E. Pickwell

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 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.

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.

Simulating the response of terahertz radiation to basal cell carcinoma using ex vivo spectroscopy measurements

Studies of basal cell carcinoma using terahertz pulsed imaging have revealed a significant difference between regions of tumor and healthy tissue. These differences are manifested in the reflected pulse due to what is thought to be changes in refractive index and absorption. We present measurements of the refractive index and absorption coefficient of excised normal tissue and basal cell carcinoma using terahertz (THz) transmission spectroscopy. We extract Debye parameters from these data and enter them into a finite difference time domain simulation to predict the shape of the waveforms reflected off the normal tissue and basal cell carcinoma and compare them with published in vivo data. Simulating the interaction of terahertz radiation with normal and cancerous tissue is a key step toward understanding the origin of contrast in terahertz images of skin cancer.

A comparison of terahertz pulsed imaging with transmission microradiography for depth measurement of enamel demineralisation in vitro.

Terahertz pulsed imaging (TPI) is a relatively new, non-ionising and non-destructive imaging technique for studying hard tissues which does not require tooth section preparation, unlike transmission microradiography (TMR). If TPI can measure the depths of caries/demineralisation lesions accurately the same tooth samples could be reused and remeasured during in vitro and in situ studies on de- and/or remineralisation. The aim of this study was to compare TPI and TMR for measuring the depths of a range of artificially induced bovine enamel demineralised lesions in vitro. Bovine slabs with artificial caries, induced to different levels of demineralisation by two different but standard demineralisation techniques (‘acid gel’ and ‘carbopol’) were measured by TPI and TMR and the readings compared. The set of TPI/TMR measurements obtained on the gel-demineralised slabs showed an extremely high coefficient of determination (r2 = 0.995). Detailed analysis of the results and theoretical considerations (involving the relationship between refractive index profiling and mineral loss profile) are used to explain the findings and show that for acid gel lesions TPI is measuring demineralisation in the range of 47% of that of TMR depth plus an intercept of 16 µm, with further calculations allowing the TMR depths to be determined to within 5% using TPI.

Terahertz pulsed imaging of cancers

Over the last decade advances in laser and semiconductor technology has allowed the investigation of terahertz region of the electromagnetic spectrum as a potential tool for medical imaging. The terahertz frequency range covers the far infrared wavelengths and is sensitive to librational and vibrational modes of molecules. Terahertz radiation is non-ionizing and is not highly scattered like visible and near infrared light. Terahertz Pulsed Imaging (TPI) has already been demonstrated as an effective tool for differentiating between tissue types in particular normal skin and basal cell carcinoma in vitro. TPI may prove advantageous in distinguishing type, lateral spread and depth of tumors. Here we present recent ex vivo results obtained with a portable TPI system in a clinical setting. It is hoped that this technique could be applied to other epithelial tissues, which give rise to more than 80% of all adult cancers and include common cancers of the skin, oral cavity, breast, colon and prostate.

Medical applications of broadband terahertz pulsed radiation

Advances in semiconductor materials and NIR ultrafast lasers have made it possible to generate and detect broadband electromagnetic pulses with frequencies ranging from 0.1 to over 3 THz (1 THz = 1012 Hz). We present recent work using these THz pulses to image exposed breast cancer and spectroscopic results that indicate differences in the properties of normal and tumourous skin tissue.

Terahertz imaging and spectroscopy of skin cancer

Studies in terahertz (THz) imaging have revealed a difference between diseased and healthy tissue in the THz regime. Since water has strong absorptions at THz frequencies, a likely contributing factor to the contrast mechanism is variation in water content. We have previously modelled the propagation of a THz waveform through water and normal skin in the time domain. In these preliminary results, we extract the complex dielectric coefficients from THz spectroscopy measurements of diseased tissue and predict the waveform differences which have been seen in THz images of skin cancer.

Development of a hand-held TPI system for medical applications

Terahertz pulsed imaging (TPI) is an emerging modality for medical applications. TPI uses pulses of electromagnetic radiation covering a frequency range of 0.1-3 terahertz. These frequencies are nonionizing, provide submillimeter resolution and penetrate several millimeters into tissue. We have developed a fiber coupled hand held TPI scanner for use in medical imaging. We report on preliminary studies using the system in dermatological applications. This study demonstrates the potential of TPI to image skin and encourages further studies in using the system as a surgical aid for identifying tumor margins.