WO2023204784A1

WO2023204784A1 - A new method for rapid estimation of cerebrospinal fluid (csf) pressure during lumbar puncture

Info

Publication number: WO2023204784A1
Application number: PCT/TR2023/050345
Authority: WO
Inventors: Duygu YÜCEL; Ali Yekta ÜLGEN
Original assignee: T.C. Erci̇yes Üni̇versi̇tesi̇; Bahçeşehi̇r Üni̇versi̇tesi̇
Priority date: 2022-04-22
Filing date: 2023-04-12
Publication date: 2023-10-26

Abstract

The present invention relates to a method that will shorten the duration of intracranial pressure (ICP) measurements made with a spinal manometer and can predict the CSF pressure value with high accuracy in cases where spinal manometer is used.

Description

A NEW METHOD FOR RAPID ESTIMATION OF CEREBROSPINAL FLUID (CSF) PRESSURE DURING LUMBAR PUNCTURE

Field of the Invention

The present invention relates to a method that will shorten the duration of intracranial pressure (ICP) measurements made with a spinal manometer and can predict the cerebrospinal fluid (CSF) pressure value with high accuracy in cases where spinal manometer is used.

State of the Art (Prior Art)

Intracranial pressure (ICP) is the pressure created by the cerebrospinal fluid within the skull and the brain. Intracranial pressure can be measured by invasive or minimally invasive methods. The minimally invasive method is based on performing an indirect measurement based on the principles of computational fluid with a manometer following the minimally invasive lumbar puncture (LP) procedure (Figure 1). In the state of the art, as shown in Figure 1, it is shown how the spinal manometer is used to measure CSF pressure in the clinic by performing lumbar puncture. Vertebra (L3-L4) (1) is the physiological region used for spinal needle insertion into the human body in measurements made via spinal manometer, which is one of the CSF pressure measurement methods when used in the clinic. The spine starts at the nape of the neck and ends at the base of the tail end. It consists of 7 necks, 12 backs, 5 lumbar vertebrates and 1 tail end bone, which are lined up on top of each other and called Vertebrae. The tail end bone consists of five vertebrae fused together. Neck region is called Cervical Vertebra, back region is called Thoracal Vertebra or Dorsal Vertebra, which is the waist region is called Lumbar Vertebra. A spinal needle (2) suitable for use in the lumbar region is used so as to reach CSF. The material used to measure CSF pressure is a spinal manometer (3). The 3- way stopcock (4), which is the apparatus that is placed on the spinal manometer (3) and enables controlling the exit point of the fluid is shown in Figure 1.

In measurements made with a spinal manometer, the measurement unit is centimeter- water (cmH20). In this invasive method, the inner diameter of the spinal manometer, the length and inner diameter of the spinal needle used are among the factors that affect the measurement time and thus the accuracy of the measurement. In intracranial pressure measurement via LP, it is aimed to measure the pressure made by the cerebrospinal fluid (CSF) inside the skull and on brain tissues. Changes in CSF, which is of vital importance, are analyzed via diagnostic LP. CSF pressure is one of the parameters that need to be measured according to the suspected disease in cases requiring diagnostic LP. Accurate and rapid measurement of CSF pressure is of great importance for the patient and clinician.

In the measurements made with diagnostic lumbar puncture method and using spinal manometer, the measurement time varies depending on the length and inner diameter of the spinal needle used to reach the CSF for the LP procedure and the inner diameter of the spinal manometer. In this method, which is standardly applied in clinics, measurement is made by waiting for the patient's CSF to rise in the spinal manometer and reach an equal pressure level according to the principles of computational fluid. In CSF pressure measurements made with a spinal manometer, after reaching the CSF from the L3-L4 region with a spinal needle from the waist of the patient, CSF pressure measurement takes a long time for this fluid to fill into a tube called a hollow spinal manometer and reach equality according to the principles of computational fluid and due to the long waiting time, the pressure values are usually measured as a value lower than the actual value; measurement can be terminated before reaching complete equality. In this invasive method, keeping the measurement time longer increases the risk of infection. In most cases, it is thought that the CSF has reached the equality in the manometer, and the actual CSF pressure value cannot be obtained. Therefore, a patient with high CSF pressure can be considered normal. There is a need for methods that will shorten the duration of the measurements made with the spinal manometer and can predict the CSF pressure value in a short time and with high accuracy in cases where the spinal manometer is used.

Brief Description of the Invention and Objects of the Invention

The present invention relates to a method, which meets the above-mentioned requirements, eliminates all disadvantages and brings some additional advantages, will shorten the duration of intracranial pressure (ICP) measurements made via a spinal manometer and can predict the CSF pressure value with high accuracy in cases where spinal manometer is used.

The main object of the present invention is to enable the CSF to move within the manometer depending on time and to provide the actual pressure value result in an accurate and short time without the need to reach the equilibrium pressure, in cases where CSF pressure is conventionally measured with a spinal manometer.

The object of the present invention is to provide a new mathematical modeling so as to predict the CSF pressure.

The present invention enables the use of the spinal manometer inner diameter and spinal needle length and inner diameter information for different manometer and needle combinations.to predict the time-dependent rise of the fluid in the spinal manometer with high accuracy and in a short time, without the need to wait for the actual pressure values.

The present invention provides high-accuracy CSF pressure results in a short time without waiting for the equilibrium position to be reached by mathematical modeling using the elements of the state of the art. For example, the pressure value of the patient whose CSF pressure is measured in the current method is 11 cmEEO. In the manometer according to the state of the art, the fluid increase between 0 and 11 will be expected and the process will be terminated after making sure that the equilibrium position has been reached. This process takes minutes; it can take 15 minutes or even half an hour depending on the needle used. Most of the time, because these times are not expected, the pressure value is ignored. The present invention provides accurate results when the CSF moves 1 unit in the manometer.

Figures of the Invention

Figure 1: Elements of the prior art are shown. It is shown how to perform a lumbar puncture for the measurement of CSF pressure in the clinic and how the measurement is made with a spinal manometer.

Figure 2: The first system in which the calculations that form the basis of the invention are made is shown.

Figure 3: The second system in which the calculations that form the basis of the invention are made is shown. The CSF model was used to model the measurement of CSF pressure in the clinic shown in Figure 1.

Definitions of the Elements and Parts according to the Invention

In order to better explain the invention, the parts and elements in the figures are numbered separately and are as follows:

1) Vertebra (L3-L4) 2) Spinal Needle

3) Spinal Manometer

4) Three-way stopcock

5) CSF Model (reservoir)

6) CSF drops

7) Beaker

8) Precision scales

Detailed Description of the Invention

In this detailed description, the CSF pressure measurement method is described only for clarifying the subject matter of the invention and is not intended to have any limiting effect.

Figure 1 shows an application on humans, and Figures 2 and 3 show how the invention was performed in the CSF model (laboratory simulation). Since it is impossible to perform the invention on humans, it has been shown how it was performed with the help of the simulation in the laboratory environment. CSF model number 5 is a simulation of spinal fluid pressure by entering from vertebra (1). The application shown in Figure 1 (measurement of CSF pressure with a spinal manometer) can be performed rapidly and accurately with the help of the present invention.

The method according to the invention relates to modeling the mechanical behavior of cerebrospinal fluid (CSF) using a spinal needle and spinal manometer for measuring cerebrospinal fluid (CSF) pressure, the method comprises of the following method steps; a) determining the total mass (mCSF) of the CSF drops (6) for a given CSF pressure value (PCSF) and the time At (seconds) taken to collect these drops, b) determining the flow rate (Q) of the cerebrospinal fluid (CSF) through the spinal needle (2) having a length (L) and an inner diameter (d) in PCSF for a selected time period At , c) calculating the flow resistance (R) of the spinal needle (2) due to the linear relationship with the pressure difference (AP) between the needle tips of CSF, which has pCSF dynamic fluid flow moving in the spinal needle (2), d) calculating the flow rate (2) of the cerebrospinal fluid (CSF) in the spinal manometer (3), e) determining a characteristic time constant ( r) for each combination of spinal needle (2) and spinal manometer (3), f) calculating the time taken for the fluid in the manometer (3) to rise a predetermined level in the manometer and obtaining the following equation in order to determine the pressure in accordance with the obtained values

and calculating the pressure by substituting the values obtained in the above steps in the equation.

An application method for measuring cerebrospinal fluid (CSF) pressure of the method according above-mentioned modelling method during lumbar puncture comprises the following method steps respectively; when the inner diameter of the manometer (3), and inner diameter and length of the spinal needle (2) are known, manually entering this information into the system and determining the time taken for the CSF to a desired level in the manometer (3) and determining the time constant (r), and calculating the CSF pressure by substituting the determined rise time and time constant (7) in equation 5 above.

The application method for measuring cerebrospinal fluid (CSF) pressure during lumbar puncture comprises the following method steps; when the flow resistance value R of the spinal needle cannot be determined and the inner diameter of the spinal manometer and the length and inner diameter of the are not known, automatically obtaining time measurements at different levels depending on the rise of the fluid in the manometer (3) with the help of at least two level sensors located at predetermined intervals on the spinal manometer (3) and obtaining the time constant from the following equation;

and calculating CSF pressure using equation 5.

CSF pressure is calculated with the help of a microprocessor and displayed on at least one screen.

The method of measuring cerebrospinal fluid (CSF) pressure during lumbar puncture is listed in detail herein as following: determining total mass (mCSF) of CSF drops (6), which is a fluid moving in the direction of gravity with the spinal needle inserted into the CSF model (5) (from the reservoir) in the simulated case, which is placed in the lumbar region in the clinic using the CSF model (5) for a given CSF pressure value (PCSF) and the time At (seconds) taken to collect these drops in a beaker (7), calculating the flow rate (Q) of the cerebrospinal fluid (CSF) through the spinal needle (2) in PCSF, for a selected time period At, by substituting the values obtained by measuring the number of cerebrospinal fluid drops and the total mass (mCSF) with a precision scale (8) in the formula below,

as another alternative method, the following steps are required; obtaining the formula due to the linear relationship with the pressure difference

(AP) between the needle tips of the CSF having dynamic fluidity of pCSF moving in the spinal needle (2) with a certain length (L) and inner diameter (d) and calculating the flow resistance of the spinal needle (2) with the formula

obtained by combining the formulas (7) and (8). For this purpose, in practice, the time constant in the laboratory environment should be determined using the CSF model. The CSF model (as shown in Figure 2) consists of a reservoir that models the CSF pressure and a fluid that has similar characteristics to the CSF. The R value is determined and the time constant r= RA/p is calculated with this method. calculating flow rate (2) of cerebrospinal fluid (CSF) in the spinal manometer with the formula

(1) or with the formula

where V(t) represents the instantaneous CSF volume collected in the manometer and

combining equation

wherein; R: resistance value against flow rate occurring in spinal needle/manometer;

AP: Pressure difference between spinal needle tips; PCSF: CSF pressure (balance pressure); p CSF density; h(t): Instant CSF height in manometer; A: the internal cross- sectional area of the manometer to obtain the following formulas;

• solving the first-order differential equation

and obtaining the homogeneous equation

solution and determining a characteristic time constant (7) for each combination of spinal needle and spinal manometer determining the time constant

T = RA/p (6),

• after the time constant (7) is determined, the user enters the manometer inner diameter, spinal needle inner diameter and length information into the system and manually starts the measurement system with the start button on the device, when the BOS starts to move at the zero point in the manometer and when it reaches the desired cm, the system is stopped with the stop button, and the cm information is entered into the information box on the screen, automatic measuring of this time calculating CSF pressure by software based on mathematical modeling and displaying the same on the screen. pCSF expresses the density of CSF and this value is reported in the literature in the range of 1.005-1.006 g/ml. If Poiseuille's Law of fluid dynamics is applied to the fluid dynamics of the CSF in the spinal needle in contact with the CSF, CSF moving in a spinal needle with a given length (L) and inner diameter (d) is linearly related to the pressure difference (AP) between the needle tips.

When the general solution of the system is expressed by the formula

the time taken for the rising CSF (h) to reach equilibrium pressure (t) in the manometer appears to be independent of PCSF for the combination of spinal needle and spinal manometer As shown in Figure 3, following the connection of the spinal needle (2) placed in the CSF model (5) with the spinal manometer (3), the CSF moves upwards within the manometer. When the pressure value determined in the CSF model is reached, the fluid in the spinal manometer (3) reaches equilibrium. When the movement of the fluid is followed in combination with the spinal needle (2) and the spinal manometer (3), it has been observed that fluid movement/behavior is exponential by using time and distance traveled by the fluid between each unit (like 0 cmH20 to 1 cmH20, to 2 cmH20, to 3cmH2O....). When this equation is expressed on a logarithmic scale, a linear line emerges. Information about two points is sufficient to define a line. Since the fluid movement will be rapid in the first minute, two points taken in this time interval will be sufficient to calculate the equilibrium pressure.

The clinician will first enter the spinal needle inner diameter, spinal needle length and spinal manometer inner diameter information into the device before the clinician performs Lumbar puncture so as to measure the CSF pressure. Although a 90 mm spinal needle is used in the routine, the spinal needle length varies between 25 mm and 150 mm according to the manufacturer. The most commonly used length is 90 mm.

The clinician will start the system with the start button on the device when the CSF starts to move upwards from the zero point in the manometer, after connecting the spinal needle (with known inner diameter and length) to the spinal manometer (with known inner diameter).

The clinician will follow the movement of CSF in the manometer according to their own comfort and will be able to press the stop button, for example, when the CSF level reaches 2 cm in the manometer. According to the example above, the value of “2” will be entered into the “cm” box that appears on the screen via the software in the microcontroller. The time taken between the clinician pressing the start and stop buttons will be automatically calculated by an electronic stopwatch built into the device. CSF pressure value predicted by the software will be indicated on the screen in cmFFO unit. Since the movement of CSF in the manometer will vary according to the patient's CSF pressure, the characteristics of the spinal needle and spinal manometer used by the clinician, the clinician, who will monitor the CSF level, decides when to press the stop button, which will provide more accurate measurements.

It is a novel and critical benefit that the pressure value can be predicted with high accuracy within seconds, depending on how many seconds it reaches other heights from the zero point (0), without the need for the CSF to reach equality in the manometer with the help of the “time constant”, which is revealed by the mathematical expression of the spinal manometer- spinal needle combination with a first-order differential equation.

The mechanical behavior of cerebrospinal fluid (CSF) is modeled using spinal needle, manometer with the help of the present invention. CSF reaches the equilibrium pressure value by moving upwards in the spinal manometer according to the principles of computational fluid; this equation shows the patient's CSF pressure value. The difference (2) between the CSF pressure and the instantaneous CSF height h(t) on the manometer determines the CSF flow rate.

Here, R (flow resistance) denotes the resistance to the flow rate occurring in the spinal needle, and p denotes the CSF density. PCSF is the abbreviation for Pressure Cerebrospinal Fluid and refers to CSF pressure (Cerebrospinal Fluid). The flow rate Q can also be expressed by the formula Q = d\'(l)/dl, V(t). A is the internal cross-sectional area of the manometer. In this case

when Formulal and Formula 2 are referred in combination, it is as follows

The solution of the above first-order differential equation is as follows.

Thus, it turns out that there is a characteristic (r) time constant for each spinal needle and spinal manometer combination. T = RA/p (6)

When the equation 5 is considered, it is seen that the time required for the CSF, which is rising inside the manometer, to reach the equilibrium pressure (equilibrium pressure), hence the height corresponding to this pressure, is independent of PCSF. In case ratio between CSF elevation and PCSF in the manometer is

(0.86%), 0.95 (95%) and 0.99 (99%), measurement times are 0.693T, T, 2T, 3t and 5T respectively.

As is known, in a given CSF pressure PCSF, for a selected time period At, the flow rate Q can be calculated by measuring the number of drops of cerebrospinal fluid and the total mass (mcsF):

PCSF denotes the density of cerebrospinal fluid CSF, and this value varies between 1.0005 g/ml to 1.0006 g/ml. Obtaining the formula due

linear

relationship between the pressure difference (AP) between the needle tips of the CSF with dynamic fluidity of pCSF moving in the spinal needle with a certain length (L) and inner diameter (d) and calculating the flow resistance of the spinal needle with the formula

With the help of this modeling, CSF pressure can be measured with much shorter lengths, for example 5 cm - 10 cm, with manometers. However, for this, the above-mentioned time constant (7) for spinal manometer and spinal needle combination must be known. For CSF pressure in the clinical setting, a manometer length of 5 cm is an acceptable choice. In practice, the clinician can reduce or increase this height as desired. In addition to the risk of not obtaining an accurate measurement, the standard measurement method also causes CSF loss due to the higher CSF volume in which the CSF is expected to reach equality in the manometer, is cumbersome, and the time to reach equality is not waited long enough. The patient's infection risk is also reduced with the help of the highly accurate CSF pressure value obtained in seconds using the time constant, without the need to wait for the time to reach equality with the present invention. It may take a long time to reach equality in measurements made with the gold standard.

Where the clinician uses a standard spinal manometer, the time constant will be calculated by the software, by entering the inner diameter of the spinal manometer used by a software and the spinal needle length and inner diameter information to the medical device and the time for the CSF to reach a height of, for example, 5 cm can be measured, and the CSF pressure can be measured with high accuracy within seconds on the screen of the device with the start and end button of the stopwatch integrated in the medical device; based on mathematical modeling, an alternative method can also be used, with the help of the sensors that detect fluid movement integrated into the manometer system. For this, instead of the clinician manually doing the fluid rise in the spinal manometer with the start and stop buttons on the first device, it is also possible to automatically measure this time with the help of fluid level detection sensors, LASER diode sensor, infrared, capacitive or vertical moving float and differential pressure transducer sensors. Therefore, in this patent application, two different medical devices based on the same principle are presented. Both of these devices are based on the formulas specified in the description. If the inner diameter of the spinal manometer and the inner diameter and length of the spinal needle cannot be reached, another advantage of the medical device, which is based on automatically detecting the rise of CSF with sensors, in addition to the automatic detection of the time, the CSF pressure value can be determined quickly and with high accuracy by calculating the time constant as expressed in equation 10 with the help of sensors that detect the fluid level.

Using the first-order equation

, using the values obtained from the tmeas measurements, the time taken until different fluid heights (hs > I12 > hi) in the manometer are reached, the time constant (7) can be calculated by extracting from the following formula:

Here, href corresponds to the initial fluid level, depending on the position of the initial fluid level detection sensor on the manometer (which may not be zero). h. represents the height at which CSF reaches balance equilibrium. The CSF pressure value for adults and healthy individuals varies between 5 - 25 cmH20 values. Although the lengths of the manometers vary according to the manufacturer, there are manometers known to be produced between 15 cm and 54 cm. It is also possible that manometers longer than 54 cm are being produced and used. According to the information reported in the literature, when the CSF pressure is lower than 5 cm H2O, it is expressed as low intracranial pressure. There is no data on the highest CSF pressure value ever measured; the preferred average length for manufacturing manometers appears to be 35 cm. Although it is not possible to specify a range of values for h, the lengths chosen for the manufacture of manometers give an idea of the average height reached by the CSF in the manometer for individuals with or without a disease. tm2: The moment when the preselected level detected by the sensor is reached tmi: The starting moment detected by the sensor for the manometer zero value tmeas = tm2 - tmi = measuring time

If more than two sensors are used, this equation will be used appropriately each time.

For these measurements, there are two fluid level detection sensors integrated into the spinal manometer and an electronic system that automatically determines the fluid height. The CSF pressure is directly displayed on the screen with the integration of the formula into the software by measuring how long it takes (seconds) to reach a height of 5 cm (this height can vary) on the manometer with the help of the sensors.

In cases where detection of the R flow resistance value of the spinal needle is failed and the inner diameter of the spinal manometer, the length or the inner diameter of the spinal needle is unknown, PCSF pressure can be measured by placing preferably four level sensors, the first of which is a reference, instead of two on the manometer, at known intervals (1 cm). Depending on the rise of the fluid in the manometer, preferably, time measurements are taken at 3 different levels automatically, and solutions for Equation 10 are evaluated together, each time by means of a Microcontroller; time constant ( r) and P_CSF pressure values are calculated mathematically.

Application method developed for the measurement of cerebrospinal fluid (CSF) pressure during lumbar puncture and the inventive system appropriate for the operation of the method comprises the following;

• at least one display, which is suitable for entering the inner diameter and length information of the spinal needle (2) and spinal manometer (3) and which shows the CSF pressure,

• a start button which is pressed when the spinal fluid starts to move from a predetermined starting point in the manometer (3) and a stop button which is pressed when the spinal fluid reaches the desired height,

• at least one first sensor detecting the moment at which the spinal fluid starts to move from a predetermined starting point in the manometer (3) when the inner diameter and length values of the spinal needle (2) and spinal manometer (3) are not known, and at least one second sensor detecting when the spinal fluid has reached the desired height,

• at least one measurement unit that automatically calculates the time taken for the fluid in the manometer (3) to pass from the starting point to the desired height,

• at least one microcontroller that calculates the CSF pressure with the help of the software operating thereon based on the data received from the measurement unit.

Claims

1. Method for modeling the mechanical behavior of cerebrospinal fluid (CSF) using a spinal needle and spinal manometer for measuring cerebrospinal fluid (CSF) pressure, characterized in that, it comprises the following method steps; a) determining the total mass (mCSF) of the CSF drops (6) for a given CSF pressure value (PCSF) and the time At (seconds) taken to collect these drops, b) determining the flow rate (Q) of the cerebrospinal fluid (CSF) through the spinal needle (2) having a length (L) and an inner diameter (d) in PCSF, for a selected time period At , c) calculating the flow resistance (R) of the spinal needle (2) due to the linear relationship with the pressure difference (AP) between the needle tips of CSF, which has pCSF dynamic fluid flow moving in the spinal needle (2), d) calculating the flow rate (2) of the cerebrospinal fluid (CSF) in the spinal manometer (3), e) determining a characteristic time constant (r) for each combination of spinal needle (2) and spinal manometer (3), f) calculating the time taken for the fluid in the manometer (3) to rise a predetermined level in the manometer and obtaining the following equation in order to determine the pressure in accordance with the values obtained

2. An application method for measuring cerebrospinal fluid (CSF) pressure of the method according to in Claim 1 during lumbar puncture, characterized in that, it comprises the following method steps; when the inner diameter of the manometer (3), and inner diameter and length of the spinal needle (2) are known, manually entering this information into the system and determining the time taken for the CSF to rise to a desired level in the manometer (3) and determining time constant (r), and calculating the CSF pressure by substituting the determined rise time and time constant (7) in the equation of Claim 1.

3. An application method for measuring cerebrospinal fluid (CSF) pressure of the method according to in Claim 1 during lumbar puncture, characterized in that, it comprises the following method steps; when the flow resistance value R of the spinal needle cannot be determined, and the inner diameter of the spinal manometer and length and inner diameter of the spinal needle are not known, automatically obtaining time measurements at different levels depending on the rise of the fluid in the manometer (3) with the help of at least two level sensors located at predetermined intervals on the spinal manometer (3) and obtaining the time constant from the following equation

and calculating the CSF pressure by substituting the same in the equation of Claim 1.

4. A method according to Claim 2 or 3, characterized in that, it comprises the following method steps; starting the measurement system via a start button with the help of a device, when the fluid in the manometer (3) starts to move from a predetermined starting point, and manually defining the level of the fluid in the manometer (3) by stopping the system via a stop button when the fluid reaches the desired level in the manometer (3), or detecting that the fluid has risen to a predetermined level by the sensors.

5. A method according to any of the Claims 2-4, characterized in that, it comprises the step of displaying the CSF pressure on at least one screen by calculating the same via a microprocessor.

6. A system suitable for operating the method according to Claims 2-4, characterized in that, it comprises; • at least one display, which is suitable for entering the inner diameter and length information of the spinal needle (2) and spinal manometer (3) and which shows the CSF pressure,

7. A system according to Claim 6; characterized in that, measurement unit is an electronic stopwatch.

8. A system according to Claim 6 or 7, characterized in that, the sensors are LASER diode sensors, or infrared, capacitive or vertical moving float or differential pressure transducer sensors.