RESUMEN
The diagnostic capability of high-resolution optical coherence tomography (OCT) may be enhanced by using extended depth-of-field (EDOF) imaging that retains high transverse resolution over long depths. A recently developed mirror-tunnel optical probe design (single-mode fiber to multimode fiber to lens structure) that generates coaxially focused modes has been previously shown to enable EDOF for endoscopic OCT applications. Here, we present ray-tracing optical modeling of this optical configuration, which has the potential to guide performance improvement through optimization. The Huygens wave propagation of the field was traced through probe components with initial lengths. The irradiance along the x-z plane was analyzed, yielding an average full width at half-maximum (FWHM) of 9 µm over a 640 µm DOF (defined as the axial range over which the beam's transverse FWHM is maintained). A custom merit function was then defined, based on the focal region illumination intensity profile that yielded the maximum possible depth having a constrained FWHM size. An orthogonal gradient descent optimization algorithm was then applied using this merit function, using the multimode fiber, spacer, and lens lengths as variables. Optimization resulted in a modeled mean 6 µm FWHM spot diameter over an EDOF of 1 mm. Following optimization, a probe was fabricated, and was validated using a custom-built near-field scanning pinhole beam profiler. The experimental results (6 µm mean FWHM over 800 µm EDOF) showed reasonable correspondence to the simulated predictions, demonstrating the potential utility of optical modeling and optimization for improving EDOF performance in mirror-tunnel endoscopic OCT probes.
RESUMEN
Raman spectra of a set of coated pharmaceutical tablets were analyzed for the purpose of calibrating the spectra to tablet coating thickness. Acetaminophen tablets were coated with a hydroxypropylmethylcellulose/polyethylene glycol film coating whose thickness was varied from 0 to 6% weight gain. Coatings were also prepared with two concentrations of TiO2 at several film thicknesses. The resulting spectral data set was analyzed using several different multivariate calibration procedures. The procedures examined in this study included spectral correction followed by target factor analysis, spectral correction with baseline subtraction followed by principal component regression, and first derivative computation followed by principal component regression. The results demonstrate that target factor analysis is a viable method for calibration of Raman spectra to tablet coating thickness. Calibration based on derivative spectra resulted in linear correlation that was equal to that of the results of target factor analysis for coatings without TiO2. However, target factor analysis was found to be superior to other methods when TiO2 was present in the tablet coatings. The effect of sample fluorescence on each of these chemometric methods was also examined. It was found that when photobleaching of fluorescent impurities due to exposure to the Raman excitation source was controlled, the tablet coating thickness could be calibrated to the intensity of the fluorescence signal. The results also demonstrate that for the samples examined here, calibration by target factor analysis is insensitive to variation in fluorescent intensity when the tablet coating emission spectrum is included in the matrix of target vectors.