Devices and methods for active surveillance of shunt-implanted patients

Abstract

A self-monitoring cerebrospinal fluid (CSF) shunt defining a fluid path; and a monitoring device arranged proximate at least a portion of the CSF shunt. The monitoring device includes at least one of an optical transmitter or an ultrasound transmitter arranged to transmit corresponding optical or acoustic waves into said fluid path, a detector arranged to detect the at least one of optical or acoustic waves after being at least one of scattered or absorbed from a plurality of particles when present in the fluid path, and an electronic module that includes a data processor configured to communicate with the detector. The data processor is further configured determine at least one of a presence of the plurality of particles, a size of the plurality of particles, a density of the plurality of particles, a type of the plurality of particles, or a motion of the plurality of particles when present in the fluid path.

Description

DEVICES AND METHODS FOR ACTIVE SURVEILLANCE OF SHUNT-IMPLANTED PATIENTSCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] The present patent application claims priority' benefit to U.S. Provisional Patent Application No. 63 / 532,519, filed on August 14, 2023, the entire content of which is incorporated herein by reference. All references cited anywhere in this specification, including the Background and Detailed Description sections, are incorporated by reference as if each had been individually incorporated.BACKGROUND1. Technical Field

[0002] The currently claimed embodiments of the present invention relate to shunt implants, and more particularly to devices and methods for active surveillance of shunt implants and shunt implants with active surveillance.2. Discussion of Related Art

[0003] Hydrocephalus patients have an excess of cerebrospinal fluid (CSF) in the ventricular system of the brain, often leading to intracranial pressures (ICP) that are higher than normal individuals. The CSF is a vital fluid which bathes the brain and spinal cord. The most common surgical treatment of hydrocephlus is the placement of a shunt device, which reroutes CSF from the ventricular system to another region of the body (most often the abdominal cavity7, or heart) where it is naturally absorbed. This will relieve pressure on the brain. There are approximately 30,000 shunt placements in the United States annually ( / ), and nearly 125,000 adult Americans are currently living with shunts.

[0004] In a study that tracked adult shunt patients over a mean of 3.9 years, 6.1% developed infections of the CSF (2). These are cases of bacterial meningitis, infection of the meninges, or tissues that encase the brain, with the additional complication of foreign hardware which can harbor bacteria indefinitely. According to the World Health Organization (WHO), around 1 in 10people who get bacterial meningitis die from the infection, even with treatment. The Centers for Disease Control and Prevention (CDC) reports that without treatment, the death rate can be as high as 70 %. The mortality rate of bacterial meningitis in children is estimated between 3-20% and can lead to other complications such as ventriculitis which drastically increases morbidity and mortality (3, 4).

[0005] Currently, the lack of a specific method of non-intrusive and / or continuous evaluation of the CSF and shunt functionality complicates the current clinical standard and makes it sorely dependent on a ‘passive’ workflow, in which patients are responsible for reporting and seeking treatments after their symptoms (e.g.. headaches, nausea, vomiting, and / or lethargy’, etc.) have developed. There is an urgent need for a novel “active” surveillance framework that can continuously and instantly identify a patient at risk at an earlier time point and substantially simplify’ the clinical workflow by pinpointing the cause of complications, avoiding timeconsuming bloodwork and CT / MRI.SUMMARY

[0006] A self-monitoring cerebrospinal fluid (CSF) shunt according to an embodiment of the current invention includes a CSF shunt defining a fluid path from a proximal end to a distal end thereof; and a monitoring device arranged proximate at least a portion of the CSF shunt. The monitoring device includes at least one of an optical transmitter or an ultrasound transmitter arranged to transmit corresponding optical or acoustic waves into said fluid path defined by the CSF shunt, a detector arranged to detect the at least one of optical or acoustic waves after being at least one of scattered or absorbed from a plurality of particles when present in the fluid path defined by the CSF shunt, and an electronic module that includes a data processor configured to communicate with the detector. The data processor is further configured determine at least one of a presence of the plurality of particles, a size of the plurality of particles, a density of the plurality of particles, a type of the plurality of particles, or a motion of the plurality' of particles when present in the fluid path of the CSF shunt.

[0007] A monitoring device for a cerebrospinal fluid (CSF) shunt according to an embodiment of the current invention includes at least one of an optical transmitter or an ultrasound transmitter arranged to transmit corresponding optical or acoustic waves into a fluid path defined by the CSFshunt, a detector arranged to detect the at least one of optical or acoustic waves after being at least one of scattered from, reflected from or partially absorbed by a plurality of particles when present in the fluid path defined by the CSF shunt, and an electronic module that includes a data processor configured to communicate with the detector. The data processor is further configured determine at least one of a presence of the plurality of particles, a size of the plurality of particles, a density of the plurality of particles, a type of the plurality of particles, a motion of the plurality of particles when present in the fluid path of the CSF shunt, or a motion of the valve compartment of the CSF shunt.

[0008] A method of monitoring a CSF shunt according to an embodiment of the current invention includes transmitting at least one of optical or acoustic waves into a fluid path defined by the CSF shunt; detecting corresponding at least one of optical or acoustic waves after being scattered from, reflected from, or partially absorbed by a plurality of particles or a valve compartment of said CSF shunt when present in the fluid path or valve defined by the CSF shunt to provide detection output; and receiving and processing the detection output to determine at least one of a presence of the plurality of particles, a size of the plurality of particles, a density of the plurality of particles, a type of the plurality’ of particles, a motion of the plurality' of particles when present in the fluid path of the CSF shunt, or a motion of the valve compartment of the CSF shunt.BRIEF DESCRIPTION OF THE DRAWINGS

[0009] Embodiments of the present invention, as well as the methods of operation and functions of the related elements of structure and the combination of parts and economies of manufacture, will become more apparent upon consideration of the following description and the appended claims with reference to the accompanying drawings, all of which form a part of this specification, wherein like reference numerals designate corresponding parts in the various figures. It is to be expressly understood, however, that the drawings are for the purpose of illustration and description only and are not intended as a definition of the limits of the invention.

[0010] FIG. 1A is a schematic illustration of a self-monitoring cerebrospinal fluid (CSF) shunt according to an embodiment of the current invention.

[0011] FIG. IB is a sectional view of FIG. 1A illustrating the shunt device and monitoring device in more detail.

[0012] FIG. 2 is a schematic illustration showing a cross-sectional side view of a monitoring device according to an embodiment of the current invention. This can be a Clip-On System to MOnitor Shunt device (COSMOS) according to some embodiments. In “a”, is an example of a case with normal CSF flowing through the COSMOS-equipped shunt device. In “b” is an example of a case with CSF flow containing excessive WBCs due to bacterial meningitis that is proportionally affecting the acoustic and optical scattering. A spatially distributed acoustic sensor (light shaded bars) recognizes the scattered energy off from the pre-calibrated energy pathway with normal CSF. Abbreviations: cerebrospinal fluid, CSF; white blood cell, WBC.

[0013] FIG. 3 shows an example of single-excitation measurement of piezoelectric (PZ) and pyroelectric (PE) effects using a conventional PZE element. Signals were successfully differentiated in time domain using different time-of-flight (TOF) of light and acoustics.

[0014] FIGS. 4A-4D are schematic illustrations of further embodiments of the current invention. These examples show representative configurations with a light transmitter that can be used in the COSMOS. FIG. 4A shows (a) light in, light out, and PE detection; FIG. 4B shows (b) light in. light and acoustic out, and PE and PZ detection; FIG. 4C shows (c) light in, acoustic out, and PZ detection of the signal reflected from a reflective layer in the shunt device; and FIG. 4D shows (d) light in, acoustic out, and PZ detection of the signal reflected from a shunt device bottom or its acoustic impedance mismatch at natural shunt-skull interface.

[0015] FIGS. 5A-5B are schematic illustrations of further embodiments of the current invention. These examples show representative configurations with an acoustic transmitter in the COSMOS. FIG. 5A shows (a) acoustic in. acoustic out, and PZ detection of the signal from a reflective layer in the shunt device; FIG. 5B shows (b) acoustic in, acoustic out, and PZ detection of the signal reflected from a shunt device bottom or its acoustic impedance mismatch at natural shunt-skull interface.

[0016] FIGS. 6A-6C describe a fundamental mechanism to identify the different energy scattering in the CSF with white-blood cell (WBC) counts in normal and bacterial meningitis cases. FIG. 6A shows (a) a scattering pattern variation due to different WBC concentration inCSF. FIG. 6B shows (b) a dual-modal detection using clinically available acoustic sensor based on pyroelectric (PE) and piezoelectric (PZ) mechanisms, clearly differentiable with distinct time- of-flight of light and sound. FIG. 6C shows (c) simulation results with a range of WBC counts in unit CSF volume. Main beam intensity reduction and spatiotemporal standard deviation were used as the core clinical metrics to prognose any complications in patients shunt implanted.

[0017] FIG. 7 is a schematic illustration showing a cross-sectional side view of a monitoring device according to another embodiment of the current invention. This can be a COSMOS embodiment. In this embodiment, two sensor clusters and bifurcated beam paths can allow continuous monitoring of WBC / RBC concentrations in the reservoir compartment and mechanical function of valve compartment through the intact scalp.DETAILED DESCRIPTION

[0018] Some embodiments of the current invention are discussed in detail below. Tn describing embodiments, specific terminology' is employed for the sake of clarity. However, the invention is not intended to be limited to the specific terminology so selected. A person skilled in the relevant art will recognize that other equivalent components can be employed, and other methods developed, without departing from the broad concepts of the present invention. All references cited anywhere in this specification are incorporated by reference as if each had been individually incorporated.

[0019] The terms “light” and “optical” are intended to have broad meanings as used in this specification which can include both visible and non-visible regions of the electromagnetic spectrum. For example, in addition to the spectrum of red to blue and violet visible light, infrared, ultraviolet and other regions of the electromagnetic spectrum are intended to be included within the broad definition of “light”.Clinical metrics

[0020] Clinical development of CSF infections in shunt patients is an emergent and unpredictable event. Patients with shunts call their neurosurgeon or present to the emergency department (ED) with headaches, nausea, vomiting, and / or lethargy and then receive further workup, fable I shows the possible disorders and CSF parameters related to the symptoms.When developing a differential diagnosis, shunt infections are almost universally bacterial. Viral meningitis is rare, and the treatment is usually supportive. Tuberculous meningitis is extraordinarily rare in the US. Clinicians are seldom worried about differentiating bacterial meningitis from hemorrhage or multiple sclerosis since the overlap between these diseases in this patient population is limited. Therefore, white blood cell (WBC) count and lack of CSF flow due to a mechanical failure of the shunt system are the primary issues that clinicians must differentiate. However, current clinical workflow is time-consuming and risky: patients will get a complete blood count to look for WBCs, an X-ray shunt series to look for mechanical breaks in their shunt system, and a CT (in adult) or MRI (in children) head to look at the distribution of CSF in their brain. If they have elevated WBC in their blood or if everything is negative, which is a very common scenario, the patient will often have to get CSF aspirated from their shunt device. A standard clinical diagnosis of an emergency case is made when there is an increase in the concentration of WBC in the CSF up to 100-1 ,000 times the normal range (5), which is very distinct compared to other components of the CSF (e.g., glucose and protein). However, such intrusive CSF sampling can also introduce bacteria into the CSF, resulting in new infection. Each of these steps cannot be skipped but contribute to delaying the decision of optimal treatment.Table 1. CSF parameters in health and some common disordersBasic configuration of shunt systems

[0021] This section includes a description of a basic configuration of a shunt system. Most of this information is directly from the Hydrocephalus Association (6). Some embodiments of the current invention can provide a shunt monitoring device that can be used in conjunction with existing shunt systems. The following includes a description of components of some current shunt systems; however, the general concepts of the current invention are not limited to only the example shunt system described. In addition, other embodiments of the current invention can provide entire shunt systems.

[0022] In a person with hydrocephalus, intracranial pressure (ICP), or pressure within the brain is higher when compared to that of an individual without hydrocephalus. This is typically due to an excess of CSF within the ventricular system of the brain. The most common treatment for hydrocephalus is the surgical placement of a medical device called a shunt. A shunt, in its simplest form, is a flexible tube called a catheter, which is placed into the area of the brain where CSF is produced. This area of the brain is known as the lateral ventricles. The tubing is then passed under the skin to another region of the body, most often the abdominal cavity, or heart, diverting the excess CSF away from the brain, where it can be absorbed naturally by the body. By draining the extra fluid to another location in the body, it is relieving pressure on the brain.

[0023] A conventional CSF shunt usually consists of four major components:• A proximal catheter drains CSF from the ventricles of the brain, leaving through a small hole drilled in the skull and then runs for a short distance under the skin.• A reservoir can be used to remove CSF samples for testing, a clinician may inject fluid into the system to test the flow and function of the shunt, and it can be used to measure CSF pressures. In addition, the reservoir can be felt through the skin and pumped manually to help keep the proximal catheter open. In general, if one pushes on the reservoir and it does not spring back, then there might be an obstruction in the proximal catheter because the reservoir is not filling with CSF. On the other hand, if the reservoir feels rather stiff and more force is needed to depress it, then the valve and / or distal catheter may be clogged. However, patients are advised not pump the reservoir unless explicitly instructed to do so by a clinical professional.• A valve mechanism regulates ICP by controlling CSF flow. This device lies underneath the skin on top or the back of the head, or behind the ear. Valves operate within a specific pressure range. Many types of valves exist but most of them operate on the principles of change in differential pressure between the proximal and distal catheter tips.A distal catheter delivers the CSF from the valve to the abdominal (peritoneal) cavity, heart, or another suitable drainage site for natural absorption.Self-monitoring CSF shunt systems and devices

[0024] A self-monitoring cerebrospinal fluid (CSF) shunt 100 according to an embodiment of the current invention is shown schematically in FIG. 1A. The self-monitoring CSF shunt 100, includes a CSF shunt 102 defining a fluid path from a proximal end to a distal end thereof. In this example, the CSF shunt 102 includes a proximal catheter 104 fluidly connected to a shunt device 106, which is fluidly connected to a distal catheter 108. The self-monitoring CSF shunt 100, further includes a monitoring device 110 arranged proximate at least a portion of the CSF shunt 102. In this embodiment, the monitoring device 110 is arranged proximate the shunt device 106 to be in optical and / or acoustic connection therewith. However, the general concepts of the current invention are not limited to only this arrangement.

[0025] The shunt device 106 includes an inlet connector 112 fluidly connecting the proximal catheter 104 to a reservoir 114 of the shunt device 106 (FIG. IB). The term “reservoir’7as used herein refers to the structure that defines a space that can accommodate cerebrospinal fluid therein. The shunt device 106 further includes a valve mechanism 116 fluidly connecting the reservoir 114 to an output connector 118 of the shunt device 106. The output connector 118 is fluidly connecting the shunt device 106 to the distal catheter 102.

[0026] In some embodiments, the monitoring device 110 can be directly connected to the CSF shunt 102 to be fully implantable therewith. In other embodiments, the monitoring device 110 can be externally mounted while the CSF shunt 102 is implanted. The monitoring device 110 can be externally mounted in many ways, for example, but not limited to, complementary magnets attached to the CSF shunt 102 and the monitoring device 110, adhesive material or tape attaching the monitoring device 110 to the skin at a desired location relative to the implanted CSF Shunt 102, or by some other type of wrapping, headband, hat, etc. to hold the monitoring device 110 in place. These are just some examples according to some embodiments, but the general concepts of the current invention are not limited to only these examples.

[0027] In some embodiments, the monitoring device 110 can include a fluid monitoring section 120, a valve monitoring section 122 and electronics components 124. The fluid monitoring section 120 can be arranged and structured to cover a portion of the reservoir 114 or even substantially an entire outwardly facing portion of the reservoir 114, as is shown is the various examples herein. How ever, the general concepts of the current invention are not limited to the examples of the fluid monitoring sections described in detail.

[0028] FIG. 2 show s an example of at least a portion of an embodiment of monitoring device 210 that can be used for monitoring device 110, for example, in the embodiment of the selfmonitoring CSF shunt 100. However, the general concepts of the current invention are not limited to only this example. The monitoring device 210 includes a fluid monitoring section 220 and electronics components 224. The fluid monitoring section 220 includes at least one of an optical transmitter or an ultrasound transmitter 226 arranged to transmit corresponding optical or acoustic waves into the fluid path defined by the CSF shunt 102. and a detector 228 arranged to detect the at least one of optical or acoustic waves after being at least one of scattered, reflected or partially absorbed from a plurality of particles when present in the fluid path defined by said CSF shunt 102.

[0029] In some embodiments, the at least one of an optical transmitter or an ultrasound transmitter 226 can be, but is not limited to, at least one PZT transducer, at least one photo-acoustic transducer, and / or one or more optical sources. In some embodiments, there can be one source (e.g.. optical or ultrasound), while in other embodiments there can be a plurality of sources (e.g., optical and / or ultrasound, and / or any combination thereof). In some embodiments, the at least one of an optical transmitter or an ultrasound transmitter 226 can be and array of a plurality7of sources, such as optical and / or ultrasound sources, and / or any combination thereof.

[0030] In some embodiments, the detector 228 can be, but is not limited to, at least one ultrasound detector and / or at least one optical detector. In some embodiments, there can be one detector (e.g., optical or ultrasound), while in other embodiments there can be a plurality of detector components (e.g., optical and / or ultrasound, and / or any combination thereof). In some embodiments, the detector 228 can be and array of a plurality of detector elements, such as optical and / or ultrasound detector elements, and / or any combination thereof.

[0031] The electronics components 224 can include transmit driver 230, data receiver 232, data processor 234 and battery 236, for example. However, the electronics components 224 can include other components and arrangements, depending on the application. For example, for fully implantable embodiments, electronics components 224 may include radio frequency (RF) external power sources to power the monitoring device 210 either directly and / or by charging implanted batteries. Furthermore, in that example, the electronics components 224 can include an RF transmitter to transmit data to be processed partially or totally externally.

[0032] FIG. 2 illustrates an example in which the detector 228 is an array of detector elements that substantially subtend an outwardly facing half of the reservoir. See the nght-hand side of FIG. 2 for bottom views showing an embodiment with one optical transmitter or one ultrasound transmitter 226 in the center and an array of concentric detector elements, in three rings, that include the element 228 at one section of one of the three rings. The changes in WBC concentrations can produce spatial features in the reflected signals that can be used for the monitoring. The top portion in FIG. 2 labeled “a” illustrates a condition in which the density of particles within the CSF in the reservoir is sparse. This shows that reflected and / or scattered energy is detected primarily by the innermost detector ring, indicated by shading in FIG. 2. The bottom portion in FIG. 2 labeled “b” illustrates a condition in which the density of particles within the CSF in the reservoir is dense. This shows that reflected and / or scattered energy is detected across all of the detector rings in this example, indicated by shading in FIG. 2. As is indicated in FIG. 2, the reservoir can include a surface that is reflective to the transmitted optical and / or acoustic waves. On the other hand, the scattering from the WBCs can produce temporal fluctuation of the recorded optical and / or acoustic signals from the sensor(s), which can also be used for the monitoring. This illustrates two potential mechanisms for detecting particle density and / or changes in particle density according to an embodiment of the current invention. However, the general concepts of the current invention are not limited to only this example.

[0033] More generally, data processor 234 can be further configured determine at least one of a presence of a plurality of particles, a size distributions of the plurality' of particles, a density of the plurality of particles, a type of the plurality of particles, a motion of the plurality of particles when the plurality of particles is present in the fluid path of the CSF shunt, or a motion of the shunt device compartment that should react to differential pressure induced from patient brain to distant organ. In some embodiments, a density of particles can be determined, for example, butnot limited to a density of WBCs. In some embodiments, the ultrasound transmitter 226 can have a least one wavelength of transmitted energy at wavelengths that can induce different scattering patterns in potential particles in CSF, e.g., WBC. red blood cells (RBC). etc., by which the morphological particle properties can be characterized. In some embodiments, density of WBCs can be detected by tracking the changes in spatial extends of reflected optical and / or acoustic signals or temporal signal fluctuation due to scattering events. In some embodiments, the optical transmitter 226 can have a least two wavelengths of transmitted energy’ one of which is more strongly absorbed by the particles of interest than the other of the two wavelengths. Using relative absorption, the particle types (WBC, RBC, etc.) and even the physiological parameters (e.g., oxygen saturation in RBCs) can be differentiated from each or plurality’ of particles. In some embodiments, the motion of the particles can be tracked using Doppler signal processing or deviating temporal features of the reflected optical and / or acoustic signals. In some embodiments, the additional optical and / or ultrasound transmitter 226 can be placed on top of the valve compartment of the shunt device to track its movement, which should represent the shunt functionality reacting to differential pressure in CSF between patient brain and distant organ.

[0034] The monitoring devices 110, 210 are shown as being arranged proximate reservoir 114 and valve structure 116 of the CSF shunt 102. However, other arrangements are possible without departing from the general concepts of the current invention.

[0035] Another embodiment of the current invention is directed to a method of monitoring a CSF shunt. The method includes transmitting at least one of optical or acoustic waves into a fluid path defined by the CSF shunt; detecting corresponding at least one of optical or acoustic waves after being scattered from, reflected from, or partially absorbed by a plurality of particles when present in the fluid path defined by the CSF shunt to provide detection output; and receiving and processing the detection output to determine at least one of a presence of the plurality of particles, a size of the plurality’ of particles, a density of the plurality of particles, a type of the plurality of particles, or a motion of the plurality of particles when present in the fluid path of said CSF shunt.

[0036] The following provides more details of some embodiments of the current invention. These are to help describe some concepts of the current invention, but are not intended to limit the scope of the invention, which is determined by the claims.

[0037] The term Clip-On System to MOnitor Shunt device (COSMOS) is also used to refer to some embodiments such as, but not limited to monitoring devices 110, 210 when they can be used to clip onto existing CSF shunts. In some embodiments, COSMOS can be used to monitor an elevation of white blood cell (WBC) count or a lack of cerebrospinal fluid (CSF) flow, respectively due to bacterial meningitis and mechanical malfunctioning. This can be used for tracking either continuously in a patient's daily life or instantly in the emergency department (ED).

[0038] Testing shunt patients wi th symptoms is the most painful, time consuming, and risky7step in the work-up and the one that may be avoidable by a wearable device evaluating an elevation of WBCs in the CSF and lack of CSF flow due to mechanical malfunctioning of the shunt device. Avoiding CT or MRI in these patients would bring significant breakthrough of the current clinical challenges.

[0039] To address an unmet clinical need, some embodiments of the current invention provide a COSMOS, in which an elevation of WBC count or a lack of CSF flow due to mechanical malfunctioning can be tracked either continuously in patient’s daily life or instantly in the ED. The reservoir of conventional shunt devices is made of a clear, flexible silicone dome (FIGS. 1A and IB) that can be a unique optical and acoustic window for non-intrusive characterization of CSF flow inside. FIG. 2 illustrates some basic concepts of the COSMOS according to an embodiment of the current invention that measures energy7scattering in the reservoir using an energy transmitter and receivers. Transmit energy can be either acoustic or optical pulse, and their beam shape would be contained by a natural focusing of the CSF reservoir or by an additional lens (top panel in FIG. 2). Here, WBC acts as a good scatterer to make a change proportional to meningitis progress: cloudy CSF is a unique feature of acute bacterial meningitis (5), which indicates optical scattering with excessive WBCs; an acoustic wave with a wavelength longer than the WBC diameter (12-15 pm) would produce acoustic scattering. Accordingly, any incident acoustic frequency lower than 102 MHz (considering sound propagation speed of 1540 m / s in biological tissue) would produce acoustic scattering when encountering WBCs. The scattering pattern of the energy pulse can be recognized by a sensor array covering the side of the reservoir. Signal sensing mechanisms can be based on piezoelectric (PZ) and pyroelectric (PE) effects which supports acoustics and optic modalities, respectively: PZ effect converts mechanical energy (acoustics) into electrical signals. On the other hand, PE effect converts optical energy7into heat,which then are converted into electrical signals. The scattering pattern and its temporal validation can provide critical information of current WBC density and valve functionality. The flexibility of the COSMOS with multi-modality can allow more room to optimize clinical accuracy, cost, system volume, and battery life. In some embodiments, there would be no physical line connection between external COSMOS and internal shunt device. Once the energy is converted into electrical signals, through-skin communication module would send the data through the COSMOS using electrical (7) or light modalities (8) and then transferred to a portable module via physical wire out of patient’s body.

[0040] Our data shows that a conventional piezoelectric material in medical ultrasound, such as lead zirconate titanate (PZT) or polyvinylidene fluoride (PVDF), can be used to measure the PZ and PE effects. FIG. 3 shows the PZ and PE effects measured by a single conventional PZT- based sensor of the clinical ultrasound array (L7-4, Philips ATL). Light energy at 800 nm was excited from Nd: Y AG laser equipped with optical parametric oscillator (OPO) to induce both light reflection and absorption at the porcine tissue about 20-mm apart from the sensor. The space between the array and target was filled with transparent couplant. Reflected light and photoacoustic signal generated by light absorbance at tissue directed back to the array and triggers PE and PZ effects to be converted into electrical signals, respectively. The data presented 13.33- ps interval between peaks, well reflecting acoustic propagation time in water over 20-mm distance (6.67 ps / cm in water). Consistency of the sensor to measure PZ and PE effects upon energy excitation was sufficient to be deployed for in vivo photoacoustic imaging calibration (9).

[0041] CSF evaluation can be performed in any directions of the reservoir compartment. Sensor array configuration is arbitrary if each element can recognize how much energy7was scattered due to WBCs, by measuring PZ and PE effects. Energy pathway is also arbitrary either through direct excitation or their reflection pathways inside the reservoir.

[0042] FIGS. 4A-4D show potential COSMOS configurations when having an optical transmitter. The light pathway aims directly into the reservoir of the shunt device, and there can be three different potential configurations: (a) light in, light out, and PE detection; (b) light in, light and acoustic out, and PE and PZ detection; (c) light in, acoustic out, and PZ detection. Note that an acoustic signal can be generated by a photoacoustic effect (10, 77) with the light absorber layer printed on top of the reservoir, for example. The energy (either light or acoustics) can bereflected at the bottom of the reservoir with special reflective coating or bare surface, which then can be converted into an electrical signal and sent to the personal device.

[0043] FIGS. 5A and 5B show potential COSMOS configurations when having an ultrasound transmitter. In this case, the multi-modal configuration as in FIG. 4B would not be available and only acoustic reflection can be detected. The identical procedures would be followed, sending acoustic energy, reflected from bottom (either by customized reflective layer in the shunt device or by natural reflection at the shunt-skull interface), and acquired by PZ detection by the sensor elements in COSMOS.

[0044] Having no physical wire can be a preferrable design goal according to some embodiments to prevent any intrusive setup of the shunt device, and a basic concept in FIGS. 1 A, IB. 4A-4D, 5 A and 5B follows this embodiment. However, this disclosure is intended to cover those possibilities. One might find benefits of having energy transmitter (eighter light or acoustic source) and / or sensor array in the shunt device to miniaturize the COSMOS part and reduce its weight for easier attachment to the shunt device. In this case, the COSMOS part may include wireless (through-skin) / wired connection for power delivery, synchronization, data communication.

[0045] In some embodiments, there will be no physical connection between extracorporeal COSMOS and intracorporeal shunt device, allowing for compatibility with commercial shunt devices with no or minimal modification, e.g., an absorptive coating layer on the reservoir dome or reflective layer on the reservoir bottom (FIG. 6A). Mechanical function of the shunt device can be easily tested by monitoring valve movement with an extra sensor on top of the valve compartment (FIG. 7).

[0046] FIG. 6B shows data detecting light and acoustic signals, respectively, generated by the reflectivity and absorbance (inducing photoacoustic (PA) phenomenon) of porcine tissue, based on PE and PZ effects in a conventional piezoelectric material in medical ultrasound. A clear separation was made based on the time-of-flight difference between light and sound. We also simulated the acoustic COSMOS device to derive changes in energy' intensity and its spatiotemporal variations due to WBCs flowing through the CSF within the reservoir (FIG. 6C). The analysis shows a loss in the acoustic energy and standard deviation of its spatiotemporalacoustic profiles, proportionally increasing with the WBC concentrations. Moreover, in other embodiments, spectroscopic measurements can be used for the PZ effect to track red blood cell (RBC) counts allowing additional differential diagnosis of brain-blood-barrier / blood-CSF- barrier in addition to the utility of COSMOS for use in bacterial meningitis and mechanical malfunctions.

[0047] FIG. 7 shows an embodiment of a COSMOS configuration that monitors both WBC / RBC counts in CSF of the shunt device and valve movement in patient’s daily life. Separated sensor clusters and bifurcated beam paths can allow simultaneous monitoring of WBC / RBC concentrations and valve function monitoring on reservoir and the valve part, respectively, of a commercial shunt device according to an embodiment of the current invention.References1. M. Paff. D. Alexandru-Abrams. M. Muhonen, W. Loudon. Ventriculoperitoneal shunt complications: A review. Interdiscip Neurosurg. 13, 66-70 (2018).2. A. E. Merkler, A. S. Reynolds, G. Gialdini, N. A. Morris, S. B. Murthy, K. Thakur, H. Kamel, Neurological complications after tuberculous meningitis in a multi-state cohort in the United States. J Neurol Sci. 375, 460-463 (2017).3. D. Luque-Paz, M. Revest, F. Eugene, S. Boukthir, L. Dejoies, P. Tattevin, P.-J. L. Reste, Ventriculitis: a severe complication of central nervous system infections. Open Forum Infect Dis. 8, ofab216- (2021).4. “The ISPN Guide to Pediatric Neurosurgery. Outcome for Meningitis and Ventriculitis in Children.” (2017).5. C. Haslett. E. R. Chilvers. N. A. Boon, N. R. Colledge. J. A. A. Hunter, Davidson 's Principles and Practice of Medicine (Churchill Livingstone, Edinburgh, 2002).6. Hydrocephalus Association, Shunt Systems, (available at https: / / www . hy droassoc. org / shunt- Stsj.etBS / )..7. J. Ormanis, K. Nesenbergs, Human skin as data transmission medium for improved privacy and usability in wearable electronics. 2018 leee Int Symposium Medical Meas Appl Memea. 3528725544. 1-6 (2018).8. A. -A. A. Boulogeorgos, S. E. Trevlakis, N. D. Chatzidiamantis, Optical Wireless Communications for In-Body and Transdermal Biomedical Applications. leee Commun Mag. 59, 119-125 (2021).9. Y. Wu, J. Kang, C. Yung, H. Le, J. Hwang, E. M. Boctor, "A Cost-Effective Spectral Equalization Method for Multispectral Photoacoustic Imaging" in IEEE International Ultrasonics Symposium (2020), p. 2232.10. P. Beard, Biomedical photoacoustic imaging. Interface Focus. 1, 602-631 (2011).11. L. V. Wang, H. Wu, Biomedical Optics (John Wiley & Sons, 2012), John Wiley & Sons.

[0048] While various embodiments of the present invention have been described above, they have been presented by way of example only, and not limitation. Thus, the breadth and scope of the present invention should not be limited by any of the above-described illustrative embodiments but should instead be defined only in accordance with the following claims and their equivalents.

[0049] The embodiments illustrated and discussed in this specification are intended only to teach those skilled in the art how to make and use the invention. In describing embodiments of the disclosure, specific terminology is employed for the sake of clarity. However, the disclosure is not intended to be limited to the specific terminology so selected. The above-described embodiments of the disclosure may be modified or varied, without departing from the invention, as appreciated by those skilled in the art considering the above insights. It is therefore to be understood that, within the scope of the claims and their equivalents, the invention may be practiced otherwise than as specifically described. For example, it is to be understood that the present disclosure contemplates that, to the extent possible, one or more features of any embodiment can be combined with one or more features of any other embodiment.

Claims

WE CLAIM:

1. A self-monitoring cerebrospinal fluid (CSF) shunt, comprising: a CSF shunt defining a fluid path from a proximal end to a distal end thereof; and a monitoring device arranged proximate at least a portion of said CSF shunt, wherein said monitoring device comprises: at least one of an optical transmitter or an ultrasound transmitter arranged to transmit corresponding optical or acoustic waves into said fluid path defined by said CSF shunt, a detector arranged to detect said at least one of optical or acoustic waves after being at least one of scattered or absorbed from a plurality of particles when present in said fluid path defined by said CSF shunt, and an electronic module comprising a data processor configured to communicate with said detector, wherein said data processor is further configured determine at least one of a presence of said plurality of particles, a size of said plurality of particles, a density of said plurality of particles, a type of said plurality of particles, or a motion of said plurality of particles when present in said fluid path of said CSF shunt.

2. The self-monitoring CSF shunt according to claim 1, wherein said CSF shunt comprises: a proximal catheter, a reservoir in fluid connection to said proximal catheter, a valve mechanism in fluid connection to said reservoir, and a distal catheter in fluid connection to said valve mechanism,wherein said proximal catheter, said reservoir, said valve mechanism and said distal catheter together define said fluid path defined by said CSF shunt, and wherein said detector is arranged proximate said reservoir to detect said plurality of particles when present in said reservoir.

3. The self-monitoring CSF shunt according to claim 1 or 2, wherein said detector comprises a plurality of detector elements arranged in a detector array pattern.

4. The self-monitoring CSF shunt according to claim 2, wherein said detector comprises a plurality of detector elements arranged in a detector array pattern of a size and shape to conform to a portion of said reservoir.

5. The self-monitoring CSF shunt according to any one of claims 1 to 4, wherein said CSF shunt is an implantable CSF shunt, and wherein at least a portion of said monitoring device is one of attached to or integral with said CSF shunt to be implantable therewith.

6. The self-monitoring CSF shunt according to any one of claims 1 to 4, wherein said monitoring device is configured to externally coupled with said CSF shunt so as to be at least one of acoustically or optically coupled to skin layers for remote sensing of said fluid path defined by said CSF shunt.

7. The self-monitoring CSF shunt according to any one of claims 1 to 6, wherein said plurality7of particles is at least one of a plurality of white blood cells, a plurality of red blood cells, or a plurality of white blood cells and a plurality of red blood cells.

8. The self-monitoring CSF shunt according to any one of claims 1 to 7, wherein said at least one of an optical transmitter or an ultrasound transmitter comprises at least one of a lightemitting diode, a laser diode, a PZT transducer, or a photoacoustic transducer.

9. A monitoring device for a cerebrospinal fluid (CSF) shunt, comprising: at least one of an optical transmitter or an ultrasound transmitter arranged to transmit corresponding optical or acoustic waves into a fluid path defined by said CSF shunt,a detector arranged to detect said at least one of optical or acoustic waves after being at least one of scattered from, reflected from or partially absorbed by a plurality of particles when present in said fluid path defined by said CSF shunt, and an electronic module comprising a data processor configured to communicate with said detector, wherein said data processor is further configured determine at least one of a presence of said plurality' of particles, a size of said plurality' of particles, a density of said plurality' of particles, a type of said plurality of particles, a motion of said plurality of particles when present in said fluid path of said CSF shunt, or a motion of said valve compartment of said CSF shunt.

10. The monitoring device according to claim 9, wherein said CSF shunt comprises: a proximal catheter, a reservoir in fluid connection to said proximal catheter, a valve mechanism in fluid connection to said reservoir, and a distal catheter in fluid connection to said valve mechanism, wherein said proximal catheter, said reservoir, said valve mechanism and said distal catheter together define said fluid path defined by said CSF shunt, and wherein said detector is configured to be arranged proximate said reserv oir to detect said plurality of particles when present in said reservoir.

11. The according to claim 9 or 10, wherein said detector comprises a plurality' of detector elements arranged in a detector array pattern.

12. The monitoring device according to claim 10, wherein said detector comprises a plurality of detector elements arranged in a detector array pattern of a size and shape to conform to a portion of said reservoir.

13. The monitoring device according to any one of claims 9 to 12, wherein said CSF shunt is an implantable CSF shunt, andwherein at least a portion of said monitoring device is one of attachable to said CSF shunt to be implantable therewith.

14. The monitoring device according to any one of claims 9 to 12, wherein said monitoring device is configured to externally coupled with said CSF shunt so as to be at least one of acoustically or optically coupled to skin layers for remote sensing of said fluid path defined by said CSF shunt.

15. The monitoring device according to any one of claims 9 to 14, wherein said plurality of particles is at least one of a plurality of white blood cells, a plurality of red blood cells, or a plurality of white blood cells and a plurality of red blood cells.

16. The monitoring device according to any one of claims 9 to 15, wherein said at least one of an optical transmitter or an ultrasound transmitter comprises at least one of a light-emitting diode or a laser diode, a PZT transducer, or a photoacoustic transducer.

17. A method of monitoring a CSF shunt, comprising: transmitting at least one of optical or acoustic waves into a fluid path defined by said CSF shunt; detecting corresponding at least one of optical or acoustic waves after being scattered from, reflected from, or partially absorbed by a plurality of particles or a valve compartment of said CSF shunt when present in said fluid path or valve defined by said CSF shunt to provide detection output; and receiving and processing said detection output to determine at least one of a presence of said plurality of particles, a size of said plurality of particles, a density of said plurality of particles, a ty pe of said plurality of particles, a motion of said plurality of particles when present in said fluid path of said CSF shunt, or a motion of said valve compartment of said CSF shunt.

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