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12MULTIMODAL TISSUE IMAGING AT OPTICAL CLEARING
VALERY V. TUCHIN
Saratov State University, Saratov, Russia National Research Tomsk State University, Tomsk, Russia Institute of Precision Mechanics and Control, Russian Academy of Sciences, Saratov, Russia
Abstract
A description of 'tissue optical virtual windows' concept and method of optical clearing (OC) based on controllable and reversible modification of tissue or cell optical properties by their soaking with a biocompatible optical clearing agent (OCA)are presented in Refs. [1-27]. Fundamentals and major mechanisms of OC allowing one to enhance optical imaging facilities and laser treatment efficiency of living tissues and cells are also discussed in the literature [1 -27].
In this work, perspectives of immersion optical clearing/contrasting technique aiming to enhance imaging of living tissues by using different imaging modalities working in the ultra-broad wavelength range from a free electron beam excitation (Cherenkov light emission) to terahertz waves aresummarized in the Fig.1 [13, 25]. OC method improves and provides:
> Quantitative estimation of the concentration of chromophores and fluorophores of tissue at various depths
> Multi-category classification of tissue properties based on the extraction of meaningful multimodal spectroscopic biomarkers
> Clinically compatible spectroscopy-based methods of tissue pathology diagnosis
> Practical recommendations for increasing in vivo efficacy of diagnostics in UV/visible/NIR (200-2000 nm), THz combined with x-ray CT and MRI.
Technique
integrating sphere spectroscopy
Diffuse reflectance & fluoresc. spectrosc ./imaging (DRFS!)
Confocal Microscopy (CM)
Raman spectrosc,/imaging
Photoacoustics (PA)
Multiphoton microscopy (MPM)
THz Spectrosc./lmaging
X-ray computer tomography (CT)
Experimental validation
Multrlayered, multimodal optical tissue phantoms
Ex vivo & in vivo studies
Healthy & pathological tissues
Animal & human tissues
Optical Clearing
M u I tic urn p one lit biocompatible optical clearing agents (OCAs) for effective tissue optical clearing (OC) and enhancement of tissue image contrast
Multimodal OCAs for (XT and contrasting of CI and MRI
Data processing
Inverse problem solution: tissue absorption, scattering & fluorescence properties
Mathematical models
Image processing (DRFSI OCT, CM, PA, Raman, MPM, THz)
Multidimensional data classification including feature extraction/selection
Figure 1: Multimodal approaches based on tissue optical clearing concept.
The enhancement of probing/treatment depth and image contrast for a number of human and animal tissues investigated by using different optical modalities, including diffuse reflectance spectroscopy, collimated transmittance, OCT, photoacoustic microscopy, linear and nonlinear fluorescence, SHG and Raman microscopies is possible. Experimental data on the diffusion and permeability coefficients of biocompatible FDA approved OCAs, such as glucose, glycerol, PEG, albumin, computer tomography (CT) contrast agents (Iohexol (OmnipaqueTM) and Iodixanol (Visipaque™)), and MRI contrast agents (Gadobutrol (Gadovist™)) in normal and pathological tissues (cancer and diabetes) are presented [127].
Optical clearing agents are beneficial for enhanced multimodal spectroscopy/imaging using different combinations of optical techniques such as Raman, OCT, FLIM, MPM, SHG, PA, Diffuse, and THz with X-ray CT and MRI.
Acknowledgment: This work was supported by RF Governmental Grant № 075-15-2019-1885 and RFBR grant 18-52-16025.Author is greatful for all his colleagues and co-authors for collaboration.
References
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