WO2010151734A2

WO2010151734A2 - Sensor for non-invasively monitoring intracranial pressure

Info

Publication number: WO2010151734A2
Application number: PCT/US2010/039930
Authority: WO
Inventors: Karla Mossi; Vivek Vijaywargi; Pooma Mane; Richard Patrick Proffit; Joseph Garthaffner; Alex Lichtenfels
Original assignee: Virginia Commonwealth University
Priority date: 2009-06-26
Filing date: 2010-06-25
Publication date: 2010-12-29
Also published as: WO2010151734A3

Abstract

An apparatus and method for measuring intracranial pressure non-invasively includes a frame that holds an acoustic sensor (e.g. a piezoelectric sensor) in place on the eyelid of a patient. The frame includes a means to adjust and control the amount of pressure that is exerted at the region of the eyelid that is in direct contact with the sensor. Changes intracranial pressure (which result in changes in dampening of acoustic signals transmitted through the cranium of the patient) are non-invasively detected by the acoustic sensor on the eyelid.

Description

SENSOR FOR NON-INVASIVELY MONITORING INTRACRANIAL PRESSURE

DESCRIPTION

BACKGROUND OF THE INVENTION

Field of the Invention The invention generally relates to an apparatus and methods for measuring intracranial pressure non-invasively. In particular, the invention provides an apparatus comprising a frame that holds acoustic sensors in place on the eyelids at an appropriate level of pressure so that acoustic signals introduced into the cranial space are detected.

Background of the Invention

Pressure increase in the brain, which is contained within the skull, is a serious medical condition that can be life threatening. The brain is surrounded by cerebrospinal fluid; the pressure of the fluid, known as intra cranial pressure (ICP), is carefully controlled by homeostatic mechanisms in the body. In pathological circumstances such as stroke or head injury, elevated ICP poses a clinical problem that must be carefully managed to prevent severe brain damage or even the death of the patient. Intra cranial pressure is currently monitored invasively, with monitoring devices implanted within the skull cavity or lumbar punctures. While these methods are effective, they also involve considerable discomfort and risk to the patient due to the invasive nature of such methods. For example, during lumbar puncture (also known as "spinal tap") a spinal needle is inserted between the lumbar vertebrae and into the subarachnoid space, permitting the pressure of the cerebrospinal fluid to be taken using e.g. a column manometer. Such invasive procedures are, unfortunately, uncomfortable for the patient, fraught with potential risks, and are not amenable to being carried out safely in emergency situations, e.g. at accident sites, on the battlefield, etc. The eye and the ear are possible alternative "windows" for monitoring ICP non- invasively. ICP is directly communicated to both the eye and ear, and various attempts have been made to develop devices which utilize these routes. For example, published US patent application 2007/0123796 (application # 10/565,852, Lenhardt and Ward, the complete contents of which is hereby incorporated by reference) describes a method and apparatus for monitoring ICP via the eye. This technology is based on the fact that the brain and the skull are coupled resonant systems that respond in a predictable fashion to pressure increases within the brain. Notably, changes in acoustic damping of acoustic signals transmitted into the brain via the skull are correlated with changes in ICP. application # 10/565,852 provides an apparatus with transducers which transmit sound waves into the brain of a patient, and an "eye patch" sensor which is fitted to the eye (either directly onto the eyeball, or onto the eyelid). The sensor detects acoustic damping of the transmitted sound waves, and the level of damping that is detected correlates with ICP. However, 10/565,852 fails to take into account the necessity of holding the sensor firmly in place on the eye, and of applying sufficient pressure to the sensor to achieve a clear, consistent reading of the changes in acoustic pressure within the eye.

SUMMARY OF THE INVENTION

An apparatus and method for reliably measuring intracranial pressure non-invasively are provided. The apparatus comprises a frame that holds an acoustic sensor (e.g. a piezoelectric sensor) in place on the eyelid(s) of a patient. The frame includes a means to adjust and control the amount of pressure that is exerted at the region of the eyelid that is in direct contact with the sensor. Thus, the sensor is held in place with a desired, defined amount of pressure. When acoustic waves are transmitted into the brain of a patient wearing the apparatus (e.g. from transducers affixed to the skull of the patient), the sensors detect acoustic signals arising from acoustic wave amplitude damping of the original signals, and the detected acoustic signals are correlated with (i.e. indicative of) ICP.

The invention provides an apparatus for non-invasively measuring intracranial pressure. The apparatus comprises: 1) at least one acoustic sensor, the at least one acoustic sensor being conformable to an eyelid of a subject; and 2) a frame for positioning or holding the at least one acoustic sensor in direct contact with the eyelid. In some embodiments, the apparatus also includes means to apply and adjust pressure at a region of contact between the acoustic sensor and the eyelid. In some embodiments, the frame is removably attachable to the head of the subject. The acoustic sensor is, in some embodiments, a piezoelectric sensor. In invention also provides a method for determining intracranial pressure. The method comprises the steps of 1) conformably adapting an acoustic sensor to at least one eyelid of a patient, the acoustic sensor being held in place by a frame that is removably attached to the subject's head; 2) transmitting acoustic signals into the head of the patient; and; 3) determining, based on acoustic signals received by the acoustic sensor, intracranial pressure of the patient or subject. In some embodiments, the method also includes a step of adjusting the pressure at a region of contact between the acoustic sensor and the eyelid. The invention also provides a conformable acoustic sensor, comprising: 1) one or more electric leads; 2) one or more insulating layers; and 3) at least one acoustic sensor. The one or more electric leads, one or more insulating layers, and at least one acoustic sensor form a structure with at least one exterior surface, and the structure is conformable to contours (e.g. the three dimensional shape) of a surface on which it is positioned (for example, the eyelid). In some embodiments, the sensor includes a covering formed from a skin-compatible material, which may be semi-adhesive. The covering is positionable on the at least one exterior surface of the conformable acoustic sensor.

The invention also provide a multilayer acoustic sensor which comprises: 1) an acoustic sensor in electrical communication with at least one electrical lead; 2) at least one layer of insulation positioned between the acoustic sensor and the at least one electrical lead; and 3) a covering formed from a semi-adhesive skin-compatible material. The covering is positionable on at least one exterior surface of the multilayer acoustic sensor. In one embodiment, the acoustic sensor is positioned between two electrical leads, which may be insulated.

BRIEF DESCRIPTION OF THE DRAWINGS

Figure IA-C. Schematic representations of exemplary embodiments of the apparatus of the invention. A, attachment to head with curved sections that fit around the ears; B, attachment to head via flexible material at back of head; C, attachment to head via a headband. Figure 2A-D. Schematic representations of exemplary embodiments of the apparatus of the invention. A, curved frame; B, raised interface; D, circular protective shield; D, rectangular protective shield. .

Figure 3. Exemplary sensor for use in the apparatus, showing layers in horizontal juxtaposition. Figure 4. Schematic of a sensor which includes (1) self-adhesive packaging material; (2) flat lead shield; (3) flat conductive lead; (4) sensor material. Figure 5. Bimorph (Actuator) used for testing. Figure 6. Experimental setup.

Figure 7. System calibration graph obtained using cantilever beam with an accelerometer. Figure 8. Typical sensor and actuator responses at 50 kHz with an input sinusoidal waveform of 1 Volt peak to peak magnitude and a sensor output of 0.23 volts.

Figure 9. Typical gain vs. frequency response plot for a PVDF sensor with Cu-Ni electrodes, 28 microns thick and 150mm² surface area with a 50 grams counterweight. Figure 10. Contour plots for Gain at 50 kHz - weight 2Og and Cu-Ni electrodes. Figure 1 1. Contour plots for Gain at 50 kHz - 45 μm thickness and Cu-Ni electrodes. Figure 12. Exemplary Design for the ICP glasses (1) sensor holder; (2) sensor; (3) reactive load; (4) pressure adjustable frame, (5) transducers that transmit acoustic signals.

DETAILED DESCRIPTION

An apparatus and method for measuring intracranial pressure non-invasively are provided. The apparatus comprises a frame that holds an acoustic sensor in place on the eyelid(s) of a patient. The frame includes means to adjust, control and consistently maintain the amount of pressure that is exerted at the point of contact between the sensor and the eyelid, i.e. at the region of the eyelid that is in direct contact with the sensor. According to the invention, acoustic signals (sound waves) are transmitted through the brain e.g. via transducers placed on the skull, and the waves are modified (dampened) within the brain to a greater or lesser degree, depending on ICP. The close, consistent placement of the sensor directly on the eyelid permits the detection, via the eye, of the modified acoustic signals. By comparing the detected signals to control (e.g. standardized or normal) signals, and/or to signals from the same patient obtained at an earlier time, changes in acoustic damping which result from changes in ICP are detected. The level or magnitude of acoustic damping is thus a function of and correlates directly with ICP, and is used as an indirect measure or indicator of ICP.

In one embodiment of the invention, the frame that holds the sensors is removably attachable to the head of the patient whose ICP is to be monitored. For example, the frame may resemble "glasses" as depicted in Figure IA. In Figure IA, frame 10 includes sensors IA and 1 B attached to a front section 2 of frame 10. Generally, both sensors 1 A and B will be present in the apparatus but this need not always be the case, as there may be circumstances in which it is preferable to monitor ICP with only one eye, e.g. if a patient's other eye is wounded, absent, occluded, etc. Due to the shape of the human head (eyes facing forward) in order to removably attach frame 10 to the head of a human patient, frame 10 generally includes side sections 3 A and 3B (generally identical, or mirror images of one another) to which front section 2 is attached. When frame 10 is fitted in place on a patient, side sections 3 A and 3B extend along opposite sides of the head of the patient. In some embodiments, attachment to the patient is by means of "hooking" an optional curved portion 4 of side sections 3 A and 3B around the patient's ears as is done with conventional glasses. In other embodiments, curved portion 4 is absent, and side sections 3 A and B are affixed to the sides of a patient's head in some other manner, e.g. by taping, or by providing a loop of material that surrounds the patient's ear, etc. In some embodiments, as depicted in Figure IB, frame LO is attached to the patient's head by means of a band of material 6 that connects side portions 3A and 3B to each other across the back of the patient's head, e.g. flexible or elastic material, a Velcro strip, etc.; or by other suitable means which will occur to those of skill in the art. In another embodiment, shown in Figure 1C, side sections 3A and 3B are connected via a top section 7 that encircles the top of the patient's head in the style of a "headband".

The overall design of frame 10 maybe any shape that reliably and correctly supports sensors IA and IB at/on the patient's eyelids when the apparatus is in place. If the design is substantially square, as depicted in Figures IA and B, front section 2 may be attached to side sections 3A and B via e.g. jointed hinges such as those used in conventional eye glasses. However, other designs are possible, include a "one-piece" design in which frame 10 is generally circular or ovoid in shape (Figure 2A). In this embodiment, frame 10 maybe made from material that is resiliently "bendable" so that the frame can be bent to conform to an individual patient's head size, and yet once bent, will retain the shape during use. The frame may also contain means for accommodating electrical components (e.g. wires), for example, within a channel on or within the frame, or the frame may be hollow or partially hollow, etc. Many other variations in design will occur to those of skill in the art, and all such variations are encompassed by the present invention. Sensors 1 A and B are generally attached to frame 10 via interfaces 5A and 5B which are interposed between front section 2 and the sensors, and are designed to support or hold the sensors on the eyelid. As depicted in Figure IA, interfaces 5 A and 5B may be in the form of a post or support which is attached by a first end to section 2 and which bears on a second end the sensor. However, alternative embodiments are possible, e.g. Figure 2B shows a design in which interfaces 5A and B project from front section 2 as raised surfaces or "bumps" onto which sensors IA and B are attached. Interfaces 5 A and 5B may have any structure, so long as sensors IA and B and adequately and stably supported thereon.

Front section 2 may also comprise various protective or shield portions on an outer face. For example, Figure 2C shows two circular protective shields 8 on the outer face of front section 2 and Figure 2D shows rectangular protective shield 9 on the outer face of front section 2. These shields may be of any shape and suitable dimension. The shields serve to protect the eye of the patient, to stabilize interfaces 5 A and B, to carry additional elements of the apparatus (e.g. electrical components or wires), etc. The shields may also be decorative, e.g. in an apparatus for a child, the shields may be brightly colored, or in a decorative shape such as a star, spiral, etc., particularly if pressure is being monitored in only one eye.

Various materials may be used to produce the frames. Generally, such materials are light-weight but durable, and include metals and metal alloys and composites (e.g. titanium, aluminum, monel, beryllium, flexonmonel, beryllium, flexonmonel, beryllium, flexon, etc.); various plastics and other polymeric materials such as zylonite, or cellulose acetate; various ceramics such as alumina, alumino-silicates, boron-nitrides, glass ceramics; and combinations of these, e.g. a metal frame maybe coated with plastic. In short, any of many suitable materials may be used, including but not limited to plastic, cellulose acetate & zylonite, cellulose propionate, nylon coated materials, metal, monel with suitable plating, titanium, beryllium, stainless steel, flexon, aluminum coatings, and even natural products such as wood, bone, buffalo or other types of horn, etc. Further, the frames may be reusable or disposable, as may be the entire apparatus. The sensors of the apparatus comprise an acoustical or pressure sensor. Preferably, the sensors used include a piezoelectric sensor capable of converting sensed pressure into an electrical signal. In some embodiments the sensor also comprises various other components, e.g. various layers of insulating, protective and conducting materials. An exemplary sensor is depicted in Figure 3, which shows a multilayer sensor comprising: sensor material 100; flat conductive leads 11; flat lead shields 12; and outer packaging material 13. Generally, in order to conform to the shape of the eyelid, the materials which make up the sensor are flat or provided in a flat substrate (e.g. wires embedded in a sheet of suitable material, mesh, etc) which is also somewhat flexible (malleable, ductile). Other components that may be included in the sensor include, for example, mylar, conductive tape, epoxy with copper filaments, Further, all components illustrated in Figure 3 need not be present, for example, a sensor may include only the sensor material (e.g. PVDF) and leads. In some embodiments, the sensor(s) are permanently attached to the frame while in other embodiments, the sensors are removable (i.e. removably attached) and can be readily replaced in the case of sensor failure, or when the frames are disposable.

Sensors which are suitable for use in the apparatus include but are not limited to piezoelectric sensors, especially piezoelectric polymers such as PVDF; accelerometers, pressure sensor (i.e. resistance based ), fiber optic sensors, strain gauges; etc.

Conductive leads and shields (insulating layers) for conductive leads are known in the art, and may include metal, mesh, and conductive polymeric materials.

The outer packaging material that surrounds the sensor may be of any suitable type. Considerations for choosing this material may include, for example, flexibility, being water- or moisture-proof, non-allergenic (e.g compatible with skin), non-irritating, and other factors. In particular, material which makes direct contact with the skin of the eyelid (i.e. at least one exterior face or outer layer of the sensor) should be removably adherent, i.e. the material should, when positioned on the eyelid, remain relatively stationary without slipping while the apparatus is in place, i.e. the material may be "semi-adhesive" or "partially adhesive", either over the entire surface, or in sections, the adhesive or semi-adhesive sections preventing the surface as a whole from slipping. In some embodiments, the sensor may be temporarily adhered to the eyelid with an adhesive. However, in other embodiments, the pressure exerted by the frame and through the interface and sensor and onto the eye will be sufficient to hold the sensor in place, particularly if the material is selected to have suitable surface properties, e.g. sufficient friction or drag between the material and the skin of the eyelid to resist lateral (tangential) motion during use of the apparatus. Examples of suitable materials include but are not limited to various synthetic polymers, silicone (e.g. silicone sheets), various fabrics, Bakelite, i.e. phenol-formaldehyde resin, Kevlar, Twaron, i.e. para-aramid, Kynar, i.e. PVDF, Mylar, i.e. polyethylene terephthalate film Neoprene i.e. polychloroprene, nylon, i.e. polyamide 6,6, orlon, i.e. polyacrylonitrile, rilsan, i.e. polyamide 11 & 12, Technora, i.e. copolyamid, Teflon, i.e. PTFE, Ultem, i.e. polyimide, Vectran, i.e. aromatic polyamide, Viton, i.e. poly-tetrafluoroethylene, Zylon, i.e. poly-p-phenylene-2,6-benzobisoxazole (PBO), semisolid moldable clay-like materials, and the like. The sensor may further comprise one or more layers of cushioning.

The sensor itself may be of any suitable shape, e.g. substantially square, rectangular, circular, ovoid, etc. and of any suitable dimensions. The sensor is generally of a size in the range of from about 0.5 to about 3 cm per in its longest dimension, e.g. the side of a square or rectangle, diameter if circular, or axis length of an oval. The total thickness of the sensor (including various layers of material) will depend on the components thereof, but is generally in the range of up to about 500 microns (0.5mm).

In some embodiments, the sensor is layered or multilayered and includes at least one acoustic sensor juxtaposed to (e.g. positioned adjacent to, side-by-side with, on, or under, adhered to, etc.) at least one electrical lead for electrical communication therewith, the electrical lead itself being generally insulated, shielded, protected or surrounded by insulating material. Generally, an acoustic sensor is positioned between two electrical leads which are themselves positioned between layers of insulation, as is depicted in Figure 3 and Figure 4. In some embodiments, an outer layer or covering is also provided on one or both exterior faces (surfaces) of the sensor, the outer layer being made from semi-adhesive, skin- compatible material as described above, since it comes into direct contact with the skin of the eyelid. In other embodiment, a layer of insulation may in and of itself be made of material suitable to serve as an outer layer in contact with skin. In some embodiments, the sensor is conformable, i.e. it is possible to bend, mold or flex the sensor to conform to the shape (curvature) of the eyelid, in order to maximize contact between the eyelid and the sensor.

The apparatus of the invention also includes a means or mechanism for adjusting or fine tuning the pressure with which the sensor is held in place on the eyelid. The frames of the apparatus may come in different sizes to accommodate different head sizes and thus make adjustments easier. The frame of the apparatus maybe bendable, allowing adjustments in the fit of the apparatus. Adjustments of pressure of the sensor on the eyelid may be made by any of several methods. For example, the side sections of the frame may be adjustable with respect to length (e.g. by being constructed of two parts, one of which slides inside or along the other) so that the distance between the front section of the apparatus and the face of the patient can be increased or decreased, thereby increasing or decreasing the pressure exerted by the sensors on the eyelids. In some embodiments, the interface between the front portion of the frame and the sensor is adjustable, allowing fine tuning of the distance. For example, the length of a post-type interface can be increased or decreased (and then locked in place) by e.g. a screw; a spring (e.g. a coiled spring that is adjustable, or that is set to a predetermined strength); a sliding mechanism; or the post may be made of a malleable material that bends or deforms within a predetermined pressure range; etc. Other mechanisms include but are not limited to: ratcheting mechanisms, buckle assemblies, multi- linked connections, hinged connections, rack and pinion mechanisms, etc.

The invention also encompasses a system for non-invasively measuring ICP in a patient in need thereof. The system comprises the apparatus described above (e.g. frame, sensors, etc.), and also other components such as: means to transmit acoustic signals into the brain of the patient, e.g. transducers that are attachable to the head of a patient to generate acoustic signals, or electromagnetic acoustic transducers (EMT), microphones, buzzers; various monitors or monitoring devices to receive electrical signals from the sensors and to display data representing the measured ICP; various computer components (hardware, software, computer programs, etc.), for processing the signals from the sensors and for calculating the ICP based on those signals; etc. As will be understood by those of skill in the art, the apparatus and/or system of the invention may be integrated into or used with other monitoring, detecting or measuring systems, e.g. systems to measure blood pressure, heart activity, etc. The invention also encompasses a method of non-invasively measuring ICP of a patient or subject. The method comprises the steps of conformably adapting an acoustic sensor to at least one eyelid of a patient, the acoustic sensor being held in place by a frame that is removably attached to a head of the subject. Acoustic signals are then transmitted into the head of said patient, hi some embodiments, an ultrasonic sweep generator is used to apply acoustic signals across the skull of the patient. The signals sent to the skull sweep at a predetermined range, for example, in the ultrasonic band (e.g. 20 kilohertz and above) and an analyzer determines the Fast Fourier Transform output such that frequency peaks and shifts for post-processing analysis are more visible. In this embodiment, the predetermined range is in the ultrasonic band and an analyzer determines a resonant frequency and a damping of the acoustic amplitude, assuming a correlation between damping and ICP. hi other embodiments, the predetermined range includes a range less than 20 kHz and the analyzer determines retinal artery pulsations, with pressure being applied to the eye until the pulsations disappear, such pressure being a measure of ICP.

In one embodiment, transmission is via transducers that are placed on the head and which send acoustic signals via the patient's skull. The acoustic waves are modulated within the brain of the patient, the extent of modulation being dependent on pressure within the cranium. Acoustic signals received by the acoustic sensor attached to the eyelid reflect this modulation and can therefore be used to determine ICP by correlating the received signals with known ICP values. Thus, the method includes a step of determining, based on acoustic signals received by said sensor, intracranial pressure of the subject.

As discussed above, the apparatus of the invention includes at least one means or mechanism to adjust the pressure with which the sensors are held in place on the eyelid. This is significant because the sensitivity and accuracy of the sensor depends on the ability to maintain stable, complete, uninterrupted contact between the surface of the sensor that contacts the eyelid and the skin at the surface of the eyelid wherein contact is made. Thus, the method of the invention may also include a step of adjusting the pressure at a region of contact between the acoustic sensor and the eyelid in order to maximize detection of acoustic signals.

Determination of the ICP based on detected acoustic signals is accomplished using previously established and standardized acoustic signal-ICP data correlations. ICP can be established by comparing the received signals with such standards. Generally, standards are developed by obtaining data in normal healthy control subjects known to not be experiencing elevated ICP. In some embodiments, the ICP of an individual patient is also monitored over time and comparisons are made between readings, e.g. to monitor the progress of treatment.

In addition to being a non-invasive technique, the apparatus of the invention is also advantageous in that it is a portable device. The apparatus is lightweight and has a small footprint. Thus, the apparatus is ideally suited for use in emergency situations and/or at locations where other methods of monitoring ICP are not available. For example, the apparatus may be used in emergency situations such as accident sites or during disasters, on the battlefield, at remote areas, etc.

The aforementioned examples are intended to provide additional description of embodiments of the invention, but should not be construed so as to limit the invention in any way. EXAMPLES EXAMPLE 1.

ABSTRACT

The brain is surrounded by cerebrospinal fluid, and when a brain tumor or a traumatic brain injury has occurred, intracranial pressure, ICP, is developed. Monitoring ICP non-invasively is a challenge. Currently, a probe is inserted through the skull, running the risk of infection, bleeding, and damage to the brain tissue with residual neurologic effects. A novel method to measure ICP using actuators and sensors has been proposed where the skull is vibrated at high frequencies and the receiving signal is measured at the surface eyelid. A design of experiments approach is used to develop the sensor part of the ICP monitoring device so that gain can be maximized using factors such as area, thickness, electrode, and applied pressure. In addition, sensor packaging is optimized to minimize dampening of the signal and ensure durability, reliability, and repeatability of the measurements. Results of this study showed that for a range of areas and thicknesses with Cu-Ni electrodes packaged with super strength durable tape are the optimum factors for the ICP sensor. These parameters are then incorporated into a design that allows ease of application and consistency of the measurements. INTRODUCTION

Intracranial pressure (ICP) is the pressure exerted by the cranium on the brain tissue, cerebrospinal fluid, and the brain's circulating blood volume. ICP is a dynamic phenomenon constantly fluctuating in response to activities such as exercise, coughing, straining, arterial pulsation, and the respiratory cycle [I]. Hence, ICP monitoring has become a vital part in the management of patients with a head injury [2]. Elevated or increased ICP is a serious complication that can result from various neurologic conditions such as head trauma, intracranial hemorrhage, and embolic stroke, alterations in cerebral spinal fluid production and/or absorption, infections, and tumors [3, 4]. Patients with increased intracranial pressure are among the most challenging patients to care for in a critical care setting. Initiating rapid and effective treatment to protect a patient from a devastating outcome depends on aggressive and thorough clinical assessment. Due to the damaging biochemical processes that activate within minutes to hours of injury, proper and rapid detection and treatment of a traumatic brain injury is critical in preventing further damage or death [5, 6]. In the United States traumatic brain injury is a leading cause of death for persons under age 45, and occurs every 15 seconds. Approximately 5 million Americans currently suffer some form of traumatic brain disability. The leading causes of it are motor vehicle accidents, falls, and sports injuries [7].

There are four standard invasive methods to monitor ICP [8]. They include: (1) Ventriculostomy; (2) Subarachnoid Screw; (3) Subdural/Epidural Catheter; (4) lntraparenchymal of a Fiber optic Transducer Tipped Catheter. The ventriculostomy method is the most commonly used to monitor ICP [9, 10] and it is known as "gold standard" [11, 12]. Care of a patient with ventriculostomy requires precise training on how to carefully level the transducer to the Foramen of Monroe to minimize risk of infusion or improper drainage [8]. One drawback to monitoring ICP with a ventriculostomy is that debris, such as tissue fragments or blood clots can obstruct the catheter. If this occurs it is likely that the obstruction will compromise the ability to monitor the ICP accurately. An obstruction can also alter proper drainage of the cerebral spinal fluid. The other techniques, Subarachnoid and epidural devices have much lower accuracy [13, 14]. Hence, there is a need for a technique that can be used to non-invasively monitor ICP.

There are two approaches to the interior of the skull for "seeing" brain pressure: the ear and the eye since the brain is directly communicated to both the eye and ear. The eye is more convenient to non-invasively monitor changes in ICP. Ear monitoring of changes in cerebral- spinal fluid pressure has been attempted but has not resulted in a feasible clinical device [15] Direct measures of skull vibration by using ultrasonic probes have also been attempted, but with limited success because it is technically complicated, and is not a promising clinical alternative [16]. Eye pressure does correlate with cerebral spinal fluid pressure [17, 18] and various approaches have been used since eye pressure assessment is a common ophthalmological procedure [19]. In this study, frequencies above 20 kHz are targeted. The sensor that is used must have a reliable and repeatable response to high frequency signals, be low noise, require no additional power supply, and fit around a human eyelid. A family of materials that fit these parameters is piezoelectric materials. Piezoelectric ceramic materials such as PZT are normally preferred because of their relatively large piezoelectric coefficients. However, their brittle nature has limited their use in a wide range of applications. Piezoelectric polymers such as PVDF can overcome some of these difficulties as they are ductile in nature and have high electromechanical coefficient. PVDF is the chosen material for this study. MATERIALS

Piezoelectric polymers PVDF are widely used in medical applications. Desired dimensions and shapes can easily be achieved through a PVDF film sheet as it is a light weight polymer and not brittle. The human eye is of spherical nature and has a radius of 12.7 mm [20, 21 , 22, 23]. These dimensions are the biggest design constraint for the sensor.

PVDF film is commercially available and Measurement Specialties Inc [24] supplies a wide range of piezoelectric film sensors. In this case, samples of PVDF were used in thicknesses of 28, and 110 μm. These values will be explained in detail on the experimental setup. Lead type and attachment to the sensor plays an important role on the sensor's performance and its ease of application on the eyelid. For this reason, flat metal leads were chosen: 0.001 mm by 0.125mm Nickel 201 of Wiretronics [25]. Since soldering to PVDF can damage the sample, electrodes are designed as a part of the sensor packaging. The sensor packaging was tested using five different types of materials: (1) High Performance Scotch Packaging tape (3M); (2) Super Strength Scotch Packaging tape (3M); (3) Magic™ Scotch tape (3M);, (4) Mylar (C-line no 64112); (5) Kapton® tape (Furon Chr); and (6) Electric tape.

The samples are constructed from three main components: the piezoelectric sample itself, electrical leads that conduct the signal, and a packaging layer. First, one piece of packaging layer is cut to the desired dimensions, is laid out, adhesive side up. To that is affixed one of the electrical leads having a shielding layer covered over it, followed by the PVDF. The other lead is then placed atop the PVDF, and the final protective layer is laid out, sealing the sample, Figure 4 shows the schematic of the sensor assembly. EXPERIMENTAL SETUP

The source of vibration, the actuator, selected for this work is a Bimorph (Figure 5). A Bimorph device consists of two thin ceramic sheets bonded with their poling directions opposed and normal to the interface. When an electric field is applied to a Bimorph, one of the plates expands while the other contracts. This mechanism creates a bending mode that mimics a piston like displacement. Bimorphs are capable of generating large bending displacements of several hundred micrometers on center or edge, but the response time (1 ms) and the generative force (1.0 N) are low [26]. In the current study, the Bimorph used is model WACl-IC-Ol manufactured by Taiheiyo Cement Corporation as shown in Figure 5. It consists of two PZT 5 A strips with parallel polarization of 80mm by 20mm with and a total thickness of 0.4mm. A fixture was designed and built to hold the Bimorph from one end using a clamp forming a cantilever beam type assembly as shown in Figure 6. In this figure, the sensor and vibration source are both connected to the Gain-Phase Analyzer model HP4194A which is connected through a GPEB interface card to a computer. The counterweight mechanism also shown in Figure 3 was used to hold the sensor in place since results are quite variable if the transmission medium is complaint. The applied weight was used in order to reduce the error caused due to the transmission medium such as double sided tape or any other adhesive. The influence of this factor is explored in this work and explained on the results section. The actuator, Bimorph, is powered with a 1 VAC signal at frequency range from 20 to 60 kHz provided by the Gain-Phase analyzer.

Since the objective of this work is to optimize the sensor's response (gain) in a predetermined frequency range, the factors selected for the study were thickness and area of the sensor, magnitude of force on the sensor in terms of weight and the sensor electrode material. Due to the continuous nature of three variables conducting a complete study for gain optimization will be time consuming and uneconomical. Thus a design of experiments approach is adopted limiting the number of experiments required.

A full factorial design of experiments study is conducted with 4 factors, β, γ, α, and τ represented by Equation 1. These variables represent the factors under study, y represents the response variable of gain, μ represent the average of all factors, and e represents the error.

y ^_m = μ + τ, + P₁ + γ_k + α, + ( τ - P)₁J + ( τ ^• γ) _ik + ( τ ^• α), +

( β - γ)_Jk + ( P - O)₁₁ + ( γ ^• α)_kl + (τ - β ^• γ)_ijk + (τ ^• β - y)^ φ - γ - α)_jkl +

(τ ^• p ^• γ ^• α)_ljkl + e _IJklm

Equation 1

Except for one factor, area, the other factors are studied at 2 levels shown in Table 1. For area (A) several levels are tested in a range from 150 - 300 mm2. Such a model design is call a 2x2x2x5 factorial design. Two replicates were also included in the design thus requiring a total of 120 experimental runs. A regression analysis is performed on the full factorial design using the gain data obtained at the actuator driving frequency at 30 kHz, and 50 kHz. The results of the analysis are presented in the following sections.

Table 1. Factors distribution.

Note that in the factors chosen, there are different categories of factors: continuous and discrete. In the case of discrete variables, the model obtained highlights the relevance of that factor, and Design of Experiments is a tool to assess its significance in conjunction with continuous variables. This approach is explained in the next section. APPROACH

Once the materials, experimental setup, factors, and response variables are chosen, a design of experiments is carried out using statistical analysis tools and the software JMP 7.0 [27]. Through this technique a full factorial design can provide information on the factors effect if any, their relevance, and even develop a model to predict the performance of the developed sensor. A 95% confidence level is used for all the analysis and relevant factors are identified through p-values on the response variables. Conventionally for this analysis the 5% (less than 1 in 20 chance of being wrong) levels or the 95% confidence internal mark has be chosen such that the p-value has to be less than 0.05 [28]. The design had a total of 120 samples and the objective is to optimize the response variable i.e. gain and to check the repeatability and reliability of the samples. RESULTS AND DISCUSSION Using the setup shown in Figure 6, a calibration of the setup is performed using an accelerometer 352A60, manufactured by PCB Piezotronics. These results indicate the developed sensor should obtain a similar type of gain and trend even though the accelerometer does change the cantilever response due to its own weight (7 grams).

After the initial characterization of the system's response, a sensors typical response curve is measured. A response curve for the sensor is shown in Figure 8. This curve shows that the sensor responds to the source with a delay of 0.7μsec.

Using the output of the sensor divided by the input to the actuator, a gain over a frequency range is obtained. A typical gain curve over the frequency is shown in Figure 9. These results show peaks in the ranges of 22 - 25kHz and 52 - 55kHz and these values are believed to be inherent to the PVDF not the Bimorph. Similar types of peak are not observed when the accelerometer was tested. In addition all the samples show the same trend.

Because of the pattern shown in Figure 9, a gain at 30 kHz was selected as a response variable to avoid errors in the area of the peaks. In this manner, statistical evaluation of all factors is possible and a model can be tested. An Analysis of Variance, ANOVA, is performed for the model shown in equation 1, and the results are summarized in Table 2. These results show that the model fitted to the data is statistically significant and the probability of the model not fitting the data is less than 0.0001.

Table 2. Analysis of Variance.

Further inspection of the statistical regression results are shown in Table 3. These results indicate that a model exists for specific combination of parameters (in bold in Table

4): thickness, weight, area, and one type of electrode are statistically significant. In particular, the interaction between weight, area, and thickness is quite significant as well as the interaction between thickness, area, and electrode. Higher order interactions were negligible, as well as the factors by themselves but are included in the model since that has an effect on the regression model overall. Table 3. Regression Estimates.

The model results from Equation 1 can be shown using contour plots. In this manner, 3 variables and their interaction can be observed with more clarity. Figure 10 shows the contour map of thickness and area as x and y variables, and the contour lines represent the gain. In this case, the electrodes are Copper Nickel electrodes with a constant weight of 20 grams. This figure shows that samples with higher thickness had more response than the thinner samples, and area is almost constant. Similarly another contour plot is formed where the x and y variables are the weight and the area shown in Figure 11, electrode was Cu-Ni and respectively, and the response variable again is gain. In this case, the thickness was 45μm, and the electrode is Cu-Ni. From this, it was observed that increase in weight when chosen carefully, does not alter the response signal, for a particular constant area line. If the weight is kept constant and the area increases, the gain is slightly less. In short these two factors can be manipulated according to the desired location of the sensors.

Once a model was developed and relevant factors are identified, the reliability and repeatability of the devices is targeted with proper packaging. In order to ensure the proper packaging of the sensor material different encasing materials were tested. These materials shown in Table 4 were chosen because they are commercially available and relatively inexpensive. To test the strength of the bond between sensor (PVDF), leads, and encasing material a peeling test is conducted with a hand held force probe (Chatillon DPP series -23 model) with a range of 5 lbs with a precision of 0.05 lbs. Results of these tests are also summarized in Table 5. It was observed that High Performance Scotch material (3M) had the highest peeling force of all the materials tested.

Table 4. Peeling test results.

DESIGN Since the performed experiments demonstrated that the applied weight to the sensor is important in combination with area, then a proposed design for recording ICP is proposed.

This design, the ICP glasses, is shown in Figure 12. The ICP glasses have a band around the patient's head that exerts pressure to keep the sensor in place. The sensor located in the spectacle part of the glasses, is isolated from the skull and is designed to touch only the eyelid of the patient. In addition, the mounting of the sensor requires no adhesive to the surface. It is expected that this technique will provide more reliable and repeatable results.

SUMMARYAND CONCLUSIONS

A PVDF sensor to monitor ICP was developed and optimized using a design of experiments approach to maximize gain in the frequencies between 20 to 60 kHz. Four factors were considered in the development of the model, sensor thickness, sensor area, sensor electrodes, and the applied counterweight. The experimental design consisted on a 2x2x2x5 experimental design and a full factorial with two replications. Using this design, the results showed that the main contributor to the gain is sensor thickness alone. All the other factors were relevant not by themselves but in combination with others. In addition, the sensor is packaged to produce reliable and repeatable results.

REFERENCES

[1] Website located at www.brainandspinalcord.org

[2] Lundberg, N., Troupp, H., and Lorin, H., 1965," Continuous recording of ventricular fluid pressure in patients with severe acute traumatic brain injury (Class II)," J Neurosurg, 75, pp.

581-590.

[3] Robertson, C.S., Valadka, A.B., Hannay, H.J., Contant, C.F., Gopinath, S.P., Cormio, M.,

Uzura, M., Grossman, R.G., 1999, "Prevention of secondary ischemic insults after severe head injury," Crit Care Med, 27,pp. 2086-95. [4] Mayhall, C.G., Archer, N.H., Lamb, V. A., Spadora, A.C., Baggett, J.W., Ward, J.D.,

Narayan, R.K., 1984, "VenfricuJostomy-reJated infections. A prospective epidemiologic study," N Engl J Med , 310(3), pp. 553-9.

[5] Park, E., Bell, J.D., Baker, AJ., 2008, 'Traumatic brain injury: Can the consequences be stopped?," Canadian Medical Association Jouraa,l, 178(9), pp. 1163-70. [6] Xiong, Y., Lee, C.P., and Peterson, P.L., 2001, "Mitochondrial dysfunction following traumatic brain injury." In Head Trauma: Basic, Preclinical, and Clinical Directions, 25, pp.

257-280.

[7] Website located at www.headinjury.com/sports.htm

[8] Smith, M., 2008; "Monitoring Intracranial Pressure in Traumatic Brain Injury," Anesth Analog, 106, pp. 240-248.

[9] Mayhall, C, Archer, N., Lamb, V., 984. "Ventriculostomy-related infections. A prospective epidemiologic study," New England Journal of Medicine, 310, pp. 553-559.

[10] Bader, M.K., Littlejohns, J., and Palmer, S., 1995, "Ventriculostomy and intracranial pressure monitoring: in search of a 0% infection rate," Heart Lung, 24(2), pp. 166-172. [11] Czosnyka, M., & Pickard, J., 2004, "Monitoring and interpretation of intracranial pressure," Journal of Neurology, Neurosurgery, and Psyciatry, 75, pp. 813-821. [12] Kocan, M., 2002, "Ask The Experts," Critical Care Nurse, 22, pp. 70-73.

[13] Munch, E., Weigel, R., Schmiedek, P., and Schurer, L.," The Comino intracranial pressure device in clinical practice: reliability, handling characteristics and complications,"

1998, Acta Neurochir 140, pp. 1113-1119. [14] Citerio G, Andrews P.J., 2004, "Intracranial pressure Part two: clinical applications and technology," Intensive Care Med, 30, pp. 1882-5.

[15] Buki, B., Chomicki, A., Dordain, M., Lemaire, J.J., Chazal, J., Avan, P., Wit, H., 2000

"Middle-ear Influence on Otoacoustic Emissions. II: Contributions of Posture and Intracranial

Pressure," Hearing Research, 140, pp. 202-211. [16] Bekesy, V.G., 1948, "Vibration of the head in a sound field and its role in hearing by bone conduction," J Acoust Soc Am, 20, pp. 749-760.

[17] Lashutka, M., Chandra, A., Murray, H., Phillips, G., Hiestand, B., 2004,"The relationship between introcular pressure to intracranial pressure," Ann Emerg Med, 43, pp.585-591. [18] Sheeran, P., Bland, J.M., Hall, G.M., 2000, "Intraocular pressure changes and alteration in intracranial pressure", Lancet, pp. 255:889.

[19] United States patent # 20070123796.

[20] Fledelius, H. C, 1992," Pre-term delivery and the growth of the eye: An oculometric study of eye size around term-time," Acta Ophthalmologica (Suppl.), 204, pp. 10-15. [21] Denis, D., Righini, M., Scheiner, C, Volot, F., Boubli, L., Dezard, X., 1993, "Ocular growth in the fetus. 1. Comparative study of axial length and biometric parameters in the fetus," Ophthalmologica, 207(3), pp. 117-124.

[22] Insler, M. S., Cooper, H. D., May, S. E., Donzis, P. B. 1987, "Analysis of corneal thickness and corneal curvature in infants," CLAO Journal, 13(3), pp. 182-184. [23] Larsen, J. S., 1971, "The sagittal growth of the eye. IV. Ultrasonic measurement of the axial length of the eye from birth to puberty," Acta Ophthalmologica (Copenh), 49(6), pp.

873-886.

[24] Website located at www.meas-spec.com/piezo-film-sensors.aspx

[25] Website located at wiretron.com/ [26] Dogan, A., Tressler, J., and Newnham, R.E., 2001 , "Solid-State Ceramic Actuator

Designs," AIAA, Vol. 39, No. 7.

[27] Website located at www.jmp.com/ [28] Devore, J.L., 2004, "Probability and Statistics for Engineering and the Sciences," Duxbury Thomson Learning

While the invention has been described in terms of its preferred embodiments, those skilled in the art will recognize that the invention can be practiced with modification within the spirit and scope of the appended claims. Accordingly, the present invention should not be limited to the embodiments as described above, but should further include all modifications and equivalents thereof within the spirit and scope of the description provided herein.

Claims

CLAIMSWe claim:

1. An apparatus for non-invasively measuring intracranial pressure, comprising, at least one acoustic sensor, said at least one acoustic sensor being conformable to an eyelid of a subject; and a frame for positioning or holding said at least one acoustic sensor in direct contact with said eyelid.

2. The apparatus of claim 1, further comprising means to apply and adjust pressure at a region of contact between said acoustic sensor and said eyelid.

3. The apparatus of claim 1, wherein said frame is removably attachable to a head of said subject.

4. The apparatus of claim 1, wherein said acoustic sensor is a piezoelectric sensor.

5. A method for determining intracranial pressure of a patient, comprising the steps of conformably adapting an acoustic sensor to at least one eyelid of said patient, said acoustic sensor being held in place by a frame that is removably attached to a head of said patient; transmitting acoustic signals into said head of said patient; and determining, based on acoustic signals received by said acoustic sensor, intracranial pressure of said patient.

6. The method of claim 5, further comprising the step of adjusting a pressure at a region of contact between said acoustic sensor and said eyelid.

7. A conformable acoustic sensor, comprising: one or more electric leads; one or more insulating layers; and at least one acoustic sensor, wherein said one or more electric leads, said one or more insulating layers, and said at least one acoustic sensor form a structure with at least one exterior surface that is conformable to contours of a surface on which said structure is positioned.

8. The conformable acoustic sensor of claim 7, further comprising: a covering formed from a skin-compatible material, said covering being positionable on said at least one exterior surface of said conformable acoustic sensor.

9. The conformable acoustic sensor of claim 8, wherein said skin-compatible material is semi-adhesive.

10. A multilayer acoustic sensor, comprising: an acoustic sensor in electrical communication with at least one electrical lead; at least one layer of insulation positioned between said acoustic sensor and said at least one electrical lead; and a covering formed from a semi-adhesive skin-compatible material, said covering being positionable on at least one exterior surface of said multilayer acoustic sensor.

11. The multilayer acoustic sensor of claim 10, wherein said acoustic sensor is positioned between two insulated electrical leads.