In Part I of this paper, a framework for multivariate selectivity was introduced that is both calculable from first principles and experimentally tractable. In this part, we employ the proposed selectivity framework for analyzing both in vitro and in vivo near-infrared experimental data. Two in vitro data sets are used to compare different methods for estimating selectivity and to demonstrate the benefits obtained from validation data with expanded interferant concentration ranges. The in vitro data also demonstrate that the experimentally estimated selectivities provide insights into the properties of the calibration models that are difficult or impossible to infer by other means. The merits of the proposed selectivity function are further demonstrated using a complex in vivo application: the noninvasive measurement of ethanol in humans. Results indicate that in vivo calibration model sensitivity, selectivity, and concentration correlations can be systematically interrogated using the proposed selectivity framework and judicious use of experimental measurements. These analyses not only provide selectivity and sensitivity information, but also the variance components of the total MSEP, which is invaluable information for both method development and analytical method characterization.
Abstract. Alcohol testing is an expanding area of interest due to the impacts of alcohol abuse that extend well beyond drunk driving. However, existing approaches such as blood and urine assays are hampered in some testing environments by biohazard risks. A noninvasive, in vivo spectroscopic technique offers a promising alternative, as no body fluids are required. The purpose of this work is to report the results of a 36-subject clinical study designed to characterize tissue alcohol measured using near-infrared spectroscopy relative to venous blood, capillary blood, and breath alcohol. Comparison of blood and breath alcohol concentrations demonstrated significant differences in alcohol concentration ͓root mean square of 9.0 to 13.5 mg/ dL͔ that were attributable to both assay accuracy and precision as well as alcohol pharmacokinetics. A first-order kinetic model was used to estimate the contribution of alcohol pharmacokinetics to the differences in concentration observed between the blood, breath, and tissue assays. All pair-wise combinations of alcohol assays were investigated, and the fraction of the alcohol concentration variance explained by pharmacokinetics ranged from 41.0% to 83.5%. Accounting for pharmacokinetic concentration differences, the accuracy and precision of the spectroscopic tissue assay were found to be comparable to those of the blood and breath assays.
A practical limitation encountered in alcohol research is the relatively small number of body compartments (e.g. blood, liver, tissue) that can be directly interrogated. In this work, an NIR spectroscopic device was investigated that provided a direct measurement of alcohol concentration in skin tissue (interstitial fluid). This work is intended to characterize the relationship of forearm interstitial fluid alcohol concentration relative to capillary blood using a first order kinetic model. Concurrent blood and tissue alcohol concentrations were collected on 101 test subjects while consuming alcohol. Estimates of the first order kinetic rate constant were calculated for each of the subjects. It is hoped that this characterization will lead to further improvements in optical based alcohol monitors for impairment detection.
Multivariate calibration transfer in spectroscopy is an active area of interest. Many current approaches rely on the measurement of a subset of calibration samples on each instrument produced, an approach that can be impractical in many applications. Furthermore, such methods attempt to model implicitly, rather than explicitly, interinstrument differences. In Part I of this work, a Fourier transform near-infrared spectroscopy (FT-NIR) system designed to perform noninvasive ethanol measurements is discussed. Optical distortions caused by self-apodization, shear, and off-axis detector field of view (FOV) are examined and equations describing their effects are given. The effects of shear and off-axis detector FOV are shown to yield nonlinear distortions of the amplitude and wavenumber axes of measured spectra that cannot be accommodated by typical wavenumber calibration procedures or background correction. The distortions forecast by these equations are verified using laboratory measurements, and an analysis of the spectral complexity caused by the distortions is presented. The theoretical and experimental aspects presented in Part I are incorporated into a new calibration transfer method whose benefits are illustrated in Part II using noninvasive alcohol measurements. Although this work discusses a specific FT-NIR instrument and application, the methods developed form a general framework for modeling the distortions of other types of optical spectrometers to improve instrument standardization and multivariate calibration transfer.
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