Ted Rogers Centre for Heart Research, Translational Biology & Engineering Program, Toronto, Canada.
Leslie Dan Faculty of Pharmacy, University of Toronto, Canada.
J Magn Reson Imaging. 2019 Apr;49(4):1174-1185. doi: 10.1002/jmri.26308. Epub 2018 Oct 9.
Ischemia-reperfusion (I/R) injury involves damage to the microvessel structure (eg, increased permeability) and function (blunted vasomodulation). While microstructural damage can be detected with dynamic contrast-enhanced (DCE) MRI, there is no diagnostic to detect deficits in microvascular function.
To apply a novel MRI method for evaluating dynamic vasomodulation to assess microvascular dysfunction in skeletal muscle following I/R injury.
Prospective, longitudinal.
Twenty-three healthy male adult Sprague-Dawley rats.
FIELD STRENGTH/SEQUENCE: Dynamic T fast field echo imaging at 3.0T with preinjection T mapping.
Injury in the left hindlimb was induced using a 3-hour I/R procedure. Longitudinal MRI scanning was performed up to 74 days, with animals completing assessment at different intervals for histological and laser Doppler perfusion validation. Pharmacokinetic parameters K and v were determined following i.v. injection of gadovist (0.1 mmol/kg). Vasomodulatory response was probed on gadofosveset (0.3 mmol/kg) using hypercapnic gases delivered through a controlled gas-mixing circuit to induce vasoconstriction and vasodilation in ventilated rats. Heart rate and blood oxygen saturation were monitored.
Two-way analysis of variance with Tukey-Kramer post-hoc analysis was used to determine significant changes in vasomodulatory response, K , and v .
This new MRI technique revealed impaired vasomodulation in the injured hindlimb. Vasoconstriction was maintained, but vasodilation was blunted up to 21 days postinjury (P < 0.05). However, DCE-MRI measured K and v were significantly (P < 0.05) different from baseline only during acute inflammation (Day 3), with severe inflammation noted on histology.
While conventional DCE-MRI shows normalization after the acute phase, our new approach reveals sustained functional impairment in muscle microvasculature following I/R injury, with compromised response in vasomotor tone present for at least 21 days.
4 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:1174-1185.
缺血再灌注(I/R)损伤涉及微血管结构(例如通透性增加)和功能(血管调节功能减弱)的损伤。虽然动态对比增强(DCE)MRI 可检测到微观结构损伤,但尚无诊断方法可检测微血管功能缺陷。
应用一种新的 MRI 方法评估动态血管调节,以评估 I/R 损伤后骨骼肌的微血管功能障碍。
前瞻性,纵向。
23 只健康雄性成年 Sprague-Dawley 大鼠。
磁场强度/序列:3.0T 下的快速场回波成像,带有预注射 T 映射。
使用 3 小时 I/R 程序诱导左后肢损伤。进行长达 74 天的纵向 MRI 扫描,动物在不同时间间隔完成评估,以进行组织学和激光多普勒灌注验证。静脉注射钆喷酸葡胺(0.1mmol/kg)后确定药代动力学参数 K 和 v。通过受控气体混合回路输送高碳酸气体,在通气大鼠中诱导血管收缩和血管舒张,探测血管舒张反应。监测心率和血氧饱和度。
采用双向方差分析和 Tukey-Kramer 事后分析,以确定血管舒张反应、K 和 v 的显著变化。
这项新的 MRI 技术显示受伤后后肢的血管调节受损。血管收缩得以维持,但血管舒张在损伤后 21 天(P<0.05)减弱。然而,DCE-MRI 测量的 K 和 v 在急性炎症(第 3 天)期间仅与基线明显不同(P<0.05),组织学检查显示严重炎症。
虽然常规 DCE-MRI 在急性期后显示正常化,但我们的新方法显示 I/R 损伤后肌肉微血管功能持续受损,血管运动张力反应受损至少持续 21 天。
4 级 技术功效:第 1 阶段 J. Magn. Reson. Imaging 2019;49:1174-1185.