System and method for magnitude-based magnetic resonance acoustic radiation force imaging

Abstract

A system and method are provided for magnetic resonance acoustic radiation force imaging. The method includes operating an ultrasound (US) system to perform a US process on a patient and operating a magnetic resonance (MR) imaging system to acquire MR data from the patient using an MR imaging process that is performed during the US process. The method further includes using magnitude of the MR data, determining tissue displacements of the patient caused by the US process and controlling the US processes using the parameters of the patient.

Description

CWRU 2024‐4276 SYSTEM^AND^METHOD^FOR^MAGNITUDE‐BASED^MAGNETIC^^ RESONANCE^ACOUSTIC^RADIATION^FORCE^IMAGING^ CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to United States Provisional Patent Application No. 63 / 623,689 filed on January 22, 2024. The entire contents of which is incorporated herein by reference. STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH

[0002] This invention was made with government support under EB028773, NS126144, MH132022, and NS135551 awarded by the National Institutes of Health. The government has certain rights in the invention. BACKGROUND

[0003] Non-invasive brain stimulation (NIBS) is a well- established approach to study and modulate brain function. Traditional NIBS methods include transcranial electric stimulation (TES) and transcranial magnetic stimulation (TMS) modalities that stimulate the brain by triggering an action potential in neurons through eletrochemical interactions. However, it is challenging to target the deep focal regions of the brain using these methods, because they produce a diffused stimulation field. Recently, transcranial ultrasound stimulation (TUS) has gained traction as a mechanical stimulation based non- invasive therapeutic neuromodulation modality that can provide sharp millimeter-level focus of the treatment region deep in the brain. In many instances, TUS uses short duration (< 10 ms), low pressure (< 1 MPa) ultrasound pulses to cause transient micron- level tissue displacement that can be tightly focused without increasing the tissue temperature. The potential therapeutic applications of TUS are expanding, with recent animal and human studies demonstrating benefits ranging from mental health conditions to motor symptoms. Studies from recent years have shown its efficacy in managing anxiety disorders, phobias, enhancing mindfulness, controlling pain, reducing tremors, improving depression, and addressing substance cravings. Unlike high intensity focused ultrasound (HIFU) applications, TUS does not cause a measurable increase in tissue temperature. Thus, traditional MR thermometry -based methods, utilized in HIFU localization, cannot be used to visualize and steer the low intensity ultrasound focus used -1- QB\155798.00444\94035423.1CWRU 2024‐4276 in TUS.

[0004] Magnetic resonance acoustic radiation force imaging (MR-ARFI) has emerged as a method to visualize the focal tissue displacements caused by the low- intensity non-thermal ultrasound pulses used in TUS applications. MR-ARFI is a phase- contrast imaging method that translates the micron-level tissue displacement into an image phase shift by applying the TUS pulse in the presence of a MRI motion encoding gradient (MEG) played along the ultrasound’s propagation direction. TUS tissue displacement maps are estimated using the linear relationship between the accrued phase shift and the tissue displacement in the presence of MEG.

[0005] In particular, MR-ARFI synchronizes one or more magnetic field gradient pulses, which are ideally aligned with the focused ultrasound propagation direction at each image location. This creates a phase shift at each spatial location in the image that depends on the tissue location, and tissue displaced by the ultrasound pulse will accrue additional phase because it will be moved to a different point along the magnetic field gradient. If a second measurement is made with the same gradient pulse but without an ultrasound pulse or if the gradient pulse is negated, the difference between the phase of the two measurements will be proportional to the tissue displacement. MR-ARFI is sensitive to tissue displacements as small as 1 micron in vivo.

[0006] Many pulse sequences have been proposed for MR-ARFI. Most are based on gradient-recalled or spin-echo pulse sequences in which the MEG’s and FUS pulses are played between the excitation and readout. Variants to these have been proposed such as methods based on steady-state free precession and split echo turbo spin echo. Most existing methods, however, have at least two weaknesses when applied in the brain. First, to avoid tissue effects, a very low duty cycle (< 1%) should be used, but most methods require much higher duty cycles since FUS is applied for every readout line. Second, existing methods require a phase reference to remove background physiological and RF coil phase, which extends imaging time and makes them susceptible to errors arising from dynamic sources such as respiration and cardiac motion. To add a further complication, most methods also require long echo times, which lead to low signal-to- noise ratio due to unwanted transverse relaxation.

[0007] Recently, MR-ARFI was demonstrated in the human head to map TUS foci using a single-shot spiral time series acquisition method. However, MR-ARFI is highly sensitive to background phase errors and physiological motion. The constant -2- QB\155798.00444\94035423.1CWRU 2024‐4276 background errors can be removed using phase subtraction of images acquired with opposite polarity MEG pulses. However, phase errors due to dynamic sources, like gradient heating and breathing, cannot be subtracted out and can saturate the displacement map, making TUS targeting difficult. Moreover, because MR-ARFI produces displacement maps without anatomical details, a separate T1- or T2-weighted acquisition is needed to register and overlay the displacement map on anatomy for precise ultrasound focus localization, which makes MR-ARFI prone to image registration errors.

[0008] Thus, there is a continuing need for systems and methods to perform imaging with TUS applications. SUMMARY OF THE DISCLOSURE

[0009] The present disclosure addresses the aforementioned drawbacks by providing a system and method for using MR-ARFI to guide TUS applications by leveraging information in magnitude data, despite MR-ARFI being a phase-contrast imaging method. In this way, a magnitude-contrast MR-acoustic radiation force imaging (Mag-ARFI) magnetization-preparation sequence, system, and method are provided. In accordance with one, non-limiting example method, the phase shift produced by ARF tissue displacement is converted to a change in longitudinal magnetization, which can then be excited and read out with a number of different pulse sequences that can all acquire multiple lines of k-space with strong signal-to-noise ratio (SNR) for every FUS pulse. Thus, a subtraction-free magnitude-contrast MR-ARFI method is provided that is insensitive to displacement errors caused by dynamic effects such as respiration-induced field shifts, and produces images with inherently fused ultrasound focus and anatomy. Mag-ARFI can locate the ultrasound focus and produce images containing inherently fused focus and anatomy in T1- and T2-weighted data.

[0010] In accordance with one aspect of the present disclosure, a system is provided for magnetic resonance acoustic radiation force imaging (MR-ARFI). The system includes a magnetic resonance imaging (MRI) system configured to acquire MRI data from a subject and an ultrasound system configured to apply ultrasound energy to the subject. The system also includes at least one processor configured to control the MRI system to perform a magnitude-contrast MR-ARFI (Mag-ARFI) pulse sequence that includes applying radio frequency (RF) pulses and magnetic field gradients to generate MRI signals, and coordinating application of ultrasound energy from the ultrasound -3- QB\155798.00444\94035423.1CWRU 2024‐4276 system and reconstruct Mag-ARFI images from the MRI signals, wherein the Mag-ARFI images depict tissue displacement caused by the ultrasound energy.

[0011] In accordance with another aspect of the present disclosure, a method provided that includes operating an ultrasound (US) system to perform a US process on a patient and operating a magnetic resonance (MR) imaging system to acquire MR data from the patient using an MR imaging process that is performed during the US process. The method further includes using magnitude data of the MR data, determining tissue displacements of the patient caused by the US process and controlling the US processes using the parameters of the patient.

[0012] In accordance with yet another aspect of the present disclosure, a non- transitory computer-readable medium storing is provided that includes instructions that, when executed by one or more processors, cause the one or more processors to perform operations for magnetic resonance acoustic radiation force imaging (MR-ARFI). The operations include controlling a magnetic resonance imaging (MRI) system to perform a pulse sequence that includes applying radio frequency (RF) pulses and magnetic field gradients to generate MRI signals coordinated with an application of ultrasound energy from an ultrasound system. The operations also include acquiring MR data that includes phase data and magnitude data and using only the magnitude data, determining tissue displacement caused by the ultrasound energy

[0013] These are but a few, non-limiting examples of aspects of the present disclosures. Other features, aspects and implementation details will be described hereinafter. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] Various objects, features, and advantages of the disclosed subject matter can be more fully appreciated with reference to the following detailed description of the disclosed subject matter when considered in connection with the following drawings, in which like reference numerals identify like elements.

[0015] Fig. 1 is a block diagram of an example MR-ARFI system configured for Mag-ARFI in accordance with the present disclosure.

[0016] Fig.2 is a further block diagram of an example MR-ARFI system of Fig.1 in accordance with the present disclosure.

[0017] Fig.3A is a pulse sequence diagram illustrating one, non-limiting example -4- QB\155798.00444\94035423.1CWRU 2024‐4276 of a pulse sequence in accordance with the present disclosure.

[0018] Fig.3B is a flow chart setting forth one, non-limiting example of a process in accordance with the present disclosure.

[0019] Fig.4 is a set of correlated images, including 2D spin-echo phase-ARFI and TSE Mag-ARFI images acquired from phantom coronal, axial, and sagittal slices.

[0020] Fig. 5 is a set of correlated images, including Multi-slice T2-weighted TSE anatomical, and Mag-ARFI images.

[0021] Fig.6 is a set of correlated images, including phase-ARFI, T1-weighted TSE and T2-weighted TSE anatomical, and Mag-ARFI images.

[0022] Fig. 7 is a set of correlated images, generated from two repeated scans comparing breathing motion artifacts in phase-ARFI and Mag-ARFI images. DETAILED DESCRIPTION

[0023] Referring to Fig. 1, an example of an MRI system 100 configured for operation in accordance with the present disclosure. The MRI system 100 includes an operator workstation 102 that may include a display 104, one or more input devices 106 (e.g., a keyboard, a mouse), and a computer or processor 108. The processor 108 may include a commercially available programmable machine running a commercially available operating system. The operator workstation 102 provides an operator interface that facilitates entering scan parameters into the MRI system 100. The operator workstation 102 may be coupled to different servers, including, for example, a pulse sequence server 110, a data acquisition server 112, a data processing server 114, and a data store server 116. The MRI system 100 also includes gradient system 118 and a radio frequency (RF) system 120. A magnet assembly 122 includes a polarizing magnet 124, which may be a low-field magnet. The gradient system 118 may control a gradient coil assembly 126. The MRI system 100 may optionally include a whole-body RF coil 128, or a local coil system (not shown) that is controlled by the RF system 120.

[0024] The pulse sequence server 110 functions in response to instructions provided by the operator workstation 102 to operate a gradient system 118 and the RF system 120. Gradient waveforms for performing a prescribed scan are produced and applied to the gradient system 118, which then excited gradient coils in the assembly 126 to produce the magnetic field gradients (e.g., ^^௫, ^^௬, and ^^௭) that can be used for spatially encoding magnetic resonance signals. -5- QB\155798.00444\94035423.1CWRU 2024‐4276

[0025] RF waveforms are applied by the RF system 120 to the RF coil 128, or a separate local coil to perform the prescribed magnetic resonance pulse sequence. Responsive magnetic resonance signals detected by the RF coil 128, or a separate local coil, are received by the RF system 120. The responsive magnetic resonance signals may be amplified, demodulated, filtered, and digitized under direction of commands produced by the pulse sequence server 110. The RF system 120 includes an RF transmitter for producing a wide variety of RF pulses used in MRI pulse sequences. The RF transmitter is responsive to the prescribed scan and direction from the pulse sequence server 110 to produce RF pulses of the desired frequency, phase, and pulse amplitude waveform. The generated RF pulses may be applied to the whole-body RF coil 928 or to one or more local coils or coil arrays.

[0026] The RF system 120 also includes one or more RF receiver channels. An RF receiver channel includes an RF preamplifier that amplifies the magnetic resonance signal received by the coil 128 to which it is connected, and a detector that detects and digitizes the ^^ and ^^ quadrature components of the received magnetic resonance signal. The magnitude of the received magnetic resonance signal may, therefore, be determinedat a sampled point by the square root of the sum of the squares of the ^^ and ^^components: ^^ ൌ ^^^^ଶ ^ ^^ଶ^

[0027] and the phase of resonance signal may also bedetermined according to the following relationship: ି^^^ ^^ ൌ tan ൬^^^

[0028] The pulsemay receive patient data from a physiological acquisition controller 130. By way of example, the physiological acquisition controller 130 may receive signals from a number of different sensors connected to the patient, including electrocardiograph (ECG) signals from electrodes, or respiratory signals from a respiratory bellows or other respiratory monitoring devices. These signals may be used by the pulse sequence server 910 to synchronize, or “gate,” the performance of the scan with the subject’s heartbeat or respiration.

[0029] The pulse sequence server 110 may also connect to a scan room interface circuit 132 that receives signals from various sensors associated with the condition of the patient and the magnet system. Through the scan room interface circuit 132, a patient -6- QB\155798.00444\94035423.1CWRU 2024‐4276 positioning system 134 can receive commands to move the patient to desired positions during the scan.

[0030] The digitized magnetic resonance signal samples produced by the RF system 120 are received by the data acquisition server 112. The data acquisition server 112 operates in response to instructions downloaded from the operator workstation 102 to receive the real-time magnetic resonance data and provide buffer storage, so that data are not lost by data overrun. In some scans, the data acquisition server 112 passes the acquired magnetic resonance data to the data processor server 114. In scans that require information derived from acquired magnetic resonance data to control the further performance of the scan, the data acquisition server 112 may be programmed to produce such information and convey it to the pulse sequence server 110. For example, during pre-scans, magnetic resonance data may be acquired and used to calibrate the pulse sequence performed by the pulse sequence server 110. As another example, navigator signals may be acquired and used to adjust the operating parameters of the RF system 120 or the gradient system 118, or to control the view order in which k-space is sampled. In still another example, the data acquisition server 112 may also process magnetic resonance signals used to detect the arrival of a contrast agent in a magnetic resonance angiography (MRA) scan. For example, the data acquisition server 112 may acquire magnetic resonance data and processes it in real-time to produce information that is used to control the scan.

[0031] The data processing server 114 receives magnetic resonance data from the data acquisition server 112 and processes the magnetic resonance data in accordance with instructions provided by the operator workstation 102. Such processing may include, for example, reconstructing two-dimensional or three-dimensional images by performing a Fourier transformation of raw k-space data, performing other image reconstruction algorithms (e.g., iterative or backprojection reconstruction algorithms), applying filters to raw k-space data or to reconstructed images, generating functional magnetic resonance images, or calculating motion or flow images.

[0032] Images reconstructed by the data processing server 114 are conveyed back to the operator workstation 102 for storage. Real-time images may be stored in a data base memory cache, from which they may be output to operator display 102 or a display 136. Batch mode images or selected real time images may be stored in a host database on disc storage 138. When such images have been reconstructed and transferred to -7- QB\155798.00444\94035423.1CWRU 2024‐4276 storage, the data processing server 114 may notify the data store server 116 on the operator workstation 102. The operator workstation 102 may be used by an operator to archive the images, produce films, or send the images via a network to other facilities.

[0033] The MRI system 100 may connect through a communication system 140 to one or more networked workstations 142. For example, a networked workstation 142 may include a display 144, one or more input devices 146 (e.g., a keyboard, a mouse), and a computer or processor 148. The networked workstation 142 may be located within the same facility as the operator workstation 102, or in a different facility, such as a different healthcare institution or clinic, and be configured for communication therebetween. Also, the networked workstation 142 may form a server or represent or be connected to any remote communication devices, including portable electronics or cloud servers. Additionally, regardless of the particular hardware or implementation, the networked workstation 142 may gain remote access to the data processing server 114 or data store server 116 via the communication system 140. Also, multiple networked workstations 142 may have access to the data processing server 114 and the data store server 116. In this manner, magnetic resonance data, reconstructed images, or other data may be exchanged between the data processing server 114 or the data store server 116 and the networked workstations 142, such that the data or images may be remotely processed by a networked workstation 142.

[0034] As will be described, the above-described 100 system may be configured as a MR-ARFI or magnitude-contrast MR-acoustic radiation force imaging (Mag-ARFI) system. As such, the system 100 may include a transducer system 150 coupled to a patient 152 when arranged for MR imaging.

[0035] Referring now to Fig.2, the transducer system 150 may be configured more particularly for transcranial ultrasound stimulation (TUS) of the patient 152. That is, the subject 152 receives ultrasound energy from one or a plurality of transducer elements 200. In one non-limiting configuration, if an array of transducers is utilized, the transducer elements 200 may be arranged in a matrix that surrounds an extent of the patient’s head. For example, the transducer system 150 may be a hemispherical array of transducer elements 200. The transducer system 150 may include a processor 202 that is in communication with an amplifier 204 and a receiver 206. The amplifier 204 may receive driving signals from the processor 202 and, in turn, direct the transducer elements of the transducer system 150 to generate ultrasound energy. The receiver 206 -8- QB\155798.00444\94035423.1CWRU 2024‐4276 may receive acoustic signals during sonications and relay these signals to the processor 202 for processing in accordance with the present disclosure. The processor 202 may also be configured to adjust the driving signals in response to the acoustic signals received by the receiver 206. For example, the phase and / or amplitude of the driving signals may be adjusted so that ultrasound energy is more efficiently transmitted through the skull of the subject 152 and into the target volume-of-interest 208. Furthermore, the acoustic signals may also be analyzed to determine whether and how the extent of the focal region should be adjusted. As will be described below in detail, MRI images 210 may also be used to guide the application of ultrasound energy to the subject 152. Thus, an MRI system described with respect to Fig. 1, generally indicated as dashed box 212, may be used to acquired MRI images 210 of the subject 152. The MRI images 210 may then be provided to the processor 202 to adjust the parameters of the sonications. For example, the phase and / or amplitude of the driving signals may be adjusted so that ultrasound energy is more efficiently transmitted through the skull of the subject 152 and into the target volume-of-interest 208.

[0036] In accordance with one non-limiting example for carrying out a process, such as using the systems described above, a particular pulse sequence may be utilized to acquire the MRI images 210. For example, referring to Fig.3A, provides an example of a pulse sequence diagram for a non-limiting example of a Mag-ARFI magnetization preparation sequence. In this non-limiting example, the pulse sequence 300 includes a series of RF pulses 302. In this example, the RF pulses 302 include three pulses, labeled “x,” “y,” and “α.” The pulse sequence 300 may build on a spin-echo, phase-contrast MR- ARFI sequence. In this example pulse sequence 300, the x-pulse and the α-pulse may be 90 degree pulses, where the x-pulse is the excitation, and the α-pulse is a restoration pulse is utilized at echo time (TE), instead of a signal readout. The y-pulse is a 180 degree refocusing pulse, as illustrated, that may be located at 1 / 2 TE.

[0037] The RF pulses 302 are played out in the presence of MR gradients 304. As illustrated, the gradients may include bipolar MEGs separated by crusher gradients applied in conjunction with the y-pulse. Finally, a spoiler gradient may be used at the end of the TE to null any transverse magnetization. Beyond the MR components 302 and 304 of the pulse sequence 300, an ultrasound transducer trigger 306 is coordinated with the MR components 302 and 304.

[0038] The spins displaced by each ultrasound pulse 308, 310 accrue a phase ∆θ -9- QB\155798.00444\94035423.1CWRU 2024‐4276 given by: ∆θ = γGt∆r

[0039] where, γ is a gyromagnetic ratio, G is a MEG amplitude, t is a duration of the ultrasound pulse, and ∆r is a spin displacement.

[0040] The restoration α-pulse can have a of phase π / 2 to flip back Msin∆θ, the sine component of the net transverse magnetization M from the displaced spins, to the longitudinal axis. While stationary spins remain in the transverse plane and their signal is nulled by the spoiler gradients. The longitudinal magnetization, modulated by spin displacement, can be readout by any of a variety of suitable MR imaging readouts 312. The restoration α-pulse phase can be adjusted to vary the relative intensity of the background tissue with respect to the ultrasound focus.

[0041] In the presence of phase errors in the restoration α-pulse, Mag-ARFI quantitative tissue displacement maps can be estimated using four acquisitions comprising images acquired with ultrasound on and off, each repeated with the nominal restoration pulse phase of 0 degrees (x-axis) 90 degrees (y-axis). Advantageously, the phase of the 90 degree tip-up RF pulse on the y-axis can be tuned to generate images with only displacement information, displacement and anatomical details, or only anatomical details.

[0042] The image phase change ∆θ caused by tissue displacement can be calculated as: ^I off , y I ^^ ^ on , y^^^^^

[0043] wherethe state of the ultrasound system, and subscripts “x” and “y” indicate the axis along which the restoration α-pulse is played out for image I.

[0044] For a restoration α-pulse with flip angle ϕ, phase “α”^and erroneous phase ∆α, the RF rotation matrix R^is given by: ^cos 2 ( ^ ^ ^ ^ ) ^ sin 2 ( ^ ^ ^ ^ )cos ^ cos( ^ ^ ^ ^ )sin( ^ ^ ^ ^ )(1 ^ cos ^ ) ^ sin( ^ ^ ^ ^ )sin ^ ^^ ^^^ ^CWRU 2024‐4276

[0045] Let M0be the initial longitudinal magnetization and ∆θ^be the phase shift from ultrasound tissue displacement in the presence of a motion encoding gradient. Assuming ideal excitation and refocusing pulses, the magnetization vector just before the restoration α-pulse in the Mag-ARFI preparation sequence 300 is given by M^= (M0sin∆θ,^M0cos∆θ,0)T. The restoration α-pulse rotates M^ by R^ to produce longitudinalmagnetization given by: Mz ^ M 0 sin^ ( sin ^ ^ sin ( ^ ^ ^ ^ ) ^ cos ^ ^ cos ( ^ ^ ^ ^ ))

[0046] The remaining transverse magnetization is nulled by the spoiler gradients at the end of the Mag-ARFI preparation sequence 300 so that Mz^is available to be readout by an imaging sequence. There are four unknowns in ∆θ = γGt∆r, which is ∆θ, ϕ, α^and ∆α.

[0047] Referring now to Fig. 3B, to estimate ∆θ from this equation, a multi-step acquisition process 320 may be performed. The process 320 begins at process block 322 by performing an acquisition with the ultrasound on and the restoration α-pulse played out on the x-axis. In this acquisition, α may be set to 0, which givesMon , x ^ ^ M 0 sin ^ cos( ^ ^ ^ ^ ^ ) . At process block 324, an acquisition isperformed with the ultrasound on, and the restoration α-pulse played out on they-axis. Setting α = π / 2 gives Mon , y ^ M 0 sin ^ sin( ^ ^ ^ ^ ^ ) . Then, at process block326, an acquisition is performed with the ultrasound off and the restoration α-pulseplayed out on the x-axis. Setting α and Δθ to 0 gives Moff , x ^ ^ M 0 sin ^ cos ^ ^ . Then,at process block 328, an acquisition is performed with the ultrasound off and the restoration α-pulse played out on the y-axis. Setting α = π / 2 and Δθ to 0 givesMoff , y ^ M 0 sin ^ sin ^ ^ .

[0048] Of course, the order of the above-listed acquisitions may be changed or adjusted. The point is to acquire sufficient data to solve for ∆θ, which is performed at process block 330. In this non-limiting example, this can be readily done by dividingMoff , y ^ M 0 sin ^ sin ^ ^ by Moff , x ^ ^ M 0 sin ^ cos ^ ^ , which gives:byCWRU 2024‐4276Mon , x ^ ^ M 0 sin ^ cos( ^ ^ ^ ^ ^ ) and subsite Δα from the above which gives:^ M off , y M o ^^ M ^ n , yM ^^ ^ ^tan^1 ^ off , x on , x ^^1M off , y M on , y ^^ ^M off , x M on ^^ , x ^

[0050] Thus, the tissue displacement ∆r can be calculated from ∆θ using ∆θ = γGt∆r and then provided in a report at process block 332. The report can be used, as described above, to carry out a Mag-ARFI process.

[0051] Thus, systems and methods are provided that can use only one signal acquisition (no subtraction), and half the scan time of conventional MR-ARFI. The anatomical image and the tissue displacement image are encoded within the same signal acquisition, leading to inherently co-registered displacement images and anatomical images. Sensitivity to background phase errors are controlled or eliminated.

[0052] EXAMPLE

[0053] In one non-limiting example, the above-described Mag-ARFI preparation module was implemented in the scanner’s native turbo spin echo (TSE) sequence. To reduce the Mag-ARFI echo time, the crusher gradients around the Mag-ARFI refocusing pulse were bridged with the positive lobes of the MEG waveforms. For comparison purposes, a native phase-contrast spin-echo MR- ARFI (phase-ARFI) sequence was also implemented. All Mag-ARFI images were reconstructed using the MRI system’s native image reconstruction pipeline. The phase-ARFI displacement maps were estimated in MATLAB (MathWorks Inc., Natick, WA) using the phase difference of two MR-ARFI acquisitions with reversed polarity MEG pulses in ∆θ = γGt∆r. The Mag-ARFI displacement maps were generated using the above-described process including four Mag-ARFI acquisitions with ultrasound on and off, each repeated with the restoration α- pulse phase of 0 degrees and 90 degrees.

[0054] The large MEG pulses used in MR-ARFI generate eddy currents16 that can cause phase errors in the Mag-ARFI restoration pulse. To tune the restoration pulse phase, a calibration sequence was implemented in Pulseq. The calibration sequence acquired a series of Mag-ARFI-prepared free induction decay (FID) signals without the ultrasound pulse and with the restoration pulse phase offset (from the x-axis) in the range of −20 degree to 20 degree, in 1 degree increments. The optimal restoration pulse phase -12- QB\155798.00444\94035423.1CWRU 2024‐4276 was set to the value that produced the maximum peak FID signal.

[0055] All images were acquired on a 3 T whole-body scanner (Vida, Siemens Healthineers, Erlangen, Germany) under institutional review board approval and with informed volunteer consent. Spin echo phase-ARFI, and T1-weighted and T2-weighted TSE Mag-ARFI images were acquired in phantom and volunteer experiments. All acquisitions used MEG pulses with an amplitude of 40 mT / m and a duration of 5 ms. The Mag-ARFI magnetization preparation sequence had a duration of 28.5 ms and used 1 ms long hard excitation and refocusing pules. The 2D T1-weighted TSE Mag-ARFI sequence had TR / TE of 600 / 9.3 ms, turbo factor of 15, 3 slice groups and scan duration of 51 seconds. The 2D T2-weighted TSE Mag-ARFI sequence had TR / TE of 6000 / 90 ms, turbo factor of 15, and scan duration of 1 minute. The 2D spin-echo phase-ARFI sequence had TR / TE of 500 / 25 ms, and acquired four dynamics comprising images with reversed polarity MEG pulses, each repeated with ultra-sound on and off, for a total acquisition time of 4 minutes and 16 seconds. All sequences acquired images from 10 slices with a field of view of 23x23 cm2, in-plane resolution of 1.8x1.8 mm2, and slice thickness of 4 mm.

[0056] Phantom Experiments

[0057] Ultrasound experiments were performed on a tissue-mimicking phantom with a diameter of 6.5 cm and a height of 12 cm, containing agar, graphite and copper sulfate. The phantom was in direct contact with a single-element, 850 kHz ultrasound transducer with a 63.2 mm radius of curvature, and a 64 mm focal length (H-115MR Sonic Concepts, Bothell, WA). To visualize the ultrasound focus in all three planes, phase-ARFI and T2-weighted TSE Mag-ARFI images were acquired in coronal, axial and sagittal orientations. Phase-ARFI tissue displacement maps were estimated and compared with the Mag-ARFI images.

[0058] Head Experiments

[0059] Volunteer experiments were performed using a two-turn, 2 cm diameter constant current-carrying loop coil to mimic the focal phase shift caused by FUS-induced tis-sue displacement. The loop coil was placed on top of the subject’s head with the loop axis parallel to the scanner’s B0 field, and was driven by a function generator to produce a constant 588 mA current in the loop for 5 ms at the second ultrasound trigger in the phase-ARFI and Mag-ARFI sequences. The Mag-ARFI volunteer scans were repeated with restoration pulse phase α of 75 degrees for T1-weighted TSE and with α of 105 degrees -13- QB\155798.00444\94035423.1CWRU 2024‐4276 for T2-weighted TSE to show the ultrasound focus blended with anatomy. In addition, T2-weighted TSE Mag-ARFI images were acquired with α of 102 degrees, 108 degrees, 114 degrees and 120 degrees to demonstrate that the restoration pulse phase can be used to change the image intensity of the background anatomy relative to the ultrasound focus.

[0060] Breathing artifacts were assessed by measuring the artifact variation across two repetitions of the phase-ARFI and T2-weighted TSE Mag-ARFI acquisitions in the same volunteer. The T2-weighted TSE Mag-ARFI scans were acquired with four averages, and TR of 6930 ms to match the phase-ARFI scan duration of 4 minutes and 16 seconds. Brain and FUS focus masks were manually defined in phase-ARFI displacement maps and the T2-weighted TSE Mag-ARFI images. The motion artifact coefficient of variation (CV) was calculated as the standard deviation of the signal difference between repetitions inside the brain mask, normalized by the mean signal inside the FUS focus mask.

[0061] Fig. 4 shows the results from the phantom ultrasound experiments. In particular, Fig. 4 shows that 2D spin-echo phase-ARFI and TSE Mag-ARFI images from phantom coronal, axial, and sagittal slices. The FUS focus (arrows) is clearly visible in Mag-ARFI images and matches the location in phase-ARFI images in all three slice orientations. The background signal seen in both phase-ARFI and Mag-ARFI relates to ultrasound reflections at the walls of the 6.5 cm diameter phantom.

[0062] More particularly, the ultrasound focus in all three planes in the Mag-ARFI images match the focus seen in the phase-ARFI images with a peak displacement of 4.7 µm. The background signal seen in both phase-ARFI and mag-ARFI images were likely caused by ultrasound reflections at the walls of the 6.5 cm diameter phantom. The Mag- ARFI image intensity correlates well with the absolute displacement in the phase-ARFI maps.

[0063] Fig. 5 shows multi-slice T2-weighted TSE Mag-ARFI and reference anatomical images. A two-turn DC loop was used to mimic the focal phase shift caused by FUS displacement. The arrows point to the focal region which is distinctly visible in the Mag-ARFI images. Mag-ARFI image intensity in the focal region rapidly decreases with increasing slice distance from the DC loop due to the drop-off of the coil’s magnetic field.

[0064] Fig.6 shows the results from phase-ARFI, T1-weighted TSE Mag-ARFI and T2-weighted TSE Mag-ARFI experiments in one of the acquired brain slices. Image 600 -14- QB\155798.00444\94035423.1CWRU 2024‐4276 shows the localizer image and the location of the imaged slice, with the loop coil placed with its axis parallel to the B0 field. A phase-ARFI displacement map 602 shows a focal region generated by the loop coil, mimicking focused ultrasound. Images 604 include T1- and T2-weighted TSE Mag-ARFI images with contrast matching the reference anatomical images, with α values set to suppress or brighten the background. The T2-weighted TSE Mag-ARFI phase image shows that the dark ring around the focal region is caused by the restoration pulse phase causing phase cancellation around the boundaries of the focal region. The focus location in all Mag-ARFI images match that in the phase-ARFI image 602. The Mag-ARFI images 604 were acquired with restoration pulse phase α of 96 degrees produced images with minimum background signal. Whereas, T1-weighted images with α of 75 degrees, and T2-weighted images with α of 105 degrees provided a good balance between visualizing the ultrasound focus and the background anatomy. The T1- and T2-weighted contrast was maintained in the Mag-ARFI images, as can be concluded from the dark CSF in the T1-weighted and bright CSF in the T2-weighted Mag- ARFI images.

[0065] Images 606 include T2-weighted TSE Mag-ARFI images acquired with a range of α values to change the relative intensity of the background anatomy. As α was increased, the background got brighter while the focal region became darker and smaller.

[0066] Fig. 7 shows images from two repetitions of phase-ARFI and Mag-ARFI acquisitions with the same scan duration. The focal region, located near the top of the brain, is visible in both phase-ARFI and mag-ARFI images. Both phase-ARFI and Mag- ARFI acquisitions were 4 min, 16 sec. long, where the Mag-ARFI scan time was extended by averaging. The ellipses on the left images show the FUS focus. Arrows point to breathing motion artifacts, which are much lower in the Mag-ARFI images. In both repetitions, the Mag-ARFI image has lower level of breathing motion artifacts which appear as streaks on the image. The difference of the two repetitions shows that Mag- ARFI is more consistent across acquisitions with a coefficient of variation (CV) of 5.8%, compared to phase-ARFI which had significantly higher artifact level with a CV of 20.1%.

[0067] It is to be understood that the invention is not limited in its application to the details of construction and the arrangement of components set forth in the following description or illustrated in the following drawings. The invention is capable of other embodiments and of being practiced or of being carried out in various ways. Also, it is to be understood that the phraseology and terminology used herein is for the purpose of -15- QB\155798.00444\94035423.1CWRU 2024‐4276 description and should not be regarded as limiting. The use of “including,” “comprising,” or “having” and variations thereof herein is meant to encompass the items listed thereafter and equivalents thereof as well as additional items. Unless specified or limited otherwise, the terms “mounted,” “connected,” “supported,” and “coupled” and variations thereof are used broadly and encompass both direct and indirect mountings, connections, supports, and couplings. Further, “connected” and “coupled” are not restricted to physical or mechanical connections or couplings.

[0068] The preceding discussion was presented to enable a person skilled in the art to make and use embodiments of the invention. Various modifications to the illustrated embodiments will be readily apparent to those skilled in the art, and the generic principles herein can be applied to other embodiments and applications without departing from embodiments of the invention. Thus, embodiments of the invention are not intended to be limited to embodiments shown but are to be accorded the widest scope consistent with the principles and features disclosed herein. The following detailed description is to be read with reference to the figures, in which like elements in different figures have like reference numerals. The figures, which are not necessarily to scale, depict selected embodiments and are not intended to limit the scope of embodiments of the invention. Skilled artisans will recognize the examples provided herein have many useful alternatives and fall within the scope of embodiments of the invention.

[0069] In some configurations, any suitable computer-readable media can be used for storing instructions for performing the functions and / or processes described herein. For example, in some configurations, computer-readable media can be transitory or non- transitory. For example, non-transitory computer-readable media can include media such as magnetic media (e.g., hard disks, floppy disks), optical media (e.g., compact discs, digital video discs, Blu-ray discs), semiconductor media (e.g., RAM, flash memory, EPROM, EEPROM), any suitable media that is not fleeting or devoid of any semblance of permanence during transmission, and / or any suitable tangible media. As another example, transitory computer-readable media can include signals on networks, in wires, conductors, optical fibers, circuits, or any suitable media that is fleeting and devoid of any semblance of permanence during transmission, and / or any suitable intangible media.

[0070] As used herein in the context of computer implementation, unless otherwise specified or limited, the terms “component,” “system,” “module,” “controller,” “framework,” and the like are intended to encompass part or all of computer-related -16- QB\155798.00444\94035423.1CWRU 2024‐4276 systems that include hardware, software, a combination of hardware and software, or software in execution. For example, a component may be, but is not limited to being, a processor device, a process being executed (or executable) by a processor device, an object, an executable, a thread of execution, a computer program, or a computer. By way of illustration, both an application running on a computer and the computer can be a component. One or more components (or system, module, and so on) may reside within a process or thread of execution, may be localized on one computer, may be distributed between two or more computers or other processor devices, or may be included within another component (or system, module, and so on).

[0071] In some implementations, devices or systems disclosed herein can be utilized or installed using methods embodying aspects of the disclosure. Correspondingly, description herein of particular features, capabilities, or intended purposes of a device or system is generally intended to inherently include disclosure of a method of using such features for the intended purposes, a method of implementing such capabilities, and a method of installing disclosed (or otherwise known) components to support these purposes or capabilities. Similarly, unless otherwise indicated or limited, discussion herein of any method of manufacturing or using a particular device or system, including installing the device or system, is intended to inherently include disclosure, as embodiments of the disclosure, of the utilized features and implemented capabilities of such device or system.

[0072] As used herein, the phrase “at least one of A, B, and C” means at least one of A, at least one of B, and / or at least one of C, or any one of A, B, or C or combination of A, B, or C. A, B, and C are elements of a list, and A, B, and C may be anything contained in the Specification.

[0073] The present disclosure has described one or more preferred embodiments, and it should be appreciated that many equivalents, alternatives, variations, and modifications, aside from those expressly stated, are possible and within the scope of the invention. -17- QB\155798.00444\94035423.1

Claims

CWRU 2024‐4276 CLAIMS 1. A system for magnetic resonance acoustic radiation force imaging (MR-ARFI), comprising: a magnetic resonance imaging (MRI) system configured to acquire MRI data from a subject; an ultrasound system configured to apply ultrasound energy to the subject; and at least one processor configured to: control the MRI system apply radio frequency (RF) pulses and magnetic field gradients coordinated with application of ultrasound energy from the ultrasound system to encode tissue displacement in the subject caused by the ultrasound energy in magnitude components of the MRI signals; and reconstruct the MRI signals into magnitude-contrast MR-ARFI (Mag-ARFI) images depicting the tissue displacement caused by the ultrasound energy.

2. The system of claim 1, wherein the pulse sequence includes a magnetization preparation module configured to convert phase shifts produced by tissue displacement caused by the ultrasound energy into changes in longitudinal magnetization.

3. The system of claim 2, wherein the pulse sequence further includes an imaging readout module configured to acquire multiple lines of k-space data for every ultrasound pulse applied.

4. The system of claim 2, wherein the sequence further includes a projection readout module configured to acquire data along three orthogonal axes to acquire projection data.

5. The system of claim 4, wherein the at least one processor is further configured to use the projection data to calculate a location of the ultrasound foci inside the subject.

6. The system of claim 1, wherein the at least one processor is further configured to reconstruct the Mag-ARFI images without using phase subtraction. -18- QB\155798.00444\94035423.1CWRU 2024‐4276 7. The system of claim 6, wherein the Mag-ARFI images depict both tissue displacement and anatomical details.

8. The system of claim 7, wherein the at least one processor is further configured to adjust a phase of a restoration radio frequency pulse in the pulse sequence to control relative intensity between tissue displacement and anatomical details in the Mag-ARFI images.

9. The system of claim 8, wherein the restoration radio frequency pulse has a phase configured to flip a component of transverse magnetization that is proportional to a sine of phase shifts induced by tissue displacement to a longitudinal axis.

10. A method comprising: operating an ultrasound (US) system to perform a US process on a patient; operating a magnetic resonance (MR) imaging system to acquire MR data from the patient using an MR imaging process that is performed during the US process; using magnitude data of the MR data, determining tissue displacements of the patient caused by the US process; and controlling the US processes using the parameters of the patient.

11. The method of claim 10, wherein the MR imaging process is configured to interact with the US process by performing a pulse sequence that converts phase shifts produced by tissue displacement to a change in longitudinal magnetization.

12. The method of claim 11, wherein the pulse sequence includes at least one of a projection sampling of k-space, a turbo spin echo (TSE) readout, an echo planar imaging (EPI) readout, a rapid gradient echo (RAGE) readout, or a steady-state free precession (SSFP) readout after a magnetization preparation pulse sequence.

13. The method of claim 11, further comprising performing a motion encoding gradient (MEG) and, wherein the US process includes a US pulse triggered with MEG pulses of the MEG process and coordinated with the pulse sequence. -19- QB\155798.00444\94035423.1CWRU 2024‐4276 14. The method of claim 13, wherein the US pulse is triggered with MEG pulses and coordinated with the pulse sequence placed before and after a 180 refocusing pulse of the pulse sequence.

15. The method of claim 13, wherein the pulse sequence includes a 90 degree pulse and a phase that is varied to tune relative amplitudes of focus and background anatomic image.

16. The method of claim 15, wherein the pulse sequence further comprises a spoiler gradient played after a magnetization preparation sequence of the pulse sequence to reduce or remove signal contributions from tissue that have not been displaced by the US pulse.

17. The method of claim 10, wherein the MR data is reconstructed into images are of background and focus or multiple mixtures, and further comprising calculating the tissue displacements from ratios of the images.

18. The method of claim 10, further comprising generating a report of tissue displacements caused by a transfer of momentum from an ultrasonic pulse / pressure field to the patient.

19. The method of claim 16, wherein the report includes at least one of: an estimate of tissue displacement created by analytically determining tissue displacements of the patient caused by the US process from the magnitudedata of the MR data; or an estimate of tissue displacement created by fitting the magnitude data of the MR data to a model.

20. The method of claim 19, wherein the MR data is acquired form MR signals measured across a range of restoration RF pulse phase values. -20- QB\155798.00444\94035423.1CWRU 2024‐4276 21. A non-transitory computer-readable medium storing instructions that, when executed by one or more processors, cause the one or more processors to perform operations for magnetic resonance acoustic radiation force imaging (MR-ARFI), the operations comprising: controlling a magnetic resonance imaging (MRI) system to perform a pulse sequence that includes applying radio frequency (RF) pulses and magnetic field gradients to generate MRI signals coordinated with an application of ultrasound energy from an ultrasound system; acquiring MR data that includes phase data and magnitude data; and using only the magnitude data, determining tissue displacement caused by the ultrasound energy.

22. The non-transitory computer-readable medium of claim 21, wherein the pulse sequence includes a magnetization preparation module configured to convert phase shifts produced by acoustic radiation force tissue displacement into changes in longitudinal magnetization.

23. The non-transitory computer-readable medium of claim 22, wherein the pulse sequence further includes an imaging readout module configured to acquire multiple lines of k-space data for every ultrasound pulse applied by the ultrasound system.

24. The non-transitory computer-readable medium of claim 21, further comprising reconstructing the MR data into images of the tissue without using phase subtraction.

25. The non-transitory computer-readable medium of claim 24, wherein the images depict both tissue displacement and anatomical tissue information.

26. The non-transitory computer-readable medium of claim 25, further comprising adjusting a phase of a restoration radio frequency pulse in the pulse sequence to control relative intensity between tissue displacement and anatomical tissue information in the images. -21- QB\155798.00444\94035423.1

Images