Label-free imaging of metabolic parameters in animals and humans

点击翻译按钮获取中文摘要

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.