Accurate measurement of total attenuation coefficient of thin tissue with optical coherence tomography

Noninvasive accurate measurements of tissue optical properties are needed for many diagnostic and therapeutic applications. Optical coherence tomography (OCT) recently proposed for high-resolution imaging in tissue can potentially be applied for accurate, noninvasive, and high-resolution measurement of tissue total attenuation coefficient. However, confocal function (dependence of OCT sensitivity on the distance of probed site from the focal plane of the objective lens) and multiple scattering substantially limit the accuracy of the measurement with the OCT technique. We studied the influence of the confocal function and multiple scattering on the accuracy of the measurement and proposed methods that provide measurement of the total attenuation coefficient with a significantly reduced systematic error. Experiments were performed in tissue phantoms and porcine and human skin in vitro and in vivo. Our data indicate that the tissue total attenuation coefficient can noninvasively be measured in vivo with the accuracy of 5%-10% in the range from 0.5 to 17 mm/sup -1/ and about 20% in the range up to 40 mm/sup -1/. These results suggest that the proper correction of the OCT-based measurement for the confocal function and multiple scattering provides absolute values of tissue total attenuation coefficient with high accuracy and resolution that may not be achievable by other optical techniques in vivo.     

Precision of measurement of tissue optical properties with optical coherence tomography

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.     

Affinity-based turbidity sensor for glucose monitoring by optical coherence tomography: toward the development of an implantable sensor

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.