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 (7) T in liver tissue, from 7.5 ± 0.2 (1.41) to 6.2 ± 0.3 (7) T in blood, from 5.6 ± 0.1 (1.41) to 4.5 ± 0.1 (7) T in urine and from 5.6 ± 0.4 (1.41) to 4.3 ± 0.6 (7) T in bile. Failing to correct for the relaxivity difference between liver tissue and blood overestimates intracellular uptake rates by a factor of 2.0 at 1.41 T, 1.8 at 1.5 T, 1.5 at 3 T and 1.2 at 4.7 T. The relaxivity values derived in this study can be used retrospectively and prospectively to remove a well‐known bias in gadoxetate rate constants. This will promote the clinical translation of MR‐based liver function assessment by enabling direct validation against reference methods and a more effective translation between in vitro findings, animal models and patient studies.

中文翻译：

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在 1.41 至 7 T 的五种磁场强度下，大鼠肝脏组织和血液中的离体钆塞酸盐弛豫。

肝细胞中钆塞酸摄取和排泄率的定量绘图显示出显着改善慢性肝病和肝癌管理的潜力。不幸的是，该技术的技术和临床验证目前由于缺乏关于钆塞酸盐弛豫的数据而受到阻碍。本研究的目的是通过测量肝组织中钆塞酸盐弛豫率来填补这一空白，该弛豫在 1.41、1.5、3、4.7 和 7 T 的磁场强度下与肝细胞、血液、尿液和胆汁中的肝细胞相似。测量是在体外进行的44 只 Mrp2 敲除雌性大鼠和 30 只雌性野生型大鼠，它们接受了 10、25 或 40 μmol/kg 钆塞酸盐的静脉推注。T1 在 NMR 仪器（1.41 和 3 T）、小动物 MRI（4.7 和 7 T）和临床 MRI（1.5 和 3 T）上在 37±3°C 下测量。钆浓度用发射光谱法或质谱法测量。通过将药代动力学模型推广到具有不同弛豫度的组织来确定对钆塞酸盐速率常数测量的影响。弛豫值 (L mmol⁻¹秒⁻¹) 显示对组织/生物流体类型和场强的预期依赖性，肝组织中的范围为 15.0 ± 0.9 (1.41) 至 6.0 ± 0.3 (7) T，肝组织中的范围为 7.5 ± 0.2 (1.41) 至 6.2 ± 0.3 (7) T血液，尿液中从 5.6 ± 0.1 (1.41) 到 4.5 ± 0.1 (7) T，胆汁中从 5.6 ± 0.4 (1.41) 到 4.3 ± 0.6 (7) T。未能校正肝组织和血液之间的弛豫差异会高估细胞内摄取率，1.41 T 时为 2.0，1.5 T 时为 1.8，3 T 时为 1.5，4.7 T 时为 1.2。可以使用本研究中得出的弛豫值回顾性和前瞻性地消除钆塞酸盐速率常数中众所周知的偏差。这将促进基于 MR 的肝功能评估的临床转化，通过参考方法的直接验证和体外发现之间更有效的转化，