Development of 20?cm sample bore size dynamic nuclear polarization (DNP)-MRI at 16?mT and redox metabolic imaging of acute hepatitis rat model

Development of 20?cm sample bore size dynamic nuclear polarization (DNP)-MRI at 16?mT and redox metabolic imaging of acute hepatitis rat model
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开发 20?cm 样品孔径的 16?mT 动态核极化 (DNP)-MRI 和急性肝炎大鼠模型的氧化还原代谢成像

DOI:
10.1016/j.freeradbiomed.2021.04.017
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发表时间:
2021
影响因子:
7.4
通讯作者:
Hyodo Fuminori
Hyodo Fuminori
中科院分区:
医学1区
文献类型:
--
作者:
Eto Hinako;Naganuma Tatuya;Nakao Motonao;Murata Masaharu;Elhelaly Abdelazim Elsayed;Noda Yoshifumi;Kato Hiroki;Matsuo Masayuki;Akahoshi Tomohiko;Hashizume Makoto;Hyodo Fuminori

文献摘要

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组织氧化还原代谢参与各种疾病,了解组织氧化还原代谢的时空动态可能有助于疾病进展的诊断和治疗。在体内动态核极化(DNP)-MRI,电子顺磁共振(EPR)照射在氮氧自由基的共振频率作为氧化还原探针诱导DNP,增加了MRI信号的强度。对于电子自旋,由于未成对电子的磁矩更高,因此必须施加比核自旋所需的共振频率高658倍的共振频率。以前的研究使用的疾病模型的小动物和体内DNP-MRI已经揭示了一个异常的氧化还原状态参与了许多疾病,它可以用来可视化氧化还原代谢的动态变化。为了在临床实践中使用当前的方法,开发用于大型动物临床前检查的原型DNP-MRI系统对于澄清DNP-MRI设备尺寸增加所特有的问题是必不可少的。因此,我们开发了一个活体DNP-MRI系统,样品孔尺寸为20 cm,磁场为16 mT,使用U形永磁体。由于NMR频率很低,我们采用了具有优良滤波器和动态范围特性的数字射频发射/接收系统,并配备了数字涡流补偿系统,以抑制大涡流。该脉冲序列基于快速自旋回波序列,并针对低频大涡流设备进行了改进。开发的体内DNP-MRI系统用于非侵入性成像氨甲酰基-PROXYL探针在重800 g的大大鼠肝脏中的氧化还原反应。此外,DNP-MRI分析能够捕获肝炎模型大鼠氧化还原代谢的显著变化。
Tissue redox metabolism is involved in various diseases, and an understanding of the spatio-temporal dynamics of tissue redox metabolism could be useful for diagnosis of progression and treatment. Inin vivodynamic nuclear polarization (DNP)-MRI, electron paramagnetic resonance (EPR) irradiation at the resonance frequency of nitroxyl radicals administered as a redox probe for induction of DNP, increases the intensity of MRI signals. For electron spin, it is necessary to apply a resonant frequency 658 times higher than that required for nuclear spin because of the higher magnetic moment of unpaired electrons. Previous studies using a disease model of small animals andin vivo DNP-MRI have revealed that an abnormal redox status is involved in many diseases, and that it could be used to visualize the dynamics of alterations in redox metabolism. To use the current methods in clinical practice, the development of a prototype DNP-MRI system for preclinical examinations of large animals is indispensable for clarifying the problems peculiar to the increase in size of the DNP-MRI device. Therefore, we developed ain vivoDNP-MRI system with a sample bore size of 20 cm and a 16-mT magnetic field using a U-shaped permanent magnet. Because the NMR frequency is very low, we adopted a digital radiofrequency transmission/reception system with excellent filter and dynamic range characteristics and equipped with a digital eddy current compensation system to suppress large eddy currents. The pulse sequence was based on the fast spin-echo sequence, which was improved for low frequency and large-eddy current equipment. Thein vivoDNP-MRI system developed was used to non-invasively image the redox reaction of a carbamoyl-PROXYL probe in the livers of large rats weighing 800 g. Furthermore, DNP-MRI analysis was able to capture significant changes in redox metabolism in hepatitis-model rats.