New methods for deep tissue imaging
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Microscopes play vital role biological science and medicine. For single photon microscopies, the scattering of photons makes regions of interest located a few hundred microns beneath the surface inaccessible. Multi-photon microscopes are widely used for minimally invasive in vivo brain imaging due to their increased imaging depth. However, multi-photon microscopes are hampered by limited dynamic range, preventing weak sample features from being detected in the presence of strong features, or preventing the capture of unpredictable bursts in sample strength. In the first part of the thesis, I present a solution to vastly improve the dynamic range of a multi-photon microscope while limiting potential photodamage. Benefits are shown in both structural and in-vivo functional mouse brain imaging applications. In the second section of the thesis work, I explore a completely different approach towards deep tissue imaging by changing the type of radiation from light to ultrasound. Inspired by an optical phase contrast technique invented in the lab, I developed an unprecedented ultrasound imaging system that can visualize the ultrasound phase contrast in the sample. The ultrasound phase contrast technique is able to visualize local sound speed variations instead of local reflectivity. Compared with existing sound speed tomography systems, our technique eliminates the cumbersome sound speed reconstruction process. The research work in this section contains three parts. In the first part, we designed a low-cost single element scanning system as proof of concept. In the second part, we implemented the ultrasound phase contrast imaging system on a commercial linear phased transducer array and an imaging apparatus designed for samples with finite thickness. In the third part, we studied the feasibility of ultrasound phase contrast imaging in arbitrarily thick tissue. We presented a complete workflow of theoretical study, simulation, prototyping and experimental testing for all three parts.