Terahertz technology in intraoperative neurodiagnostics:A review

Terahertz(THz)technology offers novel opportunities in biology and medicine,thanks to the unique features of THzwave interactions with tissues and cells.Among them,we particularly notice strong sensitivity of THz waves to the tissue water,as a medium for biochemical reactions and a main endogenous marker for THz spectroscopy and imaging.Tissues of the brain have an exceptionally high content of water.This factor,along with the features of the structural organization and biochemistry of neuronal and glial tissues,makes the brain an exciting subject to study in the THz range.In this paper,progress and prospects of THz technology in neurodiagnostics are overviewed,including diagnosis of neurodegenerative disease,myelin deficit,tumors of the central nervous system(with an emphasis on brain gliomas),and traumatic brain injuries.Fundamental and applied challenges in study of the THz-wave–brain tissue interactions and development of the THz biomedical tools and systems for neurodiagnostics are discussed.

Introduction to the special issue on celebrating the 15th anniversary of JIOHS and the 70th anniversary of HUST

Since launching in 2008,Journal of Innovative Optical Health Sciences(JIOHS)has been published for 15 years umtil 2022.Supported by the founding advisor Prof.Britton Chance and other founding Editorial Members,JIOHS was quickly embraced by the biomedical optics community,especially in Asia.Authors submitted some of their high quality papers to JIOHS,which led to a constant Impact Factor(IF)increase frcom the first IF 0.632 to IF 2396(Journal Citation Report 2021).

OPTICAL PROPERTIES OF SKIN,SUBCUTANEOUS,AND MUSCLE TISSUES:A REVIEW

The development of optical methods in modern medicine in the areas of diagnostics,therapy,and surgery has stimulated the investigation of optical properties of various biological tissues,since the efficacy of laser treatment depends on the photon propagation and fluence rate distribution within irradiated tissues.In this work,an overview of published absorption and scattering properties of skin and subcutaneous tissues measured in wide wavelength range is presented.Basic principles of measurements of the tissue optical properties and techniques used for processing of the measured data are outlined.

Glycerol effects on optical,weight and geometrical properties of skin tissue

Complex study of glycerol effects on the skin tissue was performed.The change in optical,weight and geometrical parameters of the rat skin under the action of the glycerol solutions was studied ex vivo.Possible mechanisms of the skin optical clearing under the action of glycerol solutions of different concentrations were discussed.The results can be helpful for refinement of models developed to evaluate the effective diffusion coefficients of glycerol in tissues.

Meso-substituted cationic 3-and 4-N-Pyridylporphyrins and their Zn(II)derivatives for antibacterial photodynamic therapy

Photodynamic inactivation of microorganisms known as antibacterial photodynamic therapy(APDT)is one of the most promising and innovative approaches for the destruction of pathogenic microorganisms.Among the photosensitizers(PSs),compounds based on cationic porphyrins/metalloporphyrins are most successfully used to inactivate microorganisms.Series of meso-substituted cationic pyridylporphyrins and metalloporphyrins with various peripheral groups in the third and fourth positions of the pyrrole ring have been synthesized in Armenia.The aim of this work was to determine and test the most e®ective cationic porphyrins and metalloporphyrins with high photoactivity against Gram negative and Gram positive microorganisms.It was shown that the synthesized cationic pyridylporphyrins/metalloporphyrins exhibit a high degree of phototoxicity towards both types of bacteria,including the methicillinresistant S.aureus strain.Zinc complexes of porphyrins are more phototoxic than metal-free porphyrin analogs.The e®ectiveness of these Zn–metalloporphyrins on bacteria is consistent with the level of singlet oxygen generation.It was found that the high antibacterial activity of the studied cationic porphyrins/metalloporphyrins depends on four factors:the presence in the porphyrin macrocycle of a positive charge(+4),a central metal atom(Zn2þÞand hydrophobic peripheral functional groups as well as high values of quantum yields of singlet oxygen.The results indicate that meso-substituted cationic pyridylporphyrins/metalloporphyrins cannd wider application in photoinactivation of bacteria than anionic or neutral PSs usually used in APDT.

Ex-vivo confocal Raman microspectroscopy of porcine skin with 633/785-NM laser excitation and optical clearing with glycerol/water/DMSO solution

Confocal Raman microspectroscopy(CRM)with 633-and 785-nm excitation wavelengths combined with optical clearing(OC)technique was used for ex-vivo study of porcine skin in the Raman fingerprint region.The optical clearing has been performed on the skin samples by applying a mixture of glycerol and distilled water and a mixture of glycerol,distilled water and chemical penetration enhancer dimethyl sulfoxide(DMSO)during 30 min and 60 min of treat-ment.It was shown that the combined use of the optical clearing technique and CRM at 633 nm allowed one to preserve the high probing depth,signal-to-noise ratio and spectral resolution simultaneously.Comparing the effect of different optical clearing agents on porcine skin showed that an optical clearing agent containing chemical penetration enhancer provides higher optical clearing efficiency.Also,an increase in treatment time allows to improve the optical clearing efficiency of both optical clearing agents.As a result of optical clearing,the detection of the amide-Ⅲ spectral region indicating well-distinguishable structural differences between the type-Ⅰ and type-Ⅳ collagens has been improved.

Optical clearing mechanisms characterization in muscle

Optical immersion clearing is a technique that has been widely studied for more than two decades and that is used to originate a temporary transparency effect in biological tissues.If applied in cooperation with clinical methods it provides optimization of diagnosis and treatment procedures.This technique turns biological tissues more transparent through two main mechanisms-tissue dehydration and refractive index(RI)matching between tissue compo-nents.Such matching is obtained by partial replacement of interstit ial water by a biocompat ible agent that presents higher RI and it can be completely rever sible by natural rehydration in vrivo or by assisted rehydration in ex vivo tissues.Experimental data to characterize and discriminate between the two mechanisms and to find new ones are necessary.Using a simple method,based on collimated transmittance and thickness measurements made from muscle samples under treatment,we have estimated the diffusion properties of glucose,ethylene glycol(EG)and water that were used to perform such char acterization and discrimination.Comparing these properties with data from literature that characterize their diffusion in water we have observed that musde cell membrane permeability limits agent and water diffusion in the muscle.The same experi-mental data has allowed to calculate the optical dearing(OC)eficiency and make an inter-pretation of the internal changes that occurred in muscle during the treatments.The same methodology can now be used to perform similar studies with other agents and in other tissues in order to solve engineering problems at design of inexpensive and robust technologies for a consider.able improvement of optical tomogr aphic techmiques with better contrast and in depth imaging.

Hidden stage of intracranial hemorrhage in newborn rats studied with laser speckle contrast imaging and wavelets

Using the laser speckle contrast imaging and wavelet-based analyses,we investigate a latent("hidden")stage of the development of intracranial hemorrhages(ICHs)in newborn rats.We apply two measures based on the continuous wavelet-transform of blood flow velocity in the sagittal sinus,namely,the spectral energy in distinct frequency ranges and a multiscality degree characterizing complexity of experimental data.We show that the wavelet-based multifractal formalism reveals changes in the cerebrovascular blood flow at the development of ICH.

WAVELET-BASED ANALYSIS OF CEREBROVASCULAR DYNAMICS IN NEWBORN RATS WITH INTRACRANIAL HEMORRHAGES

Intracranial hemorrhage(I)is a major problem of neonatal intensive care.The incidence of Iistypically asymptomatic and'canmot be effectively detected by standard diagnostic methods.The mechanisms underlying IH are unknown but there is evidence that stress-induced disorders inadrenergic regulation of cerebral venous blood flow (CVBF) are among the main reasons.Quantitative and qualitative:could significantly advance understanding ofthe nature of I in newbornslth1sions of CVBF in newborn rats withan experimental model of stinjection.Our analysis is bas ed on theDoppler optical coheavelet-based approachthat provides sensitiv external factors.Theobtained resultsccompanied by asupprectivity to adrenaline.Weintroducd show that the values0<1.23 estimated ithelodinto the sympathicusindicate abnormal reactions associated with the developent of I.We conclude that t he revealed areactivity of the cerebral veins to adrenaline represents a possible mechanism responsible forpat hological changes in CVBF.

ASSESSMENT OF TISSUE OPTICAL CLEARING AS A FUNCTION OF GLUCOSE CONCENTRATION USING OPTICAL COHERENCE TOMOGRAPHY

One of the major challenges in imaging biological tissues using optical techniques,such as optical coherence tomography(OCT),is the lack of light penetration due to highly turbid structures within the tissue.Optical clearing techniques enable the biological samples to be more optically homogeneous,allowing for deeper penetration of light into the tissue.This study investigates the effect of optical clearing utilizing various concentrations of glucose solution(10%,30%,and 50%)on porcine skin.A gold-plated mirror was imaged beneath the tissue and percentage clearing was determined by monitoring the change in reflected light intensity from the mirror over time.The ratio of percentage clearing per tissue thickness for 10%,30% and 50% glucose was determined to be 4.7±1.6%mm^(−1)(n=6),10.6±2.0%mm^(−1)(n=7)and 21.8±2.2%mm^(−1)(n=5),respectively.It was concluded that while higher glucose concentration has the highest optical clearing effect,a suitable concentration should be chosen for the purpose of clearing,considering the osmotic stress on the tissue sample.

The morphological changes in the internal organs of laboratory animals after prolonged oral administration of gold nanoparticles

Recently gold nanoparticles(GNPs)have been actively studied as photot hermal converters,drug carriers,and imaging agents in a wide range of applications in cancer diagnosis and ther apy.The prolonged peroral administration of GNPs in a range of sizes was performed to investigate the morphological changes and their reversibility in the internal organs of laboratory animals.In this study,GNP's with average diameters of 2 nm,15 nm and 50nm were administered during 30 days,and the reversibility of morphological changes was investigated 14 days after administration.After the prolonged administration of GNPs,the severity of morphological changes in the liver,kidney,spleen and lymph nodes depended on the nanoparticle size.Specifically,50 nm nano-particles caused the most pronounced dystrophic and necrobiotic effects,whereas the smallest 2 nm nanoparticles caused proliferative changes.Most importantly,the development of patho-logical processes was reversible,as evidenced by the gradual restoration of the organ structure at 14 days after the end of GNPs administration.

Alterations of morphology of lymphoid organs and peripheral blood indicators under the influence of gold nanoparticles in rats

At present,gold nanoparticles(GNPs)are widely used in biomedical applications such as cancer diagnostics and therapy.Accordingly,the potential toxicity hazards of these nanomaterials and human safety concerns are gaining significant attention.Here,we report the effects of prolonged peroral administration of GNPs with different sizes(2,15 and 50 nm)on morphological changes in lymphoid organs and indicators of peripheral blood of laboratory animals.The experiment was conducted on 24 white mongrel male rats weighing 180–220 g,gold nanospheres sizes 2,15 and 50nm were administered orally for 15 days at a dosage of 190
g/kg of animal body weight.The GNPs were conjugated with polyethylene glycol to increase their biocompatibility and bioavailability.The size-dependent decrease of the number of neutrophils and lymphocytes was noted in the study of peripheral blood,especially pronounced after administration of GNPs with size of 50 nm.The stimulation of myelocytic germ of hematopoiesis was recorded at morphological study of the bone marrow.The signs of strengthening of the processes of differentiation and maturation of cellular elements were found in lymph nodes,which were showed as the increasing number of immunoblasts and large lymphocytes.The quantitative changes of cellular component morphology of lymphoid organs due to activation of migration,proliferation and di®erentiation of immune cells indicate the presence of immunostimulation effect of GNPs.

Quantification of glucose and glycerol diffusion in myocardium

The results on determination of glucose and glycerol difusion cofficients in myocardium tissuse are presented.The method is based on the measurement and analysis of temporal dependence of tissue optical collimated transmittance umder action of a hyperosmotic agent.This temporal tissue response is related to the rate of the agent and water diffusion in a tissue.The diffusion coefficients for tssue fAuid fluxes at glucose and glycerol application to the myocardium at 20℃ have been estimated as(4.75±3.40)×10^(-7) and(7.71±4.63)×10^(-7) cm^(2)/s,respectively.

THE EXPERIMENTAL STUDY OF STRESS-RELATED PATHOLOGICAL CHANGES IN CEREBRAL VENOUS BLOOD FLOW IN NEWBORN RATS ASSESSED BY DOCT

In experiments on newbom rats with stress related intracrani al hemorhage(ICH)using Doppler optical coberence tomognaphy(DOCT)we have shown that latent stage of ICH(4 h after stress)is characterized by decrease of venous blood outflow and the loss of sensitivity of sagittal vein to vasoconstrictor ffect of adrenaline.The incidence of ICH(24 h after stress)was accompanied by progressi on of early pathological changes in cerebral venous blood flow(CVBF)and development of venous insufficiency.Taking into consideration of this fact,we suggest that the suppression of CVBF related to the severity to the deleterious effect of stress on the brain hemodynamics in newborn rats.These facts allow us to conclude that the venous insufficiency with the loss of vasoconstrictor response to adrenaline is an informative and sensitive component of pattern of CVBF that can be important diagnostic criteria of risk of ICH development in newborns.

OPTICAL COHER ENCE TOMOGRAPHY OF ADIPOSE TISSUE AT PHOTODYNAMIC/PHOTOTHERMAL TRE ATMENT IN VITRO

Temporal changes in structure and refractive index distribution of adipose tissue at photo-dynamic/photothermal treatment were studied with OCT in vitro.Ethanol-water solutions of indocyanine green(ICG)and brilliant green(BG)were used for fat tissue staining.CW laser diode(808 nm)and LED light source(442 and 597 nm)were used for ir adiation of stained tissue slices.The data received supporting the hypothesis that photodynamic/photothermal treatment,induces fat cell lipolysis during a certain period of time after light exposure.

PHOTOTHERAPY OF GINGIVITIS:PILOT CLINICAL STUDY

The goal of this work was to evaluate the safety and efficacy of the Red Light Emitted Toothbrush(R-LETB)emitting at wavelength of 663 nm with power density of 3.3mW/cm2 in combination with 0.1%-methylene blue(MB)solution for the reduction of plaque and treatment of gingivitis.A microbiological in vitro study and a pilot clinical study were conducted.The microbiological study has shown total suppression of pathogenicflora after a 3-min exposure to the dye solution followed by a 20-sec treatment with the R-LETB.For the clinical study,37 subjects of both sexes with gingivitis were enrolled and randomly assigned to one of two groups.Subjects in thefirst(treatment)group were instructed to rinse their mouth with MB solution provided for 1 min and then brush the teeth with the R-LETB and standardized toothpaste.The second(control)group used only the toothpaste and a regular toothbrush.Subjects in both groups followed their respective procedures 2 times a day(morning and evening)for 30 days.Indices of plaque,gingival bleeding,and inflammation were evaluated at 14-day and 30-day timepoints.In the both groups,all indices improved in comparison with baseline.However,the treatment group demonstrated more pronounced improvement of the studied indices that was attributed to additional anti-microbial action of red light and MB on gum tissue.Thus,the use of R-LETB with MB appears to have a multifactor therapeutic action on oral pathological microflora:mechanical removal of the bacteria and suppressing action on microorganisms due to photodynamic reaction.

Introduction to the Special Issue on Advances in Biophotonics and Biomedical Optics:Part II

The 9th Chinese–Russian Workshop on Biophotonics and Biomedical Optics was held online on 28–30 September 2020.The bilateral workshop brought together both Russian and Chinese scientists,engineers,and clinical researchers from a variety of disciplines engaged in applying optical science,photonics,and imaging technologies to problems in biology and medicine.During the workshop,2 plenary lectures,35 invited presentations,5 oral presentations,and 8 internet reports were presented.This special issue selects some papers from the attendees and includes both research and review articles.

Introduction to the Special Issue on Advances in Biophotonics and Biomedical Optics

The 9th Chinese-Russian Workshop on Biopho-tonics and Biomedical Optics was held online on 28-30 September 2020.The bilateral workshop brought together both Russian and Chinese scientists,engineers,and clinical researchers from a variety of disciplines engaged in applying optical science,photonics,and imaging technologies to problems in biology and medicine.During the workshop,2 ple-nary lectures,35 invited presentations,5 oral pre-sentations,and 8 internet reports were presented.This special issue selects some papers from the attendees and includes both research and review articles.

Foreword to the Special Issue on Optical Technologies in Biophysics and Medicine

We are pleased to present the third issue of JIOHS,which focuses on optical technologies of diagnosticsand therapy,These are selected papers presented during Saratov Fall Meeting,1t International Sym-posium on Optics and Biophotonics(September 24-28,2013,Saratov,Russia)in the framework of the Workshops:"Optical Technologies in Biophysics_and Medicine,"Nanobiophotonics,"and"Internet Biophotonics."

INTRODUCTION:SPECIAL ISSUE ON ADVANCES IN BIOPHOTONICS AND BIOMEDICAL OPTICS-PART I

The 5th Russian-Chinese Workshop on Biophotonics and Biomedical Optics was hosted in Saratov,Russia on 26-28,September,2012.The bilateral Workshop brought together both Russian and Chinese scientists,engineers and clinical researchers from a variety of disciplines engaged in applying optical science,photonics and imaging technologies to problems in biology and medicine.During the W orkshop,2 plenary lectures,11 invited presentations,4 oral presentations and 13 poster reports were presented.A special Internet session with 5 presentations-1 plenary,2 invited,and 2 posters was also organized.This special issue selects some papers from the attendees,and is made up of 12 original research articles and one review.Seven articles will be presented in Vol.6 No.1 of JIOHS,while the remaining five articles will be presented in Vol.6 No.2.