KEYWORDS: Glucose, Blood, Optical coherence tomography, Signal attenuation, Magnesium, In vitro testing, Statistical analysis, In vivo imaging, Data modeling, Multiple scattering
As diabetes causes millions of deaths worldwide every year, new methods for blood glucose monitoring are in demand. Noninvasive approaches may increase patient adherence to treatment while reducing costs, and optical coherence tomography (OCT) may be a feasible alternative to current invasive diagnostics. This study presents two methods for blood sugar monitoring with OCT in vitro. The first, based on spatial statistics, exploits changes in the light total attenuation coefficient caused by different concentrations of glucose in the sample using a 930-nm commercial OCT system. The second, based on temporal analysis, calculates differences in the decorrelation time of the speckle pattern in the OCT signal due to blood viscosity variations with the addition of glucose with data acquired by a custom built Swept Source 1325-nm OCT system. Samples consisted of heparinized mouse blood, phosphate buffer saline, and glucose. Additionally, further samples were prepared by diluting mouse blood with isotonic saline solution to verify the effect of higher multiple scattering components on the ability of the methods to differentiate glucose levels. Our results suggest a direct relationship between glucose concentration and both decorrelation rate and attenuation coefficient, with our systems being able to detect changes of 65 mg/dL in glucose concentration.
KEYWORDS: Optical coherence tomography, Glucose, Signal attenuation, In vitro testing, Interferometry, Diagnostics, Blood, Statistical analysis, Radar, Analytical research, Data modeling, Chemical vapor deposition, Refractive index
Development of non-invasive techniques for glucose monitoring is crucial to improve glucose control and treatment
adherence in patients with diabetes. Hereafter, Optical Coherence Tomography (OCT) may offer a good alternative for
portable glucometers, since it uses light to probe samples. Changes in the object of interest can alter the intensity of light
returning from the sample and, through it, one can estimate the sample's attenuation coefficient (μt) of light. In this work,
we aimed to explore the behavior of μt of mouse's blood under increasing glucose concentrations. Different samples
were prepared in four glucose concentrations using a mixture of heparinized blood, phosphate buffer saline and glucose.
Blood glucose concentrations were measured with a blood glucometer, for reference. We have also prepared other
samples diluting the blood in isotonic saline solution to check the effect of a higher multiple-scattering component on the
ability of the technique to differentiate glucose levels based on μt. The OCT system used was a commercial Spectral
Radar OCT with 930 nm central wavelength and spectral bandwidth (FWHM) of 100 nm. The system proved to be
sensitive for all blood glucose concentrations tested, with good correlations with the obtained attenuation coefficients. A
linear tendency was observed, with an increase in attenuation with higher values of glucose. Statistical difference was
observed between all groups (p<0.001). This work opens the possibility towards a non-invasive diagnostic modality
using OCT for glycemic control, which eliminates the use of analytes and/or test strips, as in the case with commercially
available glucometers.
Red and near-infrared light have been widely employed in optical therapies. Skin is the most common optical barrier in non-invasive techniques and in many cases it is the target tissue itself. Consequently, to optimize the outcomes brought by lightbased therapies, the optical properties of skin tissue must be very well elucidated. In the present study, we evaluated the dorsal skin optical properties of albino (BALB/c) and pigmented (C57BL/6) mice using the Kubelka-Munk photon transport model. We evaluated samples from male and female young mice of both strains. Analysis was performed for wavelengths at 630, 660, 780, 810 and 905 nm due to their prevalent use in optical therapies, such as low-level light (or laser) and photodynamic therapies. Spectrophotometric measurements of diffuse transmittance and reflectance were performed using a single integrating sphere coupled to a proper spectrophotometer. Statistic analysis was made by two-way ANOVA, with Tukey as post-test and Levenne and Shapiro-Wilks as pre-tests. Statistical significance was considered when p<0.05. Our results show only a slight transmittance increment (<10 %) as wavelengths are increased from 630 to 905 nm, and no statistical significance was observed. Albino male mice present reduced transmittance levels for all wavelengths. The organization and abundance of skin composing tissues significantly influence its scattering optical properties although absorption remains constant. We conclude that factors such as subcutaneous adiposity and connective tissue structure can have statistically significant influence on mice skin optical properties and these factors have relevant variations among different gender and strains.
Metabolic syndrome comprises a constellation of morbidities such as insulin resistance, hyperinsulinemia, atherogenic
dyslipidemia, dysglycemia and obesity (especially abdominal). Metabolic alterations are observed in major insulin target
organs, increasing the risk of cardiovascular diseases, type-2 diabetes and therefore mortality. Tissue alterations are
characterized by immune cells infiltrates (especially activated macrophages). Released inflammatory mediators such as
TNF-α induce chronic inflammation in subjects with metabolic syndrome, since inflammatory pathways are activated in
the neighboring cells. The intra-abdominal adipose tissue appears to be of particular importance in the onset of the
inflammatory state, and strategies contributing to modulate the inflammatory process within this adipose tissue can
mitigate the metabolic syndrome consequences. Considering the low level light therapy (LLLT) recognized benefits in
inflammatory conditions, we hypothesized this therapeutic approach could promote positive effects in modulating the
inflammatory state of metabolic syndrome. That being the scope of this study, male C57BL/6 mice were submitted to a
high-fat/high-fructose diet among 8 weeks to induce metabolic syndrome. Animals were then irradiated on the
abdominal region during 21 days using an 850 nm LED (6 sessions, 300 seconds per session, 60 mW output power,
~6 J/cm2 fluence, ~19 mW/cm2 fluence rate). Before and during treatment, blood was sampled either from the retroorbital
plexus or from tail puncture for glucose, total cholesterol and triglycerides analysis. So far our results indicate no
alterations on these metabolic parameters after LLLT. For further investigations, blood was collected for plasma
inflammatory cytokine quantification and fresh ex vivo samples of liver and intra-abdominal adipose tissue were
harvested for immunohistochemistry purposes.
Over the last few years, low-level light therapy (LLLT) has shown an incredible suitability for a wide range of applications for central nervous system (CNS) related diseases. In this therapeutic modality light dosimetry is extremely critical so the study of light propagation through the CNS organs is of great importance. To better understand how light intensity is delivered to the most relevant neural sites we evaluated optical transmission through slices of rat brain point by point. We experimented red (λ = 660 nm) and near infrared (λ = 808 nm) diode laser light analyzing the light penetration and distribution in the whole brain. A fresh Wistar rat (Rattus novergicus) brain was cut in sagittal slices and illuminated with a broad light beam. A high-resolution digital camera was employed to acquire data of transmitted light. Spatial profiles of the light transmitted through the sample were obtained from the images. Peaks and valleys in the profiles show sites where light was less or more attenuated. The peak intensities provide information about total attenuation and the peak widths are correlated to the scattering coefficient at that individual portion of the sample. The outcomes of this study provide remarkable information for LLLT dose-dependent studies involving CNS and highlight the importance of LLLT dosimetry in CNS organs for large range of applications in animal and human diseases.
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