Purpose

Metabolic alterations underlie many pathophysiological conditions, and their understanding is critical for the development of novel therapies. Although the assessment of metabolic changes in vivo has been historically challenging, recent developments in molecular imaging have allowed us to study novel metabolic research concepts directly in the living subject, bringing us closer to patients. However, in many instances, there is need for sensors that are in close proximity to the organ under investigation, for example to study vascular metabolism.

Methods

In this study, we developed and validated a metabolic detection platform directly in the living subject under an inflammatory condition. The signal collected by a scintillating fiber is amplified using a photomultiplier tube and decodified by an in-house tunable analysis platform. For in vivo testing, we based our experiments on the metabolic characteristics of macrophages, cells closely linked to inflammation and avid for glucose and its analog ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG). The sensor was validated in New Zealand rabbits, in which inflammation was induced by either a) high cholesterol (HC) diet for 16 weeks or b) vascular balloon endothelial denudation followed by HC diet.

Results

There was no difference in weight, hemodynamics, blood pressure, or heart rate between the groups. Vascular inflammation was detected by the metabolic sensor (Inflammation: 0.60 ± 0.03 AU vs. control: 0.48 ± 0.03 AU, p = 0.01), even though no significant inflammation/atherosclerosis was detected by intravascular ultrasound, underscoring the high sensitivity of the system. These findings were confirmed by the presence of macrophages on ex vivo aortic tissue staining.

Conclusion

In this study, we validated a tunable very sensitive metabolic sensor platform that can be used for the detection of vascular metabolism, such as inflammation. This sensor can be used not only for the detection of macrophage activity but, with alternative probes, it could allow the detection of other pathophysiological processes.

中文翻译：

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研究血管损伤中FDG摄取的代谢性血管内平台。

目的

代谢改变是许多病理生理条件的基础，对新疗法的发展至关重要。尽管评估体内代谢变化在历史上一直具有挑战性，但是分子成像的最新发展使我们能够直接在活体受试者中研究新颖的代谢研究概念，从而使我们更接近患者。然而，在许多情况下，需要与所研究的器官非常接近的传感器，例如以研究血管代谢。

方法

在这项研究中，我们开发并验证了炎症条件下直接在活体受试者体内的代谢检测平台。闪烁光纤收集的信号使用光电倍增管放大，并通过内部可调谐分析平台进行解码。对于体内测试，我们基于巨噬细胞，与炎症紧密相关并热衷于葡萄糖及其类似物¹⁸ F-氟脱氧葡萄糖（¹⁸ F-FDG）的细胞的代谢特征进行实验。该传感器已在新西兰兔中得到验证，其中a）高胆固醇（HC）饮食持续16周或b）血管球囊内皮剥脱继之以HC饮食诱发炎症。

结果

两组之间的体重，血液动力学，血压或心率无差异。 即使通过血管内超声未检测到明显的炎症/动脉粥样硬化，代谢传感器仍可检测到血管炎症（炎症：0.60±0.03 AU，对照组：0.48±0.03 AU，p = 0.01），这突出了系统的高灵敏度。这些发现被离体主动脉组织染色上巨噬细胞的存在所证实。

结论

在这项研究中，我们验证了可调节的非常敏感的代谢传感器平台，该平台可用于检测血管代谢（例如炎症）。该传感器不仅可以用于检测巨噬细胞活性，而且可以与其他探针一起使用，从而可以检测其他病理生理过程。