Donald D. Arnone

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.

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.

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.

Applications of terahertz (THz) technology to medical imaging

An imaging system has been developed based on pulses of Terahertz (THz) radiation generated and detected using all- optical effects accessed by irradiating semiconductors with ultrafast pulses of visible laser light. This technique, commonly referred to as T-Ray Imaging or THz Pulse Imaging (TPI), holds enormous promise for certain aspects of medical imaging. We have conducted an initial survey of possible medical applications of TPI and demonstrated that TPI images show good contrast between different animal tissue types. Moreover, the diagnostic power of TPI has been elicidated by the spectra available at each pixel in the image, which are markedly different for the different tissue types. This suggests that the spectral information inherent in TPI might be used to identify the type of soft and hard tissue at each pixel in an image and provide other diagnostic information not afforded by conventional imagin techniques. Preliminary TPI studies of pork skin show that 3D tomographic imaging of the skin surface and thickness is possible, and data from experiments on models of the human dermis are presented which demonstrate that different constituents of skin have different refractive indices. Lastly, we present the first THz image of human tissue, namely an extracted tooth. The time of flight of THz pulses through the tooth allows the thickness of the enamel to be determined, and is used to create an image showing the enamel and dentine regions. Absorption of THz pulses in the tooth allows the pulp cavity region to be identified. Initial evidence strongly suggests that TPI my be used to provide valuable diagnostic information pertaining to the enamel, dentine, and the pump cavity.

Terahertz imaging and spectroscopy of human skin in vivo

We demonstrate the application of terahertz pulse imaging for the in-vivo study of human tissue, in this case the upper layers of human skin. The terahertz pulses comprise frequencies from below 100 GHz to over 2 THz and are generated using optical pulse excited semiconductor devices with a conversion efficiency of better than 10-3. The terahertz pulses are used to obtain tomographic information on the skin surface tissue. From the data the stratum corneum thickness and hydration may be mapped or cross-sectional images displayed.

Biomedical applications of Terahertz Pulse Imaging

We present Terahertz Pulse Imaging (TPI) results of different human tissue types. Our results are part of an initial study to explore the potential of TPI for biomedical applications. A survey of different tissue types has demonstrated the various contrast mechanisms that are available in TPI, allowing different tissue types to be readily identified. This encourages the pursuit of further studies of TPI for a variety of biomedical applications.

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.

Effect of terahertz irradiation on ballistic transport through one‐dimensional quantum point contacts

A one‐dimensional ballistic constriction has been fabricated from a two‐dimensional electron gas formed at the interface of a GaAs/AlGaAs heterostructure. The constriction was induced via a pair of front gates which also served as a broadband far‐infrared (FIR) antenna. The photocurrent through the constriction was recorded as a function of source‐drain bias at various FIR frequencies, one‐dimensional subband spacings, and for orthogonal FIR polarizations. The photocurrent was compared to the derivative of dc conductance with respect to source‐drain bias. While dc rectification is shown to dominate the photocurrent, deviations from this model occur at frequencies above ∼1 THz, yielding an estimate of the upper limit of the electron scattering time in the constriction region.

Far‐infrared study of a quasi‐one‐dimensional electron gas formed on (100)GaAs facets with hole gas sidegates on a (311)A GaAs substrate

A new type of quasi‐one‐dimensional electron gas has been realized by using molecular beam epitaxy to grow a high mobility heterostructure on a (311)A GaAs substrate selectively etched to expose (100) facets. The electron gas formed on the (100) facets is confined in one lateral dimension by the p–n junctions formed with the adjacent two‐dimensional hole gases on (311)A, thereby forming a p–n–p structure. Far‐infrared cyclotron resonance spectra demonstrate the dimensionality of such structures and yield typical lateral confinement energies of 22.3 cm−1 and electronic widths of ∼900 nm. These estimates are supported by cathodoluminescence data.

Terahertz imaging of breast cancer, a feasibility study

We have developed a portable terahertz pulsed imaging system (TPI) for use in a hospital environment. The system uses photoconduction to generate and detect terahertz with a frequency content from 0.1-4 THz. In this paper, we report on a feasibility study using TPI for imaging tumours of the breast. Several breast samples were imaged and parameters from the time domain impulse functions were used to provide a contrast with good agreement to histology. This preliminary study demonstrates the potential of TPI to image breast tumours and encourages further studies to determine the ability of the technique to discriminate different types of tumour.