Surgery – Diagnostic testing – Measuring or detecting nonradioactive constituent of body...
Reexamination Certificate
1997-02-13
2001-07-17
Shay, David M. (Department: 3739)
Surgery
Diagnostic testing
Measuring or detecting nonradioactive constituent of body...
C600S323000, C600S336000
Reexamination Certificate
active
06263221
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention relates to quantitative analyses of absorptive constituents in biological tissues by employing a phase modulation spectroscopy.
Continuous wave (CW) tissue oximeters have been widely used to determine in vivo concentration of an optically absorbing pigment (e.g., hemoglobin, oxyhemoglobin) in biological tissue. The CW oximeters measure attenuation of continuous light in the tissue and evaluate the concentration based on the Beer Lambert equation or a modified Beer Lambert absorbance equation. The Beer Lambert equation (1) describes the relationship between the concentration of an absorbent constituent (C), the extinction coefficient (&egr;), the photon migration pathlength <L>, and the attenuated light intensity (I/I
o
).
log
[
I
/
I
0
]
⟨
L
⟩
=
∑
ε
i
C
i
(
1
)
The CW spectrophotometric techniques can not determine &egr;, C, and <L> at the same time. If one could assume that the photon pathlength were constant and uniform throughout all subjects, direct quantitation of the constituent concentration (C) using CW oximeters would be possible.
In tissue, the optical migration pathlength varies with the size, structure, and physiology of the internal tissue examined by the CW oximeters. For example, in the brain, the gray and white matter and the structures thereof are different in various individuals. In addition, the photon migration pathlength itself is a function of the relative concentration of absorbing constituents. As a result, the pathlength through an organ with a high blood hemoglobin concentration, for example, will be different from the same with a low blood hemoglobin concentration. Furthermore, the pathlength is frequently dependent upon the wavelength of the light since the absorption coefficient of many tissue constituents is wavelength dependent. Thus, where possible, it is advantageous to measure the pathlength directly when quantifying the hemoglobin concentration in tissue.
SUMMARY OF THE INVENTION
In general, in one aspect, a spectroscopic system for quantifying in vivo concentration of an absorptive pigment in biological tissue includes an oscillator constructed to generate a first carrier waveform of a first frequency on the order of 10
8
Hz (i.e., in the range of 10 MHz to 1 GHz), a light source, operatively coupled to the oscillator, constructed to generate electromagnetic radiation of a selected wavelengths modulated by the carrier waveform, and a detector constructed to detect radiation that has migrated over photon migration paths in the tissue from an input port to a detection port spaced several centimeters apart. The wavelength is sensitive to concentration of the absorptive pigment present in the tissue. A phase detector is constructed to compare the detected radiation with the introduced radiation and determine therefrom the phase shift of the detected radiation at each wavelength. A processor is constructed to receive the phase shift and a scattering property of the portion of the tissue and calculate a value of the absorption coefficient, at the wavelength, using Eq. 4.
In another embodiment, the spectroscopic system includes a light source further constructed to generate electromagnetic radiation of a second wavelengths modulated by the carrier waveform. At least one of the wavelengths is sensitive to concentration of an absorptive pigment present in the tissue, while the tissue exhibits similar scattering properties at the two wavelengths. The detector is constructed to detect the radiation at the second wavelength. The phase detector is constructed to compare the detected radiation with the introduced radiation and determine therefrom the phase shift at the second wavelength. The processor is constructed to receive the phase shift at the second wavelength and calculate a value of the absorption coefficient, at the second wavelength, using Eq. 4.
In general, in one aspect, a spectroscopic system for quantifying in vivo concentration of an absorptive pigment in biological tissue includes an oscillator constructed to generate a first carrier waveform of a first frequency on the order of 10
8
Hz (i.e., in the range of 10 MHz to 1 GHz), a light source, operatively coupled to the oscillator, constructed to generate electromagnetic radiation of a selected wavelengths modulated by the carrier waveform, and a detector constructed to detect radiation that has migrated over photon migration paths in the tissue from an input port to a detection port spaced several centimeters apart. The wavelength is sensitive to concentration of the absorptive pigment present in the tissue. The spectroscopic system also includes a phase splitter, two double balanced mixers, and a processor. The phase splitter is constructed to receive the carrier waveform and produce first and second reference phase signals of predefined substantially different phases. The first and second double balanced mixers are connected to receive from the phase splitter the first and second reference phase signals, respectively, and are connected to receive from the detector the detector signal, in order to produce therefrom a real output signal and an imaginary output signal, respectively. The processor is constructed to receive a scattering property of the portion of the tissue and is constructed to quantify the concentration of the absorptive pigment by calculating phase shift (&thgr;) of the detected radiation as the inverse tangent of the ratio of the imaginary output signal and the real output signal. The processor also calculates a value of the absorption coefficient, at the wavelength, using Eq. 4.
In another embodiment, the spectroscopic system includes a light source further constructed to generate electromagnetic radiation of a second wavelengths modulated by the carrier waveform. At least one of the wavelengths is sensitive to concentration of an absorptive pigment present in the tissue, while the tissue exhibits similar scattering properties at the two wavelengths. The detector is constructed to detect the radiation at the second wavelength. The first and second double balanced mixers are connected to receive from the phase splitter the first and second reference phase signals, respectively, and connected to receive from the detector the detector signal at the second wavelength. The mixers are constructed to produce therefrom a real output signal and an imaginary output signal, respectively, at the second wavelength. The processor is constructed to quantify the concentration of the absorptive pigment by calculating phase shift (&thgr;) of the detected radiation as the inverse tangent of the ratio of the imaginary output signal and the real output signal and by calculating a value of the absorption coefficient, at the wavelength, using Eq. 4.
As different embodiments, the spectrophotometer may be a dual wavelength, single frequency system or a dual wavelength, dual frequency system. Each system can measure data for a single source-detector separation (i.e., separation of the input port and the detection port) or for several source-detector separations.
Different embodiments of the spectrophotometer may include one or more of the following features.
The spectrophotometer may include a second oscillator constructed to generate a second carrier waveform of a second selected frequency on the order of 10
8
Hz, while the tissue exhibits similar scattering properties at the selected frequencies. The source is operatively coupled to the second oscillator and is constructed to generate electromagnetic radiation of the two wavelengths modulated by the second carrier waveform. The detector is further constructed to detect the radiation modulated by the second carrier waveform. The phase detector is further constructed to compare, at each the wavelength, the detected radiation of the second carrier waveform with the introduced radiation and determine therefrom the phase shift of the detected radiation.
The processor may calculate a ratio of absorption coefficients at the two wav
Chance Britton
Ntziachristos Vasilis
Fish & Richardson P.C.
Non-Invasive Technology
Shay David M.
LandOfFree
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