Vincent P. Wallace

Terahertz pulse imaging in reflection geometry of human skin cancer and skin tissue

We demonstrate the application of terahertz pulse imaging (TPI) in reflection geometry for the study of skin tissue and related cancers both in vitro and in vivo. The sensitivity of terahertz radiation to polar molecules, such as water, makes TPI suitable for studying the hydration levels in the skin and the determination of the lateral spread of skin cancer pre-operatively. By studying the terahertz pulse shape in the time domain we have been able to differentiate between diseased and normal tissue for the study of basal cell carcinoma (BCC). Basal cell carcinoma has shown a positive terahertz contrast, and inflammation and scar tissue a negative terahertz contrast compared to normal tissue. In vivo measurements on the stratum corneum have enabled visualization of the stratum corneum-epidermis interface and the study of skin hydration levels. These results demonstrate the potential of terahertz pulse imaging for the study of skin tissue and its related disorders, both in vitro and in vivo.

Biomedical applications of terahertz technology

We review the development of terahertz (THz) technology and describe a typical system used in biomedical applications. By considering where the THz regime lies in the electromagnetic spectrum, we see that THz radiation predominantly excites vibrational modes that are present in water. Thus, water absorption dominates spectroscopy and imaging of soft tissues. However, there are advantages of THz methods that make it attractive for pharmaceutical and clinical applications. In this review, we consider applications ranging from THz spectroscopy of crystalline drugs to THz imaging of skin cancer.

In vivo study of human skin using pulsed terahertz radiation

Studies in terahertz (THz) imaging have revealed a significant difference between skin cancer (basal cell carcinoma) and healthy tissue. Since water has strong absorptions at THz frequencies and tumours tend to have different water content from normal tissue, a likely contrast mechanism is variation in water content. Thus, we have previously devised a finite difference time-domain (FDTD) model which is able to closely simulate the interaction of THz radiation with water. In this work we investigate the interaction of THz radiation with normal human skin on the forearm and palm of the hand in vivo. We conduct the first ever systematic in vivo study of the response of THz radiation to normal skin. We take in vivo reflection measurements of normal skin on the forearm and palm of the hand of 20 volunteers. We compare individual examples of THz responses with the mean response for the areas of skin under investigation. Using the in vivo data, we demonstrate that the FDTD model can be applied to biological tissue. In particular, we successfully simulate the interaction of THz radiation with the volar forearm. Understanding the interaction of THz radiation with normal skin will form a step towards developing improved imaging algorithms for diagnostic detection of skin cancer and other tissue disorders using THz radiation.

Terahertz pulsed spectroscopy of freshly excised human breast cancer

The complex refractive indices of freshly excised healthy breast tissue and breast cancers collected from 20 patients were measured in the range of 0.15 - 2.0 THz using a portable terahertz pulsed transmission spectrometer. Histology was performed to classify the tissue samples as healthy adipose tissue, healthy fibrous breast tissue, or breast cancers. The average complex refractive index was determined for each group and it was found that samples containing cancer had a higher refractive index and absorption coefficient. The terahertz properties of the tissues were also used to simulate the impulse response functions expected when imaging breast tissue in a reflection geometry as in terahertz pulsed imaging (TPI). Our results indicate that both TPS and TPI can be used to distinguish between healthy adipose breast tissue, healthy fibrous breast tissue and breast cancer due to the differences in the fundamental optical properties.

Terahertz Pulsed Imaging of Skin Cancer in the Time and Frequency Domain

Terahertz Pulsed Imaging(TPI) is a new medical imaging modality forthe detection of epithelial cancers. Overthe last two years this technique has beenapplied to the study of in vitrobasal cell carcinoma (BCC). Usingtime-domain analysis the contrast betweendiseased and normal tissue has been shownto be statistically significant, andregions of increased terahertz (THz)absorption correlated well with thelocation of the tumour sites in histology.Understanding the source of this contrastthrough frequency-domain analysis mayfacilitate the diagnosis of skin cancer andrelated skin conditions using TPI. Wepresent the first frequency-domain analysisof basal cell carcinoma in vitro,with the raw power spectrum giving aninsight into the surface features of theskin. Further data manipulation is requiredto determine whether spectral informationcan be extrapolated at depth. These resultshighlight the complexity of working inreflection geometry.

Terahertz pulsed imaging of basal cell carcinoma ex vivo and in vivo

Background  Terahertz radiation lies between the infrared and microwave regions of the electromagnetic spectrum and can be used to excite large amplitude vibrational modes of molecules and probe the weak interactions between them. Terahertz pulsed imaging (TPI) is a noninvasive imaging technique that utilises this radiaton.

Influence of optical properties on two-photon fluorescence imaging in turbid samples

A numerical model was developed to simulate the effects of tissue optical properties, objective numerical aperture (N.A.), and instrument performance on two-photon-excited fluorescence imaging of turbid samples. Model data are compared with measurements of fluorescent microspheres in a tissuelike scattering phantom. Our results show that the measured two-photon-excited signal decays exponentially with increasing focal depth. The overall decay constant is a function of absorption and scattering parameters at both excitation and emission wavelengths. The generation of two-photon fluorescence is shown to be independent of the scattering anisotropy, g, except for g > 0.95. The N.A. for which the maximum signal is collected varies with depth, although this effect is not seen until the focal plane is greater than two scattering mean free paths into the sample. Overall, measurements and model results indicate that resolution in two-photon microscopy is dependent solely on the ability to deliver sufficient ballistic photon density to the focal volume. As a result we show that lateral resolution in two-photon microscopy is largely unaffected by tissue optical properties in the range typically encountered in soft tissues, although the maximum imaging depth is strongly dependent on absorption and scattering coefficients, scattering anisotropy, and objective N.A..

Terahertz Pulsed Spectroscopy of Human Basal Cell Carcinoma

Good contrast is seen between normal tissue and regions of tumor in terahertz pulsed imaging of basal cell carcinoma (BCC). To date, the source of contrast at terahertz frequencies is not well understood. In this paper we present results of a spectroscopy study comparing the terahertz properties (absorption coefficient and refractive index) of excised normal human skin and BCC. Both the absorption coefficient and refractive index were higher for skin that contained BCC. The difference was statistically significant over the range 0.2 to 2.0 THz (6.6 cm−1 to 66.6 cm−1) for absorption coefficient and 0.25 to 0.90 THz (8.3 cm−1 to 30 cm−1) for refractive index. The maximum difference for absorption was at 0.5 THz (16.7 cm−1). These changes are consistent with higher water content. These results account for the contrast seen in terahertz images of BCC and explain why parameters relating to the reflected terahertz pulse provide information about the lateral spread of the tumor. Knowing the properties of the tissue over the terahertz frequency range will enable the use of mathematical models to improve understanding of the terahertz response of normal and diseased tissue.

Three-dimensional terahertz pulse imaging of dental tissue

There are unresolved clinical problems that require the provision of accurate 3-D images of tissue structures such as teeth. In particular, measurements of dental enamel thickness are necessary to quantify problems associated with enamel erosion, yet currently there is no nondestructive method to obtain this information. We present a method that relies on the use of pulsed terahertz radiation to gain 3-D information from dental tissues. We discuss results from 14 samples and demonstrate that we can reliably and accurately quantify enamel thickness. We show that in a series of 22 surfaces, we can image pertinent subsurface features 91% of the time. Example images are shown where structures in teeth at depth are rendered accurate to within 10 microm. We discuss issues that arise using this imaging method and propose ways in which it could be used in clinical practice.

Simulation of terahertz pulse propagation in biological systems

Studies in terahertz (THz) imaging have revealed a significant difference between skin cancer (basal cell carcinoma) and healthy tissue. Since water has strong absorptions at THz frequencies and tumor affects the water content of tissue, a likely contrast mechanism is variation in water content. Modeling the propagation of a THz pulse through water is the first step toward understanding the origin of contrast in terahertz pulsed images of skin cancer. In this letter, we develop a finite-difference-time-domain simulation to model the propagation of a THz pulse and incorporate double Debye theory to model the behavior of water subject to THz radiation. Furthermore, we apply this model to skin.