Patent ID: 12207936

DETAILED DESCRIPTION

It will be appreciated that for simplicity and clarity of illustration, where appropriate, reference numerals and/or names have been repeated among the different figures to indicate corresponding or analogous elements. In addition, numerous specific details are set forth in order to provide a thorough understanding of the embodiments described herein. However, it will be understood by those of ordinary skill in the art that the embodiments described herein can be practiced without these specific details. In other instances, methods, procedures and components have not been described in detail so as not to obscure the related relevant feature being described. The drawings are not necessarily to scale and the proportions of certain parts may be exaggerated to better illustrate details and features. The description is not to be considered as limiting the scope of the embodiments described herein. It should be noted that references to “an” or “one” embodiment in this disclosure are not necessarily to the same embodiment, and such references mean at least one.

Several definitions that apply throughout this disclosure will now be presented.

The term “coupled” is defined as connected, whether directly or indirectly through intervening components and is not necessarily limited to physical connections. The connection can be such that the objects are permanently connected or releasably connected. The term “electrically coupled” is defined as being in structural electrical contact, whether directly or indirectly through intervening components, to allow the flow of electrons between the respective elements. The connection can be such that the objects are also “coupled”. The term “outside” refers to a region that is beyond the outermost confines of a physical object. The term “inside” indicates that at least a portion of a region is partially contained within a boundary formed by the object. The term “substantially” is defined to be essentially conforming to the particular dimension, shape or other word that substantially modifies, such that the component need not be exact. For example, substantially cylindrical means that the object resembles a cylinder, but can have one or more deviations from a true cylinder. The term “comprising” means “including, but not necessarily limited to”; it specifically indicates open-ended inclusion or membership in a so-described combination, group, series and the like.

As can be seen inFIG.25, a representation of the fixational eye movements. To give scale, the radius of the circle is just 25 micrometers, approximately the size of one human hair. The eye is typically always moving about. The larger movements are drift and MS. The drift is a very slow movement, while the long, quick and substantially linear movements are the MS. The OMT and the drift occur at the same time. Ocular drift is the fixational eye movement characterized by a smoother, slower, roaming motion of the eye. The exact movement of ocular drift is often compared to Brownian motion, which is the random motion of a particle suspended in fluid as a result of its collision with the atoms and molecules that comprise that fluid. The movement can also be compared to a random walk, characterized by random and often erratic changes in direction. Although the frequency of ocular drifts is usually lower than the frequency of OMT (from 20 to 40 Hz compared to from 40 to 100 Hz), it is problematic to distinguish ocular drifts and ocular microtremors in the range from 30 to 40 Hz. Resolution of intersaccadic eye movements is technically challenging. The OMT are small, quick, and synchronized oscillations of the eyes occurring at frequencies in a range of 40 to 100 Hz, although they typically occur at around 90 Hz in the average healthy individual. The MS, also known as “flicks”, are saccades, involuntarily, produced during the fixation periods. They are the largest and fastest of the fixational eye movements.

Referring initially toFIG.1of the drawings, there is shown a monitor such as healthcare practitioner, an anesthesiologist, intensivist, clinician, or the like, monitoring a patient who is unconscious and sedated. The monitor is able to acquire eye signal information, process it with pre-programmed routines, store and display multiple parameters simultaneously. The monitor is able to determine the brain stem activity and altered brainstem state of the patient to measure his level of sedation, consciousness, and responsiveness by virtue of a compact, low cost and highly compliant eye sensor1. The eye sensor1is shown inFIG.1positioned at the eyelid20of the patient so as to be advantageously able to reliably sense the fixational eye movements of the patient's eyeball in order to provide the monitor with an indication of the patient's awareness during a medical procedure (e.g., in an operating room or intensive care facility). Fixational eye movements are present always (except on death and a few rare conditions) even when the eyes are apparently at rest, and occur involuntarily. Similarly, the body is nearly always undergoing stimulation, whether from the outside world, exogenously, or whether from within the body, endogenously. For example, hypoxic stimuli, which originate in the periphery, facilitate cardiopulmonary regulation and are processed continuously by the brainstem. Since the brainstem is constantly stimulated and since the fixational movements are always present, we can employ microsaccades and OMT and combinations thereof through the use of this invention productively in nearly all clinical and behavioral conditions.

However, it is to be understood that the eye sensor1herein disclosed can also be used to monitor and provide an indication of the alertness, awareness, arousal, diagnosis of injury and behavior modification of an individual in both medical and industrial environments. The eye sensor1also is also capable of monitoring any condition or circumstance in which it is desirable to obtain a measurement of brain stem activity of an individual to be compared against a known reference. To this end, the eye sensor1of this invention is advantageously capable of being attached directly over the patient's closed eyelid or in the tissue folds adjacent the patient's eyelid. While the eye sensor1will sometimes be referred to herein as having particular application for use by a patient in the care of a monitor or similar healthcare practitioner, it is to be once again understood that the eye sensor1can also be used in an industrial or other non-medical environments to test the alertness of one wishing to drive, operate machinery, perform complex tasks, etc.

The eye sensor1ofFIG.1comprises a detector11and an amplifier3. The detector11comprises a sensor (designated16inFIGS.8-10). In some embodiments, the sensor16(designated16inFIGS.8-10) comprises a multi-layer piezoelectric element that is electrically coupled to an amplifier3by way of a ribbon5. The output of the amplifier3is supplied to a signal processor9(best shown inFIG.17) by means of a shielded cable7. The signal processor9, in turn, is electrically connected to a visual display10. The details of the sensor16, the ribbon5, as well as the amplifier3to which the sensor16is coupled to form the eye sensor1will be described in greater detail hereinafter.

FIG.1shows an embodiment of the visual display10which communicates with the signal processor9(ofFIG.17) to display information generated by the eye sensor1. The display10can also provide information during a preliminary baseline test and/or when the patient is semi-conscious or fully conscious, alert and not sedated. By way of example only, the display10shows a fixational eye movement biosignal12that is generated by the eye sensor1in response to fixational eye movements of the patient's eyeball. The shape and amplitude/power/reactivity of the fixational eye movement biosignal12provide a graphical representation of the patient's brain stem activity and his level of consciousness over a particular sampling time. The fixational eye movements comprise of MS and OMT. The OMT biosignal is generally an alternating voltage waveform that is reflective of the OMT of the patient's eyeball to which the eye sensor1is responsive by way of the patient's eyelid. The combined OMT/MS power reactivity signal tends to be erratic and eventful, with long steady calm periods interrupted by the rapid onset of steep increases, peaks, and valleys.

In addition, the display10also shows a discrete reference number14to be computed by the signal processor9for easy visual reference by the monitor. By way of example, the reference number14being displayed is dependent upon the fixational eye movements of the eyeball and the corresponding frequency of the waveform of the fixational eye movement biosignal12in order to provide another indication of the patient's brain stem activity and his level of consciousness, sedation, and responsiveness.

Turning now toFIGS.2-4of the drawings, an embodiment of the sensor16(ofFIGS.8-10) is shown attached to a closed eyelid of an individual, such as a patient who is heavily sedated while undergoing an operation in an operating room. However, and as indicated previously, the sensor16can also be attached to the eyelid of an individual undergoing evaluation in many settings (e.g. intensive care unit, industrial and other non-medical environments). In some embodiments, the patient's eyelid20is held closed prior to the attachment of the sensor16. A double-sided pressure sensitive adhesive patch100(shown in inFIGS.3A and13) can be used to hold the sensor16against the patient's closed eyelid above the patient's eyeball at which to be responsive to the fixational eye movements of the eyeball and thereby provide the fixational eye movement biosignal12(ofFIG.1) by way of the ribbon5to the amplifier3. The amplifier3provides an amplified analog signal of the fixational eye movement biosignal12to the signal processor9so that both graphical and numerical representations of the patient's brain stem activity including his level of consciousness, sedation, and responsiveness are visually available to the monitor on the display10.

However, there are instances when it would be desirable to be able to use the eye sensor1to measure and indicate the patient's brain stem activity and his level of consciousness when his eyelid is fully or partially open. In this case, and referring toFIGS.5and6of the drawings, the eye sensor1is shown attached to the patient's rolled up eyelid. For example, the eye sensor1is shown being used in the manner shown inFIGS.5and6at those times when the patient is lightly, moderately or not sedated, when the patient's eyelid is alternately being opened and closed, or when the patient's eyelid is fully open, such as while a preliminary baseline test is being conducted.

By virtue of the foregoing, the patient's brain stem activity and level of consciousness can be continuously monitored to enable intervention by the monitor or other healthcare practitioner when necessary. Because the eye sensor1including the sensor16(ofFIGS.8-10) and the ribbon5is thin and compliant, the sensor16may be advantageously attached, as shown inFIGS.5and6, between the tissue folds of the patient's opened eyelid at which the sensor16of detector11is responsive to the fixational eye movements of the patient's eyeball.

InFIGS.1-6, the amplifier3is shown as being connected to a signal processor (designated9inFIG.17) by means of a shielded cable7. However, as shown inFIG.7of the drawings, it is within the scope of this invention for the amplifier3to be replaced by a wireless eye signal amplifier3-1. In this case, the shielded cable (designated7inFIG.5) will now be eliminated. Moreover, in some embodiments, the wireless eye signal amplifier3-1is provided with an analog-to-digital converter (designated110inFIG.18) and a conventional wireless transmitter (designated116inFIG.18), and the signal processor (designated9-1inFIG.18) is provided with a complimentary wireless transceiver118. In this manner, the amplified fixational eye movement biosignal12can be transmitted from the amplifier3-1to the signal processor9-1at a remote location and over a wireless communication path.

Details of an embodiment the sensor16shown inFIGS.1-6are now disclosed while referring toFIGS.8-10of the drawings. As was previously explained, the sensor16is held against the moving surface of the patient's opened or closed eyelid (represented generally by reference numeral20inFIGS.8-10) so as to be responsive to the fixational eye movements of the patient's eyeball which have an amplitude of an eyeball arc length excursion between 0.1 and 400 micrometers and thereby provide a corresponding alternating voltage fixational eye movement biosignal to the soon-to-be-described eye signal amplifier (designated3inFIG.1).

In some embodiments, an electrically conductive (e.g., copper) top surface28is applied to the top of the sensing element30to establish a first output terminal. An electrically conductive (e.g., copper) bottom surface32is applied to the bottom of the sensing element30to establish a second output terminal.

In some embodiments, the sensor16comprises a piezo-electric thin planar top layer22, a thin planar bottom layer24and an intermediate bonding agent26(e.g., epoxy) located therebetween to form a layered-type structure. A first electrically conductive (e.g., copper) top surface28is applied to the outside of a flexible first piezoelectric (e.g., PVDF) film30from the top layer22of the sensor16to establish a first output terminal. An electrically conductive (e.g., copper) bottom surface32is applied to the outside of a flexible second piezoelectric film34from the bottom layer24of sensor16to establish a second output terminal. Each of the first piezoelectric film30and second piezoelectric film34of the top layer22and bottom layer24of sensor16which face one another are held in opposing alignment by the intermediate bonding agent26. The length and width of the first piezoelectric film30and second piezoelectric film34may be larger than the respective length and width of the top surface28and the bottom surface32so as to avoid undesired electrical communication between the top surface28and bottom surface32. In some embodiments, the thickness of the sensor16shown inFIGS.8-10is between 20 to 150 microns.

In some embodiments, the sensor16is able to generate a voltage as the sensing element is deflected in response to the fixational eye movements of the patient's eyeball which create a corresponding motion through the eyelid20above which the sensor16is attached. That is to say; the sensor16is deformed and deflected by the movements of the patient's eyelid20caused by the fixational eye movements of the eyeball. In the case where the sensor16is at rest as shown inFIG.8, no voltage is generated by the sensor16between the first and second output terminals at the top surface28and bottom surface32. In the case where the sensor16is deflected in a first direction by the movement of the patient's eyelid20in the same first direction as shown inFIG.9, a positive voltage is generated by the sensor16between the output terminals at the top surface28and bottom surface32. In the case where the sensor16is deflected in the opposite direction by the movement of the patient's eyelid20in the same opposite direction as shown inFIG.10, a negative voltage is generated by the sensor16between the output terminals at the top surface28and bottom surface32.

Because the fixational eye movements of the patient's eyeball typically occur at nanometer and micrometer levels across a range of frequencies and with variable intensity, the sensor16is designed to be flex back and forth at in like correspondence, so as to generate biosignals. The amplitude, positive or negative direction, and frequency of the fixational eye movements to which the sensor16is responsive are isolated, processed and re-integrated and reflected graphically in a time synchronized manner so as to illustrate various events and patterns and numerically by the displayed traces e.g.12and the summary reference values e.g.14that are visually accessible to the user on the display10ofFIG.1.

It is to be expressly understood while the sensor16is shown as comprising a pair of piezoelectric elements (the first piezoelectric film30and second piezoelectric film34), in the drawings, it is disclosed that sensor16can comprise one or more piezoelectric elements, and the top and bottom thereof will have electrically conductive surfaces which lie thereon to establish the aforementioned first and second output terminals between which the fixational eye movement biosignal is generated. In some embodiments, the sensor16comprises a single piezoelectric element, in others, the sensor comprises of 3 or more piezoelectric elements.

Referring specifically toFIGS.3and3Aof the drawings, a position is described in which the sensor16of the detector11shown inFIGS.8-10is held against the patient's fully closed eyelid. As an important feature of some embodiments, the sensor16is sufficiently thin (as explained when referring toFIGS.8-10) and compliant to assume a generally arcuate (e.g., curved) configuration in order to conform to the shape of the patient's eyelid when the sensing element is attached thereto by means of the adhesive100. The adhesive can be a double-sided pressure sensitive adhesive patch. In some embodiments, the sensor16surrounds at least some of the patient's closed eyelid and is sized so as to be large enough to cover angular excursions of the eyeball yet small enough to be placed within the eye socket.

In this regard, the sensor16of this can be sized such that it will cover a relatively large surface area of the eyelid so as to be responsive to a full range of motion of the patient's eyeball transmitted through the eyelid. Moreover, the pressure applied to the eyelid by the sensor16is more uniformly distributed around the eyelid than some conventional focused pressure sensing elements. Accordingly, the sensor16will be more comfortable to wear for longer periods, is less costly and easier to accurately position at the eyelid to achieve a reliable response than some conventional focused pressure sensing elements. Therefore, the eye sensor1can be comfortably fitted to the patient such that the sensor16thereof is unlikely to be noticed or objected to.

The sensor16is shown inFIG.3Aconforming to the shape of the patient's eyelid and being coupled to the ribbon5. As will be described in greater detail when referring toFIGS.16-18, the sensor16is surrounded by upper strip62and lower strip64of the ribbon5. The top shielding layer70and the bottom shielding layer72lay over the outside surfaces of respective ones of the upper strip62and lower strip64to provide the ribbon5with shielding. The shielding will avoid subjecting the biosignal generated by the sensor16and transmitted via the ribbon5to electrical and electromagnetic noise and other interference.

An embodiment of the amplifier3is described while referring toFIGS.11and12. To isolate the electrical components of the amplifier3and thereby prevent environmental electrical and electromagnetic interference from altering the information contained by the eye biosignal, the amplifier3is provided with a conductive amplifier housing38having a removable lid40. The sensor16is electrically connected to the amplifier3by way of the ribbon5(best shown inFIGS.13-16).

When in use ribbon5can be of such a length that slack is present between the sensor16and the amplifier3so as to avoid applying loads or pulling forces to the patient's eyelid and thereby inducing a possible unintended response by the sensor16.

In some embodiments, an amplifier grounding electrode44comprising a flat conductive base45is to abut the patient's skin. In some embodiments, an electrically conductive adhesive patch46(e.g., a common EKG electrode patch) attaches the bottom of the amplifier housing38to the patient. The amplifier3can be located near the sensor16so as to reduce the overall area of the ribbon cable but in a slack manner so as to avoid applying a pulling force against the ribbon5. An electrical receptacle56inside the amplifier housing38is coupled to the amplifier grounding electrode44. The adhesive patch46anchors the amplifier3in place and the conductive base against the patient's skin. The attachment helps prevent a displacement of the amplifier3relative to the ribbon5during monitoring. It should be recognized that other conventional electrical and mechanical (e.g., straps, glue, suction) amplifier attachment means can be substituted for the electrically conductive adhesive patch46just so that the amplifier is grounded.

To ensure that the amplified alternating voltage signals generated by the amplifier3are not altered by the environment, the electrically conductive amplifier housing38, the top shielding layer70, and the bottom shielding layer72can be electrically coupled to electrical ground. In some embodiments, electrical paths are established to ground from top shielding layer70and the bottom shielding layer72of the ribbon5and the amplifier housing38of the amplifier3to the patient's skin at the amplifier grounding electrode44which is held in place against the skin by the electrically conductive adhesive patch46. In some embodiments, the electrically conductive amplifier housing38, the top shielding layer70, and the bottom shielding layer72are electrically coupled to a grounded item besides the patient. Details of these electrical paths to ground at the patient's skin are described below.

In the embodiment shown inFIG.12, the ribbon5is connected at a proximal end thereof to the sensor16(best shown inFIG.13) and at the terminal end51to an electrical connector block48that is located in the interior of the amplifier housing38. A first electrically conductive (e.g., mesh) pillow50is positioned within amplifier housing38so as to lie between the removable lid40thereof and the top shielding layer70that runs over the top of the ribbon5. A second electrically conductive pillow52is positioned within amplifier housing38so as to lie between the electrically conductive shielding72that runs over the bottom of the ribbon5and a printed circuit board54that is positioned at the bottom of the amplifier housing38of the amplifier3. The aforementioned amplifier grounding electrode44is detachably connected to the amplifier3through the bottom of amplifier housing38and to the printed circuit board54at the electrical receptacle56, such that the flat conductive base45of the amplifier grounding electrode44is connected to ground against the patient's skin.

In some embodiments, the amplifier3comprises first and second electrically conductive pillows50and52that lie in electrical contact with respective ones of the aforementioned electrically conductive top shielding layer70and the bottom shielding layer72. Thus, the top shielding layer70at the top of the ribbon5is connected to ground at the patient's skin by way of a first electrical path to ground that comprises the first conductive pillow50, the electrically conductive amplifier housing38, a first jumper wire60that connects amplifier housing38to the electrical receptacle56, and finally the amplifier grounding electrode44and the base45lying against the patient's skin. The bottom shielding layer72at the bottom of the ribbon5is also connected to ground by way of a second electrical path to ground that comprises the second conductive pillow52and a second jumper wire61that connects pillow52to the electrical receptacle56, and finally the amplifier grounding electrode44and the base45thereof against the user's skin. In this same regard, it may be appreciated that top shielding layer70and the bottom shielding layer72at the top and bottom of the ribbon5are electrically connected to one another by way of the electrically conductive pillows50and52and the electrically conductive amplifier housing38.

The resilient characteristic of the electrically conductive (e.g., mesh) pillows50and52which overlay the top shielding layer70and the bottom shielding layer72of the ribbon5accommodate and absorb bending forces to which the ribbon5is subjected. The pillows50and52also support the ribbon5within the amplifier housing38and suspend the ribbon5above the printed circuit board54so as to lie in axial alignment with the electrical connector block48. The electrical connector block48to which the terminal end51of the ribbon5is connected is, in turn, electrically connected to the printed circuit board54by way of an upstanding connector post58. The printed circuit board54contains conventional signal conditioning and amplifier circuitry by which the fixational eye movement biosignal is alternating voltage biosignal carried by the ribbon5is amplified, in some embodiments by a factor of at least ten. An amplified analog fixational eye movement biosignal is supplied from the amplifier3, shown inFIG.12, to the signal processor9and display10, ofFIG.17, by means of the shielded cable7that extends from the printed circuit board54. However, as earlier explained the fixational eye movement biosignal might also be transmitted from the amplifier3to the signal processor9over a wireless communication path illustrated inFIG.18.

Referring concurrently toFIGS.13-16of the drawings, details are now provided of an embodiment of the ribbon5, which is electrically connected at the proximal end thereof to the sensor16(previously described while referring toFIGS.8-10) and at the opposite terminal end51to the amplifier3(as described while referring toFIG.12). The ribbon5is disposed in surrounding engagement with and connected between the top surface28and bottom surface32of the sensor16and the electrical connector block48that is held, by the connector post58, above the printed circuit board54, that is positioned inside and at the bottom of the shielded housing38of the amplifier3shown inFIG.12.

Some embodiments of the ribbon5comprise upper and lower elongated and upper strip62and lower strip64that are attached one above the other. By way of example, the bottom of the upper strip62and the top of the lower strip64can be bonded face-to-face one another by a conventional thin layer of adhesive (designated65inFIG.15). Each of the upper and lower strips62and64of ribbon5comprises an upper non-conductive layer66and bottom non-conductive layer68that can be manufactured from an electrical insulating polyimide or any other suitable non-conductive material. Both the top and the bottom of each of the upper non-conductive layer66and the bottom non-conductive layer68of the upper and lower strips62and64are initially covered by an electrically conductive (e.g., aluminum or gold) coating.

As shown in the embodiment shown inFIG.15, top shielding layer70and the bottom shielding layer72which cover the outwardly facing top of the upper non-conductive layer66of the upper strip62and the outwardly facing bottom of the bottom non-conductive layer68of the lower strip64of the ribbon5are left intact to create shielding surfaces. The top shielding layer70and the bottom shielding layer72were previously described while referring toFIG.12as being connected to each other and to ground at the individual's skin to shield the ribbon5against electrical and electromagnetic energy that might interrupt or distort the biosignal generated by the sensor16and supplied to the amplifier3by ribbon5.

As shown in the embodiment shown inFIG.13, portions of the shielding, which can initially cover the inwardly facing bottom of the upper non-conductive layer66of the upper strip62and the opposing inwardly facing top of the bottom non-conductive layer68of the lower strip64, can be etched away to leave respective longitudinally extending electrically conductive traces74and76running along the upper non-conductive layer66and the bottom non-conductive layer68of the upper and lower strips62and64. During the aforementioned etching process, pairs of relatively wide electrically conductive upper terminals78,79and conductive lower terminals80,81are formed at first and opposite ends of each of the conductive traces74and76. With the upper and lower strips62and64of the ribbon5bonded together by the intermediate adhesive layer65(ofFIG.15), the longitudinally extending electrically conductive traces74and76formed on the bottom and on the top of the upper non-conductive layer66and the bottom non-conductive layer68lie in parallel alignment and in electrical isolation from one another. The aforementioned etching process is an example of a technique for forming the electrically conductive traces74and76. However, it should be understood that other conventional techniques can be used to form the traces74and76on the upper non-conductive layer66and the bottom non-conductive layer68.

As shown in the embodiment shown inFIG.15, the sensor16can be a multi-layer piezo-active element and located, in some embodiments sandwiched, between first ends of the upper and lower strips62and64at the proximal end of the ribbon5. In some embodiments, an electrically conductive upper pad82is adhesively bonded between the upper terminal78located at a first end of the upper trace74, on the bottom of the upper strip62, and the top surface28, on the top of the sensor16. An electrically conductive lower pad83is located between the bottom surface32, which lies at the bottom of the sensor16, and the lower terminal80, located at a first end of the lower trace76, on the top of the lower strip64. The upper and lower terminals78and80at the first ends of traces74and76and the upper pad82and the lower pad83, on the top and the bottom of the sensor16, are all aligned with one another in a stack at the proximal end of the ribbon5.

In some embodiments, an electrically conductive upper terminal pad84is adhesively bonded between the upper terminal79formed at the opposite end of the upper trace74on the bottom of the upper strip62and an opposing upper terminal86formed on the top of a flexible transition circuit board88(ofFIG.13). The circuit board88is located, in some embodiments sandwiched, between opposite ends of the upper strip62and lower strip64at the terminal end51. An electrically conductive lower terminal pad85is located between the lower terminal81, located at the opposite end of the lower trace76on the top of the lower strip64, and an opposing lower terminal90, located on the bottom of the flexible transition circuit board88. The terminals79and81, at the opposite ends of the upper trace74and the bottom trace76, the upper terminal pad84, the lower terminal pad85, located above and below the circuit board88, the opposing upper terminal86and the circuit board lower terminal90, of the circuit board88, are all aligned with one another in a stack at the terminal end51of the ribbon5.

The upper terminal86of the transition circuit board88(e.g., a first output terminal of the ribbon5) is electrically connected to the electrical connector block48that is surrounded by the electrically conductive shielded amplifier housing38(ofFIG.12) by way of a first conductive trace92lying on the top of circuit board88and a first electrical contact94of electrical connector block48. The circuit board lower terminal90of the transition circuit board88(e.g., a second output terminal of the ribbon5) is electrically connected to the electrical connector block48by way of a second conductive trace96lying on the bottom of circuit board88and a second electrical contact98of electrical connector block48. As was previously explained while referring toFIG.12, the electrical connector block48is electrically connected to the printed circuit board54that lies at the bottom of the amplifier housing38of amplifier3. Therefore, it may be appreciated that the alternating voltage biosignal generated by the sensor16can be transmitted from the top surface28and bottom surfaces32at the top and at the bottom of sensor16to the amplifier3by way of the electrically conductive traces74and76which run along the upper and lower strips62and64between the proximal and terminal end51of the ribbon5.

It is to be understood that the electrically conductive upper trace74, which runs along the bottom of the upper non-conductive layer66, may be electrically isolated from the top shielding layer70that covers the top of the upper non-conductive layer66. Likewise, the electrically conductive lower trace76which runs along the top of the bottom non-conductive layer68of the lower strip64of the ribbon5, may be electrically isolated from the bottom shielding layer72that covers the bottom of the bottom non-conductive layer68. Moreover, the top shielding layer70and the bottom shielding layer72, that cover the top of the upper non-conductive layer66and the bottom of the bottom non-conductive layer68, almost completely surround the ribbon5and enclose the electrically conductive traces74and76thereof as well as the sensor16lying therebetween so as to avoid an alteration of the alternating voltage biosignal as could be caused by external electrical and electromagnetic interference.

The adhesive100can be attached, at one side thereof, to the outwardly facing bottom of the lower strip64. The opposite side of the adhesive100can be covered by a pull off release film strip42. When the film strip42is pulled off and removed from the adhesive100, the eye sensor1including the ribbon5and the sensor16that is located, in some embodiments sandwiched, between the upper strip62and the lower strip64at the proximal end of ribbon5, can be adhesively attached to the patient's eyelid in such a way to permit the fixation movements of the eyeball of the patient to be sensed, amplified, processed and/or displayed.

By virtue of the ribbon5herein disclosed, the sensor16can be substantially isolated from mechanical forces that might otherwise be transmitted thereto from the amplifier3. By way of example, muscular actions, seismic activity and other mechanical motions and vibrations could introduce unwanted artifact noise to the alternating voltage biosignal produced by the sensor16. To this end, a minimum flexural rigidity depending upon the dimensions and material electricity of the ribbon5are preferable in order to avoid the transmission of such mechanical forces to the sensor16via ribbon5.

In some embodiments, the thickness of the ribbon5is less than or equal to 25 microns, while the width is about 4-8 mm. In some embodiments, the flexural rigidity of the ribbon5is less than or equal to 10×10−4-in4. As indicated earlier, the ribbon5should be provided with slack or strain relief to avoid applying force to the sensor16. That is the length of the ribbon5longer than the straight line distance between the sensor16and the amplifier3. In some embodiments, the length is at least 5% longer than the straight line distance.

InFIG.13B, an embodiment of a detector11is shown. The detector11comprises terminal end51, a ribbon5and a sensor16. The terminal end51comprises a terminal end backing187, top shielding pad186, a bottom shielding pad185, and an attachment means190. The sensor16comprises a top surface28and a bottom surface232that are conductive; a sensing element30; and a bottom conductive surface terminal180. The bottom conductive surface terminal180is electrically coupled to the terminal78. In some embodiments, the bottom conductive surface terminal180and the upper terminal78are connected via the conductive upper pad82. In some embodiments, a portion, if not all, of the sensor16is covered by the ribbon5. In some embodiments, the sensor16comprises a bottom conductive surface232, a conductive bridge181that couples the bottom conductive surface232with the bottom conductive surface terminal180.

An embodiment of the ribbon5, as shown in FIG X, comprises a top shielding layer70, an upper non-conductive layer66, a conductive upper trace74, a bottom non-conductive layer68, and a bottom shielding layer72.

InFIG.13C, an embodiment of a sensor16and an embodiment of a ribbon5is shown. The ribbon5comprises a top shielding70; an upper non-conductive layer66; a conductive upper trace74; a bottom non-conductive layer68; a conductive upper trace74; and a bottom shielding72. The sensor16comprises a conductive upper pad82; a non-conductive layer260; a top surface28and a bottom conductive surface terminal180electrically coupled to the conductive upper pad82; a bottom conductive surface232coupled to the sensing element30. The conductive pad82, while electrically coupled to the top surface28and bottom conductive surface232, insulates the top surface28from bottom conductive surface232and individually couples the top surface28and bottom conductive surface232, via the bridge181, to the conductive upper trace74and the bottom shielding layer72. In some embodiments, the top shielding layer70and the upper non-conductive layer66of ribbon5extend over the sensor16so that it is fully covered by a top shielding layer70and will be shielded by the top shielding layer70.

One difference of the embodiment shown inFIG.13C, as compared to other embodiments of the sensor16disclosed, is that bottom shielding layer72of the ribbon5is able to act as both a trace and electromagnetic shielding for the ribbon5. This can be an advantage over other ribbons5in that there is one less trace or electrical pathway required. This can result in a thinner, more flexible ribbon5. As mentioned above, the mechanical movement transmitted by the ribbon5to the sensor16will corrupt readings. Thus, a thinner and/or flexible ribbon5will result in more accurate readings. In some embodiments, the bottom shielding layer72is grounded by the amplifier3.

Also shown in inFIG.13C, an embodiment of the terminal end51is shown. The terminal end51comprises a top shielding pad186, coupled to the top shielding layer70; a bottom shielding pad185, coupled to the bottom shielding layer72; and a terminal191coupled to the conductive upper trace74. Some embodiments further comprise an attachment means190that is electrically conductive. In some embodiments, the attachment means190comprises an electrically conductive magnet. Some embodiments further comprise a terminal end backing187.

InFIG.13D, an embodiment of a terminal end and an embodiment of an amplifier3are shown. The amplifier3comprises an outer housing193; an electrical receptacle56; and a printed circuit board54. Some embodiments further comprise a housing38. The amplifier3can be attached to a grounding electrode44that abuts, and grounded to, the patient's skin. In some embodiments, the amplifier3comprises the grounding electrode44and/or a conductive adhesive patch46, while in other embodiments, the grounding electrode44and/or adhesive patch46is provided separately. The aforementioned amplifier grounding electrode44is detachably connected to the amplifier3. The grounding electrode44is electrically coupled to the printed circuit board54via the electrical receptacle56, such that the amplifier grounding electrode44acts as the ground when attached to the against the patient's skin.

The outer housing193will be grounded to the patient via the conductive adhesive patch46. This effectually serves to ground the shielding of the ribbon5and, effectively a side of the sensing element30, shown as the bottom surface232. However, it is understood that either side of the sensing element30can be grounded by the ribbon shielding. As shown, the top shielding layer70, at the top of the ribbon5, is connected to ground at the patient's skin by way of a first electrical path to ground that comprises the top shielding pad186, the electrically conductive outer housing193, and the conductive adhesive patch46. The bottom shielding layer72at the bottom of the ribbon5is also connected to ground by way of a partially shared path. The bottom shielding layer72at the bottom of the ribbon5is coupled to the bottom shielding pad185, and the bottom shielding pad185is also coupled to the outer housing193. Other embodiments further comprise an attachment means190to which both the top shielding pad186and the bottom shielding pad185is coupled to the attachment means, which is also coupled to the outer housing193. In this same regard, it may be appreciated that top shielding layer70and the bottom shielding layer72are electrically coupled the outer housing193.

The printed circuit board is, when attached, electrically coupled to the sensing element30via the conductive trace and the terminal191. The printed circuit board54contains conventional signal conditioning and amplifier circuitry by which the fixational eye movement biosignal is alternating voltage biosignal carried by the ribbon5is amplified, in some embodiments, by a factor of at least ten. An amplified analog fixational eye movement biosignal is supplied from the amplifier3to the signal processor9and display10ofFIG.17by means of the shielded cable7that extends from the printed circuit board54and outwardly through a side of the amplifier housing38. However, as earlier explained, the fixational eye movement biosignal may also be transmitted from the amplifier3to the signal processor9over a wireless communication path illustrated inFIG.18.

FIG.17of the drawings shows an embodiment of the eye sensor1connected to the previously mentioned signal processor9. More particularly, and as previously disclosed, the alternating voltage biosignal generated in response to a deflection of the piezoelectric film30(shown inFIGS.8-13) of the sensor16is first supplied to and amplified by the amplifier3. In one embodiment, the amplifier3is capable of filtering the raw fixational eye movement biosignal data and eliminating basic artifacts, such as those caused by head movements and large voluntary eye movements. The signal processor9should be capable of clock timing, buffering, windowing and filtering the amplified fixational eye movement biosignal and eliminating the same and other artifacts (such as those caused by undesired eye movements and electrical or electromagnetic interference). The processor and routines114are capable of parsing between the different types of fixational eye movements, analyzing individual and combined signal components and computing various parameters such as the dominant high frequency of the OMT component or by computing the combined amplitude and power rate of the MS and OMT eye movements. Further the processor and routines114are able to identify events, evaluate events using such amplitude, power and frequency parameters and others in order to compute additional values related to events and trends, such computations often including the use of multiple types of fixational eye movement data. In some embodiments, the eye sensor1provides numerical values such as reactivity energy of an event, long term, and short term ratios, before-during- and after event comparative analyses, frequency numbers and displaying the multi-parameter and numerical values results at the display10. Likewise, a real-time graphical representation of the eye signal waveform (designated12inFIG.1) is also displayed so that a recent history of the patient's brain stem activity and level of consciousness is visually available on the display10. Further the processor and routines114contain stored reference values pertaining to various clinical diagnoses. The processor and routines are capable of comparing data streams in a time-synchronized manner deriving paired combinations of multiple parameters and comparing those computed results against the stored known references in order to support clinical decisions, such as whether to increase decrease or maintain the administration of a drug, or to alert a clinician of an unexpected state of the patient's brainstem and condition.

In some embodiments, the routines114comprise frequency and amplitude bandpass filters that are used to provide the information to the monitor on the display10(ofFIG.1) which is connected to signal processor9. By way of example, the amplitude bandpass filters of signal processor9are adapted to recognize the input waveform generated by the sensor16. Any waveform having an amplitude greater than a predetermined threshold (such as that caused by microsaccades) are filtered and eliminated as not being representative of reliable eye information.

A conventional processing technique (e.g., fast Fourier transform analysis, linear predictive modeling or peak counting) is used to compute the frequency of the digital eye biosignal. In a peak counting approach, the fixational eye movement biosignal is sampled during a predetermined time interval. A count of the signal peaks is maintained and incremented during the sampling time. The peak frequency in numerical form (designated14inFIG.1) is displayed on the display10(best shown inFIG.1). Any portion of the fixational eye movement biosignal which is determined to be indicative of gross eye movements and microsaccades is eliminated.

The amplified alternating voltage fixational eye movement biosignal can be supplied from the amplifier3to an analog to digital (A/D) converter110of the signal processor9ofFIG.17by the shielded cable7connected therebetween. The A/D converter110converts the analog alternating voltage biosignal to a digital signal to facilitate processing. The digital signal produced by A/D converter110is supplied to a digital isolator112which isolates the information content of the fixational eye movement biosignal from interference that might be produced by a source of power needed to drive the hardware required to perform the signal processing. The digital isolator112also serves an electrical safety purpose of electrically isolating the patient facing portions from the AC main powered portions in the case of an unintended circuit fault.

In some embodiments, the routines114comprise frequency and amplitude bandpass filters that are used to provide the information to the monitor on the display10(ofFIG.1) which is connected to signal processor9. By way of example, the amplitude bandpass filters of signal processor9are adapted to recognize the input waveform generated by the sensor16. Any waveform having an amplitude greater than a predetermined threshold (such as that caused by microsaccades) are filtered and eliminated as not being representative of reliable eye information.

A conventional processing technique (e.g., fast Fourier transform analysis, linear predictive modeling or peak counting) is used to compute the frequency of the digital eye biosignal. In a peak counting approach, the fixational eye movement biosignal is sampled during a predetermined time interval. A count of the signal peaks is maintained and incremented during the sampling time. The peak frequency in numerical form (designated14inFIG.1) is displayed on the display10(best shown inFIG.1). Likewise, a real-time graphical representation of the eye signal waveform (designated12inFIG.1) is also displayed so that a recent history of the patient's brain stem activity and level of consciousness is visually available on the display10.

The processed values frequency of the fixational eye movement biosignal being sampled is tested for validity so that spurious signals can be filtered and eliminated. For example, the frequency of the fixational eye movement biosignal can be inspected and compared with a predetermined frequency range that is known to conform to recognized physiological conditions. What is more, if the patient is subjected to a baseline test prior to being anesthetized, the fixational eye movement biosignal can be compared with the baseline test results. Any portion of the fixational eye movement biosignal which is determined to be indicative of gross eye movements and microsaccades is eliminated.

The amplified alternating voltage fixational eye movement biosignal can be supplied from the amplifier3to an analog to digital (A/D) converter110of the signal processor9ofFIG.17by the shielded cable7connected therebetween. The A/D converter110converts the analog alternating voltage biosignal to a digital signal to facilitate processing. The digital signal produced by A/D converter110is supplied to a digital isolator112which isolates the information content of the fixational eye movement biosignal from interference that might be produced by a source of power needed to drive the hardware required to perform the signal processing. The digital isolator112also serves an electrical safety purpose of electrically isolating the patient facing portions from the AC main powered portions in the case of an unintended circuit fault.

The processed values of the fixational eye movement biosignal being sampled are tested for validity so that spurious signals can be filtered and eliminated. For example, the frequency of the fixational eye movement biosignal can be inspected and compared with a predetermined frequency range that is known to conform to recognized physiological conditions. What is more, if the patient is subjected to a baseline test prior to being anesthetized, the fixational eye movement biosignal can be compared with the baseline test results.

FIG.18of the drawings shows an embodiment of the sensor16communicating with a signal processor9-1, which is capable of receiving the amplified analog fixational eye movement biosignal from the amplifier3-1over a wireless communication path. In embodiments where the amplifier3-1communicates with the signal processor9-1over a wireless communication path, the previously described a/d converter110is removed from the processor9(FIG.17) and located in the amplifier3-1to receive the fixational eye movement biosignal from the ribbon5. The A/D converter110of amplifier3-1ofFIG.18is electrically coupled to a wireless transmitter116which is also located in the amplifier3-1along with a battery, microcell, or suitable power source, and an antenna. In this case, the shielded cable (designated7inFIGS.7and17) is eliminated. Likewise, the signal processor9-1ofFIG.18is provided with a wireless transceiver118which is compatible to and capable of communicating with the wireless transmitter116of amplifier3-1. Thus, the signal processor9-1may be located remotely from the eye sensor1(e.g., at a nurses' station) so that the patient can be monitored as he recovers from an operation or other procedure and returns to consciousness.

It has been disclosed herein that the sensor16is attached to the eyelid of the individual being tested such that the sensor16is deflected by the fixational eye movements of an individual's eyeball to generate a biosignal. However, rather than having the fixational eye movements applied from the individual's eyeball directly to the sensor16to cause a deflection thereof, the fixational eye movements can instead be applied to an intermediate mechanical actuator.FIG.19of the drawings shows an embodiment of the detector130which comprises a mechanical arm actuator132that is attached to the individual's eyelid so as to concentrate forces and stress on a relatively small sensing element134. In some embodiments, the fixational eye movements are applied from the eyeball to the mechanical arm actuator132rather than directly to the sensing element134.

The mechanical arm actuator132ofFIG.19can be manufactured from a non-conductive medical grade plastic. The mechanical arm actuator132is attached to the individual's closed eyelid so as to conform to the shape of the eyelid at which to be deflected in response to the fixational eye movements of the individual's eyeball. The motion sensing element134ofFIG.19, which may be identical in construction to the sensing element30shown inFIGS.8-10, is located between the mechanical arm actuator132and the ribbon5. The ribbon5may be identical to that previously disclosed when referring toFIG.13. However, since it is now the lever advantage offered by the mechanical arm actuator132of detector130which causes the motion sensing element134to be deflected, the motion sensing element134can be made smaller and require less shielding when compared to the size and shielding. Moreover, the mechanical arm actuator132which is not subjected to electrical or electromagnetic interference need not be shielded.

The deflection of the mechanical arm actuator132in response to the fixational eye movements of the individual's eyeball through the individual's eyelid below mechanical arm actuator132is transmitted to the sensing element134. The biosignal generated by the motion sensing element134is supplied to the amplifier3(FIGS.11and12) by way of the ribbon5as previously described.

An embodiment of a detector140comprises a surface-mounted piezoelectric cable element and for the sensor142is described while referring concurrently toFIGS.20-23of the drawings. The sensor142of detector140is a tubular sleeve rather than planar element as in the case of sensor16as shown inFIGS.8-10. More particularly, the sensor142is subjected to having its original tubular shape distorted in order to generate a biosignal in response to the fixational eye movements of the individual's eyeball. As shown in the embodiment shown inFIG.21, the sensor142comprises a flexible, electrically conductive interior area144which functions as a first electrical terminal. The electrically conductive interior area144of arm sensor142is surrounded by a flexible intermediate piezoelectric material146that is adapted to be compressed and deformed. An electrically conductive exterior surface148surrounds the intermediate piezoelectric material146. The electrically conductive exterior surface148of the arm sensor142which functions as a second electrical terminal may be surrounded by shielding material (not shown). By way of example only, each of the electrically conductive interior area144and exterior surface148(e.g., the first and second terminals) of the sensor142of the detector140can be manufactured from a thin electrically conductive metal mesh.

The tubular surface-mounted piezoelectric sensor142of the detector140can be located in the folds of the individual's eyelid where it will be responsive to the fixational eye movements of the individual's eyeball transmitted through the eyelid so as to undergo a compression and a deformation by which to generate a corresponding voltage. With the sensor142initially in a relaxed state, the electrically conductive interior area144and an exterior surface148as well as the intermediate piezoelectric material146lying therebetween all have a cylindrical configuration (not shown). However, when the tubular sensor142receives a compressive force in response to fixational eye movements of the individual's eyeball, the shape of each of the electrically conductive interior area144, exterior surface148and intermediate piezoelectric material146is distorted and thereby assumes an elliptical configuration as shown inFIGS.21and22.

The distortion and change of shape of the intermediate piezoelectric material146produces a biosignal between the first and second terminals (e.g., the electrically conductive interior area144and the electrically conductive exterior surface148) of the surface-mounted piezoelectric element sensor142. The biosignal generated by the arm sensor142of the detector140is supplied to the amplifier3by way of a tubular-to-planar strain relief adapter150(ofFIG.20) of the detector140.

Referring specifically to an embodiment shown inFIG.23, details of the tubular-to-planar strain relief adapter150of the detector140ofFIG.20are shown by which the electrically conductive interior area144and the electrically conductive exterior surface148of the sensor142are connected to the printed circuit board54(FIG.12) of amplifier3in substitution of the ribbon5. The strain relief adapter150comprises a flexible substrate151manufactured from a non-conductive material and having an arcuate (e.g., curved) configuration. The curved substrate151is adapted to be flexed in response to mechanical forces applied thereto to absorb pulling forces that could otherwise be applied to the sensor142. A first electrically conductive trace152runs longitudinally along the substrate151from an electrically conductive first contact pad154to the amplifier3. An electrically conductive second trace156runs longitudinally along the substrate151from an electrically conductive second contact pad158to the amplifier3. The first and second electrically conductive traces152and156are arranged in spaced side-by-side parallel alignment along the substrate151of strain relief adapter150so as to be electrically isolated from one another.

The electrically conductive interior area144is connected (e.g., pushed into locking engagement) at an attachment (e.g. a groove formed in the first contact pad154) on substrate151. The second contact pad158extends laterally across the substrate151so as to lie in front of and in axial alignment with the first contact pad154. Therefore, at the same time that the conductive inner area144of the sensor142contacts the first contact pad154, the electrically conductive exterior surface (e.g., the second terminal)148of the tubular sensor142will be automatically aligned to lie on and contact the second contact pad158. Accordingly, when the tubular sensor142undergoes a distortion and a change of its shape in response to fixational eye movements of the individual's eyeball, the corresponding biosignal generated by the arm sensor142between the electrically conductive interior area144and electrically conductive exterior surface148thereof is transmitted for amplification to the amplifier3by way of respective ones of the first and second conductive traces152and156of the strain relief adapter150which run along the substrate151.

FIG.24shows an embodiment of a detector160comprising a mechanical actuator and a piezo-active sensing element. Like the detector130, that was described while referring toFIG.19, the detector160ofFIG.24comprises a mechanical force transmitting actuator that is responsive to the fixational eye movements of the individual's eyeball. In this case, however, rather than an arm actuator attached to the individual's closed eyelid, a cylindrical force transmitting actuator162is located within the folds of the eyelid to lie closer to the eyeball than the piezo-active sensing element.

The cylindrical force transmitting actuator162of detector160is adapted to be compressed and undergo a deformation in response to the fixational eye movements of the individual's eyeball transmitted through the individual's eyelid. The cylindrical force transmitting actuator162can be manufactured from a compressible material, such as a medical grade foam rubber, or the like. By way of a second example, the cylindrical force transmitting actuator162is filled with a compressible liquid, such as a gel, or the like. In the event that the cylindrical force transmitting actuator162is filled with liquid, the actuator is preferably surrounded by a flexible envelope164(shown in broken lines inFIG.24).

The detector160comprises a sensor166that is generally planar so as to be adhesively attached over and conform to the shape of the cylindrical force transmitting actuator162. The sensor166, which can be a piezo-active sensing element, may be identical to the sensor16that was previously described while referring toFIGS.8-10. However, to reduce the size of the detector160, the sensor166embodiment that is shown inFIG.24comprises an upper electrically conductive surface168which functions as a first terminal and a lower electrically conductive surface170which functions as a second electrical terminal. An intermediate piezoelectric material portion172is located between the upper and lower electrically upper electrically conductive surface168and lower electrically conductive surface170.

The fixational eye movements of the individual's eyeball are applied through the individual's eyelid and result in a deformation and a change of shape of the cylindrical force transmitting actuator162. The deformations of the cylindrical force transmitting actuator162are transmitted to the sensor166which lies over and against the force transmitting actuator162. Accordingly, the intermediate piezoelectric material portion172of the sensor166is correspondingly deflected so that a biosignal is produced between the first and second terminals (e.g., the upper and lower electrically conductive surfaces168and170) lying on opposite sides of the intermediate piezoelectric material portion172. The biosignal may then be supplied to an amplifier (like that designated3inFIGS.11and12) by way of a flexible (like that designated5inFIG.13).

The electrically active sensing element for the eye sensor1has been described as typically being a sensor16that is configured to generate a voltage in response to the sensing element being deflected by the fixational eye movements of the patient's eyeball. However, any of the sensors (e.g.16,166,142) disclosed herein may comprise, and any of the sensing elements (e.g.30) disclosed herein may be, other types of electrically active devices, such as a variable resistance element (e.g., a strain gauge), a variable capacitor, accelerometer or a variable inductor just as long as the outputs of which will be indicative of the fixational eye movements of the eyeball of the individual undergoing testing.

Referring now toFIG.26where an embodiment of the processor and routines114is shown. The fixational eye movement data is obtained by the sensor, amplified and converted into valuable information through the use of the processor and a pair of first and second routines designed to derive certain components and generate two separate parameters. A third routine is used to integrate and synchronize the data streams so that joint values may be considered and analyzed simultaneously so as to provide better more accurate views of the state of the patient's brainstem and condition. The paired or joint values often provide superior benefit than either of the individual or component values. Fourth and fifth event detection and evaluation routines interact dynamically with the third integrating and synchronizing routine so as to be able to establish time windows relating to certain events and patterns. Examples include surgical stimuli, other endogenous or exogenous stimuli, trend-based shifts in values, procedural events, snoring patterns, sleep, and drug-related events and the like. It is found that certain analyses such as the reactivity energy of an event, or the long term average of a parameter before and after an event, relating to and requiring the identification and evaluation of these events are quite important indicators of patient conditions, past, current or predicted. An embodiment may provide an early display of parameters so as to allow clinicians to visualize and interpret data, may display data further in the processing routines so as to present individual numerical values and or real time streaming parameters. It is also expressly understood that pre-determined set points and user input values may be combined to produce the desired results.

In some embodiments, the fixational eye movement data comprises of OMT and MS. The fixational eye movement data can be continuously obtained from a subject via the detector, amplified in a first stage, filtered with an analog filter to remove low-frequency noise components below 5 Hz, then further amplified to achieve an overall amplification in the range of 2000 to 2500 gain. After converting the amplified analog signal to a digital signal with the use of 16-bit low noise converter and 1000 cps acquisition rate. The fixational eye movement data is processed by an amplitude power calculator (APC) and a frequency analyzer parser (FAP). Both of the APC and FAP employ a set of conditioning and filtering routines that can be set to a variety of values and present either common or differing resultant filtered data streams to each or one or the other of the APC and FAR. The result data streams may be comprised of isolated eye movement components or combined components as joint signals or joint signal data. The derived and generated individual components, joint signals and parameters and combinations are selected to provide the most accurate and beneficial perspectives on the brainstem activity.

The filters can employ a bandpass filter, notch, and amplitude filter to filter out data of frequency and amplitude components with values above and below and even within those values known for OMT and MS jointly. Notch filters can be used to filter out specific known artifacts such as that of AC mains or other known unwanted interferences. Additionally, a variety of known filtering and signal processing techniques are known and may be employed such as wavelet denoising, frequency band grouping and the like.

The aforementioned features of the eye sensor such as conforming application to the noise-deadening eyelid tissue, shielding, flexible ribbon mechanical vibration separation, grounding, and the like can operate together with the conditioning and filtering routines ensure that only eye movement signal data is presented. In an embodiment, the joint signal resulting comprises the data represented by the two OMT and MS fixational eye movement components and only the data represented by the two movements contained within the biosignal generated by the eye and received by the sensor.

The APC employs a pre-set data window, buffers the voltage vs. time data for that window and conducts an initial bandpass frequency filtering routine set between in a manner that, when accounting for digital filter rolloffs and resonances, allows the full range of low-frequency MS and high-frequency OMT fixational eye movement data to be presented. While the overall average frequency of the MS is known to be in a range between below 1 hertz to 5 hertz, it is the observation of the applicant that the MS bursts combined with resonance of the eyeball tend to increase the effectively measured frequency value of the MS to a range between 5 to 25 hertz, often 13 to 22 hertz. The APC computes the two-second average power or total eye power using the frequency filtered conditioned joint signal comprising both OMT and MS components. First, the conditioned filtered voltage values generated by the sensor at a rate of 1000 cps are converted to their absolute values and then summed over a time windowing period, such as two seconds. The resultant power value represents the work accomplished by the eye over the time period. It is discovered that this power value reflects a significant portion of the power of the fixational movement as derived from the OMT and MS amplitudes and is a sensitive measurement of the brainstem reaction to stimuli. The parameter is especially useful in depressed conditions where a patient demonstrates no observable physiological responses or reactions to intentional or other stimuli, effectively assessed to be “non-responsive.” However, it is discovered that when the combined total eye power parameter is employed, that actually below visible or observationally-detectable levels a brainstem response is present and can be illustrated on the display. In addition, data suggests that not only can the system “see the useable” but that the resultant signal or joint signals can be used to determine a proportionality or relative value of the response. A further feature of the system calls upon the event detection and evaluator routines so as to calculate the total energy of the response or the reactivity energy. This calculation, comparison of the calculated value beneficial employment of the proportionality characteristic is described later.

In The FAP runs in tandem with the APC. Whereas in a different regime, the FAP operates predominantly in the frequency regime whereas it can be seen that the APC operates predominantly in the amplitude regime, the FAP operates predominantly in the frequency regime. The FAP comprises a pre-conditioning and filtering routine of the general description provided with that of the APC. In one embodiment the initial eye sensor system working together with the initial frequency filtering results in the same filtered data stream as is presented in the APC and described above. However, the FPC runs additional filtering steps so as to isolate only the OMT component of the signal. Dual amplitude filters are employed. One filters out the low end noise component associated with the electronic circuits. While immaterial in the case of the APC and amplitude regime, low end noise interferes in the frequency regime and must be removed. A second an amplitude filter that is capable of isolating the dominant high-frequency component and/or the peak count frequency of the OMT.

One signal processor9which is suitable to be connected to the amplifier3to receive the amplified biosignal and perform the aforementioned processor functions is shown and described in U.S. Pat. No. 7,011,410 issued Mar. 14, 2006, the details of which are incorporated herein by reference. Therefore, only a brief description of the signal processor9will be provided below.

A conventional processing technique (e.g., fast Fourier transform analysis, linear predictive modeling or peak counting) is used to compute the frequency of the digital eye biosignal. In a peak counting approach, the fixational eye movement biosignal is sampled during a predetermined time interval. A count of the signal peaks is maintained and incremented during the sampling time. The peak frequency in numerical form (designated14inFIG.1) is displayed by the display10(best shown inFIG.1). Any portion of the fixational eye movement biosignal which is determined to be indicative of gross eye movements and microsaccades is eliminated in this case. The frequency parser is able in this manner to compute what is known as the dominant high frequency component of the fixational eye movement signal as is known to be represented by the highest frequency OMT component.

OMT frequency is an excellent indicator of the current continuous level of brainstem activity. It drops rapidly upon propofol administration or the loss of consciousness. It is indiscriminatory in the sense that any means of attenuating the brainstem activity lowers the peak count frequency—a combination of different drugs, sleep states, drowsiness, injury and the like described by Bolger. Conversely, lightening of drug concentration, awakenings, and stimuli serve to raise the OMT frequency values. As such OMT frequency provides unique insights as to the state of the patient, but it is hereto disclosed that certain clinical diagnoses are improved when the isolated OMT peak frequency is considered in a time synchronized manner about certain events in conjunction with the total eye power parameters delivered by the APC. The FPC thereby delivers a continuous data stream.

In some embodiments, a display10comprises a simultaneous data integrator (SDI) that can integrate each of the results of the APRC, FAP, event detector (ED), and/or the event evaluator (EV). In some embodiments, the two or more of results of the APRC, FAP, event detector, and/or the event evaluator can be combined into a combination result. The presentation of one or more of the results, can be shown with one or more on the same screen, alternating screen of the same display unit, and/or on different screens. The presentation can take the form of a track line, FTT, a spectral analysis, a quantitative number, multiple track lines and/or combination track lines. The presentation can be shown so that the time is synchronized for all the items presented. Additional methods of computing and displaying combined parameters of frequency and amplitude have been used effectively. For example what is commonly known as a spectrogram displays colored toned images that represent synchronized time information, frequency and amplitude data. In the case of surgeries, such techniques receiving the conditioned filtered eye signal data provide effective means of illustrating events, trends and changes to the patient's brainstem and sedation or anesthetic state.

Some embodiments comprise an event detector. The event detector can register an LTA and/or an STA. The event detector, in some embodiments, include a predetermined value or multiple for which the STA exceeds the STA so as to register an event. Tertiary clinical input methods can also be used.

Some embodiments include an event evaluator that can quantify the events. This quantification can be based upon previously obtained data that can be stored locally, in the cloud and or the Internet. The event evaluator has the ability to analyze fold changes, frequency of events, and/or energy of the event(s) in quantifying the events.

In some embodiments, the APRC and FAP is used to present a displayed results for a user.

In some embodiments, a comparator compares the fixational eye movement data and/or the results to known data patterns. The comparison can be presented on the display. The comparator can output alarms, instruction, and/or cause an action by an automated system. For example, the comparator may compare the current data points to known data points. If the comparator determines that a negative situation has arrived, or notices something that may be a forbearer of, it can instruct the display10to present an alarm and/or suggested instruction. In other embodiments, the comparator can autonomously alter drugs being supplied to the patient.

Some embodiments comprise an eye sensor1, to measure the amplitude of the fixational eye movements, specifically microsaccades together with ocular microtremors, and a processor9, having pre-programmed routines to isolate certain components, manipulate and recombine data and present results. The ARPC performs a power calculator method and the FAR runs a frequency analyzer method to simultaneously produce two data streams. In some embodiments, the data streams are the amplitude of the fixational eye movement and a frequency component of the OMT. Each of the two data streams can provide raw or computed values of each of power and frequency parameters, and the data streams represent distinct but interrelated parameters of the eye movement signal and therefore distinct but interrelated parameters of brainstem activity. In some embodiments, the comparator performs a method that comprises matching brainstem activity patterns with closest known reference pattern and may respond according to pre-programmed rules.

In some embodiments the SDI runs a simultaneous calculation method. The data integrator interacts with a fifth routine; event evaluator that employs event data and analysis window from the event detector to convert power data into reactivity data and presents integrated paired combinations of reactivity and frequency parameters, collectively representing brainstem activity patterns.

The combined simultaneous measurement and analysis of the individual and two types of fixational eye movements and interpretation of combined patterns provides new and useful insights and enables the parsing between heretofore indistinguishable conditions and new diagnoses. Many workers have used MS fixational movements to measure attentional response, determine states and to diagnose neurological conditions. This work centers on those conditions where MS play an important role in visual perception and visual acuity. As such, the study of MS is limited predominantly to measurement systems used with healthy awake subjects with open eyes, or in ways that connect to vision processes. It is important to note that MS have different characteristics than OMT, which make each more suitable for some tasks and less so for others. For example MS motions measured directly from the eyeball on awake subjects are easier to measure with general purpose instruments of resolution limited to the micron range and instruments tuned for that specific size range. OMT on the other hand is a nanometer level amplitude, about 40 times smaller in amplitude than MS, and requires high sensitivity sensors, hi-gain amplifiers, and precautionary elements to eliminate or reduce noise artifacts, more so that general instruments. The MS are so large comparatively, that they render measurements OMT inaccurate unless the large waves are removed via filtering or other known means. Conventional OMT sensor systems are tuned for that range of motion as required for systems dedicated to measuring nanometer to 1 micron level movements and are primarily focused on the frequency, not the amplitude of the OMT. Also given that OMT is measured predominantly with frequency units of values higher than those known for MS, prior art teaches one to avoid including microsaccadic low-frequency counts to avoid inaccurately biasing the higher counts from OMT. Thus, according to the prior art and the purposes thereof, the MS provides no useful information and should be filtered out in order to isolate the amplitude of OMT.

FIGS.27A-27Cdemonstrate one example of an embodiment in use is wherein the combined use of two fixational eye movement and associated parameters can yield superior diagnoses than can the use of either of the components alone is managing the proper administration of sedatives for critically ill patients in the intensive care unit (ICU). The results of significant experimental piloting by sifting through a vast variety of potential parameters and variants of fixational eye movements and the statistical results of a controlled clinical study are depicted inFIGS.27A-27C. This study was designed to demonstrate the validity and reliability of ocular microtremor “OMT” during anesthesia and intensive care sedation. The primary endpoint was the correlation between OMT data and the current standard of care; a proven valid and reliable subjective physiological assessment instrument called the Richmond Agitation Sedation Scale (RASS). Hence the applicant sought to demonstrate a statistically significant correlation between OMT values and the RASS standard that was administered as a controlled form of stimulus according to an approved research protocol.

Turning nowFIG.27Bit is reported that the first correlation between the traditional OMT signal frequency peak count alone and the RASS standard where the R2 value is 28% The correlation statistics are significant but the range of scores is high.

The applicant hypothesized that RASS is a measure of patient reactivity and developed a frequency-independent measure of reactivity based on the microsaccade component of fixational eye movements. The MS component of the biosignal had been omnipresent in the raw eye movement data, but the prior art taught to eliminate the MS component, by way of strong frequency and amplitude filtering. The new parameter employs the processor and routines best shown inFIG.26so as to compute the reactivity energy of a stimulus event. The SDI receives the total eye power data from the APC, incorporates event information from the ED and EV and computes a normalized energy value. The LTA of the total eye power up to the event is calculated and added together over a designated time window leading up to the event and results in the pre-event energy. The eye energy corresponding to the event is calculated by summing the power values over a same designated time period during the event. The change in energy from the pre and during periods are determined by subtracting the pre-from the during value to result in the change in energy due to the event. This change can be divided by the incoming LTA of the energy or suitable value so as to normalize across patient variations. The log10of this normalized change in energy is an example of a useful and accurate event evaluation. This parameter embodiment, reactivity energy of event, is shown on the left axis ofFIG.27AApplicant conducted secondary analysis incorporating the new measure of reactivity. Again, inFIG.27Ait can be seen readily by the trained eye that the correlation statistics are R2 value is 70%—known to be significant, but there remains a wide range of scores. Finally it was realized that both measures together provide a superior result than either of the two parameters individually.FIG.27Cshows the correlation statistics when both parameters are used together. In this case, when parameters are combined the correlation statistics r2 value increased by 10% to over 80% which is determined to be an excellent correlation and the basis for new clinical practices. In this case, the OMT frequency was multiplied with the reactivity energy of event parameter to produce a new unitless index named fixational eye movement sedation index and shown on the left axis of the graph inFIG.27C. It can now be seen that one can adapt this technique with the use of the comparator to resolve a long standing problem of mismanagement of medication in the ICU. Current values for the patient can be computed using the methods and apparatus described herein and they can be compared against the present correlational references now known in the form of a database. Comparisons can yield directions to drug administration. Should the index value exceed a target level, then the drug is increased. Conversely, should the measured index value be below the target level, then the drug rate should be lowered or discontinued altogether until the patient achieves the desired state. In the case where the index value matches the target value, then the drug level is maintained as it is.

Subsequently it has become clear that one of the reasons for the above described discrepancy is that the use of OMT peak frequency alone does not discriminate well between the conditions of sleep-induced brainstem depression and that depression state caused by drug depressions. Drug depressions are more forceful in maintaining brainstem depression than are sleep-induced mechanisms. The applicant has measured patient OMT values for deeply sleeping naturally subjects to be in the same low frequency range as for patients who are highly anesthtized with powerful drugs. However, importantly, the sleeping patient is arousable with a stimulus of the same approximate strength than that given to an anesthetized patient who does not even respond let alone become aroused. Drugs attenuate the brainstem more forcefully than do natural sleep mechanisms. In a similar manner the reactivity energy and power derived from the MS component tends to be less discerning in more awake zones where the relative increases in MS amplitudes are less if not pronounced as if they are already “full on” and so that additional provocation stimuli do not dramatically further enhance the amplitude. The OMT frequency however is an excellent measure of activity at awake levels and fully proportional to changes at that level. Hence again, the explanation for why the combination of signal parameters is of greater value and used for new unexpected purposes than are either of the individual values alone. This combinatorial value becomes especially pronounced when for the first time multiple fixational eye movement data is taken together and employed across the full range of arousal scale from near death as in deep anesthesia or coma through to wide awake and even aroused above normal states. This is the reason that the addition of the reactivity parameter derived from the MS component considered in concert with the OMT value enhances overall statistical diagnostic performance.

Consistent with the embodiments of the present invention and the disclosed ICU sedation example, an embodiment includes a simple decision matrix that allows the comparator to easily identify one of three sedation states being deep, moderate and light. Values of OMT frequency below a certain threshold around 43 hertz, accompanied by low reactivity values below 1.5 indicate together a deep state. OMT values above 43 hertz accompanied by reactivity values greater than 2.5 indicate a light state. Frequency values below 43 but accompanied by high reactivity between 1.5 and 2.5 are most consistent with a light state. Intermediate values of reactivity between 1.5 and 2.5 coupled in time synchronized fashion with OMT frequencies below 43 hertz are most consistent with a moderate state, and so forth.

Similarly consistent with the current invention, circadian rhythms and sleep states can be illustrated for ICU patients and the sleep state may be parsed from the drug induced swedation state so as to facilitate the accumulation of proper rest or to enable the earlier diagnosis of prevalent co-morbid conditions such as delirium.

Sleep analysis using embodiments of the present invention is not limited to to ICU sedated patients. In some embodiments the invention is capable of identifying respiratory-related events during sleep that are used in the diagnosis of sleep related disorders. In yet some embodiments, the amplifier3is reduced in size so as to match the smaller anatomy of a neonatal late premature infant used to detect apnea of prematurity and to map the trend of brainstem development during a stay in the NICU and after discharge for periods long enough for the patient to achieve full mature brainstem development.

In yet another example, as can be seen inFIG.28, the effectiveness of the use of combination of the reactivity and OMT vs using reactivity and OMT independently are illustrated in the case of an outpatient colonoscopy diagnostic procedure. The embodiments of the invention provide a superior means for adjusting medications. A time period of approximately one minute is illustrated, with the left axis charting OMT peak count frequency as derived and generated with the use of the FAP and methods and the right axis the total eye power as derived and generated with the use of the APC and methods described previously. The ED and EV were used to identify two separate subsequent clinical events as demarked by event A followed by event B. Event A is the resulting reaction of the brainstem to a stimulus applied by the clinician, which was the application of a pressure cuff used to measure blood pressure. Simultaneous review of event A using a comparator shows that over a period of approximately 25 seconds both the OMT frequency value and the Eye power value were relatively steady and low, sharply increased in response to the stimulus and then rapidly fell back to the same values as they were previously. In this case the compared combined data value set comprising values derived from the OMT component and from the MS component considered together in time are compared against a known reference to determine an instruction. In this case when both values rise and fall as described in harmony it is shown statistically to be associated with an external transient stimulus and that no changes to the drug level are required as a result. Up down and back to the same went the values. It should be noted that time synchronization is important and can mean phase retarded, advanced, proportional between before and after etc. or any number of more complicated time based relationships. So long as the multiple data parameters derived from the multiple fixational eye movement components are of a known relationship in time, it is consistent with the present invention.

Turning now the second event depicted inFIG.28, event B, a true lightening or “wearing off” of the propofol plasma level is occurring. Again through a similar use of the eye sensor processor and routines a comparable constituted combined data set is derived generated and compared. However in this case the pattern recognized by the event SDI is quite different. First the OMT frequency does not return to its previous level, rather notably it is elevated by 10 counts. Secondly, the peak OMT values are not as high, which suggests a more subtle change in frequency associated with a change in brainstem attenuation rather than the pronounced peaks presented in event A. A third characteristic of the pattern is that the Eye power values achieved are higher and more sustained than those of event A. In other words, the total reactivity energy of event B is several fold that of event A. Taken together this combined data pattern including derived values of multiple fixational eye movement components compared in time provide quite different results than the pattern of event A and from the conclusions suggested by the evaluation of either parameter alone. In this case the anesthesiologist administered an additional bolus of propofol just after event B and the signal patterns returned to target levels. It can now be seen that this invention has predictive utility superior to that of the trained professional attending this case, or at least confirmatory utility which is also of tremendous benefit. To review the individual traces shown during event B, the reactivity information as measured by total eye power and energy for sure are larger, but the event appears to return largely to within a few percent of previous values. As such the clinician or operating system is left wondering whether or not to increase medication unnecessarily. Similarly while the OMT value does achieve a new sustained level above that prior to the event, it is level, rather than continuing to climb, again leaving doubt to the operator or system as to what drug administration strategy to follow. Taken together the two parameters increase the confidence of conclusion. This demonstrated result is proven in the statistical analysis of the colonoscopy example where a controlled study was conducted across multiple patients.

It should be noted that propofol used in the colonoscopy case just described is known to be rapid acting and rapid dissipating drug. This is a main driver in its widespread use. It is also dangerous and can lead to immediate catastrophic outcomes. Many other drugs have been measured and can be controlled by the present invention. These include dexmeditomine, sevoflurane, opioids, neuromuscular blockers/paralytics and a range of other agents any of which affect the brainstem of mammals.

Turning now toFIG.29, there is shown one embodiment of a display consistent with the present invention that receives information from the eye sensor processor9and routines114and displays the information thus making the information accessible to a clinician. The display9provides for the real time continuous display of one or more combined parameters derived from fixational eye movement components. The horizontal scale represents clock time or any other measure of time or time-based units. Each of the axes are time-synchronized so as to maintain a relationship between the two in normal operating mode. The horizontal scale is typically set to a default of 20 minutes and displays the most recent 20 minutes of continuously charted data. The duration scale can be varied to show shorter or longer periods or to zoom in on a particular event or time point. The current time period and the current value being recorded and displayed is at the far right most portion of each graph area, and the signal shifts leftward as each 2 second analysis window and recording elapses, as such the displayed trace appears to be moving across the screen from right to left. At the time where the leftmost data point is superseded by the next current new value, the oldest data point drops off the screen out of view.

In an embodiment the upper chart area displays the OMT frequency in units of hertz on the vertical left axis. Proximate to the upper graph area and of a large size to be readable from a 15-20 foot distance is contained a numerical display of the current frequency value being recorded. The frequency value can be the instantaneous value, a 2-second average or a longer average which allows a flexible approach to optimize between real-time precision and stability of the displayed figure. The frequency value in the display box proximate to the upper chart area can also flash, turn to an alternate color or otherwise alert the user in the case that the system detects data portions which are outside of preset values or exceeds filtering conditions.

The lower chart displays a continuously calculated total eye power, calculated using embodiments previously described. The vertical axis of the lower chart depicts the same units of total eye power as was described inFIG.28and are measured in units proportional to watts in an embodiment. Proximate to the upper graph area and of a large size to be readable from a 15-20 foot distance is contained a numerical display of the current frequency value being recorded. The frequency value can be the instantaneous value. Proximate to the upper graph area and of a large size to be readable from a 15-20 foot distance is contained a numerical display of the energy change of the most recent event identified by the event detector. In an embodiment, the energy change value can be calculated and displayed in units of fold change. Fold change is similar to the reactivity energy of the event, and is calculated in the same manner. The total energy of the event is computed and the difference in the energy of the event less the energy in the previous most segment is computed and divided by the energy of the previous most segment. In effect to provide the multiple or multi-fold change in energy of the event compared to baseline normal. The value is normalized by dividing by the baseline non-reactive period in order to account for variations between patients and amplitude variations associated with differing levels of sedation and the like.

In another embodiment, the display presents a single continuous live parameter received from the processor9and routines114, but a combined derived computed value derived from the OMT component and the microsaccadic component. The fixational eye movement sedation index is consistent with this embodiment and invention. The numerical display box proximate and large to be seen as described above displays the current value related to the most recent event. The screen is divided into three generally equal portions the uppermost corresponding to light sedation, the middle portion to moderate sedation and the lower portion corresponding to deep sedation. As the sedation index value shifts with clinical circumstance the corresponding portion of the screen is activated in a manner as to illustrate the patient's general state in one of the three zones; light, moderate or deep, and shifts accordingly upon transition there between.

Several other conditions that can be diagnosed or managed in a superior manner over current standards and more effectively than by the use of conventional eye movement sensing techniques will now be disclosed. There are now known derived and generated patterns derived from the frequency, speed, amplitude, power peak velocity, average values, rise times, slopes, fitted curves, ratios, fourier and spectral analyses and the like combinations that indicate statistically significant results. The definitive mark of loss of consciousness, for example is marked by a rapid drop in dominant high frequency peak count followed thereafter by approximately few seconds a rapid exponential or logarithmic decay in the amplitude of the MS component. Regain of consciousness tends to follow a mirrored pattern, but in a nearly square wave fashion, where a preceding strong rise in OMT frequency is followed by a dramatic increase of MS amplitudes.

The embodiments shown and described above are only examples. Even though numerous characteristics and advantages of the present technology have been set forth in the foregoing description, together with details of the structure and function of the present disclosure, the disclosure is illustrative only, and changes may be made in the detail, including in matters of shape, size and arrangement of the parts within the principles of the present disclosure up to, and including, the full extent established by the broad general meaning of the terms used in the claims.

It should also be noted that elements of embodiments may be described in reference to the description of a particular embodiment; however it is disclosed that elements of disclosed embodiments can be switched with corresponding elements of embodiments with the same name and/or number of other disclosed embodiments. For example, it is hereby disclosed the identified as16the sensor identified as166, and the sensor identified as142are interchangeable with each other in any embodiment where a sensor is disclosed.

Depending on the embodiment, certain steps of methods described may be removed, others may be added, and the sequence of steps may be altered. It is also to be understood that the description and the claims drawn to a method may include some indication in reference to certain steps. However, the indication used is only to be viewed for identification purposes and not as a suggestion as to an order for the steps. It should also be noted that elements with the use of the terms “upper”, “top”, “lower”, and “bottom” are not to be held as an indication of position; the terms were just employed in the element names for ease of description. For example, an upper element could be located below a lower element.