Towards non‐invasive monitoring of mitochondrial function

Abstract

__Abstract__ The work presented in this thesis describes the development of a non‐invasive and clinically usable system to monitor important aspects of mitochondrial function. This translational research project started with the validation of PpIX‐TSLT for cutaneous use in an animal model and finished with the first study performed in healthy human volunteers. Chapter 1 explores the possibility of using PpIX‐TSLT to measure oxygen‐dependent delayed fluorescence in skin after topical application of the PpIX precursor 5‐ aminolevulinic acid. To enable reliable cutaneous mitoPO2 measurements on the skin, calibration of the signals was necessary. Previous calibrations of PpIX‐TSLT were performed in cultured cells [10], heart and liver [11, 12]. However, the calibration procedures used for cultured cells and isolated organs were not applicable in skin tissue. Therefore, we developed a novel approach that enables simultaneous measurements of cutaneous mitoPO2 and microvascular oxygen tension in rats (Chapter 2). Subsequently, in Chapter 3, we validated the previously found calibration constants for application on skin by means of these simultaneous measurements. The absolute value of mitoPO2 is an important physiological parameter indicating mitochondrial oxygen availability. However, as investigated in Chapter 4, measurement of the kinetics of delayed fluorescence lifetime (indicative of changes in mitoPO2) after artificially blocking local oxygen supply, provides additional information on mitochondrial oxygen consumption (mitoVO2) and oxygen affinity of the respiratory chain. Having established the feasibility of me