MR & CT Contrast Media Research, Bayer AG, Berlin, Germany.
Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK.
NMR Biomed. 2021 Jan;34(1):e4401. doi: 10.1002/nbm.4401. Epub 2020 Aug 26.
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 s ) 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.
定量研究显示，钆塞酸摄取和排泄率在肝细胞中的变化具有显著改善慢性肝病和肝癌管理的潜力。然而，该技术的临床和技术验证目前受到缺乏关于钆塞酸弛豫率数据的阻碍。本研究旨在通过测量近似于肝细胞的肝组织中的钆塞酸弛豫率来填补这一空白，分别在 1.41、1.5、3、4.7 和 7 T 场强下测量血液、尿液和胆汁中的钆塞酸弛豫率。在 44 只雌性 Mrp2 敲除大鼠和 30 只雌性野生型大鼠中进行了离体实验，这些大鼠均静脉注射了 10、25 或 40 μmol/kg 的钆塞酸。在 37°C ± 3°C 下，使用 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）测量 T1 值。使用原子发射光谱或质谱法测量镓浓度。通过将药代动力学模型推广到具有不同弛豫率的组织中，确定了钆塞酸速率常数测量的影响。弛豫率值（L mmol s）表现出与组织/生物流体类型和场强的预期依赖性，范围从肝组织中的 15.0 ± 0.9（1.41）至 6.0 ± 0.3（7）T，血液中的 7.5 ± 0.2（1.41）至 6.2 ± 0.3（7）T，尿液中的 5.6 ± 0.1（1.41）至 4.5 ± 0.1（7）T，以及胆汁中的 5.6 ± 0.4（1.41）至 4.3 ± 0.6（7）T。在 1.41 T 时，未能校正肝组织与血液之间的弛豫率差异会使细胞内摄取率高估 2.0 倍，在 1.5 T 时高估 1.8 倍，在 3 T 时高估 1.5 倍，在 4.7 T 时高估 1.2 倍。本研究中得出的弛豫率值可用于回顾性和前瞻性研究，以消除钆塞酸速率常数中的一个已知偏差。这将通过允许与参考方法直接验证以及在体外发现、动物模型和患者研究之间更有效地转换，从而促进基于磁共振的肝功能评估的临床转化。
