Patent Application
20240424265
This disclosure relates to solid state shunt valve with active outflow regulator, ventricular catheters, and other embodiments, in the context of regulating flow of biological fluids in organs or tissues, such as cerebrospinal fluid in brain tissue, and/or blood in the circulatory system. It further relates to improvements in systems, system elements (such as catheters and valves), and methods related to fluid flow and circulation of fluids.
Hydrocephalus, an imbalance between cerebrospinal fluid (CSF) production and absorption, is diagnosed in more than 1 in 500 people in the United States. Approximately 80% of these patients will suffer long-term neurological deficits. Genetic diseases, meningitis, subarachnoid hemorrhage, stroke, traumatic brain injury, or tumors, cause hydrocephalus.
The common treatment for all hydrocephalus patients is CSF drainage by shunting. Despite all efforts to date, shunts still have the highest failure rate of any neurological device. A shocking 98% of shunts fail after just ten years, a rate bumped up by the 80% of patients who suffer from tens if not hundreds of repetitive shunt failures. Shunts fail after becoming obstructed with attaching glia, creating a substrate for more glia or other cells and tissues (e.g. choroid plexus) to secondarily bind and block the flow of CSF through the shunt. For additional discussion, see US Patent Publication No. 2012/0060622 (Harris et al.).
Hydrocephalus patients can have a diminished quality of life and suffer from long-term neurologic deficits because of the failure of current treatments in the field, most of which involve diversion of cerebrospinal fluid (CSF) with shunts. Despite our efforts for nearly seven decades, shunts still have the highest failure rate of any neurological device: 50% of shunts fail within two years, and 98% of all shunts fail after ten years. This failure rate is the dominant contributor to the $2 billion-per-year cost that hydrocephalus incurs on our health care system.
While many factors such as infection and disconnection could lead to shunt obstruction and eventual failure, the statistics tell us that most shunts fail by becoming blocked with cells and tissues. But how does this happen? The literature predicts that there are four mechanisms: (1) cells coming from the brain, attaching and blocking the ventricular catheter; (2) cells, protein, and debris from the CSF attaching and blocking the ventricular catheter; (3) blockage by the ventricular catheter laying on the ventricular wall's epithelial cells; (4) blockage by the choroid plexus (lined with epithelial cells).
Shunts are far from ideal even when they are not occluded, and patients often experience discomfort such as headaches and pain on a regular basis which directly impact their quality of life. While valves are necessary components of a shunt system, their outdated design results in sudden pressure changes that have been shown to significantly increase the rate of shunt failure through at least three of the mechanisms mentioned earlier. In addition, regular valves offer no protection against over-drainage and under-drainage; two of the most common causes of serious conditions including but not limited to chronic headache hemorrhage
There is an ongoing urgent need to improve hydrocephalus treatment.
This Summary is provided to introduce a selection of concepts in a simplified form that is further described below in the Detailed Description. This Summary is not intended to identify all key features or essential features of the claimed subject matter, nor is it intended to be used alone as an aid in determining the scope of the claimed subject matter.
Systems and methods for regulating fluid flow are provided herein can match CSF outflow to CSF inflow (CSF production). Activity-based changes in pressure (such as sneezing, coughing, straining from constipation, exercising, and standing up) will not impact the outflow rate of the system. Techniques described herein can improve patients' quality of life in the short term by stopping drainage induced headaches and in the long term by reducing the shunt failure rate.
The present disclosure provides a valve for regulating fluid flow. In some examples, the fluid includes cerebrospinal fluid (CSF). The valve includes tubing, a regulating element, and an actuator. The tubing is configured to allow fluid flow therethrough. The regulating element is arranged proximate to the tubing. In some examples, the tubing is arranged around the regulating element in a spiral manner. The actuator is arranged proximate to the regulating element. The actuator is configured to manipulate a parameter associated with the regulating element. In some examples, the parameter associated with the regulating element is temperature associated with the regulating element.
In some examples, the valve further includes a control component, configured to communicate with other devices and to control the actuator.
In some examples, the valve can further include a housing, configured to accommodate the tubing, the regulating element, the actuator, and the control component.
In some examples, the housing further includes an insulating element, configured to reduce heat conduction between the housing and an environment.
In some examples, the valve further includes a sensor. The sensor includes at least one of a temperature sensor, a flowrate sensor, or a pressure sensor.
In some examples, the control component is further configured to communicate with a data processing device. In some examples, the control component receives a desired value from the processing device. In some examples, the desired value includes a desired temperature.
In some examples, the control component is further configured to communicate with the other devices via Bluetooth or other wireless manners.
In some examples, the regulating element includes wax and at least one additive. In some examples, the regulating element is configured to regulate resistance to the fluid flowing through the tubing. The resistance is independent of intracranial pressure associated with a patient.
In some examples, the sensor includes at least one of a temperature sensor, a flowrate sensor, or a pressure sensor.
In some examples, the actuator includes at least one of a temperature actuator, a mechanical actuator, and an electro-mechanical actuator.
In some examples, the valve further includes a power unit configured to provide power for the valve. In some examples, the power unit includes a Lithium battery.
The present disclosure provides a system for regulating fluid flow. In some examples, the fluid includes cerebrospinal fluid (CSF). In some examples, the system includes a valve for regulating fluid flow, a data processing device, a terminal device, and/or a server.
The valve includes a tubing, a regulating element, and an actuator. The tubing is configured to allow fluid flow therethrough. The regulating element is arranged proximate to the tubing. In some examples, the tubing is arranged around the regulating element in a spiral manner. The actuator is arranged proximate to the regulating element. The actuator is configured to manipulate a parameter associated with the regulating element. In some examples, the parameter associated with the regulating element is temperature associated with the regulating element.
In some examples, the data processing device includes a wearable device.
In some examples, the data processing device is further configured to collect one or more biometric indicators associated with a patient, calculate an estimated fluid production rate based on the one or more biometric indicators associated with the patient, calculate a desired value based on the estimated fluid production rate, and send the desired value to the control component.
In some examples, the one or more biometric indicators associated with the patient include a heart rate, a blood pressure, a posture indicator, an exercise indicator, and/or an endogenous brain pressure.
In some examples, the control component is further configured to communicate with a terminal device and/or a server, the terminal device being configured to run an application (App) and communicate with the server.
The present disclosure provides a method for regulating fluid flow. The method includes the following operations. One or more biometric indicators associated with a patient are collected. An estimated fluid production rate based on the one or more biometric indicators associated with the patient is calculated. A desired value based on the estimated fluid production rate is calculated. The desired value is sent to a valve to regulate fluid flowing therethrough.
The method further includes the following operations. A control component of the valve receives the desired value from the data processing device. The control component of the valve controls the actuator to actuate the regulating element. A sensor of the valve senses a parameter associated with the regulating element. The control component of the valve determines that the parameter associated with the regulating element is within a threshold range of the desired value. The control component of the valve stops the actuator upon determining that the parameter associated with the regulating element is within a threshold range of the desired value.
The present disclosure provides a computer-readable storage medium storing computer-readable instructions executable by one or more processors, that when executed by the one or more processors, causes the one or more processors to perform the following acts. One or more biometric indicators associated with a patient are collected. An estimated fluid production rate based on the one or more biometric indicators associated with the patient is calculated. A desired value based on the estimated fluid production rate is calculated. The desired value is sent to a valve for regulating fluid flowing therethrough. A control component of the valve receives the desired value from the data processing device. The control component of the valve controls the actuator to actuate the regulating element. A sensor of the valve senses a parameter associated with the regulating element. The control component of the valve determines that the parameter associated with the regulating element is within a threshold range of the desired value. The control component of the valve stops the actuator upon determining that the parameter associated with the regulating element is within a threshold range of the desired value.
The detailed description is set forth with reference to the accompanying figures. In the figures, the left-most digit(s) of a reference number identifies the figure in which the reference number first appears. The use of the same reference numbers in different figures indicates similar or identical items or features.
Hydrocephalus, an imbalance between cerebrospinal fluid production and absorption, is diagnosed in more than 1 in 500 people in the United States. Approximately 80% of these patients will suffer long-term neurological deficits. Genetic diseases, meningitis, subarachnoid hemorrhage, stroke, traumatic brain injury, or tumors cause hydrocephalus. The common treatment for all hydrocephalus patients is CSF drainage by shunting.
Despite all prior efforts, shunts still have the highest failure rate of any neurological device. A shocking 98% of shunts fail after just ten years, a rate bumped up by the 80% of patients who suffer from tens if not hundreds of repetitive shunt failures. Shunts fail after becoming obstructed with attaching glia, creating a substrate for more glia or other cells and tissues (e.g. choroid plexus) to secondarily bind and block the flow of CSF through the shunt.
A valve provided herein is capable of matching CSF outflow to CSF inflow (CSF production). Activity-based changes in pressure (such as sneezing, coughing, straining from constipation, exercising, and standing up) will not impact the outflow rate of the valve. This valve can improve patients' quality of life in the short term by stopping drainage induced headaches and in the long term by reducing the shunt failure rate.
A benchtop model testing device was used to test the impact of regular shunt valves in comparison to the described valve on shunt failure. Furthermore, the UTD can simulate changes in pressure within the head based on activities (such as standing up, jogging, or sneezing) that are typically associated with chronic headaches and accurately measure the performance of each valve against over-drainage and under-drainage.
Also provided herein is a system including the solid state valve with active outflow regulator, for instance for regulating flow of cerebral spinal fluid (CFS) or another fluid. Described improvements in various embodiments include using a regulating element (such as a formula including wax and additives) to increase/decrease resistance around catheter tubing to the valve. The regulating element may be manipulated by an actuator arranged proximate to the regulating element. The regulating element in embodiments is controlled based on an estimated CSF production rate, which can be calculated based on biometric indicators associated with the patient. Methods are described for estimating CSF production rate using an algorithm based at least on biometric indicators such as a heart rate and a blood pressure associated with the patient.
In representative embodiments, the shunt catheter design is improved in terms of the shape of the catheter and/or the hole sizes, which can be tailored to manipulate the flow velocity and shear rate/shear stress through the catheter holes and the internal lumen of the ventricular catheter.
Aspects of the current disclosure are now described in additional detail, as follows: (I) Structure and Function of the Valve; (II) Overview of the System Comprising the Valve; (III) Methods and Operations of Controlling the Valve System; (IV) Formula of the Regulating Element; (V) Algorithm for Controlling the Valve; (VI) Kits; (VII) Catheter Design; (VIII) Example(s); (IX) References; (X) Example Clauses; and (XI) Closing Paragraphs.
As described above, CSF drainage by shunting is a common treatment for hydrocephalus patients, and can be implemented with a shunt. The shunt usually includes a ventricular catheter, a valve, and a distal catheter. In some cases, hydrocephalus patients can experience high failure rate of shunts which can lead to diminished quality of life and suffering from long-term neurologic deficits. In some instances, conventional shunt valve controls CSF outflow by total pressure within the ventricles. The conventional shunt's one-way pressure valve is set to relieve pressure from the ventricles based off of total pressure, where total pressure=hydrostatic pressure+(intracranial pressure (ICP)−intraabdominal pressure (IAP)). If the total pressure within the ventricles exceeds that of the conventional valve, the conventional valve will open. It will remain open unless the pressure drops below the set valve pressure. However, many events such as sneezing, coughing, straining from constipation, exercising, and standing up of the patient can cause changes in pressure, without increasing the production of the CSF. As a result, the conventional shunt valve can over-drain the CSF because it is pressure-based rather than matching the CSF production. Moreover, tissue contact could happen between the catheter tip and surrounding tissue because of the over-drainage. As such, the tissue can be pulled into the catheter holes and block the catheter.
Therefore, this disclosure provides a shunt valve with active outflow regulator. The valve according to this disclosure is capable of controlling the CSF outflow by regulating the resistance of the tubing which is independent of the intracranial pressure. Tissue contact can be attenuated with the valve that minimizes over-drainage by matching the CSF outflow to the physiologic CSF production. This valve offers protection against activity-based changes in pressure, and thus can improve patients' quality of life in the short term by preventing over-drainage induced headache and in the long term by reducing the shunt failure rate.
Moreover, other applications outside of hydrocephalus are also possible. For example, the valve provided by this disclosure can be used at downstream from proximal (ventricular) tip of a ventriculoperitoneal shunt, a ventriculoatrial shunt, a lumbarperitoneal shunt, or the like.
Referring to
The housing 102 is configured to accommodate the tubing 104, the regulating element 106, the actuator 108, and the control component. In some examples, the housing further includes an insulating element (not shown), configured to reduce heat conduction between the housing and an environment such as the ventricle. In some examples, since the valve can be implanted into the patient's brain, and the valve 100 may generate heat in use, the insulating element can inhibit the heat conduction from the valve 100 to the surrounding environment (such as brain ventricles). In some examples, the internal temperature needed for valve closure is 70° C. In some examples, the operating temperature for the valve can be 50-70° C. In some examples, the operating temperature for the valve can be 90-110° C. For examples, polyethylene which has a relatively low thermally conductivity of 0.33-0.5 W/m K can be used as the insulating element. As another example, polypropylene which has a relatively low thermally conductivity of 0.11 W/m K can be used as the insulating element.
In some examples, the housing 102 can further include a heat sink (not shown), configured to dissipate away the heat generated the valve 100, thereby decreasing of the temperature of the valve 100. Examples of heat sinks can include passive heat sinks, active heat sinks, metal heat sinks (such as aluminum heat sinks, copper heat sinks, or the like), heat sinks with coolant, or the like. Passive heat sinks are those that do not rely on forced air flow (fans). Active heat sinks have a powered device such as a fan or blower in close proximity to the heat exchanger surface.
The tubing 104 is configured to allow fluid flow therethrough. In some examples, biological fluid can flow through the tubing 104 such as cerebrospinal fluid (CSF) in brain tissue, blood in the circulatory system, and so on. In some examples, a first end 112 and a second end 114 of the tubing can connect to catheters such as a ventricular catheter, a distal catheter, or the like.
The regulating element 106 is arranged proximate to the tubing 104. In some examples, the regulating element 106 includes materials that are suitable to squeeze and/or release the tubing to regulate resistance to the fluid flowing through the tubing 104. The resistance is independent of intracranial pressure associated with a patient. For example, the regulating element 106 includes wax and at least one additive (such as graphite and the like). Additional details regarding the materials of the regulating element are described throughout this disclosure, such as in section (V).
The actuator 108 is configured to manipulate a parameter associated with the regulating element. In some examples, the parameter associated with the regulating element can be the temperature associated with the regulating element. The actuator 108 is arranged proximate to the regulating element. In some examples, the actuator 108 includes a temperature actuator such as a heating element. Note that other types of actuators can also be used in the valve 100 such as mechanical actuators, electro-mechanical actuators, or the like. In implementations, since the valve can be implanted into a brain of a patient, it is preferable that the actuator 108 is magnetic resonance imaging (MRI) compatible such that when the patient goes through an MRI procedure, the actuator 108 would not interfere with the procedure.
The sensor 110 is configured to sense the parameter associated with regulating element 106. In some examples, the sensor 110 includes a temperature sensor. In some instances, the sensor 110 is arranged proximate to the regulating element 106. Note that other types of sensors can be used to detect parameters associated with the fluid flowing through the valve 100, such as a flowrate sensor, or a pressure sensor, or the like. In some instances, sensor 110 is arranged proximate to the tubing 104 or inside the tubing 104.
The control component (not shown) is configured to communicate with other devices and to control the actuator 108. In some examples, the control component can communicate with the other devices via networks such as the Internet, a Mobile Telephone Network (MTN), Wi-Fi, a cellular network (e.g., 2G, 3G, 4G, 4G LTE, 5G, etc.), a mesh network, a Local Area Network (LAN), a Wide Area Network (WAN), a Virtual LAN (VLAN), a private network, short range wireless frequencies such as Bluetooth, and/or other various wired or wireless communication technologies. For example, the control component can communicate with a data processing device (such as a wearable device) to receive data or instructions useful for controlling the valve 100.
The control component can control the actuator 108 to actuate the regulating element. For example, the control component can receive a desired value (such as a desired temperature) from other devices (such as the data processing device). The sensor 110 can sense the parameter (such as the temperature) associated with the regulating element 106. The control component can determine that the parameter (such as the temperature) associated with the regulating element 106 is within a threshold range of the desired value (such as the desired temperature). The control component can stop the actuator 108 from actuating upon determining that the parameter (such as the temperature) associated with the regulating element 106 is within a threshold range of the desired value (such as the desired temperature). The threshold range can be set arbitrarily.
The valve 100 further includes a power unit (not shown), configured to provide power for the valve 100. In some instances, the power unit comprises a Lithium battery. In some examples, the power unit can be percutaneous recharged.
Referring to
Referring to
The housing 102″ is configured to accommodate the tubing 104″, the regulating element 106″, the actuator 108″, and the control component. In some examples, the housing further includes an insulating element (not shown), configured to reduce heat conduction between the housing and an environment such as the ventricle. In some examples, since the valve can be implanted into the patient's brain, and the valve 100″ may generate heat in use, the insulating element can inhibit the heat conduction from the valve 100″ to the surrounding environment (such as brain ventricles). In some examples, the internal temperature needed for valve closure is 70° C. For examples, polyethylene which has a relatively low thermally conductivity of 0.33-0.5 W/m K can be used as the insulating element. As another example, polypropylene which has a relatively low thermally conductivity of 0.11 W/m K can be used as the insulating element.
The tubing 104″ is configured to allow fluid flow therethrough. In some examples, biological fluid can flow through the tubing 104″ such as cerebrospinal fluid (CSF) in brain tissue, blood in the circulatory system, and so on. In some examples, a first end 112″ and a second end 114″ of the tubing can connect to catheters such as a ventricular catheter, a distal catheter, or the like.
The regulating element 106″ is arranged proximate to the tubing 104″. In some examples, the regulating element 106″ includes materials that are suitable to squeeze and/or release the tubing to regulate resistance to the fluid flowing through the tubing 104″. The resistance is independent of intracranial pressure associated with a patient. For example, the regulating element 106″ includes wax and at least one additive (such as graphite and the like). Additional details regarding the materials of the regulating element are described throughout this disclosure, such as in section (V).
The actuator 108″ is configured to manipulate a parameter associated with the regulating element. In some examples, the parameter associated with the regulating element can be the temperature associated with the regulating element. The actuator 108″ is arranged proximate to the regulating element. In some examples, the actuator 108″ includes a temperature actuator such as a heating element. Note that other types of actuators can also be used in the valve 100″ such as mechanical actuators, electro-mechanical actuators, or the like. In implementations, since the valve can be implanted into a brain of a patient, it is preferable that the actuator 108″ is magnetic resonance imaging (MRI) compatible such that when the patient goes through an MRI procedure, the actuator 108″ would not interfere with the procedure.
The sensor 110″ is configured to sense the parameter associated with regulating element 106″. In some examples, the sensor 110″ includes a temperature sensor. In some instances, the sensor 110″ is arranged proximate to the regulating element 106″. Note that other types of sensors can be used to detect parameters associated with the fluid flowing through the valve 100″, such as a flowrate sensor, or a pressure sensor, or the like. In some instances, sensor 110″ is arranged proximate to the tubing 104″ or inside the tubing 104″.
The control component (not shown) is configured to communicate with other devices and to control the actuator 108″. In some examples, the control component can communicate with the other devices via networks such as the Internet, a Mobile Telephone Network (MTN), Wi-Fi, a cellular network (e.g., 2G, 3G, 4G, 4G LTE, 5G, etc.), a mesh network, a Local Area Network (LAN), a Wide Area Network (WAN), a Virtual LAN (VLAN), a private network, short range wireless frequencies such as Bluetooth, and/or other various wired or wireless communication technologies. For example, the control component can communicate with a data processing device (such as a wearable device) to receive data or instructions useful for controlling the valve 100″.
The control component can control the actuator 108″ to actuate the regulating element. For example, the control component can receive a desired value (such as a desired temperature) from other devices (such as the data processing device). The sensor 110″ can sense the parameter (such as the temperature) associated with the regulating element 106″. The control component can determine that the parameter (such as the temperature) associated with the regulating element 106″ is within a threshold range of the desired value (such as the desired temperature). The control component can stop the actuator 108″ from actuating upon determining that the parameter (such as the temperature) associated with the regulating element 106″ is within a threshold range of the desired value (such as the desired temperature). The threshold range can be set arbitrarily.
The valve 100″ further includes a power unit (not shown), configured to provide power for the valve 100″. In some instances, the power unit comprises a Lithium battery. In some examples, the power unit can be percutaneous recharged.
As an example, the tubing 104″ can be quizzed due to the deformation of the regulating element 106″. Similar to the valve 100, the valve 100″ receives a desired value (such as a desired temperature) from a data processing device. Then, the control component (not shown) controls the actuator 108″ (such as a heating element) to heat the regulating element 106″ to the desired value. As an example, the regulating element 106″ includes materials (such as wax and additives) that melts when the temperature increases and compresses the tubing 104″. As such, the fluid flow (such as CSF flow) through the tubing 104″ is reduced. The sensor 110″ can sense the temperature associated with the regulating element 106″. When the control component determines that the temperature associated with the regulating element 106″ is within a threshold range of the desired value (such as the desired temperature), the control component can stop the actuator 108″ from heating the regulating element 106.
This disclosure also provides a system including the valve for regulating biological fluid flow as described above. In some instances, the system can be used to treat hydrocephalous patients. At least a part of the system can be implanted into a patient's brain. Such a system offers protection against activity-based changes in pressure, and is specifically engineered to improve patients' quality of life in the short term by stopping drainage induced headache and in the long term by reducing the shunt failure rate. In some instances, the system can also be used to conduct in vitro experiments, to collect analytic data, to validate shunt valve functions, etc.
The valve 202 for regulating fluid flow can be the same as the valve 100, the valve 100′, and/or the valve 100″ as described with respect to
The valve 202 includes a housing 212, a tubing 214, a regulating element 216, an actuator 218, a sensor 220, and a control component 222. As described herein, the structure of the valve 202 is exemplary, and the valve 202 can further include other components.
The housing 212 is configured to accommodate the tubing 214, the regulating element 216, the actuator 218, and the control component 222. In some examples, the housing further includes an insulating element (not shown), configured to reduce heat conduction between the housing and an environment such as the ventricle. In some examples, since the valve can be implanted into the patient's brain, and the valve 202 may generate heat in use, the insulating element can inhibit the heat conduction from the valve 202 to the surrounding environment (such as brain ventricles). In some examples, the internal temperature needed for valve closure is 70 ° C. For examples, polyethylene which has a relatively low thermally conductivity of 0.33-0.5 W/m K can be used as the insulating element. As another example, polypropylene which has a relatively low thermally conductivity of 0.11 W/m K can be used as the insulating element. Note that any material that is suitable for inhibiting the heat conduction from the valve 202 to the surrounding environment (such as brain ventricles) can be used as the insulating element.
The tubing 214 is configured to allow fluid flow therethrough. In some examples, biological fluid can flow through the tubing 214 such as cerebrospinal fluid (CSF) in brain tissue, blood in the circulatory system, and so on. In some examples, the tubing 214 can connect to catheters such as a ventricular catheter, a distal catheter, or the like.
The regulating element 216 is arranged proximate to the tubing 214. In some examples, the regulating element 216 includes materials that are suitable to squeeze and/or release the tubing to regulate resistance to the fluid flowing through the tubing 214. The resistance is independent of intracranial pressure associated with a patient. For example, the regulating element 216 includes wax and at least one additive (such as graphite and the like). Additional details regarding the materials of the regulating element are described throughout this disclosure, such as in section (V).
The actuator 218 is configured to manipulate a parameter associated with the regulating element 216. In some examples, the parameter associated with the regulating element 216 can be the temperature associated with the regulating element 216. The actuator 218 is arranged proximate to the regulating element 216. In some examples, the actuator 218 includes a temperature actuator such as a heating element. Note that other types of actuators can also be used in the valve 202 such as mechanical actuators, electro-mechanical actuators, or the like. In implementations, since the valve 202 can be implanted into a brain of a patient, it is preferable that the actuator 118 is magnetic resonance imaging (MRI) compatible such that when the patient goes through an MRI procedure, the actuator 118 would not interfere with the procedure.
The sensor 220 is configured to sense the parameter associated with regulating element 216. In some examples, the sensor 220 includes a temperature sensor. In some instances, the sensor 220 is arranged proximate to the regulating element 216. Note that other types of sensors can be used to detect parameters associated with the fluid flowing through the valve 202, such as a flowrate sensor, or a pressure sensor, or the like. In some instances, sensor 220 is arranged proximate to the tubing 214 or inside the tubing 214.
The control component 222 is configured to communicate with other devices and to control the actuator 218. In some examples, the control component 222 can communicate with the other devices via network(s) 210. For example, the control component 222 can communicate with the data processing device (such as a wearable device) 204 to receive data or instructions useful for controlling the valve 202.
The control component 222 can control the actuator 218 to actuate the regulating element 216. For example, the control component 222 can receive a desired value (such as a desired temperature) from the data processing device 204. The sensor 220 can sense the parameter (such as the temperature) associated with the regulating element 216. The control component 222 can determine that the parameter (such as the temperature) associated with the regulating element 216 is within a threshold range of the desired value (such as the desired temperature). The control component 222 can stop the actuator 218 from actuating upon determining that the parameter (such as the temperature) associated with the regulating element 216 is within a threshold range of the desired value (such as the desired temperature). The threshold range can be set arbitrarily. As an example, the regulating element 216 includes materials (such as wax and additives) that melts when the temperature increases and compresses the tubing 214. As such, the fluid flow (such as CSF flow) through the tubing 214 is reduced. The sensor 220 can keep sensing the temperature associated with the regulating element 216. When the control component 222 determines that the temperature associated with the regulating element 216 is within a threshold range of the desired value (such as the desired temperature), the control component 222 can stop the actuator 218 from heating the regulating element 106.
The valve 202 further includes a power unit 224, configured to provide power for the valve 202. In some instances, the power unit 224 comprises a Lithium battery. In some examples, the power unit 224 can be percutaneous recharged.
The control component 222 includes one or more processors 226, a memory 228, a communication component 230. The processor(s) 226 can be a single processing unit or a number of units, each of which could include multiple different processing units. The processor(s) 00 can include a microprocessor, a microcomputer, a microcontroller, a digital signal processor, a central processing unit (CPU), a graphics processing unit (GPU), a security processor etc. Alternatively, or in addition, some or all of the techniques described herein can be performed, at least in part, by one or more hardware logic components. For example, and without limitation, illustrative types of hardware logic components that can be used include a Field-Programmable Gate Array (FPGA), an Application-Specific Integrated Circuit (ASIC), an Application-Specific Standard Products (ASSP), a state machine, a Complex Programmable Logic Device (CPLD), pulse counters, resistor/coil readers, other logic circuitry, a system on chip (SoC), and/or any other devices that perform operations based on instructions. Among other capabilities, the processor(s) 226 can be configured to fetch and execute computer-readable instructions stored in the memory.
The memory 228 can include one or a combination of computer-readable media. As used herein, “computer-readable media” includes computer storage media and communication media. Computer storage media includes volatile and non-volatile, removable and non-removable media implemented in any method or technology for storage of information, such as computer-readable instructions, data structures, program modules, or other data. Computer storage media includes, but is not limited to, Phase Change Memory (PRAM), Static Random-Access Memory (SRAM), Dynamic Random-Access Memory (DRAM), other types of Random-Access Memory (RAM), Read Only Memory (ROM), Electrically Erasable Programmable ROM (EEPROM), flash memory or other memory technology, Compact Disk ROM (CD-ROM), Digital Versatile Disks (DVD) or other optical storage, magnetic cassettes, magnetic tape, magnetic disk storage or other magnetic storage devices, or any other medium that can be used to store information for access by a computing device. In contrast, communication media includes computer-readable instructions, data structures, program modules, or other data in a modulated data signal, such as a carrier wave. As defined herein, computer storage media does not include communication media.
The memory 228 can include an operating system configured to manage hardware and services for the benefit of other components and devices.
The communication component 230 is configured to communicate with other devices (e.g., in the data processing device 204, the terminal device 206, the server(s) 208, and so on) the network(s) 210. For example, the communication component 230 can perform compression, encryption, and/or formatting of the data received and/or generated by the sensors 236. In some embodiments, the communication component 230 can transmit data using one or more protocols or languages, such as an extensible markup language (XML), Modbus, HTTP, HTTPS, USB, etc.
The data processing device 204 is configured to collect one or more biometric indicators associated with a patient. In some examples, the one or more biometric indicators associated with the patient include a heart rate, a blood pressure, a posture indicator, an exercise indicator, and/or an endogenous brain pressure. In some examples, data processing device 204 includes, but is not limited to, smart watches, smart accessories (e.g., smart rings, smart wristbands, smart pins, smart bracelets, or the like), body-mounted sensors, fitness trackers, smart clothing (e.g., smart shirt, smart pants, smart belt, or the like), smart headband, smart headsets, smart footwears, smart glasses, or the like.
The data processing device 204 includes one or more processors 232, a memory 234, one or more sensors 236, and a communication component 238. The processor(s) 232, the memory 234, and the communication component 238 can be implemented in the same manner as the processor(s) 226, the memory 228, and the communication component 230.
The sensor(s) 236 include a heart rate sensor 240, a blood pressure sensor 242, an exercise sensor 244, endogenous brain pressure sensor 246 (such as a telemetric Intracranial pressure sensors), and other sensors suitable for detecting biometric indicators associated with the patient.
The data processing device 204 is further configured to calculate an estimated fluid production rate based on the one or more biometric indicators associated with the patient. The memory 234 includes a calculation component 248 storing computer-readable instructions executable by one or more processors, that when executed by the one or more processors, causes the one or more processors to perform acts. For example, the calculation component 248 can implement algorithms to calculate an estimated fluid production rate based on the one or more biometric indicators associated with the patient. The calculation component 248 can implement algorithms to calculate a desired value based on the estimated fluid production rate. Additional details of algorithms are provided throughout this disclosure such as in section (VI).
The data processing device 204 is further configured to send the desired value to the control component 222 of the valve 202.
The terminal device 206 includes one or more processor(s) 250, a memory 252, and a communication component 254, each of which can be implemented similar to the processor(s) 226, the memory 228, and/or the communication component 230 of the control component 222 of the valve 202. Furthermore, the terminal device 206 can include a display component 256 configured to display a graphical user interface on the terminal device 206.
The terminal device 206 can run one or more applications (Apps) to facilitate user interaction via the user interface and/or collect data. In some examples, the terminal device 206 can generate reports and present the reports via the user interface. For example, the reports can include information like the patient identification (ID), shunt ID, biometric indicators associated with the patient, settings associated with the valve, or the like. In some examples, the terminal device 206 can provide interactive functionality (e.g., input boxes, dropdown lists, selectable fields, or the like) via the user interface to allow the user to change settings of the valve.
The terminal device 206 can perform security functions. For example, terminal device 206 can be configured to perform multi-factor authentication (such as two-factor authentication, or the like) when a user is logging in to the App. Multi-factor authentication is an authentication method in which a user is granted access to a website or application after successfully presenting two or more pieces of evidence to an authentication mechanism such as passwords, security question answers, verification codes, or the like.
A user (e.g., a patient, a care giver, a physician, or the like) can interact with the terminal device 206 via the user interface to perform a variety of operations. In some examples, the user can review reports generated by the terminal device 206, the biometric indicators provided by the data processing device 204, or the like. In some examples, the user can make changes to the settings of the valve 202 via the user interface.
The server(s) 208 is configured to perform back-end control over other devices, such as providing security functions, updating software and/or algorithms, or the like. In some examples, the server(s) 208 can include computing devices that operate within a network service (e.g., a cloud service), or can form a mesh network, etc. In some examples, the servers 208 is configured to communicate with the terminal device to perform security function. For example, the servers 208 can store information like user ID, shunt ID, authentication information (e.g., passcodes, security questions and answers, fingerprint features, facial features, or the like). When the user is logging in an App on the terminal device 206, the terminal device 206 can communicate with the server(s) 208 to get the authentication information to verify the user's identity.
The servers 208 is configured to update software and/or algorithms on different devices such as the control component, the data processing device 00, the terminal device 00, or the like. In implementations, the software and/or algorithms can be improved to provide more accurate calculation of the CSF production, more precise control over the value, or the like. Therefore, it may be beneficial to update the software and/or algorithms constantly.
The techniques discussed above can be implemented in hardware, software, or a combination thereof. In the context of software, operations represent computer-executable instructions stored on one or more computer-readable storage media that, when executed by one or more processors, configure a device to perform the recited operations. Generally, computer-executable instructions include routines, programs, objects, components, data structures, and the like that perform particular functions or implement particular abstract data types.
Methods and operations described herein can be used to control the system as described above to regulate biological fluid flow (e.g., CSF, or the like). In some examples, methods and operations described herein can be implemented to match the CSF outflow of a valve system to CSF inflow (CSF production) associated with a patient. Activity-based changes in pressure such as a sneezing, coughing, and standing up will not impact the outflow rate of the valve. In some examples, methods and operations described herein can be used to treat hydrocephalous patients, improving patients' quality of life in the short term by stopping drainage induced headache and in the long term by reducing the shunt failure rate.
The example processes (e.g., in
Referring to
At 304, operations include calculating an estimated fluid production rate based on the one or more biometric indicators associated with the patient.
At 306, operations include calculating a desired value based on the estimated fluid production rate. In some examples, the desired value comprises a desired temperature.
At 308, operations include communicating with a valve to regulate fluid flowing therethrough based on the desired value. The valve can correspond to the valve 100, the valve 100′, and the valve 100″ described with respect to
Referring to
At 312, operations include controlling, by the control component of the valve, the actuator to actuate the regulating element. In some examples, the regulating element comprises wax and at least one additive. In some examples, the actuator comprises at least one of a temperature actuator, a mechanical actuator, an electro mechanical actuator. In implementations, since the valve can be implanted into a brain of a patient, it is preferable that the actuator is magnetic resonance imaging (MRI) compatible such that when the patient goes through an MRI procedure, the actuator would not interfere with the procedure. In some examples, the actuator can manipulate the regulating element to regulate resistance to the fluid flowing through the tubing. In some examples, the resistance is independent of intracranial pressure associated with the patient.
At 314, operations include sensing, by the sensor, a parameter associated with the regulating element. In some examples, the parameter associated with the regulating element is temperature associated with the regulating element.
At 316, operations include determining, by the control component of the valve, that the parameter associated with the regulating element is within a threshold range of the desired value.
At 318, operations include stopping, by the control component of the valve, the actuator upon determining that the parameter associated with the regulating element is within a threshold range of the desired value.
As described herein, the reregulating element includes materials that are suitable to squeeze and/or release the tubing to regulate resistance to the fluid flowing through the tubing. For example, the regulating element includes wax and at least one additive (such as graphite and the like). These additives can improve thermal conductivity of the wax. They may not have a noticeable impact on the melting temperature of the wax. Table 1 shows examples of additives, and their proportion by mass.
Note that the examples shown above are illustrative rather than limiting. There can be other types of additives. Moreover, the proportions of additives can various based on actual needs.
As described herein, systems and method described herein can match CSF outflow to CSF inflow (CSF production). A shunt with a valve according to this disclosure can regulate the CSF outflow for an individual patient and live over time. Activity-based changes in pressure (such as a sneezing, coughing, straining from constipation, exercising, and standing up) will not impact the outflow rate of the valve. Systems and method described herein can improve patients' quality of life in the short term by stopping drainage induced headache and in the long term by reducing the shunt failure rate. Algorithm for estimating CSF production can be used to control the valve in accordance with this disclosure. In some examples, the algorithm for estimating CSF production can include the following: Cerebral blood flow->CSF inflow (production).
The cerebral blood flow can be used to estimate CSF inflow (production). At baseline, Baghbani assumption is used that cerebral blood flow is to CSF production just as electrical voltage is to voltage with resistors. CSF production is cerebral blood flow with resistance due to capillaries, tissue compliance, arterial resistance, venous resistance, resistance from arachnoid, granulations.
CSF production rate is a function of mean arterial pressure (MAP). CSF production rate and intracranial pressure (ICP) are directly dependent on blood pressure. However, normal patients and hydrocephalic patients have different relationship of the CSF production rate with the blood pressure.
CSF inflownormal->CSF inflowhydrocephalus
The normal CSF inflow rate is used to estimate the hydrocephalous CSF inflow rate. CSF production (based on calculated and recorded resistances) is used as input to modify based on hydrocephalic bulk flow rate, flow amplitude, ICP in mild, moderate, severe hydrocephalus (Silverberg 2002, Juhler 2020, others).
CSF inflowhydrocephalus->CSF outflowhydrocephalus
The CSF inflow can be used to determine the CSF outflow of the valve.
As an example, an average CSF production rate can be 0.3-0.6 milliliter (mL)/min for normal people, 0.4±0.13 mL/min for acute hydrocephalus to moderate/mild hydrocephalus patients, and 0.25±0.08 mL/min for chronic hydrocephalus to severe hydrocephalus patients. (Silverberg et al., 2002).
Based on nine studies, reviewed by M Czosnyka and M Juhler et al., some intracranial pressures are: (1) supine position with a mean ICP of 8.6 mmHg (standard deviation (SD) 4.7, reference interval 0.9 to 16.3 mmHg), (2) upright position with a mean ICP of 1.0 mmHg (SD 4.3, reference interval 5.9 to 8.3 mmHg), (3) continuous daytime measurement with a mean ICP of 0.1 mmHg (SD 7.4, reference interval 12.0 to 12.2 mmHg), and (4) continuous nighttime measurement with a mean ICP of 6.3 mmHg (SD 13.3, reference interval 15.8 to 28.2).
CSF outflowhydrocephalus->Temperature
The CSF outflow of the valve can be used to calculate the desired temperature of the regulating element.
Also provided are kits useful for treating hydrocephalus patients. An example of the kit includes one or more of: a wearable device, a shunt valve which can be sterile and vacuum sealed, and a lithium battery pack which is sterile, vacuum sealed.
More generally, kits can include instructions, for example written instructions, on how to use the material(s) therein. Material(s) can be, for example, any substance, composition, polynucleotide, solution, etc., herein or in any patent, patent application publication, reference, or article that is incorporated by reference.
A kit can include a device as described herein, and optionally additional components such as buffers, reagents, and instructions for carrying out the methods described herein. The choice of buffers and reagents will depend on the particular application, e.g., setting of the assay (point-of-care, research, clinical), analyte(s) to be assayed, the detection moiety used, the detection system used, etc.
The kit can also include informational material, which can be descriptive, instructional, marketing, or other material that relates to the methods described herein and/or the use of the devices for the methods described herein. In embodiments, the informational material can include information about production of the device, physical properties of the device, date of expiration, batch or production site information, and so forth.
Provided herein is an improved catheter that can be used to treat hydrocephalus patients. The shape of the catheter and/or the sizes of the plurality of holes are configured to regulate one or more parameters of the fluid flowing through the catheter holes and/or the catheter. In some examples, the one or more parameters include at least one of a flow velocity, a shear rate, or a shear stress of the fluid flowing through the catheter holes and the catheter.
CSF shunt implantation is the most common treatment option for hydrocephalus, yet shunts are plagued by high failure rates: 40% in the first year, and 90% in the first 10 years. Hydrocephalus treatment fails most often because the outflow pathway created by the holes in the shunt's ventricular catheter becomes obstructed with tissue. Up until a few years ago, the most significant studies on shunt failure revealed that shunts most commonly harbor inflammatory glia, lymphocytic inflammation, and foreign body giant cells. Our work shows that the tissue occluding shunts is predominately composed of astrocytes and macrophages, has only sparse microglia, has more activated cells on obstructed shunts than unobstructed, stain positive for proliferative markers, has reactivity that follows the flow, and predominately obstructs shunts as large tissue masses.
Recent long-term in vivo data collected in our lab indicate that inflammatory astrocytes are ubiquitous on all shunts. Inflammatory astrocytes make up more than 21% of cells bound to obstructed shunts, and of the occluded masses blocking ventricular catheter holes, a vast majority of the cells are astrocytes, and their number and reactivity peak on failed shunts. Data suggests that inflammatory astrocyte activation on shunts is correlated to a change in flow rate through the shunt holes and indirectly, the shear rate through these holes (Harris et al., Childs Nerv. Syst., 2011; doi.org/10.1007/s00381-011-1430-0; Harris et al., Exp. Neurol. 222:204-210, 2010; Harris et al., J. Biomed. Mater. Res. A 97:433-440, 2011; Harris et al., Fluids Barriers CNS. 2015, doi.org/10.1186/s12987-015-0023-9). Astrocytes have an increased attachment propensity in vitro with increasing flow-induced shear stress. Astrocyte markers have been observed in obstructive masses to be co-localized with proliferative markers, indicating that astrocytes are active on the shunt surface: they produce inflammatory cytokine IL-6 and proliferate.
Most of the CSF volume flows through the proximal holes of the shunt's ventricular catheter, i.e., holes located furthest from the tip of the shunt with less resistance to flow. Computational fluid dynamics simulations have shown that in CSF shunts, the wall shear stress at the proximal holes is greater than 0.5 dyne/cm2 (Harris et al., Childs Nerv. Syst., 2011; doi.org/10.1007/s00381-011-1430-0; Lin et al., J. Neurosurg. 99:426-431, 2003; Lee et al., J. R. Soc. Interface 17, 20190884, 2020). This fact increases the shear stress at the proximal segment and is a key driver of a dense glial scar formation around devices causing failure via obstruction (Lin et al., J. Neurosurg. 99:426-431, 2003; Giménez et al., Philos. Trans. A Math. Phys. Eng. Sci. 375:20160294, 2017; Marimuthu et al., Anal. Biochem. 437:161-163, 2013).
CSF shunts removed for obstruction show occlusions to occur most often at the proximal holes (holes located furthest from the tip) with the highest flow (Kestle et al., Pediatr. Neurosurg. 33:230-236, 2000). These observations led to a suggestion that shunt geometry with a more uniform flow rate distribution among the shunt's inlet holes would reduce the obstruction occurring at the critical proximal inlet holes, thereby reducing shunt failure rates. As an example of an existing shunt catheter, the Rivulet® (Medtronic Neurosurgery) shunt was developed with a design consisting of decreasing hole diameters from the distal to proximal end (Lin et al., J. Neurosurg. 99:426-431, 2003). However, shear stress will be higher in the proximal holes of these shunts. Based on the fluid shear stress equation of T=μdu/dy, where μ is dynamic viscosity, and du/dy is the gradient of velocity in the direction perpendicular to the flow, since the gradient velocity of the decreasing hole diameters is higher, shear stress will be higher for the proximal holes. Based on our hypothesis and other reports of the correlation between increased shear stress along the shunt/CSF interface to result in increased occlusion (Harris et al., Childs Nerv. Syst., 2011; doi.org/10.1007/s00381-011-1430-0; Harris et al., Exp. Neurol. 222:204-210, 2010; Harris et al., J. Biomed. Mater. Res. A 97:433-440, 2011; Galarza et al., Child' Nerv. Syst. 34:267-276, 2018; Weisenberg et al., J. Neurosurg. 2017, doi.org/10.3171/2017.5.JNS161882), it may be necessary to improve shunt design to decrease shear stress through all its holes or at best the proximal holes.
In implementations, hydrocephalus shunts come in various shapes and designs.
Among the multiple holes, the quantity of fluid increases as the fluid flows closer to the holes far from the tip end 802 (such as the holes 804′), which means the velocity of the fluid needs to increase. Increase in fluid velocity results in a reduction in pressure. A pressure gradient is created in the lumen 804 as the result of the flow pattern inside the lumen 804 of the catheter 800. This results in preferential flow through the holes with the highest fluid velocity (the lowest pressure). That is, the holes that are farthest from the tip end 802 (such as the holes 804′) can have more fluid flow therethrough than other holes. As such, the blockage can occur more often around the holes (such as the holes 804′) furthest from the catheter tip.
Therefore, there is a need to reduce the pressure gradient by maintaining a constant low velocity inside the lumen which can result in flow through all the catheter holes and can introduce additional pathways for fluid to go through. This can be done by optimizing the geometry of the catheter.
Referring to
As shown in
In some examples, the ratio of the first diameter 912 to the second diameter 914 can be between 1:3 and 3:5. In some examples, instead of having a linear sloped sidewall, the first portion 908 can have a curved sidewall. In some examples, the first portion 908 can have a step-wise sidewall.
Referring to
As an example, referring to
In some examples, the first hole 926, the second hole 928, the third hole 930, the fourth hole 932, the fifth hole 934, the sixth hole 936, the seventh hole 938, and an eighth hole 940 can be placed with constant intervals. In some examples, the first hole 926, the second hole 928, the third hole 930, the fourth hole 932, the fifth hole 934, the sixth hole 936, the seventh hole 938, and an eighth hole 940 can be placed with various intervals. In some examples, the intervals between the holes can be between 0.5 mm to 4 mm. Examples of the intervals can include 3.7 mm, 3.45 mm, 1.1 mm, 0.8 mm, or the like.
Though
As described herein, the common treatment for hydrocephalus patients is CSF drainage by shunting. A shunt system can be implemented into a patient's brain by surgical insertion to treat hydrocephalous patients.
This disclosure further provides a shunt system comprising the catheter for shunting biological fluid flow as described above. Such a shunt system offers a more uniform flow rate distribution among the inlet holes of the catheter, and would reduce the obstruction occurring at the inlet holes, thereby reducing shunt failure rates. The shunt system is can improve patients' quality of life by reducing the shunt failure rate. In some instances, the system can also be used to conduct in vitro experiments, collect analytic data, validate shunt functions, etc.
The ventricle catheter 1102 can be implemented into a patient's brain ventricle. The ventricle catheter 1102 includes multiple holes 1108 that allow biological fluid flowthrough into the ventricle catheter 1102. The ventricle catheter 1102 can be configured in the same way as the catheter 300 described with respect to
The valve 1104 is configured to regulate the biological fluid (such as CSF) flowing therethrough. In some examples, the valve 1104 can be opened and closed. In some examples, the valve 1104 can regulate the flow rate of the biological fluid. In some examples, the valve 1104 can be a conventional valve. In some examples, the valve 1104 can be a solid state valve described throughout this application.
The distal catheter 1106 is configured to introduce the biological fluid to another part of the body, such as the abdomen through the peritoneum of the patient. As such, excess CSF of the hydrocephalous patient can be drained from the brain to another part of the body where CSF can be more easily absorbed.
Example shunts are composed of two polydimethylsiloxane (PDMS, silicone) shunt catheters connected by a pressure valve. One catheter remains in the ventricles, while the other is tunneled subcutaneously into the peritoneum or atrium.
Also provided are kits useful for treating hydrocephalus patients. An example of the kit includes one or more of: a ventricular catheter, a shunt valve, and a distal catheter, each of which is sterile, and vacuum sealed. The ventricular catheter can be configured in the same way as the catheter 900 described with respect to
More generally, kits can include instructions, for example, written instructions, on how to use the material(s) therein. Material(s) can be, for example, any substance, composition, solution, etc., herein or in any patent, patent application publication, reference, or article that is incorporated by reference.
A kit can include a shunt system as described herein, and optionally additional components such as buffers, reagents, and instructions for carrying out the methods described herein. The choice of buffers and reagents will depend on the particular application, e.g., setting of the assay (point-of-care, research, clinical), analyte(s) to be assayed, the detection moiety used, the detection system used, etc.
The kit can also include informational material, which can be descriptive, instructional, marketing, or other material that relates to the methods described herein and/or the use of the devices for the methods described herein. In embodiments, the informational material can include information about the production of the device, physical properties of the device, date of expiration, batch or production site information, and so forth.
As described herein, catheters and systems including the same were developed to reduce the pressure gradient by maintaining a constant low velocity inside the catheter. Such a system could facilitate flow through all the catheter holes and introduce additional pathways for fluid to go through. The shunt geometry was designed to facilitate a more uniform flow rate distribution among the shunt's inlet holes which would reduce the obstruction at the inlet holes, thereby reducing shunt failure rates. To validate whether the techniques described herein could work as expected, simulations were conducted, and data were collected.
In some examples, the simulations were conducted using commercial software such as ANSYS, COMSOL, or the like.
The Example(s) and Exemplary Clauses below are included to demonstrate particular embodiments of the disclosure. Those of ordinary skill in the art should recognize in light of the present disclosure that many changes can be made to the specific embodiments disclosed herein and still obtain a like or similar result without departing from the spirit and scope of the disclosure.
Shunt valves and systems including the same were developed to regulating biological fluid flow such as CSF flow in a patient's brain. Such a system offered protection against activity-based changes in pressure, and was specifically engineered to improve patients' quality of life in the short term by stopping drainage induced headache and in the long term by reducing the shunt failure rate. To validate whether techniques described herein could work as expected, an in vitro system was established, and data were collected.
The in vitro system 400 was configured to include a chamber 402, a pump 404, a tube 406, a reservoir 408, a meter 410. The pump 404 was configured to move the fluid through the tube 406 to the chamber 402. In some examples, the pump 404 was a peristatic pump. Note that other types of pumps can be used to push the fluid circulating in the vitro system 400, and this disclosure is not limited thereto. The reservoir 408 was configured to store the fluid. The tube 406 was connected between the chamber 402, the pump 404, the reservoir 408, and the meter 410. The meter 410 was configured to measure characteristics associated with the fluid such as the flowrate associated with the fluid, the frequency associated with the fluid, or the like. Note that other parameters/characteristics associated with the fluid can be measured by the meter 410.
In implementations, a catheter 412 to be tested and a valve 414 to be tested were placed in the chamber 402. The valve 414 was arranged around the catheter 412. The valve 414 was configured to regulate the fluid flowing through the catheter 412. In some examples, the valve 414 can correspond to the valve 100, the valve 100′, and/or the valve 100″ as described with respect to
As described above, conventional shunt valve controlled CSF outflow by total pressure within the ventricles. The conventional shunt's one-way pressure valve was set to relieve pressure from the ventricles based off of total pressure, where total pressure=hydrostatic pressure+(intracranial pressure (ICP)−intraabdominal pressure (IAP)). If the total pressure within the ventricles exceeds that of the conventional valve, the conventional valve will open. It will remain open unless the pressure drops below the set valve pressure. However, many events such as sneezing, coughing, straining from constipation, exercising, and standing up of the patient can cause changes in pressure, without increasing the production of the CSF. As a result, the conventional shunt valve can over-drain the CSF because it was pressure-based rather than matching the CSF production.
Referring to
Graph 504 shows the flow rate change of a conventional shunt valve. The horizontal axis in graph 504 represents relative time in seconds. The vertical axis in graph 504 represents the flow rate in mL/min. In graph 504, line 508 represents the CSF production which was 0.3 mL/min in this example. Plot 510 represents the flow rate of the conventional shunt valve along time. As shown in graph 504, though the patient changed position from standing up to laying down at the time of 300 seconds, the CSF production (see 506) did not change. However, at the time of 300 seconds the flow rate (see 510) of the conventional shunt valve changed suddenly to match the pressure change (see 506). Therefore, over-drainage occurs during the period 0-300 seconds.
Referring to
Graph 514 shows the flow rate change of a valve according to this disclosure. The horizontal axis in graph 514 represents relative time in seconds. The vertical axis in graph 514 represents the flow rate in mL/min. It can be seen that the flow rate of the valve according to this disclosure did not change because of the pressure change at the time of 300 seconds. Line 516 shows that CSF production which was 0.3 mL/min in this example. Though the patient changed her position from standing up to laying down at the time of 300 seconds, the CSF production (see 516) did not change. It can be seen that the flow rate of the valve according to this disclosure matched the CSF production (see 516) despite the pressure change at the time of 300 seconds. As pressure changed, the flow rate of the valve according to this disclosure did not change, because it was dependent on temperature of the regulating element rather than the pressure. Therefore, there was no over-drainage due to the position change of the patient.
The valve according to this disclosure was capable of controlling the CSF outflow by regulating the resistance of the tubing which was independent of the intracranial pressure. Tissue contact could be attenuated with the valve that minimizes over-drainage by matching the CSF outflow to the physiologic CSF production. The valve offered protection against activity-based changes in pressure, and thus could improve patients' quality of life in the short term by preventing over-drainage induced headache and in the long term by reducing the shunt failure rate.
Note that the position change of the patient discussed here was an example, and how the valve performs in other situations such as exercising (such as walking, running, lifting, or the like), sneezing, coughing, straining from constipation can be tested and the results incorporated into embodiments of the system.
Specific descriptions provided herein and in the herewith filed documents are included to demonstrate particular embodiments of the disclosure. Those of ordinary skill in the art should recognize in light of the present disclosure that many changes can be made to the specific embodiments disclosed herein and still obtain a like or similar result without departing from the spirit and scope of the disclosure.
As will be understood by one of ordinary skill in the art, each embodiment disclosed herein can comprise, consist essentially of or consist of its particular stated element, step, ingredient or component. Thus, the terms “include” or “including” should be interpreted to recite: “comprise, consist of, or consist essentially of.” The transition term “comprise” or “comprises” means includes, but is not limited to, and allows for the inclusion of unspecified elements, steps, ingredients, or components, even in major amounts. The transitional phrase “consisting of” excludes any element, step, ingredient, or component not specified. The transition phrase “consisting essentially of” limits the scope of the embodiment to the specified elements, steps, ingredients or components and to those that do not materially affect the embodiment.
Unless otherwise indicated, all numbers expressing quantities of ingredients, properties such as molecular weight, reaction conditions, and so forth used in the specification and claims are to be understood as being modified in all instances by the term “about.” Accordingly, unless indicated to the contrary, the numerical parameters set forth in the specification and attached claims are approximations that may vary depending upon the desired properties sought to be obtained by the present invention. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. When further clarity is required, the term “about” has the meaning reasonably ascribed to it by a person skilled in the art when used in conjunction with a stated numerical value or range, i.e. denoting somewhat more or somewhat less than the stated value or range, to within a range of ±20% of the stated value; ±19% of the stated value; ±18% of the stated value; ±17% of the stated value; ±16% of the stated value; ±15% of the stated value; ±14% of the stated value; ±13% of the stated value; ±12% of the stated value; ±11% of the stated value; ±10% of the stated value; ±9% of the stated value; ±8% of the stated value; ±7% of the stated value; ±6% of the stated value; ±5% of the stated value; ±4% of the stated value; ±3% of the stated value; ±2% of the stated value; or ±1% of the stated value.
Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. Any numerical value, however, inherently contains certain errors necessarily resulting from the standard deviation found in their respective testing measurements.
The terms “a,” “an,” “the” and similar referents used in the context of describing the invention (especially in the context of the following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. Recitation of ranges of values herein is merely intended to serve as a shorthand method of referring individually to each separate value falling within the range. Unless otherwise indicated herein, each individual value is incorporated into the specification as if it were individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g., “such as”) provided herein is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention otherwise claimed. No language in the specification should be construed as indicating any non-claimed element essential to the practice of the invention.
Groupings of alternative elements or embodiments of the invention disclosed herein are not to be construed as limitations. Each group member may be referred to and claimed individually or in any combination with other members of the group or other elements found herein. It is anticipated that one or more members of a group may be included in, or deleted from, a group for reasons of convenience and/or patentability. When any such inclusion or deletion occurs, the specification is deemed to contain the group as modified thus fulfilling the written description of all Markush groups used in the appended claims.
Certain embodiments of this invention are described herein, including the best mode known to the inventors for carrying out the invention. Of course, variations on these described embodiments will become apparent to those of ordinary skill in the art upon reading the foregoing description. The inventor expects skilled artisans to employ such variations as appropriate, and the inventors intend for the invention to be practiced otherwise than specifically described herein. Accordingly, this invention includes all modifications and equivalents of the subject matter recited in the claims appended hereto as permitted by applicable law. Moreover, any combination of the above-described elements in all possible variations thereof is encompassed by the invention unless otherwise indicated herein or otherwise clearly contradicted by context.
Furthermore, references have been made to patents, printed publications, journal articles and other written text throughout this specification (referenced materials herein). Each of the referenced materials is individually incorporated herein by reference in their entirety for their referenced teaching.
It is to be understood that the embodiments of the invention disclosed herein are illustrative of the principles of the present invention. Other modifications that may be employed are within the scope of the invention. Thus, by way of example, but not of limitation, alternative configurations of the present invention may be utilized in accordance with the teachings herein. Accordingly, the present invention is not limited to that precisely as shown and described.
The particulars shown herein are by way of example and for purposes of illustrative discussion of the preferred embodiments of the present invention only and are presented in the cause of providing what is believed to be the most useful and readily understood description of the principles and conceptual aspects of various embodiments of the invention. In this regard, no attempt is made to show structural details of the invention in more detail than is necessary for the fundamental understanding of the invention, the description taken with the drawings and/or examples making apparent to those skilled in the art how the several forms of the invention may be embodied in practice.
Definitions and explanations used in the present disclosure are meant and intended to be controlling in any future construction unless clearly and unambiguously modified in the example(s) or when application of the meaning renders any construction meaningless or essentially meaningless. In cases where the construction of the term would render it meaningless or essentially meaningless, the definition should be taken from Webster's Dictionary, 3rd Edition or a dictionary known to those of ordinary skill in the art, such as the Oxford Dictionary of Biochemistry and Molecular Biology (Ed. Anthony Smith, Oxford University Press, Oxford, 2004).
This application is the 371 National Phase of International Application No. PCT/US22/76230, filed on Sep. 9, 2022, which claims priority to and the benefit of the earlier filing of U.S. Provisional Application No. 63/242,468, filed on Sep. 9, 2021, which is incorporated by reference herein in its entirety.
This invention was made with government support under Grant No. 5R01NS094570-05 awarded by the National Institutes of Health (National Institute of Neurological Disorders and Stroke; NINDS). The government has certain rights in the invention.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/US22/76230 | 9/9/2022 | WO |
| Number | Date | Country | |
|---|---|---|---|
| 63242468 | Sep 2021 | US |
