Detecting neural activity

Abstract

An interventional device (110) for detecting neural activity is provided. The interventional device includes a magnetic sensor (120) coupled to an insertable portion of the interventional device. The magnetic sensor (120) is configured for generating a signal in response to a magnetic field generated by neural activity. The invention also provides a system (200). The system includes an interventional device (110) and a controller (140) configured to receive a signal generated by the magnetic sensor (120) and output a detection result indicative of neural activity in response to the received signal.

Description

Technical Field

[0001] The present disclosure relates to the detection of neural activity. An interventional device, a system, a computer-implemented method and a computer program product are disclosed. Background Art

[0002] Neural activity assessment is performed during various medical procedures to study neural behavior. For example, brain function is monitored by electroencephalogram (EEG). Neural activity can also be monitored during renal denervation surgery. Renal denervation is an interventional procedure for the treatment of drug-resistant hypertension (i.e., elevated blood pressure). Renal denervation is usually performed by ablating the (sympathetic) nerves between the central nervous system and the kidneys (usually near the renal artery). The procedure is usually performed using an interventional device (e.g., an ablation catheter). The effect of the ablation procedure is to remove the stimulus that causes the blood pressure to rise. However, the relatively low clinical success rate of renal denervation (measured by long-term blood pressure reduction), coupled with the high cost of the procedure, has hindered its widespread use. Quantification of neural activity may help improve the clinical success rate of renal denervation. Surgical improvements may involve more accurate nerve localization, better stratification of patients undergoing denervation treatment, and more direct and comprehensive verification of the success of the procedure.

[0003] When a nerve is activated, it triggers an electrical impulse (often called an "action potential") that propagates along the associated nerve fiber in a forward direction, thus appearing to transmit an impulse. Action potentials are difficult to quantify without piercing the tissue to bring electrodes very close to or in contact with the nerve fiber. These shortcomings have hampered electrical measurement of nerve activity. However, time-varying electrical impulses in nerve fibers generate a magnetic field around the nerve fiber. This magnetic field is in the sub-picotesla range and allows the use of magnetic sensors to measure nerve activity.

[0004] Various magnetic sensors have been used to measure the activity of nerve cells (i.e., neurons). For example, in the magnetoencephalogram "MEG" system, surface sensors are positioned around the head. Magnetic sensors such as inductive sensors, superconducting quantum interference devices "SQUID" sensors, and optically pumped magnetometers "OPM" sensors have been used to sense the magnetic field generated by neuronal activity in the brain. The intensity of the magnetic field decreases rapidly with the distance from the neurons or nerves. However, the cumulative field generated by a large number of neurons can be detected by a magnetic sensor located on the skin (i.e., a few centimeters away from the source). Similar sensors have been used in the magnetocardiogram "MCG" system to monitor the magnetic field emitted by a beating heart from a surface position. In the MCG system, the magnetic sensor is located in the chest and close to the heart. In this setting, millions of nerves and muscle fibers are active at the same time, thereby generating a cumulative signal that is strong enough to be detected by a sensor placed on the skin a few centimeters away from the nerves.

[0005] However, the magnetic field emitted by some nerves may be much smaller. This is the case with the renal nerves, which contain only hundreds to thousands of nerve fibers. The renal nerves are located in the adventitia (outer layer) of the renal artery wall and extend next to the renal artery. The magnetic fields generated by the renal nerves decay rapidly with distance, so they are too small to be sensed by surface sensors located on the skin. Therefore, in order to detect the magnetic fields generated by some types of nerves (e.g., renal nerves), it is necessary to insert a magnetic sensor into the body and position the magnetic sensor close to the nerve of interest. This in turn limits the size of the magnetic sensor that can be used to detect neural activity in an interventional setting. Moreover, the magnitude of the magnetic field close to the nerves varies greatly with the sensing location. In addition, in the presence of magnetic interference from other sources, it may be challenging to obtain accurate measurements of the magnetic field from the nerves.

[0006] WO2013 / 096461A1 describes a device for local monitoring of nerve activity that can be incorporated into a nerve ablation catheter. The catheter is equipped with a magnetic sensing device for identifying nerves and assessing the success of ablation. The catheter is also equipped with an ablation device for stimulating and destroying nerve tissue. In the disclosed device, the magnetic sensor is configured to sense a magnetic field generated in response to artificial activation of the nerve by the ablation device.

[0007] However, there remains a need for improved detection of induced and / or natural neural activity in interventional devices. Summary of the invention

[0008] According to one aspect of the present disclosure, an interventional device for detecting neural activity is provided. The interventional device includes a magnetic sensor. The magnetic sensor is coupled to an insertable portion of the interventional device. The magnetic sensor is configured to generate a signal in response to a magnetic field generated by neural activity.

[0009] According to another aspect of the present disclosure, a system is provided. The system includes an interventional device and a controller. The controller is configured to receive a signal generated by a magnetic sensor and output a detection result indicating neural activity in response to the received signal.

[0010] Other aspects, features and advantages of the present disclosure will become apparent from the following description of examples with reference to the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] Figure 1 is a diagram showing a neural fiber bundle BNF according to some aspects of the present disclosure 1..3 Schematic diagram of an example of a cross section of an overlaid blood vessel VES and interventional device ID.

[0012] Figure 2is a schematic diagram illustrating an example of a typical action potential signal on a nerve fiber according to some aspects of the present disclosure.

[0013] Figure 3 is a schematic diagram showing an example of a) a model of a nerve fiber extending along and adjacent to a blood vessel lumen, and b) modeled electric dipole currents representing depolarization and repolarization of the nerve fiber, according to some aspects of the present disclosure.

[0014] Figure 4 is a schematic diagram showing examples of a) simulated magnetic flux density and b) corresponding streamlines around a nerve fiber according to some aspects of the present disclosure.

[0015] Figure 5 Schematic diagram showing examples of a) a model of dipole currents in a nerve fiber with a sensor located at a radial distance r, b) a predicted magnetic flux density resulting from the modeled dipole currents, c) the predicted magnetic flux density at different radial distances r, and d) the distribution of magnetic flux density arrival times used to generate the predicted magnetic flux density in c) according to some aspects of the present disclosure.

[0016] Figure 6 is a schematic diagram illustrating an example of an interventional device 110 for detecting neural activity according to some aspects of the present disclosure.

[0017] Figure 7 is a schematic diagram illustrating a first example of a magnetic sensor 120 including an optically pumped magnetometer according to some aspects of the present disclosure.

[0018] Figure 8 is a schematic diagram illustrating a second example of a magnetic sensor 120 including an optically pumped magnetometer according to some aspects of the present disclosure.

[0019] Fig. 9 is a schematic diagram illustrating a third example of a magnetic sensor 120 including an optically pumped magnetometer according to some aspects of the present disclosure.

[0020] Fig.10 is a schematic diagram illustrating a fourth example of a magnetic sensor 120 including an optically pumped magnetometer according to some aspects of the present disclosure.

[0021] Fig.11 is a schematic diagram illustrating an example of a system 200 including an interventional device 110 for detecting neural activity and a controller 140 according to some aspects of the present disclosure.

[0022] Fig.12 is a diagram showing a) the power P applied to the heater of the optical unit of the OPM according to some aspects of the present disclosure HEATERb) the temperature T generated by the optical unit CELL , c) Magnetic field B generated by activated nerves NERVE and d) in response to magnetic field B NERVE The signal B generated by OPM is the result of the detection DETECTED Schematic diagram of an example.

[0023] Fig.13 is a diagram showing a neural fiber bundle BNF according to some aspects of the present disclosure 1..3 Schematic diagram of an example of a cross section of an overlaid blood vessel VES and an interventional device ID including an expandable balloon.

[0024] Fig.14 are graphs showing a) characteristics of a pulse train representing a magnetic field detected from renal nerves of a non-hypertensive subject and b) characteristics of a pulse train representing a magnetic field detected from renal nerves of a hypertensive subject with increased renal nerve activity according to aspects of the present disclosure.

[0025] Fig.15 A graph showing the pulse repetition time Rt within a pulse train versus the number of pulses nP within a pulse train for a simulated magnetic field in a group of non-hypertensive subjects (circular symbols) and hypertensive subjects (asterisks) according to aspects of the present disclosure.

[0026] Fig.16 An example of a system 200 including nested magnetic field shielding devices according to some aspects of the present disclosure is shown.

[0027] Fig.17 An example of a system 200 is shown that includes an interventional device 110 , a motion sensor 160 , and one or more coils 150 , SSL, configured to generate a magnetic field to compensate for a background magnetic field detected by a magnetic sensor 120 , according to some aspects of the present disclosure. DETAILED DESCRIPTION

[0028] Examples of the present disclosure are provided with reference to the following description and accompanying drawings. In this description, for the purpose of explanation, many specific details of some examples are set forth. References in the specification to "examples," "implementations," or similar language mean that features, structures, or characteristics associated with the example are included in at least one example. It should also be understood that features associated with one example may also be used in another example, and for the sake of brevity, all features are not necessarily repeated in each example. For example, features described in connection with an interventional device may be implemented in a system in a corresponding manner, and may also be implemented in a computer-implemented method and a computer program product.

[0029] In the following description, interventional devices including magnetic sensors are mentioned. The magnetic sensors are configured to generate signals in response to a magnetic field generated by neural activity. In some examples, interventional devices in the form of ablation devices are mentioned. In some examples, the ablation device is an ablation catheter. However, it should be understood that the interventional device may alternatively be a device of a different type from the (RF / high frequency ultrasound "HIFU" / microwave) ablation device. For example, the interventional device may alternatively be a (guide) catheter, a (RF / high frequency ultrasound "HIFU" / microwave) ablation catheter, a guidewire, an intravascular ultrasound "IVUS" device, an optical coherence tomography "OCT" device, a blood pressure sensing device and / or a blood flow sensing device, a TEE probe, etc. Therefore, the interventional device can generally be any type of interventional device.

[0030] This article also mentions an example of an interventional device in the form of an ablation device for use in a renal denervation surgery. The example ablation device is provided in the form of an ablation catheter that is suitable for insertion into a renal artery. However, it should be understood that this is only an example, and the interventional device may generally be suitable for insertion into the body. The interventional device may be suitable for insertion into various tissues in the body, or it may be suitable for insertion into various lumens in the body. In some examples, the interventional device is suitable for intravascular insertion, i.e., insertion into a vein or artery. It is also contemplated that the interventional device may alternatively be suitable for insertion into other lumens in the body, including, for example, the digestive tract, colon, esophagus, lungs, urinary tract, nasal cavity, etc. It is also contemplated that in some applications, the interventional device may be used for open surgery. In addition, it should be understood that the interventional device may generally be used in clinical procedures, and the device is not limited to use in the example renal denervation surgery described herein. The interventional device may, for example, be a sensing device that senses a magnetic field and does not perform treatment at all.

[0031] The operations performed by the controller are also mentioned herein. As described in more detail below, the controller may include one or more processors for performing some of these operations. It should be noted that the operations performed by the controller may be provided in the form of a computer-implemented method. The computer-implemented method may be provided as a non-temporary computer-readable storage medium, which includes a computer-readable instruction stored thereon, and when executed by at least one processor, the instruction causes at least one processor to perform the method. In other words, the computer-implemented method may be implemented in a computer program product. The computer program product may be provided by dedicated hardware or hardware capable of running the software in association with appropriate software. When provided by a processor or controller, the function of the method feature may be provided by a single dedicated processor, a single shared processor, or a plurality of separate processors (some of which may be shared). For example, one or more functions in the method feature may be provided by a processor shared within a network processing architecture (e.g., client / server architecture, peer-to-peer architecture, the Internet, or a cloud).

[0032] The explicit use of the term "processor" or "controller" should not be interpreted as referring only to hardware capable of running software, and may implicitly include, but is not limited to, digital signal processor "DSP" hardware, read-only memory "ROM" for storing software, random access memory "RAM", non-volatile storage devices, etc. In addition, examples of the present disclosure may take the form of a computer program product accessible from a computer-usable storage medium or a computer-readable storage medium, which provides program code for use by or in connection with a computer or any instruction execution system. For the purposes of this specification, a computer-usable storage medium or a computer-readable storage medium may be any device that can contain, store, transmit, propagate or transmit a program for use by or in connection with an instruction execution system, device or apparatus. The medium may be an electronic, magnetic, optical, electromagnetic, infrared or semiconductor system or device or a propagation medium. Examples of computer-readable media include semiconductor or solid-state memory, magnetic tape, removable computer disk, random access memory "RAM", read-only memory "ROM", hard disk, and optical disk. Current examples of optical disks include compact disk read-only memory "CD-ROM", compact disk read / write "CD-R / W", Blu-ray TM and DVD.

[0033] As discussed above, there remains a need for improved detection of induced and / or natural neural activity in interventional devices.

[0034] Figure 1 is a diagram showing a neural fiber bundle BNF according to some aspects of the present disclosure 1..3 Schematic diagram of an example of a cross section of a covered blood vessel VES and an interventional device ID. As an example, Figure 1 The blood vessel VES shown in FIG. 1 may represent a renal artery in a subject, and the nerve fiber bundle BNF 1..3 During clinical studies, it may be desirable to measure the BNF of nerve fibers. 1..3 The activity of the renal nerves represented. For example, it may be desirable to measure the activity of the renal nerves in order to stratify patients for treatment by a given procedure. The stratification of patients may include criteria based on which it may be predicted or inferred whether the patient is eligible for successful renal denervation treatment. The interventional device ID may, for example, be a sensing catheter that is inserted into the body from the groin area and navigated through the vascular system to the renal artery VES. The interventional device ID may be advanced to the renal artery through the vascular system via a guide catheter. Having reached the renal artery VES, a portion of the interventional device ID may be positioned proximate to the wall of the vessel VES in order to measure the activity of the renal nerves represented by the renal artery VES. 1..3 As another example, during treatment of the renal nerve, the magnetic field emitted by the nerve fiber bundle BNF is measured. 1..3One of the representations of the magnetic field emitted by the renal nerves may be useful. In this example, the interventional device ID may be an ablation catheter. Figure 1 Treatment of the renal nerve may involve applying energy from an ablation catheter to the nerve fiber bundle BNF 1..3 One of the ablation catheters may be used to inhibit its activation, thereby treating the subject's hypertension. The ablation catheter may treat the nerve fiber bundle BNF1 by applying heat, high frequency ultrasound "HIFU", microwaves, radio frequency "RF" or another form of ablation energy to the nerve fiber bundle BNF1 through the wall of the blood vessel VES. During the ablation treatment, it may be useful to measure the activity of the treated nerve fiber bundle BNF1 in order to determine the effectiveness of the treatment.

[0035] As mentioned above, when a nerve is activated, it transmits an electrical impulse (often called an "action potential") along the associated nerve fiber. Figure 2 is a schematic diagram showing an example of a typical action potential signal on a nerve fiber according to some aspects of the present disclosure. For example, Figure 2 The action potential shown can be represented by Figure 1 The nerve fiber bundle BNF is shown 1..3 One of them is generated. Figure 2 The action potential shown represents the potential at a point on a nerve fiber when an electrical pulse passes through it. Before any activation, the potential on the nerve fiber is at a resting potential of about -70 mV. A stimulus is applied at time T0. If the stimulus is large enough, i.e., greater than the threshold potential V of about -55 mV, TH , then in Figure 2 Depolarization occurs during period I in the retrieval system, followed by repolarization during period II. After a refractory period III, the potential on the nerve fiber returns to a resting potential of approximately -70 mV during period IV.

[0036] Figure 2 The action potential signal shown can be viewed as a wave generated by the successive depolarization and repolarization of the nerve cell membrane (axon) and caused by the movement of its ions through its successive ion channels. There is no net current flowing along the nerve fiber as would be expected in an electrical wire. The propagating wave nature of the action potential signal is due to the short delay between depolarization and repolarization and the inability to immediately reactivate the previous channel (because it has not yet repolarized). The movement (or switching) of ions in / out of one channel in the cell membrane triggers the next channel after a certain delay, and so on. Starting from a fixed point on the nerve, the electrical impulse appears as an action potential that varies over time.

[0037] Figure 2 The typical action potential signal shown in is used to generate a model that simulates the magnetic field that can be measured near a nerve fiber. Figure 3Various aspects of the model are shown in Figure 3 is a schematic diagram showing an example of a) a model of a nerve fiber extending along and adjacent to a blood vessel lumen, and b) modeled electric dipole currents representing depolarization and repolarization of the nerve fiber, according to some aspects of the present disclosure. Typically, the wave-like propagation of action potentials along nerve fibers is difficult to capture in biophysical models because it involves charges (ions) switching in multiple channels located on the nerve at different times. This makes the problem unstable over relatively large spatial distances along the nerve fiber. Therefore, in Figure 3 In the model shown, an estimate of the magnetic field distribution around the renal nerve is modeled by approximating the action potential with currents flowing in opposite electric dipoles aligned with the direction of the nerve fiber, as Figure 3 As shown in a). Figure 3 The electric dipole shown in a) has a combined length L. Figure 3 The resulting currents I and I' are shown in b). This approximation converts the unstable problem into a steady-state model, where the opposite dipoles model the depolarization and repolarization as if they were permanent.

[0038] use Figure 3 The simulation results are shown in Figure 4 It is shown in Figure 4 is a schematic diagram showing examples of a) simulated magnetic flux density and b) corresponding streamlines around a nerve fiber according to some aspects of the present disclosure. Figure 4 Represents a snapshot at a fixed position next to the nerve at a specific time. Figure 4 The simulated magnetic flux density shown in has an axisymmetric magnetic field around the nerve fiber.

[0039] However, in practice, the electrical impulses and magnetic fields generated by the activation of nerves propagate along the nerve fibers. Figure 4 The magnetic field shown in represents only the magnetic field generated by a single nerve fiber. These shortcomings of the model are captured in a more detailed model.

[0040] In a more detailed model, the propagation of the magnetic field is modeled by assigning a constant propagation velocity v to the opposite dipoles of the pair. An electromotive force is also prescribed inside the dipoles so as to generate a local current between 50 and 100 nA. Furthermore, in practice, a bundle of nerves contains thousands of fibers. Although the activation of the nerves within the bundle is synchronized, the differences between the nerve fibers within the bundle result in a dynamic magnetic field signal due to the propagation of the action potential and the different arrival times to each fiber. In a more detailed model, the effect of a bundle of nerve fibers is modeled using a Gaussian distribution of the arrival times of the magnetic field signals of the fibers within the bundle.

[0041] The simulation results using this more detailed model are Figure 5 It is shown in Figure 5 Graphs showing examples of a) a model of dipole currents in a nerve fiber where a sensor is located at a radial distance r, b) a predicted magnetic flux density resulting from the modeled dipole currents, c) the predicted magnetic flux density at different radial distances r, and d) the distribution of magnetic flux density arrival times used to generate the predicted magnetic flux density in c) according to some aspects of the present disclosure. Figure 5 The amplitude of the magnetic flux density signal shown in c) is up to about 1.5 pT, depending on the radial distance between the sensor and the nerve bundle. This is consistent with the typical radial decrease of the magnetic field around a dipole reported in the literature. In addition, it follows 1 / r n The simulations showed that the magnetic field generated by the renal nerves could be measured using a magnetic sensor with a sensitivity of a few picoTesla, if the sensor was within a few millimeters of the nerve bundle. The results of this more detailed model were then used to design magnetic sensors for detecting nerve activity.

[0042] Various examples of interventional devices including magnetic sensors for detecting neural activity are described below. The magnetic sensors can be used to measure the magnetic field generated by neural activity (e.g., activity of renal nerves), as described above with reference to Figure 1 Typically, a magnetic sensor disposed on an interventional device can be used to measure a magnetic field generated in response to artificial activation of a nerve, or can be used to measure a magnetic field generated by natural (ie, spontaneous) activation of a nerve.

[0043] Figure 6 1 is a schematic diagram showing an example of an interventional device 110 for detecting neural activity according to some aspects of the present disclosure. In the illustrated example, the interventional device includes a magnetic sensor 120. The magnetic sensor 120 is coupled to an insertable portion of the interventional device, i.e., insertable into a body lumen (e.g., a renal artery). The magnetic sensor 120 is configured to generate a signal in response to a magnetic field generated by neural activity.

[0044] Reference Figure 6 In this example, the interventional device 110 is a catheter. The catheter includes an insertable portion that is inserted into Figure 6In the lumen LUM of the blood vessel VES shown in . Therefore, in this example, the insertable portion of the interventional device is sized to be inserted into the blood vessel. The magnetic sensor 120 can generally be coupled to any position on the insertable portion of the interventional device. For example, the magnetic sensor 120 can be coupled to the distal end of the insertable portion, or to a position proximal to the distal end of the insertable portion. In the illustrated example, the magnetic sensor 120 is coupled to the interventional device at a position proximal to the distal end of the insertable portion of the catheter. Typically, the magnetic sensor 120 can be coupled to any position on the insertable portion of the interventional device, and the interventional device can be inserted into any area of ​​the anatomical structure.

[0045] Continue to refer to Figure 6 , the magnetic sensor 120 generates a signal in response to the magnetic field generated by the neural activity. The signal can be transmitted to a controller, such as Figure 6 Controller 140 shown in . In general, the generated signals can be optical signals or electrical signals. For example, in the embodiment described below where the magnetic sensor is provided by an optically pumped magnetometer "OPM", the generated signals are optical signals, and these signals are optically transmitted to the controller 140 via optical fibers, which transmit the optical radiation to the optical unit of the OPM. Transmitting the signals optically avoids the risk of generating magnetic fields that may interfere with the operation of the magnetic sensor 120. The signals can alternatively be transmitted wirelessly. The controller 140 can process the signals to output detection results indicative of neural activity, as described in more detail below.

[0046] The magnetic field sensed by the magnetic sensor 120 may be generated by nerves, e.g. Figure 6 The nerve fiber bundle BNF1 shown in . Typically, neural activity can be triggered artificially, or it can be triggered naturally, i.e., spontaneously. In the former case, the neural activity can be triggered by applying stimulation within the blood vessel VES (i.e., from an intravascular location, or more generally, from an in vivo location), or alternatively, it can be triggered by applying stimulation from a location outside the body (i.e., from an in vitro location). Neural activity can be triggered using a variety of techniques, including by delivering electrical energy, RF energy, thermal energy, and tactile stimulation. In one example, the interventional device is an intravascular RF ablation device, and the neural activity is stimulated by applying RF energy to the nerve from the intravascular RF ablation device.

[0047] Continue to refer to Figure 6 , the magnetic sensor can be arranged in the blood vessel VES so that the magnetic sensor is adjacent to or even in contact with the wall of the blood vessel VES in order to detect the magnetic field generated by the nerve fiber bundle BNF1. The magnetic field decays rapidly with the spacing between the nerve fibers and the magnetic sensor, so when the magnetic sensor 120 is in the position shown, it can detect that the contribution from the nerve fiber bundle BNF2 is much weaker than the contribution from the nerve fiber bundle BNF1.

[0048] Figure 6 The magnetic sensor 120 shown in FIG. 1 may be provided by various types of magnetic sensors. For example, the magnetic sensor 120 may be provided by an optically pumped magnetometer “OPM” as described above. Figure 7 is a schematic diagram illustrating a first example of a magnetic sensor 120 including an optically pumped magnetometer according to some aspects of the present disclosure. Figure 7 The OPM includes an optical unit 130 that contains an alkali metal in a liquid phase and / or a gas phase. The alkali metal may be, for example, rubidium, cesium, or potassium. The OPM is configured to generate a signal in response to a magnetic field generated by neural activity by measuring a magnetic field-dependent optical property of the alkali metal. For example, the magnetic field-dependent optical property may be the orientation of atomic spins of the alkali metal.

[0049] Reference Figure 7 , the exemplary optical unit 130 comprises a tubular member, the tubular member being defined at its axial ends by an optical window, and the optical window is combined with the tubular member for containing the alkali metal in its liquid and / or gas phase. As an example, Figure 7 The optical unit 130 shown in FIG. 1 can have a diameter of about 1 mm or less so that the optical unit 130 can be coupled to an interventional device and inserted into a subject. In some examples, the optical unit 130 has a diameter of about 0.5 mm or less, a length of about 3 mm, and a resulting volume of 1 cubic mm or less. Figure 7 Also shown is the nerve fiber bundle BNF1. Figure 4 As described above, the neural activity in the nerve fiber bundle BNF1 generates a magnetic field. In order to detect the magnetic field generated by the nerve fiber bundle BNF1, optical radiation is input to the optical unit 130 through the input optical fiber IPF and the input lens IPL. The optical radiation irradiates the alkali metal in its liquid phase and / or gas phase in the optical unit 130. The optical radiation can be generated by a laser ( Figure 7 The laser light is provided by a laser beam (not shown) having a wavelength corresponding to the resonant frequency of the atoms of the alkali metal. The laser light can be provided by Figure 6 The laser provides a polarized light beam that passes through the optical unit 130. In some examples, the light beam may have circular polarization. At resonance, the atomic spins of the alkali metal atoms in the optical unit 130 are aligned with the propagation direction of the laser radiation. Changes in the magnetic field near the optical unit deflect the atomic spin direction, which in turn causes changes in the amount of radiation transmitted through the optical unit 130. In other words, the spin direction of the alkali metal atoms is susceptible to the magnetic field. Figure 7 In the example shown, the radiation transmitted through the optical unit is collected by the output lens OPL and coupled to the optical detector ( Figure 7130). A polarizer may be included in the optical path to measure the transmission of a specific polarization. In one example, the optical detector may be provided by a polarimeter. The optical detector measures the amount of radiation having a specific polarization transmitted through the optical unit 130, thereby determining the magnetic field strength near the optical unit in a specific plane.

[0050]

[0066] Variations on the implementation of the OPM described above are also contemplated.

[0051] In one example, the optical unit 130 of the OPM also includes a background gas. In this example, the OPM is also configured to generate a signal in response to a magnetic field generated by neural activity by measuring optical properties related to the magnetic field of the background gas. For example, the background gas may include helium. In this example, the atomic spin direction of the background gas (e.g., helium) is also susceptible to changes in the magnetic field. The magnetic field generated by neural activity can be detected by changes in the spin of helium atoms in the optical unit 130 in a manner similar to that described above with respect to alkali metal atoms. In other words, by irradiating the optical unit 130 including helium and alkali metals in liquid and / or gas phases, the transmission changes of the optical unit caused by the deflection of the atomic spin direction of both helium and alkali metals can be measured to detect the magnetic field. Different laser radiation wavelengths can be used to induce resonance in helium atoms compared to the resonance of alkali metal atoms. This allows transmission measurements of helium and alkali metals to be performed separately.

[0052] By using the above reference Figures 2 to 5 Based on the model described, the inventors have determined that the magnetic field generated by the renal nerves can be detected from a location within the renal artery by positioning a magnetic sensor with sub-picotesla sensitivity a few millimeters away from the nerve fiber bundle. The inventors have also determined that the magnetic field sensitivity of the OPM unit is determined by the density of atoms per unit volume in the gas phase of the unit. The magnetic field sensitivity of the OPM unit can be described by the following formula:

[0053]

[0054] Where n represents the density of atoms per unit volume in the gas phase in the cell, and V represents the volume of the cell. In this formula, lower resolution values ​​correspond to more sensitive OPM cells. In addition, in order to allow free rotation in the appropriate quantum state, the atoms must be in the gas phase. For alkali metals such as rubidium, the boiling point is higher than room temperature. Therefore, the optical cell must be heated to reach the gas phase. Above the boiling temperature, the density of atoms per unit volume n in the gas phase in the cell depends significantly on the temperature. Further increasing the temperature of the cell will result in a lower density n, which increases the sensitivity of the OPM. In contrast, the boiling point of helium is much lower than room temperature or body temperature, so at these temperatures, almost all helium atoms are in the gas phase. Therefore, the magnetic field can be detected by the change in the spin of helium atoms at room temperature or body temperature. Heating has little effect on the sensitivity of the optical cell containing helium. The pressure in the optical cell containing helium can be increased to increase the density of atoms per unit volume n in the gas phase (assuming that the helium remains in the gas phase). However, n is lower than that of heated alkali metals (such as rubidium, cesium, or potassium), so the expected sensitivity of an OPM with helium will be lower than that of an OPM containing alkali metals.

[0055] In general, a higher atomic density n increases the relaxation time for atoms to transition between quantum states. Therefore, the bandwidth of an OPM is inversely proportional to the atomic density n. Therefore, there is an upper limit to the atomic density in the optical cell for sufficient bandwidth of this device.

[0056] By providing the OPM with an optical unit that contains both a background gas (e.g., helium) and an alkali metal in a liquid phase and / or a gas phase, an OPM can be provided that can operate in a relatively low sensitivity mode and a relatively high sensitivity mode, in which the optical unit is not heated and the magnetic field generated by neural activity is detected by changes in the atomic spins of the background gas (e.g., helium), and in which the optical unit is heated and the magnetic field generated by neural activity is detected by changes in the atomic spins of the alkali metal.

[0057] Therefore, in some examples, reference Figure 7 The described OPM also includes a heater, and the heater is configured to provide heat to the optical unit. In this regard, it is contemplated that various types of heaters may be used. The heater may, for example, include a resistive element that is thermally coupled to the housing of the optical unit 130. In this example, electrical energy may be delivered to the resistive element via wires extending along the length of the interventional device to the controller 140. To avoid the risk of interference between the magnetic field generated by the current in the resistive heater and the magnetic sensor 120, the heater may be operated in a pulsed mode, as described later. Fig.12A description is given, wherein the magnetic sensor 120 senses the magnetic field during a period of time after the power supply to the heater is turned off. Alternatively, the heater may be provided by a light absorber thermally coupled to the housing of the optical unit. In this example, a light source is coupled to the light absorber, which light source may be, for example, the same laser used to illuminate the optical unit, or may be a second laser that emits a light wavelength different from the wavelength of the laser illuminating the optical unit. The light absorber is configured to absorb the light wavelength emitted by the light source. In the case where the same laser is used to illuminate the optical unit and to heat the optical unit, the input optical fiber IPF may transmit the light radiation from the laser to a beam splitter that directs a first portion of the radiation from the laser to the light absorber and directs a second portion of the radiation from the laser to the optical unit. In the case where a second laser is used to heat the optical unit, a second optical fiber may be used to couple the radiation from the second laser to the light absorber. Using a second laser isolates the operation of heating the optical unit from the operation of detecting the magnetic field by changes in the spin directions of atoms in the optical unit. Using a light absorber in conjunction with such a light source may provide a heater having a smaller geometry than a resistive heater, and may also reduce the risk of generating a magnetic field that may interfere with the magnetic sensor 120 .

[0058] The inventors have also determined that while significant improvements in the sensitivity of the above-mentioned OPM can be achieved by heating the optical unit as described above, these improvements are at the expense of the need to thermally insulate the OPM or remove the heat dissipated by the OPM to prevent damage to the tissue. For example, in one design, at a temperature of 50 degrees Celsius, the OPM unit can achieve a sensitivity of about 150 femtotesla, while by heating the OPM unit to a temperature of about 100 degrees Celsius, the OPM unit can achieve a five-fold sensitivity improvement of about 30 femtotesla. In order to achieve such optical unit temperatures in an interventional device without damaging tissue, in one method, thermal insulation can be provided to limit the rate of thermal energy escaping from the OPM, thereby limiting the temperature rise of the outer surface of the OPM. In another method that can be combined with the previous method, a cooling device can be used to remove the heat dissipated by the OPM from the OPM. In this regard, it is contemplated to use various cooling devices. In some of these cooling devices, a medium inserted into the interventional device is used to remove the dissipated heat. In one example, the OPM includes a housing configured to provide thermal contact between the OPM and the medium inserted into the interventional device. In this example, heat is removed from the OPM through the medium. For example, in the case where the medium is blood, flowing blood can be used to remove a large amount of heat. Thermal contact can be provided by forming the shell of the OPM with various heat-conducting materials (e.g., metals), and a thermal path can be formed between the OPM shell and the medium. In a related example that can be used in conjunction with the previous example, the OPM is in thermal contact with the outer surface of the interventional device 110 so as to cool the OPM through the outer surface of the interventional device. By providing such thermal contact with the interventional device, heat is dissipated through the interventional device, which limits the temperature of the OPM, thereby reducing the risk of damaging tissue in thermal contact with the OPM. In another example that can also be used in conjunction with the previous example, the interventional device includes a channel configured to supply a cooling fluid to the OPM. The channel can extend along the length of the interventional device so that the cooling fluid can be supplied to the OPM from a position outside the subject. The channel can be connected to a cooling fluid source, such as an open circuit source of cooling fluid or a closed circuit heat exchanger. For example, the cooling fluid may include water or saline.

[0059] In those examples that include a heater, the interventional device may also include a temperature sensor in thermal contact with i) an outer surface of the interventional device or ii) the optical unit 130. The temperature sensor may be used to monitor the temperature of the outer surface of the interventional device or the optical unit 130, respectively, and control the temperature of the outer surface of the interventional device or the optical unit 130 as described later.

[0060] Reference Figure 7The sensitivity of the described OPM can also be improved by measuring the transmission of the light beam through the optical unit 130 multiple times. In this case, each pass of the light beam will have an incremental effect on the measured transmission. Therefore, in one example, the OPM is configured to measure the transmission of the light beam through the optical unit 130 so as to generate a signal in response to a magnetic field generated by neural activity; and the OPM includes multiple optical elements that are configured to provide multiple passes of the light beam through the optical unit 130.

[0061] In this example, the optical element may be provided by a reflective element and / or a lens combined with an optical fiber. Figure 8 and Fig. 9 Two implementations of this example are described. Figure 8 is a schematic diagram illustrating a second example of a magnetic sensor 120 including an optically pumped magnetometer according to some aspects of the present disclosure. Figure 8 The examples shown in Figure 7 Elements are also shown. Figure 8 In Figure 7 Like numbered components are provided with reference to Figure 7 Same functionality as described in Figure 7 compared to, Figure 8 The example further includes a plurality of reflective elements MIR 1..4 , which is arranged to provide multiple passes of the light beam illuminating the optical unit through the optical unit 130. Fig. 9 is a schematic diagram illustrating a third example of a magnetic sensor 120 including an optically pumped magnetometer according to some aspects of the present disclosure. Fig. 9 The examples shown in include Figure 7 Elements are also shown. Fig. 9 In Figure 7 Like numbered components are provided with reference to Figure 7 Same functionality as described in Figure 7 compared to, Fig. 9 The example further includes a plurality of lenses LEN 1..4 and optical fibers LOF, which are arranged to provide multiple passes of the light beam illuminating the optical unit through the optical unit 130.

[0062] The inventors have also observed that a disadvantage of some existing magnetic sensors is that they are unable to provide information about the location of the nerves that contribute most to the detected magnetic field level. Figure 1As can be seen in the figure, the magnetic sensor arranged on the interventional device ID in the position shown can detect the magnetic field generated by the nerve fiber bundle BNF1. However, the signal generated by such a sensor can hardly provide information about the direction of the nerve fiber bundle BNF1. The doctor only needs to move the magnetic sensor toward the nerve fiber bundle and observe the associated increase in the detected magnetic field to know the direction of the nerve fiber bundle BNF1. If the direction of the nerve fiber bundle BNF1 is known before moving the magnetic sensor, it will help the doctor to position the magnetic sensor closer to the nerve fiber bundle.

[0063] In one example, the magnetic sensor 120 includes a plurality of magnetic sensor elements, and each magnetic sensor element is configured to detect a magnetic field of a different volume that intercepts the interventional device.

[0064] This example can be used to improve the positioning of sensors relative to nerve fiber bundles. Fig.10 Describe this example. Fig.10 is a schematic diagram illustrating a fourth example of a magnetic sensor 120 including an optically pumped magnetometer according to some aspects of the present disclosure. Fig. 9 The examples shown in Figure 7 Elements are also shown. Fig.10 With Figure 7 Like numbered components are provided with reference to Figure 7 Same functionality as described above. Fig.10 There are four magnetic sensor elements. Each magnetic sensor element includes an input lens IPL 1..4 and input fiber IPF 1..4 (which are configured to couple optical radiation into a portion of the optical unit 130), and a corresponding output lens OPL 1..4 and output optical fibers (which are configured to collect optical radiation from that portion of the optical cell and couple the collected optical radiation to an optical detector). Each portion of the optical cell represents a sensing volume within which the magnetic field is sensed by the magnetic sensor element. The portion of the optical cell is defined by the cell wall CWL 1..4 The cell walls confine the gas in the optical cell to a discrete sensing volume. Figure 7 In a manner related to that described, the strength of the magnetic field intercepting each sensing volume is determined by measuring the transmission of optical radiation through the corresponding portion of the optical unit. Fig.10 The OPM 120 shown in FIG. 1 is also coupled to an interventional device as described above. In this way, each magnetic sensor element can be used to detect a different volume of magnetic field that intercepts the interventional device.

[0065] In the example above, the measurements of the magnetic field strength within each of the different volumes of the interventional device provide the user with information on how to reposition the interventional device to move it toward the nerve. Fig.10 In the example shown, since the uppermost optical path is closest to the nerve fiber bundle BNF1, the magnetic field measured in this optical path will be higher than that in the lowermost optical path due to the neural activity in the nerve fiber bundle BNF1. Fig.10 The magnetic field measured in the lower optical path in the interventional device. Therefore, the direction of the nerve can be determined based on the comparison of the magnetic field strength values ​​measured in different volumes of the interventional device.

[0066] In another example, referring to Figure 6 The described interventional device also includes an expandable balloon or basket. The balloon or basket is coupled to the insertable portion of the interventional device so as to fix the inserted portion of the interventional device in the lumen when the expandable balloon or basket is in an expanded state. This example can be used to provide magnetic field measurements at a fixed position in the lumen, while, for example, the position of the interventional device is not affected by subject motion, heart motion, blood flow, etc.

[0067] The example interventional devices described above may also form part of a system 200 that includes a controller 140. The controller 140 receives the signals generated by the magnetic sensors and outputs detection results indicative of neural activity in response to the received signals.

[0068] Fig.11 is a schematic diagram illustrating an example of a system 200 including an interventional device 110 and a controller 140 for detecting neural activity, according to some aspects of the present disclosure. Fig.11 The examples shown in include Figure 6 The elements are also shown in FIG. Fig.11 In the system 200, the system 200 includes Figure 6 The interventional device 110 is described and also includes a controller 140 . Fig.11 With Figure 6 Like labeled elements (eg, interventional device 220) are provided as described above with reference to Figure 6 Same functionality as described. Fig.11 The controller 140 shown in the figure may include one or more processors and / or electronic circuits. The one or more processors and / or electronic circuits are configured to perform various operations described with respect to the controller. For example, the controller may include an optical detector and an electronic circuit that detects and amplifies received signals, respectively. The controller may also include an analog-to-digital converter "ADC" that digitizes the signal and a processor that converts the digitized signal and / or performs further operations on the digitized signal so that they can be displayed as detection results on a display device such as a monitor.

[0069] The controller 140 can output various detection results. In one example, the detection result includes a time-correlated signal that represents the signal generated by the magnetic sensor 120, or in other words, represents the time-correlated magnetic field generated by the neural activity. In another example, the detection result includes a signal that represents the magnitude of the signal generated by the magnetic sensor 120, or in other words, represents the magnitude of the magnetic field generated by the neural activity. In another example, the detection result includes an estimate of the interval between the magnetic sensor 120 and the nerve that generates the neural activity. The estimate of the interval between the magnetic sensor 120 and the nerve can be determined based on the magnitude of the signal generated by the magnetic sensor. Figures 2 to 5 The model described can be used to provide a way to relate the magnitude of a signal to Figure 5 In another example, the detection result includes an indication of the state (e.g., healthy, unhealthy) of the nerve that generated the neural activity. In another example, the detection result includes a measurement of sympathetic overdrive in the nerve that generated the neural activity. In another example, the detection result includes the suitability of the nerve that generated the neural activity for treatment by renal denervation therapy. The suitability can be assessed by determining the distance between the magnetic sensor 120 and the nerve that caused the detected neural activity based on the detected magnetic field strength. If the distance is too large, the cell wall may be damaged by activating the ablation device and / or the nerve may not be adequately ablated. Alternatively or in addition, suitability can be assessed based on characteristics of the detected signal, as described later with reference to Fig.14 For example, the amount of sympathetic nerve overdrive can be determined from the feature and used to determine whether the nerve is suitable for treatment via renal denervation therapy. In another example, the detection result includes a measurement of the effect of a renal denervation therapy procedure that has been performed on a nerve that produces neural activity. The measurement of the effect of the renal denervation therapy procedure can be determined based on a comparison of the signals generated by the magnetic sensor before and after the renal denervation therapy procedure. As treatment progresses, the amplitude of the detected magnetic signal decreases until the treated nerve is destroyed. In addition, as later described with reference to Fig.14 As described, the characteristics of the magnetic field pulses generated by the nerves, i.e., the pulse frequency in the pulse train and the number of pulses in the pulse train, will also change during the treatment. Therefore, a measurement of the effectiveness of the treatment can be determined by measuring the amplitude and / or characteristics of the pulses. The user of the system can also be informed that the treatment can be terminated when the desired level of therapeutic effect has been achieved, i.e., when the amplitude and / or characteristics of the pulses have reached the desired state. The controller 140 can also output other test results. The test results can be output in various ways, such as to a computer-readable storage medium, a printer, or a display device such as a monitor.

[0070] In reference Fig.11 In one example of the described system 200, the interventional device can be translated along the axis of the lumen while generating detection results to provide a 2D or 3D graph of the detection results. Various manipulators can be used to translate the interventional device. It is expected that the changes in the strength and direction of the magnetic field from the nerve along the scanning path are reproducible. Therefore, by translating the interventional device along the axis of the lumen multiple times and generating corresponding graphs, detected features that do not appear in multiple graphs can be identified as noise or interference and discarded. Then, a combined graph can be generated from each graph by selecting (e.g., averaging) a graph that does not contain the identified noise or interference, or by combining graphs from which interference has been removed. The controller 140 can output a 2D or 3D graph of the detection results.

[0071] As described above with respect to the interventional device 110, in some examples, the magnetic sensor 120 includes an OPM, and the OPM further includes a heater configured to provide heat to the optical unit 130. Fig.11 In one example of the described system 200, the controller 140 may be configured to selectively operate the OPM in a relatively low sensitivity mode and a relatively high sensitivity mode to generate a signal in response to a magnetic field generated by neural activity, wherein in the relatively low sensitivity mode the heater provides a relatively low power level to the optical unit 130 and in the relatively high sensitivity mode the heater provides a relatively high power level to the optical unit 130.

[0072] In this example, the optical unit 130 may include a type of alkali metal in a liquid and / or gas phase. For example, the alkali metal may be rubidium. The two sensitivity levels provided in this manner may be used, for example, to first identify the location of a nerve fiber bundle in a relatively low sensitivity mode, and after the nerve fiber bundle has been identified, the OPM is switched to operation in a relatively high sensitivity mode so as to quantitatively analyze the identified nerve fiber bundle. In this example, the relatively low power level may be negligible, or, for example, zero power. In this example, the magnetic field changes near the optical unit are detected by changes in the magnetic field-related optical properties (i.e., atomic spin directions) of atoms of the same alkali metal in a relatively low sensitivity mode and a relatively high sensitivity mode. By operating the OPM in this manner, the temperature or power consumption of the OPM can be reduced because the OPM consumes lower power when a relatively low power is applied to the heater. Limiting the temperature or power consumption in this manner also limits the risk of the OPM damaging tissue. In this example, the controller may automatically switch between a relatively low sensitivity mode and a relatively high sensitivity mode in response to detecting a magnetic field above a predetermined threshold in a relatively low sensitivity mode.

[0073] Alternatively, in this example, the optical unit 130 may instead include two different types of alkali metals in liquid and / or gas phases, such as rubidium and cesium, or the optical unit 130 may include one type of alkali metal in liquid and / or gas phases and a background gas (e.g., helium). Then, two types of alkali metals or one type of alkali metal and background gas may be used in a similar manner to provide a relatively low sensitivity mode and a relatively high sensitivity mode. In this example, in each of the relatively low sensitivity mode and the relatively high sensitivity mode, changes in the magnetic field near the optical unit are detected by changes in the magnetic field-related optical properties (i.e., atomic spin directions) of atoms of different materials (i.e., different alkali metals, or background gas and alkali metal).

[0074] In these examples, the optical unit 130 includes an alkali metal in a liquid and / or gas phase and a background gas; and the OPM is configured to generate a signal in response to a magnetic field generated by neural activity by measuring optical properties of the alkali metal and the background gas related to the magnetic field, and senses the optical properties of the background gas in a relatively low sensitivity mode, and senses the optical properties of the alkali metal in a relatively high sensitivity mode; or alternatively: the optical unit 130 includes a first alkali metal in a liquid and / or gas phase, and a second alkali metal in a liquid and / or gas phase; and the OPM is configured to generate a signal in response to a magnetic field generated by neural activity by measuring optical properties of the first alkali metal and the second alkali metal related to the magnetic field, and senses the optical properties of the first alkali metal in a relatively low sensitivity mode, and senses the optical properties of the second alkali metal in a relatively high sensitivity mode.

[0075] As described above, in some examples, the OPM includes a heater configured to provide heat to the optical unit 130. In these examples, the interventional device may also include a temperature sensor. The temperature sensor may be in thermal contact with i) an outer surface of the interventional device or ii) the optical unit 130. Fig.11 In one example of the described system 200, the controller 140 is configured to operate the heater in response to the temperature measured by the temperature sensor. For example, the heater can be turned on until the temperature sensed by the sensor reaches a predetermined value. At this point, the heater can be turned off. Then, due to heat diffusion and / or active cooling, the temperature of the heater drops, and the heating cycle is then repeated. The controller 140 can alternatively or additionally be configured to control the above-mentioned cooling device in response to the temperature measured by the temperature sensor. For example, if the temperature measured by the temperature sensor exceeds a predetermined threshold, the cooling device can be activated.

[0076] By operating the heater in response to the temperature measured by the temperature sensor, the risk of tissue damage can be reduced. The controller can operate the heater in a continuous mode or a pulsed mode. When operating in a continuous mode, the controller can operate the heater digitally so that the heater turns on when the temperature measured by the temperature sensor is below a desired temperature threshold, and so that the heater turns off when the temperature measured by the temperature sensor reaches the desired temperature threshold. The controller can alternatively operate the heater in a continuous mode and operate the heater in an analog manner by using a proportional integral derivative controller "PID" feedback loop.

[0077] The controller may alternatively operate the heater in a pulsed mode and use the temperature measured by the temperature sensor to determine when to turn the heater off. Fig.12 describes an example of the operation of the heater in pulse mode, Fig.12 is a diagram showing a) the power P applied to the heater of the optical unit of the OPM according to some aspects of the present disclosure HEATER b) the temperature T generated by the optical unit CELL , c) Magnetic field B generated by activated nerves NERVE and d) in response to a magnetic field B NERVE The signal B generated by the OPM is the result of the detection DETECTED .

[0078] Fig.12 shows a) the power P applied to the heater of the optical unit of the OPM HEATER The value of power P HEATER is applied in a pulsed mode in order to limit the amount of power dissipated into the medium in which the OPM is inserted, and also to limit the power consumption of the OPM. A constant level of power is applied to the heater during intervals t0-t1, t2-t3, and t4-t5. Fig.12 b shows the generated temperature T of the optical unit CELL . The temperature may be measured by a temperature sensor in thermal contact with the optical unit 130. Alternatively, the temperature may be measured by a temperature sensor in thermal contact with an outer surface of the interventional device. In the illustrated example, the heater periodically applies heat to the optical unit. Heater power is turned on at times t0, t2, and t4. During the intervals during which power is applied to the heater, i.e., t0-t1, t2-t3, and t4-t5, the temperature of the unit increases until a threshold temperature T is reached. Th When the unit temperature T CELL Reaching the threshold temperature T Th When the power P applied to the heater HEATER During the intervals when no power is applied to the heater, i.e., t1–t2 and t3–t4, the temperature of the unit T CELLIt may be reduced due to heat losses to the medium in which the OPM is inserted or due to heat losses to the cooling fluid, as described above. Fig.12 c shows the magnetic field generated by the activated nerve B NERVE In this example, the nerve is activated spontaneously and includes a first set of pulses that overlaps the interval between t0 and t3 and the interval between t4 and t5. Fig.12 As shown in d, the response to the magnetic field B NERVE The test results (in Fig.12 c) and the signal B generated by the OPM DETECTED The magnitude of is higher in the time periods corresponding to the intervals t0–t1, t2–t3, and t4–t5 than in the time periods outside these intervals. This is due to the heating of the optical unit of the OPM and the consequent increase in the sensitivity of the OPM in these intervals. In fact, if Fig.12 As shown in d, when power is applied to the heater, the signal B generated by the OPM DETECTED is delayed compared to the intervals t0–t1, t2–t3, and t4–t5. This delay is caused by the time between the application of heat to the heater and the resulting cell temperature T CELL The time lag between Fig.12 As shown in d, in some cases, the sensitivity increase may only be at the cell temperature T CELL Exceeding the specific temperature T T Because of the time lag of the unit temperature after power is applied to the heater, the signal B generated by the OPM DETECTED May lag behind signal P HEATER ,like Fig.12 Thus, in the example shown, at least some of the spontaneous activations of the nerves in c) are detected. It is understood that by adjusting Fig.12 A power P is applied to the heater HEATER The frequency and threshold temperature T Th , the desired power consumption, unit temperature, and duration of the sensing period can be achieved. Fig.12 The OPM may alternatively be operated in a continuous mode as described above, wherein the OPM is responsive to the measured cell temperature T CELL The applied power P is adjusted continuously during all time periods. HEATER .

[0079] As described above with respect to interventional device 110, in some examples, magnetic sensor 120 includes an optically pumped magnetometer OPM, and OPM includes an optical unit 130, optical unit 130 includes an alkali metal in a liquid phase and / or a gas phase, and OPM is configured to generate a signal in response to a magnetic field generated by neural activity by measuring a magnetic field-related optical property of the alkali metal. Fig.11 In one example of the described system 200, the OPM includes a light source configured to provide an optical pump beam, and the OPM is configured to measure a magnetic field-related optical property of the alkali metal in response to the excitation of the alkali metal in the optical unit 130 by the optical pump beam, and the controller 140 is further configured to:

[0080] - modulating the intensity of the optical pump beam between a relatively low intensity and a relatively high intensity; and

[0081] The OPM is configured for measuring magnetic field-dependent optical properties of the alkali metal by determining the transmission of the optical pump beam through the optical unit 130 when the optical pump beam excites the alkali metal with a relatively high intensity.

[0082] In this example, rather than operating the light source of the OPM in a continuous mode, the light source is operated in a pulsed mode. This has the effect of allowing the system 200 to operate at a reduced power level. The relatively low intensity may be negligible, or zero intensity. This example may also be performed in conjunction with the previous example. Thus, Fig.12 The pulsing of the heater shown in a can also be performed in combination with the modulation of the optical pump beam. Thus, the pulsing of the heater can be synchronized with the modulation of the intensity of the optical pump beam, so that when the optical pump beam has a relatively high intensity, the heater applies heat to the optical unit.

[0083] As described above with respect to the interventional device 110, in some examples, the magnetic sensor 120 includes a plurality of magnetic sensor elements. Each magnetic sensor element is configured to detect a magnetic field that intercepts a different volume of the interventional device 110. These examples are referenced to Fig.10 Described in reference Fig.11 In one example of the described system 200, the controller 140 may also be configured to:

[0084] - measuring the signal-to-noise ratio of the signal generated by the magnetic sensor element; and

[0085] - Using the signal from one or more of the magnetic sensor elements having the highest signal-to-noise ratio to generate a detection result.

[0086] Reference Fig.10 In this example, the example of a magnetic sensor element is provided by the uppermost optical path of the optical unit 130 closest to the nerve fiber bundle BNF1, together with its associated input and output optical fibers IPF1, OPF1 and lenses IPL1, OPL1. In this example arrangement, activation of the nerve fiber bundle BNF1 is expected to generate a magnetic field having a relative Fig.10The signal from the uppermost magnetic sensor element with the highest signal-to-noise ratio will be used to generate the detection result. By using one or more sensor elements with the highest signal-to-noise ratio to generate the detection result, the overall signal-to-noise ratio of the detection result can be improved. This in turn improves the accuracy of the detection result.

[0087] In this example, the signal-to-noise ratio of the signal generated by the magnetic sensor element can be measured in various ways. For example, a scanning procedure can be used in which each individual signal from a separate magnetic sensor element is measured in sequence. For example, the scanning procedure may include measuring the signal generated by each magnetic sensor element in the order of advancing around the axis of the interventional device. Alternatively, the individual signals from the separate magnetic sensor elements can be measured simultaneously. By further determining and outputting the signal of the magnetic sensor element indicating the signal with the highest signal-to-noise ratio, the direction in which the activated nerve is located can be determined. The physician can use this information to determine in which direction to manipulate the interventional device in order to treat the activated nerve.

[0088] Thus, in one example, the sensor elements are distributed around the axis of the interventional device 110 such that the sensor elements generate signals in response to magnetic fields generated at different orientations around the axis; and the controller 140 is further configured to identify the orientation around the axis of the interventional device 110 at which the signal measured has a maximum signal-to-noise ratio.

[0089] In this example, the controller 140 can identify the orientation of the maximum signal-to-noise ratio in various ways. For example, the controller can output a graphical representation of the orientation with the maximum signal-to-noise ratio to a display device. The graphical representation can, for example, include an icon representing the interventional device and the relative orientation at which the measured signal with the maximum signal-to-noise ratio has been measured.

[0090] In this example, the interventional device 110 may also include one or more actuators for adjusting the position and / or orientation of the insertable portion of the interventional device. The one or more actuators may also be used with Figure 7 The one or more actuators are configured to automatically steer the insertable portion to a direction that has a maximum signal-to-noise ratio.

[0091] Thus, this example provides for automatically repositioning an interventional device toward a bundle of nerve fibers generating a magnetic field. The actuator can be provided by an expandable balloon (e.g., an angioplasty balloon), or alternatively by an actuator such as a steerable catheter or guidewire manipulator. In the former case, one or more expandable balloons can be positioned about the axis of the interventional device 110 such that when expanded, the expandable balloons transaxially force the magnetic sensor elements on opposite sides of the axis in a direction having an orientation with a maximum signal-to-noise ratio. Reference Fig.13 To describe this example, Fig.13 is a diagram showing a neural fiber bundle BNF according to some aspects of the present disclosure 1..3 Schematic diagram of an example of a cross section of a covered blood vessel VES and an interventional device ID including an expandable balloon. Fig.13 As shown, the interventional device includes a plurality of magnetic sensors 120 1..4 In this example, the orientation with the maximum signal-to-noise ratio has been identified as the direction of the nerve fiber bundle BNF2. In response to this identification, the expandable balloon BAL has been automatically inflated to turn the insertable portion of the interventional device in the direction along the nerve fiber bundle BNF2. The interventional device ID may also include one or more additional expandable balloons ( Fig.13 In one example, one or more expandable balloons operating in a similar manner to the expandable balloon BAL are positioned in contact with the corresponding magnetic sensor 120. 1..4 The magnetic sensor 120 is connected to the interventional device at a diametrically opposite position. Therefore, when the expandable balloon BAL is expanded, the interventional device moves within the lumen, causing the magnetic sensor 120 to move within the lumen. 1..4 Move closer to the blood vessel wall.

[0092] Through the expandable balloon Fig.13 After the interventional device ID shown in is moved closer to the vessel wall, a magnetic field map around the periphery of the vessel can be generated by rotating the interventional device ID around the longitudinal axis of the interventional device. Similarly, a magnetic field map along the vessel can be generated by translating the interventional device ID along the axis of the vessel. The user can provide rotation and translation in response to instructions provided by the controller 140. Alternatively, the controller can generate control signals for controlling a manipulator or robot to provide the desired rotation / translation. For example, the balloon can be expanded so that the magnetic sensor 120 1..4 By using an expandable balloon, the magnetic sensor 120 is placed in this manner. 1..4 Move closer to the blood vessel wall, reducing the magnetic sensor 120 1..4 The magnetic sensor 120 is spaced from the nerves generating the magnetic field, which results in an increase in the strength of the detected magnetic field.1..4 In contact with the vessel wall, the reliability of the magnetic field map is improved because the magnetic sensor 120 1..4 The spacing from the nerves that generate the magnetic field is controlled.

[0093] An interventional device including a single magnetic sensor 120 and one or more expandable balloons may be used to generate a magnetic field map around or along a blood vessel in a similar manner. Thus, a magnetic field map may be generated by attaching one or more expandable balloons to a blood vessel. Figure 7 and rotating or translating the interventional device as described above to generate similar figures.

[0094] As mentioned above Figure 6 As described, the neural activity sensed by the sensor 120 via the detected magnetic field may be artificially triggered, or may be naturally triggered, i.e., spontaneously triggered. The inventors have determined that for spontaneously activated nerves, the characteristics of the signal generated by the magnetic sensor 120 can be used as a measure of sympathetic overdrive of the renal nerves. As described above, sympathetic overdrive of the renal nerves is an indicator of hypertension (i.e., elevated blood pressure).

[0095] Fig.14 is a graph showing a) characteristics of a pulse train representing a magnetic field detected from a renal nerve of a non-hypertensive subject and b) characteristics of a pulse train representing a magnetic field detected from a renal nerve of a hypertensive subject with increased renal nerve activity according to some aspects of the present disclosure. Fig.14 In the , the standardized magnetic field strength of non-hypertensive subjects and hypertensive subjects is plotted on each vertical axis, and the time in seconds is plotted on each horizontal axis. Significant differences can be observed between the upper figure for non-hypertensive subjects and the lower figure for hypertensive subjects. These differences include: pulse period, duration of pulse train and number of pulses in pulse train. Therefore, these differences can be used to distinguish non-hypertensive subjects from hypertensive subjects.

[0096] In reference Fig.11 In one example of the described system 200, the controller 140 may also be configured to identify features in the received signal; and output a detection result indicative of neural activity in response to the received signal by outputting a measure of sympathetic nerve overdrive of the renal nerves based on the identified features.

[0097] In this example, the characteristics of the received signal may include, for example, one or more of the following: the period of one or more pulses in a pulse train in a signal generated in response to a magnetic field generated by spontaneous neural activity, the duration of a pulse train in a signal generated in response to a magnetic field generated by spontaneous neural activity, and a count of the number of pulses in a pulse train in a signal generated in response to a magnetic field generated by spontaneous neural activity. Moreover, the number of pulses per second measured, for example, over a one-minute period of time differs significantly between the two groups. Fig.15 showed clear distinctions between the subjects in these groups, Fig.15 Shown is a graph of pulse repetition time Rt within a pulse train versus number of pulses nP within a pulse train for a simulated magnetic field in a group of non-hypertensive subjects (circular symbols) and hypertensive subjects (asterisks) according to aspects of the present disclosure.

[0098] The inventors also determined that: Figure 6 and Fig.11 The signals measured by the described magnetic sensor 120 are susceptible to interference from various magnetic field sources that are unrelated to neural activity. In general, magnetic fields are ubiquitous, including from the earth's magnetic field and electronic devices. Magnetic fields may also be generated in the subject by physiological signals having a different source than the nerves of interest. Magnetic fields may also be generated by physiological signals in other subjects located near the subject of interest. The presence of large background magnetic fields poses a challenge to sensitive magnetic field sensors because these magnetic fields may saturate the magnetic sensors. In the examples described below, various embodiments are described that use magnetic field compensation to compensate for such magnetic field interference.

[0099] In one example, active compensation of the global magnetic field is used to reduce the effect of magnetic field interference on the magnetic sensor 120. In this example, the interventional device 110 and the subject in which neural activity is measured are surrounded by multiple Helmholtz coils. For example, three pairs of Helmholtz coils can be used, where each pair is separated along one of the orthogonal axes x, y, and z. Fig.16 An example of such an arrangement is shown, which comprises three pairs of Helmholtz coils HH x,x’ , HH y,y’ and HH z,z’ , where each pair is separated along respective orthogonal axes x, y and z. Active compensation of magnetic field disturbances is achieved by adjusting the current in each coil in real time in response to measurements of magnetic field disturbances. The current in the coil generates a magnetic field within the volume enclosed by the coil, which has the effect of reducing magnetic field disturbances. In this way, Helmholtz coils can be used to compensate for static magnetic field disturbances from, for example, the earth's magnetic field, as well as deterministic magnetic field disturbances caused by, for example, electronic devices.

[0100] In another example, a passive magnetic field shield is used to reduce the effects of magnetic field interference on the magnetic sensor 120. In this example, the interventional device 110 and the subject in which neural activity is measured are surrounded by magnetic shielding material. For example, the interventional device 110 and the subject can be surrounded by a magnetic shielding material in the form of a cylinder. Effective magnetic shielding materials generally have high magnetic permeability values. An example of such a material is MuMetal, which is a nickel-iron alloy. Some nickel-iron MuMetals that provide a high degree of magnetic shielding have more than 40% nickel.

[0101] In another example, active compensation of local magnetic fields is used to reduce the effects of magnetic field interference on magnetic sensor 120. In this example, interventional device 110 and a portion of a subject in which neural activity is measured are surrounded by multiple Helmholtz coils. This example is similar to the above example of active compensation of a global magnetic field as described above, except that only a portion of the subject, rather than the entire subject, is surrounded by multiple Helmholtz coils. This example operates in the same manner as the active compensation of the global magnetic field described above. In this example, the compensated local magnetic field may include a magnetic field generated within the subject, rather than the nerves of interest. For example, this example may be used to reduce the effects of magnetic field interference from the beating heart of the subject.

[0102] All three magnetic shield examples can also be used together to provide improved shielding against magnetic field disturbances. Fig.16 An example of an arrangement in which these three types of magnetic shields are used together is described. Fig.16 An example of a system 200 including a nested magnetic field shielding device according to some aspects of the present disclosure is shown. In this example, the system 200 includes a nested magnetic field shielding device, which includes a first layer (outermost layer) magnetic shield FSL, which includes a plurality of Helmholtz coils, which are configured to provide active compensation for a global magnetic field generated outside a subject; a second layer (innermost layer) magnetic shield SSL, which includes a plurality of Helmholtz coils, which are configured to provide active compensation for a local magnetic field generated inside a subject; and a third layer of magnetic shield CSL, which is sandwiched between the first layer and the second layer, and the third layer of magnetic shield includes a passive magnetic shielding material.

[0103] In this way, the output of the magnetic field sensor 120 can be provided to remain sensitive to weak magnetic fields generated by neural activation, while also avoiding saturation due to magnetic field interference.

[0104] The inventors have also determined that despite the use of the above-described arrangement to compensate for magnetic field interference, some residual magnetic field interference may exist within the volume enclosed by the second (innermost) magnetic shield SSL. The source of this interference may be located outside the second (innermost) magnetic shield SSL, or alternatively the source may be located within the second (innermost) layer. For example, this interference may originate from the earth's magnetic field, or may be generated within the subject by other sources other than the nerves of interest. For example, it may originate from the subject's beating heart. This interference may vary with the position within the volume enclosed by the second (innermost) magnetic shield SSL. For example, this interference may increase as the magnetic sensor 120 moves toward the heart. In order to compensate for this spatial dependence of the interference, in one example, a system is provided in which the interventional device includes a motion sensor 160. Referring to Fig.17 Describe the example. Fig.17 An example of a system 200 according to some aspects of the present disclosure is shown, the system comprising an interventional device 110, a motion sensor 160, and one or more coils 150, SSLs configured to generate a magnetic field to compensate for a background magnetic field detected by a magnetic sensor 120. In this example, the system 200 comprises one or more coils 150, SSLs configured to generate a magnetic field to compensate for a background magnetic field detected by the magnetic sensor 120 (i.e., to reduce the magnitude of the background magnetic field). The interventional device 110 further comprises the motion sensor 160. The motion sensor 160 is mechanically coupled to the interventional device 120 for detecting movement of the magnetic sensor 120. The controller 140 is further configured to:

[0105] - measuring the background magnetic field based on the signal generated by the magnetic sensor 120 in the absence of a magnetic field generated by neural activity;

[0106] - applying a signal to the one or more coils 150, SSL, during measurement of the magnetic field generated by neural activity, in order to compensate for the background magnetic field; and

[0107] - In response to detecting movement of the interventional device 110 by the motion sensor, repeatedly measuring the background magnetic field and applying signals to the one or more coils accordingly.

[0108] In this example, the effect of the operations performed by the controller is to recalibrate the magnetic field compensation provided by the one or more coils in the event that the interventional device moves. In this way, when the interventional device moves within the volume surrounded by the second (innermost) magnetic shield SSL, changes in magnetic field interference caused by, for example, changes in proximity between the magnetic sensor and the beating heart can be compensated. In this example, the one or more coils 150, SSL can be provided, for example, by the second (innermost) magnetic shield SSL, which includes a plurality of Helmholtz coils and as described above with reference to Fig.16 Alternatively, one or more coils 150, SSL may form part of the interventional device. For example, one or more coils 150, SSL may be coupled to a guide catheter, and the interventional device 110 is inserted into the subject through the guide catheter.

[0109] In this example, the motion sensor can be provided by various devices, such as one or more of an accelerometer, a gyroscope, and a fiber-based position tracking system. An example of a fiber-based position tracking system is described in document WO2013 / 136247A1. The system determines the position and shape of an object based on the amount of strain induced in one or more fiber Bragg gratings.

[0110] In a related example, refer to Fig.17 The described system provides compensation for magnetic field disturbances generated by cardiac activity of a subject, wherein an electrocardiogram (ECG) signal is used to measure neural activity. In this example, the signal generated by the magnetic sensor 120 is generated in response to a magnetic field generated by neural activity in the subject, and a background magnetic field is generated at least in part by cardiac activity in the subject. In this example, the controller 140 is also configured to receive an electrocardiogram (ECG) signal of the subject; and the controller 140 is configured to apply a signal to one or more coils to compensate for the background magnetic field during the measurement of the magnetic field generated by the neural activity by applying a time-related signal to one or more coils synchronously with the received ECG signal to compensate for the cardiac activity.

[0111] In this example, an electrocardiogram (ECG) signal of a subject can be generated using various devices, including using ECG electrodes applied to the subject. The heart can be considered to be the strongest common source of magnetic interference near the kidneys. The magnetic field generated by the heart has a peak during ventricular depolarization. This magnetic field may exceed the dynamic range of some magnetic sensors, so there is a risk of saturating the output of these sensors. The implementation described in this example reduces the risk of saturation by reducing the impact of the heart magnetic field on the magnetic sensor. In this example, for example, the compensation magnetic field can be applied synchronously with the position on the received ECG signal (e.g., the R peak of the ECG signal).

[0112] In another related example, refer to Fig.17 The described system provides compensation for magnetic field disturbances using a 3D background magnetic field map. In this example, the controller 140 is also configured to:

[0113] - receiving tracking data representing the position of the magnetic sensor 120 within the sensing area;

[0114] - receiving a 3D background magnetic field map representing the background magnetic field distribution within the sensing area; and

[0115] - estimating the magnitude of the background magnetic field distribution at the location of the magnetic sensor 120 within the sensing area based on the received tracking data and the received 3D background magnetic field map; and

[0116] The controller 140 is configured to apply a signal to the one or more coils to compensate for the background magnetic field during measurement of the magnetic field generated by neural activity based at least in part on the estimated magnitude of the background magnetic field distribution at the location of the magnetic sensor 120 .

[0117] In this example, the tracking data can be provided by various tracking systems, including the aforementioned fiber-based position tracking system described in document WO2013 / 136247A1, or by using an imaging system to track the position of the magnetic sensor 120. The imaging system can be, for example, a projection X-ray imaging system, or a CT imaging system, or an ultrasound imaging system. For example, the shape of the magnetic sensor or the shape of the reference marker identifying its position can be tracked in the image data generated by such an imaging system to determine the position of the magnetic sensor. The magnetic sensor 120 can be used to measure the 3D background magnetic field map by positioning the magnetic sensor at multiple positions within the volume, where the magnetic field will be compensated by one or more coils 150, SSL in the absence of a patient in the volume. After the subject is positioned in the volume, the position of the magnetic sensor 120 determined by the tracking data is used to estimate the value of the background magnetic field at the current position of the magnetic sensor by querying the 3D background magnetic field map. Then, the controller 140 applies a signal to one or more coils to compensate for the background magnetic field by providing a field that compensates for the estimated value of the background magnetic field at the current position of the magnetic sensor, which is determined by querying the 3D background magnetic field map.

[0118] The above operations performed by the controller 140 may be provided in the form of a computer-implemented method for use with the above-mentioned system 200. Therefore, in one example, a computer-implemented method for the system 200 includes the following instructions:

[0119] - receiving a signal generated by the magnetic sensor 120 and outputting a detection result indicative of neural activity in response to the received signal.

[0120] The other operations described above and performed by the controller 140 may similarly be provided as instructions for a computer-implemented method.

[0121] The above operations performed by the controller 140 may be provided in the form of a computer program product for use in the above system 200. Therefore, in one example, a computer program product for the system 200 includes instructions that, when executed by one or more processors, cause the one or more processors to:

[0122] - receiving a signal generated by the magnetic sensor 120 and outputting a detection result indicative of neural activity in response to the received signal.

[0123] The other operations described above and performed by the controller 140 may similarly be provided as instructions of a computer program product.

[0124] The above examples should be understood as illustrative of the present disclosure, rather than limiting. Additional examples are also contemplated. For example, the examples described in relation to the interventional device 110 may also be included in the system 200. In addition, it should be noted that the examples described in relation to the system 200 include operations performed by a controller. These operations may be provided in the form of instructions on a computer program product, and when the computer program is executed by one or more processors, the one or more processors are caused to execute the instructions. Similarly, these operations may be provided in the form of instructions stored on a non-transitory computer-readable storage medium, and when executed by at least one processor, the at least one processor is caused to execute the instructions. It should be understood that the features described in relation to any one example may be used alone or in combination with the features described elsewhere, and may be used in combination with one or more features of another example, or in combination with a combination of other examples. In addition, equivalents and modifications not described above may also be adopted without departing from the scope of the present invention, which is defined by the appended claims. In the claims, the word "comprising" does not exclude other elements or operations, and the indefinite article "one" or "an" does not exclude a plurality. The mere fact that certain features are recited in mutually different dependent claims does not indicate that a combination of these features cannot be used to advantage. Any reference signs in the claims should not be construed as limiting their scope.

Claims

1. An interventional device (110) for detecting neural activity, the interventional device comprising: A magnetic sensor (120); wherein the magnetic sensor (120) is coupled to an insertable portion of the interventional device; and Wherein the magnetic sensor (120) is configured to generate a signal in response to a magnetic field generated by neural activity.

2. The interventional device (110) according to claim 1, wherein: The magnetic sensor (120) comprises an optically pumped magnetometer OPM; wherein the OPM comprises an optical unit (130), wherein the optical unit (130) comprises an alkali metal in a liquid phase and / or a gas phase; and Wherein, the OPM is configured to generate the signal in response to a magnetic field generated by neural activity by measuring a magnetic field-dependent optical property of the alkali metal.

3. The interventional device (110) according to claim 2, wherein: The optical unit (130) further comprises a background gas; and Wherein, the OPM is further configured to generate the signal in response to a magnetic field generated by neural activity by measuring magnetic field-related optical properties of the background gas.

4. The interventional device (110) according to claim 2 or 3, wherein: The OPM also includes a heater; Wherein, the heater is configured to provide heat to the optical unit (130).

5. A system (200) comprising a controller (140) and an interventional device (110) according to any one of the preceding claims; in, The controller is configured to receive the signal generated by the magnetic sensor (120) and output a detection result indicative of neural activity in response to the received signal.

6. The system (200) of claim 5 when dependent on claim 4, wherein: The controller (140) is also configured to selectively operate the OPM in a relatively low sensitivity mode and a relatively high sensitivity mode to generate the signal in response to a magnetic field generated by neural activity, wherein in the relatively low sensitivity mode the heater provides a relatively low power level to the optical unit (130) and in the relatively high sensitivity mode the heater provides a relatively high power level to the optical unit (130).

7. The system (200) of claim 6, wherein: The optical unit (130) comprises an alkali metal and a background gas in a liquid phase and / or a gas phase; and the OPM is configured to generate the signal in response to a magnetic field generated by neural activity by measuring magnetic field-related optical properties of the alkali metal and the background gas, wherein the optical properties of the background gas are sensed in the relatively low sensitivity mode and the optical properties of the alkali metal are sensed in the relatively high sensitivity mode; or The optical unit (130) includes a first alkali metal in a liquid phase and / or a gas phase and a second alkali metal in a liquid phase and / or a gas phase; and the OPM is configured to generate the signal in response to a magnetic field generated by neural activity by measuring magnetic field-related optical properties of the first alkali metal and the second alkali metal, wherein the optical properties of the first alkali metal are sensed in the relatively low sensitivity mode, and the optical properties of the second alkali metal are sensed in the relatively high sensitivity mode.

8. The system (200) of claim 5 when dependent on claim 4, wherein: The interventional device also includes a temperature sensor; wherein the temperature sensor is in thermal contact with i) an outer surface of the interventional device or ii) the optical unit (130); and Wherein the controller (140) is configured to operate the heater in response to the temperature measured by the temperature sensor.

9. The system (200) of claim 5 when dependent on claim 2, wherein: The OPM includes a light source configured to provide an optical pump beam, and the OPM is configured to measure the magnetic field-related optical property of the alkali metal in response to the excitation of the alkali metal within the optical unit (130) by the optical pump beam; wherein the controller (140) is configured to modulate the intensity of the optical pump beam between a relatively low intensity and a relatively high intensity; and The OPM is configured to measure the magnetic field-related optical property of the alkali metal by determining the transmission of the optical pump beam through the optical unit (130) when the optical pump beam excites the alkali metal at a relatively high intensity.

10. The system (200) of claim 5, wherein: The magnetic sensor (120) includes a plurality of magnetic sensor elements; and wherein each magnetic sensor element is configured to detect a different volume of magnetic field intercepting the interventional device (110); and Wherein, the controller (140) is further configured to: measuring a signal-to-noise ratio of the signal generated by the magnetic sensor element; and The detection result is generated using the signal or signals from the magnetic sensor elements having the highest signal-to-noise ratio.

11. The system (200) of claim 10, wherein: The sensor elements are distributed around an axis of the interventional device (110) such that the sensor elements generate signals in response to magnetic fields generated at different orientations around the axis; as well as The controller (140) is further configured to identify a position around the axis of the interventional device (110), wherein the signal measured at the position has a maximum signal-to-noise ratio.

12. The system (200) of claim 5, wherein: The controller (140) is further configured to identify a feature in the received signal; as well as The detection result indicative of neural activity is output in response to the received signal by outputting a measure of renal nerve sympathetic nerve overdrive based on the identified feature.

13. The system (200) of claim 5, wherein: The system (200) further comprises one or more coils (150, SSL) configured to generate a magnetic field for compensating for a background magnetic field detected by the magnetic sensor (120); as well as Wherein, the intervention device (110) further comprises a motion sensor (160); wherein the motion sensor (160) is mechanically coupled to the interventional device (120) so as to detect the motion of the magnetic sensor (120); and Wherein, the controller (140) is further configured to: measuring the background magnetic field based on a signal generated by the magnetic sensor (120) in the absence of a magnetic field generated by neural activity; During measurement of a magnetic field generated by neural activity, applying a signal to the one or more coils (150, SSL) to compensate for the background magnetic field; and In response to detecting movement of the interventional device (110) by the motion sensor, the background magnetic field is repeatedly measured and signals are correspondingly applied to the one or more coils.

14. The system (200) of claim 13, wherein: The signal is generated in response to a magnetic field produced by neural activity in the subject, and the background magnetic field is generated at least in part by cardiac activity in the subject; as well as Wherein, the controller (140) is further configured to receive an electrocardiogram (ECG) signal of the subject; and The controller (140) is configured to apply a signal to the one or more coils to compensate for the background magnetic field by applying a time-related signal to the one or more coils synchronously with the received ECG signal to compensate for the cardiac activity during the measurement of the magnetic field generated by the neural activity.

15. The system (200) according to claim 13 or 14, wherein: The controller (140) is also configured to: receiving tracking data representing a position of the magnetic sensor (120) within a sensing area; receiving a 3D background magnetic field map representing background magnetic field distribution within the sensing area; and estimating a magnitude of the background magnetic field distribution of the magnetic sensor (120) at the location within the sensing area based on the received tracking data and the received 3D background magnetic field map; as well as Wherein the controller (140) is configured to apply a signal to the one or more coils based at least in part on the estimated magnitude of the background magnetic field distribution at the location of the magnetic sensor (120) so as to compensate for the background magnetic field during measurement of the magnetic field generated by neural activity.

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