This application claims the benefit of U.S. provisional patent application No. 62/795,607 filed on 23.1.2019, the entire contents of which are incorporated herein by reference.
Detailed Description
The present disclosure relates generally to an aiming energy transmission method. More particularly, but not by way of limitation, the present disclosure relates to a method for focusing ultrasonic energy and communicating with an implantable device using one or more ultrasonic transducers (e.g., a rigid or flexible ultrasonic transducer array). It is an object of the present disclosure to maximize the efficiency of ultrasonic energy transmission by focusing the ultrasonic waves at the implantable device.
In the following embodiments, targeted energy transmission (targeted energy transmission) methods are merely exemplary and are not intended to limit the present disclosure or its applications and/or uses. It will be appreciated that a vast number of variations exist. The detailed description will enable one skilled in the art to practice the exemplary embodiments of the disclosure without undue experimentation, and it should be understood that various changes or modifications can be made in the function and arrangement of the methods described in the exemplary embodiments without departing from the scope of the disclosure as set forth in the appended claims. In view of this disclosure, the different embodiments described herein can be combined to form further embodiments of the invention. The headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.
The benefits, advantages, solutions to problems, and any element(s) that may cause any benefit, advantage, or solution to occur or become more pronounced are not to be construed as a critical, required, or essential feature or element of any or all the claims. The invention is defined solely by the appended claims including any amendments made during the pendency of this application and all equivalents of those claims as issued.
For purposes of simplicity and clarity, relational terms such as "first," "second," "third," and the like, if any, are used solely to distinguish one item, or device from another item, or device without necessarily requiring any actual such relationship or order between such items, or devices.
As used herein, the terms "coupled" or "connected," or any variant thereof, encompass any direct or indirect coupling or connection between two or more elements, unless otherwise indicated or clearly contradicted by context.
The present disclosure generally describes the transmission and communication of ultrasonic energy to and from one or more implantable devices. The term "implantable device" is used to describe a device in a subject for identifying an identity, sensing a physiological condition (e.g., temperature, pressure, pH, pulse rate, oxygen, analyte, strain, glucose, or any combination thereof). The implantable device may include a plurality of channels, sensors, emitters or detectors. Implantable devices can perform other functions, such as releasing drugs or chemicals into the body, stimulating nerves and tissues, or treating cardiac problems. The implantable device is implanted in a living subject, wherein the subject may be a human or an animal. As used herein, the term "ultrasonic energy" generally refers to energy transmitted by sound waves having a frequency between 20kHz and 1 GHz. The term "acoustic wave" refers to a broadband acoustic wave having a frequency between 10kHz and 1 GHz.
In certain embodiments, the implantable device includes one or more sensors for detecting the amount of analyte, strain, or pH.
In some embodiments, the implantable device includes an optical detector for detecting blood pressure, blood oxygenation, melanin level, glucose, pulse rate, any other spectral change signal associated with health, or any light absorption change associated with health.
In some embodiments, the implantable device includes a temperature sensor, such as a thermistor or thermocouple, for detecting temperature.
In certain embodiments, the implantable device includes a pressure sensor, such as a microelectromechanical system (MEMS) sensor, for measuring blood pressure, intracranial pressure, pulse rate, or other pressure in the body.
In certain embodiments, the implantable device includes a potentiometric or amperometric chemical sensor for detecting oxygen levels, pH, or glucose.
In certain embodiments, the implantable device includes a drug-releasing dispenser for releasing a drug or chemical substance into the body.
In certain embodiments, the implantable device includes microstimulators or electrodes for stimulating nerves or tissue or treating cardiac problems.
In certain embodiments, the implantable device may emit electromagnetic or mechanical waves to stimulate a tissue, nerve, or organ.
In certain embodiments, the implantable device may cause a local or large site temperature change.
In some embodiments, the implantable device can introduce pressure changes in the body system using components that require real-time pressure changes, such as actuators or clamps.
In certain embodiments, the implantable device may introduce or detect a magnetic field, such as an inductor or coil.
A. Ultrasonic transducer array
Fig. 1A and 1B show a rigid ultrasonic transducer array 101 and a flexible ultrasonic transducer array 102, respectively, placed on a living body. The ultrasound transducer array includes a plurality of ultrasound transducers 111, which may be piezoelectric elements, Capacitive Micromachined Ultrasound Transducers (CMUTs), optical based transducers, or other materials. In some embodiments, the flexible ultrasound transducer array 102 may include one single ultrasound element, such as a CMUT known as "Sonic Paper". In some other cases, a single ultrasound transducer 111 may be used instead of an array. Each ultrasonic transducer 111 in the array is controlled by a processor, which may configure each ultrasonic transducer to receive or transmit ultrasonic waves. This allows one or more ultrasound transducers 111 to transmit ultrasound waves with different time delays, phase shifts, pulse frequencies, amplitudes, and/or wavelengths. In some embodiments, one or more of the ultrasound transducers 111 in the array may have regular spacing, irregular spacing, or be placed sparsely.
One or more ultrasound transducers 111 are connected to a processor or computing system that is configured to be selectively communicable with each or all of the ultrasound transducers 111 to transmit or receive ultrasound waves. The processor may be formed as one or more Central Processing Units (CPUs), microcontroller units (MCUs), general purpose microprocessors, Application Specific Integrated Circuits (ASICs), field programmable logic arrays (FPGAs), programmable I/O devices, or other equivalent integrated or discrete electronic circuitry. In some embodiments, a processor or computing system may also include other components, such as analog-to-digital converters (ADCs), digital-to-analog converters (DACs), memory, a display panel, power supplies, and I/O ports.
The flexible ultrasound transducer array 102 can be considered to have one or more ultrasound transducers 111 attached to a flexible and stretchable material, a flexible Printed Circuit Board (PCB) or Kapton polyimide film that allows the ultrasound transducers 111 to be relatively moved adjacent to each other in position and orientation. Thus, the flexible ultrasound transducer array 102 may allow for better flexing and fitting to complex geometries of a living body surface than the rigid ultrasound transducer array 101. The exemplary flexible ultrasound transducer array 102 includes an array of 128 ultrasound transducers 111, as shown in fig. 2.
The ultrasound transmitted from the ultrasound transducer 111 interacts with body tissue after entering the living body. This interaction can lead to reflection, scattering and refraction of the ultrasound wave. This occurs at tissue boundaries where the tissue or medium has different acoustic impedance. Absorption may also cause attenuation to occur, which may occur in the same medium. The acoustic impedance deviation determines the amount of reflection, while the acoustic impedance (Z) is determined by the tissue density (ρ) and the acoustic velocity (c), the equation is as follows:
Z=ρc (1)
a more significant change in density between the two tissues will result in a greater change in acoustic impedance. The change in impedance between the two media is called an acoustic impedance mismatch. This difference in acoustic impedance between the two tissues accounts for the amount of reflection that occurs at the tissue boundary.
Since the vertebra 121 has a higher density than adjacent tissues, the vertebra 121 may reflect the incident ultrasonic waves from the ultrasonic transducer 111. The reflected ultrasonic waves may be picked up by the ultrasonic transducers 111 on the array. Since the flexible ultrasound transducer array 102 can provide better angular coverage of the living body, it can collect more acoustic information than the rigid ultrasound transducer array 101. Therefore, in most applications, a flexible ultrasound transducer array 102 is preferred over a linearly arranged rigid ultrasound transducer array 101.
By using an ultrasound transducer array (rigid or flexible), one or more ultrasound transducers 111 may be configured to transmit ultrasound waves each having a different time delay, phase modulation, and waveform modulation. By applying a time delay, the phases of the ultrasound waves may be added at the target ultrasound focal zone so that the ultrasound energy may have a maximum intensity at a defined focal point.
Referring to fig. 3A, the rigid ultrasound transducer array 101 focuses the ultrasound beam onto an implantable device 131 inside the living body by applying a different time delay to each ultrasound transducer 111. Since the rigid ultrasound transducer array 101 does not make good contact with the surface of the living body, there is acoustic coupling between some ultrasound transducers 111 and the living body. Similarly, as shown in fig. 3B, the flexible ultrasound transducer array 102 also focuses the ultrasound beam onto the implantable device 131 inside the living body by applying a different time delay to each ultrasound transducer 111.
In order to aim the ultrasound waves at the implantable device 131, the position of the implantable device 131 needs to be dynamically monitored. Dynamic monitoring means capturing real-time information related to the position of the implantable device 131, which is then used to calculate the targeted ultrasound transfer. Methods of monitoring the position of the implantable device 131 and focusing ultrasound are described in more detail below. The method may also be applied to the case where two or more ultrasonically driven implantable devices 131 are implanted in the body.
One method for focusing the ultrasound energy to the aim position is time reversed focusing (time reversed focusing). The concept of time-reversal focusing is a reciprocity-based approach. To target energy onto the implantable device 131 within the living body, ultrasound waves originating from a sound source are first propagated to the implantable device 131, wherein the implantable device 131 reflects or transmits the ultrasound waves. In the case of reflected waves, time reversal is achieved using passive methods. For the case of a transmitted wave, the active method is used instead.
B. Time-reversal focusing
Referring now to fig. 4A-4C, the concept of time-reversal focusing is illustrated. The array of ultrasound transducers 100 may be arranged linearly or otherwise in other shapes. As exemplarily shown in fig. 4A, one of the ultrasonic transducers 111 generates an ultrasonic wave having at least one frequency and at least one amplitude and transmits the ultrasonic wave into the living body having the implantable device 131 therein. In certain embodiments, ultrasound waves may be transmitted into a living body having a plurality of implantable devices 131 therein, so long as all of the implantable devices 131 are within the field of view. The frequency produced by the ultrasonic transducer 111 refers to frequencies above audible sound. In other alternative embodiments, two or more ultrasound transducers 111 may be used to generate plane waves or random time delayed waves, rather than using a single ultrasound transducer 111. In certain embodiments, the center frequency of the ultrasonic transducer 111 is about 5 MHz. The transmitted ultrasound may be a pulse or tone burst. Between the ultrasound transducer 111 and the implantable device 131, there is a scattering medium 141 of body tissue. Refraction occurs when the ultrasonic wave is deflected from a straight path into the scattering medium 141 to a direction having a deflection angle. Generally, an ultrasonic wave is refracted at media having different acoustic impedances. The ultrasound energy may also be absorbed, reflected or scattered by the tissue. After passing through the scattering medium 141, the ultrasound waves are incident on the implantable device 131. In one embodiment, implantable device 131 is a device with acoustic impedance significantly higher than adjacent tissue because of the significantly higher density. The implantable device 131 may act as a reflector and reflect the ultrasound waves back as echo signals using passive methods. In alternative embodiments, implantable device 131 may receive ultrasonic energy and convert it to electrical energy; such that the ultrasound transducer in the implantable device 131 generates ultrasound waves in the opposite direction. Since the ultrasound waves are generated by the implantable device 131, this method is an active method using more complex electronic components.
As shown in fig. 4B, the echo signals or generated ultrasound waves from the implantable device 131 travel in a scattering path through the scattering medium 141 back to the ultrasound transducer array 100. The scattering medium 141 has the same scattering and transmission characteristics when the ultrasonic waves travel through in a forward or backward manner. Thus, by using a time-reversal method, the focus at the reflection point can be located.
One or more ultrasound transducers 111 acquire echo signals or generated ultrasound waves, each having different amplitude and time delay characteristics. The received signal 151 is coupled to a processor to produce a time-reversed signal 152. As shown in fig. 4C, the time-reversed signal 152 is coupled from the processor to one or more ultrasound transducers 111 to produce a time-reversed wave that is transmitted into the living body and dynamically focused at the implantable device 131. After passing through the scattering medium 141, the time-reversed waves from the one or more ultrasound transducers 111 may undergo constructive interference, where the phase increases at the location from which the reflection originally came; and produces a focal point of ultrasonic energy at the point of reflection. In the case of one single ultrasound transducer 111, the time-reversed wave and any scattered or refracted waves thereof may undergo constructive interference at the location from which the reflection originally came. For example, if the ultrasound transducer 111 in the ultrasound transducer array 100 receives a pressure field of p (x, T), where x is the position of the ultrasound transducer 111 and T is time, the corresponding time-reversed signal will be p' (x, T-T), where T is the total delay constant required by the system. The focused intensity at each location is proportional to the reflected intensity plus the attenuation factor.
For purposes of initial activation, the ultrasound field generated from the ultrasound transducer array 100 may be modulated with different time delays to achieve dynamic focusing onto the implantable device 131. If a flexible ultrasound transducer array 102 is used and the ultrasound transducers 111 are not arranged linearly (e.g. in a concave shape), the modulation of the ultrasound may improve the transmission quality. The concave array of ultrasound transducers 100 naturally has a focal point where the ultrasound intensity is highest compared to other adjacent regions, as shown by the sound intensity distribution in fig. 5A. This is particularly problematic for time-reversal focusing methods because any reflected ultrasound waves from a region with a natural focus have a higher intensity than reflected ultrasound waves from other regions.
To overcome this problem, the present disclosure provides a method of applying time delay focusing to different locations within the field of view by sweeping the ultrasound beam across all locations. However, this method may require a long delay, which takes a lot of time to scan the ultrasonic beam. Furthermore, accurate information of each ultrasound transducer 111 in the ultrasound transducer array 100 is required, which would be difficult or even impossible for the flexible ultrasound transducer array 102.
In one embodiment, as shown in fig. 5B and 5C, the natural focus may be removed by configuring the ultrasound transducer 111 to modulate the ultrasound field and generate a plane wave or random time delay field. A plane wave is a flat wavefront produced by the ultrasound transducer array 100 with parallel and unfocused transmission. A random time delay field is generated by activating each ultrasonic transducer 111 with a random delay. In another embodiment, as shown in fig. 5D, the natural focus may also be removed by configuring only one single ultrasonic transducer 111 to transmit a single ultrasonic wave. This method has a weak or no focusing effect.
In addition to the reflection of ultrasound waves by the implantable device 131, undesirable reflections may also occur when ultrasound waves interact with body tissue inside the living body that has an acoustic impedance mismatch. In particular, body structures, such as bone and muscle tissue, may reflect ultrasound. Such reflections are unavoidable. Therefore, it is important to ensure that implantable device 131 can reflect more ultrasound than other structures in the body. A simple way is by choosing a material with a higher impedance mismatch than the surrounding medium.
Since the reflection of ultrasound is a result of acoustic impedance mismatch between the two media. The fraction R of energy reflected at the boundary between two media can be described by the equation:
wherein z is1And z2Is the acoustic impedance of medium 1 and medium 2.
It can be seen from equation (2) that the larger the acoustic impedance mismatch, the stronger the reflected echo can be produced. Thus, by having at least a portion of the implantable device 131 made of a higher acoustic impedance material mismatched to human tissue, the implantable device 131 can produce a stronger reflection of the echo signal. For example, an implantable device 131 for monitoring or stimulating muscle tissue is implanted in an area having targeted human muscle tissue. Acoustic impedance of human muscle tissue of 1.68x106kg/(sec.m2). The material used for the implantable device 131 should have a higher acoustic impedance difference, e.g., 46.02x106kg/(sec.m2) Stainless steel for acoustic impedance of (1). With this arrangement, the implantable device 131 can reflect ultrasound waves with strong echo signals.
Assuming that the implantable device 131 can produce significantly stronger ultrasound reflections than other physiological structures in the living body, the majority of the acoustic energy reflected to the ultrasound transducer array 100 comes from the reflections at the implantable device 131. Then, time-reversal focusing is performed using the received echo signals. Most of the acoustic energy transmitted from the ultrasound transducer array 100 may then be targeted back to the reflection point at the implantable device 131. Advantageously, variations due to the position and orientation of each ultrasound transducer 111 can be compensated for. Therefore, measurements and details of the precise physical position and orientation of the ultrasound transducer 111 are not necessary; thus, the method enables the use of a flexible ultrasound transducer array 102 without requiring any details of each ultrasound transducer 111.
Fig. 6 shows a system diagram of a passive time-reversal focusing method for achieving maximum focus on an implantable device 131. This is an alternative iterative method for optimizing focus. This passive time-reversal focusing approach may iteratively increase the acoustic energy focused onto the implantable device 131 after each iteration cycle, given that the implantable device 131 reflects more ultrasound than other structures in the medium.
The passive time-reversal focusing method may be used to transmit acoustic energy to the implantable device 131 using an ultrasound transducer array 600 placed on the living body. Ultrasonic energy from the time-reversed waves is converted to electrical current by piezoelectric elements, CMUTs, optical-based transducers, or other materials. The ultrasound transducer array 600 may be a rigid ultrasound transducer array 101 or a flexible ultrasound transducer array 102. The ultrasound transducer array 600 may be configured to transmit plane waves, random time delay fields, or single ultrasound waves. In the case of transmitting ultrasonic energy to a living body having a plurality of implantable devices 131 at the same time, the time-reversal waves undergo constructive interference at a plurality of positions where the plurality of implantable devices 131 are located. In certain embodiments, each of the plurality of implantable devices 131 is selectively responsive to a particular frequency range to selectively activate a particular one or more implantable devices 131.
In one embodiment, two or more ultrasound transducers 111 are activated simultaneously to produce plane waves in the form of flat wavefronts. The transmission of the ultrasound signal has no focus and does not produce natural focusing.
In one embodiment, two or more ultrasound transducers 111 are activated and each ultrasound transducer 111 transmits an ultrasound signal with a random and different time delay. The intensity distribution is not focused at any point and a random time delay field can be transmitted.
In one embodiment, only one signal ultrasound transducer 111 is activated to transmit an ultrasound signal. The other ultrasound transducers 111 in the ultrasound transducer array 600 are still enabled to act as receivers and acquire echo signals to determine the location of the implantable device 131.
Ultrasound transmitted from the ultrasound transducer array 600(Tx) enters the medium 610 of the body tissue and may undergo refraction, scattering, attenuation, and reflection. Since the implantable device 131 has a high acoustic impedance difference, the reflected echo signal mainly comes from the implantable device 131. The echo signals are picked up by the ultrasound transducer array 600 and a plurality of received signals are obtained by one or more ultrasound transducers 111 of the ultrasound transducer array 600(Rx) for analysis.
The received signal is coupled to a processor 620. Each ultrasonic transducer 111 may provide direct information of the phase and intensity of the received echo signals at its position and orientation and compensate for any changes thereto. The processor 62 is configured to perform time-reversal focusing on each echo signal. In certain embodiments, processor 620 is further configured to perform post-processing filtering of noise and correct the linearity and frequency response of the ultrasound generated by ultrasound transducer 111. The time-reversed signals are coupled back to the ultrasound transducer array 600(Tx) to transmit ultrasound waves to the body tissue medium 610 and dynamically focused at the implantable device 131 according to the time-reversed echo signals. During this transmission, the previously receiving ultrasound transducer 111 is now configured to transmit ultrasound. Since the transmission is based on time-reversed echo signals, the acoustic energy transmitted from the ultrasound transducer array 600 may be advantageously targeted back to the implantable device 131.
The iterative method can be used in combination with a passive time-reversal focusing method, so that the accuracy of aiming can be improved. Since the implantable device 131 may reflect more ultrasound than other structures in the medium 610, iteratively applying the time reversal method may increase the focused ultrasound energy at the implantable device 131 in each iteration. During each iteration, the processor 620 determines whether the ultrasound energy targeting is improved. The iteration is repeated until the energy aim is not further improved. Such an iterative approach may advantageously enhance the accuracy of the focusing to achieve maximum focusing on the implantable device 131.
FIG. 7A illustrates a system for performing time-reversal focusing, according to one embodiment. The echo signals received by the ultrasonic transducer 111 are converted into digital signals using the ADC 711. The ADC 711 is typically implemented using a mix of integrated circuit devices and discrete components or integrated into the processor 620. The digital signal is then written to the memory 712 of the processor 620 for processing the time domain inverse 713. Time domain flipping 713 is performed by time flipping the digital signal from left to right to obtain a flipped digital signal. By coupling the flipped digital signal to DAC 714, a time-reversed signal can be obtained. Preferably, the ADC 711 and DAC 714 have the same number of bits in the digital domain. In certain embodiments, the time-reversed signals may perform post-processing filtering of noise and correct for ultrasound-generated linearity and frequency response of the ultrasound transducer 111.
FIG. 7B illustrates another system for performing time-reversal focusing according to one embodiment. The echo signals received by the ultrasonic transducer 111 are coupled to a fourier transform circuit 721 and an envelope detector 722 arranged in parallel with the fourier transform circuit 721. The fourier transform circuit 721 is configured to generate a frequency component of the echo signal, and the circuit may include components such as a multiplier and a calculation unit. Alternatively, the fourier transform circuit 721 may be implemented as an algorithm or software executable by the processor 620 or a computer system. The envelope detector 722 is configured to receive the echo signal, track the voltage envelope of the echo signal, and produce an amplitude component of the echo signal.
A Digital Signal Processing (DSP) circuit 723 receives the frequency component and the amplitude component of the echo signal from the fourier transform circuit 721 and the envelope detector 722 to flip the echo signal. The DSP circuit 723 may be implemented as an integrated circuit and operates to obtain a conjugate of the fourier transform of the echo signal. By using the inverse fourier transform circuit 724, the time domain of the time-reversed signal can be obtained. Preferably, fourier transform circuit 721 and inverse fourier transform circuit 724 have the same number of data samples. Alternatively, the inverse fourier transform circuit 724 may be implemented as an algorithm or software executable by the processor 620 or a computer system.
Fig. 8 shows a system diagram of an active time-reversal focusing method using an active implantable device 810 transmitting ultrasound. The active time-reversal focusing method is similar to the passive time-reversal focusing method, but in the opposite manner. Initially, at least one ultrasound transducer 111 is activated and transmits ultrasound waves into the living body. The active implantable device 810 includes a built-in ultrasound transducer for receiving ultrasound waves. The ultrasound waves transmit electrical energy to charge the active implantable device 810. In certain embodiments, the ultrasound transducer 111 may perform synchronization with the active implantable device 810. In some embodiments, electrical energy used to charge the active implantable device 810 can be harvested from other sources (e.g., heat, ions, kinetic motion, or magnetic fields).
Once the active implantable device 810 is charged with sufficient electrical energy, the built-in transducer of the active implantable device 810 may generate a second ultrasound wave in a direction opposite the incident ultrasound wave from the ultrasound transducer 111. In some embodiments, the built-in transducer may emit a second ultrasonic wave of approximately the same intensity in all directions to reach all of the ultrasonic transducers 111 in the ultrasonic transducer array 800, thereby maximizing efficiency. The second ultrasonic wave travels through the tissue of the living body and is then picked up by the ultrasonic transducer array 800. It is not necessary that all of the ultrasonic transducers 111 in the ultrasonic transducer array 800 pick up the second ultrasonic waves. The ultrasound transducer array 800, which may be a rigid or flexible shape, may then perform time-reversal focusing with a more focused and higher energy back to the active implantable device 810. In certain embodiments, one or more ultrasound transducers 111 acquire a plurality of received signals, which are coupled to processor 820. The processor 820 is configured to perform time-reversal focusing on each received signal. The time-reversed signal is coupled back to the ultrasound transducer 111(Tx) for transmitting ultrasound waves accordingly, so that acoustic energy can be advantageously dynamically focused at the active implantable device 810 and aimed back onto the active implantable device 810.
The iterative method can be used in combination with the active time-reversal focusing method, so that the aiming accuracy can be improved. During each iteration, the built-in transducer of the active implantable device 810 may transmit ultrasound waves in accordance with the incident ultrasound waves. By iteratively applying the time reversal method, the ultrasound energy may be more focused on the active implantable device 810. During each iteration, the processor 820 determines whether the energy aim is improved. The iteration is repeated until the energy aim is not further improved. Such an iterative approach may advantageously improve the accuracy of the focusing to achieve maximum focusing on the active implantable device 810.
When a first ultrasonic wave is picked up by the built-in transducer, the ultrasonic wave is converted into a current and coupled to an Alternating Current (AC) time delay circuit. An exemplary circuit diagram of the AC time delay circuit is shown in fig. 9. Other electronic circuits including resistor-capacitor (RC) pairs, transistors, FPGAs, ASICs, flip-flops, or other electronic components may be used to introduce time delays without departing from the spirit of the present disclosure. The purpose of using an AC time delay circuit is to introduce a time delay for the received ultrasonic waves so that the ultrasonic transducers 111 dissipate the originally transmitted ultrasonic waves during the transmission period. Accordingly, the active implantable device 810 may transmit a second ultrasound wave back to the ultrasound transducer array 800 during the detection period without interference from the ultrasound or any reflections thereof from the transmission period. In certain embodiments, the second ultrasound wave includes a synchronization signal with information about the time delay that is received by the ultrasound transducer array 800 for the processor 820 to determine the time required for the ultrasound to travel to the active implantable device 810.
In the case of simultaneous transmission of ultrasound energy to a living body having a plurality of active implantable devices 810, the time-reversed waves experience constructive interference at a plurality of locations where the plurality of active implantable devices 810 are located. In certain embodiments, each of the plurality of active implantable devices 810 is selectively responsive to a particular frequency range to selectively activate a particular one or more of the active implantable devices 810.
Fig. 10A provides a brightness mode (B-mode) ultrasound image reconstructed from plane wave activation using a rigid ultrasound transducer array 101. The experiment was performed on a chicken breast sample with a stainless steel surface embedded to simulate an implantable device. From the experimental results, it can be seen that the device with higher acoustic impedance difference can be seen on the upper right side of the strong reflection ultrasound image. FIG. 10B shows the time-reversed field produced from the B-mode ultrasound image shown in FIG. 10A. The experiment was performed using a Vantage 128TM (Verasonics corporation), a 128 channel ultrasound system, and a 5MHz linear transducer with an array of 128 ultrasound transducers. Although the figure is shown in grayscale (no color shown), the colors of the figure are blue (darker areas) and yellow (lighter areas). The blue areas represent low ultrasound intensity, while the yellow areas represent high ultrasound intensity. The intensity on the time-reversed field is generated by computer simulation at a homogeneous medium and shows the time-averaged intensity over the entire burst and acoustic wave travel period.
The time-reversal focusing method of the present invention may also take into account inhomogeneities in the body tissue medium. In contrast to conventional time delay focusing methods, which focus ultrasound waves by assuming a uniform and known velocity across the medium, time reversal focusing methods can advantageously take into account any effects, such as scattering and acoustic velocity variations as they propagate through the medium. Thus, using the time-reversal focusing method can mitigate noise and distortion of the ultrasound signal.
To demonstrate this difference, (1) the transient pulse and (2) the signal of the acoustic source with 7 cycles of 1MHz tone bursts were used and focused at a location inside the tissue medium at a depth of 10 cm. The results of the time-reversal focusing method and the time-delay focusing method were compared. Simulations were performed using a k-Wave simulation toolkit. Assume that the acoustic speed of sound of the medium is 1540m/s and the density is 1000kg/m3And the sound velocity of the scattering medium is 1800m/s and the density is 1500kg/m3. The scattering medium is randomly distributed in the medium occupying about medium space 1/4. The time-reversal focusing method is performed by simulating an acoustic wave focused at a depth position of 10cm inside the medium. The reflected sound waves are picked up and acquired by 216 ultrasonic transducers linearly aligned in analog space. By performing time-reversal focusing on the received ultrasound signals, time-reversed ultrasound waves are emitted from each ultrasound transducer. For time-delayed focusing, the signals from 216 ultrasound transducers have time-delayed signals corresponding to the distance to the focal point. By assuming a sound speed of 1540m/s, a time delay can be set such that the ultrasound signals will arrive at the focal point at the same time.
Fig. 11A and 11B show a comparison between the time reversal focusing method using a temporal pulse and the time delay focusing method. Fig. 12A and 12B show a comparison between the time reversal focusing method and the time delay focusing method using a sound source having 1MHz tone bursts of 7 periods. By calculating the root mean square of the time between signals and dividing by the maximum signal strength, the signal-to-noise ratio (SNR) can be obtained. For the transient pulse case, the SNR using the time-reversal focusing method is 3.01%, while the SNR using the time-delay method is 5.61%. The SNR of the tone burst is 5.01% for using the time-reversal focusing method and 12.92% for using the time-delay method.
C. Image formation and aiming energy delivery
The position of the implantable device 131 can also be monitored by forming ultrasound images. This is accomplished by reflecting the ultrasound waves from the surface of the implantable device 131. Due to acoustic impedance mismatch of the implantable device 131 and adjacent tissue, ultrasound waves traveling to the surface are reflected at the boundary. Advantageously, the reflection of the acoustic waves may provide positional and structural information of the implantable device 131, as well as other physical characteristics such as stiffness, temperature, and speed of sound.
Referring to fig. 13A, a flexible ultrasound transducer array 102 operating as an acoustic wave source is configured to generate acoustic waves. The acoustic waves generated at each ultrasound transducer 111 are determined based on the relative position, orientation and directionality of each ultrasound transducer 111 so that time delay focusing and/or electronic beamforming may be performed. Time delay focusing and electron beamforming are performed by controlling the timing and/or phase of the ultrasound generation by the processor. In certain embodiments, time delay focusing is performed by calculating a relatively central position from the flexible ultrasound transducer array 102 to the focal point 1301, determining the delay of each ultrasound transducer 111, and generating a plurality of ultrasound waves by the ultrasound transducers 111 each having a delay, such that the acoustic front 1302 propagating to the focal point 1301 can be obtained by constructive interference of the ultrasound waves at the focal point 1301. Constructive interference of the ultrasonic waves may produce stronger energy at the focal point 1301. By repeatedly and iteratively performing the ultrasound focusing method at different positions and depths, a complete scan of the entire field of view can be performed. The echoes received from each location can be combined with the reflection times to produce a complete ultrasound image over the beam intensity profile.
Referring to fig. 13B, an alternative method for forming an ultrasound image is depicted. Either a rigid transducer array 101 or a flexible transducer array 102 may be used. For the flexible transducer array 102, the method is performed by calculating the relative position and orientation between the plurality of ultrasonic transducers 111 in real time, determining the delay of each ultrasonic transducer 111, and generating a plurality of ultrasonic waves each having a delay by the ultrasonic transducers 111, so that a plane acoustic wave front 1312 can be obtained. The plane acoustic wave front 1312 is a flat wave front. For a rigid transducer array 101, a planar acoustic wavefront 1312 may be obtained by simultaneously generating multiple ultrasonic waves by the ultrasonic transducer 111. By changing the steering angle of the ultrasonic transducer 111, the reflection surface inside the living body can form a reflection matrix. The reflection matrix, along with position and orientation information for the transducer array, may be used to calculate the physical position of each reflective surface and thereby form an ultrasound image.
After the ultrasound image is formed, image analysis is performed to identify the implantable device 131 in the ultrasound image. Information such as brightness, shape, thickness, stiffness, etc. may be used to identify the implantable device 131 within the ultrasound image. Pattern recognition may also be used to determine a location on the implant based on the particular shape and size of the implantable device 131. Furthermore, by manipulating the surface of the implantable device 131 or using different materials, the reflection pattern of the echo signal can be made unique so that the echo signal can be easily distinguished from other echoes from other surrounding tissues. Classification, such as big data analysis, can be used to classify objects under ultrasound images and perform accurate identification of the implantable device 131. In addition to pattern recognition, other imaging techniques (e.g., shear wave elastography, phase contrast methods) may be used to improve the determination of the position of the implantable device 131 from the images.
After determining the position and orientation of the implantable device 131, the focused energy is transferred to the implantable device 131 with maximum efficiency. The method includes focusing ultrasonic energy to the implantable device 131 and converting the ultrasonic energy into an electrical current through a piezoelectric element, CMUT, optical based transducer or other material. The ultrasound transducer in the implantable device 131 typically has a particular frequency response. A typical voltage generated by an ultrasonic transducer per unit sound pressure is shown in fig. 14. The energy transfer efficiency can be optimized by selecting the resonant frequency at which the ultrasonic transducer transmits ultrasonic waves. In some embodiments, the usable frequency range of the ultrasonic transducer may also be selected for transmission if linear conversion of ultrasonic energy into electrical current is desired.
Referring now to fig. 15A and 15B, after selecting a frequency range, a focused ultrasound field may be generated by calculating a travel time of an acoustic wave from the ultrasound transducer 111 to a focal point. Fig. 15A shows an example of focusing ultrasound to an implantable device 131 by activating all ultrasound transducers with a time delay. Similarly, fig. 15B shows an example of focusing ultrasound to an implantable device 131 by activating a plurality of ultrasound transducers 111. In both cases, different time delays are applied to different ultrasound transducers 111 when transmitting ultrasound, so that the ultrasound from the ultrasound transducers 111 adds up to obtain a front 1501, 1502 of the acoustic wave propagating to the focal point at the implantable device 131 with maximum energy transmission. The number of ultrasound transducers 111 activated for transmission is determined according to the depth, position and orientation of the implantable device 131.
Fig. 16 shows a system diagram of an active time delay focusing method using an active implantable device 1610 transmitting ultrasound. Initially, at least one ultrasound transducer 111 is activated and transmits ultrasound waves into the living body. The active implantable device 1610 includes a built-in ultrasound transducer for receiving ultrasound waves. The ultrasound waves transmit electrical energy to charge the active implantable device 1610. In certain embodiments, the ultrasound transducer 111 may perform synchronization with the active implantable device 1610. In some embodiments, the electrical energy used to charge the active implantable device 1610 may be harvested from other sources (e.g., heat, ions, kinetic motion, or magnetic fields).
Once the active implantable device 1610 is charged with sufficient electrical energy, the built-in transducer of the active implantable device 1610 may emit a second ultrasound wave. The second ultrasonic wave travels through the tissue of the living body and is then picked up by the ultrasonic transducer array 1600. It is not necessary for all of the ultrasonic transducers 111 in the ultrasonic transducer array 1600 to pick up the second ultrasonic waves. The ultrasound transducer array 1600, which may be a rigid or flexible shape, may then perform reconstruction to obtain information of the position and/or orientation of the active implantable device 1610. In certain embodiments, the plurality of ultrasound transducers 111 acquire a plurality of received signals, which are coupled to a processor 1620. The processor 1620 is configured to perform image analysis and image focusing to reconstruct an image of the active implantable device 1610. The step of image focusing includes time delay focusing and analog scatter correction focusing. The phase delay focusing equation may be applied to all ultrasound transducers 111 so that the ultrasound energy may be focused onto the active implantable device 1610 with a desired waveform. The phase delay focusing equation is formulated such that the phase delay at each ultrasonic transducer 111 can be set such that when an acoustic wave is incident on the focal point, all the waves constructively interfere. More particularly, a time delay or phase delay is introduced by taking into account the time of flight of the acoustic wave from each ultrasonic transducer 111 to the focal point. In general, the phase delay focusing equation is based on the relative position and orientation between one or more ultrasound transducers 111.
In the case of transmitting ultrasonic energy to a living body having a plurality of active implantable devices 1610 simultaneously, the phase delay at each ultrasonic transducer 111 may be set so that constructive interference occurs at a plurality of positions where the plurality of active implantable devices 1610 are located. In certain embodiments, each of the plurality of active implantable devices 1610 is selectively responsive to a particular frequency range to selectively activate a particular one or more of the active implantable devices 1610.
An advantage of the active time delay focusing approach is that the waveform delivered to the active implantable device 1610 can be fully controlled. The waveform may be fully modulated in a manner that facilitates signal transduction and provides electrical energy to activate and communicate with the active implantable device 1610.
The iterative method can be used in combination with the active time delay focusing method, so that the accuracy of aiming can be improved. During each iteration, the built-in transducer of the active implantable device 1610 may transmit ultrasound waves to the ultrasound transducer array 1600, and the processor 1620 may determine whether energy targeting is improved. The iteration is repeated until the energy aim is not further improved. Such an iterative approach may advantageously enhance the accuracy of the focus to achieve maximum focus onto the active implantable device 1610.
D. Additional features and Experimental results
In certain embodiments, the second ultrasound waves emitted by the active implantable device 1610 may carry other data, such as temperature, pressure, pH, glucose level, or other sensed data. The electrical energy received from the ultrasound waves may power the sensor. While ultrasound has been used for signal conversion, the sensed data is targeted for signal transmission to the ultrasound transducer 111. Even when a weak second ultrasonic wave with sensing data is received, the sensitivity can be significantly improved.
In some embodiments, different data modulations of the ultrasound waves, such as amplitude modulation, frequency modulation, and pulse modulation, may be used to transmit data or signals to the active implantable device 1610. Sensors in the active implantable device 1610 may receive commands from the processor 1620, such as adjusting the gain of a sensor amplifier or periodically enabling the sensors. Because the present invention provides a way to target ultrasound energy at the active implantable device 1610, efficient communication and low noise due to multiple scattering can be achieved. Bidirectional communication between the active implantable device 1610 and the ultrasound transducer array 1600 may be established.
In certain embodiments, implantable device 131 (active or passive) may have a nonlinear effect on ultrasound sonication (sonication). This can be achieved by introducing materials or substances with nonlinear ultrasound properties, for example microbubbles are known to have ultrasound nonlinear effects. These non-linear characteristics will generate harmonics of the reflected ultrasound waves. The frequencies of these harmonics are typically half or integer multiples of the sonication frequency.
As shown in fig. 17, the frequency spectra of the fundamental frequency signal and the first harmonic signal are shown. Since the harmonic signals are frequency spectra that do not overlap with the fundamental frequency signals (originally emitted from the ultrasound transducer array 100), by selecting the frequency spectrum of the harmonic signals, the implantable device 131 can be identified from other structures. The harmonic spectrum can then be image reconstructed or time-reversed to provide more specific monitoring and/or targeting.
For active implantable devices 810, 1610, the generated ultrasound may have an ultrasound frequency different from the charged ultrasound waves using a transducer. This may allow to distinguish between the generated signal and the backscattered charging signal. In certain embodiments, generating ultrasound after charging the active implantable device 810, 1610 requires less or no latency.
There may be multiple implantable devices 131 in the field of view of the ultrasound transducer array 100. In order to identify the implantable device 131, in addition to analyzing possible shape and structural features, the active implantable devices 810, 1610 may be encoded with different frequencies to make them identifiable. The ultrasound transducer array 100 can identify active implantable devices 810, 1610 with different frequency transmissions by simple frequency filtering of the signal.
Frequency coding may also be used to selectively activate particular implantable devices 131. For example, the ultrasound sensors of each implantable device 131 may have different resonant frequencies that will only be activated by ultrasound waves of a particular frequency. In one embodiment, a filtering circuit or computerized design within the receiving portion of the implantable device 131 may be used to allow activation of the implantable device 131 only when receiving ultrasound waves of a particular frequency. This may allow for different activation times of the implantable device 131 within the field of view of the ultrasound transducer array 100 through frequency selection.
Fig. 18A shows an image reconstructed from a known convex ultrasound transducer array 100. Figure 18B shows another image reconstructed from the known S-shaped ultrasound transducer array 100. Fig. 18C shows another image reconstructed from the known concave ultrasound transducer array 100. In all three cases, plane waves are used for activation.
Fig. 10A and 10B show reconstructed ultrasound images of a sample of chicken breast embedded with a stainless steel surface. Fig. 19A and 19B show a B-mode ultrasound image and a time-reversed field generated for another similar experiment. The ultrasound was aimed back to the stainless steel surface using a time reversal method. The intensity distribution at the stainless steel site is about 2 times that of the adjacent tissue.
The present disclosure may be embodied in other specific forms without departing from its spirit or essential characteristics. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive. The scope of the disclosure is indicated by the appended claims rather than by the foregoing description, and all changes that come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein.