Patent Grant
11637527
This application is a U.S. National Stage Application filed under 35 U.S.C. § 371 of International Application No. PCT/EP2019/065410, filed Jun. 12, 2019. This application is hereby incorporated by reference in its entirety.
The invention relates to a system for imaging, in particular brain imaging, and a wireless detection unit for use in a magnetic-resonance (MR) measurement.
Modern medicine and research apply a variety of imaging techniques for the animal or human body. The group of electrobiological measurements comprises magnetic resonance imaging (MRI), functional MRI (fMRI), computer tomography (CT), and electroencephalography (EEG). In particular for neurological studies of animals as well as humans, magnetic resonance imaging (MRI), functional MRI (fMRI) and electroencephalography (EEG) are well-established imaging techniques.
Magnetic resonance imaging (MRI), or Nuclear magnetic resonance imaging (NMRI), is an imaging technique to visualize the structure and function of tissue. This imaging technique provides detailed images of the tissue in any plane and a greater contrast between the different soft tissues compared to computer tomography (CT). Thus, it is especially favorable in neurological (brain), musculoskeletal, cardiovascular and oncological (cancer) imaging. MRI utilizes a powerful magnetic field B0 to align the nuclear magnetic moments or spins, in particular of hydrogen atoms in the tissue. Wherein the nuclear spins process with the so-called Larmour frequency about the magnetic field direction like gyroscopes. By applying a radio frequency (RF)-pulse, perpendicular to said magnetic field B0, the magnetic moments are tilted away from the alignment direction. After the removal of the RF-pulse, the nuclear spins relax to their equilibrium direction. Due to the relaxation, the nuclei need to lose energy in the form of emit-ting an RF-signal. This signal is detected by a receiving coil and used for the imaging. In order to encode the axial direction, a further gradient magnetic field is applied, which causes the Larmour frequency to change linearly in the axial direction.
Standard MRI imaging is often limited by its detection sensitivity which determines the achievable spatial resolution. A better local sensitivity may be achieved by placing the detection coil in close proximity to the object of interest. Such a detection coil typically sends the received signals to an evaluation device by way of an attached coaxial cable. The presence of such cables can lead to an unwanted heating of the detection coils, due to a coupling of the RF filed from the MRI system to the cable. In order to avoid the cables, there have been attempts to wirelessly transmit MRI signals received from the detection coils. In the document WO 2009/043034 A1, such a wireless device is disclosed. The disadvantage of such a device is that it requires extra components to provide DC power source for proper operation.
Electroencephalography (EEG) is a brain activity recording technique that reads scalp electrical activity generated by brain structures. The electroencephalogram (EEG) is defined as electrical activity of an alternating type, recorded from the scalp surface after being picked up by electrodes and conductive media. When brain cells (neurons) are activated, local current flows are produced. Such currents, that flow during synaptic excitations of the dendrites of many pyramidal neurons in the cerebral cortex, may be detected by an EEG measurement. The electrical current consists mostly of Na+, K+, Ca++, and Cl-ions that are pumped through channels in neuron membranes in the direction governed by membrane potential. The measured differences of electrical potentials are caused by summed postsynaptic graded potentials from pyramidal cells that create electrical dipoles between the body of the neuron and the neural branches. In most of the cases, due to the electromagnetic (EM) interference, the EEG signal detection picks up the gradient and RF pulse signals during MRI imaging. Thus an off-line post-processing method is necessary to remove the EM interference.
The object of the invention is to provide a system for imaging, in particular brain imaging, which may facilitate different imaging techniques, and which overcomes the above-mentioned disadvantages.
The problem is addressed by a system for imaging, in particular for brain imaging, comprising a pump signal generator which emits at least one pump signal in the radio frequency (RF)-range with a first power P1 and a second power P2, a wireless detection unit, which comprises at least one parametric resonator circuit with multiple resonance modes, wherein the at least one parametric resonator circuit comprises at least two varactors, at least one capacitor and at least one inductance, wherein, in a first detection mode, the pump signal, having a first power P1, induces a first pump current in the at least one parametric resonator circuit, wherein the at least one parametric resonator circuit is operated below its oscillation threshold and generates a first output signal by amplifying a first input signal, which is provided due to a magnetic resonance (MR) measurement, wherein an external receiving device receives the first output signal, wherein, in a second detection mode, the pump signal, having a second power P2, induces a second pump current in the at least one parametric resonator circuit, wherein the at least one parametric resonator circuit is operated above its oscillation threshold and generates a second output signal, wherein the second output signal is modulated with a second input signal, wherein the second input signal is provided by at least one neuronal probe device, connected to the at least one parametric resonator circuit, wherein the external receiving device receives the second output signal.
According to the invention, the first and the second output signals are transmitted wirelessly by an emission of the first and second output signals. The first and the second output signals are preferably signals in the radio frequency (RF)-range. The necessary power supply for operation of the wireless detection unit is provided by the pump signal, which is also a signal in the radio frequency (RF)-range. Thus, there is no need to provide the wireless detection unit with a cable. The unwanted heating of the detection unit, due to the use of such coaxial cables, may be avoided. Further, the wireless detection unit does not need to be equipped with a power source in the form of a battery, which allows a simpler and cost-effective design of the wireless detection unit.
Further, the detection mode of the wireless detector may be switched, simply by varying the pump power of the pump signal. When operated at pump levels below oscillation, the parametric resonator can amplify the MRI signal. Parametric oscillation occurs when the parametric amplification compensates the loss of a resonator at one of the resonance frequencies. The parametric resonator then becomes a parametric oscillator.
In the first detection mode, the power of the pump signal has a value P1, such that the at least one parametric resonator circuit is operated below its oscillation threshold. Thus, the at least one parametric resonator circuit is operated as a parametric amplifier circuit. In this detection mode, the first input signal in the form of an NMR-signal is amplified. The first input signal/NMR-signal is preferably an RF-signal and stems from coherent precession of the nuclear magnetic moments in its mixed states.
By applying a pump signal with a value P2, the one parametric resonator circuit may be operated above its oscillation threshold. Thus, it may also be called a parametric oscillator circuit. Parametric oscillation occurs when the parametric amplification compensates the loss of a resonator at the resonance frequency. Advantageously, it is driven by varying the varactors' capacitance by varying the bias voltage. Due to the oscillation, a second output signal is generated. Preferably, the oscillation frequency is half of the frequency of the externally provided pump signal. This second output signal is preferably an RF-signal and modulated by a second input signal, wherein the second input signal is provided by a neuronal probe device, connected to the at least one parametric resonator circuit. The neuronal probe device may preferably comprise at least one EEG-probe, which detects the differences of electrical potentials due to brain activity.
Preferably, such a modulation is a modulation of the amplitude of the second output signal and/or the frequency of the second output signal. Advantageously, the second input signal is encoded as sidebands of the oscillation peak of the second output signal.
Thus, the detection mode of the wireless detection unit may easily be switched and it is possible to detect and transmit an NMR signal as well as an EEG-signal with the same device.
Advantageously, the receiving device is connected with an evaluation device which evaluates the first and the second output signal and calculates the corresponding imaging data.
The term radio frequency (RF) is understood as the oscillation rate of a magnetic, electric or electromagnetic field in the frequency range from around twenty thousand times per second (20 kHz) to around three hundred billion times per second (300 GHz).
The present invention provides a broadband wireless system for multi-modal imaging, which advantageously contributes to a new application for brain imaging in a multi-modality neuroimaging environment. In particular, it may be used in the invasive brain surgical environment when the craniotomy is required for optical fiber or electrode insertion for brain functional studies. In many cases of animal brain studies, the skull will be exposed for electrode recording or two-photon imaging for craniotomy preparation. In this case, the present invention may serve as a multi-modality signal transmission platform, including MRI and electrophysiological signals concurrently based on one electronic device, implanted on or in the skull.
This has the advantage that the distance of the RF coil detector and the tissue (brain) may be reduced, which can significantly increase the SNR for a detector with a preferably small diameter (i.e. penetrating depth). Preferably, the detector can be directly used for multisite EEG signaling detection based on the wireless resonators at different frequency bandwidth, producing a highly compatible signal transmission scheme. Advantageously, such a device can be switched to either the first (NMR) or the second (EEG) detection mode, just by alternating the pump power of the pump signal.
According to a preferred embodiment, the first input signal has a first frequency ω1, wherein the parametric resonator circuit resonates at the first frequency ω1 and generates a first input current. Advantageously, the pump signal has a third frequency ω3, wherein the parametric resonator circuit resonates at the third frequency ω3 and generates the first pump current or the second pump current, depending on the first power P1 and a second power P2. Thus, when the parametric resonator circuit is operated below the oscillation threshold, the pump signal, which serves as power source, has a power P1 and preferably a third frequency ω3.
Preferably, a varactor generates a resulting current based on the first input current and the first pump current. Preferably, the resulting current is generated by mixing the first input current and the first pump current. It is further preferable that the parametric resonator circuit resonates at a second frequency ω2, in response to the resulting current to generate the first output signal. The first output signal, also called “idler signal”, preferably has the frequency ω2=ω3−ω1 or ω2=ω3+ω1. It is preferred that the first output signal mixes again with the pump signal at ω3 to create a secondary first output signal with a frequency ω4, which is essentially equal to the first frequency ω1: ω4=|ω3−ω2|=|ω3−(ω3±ω1)|=|ω1|. Thus, an amplified signal with the frequency ω1 may be generated and emitted by the parametric resonator circuit.
According to a preferred embodiment, the second frequency ω2 is nearly equal to the first frequency ω1, wherein the second frequency ω2 differs from the first frequency ω1 by a difference frequency ωd, which is in the range between 5 kHz to 100 kHz, preferably between 20 kHz to 80 kHz, more preferably between 40 kHz to 80 kHz. Preferably, the difference frequency ωd is larger than the receiver bandwidth of the MRI-system. The MRI-signal is typically frequency-encoded by a spatially varying gradient field. This gradient slightly alters the precession frequencies of the nuclear spins. The bandwidth of the gradient field is typically in the range between 5 kHz to 100 kHz, preferably 50 kHz. Advantageously, the difference frequency ωd is about 5 kHz to 20 kHz larger than the bandwidth of the gradient field. Preferably, the difference frequency ωd is about 10 kHz larger than the bandwidth of the gradient field. Thus, given a typical bandwidth of 50 kHz, the difference frequency ωd would preferably be 60 kHz. The advantage of such a design is that the frequencies ω1 and ω2 may conveniently be differentiated.
Advantageously, the third frequency ω3 is essentially twice the first frequency ω1. By making the idler frequency ω2 close enough to the Larmour frequency ω1, and making ω3 approximately twice ω1, it is possible for ω1 and ω2 to share a single circuit mode. Preferably, the parametric resonator circuit is then a double frequency resonator.
According to a further preferred embodiment, the system comprises a device for image processing. Preferably, the external receiving device transmits the first and/or the second output signal to the device for image processing. The first and the second output signal are received by an external receiving device. Advantageously, the external receiving device is a receiving coil. Thus, it is preferred that the transmission of the first and second output signal relies on inductive coupling between the parametric resonator circuit and the receiving coil.
According to a further preferred embodiment, the at least one parametric resonator is a parallel circuit comprising two varactors and one capacitor in the center leg of the parallel circuit. Preferably, the cathode of the first varactor is connected with the first terminal of the capacitor and the cathode of the second varactor by a first connection. It is further preferred that the anode of the first varactor is connected with the second terminal of the capacitor and the anode of the second varactor by a second connection. Advantageously, the first and the second connection form a first and a second inductance. Preferably, the at least one parametric resonator circuit is a wire loop by which the two varactors are connected, and with a center leg in which the capacitor is arranged. Preferably, said wire loop is circular.
It would be conceivable that said capacitor in the center leg has an adjustable capacitance. It is conceivable that the varactors are MOS or CMOS devices and the capacitor is a chip capacitor.
According to a further preferred embodiment, the at least one neuronal probe device is connected to the first terminal of the capacitor in the center leg of the parallel circuit. Preferably, the second terminal of the capacitor in the center leg of the parallel circuit is connected to a ground electrode, wherein the neuronal probe device may preferably comprise at least one EEG-probe, which detects the differences of electrical potentials due to brain activity.
According to a further preferred embodiment, the at least one parametric resonator circuit is embedded in a planar thin film element. Preferably, the thin film element consists of a polyimide, more preferably of a copper-clad polyimide. Advantageously, the at least one parametric resonator circuit in the form of a wire loop, by which the two varactors are connected, and with a center leg in which the capacitor is arranged, is laminated by the polyimide or another suitable material. Advantageously, such a thin film element has a diameter in the range between 2 to 20 mm, preferably between 5 to 15 mm, more preferably between 8 to 12 mm. Advantageously, such a thin film element has a thickness in the range between 1 to 6 mm, preferably between 2 to 4 mm.
According to a preferred embodiment, the system comprises an MRI scanner device that enables the visualization of organs, organ function, and/or other tissue within a body, in particular a brain of a subject. The subject may be an animal, such as a rat, a monkey or a human. The MRI scanner device preferably comprises a primary magnet that generates a uniform magnetic field that is applied across the body of the subject under observation. It is preferred that the MRI scanner device further comprises at least one smaller gradient magnet that allows the magnetic field to be altered very precisely. The at least one gradient magnet allows image “slices” of the body to be created. By altering the at least one gradient magnet, the magnetic field can be specifically encoded on a selected part of the body. Advantageously, the MRI scanner device comprises an RF-signal generator which applies a radio frequency (RF)-pulse, preferably perpendicular to the magnetic field B0 of the primary magnet. This RF-pulse causes the nuclear spins to tilt away from the alignment direction.
According to a further preferred embodiment, the wireless detection unit comprises at least two parametric resonator circuits. Preferably, the at least two parametric resonator circuits overlap spatially. Advantageously, no electrical connection exists between the two parametric resonator circuits. It is further preferred that each parametric resonator circuit is tuned to resonate at a different third frequency ω3a, ω3b, such that, by applying a pump signal with the third frequency ω3a, ω3b, one parametric resonator circuit can be activated. By such an arrangement, the field of view of the wireless detection unit may be enlarged beyond an individual detector without sacrificing detection sensitivity. The mentioned overlap of the at least two parametric resonator circuits small and has the purpose of minimizing signal voids. Preferably, only one of the at least two parametric resonators is connected with at least one neuronal probe device. It is also conceivable that more of the at least two parametric resonator circuits are connected with the neuronal probe device. Finally, it is also conceivable that all of the at least two parametric resonator circuits are connected with the neuronal probe device.
According to a further preferred embodiment, the wireless detection unit comprises four parametric resonator circuits. Preferably, said wireless detection unit is arranged in a quadrilateral. Advantageously, each resonator circuit overlaps spatially with at least one adjacent resonator circuit. It is further preferred that each parametric resonator circuit is tuned to resonate at a different third frequency ω3a, ω3b, ω3c, ω3d, such that, by applying a pump signal with a third frequency ω3a, ω3b, ω3c, ω3d, one parametric resonator circuit can be activated. By such an arrangement, the field of view of the wireless detection unit may be enlarged beyond an individual detector without sacrificing detection sensitivity. The mentioned overlap of the at least two parametric resonator circuits small and has the purpose of minimizing signal voids.
According to a further preferred embodiment, the parametric resonator circuit is sequentially or simultaneously activatable Preferably, for a simultaneous activation of at least two parametric resonator circuits, at least two different pump signals with a third frequency ω3a, ω3b, ω3c, ω3d, are used at the same time.
According to a preferred embodiment, the wireless detection unit with at least two or four parametric resonator circuits is used for focal or collateral MRI measurements of the brain. For focal measurement, the excitation slice is adjusted to excite nuclei spins, only from one side of the brain. For contralateral measurement, the excitation slice is adjusted to excite nuclei spins from both sides of the brain. Preferably, said excitation slice may be adjusted by the gradient magnetic field of the MRI system. It will highlight the specific region of interest by acquiring signals from one side, however, it is faster to acquire signals from both sides at the same time.
Preferably, in a sequential acquisition mode, only a single parametric resonator circuit is responding to the pumping frequency at ω3a, so that only signals detectable by this resonator are amplified. In order to observe contralateral sides of the brain without increasing total acquisition time, the imaging slices, perpendicular to the individual parametric resonator circuits, are sequentially activated. At the same time, the corresponding individual parametric resonator circuits, which are in direct contact with the image slice, are selectively activated.
Advantageously, for simultaneous acquisition mode, a slice perpendicular to two parametric resonator circuits on the contralateral sides of the brain are excited. At the same time, the two parametric resonator circuits are simultaneously activated by two pump signals at ω3a and ω3b. The output signal at the idler frequency ω3-ω1 of each parametric resonator circuit is individually encoded, such that it is unique to each parametric resonator circuit. By mathematically separating their signal contributions at their respective frequency bands, the single-channel receiver is multiplexed into multiple channels, but without the need for the expensive console upgrade.
Preferably, the sequential acquisition mode and the simultaneous acquisition mode may be combined by sequentially exciting image slices perpendicular to a pair of two parametric resonator circuits at the top and bottom of the quadrilateral. For each selected slice, the input signals from the left and right sides of the quadrilateral can be simultaneously amplified. These acquisition paradigms allow to run specific imaging sequences based on the acquisition modes.
The object is also addressed by a wireless detection unit for use in a magnetic-resonance (MR) measurement, comprising at least one parametric resonator circuit with multiple resonance modes, wherein the at least one parametric resonator circuit comprises at least two varactors and at least one inductance, wherein, in a first detection mode, a pump signal, having a first power P1, induces a first pump current in the at least one parametric resonator circuit, wherein the at least one parametric resonator circuit is operated below its oscillation threshold and generates a first output signal by amplifying a first input signal, which is provided due to a magnetic-resonance (MR) measurement, wherein, in a second detection mode, the pump signal, having a second power P2, induces a second pump current in the at least one parametric resonator circuit, wherein the at least one parametric resonator circuit is operated above its oscillation threshold and generates a second output signal, wherein the second output signal is modulated with a second input signal, wherein the second input signal is provided by a neuronal probe device, connected to the at least one parametric resonator circuit.
The wireless detection unit may comprise the single features or combinations of the features described above for the system for imaging. Furthermore, the system for imaging may comprise the single features or combinations of the features described for the wireless detection unit. Further, the same advantages may apply for the wireless detection unit, as described above for the system for imaging.
According to a preferred embodiment, the first input signal has a first frequency ω1, wherein the parametric resonator circuit resonates at the first frequency ω1 and generates a first input current. Advantageously, the pump signal has a third frequency ω3, wherein the parametric resonator circuit resonates at the third frequency ω3 and generates the first pump current or the second pump current, depending on the first power P1 and a second power P2. Thus, when the parametric resonator circuit is operated below the oscillation threshold, the pump signal, which serves as power source, has a power P1 and a preferably the third frequency ω3.
Advantageously, the third frequency ω3 is essentially twice the first frequency ω1. By making the idler frequency ω2 close enough to the Larmour frequency ω1, and making ω3 approximately twice ω1, it is possible for ω1 and ω2 to share a single circuit mode. Preferably, the parametric resonator circuit is then a double frequency resonator.
According to a further preferred embodiment, the at least one parametric resonator circuit is a parallel circuit comprising two varactors and a capacitor in the center leg of the parallel circuit. Preferably, the cathode of the first varactor is connected with the first terminal of the capacitor and the cathode of the second varactor by a first connection. It is further preferred that the anode of the first varactor is connected with the second terminal of the capacitor and the anode of the second varactor by a second connection. Advantageously, the first and the second connection form a first and a second inductance. Preferably, the at least one parametric resonator circuit is a wire loop by which the two varactors are connected, and with a center leg in which the capacitor is arranged. Preferably, said wire loop is circular.
It would be conceivable that said capacitor in the center leg has an adjustable capacitance. It is conceivable that the varactors are MOS or CMOS devices and the capacitor is a chip capacitor.
According to a further preferred embodiment, the at least one neuronal probe device is connected to the first terminal of the capacitor in the center leg of the parallel circuit. Preferably, the second terminal of the capacitor in the center leg of the parallel circuit is connected to a ground electrode, wherein the neuronal probe device may preferably comprise at least one EEG-probe, which detects the differences of electrical potentials due to brain activity.
According to a further preferred embodiment, the at least one parametric resonator is embedded in a planar thin film element. Preferably, the thin film element consists of a polyimide, more preferably of a copper-clad polyimide. Advantageously, the at least one parametric resonator circuit in the form of a wire loop, by which the two varactors are connected and with a center leg in which the capacitor is arranged, is laminated by the polyimide or another suitable material. Advantageously, such a thin film element has a diameter in the range between 2 to 20 mm, preferably between 5 to 15 mm, more preferably between 8 to 12 mm. Advantageously, such a thin film element has a thickness in the range between 1 to 6 mm, preferably between 2 to 4 mm.
According to a further preferred embodiment, the wireless detection unit comprises at least two parametric resonator circuits. Preferably, the at least two parametric resonator circuits overlap spatially. Advantageously, no electrical connection exists between the two parametric resonator circuits. It is further preferred that each parametric resonator circuit is tuned to resonate at a different third frequency ω3a, ω3b, such that, by applying a pump signal with the third frequency ω3a, ω3b, one parametric resonator circuit can be activated. By such an arrangement, the field of view of the wireless detection unit may be enlarged beyond an individual detector without sacrificing detection sensitivity. The mentioned overlap of the at least two parametric resonator circuits small and has the purpose of minimizing signal voids.
According to a further preferred embodiment, the wireless detection unit comprises four parametric resonator circuits. Preferably, said four parametric resonator circuits are arranged in a quadrilateral. Advantageously, each resonator circuit overlaps spatially with at least one adjacent resonator circuit. It is further preferred that each parametric resonator circuit is tuned to resonate at a different third frequency ω3a, ω3b, ω3c, ω3d, such that, by applying a pump signal with the third frequency ω3a, ω3b, ω3c, ω3d, one parametric resonator circuit can be activated. By such an arrangement, the field of view of the wireless detection unit may be enlarged beyond an individual detector without sacrificing detection sensitivity. The mentioned overlap of the at least two parametric resonator circuits small and has the purpose of minimizing signal voids.
According to a further preferred embodiment, the parametric resonator circuits are sequentially or simultaneously activatable. Preferably, for a simultaneous activation of at least two parametric resonator circuits, at least two different pump signals with a third frequency ω3a, ω3b, ω3c, ω3d, are used at the same time.
Further advantages, aims and properties of the present invention will be described by way of the appended drawings and the following description.
In the drawings:
a, b, c show a wireless detection unit according to one embodiment.
The system comprises an MRI scanner device 23 that enables the visualization of organs, organ function, and/or other tissue within a body, in particular a brain of a subject 24. The subject may be an animal, such as a rat, a monkey or a human. The MRI scanner device 23 comprises a primary magnet 25 that generates a uniform magnetic field B0 that is applied across the body of the subject 24 under observation. The magnetic field B0 is preferably in the range of between approx. 3 T to approx. 21 T, more preferably in the range of between approx. 7 T to approx. 14 T. The subject is arranged in a bore. In case of animal studies, the bore has a bore diameter of preferably in the range of between 50 cm to 6 cm, more preferably 12 cm.
The MRI scanner device 23 further comprises at least one smaller gradient magnet 26 which generates a gradient magnetic field BG. The magnetic field B0 aligns the nuclear spins, in particular of the hydrogen atoms, in the tissue. The nuclear magnetic spins precess with the so-called Larmour frequency about the magnetic field direction like gyroscopes. Due to the additional gradient magnetic field BG, the Larmour frequency is altered along the gradient magnetic field BG. Thus, the gradient magnet allows image “slices” of the body to be created.
The MRI scanner device 23 further comprises an RF-signal generator 27, which applies a radio frequency (RF)-pulse BRF, perpendicular to said magnetic field B0 of the primary magnet. This RF-pulse causes the nuclear spins to tilt away from the alignment direction. In the absence of the RF-pulse BRF, the nuclear spins relax to the lower energy state and align with the magnetic field B0. The surplus energy gained by the RF-pulse is emitted by a RF-signal. This signal is the first input signal of the wireless detection unit 4.
The system 1 comprises a device for image processing 20. The external receiving device 17 transmits the first 11 and the second output signal 14 to the device for image processing 20. The external receiving device 17 comprises a receiving coil, which detects the first 11 and the second output signal 14 inductively. The system 1 may further comprise a user interface 28 which comprises an input device, such as a keyboard, and/or an output device, such as a display.
The pump signal generator (2) may also be able to emit more than one pump signals (3, 3a, 3b) with a first power P1 and a second power P2 simultaneously.
Embodiments of the wireless detection unit 4 are shown in the
The at least one parametric resonator circuit 5 is a parallel circuit comprising two varactors 6, 7 and one capacitor 8 in the center leg 21 of the parallel circuit. The cathode of the first varactor 6 is connected with the first terminal of the capacitor 8 and the cathode of the second varactor 7 by a first connection. The anode of the first varactor 6 is connected with the second terminal of the capacitor 8 and the anode of the second varactor 7 by a second connection. The first and the second connection form a first 9a and a second inductance 9b. Thus, the parametric resonator circuit 5 is a LC-circuit with multiple resonance modes. The at least one parametric resonator circuit is a wire loop by which the two varactors 6, 7 are connected, and with a center leg 21 in which the capacitor 8 is arranged. The wire loop has a diameter in the range of between 5 mm to 15 mm, preferably 9 mm. For a 9 mm loop, a capacitor 8 with a capacity of 7.5 pF may be chosen. The capacitor 8 may be in the form of a chip capacitor.
The wireless detector 4 in
The device shown in
The at least one neuronal probe device 16 is connected to the first terminal of the capacitor 8 in the center leg 21 of the parallel circuit, wherein the second terminal of the capacitor 8 in the center leg of the parallel circuit is connected to a ground electrode 22. Alternatively, the neuronal probe device 16 could be connected to the first and the second terminal of the capacitor 8.
The neuronal probe device may preferably comprise at least one EEG-probe, which detects the differences of electrical potentials due to brain activity.
In the first detection mode, the power P1 of the first pump signal 3, 3a does not provide enough gain to compensate for the resonator loss. Thus, the parametric resonator circuit is operated in the amplifier mode. Parametric oscillation occurs when the parametric amplification compensates the loss of a resonator at the resonance frequency. Thus, the parametric resonator circuit is operated in the oscillator mode. This is the case in the second detection mode, when the power P2 of the second pump signal 3, 3b does provide enough gain to compensate for the resonator loss.
The first 3, 3a and the second pump signal 3, 3b have a third frequency ω3, wherein the parametric resonator circuit 5 resonates at the third frequency ω3 and generates the first pump current 10 or the second pump current 12, depending on the first power P1 and a second power P2. In the first resonance mode, the parametric resonator circuit 5 is tuned to match the pump signal. Thus, when the parametric resonator circuit 5 is operated below the oscillation threshold, the pump signal 3a, which serves as power source, has a power P1 and the third frequency ω3.
The first input signal 11 has a first frequency ω1, wherein the parametric resonator circuit 5 resonates at the first frequency ω1 and generates a first input current 18. Thus, in the second resonance mode, the parametric resonator circuit 5 is tuned to match a first input signal, which is provided due to a magnetic-resonance (MR) measurement. The varactor 6, 7 generates a resulting current 19, based on the first input current 18 and the first pump current 10. The varactor 6,7 has a high Q zero biased condition and performs frequency mixing. Thus, the resulting current 19 is generated by mixing the first input current 18 and the first pump current 10. The parametric resonator circuit 5 resonates at a second frequency ω2, in response to the resulting current 19, to generate the first output signal 11. The first output signal, also called “idler signal”, preferably has the frequency ω2=ω3−ω1 or ω2=ω3+ω1. It is preferred that the first output signal/the corresponding resulting current 19 mixes again with the pump signal at ω3/the corresponding pump current 10. In doing so, a secondary resulting current 19a and a corresponding secondary first output signal 11a with a frequency ω4 are generated. The frequency ω4 is essentially equal to the first frequency ω1: ω4=|ω3−ω2|=|ω3−(ω3±ω1)|=|ω1|. Thus, an amplified signal 11a with the frequency ω1 may be generated and emitted by the parametric resonator circuit 5.
Preferably, the second frequency ω2 is nearly equal to the first frequency ω1, wherein the second frequency ω2 differs from the first frequency ω1 by a difference frequency ωd, which is in the range between 5 kHz to 100 kHz, preferably between 20 kHz to 80 kHz, more preferably between 40 kHz to 80 kHz. Preferably, the difference frequency ωd is larger than the receiver bandwidth of the MRI-system. The MRI-signal is typically frequency-encoded by a spatially varying gradient field. This gradient slightly alters the precession frequencies of the nuclear spins. The bandwidth of the gradient field is typically in the range between 5 kHz to 100 kHz, preferably 50 kHz. Advantageously, the difference frequency ωd is about 5 kHz to 20 kHz larger than the imaging bandwidth. Preferably, the difference frequency ωd is about 10 kHz larger than the imaging bandwidth. Thus, given a typical bandwidth of 50 kHz, the difference frequency ωd would preferably be 60 kHz. The advantage of such a design is that the frequencies ω1 and ω2 may conveniently be differentiated.
Advantageously, the third frequency ω3 is essentially twice the first frequency ω1. By making the idler frequency ω2 close enough to the Larmour frequency ω1, and making ω3 approximately twice ω1, it is possible for ω1 and ω2 to share a single circuit mode. Preferably, the parametric resonator circuit 5 is then a double frequency resonator. The pumping frequency is preferably in the range between 1 GHz to 1.2 GHz. The frequencies ω1, ω2 would therefore be in the range between 500 MHz to 600 MHz.
In another embodiment shown in
In the second detection mode, the parametric resonator (oscillator) circuit 5 oscillates at the frequency ωc, which is half the frequency of the pump signal ω3. For example, ωc is 600 MHz. Naturally, the output signal 14 would then have a carrier frequency ωc of 600 MHz. Due to the second input signal 15 provided by the neuronal probe, the sidebands of the oscillation peak of the second output signal are modulated. The amplitude of sidebands will change linearly with the strength of the neuronal signal.
Preferably, such a modulation is a modulation of the amplitude of the second output signal and/or the frequency of the second output signal. Advantageously, the second input signal is encoded as sidebands of the oscillation peak of the second output signal. The frequency of the signal from the neuronal probe device 16 is within +/−1 kHz from the carrier frequency ωc.
Although, during MRI detection, the MR signal intensity is slightly modulated by EEG signal, this modulation will not affect the results of most MR experiments. Furthermore, this intensity modulation may be removed from the output signal 11 by comparing multi-band signals generated by the parametric resonator circuit. During EEG detection, the contribution of MRI signals on the oscillation signal is negligible.
The at least one parametric resonator may be embedded in a planar thin film element. Preferably, the thin film element consists of a polyimide, more preferably of a copper-clad polyimide. The at least one parametric amplifier circuit in the form of a wire loop, by which the two varactors are connected, and with a center leg in which the capacitor is arranged, is laminated by the polyimide or another suitable material. Advantageously, such a thin film element has a diameter in the range between 2 to 20 mm, preferably between 5 to 15 mm, more preferably between 8 to 12 mm. Advantageously, such a thin film element has a thickness in the range between 1 to 6 mm, preferably between 2 to 4 mm.
The wireless detection unit 4 may comprise at least two parametric resonator circuits 5, 5a, 5b. The at least two parametric resonator circuits 5, 5a, 5b overlap spatially and no electrical connection exists between the at least two parametric resonator circuits 5, 5a, 5b. Hereby, each parametric resonator circuit 5, 5a, 5b is tuned to resonate at a different third frequency ω3a, ω3b, such that, by applying a pump signal 3, 3a, 3b with the third frequency ω3a, ω3b, one parametric resonator circuit 5, 5a, 5b can be activated.
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In
All the features disclosed in the application documents are claimed as being essential to the invention if, individually or in combination, they are novel over the prior art.
This invention was made with government support under EB016753 awarded by the National Institutes of Health. The government has certain rights in the invention.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/EP2019/065410 | 6/12/2019 | WO |
| Publishing Document | Publishing Date | Country | Kind |
|---|---|---|---|
| WO2020/249210 | 12/17/2020 | WO | A |
| Number | Name | Date | Kind |
|---|---|---|---|
| 20140066753 | Qian et al. | Mar 2014 | A1 |
| 20220311383 | Yu | Sep 2022 | A1 |
| Number | Date | Country |
|---|---|---|
| 2005116676 | Dec 2005 | WO |
| 2009043034 | Apr 2009 | WO |
| 2014030084 | Feb 2014 | WO |
| WO-2014030084 | Feb 2014 | WO |
| Entry |
|---|
| PCT/EP2019/065410—International Search Report and Written Opinion—dated Feb. 24, 2020. |
| Syms, et al., “Parametric Amplification of Magnetic Resonance Images,” in IEEE Sensors Journal, vol. 12, No. 6, pp. 1836-1845, Jun. 2012, doi: 10.1109/JSEN.2011.2176928. |
| Mandal, et al., “Adaptive and Wireless Recordings of Electrophysiological Signals During Concurrent Magnetic Resonance Imaging,” in IEEE Transactions on Biomedical Engineering, vol. 66, No. 6, pp. 1649-1657, Jun. 2019, doi 10.1109/TBME.2018.2877640. |
| Number | Date | Country | |
|---|---|---|---|
| 20220311383 A1 | Sep 2022 | US |
