Medical Terahertz Pulsed Imaging in Reflection Geometry

The terahertz band lies between the microwave and infrared regions of the electromagnetic spectrum. This radiation has very low photon energy and thus it does not pose any ionization hazard for biological tissues. It is strongly attenuated by water and very sensitive to water content. Unique absorption spectra due to intermolecular vibrations in this region have been found in different biological objects. These distinctive advantages over other techniques like x-ray and ultrasound make terahertz very attractive for medical applications. In fact, terahertz imaging and spectroscopy techniques have only a history of about two decades for a previous lack of terahertz sources. Due to strong water absorptions, terahertz radiation cannot penetrate very far into biological samples with high water content. The majority of the limited reported terahertz studies in biomedicine were carried out in transmission mode. In contrast, imaging and spectroscopy in reflection mode remain even less mature. However, if terahertz imaging is to be used in the future for medical purposes, it is likely to be more feasible if conducted in reflection geometry.;Consequently, the objective of this thesis was to develop systematic methods to improve the accuracy of terahertz pulsed imaging based on theoretical calculations, and to further verify them with experimental results. Meanwhile, we have initiated pilot studies for tissue characterization. First of all, algorithms were refined to analytically extract the frequency dependent optical parameters including refractive index and absorption coefficient from measured electric fields. It incorporated the angle of incidence to improve the calculations.;Optical parameters are very sensitive to background noise and other artefacts. The system performances were evaluated and a 5% variation over the raster scanning plane was observed. By comparing the distribution of the intensities measured from homogeneous samples, a new data acquisition protocol and a general data processing algorithm were proposed to solve this problem. With this improvement, the system's percentage variation over different locations was successfully reduced by a factor of 3. To further study the impact of noise on the calculation of optical parameters, simulation work was performed and a method was developed to quantitatively assess the accuracy from the dynamic ranges of the sample signal. Ringing artefacts are introduced by the lower surface of the sample window required in many reflection imaging and spectroscopy systems, thus we devised a new baseline approach to account for this effect. The straightforward protocol in our method enables the reference measurements to be taken reliably and easily such that ringing effects can be determined and excluded in our calculations.;Based on theoretical calculations and experiments, the time of flight formula in our system was established, by which the relationship between layer thickness, optical delay and the refractive index was correctly given. For those samples with layered structures, the thickness information can be readily determined with this formula. In this regard, an in vivo experiment with Tegaderm plaster and the palm of a hand was designed to study the feasibility for burn wound assessment using this time of flight technique.;Finally, to better understand the origin of image contrast as well as for starting potential medical applications, terahertz imaging was applied to study healthy and diseased biological tissues. To this end, protocols and methods were designed for facilitating THz measurements of fresh tissue samples. Using them we first investigated the ability of TPI to differentiate between healthy tissue types from laboratory rats. Parameters in both the time domain and frequency domain were quantified, including their percentage differences and the 95% confidence intervals. Two sample t-tests were used to assess their statistical significance. In the second step, TPI was further employed to quantitatively characterize the difference between healthy and diseased liver samples. Histological examinations were performed to confirm and understand the differences.;In summary, we have refined the algorithms for extracting the optical parameters in reflection geometry. The system performance has been evaluated and several original approaches have been developed to improve the accuracy of the calculation. Thirdly, the time of flight equation in our system has been established and it can be further employed to characterize samples with layered structure. Finally, healthy and diseased tissues have been investigated and protocols for fresh tissue measurements have been studied.