The terahertz (THz) frequency range lies between the infrared and microwave regions of the spectrum and corresponds to wavelengths from millimeters to microns. The associated low energies interact with low-frequency motions in molecular systems such as the flexing of individual molecules or intermolecular interactions through either weak van der Waals forces or the stronger hydrogen bonds. This interactivity makes THz-frequency radiation highly sensitive to water concentration as evident in the properties of soft tissues.1 THz radiation is nonionizing and not highly scattered in tissues (unlike optical emission), thus making it attractive for use in biomedical applications.2 The development in the last few years of practical methods to generate and detect broadband pulses of THz radiation that can be contained within portable systems suitable for clinical studies has led to its use in the detection of skin and breast cancers.3,4
THz radiation is generated using a photoconductive emitter consisting of a small piece of semiconductor crystal (commonly gallium arsenide) on which two planar metal electrodes form an antenna supporting a large electric field across its surface (see Figure 1). Ultrafast (approximately 100fs) pulses of light (commonly from a titanium/sapphire laser at a wavelength of 800nm) are then focused onto the gap between the electrodes. This generates charge carriers in the form of electron–hole pairs. The application of a bias voltage accelerates these charge carriers, producing a THz pulse that is radiated into free space.5 A number of detection techniques can be used, including bolometric measurement, electrooptic sampling, and photoconductive receivers (with the latter essentially operating in reverse to photoconductive emitters).
Figure 1. Schematic diagram showing the process of terahertz (THz)-radiation generation. Vbias: Bias voltage applied to the gallium-arsenide (GaAs) substrate.
Cancer of the colon, which is part of the gastrointestinal (GI) tract, is the third most common cancer in both men and women and the third leading cause of cancer-related mortality in the USA. The number of newly diagnosed cases of GI cancer is increasing. As with most cancers, early detection is essential for improved survival rates, but symptoms only tend to appear at advanced stages of the disease. Improved screening has enhanced detection rates, but problems remain in detecting flat adenomas and dysplasias, and in differentiating lesions from inflammatory conditions. Endoscopy is the accepted gold standard for screening and surveillance of these cancers, but the technique is far from perfect. Despite significant technological improvements, lesions are often missed and this approach cannot provide an instant diagnosis. During routine endoscopy, multiple random biopsies (where small pieces of tissue are cut out) are often required, which increases the risk of bleeding/perforation during the procedure. These biopsies are processed, cut into thin slices, and observed under a microscope (histopathology). A large proportion may turn out normal and thus were not required. There is a need for better endoscopic visualization in specific circumstances such as the detection of dysplastic lesions (precancerous tissue), with the ultimate goal of improving sensitivity and specificity compared with histopathology. There is also a clinical need to accurately define disease margins to conserve normal tissue and minimize the number of unnecessary biopsies (which require additional hospital resources and increase the risk of patient morbidity).
Figure 2. The THz system used to image excised colon tissue.
We compared THz images with results from standard histological examinations to determine the feasibility of this technique in diagnosing colon cancer. This study was performed in collaboration with surgeons and histopathologists at St Mary's Hospital of Imperial College London. The THz system used was a TPI Imaga1000 TM from TeraView Ltd., Cambridge, UK (see Figure 2). This time-domain imaging system uses photoconductive antennas for the generation and detection of THz radiation. It produces short pulses with excellent signal-to-noise ratio and high dynamic range. The instrument generates pulses of broadband radiation from 0.05 to 4THz with a spectral resolution of 0.03THz. The pulse is reflected from the sample and the THz optics are raster scanned in the x–y plane to collect a grid of pulses. The dataset is 3D, with time as the third axis. The sample is placed on a quartz imaging plate and a 2cm2 area can be scanned in a few minutes.
Patients undergoing elective large-bowel resection were recruited to the study. Samples of normal colon, polyps (abnormal growths), and cancer were taken from the specimens and scanned. All scanned specimens then underwent histological examination. Eighty three biopsy samples were retrieved from 28 patients. Twenty one patients had malignant disease. Of the remaining seven patients, three suffered from inflammatory conditions. THz images of excised colon tissue show a contrast between regions of tumor and normal tissue (see Figure 3). A number of parameters from the data were identified that show statistically significant differences between data from tumor and normal regions. These results, to be presented at Photonics West 2009, have shown—for the first time—that images generated with radiation in the THz range can reliably distinguish between normal colon, tumor, and even dysplastic tissue in excised tissue samples.
Figure 3. THz false-color image of excised colon tissue. The light-green region on the left is normal colon. The red region on the right is dysplastic tissue from a region adjacent to a tumor. There is a clear contrast between the two tissue types.
THz-radiation imaging is just one of several methods under investigation for use in detecting early cancer of the GI tract. However, these findings open up exciting new medical applications for THz technology. With further development we aim for the technology to be used during endoscopic and surgical procedures to enable complete removal of diseased tissues. Further work is required to fully understand the contrast between diseased and healthy tissue. We note that both the absorption coefficient and refractive index were higher for tissue that contained tumor. These changes are consistent with higher water content and structural changes, like increased cell and protein density.
Optical and Biomedical Engineering Laboratory
University of Western Australia
Vincent Wallace was previously with TeraView Ltd. He currently works in biomedical optics.
1. A. J. Fitzgerald, E. Berry, N. N. Zinov'ev, S. Homer-Vanniasinkam, R. E. Miles, J. M. Chamberlain, M. A. Smith, Catalogue of human tissue optical properties at terahertz frequencies, J. Biol. Phys. 29, no. 2–3, pp. 123-128, 2003.
3. V. P. Wallace, A. J. Fitzgerald, S. Shankar, N. Flanagan, R. Pye, J. Cluff, D. D. Arnone, Terahertz pulsed imaging of basal cell carcinoma ex vivo and in vivo, Brit. J. Dermatol. 151, no. 2, pp. 424-432, 2004.
4. A. J. Fitzgerald, V. P. Wallace, M. Jimenez-Linan, L. Bobrow, R. J. Pye, A. D. Purushotham, D. D. Arnone, Terahertz pulsed imaging of human breast tumors, Radiology 239, no. 2, pp. 533-540, 2006.