Purpose

Myocardial healing following myocardial infarction (MI) is a complex process that is yet to be fully understood. Clinical attempts in regeneration of the injured myocardium using cardiac stem cells faced major challenges, calling for a better understanding of the processes involved at a more basic level in order to foster translation.

Procedures

We examined the feasibility of volumetric optoacoustic tomography (VOT) in studying healing of the myocardium in different models of MI, including permanent occlusion (PO) of the left coronary artery, temporary occlusion (ischemia-reperfusion—I/R) and infarcted c-kit mutants, a genetic mouse model with impaired cardiac healing. Murine hearts were imaged at 100 Hz frame rate using 800 nm excitation wavelength, corresponding to the peak absorption of indocyanine green (ICG) in plasma and the isosbestic point of haemoglobin.

Results

The non-invasive real-time volumetric imaging capabilities of VOT have allowed the detection of significant variations in the pulmonary transit time (PTT), a parameter affected by MI, across different murine models. Upon intravenous injection of ICG, we were able to track alterations in cardiac perfusion in I/R models, which were absent in wild-type (wt) PO or kit^W/kit^W-v PO mice. The wt-PO and I/R models further exhibited irregularities in their cardiac cycles.

Conclusions

Clear differences in the PTT, ICG perfusion and cardiac cycle patterns were identified between the different models and days post MI. Overall, the results highlight the unique capacity of VOT for multi-parametric characterization of morphological and functional changes in murine models of MI.

中文翻译：

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体积光声断层扫描区分心肌重构。

目的

心肌梗死 (MI) 后的心肌愈合是一个复杂的过程，尚未完全了解。使用心脏干细胞再生受损心肌的临床尝试面临重大挑战，需要在更基础的层面上更好地理解所涉及的过程，以促进转化。

程序

我们研究了体积光声断层扫描 (VOT) 在研究不同 MI 模型中心肌愈合的可行性，包括左冠状动脉永久闭塞 (PO)、临时闭塞 (缺血-再灌注 - I/R) 和梗死 c- kit突变体，一种心脏愈合受损的遗传小鼠模型。使用 800 nm 激发波长以 100 Hz 帧速率对鼠心脏进行成像，对应于血浆中吲哚菁绿 (ICG) 的峰值吸收和血红蛋白的等吸收点。

结果

VOT 的非侵入性实时体积成像功能允许检测不同小鼠模型中受 MI 影响的参数肺通过时间 (PTT) 的显着变化。静脉注射 ICG 后，我们能够追踪 I/R 模型中心脏灌注的变化，而野生型 ( wt ) PO 或kit ^W /kit ^W-v PO 小鼠不存在这种变化。的重量PO和I / R模型进一步表现出在它们的心动周期的不规则性。

结论

在不同模型和 MI 后天数之间确定了 PTT、ICG 灌注和心动周期模式的明显差异。总体而言，结果突出了 VOT 对 MI 小鼠模型中形态和功能变化的多参数表征的独特能力。