Richard J. Pye

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.

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.

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.

Terahertz pulsed imaging and spectroscopy for biomedical and pharmaceutical applications

Terahertz (THz) radiation lies between the infrared and microwave regions of the electromagnetic spectrum. Advances in THz technology have opened up many opportunities in this scientifically and technologically important spectroscopic region. The THz frequency range excites large amplitude vibrational modes of molecules as well as probing the weak interactions between them. Here we describe two techniques that utilize THz radiation, terahertz pulsed imaging (TPI) and terahertz pulsed spectroscopy (TPS). Both have a variety of possible applications in biomedical imaging and pharmaceutical science. TPI, a non-invasive imaging technique, has been used to image epithelial cancer ex vivo and recently in vivo. The diseased tissue showed a change in absorption compared to normal tissue, which was confirmed by histology. To understand the origins of the differences seen between diseased and normal tissue we have developed a TPS system. TPS has also been used to study solids of interest in the pharmaceutical industry. One particularly interesting example is ranitidine hydrochloride, which is used in treatment of stomach ulcers. Crystalline ranitidine has two polymorphic forms known as form 1 and form 2. These polymorphs have the same chemical formula but different crystalline structure that give rise to different physiochemical properties of the material. Using TPS it is possible to rapidly distinguish between the two polymorphic forms.

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.

Terahertz pulse imaging of in-vitro basal cell carcinoma samples

Summary form only given. The use of Terahertz Pulse Imaging (TPI) for the analysis of skin cancer has been investigated. Our initial experiments have focused on the analysis of basal cell carcinoma (BCC), the most common form of skin cancer. BCC seldom metastasize but can be locally very invasive. The current diagnosis of carcinomas is by visual examination, where suspicious lesions require biopsy and subsequent histological diagnosis, which is painful, time consuming and may require additional tissue removal. The use of TPI as a diagnostic tool for skin cancer is of particular interest as its long wavelengths lead to a reduction in Rayleigh scattering and a resultant axial resolution of approximately 80 /spl mu/m. The spectroscopic information of TPI may prove to be advantageous in the discrimination between tumor types, which is unattainable using other methods such as ultrasound. Through the use of TPI, unnecessary biopsies could be avoided, by providing in-vivo measurements before surgery to identify the type and depth of tumor present.

Terahertz pulse imaging in reflection geometry of skin tissue using time-domain analysis techniques

We demonstrate the application of Terahertz Pulse Imaging (TPI) in reflection geometry for the study of skin tissue and related cancers. The terahertz frequency regime of 0.1-100THz excites the vibrational modes of molecules, allowing for spectroscopic investigation. The sensitivity of terahertz to polar molecules, such as water, makes TPI suitable for studying the hydration levels in the stratum corneum 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). Measurements on scar tissue, which is known to contain less water than the surrounding skin, and on regions of inflammation, show a clear contrast in the THz image compared to normal skin. We discuss the time domain analysis techniques used to classify the different tissue types. Basal cell carcinoma shows a positive terahertz contrast, and inflammation and scar tissue shows a negative terahertz contrast compared to normal tissue. This demonstrates for the first time the potential of TPI both in the study of skin cancer and inflammatory related disorders.

Biomedical applications of terahertz pulse imaging

Over the last decade advances in laser and semiconductor technology has allowed us to investigate the 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 nonionizing and is not highly scattered like visible and near infrared light. Terahertz pulse imaging has already demonstrated it effectiveness in vivo and by differentiating between tissue types in particular, benign and malignant tissue in vitro.

Biomedical applications of terahertz technology

We present results which demonstrate the ability of Terahertz Pulse Imaging (TPI) to distinguish between carcinoma and normal tissue. This technique is the first to be used to identify basal cell carcinoma macroscopically in the terahertz frequency regime. The increase in absorption observed in the diseased tissue is attributed to an increase in the amount or a change in the binding of water within the basal cell carcinoma. This makes water an important molecular marker for TPI. Our results represent a new application for the use of terahertz radiation in distinguishing carcinoma from normal tissue.

Biomedical applications of THz imaging

The technology behind optically-driven terahertz (THz) system is now well developed and commercial applications of this new technology are now beginning to emerge. The terahertz frequency range (0.1 to 10 THz) covers far infrared wavelengths. Terahertz light has the advantages that it is non-ionizing and is not highly scattered like visible and near-infrared light. Terahertz pulsed imaging (TPI) is a reflection imaging method that has been used successfully in the past for non-medical applications. More recently, a portable TPI has been used to image a variety of human tissues, like teeth, skin and breast.