Surgery – Diagnostic testing – Measuring or detecting nonradioactive constituent of body...
Reexamination Certificate
2001-04-30
2002-09-24
Winakur, Eric F. (Department: 3736)
Surgery
Diagnostic testing
Measuring or detecting nonradioactive constituent of body...
C600S323000, C250S341500
Reexamination Certificate
active
06456862
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Technical Field
This invention relates to methods for non-invasively determining biological tissue oxygenation in general, and to non-invasive methods utilizing near-infrared spectroscopy (NIRS) techniques in particular.
2. Background Information
The molecule that carries the oxygen in the blood is hemoglobin. Oxygenated hemoglobin is called oxyhemoglobin (HbO
2
) and deoxygenated hemoglobin is deoxyhemoglobin (Hb). Total hemoglobin is the summation of the two states of hemoglobin (Total Hb=HbO
2
+Hb), and is proportional to relative blood volume changes, provided that the hematocrit or hemoglobin concentration of the blood is unchanged. The mammalian cardiovascular system consists of a blood pumping mechanism (the heart), a blood transportation system (blood vessels), and a blood oxygenation system (the lungs). Blood oxygenated by the lungs passes through the heart and is pumped into the arterial vascular system. Under normal conditions, oxygenated arterial blood consists predominately of HbO
2
. Large arterial blood vessels branch off into smaller branches called arterioles, which profuse throughout biological tissue. The arterioles branch off into capillaries, the smallest blood vessels. In the capillaries, oxygen carried by hemoglobin is transported to the cells in the tissue, resulting in the release of oxygen molecules (HbO
2
→Hb). Under normal conditions, only a fraction of the HbO
2
molecules give up oxygen to the tissue, depending on the cellular metabolic need. The capillaries then combine together into venuoles, the beginning of the venous circulatory system. Venuoles then combine into larger blood vessels called veins. The veins further combine and return to the heart, and then venous blood is pumped to the lungs. In the lungs, deoxygenated hemoglobin Hb collects oxygen becoming HbO
2
again and the circulatory process is repeated.
Oxygen saturation is defined as:
O
2
saturation
%
=
HbO
2
(
HbO
2
+
Hb
)
×
100
%
(Eqn. 1)
In the arterial circulatory system under normal conditions, there is a high proportion of HbO
2
to Hb, resulting in an arterial oxygen saturation (defined as SaO
2
%) of 95-100%. After delivery of oxygen to tissue via the capillaries, the proportion of HbO
2
to Hb decreases. Therefore, the measured oxygen saturation of venous blood (defined as SvO
2
%) is lower and may be about 70%.
One spectrophotometric method, called pulse oximetry, determines arterial oxygen saturation (SaO
2
) of peripheral tissue (i.e. finger, ear, nose) by monitoring pulsatile optical attenuation changes of detected light induced by pulsatile arterial blood volume changes in the arteriolar vascular system. The method of pulse oximetry requires pulsatile blood volume changes in order to make a measurement. Since venous blood is not pulsatile, pulse oximetry cannot provide any information about venous blood.
Near-infrared spectroscopy (NIRS) is an optical spectrophotometric method of continually monitoring tissue oxygenation that does not require pulsatile blood volume to calculate parameters of clinical value. The NIRS method is based on the principle that light in the near-infrared range (700 to 1,000 nm) can pass easily through skin, bone and other tissues where it encounters hemoglobin located mainly within micro-circulation passages; e.g., capillaries, arterioles, and venuoles. Hemoglobin exposed to light in the near infra-red range has specific absorption spectra that varies depending on its oxidation state; i.e., oxyhemoglobin (HbO
2
) and deoxyhemoglobin (Hb) each act as a distinct chromophore. By using light sources that transmit near-infrared light at specific different wavelengths, and measuring changes in transmitted or reflected light attenuation, concentration changes of the oxyhemoglobin (HbO
2
) and deoxyhemoglobin (Hb) can be monitored. The ability to continually monitor cerebral oxygenation levels is particularly valuable for those patients subject to a condition in which oxygenation levels in the brain may be compromised, leading to brain damage or death.
The apparatus used in NIRS analysis typically includes a plurality of light sources, one or more light detectors for detecting reflected or transmitted light, and a processor for processing signals that represent the light emanating from the light source and the light detected by the light detector. Light sources such as light emitting diodes (LEDs) or laser diodes that produce light emissions in the wavelength range of 700-1000 nm at an intensity below that which would damage the biological tissue being examined are typically used. A photodiode or other light source detector is used to detect light reflected from or passed through the tissue being examined. The processor takes the signals from the light sources and the light detector and analyzes those signals in terms of their intensity and wave properties.
It is known that relative changes of the concentrations of HbO
2
and Hb can be evaluated using apparatus similar to that described above, including a processor programmed to utilize a variant of the Beer-Lambert Law, which accounts for optical attenuation in a highly scattering medium like biological tissue. The modified Beer-Lambert Law can be expressed as:
A
&lgr;
=−log(
I/I
o
)
&lgr;
=&agr;
&lgr;
*C*d*B
&lgr;
+G
(Eqn.2)
wherein “A
&lgr;
” represents the optical attenuation in tissue at a particular wavelength &lgr; (units: optical density or OD); “I
o
” represents the incident light intensity (units: W/cm
2
); “I” represents the detected light intensity; “&agr;
&lgr;
” represents the wavelength dependent absorption coefficient of the chromophore (units: OD * cm
−1
* &mgr;M
−1
); “C” represents the concentration of chromophore (units: &mgr;M); “d” represents the light source to detector (optode) separation distance (units: cm); “B
&lgr;
” represents the wavelength dependent light scattering differential pathlength factor (unitless); and “G” represents light attenuation due to scattering within tissue (units: OD).
Absolute measurement of chromophore concentration (C) is very difficult because G is unknown or difficult to ascertain. However, over a reasonable measuring period of several hours to days, G can be considered to remain constant, thereby allowing for the measurement of relative changes of chromophore from a zero reference baseline. Thus, if time t
1
marks the start of an optical measurement (i.e., a base line) and time t
2
is an arbitrary point in time after t
1
, a change in attenuation (&Dgr;A) between t
1
and t
2
can be calculated, and variables G and I
o
will cancel out providing that they remain constant.
The change in chromophore concentration (&Dgr;C=C(t
2
)−C(t
1
)) can be determined from the change in attenuation &Dgr;A, for example using the following equation derived from the Beer-Lambert Law:
&Dgr;
A
=−log(
I
t2
/I
t1
)
&lgr;
=&agr;
&lgr;
*&Dgr;C*d*B
&lgr;
(Eqn.3)
Presently known NIRS algorithms that are designed to calculate the relative change in concentration of more than one chromophore use a multivariate form of Equation 2 or 3. To distinguish between, and to compute relative changes in, oxyhemoglobin (&Dgr;HbO
2
) and deoxyhemoglobin (&Dgr;Hb), a minimum of two different wavelengths are typically used. The concentration of the HbO
2
and Hb within the examined tissue is determined in &lgr;moles per liter of tissue (&mgr;M).
The above-described NIRS approach to determining oxygen saturation levels is useful, but it is limited in that it only provides information regarding a change in the level of blood oxygen saturation within the tissue. It does not provide a means for determining the total level of blood oxygen saturation within the biological tissue.
At present, information regarding the relative contributions of venous and arterial blood within tissue examined by NIRS is either arbitrarily chosen or is determined by invasive sampling of the blood as a process independent
CAS Medical Systems, Inc.
McCormick Paulding & Huber LLP
Winakur Eric F.
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