Biomedical application of terahertz imaging technology: a narrative review

Abstract

Background and objective: Terahertz (THz) imaging has wide applications in biomedical research due to its properties, such as non-ionizing, non-invasive and distinctive spectral fingerprints. Over the past 6 years, the application of THz imaging in tumor tissue has made encouraging progress. However, due to the strong absorption of THz by water, the large size, high cost, and low sensitivity of THz devices, it is still difficult to be widely used in clinical practice. This paper provides ideas for researchers and promotes the development of THz imaging in clinical research.

Methods: The literature search was conducted in the Web of Science and PubMed databases using the keywords "Terahertz imaging", "Breast", "Brain", "Skin" and "Cancer". A total of 94 English language articles from 1 January, 2017 to 30 December, 2022 were reviewed.

Key content and findings: In this review, we briefly introduced the recent advances in THz near-field imaging, single-pixel imaging and real-time imaging, the applications of THz imaging for detecting breast, brain and skin tissues in the last 6 years were reviewed, and the advantages and existing challenges were identified. It is necessary to combine machine learning and metamaterials to develop real-time THz devices with small size, low cost and high sensitivity that can be widely used in clinical practice. More powerful THz detectors can be developed by combining graphene, designing structures and other methods to improve the sensitivity of the devices and obtain more accurate information. Establishing a THz database is one of the important methods to improve the repeatability and accuracy of imaging results.

Conclusions: THz technology is an effective method for tumor imaging. We believe that with the joint efforts of researchers and clinicians, accurate, real-time, and safe THz imaging will be widely applied in clinical practice in the future.

Keywords: Terahertz (THz) image; brain; breast; cancer; skin.

Figure 1

Schematic diagram of the THz device. (A) Schematic illustration of the experimental setup (34). (B) Changes in cell morphology during natural drying: (i) optical image; (ii-iv) THz image of cells dried for 1, 3, 5 h (34). (C) Schematic of THz single pixel imaging. A spatial modulator is made by combining graphene, silicon and gold to improve image quality (35). (D) Schematic of the imaging setup. Remove all OAPMs and illuminate the sample directly. Images were captured using a lens designed specifically for RIGI cameras (36). TPX, methyl pentene copolymer; THz, terahertz; CW, continuous wave; TX, transmitter; OAPMs, off-axis parabolic mirrors.

Figure 2

Imaging of breast tissue at THz. (A) (i) Schematic diagram of a THz handheld probe system; (ii) localization of samples for terahertz imaging; (iii) pulse spectra from breast tissue, respectively, for tumors, fibrocytes and adipocytes, and air (63); (B) (i) SPoTS microscope; (ii) comparison of HES and THz images of invasive ductal carcinoma (64); (C) (i) schematic of a system with Schottky diode detectors; (ii) THz images of breast cancer in a mouse model (22). THz, terahertz; HES, hematoxylin-eosin-saffron; PE, polyethylene; YIG, yttrium iron garnet; SPoTS, schematic of scanning point terahertz source.

Figure 3

THz imaging of brain tissue. (A) (i) White-field images of paraffin-embedded brain coronal sections from normal and EAE monkeys. “1-5” are the randomly measured five comparable regions of interest. (ii) THz spectra of normal and EAE tissues (81). (B) THz absorption and reflection spectra of AD and normal brain tissue placed on a quartz substrate plate (82). (C) (i,ii) represent visual images of fresh and paraffin-embedded brain tissues, respectively; the three points of the terahertz spectroscopy experiment are shown in red circles. (iii,iv) correspond to its THZ image (83). (D) Images from different imaging modalities (84); (E) imaging of brain tissue from living mice (84); (F) (i) Diagram of experimental equipment; numbers 1–3 in the figure are the off-axis parabolic reflector. THz-ATR was used to distinguish brain tumor tissues from fresh rats: white light (ii), THz-ATR (iii), H&E (iv) the tumor regions marked by dashed lines. (85); (G) (i) effect of temperature on THZ imaging images. Tumor and normal regions, as the marked with dotted boxes 1 and 2. (ii) Reflection spectra of different tissues at different temperatures (86); (H) (i) photo of the freshly-excised tissues; “V” and “VI” are necrosis zone and hemorrhage zone, respectively. (ii) THz microscopy of the freshly-excised tissues (23). ***, P<0.001. R_ave: the averaged reflectivity. EAE, experimental autoimmune encephalomyelitis; AD, Alzheimer’s disease; THz, terahertz; GFP, green fluorescent protein; H&E, hematoxylin and eosin; TRI, terahertz reflectometry imaging; TPI, THz pulse imaging; ppIX, protoporphyrin IX; ATR, attenuated total reflection.

Figure 4

Methods to improve the sensitivity of imaging. (A) (i) Experimental map of metamaterials; THz reflection images using (ii) a bare Si substrate and (iii) a nano-slot chip; reflection values from images (ii) and (iii) along the dashed lines (iv) a and (vi) b (88). The reflectance spectroscopy experiment is performed with the asterisk. (B) (i) Experimental procedure for metamaterial imaging; THz reflection images using (ii) a bare Si substrate and (iii) metamaterials (100). (C) Tumor boundaries obtained by PCA algorithm (93); (D) preprocessing of THz images consisting of rotation rectification (89). PDMS, polydimethylsiloxane; THz, terahertz; ROI, region of interest; PCA, principal component analysis.

Figure 5

THz imaging of skin tissue. (A) (i) Experiment setup; THz images of hyperplastic (ii) and normal (iii) scars (104). The scar tissue is marked with a black circle. (B) THz imaging of malignant melanoma tissue sections (105). (C) (i) Schematic diagram of the device; slices of the 3D image across the thickness of a healthy skin sample (ii) and basal cell carcinoma skin sample (iii) (106). (D) (i) The cross-polarized THz reflectance image; the location of the tumor is indicated by the arrows; (ii) the cross-polarized optical image; (iii) H&E image (107). Scale bar: 10 mm. THz, terahertz; H&E, hematoxylin and eosin.