WO2009021535A1

WO2009021535A1 - Medical devices, systems and methods for blood pressure regulation

Info

Publication number: WO2009021535A1
Application number: PCT/EP2007/007180
Authority: WO
Inventors: Manfred Frischholz; Ernst Wellnhofer
Original assignee: Campus Micro Technologies Gmbh
Priority date: 2007-08-14
Filing date: 2007-08-14
Publication date: 2009-02-19

Abstract

The invention provides a medical device comprising a first wave signal transducer to generate a target receptor localization wave signal, and to receive the reflected localization wave signal; and a second wave signal transducer to generate a target receptor stimulation wave signal for stimulating a localized target receptor.

Description

Medical devices, systems and methods for blood pressure regulation

FIELD OF THE INVENTION

The present invention generally relates to medical devices, systems and methods for the treatment and/or management of cardiovascular and renal disorders. Specifically, the present invention relates to devices and methods for stimulating target receptors, for example baroreceptors for blood pressure regulation.

BACKGROUND OF THE INVENTION

Hypertension, or high blood pressure, is a major cardiovascular disorder, often resulting in heart failure or heart stroke. Hypertension may occur when blood vessels constrict which results in an increased blood pressure due to the reduced cross-section of the vessel. This may lead to a heart attack, and sustained high blood pressure may eventually result in an enlarged and damaged heart, and finally to heart failure.

The wall of the carotid sinus contains so-called baroreceptors which are stretch receptors that are sensitive to the blood pressure. These receptors send signals via the carotid sinus nerve to the brain, which in turn regulates the cardiovascular system to maintain normal blood pressure.

US-A-2007/0038262 describes systems and methods for treating a patient by inducing a baroreceptor signal to effect a change in the baroreflex system. The baroreceptor signal is activated or otherwise modified by selectively activating baroreceptors. To accomplish this, it is suggested to utilize a baroreceptor activation device positioned near a baroreceptor in the carotid sinus, aortic arch, heart, common carotid arteries, subclavian arteries, and/or brachiocephalic artery. For example, the baroreceptor activation device is located in the right and/or left carotid sinus or the aortic arch. In more detail, US-A-2007/0038262 describes an implantable medical device comprising a pulse generator to generate a baroreflex stimulation signal as part of a baroreflex therapy; a lead to be electrically connected to the pulse generator and to be intravascularly fed into a heart, the lead including an electrode to be positioned in or proximate to the heart to deliver the baroreflex signal to a baroreceptor region in or proximate to the heart; a sensor to sense a physiological parameter regarding an efficacy of the baroreflex therapy and to provide a signal indicative of the efficacy of the baroreflex therapy; and a controller connected to the pulse generator to control the baroreflex stimulation signal and to the sensor to receive the signal indicative of the efficacy of the baroreflex therapy.

The local baroreflex stimulation using an electrode as suggested in US-A-2007/0038262 is, however, disadvantageous due to high invasiveness which is necessary in order to place the electrodes in close contact or neighborhood to the baroreceptors. This additionally causes a higher risk of complications in case of infections because of the direct neighborhood of the electrodes to central vessels. Moreover, implanting the electrodes around the baroreceptors causes substantial risks and costs.

SUMMARY OF THE INVENTION

According to a first aspect, the invention provides a medical device.

A preferred medical device according to the invention comprises (a) a first wave signal transducer to generate a target receptor localization wave signal, and to receive the reflected localization wave signal; and (b) a second wave signal transducer to generate a target receptor stimulation wave signal for stimulating a localized target receptor.

It is preferred that at least one of the first wave transducer and second wave transducer generates a mechanical wave signal. As an example, at least one of the first wave transducer and second wave transducer is an ultrasound transducer. Alternatively, at least one of the transducer is a surface acoustic wave (SAW) transducer.

With the first wave signal transducer, a first wave signal is generated and emitted that is used for target receptor localization. For example, in case of an ultrasound transducer, the ultrasound transducer emits ultrasounds waves in a specific frequency range suitable for target receptor localization. Such frequency range is preferably a "diagnostic" frequency range. A "diagnostic" frequency range typically comprises frequencies that are larger than ultrasound frequencies used for therapeutic purposes, i.e. "therapeutic" frequencies. Such lower therapeutic frequencies are used according to the invention for target receptor stimulation with the second wave signal transducer. Preferred frequency ranges are described further below.

According to a preferred embodiment of the medical device of the invention, the first wave transducer and the second wave transducer are integrally formed by a single wave transducer, for example integrated on a single chip. For example, the single wave transducer is an ultrasound transducer array comprising a plurality of ultrasound transducer elements. The ultrasound transducer array may be a one-dimensional array or a two-dimensional array. Such array is shown, for example, in DE-A-101 22 765, which is incorporated herein by reference. Thus, the above-mentioned "diagnostic" transducer for target receptor localization and the "therapeutic" transducer for target receptor stimulation are preferably provided in an integrated manner, for example on the same chip or wafer. The different transducer can then be intermittently operated, first the first transducer for localization and then, once the target receptor is localized, the second transducer for stimulation. The term "intermittently" means in this context that after the target receptor has been stimulated for a particular, preferably predefined, period of time, the localization transducer may be activated again, for re-localization. This is particularly advantageous in case the patient moves or in some other way changes its position during receptor stimulation so that the stimulation wave beam becomes offset from or misaligned with the target receptor.

In the preferred example of having a transducer array, for example an array of ultrasound transducers, the individual transducer elements are operable as "diagnostic" transducers or "therapeutic" transducers, i.e., for target receptor localization or stimulation. This depends on the circuitry and way of controlling or driving the individual elements. The invention, however, also encompasses arrays of transducer elements comprising two distinct kinds of transducer elements which are operable as "diagnostic" or "therapeutic" transducer elements, respectively, only. The individual transducer elements can be operated in different patterns or subsets of elements, a first subset for target localization, and a second, preferably different subset for stimulation. The patterns may change or may be adapted depending on the position of the target receptor to be stimulated. For example, a receptor being positioned more closely to the skin of the patient may require a different localization and/or stimulation pattern than a receptor lying farther away from the medical device. For example, it may be desired to have a higher reception power, or a higher transmission power; depending to the individual needs the number of transmitting or receiving transducer elements can be increased (or reduced). The array of transducer elements may further be used for beam focusing, beam forming, beam steering, and beam sweeping in the process of receptor localization, and also for beam focusing for receptor stimulation. For example, the individual elements can be operated with a certain phase delay. Details thereof are explained below with reference to the accompanying figures. The selection of specific subsets is also helpful for intensity variations.

As already mentioned, the medical device of the invention encompasses that a first sub-set of ultrasound transducer elements of the array is operable in a first frequency range for target receptor localization, and a second-subset of ultrasound transducer elements is operable in a second frequency range for target receptor stimulation. The first frequency range and the second frequency range are, for example, in the range of 40 kHz to 40 MHz. Preferably, the first frequency range for target receptor localization is in the range of 1 MHz to 10 MHz. The second frequency range for target receptor stimulation is in the range of 100 kHz to 1 MHz. Furthermore, it is preferred that a first sub-set of ultrasound transducer elements is operable in a first energy density for target receptor localization, and a second-subset of ultrasound transducer elements is operable in a second energy density range for target receptor stimulation. For example, the first energy density and the second energy density are in the range of 0.1 mW/cm² to 10 W/cm², and more preferably 0.1 W/cm² to 3.0 W/cm². Preferably, the frequency range for target localization is higher than the range used for stimulation, but the energy density for target localization is lower compared to the energy density for target stimulation.

As mentioned, the individual transducer elements are preferably operated with a phase shift for beam shaping, beam focusing, and beam sweeping.

The medical device according to the invention can be located remotely from the target receptor to be stimulated. For example, the medical device is a non-invasive medical device. Such a noninvasive medical device is highly advantageous as it does not require the surgical procedure for implantation of the medical device into the patient, for example in close contact to the receptor as it is suggested in the prior art. There is further no risk for the patient of suffering from any infections occurring in this process. In contrast to the prior art, the non-invasive medical device according to the invention provides improved receptor stimulation in combination with a distant effect or remote effect. The medical device may also be an implantable medical device. For example, the implantable medical device is subcutaneously placeable. A subcutaneously placed medical device according to the invention enjoys the advantages of the distant effect or remote effect, respectively, provided by the medical device of the invention and does still not require a severe surgical procedure for placing the device at the receptor site. Placing the medical device subcutaneous is minimally invasive. Moreover, a subcutaneously placed medical device is advantageous in that the coupling of the wave signals into the tissue is more efficient.

According to one preferred embodiment of the invention, the medical device generates ultrasound imaging when connected to a computer interface. Alternatively or in addition, it may generate ultrasound imaging when telemetrically connected to a computer interface. Such imaging may support diagnostic evaluations.

It is preferred according to the invention that the stimulation signal comprises a series of pulses having a pulse frequency and an amplitude. Moreover, the stimulation signal may have a pulse width. The stimulation signal may also comprise a series of pulses delivered in bursts having a burst frequency. Furthermore, the stimulation signal is preferably at least one of amplitude modulated and phase modulated.

In the medical device of the invention, at least one of the first and second transducer is preferably a piezoelectric transducer or a capacitive membrane transducer, or in case of a transducer array comprises respective piezoelectric transducer elements or capacitive membrane transducer elements.

The medical device of the invention is preferably for localization and stimulation of a target receptor. Such target receptor is, for example, a baroreceptor. A baroreceptor to be stimulated is, for example, selected from the group comprising carotid sinus receptors, aortic arch receptors, subclavia receptors, or combinations thereof. The use of the medical device for baroreceptor stimulation is particularly advantageous. In particular the remote effect provided by the medical device of the invention makes the medical device of the invention particularly useful for baroreceptor stimulation as a risky surgical procedure for stimulator location in closest contact to the receptor is no longer required.

It is preferred according to the invention that at least one of the first wave signal transducer and the second wave signal transducer are useable to generate an image of the volume of stimulation and/or localisation. Such image can either be a ID, 2D cross section of the volume or a full 3D image of the volume. The image or at least part of the image can be used by an electronic signal processing circuitry for localisation for the purpose of beam steering, beam shaping, and/or beam focusing. The image can be a physical image representing a certain property of the tissue and blood vessels (e.g. density, water content) but it can also be a representation of any other physical parameter (e.g. velocity distribution). The image provided by the medical device may be used in the closed feedback control of the medical device or used as a diagnostic instrument or method by itself.

According to a second aspect, the invention provides a system comprising at least one medical device according to the first aspect, and further comprising signal processing circuitry for controlling the medical device. For example, the system may comprise more than just a single medical device so that a particular receptor can be localized and stimulated from different positions/directions. This may improve localization speed (reduced localization time) and stimulation efficiency. The individual medical devices may also be used to stimulate different receptors at the same time. The system is preferably a closed-loop system using feedback from the first wave signal transducer for target receptor localization for controlling target receptor stimulation by the medical device.

According to a preferred embodiment of the invention, the system further comprises at least one sensor for sensing a physiological parameter. The additional sensor or sensors is/are helpful in two ways. First of all, additional input data may be provided so that, for example, a synchronized stimulation may be performed, for example synchronized with respect to a pulsating blood pressure. On the other hand, the additional sensor(s) provide(s) additional feedback on the effect of the stimulation.

Alternatively, instead of providing a sensor in the form of a separate component, at least one of the first wave signal transducer and the second wave signal transducer of the medical device can be used according to the invention to simultaneously measure a physiological parameter. Potential parameters for this type of measurement are e.g. related to blood flow (for example in the case of Doppler measurements) and blood pressure (for example if surface acoustic waves are used). Surface acoustic waves could also be used for stimulation if the transducer is in reasonably close contact with the receptor.

In the case of having a separate sensor, it is preferred that the first wave signal transducer, the second wave signal transducer and the sensor are integrally formed by a wave single transducer. For example, the sensor is a piezoresistive or capacitive sensor and is integrated on a single chip as part of the array of transducers, sufficient mechanical decoupling from the wave generators provided.

The sensed physiological parameter is, for example, systolic blood pressure, diastolic blood pressure, heart rate, blood flow rate, blood flow velocity, blood vessel cross-sectional changes. The sensor is preferably a heart rate sensor, blood pressure sensor, electrocardiography sensor, ultrasonic flow rate transducer.

As an option encompassed by the invention, the signal processing circuitry simulates a complex physiological model.

It is also encompassed by the invention that the signal processing circuitry provides synchronization between the baroreceptor stimulation and the sensed blood pressure pulses.

In terms of hardware, the system of the second aspect of the invention may further comprise telemetry circuitry for providing telemetry signals for signal transmission between the signal processing circuitry and the medical device. This is particularly advantageous if the medical device is a subcutaneous medical device.

In a preferred embodiment of the invention, the first wave signal transducer, the second wave signal transducer, the sensor and signal processing circuitry and/or telemetry circuitry as well as preferably electrical interconnects and passive components are monolithically integrated in a single component. Such integration is, however, only possible if the respective technology is compatible. For example, conventional piezo-ultrasound transducer cut from crystals or formed from polymers are not compatible for such monolithic integration on a wafer.

In the system of the invention, it is preferred that when the medical device is connected to a computer interface, it generates ultrasound imaging. Similarly, when the medical device is telemetrically connected to a computer interface, it may generate ultrasound imaging, as also mentioned above.

The signal processing circuitry may further coupled with a cardiac pacemaker. Thus, the baroreceptor stimulation can be synchronized with the pacemaker signal. It is furthermore preferred that in the system of the invention, once the reflected wave signal is stored within an external computer interface, it may be altered to suit the user's needs through manipulation of the image processing controls.

According to a third aspect of the invention, a target receptor stimulation method is provided.

The invention provides a method of stimulating target receptors with at least one target receptor stimulation wave signal being generated remote or distant, respectively, from the target receptor. The at least one target receptor stimulation wave signal preferably comprises a mechanical wave signal, for example an ultrasound wave signal. The ultrasound target receptor stimulation wave signal is generated extracorporeal or subcutaneous. Thus, according to the method of the invention, the receptor stimulation, for example baroreceptor stimulation, is remotely performed.

The method may further comprise the preceding step of localizing with an ultrasound wave signal the target receptor to be stimulated. The steps of target receptor localization and target receptor stimulation are preferably intermittently performed, as already described above with reference to the medical device. Target localization is performed, for example, by comparing (a) received reflection pattern(s) with a reference reflection pattern for the target receptor to be stimulated. The reflection pattern is preferably a Doppler flow profile of the vessel the receptor is located at. The comparison result is then used for stimulation signal direction and focus adjustment. Target signal adjustment may also be performed with reference to at least one reference object.

As described above, it is preferred according to the invention to have a transducer array, for example an array of ultrasound transducers. In such example, according to the method of the invention, the individual transducer elements are operable as diagnostic transducers or therapeutic transducers, for target receptor localization or stimulation. According to a preferred embodiment of the method of the invention, the individual transducer elements are operated in different patterns or subsets of elements, a first subset for target localization, and a second, preferably different subset for stimulation. The patterns may vary depending on the position of the target receptor to be stimulated. The array of transducer elements is preferably operated to provide for beam focusing, beam forming, beam steering, and beam sweeping in the process of receptor localization, and also for beam focusing and beam forming for receptor stimulation. According to a preferred embodiment, target receptor localization is performed in a first frequency range, and target receptor stimulation is performed in a second frequency range. The first frequency range and the second frequency range are preferably in the range of 40 kHz to 40 MHz. More preferably, the first frequency range for target receptor localization is in the range of 1 MHz to 10 MHz. The second frequency range for target receptor stimulation is preferably in the range of 100 kHz to 1 MHz.

It is also a preferred feature of the method that target receptor localization is performed with a first energy density range, and target receptor stimulation is performed with a second energy density range. The first energy density and the second energy density are preferably in the range of 0.1 mW/cm² to 10 W/cm², and more preferably 0.1 W/cm² to 3.0 W/cm².

In the method of the invention, the stimulation signal comprises a series of pulses having a pulse frequency and an amplitude. The stimulation signal may also have a pulse width. Furthermore, the stimulation signal may comprise a series of pulses delivered in bursts having a burst frequency. The stimulation signal is preferably at least one of amplitude modulated and phase modulated.

The method of the invention is preferably applicable to target receptors being baroreceptors. As mentioned above, such baroreceptor are preferably selected from the group comprising carotid sinus receptors, aortic arch receptors, subclavia receptors, or combinations thereof.

For the reasons mentioned above, the method of the invention may further comprise the step of sensing at least one physiological parameter. Such physiological parameter is, for example, systolic blood pressure, diastolic blood pressure, heart rate, blood flow rate, blood flow velocity, blood vessel cross-sectional changes.

The method of the invention furthermore uses feedback from the sensed physiological parameter for controlling generation of the baroreceptor stimulation signal. As another option, the baroreceptor stimulation is synchronized with the sensed blood pressure pulses.

According to a fourth aspect, the invention provides a method of blood pressure regulation. The method of blood pressure regulation preferably comprises the steps of (a) providing a first target receptor localization wave signal transducer to generate a target receptor localization wave signal, and to receive the reflected localization wave signal; (b) providing a second wave signal transducer to generate a target receptor stimulation wave signal for stimulating a localized target receptor; (c) positioning the first and second wave signal transducer so that a respective wave signal beam is directable onto the target receptors to be simulated; (d) emitting a signal beam from the first signal transducer onto the target receptors to be simulated; (e) determining localization of the target receptor to be stimulated on the basis of the reflected beam emitted from the first signal transducer; (f) adjusting direction and focus of the second signal transducer with respect to the determined localization of the target receptor; and (g) emitting a stimulation signal beam from the second signal transducer onto the target receptor.

The first and second wave signal transducer are preferably positioned extracorporeal in contact or close to the patient's skin in an area in proximity to the target receptors to be simulated.

Preferably, target localization is performed by comparing (a) received reflection pattern(s) with a reference reflection pattern for the target receptor to be stimulated. The reflection pattern is for example a Doppler flow profile of the vessel the receptor is located at. The target receptor may be a barorecptor.

At least one of the first wave signal transducer and second wave signal transducer generates a mechanical wave signal. Preferably, at least one of the first wave signal transducer and second wave signal transducer is an ultrasound transducer. It is preferred that the first wave signal transducer and the second wave signal transducer are integrally formed by a single wave signal transducer. The single wave signal transducer may be an ultrasound transducer array comprising a plurality of ultrasound transducer elements. The ultrasound transducer array is, for example, a one-dimensional array or a two-dimensional array.

According to a fifth aspect, the invention provides a medical device, preferably according to the first aspect of the invention, the medical device comprising a first wave transducer, second wave transducer, and sensor, wherein first wave transducer, second wave transducer and sensor are integrally formed by a wave single transducer; e.g. realised as one single chip on a silicon wafer. The wave single transducer array is preferably a one-dimensional array or a two-dimensional array. Thus, the invention encompasses a medical device, wherein the first wave signal transducer, second wave signal transducer and the sensor are identical in terms of the technology used for their fabrication (e.g. formed in the same process sequence in parallel on a wafer rather than sequentially or even completely separate production and later integration) but differ in their specific design (e.g. piezoresistive pressure sensor, piezoresisitive ultrasound transducer or capacitive pressure sensor and capacitive pressure sensor).

The invention is advantageous and provides substantial improvements with respect to blood pressure regulation in that it realizes treatment of the generally difficult blood pressure regulation by providing baroreceptor stimulation with controllable focused waves, such as mechanical waves, for example ultrasound waves, applied onto the physiological receptors. This is in contrast to prior art approaches that provide local electrical stimulation that only simulates nerve pulses. The concept of the invention is further advantageous in that it is applicable transcutaneous but can also implanted subcutaneous which is minimally invasive.

The details of one or more embodiments of the invention are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the invention will be apparent from the description and drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

Fig. 1 is a schematic illustration of the location of arterial baroreceptors;

Fig. 2 shows as an example the result of the application of a conventional ultrasound probe for the purpose of the invention;

Fig. 3 shows as another example the result of the application of a conventional ultrasound probe for the purpose of the invention;

Fig. 4 shows details of a preferred system of the invention; Fig. 5 shows three different Doppler profiles in the area of the carotid sinus; Fig. 6 shows an exemplary ultrasound transducer array of a preferred embodiment of the invention; Fig. 7 shows four different patterns of ultrasound transducer elements used according to a preferred embodiment for target receptor localization and stimulation; Fig. 8 shows a first alternative of ultrasound beam focusing according to a preferred embodiment of the invention; and Fig. 9 shows another alternative of ultrasound beam focusing according to a preferred embodiment of the invention.

DETAILED DESCRIPTION OF THE INVENTION

The following detailed description should be read with reference to the drawings in which similar elements in different drawings are numbered the same. The drawings, which are not necessarily to scale, depict illustrative embodiments and are not intended to limit the scope of the invention.

Some details of the basic vascular anatomy associated with the cardiovascular system are first explained with reference to Fig. 1. FIG. 1 is a schematic illustration of the location of arterial baroreceptors. As already mentioned above, baroreceptors sense stretch and rate of stretch by generating action potentials, i.e. voltage spikes. The baroreceptors are located in highly distensible regions of the blood circulation to maximize sensitivity. Fig. 1 shows the baroreceptors located at the left and right carotid sinus and the aortic arch. Further baroreceptors are subclavia receptors. However, the invention is not limited to baroreceptor localization and stimulation. The stimulation of other receptors is also encompassed by the invention, such as veno-atrial mechanoreceptors, unmyelinated mechanoreceptors, heart chemosensors, arterial chemosensors, or lung stretch receptors.

Fig. 2 shows as an example the result of the application of a ultrasound probe for the purpose of the invention. A medical device being an ultrasound probe (8 - 11 MHz) was used transcutaneous to stimulate carotid sinus baroreceptors. After a quiescent phase R the stimulation is initiated at D which results in an immediate drop of the blood pressure and frequency which continues even during a following recovery phase starting at E. The ultrasound stimulation is comparable to a manual stimulation M..

Fig. 3 shows another example. A non-invasive ultrasound probe (8 - 11 MHz) was used to stimulate carotid sinus baroreceptors. After a quiescent phase R the stimulation is initiated at D which results in an immediate drop of the blood pressure and frequency. Whereas the frequency drop persists blood pressure rises again during the late stimulation phase and after stop of stimulation at E. The effect is early counter-regulation of blood pressure in a context of auto- regulation at rather low pressures. The vagal stimulation is effective as may be seen from frequency.

A schematic diagram showing details of a preferred system of the invention is shown in Fig. 4.

A sensor unit provides input data, for example with respect to blood pressure, pulse pressure, pulse frequency, blood flow and/or velocity, or about the vascular diameter of the vessel of interest. Such sensor data is supplied to a control unit that provides for further processing of the sensed input data. For example, a complex physiological model or a training algorithm is simulated by the control unit. Such processing in the control unit may take into account additional information such as medication of the patient. For example, betablockers are known to curb frequency regulation so that the pulse frequency as input data is of limited use with respect to patients that are on betablockers.

Another input to the control unit in this example is stored data and presettings, such as stimulation protocols, stimulation duration, stimulation frequency and intensity, pulse frequency, and time length during intermittent application of the transducer as stimulator and localization sensor.

The control unit then determines and decides on the individual stimulation of the patient, such as selection of an appropriate stimulation protocol, decision with respect to triggered stimulation, and stimulation settings.

A stimulation unit then performs stimulation. In accordance with the invention, the stimulation unit may also be used for target localization.

Fig. 5 shows Doppler flow profiles in three different areas at the carotid sinus and nicely shows how these profiles differ with respect to their characteristics. Such distinguishing Doppler profile characteristics are according to the invention used for target receptor localization. The arteria carotid communis bifurcates at the carotid sinus into the arteria carotid interna and the arteria carotid externa. The Doppler flow profiles differ from each other in a characteristic way: There is diastolic flow in the arteria carotid communis, the is no diastolic flow in the arteria carotid externa, and there is an increased diastolic flow in the arteria carotid interna. Theses three patterns are thus used according to the invention for ultrasound beam adjustment towards the target receptor.

Fig. 6 shows a schematic perspective view of an example of an ultrasound transducer array according to an embodiment of the invention. In this example, the array consists of nine transducer elements in a 3x3 arrangement. The individual transducer elements are individually operable and controllable.

As mentioned above, the transducer elements of the array can be operated in different patterns or subsets, for example as diagnostic transducer elements or therapeutic transducer elements, or for providing desired transmission or reception powers. Four different patterns are schematically shown in Fig. 7, for a transducer array having 5x5 transducer elements.

Beam focusing or beam shaping is shown by means of an example in Figs. 8 and 9. Figs. 8 and 9 are schematic cross-sectional views of a transducer array. The transducer array may have a plurality of transducer elements arranged in rows and columns but for simplification purposes only three transducer elements are shown in these cross-sectional views.

In the example of Fig. 8, the individual transducer elements are driven with a certain phase shift, starting with element "3" (at the right hand side), followed by the centre element "2", and finally element "1". Thus the final beam sweeps from the right to the left, the beam focus sweeps form the right to the left. Such transducer operation is particularly useful for receptor localization.

Another example is shown in Fig. 9. In this example, the ultrasound waves are emitted such that the beam focus move along an axis perpendicular to the surface of the array. With such an operation of the ultrasound transducer the beam focus can be targeted to different depths of the tissue, for example.

Various embodiments of the invention have been described. These and other embodiments are within the scope of the following claims.

Claims

1. A medical device comprising a. a first wave signal transducer to generate a target receptor localization wave signal, and to receive the reflected localization wave signal; and b. a second wave signal transducer to generate a target receptor stimulation wave signal for stimulating a localized target receptor.

2. The medical device of claim 1, wherein at least one of the first wave transducer and second wave transducer generates a mechanical wave signal.

3. The medical device of claim 2, wherein at least one of the first wave transducer and second wave transducer is an ultrasound transducer.

4. The medical device of any of the preceding claims, wherein the first wave transducer and the second wave transducer are integrally formed by a single wave transducer.

5. The medical device of claim 4, wherein the single wave transducer is an ultrasound transducer array comprising a plurality of ultrasound transducer elements.

6. The medical device of claim 5, wherein the ultrasound transducer array is a one- dimensional array or a two-dimensional array.

7. The medical device of claim 5 or 6, wherein a first sub-set of ultrasound transducer elements is operable in a first frequency range for target receptor localization, and a second-subset of ultrasound transducer elements is operable in a second frequency range for target receptor stimulation.

8. The medical device of claim 7, wherein the first frequency range and the second frequency range are in the range of 40 kHz to 40 MHz.

9. The medical device of claim 8, wherein the first frequency range for target receptor localization is in the range of 1 MHz to 10 MHz.

10. The medical device of claim 7 or 8, wherein the second frequency range for target receptor stimulation is in the range of 100 kHz to 1 MHz.

11. The medical device of any of claim 5 to 10, wherein a first sub-set of ultrasound transducer elements is operable in a first energy density for target receptor localization, and a second- subset of ultrasound transducer elements is operable in a second energy density range for target receptor stimulation.

12. The medical device of claim 11, wherein the first energy density and the second energy density are in the range of 0.1 mW/cm² to 10 W/cm², and preferably 0.1 W/cm² to 3.0

W/cm².

13. The medical device of any of claims 5 to 12, wherein the individual ultrasound transducer elements are operated with a phase shift for beam shaping, beam focusing, and beam sweeping.

14. The medical device of any of the preceding claims, wherein the medical device is remotely locatable from the target receptor to be stimulated.

15. The medical device of any of the preceding claims, the medical device being a noninvasive medical device.

16. The medical device of any of the preceding claims, the medical device being an implantable medical device.

17. The medical device of claim 16, wherein the implantable medical device is subcutaneously placeable.

18. The medical device of any of the preceding claims, wherein when connected to a computer interface, generates ultrasound imaging.

19. The medical device of any of the preceding claims, wherein when telemetrically connected to a computer interface, generates ultrasound imaging.

20. The medical device of any of the preceding claims, wherein the stimulation signal comprises a series of pulses having a pulse frequency and an amplitude.

21. The medical device of any of the preceding claims, wherein the stimulation signal has a pulse width.

22. The medical device of any of the preceding claims, wherein the stimulation signal comprises a series of pulses delivered in bursts having a burst frequency.

23. The medical device of any of the preceding claims, wherein the stimulation signal is at least one of amplitude modulated and phase modulated.

24. The medical device of any of the preceding claims, wherein at least one of the first and second transducer is a piezoelectric transducer or a capacitive membrane transducer.

25. The medical device of any of the preceding claims, wherein the target receptor is a baroreceptor.

26. The medical device of claim 25, wherein the baroreceptor to be stimulated is selected from the group comprising carotid sinus receptors, aortic arch receptors, subclavia receptors, or combinations thereof.

27. The medical device according to any of the preceding claims, wherein at least one of the first wave signal transducer and the second wave signal transducer are useable to generate an image of the volume of stimulation and/or localisation.

28. System comprising at least one medical device according to any of the preceding claims, and further comprising signal processing circuitry for controlling the medical device.

29. The system of claim 28, the system being a closed-loop system using feedback from the first wave signal transducer for target receptor localization for controlling target receptor stimulation by the medical device.

30. The system of claim 28 or 29, further comprising at least one sensor for sensing a physiological parameter.

31. The system of claim 28 or 29, wherein at least one of the first wave signal transducer and the second wave signal transducer can be used to simultaneously measure a physiological parameter.

32. The system of claim 30, where first wave signal transducer, second wave signal transducer and sensor are integrally formed by a wave single transducer.

33. The system of claim 30, 31, or 32, wherein the physiological parameter is systolic blood pressure, diastolic blood pressure, heart rate, blood flow rate, blood flow velocity, blood vessel cross-sectional changes.

34. The system of claim 30, wherein the sensor is a heart rate sensor, blood pressure sensor, electrocardiography sensor, ultrasonic flow rate transducer.

35. The system of any of claims 28 to 34, wherein the signal processing circuitry simulates a complex physiological model.

36. The system of claim 34 or 35, wherein the signal processing circuitry provides synchronization between the baroreceptor stimulation and the sensed blood pressure pulses.

37. The system of any of claims 28 to 36, further comprising telemetry circuitry for providing telemetry signals for signal transmission between the signal processing circuitry and the medical device.

38. The system of claim 37, wherein first wave signal transducer, second wave signal transducer, sensor and signal processing circuitry and/or telemetry circuitry as well as electrical interconnects and passive components are monolithically integrated in a single component.

39. The system of any of claims 28 to 38, wherein when the medical device is connected to a computer interface, it generates ultrasound imaging.

40. The system of any of claims 28 to 39, wherein when the medical device is telemetrically connected to a computer interface, it generates ultrasound imaging.

41. The system of any of claims 28 to 40, the signal processing circuitry further being coupled with a cardiac pacemaker.

42. The system of any of claims 28 to 41, once the reflected wave signal is stored within an external computer interface; it may be altered to suit the user's needs through manipulation of the image processing controls.

43. A method of stimulating target receptors with at least one target receptor stimulation wave signal being generated remote from the target receptor.

44. The method of claim 43, wherein the at least one target receptor stimulation wave signal comprises a mechanical wave signal.

45. The method of claim 44, wherein the mechanical wave signal comprises an ultrasound wave signal.

46. The method of claim 45, wherein the at least one ultrasound target receptor stimulation wave signal is generated extracorporeal or subcutaneous.

47. The method of any of claims 43 to 46, further comprising the preceding step of localizing with an ultrasound wave signal the target receptor to be stimulated.

48. The method of claim 47, wherein the steps of target receptor localizations and target receptor stimulation are intermittently performed.

49. The method of claim 47 or 48, wherein target localization is performed by comparing received reflection patterns with a reference reflection pattern for the target receptor to be stimulated.

50. The method of claim 49, wherein the reflection pattern is a Doppler flow profile of the vessel the receptor is located at.

51. The method of claim 49 or 50, wherein the comparison result is used for stimulation signal direction and focus adjustment.

52. The method of any of claims 43 to 51, wherein target signal adjustment is performed with reference to at least one reference object.

53. The method of any of claims 47 to 52, wherein target receptor localization is performed in a first frequency range, and target receptor stimulation is performed in a second frequency range.

54. The method of claim 53, wherein the first frequency range and the second frequency range are in the range of 40 kHz to 40 MHz.

55. The method of claim 54, wherein the first frequency range for target receptor localization is in the range of 1 MHz to 10 MHz.

56. The method of claim 53 or 54, wherein the second frequency range for target receptor stimulation is in the range of 100 kHz to 1 MHz.

57. The method of any of claim 47 to 56, wherein target receptor localization is performed with a first energy density range, and target receptor stimulation is performed with a second energy density range.

58. The method of claim 57, wherein the first energy density and the second energy density are in the range of 0.1 mW/cm² to 10 W/cm², and preferably 0.1 W/cm² to 3.0 W/cm².

59. The method of any of claims 43 to 58, wherein the stimulation signal comprises a series of pulses having a pulse frequency and an amplitude.

60. The method of any of claims 43 to 59, wherein the stimulation signal has a pulse width.

61. The method of any of claims 43 to 60, wherein the stimulation signal comprises a series of pulses delivered in bursts having a burst frequency.

62. The method of any of claims 43 to 61, wherein the stimulation signal is at least one of amplitude modulated and phase modulated.

63. The method of any of claims 43 to 62, wherein the target receptor is a baroreceptor.

64. The method of claim 54, wherein the baroreceptor to be stimulated is selected from the group comprising carotid sinus receptors, aortic arch receptors, subclavia receptors, or combinations thereof.

65. The method of any of claims 43 to 64, further comprising sensing at least one physiological parameter.

66. The method of claim 65 wherein the at least one physiological parameter is systolic blood pressure, diastolic blood pressure, heart rate, blood flow rate, blood flow velocity, blood vessel cross-sectional changes.

67. The method of 64 or 65, using feedback from the sensed physiological parameter for controlling generation of the baroreceptor stimulation signal.

68. The method of claim 66 or 67, wherein the baroreceptor stimulation is synchronized with the sensed blood pressure pulses.

69. A method of blood pressure regulation, comprising the steps of: a. providing a first target receptor localization wave signal transducer to generate a target receptor localization wave signal, and to receive the reflected localization wave signal; b. providing a second wave signal transducer to generate a target receptor stimulation wave signal for stimulating a localized target receptor; c. positioning the first and second wave signal transducer so that a respective wave signal beam is directable onto the target receptors to be simulated; d. emitting a signal beam from the first signal transducer onto the target receptors to be simulated; e. determining localization of the target receptor to be stimulated on the basis of the reflected beam emitted from the first signal transducer; f. adjusting direction and focus of the second signal transducer with respect to the determined localization of the target receptor; and g. emitting a stimulation signal beam from the second signal transducer onto the target receptor.

70. The method of claim 69, wherein the first and second wave signal transducer are positioned extracorporeal in contact or close to the patient's skin in an area in proximity to the target receptors to be simulated.

71. The method of claim 69 or 70, wherein target localization is performed by comparing received reflection patterns with a reference reflection pattern for the target receptor to be stimulated.

72. The method of claim 71, wherein the reflection pattern is a Doppler flow profile of the vessel the receptor is located at.

73. The method of any of claims 69 to 72, wherein the target receptor is a barorecptor.

74. The method of any of claims 69 to 73, wherein at least one of the first wave signal transducer and second wave signal transducer generates a mechanical wave signal.

75. The method of claim 74, wherein at least one of the first wave signal transducer and second wave signal transducer is an ultrasound transducer.

76. The method of any of claims 69 to 75, wherein the first wave signal transducer and the second wave signal transducer are integrally formed by a single wave signal transducer.

77. The method of claim 76, wherein the single wave signal transducer is an ultrasound transducer array comprising a plurality of ultrasound transducer elements.

78. The method of claim 77, wherein the ultrasound transducer array is a one-dimensional array or a two-dimensional array.

79. A medical device, preferably according to any of claims 1 to 27, the medical device comprising a first wave transducer, second wave transducer, and sensor, wherein first wave transducer, second wave transducer and sensor are integrally formed by a wave single transducer.

80. The medical device of claim 79, wherein the wave single transducer array is a one- dimensional array or a two-dimensional array.