Non-invasive evaluation of liver steatosis with imaging modalities: New techniques and applications

Table 1 Characteristics of imaging techniques for hepatic steatosis evaluation

Techniques	Clinical characteristics	Limitations
CAP	Low cost; High availability; Time-saving	High measurement failure rate
	Allows simultaneous evaluation of steatosis and fibrosis	Measurement without B-mode ultrasound image
	Moderate to high diagnostic accuracy for detecting and grading steatosis	The cutoff value for diagnosing steatosis is poorly standardized
	Moderate to high repeatability and reproducibility
	Well validated
ATI, ATT and UGAP	Outperform or have comparable diagnostic accuracy compared with CAP	The measurement may be influenced by liver fibrosis
	High repeatability and reproducibility	Fairly small number of studies
	Strong correlation with liver histology or MRI-PDFF
	Low measurement failure rate
	Measured on B-mode ultrasound images
Att. PLUS	Measurement is obtained at the same time as the sound speed measurement	Fairly small number of studies
	Comparable diagnostic accuracy with CAP	No study comparing this technique with liver histology or MRI-PDFF
TAI and TSI	High diagnostic accuracy for detecting and grading steatosis	Fairly small number of studies
	Strong correlation with MRI-PDFF
	High repeatability and reproducibility
BSC	Uses a reference phantom to reduce sources of variability due to ultrasound systems or operators	Fairly small number of studies
	High diagnostic accuracy for detecting and grading steatosis
	Strong correlation with liver histology or MRI-PDFF
	High repeatability and reproducibility
UDFF	Is a combination of both attenuation coefficient and backscatter coefficient	Fairly small number of studies
	UDFF approximates MRI-PDFF
ASQ and NLV	Moderate to high diagnostic accuracy for detecting and grading steatosis	Weak correlation with liver histology
	Strong correlation with CAP	The correlation with MR-based techniques is controversial
		The influence of fibrosis on measurement is controversial
		Fairly small number of studies
SS	Moderate to high diagnostic accuracy for detecting and grading steatosis	Fairly small number of studies
	Strong correlation with CAP
MRS and MRI-PDFF	High diagnostic accuracy for detecting and grading steatosis	High cost; low availability
	Considered as the reference standard	Time-consuming

CAP: Controlled attenuation parameter; ATI: Attenuation imaging; ATT: Attenuation measurement function; UGAP: Ultrasound-guided attenuation parameter; Att. PLUS: Attenuation plane-wave ultrasound; TAI: Tissue attenuation imaging; TSI: Tissue scatter distribution imaging; BSC: Backscatter coefficient; UDFF: Ultrasound-derived fat fraction; ASQ: Acoustic structure quantification; NLV: Normalized local variance; SS: Speed of sound; MRS: Magnetic resonance spectroscopy; MRI-PDFF: Magnetic resonance imaging-proton density fat fraction.

Table 2 Summary of studies using ultrasound methods to evaluate hepatic steatosis

Ref.	No.	Method	Reference standard	Grade of steatosis	Optimal cutoff value	AUROC
Bae et al[59], 2019	108	ATI	LB	≥ S1	0.64	0.84
				≥ S2	0.70	0.89
				≥ S3	0.75	0.93
Bae et al[60], 2022	120	ATI	LB	≥ S1	0.66	0.91
				≥ S2	0.66	0.91
Tada et al[62], 2019	148	ATI	LB	≥ S1	0.66	0.85
				≥ S2	0.67	0.91
				≥ S3	0.68	0.91
Tada et al[63], 2020	119	ATI	MRI-PDFF	≥ S1	0.63	0.81
				≥ S2	0.73	0.87
				≥ S3	0.75	0.94
Jeon et al[61], 2019	87	ATI	MRI-PDFF	≥ S1	0.59	0.76
Ferraioli et al[65], 2019	129	ATI	MRI-PDFF	≥ S1	0.63	0.91
				≥ S2	0.72	0.95
Ferraioli et al[66], 2021	72	ATI-GEN	MRI-PDFF	≥ S1	0.62	0.92
		ATI-PEN	MRI-PDFF	≥ S1	0.69	0.90
Sugimoto et al[67], 2021	111	ATI	LB	≥ S1	0.67	0.88
				≥ S2	0.72	0.86
				≥ S3	0.86	0.79
Hsu et al[70], 2021	28	ATI	LB	≥ S1	0.69	0.97
				≥ S2	0.78	0.99
				≥ S3	0.82	0.97
Kwon et al[57], 2021	100	ATI	MRI-PDFF	≥ S1	0.62	0.91
				≥ S2	0.72	0.94
Jang et al[58], 2022	57	ATI	LB	≥ S1	0.62	0.81
Koizumi et al[73], 2019	89	ATT	LB	≥ S1	0.68	0.74
				≥ S2	0.72	0.80
				≥ S3	0.78	0.96
Tamaki et al[54], 2018	351	ATT	LB	≥ S1	0.63	0.79
				≥ S2	0.69	0.87
				≥ S3	0.85	0.96
Fujiwara et al[75], 2018	163	UGAP	LB	≥ S1	0.53	0.90
				≥ S2	0.60	0.95
				≥ S3	0.65	0.96
Imajo et al[76], 2022	1010	UGAP	MRI-PDFF	≥ S1	0.65	0.91
				≥ S2	0.71	0.91
				≥ S3	0.77	0.89
Kuroda et al[79], 2021	202	UGAP	LB	≥ S1	0.49	0.89
				≥ S2	0.65	0.91
				≥ S3	0.69	0.92
Tada et al[80], 2019	126	UGAP	MRI-PDFF	≥ S1	0.60	0.92
				≥ S2	0.69	0.87
				≥ S3	0.69	0,89
Jeon et al[83], 2021	120	TAI	MRI-PDFF	≥ S1	0.88	0.86
		TSI	MRI-PDFF	≥ S1	91.2	0.96
Rónaszéki et al[84], 2022	110	TAI	MRI-PDFF	≥ S1	0.59	0.92
		TSI	MRI-PDFF	≥ S1	99.7	0.91
Şendur et al[85], 2023	80	TAI	MRI-PDFF	≥ S1	0.75	0.95
				≥ S2	0.86	0.97
				≥ S3	0.96	0.97
		TSI	MRI-PDFF	≥ S1	92.44	0.96
				≥ S2	96.64	0.91
				≥ S3	99.45	0.94
Lin et al[91], 2015	204	BSC	MRI-PDFF	≥ S1	0.0038	0.98
Dillman et al[94], 2022	56	UDFF	MRI-PDFF	≥ S1	5%	0.90
Labyed et al[37], 2020	101	UDFF	LB	≥ S1	8.1%	0.94
				≥ S2	15.9%	0.88
				≥ S3	16.1%	0.83

AUROC: Area under the receiver operating characteristic curve; LB: Liver biopsy; MRI-PDFF: Magnetic resonance imaging-proton density fat fraction; ATI: Attenuation imaging; ATT: Attenuation measurement function; UGAP: Ultrasound-guided attenuation parameter; TAI: Tissue attenuation imaging; TSI: Tissue scatter distribution imaging; BSC: Backscatter coefficient; UDFF: Ultrasound-derived fat fraction.

Table 3 Summary of techniques for liver fat quantification and their mechanisms

Technique	Mechanism for liver fat quantification	Principle of the techniques
CAP	Spectral based technique (AC)	CAP measures the attenuation of or reduction in the amplitude of the ultrasound waves on their way through the liver
ATI	Spectral based technique (AC)	ATI quantifies the degree of the ultrasound beam attenuation. The attenuation of the ultrasound beam is calculated by analyzing echo signals received by the transducer
ATT	Spectral based technique (AC)	Two ultrasonic waves of different frequencies (F0, F1; F0 < F1) are transmitted to the same beamline and the received signal is obtained. ATT estimates the attenuation coefficient it by calculating the slope of the received signal ratio (F0/F1)
UGAP	Spectral based technique (AC)	UGAP compares the measured liver signal and the referential signal (measured on the reference phantom with known attenuation and backscatter coefficients)
Att. PLUS	Spectral based technique (AC)	Att. PLUS measures the decrease in amplitude of ultrasound waves as they propagate throughout the tissue
TAI	Spectral based technique (AC)	TAI is determined based on the attenuation properties of different frequency components in the tissue, and the spectrum of radiofrequency signals provides a downshift of the center frequency according to depth. The TAI parameter indicates the slope of the ultrasound center frequency downshift
BSC	Spectral based technique (BSC)	BSC measures the ultrasound energy returned from the tissue
UDFF	Spectral based technique (BSC)	UDFF is obtained by combining both AC and BSC and the result is presented as the percentage of hepatic steatosis. Reference phantom data is integrated into the ultrasound system and fixed-acquisition region of interest is applied
TSI	Envelope Statistic based technique	The TSI is based on the shape parameter of the Nakagami distribution which reflects the local concentration and arrangement of ultrasound scatterers
ASQ	Envelope Statistic based technique	ASQ measures the FD ratio, which is based on the difference between theoretical and real echo amplitude distributions
NLV	Envelope Statistic based technique	NLV parameter was derived from ASQ, which analyzed ultrasound amplitudes sampled from gray-scale ultrasound images
SS	Envelope Statistic based technique	SS calculates the speed of sound through the liver
SSp.PLUS	Envelope Statistic based technique	SSp.PLUS is a novel technique that allows quantification of the intrahepatic speed of sound which is correlated with the liver fat content

AC: Attenuation coefficient; BSC: Backscatter coefficient; CAP: Controlled attenuation parameter; ATI: Attenuation imaging; ATT: Attenuation measurement function; UGAP: Ultrasound-guided attenuation parameter; Att.PLUS: Attenuation plane-wave ultrasound; TAI: Tissue attenuation imaging; UDFF: Ultrasound-derived fat fraction; TSI: Tissue scatter distribution imaging; ASQ: Acoustic structure quantification; NLV: Normalized local variance; SS: Speed of sound; SSp.PLUS: Sound speed plane-wave ultrasound; FD: Focal disturbance.