Terahertz imaging of excised oral cancer at frozen temperature

Abstract

The feasibility of terahertz (THz) imaging at frozen temperature for the clinical application of oral cancer detection was investigated by analyzing seven oral tissues resected from four patients. The size, shape, and internal position of the oral cancers were mapped by THz radiation in the frequency range of 0.2-1.2 THz at -20 °C and 20 °C, and compared with those identified in the histological examination. THz imaging of frozen tissue was found to offer greater sensitivity in distinguishing cancerous areas from surrounding tissue and a larger THz-frequency spectral difference between the oral cancer and normal mucosa than room-temperature THz imaging. A cancerous tumor hidden inside tissue was also detected using this method by observing the THz temporal domain waveform. The histological analysis showed that these findings resulted from cell structure deformations involving the invasion of oral tumor and neoplastic transformations of mucous cells. Therefore, a cytological approach using THz radiation at a frozen temperature might be applied to detect oral cancer.

Keywords: (040.2235) Far infrared or terahertz; (110.6795) Terahertz imaging; (160.1435) Biomaterials; (170.3880) Medical and biological imaging; (300.6495) Spectroscopy, terahertz.

Fig. 1

Oral cancer diagnosis in the operating room. The cancer is located on the lateral surface of the tongue and a safety margin of 1.5 cm is marked.

Fig. 2

THz imaging setup for detecting oral cancer at −20 °C and 20 °C. The setup is designed in reflection mode and the sealed chamber is utilized to control the temperature inside. The aluminum film in the chamber is used to reflect the reference signal. (SC: sealed chamber, S: specimen, AL: aluminum film, QP: quartz plate, GC: gas controller, TL: Ti:sapphire laser, BS: beam splitter, M: mirror, G: THz generator, THz: THz radiation, OM: oscillating mirror, D: THz detector, PA: preamplifier)

Fig. 3

(a) Optical images, (b) frozen and (c) room temperature THz images, and (d) histopathological images of six oral samples. THz images are displayed by the index of refraction at 0.5 THz, and the cancerous areas are marked with blue loops in the histological images.

Fig. 4

The correlation of cancerous areas from THz imaging at −20 °C and histological imaging. The correlation factor is the area ratio of the whole size of specimen and the cancerous area (or purple area) within it on both images.

Fig. 5

(a) A nest of deformed mucosal cells with hyperchromatic nuclei from sample #1 ( × 400), (b) a mixture of inflammatory cells from sample #2 ( × 400), (c) mucoepidermoid carcinoma of the tongue showing subepithelial invasion from sample #1 ( × 40).

Fig. 6

The THz refractive indices and absorptions of normal mucosa and oral cancer of the six oral samples at (a) 20 °C and (b) −20 °C in the frequency range of 0.2–1.2 THz. The dots are the average values and the error bars represent the 95% confidence interval.

Fig. 7

A cancerous tumor inside sample #7 was detected by observation of the THz time-domain waveform obtained at frozen temperature. (a) Optical image, (b) frozen, and (c) room temperature THz images, and (d) a pathological image of a perpendicular section. (e) The THz waveforms from regions indicated by the red arrow in (b) and (c). The second pulse in the THz waveform of (b) indicated by the arrow was reflected by the cancerous tumor inside the sample. (THz: THz radiation, QP: quartz plate).