New Techniques in EUS: Real-Time Elastography, Contrast-Enhanced EUS, and Fusion Imaging

Key Points

  • Endoscopic ultrasound (EUS) has improved considerably in the past years through development of real-time EUS elastography, contrast-enhanced EUS and fusion EUS imaging.

  • Real-time EUS elastography provides qualitative and semi-quantitative data about tissue stiffness, possibly allowing differentiation of benign and malignant tumors.

  • Contrast-enhanced harmonic EUS using specific software (with low mechanical index capabilities) is already established as a procedure useful for the differential diagnosis of focal pancreatic masses.

  • Fusion EUS imaging represents a combination of EUS and computed tomography/magnetic resonance imaging (CT/MRI), which is still under development, with the aim of decreasing the difficult learning curve of EUS, but also increasing diagnostic confidence and better orientation of multiple target lesions.

Endoscopic ultrasound (EUS) represents a high-resolution imaging technique used mainly for the diagnosis and staging of digestive cancers situated in the vicinity of the gastrointestinal (GI) tract. The method is increasingly used in medical centers around the world due to a significant clinical impact, especially after the addition of EUS-guided fine-needle aspiration (EUS FNA), which is able to confirm a tissue diagnosis of malignancy. Due to the increased resolution of EUS technology, even as compared to other cross-sectional imaging methods (such as computed tomography [CT] or magnetic resonance imaging [MRI]), several other methods were further developed to extend its capabilities, including real-time EUS elastography, contrast-enhanced EUS, and fusion imaging.

Real-Time Endoscopic Ultrasound Elastography

Elasticity imaging has been reported useful for the characterization and differentiation of benign and malignant tissues due to the inherent differences in the hardness of tissues. Thus, malignant tumors are usually stiffer as compared with benign masses, whereas the strain information induced by small tissue deformations can be computed and displayed in real time. Initial clinical applications included breast and prostate cancer, as well as lymph nodes, thyroid masses, or focal liver lesions. Recently, real-time elastography was extensively used to characterize liver fibrosis in chronic liver diseases, including chronic hepatitis B or C, and also liver cirrhosis. The technique has the distinct advantage that it can be used with various ultrasound transducers, thus extending the method to virtually all organs. The method has been successfully applied with intraoperative or intracavitary transducers, as well as EUS probes.

Technical Details

Real-time sonoelastography represents a certain technical improvement over gray-scale ultrasound, allowing the estimation of tissue strain, during slight compressions induced by transducer or small heart/vessel movements. The method works in real time in a similar manner as color Doppler, the strain information being visually converted into a hue color scale and displayed as a transparent overlay imposed on the gray-scale ultrasound information. The principle of real-time elastography consists of measurement of tissue displacement induced by small compressions, which are inducing strain that is usually smaller in harder tissues as compared to soft tissues ( Fig. 5.1 ). A complex algorithm called combined autocorrelation method allows the calculation of axial strain along the direction of ultrasound waves, which also corresponds to the direction of compressions. Consequently, soft tissues are easy to compress being displayed in low-hue values approaching green, whereas hard tissues are difficult to strain, thus being displayed in high-hue values approaching blue. The information can be further quantified by taking into consideration a numerical hue scale from 0 to 255. Both the basic principles, as well as the clinical applications for the usage of ultrasound elastography, are carefully reviewed in two comprehensive guidelines and recommendations issued by the European Federation Societies in Ultrasound in Medicine and Biology (EFSUMB).

Fig. 5.1

Benign mediastinal lymph node. Endoscopic ultrasound elastography showing a relatively homogeneous mixture of green and yellow, indicating a relatively soft structure as compared to the surrounding tissues (left).

EUS elastography equipment includes a state-of-the-art ultrasound system with real-time sonoelastography capabilities, coupled with conventional endoscopic radial or linear EUS transducers. The usual setting includes a two-panel EUS image, with the conventional gray-scale (B-mode) image on the right panel and the transparent overlay elastography image on the left side ( Fig. 5.2 ). The elastography region of interest is trapezoidal in shape and can be freely selected to encompass at least half of the examined targeted lesion, as well as the surrounding tissues. Tissue elasticity values are represented in a hue color scale, with values from 0 to 255. Consequently, the color information can be semi-quantified as average values, whereas all the necessary statistical data (average strain histograms and standard deviation) can be easily calculated by using the latest versions of software ( Figs. 5.3 to 5.5 ). The system also includes the possibility of calculation of strain ratio (i.e., an estimation of the modulus ratio between two user-defined areas of interest), thus representing a semi-quantitative evaluation of strain differences between the areas. However, it should be taken into consideration that changing the reference area to a deeper position significantly influences strain ratio measurements, which are otherwise independent of the size and other parameters (for example, the elastography dynamic range). It is not yet clear if the usage of strain ratios or strain histograms should be the preferred method, while further studies will be necessary to show the differences between various methodologies.

Fig. 5.2

Malignant mediastinal lymph node. Endoscopic ultrasound elastography showing a relatively homogeneous mixture of blue, indicating a relatively hard structure as compared to the surrounding tissues (left).

Fig. 5.3

Malignant mediastinal lymph node. Endoscopic ultrasound elastography with EUS-guided FNA showing a relatively hard (blue) homogeneous lymph node (left). A smaller rectangular region of interest is selected at the level of the lymph node and a hue histogram can be displayed, showing low mean elasticity (strain) values.

Fig. 5.4

Chronic pseudotumoral pancreatitis. Endoscopic ultrasound elastography showing a relatively heterogeneous mixture of blue, green, and red, indicating a relatively intermediate elasticity structure as compared to the surrounding tissues (left). Hue histogram analysis can be also performed to obtain semiquantitative data on the elasticity of the focal mass (mean 63.4, SD 62.3).

Fig. 5.5

Pancreatic adenocarcinoma. Endoscopic ultrasound elastography showing a relatively homogeneous hard (blue) mass, indicating a relatively hard elasticity structure as compared to the surrounding tissues (left). Hue histogram analysis can be also performed to obtain semiquantitative data on the elasticity of the focal mass (mean 15.8, SD 28.7).

Clinical Applications

Real-time EUS elastography was initially reported to be useful in a pilot study, which included a low number of patients with focal pancreatic masses ( n = 24) and lymph nodes ( n = 25). A high sensitivity of 100% but a low specificity of 67% and 50% for pancreatic masses and lymph nodes, respectively, determined criticism of the study methodology, including qualitative pattern evaluation and establishment of diagnostic criteria in the same group of patients. The study was, however, continued with a multicenter trial that analyzed 222 patients with focal pancreatic masses ( n = 121) and lymph nodes ( n = 101), accompanied by interobserver variability data that indicated good values of the κ coefficient of 0.785 for pancreatic masses and 0.657 for lymph nodes. EUS elastography was proven to have higher sensitivity and specificity values as compared with conventional gray-scale EUS images of 92.3% and 80.0% for the differential diagnosis of focal pancreatic masses and of 91.8% and 82.5% for the differential diagnosis of lymph nodes. Based on the published data, EUS elastography was thus suggested to be superior as compared with conventional B-mode (gray-scale) imaging that might be utilized in patients with pancreatic masses and negative EUS FNA and also to increase the yield of EUS FNA for patients with multiple lymph nodes. Moreover, several prospective studies using qualitative or quantitative criteria were subsequently published and supported the value of real-time EUS elastography in larger patient subgroups and multicenter trial designs ( Tables 5.1 and 5.2 ).


Sensitivity and Specificity of Endoscopic Ultrasound Elastography for the Differential Diagnoses of Lymph Nodes

Reference Number of Lymph Nodes Sensitivity (%) Specificity (%)
Giovannini and coworkers 25 100 50
Săftoiu and coworkers 42 91.7 94.4
Janssen and coworkers 66 87.9 86.4
Săftoiu and coworkers 78 85.4 91.9
Giovannini and coworkers 101 91.8 82.5
Larsen and coworkers 56 55 82
Okasha and coworkers 88 79.3 100
Sazuka and coworkers 115 91.2 94.5


Sensitivity and Specificity of Endoscopic Ultrasound Elastography for the Differential Diagnoses of Focal Pancreatic Masses

Reference Number of Patients Sensitivity (%) Specificity (%)
Giovannini and coworkers 24 100 67
Hirche and coworkers 70 41 53
Săftoiu and coworkers 43 93.8 63.6
Giovannini and coworkers 121 92.3 80.0
Iglesias-Garcia and coworkers 130 100 85.5
Iglesias-Garcia and coworkers 86 100 92.9
Săftoiu and coworkers 54 84.8 76.2
Schrader and coworkers 86 100 100
Săftoiu and coworkers 258 93.4 66.0
Dawwas and coworkers 111 100 16.7
Kongkam and coworkers 38 86.2 66.7
Kim and coworkers 157 95.6 96.3

Lymph Nodes

An initial feasibility study that aimed to establish the value of EUS elastography for the differential diagnosis of lymph nodes was based on qualitative pattern analysis of 42 cervical, mediastinal, or abdominal lymph nodes, taking into consideration five characteristic patterns previously described for breast lesions, which allowed the establishment of a provisional diagnosis of benign (see Fig. 5.1 , Video 5.1 ) or malignant ( Fig. 5.2 , Video 5.2 ) lymph nodes. Sensitivity, specificity, and accuracy for the qualitative pattern analysis were 91.7%, 94.4%, and 92.86%, respectively, with an area under receiver operating characteristic (AUROC) curve of 0.949. Several limitations of the method were acknowledged, including selection bias of the best EUS images, chosen arbitrarily by the examiner from a longer EUS elastography video. Similar results were obtained by another group that analyzed 66 mediastinal lymph nodes based on the same qualitative analysis of color patterns. The accuracy was variable for three examiners, between 81.8% and 87.9% for benign lymph nodes and between 84.6% and 86.4% for malignant lymph nodes, with an excellent interobserver analysis (κ = 0.84).

Video 5.1

Benign Mediastinal Lymph Node

Endoscopic ultrasound elastography showing a relatively homogeneous mixture of green and yellow, indicating a relatively soft structure as compared to the surrounding tissues (left).

Video 5.2

Malignant Mediastinal Lymph Node

Endoscopic ultrasound elastography showing a relatively homogeneous mixture of blue, indicating a relatively hard structure as compared to the surrounding tissues (left).

A recent qualitative study also analyzed the role of elastography for prediction of lymph node malignancy. Thus, consideration of different scores for the differential diagnosis indicated a sensitivity of 79.3% and specificity of 100%. For the patients with esophageal cancer only, the sensitivity and specificity of EUS elastography were 91.2% and 94.5%, respectively, significantly higher than the values of conventional B-mode EUS examinations.

Another prospective study was designed to test the accuracy of computer-enhanced dynamic analysis of EUS elastography movies for the differential diagnosis between benign and malignant lymph nodes. A total number of 78 lymph nodes were included, and average hue histograms were calculated for each EUS elastography video in order to better describe the elasticity of each lymph node according to calculations based on the hue scale of the ultrasound system. The ROC analysis for the average hue histogram values inside lymph nodes yielded an AUROC of 0.928 for the differential diagnosis, with a sensitivity, specificity, and accuracy of 85.4%, 91.9%, and 88.5%, respectively, based on a cutoff level situated in the middle of the green-blue rainbow scale. The study also reported a high positive predictive value (PPV) of 92.1% and a high negative predictive value (NPV) of 85%, implying that the most probable malignant lymph nodes could be targeted by EUS FNA (see Fig. 5.3 ), whereas EUS FNA could be avoided in the lymph nodes that are considered most probably benign.

Another group looked at the intraobserver and interobserver agreement of EUS elastography, including the values of strain ratios, for the differential diagnosis of benign and malignant lymph nodes. Both elastography and elastography strain ratio evaluations of lymph nodes were feasible and had a good interobserver agreement of 0.58 and 0.59 (based on a cutoff of 3.81 for the strain ratio), respectively. The same group further looked at EUS elastography and elastography strain ratios based on histology results after marking of lymph nodes with EUS FNA. The sensitivity of EUS was higher than elastography, whereas the specificity was lower as compared to elastography and strain ratios.

A recent meta-analysis that included 368 patients with 431 lymph nodes was also published, indicating a pooled sensitivity of EUS elastography of 88% with a specificity of 85% for the differential diagnosis of benign and malignant lymph nodes. After subgroup analysis with exclusion of outliers, the sensitivity and specificity were 85% and 91%, respectively, leading the authors to conclude that EUS elastography is a valuable noninvasive method used to differentiate benign and malignant lymph nodes.

Pancreatic Masses

Similar qualitative pattern analysis was used for the visualization and differentiation of pancreatic lesions in a prospective study that included 73 patients: 20 with normal pancreas, 20 with chronic pancreatitis, and 33 with focal pancreatic lesions. Although EUS elastography videos were considered reproducible and could be easily obtained in all the patients included, there was no visible difference between chronic pancreatitis and pancreatic adenocarcinoma. Another study included 70 patients with focal pancreatic masses assessed by qualitative EUS elastography. Again, only 56% of the patients with solid pancreatic lesions had reproducible elastographic tracings, probably because of an incomplete delineation of large lesions (>35 mm in diameter) or due to the large distance from transducer.

Semi-quantitative analysis based on average hue histograms of the EUS elastography videos showed that the method can be reliably used for the differentiation of normal pancreas, chronic pancreatitis (see Fig. 5.4 , Video 5.3 ), and pancreatic cancer (see Fig. 5.5 , Video 5.4 ). A subgroup analysis performed for the patients with focal pancreatic masses (pseudotumoral chronic pancreatitis and pancreatic cancer) yielded an AUROC of 0.847, with good sensitivity, specificity, and accuracy rates of 93.8%, 63.6%, and 86.1%, respectively. The PPV and NPV were 88.2% and 77.8%, respectively. To increase the accuracy, an artificial neural network (ANN) model was further applied and showed a good testing performance of 90% on average, with a very good stability of the ANN model and an AUROC of 0.965, indicating also a very good classification performance. EUS elastography thus offers complementary information added to the conventional gray-scale information.

Video 5.3

Chronic Pseudotumoral Pancreatitis

Endoscopic ultrasound elastography showing a relatively heterogeneous mixture of blue, green, and red, indicating a relatively intermediate elasticity structure as compared to the surrounding tissues (left). Hue histogram analysis can be also performed to obtain semiquantitative data on the elasticity of the focal mass (mean 63.4, SD 62.3).

Video 5.4

Pancreatic Adenocarcinoma

Endoscopic ultrasound elastography showing a relatively homogeneous hard (blue) mass, indicating a relatively hard elasticity structure as compared to the surrounding tissues (left). Hue histogram analysis can also be performed to obtain semiquantitative data on the elasticity of the focal mass (mean 15.8, SD 28.7).

Several other studies using various methodologies also tested the value of real-time EUS elastography in the clinical practice. A large, single-center study involving 130 patients used qualitative pattern analysis with four patterns (homogeneous or heterogeneous, predominantly green or blue patterns) to yield a sensitivity, specificity, and accuracy of 100%, 85.5%, and 94%, respectively. Due to the large subjectivity of the method, the same group published a further study with semi-quantitative EUS elastography based on strain ratio, calculated as a quotient between two regions of interest (ROIs): the representative reference area and the focal mass. Based on a total number of 86 consecutive patients with solid focal pancreatic mases, the method was found to be useful with an AUROC of 0.983 and very high sensitivity and specificity of 100% and 92.9%, respectively. Strain ratio measurements were recently used by another group in 109 patients with pancreatic lesions (normal pancreas, chronic pancreatitis, pancreatic cancer, and neuroendocrine tumors). A separate analysis for the red, green, and blue channels achieved a better separation between the groups with normal pancreas and malignant pancreatic lesions, with a high sensitivity and specificity of 100%. Based on quantitative morphometry for pancreatic fibrosis, another group tried to correlate it with pancreatic stiffness but found no relationship. Although important, this study lacked a group of patients with chronic pancreatitis and thus lacked the most significant and difficult cases for differential diagnosis. A combination of contrast-enhanced power Doppler and real-time EUS elastography also yielded good results for the differentiation of focal pancreatic masses, even though the sensitivity, specificity, and accuracy of elastography had lower values of 84.8%, 76.2%, and 81.5%, respectively, as compared to the combined approach. A recent prospective study included 111 semi-quantitative EUS elastography procedures based on strain ratio measurements performed in 104 patients with solid pancreatic masses with the final diagnosis confirmed by pancreatic cytology or histology. The reported areas under the ROC curves for detection of pancreatic malignancy were 0.69 and 0.72 for strain ratio and mass elasticity, respectively, with an overall accuracy of 86.5% and 83.8% (based on cutoffs of 4.65 for strain ratio [SR] and 0.27% for mass elasticity), respectively. In concordance with previous studies, the authors suggested that the modest diagnostic role indicates that EUS elastography could supplement EUS FNA and does not replace tissue sampling. Indeed, a recent study showed that negative results of the combination of EUS FNA and EUS elastography are more reliable to exclude malignancy in focal pancreatic masses. Another option is to use two separate cutoffs for the reliable diagnosis of chronic pancreatitis and pancreatic cancer, although there will be a gray zone in between the cutoffs, where diagnosis should still depend on other imaging tests or EUS FNA.

Although EUS elastography brings significant complementary information when added to conventional EUS imaging, the methodology is not yet firmly established, and the choice of either qualitative or semi-quantitative methods of evaluation for EUS elastography images or movies is not yet clear. This explains the significant heterogeneity between the published studies (see Table 5.2 ) and also the variability of the results encountered for sensitivity, specificity, and accuracy. Nevertheless, a large European, prospective, multicenter trial was performed by the European EUS elastography study group comprising 13 centers and 258 patients. Both a qualitative evaluation by two doctors and also a semi-quantitative evaluation by average hue histograms of three separate videos were performed blindly in order to test intraobserver and interobserver variability. For interobserver analysis, qualitative diagnosis of the recorded videos revealed a κ value of 0.72, whereas for intraobserver analysis the single measure intraclass coefficient ranged between 0.86 and 0.94. Based on a cutoff of 175 for the average hue histograms, the sensitivity, specificity, and accuracy were 94.4%, 66.0%, and 85.4%, respectively, with a corresponding AUROC of 0.894. The PPV was 92.5%, whereas the NPV was 68.9%, implying that EUS elastography could be used in cases with a strong suspicion of pancreatic cancer and negative EUS FNA (which represent up to 25% of focal pancreatic masses). Thus the patients with negative EUS FNA and high-hue histogram values (>185) might be referred to repeat EUS FNA ( Fig. 5.6 ) or even directly to surgery, whereas those with negative EUS FNA and lower high-hue histogram values (<170) could be followed-up.

Fig. 5.6

Pancreatic adenocarcinoma. Endoscopic ultrasound elastography with EUS-guided FNA, showing the same appearance of a relatively homogeneous hard (blue) focal pancreatic mass as compared to the surrounding tissues (left).

Four meta-analyses have been published concerning the value of EUS elastography for the differential diagnosis of benign and malignant focal pancreatic masses. Besides the fact that the meta-analyses are based on the same original studies included, they all found a high pooled sensitivity (85% to 99%) and lower pooled specificity (64% to 76%). Different values of the AUROC curve (0.8695 to 0.9624) were dependent on the qualitative or semi-quantitative analysis (based on strain ratios or strain histograms), although there was no significant difference between methods. Consequently, all authors concluded that EUS elastography might bring additional information to EUS FNA for the differential diagnosis of focal pancreatic masses, without being able to exclude EUS FNA for the confirmation of malignancy.

A few recent studies also looked at the utility of EUS elastography for the evaluation of chronic pancreatitis. Thus, there is a linear correlation between the number of EUS criteria of chronic pancreatitis and the strain ratio calculated through EUS elastography, leading to an overall accuracy for the diagnosis of chronic pancreatitis of 91.1%. A similar value was reported for strain histograms obtained with EUS elastography of the pancreatic body, with values over 50 having a high accuracy of 99.3% for the differentiation between chronic pancreatitis and healthy pancreatic tissue in people aged over 60. Moreover, a direct relationship has been shown between the probability of pancreatic exocrine insufficiency (measured by [13] C-mixed triglyceride breath test) and strain ratio based on EUS elastography, reaching 92.8% for strain ratio values higher than 5.5.

Other Applications

The feasibility of EUS elastography for the characterization of focal liver lesions was reported in only a few papers and case presentations. The left liver lobe and part of the right liver lobe can be examined by EUS during staging of other GI tract tumors, with malignant liver masses (especially metastasis) showing a consistent “hard” pattern surrounded by “soft” tissue.

Other indications were proposed for EUS elastography because most of the solid tumors have a “hard” appearance, including esophageal tumors, gastric tumors ( Fig. 5.7 ), gastrointestinal stromal tumors (GISTs) ( Fig. 5.8 ), or adrenal tumors. However, the clinical utility of these findings remains to be established in further studies.

Fig. 5.7

Gastric adenocarcinoma. Endoscopic ultrasound elastography at the level of the enlarged and invaded gastric wall showing a relatively homogeneous hard (blue) mass, indicating a relatively hard elasticity structure as compared to the surrounding tissues (left).

Fig. 5.8

Malignant gastrointestinal stromal tumor. Endoscopic ultrasound elastography showing a relatively heterogeneous hard (predominantly blue) mass, indicating a relatively hard elasticity structure as compared to the surrounding tissues (left). Areas of necrosis are not displayed by the elastography software.

Future Techniques

Three-dimensional EUS elastography is a feasible technique, implementing either freehand or automatic reconstruction techniques, through use of the usual transducers or high-quality transducer arrays. The technology is already available in real-time for transabdominal ultrasound (four-dimensional real-time elastography) by using dedicated transducers, thus raising the hope that it will soon be available for EUS, as well. A significant advantage might be conferred during the follow-up of radiofrequency ablation (RFA) lesions, which are extremely difficult to visualize through conventional ultrasound methods.

Contrast-Enhanced Endoscopic Ultrasound Elastography

This technique was initially established using the usual Doppler techniques (color or power Doppler flow imaging) in combination with administration of second-generation microbubble ultrasound contrast agents (UCAs) as Doppler signal enhancers. Due to recent advances in EUS systems, second-generation intravenous UCAs can now be used in association with low mechanical index (MI) techniques in order to improve visualization of tissue perfusion and to differentiate benign from malignant focal lesions, as well as to guide therapeutic procedures. Contrast-enhanced EUS (CE-EUS) has become an established indication for the discrimination of focal pancreatic masses (especially hypoenhancing pancreatic adenocarcinomas as compared to other isoenhancing or hyperenhancing lesions, including mass-forming chronic pancreatitis or neuroendocrine tumors) and possibly for the discrimination of pseudocysts from pancreatic cystic tumors. Furthermore, dynamic quantification of microvascularization and tissue perfusion can be easily performed based on various software programs embedded in the ultrasound systems or available for off-line use with visualization of time-intensity curves (TIC analysis) and calculation of various quantitative variables.

Technical Details

CE-EUS examinations should be performed in association with a careful evaluation of the lesions through conventional gray-scale examinations. There are several techniques used for EUS examinations based on second-generation microbubble UCAs. Initially, these consisted of Doppler signal enhancement during color Doppler and/or power Doppler, although the usage of these high-MI methods was hampered by the presence of both flash (induced by tissue motion) and blooming (induced by signal saturation) artifacts. Recently, the same specific contrast harmonic imaging techniques used in transabdominal ultrasound (US) have been developed for usage with both radial and linear EUS transducers. Contrast-specific EUS modes are based on separation of linear ultrasound signals induced by the tissues and utilization of the nonlinear response produced by the microbubbles, thus obtaining a better signal (contrast to tissue) to noise ratio.

The most commonly used agent in Europe contains phospholipid-stabilized microbubbles of sulfur hexafluoride (SonoVue), which are injected into a large peripheral vein and able to pass through the lung circulation without being destroyed. This agent is classified as a blood pool agent and is restricted in the intravascular compartment until it is eliminated through expired air. Dosage for EUS examinations should be higher than transabdominal US due to the high frequency of EUS transducers, being usually 4.8 mL of SonoVue. For the pancreas and other GI tract organs (except the liver, which has a dual blood supply), there is an initial early arterial phase (usually 10 to 30 seconds after contrast injection), followed by a late venous phase usually lasting from approximately 30 to 120 seconds.

Further details of the examination techniques are outside the scope of this chapter and are described in detail elsewhere. Thus, the examination uses a low MI (usually below 0.3), defined as a standard measure of the acoustic power, that is, the amplitude of an ultrasound wave at peak negative pressure (PNP) estimated in situ, divided by the square root of the center frequency (Fc) of the ultrasound wave. Examinations are based on nondestructive low-MI nonlinear imaging techniques, whereas the MI can be set up to values between 0.08 and 0.12. Relatively higher values are used by most studies (usually between 0.1 and 0.2), but some microbubbles will be destroyed, although the enhancement will be better delineated. The usual method of low-MI ultrasound examination is called dynamic contrast harmonic imaging (dCHI) and uses a wideband pulse inversion technique, including two pulses with inverted phase and received information with addition of the frequency spectrum of the pulses, thus eliminating the linear information from the tissues and showing the harmonic information produced by the microbubbles.

Clinical Applications

Initial feasibility studies proved the value of CE-EUS, using a technique that is quite similar to contrast-enhanced transabdominal ultrasound. The first pilot study used a linear EUS prototype and low MI (0.09 to 0.25) in conjunction with a second-generation microbubble contrast agent (SonoVue or Sonazoid), allowing the delineation of the arterial and venous phase of the pancreas. The same results were obtained by using a different radial EUS prototype system, showing the real-time continuous images of finely branching vessels of the pancreas, with a slightly higher MI (0.4) and the same second-generation contrast agent (SonoVue).

This opened up the clinical usage of CE-EUS, although some of the contrast agents are still considered off-label indications. Thus, SonoVue is registered in the European Union for liver, breast, and vascular applications, but pancreatic imaging is not mentioned specifically. Consequently, as mentioned in the current EFSUMB guidelines, an informed consent should be obtained from the patient for the usage of second-generation contrast agents during CE-EUS with examinations of pancreas and GI tract; the examination and safety of the patient are within the responsibility of the examining doctor. A recent (2016) FDA approval has been obtained for LUMASON (sulfur hexafluoride lipid-type A microspheres, known globally as SonoVue) examinations of the liver (and also pediatric examinations), thus paving the way for CE-EUS procedures, as well. However, a specific institutional review board (IRB) approval should be obtained for individual studies.

Pancreatic Diseases

There are several reports in the literature concerning the usage of CE-EUS for detection, characterization, and assessment of staging and resectability of focal pancreatic masses, using the technique as a one-stop shop for complete analysis of the tumors. This is based on the proven hypovascular nature of pancreatic adenocarcinomas in more than 90% of cases, a feature that was reliably and consistently shown by contrast-enhanced CT or angiography. However, none of the cross-sectional techniques (including dynamic contrast-enhanced CT or MR imaging) reaches the high resolution of EUS examinations, which usually allow a confirmation of the final cytologic or micro-histologic diagnosis through EUS FNA.

Initial studies used color Doppler or power Doppler with the addition of the second-generation contrast agent and usage of conventional software, with high-MI values that usually destroy the microbubbles quickly. Also, there are certain artifacts (flash or blooming artifacts), usually induced by movement or saturation of the transducer. An initial feasibility study of power Doppler EUS-assessed perfusion by contrast-enhanced power Doppler EUS in 23 patients with inflammatory pseudotumor ( Fig. 5.9 , Video 5.5 ) and pancreatic carcinoma ( Fig. 5.10 , Video 5.6 ), with a sensitivity and specificity of 94% and 100%, respectively. These results were further confirmed by other authors using the same qualitative approach ( Table 5.3 ). Another study showed the same hypovascular pattern encountered in most of the pancreatic adenocarcinomas, whereas an isovascular or hypervascular pattern was displayed in all other masses (neuroendocrine tumors, serous microcystic adenomas, and even one teratoma). Considering hypovascularity as a sign of malignancy in pancreatic tumors led to a sensitivity of 92% and a specificity of 100%. The method is useful in small pancreatic carcinomas (less than 2 cm), with a sensitivity of 83.3%, significantly higher than the sensitivity of contrast-enhanced CT, which was only 50%.

Feb 19, 2020 | Posted by in GASTROENTEROLOGY | Comments Off on New Techniques in EUS: Real-Time Elastography, Contrast-Enhanced EUS, and Fusion Imaging

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