On the 6th of March 2024 Bas van Kraaij successfully defended his PhD thesis titled: Evaluating the microcirculation in early phase clinical trials: novel methodologies and interventions. The thesis focuses on imaging techniques to measure changes in the vascular system in early phase clinical research. The vascular system is regulated by the endothelium, a single layer of cells within blood vessels, in which nitric oxide (NO) signaling plays a crucial role. NO is an important target that is difficult to measure due to its short half-life and low concentrations available.
The first chapters of the thesis explore various imaging methods that can be used to characterize NO signaling. The chapters investigate the reliability of imaging in evaluating NO-dependent processes and assess physiological challenges or interventions to influence these processes. The chapters discuss various imaging modalities such as laser speckle contrast imaging (LSCI), passive leg movement (PLM), side-stream dark field microscopy (SDFM), near infrared spectroscopy (NIRS), flow mediated skin fluorescence measurements (FMSF) and highlights the necessity for their combined use.
The later chapters explore how the NO-soluble guanylyl cyclase cyclic guanosine monophosphate (NO-sGC-cGMP) system can be altered by a variety of therapeutic interventions. The NO-sGC-cGMP system plays an integral role in cardiovascular, immunological, and neurodegenerative diseases and is therefore an interesting target. The interventions aim to increase the availability of NO which is possible via altering a multitude of targets within the NO-sGC-cGMP system which can best be imaged by employing a combination of imaging techniques.
Overall, this thesis provides an in-depth analysis of the use of wide variety of imaging techniques. This can be used in future research to make informed decisions on the most suitable imaging techniques to provide early pharmacodynamic insight of NO signaling in clinical research.
Read the thesis here
