Optical Sensing of Tissue Freezing Depth by Sapphire Cryo-Applicator and Steady-State Diffuse Reflectance Analysis.

This work describes a sapphire cryo-applicator with the ability to sense tissue freezing depth during cryosurgery by illumination of tissue and analyzing diffuse optical signals in a steady-state regime. The applicator was manufactured by the crystal growth technique and has several spatially resolved internal channels for accommodating optical fibers. The method of reconstructing freezing depth proposed in this work requires one illumination and two detection channels. The analysis of the detected intensities yields the estimation of the time evolution of the effective attenuation coefficient, which is compared with the theoretically calculated values obtained for a number of combinations of tissue parameters. The experimental test of the proposed applicator and approach for freezing depth reconstruction was performed using gelatin-based tissue phantom and rat liver tissue in vivo. It revealed the ability to estimate depth up to 8 mm. The in vivo study confirmed the feasibility of the applicator to sense the freezing depth of living tissues despite the possible diversity of their optical parameters. The results justify the potential of the described design of a sapphire instrument for cryosurgery.

Proof of concept for the sapphire scalpel combining tissue dissection and optical diagnosis.

OBJECTIVES: The development of compact diagnostic probes and instruments with an ability to direct access to organs and tissues and integration of these instruments into surgical workflows is an important task of modern physics and medicine. The need for such tools is essential for surgical oncology, where intraoperative visualization and demarcation of tumor margins define further prognosis and survival of patients. In this paper, the possible solution for this intraoperative imaging problem is proposed and its feasibility to detect tumorous tissue is studied experimentally. METHODS: For this aim, the sapphire scalpel was developed and fabricated using the edge-defined film-fed growth technique aided by mechanical grinding, polishing, and chemical sharpening of the cutting edge. It possesses optical transparency, mechanical strength, chemical inertness, and thermal resistance alongside the presence of the as-grown hollow capillary channels in its volume for accommodating optical fibers. The rounding of the cutting edge exceeds the same for metal scalpels and can be as small as 110 nm. Thanks to these features, sapphire scalpel combines tissue dissection with light delivering and optical diagnosis. The feasibility for the tumor margin detection was studied, including both gelatin-based tissue phantoms and ex vivo freshly excised specimens of the basal cell carcinoma from humans and the glioma model 101.8 from rats. These tumors are commonly diagnosed either non-invasively or intraoperatively using different modalities of fluorescence spectroscopy and imaging, which makes them ideal candidates for our feasibility test. For this purpose, fiber-based spectroscopic measurements of the backscattered laser radiation and the fluorescence signals were carried out in the visible range. RESULTS: Experimental studies show the feasibility of the proposed sapphire scalpel to provide a 2-mm-resolution of the tumor margins' detection, along with an ability to distinguish the tumor invasion region, which results from analysis of the backscattered optical fields and the endogenous or exogenous fluorescence data. CONCLUSIONS: Our findings justified a strong potential of the sapphire scalpel for surgical oncology. However, further research and engineering efforts are required to optimize the sapphire scalpel geometry and the optical diagnosis protocols to meet the requirements of oncosurgery, including diagnosis and resection of neoplasms with different localizations and nosologies.

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.

Optical coefficients as tools for increasing the optical coherence tomography contrast for normal brain visualization and glioblastoma detection.

The methods used for digital processing of optical coherence tomography (OCT) and crosspolarization (CP) OCT images are focused on improving the contrast ratio of native structural OCT images. Such advances are particularly important for the intraoperative detection of glioma margins where the visual assessment of OCT images can be difficult and lead to errors. The aim of the study was to investigate the application of optical coefficients obtained from CP OCT data for the differentiation of glial tumorous tissue from a normal brain. Pseudocolor en-face OCT maps based on two optical coefficients (the commonly used rate of attenuation in the cochannel, and in addition, the interchannel attenuation difference) were constructed for normal rat brain coronal cross sections and for brains with a 101.8 rat glioblastoma model. It was shown that the use of optical coefficients significantly increased the available information from the OCT data in comparison with unprocessed images. As a result, this allowed contrasting of the white matter from the gray matter and tumorous tissue ex vivo, and for this purpose, the interchannel attenuation difference worked better. The interchannel attenuation difference values of white matter were at least seven and two times higher than corresponding values of the cortex and tumorous tissue, whereas the same parameter for cochannel attenuation coefficient values of white matter are about 4 and 1.4. However, quantitative analysis shows that both coefficients are suitable for the purpose of glioblastoma detection from normal brain tissue regardless of whether a necrotic component was present (in all compared groups p < 0.001 ).