# Selected Applications of Terahertz Pulses in Medicine and Industry
## 2 Terahertz Imaging and Spectroscopy in Medicine and Biology  
There is considerable interest in applying terahertz imaging and spectroscopy in medicine and biological sciences. The subject has advanced considerably in the approximate 20-year period since the earliest results of [PERSON] and co-workers, showing that cancerous and healthy tissues differed in their terahertz response [1; 2; 3; 4; 5; 6; 7; 8; 9; 10; 11; 12; 13; 14; 15] and the first human organ, a tooth, was imaged. This image, which is on the BBC News website, ([[http://news.bbc.co.uk/1/hi/sci/tech/368558.stm](http://news.bbc.co.uk/1/hi/sci/tech/368558.stm)]([http://news.bbc.co.uk/1/hi/sci/tech/368558.stm](http://news.bbc.co.uk/1/hi/sci/tech/368558.stm)) (accessed on 20 February 2022)), is important as the images showed that erosion of the surface enamel had occurred in specific locations, allowing bacteria to enter and cause decay. The traditional method of X-ray imaging is not as sensitive to the presence of enamel, as the change in contrast is not significant [16]. [PERSON] et al. [17; 18] from GlaxoSmithKline were able to correlate the strength of terahertz reflection from the tooth surface and the mineral changes within the tooth, thus monitoring the remineralisation of teeth. Interest in medical applications of terahertz has also been generated because the low energy of terahertz radiation results in an absence of ionisation damage to molecules. The imaging is non-invasive and the sensitivity of coherent detection allows the observation of small changes in the tissue properties, which create a reflection interface. There have been suggestions that a molecular resonance may occur in the terahertz region but its presence is not clear. The terahertz spectroscopy of human basal cell carcinoma (BCC) was reported by [PERSON] et al. [4] The authors were able to observe clear differences in both the absorption coefficient and the refractive index of diseased and healthy tissue over the range 0.1 to 2 THz. Most terahertz work has focused on imaging, as spectroscopic studies of proteins [19] and large molecules, such as DNA, do not in general produce sharp resonant structure but rather a broadband absorption [20]. For proteins, this can be affected by conformational changes, and insight is gained by the terahertz absorption of an aqueous solution, as the presence of protein displaces the water and reduces absorption [21; 22; 23]. Similarly, bonding between proteins and the hydrated surrounding layer results in a frequency shift of the water absorption in contrast to normal water absorption. Cellular studies have been performed, as the hydration state of the cell alters terahertz sensitivity due to the various vibrational modes of water molecules. There are reports that methylated malignant DNA [24; 25; 26] has a resonant structure at approximately 1.65 THz, which could serve as an indicator of the subsequent formation of a tumour. Markers that preferentially attach to tumours have been important for enhancing other imaging modalities, such as MRI, and in the terahertz regime, gold nanorods designed for attachment to tumour growth factor receptors have enhanced absorption [27; 28]. Tryptophan has been used as a marker for skin cancer as it has well defined absorption peaks. Advances in instrumentation have resulted in the development of hand-held devices for both medical diagnostics and security applications. Endoscopic systems have been demonstrated to work well for excised tissue, but moisture would be a problem in clinical use, for example with gastroscopy [29]. An octoscope for investigations of the ear has already been demonstrated [30]. The penetration depth of terahertz pulses in excised tissues is limited by the strong water absorption. Freezing the samples has resulted in a marked increase in range, due to the suppression of the water modes of vibration. Although the earliest investigations of cancerous tissue showed strong absorption compared with healthy tissue, these experiments were performed with excised basal cell carcinoma samples.