Radiant energy – Infrared-to-visible imaging
Reexamination Certificate
1999-04-08
2001-09-18
Epps, Georgia (Department: 2873)
Radiant energy
Infrared-to-visible imaging
C250S341700
Reexamination Certificate
active
06291824
ABSTRACT:
This invention pertains to the rapid imaging of samples such as living biological tissues, particularly to imaging by optical tomography.
Biological tissues, particularly mammalian tissues, are relatively permeable to light in the near infrared (NIR) spectrum (~700-900 nm). Photon transport through tissue at these wavelengths is dominated by scattering rather than by absorption. What light absorption does occur in this region is primarily attributable to the heme groups of hemoglobin. Deoxyhemoglobin and oxyhemoglobin have different NIR absorption spectra. These differences have been exploited in commercial “oximeters,” devices that non-invasively monitor hemoglobin oxygen saturation. Existing oximeters measure global changes in hemoglobin saturation and blood volume, but do not resolve spatial details.
Conventional geometrical optics cannot be employed with infrared oximetry to image discrete hypoxic regions, especially deeper regions, because of the turbid nature of mammalian tissue. Prior suggestions to overcome these limitations have included proposals for time-resolved and frequency methods. In the time-resolved method, the path and time of flight of a photon through tissue depend on the absorptive and scattering substances inside the turbid sample . The different trajectories of photons through the tissue require different lengths of time to reach a detector because of their different path lengths. Direct-flight or “ballistic” photons arrive at the detector first, followed by scattered photons that have taken longer paths. Absorbed photons, of course, are not detected at all. Examining the temporal distribution of detected photons reveals information about what lies in the path between the emitter and the detector. For example, an absorbing occlusion in the direct path between the emitter and the detector would absorb “ballistic” photons preferentially, while photons that scattered around the occlusion could still reach the detector, although at a later time. Similarly, the frequency-domain method, which uses an intensity-modulated light emitter with a detection system tuned to the modulation frequency, relies on phase and amplitude changes between the emitter and the detector to locate inhomogeneities inside the sample. In both the time-resolved and the frequency,-domain methods, images of the interior of the sample may be constructed by moving the axis between the emitter and the detector across the sample. All known prior NIR tomographic imaging techniques have used mechanical scanning to reposition the emitter, the detector, or the sample. The mechanical scanning limits the speed at which data may be acquired.
R. Grable, “Optical Tomography Improves Mammography,”
Laser Focus World
,” pp. 113-118 (October 1996) discloses an optical tomography system for mammography, in which laser light was delivered by an optical fiber to a rotating polygon mirror, producing a fan beam, and the detector consisted of an array of several hundred avalanche photoditodes. In an alternative embodiment, the avalanche photodiodes were replaced with large-area photodiodes, laser illumination was provided by a single beam, and the detectors and laser beam orbited around the object being scanned. The author noted that construction of suitable scanning apparatus was not trivial; that the rotary motion of the lager beam and detectors must be precise.
X. Zhu et al., “Imaging Objects in Tissuelike Media with Optical Tagging and the Diffuse Photon Differential Transmittance,”
J: Opt. Soc. Am. A
, vol. 14, pp. 300-305 (1997) discloses measuring differential transmittance of light through a scattering medium at two different wavelengths to enhance the ability to image optically-tagged objects within the scattering medium.
J. Hebden et al., “Time-Resolved Optical Tomography,”
Appl. Opt
., vol. 32, pp. 372-380 (1993) discloses the use of time-resolved optical tomography to image objects inside a scattering medium by measuring only transmitted photons having the shortest time of flight, i.e., the small fraction of photons that travels through the sample in approximately a straight line.
P. McCormick, “Intracerebral Penetration of Infrared Light,”
J. Neurosurg
., vol. 76, pp. 315-318 (1992) presents one of the earlier reports on the transmission of near-infrared light through human cerebral tissue, and on the application of such techniques to the measurement of hemoglobin and hemoglobin oxygen saturation. See also F. Okada et al., “Impaired Interhemispheric Integration in Brain Oxygenation and Hemodynamics in Schizophrenia,”
Eur. Arch. Psych. Clin. Neurosci
., vol. 244, pp. 17-25 (1994).
M. Takada et al. (Shimadzu Corporation), “Optical Tomographic Image System,” technical paper (Jun. 22, 1995, English translation) describes in general terms an optical tomographic imaging system, its components, and experiments performed with the system.
S. Colak, “Tomographic Image Reconstruction from Optical Projections in Light-Diffusing Media,”
Appl. Opt
., vol. 36, pp. 180-213 (1997); and S. Walker, “Image Reconstruction by Backprojection from Frequency-Domain Optical Measurements in Highly Scattering Media,”
Appl. Opt
., vol.36, pp. 170-179 (1997); disclose algorithms for reconstructing the location and optical properties of objects in a scattering medium following measurements with near infrared light.
A. Gandjbakhche et al., “Resolution Limits for Optical Transillumination of Abnormalities Deeply Embedded in Tissues,”
Med. Phys
., vol. 21, pp. 185-191 (1994); J. Hebden, “The Spatial Resolution Performance of a Time-Resolved Optical Imaging System using Temporal Extrapolation,”
Med. Phys
., vol. 22, pp. 201-208 (1995); and A. Jobin, “Method of Calculating the Image Resolution of a Near-Infrared Time-of-Flight Tissue-Imaging System,”
Appl. Opt
., vol. 35, pp. 752-757 (1996) discuss spatial resolution in reconstructing the location and optical properties of objects in a scattering medium following measurements with near infrared light, including measurements made with both “line-of-sight” photons and with photons scattered along a somewhat longer path than line-of-sight.
E. Sevick et al., “Quantitation of Time- and Frequency-Resolved Optical Spectra for the Determination of Tissue Oxygenation,”
Anal. Biochem
., vol. 195(2), pp. 330-351 (1991) discusses algorithms for the quantitation of hemoglobin saturation from photon decay rates obtained from dual wavelength, time-resolved and frequency-resolved spectra using multiple emitters and detectors. This reference discusses only means for measuring absorptivity, not for acquiring images. The authors noted that the instrument was slow (requiring more than 30 seconds for one measurement).
D. Benaron et al., “Optical Time-of-Flight and Absorbance Imaging of Biologic Media,”
Science
, vol. 259, pp. 1463-1466 (1993) discloses an optical tomography technique using a variable-interval time collection window for photons arriving at the detector, to collect photons until a fixed percentage of the total transmitted photons had been received. Images were made both of model systems, and of internal structure of a dead, 10-day-old rat pup suspended in blood.
G. Müller et al., “Laser-Generated Diffusion Tomograms in the Near Infrared,”
Laser Physics
, vol. 6, pp. 589-595 (1996) discloses a method for laser-generated tomography using photon density waves and an algorithm for reconstructing the image. An optical tomogram of a rat brain ex vivo without skull was illustrated. See also M. O'Leary et al., “Experimental Images of Heterogeneous Turbid Media by Frequency-Domain Diffusing-Photon Tomography,”
Optics Lett
., vol. 20, pp. 426-428 (1995).
A. Yodh et al., “Spectroscopy and Imaging with Diffusing Light,”
Physics Today
, pp. 34-40 (March 1995) provides an overview of techniques currently available using near infrared light for imaging and spectroscopy of biological specimens.
There has been recent interest in developing optical devices that can monitor tissue function, and that can display the measurements as cross-sectional images. If an effective means were avail
Battarbee Harold D.
Rodriguez Juan G.
Board of Supervisors of Louisiana State University and Agricultu
Epps Georgia
Hanig Richard
Runnels John H.
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