TECHNICAL FIELD

The invention relates to a device for measuring intracranial pressure that may be connected to the shunt during placement of the shunt without the need of a new surgical intervention, without carcinogenic effects, such as an X-ray, with the implanted part being a passive component.

STATE OF ART

Cerebrospinal fluid (CSF) is a clear, colorless fluid filling the brain ventricles and cranial and spinal subarachnoid spaces and forming 10% of the intracranial volume. In addition to providing hydromechanical support for the brain, it plays an important role in neural metabolic activities (Puntis, Reddy, and Hirsch 2016). This fluid is produced in the body at 0.5 ml per minute (Toma 2015). Problems in the cerebrospinal fluid circulation lead to local accumulations and increased intracranial pressure.

In emergencies related to this, Computed Tomography (CT) is the main method used for diagnosis. Hydrocephalus is diagnosed when, by reviewing the CT scans, one observes that dilation of frontal horns and third ventricle, enlargement of temporal horns more than 2 mm, periventricular transparency, and an Evans index (the ratio of the maximum width of the frontal horns to the distance of inner tables of the cranium) higher than 0.3 (Capone, Bertelson, and Ajtai 2020) (Toma 2015).

In this case, the excess cerebrospinal fluid should be drained therefrom. Ventriculoperitoneal shunts, one end of which is placed in the skull and the other one extends to body cavities (such as the abdominal region), are used for transferring this excess fluid, which were first used in 1905 (Robertson, Maraqa, and Jennett 1973). However, shunts are among the medical devices that frequently cause complications due to their location in the brain and as they stay a long time in the body. In pediatric patients, there is a risk for complications of 30-40% in 1 year, and 50% in 2 years (Hanak et al. 2017). Following an administration with such high risks, the intracranial pressure may re-increase due to obstruction. If a patient presents to a doctor’s office with complaints similar to the previous ones, they should have the CT again and should be exposed to X-rays (Aw-Zoretic et al. 2014). In pediatric administrations, cumulative doses of 50 mGy due to consecutive CT scans triple the risk for leukemia, and a dose of about 60 mGy triple the risk of brain cancer (Pearce et al. 2012).

Shunt obstruction during treatment of patients diagnosed with hydrocephalus is the most common complication and it is a neurosurgical emergency. Shunt obstruction may arise due to mechanical problems, such as cover failure or obstruction or distal catheter obstruction or retrieval, and due to misplacement. Patients may get worse and even die due to increased pressure due to this obstruction. If suspected, intracranial pressure measurement plays a crucial role in this process. Moreover, in infants, whose skulls are not hardened yet imaging may be performed by ultrasonography method through anterior fontanelle. If the patient is a child or an adult, this method cannot be used because of the hardened skull. Computed Tomography using X-ray for measurement, is the method generally used for diagnosis. This is also a very common method used in emergencies (Toma 2015). Since hydrocephalus is a chronic condition, it requires that recurrent CT scans should be performed throughout a lifetime. Exposure to cumulative X-ray doses leads to different severe diseases, such as leukemia or brain cancer (Pearce et al. 2012). Such complications paved the way to develop telemetric devices for measuring intracranial pressure. In this regard, providing information from inside of the body using telemetry method was first proposed in 1959 (Mackay 1959). In accordance with the views developed in this way, the implantation of different electronic devices to the intracranial region for measurement was considered. These can be systems that can perform measurement from inside and produce signals and systems that can also be stimulated externally. The devices with power supply and measurement equipment inside are relatively large and have a short lifespan. Furthermore, having a passive component and performing an electromagnetic measurement is a more common method (Antes et al. 2016). The passive component developed by Neurovent having a piezoresistive pressure sensor may be placed into the skull by an incision of 4 cm on the skull surface, followed by making a precoronal and parasagittal burr hole. The need for undergoing another surgery under general or local anesthesia besides shunt insertion is the reason for patients not to prefer this method. Moreover, according to the regulations in Europe, such a system should not stay for more than 90 days inside the patient body. Therefore, another surgical intervention is required for removal operation. This is the reason why the patients do not prefer this method (Antes et al.

2016) (Beez et al. 2016).

Moreover, another disadvantage of such electronic devices placed to the intracranial region is that their measurements increase cumulatively and the zero points thereof are shifted in time (Eide and Bakken 2011). The measurement problems due to material fatigue, contact of the electronic device with fluids, temperature changes, and movement may arise, and intracerebral hemorrhage, new-onset seizures, infections due to incision and wounds and brain abscess may develop in patients whose skull and brain is punctured to place the same (Antes et al. 2016).

National Institute of Neurological Disorders and Stroke (NINDS) associated with The National Institute of Health (NIH) in America reports that 1 or 2 of every 1000 babies is born with hydrocephalus.

Shunts used for the treatment of hydrocephalus are among the medical devices that are most prone to complications during placement and during their presence in the brain. In pediatric patients, there is a risk for complications of 30-40% within 1 year and 50% in 2 years (Kahle et al. 2016) (Hanak et al. 2017). Following an administration with such error rates, the intracranial pressure may re-increase due to obstruction. Patients have to check their intracranial pressure many times during their lifetime.

BRIEF DESCRIPTION OF THE INVENTION

The present invention is relates to an intracranial pressure measurement assembly that eliminates the disadvantages mentioned above and bring new advantages to the related technical field.

The invention, which is the said intracranial pressure monitoring device, is a device for measuring intracranial pressure that may be connected to the shunt during placement of the shunt without the need of a new surgical intervention, without carcinogenic effects, such as an X-ray, with the implanted part being a passive component. Pressure is measured by an magnetic field exerted upon this passive component externally. The said invention may be used in the treatment and monitoring of brain diseases in humans and/or animals in medicine. It is in the field of neurological and neurosurgical diseases. This invention will prevent the patients (particularly children) from continuous X-ray exposure during the treatment course, thereby protecting the patients taking hydrocephalus treatment from side effects during the treatment courses.

The pressure change may be monitored by analyzing deformations of a capsule contained in the chamber to be located on the reservoir region in the front part of the valve, instead of placing electronic measurement devices into the brain.

A system to be placed without the need of another surgical operation during the placement of the shunt in the intracranial region, and not including an electronic component in the body, constitutes the inventive parts.

Patients have to check their intracranial pressure many times during their lifetime. Instead of an electronic device to be placed into the brain, addition of a capsule with lower error possibility and having less equipment, is an advantage compared to other measurement sensors. Moreover, patient’s exposure to cumulative X-ray during this process may be prevented.

REFERENCE NUMBERS

The element/part numbers of the invention and their descriptions are shown below for a better understanding of the invention.

1 Ventricular catheter

2 Intracranial pressure monitoring device

3 Valve and reservoir chamber

4 Distal end

5 Chamber

6 Flexible part

7 Valve and the end connected to the reservoir

8 Rigid Cover

9 Flexible tube BRIEF DESCRIPTION OF THE DRAWINGS

The drawings are described below for a better understanding of the intracranial pressure monitoring device for measuring intracranial pressure developed by the said invention.

Figure 1 Cross-sectional view of parts of intracranial pressure monitoring device (2) integrated into valve and reservoir chamber (3)

Figure 2 a) Initial state of the capsule containing nanoparticles, b) Representation of the deformation of the flexible capsule (6) under increased pressure.

Figure 3 a) Initial state of the cylindrical flexible tube (9) containing nanoparticles, b) Measurement resulting from the deformation of the cylindrical flexible tube (9) under increased pressure.

Figure 4 a) Initial state of the cylindrical flexible tube (9) crossing over the capsule containing nanoparticles, b) Indirect measurement resulting from the deformation of the cylindrical tube under increased pressure can be seen. The diameter of the cylindrical flexible tube (9) increases as the fluid passing through there increases. The shape of the capsule below it will change due to this increase.

DETAILED DESCRIPTION OF THE INVENTION

In this detailed description, novelty of the invention is explained with non-limiting examples only for a better understanding of the subject.

The invention is relates to a device for measuring intracranial pressure that may be connected to the shunt during placement of the shunt without the need of a new surgical intervention, without carcinogenic effects, such as an X-ray, with the implanted part being a passive component. In other words, the device is an intracranial pressure monitoring device (2).

During the treatment course following diagnosis, a shunt is placed to the skull of the patient. In this process there is a capsule inside the chamber (5) that may be inserted into the shunt. The chamber (5) contains a capsule comprising magnetic particles, such as Fe2O3, FesCh, and gadolinium, that exhibit magnetic saturation to some extent. If the intracranial pressure changes, the volume of the capsule will change. With the said difference in volume, the density of magnetic particles in the constant amount will change. By analyzing these particles by magnetic particle imaging system, the extent of deformation in the capsule inserted into the reservoir region can be determined. The pressure increase may be measured according to the deformation. Therefore, it can be decided whether the shunt is working correctly or not, and the progress of the disease may be monitored without causing any harm to the patient.

The developed system does not include X-rays as in CT, and thus, the patient’s exposure to X-rays in cumulative doses is prevented during hydrocephalus treatment.

Electronic Intracranial Pressure (ICP) measurement devices are systems that are placed into the brain, require energy, contain a communicating system for sending the obtained data out, and leads to measurement uncertainties resulting from cumulative measurement errors. Instead of placing such a complex system into the skull, the deformations of flexible capsules under pressure which are positioned into reservoir under the skin by mounting a portion of the shunt and placed into a chamber (5), may be measured by externally by another device. Since shunt is a structure that can be inserted to the valve and reservoir chamber (3), no new surgical operation or intervention is required.

The deformations of the capsule under pressure which is connected to the shunt, are monitored by Magnetic Particle Imaging (MPI) method. The MPI method is based essentially on two different laws of physics. One of them is the nonlinear magnetization behavior of magnetic particles (SPIONs) and the second one is the creation of a certain field free point (FFP) in the workspace (Gleich and Weizenecker 2005). Thus, FFP may be moved to the capsule (6) region in the workspace and the reaction of magnetic particles it contains to an external magnetic field will be monitored. There are academic studies that apply MPI method for brain applications (Mason et al. 2017), (Graser et al. 2018), however, there is no study conducted on the measurement of the intracranial pressure.

Different methods may be used in addition to the design that surrounds the head. A singlesided magnetic particle imaging system (Sattel et al. 2009) (Rudd and Tonyushkin 2018) is used for particularly superficial regions. A superficial measurement may be ensured by a system belonging to the shunt placed close to the skin, such as subcutaneously, instead of intracranial region.

Following diagnosing the disease, the change in pressure may be monitored by a capsule added into the reservoir of the inserted shunt to remove excess CSF from the intracranial region. This capsule contains superparamagnetic iron oxide nanoparticles (SPIONs), such as Fe2O3, FcaCU. and gadolinium. These SPIONs are stimulated by an external magnetic field and can be monitored in the chamber. The change in the volume of SPIONs in the capsule at a constant proportion provides information regarding the concentration of the particles. The relationship between pressure and volume of this capsule can be defined by a polytropic process with no heat transfer on the boundary layer.

PV ¹ = Constant (1)

PlVl ⁿ = P2V2 ⁿ (2)

In Formula 1, P represents pressure, V represents the volume, and n (1.4 for air) represents the polytropic index (Li, Wei, and He 2016). Magnitudes of intracranial pressure are defined as 7- 15 mmHg for a healthy person (Albeck et al. 1991). For hydrocephalus patients, 15 mmHg, 20 mmHg and 25 mmHg are accepted, respectively, as pressure values representing increase, being abnormal and requiring aggressive medical treatment (Czosnyka and Pickard 2004). The effect of pressure change of the capsule on the volume may be calculated by Formula 2.

The chamber (5) shown in Figure 1 is biocompatible, and flexible or rigid.

The capsule containing nanoparticles shown in Figure 1 is the flexible part changing its volume as the intracranial pressure changes, deformations of which under pressure can be monitored. This flexible part is a flexible capsule or flexible film.

The valve and the end connected to the reservoir (7) shown in Figure 1 is the end that is connected to the reservoir of the intraventricular shunt used in the treatment of hydrocephalus. An end (7) element should be connected inbetween due to the intracranial pressure monitoring device (2) element placed between the ventricular catheter (1) and reservoir chamber (3) elements of the shunt. It ensures the device connection. The valve and the end connected to the reservoir (7) are between the intracranial pressure monitoring device (2) and valve and reservoir chamber (3) elements, thereby providing CSF flow. The ventricular catheter (1) - distal end (4), and valve and the end connected to the reservoir (7) elements of the shunt play no other role than transferring the fluid and connecting discrete parts.

Upon scanning with MPI system on the study carried out, different results may be achieved according to the shape of the chamber. Figure 2 shows the system that enables direct pressure exposure of the capsule. As the pressure of the cerebrospinal fluid in the chamber (5) increases, the shape of the capsule changes.

A system that enables fluid flow within a tube in the chamber (5) may be designed. The pressure increase in the cylindrical flexible tube (9) containing nanoparticles leads to an increase in the diameter of the flexible tube (9). Because of this increase, the pressure increase is estimated. Figure 3 shows the effect resulting from the deformation of the flexible tube.

Because of the flexible tube’s (9) capsule structure containing nanoparticles placed to contact each other, the deformation of the flexible tube (9) leads to a deformation in the capsule. Therefore, the pressure will be indirectly increased. The pressure increase may be measured by observing this deformation outside the body. Figure 4 shows this deformation of the flexible structure.

Some distinctive features of the said invention are listed below. These include:

• Being an implantable device for measuring intracranial pressure,

• Chamber, capsule/film system integrated into the shunt,

• Pressure measurement integrated into the reservoir,

• Being a system that may be integrated into the shunt,

• Determining pressure change from volume change,

• Measuring pressure by Magnetic Particle Imaging, Magnetic Resonance Imaging, Ultrasound Imaging systems.

A subcutaneous device for measuring intracranial pressure having a valve, which can be implanted to the shunt placed into the brain of a patient and can work together with a reservoir that allows fluid drainage by an injector if needed, a distal end (4) that helps to transfer cerebrospinal fluid (CSF) from the brain to peritoneal, pleural, pericardial and biliary cavities and valve elements, opening of which can be adjusted according to pressure increase or decrease and that allow the transfer of cerebrospinal fluid (CSF) to the distal end (4), characterized in that it comprises the following elements:

• A flexible part (6) mounted between the ventricular catheter (1), and valve and reservoir chamber (3) of the shunt, containing superparamagnetic iron oxide nanoparticles, changing its volume as the intracranial pressure changes due to its flexibility, comprising biocompatible nanoparticles, such as RTV (mould silicone), PDMS (poly dimethylsiloxane), silicone, etc., deformation of which under pressure between 10% and 90% can be monitored (It could be a flexible film or flexible tube (9) or capsule changing its volume as the pressure of the fluid therein increases, and containing nanoparticles enabling deformation, which can be inserted between ventricular catheter (1) and valve and reservoir chamber (3)),

• A chamber (5) with a flexible part (capsule) (6) enabling deformation as the pressure of the fluid therein increases which is inserted to the shunt and containing nanoparticles,

• A distal end (4) enabling the transfer of cerebrospinal fluid from the brain to the peritoneal, pleural, pericardial and biliary cavities,

• Valve and an end connected to the reservoir (7) which is placed between intracranial pressure monitoring device (2), and valve and reservoir chamber (3), and ensures the flow of cerebrospinal fluid and the device connection,

• A monitor which enables monitoring the deformation in the flexible part externally by magnetic or ultrasound methods,

• A rigid cover (8) protecting the chamber (5) and the flexible part (6) (may be a capsule, etc.) from external factors and pressure changes.

The said monitor is software that calculate the pressure by reading the deformations in the device from the images obtained by medical magnetic or ultrasound imaging methods.

By the said flow in the chamber described above, the cerebrospinal fluid is transferred from the brain to the peritoneal, pleural, pericardial, and biliary cavities. The pressure change may be calculated by the deformation of the flexible structure within the chamber placed either between the ventricular catheter (1) and reservoir or within the reservoir. In general, the chamber (5) with a flexible film or capsule constitutes the inventive parts. An ordinary shunt consists of the ventricular catheter (1), valve and reservoir chamber (3), and a distal end (4). A separate chamber (5) to be placed between ventricular catheter (1), and valve and reservoir chamber (3) constitutes the scope of the patent. As the cerebrospinal fluid flows toward body cavities, it passes through the chamber (5) and deforms the flexible capsule (6) and flexible tube (9) therein. The flexible part should contain iron oxide-based magnetic field materials for monitoring.

Other embodiments of the invention include:

• The flexible part contains other magnetic contrast agents, such as superparamagnetic iron oxide nanoparticles like Fe2O3, Fe3O4, and gadolinium.

• The superparamagnetic iron oxide nanoparticles within the said flexible part are Fe2O3, Fe3O4, and gadolinium ranging between O.lng and 5mg.

• The said flexible part is a flexible capsule or flexible tube (9) or flexible film.

• The said flexible capsule is either cylindrical or spherical.

• The flexible film which is the said flexible part, contains superparamagnetic iron oxide nanoparticles of Fe2O3, Fe3O4, and gadolinium.

• The deformations occur as the cylindrical tube contacts the flexible capsule.

• It contains a flexible tube in the chamber where the flow passes over, which is placed on the capsule and enables movement of the particles to right or left in the capsule made from an elastic material as the pressure therein increases.

• The said flexible capsule contains magnetic contrast agents.

• The said flexible tube (9) contains magnetic contrast agents.

• The said flexible tube (9) has circular, ellipsoid, half-moon, square, rectangular, or polygonal cross-sections.

• The said flexible capsule contains a flexible film covered with superparamagnetic iron oxide nanoparticles and placed on the rigid cylinder to ensure its flexibility in case of pressure increase.

• The flexible capsule (6) consists of mould silicone, polydimethylsiloxane, or silicone.

• It contains a flexible capsule (6) deformations of which under pressure between 10% and 90% can be monitored.

• The said flexible part (6) in the chamber is a flexible capsule.

• The said tube is cylindrical. • The said flexible capsule or flexible tube (9) or flexible film contains superparamagnetic iron oxide nanoparticles of Fe2O3, FesCU, and gadolinium.

• It contains the flexible tube (9) in the chamber (5) where the flow passes over and the capsule (6) below it containing nanoparticles with the deformation of the flexible tube (9).

• It contains the flexible tube (9) in the chamber (5) where the flow passes over and which contains nanoparticles and changes its shape according to the flow pressure.

• The said capsule contains a flexible film covered with superparamagnetic iron oxide nanoparticles and placed on the rigid cylinder to ensure its flexibility in case of pressure increase.

In the device for measuring intracranial pressure, the deformation of the flexible part contained therein can be determined outside the body. By monitoring this, any change may be detected. By external magnetic stimulation, information on a possible increase in the cerebrospinal fluid may be obtained by locating the flexible part.

An operation method of the device for measuring intracranial pressure, characterized in that it comprises the following operation steps:

• Following diagnosing the disease, placing the device either between the ventricular catheter (1), and valve and reservoir chamber (3) of the shunt placed on the patient or within the reservoir

Transferring excess cerebrospinal fluid from the brain to the body cavities,

• Determining the deformation because of the pressure in the chamber placed before the reservoir during this transfer,

• Observing the extent of deformation of the flexible part with contrast agent outside the body with methods such as magnetic particle imaging, magnetic resonance imaging,

• Increasing the valve opening in the reservoir in case of increased pressure and reducing the valve opening in case of excess drainage (Therefore, the valve may be adjusted in a controlled manner).

The flexible tube shows that the capsule, the basic element of the invention, may be produced and used having the same physical feature but in different shapes. In other words, the capsule containing nanoparticles may be implemented in a form like a tube. The cross-section of this tube may be similar or different such as a half-moon shape.

3 different measurement methods were suggested. These are shown in Figure 2 - Figure 3 - Figure 4. It is suggested essentially that the deformation of the flexible part (film, capsule, cylindrical or spherical, ellipsoid, half-moon, square, rectangular, or polygonal tube) coated with nanoparticles is measured.