Magnetization preparation system and method for magnetic resonance imaging

Abstract

A method for magnetization-prepared magnetic resonance imaging comprises using a magnetic resonance imaging (MRI) system to acquire magnetic resonance (MR) data for at least two images of the region of interest in the subject. Each of the at least two images is acquired using a different magnetization preparation pulse or a different timing for the magnetization preparation pulse. The method further comprises generating the at least two images using the corresponding MR data and generating an image by comparing the at least two images. In some embodiments, the magnetization preparation pulse is a T2 preparation pulse, and the at least two images are used to generate an image having a signal representing water exchange. In some embodiments, the magnetization preparation pulse is a velocity-selective preparation pulse, and the at least two images are used to generate an image having a signal representing perfusion.

Description

[Technical Field]

[0001] (Cross-reference of related applications) This application claims priority to U.S. Patent Application No. 63 / 489,359, filed on 9 March 2023, titled "System and Method for Imaging Tissue-to-Body Fluid Water Exchange by T2 Labeling," and U.S. Patent Application No. 63 / 510,239, filed on 26 June 2023, both of which are incorporated herein by reference in their entirety.

[0002] (Description of research funded by the federal government) none. [Background technology]

[0003] This disclosure relates primarily to magnetic resonance imaging, and more specifically to systems and methods for magnetization-prepared magnetic resonance imaging, including, for example, the purpose of imaging tissue-to-body fluid water exchange using T2 labeling, and the purpose of imaging tissue perfusion using velocity-selective arterial spin labeling. [Overview of the Initiative] [Problems that the invention aims to solve]

[0004] The exchange of water between interstitial spaces and surrounding fluids is a vital physiological function. In the brain, water exchange in the choroid plexus and other possible sites supports the production and absorption of cerebrospinal fluid (CSF). The choroid plexus (CP), as the primary source of CSF production in the brain, plays a crucial role in brain homeostasis and waste removal. Abnormal production or absorption of cerebrospinal fluid by the choroid plexus can lead to increased intracranial pressure, hydrocephalus, and dysfunction of the brain's glymphatic drainage system, which has been suggested as a potential cause of Alzheimer's disease. In the kidneys, water exchange with the urinary collecting system is critical for maintaining fluid balance and concentrating urine. In both cases, this water exchange is thought to be facilitated by specialized passive transporters called aquaporins present in the cell membrane. In the absence of aquaporins, membrane-mediated water exchange becomes very slow, with water exchange at the interface of the interstitial fluid containing aquaporins becoming dominant.

[0005] Currently, there are few methods available to use as cautionary criteria for evaluating water exchange. While it is possible to inject radioactive water into animals in experiments, its widespread application is problematic. In the brain, CSF production can be measured using phase-contrast MRI, but the high pulsation of CSF flow results in a lot of noise, making measurement difficult. Recently, researchers have demonstrated the ability of arterial spin labeling to detect the exchange of labeled arterial blood into the CSF space, as discussed, for example, in "Pharmacological MRI with Simultaneous Measurement of Cerebral Perfusion and Blood-Cerebrospinal Fluid Barrier Function Using Interleaved Echo-Time Arterial Spin Labeling" by Evans, P. et al., Neuroimage, September 2021, 238:118270; and in "Ultra-long-TE arterial spin labeling reveals rapid and brain-wide blood-to-CSF water transport in humans" by Petitclerc, L. et al., Neuroimage, December 15, 2021, 15;245:118755. A key insight was that because the fluid's T2 (transverse relaxation time) is very long, images acquired with very long echo times (TE) contain fluid signals but attenuate tissue signals. Although this effect is very small in humans, it suggests the possibility of imaging water exchange using non-invasive MRI.In another group, instead of arterial labeling, magnetization transfer (MT) pulses are applied to propose labeling of tissue water itself for imaging water exchange in animal models. For example, in "Age-dependent Cerebrospinal Flid-Tissue Water Exchange Detected by Magnetization Transfer Indirect Spin Labeling MRI" by Li, A.M., etc., Magn Reson Med., May 2022, 87(5):2287-2298. Although MT has been discussed, it requires high power and has a lower efficiency of saturating tissues, especially blood, compared to T2 preparation pulses. Water exchange is one of the factors contributing to signal dynamics in bolus injection of MRI contrast agents, but its effect is mixed with many other factors that require complex and uncertain models. Other MRI techniques for imaging exchanges and transports between tissues, tissues and body fluids using contrast agents (e.g., arterial spin labeling (ASL)) may also face challenges.

Means for Solving the Problems

[0006] According to one embodiment, a method for magnetic resonance imaging of water exchange from tissue to body fluid in a region of interest in a subject uses a magnetic resonance imaging (MRI) system, applies different T2 preparation pulses for each image to obtain magnetic resonance (MR) data regarding at least two images of the region of interest in the subject, generates the at least two images using the corresponding MR data, and generates an image having a signal representing water exchange by comparing the at least two images.

[0007] According to another embodiment, a method for magnetic resonance imaging of fluid exchange from tissue to body fluid within a region of interest in a subject includes using a magnetic resonance imaging (MRI) system and using different timings for the application of T2 preparation pulses for each image to acquire magnetic resonance (MR) data for at least two images of the region of interest in the subject, generating the at least two images using the corresponding MR data, and generating an image having a signal representing fluid exchange by comparing the at least two images.

[0008] In another embodiment, the magnetic resonance imaging (MRI) system includes: a magnet system configured to generate a polarization magnetic field with respect to at least a portion of a subject; a magnetic gradient system comprising a plurality of magnetic gradient coils configured to apply at least one gradient magnetic field to the polarization magnetic field; a radio frequency (RF) system configured to apply a radio frequency electromagnetic field to the subject and to receive magnetic resonance signals from the subject using a coil array; and a computer system programmed to acquire magnetic resonance (MR) data for at least two images of the region of interest in the subject using different T2 preparation pulses for each image; generate the at least two images using the corresponding MR data; and generate an image having signals representing water exchange by comparing the at least two images.

[0009] According to other embodiments, a magnetic resonance imaging (MRI) system includes a magnet system configured to generate a polarization magnetic field for at least a part of a subject, a magnetic gradient system including a plurality of magnetic gradient coils configured to apply at least one gradient magnetic field to the polarization magnetic field, a radio frequency (RF) system configured to apply a radio frequency electromagnetic field to the subject and receive a magnetic resonance signal from the subject using an array of coils, and a computer system programmed to acquire magnetic resonance (MR) data regarding at least two images of the region of interest in the subject using different timings for applying T2 preparation pulses for each image, generate the at least two images using the corresponding MR data, and generate an image having a signal representing water exchange by comparing the at least two images.

[0010] According to other embodiments, a method for velocity selective arterial spin labeling magnetic resonance imaging of tissue perfusion in a region of interest in a subject includes using a magnetic resonance imaging (MRI) system to acquire magnetic resonance (MR) data regarding at least two images of the region of interest in the subject using different timings for applying a velocity selective preparation pulse for each image, generating the at least two images using the corresponding MR data, and generating an image having a signal representing water exchange by comparing the at least two images.

[0011] The present disclosure will be described with reference to the following accompanying drawings, where like reference numerals refer to like elements. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] [Figure 1] FIG. 1 is a block diagram of an example of a magnetic resonance imaging (Magnetic Resonance Imaging, MRI) system according to one embodiment. [Figure 2] This figure shows a method for magnetic resonance imaging of water exchange from tissue to body fluids within a region of interest in a subject, according to one embodiment. [Figure 3] This figure shows an example of a T2-preparation inversion recovery pulse sequence according to one embodiment. [Figure 4] This figure shows a method for magnetic resonance imaging of water exchange from tissue to body fluids within a region of interest in a subject, according to one embodiment. [Figure 5] This figure shows a T2-preparation length echo time inversion recovery pulse sequence having a T2-preparation module applied before the inversion recovery pulse according to one embodiment. [Figure 6] This figure shows a T2-preparation length echo time inversion recovery pulse sequence having a T2-preparation module applied after the inversion recovery pulse according to one embodiment. [Figure 7] An example of a graph showing the derivative of 1 / T1 versus T2-preparation pulse termination time according to one embodiment is shown. [Figure 8] An example of a graph showing the derivative of 1 / T1 versus T2-preparation pulse termination time according to one embodiment is shown. [Figure 9] An example of a graph showing the sensitivity of water exchange as a function of the end time of the T2-preparation pulse, according to one embodiment, is shown. [Figure 10] This figure shows an example of a magnetic preparation sequence according to one embodiment. [Figure 11] This figure shows an example of a magnetic preparation inversion recovery pulse sequence configured to include a plurality of inversion recovery (IR) pulses according to one embodiment. [Figure 12] This figure shows an example of a magnetic preparation inversion recovery pulse sequence configured to include a plurality of inversion recovery (IR) pulses according to one embodiment. [Figure 13] This figure shows a method for velocity-selective arterial spin-labeling magnetic resonance imaging of tissue perfusion within a region of interest in a subject, according to one embodiment. [Figures 14A-14B]Figure 14A shows an example of a graph showing magnetization as a function of time before readout, with and without T2 preparation, according to one embodiment. Figure 14B shows an example of a graph showing the difference in magnetization between tissue and body fluid, with and without T2 preparation, according to one embodiment. [Figure 15] A block diagram showing an example of a computer system as described above. [Modes for carrying out the invention]

[0013] Referring to Figure 1, the disclosed system and method can be implemented using a magnetic resonance imaging ("MRI") system 100 as shown in Figure 1, or designed to be associated with this system 100. The MRI system 100 typically includes an operator workstation 102, which includes a display 104, one or more input devices 106 (keyboard, mouse, etc.), and a 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 enables scanning of prescriptions entered into the MRI system 100. Generally, the operator workstation 102 can be coupled to a plurality of servers, including a pulse sequence server 110, a data acquisition server 112, a data processing server 114, and a data storage server 116. The operator workstation 102 and each of the servers 110, 112, 114, and 116 are connected to communicate with each other. For example, servers 110, 112, 114, and 116 can be connected via the communication system 140 by including any appropriate network connection, such as wired, wireless, or a combination of both. As an example, the communication system 140 may include its own network, a dedicated network, or even an open network such as the Internet.

[0014] The pulse sequence server 110 responds to commands downloaded from the operator workstation 102 to operate the gradient system 118 and the radio frequency field (RF) system 120. A gradient waveform is generated to perform a predetermined scan and applied to the gradient system 118. The gradient system 118 excites the gradient coil in assembly 122 and the magnetic field gradient G used for position encoding of the magnetic resonance signal. x , G y , G z The gradient coil assembly 122 generates a gradient coil assembly, which is part of a magnet assembly 124 that includes a polarization magnet 126 and a full-body RF coil 128.

[0015] To execute a predetermined magnetic resonance pulse sequence, an RF waveform is applied by the RF system 120 to the RF coil 128 or a separate local coil (not shown in Figure 1). The response magnetic resonance signal detected by the RF coil 128 or the separate local coil is received by the RF system 120 and then amplified, demodulated, filtered, and digitized according to the instructions of the commands generated by the pulse sequence server 110. The RF system 120 includes an RF transmitter for generating a wide variety of RF pulses used in the MRI pulse sequence. The RF transmitter generates RF pulses of the desired frequency, phase, and pulse amplitude waveform in response to the scan prescription and instructions from the pulse sequence server 110. The generated RF pulses can be applied to the whole-body RF coil 128 or to one or more local coils or coil arrays.

[0016] The RF system 120 also includes one or more RF receiving channels. Each RF receiving channel comprises an RF preamplifier that amplifies the magnetic resonance signal received by the connected coil 128, and a detector that detects and digitizes the I and Q components of the received magnetic resonance signal. The amplitude of the received magnetic resonance signal can therefore be determined at any sample point by the square root of the sum of the squares of the I and Q components.

number

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[0017] The pulse sequence server 110 optionally receives patient data from the physiological acquisition controller 130. For example, the physiological acquisition controller 130 may receive signals from multiple different sensors connected to the patient, such as electrocardiogram (ECG) signals from electrodes and respiratory signals from respiratory bellows or other respiratory monitoring devices. These signals are typically used by the pulse sequence server 110 to synchronize, or "gate," the execution of a scan with the subject's heart rate or respiration.

[0018] The pulse sequence server 110 is also connected to a scan room interface circuit 132 that receives signals from various sensors related to the patient's condition and the magnet system. Furthermore, via the scan room interface circuit 132, the patient positioning system 134 receives commands to move the patient to a desired position during the scan.

[0019] The digitized magnetic resonance signal samples generated by the RF system 120 are received by the data acquisition server 112. The data acquisition server 112 operates in response to commands downloaded from the operator workstation 102, receiving real-time magnetic resonance data and providing buffer storage to prevent data loss due to data overruns. In some scans, the data acquisition server 112 does little more than pass the acquired magnetic resonance data to the data processing server 114. However, in scans where information derived from the acquired magnetic resonance data needs to be used to control the subsequent performance of the scan, the data acquisition server 112 is programmed to generate such information and pass it to the pulse sequence server 110. For example, magnetic resonance data may be acquired during a pre-scan and used to calibrate the pulse sequence executed by the pulse sequence server 110. Another example is the acquisition of navigator signals, which can be used to adjust the operating parameters of the RF system 120 or the gradient system 118, or to control the view order for sampling k-space. As yet another example, the data acquisition server 112 can also be used to process magnetic resonance signals used to detect the arrival of contrast agent in a magnetic resonance angiography ("MRA") scan. For example, the data acquisition server 112 acquires magnetic resonance data and processes it in real time to generate information used to control the scan.

[0020] The data processing server 114 receives magnetic resonance data from the data acquisition server 112 and processes it according to instructions downloaded from the operator workstation 102. Such processing may include, for example, performing a Fourier transform on raw k-space data to reconstruct a two- or three-dimensional image, performing other image reconstruction methods such as iterative or back-projection reconstruction techniques, applying filters to raw k-space data or reconstructed images, generating functional magnetic resonance images, and computing motion or flow images.

[0021] Images reconstructed by the data processing server 114 are sent back to the operator workstation 102. These images are output to the operator display 112 or to a display 136 located near the magnet assembly 124 for use by the attending physician. Batch mode images or selected real-time images are stored in a host database on disk storage 138. When these images are reconstructed and transferred to storage, the data processing server 114 notifies the data storage server 116 on the operator workstation 102. The operator workstation 102 can be used by the operator to archive images, create films, or transmit them to other facilities over the network.

[0022] The MRI system 100 may also include one or more networked workstations 142. For example, a networked workstation 142 may include a display 144, one or more input devices 146 (such as a keyboard and mouse), and a processor 148. The networked workstation 142 may be located in the same facility as the operator workstation 102, or in different facilities such as different medical institutions or clinics. The networked workstation 142 may include mobile devices such as mobile phones and tablets.

[0023] Networked workstations 142 can remotely access data processing servers 114 or data storage servers 116 via communication systems 140, regardless of whether they are located in the same facility as operator workstations 102 or in different facilities. Therefore, multiple networked workstations 142 can access data processing servers 114 and data storage servers 116. Thus, magnetic resonance data, reconstructed images, or other data are exchanged between the data processing servers 114 or data storage servers 116 and the networked workstations 142 so that data or images are processed remotely by the networked workstations 142. This data is exchanged in any suitable format according to Transmission Control Protocol ("TCP"), Internet Protocol ("IP"), or other known or suitable protocols.

[0024] This disclosure describes a system and method for magnetization-prepared magnetic resonance imaging (MRI). In some embodiments, the disclosed magnetization-prepared MRI techniques can be used in a system and method for velocity-selective arterial spin-labeling magnetic resonance imaging of tissue perfusion. For example, two or more images of a subject's region of interest can be acquired, with different timings for applying velocity-selective preparation for each image. Images containing signals representing perfusion can be generated by comparing at least two of the images.

[0025] In some embodiments, the disclosed magnetization-prepared MRI technique can be used in systems and methods for magnetic resonance imaging of tissue-to-fluid water exchange in a region of interest in a subject, where imaging of water exchange is based on the difference in transverse relaxation (T2) between fluid and tissue / blood components. Advantageously, the T2 preparation pulse can be used to impart sensitivity to tissue-to-fluid water exchange. In some embodiments, an MRI system can be used to acquire at least two images of a region of interest in a subject. Each of the at least two images can be acquired using different T2 preparation pulses (e.g., with or without a T2 preparation pulse, T2 preparation pulses of different durations) or T2 preparation pulses of different timings. Images containing signals representing water exchange can be generated by comparing at least two images (e.g., by subtraction, fitting to a model, or other comparison algorithms). In some embodiments, the disclosed systems and methods can provide an approach for highly sensitive measurement of water exchange within a region of interest, for example, from short to long echo time (TE) compartments, to evaluate water exchange within the region of interest.

[0026] In some embodiments, a T2 preparation pulse can be applied at a predetermined time before the acquisition (i.e., readout pulse) of a first image (e.g., a highly weighted T2 image). As used herein, the first image acquired using the T2 preparation pulse can also be called a label image. A second image can be acquired and compared with the first image. As used herein, the second image can also be called a control image. In some embodiments, the second image can be acquired using a different T2 preparation pulse (e.g., no T2 preparation pulse (T2 preparation pulse turned off), T2 preparation pulse of a different duration). In some embodiments, the second image can be acquired using a T2 preparation pulse applied at a different time than the T2 preparation pulse for the first image. The comparison of the first and second images can be used to infer the water exchange that occurred between tissues and body fluids. In some embodiments, this comparison can be used to generate an image containing signals representing water exchange.

[0027] In some embodiments, the acquisition of the first and second images also includes the application (or replay) of one or more inversion recovery (IR) pulses. Inversion recovery can reduce the fluid signal to near zero, for example, as used in fluid-attenuated inversion recovery (FLAIR) pulse sequences. Because the fluid signal is significantly attenuated by inversion recovery, associated motion and other large fluid signal artifacts can be significantly reduced. In some embodiments, when both the first and second images are acquired using T2 preparation pulses, the T2 preparation pulse for the first image can be applied at an optimal timing before the IR pulse(s), and the T2 preparation pulse for the second image can be applied at an optimal timing after the IR pulse(s). Acquiring two images with T2 preparation pulses applied before the IR pulse (in the first image) and after the IR pulse (in the second image) allows for equal sensitivity to systematic effects, for example, due to incomplete T2 preparation pulses and variable T2 in bodily fluids, and enables control of system errors in the T2 preparation pulse. In some embodiments, the timing of the inversion pulse can be selected (e.g., optimized) to reduce system errors over the ranges of T1 and T2. In some embodiments, the comparison of two images can be performed by subtracting two images that can give a signal reflecting water exchange. In some embodiments, dividing the subtraction of the two images by a reference image that does not have an inversion recovery or T2 preparation pulse can provide a semi-quantitative ratio image. In some embodiments, the method can be configured to reduce sensitivity to variable longitudinal magnetization (at T1) of the fluid. In some embodiments, varying the repetition time (TR) of one of the two images relative to the other can reduce the T1 sensitivity of the measurement, and setting the TR of the second image (or control image) to a different value can reduce potential errors due to differences in fluid T1.For example, the TR of the second image (or control image) can be a different value (e.g., longer) than the TR of the first image (or label image).

[0028] In some embodiments, quantification of water exchange can be performed using images containing signals representing water exchange generated by comparing two images. For quantification, a model can be used in which tissue-body fluid water exchange contributes to the MRI signal. In some embodiments, the semi-quantifiable ratio can be associated with the exchange rate.

[0029] In some embodiments, the region of interest in which tissue-to-fluid fluid exchange is imaged may be, for example, the brain or the kidney. In one example, the disclosed system and method can be used for the quantitative assessment of intrarenal fluid exchange, which may serve as a biomarker for the diagnosis and prognosis of renal disease. Furthermore, the disclosed system and method can provide a non-invasive assessment of renal filtration and fluid exchange, which may complement other indicators of renal function. In another example, the disclosed system and method can be used for in vivo studies of CSF exchange, which may reflect changes in glymphatic clearance or CSF production associated with aging, Alzheimer's disease, increased intracranial pressure, and other diseases. While the following descriptions of Figures 2–10 may relate to exemplary applications for imaging fluid exchange between tissues and fluids in the brain (e.g., fluid exchange between the choroid plexus (CP) and cerebrospinal fluid (CSF)), it should be understood that the disclosed system and method can be used to image fluid exchange in any region of the anatomical structure of a subject.

[0030] Figure 2 shows a method for magnetic resonance imaging of tissue-to-fluid exchange in a region of interest in a subject, according to one embodiment. Although the blocks of the process shown in Figure 2 are shown in a specific order, in some embodiments one or more blocks may be performed or bypassed in an order different from that shown in Figure 2.

[0031] In block 202, MR data can be acquired for at least two images from a region of interest in a subject using, for example, an MRI system (e.g., MRI system 100 shown in Figure 1). MR data for each image can be acquired using a pulse sequence performed by the MRI system, and each image's MR data can be acquired using different T2 preparation pulses. For example, in some embodiments, MR data for the first image (or label image) can be acquired using a T2 preparation pulse applied at a predetermined time before acquisition (i.e., readout pulse), while MR data for the second image (or control image) can be acquired without a T2 preparation pulse (e.g., with the T2 preparation pulse turned off). In some embodiments, MR data for each image can be acquired using T2 preparation pulses of different durations. While the following description of Figures 2-4 describes the acquisition and reconstruction of two images, it should be understood that in some embodiments, more than two images can be acquired, reconstructed, and compared to generate an image containing signals representing water exchange. As mentioned above, in some embodiments, MR data for the first image can be acquired from the subject using a pulse sequence including a T2 preparation module applied at a predetermined time before the readout pulse. In some embodiments, the T2 preparation module can be implemented using known pulses and techniques for the T2 preparation pulse. For example, the T2 preparation module (e.g., the T2 preparation module 302 shown in Figure 3) may include a 90-degree hard pulse, followed by four adiabatic hyperbolic secant refocusing pulses, and one final 90-degree hard pulse. The readout pulse of the pulse sequence may be, for example, a three-dimensional fast spin echo readout. In some embodiments, the pulse sequence may also include one or more inversion recovery pulses applied after a predetermined time from the T2 preparation pulse. Figure 3 shows an example of a T2 preparation inversion recovery pulse sequence according to one embodiment. The pulse sequence 300 shown in Figure 3 has a duration T T2prepThe pulse sequence 300 includes a T2 preparation module 302 having 308, an IR pulse 304, a readout pulse 306 with an echo time TE314, an inversion time 310, and a repetition time 312. In some embodiments, the echo time TE314 may be a long echo time. Although Figure 3 shows one IR pulse 304, it should be understood that in some embodiments, the pulse sequence 300 may include multiple IR pulses 304.

[0032] Returning to Figure 2, in block 202, MR data for a second image (or control image) can be acquired from the subject using a pulse sequence including different T2 preparation pulses. For example, the MR data for the second image can be acquired using a pulse sequence that does not include a T2 preparation module (e.g., pulse sequence 300 that does not include the T2 preparation module 302 shown in Figure 3), or the MR data for the second image can be acquired using a pulse sequence that uses a T2 preparation pulse with a different duration than the pulse sequence for the first image (e.g., pulse sequence 300 with a different duration 308 for the T2 preparation module 302, as shown in Figure 3). The readout pulse may be, for example, a three-dimensional fast spin echo readout pulse. In some embodiments, the pulse sequence may also include one or more inversion recovery pulses applied a predetermined time before the readout pulse. The MR data acquired for at least two images, e.g., a first image and a second image, can be stored, for example, in the data storage device of the MR system (e.g., the MRI system 100 shown in Figure 1) or in the data storage device of another computer system.

[0033] In block 204, at least two images, for example, a first image and a second image, can be generated (or reconstructed) using known reconstruction methods based on the corresponding MR data of each image acquired in block 202. In some embodiments, the first and second images can be reconstructed using, for example, a data processing server 114 of the MRI system 100. In some embodiments, the first and second images can be reconstructed using a computer system (for example, the computer system 1400 shown in Figure 14) configured to access or receive MR data acquired by the MR system. The generated first and second images can be stored, for example, in the data storage of the MR system (for example, the MRI system 100 shown in Figure 1) or in the data storage of another computer system.

[0034] In block 206, an image containing a signal representing water exchange can be generated by comparing at least two images acquired in block 202 and generated in block 204, for example, by comparing the first image and the second image. In some embodiments, this comparison may be implemented by subtracting the second image from the first image. In some embodiments, this comparison may be implemented by fitting the first and second images to a model or by using other comparison algorithms. The image containing the signal representing water exchange generated in block 206 can be stored, for example, in the data storage of an MR system (e.g., MRI system 100 shown in Figure 1) or in the data storage of another computer system. In block 208, the exchange signal ratio can be determined using the image containing the signal representing water exchange. In block 210, the generated image containing the signal representing water exchange can be displayed on a display, for example, the display of an MRI system (e.g., displays 104, 136, and / or 144 of MRI system 100 shown in Figure 1) or on the display of another computer system.

[0035] The movement of fluid from one compartment to another is potentially of great interest in understanding physiology and pathophysiology, testing drug therapies, and, in some cases, diagnosing individual patients. Furthermore, fluid exchange is a crucial function for systems that require fluid movement for their own function. In the choroid plexus, and potentially at other boundaries of the central nervous system, fluid exchange with CSF is a vital component for CSF production. This production is important for maintaining CSF pressure and potentially for removing larger molecules from the brain through a process called glymphatics. In the kidneys, fluid exchange plays an essential role in regulating fluid balance through exchange with the collecting duct system, which leads to urine production.

[0036] As described above, if one compartment can be selectively attenuated or labeled before selectively imaging the other compartment, MRI can become more sensitive to water exchange. Normally, there is a substantial offset to the measurement, so the labeled image can be compared to a second image in which the other compartment is not labeled. However, (as described above with respect to Figure 2) simply not labeling the control image is insufficient because labeling is not entirely selective and rather attenuates the imaged compartment more weakly.

[0037] As described above, in some embodiments, sensitivity to water exchange can be varied by acquiring at least two images with T2 preparation pulses at different timings, rather than images without a T2 preparation pulse or with different T2 preparation pulse durations. In these embodiments, each acquired image can be applied at different times while using the same T2 labeling strategy. Since the water exchange effect can rise over time, the differences between images are still sensitive to water exchange. However, equalizing the saturation of the image pool at different times can lead to different effects depending on the relaxation and recovery times of the MRI. To overcome this limitation, in some embodiments, labeling and control preparation can be applied to opposite sides of the inversion recovery pulse. In some embodiments, with appropriate optimization of timing, this strategy can control a favorable range of saturation and relaxation parameters.

[0038] Figure 4 shows a method for magnetic resonance imaging of tissue-to-fluid exchange in a region of interest in a subject, according to one embodiment. Although the blocks of the process shown in Figure 4 are shown in a specific order, in some embodiments, one or more blocks may be performed or bypassed in an order different from that shown in Figure 4.

[0039] In block 402, MR data for at least two images can be acquired from a region of interest in a subject using, for example, an MRI system (e.g., MRI system 100 shown in Figure 1). MR data for each image can be acquired using a pulse sequence performed by the MRI system, and the MR data for each image can be acquired by varying the timing of the T2 preparation pulse application. The following description of Figures 4-9 describes the acquisition and reconstruction of two images (e.g., a label image and a control image), but it should be understood that in some embodiments, more than two images can be acquired, reconstructed, and compared to generate an image containing signals representing water exchange. In some embodiments, for example, MR data for a first image (or label image) can be acquired from a subject using a pulse sequence including a T2 preparation module applied at a first predetermined time before the readout pulse. In some embodiments, the first pulse sequence includes at least one inversion recovery pulse, and the T2 preparation pulse can be applied at a first time before the IR pulse(s). In some embodiments, the T2 preparation module can be implemented using known pulses and techniques for T2 preparation. In some embodiments, the preparation module can be any pulse that imparts a multiplicative change to the longitudinal magnetization. The readout pulse may be, for example, a three-dimensional fast spin echo readout pulse. Figure 5 shows an example of a T2-preparation module-length echo-time inversion recovery pulse sequence according to one embodiment, in which the T2-preparation module is applied before the inversion recovery pulse. The pulse sequence 500 shown in Figure 5 includes a T2-preparation module 502, an IR pulse 504, and a readout pulse 506. In Figures 5 to 9, for all parameters, the suffix "L" used herein refers to label image acquisition, and the suffix "C" refers to control image acquisition (described later). In Figure 5, time increases from left to right. Sequence 500 can have various magnetizations and timings, for example, acquisition start time TR L -T read (508) T2 preparation pulse start time TpstartL +T prep (510), the end time T of the T2 preparation pulse pstartL (512), the inversion recovery time TI L (514), and the magnetization end time M end (516). The labeled T2 preparation pulse 502 can be applied over a period T prep . In some embodiments, the preparation module 502 may be any pulse that gives a multiplicative change to the longitudinal magnetization. In some embodiments, the preparation module 502 can be configured to convert the magnetization. Although only one IR pulse 504 is shown in FIG. 5, in some embodiments, as will be further discussed with respect to FIG. 11 below, it should be understood that more than one IR pulse 504 can be included after the T2 preparation module 502 and before the readout pulse 506.

[0040] Returning to Figure 4, in block 402, MR data for the second image (or control image) can be acquired from the region of interest in the subject using a pulse sequence including a T2 preparation module applied at a second predetermined time before the readout pulse, where the second time is different from the first time. In some embodiments, the second pulse sequence may include at least one inversion recovery pulse, and the T2 preparation pulse may be applied at a second time after the IR pulse(s) and before the readout pulse. In some embodiments, the T2 preparation module may be implemented using known pulses and techniques for T2 preparation. In some embodiments, the preparation module may be any pulse that gives a multiplicative change to the longitudinal magnetization. The readout pulse may be, for example, a three-dimensional fast spin echo readout pulse. Figure 6 shows an example of a T2-preparation-length echo-time inversion recovery pulse sequence including a T2-preparation module applied after the inversion recovery pulse according to one embodiment. In Figure 6, time increases from left to right. The pulse sequence 600 shown in Figure 6 includes an IR pulse 602, a T2 preparation module 604, and a readout pulse 606. Sequence 600 can vary in magnetization and timing, for example, acquisition start time TR C -T read (608) T2 preparation pulse start time T pstartC +T prep (612), reversal recovery time TI C (610) T2 preparation pulse end time T pstartC (614), and magnetization end time M end (616) is included. Although only one IR pulse 602 is shown in Figure 6, it should be understood that in some embodiments, more than one IR pulse 602 may be included before the T2 preparation module 604, as will be discussed further with reference to Figure 12 below.

[0041] Referring to both Figure 5 and Figure 6, M end (516,616) must be equal in both image acquisitions, but in principle, TR and Mstart This may differ for label and control images. By using the same acquisition sequence, image parameters match across spatial encodings, so T read They are likely to be equal. In some embodiments, the imaging saturation effect is usually imperfect and sensitive to parameters such as RF field amplitude, so by applying non-selective saturation to both compartments, M start It is advantageous to make it virtually zero. Also, when a larger background is present, it is usually difficult to measure small signals, so M end It is also advantageous in keeping it small.

[0042] In some embodiments, the acquisition of label and control images in block 402 may presuppose selective imaging of target compartments (e.g., tissues such as CP and bodily fluids such as CSF). In the case of CSF imaging with T2 selectivity, this can be efficiently achieved, for example, by very long TE imaging using multispin echo sequences.

[0043] In some embodiments, it can be assumed that, for the acquisition of the first image (or label image) in block 402, there is no Z-recovery, only multiplicative decay, or potentially inversion occurs. In some embodiments, this effect has a coefficient α, which is between -1 and 1, and is described later. prep It can be described by the T used here. pstartL This can be defined as the time after the completion of the preparation pulse for acquiring the first image or label image.

[0044] In some embodiments, the inversion time (TI shown in Figure 5) for acquiring the first image or label image is used. L (514)) can be determined by tracking the evolution of magnetization according to Bloch equations.

number

[0045] Specific M end If the goal is TI, then reverse this formula L (514) can be solved.

number

[0046] In some embodiments, the relaxation time differs across the region, and the preparation efficiency changes due to imperfections in the RF magnetic field, for reasons such as α prep It may not be possible to know T1 with high accuracy. It may be desirable to reduce, minimize, or optimize the sensitivity of these parameters to variations. First, these can be calculated as follows and determined by their first derivatives.

number

[0047] In some embodiments, it can be assumed that there is no Z recovery and only T2 decay occurs during the preparation period for acquiring the second image (or control image) in block 402. pstartC This can be defined as the end time of T2prep in acquiring the second image (or control image). In this way, T pstartC A value of =0 can be interpreted as T2prep being applied immediately before acquiring the control image.

[0048] The evolution of magnetization can be traced according to Bloch's equation, as shown below.

number

[0049] In some embodiments, α prepTo obtain sensitivity to the target, it may be desirable to match the acquisition of the label image (i.e., sequence 500) and the acquisition of the control image (i.e., sequence 600). In some embodiments, in order to match the two acquisitions, first the M between the two sequences (500, 600) end These need to be matched. Since these equations do not take exchange effects into account, any difference could become a system error. Next, α prep The derivatives with respect to can be made to match.

[0050] The process for obtaining the label image is as follows:

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[0051] The method for acquiring the control image is as follows:

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[0052] In some embodiments, this is M end It can be simplified by inserting it into the formula for that purpose.

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[0053] This is TI C or TR C It has an advantage in that it is not directly sensitive to that.

[0054] When the two derivatives are made to coincide, we get the following:

number

[0055] In some embodiments, any T pstartL Given T pstartC This is calculated, and α for the two acquisitions (500, 600) prep The inversion time, which is consistent with the derivative of the signal with respect to , can be determined.

[0056] In some embodiments, it may be desirable to match the two acquisitions (500, 600) with respect to sensitivity to T1. For example, to investigate the change in sensitivity of end magnetization with respect to T1, it is convenient to numerically evaluate the equation of the derivative with respect to 1 / T1. Generally, although the dependence on T1 is small, a T1 that is very close to T1 is desirable. pstarts So, we can see that they are almost a perfect match. pstarts When the element is moved away from T1, the sensitivity to T1 becomes higher for the label image than for the control image.

[0057] Figure 7 is an example of a graph showing the relationship between the derivative of 1 / T1 and T2-the end time of the preparation pulse, according to one embodiment. Graph 700 shows the relationship between experimental parameters and T pstartL The derivatives with respect to 1 / T1 for an example set of (units are ms) are shown. The upper curve 702 represents label image acquisition, and the lower curve 704 represents control image acquisition. In some embodiments, the derivatives do not match T pstartL When the interval is long, the optimized water exchange sensitivity is obtained. The derivative remains small, but for a certain T pstartLTo match the T1 dependency in the control image acquisition 700, in some embodiments, a different TR (e.g., a slightly longer TR) can be used. As mentioned above, using a different TR for the control image can reduce potential errors due to differences in fluid T1. Figure 8 is an example graph showing the derivative of 1 / T1 versus T2-preparation pulse end time according to one embodiment. Graph 800 plots similarly to graph 700 in Figure 7, but a different TR, a 50ms longer TR in this example, is used for control image acquisition. Curve 802 shows the label image acquisition, and curve 804 shows the control image acquisition. In this example with a slightly longer TR, the T1 dependency is greater than that of the longer T pstartL This can be achieved by matching the values. In some embodiments, the dependence on T1 is relatively weak, so this may not be necessary for practical exchange imaging. In some embodiments, the labeling efficiency between the two acquisitions can be evaluated to optimize the R1 derivative or signal.

[0058] The discussed concept may be useful when label and control image acquisition is indeed sensitive to water exchange. For example, if some of the magnetization in the final CSF is generated from tissue with shorter T1 and T2 times and then exchanged with tissue, it is reasonable that the final acquired signals would be different.

[0059] The simplest way to describe water exchange is to assume there are two large compartments, such as CSF (fluid) and tissue (or choroid plexus). When these compartments are large and well mixed, the effect of water exchange is small, and assuming magnetization is present in the tissue, the exchange effect can be estimated linearly. First, the magnetization of the tissue and CSF is determined as a function of time, and then the small effect of exchange can be calculated according to the following differential equation.

number

[0060] Returning to Figure 4, in block 404, at least two images, for example, a first image and a second image, can be generated (or reconstructed) based on the MR data corresponding to each image using known reconstruction methods. In some embodiments, the first and second images can be reconstructed using, for example, a data processing server 114 of the MRI system 100. In some embodiments, the first and second images can be reconstructed using a computer system (for example, the computer system 1400 shown in Figure 14) configured to access or receive MR data acquired by the MR system. The generated first and second images can be stored, for example, in the data storage of the MR system (for example, the MRI system 100 shown in Figure 1) or in the data storage of another computer system.

[0061] In block 406, an image containing signals representing water exchange can be generated by comparing at least two images acquired in block 402 and generated in block 404, for example, by comparing a first image (or label image) and a second image (or control image). In some embodiments, this comparison can be implemented by subtracting the second image from the first image. In some embodiments, this comparison can be implemented by fitting the first and second images to a model or by using other comparison algorithms. The image containing signals representing water exchange generated in block 406 can be stored, for example, in the data storage of an MR system (e.g., the MRI system 100 shown in Figure 1) or in the data storage of another computer system. In block 408, the exchange signal ratio can be determined using the image containing signals representing water exchange. An example of determining the exchange signal ratio for an image containing signals representing water exchange between the CP and CSF of the brain is described in detail below. In block 410, water exchange can be quantified. For example, in some embodiments, water exchange can be quantified using a generated image containing signals representing water exchange, a reference image (e.g., an image acquired without T2 preparation and inversion / recovery pulses), and a physical model. In some embodiments, the quantification can be used to correlate the exchange signal ratio with the exchange rate. In some embodiments, the quantified water exchange information can be stored, for example, in the data storage of the MRI system 100 shown in Figure 1, or in the data storage of another computer system.

[0062] The generated image, which includes signals representing water exchange and / or quantified water exchange information in block 412, is displayed, for example, on the display of the MRI system (e.g., displays 104, 136, and / or 144 of the MRI system 100 shown in Figure 1) or on the display of another computer system.

[0063] As described above with respect to Figures 2 to 9, the acquisition of the first and second images can include inversion recovery (IR) pulses. In some embodiments, it is preferable that the pulse sequence includes multiple IR pulses (i.e., multiple inversion pulses). The following description of Figures 10 to 12 describes the acquisition of two images (e.g., a label image and a control image), but it should be understood that in some embodiments, more than two images can be acquired and compared to generate an image containing signals representing moisture exchange.

[0064] Figure 10 shows an example of a magnetization preparation sequence according to one embodiment. In some embodiments, the magnetization preparation sequence shown in Figure 10 is a generalization of the inversion recovery sequence described above. In Figure 10, time increases from left to right. Preparation A (PrepA) 1002 and Preparation B (PrepB) 1006 can be T2 preparation sequences, such as BIR-8, MLEV, or other sequences for adding T2 sensitivity. In some embodiments, PrepA 1002 and PrepB 1006 may have different T2 sensitivities, and one of them can have zero sensitivity by not applying an RF pulse and setting the duration to zero.

[0065] Here, we consider two different images acquired with different preparation pulses. In some embodiments, in the first image (e.g., the labeled image), strong T2 encoding may be applied to PrepA1002 and short (or zero) T2 encoding may be applied to PrepB1006. In this case, the magnetization after sequencing is expressed as follows:

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[0066] In some embodiments, the TI can be selected (e.g., optimized) such that the term on the right-hand side of Equation 28 is less than 0.01 over a wide range of T1. In fact, even with two inversions (e.g., inversion (IR) pulses), the T1 sensitivity can be significantly reduced, and this term can be reduced to less than 1% in most tissues. As a result, the sensitivity to the error term (β-α) can be reduced by more than 1 / 100th. This allows for measuring exchanges with more modest echo times (TE) because it is not necessary to completely remove shorter T2 tissue signals.

[0067] Figure 11 shows an example of a magnetization preparation inversion recovery pulse sequence configured to include multiple inversion recovery (IR) pulses according to one embodiment. In Figure 11, time increases from left to right. In some embodiments, the exemplary sequence 1100 in Figure 11 can be used to acquire a first image or a label image. The pulse sequence 1100 shown in Figure 11 includes a preparation module (PrepA) 1102 (e.g., a T2 preparation module), an inversion pulse 1104 containing one or more inversion (IR) pulses (e.g., "n" IR pulses), and a readout pulse 1106. As described above, the magnetization preparation module 1102 can be applied before the inversion pulse 1104. Figure 12 shows an example of a magnetization preparation inversion recovery pulse sequence configured to include multiple inversion recovery (IR) pulses according to one embodiment. In Figure 12, time increases from left to right. In some embodiments, the exemplary sequence 1200 in Figure 12 can be used to acquire a second image or a control image. The pulse sequence 1200 shown in Figure 12 may include an inversion pulse 1202 containing one or more inversion (IR) pulses (e.g., "n" IR pulses), a magnetization preparation module (PrepA) 1204 (e.g., a T2 preparation module), and a readout 1206. As described above, the magnetization preparation module 1204 may be applied after the inversion pulse 1202.

[0068] In Figures 11 and 12, the exchange times TS1110,1210 (corresponding to TS1010 from Figure 10) may be within a larger inversion recovery sequence. In the examples shown in Figures 11 and 12, PrepB is assumed to be zero TE, no RF preparation, so the conceptual PrepB has a duration of zero and is not shown in the sequence. In this notation, the pre-preparation time (Tpre(1108,1208)), post-preparation time (Tpost(1112,1212)), and TS can be used to optimize contrast during imaging (e.g., zero CSF). As mentioned above, additional inversion pulses can be added to the exchange time TS(1110,1210) to improve T1 robustness.

[0069] With respect to Figures 10-12, in the embodiments described above, multiple inversion pulses can be applied, for example, to reduce errors from T1 of different tissues. In some embodiments, the timing of the inversion pulse(s) can be selected (e.g., optimized) to reduce system errors over the T1 and T2 ranges. Since the disclosed control strategies are applicable to a wide range of T1s, it is not necessary to strongly attenuate shorter T2 types, and in some embodiments, it is possible to use more moderate, and possibly shorter, TEs. In some embodiments, better control over errors across T2 and T1 of tissues makes other types of contrast, such as velocity-selective ASL, more widely available, along with the disclosed techniques for magnetization-prepared MRI, which are described further below.

[0070] Referring to Figures 10–12, in some embodiments, any preparation that attenuates longitudinal magnetization that does not allow recovery, i.e., any preparation whose effect can be approximated as reducing longitudinal magnetization by a certain scale factor, can be used in the disclosed magnetization preparation MRI technique. For example, using BIR-8 preparations with TE fixed in both PrepA1002,1102,1204 and PrepB1006, while adding a motion encoding gradient to attenuate fluid spin in PrepA1002,1102,1204, allows for selective attenuation of vascular spin. The exchange from vessel to tissue over exchange time TS(1010,1110,1210) is then associated with perfusion, and this constitutes a novel form of velocity-selective ASL. A particular advantage of this control strategy is that errors due to small eddy currents or pulse imperfections are compensated for, and unlike other strategies, system errors due to the motion effect of any subject on preparation efficiency can be eliminated (although they are still potential noise sources). In some embodiments, these preparations (e.g., PrepA1002, 1102, 1204) can be infused with virtually any MRI contrast agent to reveal tissue exchange or transport. For example, as described above, the velocity-selective preparation can be used as magnetization preparation modules PrepA1002, 1102, 1204 for performing velocity-selective ASL imaging of perfusion.

[0071] Figure 13 shows a velocity-selective arterial spin-labeling magnetic resonance imaging method for tissue perfusion in a subject's region of interest according to one embodiment. Although each block of the process shown in Figure 4 is shown in a specific order, in some embodiments one or more blocks may be performed or bypassed in an order different from that shown in Figure 4.

[0072] In block 1302, for example, an MRI system (e.g., MRI system 100 shown in Figure 1) can be used to acquire MR data of at least two images from a region of interest in a subject. The MR data of each image can be acquired using a pulse sequence performed by the MRI system, and the MR data of each image can be acquired at different timings for the application of velocity-selective preparation. The following description of Figure 13 describes the acquisition and reconstruction of two images (e.g., a label image and a control image), but it should be understood that in some embodiments, more than two images can be acquired, reconstructed, and compared to generate an image containing signals representing perfusion. In some embodiments, for example, the MR data of the first image (or label image) can be acquired from the subject using a pulse sequence that includes a velocity-selective preparation module applied at a first predetermined time before readout. In some embodiments, the first pulse sequence includes at least one inversion recovery pulse, and the velocity-selective preparation can be applied at a first time before the IR pulse(s). In some embodiments, the velocity-selective preparation module can be implemented using known pulses and techniques for velocity-selective preparation. In some embodiments, the preparation module can be any pulse that imparts a multiplicative change to the longitudinal magnetization. The readout pulse can be, for example, a three-dimensional high-speed spin echo readout pulse.

[0073] In block 1302, MR data of a second image (or control image) can be acquired from a region of interest in a subject using a pulse sequence that includes a velocity-selective preparation module applied at a second predetermined time before readout, where the second time is different from the first time. In some embodiments, the second pulse sequence may include at least one inversion recovery pulse, and the velocity-selective preparation may be applied after the IR pulse(s) and at the second time before readout. In some embodiments, the velocity-selective preparation module may be implemented using known pulses and techniques for velocity-selective preparation. In some embodiments, the preparation module may be any pulse that imparts a multiplicative change to the longitudinal magnetization. The readout pulse may be, for example, a three-dimensional high-speed spin echo readout.

[0074] In block 1304, at least two images, for example, a first image and a second image, are generated (or reconstructed) using known reconstruction methods based on the corresponding MR data for each image. In some embodiments, the first and second images can be reconstructed using, for example, a data processing server 114 of the MRI system 100. In some embodiments, the first and second images can be reconstructed using a computer system (for example, the computer system 1400 shown in Figure 14) configured to access or receive MR data acquired by the MR system. The generated first and second images can be stored, for example, in the data storage of the MR system (for example, the MRI system 100 shown in Figure 1) or in the data storage of another computer system.

[0075] In block 1306, an image containing a signal representing perfusion can be generated by comparing at least two images acquired in block 1302 and generated in block 1304. For example, a first image (or label image) and a second image (or control image) are compared. In some embodiments, this comparison can be performed by subtracting the second image from the first image. In some embodiments, this comparison can be performed by fitting the first and second images to a model or by using other comparison algorithms. The image containing the signal representing perfusion generated in block 1306 can be stored, for example, in the data storage of an MR system (e.g., MRI system 100 shown in Figure 1) or in the data storage of another computer system. In block 1308, the generated image containing the signal representing perfusion can be displayed on a display, for example, the display of an MRI system (e.g., displays 104, 136, and / or 144 of MRI system 100 shown in Figure 1) or a display of another computer system.

[0076] The following embodiments illustrate in detail the methods by which the Disclosure has been evaluated and the methods by which the Disclosure is used or implemented, and are intended to make the principles of the Disclosure more readily understandable to those skilled in the art. The following embodiments are presented as examples only and are not intended to limit the Invention in any way.

[0077] (Example 1) As described above, in some embodiments, the magnetic resonance imaging method for fluid exchange from tissue to body fluid in a subject region of interest, as shown in Figure 2, can be implemented to image fluid exchange between the CP and CSF in the brain. In this exemplary study, fluid exchange between the CP and CSF can be imaged and evaluated using a T2-prepared long-TE fluid attenuated inversion recovery (FLAIR) sequence. Advantageously, in this example, the disclosed method for imaging fluid exchange yielded high SNR, high-resolution images of the choroid plexus, and the signal difference determined between the T2-prepared image (i.e., the first, labeled image) and the control image (e.g., an image acquired without T2-preparation) suggested fluid exchange between the CP and CSF.

[0078] In the absence of exchange, the CSF signal can be zeroed by the inversion timing, and the CP signal can be effectively zeroed by T2 decay over a very long TE. However, the magnetization that starts in the CP during the preparation time and is exchanged in the CSF is never completely zeroed. Approximating water exchange as an immediate exchange with no return of spin between the CSF and CP, the water exchange signal can be the pre-imaging time integral of the difference in magnetization between the CP and CSF multiplied by the T1 decay coefficient of the CSF before imaging. An IR pulse can effectively invert the contribution before the IR pulse. If a T2 preparation pulse is applied before the inversion pulse, it is possible to substantially zero out the shorter T2 tissue, including the CP. Figure 14A shows an example of graph 1402 showing the magnetization as a function of time before readout for acquisition with and without T2 preparation according to one embodiment, and Figure 14B shows an example of graph 1404 showing the magnetization difference between tissue and body fluid with and without T2 preparation according to one embodiment. In Figure 14A, Graph 1402 shows the longitudinal magnetization (M) of CSF (curve 1406) and CP with T2 preparation (curve 1410) and without T2 preparation (curve 1408). zThis shows the time evolution of ). For this study example, graph 1404 in Figure 14B shows that the difference between CP and CSF magnetization is multiplied by the T1 attenuation coefficient (when the difference is reversed before the reversal pulse) for both with T2 preparation (curve 1414) and without T2 preparation (curve 1412). From graphs 1402 and 1404, it can be seen that without T2 preparation, the exchange contribution after the reversal pulse almost cancels out the previous contribution. However, when T2 preparation is applied, the positive contribution after the reversal pulse increases significantly, resulting in a large net positive exchange signal.

[0079] In this study example, for instance, a 48-channel head coil can be used to perform a scan at 3T. In this example, 3D-FSE T2-FLAIR data (TI / TR / TE=1785 / 6000 / 107ms, ETL=220, linear display order) is acquired, along with a pair of long TE FLAIRs with and without T2-preparation, using reverse-centric view-ordering. These include 25 discarded echoes to avoid the propagation of high-frequency characteristics during early echoes, with ETL=245, TR / TE=6 / 1s, a first refocus flip angle of 120 degrees, and a gradient that gradually decreases to 75 degrees. For example, TI can be automatically adjusted on a case-by-case basis depending on the duration of the echo-train, with a null target of T1=4.27 seconds considering T2-preparation (TI is approximately equal to 1737-1770ms). An additional reference volume that does not have IR or T2 preparation can also be acquired and used as a reference image.

[0080] In this example, the T2-preparation can consist of a 90-degree hard pulse, followed by four adiabatic hyperbolic secant reconverging pulses, and finally one -90-degree hard pulse. As previously mentioned, a second separate FLAIR volume without T2-preparation is also acquired, and the TI can be adjusted for CSF nulling without T2-preparation (TI is approximately equal to 1850-1890 ms). In this example, the common parameters are 136 sagittal slices (1.3 mm). 3 The resolution obtained was achieved by parallel imaging with 2x2 acceleration in both phase-encoded directions, using a matrix of 192x192, with an acquisition time of 3 minutes 21 seconds per volume (total scan time of 16.5 minutes).

[0081] The first image with T2 preparation (label image) and the second image without T2 preparation (control image) can be reconstructed using known methods, and then the difference between the T2-prepared image (label image) and the control volume (or image) can be calculated. The exchange signal fraction (ESF) can be calculated as follows.

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[0082] In some embodiments, T2-preparation data can be acquired with a significantly longer TE of 1.8 seconds to eliminate any possibility of residual CP signal contamination. The presence of a strong residual signal in the CP at such a TE confirms that moisture exchange is the source of the strong signal in the CP.

[0083] In this study example, evidence of water exchange in the choroid plexus was demonstrated using long-TE FLAIR imaging with T2-prepared imaging. This study, by generating high-resolution images of the choroid plexus, can complement other techniques such as ASL, which have recently gained attention in functional studies of the choroid plexus, for example, for functional studies of the choroid plexus. In some embodiments, it is possible to provide control to appropriately match CSF signal levels to T2-prepared acquisitions to support quantification. This quantification can be used for various applications, such as in pathology, including Alzheimer's disease.

[0084] (Example 2) Changes in fluid transport and exchange in the kidney may reflect renal function and renal disease. In some embodiments, a magnetic resonance imaging method for tissue-to-fluid exchange in a region of interest in a subject, as shown in Figure 4, can be implemented for quantitative assessment of intrarenal fluid exchange. In this study example, the images showed a characteristic signal spatial distribution with increased signal in the renal medulla, supported by its detection and evaluation. Therefore, the disclosed MR imaging technique enables the study of intrarenal fluid exchange and may serve as a biomarker for the diagnosis and prognosis prediction of renal disease.

[0085] As described above with respect to Figures 4-6 and 11-12, the disclosed technique can be used for T2-selective labeling using a second image having a T2 saturation pulse (i.e., a T2 preparation pulse) applied at a different time (e.g., later) as a control pulse. In this example, the first image (or labeled image) is acquired from the subject using a pulse sequence including a T2 preparation module applied at a first predetermined time before the readout pulse, and the second image (or control image) is acquired from the subject using a pulse sequence including a T2 preparation module applied at a second predetermined time before the readout pulse, where the second time is different from the first time, for example, the T2 preparation for the second image may be applied at a later time. For example, in the pulse sequence of the first image or labeled image, the T2-selective saturation (i.e., T2 preparation) is applied at a mixing time T mix It can be applied before (i.e., before the exchange time such as the TS mentioned above), and in the pulse sequence of the control image, T2 selective saturation can be applied at a different time, for example, after the mixing time. If no exchange occurs during the mixing time, the magnetization after the label sequence and the control sequence is M, respectively. 2lbl and M 2ctl It can be expressed as follows.

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[0086] In this embodiment, label and control images can be acquired using a 2D SSFSE (RARE) sequence. T2 preparation can be acquired, for example, using a 100ms or 200ms BIR8 adiabatic sequence, and four hyperbolic tangent adiabatic inversion pulses can be applied at optimal timing to minimize recovered magnetization. In this example, T2 preparation is preceded by non-selective saturation 5 seconds before imaging and a T2 inversion recovery pulse optimized to bring the renal fluid M1 to near zero. Following T2 preparation, in this example, a 200ms period is provided to allow some tissue magnetization recovery, and three fat saturation pulses are applied immediately before imaging. In this example, a 10-second TR and variable TE with interleaving for label and control image acquisition was used. TE can be controlled by skipping several echoes before acquisition. In this example, a total of 4 minutes was required per sequence to acquire 11 label, control, and reference images. In this example, the label image was averaged, the control image was averaged, and the averaged control image was subtracted from the averaged label image to create an image containing signals representing water exchange.

[0087] In this example, the images showed that the signal increased primarily within the renal medulla, particularly at longer labeling times, and was distributed throughout the medullary collecting duct system. Cortical signals were relatively more prominent at shorter labeling times (1000 ms exchange or mixing time). This spatial distribution of the signal can be explained by the mixing of water exchange and filtrate bulk flow in the proximal tubule and collecting duct. In this study example, the disclosed method demonstrated that it can provide a highly sensitive method for measuring exchange from short-TE compartments to long-TE compartments, which can be used to assess water exchange within the kidney. The disclosed technique can provide a non-invasive assessment of renal filtration and water exchange that may complement other indicators of renal function.

[0088] (Example 3) As described above, water exchange between tissues and CSF can contribute to CSF ​​production and glymphatic clearance. The large difference in T2 values ​​between tissues and body fluids suggests that T2 magnetization transfer may be used to image the exchange. In some embodiments, the magnetic resonance imaging method for tissue-to-body fluid water exchange in a region of interest in a subject, as shown in Figure 4, can be implemented for the study of CSF exchange that may reflect changes in glymphatic clearance or CSF production associated with aging, Alzheimer's disease, intracranial hypertension, and other diseases. As described above, the disclosed technique can be advantageously used to control system errors caused by the direct effect of T2 saturation pulses on body fluids. In this example study, three-dimensional images at longer TEs can show exchange signals surrounding the choroid plexus, and can also show slower exchanges near the cerebellar vermis, cerebellar cortex, and cerebral cortex.

[0089] As described above with respect to Figures 4-6 and 11-12, the disclosed technique can be used in some embodiments for T2-selective labeling that utilizes a second image having a T2 saturation pulse (i.e., a T2 preparation pulse) applied as a control pulse at a different time (e.g., later). In this example, the first image (or labeled image) is acquired from the subject using a pulse sequence including a T2 preparation module applied at a first predetermined time before the readout pulse, and the second image (or control image) is acquired from the subject using a pulse sequence including a T2 preparation module applied at a second predetermined time before the readout pulse, where the second time is different from the first time, for example, the T2 preparation for the second image may be applied at a later time. For example, in the pulse sequence of the first image or labeled image, the T2-selective saturation pulse (i.e., T2 preparation pulse) is applied at a mixing time T mix (i.e., before the exchange time such as the TS mentioned above), and in the pulse sequence of the control image, the T2-selective saturation pulse can be applied at a different time, for example, after the mixing time. If no exchange occurs during the mixing time, the magnetization after the label sequence and the control sequence is M, as shown in equations 30 and 31 above, respectively. 2lbl and M 2ctl It can be expressed as follows: The difference between the two final magnetizations is not zero by the recovery term R alone, but can be expressed in equation 32 above. If n inversion pulses (or inversions) are added during the mixing time (or exchange time), the M1 term in equations 30 to 32 above is simply multiplied by a power of the inversion efficiency coefficient. The timing of the inversion pulses is selected (e.g., optimized) so that R approaches zero. For three or more inversion pulses (or inversions), R can be reduced to less than 1% at T1, for example, from pure water to fat (see equation 33 above). As mentioned above, subtraction can eliminate the direct effect of labeling on spin exchange, so that any difference between the labeled image and the control image can reflect exchanges during the exchange time or mixing time, for example, such that T2 and / or T1 are not the same.

[0090] In this study example, label and control images can be acquired using a 3DFSE(RARE) sequence. In this example, T2 preparation is implemented using a 200ms TE BIR8 adiabatic sequence, and four adiabatic hyperbolic secant inversion pulses can be applied at optimal timing to minimize recovery magnetization. T2 preparation can be preceded by non-selective saturation 5 seconds before acquisition, and T2 selective inversion recovery can be optimized to bring CSF M1 to near zero. After T2 preparation, a 200ms period is provided to allow some tissue magnetization recovery, and three fat saturation pulses are applied immediately before acquisition. In this example, a 10-second TR, 2x2 parallel acquisition acceleration, an asymptotic 70-degree flip angle train with an echo interval of 3.3ms, and TE-controlled centric phase ordering by skipping echoes before acquisition were selected. In this example, acquisition of label, control, and unprepared reference images required 5 minutes and 20 seconds. In this example, images were acquired from three healthy volunteers at TEs of 106.5, 213.0, and 319.5 ms, with Tmixes of 2 and 1.5 seconds, and a Tmix of 1 second for the two longer TEs. Subsequently, Gaussian smoothing was performed to a resolution of 3 × 3 × 3 mm. In this study, the label and control images were subtracted and divided by the signal at the center of the ventricle on the reference image.

[0091] In this study, all images showed elevated signals surrounding the choroid plexus and distributed throughout the cortical and brainstem regions. Negative white matter signaling was prominent in the TE106.5ms image, but its effect diminished in the 213ms image and became negligible in the 319.5ms image. This effect likely reflects incomplete suppression of recovery magnetization due to the very short T1 component in the white matter. Exchange signals near the choroid plexus and cortex appeared to increase slightly with TE, consistent with a partial decrease in the volume of blurred negative white matter signaling. While exchange signals were present only in regions known to contain the CSF, this signal could not simply be a system error of the CSF, as the spatial intensity changes differed significantly from the unsubtracted label or control and reference images. 3D images averaged across all subjects show the distribution of exchange signals throughout the brain. In this study, the spatial distribution of exchange signals was consistent across subjects, with the highest signal around the choroid plexus in the lateral ventricles. The signaling was also prominent around the fourth ventricle and the cerebellar vermis. In this case, significant exchange can be observed around the cerebellum and cerebral cortex.

[0092] This study demonstrates that the disclosed method provides a highly sensitive approach to measuring exchange from short T2 compartments to long T2 compartments and can be used to assess water exchange from tissues and blood to CSF. The disclosed method may be useful in understanding and diagnosing disorders of CSF production and the glymphatic clearance system.

[0093] Figure 15 is a block diagram showing an example of a computer system according to one embodiment. The computer system 1500 can be used to carry out embodiments of the systems and methods described herein. In some embodiments, the computer system 1500 may be a workstation, a laptop computer, a tablet device, a mobile device, a multimedia device, a network server, a mainframe, one or more controllers, one or more microcontrollers, or other general-purpose or application-specific computing device. The computer system 1500 may operate autonomously or semi-autonomously, read executable software instructions from memory or storage device 1516 or computer-readable media (e.g., hard drive, CD-ROM, flash memory), or receive instructions from a user via input device 1520, or from other sources such as another networked computer or server logically connected to the computer or device. Thus, in some embodiments, the computer system 1500 may also include any suitable device for reading computer-readable storage media.

[0094] For example, data such as data acquired by an imaging system (e.g., a magnetic resonance imaging (MRI) system) is provided from the data storage device 1516 to the computer system 1500, and this data is received by the processing unit 1502. In some embodiments, the processing unit 1502 includes one or more processors. For example, the processing unit 1502 may include one or more of a digital signal processor (DSP) 1504, a microprocessor unit (MPU) 1506, and a graphics processing unit (GPU) 1508. The processing unit 1502 also includes a data acquisition unit 1510 configured to electronically receive the data to be processed. The DSP 1503, MPU 1506, GPU 1508, and data acquisition unit 1510 are all coupled to a communication bus 1512. The communication bus 1512 may be, for example, a group of wires, or hardware used to switch data between peripherals or between any components within the processing unit 1502.

[0095] The processing unit 1502 also includes a communication port 1514 for electronically communicating with other devices, which may include a storage device 1516, a display 1518, and one or more input devices 1520. Examples of input devices 1520 include, but are not limited to, a keyboard, a mouse, and a touchscreen on which the user can input. The storage device 1516 is configured to store data that is provided to or processed by the processing unit 1502, such as MR data, MR images (e.g., label images, control images, images containing signals indicating moisture exchange). The display 1518 may be used to display images or other information, such as patient health data.

[0096] The processing unit 1502 can also communicate electronically with the network 1522 to send and receive data and other information. The communication port 1514 can also be connected to the processing unit 1502 via a switched central resource, such as a communication bus 1512. The processing unit 1502 may also include a temporary storage device 1524 and a display controller 1526. The temporary storage device 1524 is configured to store temporary information. For example, the temporary storage device may be random access memory.

[0097] Computer-executable instructions for magnetic resonance imaging, magnetized and prepared according to the method described above, can be stored in the form of computer-readable media. Computer-readable media include volatile and non-volatile, removable and non-removable media implemented in any method or technique for storing information such as computer-readable instructions, data structures, program modules, or other data. Computer-readable media include, but are not limited to, random access memory (RAM), read-only memory (ROM), electrically erasable programmable ROM (EEPROM), flash memory or other memory technologies, compact disk ROM (CD-ROM), digital volatile disk (DVD) or other optical storage devices, magnetic cassettes, magnetic tapes, magnetic disk storage devices or other magnetic storage devices, or other media that can be used to store desired instructions and are accessible by a system (e.g., a computer), including the Internet or other computer network access formats.

[0098] Although the present invention has been described based on one or more preferred embodiments, it should be understood that many equivalents, substitutes, variations, and modifications other than those explicitly stated are possible and fall within the scope of the invention.

Claims

1. A method for magnetic resonance imaging of water exchange from tissue to body fluid within a region of interest in a subject, Using a magnetic resonance imaging (MRI) system, different T values ​​are used for each image. ２ Using a preparation pulse, magnetic resonance (MR) data is acquired for at least two images of the region of interest in the subject. Using the corresponding MR data, the at least two images are generated. A method comprising generating an image having a signal representing moisture exchange by comparing at least two of the aforementioned images.

2. Acquiring MR data for at least two images of the region of interest in the subject is: T ２ Using a first pulse sequence including a preparation pulse, MR data relating to a first image of the region of interest in the subject is acquired. T ２ This includes acquiring MR data relating to a second image of the region of interest in the subject using a second pulse sequence that does not include a preparation pulse, The method according to claim 1.

3. Acquiring MR data for at least two images of the region of interest in the subject is: T with a first duration ２ Using a first pulse sequence including a preparation pulse, MR data relating to a first image of the region of interest in the subject is acquired. T with a second duration ２ This includes using a second pulse sequence including a preparation pulse to acquire MR data relating to a second image of the region of interest in the subject, The method according to claim 1.

4. The method according to claim 2, wherein the first pulse sequence and the second pulse sequence further include at least one inversion recovery (IR) pulse.

5. The method according to claim 3, wherein the first pulse sequence and the second pulse sequence further include at least one inversion recovery (IR) pulse.

6. The method according to claim 1, wherein comparing the at least two images includes subtracting at least one of the at least two images from at least one of the other images.

7. T ２ Search for reference images acquired without preparation pulses and inversion / recovery pulses. The method according to claim 6, further comprising settling the exchange signal ratio based on the subtraction of the reference image and the at least two images.

8. The method according to claim 1, further comprising displaying the image having a signal representing moisture exchange.

9. The method according to claim 2, wherein the first pulse sequence and the second pulse sequence further include readout pulses having a long echo time.

10. The method according to claim 3, wherein the first pulse sequence and the second pulse sequence further include readout pulses having a long echo time.

11. The method according to claim 1, wherein the region of interest is the brain of the subject.

12. The method according to claim 1, wherein the region of interest is the kidney of the subject.

13. A method for magnetic resonance imaging of water exchange from tissue to body fluid within a region of interest in a subject, Using a magnetic resonance imaging (MRI) system, T for each image ２ Using different timings for applying the preparation pulse, magnetic resonance (MR) data are acquired for at least two images of the region of interest in the subject. Using the corresponding MR data, the at least two images are generated. A method comprising generating an image having a signal representing moisture exchange by comparing at least two of the aforementioned images.

14. Acquiring MR data for at least two images of the region of interest in the subject is: T is given at the first time step. ２ Using a first pulse sequence including a preparation pulse, MR data relating to a first image of the region of interest in the subject is acquired. T applied at the second time ２ obtaining MR data regarding a second image of the region of interest in the subject, using a second pulse sequence including a preparation pulse The second time is different from the first time. The method according to claim 13.

15. The first pulse sequence further includes at least one inversion recovery (IR) pulse, The method according to claim 14, wherein the first time is earlier than the at least one IR pulse.

16. The second pulse sequence further includes at least one inversion recovery (IR) pulse, The method according to claim 14, wherein the second time is after the at least one IR pulse.

17. The method according to claim 13, wherein comparing the at least two images includes subtracting at least one of the at least two images from at least one of the other images.

18. Acquiring MR data for at least two images of the region of interest in the subject is: MR data for the first image is acquired using a first pulse sequence including a first repetition time (TR). This includes acquiring MR data for a second image using a second pulse sequence that includes a second repetition time (TR), The method according to claim 13, wherein the second TR is different from the first TR.

19. The method according to claim 13, further comprising quantifying water exchange based on the image and physical model having signals representing water exchange.

20. The method according to claim 13, further comprising displaying the image having a signal representing moisture exchange.

21. Acquiring MR data for at least two images of the region of interest in the subject is: MR data for the first image is acquired using a first pulse sequence that includes readout pulses with long echo times. This includes acquiring MR data for a second image using a second pulse sequence that includes a readout pulse with a long echo time, The method according to claim 13.

22. The method according to claim 13, wherein the region of interest is the brain of the subject.

23. The method according to claim 13, wherein the region of interest is the kidney of the subject.

24. A magnet system configured to generate a polarization magnetic field with respect to at least a portion of the subject, A magnetic gradient system comprising a plurality of magnetic gradient coils configured to apply at least one gradient magnetic field to the polarization magnetic field, A radio frequency (RF) system configured to apply a radio frequency electromagnetic field to the subject and receive a magnetic resonance signal from the subject using a coil array, A computer system, Adult content for each image ２ Using a preparation pulse, magnetic resonance (MR) data is acquired for at least two images of the region of interest in the subject. Using the corresponding MR data, the at least two images are generated. A computer system programmed to generate an image having a signal representing water exchange by comparing at least two of the aforementioned images, Magnetic resonance imaging (MRI) system.

25. A magnet system configured to generate a polarization magnetic field with respect to at least a portion of the subject, A magnetic gradient system comprising a plurality of magnetic gradient coils configured to apply at least one gradient magnetic field to the polarization magnetic field, A radio frequency (RF) system configured to apply a radio frequency electromagnetic field to the subject and receive a magnetic resonance signal from the subject using a coil array, A computer system, T for each image ２ Using different timings for applying the preparation pulse, magnetic resonance (MR) data are acquired for at least two images of the region of interest in the subject. Using the corresponding MR data, the at least two images are generated. A computer system programmed to generate an image having a signal representing water exchange by comparing at least two of the aforementioned images, Magnetic resonance imaging (MRI) system.

26. A method for velocity-selective arterial spin-labeling magnetic resonance imaging of tissue perfusion in a region of interest in a subject, Using a magnetic resonance imaging (MRI) system, magnetic resonance (MR) data is acquired for at least two images of the region of interest in the subject, using different timings for applying speed-selective preparation for each image. Using the corresponding MR data, the at least two images are generated. A method comprising generating an image having a signal representing moisture exchange by comparing at least two of the aforementioned images.

27. Acquiring MR data for at least two images of the region of interest in the subject is: Using a first pulse sequence including a rate-selective preparation applied at a first time step, MR data relating to a first image of the region of interest in the subject is acquired. The process includes acquiring MR data relating to a second image of the region of interest in the subject using a second pulse sequence that includes a rate-selective preparation applied at a second time step, The second time is different from the first time. The method according to claim 26.

28. The first pulse sequence further includes at least one inversion recovery (IR) pulse, The method according to claim 27, wherein the first time is earlier than the at least one IR pulse.

29. The second pulse sequence further includes at least one inversion recovery (IR) pulse, The method according to claim 27, wherein the second time is after the at least one IR pulse.

30. The method according to claim 26, wherein comparing the at least two images includes subtracting at least one of the at least two images from at least one of the other images.

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