Introduction
Endoscopic ultrasonography (EUS) has evolved into a highly valuable diagnostic and
therapeutic tool in gastroenterology, offering high spatial resolution that overcomes
the limitations of transabdominal ultrasound.[1]
[2] While standard B-mode EUS is effective, it has limitations in characterizing solid
lesions, as they often appear as hypoechoic, hyperechoic, isoechoic, or heteroechoic
without providing detailed information about their nature. This can lead to inaccuracies,
especially when inflammation or other features of the lesion, such as fibrosis, neoplasm,
or necrosis, obscure the diagnosis. The assessment of vascularity and elasticity enhances
the characterization of solid lesions. Ancillary imaging techniques, such as elastography
and contrast enhancement, provide detailed insights into lesion characteristics, thus
improving the diagnostic utility of EUS.
This article explores EUS-guided elastography (EUS-E) in detail, covering its underlying
principles, various techniques, and limitations. A thorough understanding of these
aspects can enable clinicians to better utilize this advanced technology for more
accurate diagnoses and improved patient outcomes.
Types and Techniques of EUS-E
There are two primary methods of EUS-E ([Fig. 1])[3]: strain elastography and Shear wave elastography (SWE).
Fig. 1 Flowchart describing different types of endoscopic ultrasound (EUS)-guided elastography
techniques.
Strain Elastography
Strain elastography measures the strain induced by compression of the target tissue
by the EUS probe. The principle is based on the idea that compression of a tissue
by an echoendoscope probe creates a strain (i.e., displacement of one tissue structure
by another), which varies according to the tissue's hardness or softness ([Fig. 2]). Strain elastography can be performed in two ways:
Fig. 2 This figure describes the basic principles of EUS-guided strain elastography. Based
on the hue color map, the hard tissues are represented as dark blue, intermediate
tissues are green, followed by soft tissues, which are red.
Procedure Steps for EUS-Guided Strain Elastography
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Image Acquisition: The following steps should be taken:
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○ Use standard EUS imaging to identify the lesion of interest.
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○ Apply manual compression to the transducer while maintaining a steady ultrasound
image.
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○ Capture images during and after compression to assess the tissue response.
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Data Analysis: The ultrasound system gives the color pattern and computes the strain ratio (SR)
and strain histogram (SH) between the target lesion and surrounding normal tissue,
providing insights into the lesion's characteristics. The following section details
how to interpret strain elastography results.
Qualitative Analysis
During EUS-E, color-coded images (red, green, and blue) are overlaid on the standard
gray-scale B-mode EUS image. Softer tissues appear red, indicating higher strain,
while harder tissues appear dark blue, indicating lower strain. A color map is used
to interpret strain values:
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Hard: Dark blue
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Medium-hard: Cyan
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Intermediate: Green
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Medium-soft: Yellow
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Soft tissue: Red
Giovannini et al proposed a scoring system for qualitative strain elastography, where
scores of 1 and 2 are grouped as benign and scores of 3 to 5 as malignant ([Fig. 3]).[4] Based on this, sensitivity, specificity, positive predictive value, and negative
predictive value for differentiating benign from malignant pancreatic masses were
92.3, 80.0, 93.3, and 77.4%, respectively. [Fig. 4A–F] shows color patterns in different clinical scenarios.
Fig. 3 Figure describing scoring system of qualitative endoscopic ultrasound-guided strain
elastography proposed by Giovannini et al.[4]
Fig. 4 (A–F)Qualitative strain elastography (color pattern) in different clinical scenarios.
(A, B) Pancreatic head malignancy showing heterogeneous predominantly blue pattern.
(C, D) Pancreatic head inflammatory mass with heterogeneous predominantly green pattern.
(E, F) Reactive lymph node mass with heterogeneous predominantly green pattern.
Limitations of Qualitative Strain Elastography
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Intraobserver variation/selection bias
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Lack of reproducibility
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Irregular application of pressure
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Inadequate representation of the surrounding tissue
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Overlapping color patterns
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Subjectivity in distinguishing between benign and malignant lesions based on color
distribution
Semiquantitative Assessment
This method involves the following:
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Strain Ratio (SR): SR compares the strain of an area of interest (A) to a reference area (B), calculated
as B/A. The SR provides a relative ratio of stiffness between the lesion and the reference
area. SR is preferred over qualitative assessment as it helps reduce subjectivity
[5]. In a study by Gracia et al, a cutoff SR value of 6.04 demonstrated 100% sensitivity
and 92.9% specificity for detecting pancreatic malignancies.[6] The strain ratio is significantly higher among patients with malignant pancreatic
tumors than those with inflammatory masses. In their study, normal pancreatic tissue
showed a mean SR of 1.68 (95% confidence interval [CI]: 1.59–1.78), Inflammatory masses
presented a strain ratio (mean 3.28; 95% CI: 2.61–3.96), which was significantly higher
than that of the normal pancreas (p <0.001), but lower than that of pancreatic adenocarcinoma (mean: 18.12; 95% CI: 16.03–20.21)
(p <0.001).[6]
[Fig. 5A–F] shows strain ratios in different clinical scenarios.
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Strain Histogram (SH): SH displays the mean strain value within a selected area. The histogram plots strain
values (on the X-axis) against the number of pixels (on the Y-axis) in the region of interest (ROI). The mean value of the histogram corresponds
to the global hardness or elasticity of the lesion. An SH value <50 favors a malignant
lesion in pancreatic masses.[6]
[Fig. 6A–F] shows the SH in different clinical scenarios.
Fig. 5 (A–F)The strain ratio in different clinical scenarios. (A, B) Pancreatic head malignancy
with a strain ratio of 10.83. (C, D) Pancreatic head inflammatory mass with a strain
ratio of 3.63. (E, F) Reactive lymph node mass with a strain ratio of 3.79.
Fig. 6 (A–F)Strain histogram in different clinical scenarios. (A, B) Pancreatic head malignancy
with a strain histogram value of 9.56. (C, D) Pancreatic head inflammatory mass with
a strain histogram value of 42.32. (E, F) Reactive lymph node mass with a strain histogram
value of 66.94. (Depth is the distance of the region of interest over the lesion from
the probe; L ax is the long axis, and S ax is the short axis diameter of the region
of interest.)
Shear Wave Elastography
In this method, instead of measuring the velocity of the returning longitudinal wave,
the velocity of the propagated shear wave is measured. A push pulse is sent by the
transducer to the focal point in the ROI. This push pulse then generates a shear wave.
The velocity of this propagated shear wave is calculated from the detection of the
shear wave arrival by the search pulses. [Fig. 7] shows how to measure SWV by the SWE technique.
Fig. 7 Describing the technique of shear wave elastography. Region of interest (ROI) should
be at 30 to 45 degrees with depth <3 cm and with width: 0.5 to 1.5 cm. Care should
be taken to avoid duct, vessels, avoid reverberation/shadows/artifacts/calcification/duct,
and avoid big wheel up. (Vs is the shear wave velocity; E is the elasticity measure
in kilopascals [kPa]; ATT is the fat attenuation index; VsN is the percentage of the
net amount of effective shear wave velocity measurement.)
Procedure Steps of SWE
Similar to strain elastography, ensure the patient is adequately prepared.
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Image Acquisition: Once the organ or the lesion is identified, the following steps should be taken:
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○ We need to keep the ROI at an angle of 30 to 45 degrees with respect to the transducer.
The depth should be less than 3 cm, and the width should be between 0.5 and 1.5 cm.
One needs to be careful to avoid ductal structure, vessels, reverberation, shadows,
artifacts, and calcification in the ROI. We should avoid causing too much tissue compression
and try to keep the big wheel in the neutral position as much as possible.
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○ Then activate the SWE mode on the ultrasound machine, which generates shear waves.
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○ The program assesses and reports the reliability of the measurement as VsN, which
is the percentage of the net amount of effective SWV measurement. For effective SWV
measurements, the VsN should be >50% for liver evaluation and > 60% for pancreas evaluation.
Five to 10 consecutive measurements should be done.
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Data Analysis: The system translates SWV into stiffness measurements, expressed in kilopascals
(kPa), which can be quantitatively compared against known values for various pathologies.
In the study by Wang and Ryou, the mean SWV values for normal pancreatic parenchyma
ranged from 1.52 to 1.99 m/s.[7] In their study, the SWV cutoff value for diagnosing chronic pancreatitis (CP) was
2.19 m/s, and for autoimmune pancreatitis, it was 2.57 m/s.[7] When comparing shear wave with strain elastography, studies have shown shear wave
to be superior for defining CP based on Rosemont criteria.[8] Further research is going on to evaluate the usefulness of EUS-SWE for the evaluation
of the severity of CP and pancreatic exocrine and endocrine dysfunction. In a study
by Schulman et al, patients with cirrhosis had significantly increased mean liver
fibrosis index compared with the fatty liver (3.2 vs. 1.7, p <0.001) and normal (3.2 vs. 0.8, p <0.001) groups.[9] The fatty liver group showed significantly increased liver fibrosis index compared
with the normal group (3.8 vs. 1.4, p <0.001). Here, the liver fibrosis index was calculated incorporating SWE values by
computer software. There is an evolving literature on the use of SWE in measuring
spleen stiffness as well.
Further Enhancements: In recent technologically advanced EUS equipments, the following additional features
are added[10]:
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iElast—makes it easier to view the elastic image even when the displacement due to
pulsation is modest.
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sFocus—reduces the change in resolution with distance from the ultrasound transducer
surface and eliminates the need to manually adjust the focal zones during the procedure.
Potential Advantages: This technique has the following advantages:
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May help the endosonographer select a site for fine needle aspiration/biopsy. This
is especially useful in CP, where the negative predictive value of standard B-mode
EUS is low (around 65–70%).
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EUS-E may reduce the number of false negative results in cases of suspicious malignant
lymph nodes, as morphology alone may be insufficient to make an accurate diagnosis.
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It is easy to learn and use.
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Applying elastography does not increase the cost of the procedure.
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It provides real-time results, and immediate information is available to the endosonographer.
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It can be combined with other techniques such as contrast-enhanced EUS.
Pitfalls and Limitations: This technique also has certain limitations:
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Operator Dependency
One significant limitation of EUS-E is its operator dependency. Accurate results require
considerable skill and experience, as the quality of elastographic measurements can
vary significantly among operators. Training and standardization of techniques are
crucial for ensuring consistent and reliable outcomes.
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Artifacts and Limitations
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Compression Artifacts: Excessive or uneven compression during the elastography process can lead to inaccurate
results, including false positives. Proper technique and patient cooperation are essential
to minimize these artifacts.
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Overlapping Pathologies: Conditions such as inflammation or fibrosis can alter tissue elasticity, complicating
the interpretation of elastography findings. This necessitates a comprehensive understanding
of the clinical context when interpreting results.
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Anatomical Limitations: The accessibility of certain lesions may restrict the application of EUS-E. Deep-seated
lesions or those located in challenging anatomical locations may pose difficulties
in obtaining reliable measurements.
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Equipment Limitations
Differences in ultrasound equipment and settings can result in variability in elastography
measurements. Standardizing equipment and protocols across institutions will enhance
the reproducibility of results.
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Lack of Standardized Protocols
Currently, there is a lack of universally accepted protocols for performing and interpreting
EUS elastography. This variability can lead to discrepancies in clinical practice
and outcomes, highlighting the need for consensus guidelines.
Pancreatic diseases: EUS is considered as gold standard in evaluating both diffuse parenchymal pancreatic
disease and focal pancreatic lesions. The chances of a false negative increase when
a pancreatic mass is seen in the background of chronic pancreatitis (CP), with the
sensitivity of B-mode EUS being around 75% in this scenario.[11] With the addition of elastography to standard EUS, its utility is further enhanced.
EUS-elastography can help narrow down the differential diagnosis of focal pancreatic
lesions and help increase the accuracy of EUS-guided tissue acquisition.[12]
Role in differentiating malignant and benign focal pancreatic mass: Initial study on utility of EUS-E in differential diagnosis of focal pancreatic
masses was described by Giovannini et al, where they analyzed all the lesion using
a subjective scoring system as described earlier.[12] Sensitivity and specificity in detecting malignancy using qualitative strain elastography
was 100 and 67%, respectively. Extrapolating this scoring system in 121 cases, Giovannini
et al found that sensitivity, specificity, positive predictive value, and negative
predictive value of the differentiation between benign and malignant pancreatic masses
were 92.3, 80.0, 93.3, and 77.4%, respectively.[13] Similarly, another study by Iglesias-Garcia et al using qualitative EUS-E showed
that sensitivity, specificity, positive and negative predictive values, and overall
accuracy of EUS elastography for detecting malignancy were 100, 85.5, 90.7, 100, and
94.0%, respectively.[6] In this study, they broadly classified color patterns into four broad types—homogeneous
green pattern, present only in normal pancreas; a heterogeneous, predominantly green
pattern with slight yellow and red lines present only in inflammatory pancreatic masses;
a heterogeneous, predominantly blue pattern with small green areas and red lines;
and a geographic appearance, present mainly in pancreatic malignant tumors; and a
homogeneous blue pattern, present only in pancreatic neuroendocrine malignant lesions.
These studies also showed good interobserver agreement in describing various color
patterns. However, certain studies have found utility of qualitative EUS-E limited
in certain clinical scenarios. The presence of lesion size >35 mm, lesion being far
away from transducer, presence of intervening fluid filled structure, etc. were some
of the limiting factors in assessing color patterns. So, we suggest that color pattern
using qualitative strain elastography should be used as an initial screening modality,
which should be further confirmed by quantitative elastography measurements. As described
earlier, strain ratio is a useful parameter. Study by Iglesias-Garcia et al showed
that strain ratio of pancreatic adenocarcinoma was significantly more than that of
inflammatory mass (18.12 vs. 3.28). Strain ratio of CP with inflammatory mass was
more than that of normal pancreas (3.28 vs. 1.68). There was good interobserver agreement
as well. They suggested using strain ratio cutoff of 6.04 had 100% sensitivity and
92.9% specificity in differentiating malignant from nonmalignant lesion.[6] In another study, mean strain ratio for malignant lesions was 39.08 ± 20.54 as compared
with 23.66 ± 12.65 for inflammatory lesions.[14] Studies describing the use of hue histogram has also been described. Using a cutoff
of 175 value for hue histogram, a multicenter study showed that sensitivity, specificity,
positive and negative predictive values, and accuracy were 93.4, 66.0, 92.5, 68.9,
and 85.4%, respectively.[15] Comparative studies have shown no difference in accuracy between the use of strain
ratio and SH. Sonthalia et al showed combined use of hypoenhance pattern on contrast-enhanced
EUS and strain ratio above 6.24 had 100% sensitivity and specificity for detecting
malignancy in pancreatic masses arising in the background of CP.[16] The use of EUS SWE for solid focal pancreatic lesions is still evolving. In a retrospective
study of 64 patients with solid pancreatic lesions who underwent both SWM and strain
elastography with images analyzed by SH, the Vs (m/s) values of solid pancreatic lesions
were 2.19 for pancreatic cancer, 1.31 for pancreatic neuroendocrine neoplasm, 2.56
for mass-forming pancreatitis, and 1.58 for metastatic tumors. Vs showed no significant
difference based on the disease. They concluded that EUS-SWM tends to be unstable
for the measurement of elasticity of solid pancreatic lesions.[8] Thus, EUS-E has a complementary role in addition to standard B-mode and contrast-enhanced
EUS to increase the diagnostic yield in cases of focal pancreatic lesions.
Role in evaluation of CP: Studies using SR by strain elastography have shown a significant difference between
values among different Rosemont categories evaluated by B-mode. SR values for cases
with “consistent with CP” based on Rosemont criteria had the highest strain ratio,
followed by those with “indeterminate for CP” and normal pancreas (3.6 vs. 2.4 vs.
1.8).[17]
[18] The use of SWE in diagnosing CP is evolving. In a study by Yamashita et al, the
cutoff values of 1.96, 1.96, and 2.34 for diagnosing CP, exocrine dysfunction, and
endocrine dysfunctions had 83, 90, and 75% sensitivity, respectively, and 100, 65,
and 64% specificity, respectively.[19] The areas under the receiver operating characteristic (AUROC) curve for the diagnostic
accuracy of EUS-SWM for CP, exocrine dysfunction, and endocrine dysfunction were 0.92,
0.78, and 0.63 in this study. In another study by the same group, EUS-SWE showed a
significant positive correlation with the EUS Rosemont criteria and the number of
EUS features.[20] The AUROC curve for the diagnostic accuracy of EUS-SWM for CP was 0.97. The cutoff
value of 2.19 had 100% sensitivity and 94% specificity. For endocrine dysfunction
in CP, the AUROC was 0.75. The cutoff value of 2.78 had 70% sensitivity and 56% specificity.[20] EUS-SWM can be a useful modality for evaluating CP in addition to standard B-mode
evaluation.
Role in lymph nodes: In a study by Giovannini et al, the sensitivity and specificity of qualitative EUS
elastography for detecting malignancy in lymph nodes were 100 and 50%, respectively.[12] In another large multicenter study evaluating 101 lymph nodes, the sensitivity,
specificity, positive predictive value, and negative predictive value for the detection
of malignancy were 91.8, 82.5, 88.8, and 86.8%, respectively, with overall diagnostic
accuracy of 88.1%.[13] In another qualitative study, the presence of predominantly green pattern was suggestive
of benign lymph nodes in 100% of cases, and the presence of predominantly blue pattern
was suggestive of malignant lymph nodes in 92.3% of cases.[21] In a meta-analysis of 431 patients, elastography had a pooled sensitivity of 88%
and specificity of 85% in differentiating benign from malignant lymph node.[22] Studies of the use of quantitative EUS elastography for differential diagnosis of
lymph nodes are few. In one of the studies, using a cutoff of 166, the sensitivity,
specificity, and accuracy in the detection of malignancy were 85.4, 91.9, and 88.5%,
respectively.[23] Further studies are needed to determine the cutoff values of SR, SH, and SWE in
different lymph nodal diseases.
Role in liver diseases: Quantitative EUS-guided shear wave measurement is a promising tool for assessing
fibrosis in chronic liver parenchymal diseases. There have been studies comparing
EUS-SWM with transcutaneous shear wave measurement. In a pilot study, 42 patients
underwent EUS-SWE, vibration-controlled transient elastography (VCTE), and liver biopsy
sampling.[24] Liver elasticity cutoffs for different stages of fibrosis were estimated. They found
that AUROCs for advanced fibrosis were similar between VCTE and EUS-SWE (0.87 vs.
0.8). AUROCs for diagnosing cirrhosis were VCTE, 0.9 (95% CI, 0.83–0.97); EUS-SWE
left lobe, 0.96 (95% CI, 0.9–1); and EUS-SWE right lobe, 0.9 (95% CI, 0.8–1).[24] Currently, a multicenter study in India is underway comparing EUS-SWE, VCTE, and
liver biopsy to find out the utility of EUS-SWM. In the era of endohepatology, incorporating
EUS-SWM for suspected parenchymal liver disease patients has the potential to provide
a one-stop solution by incorporating diagnosis of cirrhosis by EUS-SWM, confirmation
of cirrhosis by EUS-guided liver biopsy, prognostication by EUS-guided portal pressure
gradient measurement, and treatment by EUS-guided variceal obliteration.
Other potential applications: There are other potential applications of EUS elastography such as (1) evaluation
of solid lesions in the left suprarenal gland, thereby helping in differentiation
of adenoma from metastasis, (2) evaluation of focal liver lesions, and (3) staging
of esophageal and gastric cancer. Further studies are needed to evaluate the role
in these conditions.
