Category Archives: Contrast-Enhanced

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:

A Quick Introduction to Subharmonic Imaging and Pressure Estimation

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Our imaging field has had access to commercial microbubble-based ultrasound contrast agents for well over twenty years by now. It is well established that these agents—combined with nonlinear contrast-specific imaging techniques—improve both the sensitivity and specificity of ultrasound diagnoses across a wide range of clinical applications.

There are currently 3 ultrasound contrast agents approved by the United States’ Food and Drug Administration (FDA) for cardiology and/or radiology applications: Optison (GE Healthcare, Princeton, NJ); Definity (Lantheus Medical Imaging, N Billerica, MA); and Lumason (marketed for more than a decade in Europe and elsewhere as SonoVue; Bracco Imaging, Milan, Italy). There are other contrast agents in commercial development around the world; in particular Sonazoid (GE Healthcare) and BR55 (Bracco Imaging). Very importantly, the safety profiles of all of these agents are also well established with a severe reaction rate of less than 0.01% (based on studies of millions of dosages injected worldwide), making them the safest of all contrast media used for imaging.

Flemming Forsberg, PhD

Ultrasound agents consist of billions of gas microbubbles (typically < 8 mm in diameter) that are each encapsulated by an outer shell for stability. Following an intravenous injection, the microbubbles can traverse the lung capillaries and circulate in the blood for 3–6 minutes (under continuous imaging—longer if intermittent imaging is employed), due to their size and the higher molecular weight gasses used as filling gasses (rather than just air as was used in earlier microbubble designs), which reduces diffusion back into solution.

The acoustic properties of the bubble filing gasses (specifically the compressibility) are very different from those of the surrounding blood (by six orders of magnitude). Hence, microbubble-based ultrasound contrast agents can enhance ultrasound signals markedly with echo signals being increased by up to 30 dB. This in turn enables signals from breast tumor neovascularity corresponding mainly to vessels 20–39 mm in diameter to be imaged.

Ultrasound contrast agents not only enhance the backscattered ultrasound signals, but at sufficient acoustic pressures (typically above 0.3 MPa) they also act as nonlinear oscillators. These oscillations generate significant energy components in the received echo signals, which span the range of possible frequency emissions from subharmonics through ultra-harmonic frequency components. These nonlinear bubble echoes can be separated from tissue echoes and used to create contrast-sensitive imaging modalities such as harmonic imaging (HI), which is commercially available on most state-of-the-art ultrasound scanners.

Multi-pulse imaging strategies, such as pulse-inversion imaging or pulse-amplitude modulation, can further improve the depiction of microvascularity compared to color Doppler imaging modes. However, HI suffers from reduced blood-to-tissue contrast resulting from second harmonic generation and accumulation in tissue. Hence, subharmonic imaging (SHI), transmitting at the fundamental frequency (f0) and receiving at the subharmonic (f0/2), becomes an attractive alternative because of the weaker subharmonic generation in tissue and the significant subharmonic scattering produced by some new contrast agents. Several ultrasound scanners (from GE Healthcare and Mindray) have now been released with commercial SHI software packages. A recent multi-center study of 3D SHI for characterizing suspicious breast lesions indicates that diagnostic accuracies up to 97% can be achieved.

Ultrasound contrast agents can be used not only as vascular tracers but also as sensors for noninvasive pressure estimation by monitoring subharmonic contrast bubble amplitude variations. This innovative technique, called subharmonic-aided pressure estimation (SHAPE), relies on the inverse linear correlation (r2 > 0.90) between the amplitude of the subharmonic signals and hydrostatic pressure (up to 186 mmHg) measured in vitro for most (but not all) commercial contrast agents. SHAPE offers the possibility of allowing pressure gradients in the heart and throughout the cardiovascular system as well as interstitial fluid pressure in tumors to be obtained noninvasively. Studies indicate that SHAPE can provide in vivo pressure estimates with errors of less than 5 mmHg in the left and right ventricles of patients. Moreover, a large multi-center clinical trial of using SHAPE to diagnose clinically significant portal hypertension in 178 subjects resulted in a sensitivity of 91% and a specificity of 82% and these subjects had a higher SHAPE gradient than participants with lower pressures (0.27 ± 2.13 dB vs -5.34 ± 3.29 dB; p<0.001) indicating SHAPE may indeed be a useful tool for the diagnosis of portal hypertension.

Flemming Forsberg, PhD, FAIUM, FAIMBE, is a Professor of Radiology at Thomas Jefferson University in Philadelphia, Pennsylvania. He also serves as a Deputy Editor of the Journal of Ultrasound in Medicine and as the Vice Chair of the American Institute of Ultrasound in Medicine’s (AIUM’s) Contrast-Enhanced Ultrasound Community (2021–2023).

Interested in learning more about Contrast-Enhanced Ultrasound? Check out the following posts from the Scan:

Pediatric Contrast-Enhanced Voiding Urosonography Tips

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Contrast-enhanced voiding urosonography (ceVUS) is most commonly used to assess for vesicoureteral reflux (VUR) and anatomic abnormalities of the urethra. Like fluoroscopic voiding cystourethrography (VCUG) examinations, in ceVUS, contrast is administered into the urinary bladder, and images are obtained of the kidneys, ureters, bladder, and urethra during filling and voiding phases.

As a department, we have performed hundreds of ceVUS exams since we began clinical studies almost 7 years ago. I have learned to ask several questions before beginning each ceVUS to help the exam go smoothly.


Does the patient/family know what will happen during the ceVUS?

Ultrasound is a workhorse for pediatric imaging because of the inherent qualities of the modality: no ionizing radiation, patients in close proximity to family members, calm and darkened exam rooms, non-imposing equipment infrastructure, and (usually) the absence of sedation or anesthesia. Most of these attributes hold for ceVUS, but bladder catheterization changes the non-invasive use of US to an invasive examination. Even so, I have been amazed by the distances that families will travel to seek ceVUS in place of VCUG for their children.

Patient and family preparation is a vital first step for ceVUS. To best image the urethra and bladder base, the probe will be positioned on the lower abdomen, perineum, and over the genitals. Discussion of catheterization and probe positioning on the body in a manner appropriate for the child’s age is critical prior to beginning. Childlife specialists can help prepare the child and family as well as provide support and distraction techniques during the examination.

Right grade 3 vesicoureteral reflux in a 3-year-old girl. Sagittal dual display grayscale (on the left) and contrast mode (on the right) of the right kidney showing echogenic ultrasound contrast in the right renal collecting system with dilation of the renal pelvis and calyces.

How will the child void during the examination?

Prior to the voiding phase images during an examination on a young adult, the patient told us that she could not void in the supine position. Unprepared for that moment, we stretched the US unit power cord (and ourselves) to follow her into the adjoining restroom and image her kidneys while she sat on the commode.

A major benefit of ceVUS over VCUG is that the patient is not confined to voiding in a supine position when imaging with ultrasound. While a small percentage of children will not void during either a VCUG or ceVUS, making a plan for how they will void will set the patient up for success during the study. Absorbent pads, bedpans, urinals, training toddler seats, and full-size commodes are all options. When planned for, we often can still obtain urethral images while permitting the patient modesty through appropriate draping.

Which probe positions will be optimal for this patient?

Another benefit of ceVUS over VCUG is that the patient’s anatomy can be visualized even when there is no VUR. When obtaining pre-contrast images, you should start by determining the best window to visualize each kidney.

When VUR occurs, the kidney-ureter unit can be observed with probe positioning from the flank. This position may allow visualization of both the right and left refluxing unit in young children. A transperineal view may not only help to see the urethra but also the bladder base and ureteral insertions.

During VCUG, an imaging team may be accustomed to placing tape on the suprapubic region to secure the bladder catheter. However, US images cannot be obtained through tape. Anticipating the best view of the urethra will help avoid an inopportune tape placement, which will obscure visualization during voiding. In the bladder filling phase, the contrast is following through the catheter, which demarcates the entire course of the urethra. Practicing probe position from a suprapubic or transperineal window during bladder filling will help identify the best window to use when voiding begins. With these preliminaries in mind, we’ve had tremendous success with ceVUS at our institution.

Susan J. Back, MD, is a pediatric radiologist at Children’s Hospital of Philadelphia.

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

Access the Portal Venous System Safely

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Transjugular intrahepatic portosystemic shunt (TIPS) placement is a well-studied procedure for patients with variceal bleeding, refractory ascites, and hepatic hydrothorax on optimal medical therapy. Despite its efficacy, TIPS remains one of the more technically challenging procedures, particularly related to safely gaining access into the portal venous system.

A typical TIPS procedure involves internal jugular venous access, hepatic vein catheterization, venography, and wedged CO2 portography, and the most challenging step—retrograde portal vein access prior to tract dilatation and stent placement. When using CO2 portography as a landmark for portal venous access, usually several needle passes are required and each additional needle pass increases the risk of adverse events, such as hepatic artery injury, hemobilia, and damage to surrounding structures (kidney, colon, and lung parenchyma).

There have been multiple ways to mitigate this issue, such as biplanar angiography, percutaneous transhepatic guidewire placement within the portal venous system, and cone-beam CT guidance. These methods have had various successes but may require increased procedure time, increased radiation dose, or alternative access sites (for example when placing a microwire into the portal venous system via the transhepatic route).

In our opinion, the best solution for accessing the portal venous system during the TIPS procedure is using intravascular ultrasound guidance with a side-firing intracardiac echocardiographic tip (ICE). The benefit of having ICE guidance is intuitive: it allows for direct visualization of the portal venous target, proper selection of the closest hepatic vein to the respective portal vein, and needle guidance using real-time ultrasound visualization. Therefore, ICE guidance reduces the number of needle passes, the risk of hitting critical structures, and the length of the procedure. Previously, ICE guidance has proven its worth in managing complicated TIPS cases, such as portal vein thrombosis, distorted anatomy from prior surgery or neoplastic disease, as well as TIPS for Budd-Chiari syndrome (direct IVC to portal venous access in these cases).

There have been a few retrospective investigations comparing fluoroscopic guidance to ICE guidance for the TIPS procedure. In a study by Kao et al., the authors did a retrospective comparison between ICE and fluoroscopic guidance. It is interesting to note that the ICE operators were only 2 and 3 years out of fellowship versus 20+ years of experience in the conventional group. The data showed that ICE catheter guidance significantly decreased the number of needle passes, contrast volume, fluoroscopy time, procedure time, and radiation exposure. More importantly, ICE largely reduced the number of “outliers” —those occasional cases in which 30+ needle passes and a few hours of fluoroscopy times are required. It is likely in clinical practice that exactly these outlier cases drive up complication rates.

In a different study, by Ramaswamy et al., the authors did a propensity-matched retrospective review. The data showed the procedure time and outcomes were not significantly different between ICE and conventional techniques. However, there was a significant reduction in contrast volume and radiation in the ICE guidance group. The major caveat of the study was that the ICE operators were much earlier in their career than the conventional group, with an average experience of 4.2 years versus 11 years. The difference in operator experience probably indicates that ICE has the potential to decrease the procedure time when adjusted for operator experience.

Based on the available retrospective studies and our experience, a few points can be confirmed.

  1. ICE decreases the number of needle passes, radiation exposure (to both the patient and operator), and contrast volume.
  2. ICE most likely decreases the procedure time, accounting for differences in operator experience.
  3. ICE will largely eliminate outlier cases that are more likely associated with complex anatomy/clinical scenario and have a higher potential to cause major complications.

In our experience, ICE catheter guidance makes the procedure safer in tough situations. Of course, ICE adds costs (~ $1,000/probe). The modality has a pretty steep learning curve, and it requires an additional venipuncture. In addition, the (more inexperienced) conventional operator can achieve excellent results in routine and/or complex scenarios without using ICE.

In our view, ICE guidance is most helpful in dealing with complex TIPS cases in which a large number of needle passes are expected and complications are frequent. Furthermore, it offers a back-up option when a conventional TIPS procedure runs into unexpected challenges. Instead of blindly sticking another 20 times, we should become familiar with using the available tool (ICE catheter guidance) in our procedural arsenal to provide a safer experience for our patients, ultimately improving outcome in the end-stage liver disease population.

This is a patient referred for re-attempt TIPS from an outside hospital, where multiple attempts of accessing the portal venous system have failed and, therefore, TIPS procedure in the outside hospital had to be aborted. Image A shows the access needle (skinny arrow) directed from the hepatic vein towards a right portal branch (fat arrow). Image B shows the access needle and Bentson guidewire (skinny arrow) within the same right portal branch (fat arrow), indicating successful cannulation. Image C confirms the guidewire (white circle) advanced into the main portal vein. Image D shows the TIPS stent connecting the right portal vein (arrow) with the hepatic vein with free flow of contrast. Portal access was successful on the second puncture with ICE guidance for this (challenging) re-attempt TIPS procedure.

All comments are welcomed; Sasan Partovi can be reached at partovs@ccf.org.

References:

Ramaswamy RS, Charalel R, Guevara CJ et al. Propensity-matched comparison of transjugular intrahepatic portosystemic shunt placement techniques: Intracardiac echocardiography (ICE) versus fluoroscopic guidance. Clin Imaging. 2019; 57:40–44.

Kao SD, Morshedi MM, Narsinh KH, Kinney TB et al. Intravascular Ultrasound in the Creation of Transhepatic Portosystemic Shunts Reduces Needle Passes, Radiation Dose, and Procedure Time: A Retrospective Study of a Single-Institution Experience. JVIR. 2016; 27:1148–1153.

Sasan Partovi, MD, is a staff physician in interventional radiology at The Cleveland Clinic Main in Cleveland, Ohio. Dr. Partovi’s research interests are focused on innovative endovascular treatment options for end-stage renal disease and end-stage liver disease patients. Dr. Partovi has been elected as secretary of the American Institute for Ultrasound in Medicine’s (AIUM’s) Interventional-Intraoperative Community of Practice.

Xin Li, MD, is a radiology resident at the Hospital of the University of Pennsylvania in Philadelphia, Pennsylvania. Dr. Li attended Case Western Reserve University School of Medicine in Cleveland, Ohio, and is pursuing a career in interventional radiology. He currently serves on the Resident, Fellow, and Student Governing Council of the Society of Interventional Radiology.

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

The Excitement of New Ultrasound Technologies and Their Effects on Imaging-Guided Interventions

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Recent advancements in ultrasound technologies have generated excitement in the field of ultrasound-guided intervention. For me, an interventional radiologist, these developments create new potential to perform needed procedures and a complementary approach to addressing our patients’ complex medical conditions. Further, benefits from these technologies include enabling us to achieve better patient outcomes, improve patient satisfaction, gain operational efficiencies, and improve stake holder’s satisfaction.azar_nami

The new technologies to which I’m referring are ultrasound contrast and ultrasound fusion. Ultrasound fusion is an element of artificial intelligence that combines the anatomic details of cross-sectional imaging like CT scan, PET scan, and MRI with the power of real-time ultrasound and is gaining more acceptance and popularity in medicine. Similar to a car’s GPS, ultrasound fusion helps a user find something. The powerful tool enables the operator to find lesions, which normally are difficult or even impossible to find on standard ultrasound. Needle navigation in the form of virtual tracking is a bonus that identifies needle location even when it is obscured by air or bone. It’s also a great teaching tool for inexperienced physicians who are interested in interventional radiology.

Ultrasound contrast is also emerging as a powerful tool in the field of interventional radiology. It enables the operator to better visualize a lesion and characterize the lesion and surrounding tissue. Now, we also can perform an ultrasound contrast sinogram to assess any cavity or catheter location, which opens new horizons in the field of ultrasound intervention, mainly in pediatric intervention.

An additional benefit for ultrasound contrast that it can be given without worrying about renal injury. This is very valuable when it comes to avoiding the toxic effect of iodinated contrast, especially in renal transplant intervention. Also, its very sensitivity to assess bleeding when compared with that of Doppler ultrasound. This technology allows us to discharge our patients home earlier after procedures when the contrast study is negative.

This is a very exciting time in the field of interventional radiology (IR). So many procedures that we could not perform using real-time ultrasound in the past now can be safely done with only ultrasound. Our patients appreciate how convenient it is. The procedures are done quickly, without the need to move the patient from their bed onto a stiff CT scan table. The lack of ionizing radiation in IR is also an attractive concept to the patient (mainly pediatric and/or pregnant), the clinician, and our IR staff.

Our institution is very supportive of utilizing advanced ultrasound technologies, as ultrasound allows us to gain operational efficiencies and is a more cost-effective alternative to CT-guided procedures. Operational efficiencies are gained by doing interventional cases portably with ultrasound, thus allowing the interventional CT suite to be utilized for diagnostic exams, which bring additional revenue to the institution. The ordering clinicians are also cognizant of radiation dose reduction, so providing an alternative to CT-guided procedures appeals to them.

Even though the implementation of contrast-enhanced ultrasound and fusion has been slower in the United States when compared with our colleagues abroad, it has brought a lot of excitement to my colleagues and me in interventional radiology. Like any new technology, the more we use, the more we appreciate its value. I predict they will become the new norm in daily practice. These advancements will continue to evolve and be an essential part of medicine.

 

Interested in reading more about contrast ultrasound? Check out the following posts from the Scan:

 

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Nami Azar, MD, MBA, is an Associate Professor of Radiology in the Department of Radiology at University Hospitals of Cleveland Medical Center in Ohio.

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.

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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.