US elastography : where do we stand?

Transcription

1 US elastography : where do we stand? Poster No.: C-1857 Congress: ECR 2014 Type: Educational Exhibit Authors: M. Wagner, C. Pellot-Barakat, S. A. RASLAN, I. HUYNH, S. EGELS, F. Frouin, O. Lucidarme; Paris/FR Keywords: Neoplasia, Cirrhosis, Physics, Ultrasound, Elastography, Ultrasound physics, Liver, Breast DOI: /ecr2014/C-1857 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 31

2 Learning objectives To understand the physical concepts of the different techniques To know the current indications and results of the different techniques To be able to compare the different commercial offers Background The aim of elastography is to assess tissue stiffness based on 3 steps: Excitation: transmission of stress in a tissue (mechanical, vibrational, shear) Acquisition: recording the signal induced by the tissue deformation due to the stress (RF or B-mode data) Analysis/post-treatment: analysis of tissue strain induced by the propagation of the stress. Human body has a mechanical behavior similar to a soft homogeneous and isotropic linear elastic material. The stiffness of tissue is assessed by the Young elastic modulus in kilopascal kpa. A stress S induces a strain e, dependent on the tissue elasticity. The Young modulus E is defined by the ratio between the stress and the strain (Fig. 1 on page 5). Young Modulus E = S / e. A stress links to 2 types of mechanical waves in the tissue: Compression wave that compresses tissue little by little, inducing a displacement parallel to the propagation direction. Shear wave: responsible of a slip of different tissue layers, relative to each other, inducing a displacement perpendicular to the wave propagation direction; The ultrasound elastography quantitative techniques do not directly measure the Young's modulus but the speed V of shear wave propagation. The velocity V of the shear wave is related to shear modulus µ (shear): 2 µ = r V with r = tissue density The shear modulus µ is itself connected to the elastic modulus: Page 2 of 31

3 E=3µ The measurement of the shear wave propagation velocity V (in m/s) allows to assess the elastic modulus E according to the formula: E = 3#V 2 For computations, the tissue density is assumed to be constant and equal to 1000 kg/ mm3. There are several methods of ultrasound elastography (Fig. 2 on page 5). 1. Strain elastography The quasi-static elastography is based on the deformation of a tissue due to a stress. A stress is applied to the tissue (through the ultrasonic probe itself) and is observed by ultrasound imaging. The strain induced by the propagation of the stress is analyzed: By comparing data before and after stress, we estimate the displacement or strain tensor e. The stress s is not measurable: the resulting map does not give the Young's modulus. The system provides parametric maps, that differentiate rigid and soft tissues. These maps are in color and grey-scale depending on the constructor (Fig. 3 on page 5, Fig. 4 on page 6). Several constructors offer this technic: Hitachi: real time tissue elastography, emode Siemens: mode esie Touch elastography imaging General electrics: Ultrasound elastography imaging Philips: strain based elastography Toshiba: Real-time elastography Ultrasonix Esaote: ElaXto 2. Transient elastography This is the technique used by FibroScanTM (Echosens). It uses a probe (3.5 MHz) containing a vibrator and an ultrasound transducer. This is not an imaging guided system and the probe is positioned randomly in the skin surface. The measures are done at a depth between 25 and 65 mm. The exam takes about 5-10 minutes and consists of 10 Page 3 of 31

4 measures at the same location. The system immediately computes a median of the 10 measures. This system is based on a mechanical pulse induced at the surface of the skin by an external vibrator which generates a transient shear wave (pulse) that propagates longitudinally. Through the ultrasound transducer, the velocity and the amplitude of the shear wave are measured in a region of interest. The velocity V is converted into kpa, and reflects the tissue stiffness (Fig. 5 on page 6). The system can also compute the wave attenuation in decibels per meter db / m. 3. ARFI = Acoustic Radiation Force Imaging This technique of elastography uses a focused ultrasound pulse. It provides an estimate of the stiffness of deep tissues, non-accessible by external compression. This system was initially developed by Siemens (ARFI Virtual Touch ). After identification of the area of interest by ultrasound imaging, a focused ultrasonic wave is applied. This wave leads to tissue displacement and a shear wave. The velocity of the shear wave is measured and expressed in m / s (Virtual Touch quantification) (Fig. 6 on page 6). Until now this technique provided only a mean value of the velocity of the shear wave in a small region of interest. Recently it became possible to obtain parametric map by multiplying the number of measurement in multiple ROIs. But because the creation of the Shear wave is only obtained in one focused point this technique remains a non real time technique. 4. Ultra-fast shear wave elastography This is the technique developed by Supersonic Imaging also based on transient elastography ultrasound pulse. However the possibility offered by the ultrafast techniques allows the generation a multiple shear wave along a same longitudinal axis (through a compression wave) leading to the propagation of a plane shear wave. The ultrafast technique allows also the measurement of the velocity of this plane in each point of the image in real time providing a 2D quantitative measure of elasticity E in real time, usually expressed through a parametric map in kpa (Fig. 7 on page 7). 5. Comparison of the elastography methods Tables 1 and 2 compare the different methods (Table 1 on page 7 Table 2 on page 8). Page 4 of 31

5 Images for this section: Fig. 1 Fig. 2 Page 5 of 31

6 Fig. 3 Fig. 4: (adapted from Fig. 5 Page 6 of 31

7 Fig. 6: (adapted from Fig. 7 Page 7 of 31

8 Table 1 Page 8 of 31

9 Table 2 Page 9 of 31

10 Findings and procedure details 1. Liver There are many applications of ultrasound elastography in liver. The main application is liver fibrosis evaluation, in which elastography techniques, and in particular FibroScan, are validated. Elastography can also be used for: Cirrhosis complications prediction Hepatitis treatment monitoring Diagnosis of complications occurring after liver transplantation Steatosis evaluation Characterization of hepatic tumors. A. Liver fibrosis evaluation For evaluation and quantification of liver fibrosis, all elastography techniques have been widely studied. Each technique, their advantages and drawbacks, and their diagnostic performance are detailed in tables 3-6 (Table 3 on page 15, Table 4 on page 15, Table 5 on page 16, Table 6 on page 16 ). It must be kept in mind that fibrosis is not the only factor that can change the stiffness of the liver. There are confounding factors such as hepatic congestion, cholestasis, and presence of acute hepatitis associated lesions, that must be considered when interpreting the data. B. Cirrhosis complications prediction For predicting cirrhosis complications, only the FibroScan and ARFI techniques were evaluated in liver and spleen. Values are highly variable and these techniques can not be used routinely as a substitute for other methods validated in these indications. However, more stifness values increase, more HCC or esophageal varices risks increase. The areas under the ROC curve for predicting esophageal varices and HCC with FibroScan and ARFI methods are presented in Table 7 on page 17. C. Hepatitis treatment monitoring Page 10 of 31

11 Regarding viral hepatitis, decreased elasticity values should be a marker of treatment response. But these results must still be interpreted with caution. D. Diagnosis of complications occurring after liver transplantation Moreover, elastography can help to highlight a liver graft injury, as graft rejection or viral recurrence after transplantation, showing an increase of stifness: graft damage by FibroScan 7.8 kpa (5.4 to 27.4) vs 5.3 kpa (3.1 to 7.4) (p <0.001) rejection SSI: ± 8.13 kpa vs ± 2.10 kpa, (p <0.001). E. Steatosis evaluation In the assessment of steatosis, only the CAP system (controlled attenuation parameter) coupled to the FibroScan Echosens system has been studied many times. This technique measures the attenuation of ultrasonic waves in decibels per meter db / m. A value is provided only if a valid measurement of shear wave velocity is obtained. This method has good performance for steatosis quantification, regardless the etiology and is reproducible (ICC = 0.84) (Table 8 on page 17). The thresholds vary across studies. It seems more efficient than simple B-mode ultrasound, SteatoTest and FLI (Fatty Liver Index). F. Characterization of hepatic tumors In focal liver lesions characterization, multiple studies are published: Some techniques with static elastography The majority with ARFI And one with the SSI technique. There are significant variations within tumor types, particularly for heterogeneous tumors and large tumors. Several studies gave different and inconsistent results. Two main studies assessed the interest of static elastography for FLL characterization. The first one is a qualitative study and showed that HCC can be distinguished from metastases, HCC appearing as soft or intermediate tumors while metastases appearing as hard tumors (Fig. 8 on page 17). The second study is a semi-quantitative study and found a strain ratio lower for benign lesions compared to malignant lesions: Page 11 of 31

12 Malignant lesions (2.82 ± 1.82) > benign lesions (1.45 ± 1.28) (p <0.001) (Fig. 9 on page 18). With the ARFI method, the results are heterogeneous and involve either the value of the shear wave velocity V, or the ratio between the velocity in the lesion and in the liver (this report seems to give better results). The results of different studies are presented on Table 9 on page 19. Differentiating benign tumors - malignant tumors is not confirmed by all studies, although the majority of studies found higher V in malignant tumors (Fig. 10 on page 18, Fig. 11 on page 19). For lesion characterization, the results are variable but trends are found: V FNH > adenoma V HCC > adenoma V metastases > adenoma. With the SSI method, only one study has been published and found that the technique could differentiate adenoma and FNH, and HCC and cholangiocarcinoma. These results should be confirmed. 2. Breast The patient is in supine position with the ipsilateral arm in an elevated position. The pressure applied with the probe must be as low as possible. All kind of elastography techniques with ultrasound guidance are applicable. The main indication in breast is the characterization of a lesion detected in B mode. It is based on the fact that malignant nodules are harder than benign lesions. Elastography increases the performance of Bi-Rads in which it will soon be integrated (only color map). It should not be used alone but in addition to the BiRads score. Its interest is mainly for lesions classed Bi-Rads 3 or 4a for which it may modify the management. Elastography has no interest in benign lesions classed Bi-Rads 2 and in moderately or highly suspicious lesions classed Bi-Rads 4b or 5. The ROI must cover the entire lesion and surrounding breast tissue to allow comparison. False positives are mainly fibrous fibroadenomas and scarring (Table 10 on page 19, Table 11 on page 20, Table 12 on page 20). False negatives are mucinous cancer, cancer with inflammatory stroma, lesion <5 mm, deep lesion, lesion in a breast parenchyma of high density. Page 12 of 31

13 Few studies have evaluated the interest of elastography in the evaluation of axillary lymph nodes: metastatic lymph appearing more rigid than the reaction lymph, in static elastography or shear wave elastography. 3. Thyroid The examination is performed with a superficial linear probe, during the conventional examination. The main indication of elastography in thyroid disease is the nodule characterization, in addition to B-mode which it does not replace. Thyroid cancers behave differently according to histology: Papillary cancer is hard; Follicular cancers do not increase stiffness. The presence of calcification can cause false positive. (Table 13 on page 21, Table 14 on page 21, Table 15 on page 22) A classification has been established using qualitative static elastography however. The interest of quantitative elastography in diffuse disease is still in the evaluation phase and is not validated. The value of elastography for cervical lymph nodes characterization is still being evaluated, but it seems that metastatic lymph nodes have a higher stiffness. 4. Kidney The use of ultrasound elastography techniques is complex in the kidney. Indeed, the stifness of the renal tissue depends on: The presence of fibrosis; The vascularization; The anisotropy (and thus the direction of the beam emission U.S. / renal structures); The presence of hydronephrosis. Few studies have reported normal values : 5.0 ± 2.9 kpa for the renal cortex, 23.6 ± 5.4 kpa for the pyelon (Arda K, AJR 2011) (SSI method) The two indications of elastography are: Page 13 of 31

14 The evaluation of intra-renal fibrosis; The characterization of kidney tumors. The applicable methods in the kidney are: ARFI and SWI Measurement performed after a B mode exam, with the convex probe. Their reproducibility are 22-24% for the ARFI system; and 12-20% for the SWI system (SSI). The non-applicable methods in the kidneys are: Static elastography systems because: - The depth of the kidneys - The inability to compare pathological and normal renal tissues in case of diffuse pathologies. FibroScan system (for native kidneys) due to the absence of ultrasound guidance. A. Kidney characterization On native kidneys, no clinical studies reporting the interest of the ultrasonic elastography in the evaluation of intra-renal fibrosis has been published. An experimental study showed an increased stiffness with renal glomerulosclerosis evolution. On kidney transplant, the results presented in the literature are contradictory and are presented in Table 16 on page 22. B. Renal tumour characterization Two studies assessed the contribution of elastography. The first study reported a series of 15 cases (2 pseudo-tumors, 2 hemorrhagic cysts, 8 renal cell carcinomas, one chromophobe cell carcinoma, 2 tubulo-papillary carcinomas), studied by ARFI technique, with values between 1.61 and 3.97 m / s, without distinction between the different types (Clevert, Clin Hemorheol Microcirc 2009). The second study compared the strain imaging and the ratios between the lesion and the adjacent parenchyma, in 28 angiomyolipomas and 19 renal cell carcinomas, and found a difference between the two groups (p <0.001) (Tan, AJR 2013)(Fig. 12 on page 23). 5. Prostate Page 14 of 31

15 The examination is performed with an endo-rectal probe,. withno special preparation. The techniques of static elastography and shear wave elastography (SWE-SSI and ARFI) are applicable (Table 17 on page 23). The rationale of using elastography in prostate is based on the fact that prostate cancers are indurated lesions. Three applications have been identified (Table 18 on page 24, Fig. 13 on page 24, Fig. 14 on page 25): Characterization of abnormal area identified on mode B or Doppler imaging Detection of hard areas Targeting biopsies to increase the rate of positive biopsies. A hard hypoechoic lesion is suspected of malignancy, but all cancers are not hard and all hard lesions are not cancers (calcifications, fibrosis). Images for this section: Table 3 Page 15 of 31

16 Table 4 Table 5 Page 16 of 31

17 Table 6 Table 7 Table 8 Page 17 of 31

18 Fig. 8 Fig. 9 Fig. 10 Page 18 of 31

19 Fig. 11 Table 9 Page 19 of 31

20 Table 10 Table 11 Page 20 of 31

21 Table 12 Table 13 Page 21 of 31

22 Table 14 Table 15 Page 22 of 31

23 Table 16 Fig. 12 Page 23 of 31

24 Table 17 Table 18 Page 24 of 31

25 Fig. 13 Fig. 14 Page 25 of 31

26 Conclusion Ultrasound elastography provides additional information for tumor characterization or diffuse disease diagnosis. In liver disease, elastography quantifies fibrosis and hepatic steatosis., Characterization of liver lesions by elastography is maybe helpful to diferenciate FNH from adenomas. Elastography should be used in addition to Bi Rads score for the characterization of breast lesions. Elastography can be used in addition to B mode for thyroid lesion characterization. Elastography is complex in renal disease because of various constraints (depth kidney, anisotropy,..) and is not recognized as a routine technique in kidney. Prostate elastography can be used to characterize a hypoechoic zone and could be useful to target ultrasound guided biopsies. Personal information mathilde.wagner@psl.aphp.fr olivier.lucidarme@psl.aphp.fr References 1. Liver Liver fibrosis evaluation Millonig, Hepatology 2008;48: Lebray, Hepatology 2008;48:2089 Arena, Hepatology 2008;47:380-4 Sagir, Hepatology 2008;47:592-5 Friedrich-Rust, J Viral Hepat 2013;20:240-7 Ferraioli, Hepatology 2012;56: Page 26 of 31

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31 Correas, poster JFR 2012 Correas, poster ECR 2012 Page 31 of 31