OBJECT OF THE INVENTION

The objects of the invention are a hand-held device and a method for preventive, non-invasive, easy-to-implement, and cost-effective acoustic cleaning of cerebrospinal fluid (CSF) shunt systems (valves and catheters) implanted in patients of hydrocephalus using focused ultrasound (sonic cleaning). It is based on optical and thermal image-guided ultrasound focusing for removal of accumulated debris, clearing obstructions and improving cerebrospinal fluid flow through implanted catheters and valves.

BACKGROUND OF THE INVENTION

Hydrocephalus is a relevant neurosurgical pathology, both in children and in the aging population. It comprises a wide set of ailments associated with alterations of the cerebrospinal fluid hydrodynamics and the biomechanical properties of the nervous central system structures.

Certain types of hydrocephalus are relatively common both in children and in the aging population. In adults, the most common is the idiopathic normalpressure. It has an estimated incidence range of 1.8-2.2 cases/100.000 adult individuals (0.41 % of the population over 65 years-old). In children, prevalence of congenital and pediatric hydrocephalus ranges to 0.5-0.8 cases/1 .000 newborn.

In many cases, these pathologies are characterized by an enlargement of the lateral ventricles of the brain (due to accumulation of fluid) and by the physiological and cognitive consequences of compression of adjacent structures, damages in surrounding tissue and other effects of increased intracranial pressure.

In the majority of cases (70%), treatment usually requires neurosurgical placement of a shunt to drain CSF from brain ventricles (proximal segment, 14-20 cm), through a small hole in the skull, to a valve under the skin (cranial vault) and an outflow catheter (up to 1 m) to a distal cavity (peritoneal, heart, pleura).

Complications of shunting are frequent, and their clinical consequences define a life-threatening medical condition. They range to a 50% failure rate 2 years after implantation in pediatric patients or to 84.5% of patients requiring 1 or more shunt revisions, and 4.7% requiring 10 or more in a 20-year follow-up.

The most common complication is occlusion (particularly of proximal catheter, 27%) due to build-up of excess proteins, clots and infection. However, symptoms of occlusion are initially similar to common diseases and early diagnosis and treatment of an obstructed catheter or shunt malfunction is a defying area.

Therefore, complications are difficult to anticipate and require immediate surgical removal because of risks of serious neurological damage and even death. Such complications have a deep social impact in the quality of life of patients, their families and caregivers, and a high economic cost. When a patient experiments a CSF drainage blockage, standard (emergency) treatment is based on the neurosurgical replacement of the shunting system.

It is known from the state of the art an existing technology of “focused ultrasound surgery”, which is based on the concentration of ultrasound energy to produce an intended temperature increase. However, this technology requires large, heavy and costly surgical and medical imaging equipment. In conclusion, early diagnosis and treatment of an obstructed catheter or shunt malfunction remains as a defying area and there is no preventive technology or protocol to avoid them.

DESCRIPTION OF THE INVENTION

The present invention describes a hand-held device for the application of image-guided, focused ultrasound, for preventive, non-invasive, easy-to- implement, and cost-effective acoustic cleaning of implanted shunts in patients of hydrocephalus. It can be used on a routine basis to any patient.

The device is based on the potential of mechanical and thermal effects of cavitation and acoustic streaming for removal of accumulated debris, clearing obstructions and improving cerebrospinal fluid flow through implanted catheters and valves.

Image guidance and monitoring are achieved by the combination of optical (visible, near infrared and thermal infrared) and medical ultrasound imaging. These technologies complement each other and their combination will allow for a fast and precise location of the shunt and catheters, located only a few millimeters under the skin (over the skull bone).

Ultrasound focusing is achieved by the overlapping of beams emitted by individual transducers (ultrasound emitters). Focusing and concentration at the location of interest (valve and catheters) can be achieved by any of the following procedures or their combination: i) location of the transducers according to a geometrical set-up equivalent to an array of emitters from a concave surface, ii) combination of individual transducers and acoustic lenses (appropriate for the frequency of emission), and iii) stimulation of individual emitters following an appropriate phase pattern. The use of acoustic lenses and appropriate phase patterns for stimulation of emitters allows for obtaining directional focusing while keeping the transducers on a flat, planar surface. The volumetric region of space in which the ultrasound beams concentrate is called “concentration volume” or “sonication volume”.

The emitters are modelled as dipolar sources or as a vibrant surface. The device achieves a desired level of amplitude (measured in Pascals, Pa) and power density (measured in watts per square meter, W/m2) of the ultrasound field at the location of the implanted catheters and valve (sonication volume) while preserving the environment of increased temperature.

Specifically, the device comprises:

- a set of emitters, preferably a set of piezoelectric ultrasound transducers;

- an ultrasound generator of control and stimulation signals connected to the emitters, that excites the emission of ultrasound with user-selectable cycles and amplitudes; - a container for a suitable fluid (e.g. gel used for medical ultrasound imaging, water, ... ) for matching ultrasound propagation from the emitters to the skin (impedance matching). The emitters are positioned inside the container, which is intended to be placed over the head of the patient, centered in the location of the valve.

Additionally, the device can comprise an optical imaging unit, which in turn, comprises:

- one or more cameras, for capturing images in the visible range (VIR), near infrared images (NIR) and thermal infrared images (TIR); and a user-controlled module for selection, overlapping and visualization of the images.

- an optically transparent viewfinder or similar optical device, with a cross-hair or similar reference mark, referenced to the sonication volume, so that the user can also aim the sonication volume using the cross-hair mark. Using the optically transparent viewfinder, the device can also be positioned over the desired location of the valve (if it can be visualized) without using the cameras. The optical imaging unit with the cameras is used to monitor and control the process, including locating and positioning the device over the valve, and monitoring the temperature in the area of application of the ultrasound.

The application (sonication) parameters can be adjusted to the specific features and clinical status of individual patients and their shunting systems, in the current paradigm of Personalized Medicine.

In an aspect of the invention, the device also comprises a simulation module, which stores data related to the arrangement and features of the emitters and of the fluid container, and the features of the valve (a library of the different types of valves).

The simulation module can be connected to and external device, like a computer or a tablet, and perform 3D simulations of the concentration of the ultrasound beams generated by the emitters, to make sure that the proper level of acoustic energy (resulting amplitude (measured in Pa) and power density (W/m2) is achieved at the location of the valve and of the catheter.

Moreover, is also object of the present invention a method, which steps can be performed in the simulation module (8), and that can be executed before the cleaning with the device on the patient.

A personalized 3D study and simulation is performed, which comprises the following steps:

- Generating a geometric model, preferably of the area where the valve is implanted, the implanted valve and the catheters, the emitters, and the frame,

- definition of material properties, to simulate for example thermal behavior, densities, sound velocities, impedances and attenuation coefficients to simulate acoustic behavior,

- creation of a mesh of elements to calculate a final solution,

- assignment of boundary conditions,

- calculation and representation of results, - if a problem is detected in the calculation: o adjustments and/or by means of artificial intelligence algorithms, o the process is repeated until the problems are solved,

- if problems are detected in achieving the objective (no concentration is achieved in the valve area, or there is excessive concentration in undesirable areas): o manual adjustments and/or by means of artificial intelligence algorithms,

- the process is repeated until the objectives are achieved.

Another aspect of the invention relates to computer-readable storage means comprising program instructions capable of making a computer perform the steps of the method of the invention.

The invention also extends to computer programs adapted so that any processing means can carry out the method of the invention. Such programs may take the form of source code, object code, an intermediate source of code, and object code, for example, as in partially compiled form, or in any other form suitable for use in implementing the processes according to the invention. Computer programs also encompass cloud applications based on this procedure.

In particular, the invention encompasses computer programs arranged on or within a carrier. The carrier can be any entity or device capable of supporting the program. When the program is incorporated in a signal that can be directly transported by a cable or other device or medium, the carrier may be made up of said cable or another device or medium. As a variant, the carrier could be an integrated circuit in which the program is included, the integrated circuit being adapted to execute, or to be used in the execution of, the corresponding processes. For example, the programs could be embedded in a storage medium, such as a ROM, a CD ROM or a semiconductor ROM, a USB memory, or a magnetic recording medium, for example, a floppy disk or a disk. Lasted. Alternatively, the programs could be supported on a transmittable carrier signal. For example, it could be an electrical or optical signal that could be transported through an electrical or optical cable, by radio or by any other means.

The invention also extends to computer programs adapted so that any processing means can carry out the method of the invention. Such programs may take the form of source code, object code, an intermediate source of code, and object code, for example, as in partially compiled form, or in any other form suitable for use in implementing the processes according to the invention.

Computer programs also encompass cloud applications based on this procedure.

Therefore, another aspect of the invention relates to a computer-readable storage medium comprising program instructions capable of causing a computer to carry out the steps of any of the methods of the invention.

Another aspect of the invention relates to a transmittable signal comprising program instructions capable of causing a computer to carry out the steps of any of the methods of the invention.

The present invention presents an innovative approach to a relevant, unsolved problem in neurosurgery and healthcare: the prevention and management of a very common complication, shunt obstruction, in patients of hydrocephalus along their life. It proposes a non-invasive, easy-to-implement, and cost- effective device for preventive or therapeutic cleaning of implanted devices (valves and catheters). It implies a significant change in the management of this pathology, with a substantial impact in the quality of life of the patients and a strong reduction of costs. The proposed solution would allow for the establishment of a new clinical, innocuous, procedure that could be performed on a routine basis in any patient to reduce the number and frequency of shunt revisions in (emergency) neurosurgical procedures. A scheduled “cleaning” treatment could be particularly useful in the first months after shunt placement, when risks of obstruction are considerably higher. This procedure could also be adapted to remove clots or other products in shunts of patients presented at emergency department with acute malfunction.

In addition, the proposed device could be extended for similar cleaning and maintenance protocols of other types of implanted devices (catheters, valves, pumps) in different clinical areas such as systems for pain control and medication delivery or fluid drainage in neurosurgery and neurology, oncology (chemotherapy), cardiology, lung and possible others.

DESCRIPTION OF THE DRAWINGS

To complement the description being made and in order to aid towards a better understanding of the characteristics of the invention, in accordance with a preferred example of practical embodiment thereof, a set of drawings is attached as an integral part of said description wherein, with illustrative and non-limiting character, the following has been represented:

Figure 1.- Shows a general schematic view of the device cleaning the shunt system of a patient.

Figure 2.- Shows and embodiment of the device, wherein it comprises three emitters oriented to the shunt system.

Figure 3.- Shows a scheme representation of the connections in the device.

Figure 4.- Shows a view of the emitters inside the container for the fluid. Figure 5.- Shows an upper view of the device.

Figure 6.- Shows a view of the fastening means of the device.

PREFERRED EMBODIMENT OF THE INVENTION

With help of figures 1 to 6 a preferred embodiment of a device for non-invasive preventive cleaning of spinal fluid shunt systems in patients with an implanted shunt (10), for example a valve and a catheter, is described below.

As shown in figures 1 and 4, the device comprises a frame (4) wherein a set of emitters are positioned. The number of emitters can be adjusted according to a selected geometrical set-up. A preferred array of emitters is that composed of four piezoelectric ultrasound transducers (1 ), located in a squared array such that their beams are emitted pointing to an imaginary axis (21 ) orthogonal to a plane containing the geometrical centers of the transducers (1 ).

This layout also requires symmetry of the transducers (1 ) with respect to the axis (21 ), which is to be called the “axis of the system” or “axis of application of the ultrasound”. This axis (21 ) is an easy-to-interpret reference to locate the sonication volume. It is important to note that, if no acoustic lens is used, concentration can only be achieved if a symmetrical number of transducers (1 ) is used. Moreover, the transducers (1 ) should preferably be located over an imaginary plane whose orthogonal axis (21 ) (of symmetry) be the axis (21 ) of the system.

To achieve concentration at a given location along that axis (21 ) (without the use of acoustic lenses or specific phase patterns) the transducers (1 ) must be tilted a certain angle so that the orthogonal directions of their emitting faces point to the desired location along the axis (21 ) of the system. Another embodiment can be with any number of transducers (1 ) symmetrically located (with respect to the axis (21 ) of the system) along a circular line contained in a plane orthogonal to the desired axis (21 ) of the system.

The device also comprises an ultrasound generator (3) of control and stimulation signals connected to the transducers (1 ), that excites the emission of ultrasound with user-selectable cycles and amplitudes.

The transducers and the ultrasound generator (3) must be selected to operate at the same frequency. The value of the frequency must be in the range of from 30 kHz to 200 kHz, but other ranges in the ultrasonic (kilohertz, kHz) and megasonic (megahertz, MHz) ranges may also be useful.

The value of the frequency is related to the relative distance between the transducers (1 ) and the distance from their plane to the desired location of the sonication volume along the axis (21 ) of the system.

For example, using transducers (1 ) at 39 kHz, arranged in a symmetrical square lay-out, with side of the square of 7 cm, with simultaneous emission (no phase delay, same amplitude for all emitters), the sonication volume (22) in water is located at 9 cm measured from the face of the transducers (1 ) along the axis (21 ) of the system. Alternatively, as shown in figure 2, the transducers (1 ) can be arranged in a triangular lay-out, or any other lay-out that facilitates the operation of the device.

The container (9), shown in detail in figure 5, is preferably made out of an optical transparent material (e.g. methacrylate) and in a cylindrical shape. It can also adopt a truncated cone or parallelepiped shape. Inside the frame (4), the device comprises an optically transparent container (9) for a suitable fluid (e.g. gel used for medical ultrasound imaging, water, ... ) for matching ultrasound propagation from the transducers (1 ) to the skin (impedance matching) of the patient. The transducers (1 ) are positioned inside the container (9) and therefore, may be partially or totally submerged in the fluid. In another embodiment, the transducers (1 ) may be located attached or adhered to a vibrant surface.

The container (9) can additionally comprise an optical lateral window to allow direct visualization by the user of its inner volume and a vertical graduated scale. The window can be located in the inner area of the holding platform (15) or in any other part of the lateral wall of the container (9).

The container (3) additionally comprises a vertical graduated scale, parallel to the axis (21 ), that allows to adjust the height of the emitters (1 ) with respect to the skin surface of the patient, to locate the sonication volume (22) on the targeted part of the shunt system (10). The combined use of this scale and the cross-hair mark (51 ) at the optical viewfinder allows for precise 3-dimensional location of the sonication volume (22) on to the desired targeted area of the shunt system (10).

The matching fluid is necessary to allow for impedance matching and, therefore, to achieve the focalization of the ultrasound beams on the desired location of the shunt system (10). However, the height of the container (9) and therefore, the volume of the fluid can be adjusted (depending on the geometry of the set-up and on the frequency of the transducers (1 ).

As shown in figure 1 , the device can comprise a set of optional acoustic lenses (6) linked to the ultrasound transducers (1 ) and allowing a better focalization of the ultrasound signal. In this case, the thickness of the fluid layer and the height container (9) can be of only a few millimeters.

Alternatively, as shown schematically in figure 1 , the container (9) can have an upper surface of concave shape, being the transducers (1 ) located on this surface and the fluid placed inside the defined volume. In this way, the concave shape of the container (9) (combined with the cylindrical walls) is the element that focalizes the ultrasound beams.

The container (9) comprises a neoprene gasket (91 ) placed at one end, and intended to contact and adapt to the skin of the patient without damage. It also comprises and inlet and outlet (92) that allow the movement (inflow an outflow) of the fluid through the container (9). As can be seen in figure 5, the frame (4) also comprises a vertical guiding element (93), linked to the transducers (1 ), to regulate the height of their plane. This element can be: grooves inside the frame (4), a rack and pinion system, or a worm screw.

The acoustic matching (impedance-matching) fluid is disposable. The perimeter of the container (9) is covered with a disposable border.

Associated to the ultrasound generator (3), the device comprises an ultrasound focalizing system (13), to control the ultrasound focalization. Several approaches can be used: a geometric control, by means of micrometric trunk, regulating the angle of inclination of the transducers (1 ); phase or beam steering control, by means of the ultrasound generator (3); and acoustic lens control, wherein an acoustic lens (6) is placed in front of each transducer (1 ) in order to focus them in the desired area.

During the concentration of ultrasound beams it is important to monitor the temperature of the skin. Image guidance and monitoring is achieved by the combination of optical (visible, near infrared and thermal infrared) imaging of the shunt (10) and catheters, located only a few millimeters under the skin (over the skull bone). To this end, and connected to the holding structure of the transducers (1 ) the device comprises an optical imaging unit (5), shown in figure 3, which in turn comprises one or more cameras (2), for capturing images in the visible range (VIR), thermal infrared images (TIR) and near infrared images (NIR). Moreover, the imaging unit (5) also comprises a user-controlled module (7), for example a micro-computer with a screen, for selection, overlapping and visualization of the images obtained by the cameras (2). It can additionally comprise a light beam multiplexer cube (using dichroic prisms or filters for combination of VIS / NIR / TIR images).

The optical imaging unit (5) monitors and controls the locating and positioning of the device over the shunt (10), and monitors the temperature in the area of application of the ultrasound.

As shown in figure 5, the imaging unit (5) also comprises an optical viewfinder with a cross-hair mark (51 ), placed on one end of the frame (4), analogous to those arranged in optical alignment and aiming systems, to adjust the device in the area to be treated.

As shown in figure 4, the device also comprises a lighting module (11 ) placed inside the frame (4) and oriented towards the patient. It comprises several light emitting diodes (LEDs), which can be placed in the form of one or more stripes or in the shape of a ring. The lighting module (11 ) also comprises a lighting controller, which allows for the regulation of the module (11 ) with a switch, a mobile app or an intensity regulator, being able to control the turning on and off of the module (11 ) as well as the intensity of the lighting.

As can be seen in figure 6, the device comprises a fastening module, linked to the frame (4), which in turn comprises lateral handles (12) for the handling of the device, and a hook (15) for operating the device with standard positioning devices or robotic arms.

The device also comprises a temperature monitoring module, shown in figure 4, and linked to the frame (4) and/or the container (9), that comprises in turn a temperature sensor (thermocouple) that measures the temperature of the zone to be treated with the device, and a control module which warns if the temperature recorded by the thermocouple exceeds a certain threshold.

The device can be operated by rechargeable battery or connected to the power supply. Also, different connection methods are available: USB, Ethernet, WiFi, Bluetooth or any other.

Finally, the device comprises a simulation module (8), as can be seen in figure 3, which stores data related to the arrangement and features of the transducers (1 ), of the fluid stored in the container (9) and of the features of the shunts (10). It can contain a library of the different types of valves.

The simulation module (8) can be connected to and external device, like a computer or a tablet, and performs 3D simulations of the concentration of the ultrasound beams generated by the transducers (1 ), to make sure that the proper level of acoustic energy (resulting amplitude (measured in Pa) and power density (W/m2)) is achieved at the location of the shunt (10) (valve and catheter).

The 3D simulation is a standard 3D mesh, suitable for numerical calculations using the method of finite elements (FE), and it can be used by commercial programs (e.g. COMSOL).

Specifically, is also object of the present invention a method, whose steps can be performed in the simulation module (8), and that can be executed before the cleaning with the device on the patient.

A personalized 3D study and simulation is performed, which comprises the following steps:

- generating a geometric model of: o the area where the shunt system (10) is implanted, including the thicknesses of the different layers of the patient's tissue (white and gray substances of the brain, cortical and trabecular bone of the skull, skin, scar tissue surrounding the valve, and the cerebrospinal fluid that circulates through it), o the implanted valve and the catheters, o the ultrasound transducers (1 ) (the number used), their relative positions to each other, and their distance from the valve. As well as the inclusion of additional elements for concentration such as acoustic lenses (6), o the structure of the device (its different possible geometries), the neoprene gasket (91 ) with the head, and the ultrasound liquid.

- definition of material properties, such as thermal conductivities and heat capacities to simulate thermal behavior, densities, sound velocities and attenuation coefficients to simulate acoustic behavior,

- creation of a mesh of elements to calculate a final solution. The elements may have different internal functions, different geometries and different number of nodes. The mesh is optimized for the calculation to be fast and at the same time precise, being its size variable according to the proximity of the areas of interest,

- assignment of boundary conditions. At the borders of the geometric model, so that the behavior of the real system is correctly captured (no reflectance) And emission of ultrasounds in the transducers (1 ) at different frequencies, performing a frequency scan, and controlling the phase of the different transducers (1 ),

- calculation of results. Being able to use different types of resolvers (direct, iterative, ...) and different calculation modules (sound pressure in the frequency domain, in the time domain, ...),

- representation of results. Using sound intensity (W/m2) and sound pressure (Pa) variables. Spatial distribution of both fields and their amplitudes.

- If a problem is detected in the calculation (unreasonable results): o manual adjustments are made and/or by means of artificial intelligence algorithms in the biological model, the model of the drainage system, the type of element, the boundary conditions, the optimization of the mesh, and the type of solver, o the process is repeated until the problems are solved,

- if problems are detected in achieving the objective (no concentration is achieved in the valve area, or there is excessive concentration in undesirable areas): o manual adjustments and/or by means of artificial intelligence algorithms are made to the model of the ultrasound emitting system, the model of the device structure, the emission of the transducers (1 ), and the calculation method.

The process is repeated until the objectives are achieved.