Metabolism monitoring of body organs

Surgery – Diagnostic testing – Measuring or detecting nonradioactive constituent of body...

Reexamination Certificate

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C600S310000, C600S309000

Reexamination Certificate

active

06738653

ABSTRACT:

FIELD OF THE INVENTION
This invention relates to a process and apparatus for not invasively probing in real time oxygen metabolism in body organs by means of a combination of light and ultrasound.
BACKGROUND OF THE INVENTION
In recent years, much effort has been devoted to find ways to non-invasively probe regions of the brain, without using MRI or CT, which involve long procedures and do not allow real time analysis, except, to some extent, in some exceptional cases. Low-cost, portable and easy-to-use devices have been based on near infrared spectroscopy of blood, which have found some use by physicians. However, such techniques only provide a global picture of the brain without the minimum resolution which should allow a reliable diagnosis to be made.
Hemoglobin oxygenation gives an insight on the proper functioning of many body organs. This invention is particularly directed to probing hemoglobin oxygenation in the brain, but this is not intended as a limitation, and the invention includes probing in similar ways other organs, such as breast, liver, heart, and so on.
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 (see M. Kempe, M. Larionov, D. Zaslatski and A. Z. Genack,
Acousto
-
optic tomography with multiply scattered light,
J. Opt. Soc. A., 14, 5, 1151 (1997)). Ballistic light decreases exponentially with distance in a scattering medium, whereas diffuse light remains roughly at the same relatively high intensity level. Therefore, diffuse light can give information to scattering medium deep inside it.
It is known in the art that information on the optical properties of the medium can be obtained by means of the said diffuse light, by focusing an ultrasound wave inside the medium at the particular region under examination. This phenomenon is exploited in U.S. Pat. No. 5,212,667 for the purpose of light-imaging in a scattering medium. Coherent light, generated as a laser beam and expanded by a beam expander, is projected into a scattering medium disposed between two parallel surfaces, in a direction perpendicular to said surfaces. Light emerging from it is a superposition of a multitude of scattered wavelets, each of which represent 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. Propagating ultrasound pulses into the scattering medium in a direction substantially parallel to said surfaces, and focusing it in the probed region, changes the position of the scatterers and this causes a change in the speckle pattern. By comparing speckle images with and without ultrasound pulse, light absorption properties of the probed region can be measured. This method, however, based as it is on a unidirectional laser beam, has a limited capability of providing information on the scattering medium, and particularly, does not permit to obtain the information in real time as to hemoglobin oxygenation. Further, it does not permit to retrieve local hemoglobin oxygenation. U.S. Pat. No. 5,212,667 does not provide any algorithm showing how to retrieve such information. In fact, if only on-axis illumination is used, that is to say, the laser source, the ultrasound probe and the detector, are on the same line, modifying the position of the ultrasound probe does not allow to determine the local changes in absorption, because the absorption has to be integrated over the whole line.
If an ultrasound wave is focused inside a scattering medium and concurrently a continuous wave laser light beam crosses said medium and is strongly diffused thereby, light frequency is shifted by the ultrasound frequency (Doppler Effect) at the region of the focused ultrasound. At the other regions, the frequency of the light is practically unchanged, and consequently, the detection of the frequency-shifted light gives direct information on the optical properties of the region under test.
U.S. Pat. No. 5,212,667 is not concerned with changes in the speckle pattern. It states that, in the region in which the ultrasound is focused, the light-scattering properties are altered, owing either to change in the index of refraction induced by the pressure fluctuation of the ultrasound pulse, or by the changes in location of the scattering centers induced by such a pulse; and consequently, the speckle intensities in the focal plane are altered. The inventors submit that the magnitude of the speckle intensity change depends on the relative light absorption between the probed region and the surrounding medium. Other patents which refer to the tagging of light by the ultrasound are U.S. Pat. No. 5,174,298 and WO 95/33987. An article by Fay A. Marks et al, in SPIE, vol. 1888, p. 500, discusses the ultrasound tagging of light (UTL) as a tool for imaging breast tissue, and concludes that much work remains to be done to explore the feasibility of using UTL as a breast cancer imaging system.
SUMMARY OF THE INVENTION
The invention is based on the fact (see Ishimaru, A.,
Wave Propagation and Scattering in Random Media,
Vol. 1, Academic Press (1978)) that hemoglobin can be found in the body in two different oxygenation states—oxyhemoglobin and deoxyhemoglobin—which have different light absorption spectra. In the near infrared (690 mm and above), the absorption coefficients of both states of hemoglobin are relatively low. At around 804 mm, both states have exactly the same absorption coefficient: 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 oxyhemoglobin absorbs more than three times than the deoxyhemoglobin: therefore, absorption at this wavelength gives a direct indication of the ratio between the two states of hemoglobin. The absorption spectra of oxyhemoglobin and deoxyhemoglobin are illustrated in FIG.
2
.
The invention is characterized by the fact that the probed region (the part of the body in which the degree of hemoglobin oxygenation is to be monitored) is irradiated with light, preferably with a wavelength between 690 and 900 nm, the light frequency is shifted by an ultrasound pulse, and the degree of hemoglobin oxygenation is determined from the change in the absorption obtained at the frequency shifted signal.
FIG. 1
schematically illustrates the interaction between diffuse light and a focused ultrasound wave. An emitter emits light of frequency &ohgr; into the probed region. An ultrasound beam, of frequency &OHgr;
US
is focused onto the probed region. Ultrasound modulated light, having a shifted frequency &ohgr;+&OHgr;
US
, and non-modulated light having frequency &ohgr; are detected by a detector, which mixes them and generates a signal modulated at the ultrasound frequency. Hereinafter, the expression “modulated signal” will means the signal, detected by the detector, representing the intensity of the ultrasound modulated light, and expression “non-modulated signal” will means the signal, detected by the detector, representing the intensity of the light not modulated by the ultrasound. The word “signal” without specification, will include both the modulated and the non-modulated signal.
This invention, therefore, provides a method for determining the local oxygenation level of hemoglobin by comparing the absorption of an ultrasound frequency-shifted signal with the absorption of hemoglobin in different states of oxygenation, at several wavelengths. Diffuse light (optionally, but not necessarily, at the isosbestic point) experiences an absorption throughout regions of the body. If an ultrasound wave is focused in a part of the body, and the frequency of the light is changed, detectors outside the part of the body under examination can selectively detect the ultr

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