Anthony J. Fitzgerald

The interaction between Terahertz radiation and biological tissue

Terahertz (THz) radiation occupies that region of the electromagnetic (EM) spectrum between approximately 0.3 and 20 THz. Recent advances in methods of producing THz radiation have stimulated interest in studying the interaction between radiation and biological molecules and tissue. Given that the photon energies associated with this region of the spectrum are 2.0 x 10(-22) to 1.3 x 10(-20) J, an analysis of the interactions requires an understanding of the permittivity and conductivity of the medium (which describe the bulk motions of the molecules) and the possible transitions between the molecular energy levels. This paper reviews current understanding of the interactions between THz radiation and biological molecules, cells and tissues. At frequencies below approximately 6 THz. the interaction may be understood as a classical EM wave interaction (using the parameters of permittivity and conductivity), whereas at higher frequencies. transitions between different molecular vibrational and rotational energy levels become increasingly important and are more readily understood using a quantum-mechanical framework. The latter is of particular interest in using THz to probe transitions between different vibrational modes of deoxyribonucleic acid. Much additional experimental work is required in order to fully understand the interactions between THz radiation and biological molecules and tissue.

An introduction to medical imaging with coherent terahertz frequency radiation

Methods have recently been developed that make use of electromagnetic radiation at terahertz (THz) frequencies, the region of the spectrum between millimetre wavelengths and the infrared, for imaging purposes. Radiation at these wavelengths is non-ionizing and subject to far less Rayleigh scatter than visible or infrared wavelengths, making it suitable for medical applications. This paper introduces THz pulsed imaging and discusses its potential for in vivo medical applications in comparison with existing modalities.

Optical properties of tissue measured using terahertz pulsed imaging.

The first demonstrations of terahertz imaging in biomedicine were made several years ago, but few data are available on the optical properties of human tissue at terahertz frequencies. A catalogue of these properties has been established to estimate variability and determine the practicality of proposed medical applications in terms of penetration depth, image contrast and reflection at boundaries. A pulsed terahertz imaging system with a useful bandwidth 0.5-2.5 THz was used. Local ethical committee approval was obtained. Transmission measurements were made through tissue slices of thickness 0.08 to 1 mm, including tooth enamel and dentine, cortical bone, skin, adipose tissue and striated muscle. The mean and standard deviation for refractive index and linear attenuation coefficient, both broadband and as a function of frequency, were calculated. The measurements were used in simple models of the transmission, reflection and propagation of terahertz radiation in potential medical applications. Refractive indices ranged from 1.5 ± 0.5 for adipose tissue to 3.06 ± 0.09 for tooth enamel. Significant differences (P < 0.05) were found between the broadband refractive indices of a number of tissues. Terahertz radiation is strongly absorbed in tissue so reflection imaging, which has lower penetration requirements than transmission, shows promise for dental or dermatological applications.

Evaluation of image quality in terahertz pulsed imaging using test objects

As with other imaging modalities, the performance of terahertz (THz) imaging systems is limited by factors of spatial resolution, contrast and noise. The purpose of this paper is to introduce test objects and image analysis methods to evaluate and compare THz image quality in a quantitative and objective way, so that alternative terahertz imaging system configurations and acquisition techniques can be compared, and the range of image parameters can be assessed. Two test objects were designed and manufactured, one to determine the modulation transfer functions (MTF) and the other to derive image signal to noise ratio (SNR) at a range of contrasts. As expected the higher THz frequencies had larger MTFs, and better spatial resolution as determined by the spatial frequency at which the MTF dropped below the 20% threshold. Image SNR was compared for time domain and frequency domain image parameters and time delay based images consistently demonstrated higher SNR than intensity based parameters such as relative transmittance because the latter are more strongly affected by the sources of noise in the THz system such as laser fluctuations and detector shot noise.

Two methods for modelling the propagation of terahertz radiation in a layered structure.

Modelling the interaction of terahertz(THz) radiation with biological tissueposes many interesting problems. THzradiation is neither obviously described byan electric field distribution or anensemble of photons and biological tissueis an inhomogeneous medium with anelectronic permittivity that is bothspatially and frequency dependent making ita complex system to model.A three-layer system of parallel-sidedslabs has been used as the system throughwhich the passage of THz radiation has beensimulated. Two modelling approaches havebeen developed a thin film matrix model anda Monte Carlo model. The source data foreach of these methods, taken at the sametime as the data recorded to experimentallyverify them, was a THz spectrum that hadpassed though air only.Experimental verification of these twomodels was carried out using athree-layered in vitro phantom. Simulatedtransmission spectrum data was compared toexperimental transmission spectrum datafirst to determine and then to compare theaccuracy of the two methods. Goodagreement was found, with typical resultshaving a correlation coefficient of 0.90for the thin film matrix model and 0.78 forthe Monte Carlo model over the full THzspectrum. Further work is underway toimprove the models above 1 THz.

Optical properties of tissue at terahertz frequencies

A pulsed terahertz imaging system has been developed for potential use in vivo. Few data are available regarding the optical properties of human tissue at terahertz frequencies. This work demonstrates transmission measurements through human ex vivo tissue sections, and determines broadband refractive indices, and broadband and frequency dependent absorption coefficients. The data presented here are the first systematic measurements of this type. Significant differences were found between a numbers of human tissue types.

Two methods for modeling the propagation of terahertz radiation in a layered structure

Terahertz (THz) radiation is being studied as an investigative tool for skin conditions. Two approaches for describing the propagation of THz radiation through skin are presented and verified using a layered water-based phantom. The skin was assumed to comprise a series of layers of tissue with differing, frequency dependent, properties; the major interaction was assumed to be between THz radiation and water. Based on these assumptions a thin film matrix model and a Monte Carlo model were developed to simulate this situation. In order to test these models, a simple three layer in-vitro phantom was used. This consisted of two 2 mm layers of TPX, encasing a 180 micrometer layer of a water/propanol-1 mixture. Spectroscopic measurements were made in a pulsed THz system for cells with thirteen different water/propanol-1 concentrations. Comparisons between the results from both models and experimental spectra show good correlation, in each case the model was able to simulate the overall trend of the spectra and more detailed features. This suggests that the models may be adapted to investigate THz irradiation of skin. Modeling modifications would include using layer dimensions that were comparable to the constituent layers of skin and using additional layers to describe the organ more thoroughly.

Effects of frequency on image quality in terahertz-pulsed images

Terahertz imaging is an emerging modality, with potential for medical applications, using broadband sub-picosecond electromagnetic pulses in the range of frequencies between 100 GHz and 100 terahertz (THz). Images can be formed using parameters derived from the time domain, or at the range of frequencies in the Fourier domain. The choice of frequency at which to image may be an important factor for clinical applications. Image quality as a function of frequency was assessed for a terahertz pulsed imaging system by means of; (i) image noise measurements on a specially designed step wedge, and (ii) modulation transfer functions (MTF) derived from a range of spatial frequency square wave patterns. It was found that frequencies with larger signal magnitude gave lower image noise, measured using relative standard deviation (standard deviation divided by mean) for uniform regions of interest of the step wedge image. MTF results were as expected, with higher THz frequency signals demonstrating a consistently higher MTF and higher spatial frequency limiting resolution than the lower THz frequencies. There is a trade-off between image noise and spatial resolution with image frequency. Higher frequencies exhibit better spatial resolution than lower frequencies, however the decrease in signal power results in a degradation of the image.