly as there are several methods by which elastography can be performed.  

In practical terms, elastography is useful in identifying lesions that are sonographically iso-dense compared to their surroundings. Such lesions, while they are therefore visually “iso-grey” (if you will tolerate a neologism), may not be iso-compressible despite their iso-density, and thus when their differential compressibility is identified by elastography it becomes possible to characterize a lesion whose greyscale appearance is not instructive. Among the most common current uses of elastography are the characterization of breast and liver lesions, and indeed the well-known Fibroscan device is, in essence, liver elastography.

There are several instances in the field of musculoskeletal (MSK)/rheumatologic ultrasound in which this technology is appealing, but more work is needed before widespread use will be advisable. I will mention only two of the most obvious examples here. 

Example One

The first example is in the interrogation of a symptomatic tendon or ligament. Such a structure, whose normal function involves incredible amounts of linear tension, when disrupted by trauma or disease, would be expected to lose integrity in the region of the insult and become softer/more compressible than normal in that area.

Traditionally, elastography is not used to measure tendons and ligaments despite the validity of the above statement. The reason for this is that the stiffness of tissue, when measured by elastography, can be expressed in terms of the speed at which a deformation (compression wave) in the tissue propagates, usually in meters per second (there are other units by which stiffness can be measured, but for simplicity’s sake, I will leave it at that).

In the classical case of breast and liver lesions, this is not an issue since the surrounding normal tissue is relatively soft and compressible, so the speed of the propagation of a compression wave is relatively slow. Thus, most elastography measurements top out at a propagation speed of about 10 meters per second, and most normal and abnormal breast/liver tissue will have stiffness values somewhat slower than this. Tendons and ligaments, on the other hand, are by nature very hard/noncompressible. Even in their “relaxed” state, these tissues are so bowstring-tight (relatively) that measuring a normal Achilles’ tendon, for example, will yield only a maxed-out value of “offscale hard” throughout the entire structure. 

It is tempting to say that one could simply recalibrate the machine to measure faster propagation speeds, but, unfortunately, we run into limitations of our current technology. It is simply not possible currently to measure velocities much faster than 10 m/s. 

While we await advancements in technology, the current workaround is to trust that a damaged region of tendon or ligament will be significantly softer, and thus transmit compression waves much more slowly. Therefore, we simply consider any propagation speed that falls out of “offscale” and into the measurable range to be an indicator of pathology.

Example Two

The second example of the potential rheumatologic utility of elastography is in the assessment of systemic sclerosis, commonly known as scleroderma. As the Greek name would suggest, this disease usually includes a characteristic hardening of the skin. The problem is that there is currently no reliable way to quantify skin stiffness. The existing gold standard is a semi-quantitative scoring of skin thickening performed by simple physical examination in which each of several predefined regions of the skin is palpated and assigned a value from 0 to 3. This results in an overall score known as the Modified Rodnan Skin Score (MRSS). Performing Rodnan scoring requires an experienced clinician, and since scleroderma is a rare disease, very few physicians have a large enough cohort in their practice to be able to consider themselves expert Rodnan scorers.

This leads to a host of problems, and one of the worst is that clinical trials in scleroderma (a devastating and potentially fatal disease for which no good treatment exists) are very difficult to conduct because one of the primary endpoints of any trial will be the degree of improvement found in this semi-quantitative and hard-to-perform examination, which is subject to severe inter-rater reliability problems.

When I first started as a rheumatology fellow, I agreed to help with a scleroderma clinical trial in the role of a blinded efficacy assessor. The sponsor brought a dozen or so of us to a hotel for training, and all morning long we cycled through a series of hotel meeting rooms, each containing a volunteer patient for us to score.

It was a disaster.

After lunch, the representative from the sponsor got up to the podium and told us to rip up our afternoon agendas—we were going back to the meeting rooms to examine the volunteers again in an effort to improve the scoring consensus.

Clearly, this situation screams for elastography. The objective measurement of skin stiffness is precisely the datum that is sorely needed. Sadly, our current technology again fails us, as present-day elastography has limitations in resolution and the skin by its anatomic location, will always be very nearly directly applied to the probe face, in a region outside the focal zone of the beam where the measurement physics work best. Further, one of the techniques for performing elastography is highly operator-dependent, because the compression waves being measured are generated by manually varying the pressure of the probe against the skin—definitely a skill that must be learned over time and one that opens the door once more to inter-rater variability.

Overall, elastography holds great promise for MSK/rheumatologic applications in the future, as described in the two examples above. For now, however, it’s currently a technology that is “not ready for prime time” in this field.

This post is intended as a companion to “What Rheumatologists Really Need for Ultrasound Is…”, which discusses advances in ultrasound technology that are sorely needed in the field of MSK ultrasound, and specifically in rheumatology.

Dr. Mandelin is an academic rheumatologist, registered in MSK ultrasound (RhMSUS) by the American College of Rheumatology and certified in MSK ultrasound (RMSK) by the Alliance for Physician Certification & Advancement. He currently serves the AIUM as secretary of the High-Frequency Clinical and Preclinical Imaging Community. Connect with him on Twitter @NU_Rheum_MSK_US.

Shear Wave Elastography and Diffuse Liver Disease

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Diffuse liver disease is a worldwide problem. The causes are several, with non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease, and viral B or C hepatitis being the most frequent. No matter what the cause is, the chronic inflammation of the liver and the cellular death lead to liver tissue scarring, namely liver fibrosis, that may progress to cirrhosis with its complications.

Staging liver fibrosis is important for the management and prognosis of diffuse liver disease. For decades, liver biopsy has been the reference standard for the staging of liver fibrosis.

Shear wave elastography (SWE) is a method able to assess the tissue stiffness by applying a mechanical stress that induces the generation of shear waves, which then propagates into the tissue with a speed that is proportional to the stiffness of the tissue. The shear waves are generated by a body-surface compression, as in transient elastography (TE), or by the push-pulse of a focused ultrasound beam, as in acoustic radiation force impulse (ARFI) techniques.

The speed of the shear waves is related to the stiffness: they travel faster in stiffer tissue. Using a formula and making some assumptions, it is possible to convert the speed into units of stiffness, ie kilopascals.

A fibrotic tissue is harder (stiffer) than a normal tissue, and an increase of fibrosis is coupled with an increase of the stiffness. Therefore, there is a close positive relationship between fibrosis and stiffness.

TE is an SWE technique performed with the FibroScan system (Echosens). This system has a probe with a tip at the end and a button on the lateral part of it. By pushing the button, the tip compresses the body surface and this deformation propagates into the liver as shear waves. An ultrasound beam tracks the shear wave speed and sends information back to the software of the system. The final reading is in kilopascals. The FibroScan quantifies the stiffness but doesn’t assess the morphology of the liver.

The ARFI techniques are implemented in ultrasound systems that are used for other diagnostic purposes when a patient with diffuse liver disease is evaluated. In fact, using an ultrasound system, it is possible to study the organ’s morphology with B-mode, the hemodynamics with Doppler, and to characterize focal liver lesions with contrast agents. ARFI techniques make use of the energy of the ultrasound beam to generate the shear waves whose speed propagation is assessed in m/s: higher the speed stiffer the tissue.

ARFI techniques include point shear wave elastography (pSWE) and two-dimensional shear wave elastography (2D-SWE). pSWE measures the stiffness in a small and fixed region of interest whereas with 2D-SWE the stiffness is obtained over a large field of view and a color-coded image, from which the stiffness value is gotten, is displayed on the monitor of the ultrasound system. The shear wave speed can be converted into kilopascals; the ultrasound systems generally provide both speed values in m/s and stiffness values in kilopascals.

The stress is made directly into the liver; therefore, the examination can be performed also in patients with ascites.

All the published studies have shown that the ARFI techniques have accuracy similar to or higher than FibroScan for the staging of liver fibrosis. Over the last years, the assessment of liver stiffness with SWE techniques, either TE or ARFI, has increasingly been used as a means to noninvasively staging liver fibrosis. Currently, guidelines have accepted that SWE techniques can safely replace liver biopsy in several clinical scenarios. SWE can safely be used also in children. It is feasible in children of all ages and has many pediatric applications in the setting of chronic liver disease.

Bibliography

  • Barr RG, Wilson SR, Rubens D, Garcia-Tsao G, Ferraioli G. Update to the Society of Radiologists in Ultrasound Liver Elastography Consensus Statement. Radiology 2020; 296:263–74.
  • Ferraioli G, Wong VW, Castera L, Berzigotti A, Sporea I, Dietrich CF, Choi BI, Wilson SR, Kudo M, Barr RG. Liver Ultrasound Elastography: An Update to the WFUMB guidelines and recommendations. U Med Biol 2018; 44:2419–2440.
  • Ferraioli G. Review of liver elastography guidelines. J Ultrasound Med 2019; 38:9–14.
  • Ferraioli G, Barr RG, Dillman JR. Elastography for pediatric chronic liver disease: a review and expert opinion. J Ultrasound Med 2020; doi: 10.1002/jum.15482

Giovanna Ferraioli, MD, FAIUM, is a researcher at Medical School University of Pavia, Italy. She’s the lead author of WFUMB guidelines on liver elastography, co-author of the SRU consensus, and of several international guidelines on elastography.

Interested in learning more? Check out the following posts from the Scan: