Label-free imaging of metabolic parameters in animals and humans

多光谱光声断层扫描（MSOT）使氧和脱氧血红蛋白的无标记成像作为一种内在的组织生物传感器，以解决氧饱和度和利用作为代谢指标。此外，它还可以成像脂质分布和水。 因此，它具有很强的潜力，提供动态测量的心脏代谢状态。然而，MSOT目前尚未优化，也未验证用于代谢研究。我们的目标是开发一种更深入的MSOT，并确认体内MSOT测定在代谢疾病的背景下体内测量组织生物能量学和脂质谱。首先，将为MSOT设计一种新的几何形状，并与扩展的波长范围相结合，以提高人体肌肉、棕色脂肪组织（BAT）和血管系统中血红蛋白和脂质成像的穿透深度和准确性-这对于确认其他子项目所需的深层MSOT至关重要。随后，这种新的MSOT能力将用于提供氧化代谢的指标，计算为不同组织隔室中氧饱和度和脂质利用率和组成的时间导数。我们将验证MSOT是否能够可靠地量化人类志愿者的皮下脂肪和肌肉脂肪，然后通过量化健康志愿者锁骨上区域的脂质和血红蛋白分布，探索无需激活即可识别BAT的存在。将测量结果与BMI和其他临床指标的相应测量结果进行对比。我们的目标是提供一个经过验证的MSOT功能集，量化局部和肌内脂质成分或BAT，与当前的临床标准相比，能够实现更准确的表征。为了验证血管系统中MSOT分辨的脂质成分，将开发一个局部光谱MSOT测试，以测量和了解食物摄入和脂质消化动力学，因为它们与项目P1，P2和P6有关。该试验将有助于确定不同群体的脂质消化动力学（例如，运动员、其他健康志愿者、心血管疾病和糖尿病患者），目的是将这些数据与组织成分和动态测量相结合（锻炼肌肉，BAT激活）来研究肥胖，BAT含量和脂质消化之间的相关性。最后，使用模拟、体模和实验测量，包括在P1、P2和P6中收集的人类和小鼠数据，将脂质/水与血红蛋白/氧合信号相关联。我们将检查我们的计算工具的性能，并监测这两个测量之间可能的串扰在休息和代谢活跃的组织，从而在一个有效的测定研究脂质代谢和血流动力学在一个无标记的方式在体内。该子项目的结果将为在其他子项目中以及更广泛地在心脏代谢医学中利用MSOT作为确认和验证的模式铺平道路。

Multispectral optoacoustic tomography (MSOT) enables label-free imaging of oxy- and deoxy-hemoglobin as an intrinsic tissue biosensor to resolve oxygen saturation and utilization as a metabolic indicator. Moreover, it images lipid distribution and water. Therefore, it has strong potential to provide dynamic measurements of cardio-metabolic status. However, MSOT is currently not optimized and not validated for metabolism studies.Our goal is to develop a deeper-reaching MSOT and confirm in-vivo MSOT assays for measuring tissue bioenergetics and lipid profiles in-vivo in the context of metabolic diseases. First, a new geometry for MSOT will be designed and combined with an extended wavelength range to improve the penetration depth and accuracy for hemoglobin and lipid imaging in human muscle, brown adipose tissue (BAT) and the vascular system – critical for confirming deep-reaching MSOT for the needs of the other sub-projects. Subsequently, this new MSOT ability will be used to provide metrics of oxidative metabolism, calculated as the time derivative of oxygen saturation and lipid utilization and composition in different tissue compartments. We will validate MSOT to reliably quantify subcutaneous and muscle fat in human volunteers and then explore the identification of BAT presence without the need of activation, by quantifying lipid and hemoglobin distributions in the supraclavicular region of healthy volunteers. Measurements will be contrasted to corresponding measurements by BMI and other clinical metrics. We aim to deliver a validated MSOT feature-set that quantifies local and intra-muscular lipid composition or BAT, enabling more accurate characterization compared to the current clinical standards.To validate MSOT-resolved lipid composition in vasculature, a localized spectroscopy MSOT test will be developed to measure and understand food intake and lipid digestion dynamics, as they relate to projects P1, P2, and P6. The test will be useful for identifying the dynamics of lipid digestion in different groups (e.g. athletes, other healthy volunteers, cardiovascular disease and diabetic patients) with the aim of combining this data with tissue composition and dynamic measurements (exercising muscle, BAT activation) to investigate correlations between obesity, BAT content, and lipid digestion.Finally, lipid/water will be correlated to hemoglobin/oxygenation signals using simulations, phantom and experimental measurements, including human and mouse data gathered in P1, P2 and P6. We will examine the performance of our computational tools and monitor against possible cross-talk between these two measurements at rest and in metabolically active tissues, resulting in a validated assay for studying lipid metabolism and hemodynamics in a label-free fashion in-vivo. The results of this sub-project will pave the way to utilize MSOT in the other sub-projects and more generally in cardiometabolic medicine as a confirmed and validated modality.