Abstract：
Distinguishing quiescent from rupture-prone atherosclerotic lesions has significant translational and clinical implications. Electrochemical impedance spectroscopy (EIS) characterizes biological tissues by assessing impedance and phase delay responses to alternating current at multiple frequencies. We evaluated invasive 6-point stretchable EIS sensors over a spectrum of experimental atherosclerosis and compared results with intravascular ultrasound (IVUS), molecular positron emission tomography (PET) imaging, and histology. Male New Zealand White rabbits (n = 16) were placed on a high-fat diet, with or without endothelial denudation via balloon injury of the infrarenal abdominal aorta. Rabbits underwent in vivo micro-PET imaging of the abdominal aorta with 68Ga-DOTATATE, 18F-NaF, and 18F-FDG, followed by invasive interrogation via IVUS and EIS. Background signal-corrected values of impedance and phase delay were determined. Abdominal aortic samples were collected for histology. Analyses were performed blindly. EIS impedance was associated with markers of plaque activity including macrophage infiltration (r = .813, p = .008) and macrophage/smooth muscle cell (SMC) ratio (r = .813, p = .026). Moreover, EIS phase delay correlated with anatomic markers of plaque burden, namely intima/media ratio (r = .883, p = .004) and %stenosis (r = .901, p = .002), similar to IVUS. 68Ga-DOTATATE correlated with intimal macrophage infiltration (r = .861, p = .003) and macrophage/SMC ratio (r = .831, p = .021), 18F-NaF with SMC infiltration (r = -.842, p = .018), and 18F-FDG correlated with macrophage/SMC ratio (r = .787, p = .036). EIS with phase delay integrates key atherosclerosis features that otherwise require multiple complementary invasive and non-invasive imaging approaches to capture. These findings indicate the potential of invasive EIS to comprehensively evaluate human coronary artery disease.
摘要：
区分静止性与易破裂的动脉粥样硬化病变具有重要的转化和临床意义。电化学阻抗谱(EIS)通过评估在多个频率下对交流电的阻抗和相位延迟响应来表征生物组织。我们评估了实验性动脉粥样硬化的侵入性6点可拉伸EIS传感器，并将结果与血管内超声（IVUS）进行了比较。分子正电子发射断层扫描（PET）成像，和组织学。雄性新西兰白兔（n=16）进行高脂肪饮食，伴有或不伴有肾下腹主动脉球囊损伤的内皮剥脱。兔用68Ga-DOTATATE对腹主动脉进行了体内显微PET成像，18F-NaF,18F-FDG,随后通过IVUS和EIS进行侵入性审讯。确定了阻抗和相位延迟的背景信号校正值。收集腹主动脉样品用于组织学。分析是盲目进行的。EIS阻抗与斑块活性标志物相关，包括巨噬细胞浸润（r=.813，p=.008）和巨噬细胞/平滑肌细胞（SMC）比率（r=.813，p=.026）。此外，EIS相位延迟与斑块负荷的解剖标志物相关，即内膜/中膜比（r=.883，p=.004）和狭窄百分比（r=.901，p=.002），类似于IVUS。68Ga-DOTATATE与内膜巨噬细胞浸润（r=.861，p=.003）和巨噬细胞/SMC比率（r=.831，p=.021）相关，18F-NaF，SMC渗透（r=-.842，p=.018），18F-FDG与巨噬细胞/SMC比值相关(r=.787,p=.036)。具有相位延迟的EIS整合了关键的动脉粥样硬化特征，否则需要多种互补的侵入性和非侵入性成像方法来捕获。这些发现表明侵入性EIS具有全面评估人类冠状动脉疾病的潜力。
