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脑温调节异常:急性缺血性卒中非人灵长类动物研究中的磁共振热成像监测

Cerebral Temperature Dysregulation: MR Thermographic Monitoring in a Nonhuman Primate Study of Acute Ischemic Stroke.

作者信息

Dehkharghani S, Fleischer C C, Qiu D, Yepes M, Tong F

机构信息

From the Departments of Radiology and Imaging Sciences (S.D., D.Q., F.T.)

Neurology (S.D., M.Y.), Emory University Hospital, Atlanta, Georgia.

出版信息

AJNR Am J Neuroradiol. 2017 Apr;38(4):712-720. doi: 10.3174/ajnr.A5059. Epub 2017 Jan 26.

Abstract

BACKGROUND AND PURPOSE

Cerebral thermoregulation remains poorly understood. Temperature dysregulation is deeply implicated in the potentiation of cerebrovascular ischemia. We present a multiphasic, MR thermographic study in a nonhuman primate model of MCA infarction, hypothesizing detectable brain temperature disturbances and brain-systemic temperature decoupling.

MATERIALS AND METHODS

Three Rhesus Macaque nonhuman primates were sourced for 3-phase MR imaging: 1) baseline MR imaging, 2) 7-hour continuous MR imaging following minimally invasive, endovascular MCA stroke induction, and 3) poststroke day 1 MR imaging follow-up. MR thermometry was achieved by multivoxel spectroscopy (semi-localization by adiabatic selective refocusing) by using the proton resonance frequency chemical shift. The relationship of brain and systemic temperatures with time and infarction volumes was characterized by using a mixed-effects model.

RESULTS

Following MCA infarction, progressive cerebral hyperthermia was observed in all 3 subjects, significantly outpacing systemic temperature fluctuations. Highly significant associations were observed for systemic, hemispheric, and global brain temperatures (-statistic, = .0005 for all regressions) relative to the time from stroke induction. Significant differences in the relationship between temperature and time following stroke onset were detected when comparing systemic temperatures with ipsilateral ( = .007), contralateral ( = .004), and infarction core ( = .003) temperatures following multiple-comparisons correction. Significant associations were observed between infarction volumes and both systemic ( ≤ .01) and ipsilateral ( = .04) brain temperatures, but not contralateral brain temperature ( = .08).

CONCLUSIONS

Successful physiologic and continuous postischemic cerebral MR thermography was conducted and prescribed in a nonhuman primate infarction model to facilitate translatability. The results confirm hypothesized temperature disturbance and decoupling of physiologic brain-systemic temperature gradients. These findings inform a developing paradigm of brain thermoregulation and the applicability of brain temperature as a neuroimaging biomarker in CNS injury.

摘要

背景与目的

脑体温调节仍未被充分理解。体温失调与脑血管缺血的增强密切相关。我们在大脑中动脉梗死的非人灵长类动物模型中进行了一项多阶段的磁共振热成像研究,假设可检测到脑温紊乱和脑 - 全身温度解耦。

材料与方法

选用三只恒河猴进行三阶段磁共振成像:1)基线磁共振成像;2)在微创血管内诱导大脑中动脉卒中后进行7小时连续磁共振成像;3)卒中后第1天的磁共振成像随访。通过使用质子共振频率化学位移的多体素质谱法(绝热选择性重聚焦半定位)实现磁共振测温。使用混合效应模型来描述脑温和全身温度与时间及梗死体积之间的关系。

结果

在大脑中动脉梗死之后,所有三只受试动物均出现进行性脑热,其升温速度明显超过全身温度波动。相对于卒中诱导后的时间,全身、半球和全脑温度均呈现高度显著的相关性(所有回归的F统计量,P = 0.0005)。在进行多重比较校正后,将全身温度与同侧(P = 0.007)、对侧(P = 0.004)和梗死核心(P = 0.003)温度进行比较时,检测到卒中发作后温度与时间关系的显著差异。梗死体积与全身(P≤0.01)和同侧(P = 0.04)脑温之间存在显著相关性,但与对侧脑温无关(P = 0.08)。

结论

在非人灵长类梗死模型中成功进行了生理性和连续性缺血后脑磁共振热成像,以促进其可转化性。结果证实了假设的温度紊乱和生理性脑 - 全身温度梯度的解耦。这些发现为脑体温调节的发展范式以及脑温作为中枢神经系统损伤中神经影像学生物标志物的适用性提供了依据。

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