Development of Models, Methods, and Materiel for Deep Tissue Imaging using Light, Ultrasound, and Spectral-Hole Burning

Abstract: The medical imaging technique called “ultrasound optical tomography” (UOT) entails light scattered in tissue that is given spatial information by interacting with an ultrasound field, thus allowing for molecular information to be imaged with ultrasonic resolution. This thesis discusses how UOT can be implemented, with most attention put toward the implementation using spectral-hole-burning filters (SHF) in rare-earth-ion-doped crystals. The thesis further details a first principle computational model – the sequential Monte Carlo (SMC) model – used to predict and assist UOT imaging.Several experimental UOT trials on tissue phantoms were conducted, the first investigating the imaging depth capabilities of UOT using SHF and the validity of the SMC model in homogeneous tissue. The second trial was performed to validate the SMC model in heterogeneous media and investigate methods using the SMC model for improving the acquired image. The final experimental trial was conducted on tissue phantoms mimicking real breast tissue with tumours, investigating how the method would perform in vivo when imaging at the optical wavelength 794 nm with SHFs in stoichiometric Tm3+:LiNbO3, which displayed a 40 dB suppression of the carrier light which does not interact with the ultrasound. This final experimental trial was also a first test of a transportable UOT system using this wavelength which can be moved to a clinical setting. UOT using SHF could, in an investigated in silico scenario, image 2 cm deeper than the other UOT implementation methods discussed. The SMC model could accurately predict the strength of the UOT signal from arbitrary simulation parameters. Using the SMC model, the inverse problem for the optical absorption could be solved in the fraction of the time required by other models. 5×5×5 mm3 large “tumours” could be imaged in 4.2 cm thick breast tissue phantoms. UOT using spectral-hole-burning filters is concluded to be a promising way forward for UOT. Furthermore, the SMC model is concluded to be a promising model for assisting UOT imaging in future endeavours, be it with SHF or another method for implementing UOT.