Accurate and noninvasive measurement of tissue optical properties can be used for biomedical diagnostics and monitoring of tissue analytes. Noninvasive measurement of tissue optical properties (total attenuation and scattering coefficients, optical thickness, etc.) can be performed with the optical coherence tomography (OCT) technique. However, speckle noise substantially deteriorates the accuracy of the measurements with this technique. We studied suppression of speckle noise for accurate measurement of backscattering signal and scattering coefficient with the OCT technique. Our results demonstrate that the precision of measurement of backscattering signals with the OCT technique can be 0.2% for homogeneously scattering media and 0.7% for skin, if spatial averaging of speckle noise is applied. This averaging allows us to achieve the precision of tissue scattering coefficient measurements of approximately +/-0.8%. This precision can be further improved by a factor of 2-3, upon optimization of OCT operating parameters.

Pulmonary fibrosis, characterized by excessive collagen deposition in the lungs, comprises a key and debilitating component of chronic lung diseases. Methods are lacking for the direct visualization of fibrillar collagen throughout the whole murine lung, a capability that would aid the understanding of lung fibrosis. We combined an optimized organ-level optical clearing (OC) approach with large-scale, label-free multiphoton microscopy (MPM) and second harmonic generation microscopy (SHGM) to reveal the complete network of fibrillar collagen in whole murine lungs. An innate inflammation-driven model based on repetitive poly(I:C) challenge was evaluated. Following OC, mosaic MPM/SHGM imaging with 3D reconstruction and whole organ quantitative analysis revealed significant differences in collagen deposition between PBS and poly(I:C) treated lungs. Airway specific analysis in whole lung acquisitions revealed significant sub-epithelial fibrosis evident throughout the proximal conductive and distal airways with higher collagen deposition in the poly(I:C) group vs PBS group. This study establishes a new, powerful approach based on OC and MPM/SHGM imaging for 3D analysis of lung fibrosis with macroscopic views of lung pathology based on microscopy and providing a new way to analyze the whole lung while avoiding regional sampling bias.

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We investigated the feasibility of constructing an implantable optical-based sensor for seminoninvasive continuous monitoring of analytes. In this novel sensor, analyte concentration-dependent changes induced in the degree of optical turbidity of the sensing element can be accurately monitored by optical coherence tomography (OCT), an interferometric technique. To demonstrate proof-of-concept, we engineered a sensor for monitoring glucose concentration that enabled us to quantitatively monitor the glucose-specific changes induced in bulk scattering (turbidity) of the sensor. The sensor consists of a glucose-permeable membrane housing that contains a suspension of macroporous hydrogel particles and concanavalin A (ConA), a glucose-specific lectin, that are designed to alter the optical scattering of the sensor as a function of glucose concentration. The mechanism of modulation of bulk turbidity in the sensor is based on glucose-specific affinity binding of ConA to pendant glucose residues of macroporous hydrogel particles. The affinity-based modulation of the scattering coefficient was significantly enhanced by optimizing particle size, particle size distribution, and ConA concentration. Successful operation of the sensor was demonstrated under in vitro condition where excellent reversibility and stability (160 days) of prototype sensors with good overall response over the physiological glucose concentration range (2.5-20 mM) and good accuracy (standard deviation 5%) were observed. Furthermore, to assess the feasibility of using the novel sensor as one that can be implanted under skin, the sensor was covered by a 0.4 mm thick tissue phantom where it was demonstrable that the response of the sensor to 10 mM glucose change could still be measured in the presence of a layer of tissue shielding the sensor aiming to simulate in vivo condition. In summary, we have demonstrated that it is feasible to develop an affinity-based turbidity sensor that can exhibit a highly specific optical response as a function of changes in local glucose concentration and such response can be accurately monitored by OCT suggesting that the novel sensor can potentially be engineered to be used as an implantable sensor for in vivo monitoring of analytes.

The results of an experimental investigation of the twofold degenerate vibrations in calcite (E,-type; phonon frequency QE/hC = 721 cm-I) by means of active spectroscopy method, including a new modification of this method are reported. Beating of a biharmonic pump consisting of Nd: YAG laser radiation and tunable (narrow band or broad band) radiation from an optical parametric oscillator (OPO) was used to excite coherent optical phonons above the thermal level. Scattering of the second harmonic of Nd: YAG was used to detect these coherent vibrations. The components of the Raman scattering tensor for Eg phonons and the absolute sign of the component of the nonresonant cubic electronic susceptibility were measured. Journal of RamanSpectroscopy 2 (1974) 239-248. All Rights Reserved Copyright 0 1974 by D. Reidel Publishing Company, Dordrecht-Holland 240 S. A. AKHMANOV ET AL. a