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Overview: Terahertz, ranging from 0.1 THz to 10 THz, is situated in the frequency regime between optical and electronic techniques. Recently, with the rapid development of terahertz technology, it is widely applied in several fields such as material science, physics, chemistry, biology, and medicine. Due to the unique characteristics including low photon energy, excellent penetration ability through non-conducting materials and distinctive molecular fingerprints identification, terahertz medical imaging has become a promising imaging modality to date. It has been a significantly complementary medical imaging method, compared to other methods like magnetic resonance imaging (MRI), computed X-ray tomography (CT) and positron emission tomography (PET). And there has been an increasing interest in terahertz imaging for medical applications within the last few years, meanwhile, more and more terahertz imaging studies are being reported. In this review, we present a brief introduction on the terahertz imaging systems, and the applications of terahertz medical imaging from in vitro to in vivo. The essential mechanisms of terahertz medical imaging are based on the differences in water content and structural variations of tissues. But the abundant water in living tissues will strongly absorb terahertz wave, and lead to severely deteriorated imaging contrast. As a result, the terahertz medical imaging is mainly used in vitro or epidermal tissues. In most cases, the in vitro tissues should be pretreated with the processes including frozen sections, paraffin sections and so on. Many tissues have been studied by terahertz medical imaging in both human and animal models. Particularly, cancerous tissues of digestive system, reproductive system, integumentary system and respiratory system are focused. Brain, liver, breast tumors, for example, have been studied after different pretreatments. Fresh tissues directly excised from these tumors are also utilized to assess both water content and structural variations. While applied in vivo, skins are the main detected projects due to the penetration limit caused by water. In addition, some other methods have also been proposed to promote the application of terahertz medical imaging in the living body, such as endoscopy and penetration enhancing agents. Particularly, the nanoparticles contrast agents for terahertz medical imaging have been developed recently. This review concluded investigation of these contrast agents, including gold nanorods, gadolinium oxide nanoparticles, and superparamagnetic iron oxide nanoparticles. It seems that these contrast agents could enhance the imaging contrast largely, and would promote the application of terahertz medical imaging in vivo. Finally, the future development of terahertz medical imaging is prospected.
Schematic illustration of terahertz imaging system. (a) Terahertz pulsed imaging system in the reflection mode[4]; (b) Continuous-wave terahertz imaging system [15]; (c) Terahertz digital holographic imaging system[16]
(a) Optical and terahertz images of a hydrated ex vivo cornea; (b) Terahertz images of an ex vivo cornea at (upper-left to lower-right) 84.74%, 78.64%, 75.27%, 70.25%, and 66.06% water content[19]
(a) Optical image and (b) processed terahertz hologram of human hepatocellular carcinoma tissue[5]
Images of infiltrating ductal carcinoma. (a) Pathology image; (b) Terahertz time-domain image; (c) Terahertz frequency domain image at 1.5 THz; (d) Terahertz frequency-domain image at 2.0 THz[4]
(a) Freshly excised tumor tissue; (b) Corresponding terahertz image[26]
(a), (b) Terahertz parametric images calculated via two different approaches of terahertz waveforms processing; (c) Image of histological examination of tissues[28]
Visual, terahertz, and MR images of whole brain of rats with glioma[29]
Terahertz transmission near-field images of mouse ears. (a) Optical image; (b) Original terahertz near-field image showing measured transmittance; (c) Normalized transmission image[20]
Images of oral sample. (a) Optical image; Terahertz images at: (b) -20 and (c) room temperature; ℃ (d) Histopathological image (the cancerous areas are marked with blue loops)[33]
TEM images of GNRs with aspect ratios of (a) 3.2, (b) 4.0, and (c) 4.2; (d) UV-visible absorption spectra of (a)~(c) [10]
Schematic diagram of GNRs enhanced terahertz imaging[21]
Cancer cell images with and without GNRs. (a) Visible image; (b) Terahertz image without IR irradiation; (c) Terahertz image with IR irradiation[10]
In vivo and ex vivo terahertz molecular images of tumors. (a), (b) Visible images of the mouse with an A431 tumor in vitro; (c) Terahertz image of (b); (d) Visible images of the tumor, liver, spleen, kidney, and brain samples; (e) Terahertz image of (d)[36]
Prostate cancer cells with and without nanoparticles. (a) Optical image; (b) Terahertz image obtained without NIR laser irradiation; (c) Terahertz image obtained after NIR laser irradiation[13]
In vivo terahertz (upper) and MRI (lower) images of a mouse 24 h after SPIO transfection[37]