WO2003009750A2

WO2003009750A2 - System and method for determining brain oxygenation

Info

Publication number: WO2003009750A2
Application number: PCT/US2002/023592
Authority: WO
Inventors: Michael Henry Brill; Christopher C. Gregory
Original assignee: Sarnoff Corporation
Priority date: 2001-07-25
Filing date: 2002-07-25
Publication date: 2003-02-06
Also published as: WO2003009750A3

Abstract

A method for determining a blood oxygenation associated with a brain of a subject, the method includes scanning a retina of the subject to identify at least one retinal blood vessel using at least a first optical energy source. In response to the identifying, identified retinal blood vessel is selectively flashed using at least a second optical energy source. At least one reflectance is detected from the flashed retinal blood vessel, and a ratio being indicative of the oxygenation using the detected at least one reflectance is determined.

Description

SYSTEM AND METHOD FOR DETERMINING BRAIN OXYGENATION

Field of the Invention

The present invention relates generally to medical diagnostic devices and methods, and particularly to systems and methods for determining brain oxygenation and utilization.

Background of the Invention

There is a need for accurate, early assessment of underprofusion of oxygen enriched blood to the brain. Lack of oxygenation to the brain may result in serious consequences such as brain damage and death.

However, oxygenation of the brain is a conventionally difficult parameter to measure. Oxygen delivery to the brain is dependant on oxygen enriched blood being supplied by way of circulation. Blood flow to the brain can not typically be accurately monitored through non-invasive measures, since the arteries lying deep within the neck supplying the brain branch just before entering the cranium.

One conventional methodology is to directly measure the metabolism of oxygen by the brain through Positron Emission Tomography (PET) scanning. Such a method is often undesirably complicated and slow though. Another conventional clinical diagnosis of decreased oxygenation to the brain (hypoxia) is performed through monitoring the oxygen content of blood in a body extremity and blood pressure. However, this method assumes that blood oxygen saturation in the extremity correlates with the oxygenation of the brain's blood supply and that the blood pressure corrolates with blood flow to the brain. A less inferential method is to make radiographs using a short-lived radio-nucleotide as an oxygen tracer, such as that described in U.S. Pat. No. 5,688,487 to K. Under, et al., which describes diagnostic imaging methods using rhenium and technetium complexes. This method is quite effective for detailed studies and for evaluating foci of anoxia within the brain. However, for routine and preliminary clinical screening purposes a less complicated and non-invasive method may be desirable.

Further, while arterial measurements of oxygen through pulse oximetry and blood gas analysis can provide a quick determination of how well the lungs are oxygenating the blood, this only provides supply side information. Catheters can be placed in the pulmonary artery to measure mixed venous oxygenation, which represents a demand side measure of how much available oxygen is being used by the body. It is known that as a patient becomes hypovolemic, loss of hemoglobin, which carries oxygen to the body, decreases and measures of mixed venous oxygen saturation decreases. In a hypovolemic state there will be a diminished supply of oxygen delivered to the brain. However, such a process is highly invasive.

Attempts at non-invasive techniques for monitoring blood loss have generally failed. As reported by Smith, et al. ("Oxygen Saturation Measurements of Blood In Retinal Vessels During Blood Loss", J. of

Biomedical Optics, Vol.3, No. 3 296-97 (1998)) conjunctival partial oxygen measurements can provide the demand side information in animal exsanguination studies, but are also somewhat invasive and not widely accepted. Summary of the Invention

A method for determining a blood oxygenation associated with a brain of a subject, the method including: scanning a retina of the subject to identify at least one retinal blood vessel using at least a first optical energy source; in response to the identifying, selectively flashing the identified retinal blood vessel using at least a second optical energy source; detecting at least one reflectance from the flashed retinal blood vessel; and, determining a ratio being indicative of the oxygenation using the detected at least one reflectance.

Brief Description of the Figures

Understanding of the present invention will be facilitated by consideration of the following detailed description of the preferred embodiments of the present invention taken in conjunction with the accompanying drawings, wherein like numerals refer to like parts and in which:

Figures 1A and 1 B illustrate views of a system according to an aspect of the present invention;

Figure 2 illustrates a method according to an aspect of the present invention and being suitable for use with the system of Figure 1 ; and,

Figures 3A and 3B illustrate application of emissions according to an aspect of the present invention.

Detailed Description of the Invention It is to be understood that the figures and descriptions of the present invention have been simplified to illustrate elements that are relevant for a clear understanding of the present invention, while eliminating, for purposes of clarity, many other elements found in typical diagnostic systems and methods relating thereto. Those of ordinary skill in the art will recognize that other elements are desirable and/or required in order to implement the present invention. However, because such elements are well known in the art, and because they do not facilitate a better understanding of the present invention, a discussion of such elements is not provided herein. The disclosure herein is directed to all such variations and modifications to such systems and methods known to those skilled in the art.

In general, the retina serves as a good indicator of oxygen supply to the brain. It can be used to determine if oxygen is getting to the tissue. It can also be used to determine if the tissue is using the oxygen. The latter can be accomplished by measuring the oxygen level in veins (a direct approach) or by measuring the effect of reduced oxygen matabolism in the tissue (an indirect approach).

In accordance with the present invention, both the direct and indirect approaches use a light source for illuminating the retina of the eye, a sensor and a measurement analyzer for calculating either the neuron's oxygen supply (direct measure of oxygenation) or its utilization (indirect measurement by using metabolism) as an indicator of a patient's condition. According to an aspect of the present invention for performing a direct measurement, there is provided a system and method for sensing profusion of oxygenated blood to the brain using reflections of emissions that may be ratioed to derive the oxygenation of blood in retinal vessels.

According to an aspect of the present invention, reflectance- spectrum change in the fundus in the presence of brain hypoxia may be objectively achieved.

The ophthalmic artery provides most of the blood supply for the orbital contents and substantially all of the blood supply for the retina. The ophthalmic artery branches off from the internal carotid artery in the cavernous sinus and passes through the optic canal within the optic nerve sheath. This artery passes behind the eye, along the superomedial wall of the orbit. A smaller artery, the central retinal artery, branches off inferior to the optic nerve, also running inside the optic nerve's dural sheath until it reaches the eyeball. This retinal artery pierces the optic nerve and emerges at the optic disc supplying the retina with oxygenated blood. The retina is dependant on its oxygen supply indirectly from the internal carotid artery within the cranium and so is subject to factors that would tend to impede delivery of oxygen to the brain, as well as blood volume and blood pressure. There is a significant uptake of oxygen by the retina, which is a substantially fixed amount determined by the high metabolic rate of retinal cells. This rate substantially matches the highest metabolic rate found in the brain. Thus, delivery of oxygen to the retina serves as a good indicator of oxygen supply to the brain.

Further, different spectra of oxygenated and non-oxygenated blood can be detected in the retina. Generally, oxygenated blood has a different spectra than unoxygenated blood. Therefore, by directly measuring the reflected or transmitted light through the blood in retinal vessels and detecting differences in the spectra of the blood, residual oxygen saturation, and oxygen metabolization, may be determined. As the retina is one of the most highly metabolic organs per gram of mass in the body, it is suitable for taking indirect measurement of brain and blood oxygenation according to an aspect of the invention. This metabolism is devoted to reconstituting photopigment molecules for further action by light. These photoreceptors are part of the neural tissue that is also brain tissue. Photopigment regeneration is a substantially direct index of the status of oxygen supply to the brain. According to an aspect of the present invention, the state of photopigments in the eye may be directly measured by densitometry and by the spectrum of fundus reflection, for example.

Direct Approach

As described above, it is desirable to measure the oxygen saturation of blood in retinal vessels using a non-invasive, rapidly applicable technique that provides a reliable index of oxygen delivery to and use by the brain. Referring now to Figures 1A and 1 B, there are shown plan views of a device 10 according to an aspect of the present invention. Device 10 is illustrated in the form of a handheld, or portable, device. Device 10 may take any suitable form however. Device 10 includes imaging sources 20, 30. Filtering and beam conditioning optics 60 may be optically coupled to source 30. One or more beam combiners 40, such as a number corresponding to the number of sources 20, may be optically coupled to sources 20 and optics 60 so as to combine output of sources 20,30 into focusing optics 50. Focusing optics 50 may focus output from optics 60 and sources 20 onto a steering, or scanning, mirror 70. The reflected output may then be incident upon a beam splitter 80.

Beam splitter 80 may direct reflected output of sources 20, 30 through focusing optics 90 onto a subject 100. Reflections from subject 100 may impinge beam splitter 80 and then upon a beam splitter 110. Beam splitter 1 10 may direct emissions impinging thereupon to a detector 130, via focusing optics 120, and imaging optics 140. Emissions through optics

140 may finally be focused using eyepiece optics 150, and be viewable by a user 160. A controller 170 may control functionality of device 10 by interacting with sources 20, 30, scanning mirror 70, beam splitter 110 and detector 120. Power source 180 may provide power for device 10. Spectral analysis of reflections from subject 100 according to the present invention may advantageously rely upon sources of emissions at a wide range of wavelengths ranging from infrared to blue or green, for example. Operating wavelengths for sources 20, 30 may be chosen in a conventional manner, such as that described by Smith in OPTIMUM WAVELENGTH COMBINATIONS FOR RETINAL VESSEL OXIMETRY,

(Applied Optics, vol. 38, No. 1., January 1999). Referring now to sources 20, a plurality of such sources may be used. In general, the greater the number of sources 20 used, the greater the reliability of measurement that may be achieved using device 10. However, as will also be readily understood by those possessing an ordinary skill in the pertinent arts, the greater the number of sources 20 used, the lower the power should be for each source 20, so as to provide a total exposure that is within generally acceptable guidelines, such as those set forth in Title 21 of the United States Code of Federal Regulations, section 1040.01. Alternatively, different wavelength emissions may be provided sequentially over generally the same area of the vessels, thereby reducing the total intensity. Semiconductor sources 20 may be used to produce wavelengths in the near infrared and red regions of the electromagnetic spectrum. For example, sources 20 may take the form of continuous operation laser diodes having operating frequencies of approximately 635,

670 and 830 nm, respectively.

Source 30 may take the form of a continuous operation laser having an operating frequency of approximately 488 nm, again taking the total exposure caused by use of device 10 into account. However, semiconductor sources may not necessarily be possible or practical for purposes of generating such a blue or green emission.

Continuous incandescent conventional sources are generally too dim for most spectroscopy applications. There are non-solid state laser sources in the blue and green spectra, however these typically are large, expensive and/or unreliable, hence rendering them undesirable, but not unusable.

According to an aspect of the present invention, a filtered flash source can be used as source 30 to create the required emissions at wavelengths shorter than may be conventionally practical with solid state sources. Relatively broadband emissions from the flash unit can be filtered using filter 60 to produce desired narrow band emissions. As will be understood by those possessing an ordinary skill in the pertinent arts, flash source 30 may be enhanced by introducing appropriate gasses, such as xenon, krypton or argon for example, to produce emission peaks at desired wavelengths. Further, phosphor enhancement of source 30 may be used to boost emissions at the desired wavelength, for example. Thus, according to an aspect of the present invention a compact inexpensive source ,for spectroscopy in the blue and green spectra may be used for spectroscopy applications, such as the monitoring of retinal oxygenation. As compared to a continuous laser having an operating wavelength of approximately 488 nm, such a filtered flash has a short operational duration. Accordingly, source 30 may be relatively unsuitable for use as a scanning source. According to an aspect of the present invention, detector 130 and controller 170 may be used to permit more than one spot to be evaluated. Device 10 may scan a subject's 100 retina using sources

20 at specified wavelengths - such as those being suitable for continuous generation using laser diodes, for example. When a region of interest is detected using detector 130 and controller 170, controller 170 may selectively operate, or trigger, flash source 130 at an appropriate moment of scanning. Detector 130 may then detect the composite, or sequential, reflection of sources 20, 30 from subject 100.

Controller 170 may take the form of a suitable combination of hardware and software for operating device 10. For example, controller 170 may take the form of a conventional microprocessor having suitable inputs and outputs, and include memory for storing one or more programs being operable by the microprocessor.

Referring now also to Figure 2, in general, operation of device 10 may be facilitated by such programming as follows. A user may suitably align 210 lens 90 with an eye of a subject 100. Device 10 may be activated 220 using any suitable user interface (not shown) such as a button, for example. In response thereto, controller 170 may activate 230 sources 20, thereby causing emissions at predetermined wavelengths. Controller 170 may conventionally steer such emissions across a subject's 100 retina, so as to conventionally scan 240 the retina, using mirror 70.

Reflections from the illuminated retina of subject 100 become incident upon splitter or movable mirror 1 10.

In the case where element 1 10 takes the form of a beam splitter as is conventionally understood, reflected emissions incident thereupon may be directed to both detector 130 and user 160 as will be readily understood by those possessing an ordinary skill in the pertinent arts.

In the case where element 110 takes the form of a movable mirror, controller 170 may selectively position mirror 110 to selectively provide reflected emissions incident upon mirror 110 to either detector 130 or user 160. For example, mirror 1 10 may be initially positioned so as to enable a user 160 to view the retina of a subject 100, and after scanning has been commenced, positioned so as to direct reflected emissions to detector 130. Further, use of a movable mirror may be utilized to reduce the operable surface area required for detector 130 - by compensating for changes in the angle of incidence of reflected emissions upon mirror 1 10 due to the scanning movement of mirror 70. Alternatively, as in the case with a beam splitter serving as element 1 10, detector 130 may be of suitable size that after focusing by optics 120, it receives emissions from the entire scan of the subject's 100 retina. Detector 130 provides 250 a signal being indicative of the portion of the subject's 100 retina being presently scanned to controller 170. Controller 170 may monitor the provided signal to identify 260 a potential retinal blood vessel, such as a retinal artery or vein, for analysis. For example, controller 170 may monitor the incoming signal for information being indicative of a change in collected flux potentially associated with a scanned retinal artery or vein. The spectroscopic pattern of reflectance of retinal blood vessels is generally well understood, hence upon detection of such a pattern the presence of such a vessel may be inferred.

Upon detection of a retinal artery, controller 170 selectively activates 270 source 30. Detector 130 collects reflected emissions from sources 20, 30 simultaneously or sequentially, provides a signal indicative thereof to controller 170, and controller 170 calculates 280 a blood oxygen saturation associated with the scanned vessel. The spectroscopic signature of a blood based upon its oxygenation is well understood. Data indicative of such spectroscopic data, or an algorithm indicative thereof, may be stored in controller memory and utilized to determine an oxygenation of the scanned retinal blood vessel.

Scanning may then continue 290 to provide 300 a signal, identify 310 a retinal vein, in response to which source 30 may again be activated 320 and a blood oxygenation determined 330. A ratio of the determined venous and arterial oxygenation levels may then be generated 340 using controller 170. The process can be done in the reverse order, vein then artery, or simultaneously.

Since one of the vessels identified 260, 340 is a retinal artery and the other is a retinal vein, the ratio calculated 340 is indicative of retinal oxygen metabolization as it represents a difference in blood oxygenation entering and leaving the retina of subject 100 - and hence is indicative of brain oxygen metabolization as it is associated with blood oxygenation entering and leaving the brain as well. Further, according to an aspect of the invention a rate of profusion of blood to the brain can be determined by injecting an optically detectable, but preferably inert, tracer into a subject's body, such as into a suitable artery in the neck for example. According to an aspect of the present invention, the injected tracer may then be sensed in the patient's retina analogously to the method used for retinal blood vessel oxygenation. The time and rate of profusion into the vessels of the retina may be used as being indicative of a rate of profusion into the brain, for example. This information may be combined with oxygen metabolization information as has been set forth, for example. Suitable tracers may include florescent dies, such as fluorescein for example. This information may be considered in combination with direct retinal oxygenation measurements, for example.

In other words, a tracer injected into the blood stream can be detected once it arrives in the retina. Such a tracer could be a fluorescent die that absorbs light and then re-emits at a different wavelength. This would be especially convenient if the excitation wavelength is in the infrared, as excitation wavelengths in the infrared that do not cause the pupil to contract could be used. Timing the transit from injection to detection in the retina may be used as a suitable measure of the rate of flow between the injection site through the skull and to the retina.

Further, reduction in the oxygen supply to the brain if the heart is beating is usually the result of restricted blood circulation to the cranium or reduced blood volume. This can be due to brain swelling and thus increased pressure inside of the cranium. That is, increased intracranial pressure will impact on cerebral delivery of oxygenated blood. The cranium or cavity containing the brain has a fixed space. When the brain swells the pressure in the cranium rises. When the cranial pressure exceeds the blood pressure, the flow of blood in the vessels supplying the oxygen is reduced down stream in the retina. Conventionally however, blood flow to the brain can not be accurately monitored since the arteries supplying the inside of the cranium are deep seated and branch just before entering the skull. Therefore there can be blood flow in these arteries but not into the cranium. Bleeding elsewhere can also reduce blood volume to the point where there is insufficient profusion to fully supply the brain with oxygen. This also frequently results in brain injury or death.

According to an aspect of the present invention, retinal oxygenation measurements may be used for classifying types of strokes that have occurred in a subject. Ischemic and hemorrhagic strokes can be differentiated by measuring the retinal venous to arterial oxygenation ratio, since an ischemic stroke should not affect the retinal oxygenation but a hemorrhagic stroke should.

As therapies for ischemic and hemorrhagic strokes are contradictory, proper diagnosis is important. Ischemic strokes are defined by the blockage of blood flow within a vessel inside of the brain preventing proper profusion of a portion of the brain. Hemorrhagic strokes are defined by the bursting of a blood vessel within the brain resulting in no direct blood supply to that portion as well as a generalized reduction of brain profusion. The generalized reduction is a result of an increase in pressure inside of the skull due to the hemorrhaging. The near term treatment for ischemic strokes is the injection of "clot busting" pharmaceuticals or blood thinning agents to allow blood to move through the blocked region and resupply the oxygen starved portion of the brain. However, this treatment would severely negatively impact the prospects of a hemorrhagic shock victim as it would cause increased bleeding leading to increased pressure and a further reduction of generalized brain profusion.

According to an aspect of the present invention, by examining oxygen saturation of blood in the arteries and veins of the retina, abnormal flow of blood through these vessels can be detected by changes in the ratio of oxygenation or oxygen metabolization. This is the result of the retina neural cells using a constant amount of oxygen. If the total oxygen supply is reduced by a reduction of the blood flow, the deficit will be made evident by the neurons pulling a greater percentage of oxygen out of the blood. This then changes the oxygenation ratio. The retinal blood flow mirrors the generalized brain blood flow since the retina gets its supply of blood from within the skull. This flow is affected by phenomena that effect the entire brain such as elevated pressure.

If the stroke victim is suffering from an ischemic stroke, there will be no expected change in the retinal oxygenation ratio. This is because the blood deficit is localized to vessels within the brain downstream of the bifurcation of the vessel feeding the retina. In a case of hemorrhagic stroke, blood escaping into the brain will tend to elevate intra-cranial pressure, tending to reduce blood flow to the retina and cause a drop in the retinal venous oxygen saturation and an increase in ratio between arterial saturation and venous oxygen saturation.

Device 10 (Fig. 1 ) may be used to derive oxygenation of the blood in the retinal vessels - and ratios between retinal arterial and venous blood oxygenation as has been set forth. Reference blood oxygenation may be derived in any conventional manner, such as by using a conventional transmitted light optical blood oxygenation meter on the finger of a subject, or a reflected light optical blood oxygenation meter on the neck of a subject, for example. The data from these two sources may be compared electronically with reference data for typical populations. If the retinal oxygenation level is determined to be abnormal, a warning may be provided to consider taking additional steps for diagnostics and care, for example.

Further, measurements need not be limited to retinal exposure. According to an aspect of the present invention, measurement of brain oxygenation may be achieved by measuring blood oxygenation in the eyelid, or surrounding tissue of a subject, for example. Since the majority of the blood supply for the eyelid and surrounding tissue is also derived from the internal carotid artery within the skull, it is subject to the factors affecting blood flow in the internal carotid artery. These factors include the pressure within the skull. The blood flow is motivated by the pressure difference between the arterial and venous systems. As long as there is sufficient pressure differential, there is continued blood flow assuming no blockages. If there is a significant increase in pressure outside of the blood carrying vessels, the vessels begin to collapse and the pressure outside of the vessel is transmitted to the blood within. If the pressure in the vessel exceeds the maximum pressure within the arterial system supplying the blood, the flow stops and the tissue down stream of the pressure rise is no longer supplied with sufficient blood. An increase in pressure within the skull will thus affect the flow of blood to the eye lids and surrounding tissue as well. Increased pressure on each side of the skull will affect the corresponding flow of blood to both the eye lids and the brain. The flow of blood to each eye lid is thus a good indication of the blood flow to the corresponding side of the brain.

Oximetry of the eyelid can be done in both a reflective and a transmissive form. Referring now also to Figures 3A and 3B, there are shown reflective and transmissive oximetry configurations according to aspects of the present invention and being suitable for use with an eyelid of a subject.

Figure 3A shows one or more sources 410 emitting light to the eyelid of a subject 440 using a mirror 420 and beam splitter 430. Emissions reflected or scattered by the eyelid are collected and directed to detector 450. Operation is largely analogous to that set forth regarding device 10. Filter 460 may be provided to remove background light. In the case of a single source, source emittance may be varied in wavelength to achieve a ratio indicative of the oxygenation level of the hemoglobin in the blood. The change in source wavelength may be effected by filter change or source change, for example. In Figure 3B, where like references refer to like elements of the invention set forth in Figure 3A, light is transmitted through the eyelid, reflected off of the eyeball, travels back through the eyelid and is collected by detector 450. It may be advantageous to align the subject's eyeball such that reflection is off of the sclera, such may not be necessary though.

As will be recognized by those possessing an ordinary skill in the pertinent arts, such a transmissive mode may give a large path length resulting in additional absorption and thus a greater signal- to- noise ratio.

Such a system and method may be used with both conscious and unconscious subjects. Such a device could be taped or otherwise fixed in place for extended periods of time with no adverse physical effects. It could be applied by unskilled personnel in adverse conditions with no significant difficulty. Such a system and method may also be realized in the form of eyewear, or a visor, that is substantially non-contacting and is conventionally adapted to take measurements when the eye is closed. This would allow for periodic measurements without interfering with the subject's vision, for example. Indirect Approaches

In general, the arteries that supply the retina of the eye originate

inside of the skull. The blood supply for the retinas flows through space

contiguous with the cranium, thus if the retinal blood is sufficiently

oxygenated then the brain blood may be inferred to be sufficiently

oxygenated. A lack of sufficient oxygen supply by way of the blood to the

retina will result in the degradation of the functioning of the retinal nerve cells. These cells are similar in behavior to brain neurons. Thus, if retina

neurons are exhibiting reduced performance due to oxygen deprivation,

then it may be inferred the brain is most likely also suffering oxygen

deprivation.

Photopigmentation

According to an aspect of the present invention, the time course of reflectance change in the eye due to photopigment bleaching may be measured in addition to, or in lieu of, direct retinal blood vessel oxygenation measurements. According to an aspect of the present invention, a subject may be dark adapted, for between 10 and 20 minutes for example. The eye may then be illuminated with a temporal step function of multiple, such as two, superposed laser light sources. Device

10 may be suitable for use, for example. These sources may have one emission having a wavelength near the rod absorption peak of 505 nm, and the other at about 620 nm, for example. The eye's lens may be illuminated so as to ensure emissions enter unimpeded by the iris, which is likely to contract. The angle of illumination should be suitable for catching a substantial density of rods - such as, about 20 degrees away from the fovea. According to an aspect of the present invention, illumination may be 20 degrees temporal, so as not to hit the blind spot, where there are no photoreceptors. Reflected light intensity may be measured, and their ratio evaluated.

Illumination of the retina may be continued for a suitable temporal period, such as for an additional 10 seconds. According to an aspect of the present invention, the same portion, or substantially the same portion, of the retina may continue to be illuminated. Reflected emission intensity may again be measured, and a ratio indicative of oxygen metabolization determined.

A ratio between the first and second metabolization ratios may be computed. As will be understood by those possessing an ordinary skill in the pertinent arts, the evaluation of a ratio of ratios eliminates calculational dependence on the absolute power of emission sources, and also influences of spectral signature (such as the color of the subject's blood) that are in common between the temporally separated measurements. A significant change between the individual ratios may be indicative that photopigments were active, and have been bleached. An insignificant change may be indicative that photopigments were not well reconstituted at the outset. This may be taken as an index of insufficient oxygen intake, if one has ruled out other diagnoses such as night blindness.

Alternatively, an analogous procedure may be performed on the foveal cones. In such case, the period of dark adaptation may be shortened, to a minute or so for example. However, because foveal cones typically do not relinquish their spent photoreceptor outer segments and sit in a dark matrix of pigment epithelium that reduces light scatter for example, the signal-to-noise ratio of such a procedure may be less for cone measurement than for rod measurement.

Physiological Responses

Further, the neural processes in the retina are similar to neural functions elsewhere in the nervous system. If they are stimulated at a rate faster than their recovery time, their response is reduced. As is well understood by those possessing an ordinary skill in the pertinent arts, neural response is not reduced if the stimulation is periodic at a rate longer than the recovery rate of the neurons. This recovery rate is a result of the chemical process allowing the "resetting" of the chemical potentials within the cells. If the nerve cells are not supplied with sufficient blood circulation, and thus oxygen, their ability to recover between stimulations is reduced. This is exhibited by reduced light sensitivity in the eye and reduced chemical sensitivity in the olfactory organs, for example.

According to an aspect of the present invention, a system and method may be utilized that periodically stimulates the optical receptors and then measures the ability of the body to respond to those stimulations.

The measured response of the body can be of several types. For example, pupil size is a physiological response to incident light. It is well known that the iris responds to light by making the pupil smaller. This is the pupilary response. It is also well known that the pupilary response depends on the frequency of the stimulation. This response changes both in amplitude and phase with changes in stimulation frequency. The frequency response in amplitude and phase will be affected by the optical nerve sensors ability to recover from stimulation. Therefore, if the retina is lacking in oxygen or other critical circulatory elements, the pupilary response may be affected in a discernable way. According to an aspect of the present invention, pupilary response may be measured and considered to determine nerve responsivity and hence oxygen metabolization. This information can be used in combination with direct measurements of retinal oxygenation, for example. Pupilary response can be measured by use of motion picture capture and image analysis. Such a system may capture images of the eye and measure the diameter of the pupil. These measurements may be correlated to the time of the stimulations. The parameters of response magnitude, size of the pupil and phase delay are indications of nerve responsivity. Intra-ocular Pressure

Another exemplary and non-limiting physiological response that is dependant on ocular nerve responsivity is intra-ocular pressure. The neural function within the optical sensors of the eye depend on the transfer of calcium. It has been shown that the release of calcium in the eye will produce increases in intra-ocular pressure. These increases or fluctuations in the intra-ocular pressure can be monitored from the exterior of the body using a tonometer and correlated to the retina's lack of oxygenation. Information indicative of such increases or decreases in intra-ocular pressure may be considered in combination with direct measurements of retinal oxygenation, for example. Such physiological responses may be used as indications of brain neural function or retinal neural function deficits even if the oxygenation of the nerves is not compromised and may serve to further elucidate direct measurements of retinal oxygenation. It should be understood that there may be some effect on the responses due to glaucoma or other diseases affecting the retina or the brain, for example.

Regardless of methodology used, by non-invasively measuring blood oxygenation in retinal vessels as has been set forth, the blood oxygenation level of retinal blood may be compared to the blood oxygenation of blood elsewhere in the body. Using this information, a degree of circulation to the brain can be inferred. If a determined oxygenation ratio is abnormal, further steps in diagnostics, such as drilling a hole in the skull for pressure measurement device may be performed, for example. It will be apparent to those skilled in the art that various modifications and variations may be made in the system and method of the present invention without departing from the spirit or scope of the invention. Thus, it is intended that the present invention cover the modification and variations of this invention provided they come within the scope of the appended claims and their equivalents.

Claims

ClaimsWhat is claimed is:

1. A method for determining a blood oxygenation associated with a brain of a subject, said method comprising: scanning a retina of said subject to identify at least one retinal blood vessel using at least a first optical energy source; in response to said identifying, selectively flashing said identified retinal blood vessel using at least a second optical energy source; detecting at least one reflectance from said flashed retinal blood vessel; and, determining a ratio being indicative of said oxygenation using said detected at least one reflectance.

2. The method of Claim 1 , wherein said first optical energy source comprises a plurality of lasers.

3. The method of Claim 2, wherein said at least second optical energy source comprises a filtered flash.

4. The method of Claim 3, wherein said lasers comprise three lasers having operating wavelengths of approximately 635nm, 670nm and 830 nm, respectively, and said second optical energy source has an operating wavelength output of approximately 488 nm.

5. The method of Claim 1 , further comprising: scanning said retina of said subject to identify at least one other selectively flashing said identified at least one other retinal blood vessel using at least said second optical energy source; and detecting at least one other reflectance from said flashed other retinal blood vessel; wherein, said ratio is determined using said detected reflectances.

6. The method of Claim 1 , further comprising comparing said ratio to data being indicative of oxygenation.

7. The method of Claim 11, wherein said data comprises information associated with at least one of said subject and information associated with a population associated with said subject.

8. A device for determining a blood oxygenation associated with a brain of a subject, said device comprising: at least a first beam emitting device; a beam steering device optically coupled to said at least first beam emitting device; a second emitting device; a detector positioned so as to receive reflections of emissions from said at least first beam emitting and second emitting devices; and, a controller operatively coupled to said at least first beam emitting device, beam steering device, second emitting device and detector and including code for: scanning a retina of a subject using said at least first beam emitting device and beam steering device to blood vessel using said at least second optical emitting device; and detecting at least one reflectance from said flashed retinal blood vessel using said detector.

9. The device of Claim 8, wherein said second emitting source comprises a flash and filter.

10. The device of Claim 9, wherein said second emitting source further comprises at least one of phosphor or gaseous enhancement of emissions.

11. The device of Claim 8, wherein said controller further comprises code for calculating at least one ratio being indicative of oxygenation using said detected reflectance.

12. A method for determining a blood oxygenation associated with a brain of a subject, said method comprising: selectively illuminating a pupil of a subject at a given rate using at least one optical energy source; and, detecting at least one pupilary response to said illumination; wherein, said given rate is such that said detected pupilary response is indicative of blood oxygenation of said brain of said subject.

13. A method for determining a blood oxygenation associated with a brain of a subject, said method comprising: selectively illuminating a retina of a subject at a given rate using at least one optical energy source; and, determining whether photopigments in said retina were active; wherein, said given rate is such that said determined photopigment activity is indicative of blood oxygenation of said brain of said subject.

14. A method for differentiating between ischemic and hemhorragic strokes, said method comprising: illuminating tissue associated with an eye of a subject using at least a first optical energy source; detecting at least one reflectance from said illuminated tissue; and, wherein, said detected at least one reflectance is indicative of either an ischemic or hemhorragic stroke.

15. A method for determining a profusion rate of blood to the brain of a subject, said method comprising: injecting a tracer into the bloodstream of said subject; scanning a retina of said subject to identify at least one retinal blood vessel using at least a first optical energy source; detecting at least one reflectance from said identified at least one retinal blood vessel; and, determining whether said detected reflectance is indicative of a presence of said injected tracer.

16. The method of Claim 15, further comprising, if sad detected reflectance is indicative of said injected tracer, determining at least one temporal period associated with said injecting and detecting.

17. The method of Claim 15, further comprising, if said detected reflectance is not indicative of said injected tracer, again scanning said retina of said subject to again identify at least one retinal blood vessel using said at least first optical energy source; again detecting at least one reflectance from said again identified retinal blood vessel; and, determining whether said again detected reflectance is indicative of a presence of said injected tracer.

18. A method for determining a blood oxygenation associated with a brain of a subject, said method comprising: selectively illuminating a tissue associated with an eye a subject at a given rate using at least one optical energy source; detecting at least one physiological response to said selective activation; and, wherein, said given rate is such that said detected response at least one response is indicative of blood oxygenation of said brain of said subject.

19. A method for differentiating between ischemic and hemhorragic strokes, said method comprising: selectively illuminating a tissue associated with an eye of a subject at a given rate using at least one optical energy source; and, detecting at least one physiological response to said selective illumination; wherein, said detected at least one response is indicative of either an ischemic or hemhorragic stroke.

20. A method for determining a profusion rate of blood to the brain of a subject, said method comprising: scanning an eyelid of a subject to identify at least one artery and at least one vein using at least one optical energy source; detecting at least one reflectance from each of said identified artery and vein; and, determining a ratio being indicative of brain metabolism using said detected reflectances.