MR 引导脉冲聚焦超声对大鼠心脏的分子和组织学影响。
Molecular and histological effects of MR-guided pulsed focused ultrasound to the rat heart.
机构信息
Frank Laboratory, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, 10 Center Dr., Bethesda, MD, 20892, USA.
National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, USA.
出版信息
J Transl Med. 2017 Dec 13;15(1):252. doi: 10.1186/s12967-017-1361-y.
BACKGROUND
Image-guided high intensity focused ultrasound has been used as an extracorporeal cardiac pacing tool and to enhance homing of stem cells to targeted tissues. However, molecular changes in the myocardium after sonication have not been widely investigated. Magnetic-resonance (MR)-guided pulsed focused ultrasound (pFUS) was targeted to the rat myocardium over a range of pressures and the microenvironmental and histological effects were evaluated over time.
METHODS
Eight-to-ten-week-old Sprague-Dawley rats received T2-weighted MR images to target pFUS to the left ventricular and septum without cardiac or respiratory gating. Rats were sonicated through the thoracic wall at peak negative pressures (PNP) from 1 to 8 MPa at a center frequency of 1 MHz, 10 ms pulse duration and 1 Hz pulse repetition frequency for 100 pulses per focal target. Following pFUS, myocardium was harvested over 24 h and subjected to imaging, proteomic, and histological measurements.
RESULTS
pFUS to the myocardium increased expression of cytokines, chemokines, and trophic factors characterized by an initial increase in tumor necrosis factor (TNF)-α followed by increases in pro- and anti-inflammatory factors that returned to baseline by 24 h. Immediately after pFUS, there was a transient (< 1 h) increase in N-terminal pro b-type natriuretic peptide (NT-proBNP) without elevation of other cardiac injury markers. A relationship between PNP and expression of TNF-α and NT-proBNP was observed with significant changes (p < 0.05 ANOVA) ≥ 4 MPa compared to untreated controls. Contrast-enhanced ex vivo T1-weighted MRI revealed vascular leakage in sonicated myocardium that was accompanied by the presence of albumin upon immunohistochemistry. Histology revealed infiltration of neutrophils and macrophages without morphological myofibril changes in sonicated tissue accompanied by pulmonary hemorrhage at PNP > 4 MPa.
CONCLUSIONS
MR-guided pFUS to myocardium induced transient proteomic and histological changes. The temporal proteomic changes in the myocardium indicate a short-lived sterile inflammatory response consistent with ischemia or contusion. Further study of myocardial function and strain is needed to determine if pFUS could be developed as an experimental model of cardiac injury and chest trauma.
背景
图像引导高强度聚焦超声已被用作体外心脏起搏工具，并增强干细胞向靶向组织的归巢。然而，超声后的心肌分子变化尚未得到广泛研究。磁共振（MR）引导的脉冲聚焦超声（pFUS）靶向大鼠心肌，在一系列压力下评估微环境和组织学效应随时间的变化。
方法
8-10 周龄 Sprague-Dawley 大鼠接受 T2 加权 MR 图像靶向左心室和室间隔，无需心脏或呼吸门控。通过胸壁在峰值负压（PNP）下对大鼠进行超声，PNP 范围为 1-8 MPa，中心频率为 1 MHz，10 ms 脉冲持续时间和 1 Hz 脉冲重复频率，每个焦点目标 100 个脉冲。pFUS 后，在 24 小时内收获心肌，并进行成像、蛋白质组学和组织学测量。
结果
pFUS 心肌增加了细胞因子、趋化因子和营养因子的表达，其特征是肿瘤坏死因子（TNF）-α 先增加，随后促炎和抗炎因子增加，24 小时内恢复到基线。pFUS 后立即（<1 小时），N 端前 B 型利钠肽（NT-proBNP）短暂升高，而其他心脏损伤标志物没有升高。观察到 PNP 与 TNF-α 和 NT-proBNP 的表达之间存在关系，与未处理对照组相比，≥4 MPa 时存在显著变化（p <0.05 ANOVA）。离体 T1 加权对比增强 MRI 显示超声心肌中的血管渗漏，免疫组化显示白蛋白存在。组织学显示在超声组织中存在中性粒细胞和巨噬细胞浸润，没有形态学肌原纤维变化，并伴有 PNP>4 MPa 时的肺出血。
结论
MR 引导的 pFUS 心肌诱导短暂的蛋白质组学和组织学变化。心肌的时间蛋白质组学变化表明，这是一种短暂的无菌性炎症反应，与缺血或挫伤一致。需要进一步研究心肌功能和应变，以确定 pFUS 是否可以作为心脏损伤和胸部创伤的实验模型。
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