Time-domain diffuse optical spectroscopy towards industrial deployment

The complexity of our body is outstanding, since the very beginning, humankind has developed methods and technologies to improve the understanding of our physiology, driven by the desire of defeating diseases and an insatiable curiosity. Enormous advances have been achieved in clinical diagnosis. Novel technologies enable us to have high detail 3D images of most organs of our body and can retrieve a clear picture of our health at a given timeframe. Less is although known about what happens to our body in action. Most non-invasive medical devices, that can access our brain and muscle behaviour, are very expensive, bulky, and require the subjects to stay still during the examinations (e.g. CT, fMRI and PET), this prevents us to know how our organs behave in real-life conditions. Our neurons need oxygen to operate, and brain behaviours can be recorded by measuring regional cerebral hemodynamic thanks to the neurovascular coupling mechanism. Our muscles functions are also dependent on oxygen delivery. Accessing tissue oxygenation is therefore paramount to improve our understanding of human physiology. Time-domain near-infrared spectroscopy (TD-NIRS) is an optical technique that exploits the temporal shape modification of picosecond laser pulses diffusing in human tissue, to retrieve hemodynamic properties up to 3 cm depth. Compared to more common diffuse optics (DO) techniques, TD-NIRS can disentangle absorption and reduced scattering coefficients, leading to more accurate DO measurements, in addition, it is less sensitive to motion artifacts. The main limitations of TD-NIRS are its complexity and bulkiness that prevent it to widely spread in the clinical environment. In this framework, my efforts have been focused on the development of a novel, compact TD-NIRS oximeter, that could be easy to use and provide direct access to real-time human tissue oxygenation in “outside of the lab” conditions. The device was deployed and tested, showing promising results also in comparison with other state-of-the-art systems. It was employed in in-vivo measurements targeting motor disorders, one of the big plagues of the modern world representing high expenses for the healthcare system of all countries. A deeper knowledge of how neuromotor mechanisms behave is needed to tackle this issue and our technology can give a contribution to that by monitoring motor cortex activity in freely moving humans. My studies, performed in collaboration with physiologists and physiotherapists, aimed to record the functional activation of the motor cortex area. The device showed to be effective and accurate in recording functional brain activation unveiling basic knowledge on brain functions in everyday-life conditions. It is the first time, to our knowledge that the cerebral motor cortex of healthy subjects was measured by TD-NIRS during freely moving walking exercises. As side projects, the system was used in other DO applications, in the veterinary field, and in the food and agriculture sector. We entered veterinary clinics, to assess equine muscles hemodynamic during stressful operations and diagnosis, lowering the risk of muscle damages due to hypoxia or ipo-perfusion of blood. Furthermore, thanks to the ability of TD-NIRS in non-destructively recording the concentration of chlorophyll in the pulp of fruits, we studied the ripening evolution of pears during post-harvest conservation in controlled atmosphere in the framework of the ESPERA project. The findings we achieved as well as the interest in technology able to satisfy the unmet need of assessing deep tissue hemodynamic lead us to the foundation of a start-up company, PIONIRS s.r.l., spin-off of Politecnico di Milano. The company aims to develop and commercialize the next generation of time-resolved tissue oximeters for clinical use making TD-NIRS technology accessible to the world. Thanks to the industrial support, it was possible to have access to multiple replicas of time-resolved oximeter products and contribute to developing specific procedures for their quality assessment. Indeed, well-structured protocols are nowadays lacking and will be cardinal in the future of industrial DO devices. Politecnico di Milano and PIONIRS are nowadays working along with other six partners in the VASCOVID European project, intending to deploy and mature a portable, non-invasive and real-time health monitoring medical device for the assessment of microvascular health in COVID-19 patients at the intensive care.