Quantitative and noninvasive assessment of chronic liver diseases using two-dimensional shear wave elastography

Table 1 Comparison of currently available noninvasive methods in patients with chronic liver disease

Content	Methods
	TE	pSWE	2D-SWE	MRE
Technical principle	TE was the first commercially available elastography method developed for measuring liver stiffness using a dedicated device that includes an amplitude modulation (A) mode image for organ localization	pSWE can be implemented on a common ultrasound diagnostic system. It uses a regular ultrasonic probe to emit a single impulse of acoustic radiation force and generates a shear wave to detect the shear wave propagation velocity	2D-SWE is the combination of a radiation force applied to the tissues by focused ultrasonic beams and a very high frame rate US imaging sequence, which is able to capture the propagation of resulting the shear waves in real time	MRE enables the measurement of liver stiffness with an MRI-compatible generator; mechanical shear waves are delivered to the tissue and displayed as elastograms using phase-contrast image sequences
Reference point	▪Young’s modulus (kPa)	▪Shear wave speed (m/s) ▪Young’s modulus (kPa)	▪Shear wave speed (m/s) ▪Young’s modulus (kPa)	▪Shear wave speed (m/s) ▪Young’s modulus (kPa)
Selected example	▪FibroScan (Echosens, France)	▪VTQ using ARFI imaging (Siemens Healthcare, Germany) ▪ElastPQ (Philips Healthcare, Netherlands) ▪Shear Wave Measurement (Hitachi Aloka Medical, Japan)	▪SWE (SuperSonic Imagine, France) ▪Virtual Touch IQ (Siemens Healthcare, Germany) ▪Logiq E9 (GE Healthcare, United Kingdom) ▪Aplio 500 (Toshiba Medical Systems, United Kingdom)	▪MR Touch (GE Healthcare, United Kingdom) ▪MRE (Philips Healthcare, Netherlands; Siemens Healthcare, Germany)
Advantages	▪Most widely used and validated technique ▪Quality criteria well defined ▪ User friendly, rapid, easy to measure at the bedside ▪Good reproducibility ▪Good performance for noninvasive assessments of liver fibrosis staging ▪Excellent diagnostic accuracy for excluding liver cirrhosis ▪Prognostic value in cirrhosis	▪Can be performed using a regular US machine ▪ The ROI can be positioned under B-mode visualization ▪Higher applicability than TE (not limited by ascites or obesity) ▪pSWE is equal to the performance of TE for significant fibrosis and cirrhosis	▪Can be performed using a regular US machine ▪ Simple and fast to use ▪ The ROI can be positioned under B-mode visualization ▪ A larger ROI than that of TE and pSWE ▪Good applicability (not limited by ascites or obesity) ▪Good stability and reproducibility ▪Generates a real-time quantitative map of liver tissue stiffness ▪Can avoid large vessels and the gallbladder ▪ High performance for cirrhosis	▪Can be performed using a regular MRI machine ▪ Good stability and reproducibility ▪Scans the whole liver ▪Higher applicability than TE (not limited by ascites or obesity) ▪Excellent diagnostic accuracy for noninvasive staging of liver fibrosis and cirrhosis
Disadvantages	▪Requires a special device and probe ▪ ROI size is rather small and cannot be chosen ▪Lack of applicability (limited by ascites, severe obesity) ▪No B-mode orientation ▪ Cannot avoid large vessels or the gallbladder ▪Unable to distinguish between intermediate stages of liver fibrosis	▪ROI size is smaller than that of TE and cannot be modified ▪Quality criteria not yet well defined ▪Narrow range of values ▪Unable to distinguish between intermediate stages of liver fibrosis	▪Quality criteria not well defined ▪ No further prospective studies published ▪ Many factors cause failed measurements in clinical practice ▪Unable to distinguish between intermediate stages of liver fibrosis	▪Time-consuming ▪Even more costly than SWE and TE ▪ Failure can occur due to claustrophobia and iron overload ▪Affected by respiratory movement ▪ Hepatic MRE signal may be so low that waves cannot be adequately visualized with a gradient-echo based MRE sequence

2D-SWE: Two-dimensional shear wave elastography; MRE: Magnetic resonance elastography; MRI: Magnetic resonance imaging; pSWE: Point shear wave elastography; ROI: Region of interest; TE: Transient elastography; US: Ultrasound; VTQ: Virtual touch tissue quantification.

Table 2 Procedures of two-dimensional shear wave elastography

Key points	Procedures
Adequate preparation	▪ Fast and rest before the exam ▪ Perform in a supine position ▪ Train the patients on breathing
Accurate positioning	▪ Scan the 6/7/8 intercostal spaces of the right liver ▪ Acquire stable and high-quality images ▪ Instruct the patient to hold the breath for 3-5 s
Stable measurement	▪ Switch to SWE mode ▪ Freeze the image and adjust the position of the ROI ▪ Calculate the LS automatically ▪ Average the repeated measurement values

LS: Liver stiffness; ROI: Region of interest; SWE: Shear wave elastography.

Table 3 Precautions and techniques of two-dimensional shear wave elastography

Key points	Precautions and techniques
Fasting and resting	▪ Patients should fast for a minimum of 2 h and rest for a minimum of 10 min before undergoing liver stiffness measurement with SWE
Position	▪ Measurement of liver stiffness by 2D-SWE should be performed in a supine position with the right arm maximally extended; this position ensures the best possible access for assessing the right liver lobe ▪ The transducer is placed in a right intercostal space to visualize the right liver lobe in B mode
Breathing train	▪ Instruct the patient not to breathe in or breathe out deeply in order to eliminate unreliable measurements induced by breathing movements ▪ It has been suggested that a breath hold for a few seconds during quiet breathing may lead to the best results
Clear 2D-US images	▪ Adequate B-mode liver image is a prerequisite for 2D-SWE measurements ▪ Must avoid the ribs, gas and other factors of routine ultrasound ▪ The appropriate pressure can be applied with the ultrasound probe to broaden the intercostal space and, thus, acquiring clear images. Contrary to the ordinary suggestion, this does not increase the liver’s stiffness, as the intervening tissues prevent distortion of the liver surface
Scale	▪ Generally, the Young’s modulus scale should not be less than 30 kPa and preferably not higher than 150 kPa
Depth	▪ Liver stiffness measured by 2D-SWE should be performed at least 10 mm under the liver capsule ▪ Measurements should not be performed too deep or too close, in order to avoid reverberation artifacts, insufficient penetration and acoustic shadow, as these factors will lead to incorrect results
Sampling frame	▪ The sampling frame should be placed in a well-visualized area of the right liver lobe, free of large vessels, the gallbladder, the liver capsule, and any other hollow organs ▪ In addition, the sampling frame should be placed in the center of the image
ROI	▪ For valid measurement quality of 2D-SWE, the ROI should be placed at a minimum of 1-2 cm and a maximum of 6 cm beneath the liver capsule ▪ The SWE acquisition is continued for 4-5 s once a stable SWE image is obtained ▪ The operator freezes the image, and the ROI should be placed in the most homogeneously colored area of the SWE ROI
Penetration mode	▪ When measuring patients with thick subcutaneous fat, fatty liver or advanced cirrhosis, SWE can be adjusted to “Pen” mode to improve the measurement success rate ▪ In 2D-SWE, if the signal is weak or unstable, the penetration mode can be activated

2D-SWE: Two-dimensional shear wave elastography; 2D-US: Two-dimensional ultrasound; Pen: Penetration; ROI: Region of interest; SWE: Shear wave elastography.

Table 4 Summary of the literature for two-dimensional shear wave elastography normal values

Ref.	Year	Country	Number	Mean age	Sex, female/male	Mean SWE, standard deviation, range	Remarks
Muller et al[19]	2009	France	15	NA	NA	2.6-6.2 kPa	No data available regarding age or sex of normal subjects
Ferraioli et al[79]	2012	Italy	42	34.8	13/29	4.92-5.39 kPa
Sirli et al[82]	2013	Romania	82	26	56/26	6.0 ± 1.4 kPa	Female: 5.7 ± 1.3 kPa
							Male: 6.6 ± 1.5 kPa
							BMI ≥ 25 kg/m²: 6.5 ± 1.5 kPa
							BMI < 25 kg/m²: 5.8 ± 1.3 kPa
Hudson et al[83]	2013	Canada	15	27	5/10	5.55 ± 0.74 kPa
Wang et al[84]	2014	China	30	36.1 ± 14.7	14/16	4.29 kPa
Suh et al[73]	2014	South Korea	196	29.2 ± 9.2	66/130	2.6-6.2 kPa
Huang et al[85]	2014	China	502	37.9	310/192	5.10 ± 1.02 kPa	Female: 5.45 ± 1.02 kPa
							Male: 4.89 ± 0.96 kPa
Yoon et al[86]	2014	South Korea	122	NA	NA	5.12 ± 1.46 kPa (session I)	No data available regarding age or sex of normal subjects
						4.95 ± 1.40 kPa (session II)
Leung et al[33]	2013	China	171	40.6 ± 10.8	103/68	5.5 ± 0.7 kPa	Female: 5.7 ± 0.5 kPa
							Male: 5.4 ± 0.7 kPa
Franchi-Abella et al[87]	2016	France	51	0-15	26/25	6.53 ± 1.38 kPa	No significant differences were observed between male and female patients, right and left lobes, or different breathing conditions

NA: Not available.

Table 5 Cut-off values of liver stiffness assessed with two-dimensional shear wave elastography in various studies

Ref.	Etiologies	Year	Country	Patients, n	≥ F1 (fibrosis)		≥ F2 (significant fibrosis)		≥ F3 (severe fibrosis)		F4 (cirrhosis)
					Cut-off, kPa	AUROC, %	Cut-off, kPa	AUROC, %	Cut-off, kPa	AUROC, %	Cut-off, kPa	AUROC, %
Leung et al[33]	HBV	2013	China	454	6.5	86	7.1	88	7.9	93	10.1	98
Herrmann et al[37]	HBV	2017	Germany	206	NA	NA	7.1	91	8.1	91	11.5	96
Zeng et al[29]	HBV	2014	China	303	NA	NA	7.2	92	9.7	95	11.7	95
Bavu et al[18]	HCV	2011	France	113	NA	NA	9.1	95	10.1	96	13.3	97
Ferraioli et al[20]	HCV	2012	Italy	121	NA	NA	7.1	92	8.7	98	10.4	98
Grgurevic et al[38]	CVH	2015	Croatia	123	NA	NA	8.1	99	NA	NA	10.8	95
Cassinotto et al[46]	NAFLD	2014	France	108	NA	NA	6.3	86	8.3	89	10.5	88
Garcovich et al[47]	NAFLD	2016	Italy	78	5.1	92	6.7	96	NA	NA	NA	NA
Thiele et al[51]	ALD	2016	Denmark	199	NA	NA	10.2	94	NA	NA	16.4	95

2D-SWE: Two-dimensional shear wave elastography; ALD: Alcoholic liver disease; AUROC: Area under the receiver operating characteristic curve; CVH: Chronic viral hepatitis; HBV: Hepatitis B virus; HCV: Hepatitis C virus; LS: Liver stiffness; NA: Not available; NAFLD: Nonalcoholic fatty liver disease.