Method for reconstructing transcranial images using a dual-mode ultrasound phased array probe

Abstract

The present invention provides a method for reconstructing transcranial images using a dual-mode ultrasound phased array probe. The method includes the steps of: controlling multiple channels to irradiate energy onto an intracranial target point in a patient; receiving backscattered energy reflected from the intracranial target point through the multiple channels to generate backscattered radio frequency data for each; and reconstructing an acoustic distribution image in real time based on the backscattered radio frequency data. Compared to pre-treatment ray tracing, the present invention can display intracranial pressure distribution in real time; compared to magnetic resonance thermometry, it can be applied to low-energy applications without temperature changes; and compared to passive cavitation imaging, it can stably present acoustic distribution images without relying on microbubbles.

Description

[Technical Field]

[0001] This invention claims priority to U.S. Provisional Patent Application No. 63 / 383,600, filed on November 14, 2022, the contents of which are incorporated in whole by reference.

[0002] The present invention relates to a method for reconstructing transcranial images using a dual-mode ultrasound phased-array probe, and more particularly to a method for presenting transcranial acoustic distribution images in real time. [Background technology]

[0003] Clinically, for central nervous system (CNS) drugs to cross the blood-brain barrier (BBB) ​​and reach the therapeutic area of ​​a brain lesion, and for the drug to achieve its expected therapeutic effect, it is necessary to temporarily disrupt the barrier function of the blood-brain barrier in the brain lesion area. Recently, focused ultrasound (FUS) technology has been applied to disrupt the blood-brain barrier with ultrasound energy in a non-invasive, localized / selective, and transient manner. Compared to making drugs lipid-soluble or injecting chemicals to increase the permeability of cerebral blood vessels, focused ultrasound technology can locally disrupt the blood-brain barrier in the target lesion area, preventing the drug from entering non-target areas. However, the focused ultrasound energy needs to be monitored and repeatedly adjusted according to the situation in the lesion area. Another application of focused ultrasound technology is the modulation of ion channels in nerve cells, where mechanical force (i.e., ultrasound) induces changes in cell membrane potential and alters the threshold of nerve operating potentials, potentially curing or alleviating clinical diseases (such as abnormal discharges in epilepsy). While disrupting the blood-brain barrier requires intravenous injection of ultrasound energy in conjunction with microbubbles, applying nerve modulation does not require the injection of microbubbles.

[0004] Currently, several techniques are applicable to the evaluation and monitoring of intracranial conditions in focused ultrasound therapy, such as pre-treatment ray tracing, magnetic resonance thermography (MR) for hyperthermia, and passive cavitation imaging (PCI) for monitoring blood-brain barrier opening. However, each of these techniques has its limitations.

[0005] First, let's discuss pre-treatment ray tracing. During treatment, in order to observe the intracranial condition of the patient, the patient needs to move repeatedly between the magnetic resonance therapy room and the treatment room equipped with a focused ultrasound transducer, and the magnetic resonance therapy room also needs to be equipped with a focused ultrasound transducer. Furthermore, current MR devices are expensive, bulky, and take at least 5 minutes per scan. These drawbacks cause inconvenience to the patient, and physicians cannot observe the intracranial condition in real time, and therefore cannot immediately perform the corresponding operations to adjust the focal position and output energy of the focused ultrasound transducer.

[0006] Magnetic resonance thermometry (MRT) is a method that uses magnetic resonance imaging to monitor temperature changes generated by focused ultrasound energy. While this method allows for real-time monitoring of transcranial focused ultrasound, it is only applicable to applications with large temperature changes (such as ablation). It is not suitable for low-energy applications with no temperature changes, such as neuromodulation. Therefore, MRT is not suitable for directly observing minute cavitation changes, nor is it suitable for in-situ prediction of results from low-intensity transcranial ultrasound energies.

[0007] On the other hand, passive cavitation imaging technology uses an ultrasonic transducer in passive reception mode (receiving energy only, without emitting it) to represent the cavitation state through the cavitation characteristics generated by microbubbles that respond to focused ultrasound. Specifically, microbubbles are micron-sized particles composed of materials such as lipids, albumin, and polymers. Due to the acoustic impedance mismatch and high compressibility of microbubbles, in an ultrasonic field, microbubbles are compressed by the positive pressure of the ultrasound and expanded by the negative pressure of the ultrasound energy. This process is known as the cavitation effect. The cavitation effect is divided into stable cavitation and inertial cavitation. Stable cavitation is when microbubbles in an ultrasonic field with low sound pressure periodically and stably contract and expand due to the positive and negative pressure of the ultrasound. Due to stable cavitation, the power levels in the low-harmonic frequency band (half the driving frequency of the ultrasonic transducer) and the superharmonic frequency band (odd-harmonic series of low harmonics) are higher than those in the non-harmonic frequency band. Inertial cavitation is a phenomenon in which microbubbles in an ultrasonic field with high sound pressure burst without synchronizing with the positive and negative pressure transitions of the ultrasound, eventually producing high temperatures, high pressures, microinjection pumps, shock waves, and broadband irradiation. These cavitation characteristics related to the cavitation effect can be extended and applied to passive cavitation imaging techniques, not only indicating the location of cavitation from the intensity of the image, but also predicting the state of cavitation to some extent and indirectly presenting the transcranial energy distribution. However, imaging based on cavitation characteristics has several disadvantages that affect accuracy. Baseband spectral leakage and different concentrations of microbubbles affect the potential levels of harmonics. The intensity of cavitation imaging depends on the cavitation conditions and the concentration of microbubbles in the blood. However, since the concentration of microbubbles gradually decreases and eventually disappears, the cavitation image becomes unstable.The time interval during which the blood-brain barrier becomes inactive is only a few minutes, and the concentration of microbubbles gradually decreases during this period and finally disappears. In conclusion, passive cavitation imaging technology can indirectly present the transcranial energy distribution, but the imaging technology restricted by microbubbles cannot provide reliability and stability.

[0008] During low-intensity transcranial ultrasound therapy, since the energy irradiated from the transducer is much smaller than the energy of hyperthermia therapy, the temperature hardly rises at the position of the ultrasound focus, and temperature monitoring by magnetic resonance imaging is impossible. Therefore, while using ultrasound to destroy the blood-brain barrier, microbubbles by intravenous injection are used to induce cavitation effects, the ultrasonic feedback signals generated by the cavitation effects are received by an ultrasonic transducer, and sound source backtracking and cavitation mapping are performed to monitor the blood-brain barrier opening process. However, in other applications such as neuromodulation and those not using microbubbles, there is neither a sufficiently high heat source due to temperature rise nor a sufficiently strong sound source due to the cavitation effect induced by microbubbles, so the current methods cannot be used for monitoring transcranial focused ultrasound therapy.

Summary of the Invention

Problems to be Solved by the Invention

[0009] In view of the above, the present invention provides a method for reconstructing a transcranial image using a dual-mode ultrasonic phased array probe that enables observation of ultrasonic energy distribution covering various applications such as ultrasonic hyperthermia therapy, blood-brain barrier opening, and neuromodulation.

Means for Solving the Problems

[0010] The present invention includes: a step (A) of controlling a plurality of channels to irradiate energy to a target point within the patient's skull; a step (B) of receiving backscattered energy reflected from the target point within the skull through the plurality of channels and generating respective backscattered radio frequency data; and a step (C) of reconstructing an acoustic distribution image in real time based on the backscattered radio frequency data.

[0011] In some embodiments, the step of reconstructing the acoustic distribution image includes: a step of calculating a reconstruction signal according to the plurality of backscattered radio frequency data; and a step of reconstructing an acoustic distribution image showing an energy distribution according to the reconstruction signal.

[0012] In some embodiments, the method further includes: a step of adjusting the focus of a dual-mode ultrasonic phased array probe and repeating steps (A) to (C) to reconstruct a plurality of acoustic distribution images corresponding to different target points within the skull; and a step of merging the plurality of acoustic distribution images to obtain a tissue image.

[0013] In some embodiments, the method further includes: a step of performing a Fourier transform on the plurality of backscattered radio frequency data to obtain a plurality of spectra; a step of filtering the signals of the plurality of spectra to obtain an ultraharmonic signal of a frequency output by the dual-mode ultrasonic phased array probe; and a step of reconstructing a cavitation distribution image according to the plurality of ultraharmonic signals.

[0014] In some embodiments, the method further includes: a step of integrating the output energy of the dual-mode ultrasonic phased array probe with respect to the target point within the skull, the elapsed time after applying the energy, and the acoustic distribution image showing the energy distribution to calculate the increase value and decrease value of the intracranial temperature induced by the energy; and a step of reconstructing a temperature distribution image within the skull.

Advantages of the Invention

[0015] The method for constructing transcranial images according to the present invention uses a dual-mode ultrasound phased array probe to transcranially monitor the energy of focused ultrasound technology, surpassing pre-treatment ray tracing methods in terms of equipment cost, occupied area, and imaging speed. The present invention passively receives backscattered ultrasound signals without using microbubbles. Passive images are reconstructed, and the transcranial pressure distribution is evaluated. After phase calibration of the reconstructed images, the transcranial pressure distribution shows a high correlation with the intensity of the baseband passive image. Therefore, even without the injection of microbubbles, the present invention can be accurately positioned in the region of interest (ROI). Furthermore, the energy distribution image of the backscattered signal can display the focal position and magnitude of the ultrasound energy after phase calibration and energy adjustment in real time.

[0016] In conclusion, the present invention has the following advantages: Compared to magnetic resonance imaging, it can display intracranial pressure distribution in real time; compared to magnetic resonance thermometry, it can be applied to low-energy applications without temperature changes; and compared to passive cavitation imaging, it can stably present energy distribution images without relying on microbubbles. [Brief explanation of the drawing]

[0017] [Figure 1] This is a schematic diagram of the dual-mode ultrasonic phased array probe used in the present invention. [Figure 2] This is a schematic diagram illustrating how multiple channels deliver energy to intracranial target points. [Figure 3] This is a flowchart of the method for constructing a transcranial image according to the present invention. [Figure 4] This is a reconstructed acoustic distribution image according to the present invention. [Figure 5] This is an image reconstructed using a hydrophone. [Figure 6]This is a flowchart illustrating a method for constructing transcranial images according to several embodiments of the present invention. [Figure 7] This is a schematic diagram illustrating how the skull deflects the energy irradiated by the channel of the present invention. [Figure 8] This is the image before focus calibration. [Figure 9] This is the image after focus calibration. [Figure 10] This figure shows the one-sided frequency spectrum of backscattered radio frequency data. [Modes for carrying out the invention]

[0018] Embodiments of the present invention are described in further detail below in conjunction with the corresponding drawings. In the drawings and this specification, the same reference numerals represent the same or similar elements whenever possible. For the convenience of simplification and labeling, the shape and thickness of elements may be exaggerated in the drawings. Elements not specifically shown in the drawings or described in the specification are in forms known to those skilled in the art, so as can be easily understood. Those skilled in the art can make various modifications and changes in accordance with the content of the present invention.

[0019] The present invention provides a method for reconstructing transcranial images using a dual-mode ultrasound phased array probe, which is used to reconstruct transcranial acoustic distribution images in real time. Acoustic distribution images include, but are not limited to, energy distribution images, tissue images, cavitation images, and temperature distribution images. See Figure 1. The dual-mode ultrasound phased array probe 1 used in the present invention comprises a processing device 10 and a plurality of transforming elements (i.e., a plurality of channels 21 of an ultrasound transducer) forming an array on a housing 20. For simplicity, in Figure 1 only channels 21 are used to illustrate the channels. The processing device 10 comprises a control unit 12, a drive unit 14, a receive unit 16, and a processing unit 18. The processing unit 18 signals to the control unit 12 to control the transmission and reception of channels 21 and signals to the receive unit 16 to control channels 21 and acquire data generated by this control. Thus, "dual-mode" indicates that these channels 21 have both transmit and receive modes. The control unit 12 signals to the channels 21 and drives the transmission and reception of channels 21 according to the instructions of the processing unit 18. Channel 21 generates sound waves in response to an electric field applied by the drive unit 14, and generates a signal representing the magnitude of the energy in response to the sound waves, which is transmitted to the receiving unit 16. In some embodiments, the processing device 10 further includes a communication unit 19 that signals to the processing unit 18 in order to allow the user to view the generated image in real time. The communication unit 19 is directly / indirectly connected to the display device 3 by wired / wireless connection to display the image.

[0020] To display the relative position of the dual-mode ultrasound phased array probe and the patient's head in real time on a display device, the dual-mode ultrasound phased array probe of the present invention may further incorporate a tracking system 2 used for tracking and guidance, thereby enabling the method of the present invention. The tracking system 2 is realized and acquired by at least one physical phenomenon, such as an optical method, an electromagnetic method, and an acoustic method. Specifically, the tracking system is an optical positioning tracking system including an infrared transceiver for emitting and receiving light, a charge-coupled device (CCD) imaging device, or a depth camera, also called a 3D camera. The steps of implementing the optical positioning tracking system are, in order, an establishment step, a registration step, and a tracking step. The establishment step is to configure or prepare a 3D computer model of the object of interest. The object of interest is the patient's head and the dual-mode ultrasound phased array probe. A 3D model of the patient's head can be realized by irradiation line 3D imaging techniques such as magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), or single-photon emission computed tomography (SPECT). The registration step involves acquiring the relative position, orientation, and focal position of the dual-mode ultrasound phased array probe and obtaining a polygon mesh of the patient's head. Specifically, a physical model of the dual-mode ultrasound phased array probe is provided, having a needle and multiple pattern labels mounted on the housing. The tip of the needle stimulates the focus position. Next, an image of the above model is taken using an imaging device, and the pattern labels and tip are recognized based on image recognition technology using the processing unit 18, thereby obtaining spatial information of the dual-mode ultrasound phased array probe 1, such as the relative position, orientation, and focal position.Then, as the tip of the model slides over the patient's head, which is covered with pattern labels, it continuously recognizes and collects spatial information, constructing polygon mesh data of the patient's head. Finally, a 3D model of the patient's head is integrated with the above data. Depending on the requirements, the tracking step can be understood as applying the spatial information and data obtained in the registration step to the dual-mode ultrasound phased array probe and the method using the same in some embodiments of the present invention. By outputting corresponding positional information with an optical positioning tracking system as an alternative to magnetic resonance imaging, the coordinates of the skull and all channels can be acquired within seconds, and phase calibration data can be calculated. Furthermore, the optical positioning tracking system and the dual-mode ultrasound phased array probe occupy less space than a magnetic resonance apparatus and are not limited by magnetic resonance technology. Of course, the above tracking system can also employ electromagnetic navigation technology.

[0021] First, we will describe the process of reconstructing energy distribution images in real time using a dual-mode ultrasound phased array probe. Refer to Figures 2 and 3 simultaneously. Figure 2 is a schematic diagram showing how multiple channels transmit energy to and receive energy from an intracranial target point. In Figure 2, the skull is omitted, and a gray block is used to represent the brain. Figure 3 is a flowchart of the method for constructing a transcranial image according to the present invention. First, in step S10, the processing device controls m channels 21a (only representative channels 21a are shown in Figure 2) to irradiate an intracranial target point in the patient, where m is a positive integer greater than or equal to 2. The intracranial target point i may be a lesional area within the patient's skull, for example, the area to be observed after the blood-brain barrier has been disrupted by concentrated ultrasound energy. In practical applications, the intracranial target point i may be a non-lesion area. The energy irradiated from each channel 21a (shown by a dotted line) is attenuated and deflected as it passes through the skull to reach the intracranial target point i. Subsequently, the energy is partially reflected at the intracranial target point i, forming longitudinal waves oriented in multiple directions. These longitudinal waves interfere with each other, generating backscattered energy (indicated by dashed arrows). Next, in step S20, the processing device controls n channels 21b (only representative channels 21b are shown in Figure 2) to receive the backscattered energy jointly generated by m channels 21a, respectively, and generate backscattered radio frequency data for each, where n is a positive integer greater than or equal to 2. Finally, in step S30, the processing device reconstructs an acoustic distribution image in real time based on the backscattered radio frequency data of these backscattered energies. As shown in Figure 4, the acoustic distribution image can represent the degree of sound pressure distribution at the intracranial target point i corresponding to the transcranial energy, and is commonly called the transcranial pressure distribution.

[0022] Since each of the n channels 21b mentioned above receives a different amount of backscattered energy, the corresponding generated backscattered radio frequency data will be different. These backscattered radio frequency data are used to reconstruct the sound pressure distribution. Furthermore, in acoustic distribution imaging, the location and intensity of the acoustic distribution can be intuitively visualized by selecting appropriate colors and brightness according to the size of the backscattered radio frequency data. Moreover, when combined with digital imaging techniques such as interpolation, the quality and resolution of the acoustic distribution image can be further optimized.

[0023] Furthermore, to evaluate the quality of the acoustic distribution image of the present invention, a hydrophone made of polyvinylidene difluoride (PVDF) is used as a reference. Referring simultaneously to Figures 4 and 5, Figure 4 is an acoustic distribution image reconstructed according to the present invention, and Figure 5 is an image of transcranial pressure distribution obtained by measuring intracranial target points using a PVDF hydrophone. The image in Figure 5 has already been phase-calibrated. In Figures 4 and 5, the brightness level is proportional to the magnitude of the sound pressure. The resolution of the image generated by the present invention is sharp and is similar to the resolution of the energy distribution image obtained by scanning with a hydrophone.

[0024] As mentioned above, passive cavitation imaging techniques allow for the examination of intracranial cavitation characteristics (such as location and state) by injecting microbubbles. While cavitation characteristics may indirectly represent the transcranial pressure distribution, they have the following drawbacks: (1) Baseband spectral leakage and differences in microbubble concentration can affect the level of harmonic signals. (2) Metabolism and the effects of ultrasound irradiating the microbubbles can gradually decrease the concentration of microbubbles in the blood, potentially leading to their eventual disappearance, thus making the cavitation image generated by cavitation characteristics unstable. (3) After the blood-brain barrier is broken, the concentration of microbubbles gradually decreases, leaving only a few minutes for examination. Compared to passive cavitation imaging techniques, the present invention does not rely on microbubbles and can reconstruct the transcranial pressure distribution based on backscattered energy, thus avoiding the above drawbacks.

[0025] In some embodiments, with reference to Figure 6, the acoustic distribution image is an energy distribution image. Specifically, during the process of reconstructing the acoustic distribution image, the processing device first pre-calculates a reconstructed signal according to the backscatter radio frequency data (step S24), and then, based on the reconstructed signal, reconstructs an acoustic distribution image showing the specific position and energy distribution of a dual-mode ultrasound array transducer focused on an intracranial target point (step S30). Preferably, the processing device obtains the reconstructed signal according to equation (1).

[0026]

number

[0027] Here, S(r i ) represents a value calculated by the processing device based on backscattered radio frequency data generated by n channels, and r i This represents the location of the intracranial target point, A ni Each represents the weight of n channels, and sn respectively represent the backscattered radio frequency data individually generated by n channels after receiving the backscattered energy, and r ni respectively represent the distances between the i-th channel and the intracranial target point i, and t i represents the time delay for each of the n channels to receive energy. According to Equation (1) of the reconstruction technique, the processing device calculates the distance r ni between each of the n channels and the intracranial target point i, the time delay t i and the weight A ni and obtains the results corresponding to the multiple energies respectively output by m channels at the same time point to reconstruct the transcranial pressure distribution. However, the present invention is not limited to the above description. Due to practical requirements, in some embodiments, the above m channels can irradiate energy at different time points, and the processing device can obtain the same results even if the time points are different. In other words, before reconstructing the energy distribution image, the present invention calculates the time delays of the m channels and / or the n channels respectively to obtain the expected calculation results.

[0028] On the other hand, ultrasonic energy may be distorted, twisted, or its intensity may attenuate when passing through the skull, resulting in a decrease in the quality and reliability of the acoustic distribution image reconstructed based on the above backscattered radio frequency data. Refer to FIG. 6. In some embodiments, before reconstructing the acoustic distribution image, the processing device averages the backscattered radio frequency data individually generated by the above n channels that receive the backscattered energy (step S22) to improve the quality of the acoustic distribution image.

[0029] Specifically, the processing device first performs a discrete Fourier transform (DFT: Discrete Fourier Transform) on the input signal according to Equation (2) to compensate for the variable of the time delay and obtain the frequency domain signal S a (k).

[0030]

Equation

[0031] Here, S a (n) represents the input signal, i.e., the backscattered radio frequency data generated by one of the n channels above, k represents each discrete frequency point in the frequency domain, typically ranging from 0 to N-1, and N represents the number of discrete sampling points contained in the input signal.

[0032] Next, the processing device repeats the above steps until it obtains all frequency-domain signals corresponding to the n channels mentioned above, and these signals are each S a (k), S b (k)···S n (k) is represented by this.

[0033] Subsequently, the processing device processes one of the n channels' frequency domain signals (S a For (k, etc.), another frequency domain signal (S) from the above n channels b Perform cross-correlation with (k, etc.) and S according to equation (3). corr[a,b] Obtain it.

[0034]

number

[0035] Next, the processing device is S a The cross-correlation between (k) and the frequency domain signals of each of the n channels, i.e., S corr[a,b] S corr[a,c] ···S corr[a,n] Repeat the above steps until you obtain S. Finally, the processing device averages these signals after cross-correlation. corr (k) is obtained. Thus, as the signals corresponding to the n channels pass through the skull, the phase aberration is reduced, i.e., spectral aberration averaging is completed.

[0036] Next, the processing device processes the remaining frequency domain signals S corresponding to the n channels. b (k)···S n The cross-correlation and averaging steps are performed on (k) to complete the averaging of spectral aberrations across all channels.

[0037] Subsequently, the processing device, according to equation (4), S corr An inverse discrete Fourier transform (IDFT) is performed on (k) to obtain the final signal in the time domain.

[0038]

number

[0039] Finally, the processing devices are determined according to equation (5), and they corr Find the maximum value from and the maximum value s corr and another s corr Perform the calculation for the maximum value s corr Time delay t for a specific channel delay[a,b] The time delay is obtained. The obtained time delay can be used to remove the phase difference between channels.

[0040]

number

[0041] Here, N is the total number of channels that receive backscattered energy.

[0042] Next, the processing device sets the maximum value s for all channels. corr Repeat the above steps until you obtain the time delay related to it.

[0043] These corr (n) and / or these t delay[a,b]This can be adapted to equation (1) for calculating the reconstructed signal to compensate for the phase difference in backscattered radio frequency data resulting from the attenuation of backscattered energy and / or the relative time delay of the channels, thereby improving the quality of the energy distribution image. For example, the t of a certain channel delay[a,b] If is greater than 0, the phase of the backscattered radio frequency data generated by that channel is shifted forward, and t delay[a,b] If the value is less than 0, the above phase is shifted backward.

[0044] As mentioned above, the focus of ultrasonic energy blurs and is deflected as it passes through the skull, which not only affects the quality of the acoustic distribution image but also causes blurring of the ultrasonic energy focus and deflection of the focal position. Therefore, the present invention also provides a phase calibration method that performs phase calibration of the above m channels that irradiate energy based on the difference between the actual phase and the predicted phase of the dual-mode ultrasonic phased array probe. Referring to Figure 6, as shown in step S01, in some embodiments, before reconstructing the acoustic distribution image, the method further includes the steps of obtaining the relative position of the dual-mode ultrasonic phased array probe and the patient's head, and calculating the phase of these channels based on the above relative position and the relationship between tissue and acoustics. The relative position can be obtained using the above optical positioning tracking system. The relationship between tissue and acoustics can be obtained through the difference between the transmitted and received information of the dual-mode ultrasonic phased array probe, such as the scattering vector as it enters and exits the skull, the density of the skull, and the sound wave velocity inside the skull. Specifically, it is known that two refractions of sound waves occur in the process of sound waves being transmitted from the dual-mode ultrasonic phased array probe to an intracranial target point. The first refraction occurs when the ultrasound enters the skull (outside the skull). The second refraction occurs when the ultrasound exits the skull (inside the skull). The processing device can acquire the physical phase of m channels in relation to the blurring and deflection of the focal position due to these two refractions, according to a method that includes the scattering vector, skull density, and intracranial sound velocity, as described later. This allows the processing device to further calculate the difference between the physical phase and the predicted phase and complete the phase calibration of the m channels in real time.

[0045] Figure 7 shows how the energy irradiated by the channel is deflected by the skull from the intracranial target point i to the displacement point d. In the initial refraction, the scattering vector T s This represents the intracranial pathway of ultrasonic energy entering the skull. Scattering vector T s This can be obtained using equations (6) and (7) of Snell's Law.

[0046]

number

[0047]

number

[0048] Here, e represents the speed ratio of sound, and C i This represents the velocity of sound waves in the incident medium, and C r V represents the velocity of sound waves in the refractive medium (i.e., the skull), and V n θ represents the vector of acoustic energy from the irradiation channel to the outside of the skull (simplified as V), N represents the normal vector, θ1 represents the angle of incidence, and θ2 represents the angle of refraction.

[0049] In one embodiment, the skull density ρ is learned and obtained from statistical records. However, the present invention is not limited to this embodiment. It is preferable to calculate the patient's skull density ρ according to equation (8) using the Hounsfield unit (HU) value measured by the patient's computed tomography before the step of calculating the channel phase.

[0050]

number

[0051] Here ,ρ min ρ represents the density of water. max HU represents the maximum density of a healthy person (e.g., 2700 kg / m3), and HU max , and HU min These represent the standard, maximum, and minimum values ​​of Hounsfield units measured by CT, respectively, while HU is a variable that changes according to the measurement location. max and HU min This is a fixed value listed in the Hounsfield Scale.

[0052] In one embodiment, the intracranial acoustic velocity c is learned and obtained from statistical records. However, the present invention is not limited to this embodiment. The intracranial sound velocity c can be calculated by introducing the density ρ of the skull into equation (9).

[0053]

number

[0054] Here, c min This represents the speed of sound in water, and c max is, ρ max This represents the speed of sound corresponding to (for example, 4000 m / s).

[0055] Based on the above discussion, by calculating the first and second refractions, the processing device can obtain the scattering vector and time of flight calculated based on the speed of sound when the energy irradiated by each channel and passing through the skull actually reaches the intracranial target point. The processing device can perform phase calibration for all channels according to the scattering vector and time of flight. Referring to Figures 8 and 9, these show the focal positions before and after Real-Time Focus Adjustment, respectively. Figures 8 and 9 are not acoustic distribution images of the present invention, but rather images based on a PVDF hydrophone, and merely show the difference between an image taken before calibration and an image taken after calibration.

[0056] In other words, the transcranial sound pressure distribution can be evaluated using a passive energy distribution image of the fundamental frequency acquired after phase calibration based on relative position acquired by a tracking system (such as a navigator that uses a light beam for tracking). This is because, after phase calibration, the passive energy distribution image of the fundamental frequency shows a high correlation with the transcranial sound pressure distribution.

[0057] In some embodiments, after the step of reconstructing an acoustic distribution image, the method further includes the step of adjusting the energy output of a dual-mode ultrasound phased array probe according to the acoustic distribution image. Specifically, the processing device can calculate transcranial attenuation rates and compensation parameters based on the acoustic distribution image showing the reflected energy to obtain the energy physically delivered to the intracranial target point. The difference between the physical energy value and the expected energy value of the dual-mode ultrasound phased array probe may serve as a criterion for adjusting the energy.

[0058] In some embodiments, the channel includes a plurality of first channels and a plurality of second channels. The first channels are used to perform the step of irradiating an intracranial target point with energy. The second channels are used to perform the step of receiving backscattered energy. For example, a dual-mode ultrasound phased array probe has 256 channels, of which 128 channels are used to irradiate an intracranial target point with energy, and the remaining 128 channels are used to continuously receive the scattered energy generated by the aforementioned energy. The number of channels that irradiate energy and the number of channels that receive energy can be adjusted according to the actual requirements. However, the present invention is not limited by this embodiment. These channels are switched and acquired in response to the processing device to alternately perform the steps of irradiating an intracranial target point with energy and receiving backscattered energy at intervals of a few milliseconds. In other words, the channel that irradiates an intracranial target point with energy and the channel that receives backscattered energy may be the same channel.

[0059] In some embodiments, the acoustic distribution image is a tissue image. Specifically, the processing device continuously adjusts the channel phase for real-time focusing, thereby reconstructing acoustic distribution images of multiple intracranial regions while the dual-mode ultrasound phased array probe scans the intracranial space. Finally, the processing device merges the acoustic distribution images using panoramic imaging or image overlay techniques to obtain a tissue image. This is because different tissues may scatter energy of different intensities for a given energy magnitude according to their acoustic properties. Whether the tissues are the same can be determined by whether the brightness levels of the scanned regions are the same. The scan starts from a geometric focus and progresses while moving outward around the geometric focus. For example, the scan may be offset by 3 mm and pulsed every 120 degrees of rotation, or offset by 6 mm and pulsed every 30 degrees of rotation, or offset by 9 mm and pulsed every 15 degrees of rotation. The acoustic distribution image is preferably obtained by the energy distribution image generation method described above. In other words, a single energy distribution image can present the transcranial pressure distribution of an intracranial target point, and by merging multiple energy distribution images from multiple regions to form a tissue image, the intracranial structure can be fully presented. It is preferable to integrate the tissue image with a 3D model of the patient's head and display the tissue image three-dimensionally on a display device.

[0060] Unlike passive cavitation imaging techniques, the transcranial imaging method of the present invention can reconstruct the intracranial sound pressure distribution without relying on the cavitation effect of microbubbles, but can be used to observe the state of cavitation. In some embodiments, the above acoustic distribution image is a cavitation distribution image. Specifically, when microbubbles are present at an intracranial target point, the energy irradiated from the above m channels causes the microbubbles to generate a cavitation effect, and as a result, the frequency spectrum obtained by the processing device after performing a Fourier transform on the backscattered radio frequency data generated by the n channels reflects several physical properties. Referring to Figure 10, this shows the amplitude information of the positive frequency portion of the backscattered radio frequency data X(t), i.e., the one-sided frequency spectrum. If the frequency of the applied ultrasonic energy is 0.5 MHz and water is used to simulate brain tissue, then in the absence of microbubbles, the frequency spectrum will only show the 0.5 MHz signal and noise (shown by the dashed line). On the other hand, if microbubbles are present, they generate ultra-harmonic signals at integer multiples of the 0.5 MHz baseband and the 0.5 MHz acoustic field frequency. Therefore, the frequency spectrum not only contains the aforementioned noise, but also shows signals corresponding to the ultraharmonics and the signal that is significantly boosted at 0.5 MHz due to interference effects (shown by solid lines). Considering the large difference between the signal and noise at 1 MHz, the processing device can filter out 1 MHz and thereby reconstruct the cavitation distribution image. If dark areas appear in the reconstructed image, it indicates that no cavitation effect is occurring. On the other hand, if bright areas appear in the reconstructed image, it indicates that a cavitation effect is occurring. In order to monitor the transcranial sound pressure distribution more safely and effectively in this invention, it is preferable to integrate the cavitation distribution image and the energy distribution image.

[0061] Unlike magnetic resonance thermometry, the present invention is applicable not only to applications with large temperature changes but also to low-energy applications with no temperature changes. In some embodiments, the acoustic distribution image is an image correlated with the temperature distribution. The relationship between the applied ultrasonic energy and the temperature change of human tissue or bone is expressed by equation (10).

[0062]

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[0063] Here, ΔT L θ represents the maximum temperature caused by the applied ultrasonic energy, τ represents the perfusion time constant, for example, 10⁹ seconds for the brain and 3260-6600 seconds for bone marrow, α represents the tissue absorption coefficient, which is used to evaluate the degree of absorption of ultrasound or other wave-type energy per unit length or unit volume of a medium, I represents the energy acting on the tissue, i.e., the intensity of the ultrasonic energy in the above acoustic distribution image representing the energy distribution, and C v This represents the heat capacity. ΔT L After obtaining ΔT L Based on the elapsed time, the current temperature of the intracranial target point (biological tissue) can be calculated. While focused ultrasonic energy is applied, the processing device calculates the temperature rise value ΔT of the biological tissue according to equation (11) using the elapsed time t.

[0064]

number

[0065] Here, t' represents the time required to reach the maximum temperature. After stopping the application of ultrasonic energy, the processing device can calculate the temperature drop of the biological tissue according to equation (12).

[0066]

number

[0067] The processing device can reconstruct a temperature distribution image of an intracranial target point according to the calculated temperature rise and fall values. In other words, the present invention enables safer and more effective monitoring of transcranial sound pressure distribution by integrating the temperature rise and fall values ​​with the energy distribution image to reconstruct a temperature distribution image of an intracranial target point.

[0068] The above embodiments are illustrative of the present invention and do not limit its scope. Embodiments that can be easily substituted or modified in accordance with the technical content disclosed herein or in the claims are also included within the scope of the present invention.

Claims

1. A method for reconstructing a transcranial image using a dual-mode ultrasound phased array probe applied to a processing device, wherein the processing device communicates with a plurality of channels forming an array on the dual-mode ultrasound phased array probe, and the method (A) controlling the plurality of channels to irradiate energy to an intracranial target point of the patient, Step (B) of receiving the backscattered energy reflected from the intracranial target point using the plurality of channels and generating backscattered radio frequency data for each, A method comprising the step (C) of reconstructing an acoustic distribution image in real time based on the plurality of backscattered radio frequency data.

2. Before the step of reconstructing the acoustic distribution image, A step of obtaining the relative position between the dual-mode ultrasound phased array probe and the patient's head, The method according to claim 1, further comprising the step of calculating the phases of the plurality of channels that irradiate the intracranial target point with energy based on the relative position and the relationship between tissue and acoustics.

3. The method of claim 2, further comprising the step of calculating the density of the patient's intracranial tissue based on the Hounsfield unit (HU) value of the patient's computed tomography, and obtaining the relationship between tissue and acoustics, prior to the step of calculating the phase of the plurality of channels that irradiate energy to the intracranial target point.

4. The method according to claim 3, further comprising the step of calculating the phases of the plurality of channels that irradiate energy to the intracranial target point, followed by the step of performing phase calibration on the plurality of channels that irradiate energy according to the relative position of the dual-mode ultrasound phased array probe and the patient's head and the relationship between tissue and acoustics.

5. The method according to claim 1, further comprising the step of adjusting the energy output of the dual-mode ultrasonic phased array probe according to the acoustic distribution image after the step of reconstructing the acoustic distribution image.

6. The method according to claim 5, wherein the processing device calculates the transcranial attenuation rate and compensation parameters according to the reflected energy and adjusts the energy output in real time.

7. The method according to claim 1, further comprising the step of calculating a delay time corresponding to each of the plurality of channels before the step of reconstructing the acoustic distribution image, wherein each delay time is used to calibrate the plurality of backscatter radio frequency data.

8. The method according to claim 1, further comprising the step of averaging the plurality of backscattered radio frequency data to improve the quality of the acoustic distribution image before the step of reconstructing the acoustic distribution image.

9. The steps include: performing a Fourier transform on the plurality of backscattered radio frequency data to obtain a plurality of spectra; and filtering the signals of the plurality of spectra to obtain an ultraharmonic signal corresponding to the frequency output by the dual-mode ultrasonic phased array probe. The method according to claim 1, comprising the step of reconstructing a cavitation distribution image according to a plurality of the aforementioned superharmonic signals.

10. The method according to claim 1, wherein the plurality of channels comprises a plurality of first channels and a plurality of second channels, the plurality of first channels used to perform the step of irradiating the intracranial target point with energy, and the plurality of second channels used to perform the step of receiving the backscattered energy.

11. The method according to claim 1, wherein the plurality of channels are configured to perform the steps of irradiating the intracranial target point with energy and receiving the backscattered energy at different times.

12. The method according to claim 1, wherein the step of reconstructing an acoustic distribution image in real time based on the plurality of backscattered radio frequency data further includes the steps of calculating a reconstructed signal according to the plurality of backscattered radio frequency data and reconstructing the acoustic distribution image showing the energy distribution according to the reconstructed signal.

13. The reconstructed signal is obtained according to equation (1), [Math 1] Here, the S(r i ) is the intracranial target point r i This represents the reconstructed signal corresponding to A ni Each of these represents the weight coefficient of the nth channel, and s n (r ni ,t i ) represents the backscattered radio frequency data generated by the nth channel, r ni represents the distance between the nth channel and the intracranial target point, and t i The method according to claim 12, wherein n represents the time interval between the time when the nth channel irradiates energy and the time when the nth channel receives backscattered energy, and n is a positive integer.

14. The steps include adjusting the focus of the dual-mode ultrasound phased array probe and repeating steps (A) to (C) to reconstruct multiple acoustic distribution images corresponding to different intracranial target points, The method according to claim 12, further comprising the step of merging the plurality of acoustic distribution images to obtain a tissue image.

15. The steps include: integrating the output energy of the dual-mode ultrasound phased array probe applied to the intracranial target point, the elapsed time after the energy is applied, and the acoustic distribution image showing the energy distribution to calculate the temperature rise and temperature fall values ​​of the intracranial target point; The method according to claim 12, comprising the step of reconstructing a temperature distribution image of the intracranial target point according to the temperature rise and temperature fall values.

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