Apparatus and method for probing light absorbing agents in...

Radiant energy – Irradiation of objects or material

Reexamination Certificate

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C600S407000, C073S901000, C073S597000, C367S007000, C356S340000

Reexamination Certificate

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06815694

ABSTRACT:

FIELD OF THE INVENTION
This invention is generally in the field of non-invasive measurement techniques, and relates to a process and apparatus for real-time imaging and sensing (probing) light absorbing agents, such as hemoglobin, in biological tissues.
The following is a list of some prior art patents, documents and articles which are relevant for the better understanding of the background of the invention, as will be described further below:
List of References
1. A. Ishimaru, “
Wave Propagation and Scattering in Random Media
”, Vol. 1, Academic Press (1978)
2. M. Kempe et al., “
Acousto
-
optic tomography with multiply scattered light
”, J. Opt. Soc. A., 14, 5, 1151 (1997)
3. WO 89/00278
4. U.S. Pat. No. 5,174,298
5. U.S. Pat. No. 5,286,968
6. U.S. Pat. No. 5,212,667
7. U.S. Pat. No. 5,951,481
8. U.S. Pat. No. 6,041,248
9. WO 95/33987
10. Fay A. Marks et al, “
Comprehensive approach to breast cancer detection using light: photon localization by ultrasound modulation and tissue characterization by spectral discrimination
”, SPIE, vol. 1888, pp.500-509.
11. G. D. Mahan et al., “
Ultrasonic tagging of light: theory
”, Proc. Natl. Acad. Sci. USA, 95, 14015, (1998).
12. D. J. Pine et al. “
Dynamical correlations of multiply
-
scattered light
”, Scattering and Localization of Classical Waves in Random Media, Ping Sheng ed. World Scientific (1990).
13. W. Leutz and G. Maret, “
Ultrasonic modulation of multiply scattered light
”, Physica B, 204, 14-19, (1995).
BACKGROUND OF THE INVENTION
In recent years, much effort has been devoted to find a technique alternative to Magnetic Resonance Imaging (MRI) or Computed Tomography (CT) for non-invasively probing living biological tissues, such as body organs. MRI and CT involve long procedures and do not always allow real time analysis of measured data. Low-cost, portable and easy-to-use devices have been developed based on near infrared spectroscopy of blood (e.g., pulse oximetry). This technique, however, provides only a global picture of the tissues with a resolution that does not allow functional imaging of the tissue and a reliable diagnosis.
It is well-known that hemoglobin can be found in the body in two different oxygenation states—oxyhemoglobin and deoxyhemoglobin—which have different light absorption spectra (A. Ishimaru, “
Wave Propagation and Scattering in Random Media
”, Vol. 1, Academic Press (1978)). In the near infrared range, (690-900 nm), the absorption coefficients of both states of hemoglobin are relatively low. At around 804 mm, both states have exactly the same absorption coefficient, and this point is called “the isosbestic point”. Therefore, measurement of blood absorption at this wavelength gives a direct indication of the blood volume being tested. At longer wavelengths, the absorption is essentially due to oxyhemoglobin. For example, at or around light wavelengths of 1 micron, the absorption of oxyhemoglobin is more than three times higher than that of the deoxyhemoglobin. Hence, absorption at these wavelengths (0.804 &mgr;m and 1 &mgr;m) gives a direct indication of the ratio between the two states of hemoglobin.
Hemoglobin oxygenation provides insight on the proper functioning of many body organs such as the brain, breast, liver, heart, etc. Other agents, such as indocyanin green, present absorption in a definite region in the near-infrared range, and can be probed also using infrared light, deeply inside the tissues.
Light propagating inside a scattering medium has two components—ballistic and diffuse light. The first component does not experience scattering, while the second corresponds to strongly multi-scattered light (M. Kempe et al., “
Acousto
-
optic tomography with multiply scattered light
”, J. Opt. Soc. A., 14, 5, 1151 (1997)). Ballistic light intensity decreases with distance in a scattering medium much more than that of the diffuse light. Therefore, diffuse light can provide information on a scattering medium deep inside it.
It is known in the art to use the diffuse (scattered) light to obtain information on the optical properties of the medium. This is implemented by utilizing an ultrasound wave focused on the particular region under examination inside the medium. Generally, this technique consists of the following: If an ultrasound wave propagates through a region in a scattering medium and an electromagnetic wave (such as a laser light beam) crosses said region and is strongly diffused thereby, the electromagnetic wave frequency is shifted by the frequency of the ultrasound wave (acousto-optic effect) at the location of said region. In other regions, where no interaction between the light and ultrasound waves occurs, the frequency of light is unchanged, and consequently, the detection of the frequency-shifted electromagnetic wave gives direct information on the absorption properties of said region.
WO 89/00278 discloses a technique of ultrasound tagging of light utilizing a continuous ultrasound wave. The manner in which this tagging of light is to be done is, however, physically difficult to implement, since the light detection is obtained using a photo-refractive crystal that requires extremely high intensities.
The ultrasound tagging of light is disclosed also in the following publications: U.S. Pat. Nos. 5,174,298; 5,286,968; 5,212,667; 5,951,481; 6,041,248; WO 95/33987; Fay A. Marks et al, “
Comprehensive approach to breast cancer detection using light: photon localization by ultrasound modulation and tissue characterization by spectral discrimination
”, SPIE, vol. 1888, pp. 500-509; and G. D. Mahan et al., “
Ultrasonic tagging of light: theory
”, Proc. Natl. Acad. Sci. USA, 95, 14015, (1998).
U.S. Pat. No. 5,286,968 discloses a technique of multi-channel analog signal detection, aimed at obtaining synchronous detection with a CCD camera. This technique is based on a fast laser modulation.
U.S. Pat. No. 5,212,667 discloses a technique of light imaging in a scattering medium using ultrasound probing and speckle image differencing. According to this technique, coherent laser light impinges onto a scattering medium, disposed between two parallel surfaces, in a direction perpendicular to said surfaces. Light emerging from the medium is a superposition of a multitude of scattered wavelets, each representing a specific scattering part. These wavelets are projected onto the viewing plane of a two-dimensional photodetector array, where they interfere with each other, giving rise to a speckle pattern. Ultrasound pulses propagate into the scattering medium in a direction substantially parallel to said surfaces, and are focused onto the probed region, thereby effecting changes in the position of the scatterers and causing a change in the speckle pattern. This method, however, based as it is on a unidirectional laser beam, has a limited capability of providing information on the scattering medium.
U.S. Pat. No. 5,951,481 discloses a technique for non-invasive measurement of a substance using ultrasound for modulating light that is back-scattered from the region of interest. Here, pulsed ultrasound and a doublet of light pulses are used, and the detected light is not a diffuse light, but a back-scattered, quasi-ballistic light.
U.S. Pat. No. 6,041,248 discloses a technique for frequency encoded ultrasound modulated optical tomography of dense turbid media. This technique utilizes frequency chirped ultrasound and modulated photomultiplier.
SUMMARY OF THE INVENTION
There is accordingly a need in the art to facilitate two- or three-dimensional mapping of a region of interest in a scattering medium by providing a novel method and apparatus based on the principle of interaction of diffused light (light that experienced a large number of scattering events in a medium) with ultrasound radiation.
The present invention provides for real-time analysis of data indicative of the detected diffused light affected by said interaction to enable real-time imaging (less than a few seconds per image) and monitoring of a region of interest in the medium (e.g., a blood volume), and/or oxygen saturation, as well as other light

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