Functional near infrared spectroscopy (fNIRS) is a non-invasive and safe method to measure hemodynamics of the cerebral cortex. The use fNIRS in combination with brain radiotherapy is currently of our high interest since it provides a method to measure tissue oxygenation levels during irradiation. This can potentially help to advance the field of personalized cancer treatment. However, one limitation of the fNIRS technique is associated with penetration depth into tissues. Tissue optical clearing (TOC) could potentially improve the efficiency of fNIRS and for this use of radiopaque solutions, such as Omnipaque™ (iohexol), Visipaque™ (iodixanol), etc., are proposed as effective optical clearing agents (OCA). The presented study experiments the feasibility of using TOC for fNIRS measurements in radiotherapy. The effectiveness of isosmotic Visipaque™ and an OCA with a high osmolarity, a solution of 70% glycerol with 10% DMSO, was evaluated when using chicken samples.
Carriers based on upconversion nanoparticles (UCNPs) and cyanine dye are suitable for theranostic application in oncology, although care must be taken for selection of the surface coating material, UCNP surface charge, size, and dosage of the material. Investigation of influence of annealing temperature of particles on the upconversion luminescence properties and cytotoxic effect are relevant. The present work demonstrates the assessment of cytotoxicity UCNPs unannealed and annealed at 550 oC on different normal and cancer murine cell lines in vitro. The cell viability is scored for cytotoxic effects of UCNPs at dark conditions. UCNPs provide a dose-dependent and time-dependent cytotoxic effect on all studied cell lines which was most pronounced for the Raw264.7 cell line. It is probably caused by the high phagocytic activity of macrophages. The statistically significant differences in cell viability after 24, 48 and 72 h of incubation of cells with particles were observed just for the macrophage cell line. It is also worth noting that annealed particles are less toxic than unannealed ones.
The knowledge of the optical properties of biological tissues in a wide spectral range is highly important for the development of noninvasive diagnostic or treatment procedures. The dispersion coefficient is one of those properties, from which various information about tissue components can be retrieved. This study is focused on the measurements of the refractive index of ex vivo cow brain gray matter samples in the visible/near-infrared (NIR) spectral range at room temperature for characteristic laser wavelengths: 480, 486, 546, 589, 644, 656, 680, 800, 930, 1100, 1300, and 1550 nm. Measurements were performed using the multiwavelength Abbe refractometer. Cow brain gray matter samples of 0.5 mm thick obtained from ex vivo cow brain were investigated. The specific increment of the refractive index depending on the temperature of the samples and the Sellmeier coefficients was calculated. The experimental results allowed us to calculate the cow brain gray matter dispersion with the Cauchy, Conrady, and Cornu equations. It was observed that all those equations provided good data fitting in the spectral range of the measurements, but differences were observed outside these limits. We validated the proposed method using distilled water and the cow brain gray matter ex vivo, and the experimental results were consistent with the reference data.
The present work demonstrates the assessment of cytotoxicity upconversion nanoparticles (UCNPs) coated by SiO2 on different normal and cancer murine cell lines in vitro. The cell viability is scored for cytotoxic effects of UCNPs at dark conditions. UCNPs coated by silica shells provide a dose-dependent cytotoxic effect on all studied cell lines which was most pronounced for the Raw264.7 cell line. It is probably caused by the high phagocytic activity of macrophages. The less sensitive cell line was 4T1. The statistically significant differences in cell viability after 24 and 48 h of incubation of cells with particles were observed just for the macrophage cell line. It is worth notifying that after 48 h of incubation the cytotoxic effect on Raw 264.7 cell line increased which shows a possible negative effect on some subpopulations on blood cells. The obtained results confirm a high sensitivity of the UCNPs to the concentration variations within cells. Carriers based on UCNPs and dyes are promising alternatives to photosensitizer for traditional photodynamic therapy and possess prominent potentials in biological and clinical applications.
Application of many optical methods, such as photoacoustics, optical coherent tomography, and terahertz spectroscopy, for tissue imaging and disease diagnostics is limited due to small probing depth caused by strong scattering and absorption in tissues [1, 2]. It is possible to increase the efficiency of optical techniques by using tissue optical clearing (TOC), which allows one to control tissue optical properties by exposing tissue to biocompatible liquids - optical clearing agents (OCAs). When exposed to an OCA with hyperosmotic properties, such as glycerol or highly concentrated glucose solution, it is possible to achieve a considerable decrease of tissue scattering within the entire spectral range and absorption on the water bands due to refractive index matching phenomenon and dehydration of the tissue, and therefore to get a significant increase of the optical and THz wave transmittance [1-3]. In vitro studies were performed on laboratory rats of the Vistar strain (sexually mature females weighing 300–400 g were used). The animals were inoculated with the tumor cells by subcutaneous injection into the area of the scapulae. Studies were conducted in 28 days after injection. The weight and thickness of the samples were measured before and after optical clearing by using a micrometer with an accuracy of ±0.001 mm and an analytical balance (Scientech, SA210, USA) with an accuracy of ±1 mg. The samples of the area 1.5*1.5 cm2 were placed in a closed sealed container, to which was added 2 ml of OCA. 70% glycerol solution, 40% glucose solution and 50% fructose in a 30% alcohol solution were used with the addition of saline as an OCA. The transmission spectrum of glycerol in the frequency range of 0.05–1.0 THz was measured by using the terahertz (THz) time-domain spectrometer. Measurements of the refractive index of OCA were carried out before the start of the experiment and every 5 minutes after placing the skin sample in the solution with OCA for 15 minutes, then every 10 minutes for another 45 minutes. It was found that the effectiveness of optical clearing of the skin over the tumor is higher compared to healthy skin. A good correlation was shown between the kinetics of the sample mass and THz absorption and refraction. An assessment of skin dehydration also showed that the concentration of water extracted from the skin above the tumor is greater compared to healthy. It is especially important that enhancing the image contrast due to dehydration and TOC in the pathology area is extremely significant in diagnosing precancerous conditions and treating early stages of tumor, due to the possibility of selective increase of the scattering contrast of cell nuclei relative to surrounding cytoplasm and interstitial fluid and thus following their size and internal rearrangements [5].
Photosensitizers (porphyrins) attack cancer cells and during photoactivation contribute to the generation of reactive oxygen species that damage various structures of cancer cells, which leads to their destruction. Porphyrins reach tumors through the blood and modelling of conditions for the transfer of porphyrins to the tumor (binding to blood proteins, the influence of pH and salt composition of the medium) is one of the most important problem of photodynamic therapy (PDT) of tumor. Ceruloplasmin (CP) is an important copper-containing plasma protein that actively binds photosensitizers (PS) and can play a certain role in the transfer of photosensitizers to the tumor. Changes in pH, as well as of salt composition in the tumor tissue and its cells can cause modifications in the complexes [CP + PS] and a possible separation of the PS from the complex can change the photodynamic process of tumor destruction. In this paper, it was shown that: 1) with a change in the pH of the medium from neutral to acidic, as well as with a change in the salt composition of the medium, significant conformational changes of ceruloplasmin and the transition of photosensitizers to the surface (for cationic porphyrins) or to the inside of the protein macromolecule (for chlorin e6) occur, with a partial separation of photosensitizers from protein; 2) CP can form complexes with photosensitizers and be an active carrier of PSs in the blood.
In this work, using 930-nm optical coherence tomography (OCT) and reflection spectroscopy in a wide wavelength range from UV to NIR, we investigated and confirmed the concept of the possibility of fast and efficient optical clearing of tissue, in particular human skin in vivo when using various agents and enhancers of skin permeability. The combination of a number of physico-chemical factors enhancing permeability increases the OCT signal several times with more than double the penetration depth. For dark skin and in the UV wavelength range, where absorption is high, optical clearing is not so effective, but everything is equally useful.
The relevance and importance of the development of new areas of tumor therapy is defined in connection with a strong increase in the level of oncological diseases. The latest global cancer data indicates a high mortality rate: the incidence of cancer increases to 18.1 million new cases and 9.6 million cancer deaths in 2018. Advances in nanostructures and nanotechnologies at the molecular scale in future can revolutionize several aspects of the diagnosis and treatment of body tumors. Search of highly specific and highly effective new therapeutic compounds is one of the most important directions in treatment of oncological diseases by noninvasive way. Currently, in clinics method of photodynamic therapy (PDT) of tumors based on photosensitizers (PSs) and light irradiation is widely used. At its application, the cancer cells are unable to develop resistance to such method of destruction.
Optical clearing of the human skin under the action of hyaluronic acid (HA) as an enhancer for optical clearing by polyethylene glycol (PEG-300) was studied in vivo by optical coherent tomography (OCT) method on the wavelength 930±5 nm. The results have showed an increase in the transparency of the epidermis at the optical depth of 50±5 μm by 44±9% within 15 min with the use of a solution of HA in combination with sonophoresis before application of PEG-300 to the skin surface. At the same time, when using PEG-300 without preliminary treatment of the skin with the HA, an increase in the transparency of the epidermis at the same depth was 21±8% within 25 min. In dermis at the depth of 500 μm the OCT signal in the experimental group increased more than 1.6 fold what indicates an increasing of optical probing depth.
The problem of extracting useful information for medical diagnosis from 2D and 3D optical imaging experimental data is of great importance. We are discussing challenges and perspectives of medical diagnosis using machine learning analysis of NIR and THz tissue imaging. The peculiarities of tissue optical clearing for tissue imaging in NIR and THz spectral ranges aiming the improvement of content data analysis, methods of extracting of informative features from experimental data and creating of prognostic models for medical diagnosis using machine learning methods are discussed.
Nowadays, dynamically developing optical (photonic) technologies play an ever-increasing role in medicine. Their adequate and effective implementation in diagnostics, surgery, and therapy needs reliable data on optical properties of human tissues, including skin. This paper presents an overview of recent results on the measurements and control of tissue optical properties. The issues reported comprise a brief review of optical properties of biological tissues and efficacy of optical clearing (OC) method in application to monitoring of diabetic complications and visualization of blood vessels and microcirculation using a number of optical imaging technologies, including spectroscopic, optical coherence tomography, and polarization- and speckle-based ones. Molecular modeling of immersion OC of skin and specific technique of OC of adipose tissue by its heating and photodynamic treatment are also discussed.
In this study, the optical properties of glycated (HbA1c) and non-glycated (Hb) hemoglobin are compared using refractometry, fluorescence and Raman spectroscopy. The fluorescence measured at an excitation wavelength of 270 nm indicates differences in the molecular structure of hemoglobins. Analysis of the spectral shift of Raman spectra also showed variations indicating differences in their molecular structure. The refractive index measured in the visible and near IR regions for different temperatures allowed for quantification of mean values of temperature increment, which are quite different as dn/dT= –(1.03 ± 0.05)×10–4 °C–1 for Hb and – (1.37 ± 0.07)×10–4 °C–1for HbA1c.The data obtained in the work can serve as a basis for further study of the optical properties of glycated hemoglobin and other glycated proteins.
This study is focused on the measurements of the refractive index of hemoglobin solutions in the visible/near-infrared (NIR) spectral range at room temperature for characteristic laser wavelengths: 480, 486, 546, 589, 644, 656, 680, 930, 1100, 1300, and 1550 nm. Measurements were performed using the multiwavelength Abbe refractometer. Aqua hemoglobin solutions of different concentrations obtained from human whole blood were investigated. The specific increment of refractive index on hemoglobin concentration and the Sellmeier coefficients were calculated.
In this study, the refractive index of hemoglobin was measured at different temperatures within a physiological range and above that is characteristic to light-blood interaction at laser therapy. Measurements were carried out using the multi-wavelength Abbe refractometer (Atago, Japan). The refractive index was measured at two NIR wavelengths of 930 nm and 1100 nm. Samples of hemoglobin solutions with concentration of 80, 120 and 160 g/l were investigated. The temperature was varied between 25 and 55 °C. It was shown that the dependence of the refractive index of hemoglobin is nonlinear with temperature, which may be associated with changes in molecular structure of hemoglobin.
This study is focused on the determination of the absorbance of oxyhemoglobin solutions at different concentrations of
glucose (from 0 to 1000 mg/dl with a step 100 mg/dl) and hemoglobin (3.2g/l) incubation with glucose from 3 hours to a
few weeks. The absorbance was determined within the wavelength range from 500 to 900 nm. Measurements of the
absorbance spectra have been performed using a double-beam double-wavelength spectrophotometer.
This study is focused on the determination of the extinction coefficient of oxyhemoglobin solutions at different
concentrations of glucose and hemoglobin incubation with glucose from 3 days to 18 days. The extinction coefficient
was determined using absorbance measurements at the wavelength range from 500 nm to 850 nm. Measurements of the
absorbance spectra have been performed using fiber-optic spectrometer USB2000 (Ocean Optics, USA).
This study is focused on the determination of the real and imaginary parts of the complex refractive index of
oxyhemoglobin and deoxyhemoglobin solutions (1.6 g/l) at different concentrations of glucose (from 0 to 1000 mg/dl
with a step of 100 mg/dl) from a few hours to over one week of incubation. The real part was measured using Abbe
refractometer. Theoretical values of real part of refractive index were calculated supposing non-interacting hemoglobin
and glucose molecules. The imaginary part was determined using transmittance measurements at the wavelength range
from 500 nm to 1000 nm. It is shown that the real and imaginary parts of the complex refractive index measurements
have a potential for the evaluation of glycated hemoglobin amount.
This study is focused on the determination of the absorption coefficients for calculating the imaginary part of the complex
refractive index of oxyhemoglobin and deoxyhemoglobin solutions (1.6g/l) at different concentrations of glucose (from 0 to
1000 mg/dl with a step 100 mg/dl) from a few hours to over two week of incubation. The absorption coefficients were
determined using transmittance measurements at the wavelength range from 500 nm to 1000 nm.
This study is focused on the determination of the absorption coefficients of oxyhemoglobin and deoxyhemoglobin
solutions (1.6g/l) at different concentrations of glucose (from 0 to 1000 mg/dl with a step 100 mg/dl) from a few hours to
over two week of incubation. The absorption coefficients were determined using transmittance measurements at the
wavelength range from 500 nm to 1000 nm.
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