Tag Archives: CEUS

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.

Lymphosonography: The use of contrast-enhanced ultrasound as a lymphatic mapping technique

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Ipsilateral axillary diagnostic ultrasound is part of the initial staging for breast cancer to evaluate lymph nodes using a b-mode classification where certain aspects, when present, increase the level of suspicion for metastatic disease, such as cortical thickening and poor hilar visibility.1–3 Diagnostic ultrasound is also used as a method to guide biopsies of the suspicious lymph nodes.1

The majority of patients will have no suspicious lymph nodes findings at the time of diagnosis, the lymphatic system mapping after the injection of blue dye and/or a radioactive tracer followed by a surgical excision becomes the only way to determine the final stage of disease. However, these methods have limitations such as the use of radiation and lack of an imaging component.

In the past, ultrasound could not be used for lymphatic mapping, since mapping requires administration of a tracer. This changed with the use of contrast-enhanced ultrasound (CEUS) to detect lymph nodes after subcutaneous injections of microbubble-based ultrasound contrast agents (UCA), termed “lymphosonography”.4–6 The development of the lymphosonography technique addressed the limitations of the currently used lymphatic mapping techniques.

Our group conducted a clinical trial to evaluate the efficacy of CEUS lymphosonography in the identification of sentinel lymph nodes (SLN) in patients with breast cancer undergoing surgical excision following the injection of blue dye and radioactive tracer as part of their standard of care using pathology results for malignancy as a reference standard.6,7

In the clinical trial, 86 subjects were enrolled and 79 completed the study. The subjects received 4 subcutaneous injections of ultrasound contrast agent around the tumor, for a total of 1.0 ml. A clinical ultrasound scanner with CEUS capabilities was used to identify SLNs. After the ultrasound study examination, the subjects received blue dye and radioactive tracer for guiding SLN excision as part of their standard of care. The SLNs excised during the standard-of-care surgical excision were classified as positive or negative for presence of blue dye, radioactive tracer and UCA, and sent for pathology to determine presence or absence of metastatic involvement.

Example of a sentinel lymph node (SLN) seen with lymphosonography. The arrow indicates the SLN. The arrowhead indicates the lymphatic channel.

A total of 252 SLNs were excised from the 79 subjects. Of the 252 SLNs excised, 158 were positive for blue dye, 222 were positive for radioactive tracer and 223 were positive for UCA. Statistical comparison showed that compared with the reference standards, lymphosonography showed similar accuracy with radioactive tracer (p > 0.15) and higher accuracy (p < 0.0001). The pathology results showed that, of the 252 SLNs excised, 34 had metastatic involvement and were determined malignant by pathology. Of these 34 SLNs, 18 were positive for blue dye (detection rate of 53%), 23 were positive for radioactive tracer (detection rate of 68%) and 34 were positive for UCA (detection rate of 100%; p < 0.0001).

The conclusion of this study indicates that lymphosonography had similar accuracy as the standard-of-care methods for identifying SLNs in breast cancer patients, with the added advantage of an imaging component that allows for a preoperative evaluation of SLNs and that lymphosonography may be a more specific and precise approach to SLN identification in patients with breast cancer.6

Larger multicenter clinical trials are necessary to be able to translate this technique to the clinical setting and to be able to incorporate it as part of the breast cancer patients’ standard of care.

  1. Voit CA, van Akkooi ACJ, Schäfer-Hesterberg G, et al. Rotterdam Criteria for sentinel node (SN) tumor burden and the accuracy of ultrasound (US)-guided fine-needle aspiration cytology (FNAC): can US-guided FNAC replace SN staging in patients with melanoma? J Clinical Oncol 2009; 27(30):4994–5000.
  2. Dialani V, Dogan B, Dodelzon K, Dontchos BN, Modi N, Grimm L. Axillary imaging following a new invasive breast cancer diagnosis—A radiologist’s dilemma. J Breast Imaging 2021; 3:645–658.
  3. Chang JM, Leung JWT, Moy L, Ha SM, Moon WK. Axillary nodal evaluation in breast cancer: state of the art. Radiology 2020; 295:500–515.
  4. Goldberg BB, Merton DA, Liu J-B, Thakur M, et al. Sentinel lymph nodes in a swine model with melanoma: contrast-enhanced lymphatic US. Radiology 2004; 230:727–734.
  5. Goldberg BB, Merton DA, Liu J-B, Murphy G, Forsberg F. Contrast‐enhanced sonographic imaging of lymphatic channels and sentinel lymph nodes. J Ultrasound Med 2005; 24:953–965. doi: 10.7863/jum.2005.24.7.953.
  6. Machado P, Liu J-B, Needleman L, et al. Sentinel lymph node identification in patients with breast cancer using lymphosonography. Ultrasound Med Biol 2023; 49:616–625. Epub 2022 Nov 26.
  7. Machado P, Liu JB, Needleman L, et al. Sentinel lymph node identification in post neoadjuvant chemotherapy breast cancer patients undergoing surgical excision using lymphosonography. J Ultrasound Med 2023; 42:1509–1517. doi: 10.1002/jum.16164. Epub 2023 Jan 2.

Priscilla Machado, MD, FAIUM, is a Research Assistant Professor in the Department of Radiology at Thomas Jefferson University in Philadelphia, PA.

Interested in learning more about ultrasound? Check out these posts from the Scan:

One More Reason to Advocate for Contrast-Enhanced Ultrasound in Children: No Current Shortage of Ultrasound Contrast Agents

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Contrast-enhanced ultrasound (CEUS) is a valuable tool to evaluate the pediatric patient as it offers many of the diagnostic benefits of other imaging modalities such as CT or MRI but avoids potential risks including radiation exposure and sedation. Furthermore, CEUS is portable and can be performed at the patient’s bedside, which is particularly important in critically ill children where transportation to the radiology department may be difficult. Currently, in the United States, only one ultrasound contrast agent is FDA-approved for use in pediatric patients for intravesical use for contrast-enhanced voiding urosonography (ceVUS) and for intravenous use for characterization of liver lesions and cardiac indications. However, off-label use has greatly expanded the applications of this technology to the betterment of patients.

Grayscale (left) and contrast-enhanced (right) ultrasound of the left kidney in a 3-year-old boy incidentally found to have a renal lesion on prior spine MRI. Images demonstrate a predominately cystic complex lesion (circle). On contrast-enhanced images, the cystic components are clearly demonstrated with faint enhancement of thin septations allowing characterization of the lesion as a minimally complex renal cyst (Bosniak type 2F). Normal diffuse homogenous enhancement is seen in the remainder of the left renal parenchyma (arrows). In this case, the use of contrast-enhanced ultrasound for lesion characterization prevented radiation exposure, which would be required for CT, and sedation, which would be required for MRI.

Multiple studies have shown the feasibility and value of CEUS in a wide variety of applications including evaluation of the neonatal brain in hypoxic-ischemic injury, intraoperative characterization of brain lesions for real-time assessment of resection margins, initial and follow-up evaluations in the setting of solid abdominal organ trauma, quantification of femoral head perfusion before and after developmental hip dysplasia reduction, and intraoperative ceVUS to visualize vesicoureteral reflux and assess the efficacy of bladder bulking agent injections and possible requirement for additional surgical procedures. This is to name just a few!

Additionally, CEUS has been utilized by Interventional Radiology departments in many troubleshooting situations including evaluation of vascular access/thrombosis, identifying solid tumor components for biopsy, visualizing non-solid abscess contents for accurate drain placement, and lymph node injection for evaluation of the lymphatic drainage pathways. Again, this is a limited list of uses! Essentially, any diagnostic or therapeutic situation that would benefit from real-time bedside evaluation of organs, lesions, vessels (or anything in the human body) could potentially benefit from CEUS.

Despite the widespread applications of CEUS, few centers regularly employ this technique or only use it in select cases. Concerns about contrast agent side effects, including anaphylaxis, have been consistently demonstrated to be minimal and lower than other contrast agents routinely utilized in imaging studies and the safety of ultrasound contrast agents has been continually proven over time. While appropriate monitoring and preparation for severe reactions is mandatory, this is not dissimilar to safety practices with CT and MRI contrast agents. Speaking of which, current CT contrast shortages and uncertain implications of gadolinium deposition with MRI contrast agents further bolster support for using CEUS as a first-line imaging modality.

Even after explaining the relatively high benefit-to-risk ratio in this patient population, advocates for CEUS continue to find resistance to broader use. Some obstacles to wider implementation include staff training and requirement of a radiologist during the CEUS, which is currently standard practice. Select institutions offer CEUS training courses for technologists and physicians to familiarize them with technique and workflow management. Like any new procedure, education, experience, and departmental support allow increasing confidence and ease of implementation. Despite adequate technologist and nursing staff familiarity, in this time of ever-growing imaging study volumes and hospital staffing shortages, requiring the physical attendance of a radiologist for a CEUS examination is less than ideal. However, this allows valuable support for the technologist and for the radiologist to communicate directly with the patient and family providing an immeasurable face-to-face interaction that cannot be replicated in the reading room.

To summarize, CEUS is an incredibly valuable tool in evaluating children with vast clinical applications, the list of which continues to grow over time. If you have a patient and ask yourself “could CEUS add information with high benefit-to-risk ratio,” the answer is often “yes.” But lack of widespread awareness and implementation lead to clinicians never asking that question or even considering the potential benefit of CEUS in pediatric patients. A growing community of Pediatric Diagnostic and Interventional Radiologists would like to change that in the future.

If you are using CEUS at your institution, what kind of scenarios (standard and unique) have you found CEUS to be helpful? If you are not using CEUS at your institution, what do you see as current obstacles? What would be required or helpful for you to implement in your practice?

Ryne Didier, MD, is a Pediatric Radiologist at the Children’s Hospital of Philadelphia (@CHOPRadiology). Her clinical and research interests include prenatal imaging and emerging ultrasound imaging techniques and applications.

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

Is it Nuts to Think About Sparing the Testicles?

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The testi-monial

On my ultrasound list today, patient X, returning for a follow-up, was recounting his ‘close shave’ from losing one of his testicles after a suspected lump was detected during an ultrasound examination at his local hospital when he had pain in the scrotum. He was initially listed for theatre for an orchiectomy and the patient was grateful that someone stopped that and referred him to us for a repeat scan, this time with an adjunct contrast-enhanced ultrasound, which showed the abnormality in his testicle was an infarct instead of a tumor (Figure 1), which improved on follow-up (Figure 2).

Figure 1: Grayscale (left) and contrast-enhanced ultrasound (right) of patient X’s right testicular focal abnormality. Contrast-enhanced ultrasound showed no enhancement within the abnormality.
Figure 2: On follow-up contrast-enhanced ultrasound, it reduced in size and again showed no enhancement, supporting the diagnosis of a resolving infarct.

Incidentally detected testicular focal abnormality inevitably generates a great amount of anxiety, both for patients and doctors involved.

Why?

Ultrasound is good at picking up lesions. The problem is that, often, we do not know what they are, or what to do with them. While the old surgical dogma of ‘if in doubt, take it out’ does a good job in dealing with the uncertainty, it does appear to be an overly aggressive anxiety-relieving strategy, and not without consequence, as orchiectomy comes with associated endocrine, reproductive, and psychological impact.

It is worth noting that this problem is further exacerbated by the increased use of ultrasound for a variety of indications, which led to an increasing number of incidentally detected small focal testicular lesions. Many incidentally detected lesions are benign.

Even with the most beneficial of intentions, is scrotal ultrasound causing harm?

What could we do?

Which test tickles your fancy?

Although a variety of tools have been at the clinician’s disposal, the preoperative diagnoses of testicular masses remain uncertain in many cases. Tumor markers are often not raised in patients with malignant testicular tumors. MRI is considered a second-line tool for the characterization of focal testicular lesions; high cost, long study time, lack of standardization, and expertise are some of the drawbacks.

In most cases, ultrasound remains the primary diagnostic test to facilitate decision-making. Lack of flow on color Doppler (CD) increases the probability of a benign lesion but must be interpreted with caution as a substantial proportion of malignant lesions show no detectible vascularity.1 Microflow techniques may increase sensitivity,2 but the evidence is lacking for its value in assessing small testicular lesions. Imaging with contrast-enhanced ultrasound (CEUS) and elastography provides additional information.3,4 CEUS is a particularly valuable technique. The unique value of CEUS is the unequivocal demonstration of the lack of vascularity likely to be encountered in benign lesions, such as an infarct,5 hematoma,6 or epidermoid cyst,7 allowing for “watchful waiting” with ultrasound.8 Contrast dynamics may help differentiate benign from malignant solid masses, but this technique is not yet sufficiently robust for routine clinical use.9 Strain elastography could potentially identify the “hard” lesion as more likely malignant and the “soft” lesion benign on strain elastography.10 Shear-wave elastography has been less extensively evaluated but may also show differences between benign and malignant testicular lesions.11

I am not advocating that these ultrasound techniques are entirely diagnostic, but I am certainly suggesting that when combined with clinical and laboratory information, ultrasound technology is available for a more accurate assessment of the risk of malignancy. This may facilitate more desirable testis-sparing management options, such as ultrasound surveillance or testis-sparing surgery (TSS), to be considered, and avoid unnecessary orchidectomies.  

It is not nuts to suggest sparing the testicles.

The ball’s in your court.

References

  1. Ma W, Sarasohn D, Zheng J, Vargas HA, Bach A. Causes of avascular hypoechoic testicular lesions detected at scrotal ultrasound: can they be considered benign? Am J Roentgenology 2017; 209:110–115.
  2. Lee YS, Kim MJ, Han SW, et al. Superb microvascular imaging for the detection of parenchymal perfusion in normal and undescended testes in young children. Eur J Radiol 2016; 85:649–656.
  3. Huang DY, Sidhu PS. Focal testicular lesions: colour Doppler ultrasound, contrast-enhanced ultrasound and tissue elastography as adjuvants to the diagnosis. Br J Radiol 2012; 85 Spec No 1:S41–S53.
  4. Huang DY, Pesapane F, Rafailidis V, et al. The role of multiparametric ultrasound in the diagnosis of paediatric scrotal pathology. Br J Radiol 2020; 93(1110):20200063.
  5. Zebari S, Huang DY, Wilkins CJ, Sidhu PS. Acute testicular segmental infarct following endovascular repair of a juxta-renal abdominal aortic aneurysm: case report and literature review. Urology 2019; 126:5–9.
  6. Yusuf GT, Rafailidis V, Moore S, et al. The role of contrast-enhanced ultrasound (CEUS) in the evaluation of scrotal trauma: a review. Insights Imaging 2020; 11:68.
  7. Patel K, Sellars ME, Clarke JL, Sidhu PS. Features of testicular epidermoid cysts on contrast-enhanced sonography and real-time tissue elastography. J Ultrasound Med 2012; 31:115–122.
  8. Shah A, Lung PF, Clarke JL, Sellars ME, Sidhu PS. Re: New ultrasound techniques for imaging of the indeterminate testicular lesion may avoid surgery completely. Clin Radiol 2010; 65:496–497.
  9. Pinto SPS, Huang DY, Dinesh AA, Sidhu PS, Ahmed K. A systematic review on the use of qualitative and quantitative contrast-enhanced ultrasound in diagnosing testicular abnormalities. Urology 2021; 154:16–23.
  10. Fang C, Huang DY, Sidhu PS. Elastography of focal testicular lesions: current concepts and utility. Ultrasonography 2019; 38:302–310.

Roy C, de Marini P, Labani A, Leyendecker P, Ohana M. Shear-wave elastography of the testicle: potential role of the stiffness value in various common testicular diseases. Clin Radiol 2020; 75:560 e9–e17.

Dr. Dean Huang, FRCR, EBIR, MD(Res), is a radiologist and the clinical lead of uroradiolgy at King’s College Hospital, London, UK. He completed his doctoral research on the clinical application of contrast-enhanced ultrasound for scrotal pathologies at King’s College London, UK.

Tweet him @DrDean_Huang

Interested in learning more about contrast-enhanced ultrasound? Check out the following posts from the Scan:

Ultrasound-Guided Cancer Imaging: The Future of Targeted Cancer Treatment

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Tumor margins and malignant grade are best defined by vascular imaging modalities such as Doppler flow or contrast enhancement combined with videomicroscopy. The following are image-guided treatment options that can be performed on breast, prostate, liver, and skin cancers.

NEW DOPPLER APPLICATIONS

Blood vessel mapping using the various Doppler modalities is routinely used in both cancer treatment and reconstructive planning. In cancer surgery, it is critical to locate aberrant veins or arterial feeders in the operative site so postoperative blood loss is minimized. Advanced 3D Doppler systems allow for histogram vessel density measurement of neoplastic angiogenesis.

VESSEL DENSITY INDEX

(Fig 1) Baseline neovascularity is a treatment surrogate endpoint and therapy is maintained, increased, or suspended based on quantitative angiogenesis data.

SOLID ORGAN CANCER IMAGING UPDATES

Breast cancer, invading the lower dermis and nipple, discovered with high-resolution probes signifies the tumor has outflanked clinical observation essential for detecting the newly discovered entity of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). This capability is also vital for diagnosing the recent epidemic of male breast cancers arising near the mammographically difficult nipple areolar complex, occurring in our 911 First Responders.

For prostate cancer, 4D ultrasound can identify low-grade cancer delimited by the capsule and with low vessel density, and should be followed serially at 6-month intervals.

CONTRAST-ENHANCED ULTRASOUND (CEUS)

In 1990, Dr. Rodolfo Campani developed ultrasound contrast for liver imaging and Drs. Cosgrove (London) and Lassau (Paris) extended the use to breast, skin, and prostate tumors. CEUS is currently used worldwide but is not Food and Drug Administration (FDA)-approved in the United States.

One use for CEUS is microbubble neovascularity, which demonstrates therapeutic response since the Response Evaluation Criteria in Solid Tumors (RECIST) studies noted tumor enlargement during treatment might be related to cell death with cystic degeneration or immune cell infiltration destroying malignant tissue. Doppler ultrasound or CEUS reliably verifies decreased angiogenesis in place of contrast CT or dynamic contrast-enhanced (DCE) MRI. If vascular perfusion ceases, thermal treatments, such as cryotherapy, high-intensity focused ultrasound (HIFU), or laser ablation, should be completed.

Four-dimensional (4D) ultrasound imaging is real-time evaluation of a 3D volume so we can show the patient immediately the depth and the probability of recurrence. Specific echoes in skin cancer generated by nests of keratin are strong indicators of aggression and analyzed volumetrically. Highly suspect areas are checked for locoregional spread and a search is performed for lymphadenopathy so we can determine if the disease is confined and whether further surgical intervention is unlikely at this time. Patients are reassured because they simultaneously see the exam proceed in systematic stages. In serious cases, the patient is forewarned that the operation involves skin grafts and tissue construction.  4D ultrasound permits image-guided biopsy of the most virulent area of the dermal tumor and allows the pathologist to focus on the most suspicious region of the lymph node mass excised from the armpit, neck, or groin. Some laboratories are using postop radiography and sonography for better specimen analysis.

VIDEO DIGITAL MICROSCOPY VS BIOPSY

Fear of complications can deter patients from seeking medical opinion and surgical intervention, so many opt for noninvasive options. Imaging can help to reduce unnecessary biopsies because it can help identify the 1 out of every 33,000 moles that is malignant, while weeding out those that are not.

Once skin cancer is diagnosed, the treatment depends on depth penetration, possibly involving facial nerves, muscles around the eye and nasal bone or ear cartilage. Verified superficial tumors are treated topically or by low dose non-scarring radiation. Many cancers provoke a benign local immune response or coexistent inflammatory reaction that simulates a much larger area of malignancy, and cicatrix accompanies the healing response. 4D imaging combined with optical microscopy (RCM (reflectance confocal microscopy) or OCT (optical coherence tomography)) defines the true border during surgery, sparing healthy tissue, resulting in smaller excisional margins and less scar formation.

 

Do you have any tips on incorporating ultrasound in cancer imaging? Comment below, or, AIUM members, continue the conversation on Connect, the AIUM’s online community.

connect_now_live_digital_graphics_e-newsletter-1

Robert Bard, MD, DABR, FASLMS, currently runs a private consulting practice in New York City. He authored Image Guided Dermatologic Treatments, Image Guided Prostate Cancer Treatment, and DCE-MRI of Prostate Cancer and is a member of multiple leading international imaging societies. Since 1972, Dr. Bard has pioneered digital imaging technologies as alternatives to surgical biopsies for dermatologic and solid organ neoplastic disease.

Sonographers and Contrast-Enhanced Ultrasound

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Now that contrast-enhanced ultrasound (CEUS) has been approved in the United States for several abdominal applications in adults and pediatrics, I decided to take a deeper look into the sonographer’s role in CEUS. Traditionally, sonographers perform ultrasound examinations based on a protocol, construct a preliminary ultrasound findings worksheet, and perhaps discuss the findings with a radiologist. And now CEUS has transformed traditional ultrasound and gives physicians and sonographers additional diagnostic information related to the presence and patterns of contrast enhancement.DSC00125

Based on sonographers’ traditional scope of practice, some questions came to mind. What is the training process for sonographers to learn CEUS? How should CEUS images be obtained and stored? How should CEUS findings be communicated?

I envision CEUS training for sonographers broken down into stages, where they begin by learning the basics and eventually transition to where they can perform and record the studies independently. The first stage for sonographers is the ‘CEUS learning curve.’ In this stage, sonographers become familiar with basic CEUS concepts, eg, understanding physics of contrast agents and contrast-specific image acquisition modes, CEUS protocols, and typical patterns of contrast enhancement seen in various organs. In addition, an important part of the training is recognizing contrast reactions, and learning IV placement, documentation and billing related to CEUS.

The next stage involves sonographers performing more patient care and gaining scanning responsibilities. Sonographers place the IV and prepare the contrast agent. The scope of sonographer responsibilities does not generally include contrast injection (although it is reasonable since CT, MR, nuclear medicine, and echocardiography technologists routinely place IV lines and inject contrast). It should be noted that CEUS examination usually requires an additional person (physician, nurse, or another sonographer) to assist with contrast injection while the sonographer performs the ultrasound examination. In the beginning of sonographer training, it is very beneficial to have a radiologist present in the room to guide scanning and appropriate image recording.

In the third stage, a well-trained sonographer is more independent. At the completion of the examination, the sonographer will either send clips or still images to a physician to document the CEUS findings and discuss the procedure. Ideally, a worksheet is filled out, comparable to what is done today with “regular” ultrasound.

The majority of CEUS examinations are performed based on pre-determined protocols, usually requiring a 30–60-sec cineloop to document contrast wash-in and arterial phase enhancement. After that continuous scanning should be terminated and replaced with intermittent acquisition of short 5–10-sec cineloops obtained every 30–60 sec to document late phase contrast enhancement. These short clips have the advantage of limiting stored data while providing the interpreting physician with real-time imaging information. Detailed information on liver imaging CEUS protocols could be found in the recently published technical guidelines of the ACR CEUS LI-RADS committee.[i] Some new users might acquire long 2–3-minute cineloops instead, producing massive amounts of CEUS data. As a result, studies can slow down a PACS system if departments are not equipped to deal with large amounts of data. In addition, prolonged continuous insonation of large areas of vascular tissue could result in significant ultrasound contrast agent degradation limiting our ability to detect late wash-out, a critical diagnostic parameter required to diagnose well-differentiated HCC. Any solution requires identifying and capturing critical moments, which will be determined by a sonographer’s expertise. Exactly how sonographers can ensure CEUS will successfully capture the most important images is a critical question that must be answered and standardized.

Ideally, leading academic institutions should provide CEUS training for physicians and sonographers. I have seen and attended CEUS continuing medical education courses and they are a great way for physicians and sonographers to learn CEUS imaging. CEUS is a step forward for sonographers and will potentially transform our scope of practice. The technology will advance the importance of sonographers and diagnostic ultrasound, and importantly it will improve the care of our patients.

Acknowledgements:
Dr. Laurence Needleman, MD
Dr. Andrej Lyshchik, MD
Dr. John Eisenbrey, PhD
Joanna Imle, RDMS, RVT

[i] Lyshchik A, Kono Y, Dietrich CF, Jang HJ, Kim TK, Piscaglia F, Vezeridis A, Willmann JK, Wilson SR. Contrast-enhanced ultrasound of the liver: technical and lexicon recommendations from the ACR CEUS LI-RADS working group. Abdom Radiol (NY). 2017 Nov 18. doi: 10.1007/s00261-017-1392-0. [Epub ahead of print]

Has CEUS helped your sonography career? How do you envision CEUS being incorporated in your work? Comment below or let us know on Twitter: @AIUM_Ultrasound.

Corinne Wessner BS, RDMS, RVT is the Research Sonographer for Thomas Jefferson University Hospital in Philadelphia, Pennsylvania. Corinne has an interest in contrast-enhanced ultrasound, ultrasound research, medical education, and sonographer advocacy.

Should You Include CEUS and Elastography in Your Liver US Practice?

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Today, the liver is regarded with high importance by our clinical colleagues. The obesity epidemic, with its considerable impact in North America, is associated with severe metabolic disturbances including nonalcoholic fatty liver disease (NAFLD). Further, liver cancer is the only solid organ cancer with an increasing incidence in North America. Where do we as ultrasonographers fit into the imaging scheme to most appropriately deal with these new challenges?

The liver is the largest organ in the body, and certainly the most easily accessed on an abdominal ultrasound (US). It has been the focus of countless publications since the introduction of abdominal ultrasound many decades ago. Exquisite resolution allows for excellent detailed liver evaluation allowing US to play an active role in the study of both focal and diffuse liver disease. Focal liver masses are often incidentally detected on US examinations performed for other reasons and on scans performed on symptomatic patients. Abdominal pain, elevated liver function tests, and nonspecific systemic symptoms may all be associated with liver disease. The introduction of color Doppler to abdominal US scanners many years ago elevated the role of US by allowing for improved capability of US to participate in assessment of the hemodynamic function of the liver as well.

malignant tumor ceus

The well-recognized value of abdominal US, including detailed morphologic liver assessment, has made this examination the most frequent study performed in diagnostic imaging departments worldwide. However, in recent years, US has been relegated to an inferior status relative to CT and MR scan, as their use of intravenous contrast agents has made them the cornerstone modalities for virtually all imaging related to the presence of focal liver masses. As we now live in an era of noninvasive diagnosis of focal liver disease, greyscale US has fallen out of favor, as it is nonspecific for liver mass diagnosis. While US is the recommended modality for surveillance scans in those at risk for development of hepatocellular carcinoma, today, all identified nodules are then investigated further with contrast-enhanced CT and/or MR scan.

In the more recent past, US has been augmented by 2 incredible noninvasive biomarkers: elastography, which measures tissue stiffness, and contrast-enhanced ultrasound, which shows perfusion to the microvascular level for the first time possible with US. These noninvasive additions are invaluable and their adoption in routine US practices may allow the reemergence of US as a major player in the field of liver imaging.

Most conventional US machines today are equipped with the capability to perform elastography, especially with point shear wave techniques (pSWE). In pSWE, an ARFI pulse is used to generate shear waves in the liver in a small (approximately 1 cm3) ROI. B mode imaging is used to monitor the displacement of liver tissue due to the shear waves. From the displacements monitored over time at different locations from the ARFI pulse, the shear wave speed is calculated in meters per second, with higher velocities associating with increased tissue stiffness. The accuracy for the determination of liver fibrosis and cirrhosis with pSWE as compared with gold standard liver biopsy is now indisputable. Because of the great significance of liver fibrosis secondary to fatty liver and the obesity epidemic, the development of this technique as a routinely available study is essential. Because of the frequent selection of US as the first test chosen for any patient suspect to have undiagnosed diffuse liver disease, the opportunity for elastography to be included with the diagnostic morphologic US test should be developed as a routine.

Contrast-enhanced US (CEUS), similarly, is available on most currently available mid- and high-range US systems, allowing for nondestructive low MI techniques to image tumor and liver vascularity following the injection of microbubble contrast agents for US. This allows for a similar algorithmic approach to contrast-enhanced CT and MR scan for noninvasive diagnosis of focal liver masses. CEUS additionally offers unique imaging benefits that include no requirement for ionizing radiation and also imaging without risk of nephrotixity, invaluable in the many patients who present for imaging with high creatinine, preventing injection of both CT and MR contrast agents.

Incorporation of pSWE and CEUS into standard liver US in patients with suspect diffuse or focal liver disease is a cost-effective and highly appropriate consideration as this is readily available, performed without ionizing radiation, and at a considerable cost saving over all other choices.

Can you diagnose a hepatocellular carcinoma or other liver tumor with CEUS?  And, can you determine if a liver is cirrhotic or not?  With the addition of pSWE and CEUS to your liver US capability, yes, you can.

What is your experience with treating liver disease? What aspect is most difficult for you? What other area do you think would benefit from the addition of CEUS? Comment below or let us know on Twitter: @AIUM_Ultrasound.

Stephanie R Wilson is a Clinical Professor at the University of Calgary.