1. Field of Invention
This present invention generally relates to cerebrospinal fluid (CSF) shunts and, more particular, to a device and method for a continuous, real-time (CRT) monitor of CSF flow through shunt tubing implanted under the skin in hydrocephalus patients.
2. Description of Related Art
Hydrocephalus is a condition in which CSF accumulates in the brain ventricles, potentially leading to brain damage and death. Approximately 69,000 people are diagnosed with hydrocephalus each year in the United States. Hydrocephalus affects 300,000 Americans and generates $2 billion in annual US healthcare costs.
Hydrocephalus is corrected by placing a ventricular-peritoneal (VP) shunt that drains excess CSF to the abdomen (
Additionally, regular, ongoing clinical management of shunted hydrocephalus patients is also complex. CSF over drainage can result in symptoms. In addition, clinical information about the performance of specific shunt valves and siphon control devices is limited. And adjustment of programmable shunt valves is a long, iterative process.
Current methods for detecting shunt malfunction and for optimizing shunt function do not meet the needs of hydrocephalus patients. Physical examination, including pumping of the shunt reservoir, is unreliable. Computed tomography (CT) scans remain the gold standard, but are expensive and cannot be used to investigate every headache, and results in repeated radiological exposures of patients (often children). Radionuclide shunt flow testing is invasive and poses a risk of infection. New technologies under development are complex (advanced magnetic imaging resonance (MRI) techniques, ultrasound tracking of bubbles), lacking in precision (forward looking infrared, FLIR) or require implantation (implanted thermal flow technologies) and have not reached the clinic.
The need for new diagnostic tools for hydrocephalus patients is highlighted by the NH announcement “Advanced Tools and Technologies for Cerebrospinal Fluid Shunts” (PA-12-190).
U.S. Patent Application No. 2013/0109998 (which is incorporated by reference in its entirety herein), owned by the same Applicant as the present application, namely, ShuntCheck, Inc., discloses a non-invasive device for determining CSF flow rate through shunts and is hereinafter referred to as “ShuntCheck”. ShuntCheck is a system that utilizes an array of thermo-sensors clustered in three sections that applies a finite cooling source (e.g., an ice cube) in close proximity to the shunt and to the thermo-sensors. The thermo-sensors are coupled to an analyzer to that utilizes the thermo-sensor data to calculate the CSF flow rate. In particular, as shown in
However, the short duration of the test limits its utility for shunt valve adjustment, investigating suspected shunt over-drainage, etc.
In contrast, a non-invasive, non-radiologic device which can track changes in CSF flow rate in real-time over extended time periods would address many ongoing clinical management needs and become a valuable tool for the neurosurgery clinic. Thus, there remains a need for a device and method capable of a continuous, real-time (CRT) monitor of CSF flow through shunt tubing implanted under the skin in hydrocephalus patients
All references cited herein are incorporated herein by reference in their entireties.
An apparatus for determining cerebrospinal fluid (CSF) flow rate in an implanted CSF shunt in real-time is disclosed. The apparatus comprises: a pad that is placed against the skin of a patient over the location of the CSF shunt, and wherein the pad itself comprises: a Peltier sensor comprising: a Peltier device that is operated continuously and which is displaced away from a first surface of the pad via a thermal resistor over the location of the shunt; and a first set of temperature sensors (e.g., thermistors) associated with the Peltier device for detecting heat generated from the patient's skin and any CSF flow through the shunt; and a sensor processing device that is electrically coupled to the pad for receiving temperature data from said first set of temperature sensors, and wherein the temperature data from the first set of temperature sensors is used by the sensor processing device to determine a continuous real-time flow rate of the CSF through the CSF shunt.
A method for determining cerebrospinal fluid (CSF) flow rate in an implanted CSF shunt in real-time is disclosed. The method comprises: applying a Peltier device, via a thermal resistor, against the skin of a patient over the location of the CSF shunt; positioning a first temperature sensor (e.g., a thermistor) between the Peltier device and the thermal resistor and positioning a second temperature sensor between the thermal resistor and the skin of the patient; energizing the Peltier device on a continuous basis and using the first temperature sensor to control the Peltier device to maintain a predetermined temperature; detecting a temperature gradient between the first and second temperature sensors from temperature data generated by the first and second temperature sensors; and processing the temperature gradient to determine a Peltier signal that corresponds to a continuous real-time flow rate of the CSF through the CSF shunt.
An apparatus for determining cerebrospinal fluid (CSF) flow rate in an implanted CSF shunt in real-time is disclosed. The apparatus comprises: a pad that is placed against the skin of a patient over the location of the CSF shunt and wherein the pad comprises: a Peltier sensor that itself comprises: a Peltier device that is operated continuously with a first set of temperature sensors (e.g., thermistors) associated with the Peltier device for detecting heat generated from the patient's skin and any CSF flow over the location of the shunt; a second set of temperature sensors (e.g., thermistors) arranged upstream and downstream of the Peltier device for detecting a temperature distribution along a path of the CSF shunt; and a sensor processing device that is electrically coupled to the pad for receiving temperature data from the first set of temperature sensors and from the second set of temperature sensors, the temperature data from the second set of temperature sensors being used by the sensor processing device to define a zero flow baseline signal for calibrating the Peltier sensor and wherein the sensor processing device further uses the temperature data from the first set of temperature sensors in conjunction with the zero flow baseline signal to determine a continuous real-time flow rate of the CSF through the CSF shunt.
The invention will be described in conjunction with the following drawings in which like reference numerals designate like elements and wherein:
The present invention 500 is termed a “continuous real-time (CRT)” CSF flow monitor and method. This device provides improved care for hydrocephalus patients by providing a rapid and non-invasive method for monitoring changes in CSF flow in shunted patients. As a result, the present invention 500 directly responds to such demands for diagnostic tools for use in a hospital or outpatient settings that work in real-time to quantitatively determine shunt function.
As is discussed in detail later, a key aspect the present invention 500 uses non-invasive thermal dilution technology to monitor changes is CSF flow over extended periods of time, enabling neurosurgeons to assess in real-time the impact of changes—of valve setting, patient position, etc.,—on shunt flow. This cannot be accomplished in any way with current technologies and represents an important new tool for managing hydrocephalus. As will also be discussed later, a “Peltier sensor” of the present invention 500 represents a breakthrough which significantly increases the accuracy and utility of the continuous real-time flow monitor and method, also referred to as “continuous real-time (CRT) ShuntCheck.” The Peltier sensor is based on Peltier cooling and continuous thermal recordings which, when monitored, are indicative of changes in shunt flow.
The present invention 500 employs a breakthrough in thermal dilution technology which enables long term, continuous, real-time measurement of CSF shunt flow. As a result, the present invention 500 forms:
More generally, the present invention can be used to establish a “normal” baseline flow pattern for each patient—similar to the current practice of establishing a normal baseline for ventricular size via imaging.
As shown most clearly in
It is within the broadest aspect of this invention 500 to include a Peltier device and fan power source within the sensor processing device 504 and that the illustrated example does not, in any way, limit the sensor processing device 504 configuration. The use of the term “sensor processing device” 504 implies all aspects of powering and controlling the Peltier device 514 as its associated heat dissipating fan 520A, as well as any and all signal conditioning (A/D conversion, filtering, etc.) of all of the temperature sensor data/signals and the processing and analysis of this data into corresponding CSF flow status/rate outputs.
The Peltier sensor 502 adheres comfortably to the patient's skin (e.g., over the patient's clavicle) for extended periods of time, e.g., 30 minutes to two hours. An alternative is overnight use.
To permit the patient to be mobile during use of the present invention, the sensor connects to a belt-worn battery pack which connects wirelessly to the CSF analyzer 504. It should be understood that the sensor processing device 504 may analyze this temperature data directly or may transmit such data to another device for CSF flow analysis.
The device must track changes in CSF flow—differentiating no flow from low flow from robust flow. Differentiating low from robust flow is important for shunt valve adjustment and over-drainage assessment.
The Peltier sensor 502 of the present invention 500 is based upon the current ShuntCheck design, e.g., cooling upstream” (via a Peltier electronic cooling device) and thermal sensors “downstream” which detect changes in CSF flow as shown in
As shown in
As shown in
In particular, the Peltier sensor 502 comprises a thermal resistor 512 (e.g., an aluminum C-shaped element) secured (e.g., glued) to the Peltier device 514 using thermo conductive epoxy. A thermistor 516 is sandwiched between the Peltier device 514 and the thermal resistor 512 to control temperature at the cold end 513 of the resistor 512. A second thermistor 518 is attached to the other end 517 of the thermal resistor 512, the part which touches skin 12. An aluminum radiator 520 with a small 520A sits atop the Peltier device 514 to remove heat (the Peltier device 514 is cool on one side, warm on the other).
The bottom part of the thermal resistor 512 (e.g., 14×5 mm) cools down the tissue 12 surrounding the CSF shunt 10. This causes a temperature gradient between CSF inside the shunt tube 10 and the surrounding tissue 12. Due to the generated temperature gradient, the thermal energy from CSF flows to the tissue 12 and eventually, via the thermal resistor 512, to the Peltier device 514. The temperature difference between the Peltier thermistor 516 and skin thermistor 518 is proportional to the amount of heat flowing through the thermal resistor 512. Therefore, the amount of heat is in a direct relationship to the CSF flow rate and permits the differentiation of low vs. robust flow rates (
While the Peltier sensor 502 has a monotonic characteristic in a wider range of flow rates (0 through 30 ml/h), it lacks a stable zero flow measurement. This is due to the fact that the tissue conductivity varies with perfusion, fat content, etc. In order to obtain stable zero two additional thermal measurements are provided. The first thermistor measures the temperature change over the shunt catheter 10 upstream of the Peltier device 514 and is positioned over the shunt 10 while the second thermistor measures temperature changes over the catheter 10 downstream of the Peltier device 514. In particular, an upstream thermistor 521 (
The Peltier device 514 cools down the area of the skin in its near proximity. When there is no CSF flow, the upstream sensor 521 is cooled down by the Peltier device 514. When CSF starts flowing underneath the upstream sensor 521, it delivers heat. The temperature of the tissue under the upstream sensor 521 increases, an increase which is related to the CSF flow rate. Flows as low as 1-2 ml/h deliver enough heat to warm up the skin. The advantage of this method is its high sensitivity to flow. No flow conditions are easily detectable by a cold upstream sensor.
The downstream measurement mimics the original ShuntCheck device (see
The important advantage of the downstream and upstream sensors is their synergistic nature. Each of the sensors is an accurate “no-flow” detector, but the balance between the upstream and downstream sensor shows even greater accuracy due to the fact that during the test, the skin temperature may fluctuate. A single up or downstream measurement would be sensitive to such changes but the ratio of those signals is insensitive to body temperature. (
The balance (ratio) between the upstream (TUP) and downstream sensors (TDN) indicates whether or not there is a flow in the shunt 10, thereby establishing an accurate zero-flow baseline regardless of the skin temperature. The vector defined by the temperature of the upstream thermistor 521 and the temperature of the downstream thermistor 522A, Vup-down (TUP, TDN) serves as a precise indicator of zero flow. Although the modulus of this vector is to a certain extent random, its phase is monotonically related to the flow rate with a precise zero value.
In particular, the graph of
The combined signal takes advantage of the monotonic response of the Peltier sensor and zero-sensitive response of the Zero Flow Signal.
The sensor processing device 504 was implemented using a data acquisition battery unit (“DAQ”) and a computer (e.g., a tablet computer). The DAQ powers and controls the Peltier device 514 and conditions and converts the analog temperature sensor signals into digital data. The computer receives the temperature sensor data and uses an application (e.g., LabView software) to display real-time results.
In view of the foregoing, the present invention 500 is able to generate smooth and non-overshooting cooling. As shown in
A bench thermal skin simulator was implemented to match long term animal model thermal responses to cooling (using a pig model which closely matches human skin). Animal skin conductivity was assessed by using geometry resembling the geometry of the shunt system. A needle probe was constructed. A stainless steel needle (pipe) heater outfitted with temperature sensors was implanted under the skin (see
where q is heat exchange between the pipe and the surrounding material, k is heat conductivity, D is pipe depth, r is the pipe radius, Tpipe is temperature of the pipe surface and Tskin is the temperature of the skin surface over the pipe. Since the geometry is known, q can be calculated from current and electrical resistance of the probe, temperatures are measured by two thermistors (one on the needle and another one on the skin surface), the equation can be solved for k.
The testing has been performed on the thermal skin simulator using 3 kg piglets which are FDA approved standard for the pediatric skin simulations. Both systems (the silicon skin simulator and the piglet skin) have been tested in order to measure thermal conductivity.
In particular,
The results showed that piglet skin conductivity is 0.395 W/K m (see Table 1 below), which is consistent with the values reported in the literature.
An artificial skin was formed to replicate natural skin thermal conductivity using silicone rubber (Freeman Mfg & Supply Co.). The slightly lower silicone rubber conductivity (which is believed to be caused by blood circulation which is absent in the bench system) was mathematically compensated for during validation testing.
The bio-heat generated by human body was simulated by an active system controlled by a close-loop feedback. (The schematic of the bench is shown in
A thermal bench related to ShuntCheck thermal testing was used to validate the prototype's ability to monitor shunt flow rate over time. As shown in
A randomize table of flow rates (0, 5, 10, 20, 30 ml/h) was used which covered a physiological range of CSF flows in shunt tubing. The bench and animal experiments were performed for approximately four hours, which resulted in 10 tests per flow rate.
Several levels of cooling temperatures were tested ranging from 6 through 14° C. below the baseline skin temperature (typical skin temperature 34° C.). The temperature of 14° C. was selected because it yielded the best signal to noise ratio while maintaining a very safe level of cooling.
The CRT sensor tracks CSF flow rate changes over prolonged periods of time. The Combined CRT Signal presents a monotonic characteristic in animal and bench testing (with the bench corrected for heat conductivity). Four-hour tests were conducted in six animals. All tests showed that several hour monitoring is possible with the CRT sensor. The CRT system can provide a wide range of outputs for real time and offline analysis. The accuracy of the system can be enhanced with calibration to zero or with smoothing algorithms.
Real Time without Calibration
As shown in
Real Time with Calibration to Zero-Flow
If a zero flow period can be established (e.g., the valve is set to its highest level or the shunt catheter is occluded for a short period of time) then results can be calibrated to reach a higher level of precision (as shown in
CRT sensor output correlated with flow rates with r2>0.9, meeting the program goal. This mode is particularly valuable in evaluating adjustable valves where zero flow can be established.
The main goal of the testing program was to demonstrate that CRT ShuntCheck prototype concept can perform continuous testing, reliably identifying periods of shunt flow and non-flow. Bench and animal models were used, along with the CRT ShuntCheck prototype, to detect randomized periods of surrogate CSF fluid flowing at 0, 5, 10, 20 ml/h for durations of 5 minutes each induced by a syringe pump. In order to show how the CRT sensor follows the flow changes in time domain the graphs of
The dynamic changes of the flow rate are followed by the CRT signal. The phase shift or time delay between the signal and the flow rate is caused by physical delay in heat transfer. The time response of the CRT system is approximately 170 seconds, sufficiently quick to track natural fluctuations in CSF flow.
The sensor delivers very little cooling (skin temperature under the cooling device was 20° C.−the skin temperature target used in cosmetic laser surgery procedures to protect surrounding epidermis) on a very small surface area (4 mm×15 mm). This level of cooling caused no any observable effects on animal skin. The skin surface after 4 hour of cooling was pink and looked healthy. The cross section of the skin revealed no pathologies.
A literature search indicates that skin and tissue cooling is safe within a wide range of temperatures from 28° C. through 10.8° C. In accordance with one source, tissue cooling wasn't harmful even if applied for prolonged periods of time. A variety of cooling techniques have been implemented and are known for research and therapeutic purposes. Those techniques range from local ice pouches to global limb or body cooling. The most analogous study demonstrated that an aluminum probe cooled to −15° C. reduced skin temperature to 0° C. Skin freezing occurs at −2.2° C. of skin temperature and therefore requires a probe temperature of approximately −17° C. The probe temperature during the test reached a temperature averaging 20.7° C. (coldest 17.8° C.), yielding no skin damage.
The amount of heat per second removed by the probe from skin is less than 0.1 J (1 Amp×2V×5% efficiency) which is equivalent of elevating the temperature of 1 g of water by 0.0239 degrees C. This amount of cold is minute and easily compensated in the tissue volume by bio-heat generated by the human body, The surrounding skin stays warm even after hours of experimentation, The human body generates 0.01 J/sec per cubic centimeter of tissue. Thus only 10 cc of human tissue would be enough to completely negate the effect of the Peltier cooling.
In accordance with all of the test data and the CRT ShuntCheck prototype, the following conclusions have been reached:
1. CRT ShuntCheck demonstrates single test accuracy equal to current ShuntCheck.
2. CRT can track changes in CSF flow and can differentiate 0, 5, 10 and 20 ml/hr flow.
3 CRT is safe—Peltier cooling is precisely controlled by the device and the modest level of skin cooling is safe for extended test periods.
CRT ShuntCheck provides a noninvasive and safe method of CSF flow rate assessment. It can be utilized as a flow detector and as a flow change sensor (tracking changes in flow rate).
While the invention has been described in detail and with reference to specific examples thereof, it will be apparent to one skilled in the art that various changes and modifications can be made therein without departing from the spirit and scope thereof.
This PCT application claims the benefit under 35 U.S.C. §119(e) of Provisional Application Ser. No. 61/742,048 filed on Aug. 2, 2012 entitled CSF FLOW MONITOR and whose entire disclosure is incorporated by reference herein.
Filing Document | Filing Date | Country | Kind |
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PCT/US2013/052018 | 7/25/2013 | WO | 00 |
Number | Date | Country | |
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61742048 | Aug 2012 | US |