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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.

Noninvasive glucose monitoring development is critical for diabetic patient continuous monitoring. However, almost all the available devices are invasive and painful. Noninvasive methods such as using spectroscopy have shown some good results. Unfortunately, the drawback was that the tungsten halogen lamps usage that is impractical if applied on human skin. This paper compared the light emitting diode (LED) to traditional tungsten halogen lamps as light source for glucose detection where the type of light source plays an important role in achieving a good spectrum quality. Glucose concentration measurement has been developed as part of noninvasive technique using optical spectroscopy. Small change and overlapping in tungsten halogen results need to replace it with a more convenient light source such as LED. Based on the result obtained, the performance of LED for absorbance spectrum gives a significantly different and is directly proportional to the glucose concentration. The result shows a linear trend and successfully detects lowest at 60 to 160 mg/dL glucose concentration.

Multivariate calibration is an important tool for spectroscopic measurement of analyte concentrations. We present a detailed study of a hybrid multivariate calibration technique, constrained regularization (CR), and demonstrate its utility in noninvasive glucose sensing using Raman spectroscopy. Similar to partial least squares (PLS) and principal component regression (PCR), CR builds an implicit model and requires knowledge only of the concentrations of the analyte of interest. Calibration is treated as an inverse problem in which an optimal balance between model complexity and noise rejection is achieved. Prior information is included in the form of a spectroscopic constraint that can be obtained conveniently. When used with an appropriate constraint, CR provides a better calibration model compared to PLS in both numerical and experimental studies.

We propose a novel optical method for glucose measurement based on diffuse photon-pair density wave (DPPDW) in a multiple scattering medium (MSM) where the light scattering of photon-pair is induced by refractive index mismatch between scatters and phantom solution. Experimentally, the DPPDW propagates in MSM via a two-frequency laser (TFL) beam wherein highly correlated pairs of linear polarized photons are generated. The reduced scattering coefficient ${\mu }_{2s}^{\prime }$ and absorption coefficient ${\mu }_{2a}$ of DPPDW are measured simultaneously in terms of the amplitude and phase measurements of the detected heterodyne signal under arrangement at different distances between the source and detection fibers in MSM. The results show that the sensitivity of glucose detection via glucose-induced change of reduced scattering coefficient ($\delta {\mu }_{2s}^{\prime }$) is 0.049%mM${}^{-1}$ in a 1% intralipid solution. In addition, the linear range of $\delta {\mu }_{2s}^{\prime }$ vs glucose concentration implies that this DPPDW method can be used to monitor glucose concentration continuously and noninvasively subcutaneously.

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 components. Such matching is obtained by partial replacement of interstitial water by a biocompatible agent that presents higher RI and it can be completely reversible by natural rehydration in vivo 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 characterization and discrimination. Comparing these properties with data from literature that characterize their diffusion in water we have observed that muscle cell membrane permeability limits agent and water diffusion in the muscle. The same experimental data has allowed to calculate the optical clearing (OC) efficiency and make an interpretation 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 considerable improvement of optical tomographic techniques with better contrast and in-depth imaging.