Material and technique development for ultrasound optical tomography using spectral hole burning filters

Sammanfattning: The molecular sensitivity provided by optical photons has potential advantages in medical diagnostics, for example, in distinguishing healthy from cancerous tissue. However, scattering resulting from inhomogeneities in the refractive index of tissues prevents spatially resolved optical measurements in biological material, except at very shallow depths. This thesis presents research on a medical imaging technique called ultrasound optical tomography (UOT), which overcomes the limit on resolution resulting from scattering by combining photons and ultrasound. Photons are locally frequency shifted (tagged) by ultrasonic waves inside the tissue. Optical contrast can be obtained with ultrasonic spatial resolution by detecting these tagged photons. In this work, the tagged photons were detected using narrowband optical passband filters created in rare-earth-ion-doped crystals using spectral hole burning techniques. The thesis presents UOT measurements using Pr3+:Y2SiO5 filters operating at 606 nm, which characterize the signal strength under various well-controlled experimental conditions. Improved understanding of the performance of an optimized UOT set-up based on spectral hole burning was obtained by fitting experimental data with theoretical models, indicating that imaging depths of several centimetres should be possible in biological tissues. A theoretical comparison of the many UOT methods described in the literature is presented. The findings indicate that spectral hole burning filters may have better contrast-to-noise scaling, and thus potentially greater imaging depths, than other UOT methods such as digital off-axis holography, photorefractive holography, and speckle contrast imaging. A major challenge for spectral-hole-burning filter-based UOT to become useful for in vivo applications, is to identify and develop crystals capable of supporting the required high-contrast filters at wavelengths within the optical window for tissue (~650-950 nm). Experimental values of the filter contrast obtained in UOT measurements in this wavelength range have so far been limited to 14 dB. Based on spectroscopic measurements, Tm3+:LaF3 is proposed as a candidate for UOT filtering at 690 and 797 nm. Measurements show that a filter contrast above 50 dB is possible at the 690 nm transition for a collimated laser beam. The high filter contrast of Tm3+:LaF3 is expected to be important for the future development of UOT using spectral hole burning filters.