Measurement of tissue optical properties in a wide spectral range: a review [Invited].

A distinctive feature of this review is a critical analysis of methods and results of measurements of the optical properties of tissues in a wide spectral range from deep UV to terahertz waves. Much attention is paid to measurements of the refractive index of biological tissues and liquids, the knowledge of which is necessary for the effective application of many methods of optical imaging and diagnostics. The optical parameters of healthy and pathological tissues are presented, and the reasons for their differences are discussed, which is important for the discrimination of pathologies and the demarcation of their boundaries. When considering the interaction of terahertz radiation with tissues, the concept of an effective medium is discussed, and relaxation models of the effective optical properties of tissues are presented. Attention is drawn to the manifestation of the scattering properties of tissues in the THz range and the problems of measuring the optical properties of tissues in this range are discussed. In conclusion, a method for the dynamic analysis of the optical properties of tissues under optical clearing using an application of immersion agents is presented. The main mechanisms and technologies of optical clearing, as well as examples of the successful application for differentiation of healthy and pathological tissues, are analyzed.

Terahertz radiation and the skin: a review.

SIGNIFICANCE: Terahertz (THz) radiation has demonstrated a great potential in biomedical applications over the past three decades, mainly due to its non-invasive and label-free nature. Among all biological specimens, skin tissue is an optimal sample for the application of THz-based methods because it allows for overcoming some intrinsic limitations of the technique, such as a small penetration depth (0.1 to 0.3 mm for the skin, on average). AIM: We summarize the modern research results achieved when THz technology was applied to the skin, considering applications in both imaging/detection and treatment/modulation of the skin constituents. APPROACH: We perform a review of literature and analyze the recent research achievements in THz applications for skin diagnosis and investigation. RESULTS: The reviewed results demonstrate the possibilities of THz spectroscopy and imaging, both pulsed and continuous, for diagnosis of skin melanoma and non-melanoma cancer, dysplasia, scars, and diabetic condition, mainly based on the analysis of THz optical properties. The possibility of modulating cell activity and treatment of various diseases by THz-wave exposure is shown as well. CONCLUSIONS: The rapid development of THz technologies and the obtained research results for skin tissue highlight the potential of THz waves as a research and therapeutic instrument. The perspectives on the use of THz radiation are related to both non-invasive diagnostics and stimulation and control of different processes in a living skin tissue for regeneration and cancer treatment.

In situ terahertz monitoring of an ice ball formation during tissue cryosurgery: a feasibility test.

SIGNIFICANCE: Uncontrolled cryoablation of tissues is a strong reason limiting the wide application of cryosurgery and cryotherapy due to the certain risks of unpredicted damaging of healthy tissues. The existing guiding techniques are unable to be applied in situ or provide insufficient spatial resolution. Terahertz (THz) pulsed spectroscopy (TPS) based on sensitivity of THz time-domain signal to changes of tissue properties caused by freezing could form the basis of an instrument for observation of the ice ball formation. AIM: The ability of TPS for in situ monitoring of tissue freezing depth is studied experimentally. APPROACH: A THz pulsed spectrometer operated in reflection mode and equipped with a cooled sample holder and ex vivo samples of bovine visceral adipose tissue is applied. Signal spectrograms are used to analyze the changes of THz time-domain signals caused by the interface between frozen and unfrozen tissue parts. RESULTS: Experimental observation of TPS signals reflected from freezing tissue demonstrates the feasibility of TPS to detect ice ball formation up to 657-µm depth. CONCLUSIONS: TPS could become the promising instrument for in situ control of cryoablation, enabling observation of the freezing front propagation, which could find applications in various fields of oncology, regenerative medicine, and THz biophotonics.

Optimal hyperosmotic agents for tissue immersion optical clearing in terahertz biophotonics.

In this work, a thorough analysis of hyperosmotic agents for the immersion optical clearing (IOC) in terahertz (THz) range was performed. It was aimed at the selection of agents for the efficient enhancement of penetration depth of THz waves into biological tissues. Pulsed spectroscopy in the frequency range of 0.1 to 2.5 THz was applied for investigation of the optical properties of common IOC agents. Using the collimated transmission spectroscopy in visible range, binary diffusion coefficients of tissue water and agent in ex vivo rat brain tissue were measured. IOC agents were objectively compared using two-dimensional nomogram, accounting for their THz-wave absorption coefficients and binary diffusion coefficients. The results of this study demonstrate an interplay between the penetration depth enhancement and the diffusion rate and allow for pointing out glycerol as an optimal agent among the considered ones for particular applications in THz biophotonics.

Terahertz spectroscopy of gelatin-embedded human brain gliomas of different grades: a road toward intraoperative THz diagnosis.

We applied terahertz (THz)-pulsed spectroscopy to study ex vivo the refractive index and absorption coefficient of human brain gliomas featuring different grades, as well as perifocal regions containing both intact and edematous tissues. Glioma samples from 26 patients were considered and analyzed according to further histological examination. In order to fix tissues for the THz measurements, we applied gelatin embedding, which allows for sustaining their THz response unaltered, as compared to that of the freshly excised tissues. We observed a statistical difference between the THz optical constants of intact tissues and gliomas of grades I to IV, while the response of edema was similar to that of tumor. The results of this paper justify a potential of THz technology in the intraoperative label-free diagnosis of human brain gliomas for ensuring the gross-total resection.

Nanoparticle-enabled experimentally trained wavelet-domain denoising method for optical coherence tomography.

We present the nanoparticle-enabled experimentally trained wavelet-domain denoising method for optical coherence tomography (OCT). It employs an experimental training algorithm based on imaging of a test-object, made of the colloidal suspension of the monodisperse nanoparticles and contains the microscale inclusions. The geometry and the scattering properties of the test-object are known a priori allowing us to set the criteria for the training algorithm. Using a wide set of the wavelet kernels and the wavelet-domain filtration approaches, the appropriate filter is constructed based on the test-object imaging. We apply the proposed approach and chose an efficient wavelet denoising procedure by considering the combinations of the decomposition basis from five wavelet families with eight types of the filtration threshold. We demonstrate applicability of the wavelet-filtering for the in vitro OCT image of human brain meningioma. The observed results prove high efficiency of the proposed OCT image denoising technique.

Wide-aperture aspherical lens for high-resolution terahertz imaging.

In this paper, we introduce wide-aperture aspherical lens for high-resolution terahertz (THz) imaging. The lens has been designed and analyzed by numerical methods of geometrical optics and electrodynamics. It has been made of high-density polyethylene by shaping at computer-controlled lathe and characterized using a continuous-wave THz imaging setup based on a backward-wave oscillator and Golay detector. The concept of image contrast has been implemented to estimate image quality. According to the experimental data, the lens allows resolving two points spaced at 0.95λ distance with a contrast of 15%. To highlight high resolution in the THz images, the wide-aperture lens has been employed for studying printed electronic circuit board containing sub-wavelength-scale elements. The observed results justify the high efficiency of the proposed lens design.