Terahertz spectroscopy and modelling of biotissue.

Abstract

Pulsed terahertz (THz, or T-ray) research has burgeoned since its inception in the mid 1980s when the first pulses of THz radiation were emitted via electro-optic sampling. At the time, this discovery was a milestone for time domain spectroscopy because existing microwave and Fourier Transform Infrared (FTIR) spectrometers were not sensitive in the 0.1–10 THz frequency range. However, it would take several years before THz generation would become practical for spectroscopic use. In recent years, THz research has progressed to such a great extent that THz generation and detection techniques are now reliable and relatively low-cost, therefore THz has the potential to be used in a vast array of real-world applications ranging from security reinforcement (detection of weapons and explosives) to medical diagnosis (identifying melanomas). Indeed many bodies of research work have successfully demonstrated the efficacy of THz, although many challenges still exist before THz matures beyond the realm of research into everyday life. This Thesis focuses on the area of THz spectroscopy and modelling of biotissue, with the aim of broadening the application of THz in medicine, particularly in the early diagnosis of Alzheimer’s disease (AD). Since the nature of biotissue is complex, THz measurements of biotissue are prone to variability. Therefore, this Thesis includes the study of simpler biological analogues that mimic aspects of biotissue. The work described in this Thesis makes five major novel contributions to THz research of biotissue: (i) the exploration of hydration and storage issues in freshly excised biotissue prior and during THz measurements; (ii) the use of snap-frozen biotissue in THz measurements for the purpose of investigating the plausibility of utilising THz sensing to distinguish between healthy and AD-afflicted human brain tissue; (iii) the use of THz spectroscopy to non-destructively differentiate between soft protein microstructures containing features of one of the known fibrillar pathogens of AD; (iv) the use of THz spectroscopy and full-wave electromagnetics simulation to study scattering from fibrillar structures akin to fibrillar pathogens of AD; and (v) transmission line modelling of THz propagation and reflection from stratified tissue layers in the human head. The first part of this Thesis provides a historical review of the development of THz technology, with emphasis on the contributions of infrared (IR) and microwave research towards the realisation of the various THz generation and detection techniques available today. The various techniques are briefly reviewed prior to a thorough discussion of the types of THz generation and detection techniques used in this Thesis: electro-optic and photoconductive. A reviewof relevant IR,microwave, and THzmedical research completes the first part of this Thesis. In the second part of this Thesis, novel THz measurements of biotissue are presented and their results discussed. Experiment protocols for the handling and storage of excised biotissue are highlighted to emphasise how storage and hydration can severely alter THz measurements. Novel alternative sample preparation techniques, in the form of lyophilisation and snap-freezing, are presented. Terahertz spectroscopic comparison of healthy and AD-afflicted human tissue reveals promise for a future THz diagnostic tool, but highlights the need to investigate simplified biotissue analogues, such as skin, fat, and proteins. This need leads to the third part of this Thesis. The third part of this Thesis involves THz spectroscopic study of one analogue of ADafflicted biotissue: synthetically manufactured microstructures that resemble the proteins associatedwith AD. Terahertz differentiation of thismicrostructure fromonewith a dissimilar shape is revealed, suggesting a new non-destructive application for THz spectroscopy in biomedicine. The mechanism behind the differentiation is believed to be that of scattering, thus the next part of this Thesis explores scattering from more controlled test samples. The penultimate part of this Thesis utilises a full-wave electromagnetics simulator to explain THz scattering from custom-built fibrillar structures. The novel use of the simulator allows a more accurate means of studying THz scattering, resulting in better agreement between measurement and simulation. The extra dimension of information that mathematical simulation provides leads to the final part of this Thesis, where a feasibility study is performed on the use of THz spectroscopy to study tissue layers in the head, with the aim of determining whether current THz systems can be used for in vivo diagnostic studies of tissue layers underneath the skin. The contributions of this Thesis are important steps in advancing the use of THz in medicine, paving the way for the next generation of experimental and mathematical modelling studies of THz interaction with biotissue, in order to develop reliable THz diagnostic tools of the future.