WO2011145128A1

WO2011145128A1 - System for acquiring and monitoring bioelectric signals from brain

Info

Publication number: WO2011145128A1
Application number: PCT/IT2011/000162
Authority: WO
Inventors: Fabio Sebastiano; Pantaleo Romanelli
Original assignee: Ab Medica S.P.A.
Priority date: 2010-05-20
Filing date: 2011-05-17
Publication date: 2011-11-24
Also published as: ITRM20100261A1

Abstract

The present invention concerns a system for acquiring and monitoring bioelectric signals from a patient's brain, in particular electroencephalographic and/or electrocorticographic signals, comprising: - a plurality (1) of bioelectrical signal sensing electrodes, capable to be connected to at least one acquisition device (3), and - at least one apparatus (8) capable to receive signals corresponding to said bioelectrical signals sensed by the plurality (1) of electrodes, the system being characterised in that said at least one acquisition device (3) is provided with wireless transmitting means (4), through which it is capable to transmit said bioelectrical signals sensed by the plurality (1) of electrodes to wireless receiving means (5) with which at least one first receiving device (6) connected to said at least one apparatus (8) is provided.

Description

SYSTEM FOR ACQUIRING AND MONITORING

BIOELECTRIC SIGNALS FROM BRAIN

The present invention relates to a system for acquiring and monitoring bioelectric signals from a patient's brain, i.e. biological and electrophysiological signals, in particular neural signals, more in particular electroencephalographic and/or electrocorticographic signals, that allows in a manner that is reliable, versatile, simple, inexpensive, and safe for the patient to monitor such signals for long time periods, even of the order of weeks and months, and in any place the same patient is, in particular in patients suffering from pathologies related to the neuroscience wherein it is useful to monitor the electrical activity of the cortex or deep cerebral nuclei such as the thalamus, the subthalamus, the pallidus, the striatum, the amygdala or the hippocampus. By way of example and not by way of limitation, possible clinical indications for an invasive monitoring made by applying the system according to the invention includes, among others, the drug-resistant epilepsy (for which the system allows an extremely accurate localisation of the main focus and possible secondary epileptic foci), the Parkinson's disease and other movement disorders, the drug- resistant major depressive disorder and other psychiatric disorders such as the obsessive-compulsive disorder, the chronic pain.

In the context of clinical neuroscience, a significant increase of application of new technologies of monitoring and cerebral electrical stimulation for diagnostic and therapeutic purposes has occurred, surgical therapy of epilepsy and Parkinson's disease has been subjected to drastic changes in last years thanks to the application of new technologies of neurophysiological mapping and cerebral stimulation which have allowed a localisation of the areas on which interventions of "resective" surgery or cerebral stimulation are to be performed. In this regard, the application of cerebral stimulation techniques is now going to be extended to other field such as psychiatry.

In fact, the first "resective" surgery intervention has been made on 1880, after anesthesiological and surgical instruments techniques have been enhanced. However, it was little more than a therapeutic "curiosity" until the end of the Thirties when the introduction of the ElectroEncephaloGraphy (EEG) caused a significant leap forward first of all for clinical epileptology and consequently also for epilepsy surgery, offering the concrete possibility of a topographic localisation of the epileptic focus. At the end of the Eighties, the availability of magnetic resonance imaging (MRI) has started a new era for epilepsy surgery. Such neuroradiological technique has simplified the pre-surgery diagnostic procedure allowing identification of epileptogenic lesions, such as the mesial sclerosis of the hippocampus and disorders of the cortical organization such as dysplasias, invisible to the other techniques of neuroimaging, such as for instance the Computed Tomography (CT).

The possibility of identifying non invasively the presence of structural cerebral abnormalities has significantly simplified the diagnostic procedure, facilitating the selection of patients to send to surgery and making their prognosis radically improve. As a result, there has been a significant increase of the percentage of patients for whom the resective surgery has become a realistic option.

The conceptual base of selective surgery is that there is an "epileptogenic area" inducing crisis (partial epilepsy) and that its surgical resection consequently abolishes crisis. The purpose of the pre-surgery assessment of a patient is to define the anatomical limits of the epileptogenic area, allowing an assessment of the practicability of a complete or partial resection and of its potential risks. While the concept of epileptogenic area owns the attractiveness of simplicity and apparent logic, practically it cannot be often defined with accuracy. In the same way, the limits of the surgical resection are often chosen on rather empiric basis.

Nevertheless, once that its limitations are known, the concept of epileptogenic area provide for a simple base that is convenient to pre- surgical investigations in most patients with epilepsy.

Two important components of the epileptogenic area are the anatomical lesion (epileptogenic lesion) and the area that is the seat of the electroencephalographic alterations (irritative area). These areas overlap to each other almost always, but they do not necessarily coincide. Hence, epilepsy may originate from a circumscribed part of the lesion, and independent electroencephalographic modifications may occur at a distance from the pathological area.

The whole method of resective surgery is based on the principle that the clinical symptomatology of partial crisis reflects the space-time organisation of the intracerebral critical discharge, and its purpose is to precisely and individually identify cortical regions participating to the initial discharge processing (Epileptogenic area), in order to make its surgical ablation, within the limits imposed by functional anatomy.

With regard to the electrophysiological investigations, it is currently demonstrated that the inter-critical ElectroEncephaloGram, in most cases, has not a value that sufficiently localises, and even less identifies lateralisation (identification of the involved hemisphere), the epilepsy of the subject, still maintaining a fundamental role in suggesting or giving confirmation the existence of a single, multiple, or diffused lesion process, and in assessing the possible presence of irritative abnormalities (localised, multiple, or diffused spikes). Recording crisis remains, in any case, a fundamental step. For such reason patients are subjected to EEG and video, synchronised, long lasting recordings, for several days, thus enabling to wait for the time necessary for occurrence of spontaneous events. In this regard, conventional Electroencephalography sensors allow to monitor the EEG signal through electrodes which are directly connected to the patient through various meters of cable connecting to the processing, monitoring and recording apparatus. The ElectroEncephaloGram is usually measured through electrodes applied on the scalp.

In the cases where it is not possible to spatially define the epileptogenic area by "non invasive" methods, conduct of investigations of "invasive" nature is used, carried out by implanting intracranial subdural electrodes (usually a grid and/or multicontacting strips resting on the cortical surface) or intraparenchymal electrodes inserted in stereotactic conditions. Such methods allows recording the electrical activity cortical or deep electrical activity during spontaneous or induced (e.g. through intracerebral electrical stimulations) crisis.

Intervention for electrode application, in general anaesthesia, consists in a localised craniotomy at level of the carrefour regions, the precise extension and seat of which has been defined on the basis of the pre-surgery investigations.

The precise localisation of the single contacts of the cerebral electrodes is defined by fusing images between pre-implant volumetric Magnetic Resonance (MR) and post-implant CT.

The patient is then subjected to a new prolonged Video-EEG monitoring, with recording of spontaneous and/or induced crisis from intracerebral electrical stimulations, and for performing the cortical electrical stimulations useful for functional mapping the eloquent areas (language areas, motion areas, visual areas, etc.).

More in particular, continuous video-EEG monitoring is usually conducted (usually with a number of channels from 1 to 128, with sampling variable in the range 400-800 Hz) under partial reduction of drug dosage, and it generally lasts about five days. Electrocorticographic and surface EEG channels are simultaneously displayed on the monitors. After identification of the so-called "seizure onset areas" (i.e. the area wherein the crisis establishes) through the analysis of the recorded spontaneous crisis, the cortical electrical stimulations are possibly performed for mapping the eloquent areas. At the end of the study of each patient, immediate analysis of electro-clinical and anatomo-radiological data is made for completing the functional mapping of the eloquent cortex and epileptogenic area.

Video-Stereo-EEG study allows to determine:

- the irritative area, i.e. the cortical structures interested by intercritical irritative abnormalities;

- the lesion area, i.e. the cortical structures interested by intercritical slow abnormalities; and

- the epileptogenic area, i.e. the cortical structures which are seat of the origin and primary organisation of the critical discharge.

At the end of the study, the surgical intervention of cortical resection of the epileptogenic area may be planned, during which also the electrodes are removed.

The invasive monitoring, based on the positioning of electrodes on the cortical surface thus recording the electrocorticographic signal, allows to obtain a signal that is devoid of the artifacts of the common ElectroEncephaloGram and that offers the possibility of a fine mapping of the epileptic focus.

However, also the technique of monitoring through

Electrocorticography suffers from some significant drawbacks.

In fact, a plurality of connecting cables start from the intracranial electrodes, are subcutaneously tunnelled and then connected to the processing, monitoring and recording apparatus. All this exposes the patient to high risks of infection (due to the presence of cables crossing the skin and getting in direct contact with the brain) and trauma (possible stripping of the connecting cables, frequent in case of seizure, may induce parenchymal trauma). Also, freedom of movement of the patient is strongly limited: the patient must remain in bed and cannot move due to the presence of the connecting cables). Due to these limitations, and in particular for avoiding devastating infections, the intracranial electrodes for the invasive monitoring may be left in situ for few days, and they then have to be necessarily removed. The short duration of monitoring and the need of maintaining the patient in bed or confined in a limited space, where regular activities cannot be carried out, strongly limits diagnostic accuracy of the recording: it is not rare that a patient subjected to intervention for implanting cortical or deep recording electrodes must be subjected to removal of the electrodes without having reached any definitive result about the localisation of the epileptic focus.

Presently, there exist systems for acquiring only EEG signals which employ telemetry for allowing monitoring of patients in hospital, such as for instance the one disclosed in US Patent 5862803.

However, even such systems suffer of many drawbacks. In fact, they are very expensive, require emission of high power for transmitting signals and operate along very limiting frequency ranges for reducing interferences with devices present within the transmission range.

Also, such systems do not completely eliminate the connecting cables, since the electrodes placed on the patient are connected via wired communication to a transmission apparatus, held by the patient, that transmit via radio the signals detected by the electrodes to a processing, monitoring and recording apparatus (e.g., the system Nihon Kohden WEE- 10007K Wireless Input Unit). As a consequence, in such systems probability is high that there is a bad connection of the electrodes to the transmission apparatus or even that a disconnection of the same cable occurs when the patient makes movements.

Consequently, the main limit of the systems presently available for monitoring, most of all invasive monitoring, of both EEG and EcoG signals is the risk of infection for the patient and the consequent limited chronological framework of exploration due to the presence of the connecting cables between electrodes and processing, monitoring and recording apparatus. As said before, in fact, the presence of subcutaneous cables needed for transmitting the signal imposes a short monitoring, at most for a few days.

It is therefore an object of the present invention to allow in a manner that is reliable, versatile, simple, inexpensive, and safe for the patient to acquire and monitor bioelectric signals from a patient's brain, i.e. biological and electrophysiological signals, in particular electroencephalographic and/or electrocorticographic signals, for long time periods, even of the order of weeks and months, and in any place the same patient is.

It is specific subject matter of this invention a system for acquiring and monitoring bioelectric signals from a patient's brain, in particular electroencephalographic and/or electrocorticographic signals, comprising:

- a plurality of bioelectrical signal sensing electrodes, capable to be connected to at least one acquisition device, and

- at least one apparatus capable to receive signals corresponding to said bioelectrical signals sensed by the plurality of electrodes, the system being characterised in that said at least one acquisition device is provided with wireless transmitting means, through which it is capable to transmit said bioelectrical signals sensed by the plurality of electrodes to wireless receiving means with which at least one first receiving device connected to said at least one apparatus is provided.

Always according to the invention, said at least one first receiving device may be connected to said at least one apparatus through either wired or wireless connection.

Still according to the invention, said at least one first receiving device may be connected to said at least one apparatus through at least one storing device, capable to store data corresponding to said bioelectrical signals sensed by the plurality of electrodes, that is capable to transmit, via either wired communication, preferably through USB connection, or wireless communication, said stored data to at least one second receiving device in turn capable to connect to said at least one apparatus.

Furthermore according to the invention, said at least one second receiving device may be capable to connect through computer network, preferably through the Internet, to said at least one apparatus.

Always according to the invention, said at least one second device may be a computer, more preferably a PC.

Still according to the invention, said at least one first receiving device and said at least one storing device may be housed in a portable apparatus.

Furthermore according to the invention, the system may have at least one battery, capable to be implanted, preferably in the bones of the cranium, that supplies power to said plurality of electrodes and to said at least one acquisition device, said at least one battery being preferably rechargeable, more preferably in a wireless mode, still more preferably by radiofrequency and/or Bluetooth technology.

Always according to the invention, said at least one acquisition device may be provided with means for sampling and analog-to-digital converting said bioelectrical signals sensed by the plurality of electrodes. Still according to the invention, said at least one acquisition device may be provided with at least one control unit capable to acquire said bioelectrical signals sensed by the plurality of electrodes through one or more terminal block mounted on a connection substrate, each terminal block being provided with an input for a connection connector comprising one or more metal leads each one of which is connected to a corresponding sensing electrode, said connection substrate comprising one or more traces for connecting said metal leads to the control unit, each metal lead being preferably connected to a respective trace through a conducting clamp.

Furthermore according to the invention, said at least one first receiving device may be provided with means for amplifying said bioelectrical signals received by said at least one acquisition device.

The system according to the invention is based on subdural or intraparenchymal wireless connected electrodes which allow an invasive detection of signals from brain of a patient suffering from cerebral pathologies, for whom it is useful to monitor the electrical activity of cortex or deep cerebral nuclei such as the thalamus, the subthalamus, the pallidus, the striatum, the amygdala or the hippocampus. Possible clinical indications for such an invasive monitoring includes the drug-resistant epilepsy, the Parkinson's disease and other movement disorders, the drug-resistant major depressive disorder and other psychiatric disorders such as the obsessive-compulsive disorder, the chronic pain, etc. The electrodes are capable to transmit in wireless mode the information acquired from cerebral cortex or intraparenchymal nuclei to apparatuses for processing, monitoring and recording the cerebral electric signal of cortical (Electrocorticography or EcoG) or deep origin.

The system according to the invention, through wireless transmission of the EEG, EcoG and deep signal, is capable to enable a prolonged and much more physiological analysis of the cerebral signal. In fact, thanks to the absence of any subcutaneously tunnelled wire and of connections via wired communication with the cerebral electrodes, the system according to the invention allows to drastically reduce the risk of infection (once the electrode has been implanted, the access wound is completely closed eliminating any direct contact between the implanted electrode, and its anatomical seat, and the outside) and the neurosurgery risks in patients allowing a signal analysis much more prolonged than what allowed by the present monitoring systems. The patient may be sent home continuously recording the cerebral signal for weeks or months. This allows the cerebral activity to be recorded in a continuous way and in physiological (instead of induced) conditions opening a new route for studying the brain.

The advantages described above in case of epileptic patients may be exploited also in other application fields, such as: the study of motion cortical activity and deep cerebral nuclei activity in patients with movement disorders such as the Parkinson's disease; the study of activity of cortical regions involved in the origin of psychiatric disorders such as depression, obsessive-compulsive disorder, schizophrenia, etc.

Moreover, the possibility of investigating the cerebral signal in an accurate, continuous and prolonged way as ensured by the system according to the invention is useful also in clinical and basic research, since chronic study of the cerebral function may provide with exceptionally valuable data for the mathematical analysis of the cerebral function, the development of new protocols of human-machine interfaces (the so-called Brain Computer interfaces BCIs and Human Computer Interfaces HCIs), preferably for rehabilitation purposes (e.g. in case of tetraplegia, SLA, Locked-ln, etc.), and the creation of artificial intelligence devices imitating the operation model of the neural networks.

Also, the embodiments of the system according to the invention which further allow the cerebral activity stimulation, through the external control of the single electrode contacts, enable to treat the aforementioned functional disorders, included the treatment of neuropsychiatric disorders such as depression, obsessive-compulsive disorders, schizophrenia, Gilles de la Tourette syndrome, substance dependencies, severe anorexia and bulimia, etc.

The system according to the invention allows optimisation of neurosurgery procedures for the study and healing of patients suffering from neurodegenerative diseases having a social impact that is more and more important and continuously increasing, because of the progressive aging of the population.

The system according to the invention is further applicable for mapping eloquent areas of the brain, i.e. for the so-called functional Brain mapping, in patients with areas of brain tumour (surrounding "strategic" areas) through electric stimulation aided by subdural electrodes.

The present invention will be now described, by way of illustration and not by way of limitation, according to its preferred embodiments, by particularly referring to the Figures of the enclosed drawings, in which:

Figure 1 schematically shows a first embodiment of the system according to the invention;

Figure 2 shows an example of implant (Fig. 2a) and a related detail in enlarged section (Fig. 2b) of the system of Figure 1 ;

Figure 3 shows a perspective view of a component of the system of Figure 1 ;

Figure 4 shows a particular of the component of Figure 3;

Figure 5 shows a perspective view of some components of the system of Figure 1 (Fig. 5a), a front view of a second component and a perspective view of a third component of the system of Figure 1 (Fig. 5b), a right side view of some components of the system of Figure 1 (Fig. 5c), and a bottom plan view of the second component of the system of Figure 1 (Fig. 5d); and

Figure 6 schematically shows a second embodiment of the system according to the invention.

In the Figures, identical reference numbers are used for alike elements.

Figure 1 schematically shows a preferred embodiment of the system according to the invention, comprising a plurality 1 of sensing electrodes connected, through interface wired connections 2, to a device 3 for acquiring and wireless transmitting, through a first antenna 4, signals sensed by the electrodes 1. In particular, the device 3 preferably comprises a unit for sampling and analog-to-digital converting the acquired signals, while power for the electrodes and the device 3 is supplied by (at least) an intracranial battery. The signals transmitted by the first antenna 4 are received by a second antenna 5 of a receiving device 6 connected to an amplification interface 7 in turn connected to a processing, monitoring and recording apparatus 8.

Figure 2a shows an example of implant of the system according to the invention, wherein the plurality 1 of electrodes, arranged as a subdural grid, is implanted through a wide craniotomy (properly programmed with the aid of three-dimensional reconstructions of the cortical surface) and the insertion of the subdural grid between dura mater and cortical surface, connected through cables 2 to the wireless transmission device 3. In particular, Figure 2b shows an enlarged section of Figure 2a in correspondence with the area of the bones 20 of the cranium wherein a seat for inserting the transmission device 3 is obtained, that is provided with the intracranial power battery (not shown in the Figures). Preferably, such battery is rechargeable, still more preferably in wireless mode (e.g. by radiofrequency or bluetooth).

Figure 3 shows a schematic perspective view of the acquisition and wireless transmission device 3 comprising a control unit 31 , provided with the first antenna (not shown in the Figure) for wireless transmitting the acquired signals. The unit 31 acquires the signals coming from the plurality of electrodes through a series of terminal blocks 35 (four of which are shown in Figure 3) mounted on a connection substrate 36. Each terminal block 35 is provided with a cylindrical hole 32 constituting the input for a multi-connector 33 for the connection to a corresponding plurality of electrodes (which are, as shown in Figure 4, in number of four). Each multi-connector 33 is preferably made as a silicone cylinder where the metal leads 34 (of the corresponding four electrodes) emerging from the outside of the cylindrical surface of the same connector are drowned. In particular, such multi-connectors 33 are preferably similar to those available from the company Ad-Tech Medical Instrument Corporation and disclosed in Patents US 4735208 and US 4850359; however, the system according to the invention may also use other devices for the connection with the electrodes, also having different shapes, size and materials.

Figure 4 shows in greater detail the structure of the connection substrate 36 of the device 3 of Figure 3, wherein the four multi-traces 44 of connection of the metal leads 34, placed in locations homologous to the corresponding multi-connectors 33, to the control unit 31 are visible. In particular, each metal lead 34 of the multi-connectors 33 is preferably connected to the respective trace 44 through a sort of conducting clamp 43, that by sticking the metal lead 34 ensures both the electrical conduction and the mechanical coupling between the latter and the respective trace 44.

Figure 5 shows in greater detail the connection between a terminal block 35 and the multi-traces 44 through the conducting clamps 43, wherein the holes 55 of input of the conducting clamps 43 in the terminal block 35 allowing its coupling with the respective metal lead 34 of the multi-connector 33 are visible.

The acquisition and wireless transmission device 3 exemplarily shown with reference to Figures 3-5 comprises four terminal blocks 35 in each one of which a multi-connector 33 comprising four metal leads 34 of connection to corresponding four electrodes is inserted, whereby the device 3 of Figures 3-5 is connectable to a total of sixteen electrodes. However, it should be noted that other embodiments of the system according to the invention may comprise a number of terminal blocks different from four and/or a number of metal leads per multi-connector different from four.

Other embodiments of the system according to the invention may have, instead of a wireless direct connection (as shown in Figure 1) between acquisition and wireless transmission device 3 and processing, monitoring and recording apparatus 8, a double or even multiple connection. By way of example, and not by way of limitation, making reference to Figure 6, it may be observed that the patient could wear a portable apparatus 61 , provided with autonomous power supply (e.g. a battery) comprising the receiving device 6, provided with the second antenna 5, connected to an amplification interface 7 in turn connected to a device 60 for storing the acquired data. In this case, the data stored in the device 60 may be transmitted to a system 63 provided with a device 62 capable to receive data from the portable apparatus 61, via wired (e.g. through USB connection) or wireless (e.g. through the antenna 5 and a respective antenna of the device 62) communication, the processing, monitoring and recording apparatus 8 being housed in the same system 63 and connected to the device 62. Moreover, the device 62 could also consists in a PC connecting via Internet to a remote apparatus 8 (e.g. a server accessed by doctors responsible for monitoring the patient in whom the electrodes 1 are implanted). This allows a greater freedom of movement to the patient, allowing him to connect the portable apparatus 61 to the device 62 for downloading the stored data only in few moments, e.g. at the end of a day.

The preferred embodiments have been above described and some modifications of this invention have been suggested, but it should be understood that those skilled in the art can make variations and changes, without so departing from the related scope of protection, as defined by the following claims.

Claims

1. System for acquiring and monitoring bioelectric signals from a patient's brain, in particular electroencephalographic and/or electrocorticographic signals, comprising:

- a plurality (1) of bioelectrical signal sensing electrodes, capable to be connected to at least one acquisition device (3), and

- at least one apparatus (8) capable to receive signals corresponding to said bioelectrical signals sensed by the plurality (1) of electrodes, the system being characterised in that said at least one acquisition device (3) is provided with wireless transmitting means (4), through which it is capable to transmit said bioelectrical signals sensed by the plurality (1) of electrodes to wireless receiving means (5) with which at least one first receiving device (6) connected to said at least one apparatus (8) is provided.

2. System according to claim 1 , characterised in that said at least one first receiving device (6) is connected to said at least one apparatus (8) through either wired or wireless connection.

3. System according to claim 1 or 2, characterised in that said at least one first receiving device (6) is connected to said at least one apparatus (8) through at least one storing device (60), capable to store data corresponding to said bioelectrical signals sensed by the plurality (1) of electrodes, that is capable to transmit, via either wired communication, preferably through USB connection, or wireless communication, said stored data to at least one second receiving device (62) in turn capable to connect to said at least one apparatus (8).

4. System according to claim 3, characterised in that said at least one second receiving device (62) is capable to connect through computer network, preferably through the Internet, to said at least one apparatus (8).

5. System according to claim 3 or 4, characterised in that said at least one second device (62) is a computer, more preferably a PC.

6. System according to any one of claims 3 to 5, characterised in that said at least one first receiving device (6) and said at least one storing device (60) are housed in a portable apparatus (61).

7. System according to any one of the preceding claims, characterised in that it has at least one battery, capable to be implanted, preferably in the bones of the cranium, that supplies power to said plurality (1) of electrodes and to said at least one acquisition device (3), said at least one battery being preferably rechargeable, more preferably in a wireless mode, still more preferably by radiofrequency and/or Bluetooth technology.

8. System according to any one of the preceding claims, characterised in that said at least one acquisition device (3) is provided with means for sampling and analog-to-digital converting said bioelectrical signals sensed by the plurality (1) of electrodes.

9. System according to any one of the preceding claims, characterised in that said at least one acquisition device (3) is provided with at least one control unit (31) capable to acquire said bioelectrical signals sensed by the plurality (1) of electrodes through one or more terminal block (35) mounted on a connection substrate (36), each terminal block (35) being provided with an input (32) for a connection connector (33) comprising one or more metal leads (34) each one of which is connected to a corresponding sensing electrode, said connection substrate (36) comprising one or more traces (44) for connecting said metal leads (34) to the control unit (31), each metal lead (34) being preferably connected to a respective trace (44) through a conducting clamp (43).

10. System according to any one of the preceding claims, characterised in that said at least one first receiving device (6) is provided with means (7) for amplifying said bioelectrical signals received by said at least one acquisition device (3).