Stephen W. Smye

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.

Do in vivo terahertz imaging systems comply with safety guidelines

Techniques for the coherent generation and detection of electromagnetic radiation in the far infrared, or terahertz, region of the electromagnetic spectrum have recently developed rapidly and may soon be applied for in vivo medical imaging. Both continuous wave and pulsed imaging systems are under development, with terahertz pulsed imaging being the more common method. Typically a pump and probe technique is used, with picosecond pulses of terahertz radiation generated from femtosecond infrared laser pulses, using an antenna or nonlinear crystal. After interaction with the subject either by transmission or reflection, coherent detection is achieved when the terahertz beam is combined with the probe laser beam. Raster scanning of the subject leads to an image data set comprising a time series representing the pulse at each pixel. A set of parametric images may be calculated, mapping the values of various parameters calculated from the shape of the pulses. A safety analysis has been performed, based on current guidelines for skin exposure to radiation of wavelengths 2.6 μm–20 mm (15 GHz–115 THz), to determine the maximum permissible exposure (MPE) for such a terahertz imaging system. The international guidelines for this range of wavelengths are drawn from two U.S. standards documents. The method for this analysis was taken from the American National Standard for the Safe Use of Lasers (ANSI Z136.1), and to ensure a conservative analysis, parameters were drawn from both this standard and from the IEEE Standard for Safety Levels with Respect to Human Exposure to Radio Frequency Electromagnetic Fields (C95.1). The calculated maximum permissible average beam power was 3 mW, indicating that typical terahertz imaging systems are safe according to the current guidelines. Further developments may however result in systems that will exceed the calculated limit. Furthermore, the published MPEs for pulsed exposures are based on measurements at shorter wavelengths and with pulses of longer duration than those used in terahertz pulsed imaging systems, so the results should be treated with caution.Techniques for the coherent generation and detection of electromagnetic radiation in the far infrared, or terahertz, region of the electromagnetic spectrum have recently developed rapidly and may soon be applied for in vivo medical imaging. Both continuous wave and pulsed imaging systems are under development, with terahertz pulsed imaging being the more common method. Typically a pump and probe technique is used, with picosecond pulses of terahertz radiation generated from femtosecond infrared laser pulses, using an antenna or nonlinear crystal. After interaction with the subject either by transmission or reflection, coherent detection is achieved when the terahertz beam is combined with the probe laser beam. Raster scanning of the subject leads to an image data set comprising a time series representing the pulse at each pixel. A set of parametric images may be calculated, mapping the values of various parameters calculated from the shape of the pulses. A safety analysis has been performed, based on curr...

Materials for phantoms for terahertz pulsed imaging

Phantoms are commonly used in medical imaging for quality assurance, calibration, research and teaching. They may include test patterns or simulations of organs, but in either case a tissue substitute medium is an important component of the phantom. The aim of this work was to identify materials suitable for use as tissue substitutes for the relatively new medical imaging modality terahertz pulsed imaging. Samples of different concentrations of the candidate materials TX151 and napthol green dye were prepared, and measurements made of the frequency-dependent absorption coefficient (0.5 to 1.5 THz) and refractive index (0.5 to 1.0 THz). These results were compared qualitatively with measurements made in a similar way on samples of excised human tissue (skin, adipose tissue and striated muscle). Both materials would be suitable for phantoms where the dominant mechanism to be simulated is absorption (approximately 100 cm(-1) at 1 THz) and where simulation of the strength of reflections from boundaries is not important; for example, test patterns for spatial resolution measurements. Only TX151 had a frequency-dependent refractive index close to that of tissue, and could therefore be used to simulate the layered structure of skin, the complexity of microvasculature or to investigate frequency-dependent interference effects that have been noted in terahertz images.

The diagnosis of early pressure sores: report of the pilot study

Thirty-four vascular and general surgical patients were recruited to a pilot study exploring skin blood flow using laser Doppler imaging and clinical assessment of skin erythema in relation to pressure sore development. Brief details of the results, sample size calculations and main study methodology are described in this mid-term report of the Tissue Viability Society Research Fellowship (1998-2000).

A mathematical model of post-canalization thrombolysis

During the initial phase of lysis of an occlusive thrombus using lytic agents such as tissue plasminogen activator, blood flow through the centre of the clot is established (the process of recanalization). Following canalization, the clot remains on the vessel wall and further lysis is required. This paper develops a multi-species mathematical model to describe the bulk chemical reactions in the bloodstream and the convective and diffusive transport of chemical species to and from the clot surface in conditions following canalization. For the steady state case, the model indicates that the process of clot lysis following initial recanalization is dominated by surface chemical reactions and the bulk reactions play little role in the lytic process. Lytic rate is dependent on the clot geometry and flow conditions. The rate of clot dissolution is greatest at the upstream end of the clot and decreases steadily downstream due to lytic agent being removed from the flowing blood as it binds to the clot surface. This model may be further developed and used to simulate and compare different lytic regimes.

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.

Modelling the propagation of terahertz radiation through a tissue simulating phantom

Terahertz (THz) frequency radiation, 0.1 THz to 20 THz, is being investigated for biomedical imaging applications following the introduction of pulsed THz sources that produce picosecond pulses and function at room temperature. Owing to the broadband nature of the radiation, spectral and temporal information is available from radiation that has interacted with a sample; this information is exploited in the development of biomedical imaging tools and sensors. In this work, models to aid interpretation of broadband THz spectra were developed and evaluated. THz radiation lies on the boundary between regions best considered using a deterministic electromagnetic approach and those better analysed using a stochastic approach incorporating quantum mechanical effects, so two computational models to simulate the propagation of THz radiation in an absorbing medium were compared. The first was a thin film analysis and the second a stochastic Monte Carlo model. The Cole-Cole model was used to predict the variation with frequency of the physical properties of the sample and scattering was neglected. The two models were compared with measurements from a highly absorbing water-based phantom. The Monte Carlo model gave a prediction closer to experiment over 0.1 to 3 THz. Knowledge of the frequency-dependent physical properties, including the scattering characteristics, of the absorbing media is necessary. The thin film model is computationally simple to implement but is restricted by the geometry of the sample it can describe. The Monte Carlo framework, despite being initially more complex, provides greater flexibility to investigate more complicated sample geometries.

A mathematical comparison of two models of the electrical properties of biological tissues

The purpose of this paper is to compare two models of the electrical properties of tissue, which may be used to relate the effective conductivity to the volume fraction f of cells in the tissue. Both models assume that tissue comprises spherical cells, which behave electrically as dipoles. The first model, developed by Hanai, describes the tissue as a concentrated suspension of weakly conducting spheres in a conducting medium, with each sphere experiencing a uniform mean field. The second approach, developed by Chiew and Glandt, explicitly describes the effect of a random but statistically homogeneous cell structure on the average field and magnitude of the dipole interaction. The two analyses are identical to first order in f, but differ in the way in which the interactions between the dipoles are accounted for. The model developed by Chiew and Glandt appears to offer a more robust theoretical framework for describing the electrical properties of tissue. The comparison aims to contribute to an improved understanding of the relationship between the electrical properties and spatial structure of tissue.

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.