Ex vivo gadoxetate relaxivities in rat liver tissue and blood at five magnetic field strengths from 1.41 to 7 T

Abstract

Quantitative mapping of gadoxetate uptake and excretion rates in liver cells has shown potential to significantly improve the management of chronic liver disease and liver cancer. Unfortunately, technical and clinical validation of the technique is currently hampered by the lack of data on gadoxetate relaxivity. The aim of this study was to fill this gap by measuring gadoxetate relaxivity in liver tissue, which approximates hepatocytes, in blood, urine and bile at magnetic field strengths of 1.41, 1.5, 3, 4.7 and 7 T. Measurements were performed ex vivo in 44 female Mrp2 knockout rats and 30 female wild-type rats who had received an intravenous bolus of either 10, 25 or 40 μmol/kg gadoxetate. T1 was measured at 37 ± 3 C on NMR instruments (1.41 and 3 T), small-animal MRI (4.7 and 7 T) and clinical MRI (1.5 and 3 T). Gadolinium concentration was measured with optical emission spectrometry or mass spectrometry. The impact on measurements of gadoxetate rate constants was determined by generalizing pharmacokinetic models to tissues with different relaxivities. Relaxivity values (L mmol −1 s −1) showed the expected dependency on tissue/biofluid type and field strength, ranging from 15.0 ± 0.9 (1.41) to 6.0 ± 0.3

Physiologically Based Pharmacokinetic Modeling of Transporter-Mediated Hepatic Disposition of Imaging Biomarker Gadoxetate in Rats

“… 39 For a given tissue τ, the relation between Δ R 1,τ ( t ) and c τ ( t ) is generally considered to be linear, as in eq 4 . 39 , 40 …”

“…To derive Δ R 1,liv , a volume fraction-weighted mean of the contributions of the gadoxetate concentration in all the compartments used to model the liver was performed. 40 In the spleen, the entire distribution space was supposed to have the same relaxivity as blood and, therefore, eq 4 can be applied directly to derive spleen concentrations from Δ R 1,spl . Concerning the blood, the blood value for r 1 in Table 1 allows Δ R 1,b to be directly related to the blood concentration.…”

“…39 The r 1,τ values are typically difficult to measure in vivo, therefore, in this study, the ex vivo values in Table 1 were used, as per ref. 40. It has to be considered that r 1,τ and ΔR 1,τ change as a function of the magnetic field strength used by the magnetic resonance machine for image acquisition.…”

“…The relationship between c ( t ) and Δ R 1 ( t ) depends on the physical interactions between the contrast agent molecules and the tissue . For a given tissue τ, the relation between Δ R 1,τ ( t ) and c τ ( t ) is generally considered to be linear, as in eq . , …”

“…40. It has to be considered that r 1,τ and Δ R 1,τ change as a function of the magnetic field strength used by the magnetic resonance machine for image acquisition . Therefore, Δ R 1 profiles acquired at different field strengths are not directly comparable.…”