Gadoxetic Acid Uptake Rate as a Measure of Global and Regional Liver Function as Compared With Indocyanine Green Retention, Albumin-Bilirubin Score, and Portal Venous Perfusion

Abstract

Purpose: Global and regional liver function assessments are important for defining the magnitude and spatial distribution of dose to preserve functional liver parenchyma and reduce incidence of hepatotoxicity from radiation therapy for intrahepatic cancer treatment. This individualized liver function-guided radiation therapy strategy is critical for patients with heterogeneous and poor liver function, often observed in cirrhotic patients treated for hepatocellular carcinoma. This study aimed to validate k₁ as a measure of global and regional function through comparison with 2 well-regarded global function measures: indocyanine green retention (ICGR) and albumin-bilirubin (ALBI).

Methods and materials: Seventy-nine dynamic gadoxetic acid enhanced magnetic resonance imaging scans were acquired in 40 patients with hepatocellular carcinoma in institutional review board approved prospective protocols. Portal venous perfusion (k_pv ) was quantified from gadoxetic acid enhanced magnetic resonance imaging using a dual-input 2-compartment model, and gadoxetic acid uptake rate (k₁) was fitted using a linearized single-input 2-compartment model chosen for robust k₁ estimation. Four image-derived measures of global liver function were tested: (1) mean k₁ multiplied by liver volume (k₁V_L ) (functional volume), (2) mean k₁ multiplied by blood distribution volume (k₁V_dis )_, (3) mean k_pv, and (4) liver volume (V_L ). The measure's correlation with corresponding ICGR and ALBI tests was assessed using linear regression. Voxel-wise similarity between k₁ and k_pv was compared using Spearman ranked correlation.

Results: Significant correlations (P < .05) with ICGR and ALBI were found for k₁V_L, k₁V_dis, and V_L (in order of strength), but not for mean $k$ _pv $.$ The mean ranked correlation coefficient between k₁ and k_pv maps was 0.09. k₁ and k_pv maps were predominantly mismatched in patients with poor liver function.

Conclusions: The metric combining function and liver volume (k₁V_L ) was a stronger measure of global liver function compared with perfusion or liver volume alone, especially in patients with poor liver function. Gadoxetic acid uptake rate is promising for both global and regional liver function.

Figure 1

Example slices of k₁ (top row) and k_pv maps (bottom row) presented in 100 quantiles of 4 patients with different indocyanine green retention at 15 minutes (ICGR15) and albumin-bilirubin (ALBI) values. Note that large vessels generally show as dark in uptake rate maps (lacking hepatocytes), while in perfusion maps they can be either dark (arterial vessels) or bright (portal venous vasculature), depending on the type of vessels. The first patient shows a weak but nonnegligible correlation. The second depicts a patient, where despite severely compromised liver function observed by ICGR, ALBI, and negligible uptake rate throughout the liver, the perfusion is relatively uncompromised. The third and fourth patients have relatively good function, but still negligible to negative correlations in terms of uptake rate and perfusion, because the regional variations often do not match.

Figure 2

Histogram of the distribution of ranked correlations between k₁ and k_pv values (mean, 0.095; median, 0.12; n = 53).

Figure 3

Log₁₀ indocyanine green retention at 15 minutes (ICGR15) plotted against: (a) mean k₁ by total volume, (b) summed K₁ = summed k₁V_dis, (c) total liver volume outside gross tumor volume (GTV), (d) mean k_pv, (e) weight (W)-normalized mean k₁ by total volume, (f) W-normalized summed K₁ = summed k₁V_dis, (g) W-normalized total liver volume outside GTV. The plotted linear regression fit in (a), (b), (e), and (f) each ignore 1 outlier in terms of k₁, and the fit for (g) ignores 4 outliers in terms of W-normalized liver volume. Correlation coefficients do not exclude outliers.

Figure 4

The raw albumin-bilirubin (ALBI) plotted against: (a) mean k₁ by total volume, (b) summed K₁ = summed k₁V_dis, (c) total liver volume outside gross tumor volume (GTV), (d) mean k_pv, (e) weight-normalized mean k₁ by total volume, (f) weight-normalized summed K₁ = summed k₁V_dis, (g) weight-normalized total liver volume outside GTV. The plotted linear regression fit in (a), (b), (e), and (f) each ignore 1 outlier in terms of k₁, and the fit for (g) ignores 5 outliers in terms of weight-normalized liver volume. Correlation coefficients do not exclude outliers.