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Robust arterial spin labeling MRI measurement of pharmacologically induced perfusion change in rat kidneys
NMR in Biomedicine ( IF 2.7 ) Pub Date : 2021-06-06 , DOI: 10.1002/nbm.4566 Fuqiang Zhao 1 , Xiaoyan Zhou 1 , Eric Messina 1 , Lufei Hu 1 , Marie A Holahan 1 , Gayathri Swaminath 1 , Catherine D G Hines 1
NMR in Biomedicine ( IF 2.7 ) Pub Date : 2021-06-06 , DOI: 10.1002/nbm.4566 Fuqiang Zhao 1 , Xiaoyan Zhou 1 , Eric Messina 1 , Lufei Hu 1 , Marie A Holahan 1 , Gayathri Swaminath 1 , Catherine D G Hines 1
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Kidney diseases such as acute kidney injury, diabetic nephropathy and chronic kidney disease (CKD) are related to dysfunctions of the microvasculature in the kidney causing a decrease in renal blood perfusion (RBP). Pharmacological intervention to improve the function of the microvasculature is a viable strategy for the potential treatment of these diseases. The measurement of RBP is a reliable biomarker to evaluate the efficacy of pharmacological agents' actions on the microvasculature, and measurement of RBP responses to different pharmacological agents can also help elucidate the mechanism of hemodynamic regulation in the kidney. Magnetic resonance imaging (MRI) with flow-sensitive alternating inversion recovery (FAIR) arterial spin labeling (ASL) has been used to measure RBP in humans and animals. However, artifacts caused by respiratory and peristaltic motions limit the potential of FAIR ASL in drug discovery and kidney research. In this study, the combined anesthesia protocol of inactin with a low dose of isoflurane was used to fully suppress peristalsis in rats, which were ventilated with an MRI-synchronized ventilator. FAIR ASL data were acquired in eight axial slices using a single-shot, gradient-echo, echo-planar imaging (EPI) sequence. The artifacts in the FAIR ASL RBP measurement due to respiratory and peristaltic motions were substantially eliminated. The RBP responses to fenoldopam and L-NAME were measured, and the increase and decrease in RBP caused by fenoldopam and L-NAME, respectively, were robustly observed. To further validate FAIR ASL, the renal blood flow (RBF) responses to the same agents were measured by an invasive perivascular flow probe method. The pharmacological agent-induced responses in RBP and RBF are similar. This indicates that FAIR ASL has the sensitivity to measure pharmacologically induced changes in RBP. FAIR ASL with multislice EPI can be a valuable tool for supporting drug discovery, and for elucidating the mechanism of hemodynamic regulation in kidneys.
中文翻译：
稳健的动脉自旋标记 MRI 测量药理学诱导的大鼠肾脏灌注变化
急性肾损伤、糖尿病肾病和慢性肾病（CKD）等肾脏疾病与肾脏微血管功能障碍导致肾血液灌注（RBP）减少有关。改善微血管功能的药物干预是潜在治疗这些疾病的可行策略。 RBP的测量是评估药物对微血管作用功效的可靠生物标志物，测量RBP对不同药物的反应也有助于阐明肾脏血流动力学调节机制。具有血流敏感交替反转恢复 (FAIR) 动脉自旋标记 (ASL) 的磁共振成像 (MRI) 已用于测量人类和动物的 RBP。然而，呼吸和蠕动运动引起的伪影限制了 FAIR ASL 在药物发现和肾脏研究中的潜力。在这项研究中，采用inactin与低剂量异氟烷的联合麻醉方案来完全抑制大鼠的蠕动，并使用MRI同步呼吸机进行通气。 FAIR ASL 数据是使用单次、梯度回波、平面回波成像 (EPI) 序列在八个轴向切片中获取的。 FAIR ASL RBP 测量中由于呼吸和蠕动运动引起的伪影已基本消除。测量了 RBP 对非诺多泮和 L-NAME 的反应，并强烈观察到非诺多泮和 L-NAME 分别引起的 RBP 增加和减少。为了进一步验证 FAIR ASL，通过侵入性血管周围流量探针方法测量了对相同药物的肾血流 (RBF) 反应。 RBP 和 RBF 中药物诱导的反应是相似的。 这表明 FAIR ASL 具有测量药物诱导的 RBP 变化的敏感性。具有多层 EPI 的 FAIR ASL 可以成为支持药物发现和阐明肾脏血流动力学调节机制的宝贵工具。
更新日期：2021-08-11
中文翻译：
稳健的动脉自旋标记 MRI 测量药理学诱导的大鼠肾脏灌注变化
急性肾损伤、糖尿病肾病和慢性肾病（CKD）等肾脏疾病与肾脏微血管功能障碍导致肾血液灌注（RBP）减少有关。改善微血管功能的药物干预是潜在治疗这些疾病的可行策略。 RBP的测量是评估药物对微血管作用功效的可靠生物标志物，测量RBP对不同药物的反应也有助于阐明肾脏血流动力学调节机制。具有血流敏感交替反转恢复 (FAIR) 动脉自旋标记 (ASL) 的磁共振成像 (MRI) 已用于测量人类和动物的 RBP。然而，呼吸和蠕动运动引起的伪影限制了 FAIR ASL 在药物发现和肾脏研究中的潜力。在这项研究中，采用inactin与低剂量异氟烷的联合麻醉方案来完全抑制大鼠的蠕动，并使用MRI同步呼吸机进行通气。 FAIR ASL 数据是使用单次、梯度回波、平面回波成像 (EPI) 序列在八个轴向切片中获取的。 FAIR ASL RBP 测量中由于呼吸和蠕动运动引起的伪影已基本消除。测量了 RBP 对非诺多泮和 L-NAME 的反应，并强烈观察到非诺多泮和 L-NAME 分别引起的 RBP 增加和减少。为了进一步验证 FAIR ASL，通过侵入性血管周围流量探针方法测量了对相同药物的肾血流 (RBF) 反应。 RBP 和 RBF 中药物诱导的反应是相似的。 这表明 FAIR ASL 具有测量药物诱导的 RBP 变化的敏感性。具有多层 EPI 的 FAIR ASL 可以成为支持药物发现和阐明肾脏血流动力学调节机制的宝贵工具。
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