Magnetic resonance elastography (MRE) pulse sequence using magnetization preparation and imaging readouts

The magnetization prepared imaging sequence with k-space encoding addresses the challenge of achieving high-resolution MRE in shorter scan times, enhancing data acquisition efficiency and suitability for pediatric brain studies.

WO2025171228A1PCT designated stage Publication Date: 2025-08-14JOHNSON CURTIS LAURENCE +1
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Patent Information

Application Number
PCT/US2025/014960
Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
Priority Date
2024-02-08
Filing Date
2025-02-07
Publication Date
2025-08-14

AI Technical Summary

Technical Problem

Existing magnetic resonance elastography (MRE) techniques face limitations in achieving high resolution and short scan times, particularly in pediatric brain studies, due to the inefficiencies of single-shot spin-echo echo planar imaging and multishot sequences that increase scan time and require costly motion-encoding gradients.

Method used

A method and system using a magnetization prepared imaging sequence with k-space encoding, incorporating a magnetization preparation block and interleaved imaging readout blocks to efficiently sample k-space data, allowing for higher resolution and shorter scan times by decoupling motion encoding from imaging readouts.

Benefits of technology

This approach enables faster data acquisition with improved resolution and reduced scan time, facilitating clinical applications, especially in uncooperative populations, by utilizing a magnetization prepared imaging sequence with rapid k-space encoding and interleaved shots.

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Abstract

A method for generating images indicative of mechanical properties of a subject tissue which is divided into a plurality of slabs each having a plurality of slices, includes performing an MRE scan on the subject tissue with an MRI system. MRE data related to the subject tissue is obtained and processed via a control device. A controller performs an MRE magnetization prepared imaging sequence comprising elastographic magnetization prepared imaging with k-space encoding in accordance with a plurality of scan parameters. The sequence includes: (a) performing a magnetization preparation block, (b) applying magnetic field gradients to spoil residual signal and minimize image artifacts, (c) performing an imaging readout block, with the plurality of scan parameters including sampling each k xy plane using a series of interleaved shots, (d) acquiring k-space data based on steps (a)-(c), and (e) applying an image reconstruction algorithm, thereby generating the images.
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Description

[0001] MAGNETIC RESONANCE ELASTOGRAPHY (MRE) PULSE SEQUENCE USING MAGNETIZATION PREPARATION AND IMAGING READOUTS

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS

[0003] This application is related to and claims priority to United States Provisional Application No. 63 / 551,142, filed February 8, 2024, the content of which is incorporated herein by reference in its entirety for all purposes.

[0004] REFERENCE TO U.S. GOVERNMENT SUPPORT

[0005] This invention was made with government support under Grant Nos. R01AG058853A and R01EB027577A, awarded by the National Institutes of Health, with other funding information U01NS112120, awarded by the National Institutes of Health. The government has certain rights in the invention.

[0006] FIELD OF THE INVENTION

[0007] Aspects of the invention relate generally to magnetic resonance elastography (MRE) and magnetic resonance imaging (MRI) systems. More particularly, aspects of the invention relate to methods and systems for generating images indicative of mechanical properties of a subject tissue.

[0008] BACKGROUND OF THE INVENTION

[0009] The mechanical properties of tissues (e.g. human brain tissue) can be indicative of overall health, including any underlying medical conditions, and as such have been used in many diagnostic capacities. Magnetic resonance elastography (MRE) is a non- invasive, in vivo, magnetic resonance imaging (MRI) technique which includes a phasecontrast MRI method to quantitatively image the mechanical properties (e.g., stiffness) of tissues by imaging a displacement of subject tissue in response to mechanical actuation. Namely, MRE uses mechanical actuation to cause micron-level displacements of tissue, which are imaged using motion encoding gradients. These MRE-derived mechanical properties can have applications in neurosurgery and neurology as well as provide insight into microstructural changes in the tissue that may be indicative of conditions related to normal brain structure and function as well as aging and disease progression.

[0010] There is a need for high resolution and high signal-to-noise ratio (SNR) MRE displacement data for enabling the use of advanced inversion algorithms to accurately recover highly heterogeneous mechanical properties. It is also important for this data to be collected in a short scan time. Particularly, in pediatric brain I RE studies, the need for short scan times to improve success in potentially uncooperative populations has become more apparent.

[0011] Single-shot spin-echo echo planar imaging (EPI) is the most common brain MRE imaging sequence which generates robust data in relatively short scan times. However, this technique is limited in resolution and flexibility. Multishot imaging sequences increase achievable spatial resolution by reducing readout time to avoid quantitative errors from distortion, but said sequences also increase scan time through the need to excite the same volume multiple times. Further, multishot sequences proposing full 3D encoding allows for higher parallel imaging acceleration factors with non-Cartesian k space sampling, but maximum efficiency and performance of such sequences are limited by the need to include large MRE motion-encoding gradients with every data readout, which is particularly costly for 3D gradient-echo based sequences that need to have increased minimum echo times and repetition times to accommodate the gradients.

[0012] Therefore, there remains a desire for improvements in systems and methods for generating images of subject tissue using an MRI system, particularly for efficiently generating images of subject tissue with higher resolution and shorter scan times.

[0013] SUMMARY OF THE INVENTION

[0014] According to an aspect of the invention, a method for generating images indicative of mechanical properties of a subject tissue using a magnetic resonance imaging (MRI) system is disclosed. The method comprises performing a magnetic resonance elastography (MRE) scan on the subject tissue with the MRI system and obtaining and processing MRE data related to the subject tissue via a control device coupled to the MRI system. The subject tissue is divided into a plurality of slabs that each include a plurality of slices. The control device is coupled to the MRI system and includes a controller configured to perform an MRE magnetization prepared imaging sequence. The imaging sequence comprises elastographic magnetization prepared imaging with k-space encoding in accordance with machine readable instructions stored in a digital memory. The instructions includes a plurality of scan parameters. The MRE magnetization prepared imaging sequence includes: (a) performing a magnetization preparation block, wherein successive radio frequency (RF) pulses are applied to the subject tissue in cooperation with applying a series of motion encoding gradients (MEGs) to the plurality of slabs, (b) applying magnetic field gradients to spoil residual signal and minimize image artifacts, (c) after performing step (a) and (b), performing an imaging readout block, wherein the plurality of scan parameters include sampling each kxy plane using a series of interleaved shots, (d) acquiring two-dimensional (2D) or three-dimensional (3D) k-space data based on steps (a), (b), and (c), and (e) applying an image reconstruction algorithm, thereby generating the images.

[0015] According to another aspect of the invention, a magnetic resonance imaging (MRI) system for generating images indicative of mechanical properties of a subject tissue is disclosed. The system includes a magnet system configured to generate a polarizing magnetic field to the subject tissue. The system also has a plurality of gradient coils configured to apply a magnetic field gradient to the polarizing magnetic field and a radio frequency (RF) system configured to apply an excitation field to the subject tissue. The system includes a driver configured to deliver a stress to the subject for propagating mechanical waves through the subject tissue. A control device is coupled to the MRI system. The control device is coupled to the MRI system and includes a controller configured to perform an MRE magnetization prepared imaging sequence (e.g., Elastographic Magnetization Prepared Imaging with Rapid Encoding, EMPIRE™). The imaging sequence comprises elastographic magnetization prepared imaging with k-space encoding in accordance with machine readable instructions stored in a digital memory. The instructions includes a plurality of scan parameters. The MRE magnetization prepared imaging sequence includes: (a) performing a magnetization preparation block, wherein successive radio frequency (RF) pulses are applied to the subject tissue in cooperation with applying a series of motion encoding gradients (MEGs) to the plurality of slabs, (b) applying magnetic field gradients to spoil residual signal and minimize image artifacts, (c) after performing step (a) and (b), performing an imaging readout block, wherein the plurality of scan parameters include sampling each kxy plane using a series of interleaved shots, (d) acquiring two-dimensional (2D) or three-dimensional (3D) k-space data based on steps (a), (b), and (c), and (e) applying an image reconstruction algorithm, thereby generating the images.

[0016] BRIEF DESCRIPTION OF THE DRAWINGS

[0017] The foregoing summary and the following description will be better appreciated and understood in conjunction with the non-limiting examples illustrated in the attached drawing figures, of which:

[0018] FIG. 1 depicts a schematic diagram of an MRI system in accordance with aspects of the invention; FIG. 2 depicts an exemplary method for generating images indicative of mechanical properties of a subject tissue using the MRI system of FIG. 1 in accordance with aspects of the invention;

[0019] FIG. 3A depicts an exemplary embodiment of I RE magnetization prepared imaging sequence in accordance with aspects of the invention;

[0020] FIG. 3B-3C depicts enlarged portions of FIG. 3A;

[0021] FIGS. 4A-4C depict results from validation testing of the system of FIG. 1 and method of FIG. 2;

[0022] FIG. 5 depicts results from tests performed on four human subjects in accordance with validation testing of the system of FIG. 1 and method of FIG. 2;

[0023] FIG. 6 depict results from tests performed on undersampled data in accordance with validation testing of the system of FIG. 1 and method of FIG. 2; and

[0024] FIG. 7 depict a comparison of selected images of a subject tissue generated by the method of FIG. 2 and images of the same subject tissue generated in accordance with prior art.

[0025] DETAILED DESCRIPTION OF THE INVENTION

[0026] Although the invention is illustrated and described herein with reference to specific embodiments, the invention is not intended to be limited to the details shown. Rather, various modifications may be made in the details within the scope and range of equivalents of the claims and without departing from the invention. Additionally, various forms and embodiments of the invention are illustrated in the figures. It will be appreciated that the combination and arrangement of some or all features of any of the embodiments with other embodiments is specifically contemplated herein. Accordingly, this detailed disclosure expressly includes the specific embodiments illustrated herein, combinations and sub-combinations of features of the illustrated embodiments, and variations of the illustrated embodiments.

[0027] In the following detailed description, numerous specific details are set forth by way of examples in order to provide a thorough understanding of the relevant design features. However, it should be apparent to those skilled in the art that the present design features may be practiced without such details. In other instances, well known methods, procedures, components, and circuitry have been described at a relatively high-level, without detail, in order to avoid unnecessarily obscuring aspects of the present design.

[0028] In general, aspects of the invention relate to systems and methods for generating a map indicative of mechanical properties of a subject tissue using a magnetic resonance imaging (MRI) system. The systems and methods described can include an ability to provide fast imaging of displacements estimation in shorter scan times by using only a single motion encoding block within a magnetization preparation step followed by an imaging readout block, including but not limited to, a rapid imaging readout block with a fast imaging sequence, such as a three-dimensional gradient echo sequence. Advantages of embodiments of the claimed invention includes permitting a more efficient data sampling schedule, thereby (1) reducing the overall time needed to acquire MRE data (e.g. MRE data that is useful for clinical adoption and applications on children) and (2) allow for higher resolution data to be achieved through additional data sampling in the same amount of time.

[0029] Referring to FIG. 1, a schematic representation is provided of an exemplary magnetic resonance imaging (MRI) system for generating images or a reconstruction indicative of a subject tissue's mechanical properties. In general, an exemplary embodiment of the MRI system, such as MRI system 1000, includes a magnet system 110, a plurality of gradient coils 120, a radio frequency (RF) system 130, a driver 140, and a control device 160.

[0030] In general, the magnet system 110 is configured to generate a polarizing magnetic field to the subject tissue 152 of patient 150. The plurality of plurality of gradient coils 120 are configured to apply a magnetic field gradient to the polarizing magnetic field generated by the magnet system 110. The RF system 130 is configured to apply an excitation field to the subject tissue 152 (e.g. brain of patient 150). The driver 140 is configured to deliver a stress to the subject 150 for propagating mechanical waves through the subject tissue 152. In an exemplary embodiment, the subject tissue 152 is divided into a plurality of slabs, or volume of excited tissue from which MRE data is acquired, wherein each slab includes a plurality of slices. One skilled in the art would understand from the description herein that number and size of slabs and slices are chosen based on the desired or predetermined imaging coverage and resolution with respect to subject tissue 152. In one non-limiting example, the plurality of slabs and plurality of slices include ten slabs of eight 2.0 mm thick slices and TR / TE = 1800 / 73 ms. See e.g., Johnson CL et. aL, 3d multislab, multishot acquisition for fast, whole-brain mr elastography with high signal-to-noise efficiency. Magnetic resonance in medicine 2014; 71 :477-485. Slabs may be interleaved and overlapped (e.g., by 25%) to reduce slab boundary artifacts. Id.

[0031] The control device 160 is coupled to the MRI system 1000. In an exemplary embodiment, the control device 160 has a controller configured to perform an MRE magnetization prepared imaging sequence. In a non-limiting example, the MRE magnetization prepared imaging sequence includes an elastographic magnetization prepared imaging with k-space encoding, such as rapid k-space encoding (i.e., EMPIRE™), in accordance with machine readable instructions stored in a digital memory. The instructions include a plurality of scan parameters.

[0032] In an exemplary embodiment, as shown in FIGS. 3A-3C, the MRE magnetization prepared imaging sequence includes performing a magnetization preparation block 3000 (FIGS. 3A, 3B) wherein successive radio frequency (RF) pulses are applied to the subject tissue 152 in cooperation with applying a series of motion encoding gradients (MEGs) to the plurality of slabs. The series of motion encoding gradients (Gx, Gy, and Gz), as shown in FIG. 3B, refer to the direction of the magnetic field as applied to the subject tissue 152 along the three spatial gradients (along the x, y, and z axes) during the exemplary MRE magnetization prepared imaging sequence described herein. For example, the motion encoding gradient Gx refers to a spatial gradient in the magnetic field which varies in the x direction (e.g., left to right). Magnetic field gradients are applied to spoil residual signal and minimize image artifact. Subsequently, an imaging readout block 4000 (FIGS. 3A, 3C) is performed in which the plurality of scan parameters include sampling each kxyplane using a series of interleaved shots. A two- dimensional (2D) or three-dimensional (3D) k-space data is then generated and an image reconstruction algorithm is applied, thereby generating the desired images indicative of the subject tissue's 152 mechanical properties.

[0033] Additional details of the plurality of operations of system 1000 will now be discussed below in the context of method 2000.

[0034] Turning now to FIGS. 1 and 2, an exemplary method 2000 of generating images indicative of mechanical properties of a subject tissue using a magnetic resonance imaging (MRI) system, such as the MRI system 1000, is disclosed. Generally, method 2000 includes step 200 of performing a magnetic resonance elastography (MRE) scan on the subject tissue 152 with the MRI system 1000 and step 300 of obtaining and processing MRE data related to the subject tissue 152 via a control device 160 coupled to the MRI system 1000. Method 2000 includes step 310 of performing an MRE magnetization prepared imaging sequence, such as an elastographic magnetization prepared imaging with k-space encoding, including but not limited to rapid k-space encoding, (i.e., EMPIRE™), in accordance with machine readable instructions stored in a digital memory.

[0035] This MRE magnetization prepared imaging sequence (i.e., EMPIRE™) includes step 320 of performing a magnetization preparation block 3000 (FIG. 3B) by applying successive radio frequency (RF) pulses are applied to the subject tissue 152 divided into a plurality of slabs, in cooperation with applying a series of motion encoding gradients (MEGs) to the plurality of slabs; step 330 of applying magnetic field gradients to spoil residual signal and minimize image artifacts; step 340 of performing an imaging readout block 4000 (FIG. 3C) and a plurality of scan parameters include sampling each kxyplane using a series of interleaved shots; step 350 of acquiring two- dimensional (2D) or three-dimensional (3D) k-space data based on steps 320 to 340; and step 360 of applying an image reconstruction algorithm, thereby generating the desired images indicative of mechanical properties of the subject tissue 152.

[0036] In an exemplary embodiment of step 200, performing the MRE scan on the subject tissue 152 with the MRI system 1000 includes the one or more of the following sub-steps of: applying a polarizing magnetic field to the subject tissue 152; irradiating the subject tissue 152 with a radio frequency (RF) excitation field for producing transverse magnetization in spins in the subject tissue 152; applying a magnetic field gradient to the spins which alternates in polarity; and applying a stress to the subject tissue 152 in cooperation with alternation of the magnetic field gradient polarity, for propagating mechanical waves through the subject tissue 152.

[0037] In a non-limiting example, the application of a polarizing magnetic field to the subject tissue 152 is performed by the magnet system 110 of MRI system 1000. Additionally or optionally, the irradiation of the subject tissue 152 with the RF excitation field for producing transverse magnetization in spins in the subject tissue 152 is performed by the RF system 130 of MRI system 1000. Additionally or optionally, the application of a magnetic field gradient to the spins which alternates in polarity is performed by the plurality of gradient coils 120 of MRI system 1000. Additionally or optionally, the application of a stress to the subject tissue 152 in cooperation with alternation of the magnetic field gradient polarity for propagating mechanical waves through the subject tissue 152 is performed by the driver 140 of MRI system 1000.

[0038] In an exemplary embodiment of step 300, the control device 160 is coupled to the MRI system 1000 and the control device 160 obtains as well as processes MRE data related to the subject tissue 152.

[0039] In a non-limiting example, step 300 further comprises step 310 of performing an MRE magnetization prepared imaging sequence, such as the elastographic magnetization prepared imaging with k-space encoding, including but not limited to rapid k-space encoding, (i.e., EMPIRE™) in accordance with machine readable instructions stored in a digital memory and via a controller of the control device 160. The instructions can include a plurality of scan parameters. Additionally or optionally, step 300 further comprises performing a stack-of-spiral (SOSP) gradient-echo imaging sequence via the controller.

[0040] In an exemplary embodiment, method 2000 comprising successively repeating steps 320 to 340, such that, for example, a first magnetization preparation (MagPrep) sequence building block 3000a is applied followed by a train of imaging readout blocks 4000. A pause is applied between the imaging readout blocks 4000 and a second MagPrep sequence building block 3000b in order to achieve the desired repetition time (TR). The driver 140 of MRI system 1000 is triggered after the train of imaging readout blocks 4000 so applied motion can reach steady-state before it is encoded.

[0041] In a non-limiting example, step 320 includes performing a MagPrep block 3000 (FIG. 3B) by applying successive radio frequency (RF) pulses to the subject tissue 152 divided into a plurality of slabs, in cooperation with applying a series of motion encoding gradients (MEGs) to the plurality of slabs. In an exemplary embodiment, the MRE data is obtained (e.g., via method 2000) with reduced repetition or scan duration with performance of step 320, than when MRE data is obtained without performance of step 320. In this way, improvements in methods 2000 for generating images of subject tissue 152 using an MRI system 1000 are achieved, particularly for efficiently generating images of subject tissue 152 with higher resolution and shorter scan times.

[0042] In an exemplary embodiment, the magnetization preparation block 3000 includes a 90ox-180°y-90°-x slab selective RF pulse train and the MEGs are applied to encode MRE displacements to the phase of the magnetization. One skilled in the art would understand from the description therein that the application of RF pulses during step 320 may vary in terms of slice-selectivity and further is not required to match the choice of RF pulses performed during step 340 of applying the imaging readout block 4000 (e.g., slab-selective RF pulses in the MagPrep block 3000 combined with non- selective pulses in the imaging readout block 4000). Further, FIGS. 3A-3C illustrate that 1-2-1 flow-compensated MEGs are applied bilaterally around the 180°ypulse to maximize encoding sensitivity, but one skilled in the art would understand from the description herein that the specific length of MEGs and timing between said MEGs is determined by the frequency of applied motion and any use of fractional encoding, for example.

[0043] Still further, in an exemplary embodiment, the MEGs in the MagPrep block 300 are synchronized to mechanical excitation applied by the external driver 140. In a nonlimiting example, mechanical excitation or stress is not applied to the subject tissue 152 during performance of step 330. Thus, mechanical vibration is only required while the MEGs are played out by the scanner during step 320, for example. Further, in a conventional I RE sequence, MEGs are played out at each and every imaging TR with the MRE excitation continuously active during the acquisition. In contrast, method 2000 facilitates an improvement in efficiency, since the MEGs are played out relatively fewer times compared to the duration of the imaging readout (step 340), mechanical vibration (e.g. by the driver 140) can be switched off during the imaging readout step 340, which could prevent imaging gradients from contributing to motion encoding and unwanted phase. In an exemplary embodiment, the MRE excitation is restarted at the end of every image encoding block 4000 to allow for the dissipation of transient motion and onset of steady-state motion prior to the motion encoding with another successive MagPrep block 3000. In practice, this means that the synchronization trigger is played at the end of each image encoding block 4000 with steady-state being achieved during the TR pause.

[0044] In an exemplary embodiment, method 2000 comprises step 330 of applying magnetic field gradients to spoil residual signal and minimize image artifacts. As best shown in FIG. 3B, step 330 of applying magnetic field gradients comprise applying a gradient RF pulse in the MagPrep block 3000 as well as a mirrored gradient RF pulse in the imaging readout block 4000. Thus, these magnetic field gradient pulses form a crusher pair which eliminate contribution from unprepared magnetization, i.e., unprepared magnetization crushers (UMCs), thereby avoiding both magnitude and phase errors in the reconstructed images generated in step 360.

[0045] In an exemplary embodiment, method 2000 comprises step 340 performing an imaging readout block 4000. In an exemplary embodiment, the imaging readout block 4000 includes a rapid imaging readout block which achieves an echo time / repetition time (TE / TR) for each GRE readout = 1.96 / 9.6 ms, which presents an advantage over existing imaging methods which uses an equivalent TR > 100 ms. After step 320 of performing the MagPrep block 3000, all accessible longitudinal magnetization in the imaging volume has the synchronized MRE motion encoded in the phase of the object. Additionally or optionally, forming an image from this magnetization can use any 2D or 3D sequence without further MRE gradients. In an exemplary embodiment, a 3D gradient echo (GRE) acquisition is applied, where longitudinal magnetization is accessed with low flip angle excitation pulses for k-space sampling and then spoiled prior to the next excitation. The short imaging readout blocks 4000 are played in series following the MagPrep block 3000 to acquire 3D k-space data for example (step 350). Additionally or optionally, as best shown in FIG. 3A, after a train of imaging readout blocks 4000a is sampled, a pause is included to achieve a desired TR, followed by another MagPrep block 3000b and imaging readouts 4000b to complete k-space sampling (step 350), for example, or encode the next repetition required for I RE.

[0046] Additionally or optionally, step 340 includes applying a plurality of scan parameters comprising sampling each kxyplane using a series of interleaved shots. In an exemplary embodiment, the series of interleaved shots comprises variable-density or constant-density spiral interleaves. In another exemplary embodiment, the series of interleaved shots comprises a Periodically Rotated Overlapping Parallel Lines with Enhanced Reconstruction (PROPELLER) readout trajectory, an Echo Planar Imaging (EPI) readout trajectory, or a radial readout trajectory. In general, the series of interleaved shots allows for significant undersampling without loss in quality of the images or reconstruction, ultimately accelerating MRE acquisitions, and achieving improved performance to a conventional EPI MRE sequence in just over one minute of scan time. Thus, as shown in FIGS. 3A-3C, the MRE magnetization prepared imaging sequence is implemented in a full pulse sequence with a 3D stack-of-spirals gradient echo (GRE) acquisition following MagPrep block 3000 for performing MRE scans of the subject tissue 152, such as the brain. In an exemplary embodiment, the plurality of scan parameters included : 240x240x120 mm3field of view (FOV), 96x96x48 matrix size, 2.5 mm isotropic resolution, echo time / repetition time (TE / TR) for each GRE readout = 1.96 / 9.6 ms, total TR = 1.323 s (time between MagPrep blocks 3000, including a pause of 800 ms after readout), 8 designed constant-density, interleaved spiral shots, spiral readout duration = 5 ms. All kzencodes (i.e. for a singlexyinplane shot) are acquired in centric order following a single motion encoding MagPrep block 3000; encoding is repeated to sample allxyspirals.

[0047] In an exemplary embodiment, method 2000 includes step 360 of applying an image reconstruction algorithm, thereby generating the desired images indicative of mechanical properties of the subject tissue 152. In a non-limiting example, the image reconstruction algorithm comprises applying a conjugate gradient sensitivity encoding algorithm and a Fourier transform to the acquired k-space data (e.g., in step 350). In another nonOlimiting example, the image reconstruction algorithm comprises applying an iterative image reconstruction algorithm or a direct reconstruction algorithm.

[0048] Additionally or optionally, method 2000 includes a further step of estimating, by the controller of control device 160, displacement fields in the subject tissue 152 based on the reconstruction or the images, and generating a map (e.g., a stiffness map) indicative of the subject tissue's 152 mechanical properties via an inversion algorithm. In a non-limiting example, the inversion algorithm comprises a non-linear inversion (NLI) algorithm. EXAMPLE

[0049] The co-inventors assessed the exemplary systems and methods as disclosed herein in a clinical or laboratory setting, to validate feasibility and functionality of the components of the subject systems, as well as verified any updates or improvements made.

[0050] In general, the inventive methods and systems described herein is different from conventional MRE imaging sequences, at least by incorporating motion encoding into a magnetization preparation step thereby, effectively decoupling motion encoding from imaging readouts. Magnetization preparation involves exciting spins, encoding the desired contrast, and then storing the encoded magnetization longitudinally. This magnetization can then be excited and sampled in a train of imaging readouts while experiencing Ti signal decay that is slower than T2 decay. Magnetization preparation has previously been used in diffusion MRI, which uses similarly large encoding gradients, and layer fMRI, with the need for fast imaging while achieving the necessary contrast. However, the inventive methods and systems described herein involve magnetization preparation, which is generally uncommon for phase-based contrasts.

[0051] In particular, the inventive methods and systems described herein comprises an MRE magnetization prepared imaging sequence combining motion sensitized magnetization preparation with batched, fast 3D stack-of-spiral gradient echo readouts called elastographic magnetization-prepared imaging with rapid encoding (EMPIRE™). Generally, the assessments (e.g., for the feasibility of a MRE magnetization prepared imaging sequence) performed by the co-inventors involved (1) analyzing the stability of signal phase across the readout train, and the recovery of high quality displacement fields and mechanical property maps with EMPIRE™ as well as (2) comparing the performance of EMPIRE™ with a standard or conventional echo planar imaging (EPI) magnetic resonance elastography (MRE) sequence to assess the ability to significantly accelerate the scan while achieving comparable image quality to existing sequences.

[0052] Theory

[0053] Magnetization Preparation Block

[0054] The inventive methods and systems described herein encompasses a magnetization preparation (MagPrep) sequence building block 3000 to prepare the longitudinal magnetization prior to an imaging readout 4000, as illustrated in general by FIGS. 3A-3C. FIG. 3A shows MagPrep blocks 3000 which incorporate motion encoding are followed by a train of imaging readout blocks for k-space encoding (e.g., rapid k space encoding), with a pause to achieve the desired repetition time (TR) before the next MagPrep blocks 3000. The external actuator 140 is triggered after the readout train so applied motion can reach steady-state before it is encoded. As best shown in FIG. 3B, the MagPrep block 3000 includes motion encoding gradients and an unprepared magnetization crusher (UMC). Further, as best shown in FIG. 3C, imaging readout block 4000 includes a low flip angle hard excitation pulse, UMC gradient to pair, and gradients for kxyand kzencoding, followed by gradients to spoil magnetization before the next readout block.

[0055] In an exemplary embodiment, the MagPrep block 3000 consists of a 90°x-180°y- 90°-xslab selective RF pulse train with motion encoding gradients (MEGs) added to encode MRE displacements to the phase of the magnetization. See e.g., Brittain JH et. aL, "Coronary angiography with magnetization-prepared t2 contrast." Magnetic Resonance in Medicine 1995; 33:689-696. Theoretically, the specific choice of RF pulses in the MagPrep block 3000 is flexible and does not need to match the choice of RF pulses in the imaging readout, specifically in terms of slice-selectivity, where soft RF pulses in the MagPrep block could be combined with hard pulses in the imaging readout. Here, 1-2-1 flow-compensated MEGs are applied bilaterally around the 180°ypulse to maximize encoding sensitivity. The specific length of gradients and timing between them is determined by the frequency of applied motion and any use of fractional encoding. See e.g., Rump J, et. aL, "Fractional encoding of harmonic motions in MR elastography." Magnetic Resonance in Medicine 2007; 57:388-395.

[0056] Non-Limiting Example of Imaging Acquisition: Rapid Imaging Acquisition

[0057] After the MagPrep block 3000 is played, all accessible longitudinal magnetization in the imaging volume has the synchronized MRE motion encoded in the phase of the object. Forming an image from this magnetization can use any 2D or 3D sequence without further MRE gradients. In an exemplary embodiment, a 3D gradient echo (GRE) acquisition is used, where longitudinal magnetization is accessed with low flip angle excitation pulses for k-space sampling and then spoiled prior to the next excitation. These short imaging readout blocks 4000 are played in series following the MagPrep block to sample 3D k space. After a train of imaging readout blocks 4000 is sampled, a pause is included to achieve a desired TR, followed by another MagPrep block 3000 and imaging readouts to either complete k-space sampling or encode the next repetition required for MRE.

[0058] As will be discussed below, known contrast equations to predict the signal evolution across the train of imaging readout blocks 4000 are similar to those of other magnetization prepared applications, including MR Multitasking and Tz-prepared multiecho FLASH. See e.g., Ma S. et. aL, "Three-dimensional simultaneous brain tl, t2, and adc mapping with mr multitasking." Magnetic Resonance in Medicine 2020; 84:72-88 and Pfaffenrot V. et. al., "Laminar fmri using t2-prepared multi-echo flash." NeuroImage 2021; 236:118163, respectively. The relevant signal across the series of imaging readouts is largely governed by Ti recovery after the MagPrep block 3000 and the amount of longitudinal magnetization that is tipped into the transverse plane is then spoiled away and thus lost for subsequent readouts. This implies that both the number and length of imaging readouts and the flip angle control the loss of signal intensity with subsequent GRE readouts after the MagPrep block 3000 is played out. There is also T2*decay that occurs within each imaging readout block after excitation before data is sampled. Note that the EMPIRE™ signal model only describes loss of signal magnitude, but the phase should be preserved across the imaging readouts.

[0059] EMPIRE™ Signal Equations

[0060] Equations to compute the magnitude signal model for the EMPIRE™ GRE readouts are listed below. Pertinent variables include: a as the flip angle of the 3D GRE readouts, TRreadout as the repetition time of a single readout block, TEMagPrep is the echo time of the MagPrep block 3000 taking into account T decay across the 90x-180y-90-xRF train, TEreadout is the echo time of the readout block accounting for T2’ decay in each GRE readout, and Ts describes the time between the final 90 degree pulse of the MagPrep block 3000 and the beginning of the readout train incorporating the final transverse magnetization spoiler.

[0061] With these variables defined, the following equations can be expressed to describe the evolution of magnetization across the EMPIRE™ encoding and readout. Ei describes the transverse signal evolution across the spin echo in the MagPrep block 3000. Es describes the longitudinal signal evolution between the final 90 degree pulse of the MagPrep block and the beginning of the GRE readout. E2 describes the longitudinal signal evolution during each GRE readout. E2. describes the transverse signal evolution during an individual GRE readout. Eshot describes the Ti recovery.

[0062] With the variables above defined, recursive equations for the longitudinal and transverse magnetizations at the respective echo times can be expressed for each readout during the 3D GRE readout train. represents the system at equilibrium prior to the experiment and is unity. M n) represents the longitudinal magnetization at the beginning of the n-th GRE readout after the magnetization preparation block. Mxy(n) represents the transverse magnetization at the echo of the nth GRE readout.

[0063] If Es and Ei are approximately equal and N is large enough to approach steady state, then the unprepared magnetization can be rewritten using the steady-state expression for longitudinal magnetization for a spoiled GRE sequence.

[0064] The transverse magnetization can then be obtained for an arbitrary echo n in the readout train. The unprepared magnetization term is assumed to be zero via the use of UMCs of reasonable amplitude crushing the unprepared magnetization.

[0065] Unprepared Magnetization Crushers (UMC)

[0066] Motion sensitized pulse sequences that use MagPrep 3000 are complicated by the recovery of unprepared magnetization via Ti recovery. In an exemplary embodiment, EMPIRE™ uses a gradient pulse in the MagPrep block 3000 as well as a mirrored gradient pulse in the readout sequences 4000, illustrated in FIGS. 3A-3C, to crush any recovered magnetization that was not motion encoded in the preparation block. Conceptually, these gradient pulses form a crusher pair analogous to free induction decay (FID) crushers used in spin-echo pulse sequences to eliminate contribution from unprepared magnetization. These crusher gradients have been demonstrated as helpful to magnetization-prepared, motion-sensitized sequences such as diffusion-prepared Turbo Spin Echo (TSE). See e.g., Van AT. et. aL, "Analysis of phase error effects in multishot diffusion-prepared turbo spin echo imaging." Quantitative imaging in medicine and surgery 2017; 7:238-250. In other contexts, they have been described as "magnitude stabilizers" as motion-sensitized sequences without these pulses often demonstrate phase cancellation that cause banding-like artifacts in the magnitude images that are "stabilized" with the crusher pair. For clarity, the unprepared magnetization crushers (UMCs) of the inventive methods and systems as described herein capture their impact in avoiding both magnitude and phase errors in the reconstructed images.

[0067] MRE Excitation and Synchronization

[0068] The motion encoding gradients in the EMPIRE™ MagPrep block are synchronized to mechanical excitation applied by a external driver. Notably, mechanical vibration is only required while the MEGs are played out by the scanner. In a conventional MRE sequence, MEGs are played out at each and every imaging TR with the MRE excitation continuously active during the acquisition. In an exemplary embodiment of EMPIRE™, since the MEGs are played out relatively fewer times compared to the duration of the rapid imaging readout 4000, mechanical vibration can be switched off during the imaging readout 4000, which could prevent imaging gradients from contributing to motion encoding and unwanted phase. The MRE excitation is restarted at the end of every rapid image encoding block 4000 to allow for the dissipation of transient motion and onset of steady-state motion prior to the motion encoding with an EMPIRE™ MagPrep block. In practice, this means that the synchronization trigger is played at the end of each rapid image encoding block 4000 with steady-state achieved during the TR pause.

[0069] Materials and Methods

[0070] Sequence Implementation and Image Reconstruction

[0071] The EMPIRE™ motion encoding strategy was implemented in a full pulse sequence as shown in FIGS. 3A-3C with a 3D stack-of-spirals gradient echo (GRE) acquisition following MagPrep 3000 for performing MRE scans of the subject tissue 152, such as the brain. In an exemplary embodiment, the imaging or scanning parameters included : 240x240x120 mm3field of view (FOV), 96x96x48 matrix size, 2.5 mm isotropic resolution, echo time / repetition time (TE / TR) for each GRE readout = 1.96 / 9.6 ms, total TR = 1.323 s (time between MagPrep blocks 3000, including a pause of 800 ms after readout), 8 designed constant-density, interleaved spiral shots, spiral readout duration = 5 ms. All kz encodes (i.e. for a single feyin-plane shot) are acquired in centric order following a single motion encoding MagPrep block 3000; encoding is repeated to sample all k / spirals. See e.g., Glover GH. "Simple analytic spiral K space algorithm." Magnetic Resonance in Medicine 1999; 42:412-415.

[0072] Acquired data was iteratively reconstructed via a conjugate gradient sensitivity encoding (SENSE) algorithm with non-uniform fast Fourier transform (NUFFT) penalized weighted least squares algorithm implemented in MATLAB with quadratic regularization. See e.g., Pruessmann KP et. aL, "Advances in sensitivity encoding with arbitrary k space trajectories." Magnetic Resonance in Medicine 2001; 461 :638-651 and Sutton BP et. aL, "Fast, iterative image reconstruction for MRI in the presence of field inhomo-geneities." IEEE Transactions on Medical Imaging 2003; 22: 178-188.

[0073] Given the very short spiral readouts used, no correction for magnetic field inhomogeneity was applied. Incorporation of scan acceleration via SENSE parallel imaging was implemented by undersamplingxyspirals. In an exemplary embodiment, a reduction factor Rx= 2 means sampling only every other designed in-planexyspiral. Given that all samples of a given kxyspiral are acquired after a single MagPrep motion encoding, undersampling means reducing total number of encodings in this implementation of EMPIRE™. No undersampling in kzwas implemented in the acquisition and SENSE reconstruction.

[0074] The images recovered with this sequence carry the MRE motion encoding in their phase, but the magnitude exhibits little contrast. To facilitate anatomical localization and further analysis of MRE data, the first image in the series incorporates an "overlay" image with the same k-space readouts but without the MagPrep motion encoding block, thereby leading to better image contrast. This fully-sampled individual image is also used to estimate coil sensitivity maps for SENSE reconstruction, removing the need for any auxiliary pre-scans. The overlay image was also used in place of dummy acquisitions to reduce steady-state effects by disrupting the rest state of the spin system prior to the acquisition.

[0075] MRE Acquisition, Processing, and Inversion

[0076] In an exemplary embodiment, when the subject tissue 152 is brain, motion was applied to the head using an acoustic driver (as manufactured by Resoundant, Inc. of Rochester, Minnesota) with a pneumatic head pillow. MEGs in the MagPrep block 3000 encoded motion at 50 Hz via 70 mT / m MRE gradients. Vibration was only applied during the shot pause between shots and during the EMPIRE™ motion encoding block, but not during the imaging readout. MEGs were applied separately in three orthogonal directions, each with positive and negative gradient polarity, and at four phase offsets for a total of 24 MRE images for each dataset. Complex harmonic displacements were computed from the phase images above following subtraction to remove background phase, phase unwrapping with FSL PRELUDE, and filtering with the time harmonic Fourier transform. See e.g., Jenkinson M. "Fast, automated, N-dimensional phaseunwrapping algorithm." Magnetic Resonance in Medicine 2003; 49: 193-197.

[0077] Displacement data quality was assessed with the octahedral shear strain-based SNR (OSS-SNR). See e.g., McGarry MDJ et. al., "An octahedral shear strain-based measure of snr for 3d mr elastography." Physics in medicine and biology 2011; 56:N153-N164. Displacement images were processed with the nonlinear inversion (NLI) algorithm to estimate the complex shear modulus, G* = G' + / G". See e.g., McGarry MDJ et. aL, "Multiresolution mr elastography using nonlinear inversion." Medical physics 2012; 39:6388-6396. From G‘ the commonly reported shear stiffness, = 2| G*|2 / (G' + | G*| ), and damping ratio, = G" / 2 G', are calculated. See e.g., Manduca A, et. aL, "MR elastography: Principles, guidelines, and terminology."; Magnetic Resonance in Medicine 2021; 85:2377-2390.

[0078] Experiments

[0079] A series of in vivo experiments was performed to demonstrate the feasibility of the inventive methods and systems incorporating EMPIRE™ as described herein and the quality of acquired MRE data. Healthy subjects (n=6, 21-28 years, 1 / 5 male / female) completed imaging sessions with a series of EMPIRE™ scans, described below. All imaging was performed on a Siemens 3T Prisma MRI scanner with 64-channel head / neck receive coil (as manufactured by Siemens Healthineers of Erlangen, Germany). All subjects provided written, informed consent for this study approved by the local Institutional Review Board.

[0080] Experiment 1 : Demonstration of EMPIRE™ phase stability

[0081] To demonstrate the preservation and stability of the signal phase across the readout train after the MagPrep motion encoding block, data was collected with a modified EMPIRE™ sequence. The train of imaging readouts was restructured such that every block following MagPrep included the same repeated k / yspiral interleave and kzblip to allow for the visualization of magnitude and phase across the readout train. This encoding was repeated with each different / cXy spiral and kzblip to allow for reconstruction of full 3D images; only a single MRE encoding was obtained to minimize acquisition time. Experiment 2: Demonstration of MRE with EMPIRE™

[0082] To demonstrate the feasibility of acquiring MRE data with MagPrep, MRE data was acquired on the subjects in a fully sampled acquisition. No SENSE undersampling was used, as the goal of this experiment was to demonstrate that EMIPRE can obtain phase images, displacement fields, and ultimately stiffness maps with good quality as measured by OSS-SNR and fidelity to anatomic structures. As the goal of this experiment was feasibility, acquisition time was not prioritized leading to a predetermined scan time, such as a 4 min 26 sec scan time. Reconstruction was accomplished using the SENSE reconstruction described above, but effectively had a reduction factor of Rxy= 1 (i.e. no reduction factor).

[0083] Experiment 3: Demonstration of retrospective undersampling with EMPIRE™

[0084] To determine what reduction factors were achievable with the inventive methods and systems incorporating EMPIRE™ as described herein, retrospective undersampling were performed on the acquired data in Experiment 1 described above. For this experiment, reconstructions with SENSE were used to determine the maximum undersampling factor (and shortest acquisition time) likely to be achievable with a prospective undersampling scheme. Retrospective undersampling was accomplished by deleting entire interleaves from the stack-of-spirals such that the number of motion encoding shots would decrease similar to a prospectively under-sampled sequence; reduction factors of / ?xy= 1, 2, and 4 were tested. Retrospective undersampling was used to minimize comparison artifacts from running multiple repetitions that could include uncertainty from both scanner- and subject-based imperfections. Additionally, by using a retrospective undersampling scheme for this experiment, comparisons at a voxel level could be made without co-registering images and the confounds introduced with the spatial smoothing of co-registration.

[0085] Experiment 4: Demonstration of prospective undersampling with EMPIRE™

[0086] With the reduction factors and undersampling scheme identified in Experiment 3 above, the co-inventors implemented prospectively undersampled EMPIRE™ with Rxy= 4 and compared the obtained stiffness maps with a commonly used spin-echo EPI MRE pulse sequence with matched resolution and field-of-view. EPI MRE imaging parameters included: 240x240x120 mm3FOV, 96x96x48 matrix size, 2.5 mm isotropic resolution, TE / TR = 69 / 6720 ms, GRAPPA R = 3. Acquisition time for the EPI scan was a first predetermined duration, such as 3 min 15 sec, while the acquisition time for the EMPIRE™ scan was a second predetermined duration, such as 1 min 20 sec, wherein the second predetermined duration is less than the first predetermined duration. Four sets of data on four subjects were acquired to demonstrate repeatability between the two sequences and stability of the acquired data. For these sequences, data was acquired during multiple experiments with the subjects being removed from the scanner and re-positioned between scans to mimic practical variability in clinical or research use of these experiments. Given that some degree of movement between runs is impossible to eliminate, voxel-wise comparisons were not made as that would require co-registration and requisite smoothing, diluting the value of comparison. Average global stiffness were selected as a comparison measure, as is common in brain MRE, and multi-scale structural similarity (MSSIM) to compare distributions of properties. See e.g., Wang Z et. aL, "Multiscale structural similarity for image quality assessment." In: The Thrity-Seventh Asilomar Conference on Signals, Systems and Computers, 2003, pp. 1398-1402 Vol.2.

[0087] Results

[0088] Experiment 1 Results

[0089] As shown in FIGS. 4A-4C, phase stability across the imaging readout train following the MagPrep motion encoding block was observed. FIG. 4A illustrates a single slice with magnitude and phase across imaging readout block (GRE echoes) from the modified EMPIRE™ sequence which demonstrates magnitude loss as predicted by the signal model but preserved phase across the readout train. FIG. 4B illustrates the magnitude signal loss for a voxel in white matter and in FIG. 4C illustrates the magnitude signal loss for a voxel in white matter with preserved phase in the same voxel.

[0090] It was observed from Experiment 1 that images created from separate echoes show expected decay in signal magnitude with increasing time after MagPrep, as expected, but very similar phase even to the end of the readout train. The evolution of the magnitude and phase in a representative voxel in white matter are also shown in FIGS 4B and 4C. The dashed exponential-like curve in FIG. 4B is modeled from the contrast equations discussed above, whereas the horizontal dashed line in FIG. 4C is a constant which is placed at the mean of the phase across echoes for the same voxel, further illustrating the stability of phase across the train is suitable for imaging. Inspecting the phase images does show some increase in the noise of the phase across echoes, which corresponds to a decrease in the magnitude signal, decreasing the SNR and also phase-to-noise ratio. Experiment 2 Results

[0091] FIG. 5 shows a representative full vector displacement images and mechanical property maps acquired from a fully sampled EMPIRE™ reconstruction. In particular, FIG. 5 illustrates exemplary MRE data from a fully-sampled EMPIRE™ pulse sequence: overlay magnitude image (Column 1), representative components of harmonic motion fields in three directions at 50 Hz vibration (Columns 2-4), and estimated stiffness (Column 5) and damping ratio map (Column 6) after inversion with NLI. Thus, it can be observed that across four subjects, displacement data was of very high quality with OSS-SNR in the range 13.2-17.5, which is well above the minimum necessary for stable and reliable property map estimation with NLI. Since the acquisition uses a full 3D k-space, there are no interslice phase discontinuities - or "slice jitter" - that can negatively impact inversion quality. Stiffness and damping ratio maps both appear of high quality with anatomical consistency, including very low apparent stiffness in the lateral ventricles due to lack of shear modulus in cerebrospinal fluid.

[0092] Experiment 3 Results

[0093] Since the original, fully-sampled EMPIRE™ data in Experiment 1 used eight interleavedxyspiral interleaves (Rxy= 1), retrospective reconstructions with four (Rxy= 2) and two (Rxy= 4) spiral interleaves were used. Retrospective undersampling was only performed in-plane by removing data fromxyspiral, and not thru plane by removing kzplanes, consistent with the configuration of prospectively undersampled EMPIRE™ (i.e. in Experiment 4). The original, Rxy= 1 data had an OSS-SNR of 17.5, while retrospective / ?xy= 2 and Rxy= 4 data had OSS-SNRs of 14.8 and 13.6, respectively, both of which are still well above the minimum OSS-SNR. FIG. 6 illustrates results from retrospective sampling of acquired data via the inventive methods and systems described herein incorporating EMPIRE™. Namely, FIG. 6 illustrates an anatomical overlay with stiffness maps from NLI of EMPIRE™ data with retrospective undersampling of Rxy= 1, 2, and 4 data sets. Stiffness maps between each case were nearly identical upon visual inspection, with normalized root mean square error (NRMSE) of 3.6% for Rxy= 2 and 7.7% for Rxy= 4. These are very low NRMSE and consistent with previous MRE acceleration techniques applied retrospectively. See e.g., Mcllvain G. et. aL, "Oscillate: A low-rank approach for accelerated magnetic resonance elastography." Magnetic resonance in medicine 2022; 88: 1659-1672. Experiment 4 Results

[0094] Prospectively undersampled EMPIRE™ data with Rxy= 4 was collected and compared to EPI MRE data on multiple subjects. FIG. 7 illustrates selected stiffness map slices from one subject from both the EMPIRE™ scan (bottom) and EPI MRE data (prior art) scan (top). The EMPIRE™ scan was performed with Rxy= 4 from one subject collected with identical resolution, field-of-view, and imaging volume, and strong similarity (e.g., by visual inspection) was observed between the two sequences in terms of the spatial distribution of the stiffness properties across the brain. The EPI MRE scan time was 3 min 15 sec and the EMPIRE™ scan time was 1 min 20 sec, which is relatively shorter than the prior art scan time.

[0095] Further, MSSIM was calculated for each set of EMPIRE™ and EPI MRE (prior art) property map pairs, for both stiffness and damping ratio, as well as percent difference in global average properties between the two scans (as shown in Table 1 below). It was discovered that for both stiffness and damping ratio, MSSIM values were consistently high between subjects and across all repetitions. Differences in average global properties were also very small, in the range of 1.0-3.5% for stiffness. Damping ratio exhibited similarly low global differences save for one subject with 8.1% average difference between EMPIRE™ and EPI MRE scans.

[0096] Table 1 : Calculation of MSSIM

[0097] Discussion

[0098] The experiment results above demonstrate a proof-of-concept implementation of the inventive methods 2000 and systems 1000 comprising EMPIRE™ as described herein. Using the exemplary MRE magnetization prepared imaging sequence, a wholebrain MRE data at 2.5 mm isotropic resolution was acquired in 1 minutes 20 seconds, which represents a significant acceleration relative to the comparable EPI MRE sequence at 3 minutes 15 seconds, without sacrificing data quality. In a nonOlimiting example, for applications where short scan time is critical, such as pediatric neurology and neurosurgery, this rapid acquisition technique can enable more widespread clinical implementation, improve scan compliance, and potentially reduce sedation time.

[0099] In general, the inventive methods 2000 and systems 1000 described herein is different from prior art MRE scans in that they comprise an MRE magnetization prepared imaging sequence combining motion sensitized magnetization preparation with batched, fast 3D stack-of-spiral gradient echo readouts, i.e., elastographic magnetization-prepared imaging with rapid encoding (EMPIRE™), thereby enabling rapid and efficient 3D k space sampling. The magnetization encoded with displacement information into its phase is longitudinally stored where it is repeatedly accessed for multiple short imaging readouts. The use of magnetization preparation for phasebased MRI contrast mechanisms is uncommon, but the above experiments demonstrate that the phase itself is very stable over many readouts, albeit subject to increased noise due to diminishing magnitude signal. This enables high quality MRE phase contrast data from the EMPIRE™ sequence, even with a train of readouts after an encoding block. It was observed that using EMPIRE™ with a magnetization preparation block and fast gradient echo readouts with interleaved stack-of-spirals allows for significant undersampling without loss of stiffness map quality, ultimately accelerating MRE acquisitions and achieving comparable performance to a common EPI MRE sequence in just over one minute of scan time.

[0100] In this way, the inventive methods 2000 and systems 1000 comprising EMPIRE™ enables the efficient use of fully 3D readout trajectories by effectively decoupling the temporal cost of the motion encoding from the design of the 3D readout trajectory, allowing a choice of both the highest quality MRE motion encoding strategy while achieving 3D k-space trajectories through many short readouts that do not result in image distortion and thus do not require onerous field correction during image reconstruction.

[0101] Acquisitions with fully 3D k-space trajectories are of interest as attractive options for brain MRE as they offer greater SNR via repeated sampling of the imaging volume. Previous approaches were limited in achievable scan time by the need to include MEGs after each excitation, which EMPIRE™ overcomes. Further, the 3D stack- of-spirals trajectory also allows for greater parallel imaging acceleration without significant aliasing artifacts, as evidenced by Experiment 3 (retrospective undersampling up to Rxy= 4 resulting in minimal error in the stiffness maps). Further optimization of k-space trajectory, and the order in which samples are acquired, would enable even further acceleration through advanced reconstruction algorithms. While the UMCs preserve the quality of the MRE phase throughout the imaging readout, they add time and associated T2* decay during the 3D GRE readout. Since the UMCs intentionally spoil away recovering phase and the 3D GRE readout is fully spoiled, there is signal loss with each additional readout, potentially limiting the number and length of the rapid imaging readouts used in this implementation of EMPIRE™ and causing each readout to experience a different signal magnitude. Thus, a centrically- reordered readout was selected to mitigate or manage this effect though a minimal slice-directed blurring remains. Other rapidly encoded readouts, turbo spin echo or steady state techniques, could recycle this magnetization by refocusing the prepared motion encoded magnetization. Finally, this implementation of EMPIRE™ using 3D GRE included a TR pause or a period of no motion encoding or readouts to allow the spin system time to recover longitudinal magnetization for another MagPrep block 3000 and associated imaging readout train. The employed 3D stack-of-spirals trajectory, and other trajectories such as blipped simultaneous multislice, would have different SNR efficiency and sampling trade-offs based on the spatial coverage of the object.

[0102] Thus, this practical implementation achieves resolutions comparable to conventional SE-EPI MRE sequences that are used for both research and translational applications. At the full RXy = 4 reduction factor, the acquisition time for EMPIRE™ is significantly less than the prior art SE-EPI MRE sequence as currently optimized. For applications where scan time is critical, such as pediatric neurology and neurosurgery, as well as more general clinical add-on applications, reasonable acquisition times are critical for expanding the use of MRE to larger clinical and research populations. Even beyond clinical applications, certain investigations in MRE typically feature multiple motion encoding parameters, such as multiple frequencies of excitation or multiple directions of actuation. Fast, accurate MRE acquisitions, such as EMPIRE™, may allow limited scan time to be used to acquire multiple parameters sets in reasonable time.

[0103] Although the invention is illustrated and described herein with reference to specific embodiments, the invention is not intended to be limited to the details shown. Rather, various modifications may be made in the details within the scope and range of equivalents of the claims and without departing from the invention.

Claims

What is claimed :

1. A method for generating images indicative of mechanical properties of a subject tissue using a magnetic resonance imaging (MRI) system, the method comprising: performing a magnetic resonance elastography (MRE) scan on the subject tissue with the MRI system, wherein the subject tissue is divided into a plurality of slabs; and obtaining and processing MRE data related to the subject tissue via a control device coupled to the MRI system, the control device comprising a controller configured to perform an MRE magnetization prepared imaging sequence comprising elastographic magnetization prepared imaging with k-space encoding in accordance with machine readable instructions stored in a digital memory, the instructions comprising a plurality of scan parameters, and wherein the MRE magnetization prepared imaging sequence includes:(a) performing a magnetization preparation block, wherein successive radio frequency (RF) pulses are applied to the subject tissue in cooperation with applying a series of motion encoding gradients (MEGs) to the plurality of slabs,(b) applying magnetic field gradients to spoil residual signal and minimize image artifacts,(c) after performing step (a) and (b), performing a imaging readout block, wherein the plurality of scan parameters include sampling each kxy plane using a series of interleaved shots,(d) acquiring two-dimensional (2D) or three-dimensional (3D) k-space data based on steps (a), (b), and (c), and(e) applying an image reconstruction algorithm, thereby generating the images.

2. The method of claim 1, wherein the controller is configured to perform a stack-of- spiral (SOSP) gradient-echo imaging sequence.

3. The method of claim 1, wherein the series of interleaved shots comprises variabledensity or constant-density spiral interleaves.

4. The method of claim 1, wherein the series of interleaved shots comprises a Periodically Rotated Overlapping Parallel Lines with Enhanced Reconstruction (PROPELLER) readout trajectory, an Echo Planar Imaging (EPI) readout trajectory, or a radial readout trajectory.

5. The method of claim 1, wherein the image reconstruction algorithm comprises applying a conjugate gradient sensitivity encoding algorithm and a Fourier transform to the acquired k-space data.

6. The method of claim 1, wherein the image reconstruction algorithm comprises applying an iterative image reconstruction algorithm or a direct reconstruction algorithm.

7. The method of claim 1, further comprising estimating, by the controller, displacement fields in the subject tissue based on the reconstruction, and generating a map indicative of the subject tissue's mechanical properties via an inversion algorithm.

8. The method of claim 7, wherein the inversion algorithm comprises a non-linear inversion (NLI) algorithm.

9. The method of claim 1, wherein performing the MRE scan comprises: applying a polarizing magnetic field to the subject tissue, irradiating the subject tissue with an RF excitation field for producing transverse magnetization in spins in the subject tissue, and applying a magnetic field gradient to the spins which alternates in polarity.

10. The method of claim 9, wherein performing the MRE scan further comprises applying a stress to the subject tissue in cooperation with alternation of the magnetic field gradient polarity, for propagating mechanical waves through the subject tissue.

11. The method of claim 10, wherein the stress is not applied to the subject tissue during performance of step (b).

12. The method of claim 1, further comprising successively repeating steps (a), (b), and (c).

13. The method of claim 12, wherein prior to repeating step (a), applying a pause for a duration until a predetermined repetition time (TR) is satisfied.

14. The method of claim 7, wherein the map comprises a stiffness map.

15. The method of claim 1, wherein MRE data is obtained with reduced repetition or scan duration with performance of step (a), than when MRE data is obtained without performance of step (a).

16. A magnetic resonance imaging (MRI) system for generating images indicative of mechanical properties of a subject tissue, the system comprising : a magnet system configured to generate a polarizing magnetic field to the subject tissue, wherein the subject tissue is divided into a plurality of slabs; a plurality of gradient coils configured to apply a magnetic field gradient to the polarizing magnetic field; a radio frequency (RF) system configured to apply an excitation field to the subject tissue; a driver configured to deliver a stress to the subject for propagating mechanical waves through the subject tissue; a control device coupled to the MRI system, the control device comprising a controller configured to perform an MRE magnetization prepared imaging sequence comprising elastographic magnetization prepared imaging with k-space encoding in accordance with machine readable instructions stored in a digital memory, the instructions comprising a plurality of scan parameters, and wherein the MRE magnetization prepared imaging sequence includes:(a) performing a magnetization preparation block, wherein successive radio frequency (RF) pulses are applied to the subject tissue in cooperation with applying a series of motion encoding gradients (MEGs) to the plurality of slabs,(b) applying magnetic field gradients to spoil residual signal and minimize image artifacts,(c) after performing step (a) and (b), performing an imaging readout block, wherein the plurality of scan parameters include sampling each kxyplane using a series of interleaved shots,(d) acquiring two-dimensional (2D) or three-dimensional (3D) k-space data based on steps (a), (b), and (c), and(e) applying an image reconstruction algorithm, thereby generating the images.

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