Quantitative Assessment of Normal Soft-Tissue Elasticity Using Shear-Wave Ultrasound Elastography

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1 Special Article Original Research Arda et al. Soft-Tissue Elasticity in Ultrasound Elastography Special Article Original Research JOURNAL CLUB Kemal Arda 1 Nazan Ciledag 1 Elif Aktas 1 Bilgin Kadri Arıbas 1 Kenan Köse 2 Arda K, Ciledag N, Aktas E, Arıbas BK, Köse K Keywords: elasticity, elastography, shear-wave ultrasound DOI: /AJR Received August 6, 2010; accepted after revision February 23, Department of Radiology, Ankara Oncology Research and Education Hospital, Demetevler, Ankara 06460, Turkey. Address correspondence to N. Ciledag (drnazangokbayrak@yahoo.com.tr). 2 Department of Biostatistics, Ankara University Medical Faculty, Ankara, Turkey. AJR 2011; 197: X/11/ American Roentgen Ray Society Quantitative Assessment of Normal Soft-Tissue Elasticity Using Shear-Wave Ultrasound Elastography OBJECTIVE. The aim of this study was to measure the elasticity of various tissues and report it in kilopascals. SUBJECTS AND METHODS. The thyroid, submandibular, and parotid glands, masseter and gastrocnemius muscles, supraspinatus and Achilles tendons, renal cortex and pelvis, pancreas, and spleen of 127 healthy volunteers (89 women, 38 men; mean age, ± 9.11 years; range, years) were evaluated with shear-wave ultrasound elastography. RESULTS. The mean elasticity values were determined to be ± 3.1 kpa for the thyroid, ± 3.1 kpa for the submandibular glands, ± 3.5 kpa for the parotid glands, 10.4 ± 3.7 kpa for the masseter muscle, 11.1 ± 4.1 kpa for the gastrocnemius muscle, 31.2 ± 13 kpa for the supraspinatus muscle, 51.5 ± 25.1 kpa for the Achilles tendons, 5.0 ± 2.9 kpa for the renal cortex, 23.6 ± 5.4 kpa for the renal pelvis, 4.8 ± 3 kpa for the pancreas, and 2.9 ± 1.8 kpa for the spleen. CONCLUSION. Elasticity values were determined for different tissues with shear-wave ultrasound elastography. Further studies comparing the elasticity values of normal and pathologic tissues are necessary to determine the diagnostic role of this technique. P athologic conditions such as inflammation and tumors can change tissue elasticity. Therefore, in vivo elasticity measurements of various tissues can be a valuable noninvasive test for the diagnosis and management of various pathologic conditions. However, only a limited number of studies have been conducted to evaluate the elasticity of various tissues [1]. With real-time ultrasound elastography, or conventional elastography, the physical properties of soft tissue are revealed through characterization of the differences in stiffness between the region of interest and the surrounding tissue on the basis of uniform, mechanically induced deformation (strain) of structures during B-mode scanning. In conventional dynamic ultrasound elastography, the region of interest in the tissue is subjected to manual compression and displays induced deformation. The degree of deformation of the underlying soft tissue is calculated to estimate the tissue stiffness, not true elasticity, in kilopascals [2, 3]. Although ultrasound elastography is not yet used in routine clinical practice, dynamic ultrasound elastography has been found useful in the differential diagnosis of cancer in the breast [4 6], thyroid [7], and prostate [8, 9] and for lymph node characterization [10]. Estimation of tissue elasticity may also be useful for characterization of normal tissue of the tendons, muscles, and salivary glands. The disadvantages of conventional dynamic ultrasound elastography include operator dependency, low reproducibility, and relatively qualitative evaluation [11]. Shear-wave ultrasound elastography is a noninvasive method for measuring tissue elasticity whereby a quantitative estimate is obtained of the elasticity of various soft tissues, including muscles, tendons, salivary glands, and abdominal organs, such as the pancreas, liver, and spleen [12]. The imaging method is based on acoustic radiation force impulses through tissue to obtain an elastic modulus (Fig. 1). The result is a local measurement, in kilopascals, of the tissue elasticity at each point of interest of an organ. This imaging method is operator independent, reproducible, and quantitative. It has been used with success in the evaluation of breast lesions. To facilitate the widespread clinical use of this tool, the elasticity values of normal soft tissues must be established so that the effect of various disease processes on the 532 AJR:197, September 2011

2 Soft-Tissue Elasticity in Ultrasound Elastography PROBE Shear waves elasticity of the affected tissue can be investigated in relation to baseline healthy tissue. Only a limited number of studies have been conducted to determine in vivo values of various soft tissues [1, 4]. The goal of this study was to assess the quantitative elasticity values of different tissues in healthy volunteers. Subjects and Methods Study Sample One hundred twenty-seven healthy volunteers (89 women, 38 men; mean age, ± 9.11 [SD] years; range, years) were examined with both shear-wave elastography and supersonic sonography. Volunteers with a history of carcinoma or systemic inflammatory disorder were excluded. The following parameters were recorded for each volunteer at the time of the study: age, sex, weight, height, and body mass index. The ethics review board at our institution approved this study, and informed written consent was obtained from all volunteers. Ultrasound and Shear-Wave Ultrasound Elastographic Technique After a dedicated sonographic examination, shear-wave ultrasound elastography of the salivary glands, muscles, and tendons was performed with a linear-array transducer (R 3.2, Supersonic Imaging System) with a frequency range of 6 13 MHz. The shear-wave ultrasound elastographic ROI Longitudinal acoustic pulse Fig. 1 Schematic shows physical principles of shearwave sonography. Transmission of longitudinal acoustic pulse leads to tissue displacement, which results in propagation of shear waves away from region of excitation. Shear-wave elasticity value is measured within defined region of interest (ROI) with ultrasound tracking beams lateral to single push beam. examination of the spleen, renal cortex and pelvis, and body of the pancreas were performed with a convex probe (Supersonic Imaging System) with a frequency of 3 MHz. The ultrasound and shear-wave ultrasound elastographic measurements of each thyroid gland, submandibular gland, parotid gland, masseter muscle, renal cortex and pelvis, pancreas, and spleen were obtained with the patient in the supine position. The supraspinatus tendon elasticity values were obtained with the patient in the erect position with forearm behind the back and elbow flexed to 90 with the palm facing in the posterior direction. The Achilles tendon and gastrocnemius muscle were examined with the patient in the prone position with the foot hanging over the edge of the examination bed in a relaxed position. All measurements were performed by two ultrasound specialist radiologists and reported in kilopascals. The tip of the transducer was covered with 5 mm of ultrasound gel and placed on the skin smoothly without compressing the tissue. Shear-wave ultrasound elastography is based on the automatic generation and analysis of transient shear waves. The acoustic radiation force of the ultrasound wave rather than the compression force (called stress) pushes the tissue, as in conventional dynamic ultrasound elastography. The acoustic displacement of tissue is free of user dependence, and the technique is reproducible and easier to learn than conventional ultrasound elastography. Statistical analyses were performed with SPSS software (version 15.0, SPSS). Pearson correlation analysis and the Student t test for independent samples were used for evaluations. Descriptive statistics were used to summarize the characteristics of the study group, including means and SD of all continuous variables. Two-sided statistical significance was defined as p < Results The mean elasticity values for the thyroid, submandibular (Fig. 2), and parotid glands were ± 3.1 kpa (range, 1 24 kpa), ± 3.1 kpa (range, 2 23 kpa), and kpa ± 3.5 kpa (range, 3 25 kpa). The mean elasticity values for the thyroid were greater for women than for men (p = 0.02), but the submandibular and parotid glands did not exhibit a significant difference between sexes (Table 1). There was no significant positive or negative correlation between age and elasticity of the thyroid (p = 0.90), submandibular (p = 0.90), or parotid (p = 0.10) glands. The mean elasticity values of the renal cortex, renal pelvis (Fig. 3), pancreas, and spleen (Fig. 4) were 5.0 ± 2.9 kpa (range, 1 26 kpa), 23.6 ± 5.4 kpa (range, 2 39 kpa), 4.8 ± 3 kpa (range, 1 14 kpa), and 2.9 ± 1.8 kpa (range, 1 10 kpa). The mean elasticity values for the renal pelvis were greater for men than for women (p = 0.03), but the renal cortex, pancreas, and spleen did not exhibit a significant difference between sexes (Table 2). There was no significant positive or negative correlation between age and elasticity of the renal cortex (p = 0.10), renal pelvis (p = 0.60), spleen (p = 0.10), or pancreas (p = 0.60). The mean elasticity values for the gastrocnemius and masseter muscles, supraspinatus tendon (Fig. 5), and Achilles tendon in both the longitudinal and transverse planes were 11.1 ± 4.1 kpa (range, 2 28 kpa), 10.4 ± 3.7 kpa (range, 2 23 kpa), 31.2 ± 13 kpa (range, 6 90 kpa), 74.4 ± 45.7 kpa (range, kpa), and 51.5 ± 25.1 kpa (range, kpa). The mean elasticity values for the gastrocnemius and masseter muscles and supraspinatus and Achilles tendons in the longitudinal plane were greater in men than in women, but the Achilles tendon in the transverse plane did not exhibit a significant difference between sexes (Table 3). There was no significant positive or negative correlation between age and elasticity for the gastrocnemius muscle (p = 0.06), masseter muscle (p = 0.50), supraspinatus tendon (p = 0.50), Achilles tendon in the longitudinal plane (p = 0.40), or Achilles tendon in the transverse plane (p = 0.90). AJR:197, September

3 Arda et al. Fig year-old male volunteer. Submandibular gland elasticity map obtained with shear-wave ultrasound elastography shows elasticity score of kpa. Discussion Palpation, one of the oldest clinical skills, yields information about the stiffness of soft tissues based on external compression and deformation of the tissue. Palpation continues to have great value in modern medicine and is practiced both by physicians and by patients performing self-examinations. The major limitation of palpation is subjectivity. Current imaging techniques such as CT, ultrasound, and MRI do not directly measure the mechanical properties of soft tissue. Elasticity measurements have been reported to be useful for the diagnosis and differentiation of many tumors, which are usually firmer than the normal surrounding tissues. In general, benign soft-tissue lesions are firmer than normal tissue but softer than malignant tumors [4, 13, 14]. Sebag et al. [11] prospectively evaluated the efficiency of shear-wave elastography in the differential diagnosis of benign and malignant thyroid nodules. The elasticity index of malignant nodules (150 ± 95 kpa; range, kpa) was significantly greater than that of benign nodules (36 ± 30 kpa; range, kpa) and normal thyroid (15.9 ± 7.6 kpa; range, 5 35 kpa) (p < 0.001). In our study, the mean elasticity of normal thyroid tissue was ± 3.1 kpa (range, 1 24 kpa), significantly lower than the elasticity index of malignant thyroid nodules reported by Sebag et al. TABLE 1: Mean Elasticity Values for Thyroid, Submandibular, and Parotid Glands Thyroid 0.02 Men 10.5 ± Women 11.9 ± Submandibular gland 0.40 Men 11.1 ± Women 10.8 ± Parotid gland 0.50 Men 10.6 ± Women 10.2 ± Fig year-old female volunteer. Renal pelvis elasticity map obtained with shear-wave ultrasound elastography shows elasticity score of 10.6 kpa. Fig year-old male volunteer. Spleen elasticity map obtained with shear-wave ultrasound elastography shows elasticity score of 3.2 kpa. Arda et al. [10] evaluated the diagnostic performance of real-time dynamic ultrasound elastography and Doppler ultrasound both individually and in combination for the differentiation of benign and malignant cervical lymph nodes. They suggested that real-time dynamic ultrasound elastography had 93.8% sensitivity and 89.5% specificity in the differentiation of benign and malignant cervical lymph nodes in patients referred for fine-needle aspiration or surgical biopsy because of suspicion of malignancy. Lyshchik et al. [7] prospectively evaluated the elastographic appearance of thyroid tumors to explore the sensitivity and specificity of ultrasound elastography for differentiating benign and malignant tumors. The results were correlated with the histopathologic findings, which were the reference standard. The authors suggested that a strain index value greater than 4 is the strongest independent predictor of thyroid malignancy (p < 0.001), having 96% specificity and 82% sensitivity. Itoh et al. [3] evaluated the diagnostic performance of real-time freehand elastography using the extended combined autocorrelation method to differentiate benign from malignant breast 534 AJR:197, September 2011

4 Soft-Tissue Elasticity in Ultrasound Elastography TABLE 2: Mean Elasticity Values for Renal Cortex and Pelvis, Pancreas, and Spleen Renal cortex 0.50 Men 5.2 ± Women 4.9 ± Renal pelvis 0.03 Men 24.7 ± Women 23.1 ± Pancreas 0.30 Men 4.3 ± Women 4.8 ± Spleen Men 3.1 ± Women 2.9 ± Fig year-old female volunteer. Supraspinatus tendon elasticity map obtained with shear-wave ultrasound elastography shows elasticity score of kpa. lesions using pathologic diagnosis as the reference standard. They reported that real-time freehand elastography had a sensitivity of 86.5% for a cutoff point between 3 and 4, which is higher than the reported values for conventional sonography. None of the foregoing studies provided information about the real elasticity value of normal or pathologic tissues measured in kilopascals. Shear-wave ultrasound elastography exploits the acoustic radiation force induced by ultrasound beams to displace tissue and generate shear waves. Acoustic pulses can be focused at different depths in the tissue at supersonic speed and are enhanced by forming a Mach cone, which increases shear-wave propagation. The Young modulus reflects the speed of shear-wave propagation and is directly related to the tissue elasticity values, in kilopascals, shown on a real-time color-coded elastographic map of the region of interest. Shear-wave ultrasound elastography is a new and exciting technology in diagnostic ultrasound. It has the advantages of operator independence, reproducibility, higher spatial resolution, and quantitative evaluation without compression artifacts. Only a small number of studies of shear-wave ultrasound elastography have been reported in the literature. Athanasiou et al. [4] evaluated the appearance of breast lesions with quantitative ultrasound elastography and supersonic shear imaging and assessed the correlation between the quantitative values of lesion stiffness and pathologic results in 46 women with 48 breast lesions. Those investigators concluded that supersonic shear imaging yielded quantitative elasticity measurements, adding complementary information that may help in breast lesion characterization. Huwart et al. [15] evaluated the feasibility of MR elastography for determining the stage of liver fibrosis in 25 consecutively registered patients who had undergone liver biopsy because of suspicion of chronic liver disease. Those investigators reported that mean hepatic shear elasticity increased with increasing stage of fibrosis. The mean elasticity was TABLE 3: Mean Elasticity Values for Gastrocnemius and Masseter Muscles, Supraspinatus Tendon, and Achilles Tendon Gastrocnemius 0.40 Men 11.4 ± Women 11.0 ± Masseter 0.30 Men 10.8 ± Women 10.3 ± Supraspinatus tendon Men 36.0 ± Women 29.1 ± Achilles tendon Longitudinal plane < 0.05 Men 98.8 ± Women 62.5 ± Transverse plane 0.80 Men 51.1 ± Women 51.7 ± AJR:197, September

5 Arda et al ± 0.23 kpa in the 11 patients without substantial fibrosis, 2.56 ± 0.24 kpa in the four patients with substantial fibrosis, and 4.68 ± 1.61 kpa in the 10 patients with cirrhosis (p 0.005). Rouviere et al. [16] evaluated MR elastography for measuring liver stiffness. They reported that mean liver shear stiffness was significantly lower in healthy participants (mean, 2.0 ± 0.3 kpa) than in patients with liver fibrosis (mean, 5.6 ± 5.0 kpa) (p < 0.001). Arndt et al. [17] evaluated transient elastography in the assessment of renal allograft fibrosis and reported that stiffness correlated significantly with extent of interstitial fibrosis. They described a linear regression model indicating the association of stiffness and interstitial fibrosis (fibrosis percentage = 0.8 stiffness in kilopascals). Shah et al. [18] used MR elastography to evaluate renal parenchymal disease in a rat model. They reported that although the shear stiffness of the renal cortex in normal rats was 3.87 kpa (95% CI, kpa), shear stiffness increased to 5.02 kpa (95% CI, kpa) after 2 weeks of exposure to ethylene glycol and to 6.49 kpa (95% CI, kpa) after 4 weeks of exposure, resulting in nephrocalcinosis (p = , α < 0.05). Mannelli et al. [19] used MR elastography to evaluate the range of normal splenic stiffness in healthy volunteers and to investigate correlation with physiologic parameters and driver position. With the driver placed on the right side of the abdomen, the mean splenic stiffness was 3565 ± 586 Pa (range, Pa). With the driver on the left side of the abdomen, the mean splenic stiffness was significantly different (4255 ± 625 Pa; range, Pa) (p < 0.004). No significant correlation was found between splenic stiffness and body mass index, mean arterial blood pressure, age, splenic volume, or liver stiffness (all p > 0.05). Talwalkar et al. [20] used MR elastography to evaluate splenic stiffness in 12 healthy participants and 38 patients with chronic liver disease of various causes. They reported that mean splenic stiffness was significantly less in the healthy subjects (mean, 3.6 ± 0.3 kpa) than in the patients with liver fibrosis (mean, 5.6 ± 5.0 kpa; range, kpa; p < 0.001). They also identified a mean splenic stiffness of 10.5 kpa or greater in all patients with esophageal varices. The investigators suggested that MR elastography of the spleen is a feasible and promising quantitative evaluation method for predicting the presence of esophageal varices in patients with advanced hepatic fibrosis. Although the role of MR elastography and transient elastography in diffuse diseases (liver fibrosis, renal allograft fibrosis, nephrocalcinosis, spleen diseases) has been studied in limited studies, to our knowledge there are no data on the utility of shear-wave ultrasound elastography in the evaluation of such diseases. We suggest that this issue be addressed in future studies. The major limitation of our study was the lack of elasticity values of pathologic tissues. Although some of the ranges in our study seem broad, our results were comparable with those in studies in which the elasticity values of normal thyroid and gastrocnemius muscle were examined [11, 21]. The study of normal thyroid gland and malignant nodules [11] showed a significant difference. Conclusion In this preliminary study, we used shearwave ultrasound elastography to determine the elasticity values of various normal soft tissues and present the measured values. Further studies with larger series of patients should be performed to compare the elasticity values of normal and pathologic tissues to determine the diagnostic role of this technique. References 1. Levinson SF, Shinagawa M, Sato T. Sonoelastographic determination of human skeletal muscle elasticity. J Biomech 1995; 28: Frey H. 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Muscle Nerve 2010; 42: FOR YOUR INFORMATION This article has been selected for the new AJR Journal Club activity. The accompanying Journal Club study guide can be viewed from the information box in the upper right corner of the article at: AJR:197, September 2011