Previous works investigated a spectroscopic technique that offered a promising alternative to blood and breath assays for determining in vivo alcohol concentration. Although these prior works measured the dorsal forearm, we report the results of a 26-subject clinical study designed to evaluate the spectroscopic technique at a finger measurement site through comparison to contemporaneous forearm spectroscopic, venous blood, and breath measurements. Through both Monte Carlo simulation and experimental data, it is shown that tissue optical probe design has a substantial impact on the effective path-length of photons through the skin and the signal-to-noise ratio of the spectroscopic measurements. Comparison of the breath, blood, and tissue assays demonstrated significant differences in alcohol concentration that are attributable to both assay accuracy and alcohol pharmacokinetics. Similar to past works, a first order kinetic model is used to estimate the fraction of concentration variance explained by alcohol pharmacokinetics (72.6-86.7%). A significant outcome of this work was significantly improved pharmacokinetic agreement with breath (arterial) alcohol of the finger measurement (mean kArt-Fin = 0.111 min−1) relative to the forearm measurement (mean kArt-For = 0.019 min−1) that is likely due to the increased blood perfusion of the finger.
InfraReDx has developed a spectroscopic cardiac catheter system capable of acquiring near-infrared (NIR) reflectance
spectra from coronary arteries in vivo for identification of lipid-rich plaques of interest (LRP). The spectral data are
analyzed with a chemometric model, producing a hyperspectral image (a chemogram) used to identify LRP in the interrogated region. In this paper, we describe a FT-IR microscopy system for measurement of the NIR scattering and absorption properties of healthy and diseased regions of human coronary arteries in small volumes (~10 μl). Scattering and absorption coefficients are obtained from sequential 140 um x 140 um regions of interest across the face of 500-micron thick, saline-irrigated fresh coronary artery sections. A customized FTIR microscope, measurement protocol, and
inversion algorithm are used for optical property determination, and the system is calibrated using measurements of tissue-simulating phantoms having well-characterized optical properties. Tissue optical properties are co-registered with brightfield transmission images as well as with stained histologic thin sections (H&E, Movat Pentachrome, and Oil Red O) acquired from an immediately-adjacent section. The ultimate goal of these experiments is to establish a mechanistic link between the multivariate model predictions displayed on the InfraReDx chemogram and the light-tissue interactions that govern the measured NIR reflectance spectra.
Although heart disease remains the leading cause of death in the industrialized world, there is still no method, even
under cardiac catheterization, to reliably identify those atherosclerotic lesions most likely to lead to heart attack and
death. These lesions, which are often non-stenotic, are frequently comprised of a necrotic, lipid-rich core overlaid with a
thin fibrous cap infiltrated with inflammatory cells. InfraReDx has developed a scanning, near-infrared, optical-fiber-based,
spectroscopic cardiac catheter system capable of acquiring NIR reflectance spectra from coronary arteries through
flowing blood under automated pullback and rotation in order to identify lipid-rich plaques (LRP). The scanning laser
source and associated detection electronics produce a spectrum in 5 ms at a collection rate of 40 Hz, yielding thousands
of spectra in a single pullback. The system console analyzes the spectral data with a chemometric model, producing a
hyperspectral image (a Chemogram, see figure below) that identifies LRP encountered in the region interrogated by the
system. We describe the system architecture and components, explain the experimental procedure by which the
chemometric model was constructed from spectral data and histology-based reference information collected from
autopsy hearts, and provide representative data from ongoing ex vivo and clinical studies.
The shift in optical absorption of hemoglobin upon binding of oxygen provides a basis for near-infrared monitoring of hemoglobin oxygen saturation, which is an important indicator of tissue oxygenation. Tumor oxygenation has long been studied, because hypoxic cells exhibit resistance to ionizing radiation therapy. The ability to measure noninvasively the oxygenation status of tumors and their response to oxygen modifiers is important in research and clinical settings. We have implemented a steady-state diffuse reflectance method of optical spectroscopy in scattering systems based on the theory of Farrell et al. (Med. Phys., 1992). In scattering phantoms containing erythrocytes, the method recovers the hemoglobin absorption spectrum (650 - 820 nm) and accurately monitors hemoglobin oxygen saturation. We have implemented a probe that individually positions several detection fibers normal to the surface of subcutaneous rodent tumors. Near-infrared absorption spectra reconstructed from diffuse reflectance measurements indicate a hemoglobin oxygen saturation of approximately 50% in R3230AC rat mammary adenocarcinomas when the anesthetized animal breathes room air. Administration of carbogen (95% oxygen, 5% carbon dioxide) via a nose cone produces a rapid and readily detectable increase in the saturation to 75% with no increase in tumor blood volume. Several methods of determining hemoglobin oxygen saturation from absorption spectra obtained by diffuse reflectance spectroscopy are compared, including singular value decomposition, which provides the ability to reconstruct the non-hemoglobin absorbing background without a priori knowledge of its structure or absolute magnitude.
We present two cw methods for localizing a source of fluorescence buried in a medium with optical properties similar to those of tissue in the near infrared region. The first approach is based on the fact that, for small excitation beam diameters, the absolute intensity at a given depth in the medium depends on the diameter of the incident beam. For a well-chosen pair of beam diameters, the ratio of these intensities in a scattering medium depends uniquely on the depth from the surface of incidence. Thus, the ratio of the fluorescence resulting from sequential excitation using two beam diameters can be used to determine the depth at which the fluorescence originated. The second method is based on spatially resolved surface measurements of the diffuse fluorescence from the buried source. Using a form of the diffusion theory analysis of Farrell et al. (Med. Phys., 1992) for the spatially resolved diffuse reflectance from a pencil beam incident on a scattering medium, it is possible to reconstruct the depth of the source from the shape of the surface fluorescence profile. Preliminary experimental results obtained using a 1.0 cm diameter sphere containing the tumor localizing fluorophore Nile Blue A show that the spatially resolved measurement reports the location of fluorescent sources as deep as 4.0 cm with an accuracy of 0.4 cm or better.
The oxygenation status of tissue is important in several medical applications. It has long been appreciated that hypoxic tumors are resistant to radiation therapy, while in photodynamic therapy (PDT), the dependence on oxygen is even more pronounced. Our laboratory studies several problems in PDT that originate with this 3O2-dependence. Use of 3O2-sensitive electrodes with small (<EQ 10 micrometers ) tip diameters enables accurate measurement of metabolic and photochemical 3O2 consumption in photosensitized tumor spheroids in vitro. The temporal response of these devices (< 1 s) is sufficient to capture rapid depletion of 3O2 during laser irradiation of individual spheroids. An important aspect of this research has been the development of appropriate mathematical models with which to interpret the microelectrode data and determine photophysical parameters. Recently, we have been establishing optical methods of measuring hemoglobin 3O2-saturation in order to monitor oxygenation in rodent tumors during PDT. We have adopted a steady-state diffuse reflectance technique, in which white light is injected into the tumor via an optical fiber, and the spatially-resolved diffuse reflectance is monitored using appropriately spaced detection fibers. The signals are spectrally dispersed onto a CCD camera by a grating spectrograph, providing simultaneous acquisition of spatially-resolved diffuse reflectance data for a 160 nm range of wavelengths. Absorption spectra reconstructed using a diffusion theory approximation are then fit to linear combinations of oxy- and deoxyhemoglobin spectra to obtain the 3O2-saturation.
We present a detailed description of ultrafast electron diffraction and its applications to study photoinduced molecular dynamics at single crystal surfaces. Experimental investigations for a new design of an ultrashort pulsed laser activated electron gun ((tau) < 5 ps) for time- resolved surface analysis are described. In addition, a novel electron detection and image analysis system, as it applies specifically to time-resolved reflection high-energy electron diffraction in the multiple-shot operation, are reviewed. The total experimental temporal resolution is discussed in terms of the electron pulse width and the time difference between an electron scattered at the front edge of the sample to an electron scattered at the trailing edge of the sample.
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