Portal hypertension may influence the registration of hypointensity of small hepatocellular carcinoma in the hepatobiliary phase in gadoxetic acid MR

Caparroz, Carla; Forner, Alejandro; Rimola, Jordi; Darnell, Anna; García-Criado, Ángeles; Ayuso, Juan Ramón; Reig, María; Bruix, Jordi; Ayuso, Carmen

doi:10.2478/raon-2022-0024

Figures & Tables

Non-adequate quality in the liver uptake of Gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA) in the 20 minutes hepatobiliary phase. (A) and (B): patient with liver cirrhosis Child-Pugh B and clinically significant portal hypertension. (A): Baseline T1w-3D VIBE sequence. (B): the liver showed poor or non-apparent contrast uptake compared to the liver before contrast injection. (C) and (D): patient with liver cirrhosis Child-Pugh A 5 points with no clinically significant portal hypertension. (C): Baseline T1w-3D VIBE sequence. (D): the liver parenchyma showed very heterogeneous uptake of the contrast media, especially in the periphery of the right hepatic lobe.

Location of the 6 regions of interest (ROIs) in the liver parenchyma, to calculate the liver signal intensity (LSI) in the pre-contrast sequence (LSIpre) (A), at 10 minutes (LSI10) (B) and at 20 minutes (LSI20) hepatobiliary phase (C). Four of the ROIs were located in the anterior and posterior segments respectively of the right hepatic lobe, and two more were placed in the lateral and medial segments of the left lobe respectively. ROIs were drawn avoiding the inclusion of vascular structures and possible focal liver lesions.

Location of the region of interest in the 20 minutes hepatobiliary phase in the spleen (A), in the right paravertebral muscle (B), and in the upper pole of the right kidney (C) to calculate the different quantitative parameters of contrast liver uptake: spleen-liver intensity (SLI) and liver-spleen contrast ratio (LSCR), muscle-liver intensity (MLI) and the liver-muscle contrast ratio (LMCR) and kidney-liver intensity (KLI) and the liver-kidney contrast ratio (LKCR), respectively.

Quantitative assessment of liver uptake of Gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA) during hepatobiliary phase (HPB) at 10 and 20 minutes in the study group considering the presence of clinically significant portal hypertension (CSPH)_ On the left, including all study cohort and on the right, considering only cirrhotic patients with preserved liver function (Child-Pugh A 5 points)_ Variables described as median and interquartile range

INDEX	No CSPH (all CP A-5 points)	CSPH	P value	No CSPH (all CP A-5 points)	CP A-5 points and CSPH	P value
N	19	43		19	25
RLE₁₀	0.73 [0.52-0.89]	0.57 [0.47-0.69]	0.027	0.73 [0.52-0.89]	0.65 [0.51-0.77]	NS
RLE₂₀	0.73 [0.56-0.85]	0.59 [0.47-0.74]	NS	0.73 [0.56-0.85]	0.66 [0.54-0.77]	NS
LSCR₁₀	1.54 [1.37-1.67]	1.23 [1.15-1.39]	< 0.001	1.54 [1.37-1.67]	1.29 [1,15-1.51]	0.014
LSCR₂₀	1.68 [1.53-1.84]	1.35 [1.20-1.57]	0.003	1.68 [1.53-1.84]	1.37 [1.26-1.74]	0.036
LMCR₁₀	2.41 [2.12-2.83]	2.06 [1.75-2.45]	0.006	2.41 [2.12-2.83]	1.88 [1.76-2.50]	0.034
LMCR₂₀	2.49 [2.24-2.96]	1.95 [1.77-2.39]	0.005	2.49 [2.24-2.96]	1.92 [1.78-2.6]	0.036
LKCR₁₀	1.15 [0.98-1.34]	0.93 [0.81-1.13]	0.001	1.15 [0.98-1.34]	1.01 [0.84-1.21]	0.032
LKCR₂₀	1.25 [1.16-1.43]	0.98 [0.88-1.28]	0.001	1.25 [1.16-1.43]	1.05 [0.88-1.03]	0.017
CEI₁₀	1.46 [1.34-1.59]	1.36 [1.26-1.52]	NS	1.46 [1.34-1.59]	1.47 [1.31-1.58]	NS
CEI₂₀	1.50 [1.38-1.71]	1.41 [1.24-1.54]	NS	1.50 [1.38-1.71]	1.48 [1.33-1.65]	NS
HUI₁₀	609.7 [501.4-970.3]	327.8 [191.7-511.8]	0.004	609.7 [501.4-970.3]	411.4 [223.4-1210.7]	NS
HUI₂₀	803.6 [678.7-1091.2]	450.5 [274.8-864.4]	0.033	803.6 [678.7-1091.2]	569.0 [341.8-987.1]	NS

Quantitative parameters evaluating the liver uptake in the 20 minutes hepatobiliary phase (HPB) of Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) according to the quality of the HBP_ In one patient the HBP at 20 minutes was not available (n = 61)_ Variables described as median and interquartile range

INDEX	Qualitative assessment adequate	Qualitative assessment Non-adequate	P value
N	49	12
RLE₂₀	0.68 [0.57-0.83]	0.40 [0.31-0.51]	< 0.001
LSCR₂₀	1.53 [1.34-1.78]	1.19 [1.06-1.22]	< 0.001
LMCR₂₀	2.34 [1.88-2.78]	1.91 [1.50-2.11]	0.002
LKCR₂₀	1.20 [0.95-1.35]	0.89 [0.78-0.98]	0.001
CEI₂₀	1.23 [1.09-1.32]	1.00 [0.90-1.10]	0.001
HUI₂₀	744.1 [444.8-1024.1]	251.5 [65-4-331.0]	< 0.001

Formulas used for qualitative assessment of liver uptake of Gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA) in the hepatobiliary phase (HPB)

	Formula	Variables definition
Relative Liver Enhancement (RLE)	RLE10=( LSI10 − LSIPRE) LSIPRE $RLE10=\frac{(\text{ }\!\!~\!\!\text{ LSI10 }\!\!~\!\!\text{ }-\text{ }\!\!~\!\!\text{ LSIPRE) }\!\!~\!\!\text{ }}{\text{ }\!\!~\!\!\text{ LSIPRE }\!\!~\!\!\text{ }}$	RLE₁₀ and RLE₂₀: RLE at 10- and 20-min HBP
Relative Liver Enhancement (RLE)	RLE20=( LSI20 - LSIPRE ) LSIPRE $RLE20=\frac{(\text{ }\!\!~\!\!\text{ LSI20 - LSIPRE }\!\!~\!\!\text{ })}{\text{ }\!\!~\!\!\text{ LSIPRE }\!\!~\!\!\text{ }}$	LSI_pre, LSI₁₀ and LSI₂₀: Liver signal intensity pre-contrast, at 10- and 20-min HBP, respectively
Liver to Spleen Contrast Ratio (LSCR)	LSCRpre = LSIPRE SSIPRE $LSCRpre\text{ }\!\!~\!\!\text{ }=\frac{\text{ }\!\!~\!\!\text{ LSIPRE }\!\!~\!\!\text{ }}{\text{ }\!\!~\!\!\text{ SSIPRE }\!\!~\!\!\text{ }}$	LSCR_pre LSCR₁₀ and LSCR_20r: LSCR pre-contrast, at 10- and 20- min HBP, respectively
	LSCR10=LSI10SSI10 $LSCR10=\frac{\text{LSI}10}{\text{SSI}10}$	LSI_pre, LSI₁₀ and LSI₂₀: Liver signal intensity pre-contrast, at 10- and 20- min HBP, respectively
	LSCR20 = LSI20 SSI20 $LSCR\text{20 }\!\!~\!\!\text{ }=\frac{\text{ }\!\!~\!\!\text{ LSI20 }\!\!~\!\!\text{ }}{\text{ }\!\!~\!\!\text{ SSI20 }\!\!~\!\!\text{ }}$	SSI_pre, SSI₁₀ and SSI₂₀: Spleen signal intensity pre-contrast, at 10- and 20- min HBP, respectively
Liver to muscle Contrast Ratio (LMCR)	LMCRpre = LSIPRE MSIPRE $LMCRpre\text{ }\!\!~\!\!\text{ }=\frac{\text{ }\!\!~\!\!\text{ LSIPRE }\!\!~\!\!\text{ }}{\text{ }\!\!~\!\!\text{ MSIPRE }\!\!~\!\!\text{ }}$	LMCR_pre, LMCR₁₀ and LMCR_20r: LMCR pre-contrast, at 10- and 20- min HBP, respectively
	LMCR10=LSI10MSI10 $LMCR10=\frac{\text{LSI}10}{\text{MSI}10}$	LSI_pre, LSI₁₀ and LSI₂₀: Liver signal intensity pre-contrast, at 10- and 20- min HBP, respectively
	LMCR20 =LSI20MSI20 $LMCR\text{20 }\!\!~\!\!\text{ }=\frac{\text{LSI}20}{\text{MSI}20}$	MSI_pre, MSI₁₀ and MSI₂₀: Muscle signal intensity pre-contrast, at 10- and 20- min HBP, respectively
Liver to Kidney Contrast Ratios (LKCR)	LKCRpre = LSIPRE KSIPRE $LKCRpre\text{ }\!\!~\!\!\text{ }=\frac{\text{ }\!\!~\!\!\text{ LSIPRE }\!\!~\!\!\text{ }}{\text{ }\!\!~\!\!\text{ KSIPRE }\!\!~\!\!\text{ }}$	LKCR LKCR and LKCR: LKCR pre-contrast, at 10- and 20- min HBP, respectively _{pre, 10 20r}
	LKCR10= LSI10 KSI10 $LKCR10=\frac{\text{ }\!\!~\!\!\text{ LSI10 }\!\!~\!\!\text{ }}{\text{ }\!\!~\!\!\text{ KSI10 }\!\!~\!\!\text{ }}$	LSI_pre, LSI₁₀ and LSI₂₀: Liver signal intensity pre-contrast, at 10- and 20- min HBP, respectively
	LKCR20 = LSI20 KSI20 $LKCR\text{20 }\!\!~\!\!\text{ }=\frac{\text{ }\!\!~\!\!\text{ LSI20 }\!\!~\!\!\text{ }}{\text{ }\!\!~\!\!\text{ KSI20 }\!\!~\!\!\text{ }}$	KSI_pre, KSI₁₀ and KSI₂₀: Kidney signal intensity pre-contrast, at 10- and 20- min HBP, respectively
Contrast Enhancement Index (CEI)	CEI10 = LMCR10 LMCRPRE $\text{CEI10 }\!\!~\!\!\text{ }=\frac{\text{ }\!\!~\!\!\text{ }LMCR\text{10 }\!\!~\!\!\text{ }}{\text{ }\!\!~\!\!\text{ LMCRPRE }\!\!~\!\!\text{ }}$	- LMCR_pre, LMCR₁₀ and LMCR_20r: LMCR pre-contrast, at 10- and 20- min HBP, respectively
Contrast Enhancement Index (CEI)	CEI20 =LMCR20 LMCRPRE $\text{CEI20 }\!\!~\!\!\text{ }=\frac{LMCR20}{\text{ }\!\!~\!\!\text{ LMCRPRE }\!\!~\!\!\text{ }}$	- CEI₁₀ and CEI₂₀: Contrast Enhancement Index at 10- and 20- min HBP, respectively
Hepatic Uptake index (HUI)	HUI10=VOLLIVER ( LSI10 SSI10)−1 $\text{HU}{{\text{I}}_{10}}=\text{VO}{{\text{L}}_{\text{LIVER }\!\!~\!\!\text{ }}}\left( \frac{\text{ }\!\!~\!\!\text{ LSI10 }\!\!~\!\!\text{ }}{\text{ }\!\!~\!\!\text{ SSI10}} \right)-1$	- HUI₁₀ and HUI₂₀: Hepatic Uptake index at 10- and 20- min HBP, respectively
	HUL20=VOLLIVER (512058120)=1 $\text{HU}{{\text{L}}_{20}}=\text{VO}{{\text{L}}_{\text{LIVER }\!\!~\!\!\text{ }}}\left( \frac{5120}{58120} \right)=1$	LSI₁₀ and LSI₂₀: Liver signal intensity at 10- and 20- min HBP, respectively
		SSI₁₀ and SSI₂₀: Spleen signal intensity at 10- and 20- min HBP, respectively

Quantitative assessment of liver uptake of Gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA) during the hepatobiliary phase (HPB) at 10 and 20 minutes considering the degree of liver function impairment according to Child-Pugh classification_ Variables described as median and interquartile range

INDEX	Study group	Child-Pugh A	Child-Pugh B	P value	Child-Pugh A-5 points	Child-Pugh A-6 points + B	P value
N	62	53	9		44	18
RLE₁₀	0.65 [0.49-0.75]	0.68 [0.51-0.81]	0.41 [0.30-0.52]	<0.001	0.68 [0.52-0.82]	0.50 [0.40-0.58]	0.005
RLE₂₀	0.63 [0.51-0.78]	0.67 [0.55-0.82]	0.41 [0.30-0.52]	<0.001	0.68 [0.56-0.83]	0.52 [0.40-0.61]	0.006
LSCR₁₀	1.32 [1.17-1.55]	1.35 [1.11-1.59]	1.20 [0.99-1.28]	0.016	1.43 [1.19-1.61]	1.20 [1,11-1.28]	0.001
LSCR₂₀	1.48 [1.23-1.71]	1.51 [1.30-1.80]	1.20 [1.01-1.43]	0.006	1.54 [1.32-1.81]	1.25 [1.17-1.53]	0.008
LMCR₁₀	2.14 [1.78-2.51]	2.16 [1.81-2.62]	1.78 [1.52-2.13]	0.030	2.26 [1.81-2.71]	2.08 [1.73-2.16]	NS
LMCR₂₀	2.25 [1.86-2.63]	2.29 [1.89-2.69]	1.79 [1.52-2.23]	0.030	2.34 [1.88-2.70]	2.05 [1.75-2.31]	NS
LKCR₁₀	1.02 [0.85-1.17]	1.04 [0.89-1.21]	0.83 [0.74-0.90]	0.005	1.06 [0.91-1.25]	0.87 [0.76-1.05]	0.008
LKCR₂₀	1.14 [0.90-1.13]	1.19 [0.96-1.33]	0.89 [0.80-0.96]	0.009	1.20 [0.96-1.38]	0.91 [0.81-1.22]	0.012
CEI₁₀	1.39 [1.27-1.57]	[1.341.43 -1.1.58]	1.26 [1.22-1.32]	0.006	1.47 [1.34-1.58]	1.33 [1.25-1.38]	0.003
CEI₂₀	1.43 [1.30-1.61]	1.45 [1.35-1.63]	1.32 [1.19-1.37]	0.007	1.50 [1.39-1.66]	1.35 [1.19-1.42]	0.001
HUI₁₀	407.3 [223.7-640.9]	486.2 [235.3-845.4]	312.4 [-3.31- 400]	0.022	522.4 [284.9-1036.4]	265.7 [130.5-383.7]	<0.001
HUI₂₀	660.5 [301.5-956.5]	697.8 [367.1-1028.9]	265 [72.5-620.4]	0.009	720.1 [450.5-1062.4]	327.2 [198.1-772.2]	0.004

Quantitative assessment of liver uptake of Gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA) during hepatobiliary phase (HPB) at 10 minutes in patients with normal liver (control group) compared with all Child-Pugh (CP) A 5 points patients (left panel) and with patients Child-Pugh A 5 points patients without clinically significant portal hypertension (CSPH)_ Variables described as median and interquartile range

INDEX	Control group	Child-Pugh A-5 points	P value	Control group	No CSPH (all CP A-5 points)	P value
N	20	44		20	19
RLE₁₀	1.06 [0.82-2.16]	0.68 [0.52-0.82]	< 0.001	1.06 [0.82-2.16]	0.73 [0.52-0.89]	< 0.001
LSCR₁₀	2,27 [2.06-2.88]	1.43 [1.19-1.61]	< 0.001	2,27 [2.06-2.88]	1.54 [1.37-1.67]	< 0.001
LMCR₁₀	3.11 [2.90-3.55]	2.26 [1.81-2.71]	< 0.001	3.11 [2.90-3.55]	2.41 [2.12-2.83]	< 0.001
LKCR₁₀	1.82 [1.51-1.99]	1.06 [0.91-1.25]	< 0.001	1.82 [1.51-1.99]	1.15 [0.98-1.34]	< 0.001
CEI₁₀	1.71 [1.55-1.85]	1.47 [1.34-1.58]	0.001	1.71 [1.55-1.85]	1.46 [1.34-1.59]	0.007
HUI₁₀	1449.6 [1259-1717.7]	522.4 [284.9-1036.4]	< 0.001	1449.6 [1259-1717.7]	609.7 [501.4-970.3]	< 0.001

Portal hypertension may influence the registration of hypointensity of small hepatocellular carcinoma in the hepatobiliary phase in gadoxetic acid MR

Figures & Tables

Figure 1

Figure 2

Figure 3

Formulas used for qualitative assessment of liver uptake of Gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA) in the hepatobiliary phase (HPB)

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