Veronika V. Sapozhnikova

In vivo study of glucose-induced changes in skin properties assessed with optical coherence tomography

Recently, our in vivo studies demonstrated a strong correlation between blood glucose concentration and the slope of the optical coherence tomography (OCT) signal when the probing beam was scanned over a straight line. To improve the sensitivity of OCT for blood glucose monitoring, two-dimensional (2D) lateral scanning of the OCT probing beam was proposed. Depth-dependent changes in pig skin properties with variation of blood glucose concentration were revealed due to significant suppression of speckle noise and motion artefacts in 2D scanning mode. The correlation coefficient of the OCT signal slope with blood glucose concentration varied periodically in the range from -0.9 to +0.9 depending on depth. The period of variation of the correlation coefficient was 100-150 microm that corresponded to the distance between neighbour collagen bundles. We also observed a decrease of skin thickness by 10 +/- 7.5 microm with an increase of blood glucose concentration by 277 +/- 56 mg dl(-1). Mechanisms of glucose-induced changes in skin properties owing to tissue layer shift caused by dehydration associated with the glucose osmotic effect were considered.

Effect on blood glucose monitoring of skin pressure exerted by an optical coherence tomography probe

We proposed to use optical coherence tomography (OCT) for continuous noninvasive blood glucose monitoring, and recently we significantly improved the sensitivity of this technique. The accuracy of OCT glucose monitoring is limited by several factors, including variation of tissue pressure exerted by the OCT probe. We studied the influence of high (>10 kPa) and low (<1 kPa) pressure levels on OCT blood glucose monitoring. We showed that controlling external pressure to <1 kPa substantially improved the accuracy and reproducibility of OCT-based glucose monitoring.

Prediction Capability of Optical Coherence Tomography for Blood Glucose Concentration Monitoring

Background: Optical coherence tomography (OCT) has been shown to be a promising optical approach to noninvasive monitoring of blood glucose concentration because of its capability of probing optical properties at different depths in tissue with high resolution. This article investigates the capability of OCT to predict changes in blood glucose concentration. Methods: We varied blood glucose concentration in the physiological range in three sets of experiments. In the first set, we investigated large variations of blood glucose concentration (=400 mg/dl) and used 2100 OCT A scans for signal averaging. In the second set, we varied blood glucose concentration by approximately 200 mg/dl and used 8400 A scans for signal averaging. In the third set, we improved OCT blood glucose monitoring by increasing and controlling skin temperature under the OCT probe. In this set of experiments we increased the glucose concentration by approximately 300 mg/dl and used 4200 A scans for averaging. Results: The predicted glucose concentrations in the first two sets were lower than actual glucose concentration by 10–20% (the mean shift), while the heating and temperature control in the third set of experiments reduced the mean shift down to 1.5%. Therefore, the mean shift was reduced substantially by tissue heating and temperature control. However, it did not depend on the number of A scans to be averaged. In contrast, the uncertainty in OCT prediction of glucose concentration (the standard deviation) did not depend on heating and temperature control, but was reduced substantially from 56 to 24 mg/dl by increasing the number of A scans from 2100 to 8400, respectively. Conclusion: These results suggest that the accuracy of OCT-based glucose monitoring is approaching that of standard invasive and minimally invasive techniques.

Influence of osmolytes on in vivo glucose monitoring using optical coherence tomography.

Diabetes mellitus and its complications are the third leading cause of death in the world, exceeded only by cardiovascular disease and cancer. Tighter monitoring and control of blood glucose could minimize complications associated with diabetes. Recently, optical coherence tomography (OCT) for noninvasive glucose monitoring was proposed and tested in vivo. The aim of this work was to investigate the influence of changes in blood glucose concentration ([glu]) and sodium concentration ([Na+]) on the OCT signal. We also investigated the influence of other important analytes on the sensitivity of glucose monitoring with OCT. The experiments were carried out in anesthetized female pigs. The OCT images were acquired continuously from skin, while [glu] and [Na+] were experimentally varied within their physiological ranges. Correlations of the OCT signal slope with [glu] and [Na+] were studied at different tissue depths. The tissue area probed with OCT was marked and cut for histological examination. The correlation of blood [glu] and [Na+] with the OCT signal slope was observed in separate tissue layers. On average, equimolar changes in [glu] produced 2.26 ± 1.15 greater alterations of the OCT signal slope than changes in [Na+]. Variation of concentrations of other analytes did not Influence the OCT signal slope. The influence of [Na+] on relative changes in the OCT signal slope was generally less than [glu]-induced changes. OCT is a promising method for noninvasive glucose monitoring because of its ability to track the influence of changing [glu] on individual tissue layers.

Correlation between optical coherence tomography images and histology of pigskin

Noninvasive imaging techniques such as optical coherence tomography (OCT) are being widely used for early diagnostics of a variety of pathologies. Traditional tissue preparation for histological evaluation alters the dimensions of histological images such that differences between the dimensions of histologic and OCT images can be as great as 2.5-fold. This discrepancy complicates quantitative interpretation of OCT images. Here we used a steel ring sewn to the pigskin to avoid tissue deformation due to excision and fixation and used a surgical suture as a fixed tissue marker. With these techniques, we achieved good correlation between OCT and histological images with differences of less than 10%. The resulting method significantly enhances the diagnostic capabilities of the OCT technique.

In vivo application of 2-D lateral scanning mode optical coherence tomography for glucose sensing

Optical Coherence Tomography (OCT) was recently proposed by our group for noninvasive, continuous monitoring of blood glucose concentration in diabetics as well as in critically ill patients (both diabetic and nondiabetic). In our previous studies we tested OCT-based glucose sensing using one-dimensional (1-D) lateral scanning of the OCT probing beam over the tissue surface. The measured OCT signal was prone to motion artifacts and had high level of speckle noise. In this study we used two-dimensional (2-D) lateral scanning of the OCT probing beam and achieved 3.6-fold reduction of the speckle noise level. We also applied a post-processing Fourier filtration technique that resulted in an additional 2-2.5-fold suppression of noise. Our data indicate that the combination of acquisition time of 30-40s and the Fourier filtration technique may provide OCT monitoring of blood glucose concentration with a sensitivity of 1mM (18 mg/dL).

Complementary use of optical coherence tomography and 5-aminolevulinic acid induced fluorescent spectroscopy for diagnosis of neoplastic processes in cervix and vulva

A new approach to improving the diagnostic value of optical methods is suggested, which is based on a complementary investigation of different optical parameters of biotissues. The aim of this paper is comparative study of the feasibility of two optical methods - fluorescence spectroscopy and optical coherence tomography - for visualization of borders of neoplastic processes in the uterine cervix and vulva. Fluorescence spectroscopy is based on the detection of biochemical and optical coherence tomography on backscattering properties in norm and pathological changes of tissues. By means of these optical methods changes in biochemical and morphological properties of tissues were investigated. A parallel analysis of these two optical methods and histology from the center of tumors and their optical borders was made. Thirteen female patients with neoplastic changes in uterine cervix and vulva were enrolled in this study. The borders of the tumor determined by optical methods (fluorescence spectroscopy and optical coherence tomography) are coinciding with the biopsy proved ones. In addition, OCT and fluorescence borders of tumor in the uterine cervix and vulva exceeds colposcopically detectable borders, the averaging difference 2 mm. In future optical methods would considerably enhance diagnostic accuracy of conventional methods used in oncogynecology.

Investigation of biological tissues using PM-fiber-based polarization sensitive optical coherence tomography

A PM fiber based PS OCT setup with simultaneous acquisition of signals in orthogonal polarization channels with an isolation ratio > 28 dB was created. The principles of measuring the tissue birefringence based on detecting only an envelope of OCT signal in the orthogonal polarization were described. The birefringence and depolarization degree of in vivo and ex vivo biotissues of different types were investigated.

New advances in optical coherence tomography for diagnostics of cervical neoplasia

Diagnostic value of standard OCT for recognizing cervical neoplasia has been evaluated: sensitivity is 82%, specificity is 78%, and diagnostics accuracy is 81%. To increase it several approaches have been suggested: application of hyperosmotic agents, cross-polarization tomography, complementary use of fluorescence spectroscopy and OCT, additional computer processing of the OCT-images and optical coherence microscipy.

Optical coherence tomography for visualization of plant tissues

First experimental results on optical coherence tomography (OCT) imaging of internal structure of plant tissues and in situ OCT monitoring of plant tissue regeneration at different water supply are reported. The OCT images are a map of backscattering coefficient 200 x 200 pixels, 1.5 mm along plant surface and up to 2 mm in depth (by analogy with ultrasound B-scan). Experiments for evaluating OCT capabilities were performed on Tradescantia blossfeldiana Mild. Using OCT device, in vivo images of plant tissues were acquired with a spatial resolution of 15 μm. These OCT images correlate with standard microscopy data from the same tissue regions. Since incident light power at a wavelength of 1.3 μm is as low as 0.5 mW, two-dimensional OCT images can be obtained directly on an intact plant not damaging it. Acquisition time for a 2D image is 1-3 s. OCT enables effective monitoring of fast reactions in plants at different water supply.