System and method for magnetization-prepared magnetic resonance imaging

Abstract

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

Description

Cross Reference to Related Applications

[0001] This application is based on U.S. Serial No. 63 / 489,359, filed March 9, 2023, and entitled “System and Method for Imaging Tissue to Fluid Water Exchange by T2 Labeling,” and U.S. Serial No. 63 / 510,239, filed June 26, 2023, and entitled “System and Method for Imaging Tissue to Fluid Water Exchange by T2 Labeling,” and claims priority thereto, and is incorporated herein by reference in its entirety. Statement as to Federally Sponsored Research

[0002] N / A TECHNICAL FIELD

[0003] The present disclosure relates generally to magnetic resonance imaging, and more particularly to systems and methods for magnetization preparation for magnetic resonance imaging, including, for example, for imaging tissue to fluid water exchange using T2 labeling, and for velocity-selective arterial spin labeling imaging of tissue perfusion. BACKGROUND

[0004] Water exchange between tissue space and surrounding fluid is a key physiological function. In the brain, water exchange in the choroid plexus and potentially other locations supports cerebrospinal fluid (CSF) production and resorption. The choroid plexus (CP), as the primary source of cerebrospinal fluid production in the brain, plays a key role in brain homeostasis and waste clearance. The choroid plexus is a small structure located in the lateral ventricles that has not been fully characterized, including its dysfunction or impairment in several pathologies or just normal aging. Abnormal CSF production or resorption can lead to intracranial hypertension, hydrocephalus, and potentially dysfunction of the brain’s glial lymphatic drainage system, which has been suggested as a potential cause of Alzheimer’s disease. In the kidney, water exchange with the urine collection system is essential to maintain water balance and urine concentration. In both cases, water exchange is thought to be facilitated by special passive transporters in the cell membrane called aquaporins. In the absence of aquaporins, water exchange through the membrane is much slower, such that tissue fluid boundaries with aquaporins tend to dominate the exchange.

[0005] Currently, there are few methods that are standard of care for assessing water exchange. Radioactive water can be used for animal studies injections, but this is problematic for widespread use. In the brain, phase-contrast MRI can be used to measure CSF production, but the measurement is noisy and difficult due to the highly pulsatile flow of CSF. Recently, researchers have demonstrated the ability to detect arterial blood exchange into the CSF space labeled by arterial spin labeling, for example, as discussed in Evans, P. et al., “Non-Invasive MRI of Blood-Cerebrospinal Fluid Barrier Function,” Nature Communications, vol. 11, article number: 2081 (2020); Perera, C. et al., “Pharmacological MRI with Simultaneous Measurement of Cerebral Perfusion and Blood-Cerebrospinal Fluid Barrier Function Using Interleaved Echo-Time Arterial Spin Labeling,” Neuroimage, September 2021; 238: 118270; and Petitclerc, L. et al., “Ultra-long-TE arterial spin labeling reveals rapid and brain-wide blood-to-CSF water transport in humans,” Neuroimage, December 15, 2021; 245: 118755. The key insight is that the T2 (transverse relaxation time) of the fluid is very long, so images acquired with very long echo times (TE) contain fluid signal, while tissue signal is attenuated away. This effect is very small in humans, but suggests the possibility of imaging water exchange using a non-invasive MRI method.Another group of suggestions marks tissue water itself by applying magnetization transfer (MT) pulses for imaging water exchange in animal models, rather than arterial labeling, such as discussed in Li, A. M., et al., “Age-dependent Cerebrospinal Flid-Tissue Water Exchange Detected by Magnetization Transfer Indirect Spin Labeling MRI,” Magn Reson Med. 2022 May; 87(5): 2287-2298. However, MT requires high power and is less efficient than T2 preparation in saturating tissues, particularly blood. Water exchange is a contributing factor to the signal dynamics when a bolus of MRI contrast agent is injected, but its effect is mixed with many other contributing factors, requiring complex and uncertain models. Other MRI techniques that utilize contrast agents to image exchange or transport between tissues, between tissues and fluids, etc. (e.g., arterial spin labeling (ASL)) also face challenges. SUMMARY

[0006] According to an embodiment, a method for magnetic resonance imaging of tissue-to-fluid water exchange in a region of interest in a subject includes acquiring, using a magnetic resonance imaging (MRI) system, magnetic resonance (MR) data of at least two images of the region of interest of the subject, generating the at least two images using different T2 preparation for each image, and generating 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 tissue-to-fluid water exchange in a region of interest in a subject includes acquiring, using a magnetic resonance imaging (MRI) system, magnetic resonance (MR) data of at least two images of the region of interest of the subject, generating the at least two images using different application timing of T2 preparation for each image, and generating an image having a signal representing water exchange by comparing the at least two images.

[0008] According to another embodiment, a magnetic resonance imaging (MRI) system comprises a magnet system configured to generate a polarizing magnetic field around at least a portion of a subject, a magnetic gradient system comprising a plurality of magnetic gradient coils configured to impose at least one magnetic gradient field on the polarizing magnetic field, a radio frequency (RF) system configured to impose an RF field on the subject and configured to receive magnetic resonance signals from the subject using a coil array, and a computer system. The computer system is programmed for acquiring magnetic resonance (MR) data of at least two images of the region of interest of the subject, using a different T2 preparation for each image, generating the at least two images using the respective MR data, and generating an image with a signal representing water exchange by comparing the at least two images.

[0009] According to another embodiment, a magnetic resonance imaging (MRI) system comprises a magnet system configured to generate a polarizing magnetic field around at least a portion of a subject, a magnetic gradient system comprising a plurality of magnetic gradient coils configured to impose at least one magnetic gradient field on the polarizing magnetic field, a radio frequency (RF) system configured to impose an RF field on the subject and configured to receive magnetic resonance signals from the subject using a coil array, and a computer system. The computer system is programmed for acquiring magnetic resonance (MR) data of at least two images of the region of interest of the subject, using a different T2 preparation for each image, generating the at least two images using the respective MR data, and generating an image with a signal representing water exchange by comparing the at least two images.

[0010] According to another embodiment, a method of velocity-selective arterial spin labeling magnetic resonance imaging of tissue perfusion in a region of interest in a subject comprises acquiring magnetic resonance (MR) data of at least two images of the region of interest of the subject using a magnetic resonance imaging (MRI) system, using a different application timing of a velocity-selective preparation for each image, generating the at least two images using the respective MR data, and generating an image with a signal representing perfusion by comparing the at least two images. BRIEF DESCRIPTION OF DRAWINGS

[0011] The present disclosure will be described with reference to the attached drawings, wherein like reference numerals represent like elements.

[0012] Figure 1 is an example magnetic resonance imaging (MRI) system according to an embodiment.

[0013] Figure 2A method for magnetic resonance imaging of tissue-to-fluid water exchange in a region of interest in a subject is shown according to an embodiment;

[0014] Figure 3 An example T2-prepared inversion recovery pulse sequence is shown according to an embodiment;

[0015] Figure 4 A method for magnetic resonance imaging of tissue-to-fluid water exchange in a region of interest in a subject is shown according to an embodiment;

[0016] Figure 5 An example T2-prepared, long echo time inversion recovery pulse sequence is shown according to an embodiment, in which the T2-preparation module is applied before the inversion recovery pulse;

[0017] Figure 6 An example T2-prepared, long echo time inversion recovery pulse sequence is shown according to an embodiment, in which the T2-preparation module is applied after the inversion recovery pulse;

[0018] Figure 7 An example graph showing the derivative with respect to 1 / T1 versus the end time of T2-preparation is shown according to an embodiment;

[0019] Figure 8 An example graph showing the derivative with respect to 1 / T1 versus the end time of T2-preparation is shown according to an embodiment;

[0020] Figure 9 An example graph showing the sensitivity of water exchange as a function of the end time of T2-preparation is shown according to an embodiment;

[0021] Figure 10 An example magnetization preparation sequence is shown according to an embodiment;

[0022] Figure 11 An example magnetization-prepared inversion recovery pulse sequence configured to include a plurality of inversion recovery (IR) pulses is shown according to an embodiment; and

[0023] Figure 12 An example magnetization-prepared inversion recovery pulse sequence configured to include a plurality of inversion recovery (IR) pulses is shown according to an embodiment;

[0024] Figure 13 A method for velocity-selective arterial spin labeling magnetic resonance imaging of tissue perfusion in a region of interest in a subject is shown according to an embodiment;

[0025] Figure 14AAn example graph is shown according to an embodiment showing the magnetization as a function of time before readout for acquisitions with and without T2 preparation;

[0026] Figure 14B An example graph is shown according to an embodiment showing the difference in magnetization between tissue and fluid with and without T2 preparation;

[0027] Figure 15 is a block diagram of an example computer system according to an embodiment. DETAILED DESCRIPTION

[0028] Reference is now made to Figure 1 The disclosed systems and methods can be implemented using or designed to work with a magnetic resonance imaging ("MRI") system 100 such as that shown in Figure 1 The MRI system 100 includes an operator workstation 102 that will typically include a display 104, one or more input devices 106 such as a keyboard and mouse, and a processor 108. The processor 108 can include a commercially available programmable machine running a commercially available operating system. The operator workstation 102 provides an operator interface that enables a scan prescription to be entered into the MRI system 100. In general, the operator workstation 102 can be coupled to a number of servers including a pulse sequence server 110; a data acquisition server 112; a data processing server 114; and a data store 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, the servers 110, 112, 114, and 116 can be connected via a communication system 140, which can include any suitable network connection whether wired, wireless, or a combination of both. As an example, the communication system 140 can include proprietary networks, dedicated networks, and open networks such as the Internet.

[0029] The pulse sequence server 110 operates in response to instructions downloaded from the operator workstation 102 to operate the gradient system 118 and the radio frequency ("RF") system 120. Gradient waveforms for performing a prescribed scan are generated and applied to the gradient system 118, which excites gradient coils in a gradient assembly 122 to produce magnetic field gradients G x , G y , G z The gradient coil assembly 122 forms part of a magnet assembly 124 that includes a polarizing magnet 126 and a whole-body RF coil 128.

[0030] The RF system 120 applies RF waveforms to the RF coil 128 or separate local coils (Figure 1 The MRI scanner 100 includes a number of components that are controlled by the pulse sequence server 110 to perform a prescribed magnetic resonance pulse sequence. Responsive magnetic resonance signals detected by the RF coil 128, or separate local coils, are received by the RF system 120, which amplifies, demodulates, filters, and digitizes the signals under the direction of commands generated by the pulse sequence server 110. The RF system 120 includes an RF transmitter for generating various RF pulses used in the MRI pulse sequence. The RF transmitter responds to the scan prescription and instructions from the pulse sequence server 110 to produce RF pulses of the desired frequency, phase, and pulse amplitude waveform. The generated RF pulses can be applied to the whole-body RF coil 128 or one or more local coils or coil arrays.

[0031] The RF system 120 also includes one or more RF receiver channels. Each RF receiver channel includes an RF preamplifier that amplifies the magnetic resonance signals received by the coil 128 to which it is connected and a detector that detects and digitizes the I and Q quadrature components of the received magnetic resonance signals. Thus, the amplitude of the received magnetic resonance signals can be determined at any sample point by the square root of the sum of the squares of the I and Q components:

[0032] (1)

[0033] And the phase of the received magnetic resonance signals can also be determined according to the relationship:

[0034] (2)

[0035] The pulse sequence server 110 also selectively receives patient data from the physiological acquisition controller 130. For example, the physiological acquisition controller 130 can receive signals from a number of different sensors connected to the patient, such as electrocardiogram ("ECG") signals from electrodes, or respiration signals from a respiratory bellows or other respiration monitoring devices. These signals are typically used by the pulse sequence server 110 to synchronize or "gate" the performance of the scan with the subject's heartbeat or respiration.

[0036] The pulse sequence server 110 is also connected to the scan room interface circuitry 132 that receives signals from various sensors associated with the patient condition and the magnet system. A patient positioning system 134 also receives commands from the scan room interface circuitry 132 to move the patient into the desired position during scanning.

[0037] The digitized magnetic resonance signal samples produced by the RF system 120 are received by the data acquisition server 112. The data acquisition server 112 operates in response to instructions downloaded from the operator workstation 102 to receive the real-time magnetic resonance data and provide buffer storage so that data is not lost due to data overflow. In some scans, the only function of the data acquisition server 112 is to pass the acquired magnetic resonance data to the data processor server 114. However, in scans that require information to be derived from the acquired magnetic resonance data to control further execution of the scan, the data acquisition server 112 is programmed to produce such information and transmit it to the pulse sequence server 110. For example, during a pre-scan, magnetic resonance data can be acquired and used to calibrate the pulse sequence being executed by the pulse sequence server 110. As another example, navigation signals can be acquired and used to adjust operational parameters of the RF system 120 or the gradient system 118, or to control the view order in which k-space is sampled. In yet another example, the data acquisition server 112 can also be employed to process magnetic resonance signals used to detect the arrival of a contrast agent in a magnetic resonance angiography ("MRA") scan. For example, the data acquisition server 112 acquires magnetic resonance data and processes it in real time to generate information used to control the scan.

[0038] The data processor server 114 receives the magnetic resonance data from the data acquisition server 112 and processes it according to instructions downloaded from the operator workstation 102. Such processing can include one or more of the following, for example: reconstructing two- or three-dimensional images by performing a Fourier transform of the raw k-space data; performing other image reconstruction techniques such as iterative or backprojection reconstruction techniques; applying filters to the raw k-space data or the reconstructed images; generating functional magnetic resonance images; calculating motion or flow images; and so on.

[0039] The images reconstructed by the data processor server 114 are transferred back to the operator workstation 102. The images can be 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 a disk storage 138. When these images are reconstructed and transferred to storage, the data processor 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 the images, produce films, or send the images to other facilities via a network.

[0040] The MRI system 100 can also include one or more networked workstations 142. For example, the networked workstations 142 can include a display 144, one or more input devices 146 such as a keyboard and mouse or similar devices, and a processor 148. The networked workstations 142 can be located within the same facility as the operator workstation 102, or in a different facility, such as a different medical facility or clinic. The networked workstations 142 can include mobile devices, including telephones or tablets.

[0041] The networked workstations 142, whether within the same facility as the operator workstation 102 or in a different facility, can remotely access the data processing server 114 or the data storage server 116 via the communication system 140. Thus, multiple networked workstations 142 can access the data processing server 114 and the data storage server 116. In this way, magnetic resonance data, reconstructed images, or other data can be exchanged between the data processing server 114 or the data storage server 116 and the networked workstations 142, such that the data or images can be processed remotely by the networked workstations 142. These data can be exchanged in any suitable format, such as according to the Transmission Control Protocol (“TCP”), the Internet Protocol (“IP”), or other known or suitable protocols.

[0042] The present disclosure describes systems and methods of magnetization-prepared magnetic resonance imaging (MRI). In some embodiments, the disclosed magnetization-prepared MRI techniques can be used in systems and methods of velocity-selective arterial spin labeling magnetic resonance imaging of tissue perfusion. For example, two or more images of a region of interest in a subject can be acquired using different application timing of velocity-selective preparation for each image. An image with signal representative of perfusion can be generated by comparing the at least two images.

[0043] In some embodiments, the disclosed magnetization-prepared MRI techniques can be used in systems and methods of 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 differences in transverse relaxation (T2) between fluid and tissue / blood components. Advantageously, T2 preparation can be used to impart sensitivity to tissue-to-fluid water exchange. In some embodiments, at least two images of a region of interest of a subject can be acquired using an MRI system. Each of the at least two images can be acquired using a different T2 preparation (e.g., with or without T2 preparation, T2 preparation of different durations) or different timing of T2 preparation. An image with signal representative of water exchange can be generated by comparing the at least two images (e.g., by subtraction, fitting a model, or other comparison algorithm). In some embodiments, the disclosed systems and methods can provide sensitive measurement of the manner of water exchange, for example, from short to long echo time (TE) compartments, to assess water exchange within a region of interest.

[0044] In some embodiments, T2 preparation can be applied at a predetermined time prior to acquisition (i.e., readout) of a first image (e.g., a reweighted T2 image). As used herein, the first image acquired using T2 preparation can also be referred to as a marker image. A second image can be acquired and compared to the first image. As used herein, the second image can also be referred to as a control image. In some embodiments, the second image can be acquired using a different T2 preparation (e.g., no T2 preparation (T2 preparation off), T2 preparation of a different duration). In some embodiments, the second image can be acquired using T2 preparation applied at a different time than the T2 preparation applied for the first image. Comparison of the first and second images can be used to infer water exchange occurring between tissue and fluid. In some embodiments, the comparison can be used to generate an image with a signal representative of water exchange.

[0045] In some embodiments, acquisition of the first and second images further includes application (or playing) of one or more inversion recovery (IR) pulses. Inversion recovery can approximately cancel fluid signal, e.g., as employed in fluid attenuated inversion recovery (FLAIR) pulse sequences. With fluid signal greatly attenuated by inversion recovery, motion and other artifacts related to otherwise large fluid signal can be greatly reduced. In some embodiments, where both the first and second images are acquired using T2 preparation, the T2 preparation for the first image can be applied at an optimal time prior to the IR pulse(s), while the T2 preparation for the second image can be applied at an optimal time after the IR pulse(s). Acquiring both images with T2 preparation applied prior to the IR pulse(s) (in the first image) and after the IR pulse(s) (in the second image) can, for example, provide the same sensitivity to systematic effects of imperfect T2 preparation and variable T2 in fluid, and can allow for control of systematic errors in T2 preparation. In some embodiments, the timing of the inversion pulses can be selected (e.g., optimized) to reduce systematic errors over the T1 and T2 ranges. In some embodiments, comparison of the two images can be performed by subtracting the two images, which can give a signal reflecting water exchange. In some embodiments, dividing the subtraction of the two images by a reference image without inversion recovery or T2 preparation can provide a semi-quantitative ratio image. In some embodiments, the method can be configured to reduce sensitivity to variable longitudinal magnetization (T1) of fluid. In some embodiments, changing the repetition time (TR) of one image compared to the other of the two images can reduce T1 sensitivity of the measurement, and having a different TR for the second (or control) image can reduce potential errors from fluid T1 differences. For example, the TR of the second (or control) image can be different (e.g., longer) than the TR of the first (or marker) image.

[0046] In some embodiments, quantification of water exchange can also be performed using images with signals representing water exchange generated by comparing two images. A model of the contribution of tissue-fluid water exchange to the MRI signal can be used for quantification. In some embodiments, a semi-quantitative ratio can be correlated with the exchange rate.

[0047] In some embodiments, the region of interest to which tissue fluid exchange is imaged can be, for example, the brain or the kidneys. In one example, the disclosed systems and methods can be used for quantitative assessment of intrarenal fluid exchange, which can serve as a biomarker for the diagnosis and prognosis of kidney disease. Furthermore, the systems and methods of this disclosure can provide a non-invasive assessment of renal filtration and water exchange, which can complement other measurements of renal function. In another example, the disclosed systems and methods can be used for in vivo studies of CSF exchange, which can reflect changes in glial lymphatic clearance or CSF production with aging, Alzheimer's disease, intracranial hypertension, and other diseases. While the following... Figures 2-10 The description can be discussed as an example application of imaging water exchange between tissues and fluids in the brain (e.g., water exchange between the choroid plexus (CP) and cerebrospinal fluid (CSF)), but it should be understood that the systems and methods disclosed herein can be used to image water exchange in any region of a subject's anatomy.

[0048] Figure 2 A method for performing magnetic resonance imaging on tissue-to-fluid water exchange in a region of interest in a subject, according to an embodiment, is shown. Although Figure 2 The blocks in the process diagram are shown in a specific order, but in some embodiments, one or more blocks may be arranged in a manner consistent with... Figure 2 The order shown may be different from the order of execution, or it may be bypassed.

[0049] In box 202, an MRI system (e.g., MRI) can be used. Figure 1 The illustrated MRI system 100 acquires MR data for at least two images from the region of interest of the subject. MR data for each image can be acquired using a pulse sequence performed on the MRI system, and different T2 preparations can be used to acquire MR data for each image. For example, in some embodiments, MR data for a first image (or marker image) can be acquired using a T2 preparation applied at a predetermined time prior to acquisition (i.e., readout), and MR data for a second image (or control image) can be acquired without T2 preparation (e.g., T2 preparation off). In some embodiments, MR data for each image can be acquired using T2 preparations of different durations. Although the following describes… Figures 2-4The discussion will refer to the acquisition and reconstruction of two images, but it should be understood that in some embodiments, more than two images can be acquired, reconstructed, and then compared to generate an image having a signal representative of water exchange. As previously mentioned, in some embodiments, the MR data for the first image can be acquired from the subject using a pulse sequence that includes a T2 preparation module applied at a predetermined time prior to readout. In some embodiments, the T2 preparation module can be implemented using known pulses and techniques for T2 preparation. In one example, the T2 preparation module (e.g., Figure 3 shown as T2 preparation module 302) can include a 90 degree hard pulse followed by four adiabatic hyperbolic secant refocusing pulses and a final 90 degree hard pulse. The readout of the pulse sequence can be, for example, a three-dimensional fast spin echo readout. In some embodiments, the pulse sequence can also include one or more inversion recovery pulses applied at a predetermined time after the T2 preparation. Figure 3 An example T2 preparation inversion recovery pulse sequence according to an embodiment is shown. Figure 3 The pulse sequence 300 shown includes a T2 preparation module 302 having a duration T T2prep 308, an IR pulse 304, a readout 306 having an echo time TE 314, an inversion time 310, and a repetition time 312. In some embodiments, the echo time TE 314 can be a long echo time. While Figure 3 One IR pulse 304 is shown, but it should be understood that in some embodiments, the pulse sequence 300 can include multiple IR pulses 304.

[0050] Returning to Figure 2 At block 202, MR data for a second image (or control image) can be acquired from the subject using a pulse sequence that includes different T2 preparation, for example, a pulse sequence that does not include a T2 preparation module (e.g., Figure 3 shown as pulse sequence 300 without T2 preparation module 302) can be used to acquire MR data for the second image, or a pulse sequence with different duration of T2 preparation (e.g., Figure 3 shown as pulse sequence 300 with T2 preparation module 302 having different duration 308 of T2 preparation) can be used to acquire MR data for the second image. The readout can be, for example, a three-dimensional fast spin echo readout. In some embodiments, the pulse sequence can also include one or more inversion recovery pulses applied at a predetermined time prior to readout. The MR data acquired for the at least two images (e.g., the first image and the second image) can be stored, for example, in a data storage of an MR system (e.g., Figure 1 shown as MRI system 100), or in a data storage of other computer systems.

[0051] At block 204, at least two images, i.e., a first image and a second image, can be generated (or reconstructed) based on the respective MR data of each image acquired at block 202 using known reconstruction methods. In some embodiments, the first image and the second image can be reconstructed using, for example, the data processing server 114 of the MRI system 100. In some embodiments, the first image and the second image can be reconstructed using a computer system configured to access or receive MR data acquired by an MR system (e.g., the computer system 1400 shown in FIG. 14). The generated first image and second image can be stored in, for example, a data storage of the MR system (e.g., the MRI system 100 shown in Figure 1 FIG. 14), or a data storage of other computer systems.

[0052] At block 206, an image with signals representing water exchange can be generated by comparing the at least two images acquired at block 202 and generated at block 204 (e.g., comparing the first image and the second image). In some embodiments, the comparison can be achieved by subtracting the second image from the first image. In some embodiments, the comparison can be achieved by fitting the first image and the second image to a model or by using other comparison algorithms. The image with signals representing water exchange generated at block 206 can be stored in, for example, a data storage of the MR system (e.g., the MRI system 100 shown in Figure 1 FIG. 14), or a data storage of other computer systems. At block 208, the image with signals representing water exchange can be used to determine an exchange signal fraction. At block 210, the generated image with signals representing water exchange can be displayed on a display, for example, a display of the MRI system (e.g., the displays 104, 136, and / or 144 of the MRI system 100 shown in Figure 1 FIG. 14), or a display of other computer systems.

[0053] The movement of water from one compartment to another has potentially great significance for understanding physiology and pathophysiology, testing drug treatments, and potentially diagnosis for individual patients. Water exchange can also be a key function of systems that require water transfer to function. In the choroid plexus, and potentially other boundaries of the central nervous system, the exchange of water with CSF can be critical for the production of CSF. Such production is important for maintaining CSF pressure and potentially clearing larger molecules in the brain through a process known as the glymphatic system. In the kidneys, water exchange can be necessary for controlling water balance through exchange with a collection system that results in the production of urine.

[0054] As discussed above, MRI can become sensitive to water exchange if it is possible to selectively attenuate or label one compartment and then selectively image the other. Because the measurements are typically offset by a significant bias, the labeled image can be compared to a second image that does not label the other compartment. However, simply not labeling the control image (as discussed above with respect to Figure 2 ) can be insufficient because the labeling is not completely selective but rather more weakly attenuates the compartment being imaged.

[0055] As described above, in some embodiments, rather than an image without T2 preparation or an image with a different T2 preparation duration, at least two images with different timing of T2 preparation can be acquired to change the sensitivity to water exchange. In these embodiments, each acquired image can use the same T2 labeling strategy but applied at a different time. Because the water exchange effect can accumulate over time, the difference between the images will still be sensitive to water exchange. However, saturating the image pools at different times can result in different effects due to the relaxation and recovery times of MRI. To overcome this limitation, in some embodiments, the labeling preparation and control preparation can be applied on both sides of the inversion recovery pulse. In some embodiments, with appropriate timing optimization, this strategy can control a reasonable range of saturation parameters and relaxation parameters.

[0056] Figure 4 A method for magnetic resonance imaging of tissue-to-fluid water exchange in a region of interest in a subject is shown in accordance with an embodiment. Although Figure 4 the blocks of the processes in Figure 4 are shown in a particular order, in some embodiments, one or more blocks can be performed in a different order than shown in or can be bypassed.

[0057] At block 402, MR data for at least two images can be acquired from a region of interest of a subject using, for example, an MRI system (e.g., the MRI system 100 shown in Figure 1 ). The MR data for each image can be acquired using a pulse sequence executed on the MRI system, and the MR data for each image can be acquired using different timing of application of T2 preparation. Although the following is described with respect to Figures 4-9The discussion will refer to the acquisition and reconstruction of two images (e.g., a marker image and a control image), but it should be understood that in some embodiments, more than two images can be acquired, reconstructed, and then compared to generate an image having a signal representative of water exchange. In some embodiments, for example, MR data for a first (or marker) image can be acquired from a subject using a pulse sequence that includes a T2 preparation module applied a predetermined time before readout. In some embodiments, the first pulse sequence can include at least one inversion recovery pulse, and the T2 preparation 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 produces a multiplicative change to the longitudinal magnetization. The readout can be, for example, a three-dimensional fast spin echo readout. Figure 5 An example T2-prepared, long echo time inversion recovery pulse sequence is shown in accordance with an embodiment, in which a T2 preparation module is applied before the inversion recovery pulse. Figures 5-9 The illustrated pulse sequence 500 includes a T2 preparation module 502, an IR pulse 504, and a readout 506. As used herein with respect to Figure 5 The suffix "L" is used to refer to marker image acquisition, while the suffix "C" is used to refer to control image acquisition for all parameters (further described below). In Figure 5 In the illustrated sequence 500, time increases from left to right. The sequence 500 includes various magnetizations and timings, including, for example, a start time of acquisition TR L -T read a start time of T2 preparation T pstartL +T prep an end time of T2 preparation T pstartL (512), an inversion recovery time TI L (514), and an end of magnetization M end (516). The marker T2 preparation 502 can be applied for a time period T prep In some embodiments, the preparation module 502 can be any pulse that produces a multiplicative change to the longitudinal magnetization. In some embodiments, the preparation module 502 can be configured to invert the magnetization. While Figure 11 Only one IR pulse 504 is shown in the illustrated sequence 500, but it should be understood that in some embodiments, more than one IR pulse 504 can be included after the T2 preparation module 502 and before the readout 506, as further discussed below with respect to Figure 4

[0058] Returning to Figure 6 ​At block 402, MR data for a second image (or control image) can be acquired from the subject using a pulse sequence including a T2 preparation module applied a second predetermined time before readout, where the second time is different from the first time. In some embodiments, the second pulse sequence can include at least one inversion recovery pulse, and the T2 preparation can be applied at the second time after the IR pulse(s) and before readout. 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 produces a multiplicative change to the longitudinal magnetization. The readout can be, for example, a three-dimensional fast spin echo readout. Figure 6 An example T2-prepared, long echo time inversion recovery pulse sequence is shown in which the T2 preparation module is applied after the inversion recovery pulse, in accordance with an embodiment. Figure 6 In the illustration, time increases from left to right. Figure 6 The illustrated pulse sequence 600 includes an IR pulse 602, a T2 preparation module 604, and a readout 606. The sequence 600 also includes various magnetizations and timings, including, for example, a start time of acquisition TR C -T read a start time of T2 preparation T pstartC +T prep a recovery time TI C (610), an end time of T2 preparation T pstartC (614), and an end of magnetization M end (616). While Figure 12 only one IR pulse 602 is shown in the illustration, it should be understood that in some embodiments, more than one IR pulse 602 can be included before the T2 preparation module 604, as discussed further below with respect to Figure 5 .

[0059] With reference to both Figure 6 and Figure 5 , while M end (516, 616) should be equal for both image acquisitions, in principle, TR and M start can be different for the marker image and the control image. T read may be equal because using the same imaging sequence will match the image parameters across the spatial encoding. In some embodiments, there is an advantage to making M start effectively zero because the saturation effects of imaging are typically imperfect and sensitive to parameters such as RF field amplitude. There can also be an advantage to keeping M end small because small signals are typically difficult to measure against a larger background.

[0060] In some embodiments, the acquisition of the labeled and control images in block 402 may assume selective imaging of target compartments (e.g., tissues such as CP and fluids such as CSF). For CSF imaging selectively via T2, this can be efficiently achieved with very long TE imaging, for example, using multi-spin echo sequences.

[0061] In some embodiments, for the acquisition of the first (or marker) image of box 402, it can be assumed that there is no z-recovery during preparation, only multiplicative decay or potentially even inversion. In some embodiments, this effect can be mitigated by a factor α with a value between -1 and 1. prep This will be described further below. As used in this article, T pstartL It can be defined as the time after the preparation for the acquisition of the first or marked image is completed.

[0062] In some embodiments, the acquisition time of the first or marked image is reversed ( Figure 7 The TI shown L (514) can be determined by following the magnetization evolution according to the Bloch equation:

[0063] (3)

[0064] (4)

[0065] (5)

[0066] (6)

[0067] If a specific M end To achieve this, the equation can be reversed to solve for TI. L (514):

[0068] (7)

[0069] In some embodiments, α prep And T1 may not be known with high precision because relaxation time can vary across regions, imperfections in the RF field can alter preparation efficiency, etc. It may be desirable to reduce, minimize, or otherwise optimize the sensitivity to variations in these parameters. For first order, these can be determined by their first derivatives, which can be calculated as follows.

[0070] (8)

[0071] (9)

[0072] In some embodiments, for the acquisition of the second (or control) image of block 402, it can be assumed that there is no z-recovery during preparation, only T2 decay. In some embodiments, T pstartC may be defined as the end of T2 preparation time for the acquisition of the second or control image. In this way, T pstartC = 0 can correspond to the T2 preparation applied just before the control image imaging.

[0073] Following the evolution of magnetization according to the Bloch equation:

[0074] (10)

[0075] (11)

[0076] (12)

[0077] (13)

[0078] (14)

[0079] (15)

[0080] (16)

[0081] In some embodiments, it can be desirable to match the acquisition of the marker image (i.e., sequence 500) with the acquisition of the control image (i.e., sequence 600) for sensitivity to a prep In some embodiments, to match the two acquisitions, it is first necessary to match the M end These equations do not take into account the exchange effect, so any difference will be a systematic error. Next, the derivative with respect to a prep may be matched.

[0082] For the marker image acquisition:

[0083] (17)

[0084] For the control image acquisition:

[0085] (18)

[0086] In some embodiments, this can be simplified by inserting from the equation of M end

[0087] (19)

[0088] or ​

[0089] (20)

[0090] Thus

[0091] (21)

[0092] This can have the advantage of not being directly sensitive to TI C or TR C .

[0093] Setting the two derivatives equal gives:

[0094] (22)

[0095] (23)

[0096] In some embodiments, given any T pstartL , one can calculate T pstartC , and one can determine the inversion time of the derivative of the signal matching the two acquisitions (500, 600) with respect to a prep .

[0097] In some embodiments, it can also be desirable to match the sensitivity of the two acquisitions (500, 600) to T1. For example, to explore the sensitivity of the end magnetization change to T1, it can be convenient to numerically evaluate the derivative equation with respect to 1 / T1. In general, one can find that the T1 dependence is small, but for T pstarts very close to T1, the match is almost perfect. When T pstarts is far from T1, one can find that the marker image is more sensitive to T1 than the control image.

[0098] Figure 8 An example graph showing the relationship of the derivative with respect to 1 / T1 versus the end time of the T2 preparation is shown in accordance with an embodiment. Graph 700 shows the relationship of the derivative with respect to 1 / T1 versus T pstartL in milliseconds, under an example set of experimental parameters. The top curve 702 shows the marker image acquisition, and the bottom curve 704 shows the control image acquisition. In some embodiments, the best water exchange sensitivity occurs at longer T pstartL where the derivative does not match. The derivative remains small, but to match the T1 dependence at a particular T pstartL , in some embodiments, a different TR (e.g., a slightly longer TR) can be used for the control image acquisition 700. As noted above, using a different TR for the control image can reduce potential errors due to fluid T1 differences. Figure 7An example graph is shown according to an embodiment, showing the derivative with respect to 1 / T1 versus the end time of T2 preparation. Graph 800 is a similar plot to graph 700 in Figure 9 but with a different TR used for control image acquisition, in this example, the TR is lengthened by 50 milliseconds. Curve 802 shows the marker image acquisition, and bottom curve 804 shows the control image acquisition. In this example, with the TR slightly longer, the T1 dependence can match at longer T pstartL In some embodiments, given the relatively weak dependence on T1, this can not be necessary for practical exchange imaging. In some embodiments, the marker efficiency between the two acquisitions can be assessed to try to optimize the R1 derivative or signal.

[0099] The concepts discussed can be useful when the marker and control image acquisitions are actually sensitive to water exchange. It is reasonable that if, for example, some of the magnetization in the CSF at the end comes from tissue (where T1 and T2 are shorter but subsequently exchanged into that tissue), then the signal at the end of the acquisition can be different.

[0100] The simplest approach to water exchange is that there are two large compartments, for example, CSF (fluid) and tissue (or choroid plexus). If these compartments are large and well mixed, then the effect of water exchange can be small, and one can assume that the magnetization is in the tissue, and estimate the exchange effect to first order. The magnetization can first be determined as a function of time for the tissue and CSF, and then the small exchange effect can be calculated according to the following differential equation:

[0101] (24)

[0102] where χ is the exchange rate parameter. In some embodiments, this can be solved piecewise between RF pulses in different experiments. Figure 9 An example graph is shown according to an embodiment, showing the sensitivity to water exchange as a function of the end time of T2 preparation. Graph 900 shows the sensitivity to water exchange as a function of T pstartL In the example shown, the sensitivity peaks at T pstartL near 3000 milliseconds. Figure 4

[0103] Returning to Figure 1 ​At block 404, at least two images (i.e., a first image and a second image) can be generated (or reconstructed) based on the respective MR data of each image using known reconstruction methods. In some embodiments, the first image and the second image can be reconstructed using, for example, the data processing server 114 of the MRI system 100. In some embodiments, the first image and the second image can be reconstructed using a computer system configured to access or receive MR data acquired by an MR system (e.g., the computer system 1400 shown in FIG. 14). The generated first image and second image can be stored in, for example, a data storage of the MR system (e.g., the MRI system 100 shown in Figure 1 FIG. 14), or a data storage of other computer systems.

[0104] At block 406, an image having signals representative of water exchange can be generated by comparing the at least two images acquired at block 402 and generated at block 404 (e.g., comparing the first (or marker) image to the second (or control) image). In some embodiments, the comparison can be achieved by subtracting the second image from the first image. In some embodiments, the comparison can be achieved by fitting the first image and the second image to a model or using other comparison algorithms. The image having signals representative of water exchange generated at block 406 can be stored in, for example, a data storage of the MR system (e.g., the MRI system 100 shown in Figure 1 FIG. 14), or a data storage of other computer systems. At block 408, the image having signals representative of water exchange can be used to determine an exchange signal fraction. Examples of determining an exchange signal fraction of an example image having signals representative of water exchange between the CP and CSF of the brain will be discussed further below. At block 410, water exchange can be quantified. For example, in some embodiments, water exchange can be quantified using the generated image having signals representative of water exchange, a reference image (e.g., acquired without T2 preparation or inversion recovery), and a physical model. In some embodiments, the quantification can be used to relate the exchange signal fraction to an exchange rate. In some embodiments, the quantified water exchange information can be stored in, for example, a data storage of the MR system (e.g., the MRI system 100 shown in Figure 1 FIG. 14), or a data storage of other computer systems.

[0105] At block 412, the generated image having signals representative of water exchange and / or the quantified water exchange information can be displayed on a display, for example, a display of the MRI system (e.g., the displays 104, 136, and / or 144 of the MRI system 100 shown in Figures 2-9 FIG. 14), or a display of other computer systems.

[0106] As discussed above with respect to Figures 10-12The acquisition of the first and second images can include an inversion recovery (IR) pulse, as discussed. In some embodiments, the pulse sequence can advantageously include multiple IR pulses (i.e., multiple inversions). While the following discussion of Figure 10 will refer to the acquisition of two images (e.g., a marker image and a control image), it should be understood that in some embodiments, more than two images can be acquired and then compared to generate an image having a signal representative of water exchange.

[0107] Figure 10 An example magnetization preparation sequence according to an embodiment is shown. In some embodiments, Figure 10 The magnetization preparation sequence shown generalizes the inversion recovery sequence described above. In Figure 11 In the sequence, time increases from left to right. Prep A (PrepA) 1002 and Prep B (PrepB) 1006 can be, for example, T2 preparation sequences such as BIR-8, MLEV, or other sequences for increasing T2 sensitivity. In some embodiments, PrepA 1002 and PrepB 1006 can have different T2 sensitivities, and one can even impart zero sensitivity by not applying an RF pulse and having zero duration.

[0108] Now consider two different images acquired using different preparations. In some embodiments, in a first image (e.g., a marker image), a strong T2 encoding can be applied to PrepA 1002 and a short (or zero) T2 encoding applied to PrepB 1006. In this case, the magnetization after the sequence can be given by:

[0109] (25)

[0110] where M start is the tissue magnetization at the beginning of the sub-sequence, T1 is the tissue relaxation time, (1-alpha) is the decay of the magnetization due to PrepA 1002 (T2 dependence), and (1-beta) is the decay of PrepB 1006. For a second image (e.g., a control image), the preparation can be inverted, with PrepB 1006 applied before TS (exchange time 1010) and PrepA 1002 applied afterwards. The corresponding tissue magnetization can be given by:

[0111] (26)

[0112] The difference between these two images (ignoring exchange effects) can be given by:

[0113] (27)

[0114] For any given TS (switching time) and T1, the inversion time (TI 1008) can be chosen such that the term in the bracket on the right side of equation 27 is zero. Thus, the difference in tissue magnetization due to inefficiencies contained in alpha and beta is eliminated. If the magnetization is switched between two compartments with different T2 / T1, the difference will not be zero. T1 is not equal in all tissue, so this solution is not perfect. For reasonably short TS (1010), the term on the right is still close to zero for a range of T1. However, in some embodiments, performance can be improved by adding more inversions. If we replace the single inversion (inversion pulse) 1004 with n inversions (n inversion pulses) between the two preparation blocks 1002, 1006, the difference between the two images becomes:

[0115] (28)

[0116] In some embodiments, the TI option can be chosen (e.g., optimized) such that the term on the right side of equation 28 is less than 0.01 for a wide range of T1. In fact, even two inversions (e.g., inversion (IR) pulses) can greatly reduce T1 sensitivity and make this term less than 1% for most tissue. As a result, the sensitivity to the error term (beta - alpha) can be reduced by more than 100 times. This makes it possible to measure the exchange at more modest echo times (TE) because there is no need to completely eliminate the shorter T2 tissue signal.

[0117] Figure 11 An inversion recovery pulse sequence configured to include multiple inversion recovery (IR) pulses is shown according to an embodiment. In Figure 11 , time increases from left to right. In some embodiments, The example sequence 1100 of Figure 11 may be used to acquire the first or marker image. Figure 12 The pulse sequence 1100 shown includes a preparation block (PrepA) 1102 (e.g., a T2 preparation block), an inversion 1104 (which can include one or more inversion (IR) pulses (e.g., “n” IR pulse(s))), and a readout 1106. As discussed above, the magnetization preparation block 1102 can be applied prior to the inversion pulse(s) 1104. Figure 12 An inversion recovery pulse sequence configured to include multiple inversion recovery (IR) pulses is shown according to an embodiment. In Figure 12 , time increases from left to right. In some embodiments, The example sequence 1200 of Figure 12 may be used to acquire the second or control image. Figure 11The illustrated pulse sequence 1200 includes an inversion 1202 (which can include one or more inversion (IR) pulses (e.g., “n” IR pulse(s))), a magnetization preparation module (PrepA) 1204 (e.g., a T2 preparation module), and a readout 1206. As discussed above, the magnetization preparation module 1204 can be applied after the inversion pulse(s) 1202.

[0118] In Figure 12 and Figure 10 , the swap time TS 1110, 1210 (corresponding to TS 1010 in Figure 11 ) can be within a larger inversion recovery sequence. In Figure 12 and Figures 10-12 the illustrated examples, PrepB is assumed to be zero TE, RF-free preparation, so the duration of the conceptual PrepB is zero and is not visible in the sequence. In this notation, the time before and after the preparation (Tpre(1108, 1208) and Tpost(1112, 1212)) and TS can be used to optimize contrast at the imaging time (e.g., to cancel CSF). Additional inversion pulses can be added to the swap time TS (1110, 1210) for improved T1 robustness, as discussed above.

[0119] In the embodiments discussed above with respect to Figures 10-12 , multiple inversion pulses can be applied, e.g., to reduce errors from different tissue T1s. In some embodiments, the timing of the inversion pulse(s) can be selected (e.g., optimized) to reduce systematic errors across the T1 and T2 ranges. Because the disclosed control strategy can be applied to a wide range of T1s, there is no need to strongly attenuate shorter T2 species, and in some embodiments, a more moderate and potentially even short TE can be used. In some embodiments, better control of errors across tissue T2 and T1 can enable other types of contrast agents (such as velocity-selective ASL) to be more widely used with the disclosed magnetization preparation MRI techniques, as discussed further below.

[0120] Referring to Figure 13In some embodiments, any preparation that attenuates longitudinal magnetization without allowing for recovery (i.e., whose effect can be approximated as reducing longitudinal magnetization by a scaling factor) can be used in the disclosed magnetization preparation MRI technique. For example, BIR-8 preparations with a fixed TE are used for PrepA 1002, 1102, 1204, and PrepB 1006, but motion-coded gradients are added to PrepA 1002, 1102, and 1204 to attenuate flow spin, which can be used to selectively attenuate vascular spin. The exchange from vessel to tissue within the exchange time TS (1010, 1110, 1210) will then be perfusion-related, and this will be a novel form of velocity-selective ASL. A specific advantage of this control strategy is that small eddy current or pulse imperfection errors will be compensated for, unlike other strategies, and any systematic errors in preparation efficiency due to subject motion effects can be eliminated (although they will still be potential sources of noise). In some embodiments, virtually any MRI contrast agent can be applied in these preparations (e.g., PrepA 1002, 1102, 1204) to reveal exchange or transport between tissues. For example, as previously described, velocity-selective preparation can be used as a magnetization preparation module PrepA 1002, 1102, 1204 for performing velocity-selective ASL imaging on perfusion.

[0121] Figure 4 A method for velocity-selective arterial spin-labeling magnetic resonance imaging of tissue perfusion in a region of interest in a subject, according to an embodiment, is illustrated. Although Figure 4 The blocks in the process diagram are shown in a specific order, but in some embodiments, one or more blocks may be arranged in a manner consistent with... Figure 1 The order shown may be different from the order of execution, or it may be bypassed.

[0122] In box 1302, an MRI system (e.g., ) can be used. Figure 13 The MRI system 100 shown acquires MR data from at least two images of the region of interest of the subject. MR data for each image can be acquired using a pulse sequence executed on the MRI system, and MR data for each image can be acquired using different timing sequences of velocity-selective preparation. Although the following... Figure 1The discussion will refer to the acquisition and reconstruction of two images (e.g., a marker image and a control image), but it should be understood that in some embodiments, more than two images can be acquired, reconstructed, and then compared to generate an image having a signal representative of perfusion. In some embodiments, for example, MR data for a first (or marker) image can be acquired from a subject using a pulse sequence that includes a velocity selective preparation module applied a first predetermined time before readout. In some embodiments, the first pulse sequence can include at least one inversion recovery pulse, and the velocity selective preparation can be applied a first time before the IR pulse(s). In some embodiments, the velocity selective preparation module can be implemented using known pulses and techniques of velocity selective preparation. In some embodiments, the preparation module can be any pulse that produces a multiplicative change to the longitudinal magnetization. The readout can be, for example, a three-dimensional fast spin echo readout.

[0123] At block 1302, MR data for a second image (or control image) can be acquired from a region of interest of a subject using a pulse sequence that includes a velocity selective preparation module applied a second predetermined time before readout, where the second time is different than the first time. In some embodiments, the second pulse sequence can include at least one inversion recovery pulse, and the velocity selective preparation can be applied a second time after the IR pulse(s) and before readout. In some embodiments, the velocity selective preparation module can be implemented using known pulses and techniques of velocity selective preparation. In some embodiments, the preparation module can be any pulse that produces a multiplicative change to the longitudinal magnetization. The readout can be, for example, a three-dimensional fast spin echo readout.

[0124] At block 1304, at least two images (i.e., the first image and the second image) can be generated (or reconstructed) based on the respective MR data for each image using known reconstruction methods. In some embodiments, the first image and the second image can be reconstructed using, for example, the data processing server 114 of the MRI system 100. In some embodiments, the first image and the second image can be reconstructed using a computer system (e.g., the computer system 1400 shown in FIG. 14) configured to access or receive MR data acquired by an MR system. The generated first image and second image can be stored, for example, in a data storage of the MR system (e.g., the MRI system 100 shown), or in a data storage of other computer systems. Figure 1

[0125] ​In box 1306, an image representing a perfusion signal can be generated by comparing at least two images acquired in box 1304 and generated in box 1304 (e.g., comparing a first (or marker) image with a second (or control) image). In some embodiments, the comparison can be performed by subtracting the second image from the first image. In some embodiments, the comparison can be performed by fitting the first and second images to a model or using other comparison algorithms. The image representing a perfusion signal generated in box 1306 can be stored, for example, in an MR system (e.g., Figure 1 The data storage device of the MRI system 100 shown may be stored in the data storage device of another computer system. In block 1308, the generated image with signals representing perfusion can be displayed on a monitor, for example, the MRI system (e.g., Figure 2 The monitor of the MRI system 100 shown (104, 136 and / or 144), or the monitor of another computer system.

[0126] The following examples illustrate in detail how to evaluate this disclosure and how it can be used or implemented, and will make its principles more readily understood by those skilled in the art. The following examples are presented in an illustrative manner and are not intended to be limiting in any way. Example 1

[0127] As described above, in some embodiments, it can be implemented Figure 14A The illustrated method uses magnetic resonance imaging to image tissue-to-fluid water exchange in regions of interest within subjects, specifically to image water exchange between the choroid plexus (CP) and cerebral fibrosis (CSF). In this example study, a T2-prepared, long TE fluid attenuation inversion recovery (FLAIR) sequence can be used to image and assess water exchange between CP and CSF. Advantageously, in this example, the disclosed method for imaging water exchange produces high SNR, high-resolution choroid plexus images, and the signal differences determined between the T2-prepared images (i.e., the first labeled images) and control images (e.g., images acquired without T2 preparation) indicate CP-CSF water exchange.

[0128] Without exchange, the CSF signal can be cancelled by reversing the timing, and the CP signal can be effectively cancelled by T2 decay within a very long TE. However, the magnetization that begins with CP and exchanges to CSF ​​during the preparation time will not be completely cancelled. If water exchange is approximated as an instantaneous exchange of spins between CSF and CP without any return, the water exchange signal can be the time integral of the difference between the magnetization of CP and CSF before imaging multiplied by the T1 decay factor of CSF before imaging. The IR pulse can effectively reverse the contribution prior to the IR pulse. When the T2 preparation pulse is applied before the reversal pulse, shorter T2 tissues, including CP, can be substantially cancelled. Figure 14B Example diagram 1402 according to an embodiment is shown, illustrating magnetization as a function of time before readout for acquisition with and without T2 preparation. Figure 14A An exemplary diagram 1404 according to an embodiment is shown, illustrating the difference in magnetization between tissue and fluid with and without T2 preparation. Figure 14B In Figure 1402, the longitudinal magnetization (M) of CSF (curve 1406) and CP under T2 preparation with (curve 1410) and without (curve 1408) is shown. z (Time evolution.) For this example study, Figure 4 Figure 1404 shows the difference between CP and CSF magnetization multiplied by the T1 attenuation factor (where the difference is reversed before the inversion pulse) with and without T2 preparation (curve 1414) and without T2 preparation (curve 1412). From Figures 1402 and 1404, it is evident that without T2 preparation, the exchange contribution after the inversion pulse roughly cancels out the previous contribution. However, when T2 preparation is applied, the positive contribution after the inversion pulse increases significantly, resulting in a large net positive exchange signal.

[0129] In this example study, the scan can be performed at 3T using, for example, a 48-channel head coil. In this example, 3D-FSE T2-FLAIR data (TI / TR / TE = 1785 / 6000 / 107 ms, ETL = 220, linear view ordering) was acquired, along with a pair of long TE FLAIR acquisitions with and without T2 preparation, using reverse center view ordering, with 25 dropped echoes to avoid propagation of high-frequency features during early echoes, ETL = 245, TR / TE = 6 / 1 sec, and a first refocusing flip angle of 120 degrees, subsequently decreasing to 75 degrees. TI can be automatically adjusted, for example, case-by-case based on echo train duration, with a counter-target of T1 = 4.27 sec preparation considering T2 preparation (TI ≈ 1737-1770 ms). An additional reference volume can be acquired as a reference image without IR or T2 preparation.

[0130] In this example study, the T2 preparation can consist of a 90-degree hard pulse, followed by four adiabatic hyperbolic secant refocusing pulses and a final -90-degree hard pulse. As mentioned, a second independent FLAIR volume can also be acquired without T2 preparation, and the TI is adjusted to counteract CSF without T2 preparation (TI ≈ 1850–1890 ms). In this example study, commonly used parameters are: 136 sagittal slices, matrix = 192x192, resulting in (1.3 mm) 3 The resolution, using 2x2 accelerated parallel imaging in both phase encoding directions, lasted for 3 minutes and 21 seconds per volume acquisition time (total scan time 16.5 minutes).

[0131] A first (marked) image with T2 preparation and a second (control) image without T2 preparation can be reconstructed using known methods, followed by subtraction between the T2-prepared (marked) volume (or image) and the control volume (or image). The exchange signal fraction (ESF) can be calculated as:

[0132] (29)

[0133] CP and CSF correspond to the average values ​​of the ROI (region of interest) located in the choroid plexus and the adjacent CSF, respectively.

[0134] In this example study, the signal in the CP is shown to be significantly higher than that in the control volume (or image) in the T2 prepared volume. In this example study, subtraction between the T2 prepared volume and the control volume reveals a higher signal in the CP than in the surrounding CSF. Subtraction experiments can allow for potential residual T2 signal in the control CP, but imperfect CSF cancellation in the control volume results in significant CSF contamination in the subtracted image. The mean ESF was found to be equal to 2.2 ± 0.4%.

[0135] In some embodiments, T2 preparation data can be acquired with a significantly longer TE (1.8 seconds) to eliminate any possibility of contamination by residual CP signals. At such a TE, the presence of a strong residual signal in the CP confirms that water exchange is the source of the strong signal in the CP.

[0136] This example study illustrates evidence of water exchange in the choroid plexus using T2-prepared, long-TE FLAIR imaging. The study yielded high-resolution images of the CP and can, for example, allow for the study of CP function, complementing other methods, such as ASL, which has recently gained attention in the study of CP function. In some embodiments, controls can be provided to adequately match CSF signal levels with T2-prepared acquisition to support quantization. Quantization can be used for various applications, such as pathology, for example, Alzheimer's disease. Example 2

[0137] Alterations in renal water transport and exchange can reflect renal function and disease. In some embodiments, this can be implemented. Figures 4-6 The method illustrated is for magnetic resonance imaging of tissue-to-fluid-water exchange in regions of interest within subjects for the quantitative assessment of intrarenal fluid exchange. In this example study, the images show the characteristic spatial distribution of the signal, with increased signal in the renal medulla supporting its detection and assessment of fluid exchange. Therefore, the disclosed MR imaging technique enables the study of intrarenal fluid exchange and potentially serves as a biomarker for the diagnosis and prognosis of kidney disease.

[0138] As mentioned above Figures 11-12 and Figure 4 The disclosed techniques discussed can be used for T2-selective labeling, which in some embodiments employs a second image with T2 saturation (i.e., T2 preparation) applied at a different time (e.g., later) as a control. In this example study, a first (or labeled) image is acquired from a subject using a pulse sequence including a T2 preparation module applied at a first predetermined time prior to readout, and a second (or control) image is acquired from the subject using a pulse sequence including a T2 preparation module applied at a second predetermined time prior to readout, wherein the second time differs from the first time; for example, T2 preparation for the second image may be applied at a later time. For example, in the pulse sequence of the first or labeled image, T2-selective saturation (i.e., T2 preparation) may be applied at a mixed time T. mix (i.e., the exchange time, such as TS, as described above) is applied before the pulse sequence of the control image, and T2 selective saturation can be applied at different times, for example, after the mixing time. In the absence of exchange during the mixing time, the magnetization after the tag and control sequences can be respectively determined by M. 2lbl and M 2ctl Given:

[0139] (30)

[0140] (31)

[0141] Where α is the saturation factor for T2 selective saturation, and R is the magnetization recovered during the mixing time period. The difference between the two termination magnetizations is non-zero only because of the recovery term R, as given below:

[0142] (32)

[0143] If n inversion pulses (or inversions) are added during the mixing time (or exchange time), the M1 term in the above equations 30-32 is simply multiplied by a power of the inversion efficiency factor. The timing of the inversion pulses can be chosen (e.g., optimized) so that R is close to zero. For three or more inversion pulses (or inversions), R can be reduced to, for example, less than 1% from pure water to fat T1.

[0144] (33)

[0145] Thus, the direct effects of the labeling can be matched by the control. As discussed above, any difference between the labeled image and the control image can be reflected in the exchange during the exchange or mixing time, for example, so that the T2 and / or T1 of the exchanged spins across the measurement region are not the same.

[0146] In this example study, the labeled and control images can be acquired using 2D SSFSE (RARE) sequences. T2 preparation can be implemented using, for example, a BIR8 adiabatic sequence of 100 milliseconds or 200 milliseconds, and 4 tanh adiabatic inversion pulses can be applied at optimized times to minimize the recovered magnetization. In this example, T2 preparation is performed 5 seconds prior to imaging with non-selective saturation, and the T2 inversion recovery is optimized to nearly cancel the M1 of the renal fluid. After T2 preparation, 200 milliseconds are allowed in this example to allow the tissue magnetization to recover somewhat, and 3 fat saturation pulses are applied immediately prior to imaging. In this example, a TR of 10 seconds is used, with the labeled and control acquisitions interleaved and variable TE. The TE can be controlled by skipping some echoes prior to acquisition. In this example, eleven acquisitions of the labeled and control images, and the reference image, require a total of 4 minutes per sequence. In this example, the labeled images are averaged, the control images are averaged, and then the averaged control images are subtracted from the averaged labeled images to create images with signal representing water exchange.

[0147] In this example, the images show signal that is primarily increased within the renal medulla, and this signal is distributed throughout the medullary collecting duct system, especially at longer labeling times. The cortical signal is relatively more pronounced at shorter labeling times (1000 milliseconds exchange or mixing time). The spatial distribution of this signal can be explained by mixing of water exchange in the proximal tubules and collecting ducts, and bulk flow of filtrate. This example study shows that the disclosed method can provide a way for sensitive measurement of exchange from short TE to long TE compartments that can be used to assess water exchange within the kidney. The disclosed techniques can provide a non-invasive assessment of kidney filtration and water exchange that can complement other measurements of kidney function. Example 3

[0148] As described above, water exchange between tissue and CSF can facilitate CSF production and colloid lymph clearance. The large difference in T2 between tissue and fluid suggests that T2 magnetization transfer can be used to image this exchange. In some embodiments, this can be implemented... Figures 4-6 The illustrated method of using magnetic resonance imaging (MRI) to study tissue-to-fluid water exchange in regions of interest within subjects is used for the study of CSF exchange, which can reflect changes in glial lymphatic clearance or CSF production with aging, Alzheimer's disease, intracranial hypertension, and other conditions. As described above, the disclosed technique can be advantageously used to control for systematic errors arising from the direct effects of T2 saturation on fluids. In this example study, three-dimensional images under longer TE can show exchange signals around the choroid plexus and also reveal more moderate exchange in the cerebellar vermis and near the cerebellar cortex and cerebral cortex.

[0149] As mentioned above Figures 11-12 and Figure 15 The disclosed techniques discussed can be used for T2-selective labeling, which in some embodiments employs a second image with T2 saturation (i.e., T2 preparation) applied at a different time (e.g., later) as a control. In this example study, a first (or labeled) image is acquired from a subject using a pulse sequence including a T2 preparation module applied at a first predetermined time prior to readout, and a second (or control) image is acquired from the subject using a pulse sequence including a T2 preparation module applied at a second predetermined time prior to readout, wherein the second time differs from the first time; for example, T2 preparation for the second image may be applied at a later time. For example, in the pulse sequence of the first or labeled image, T2-selective saturation (i.e., T2 preparation) may be applied at a mixed time T. mix (i.e., the exchange time, such as TS, as described above) is applied before the pulse sequence of the control image, and T2 selective saturation can be applied at different times, for example, after the mixing time. In the absence of exchange during the mixing time, the magnetization after the tag and control sequences can be respectively determined by M. 2lbl and M 2ctlGiven as in equations 30 and 31 above. The difference between the two terminal magnetizations is non-zero only because of the recovery term R, and can be given by equation 32 above. If n inversion pulses (or inversions) are added during the mixing time (or exchange time), the M1 term in equations 30-32 above is simply multiplied by a power of the inversion efficiency factor. The timing of the inversion pulses can be chosen (e.g., optimized) so that R is close to zero. For three or more inversion pulses (or inversions), R can be reduced to less than 1% of the T1 from pure water to fat, for example (see equation 33 above). As discussed above, since the subtraction can eliminate any direct effects of the label on the exchange spins, any difference between the label image and the control image can reflect exchange during the exchange or mixing time, for example, so that T2 and / or T1 are not the same.

[0150] In this example study, the label and control images can be acquired using a 3D SSFSE (RARE) sequence. In this example, T2 preparation can be implemented using a 200 ms TE BIR8 adiabatic sequence, and 4 tanh adiabatic inversion pulses can be applied at optimized times to minimize the recovered magnetization. The T2 preparation is preceded by 5 seconds of non-selective saturation, and the T2 selective inversion recovery can be optimized to nearly null the CSF M1. After the T2 preparation, 200 ms is allowed to allow the tissue magnetization to recover somewhat, and 3 fat saturation pulses are applied immediately prior to imaging. In this example, a TR of 10 seconds is chosen, 2x2 parallel imaging acceleration, an asymptotic 70° flip angle sequence (echo spacing of 3.3 ms), and a center phase ordering of the TE by skipping echoes prior to acquisition. In this example, the acquisition of the label image, control image, and unprepared reference image takes 5 minutes and 20 seconds. In this example, the images are acquired in 3 healthy volunteers, and for T mix are 106.5 ms, 213.0 ms, and 319.5 ms for TE of 2 seconds and 1.5 seconds, and for T mix are 106.5 ms, 213.0 ms, and 319.5 ms for TE of 2 seconds and 1.5 seconds, and for T

[0151] In this example study, all images show elevated signal around the choroid plexus and distributed throughout the cortical and brainstem regions. There is a clear presence of negative white matter signal on the TE 106.5 msec images, but this effect is diminished on the 213 msec images and negligible on the 319.5 msec images. This effect can reflect incomplete suppression of the recovered magnetization due to very short Tl components in the white matter. The exchange signal in the choroid plexus and near the cortex appears to increase slightly with TE, consistent with the reduced volume of the ambiguous negative white matter signal. Although the exchange signal is only present in regions known to contain CSF, this signal cannot be a simple systematic error in the CSF because the intensity spatial variation is very different from the un-subtracted label or control images and the reference images. The 3D images averaged across subjects show the whole brain distribution of the exchange signal. In this example study, the spatial distribution of the exchange signal is consistent across subjects, with the highest signal around the choroid plexus of the lateral ventricles. The signal in the fourth ventricle and around the cerebellar vermis is also prominent. In this example, a clear exchange can be seen around the cerebellar cortex and the cerebral cortex.

[0152] This example study shows that the disclosed methods can provide a way for sensitive measurement of exchange from short to long T2 compartments that can be used to assess water exchange from tissue and blood to CSF. The disclosed methods can be used to help understand and diagnose diseases of CSF production and the glymphatic clearance system.

[0153] ​ is a block diagram of an example computer system according to embodiments. The computer system 1500 can be used to implement various aspects of the systems and methods described herein. In some embodiments, the computer system 1500 can be a workstation, a notebook computer, a tablet device, a mobile device, a multimedia device, a network server, a mainframe, one or more controllers, one or more microcontrollers, or any other general- or special-purpose computing device. The computer system 1500 can operate autonomously or semi-autonomously, or can read executable software instructions from memory or storage device 1516 or computer-readable media (e.g., hard disk drive, CD-ROM, flash memory), or can receive instructions from a user via input device 1520 or any other source logically connected to the computer or device, such as another networked computer or server. Thus, in some embodiments, the computer system 1500 can also include any suitable device for reading computer-readable storage media.

[0154] Data, such as, for example, data acquired using, for example, an imaging system (e.g., a magnetic resonance imaging (MRI) system, etc.), can be provided to the computer system 1500 from the data storage device 1516, and this data is received in the processing unit 1502. In some embodiments, the processing unit 1502 includes one or more processors. For example, the processing unit 1502 can 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 that is configured to electronically receive data to be processed. The DSP 1503, the MPU 1506, the GPU 1508, and the data acquisition unit 1510 are all coupled to a communication bus 1512. The communication bus 1512 can be, for example, a set of wires, or hardware for switching data between peripheral devices or between any components in the processing unit 1502.

[0155] The processing unit 1502 can also include a communication port 1514 that is in electronic communication with other devices, which can 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 through which a user can provide input. The storage device 1516 can be configured to store data, which can include data such as, for example, MR data, MR images (e.g., marker images, control images, images with signals representative of water exchange), etc., whether this data is provided to or processed by the processing unit 1502. The display 1518 can be used to display images and other information, such as patient health data, etc.

[0156] The processing unit 1502 can also be in electronic communication with a network 1522 to send and receive data and other information. The communication port 1514 can also be coupled to the processing unit 1502 through a switched central resource (e.g., the communication bus 1512). The processing unit 1502 can also include a temporary storage 1524 and a display controller 1526. The temporary storage 1524 is configured to store temporary information. For example, the temporary storage can be a random access memory.

[0157] Computer executable instructions for magnetizing in preparation for magnetic resonance imaging according to the above described methods can be stored on a computer readable medium in the form of a computer program product. The computer readable medium includes volatile and non-volatile, removable and non-removable media implemented in any method or technology for storage of information such as computer readable instructions, data structures, program modules or other data. The computer readable medium includes, but is not limited to, random access memory (RAM), read only memory (ROM), electrically erasable programmable ROM (EEPROM), flash memory or other memory technology, compact disc ROM (CD-ROM), digital versatile disks (DVD) or other optical storage, magnetic cassettes, magnetic tape, magnetic disk storage or other magnetic storage devices, or any other medium that can be used to store the desired information and that can be accessed by a system (e.g., a computer) including via the Internet or other computer network forms of access.

[0158] The application has been described in terms of one or more preferred embodiments and, notwithstanding particularization of the present application, numerous equivalents, alternatives, variations, and modifications are possible and contemplated in the scope of the application.

Claims

1. A method for performing magnetic resonance imaging on tissue-to-fluid water exchange in a region of interest in a subject, comprising: At least two images of the region of interest of the subject were acquired using a magnetic resonance imaging (MRI) system, with each image prepared using a different T2. The at least two images are generated using the corresponding MR data; as well as By comparing the at least two images, an image with a signal representing water exchange is generated.

2. The method of claim 1, wherein acquiring MR data from at least two images of the region of interest of the subject comprises: Using a first pulse sequence including T2 preparation, MR data of a first image of the region of interest of the subject were acquired; as well as Using a second pulse sequence without T2 preparation, MR data of a second image of the region of interest of the subject were acquired.

3. The method of claim 1, wherein acquiring MR data from at least two images of the region of interest of the subject comprises: MR data of a first image of the region of interest of the subject are acquired using a first pulse sequence prepared with a first pulse of a first duration of T2. as well as MR data of a second image of the region of interest of the subject are acquired using a second pulse sequence that includes a T2 preparation with a second duration.

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

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

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

7. The method of claim 6, further comprising: Retrieve reference images acquired without T2 preparation and inversion recovery; The exchange signal fraction is calculated based on the subtraction of the reference image and the at least two images.

8. The method of claim 1, further comprising displaying an image having a signal representing water exchange.

9. The method of claim 2, wherein the first pulse sequence and the second pulse sequence further include readouts with long echo times.

10. The method of claim 3, wherein the first pulse sequence and the second pulse sequence further include readouts having long echo times.

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

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

13. A method for performing magnetic resonance imaging on tissue-to-fluid water exchange in a region of interest in a subject, comprising: At least two images of the region of interest of the subject were acquired using a magnetic resonance imaging (MRI) system, with different application timings prepared for T2 for each image; The at least two images are generated using the corresponding MR data; as well as By comparing the at least two images, an image with a signal representing water exchange is generated.

14. The method of claim 13, wherein acquiring MR data from at least two images of the region of interest of the subject comprises: MR data of a first image of the region of interest of the subject are acquired using a first pulse sequence prepared with a T2 applied at a first time. as well as MR data of a second image of the region of interest of the subject are acquired using a second pulse sequence prepared with a T2 applied at a second time, wherein the second time is different from the first time.

15. The method of claim 14, wherein the first pulse sequence further comprises at least one inversion recovery (IR) pulse, and the first time precedes the at least one IR pulse.

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

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

18. The method of claim 13, wherein acquiring MR data from at least two images of the region of interest of the subject comprises: MR data of the first image is acquired using a first pulse sequence including a first repetition time (TR); as well as MR data of a second image are acquired using a second pulse sequence that includes a second repetition time (TR), wherein the second TR is different from the first TR.

19. The method of claim 13, further comprising quantifying water exchange based on an image and a physical model having signals representing water exchange.

20. The method of claim 13, further comprising displaying an image having a signal representing water exchange.

21. The method of claim 13, wherein acquiring MR data from at least two images of the region of interest of the subject comprises: MR data of the first image is acquired using a first pulse sequence that includes readouts with long echo times; as well as MR data for the second image is acquired using a second pulse sequence that includes readouts with long echo times.

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

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

24. A magnetic resonance imaging (MRI) system, comprising: A magnet system configured to generate a polarized magnetic field around at least a portion of the subject; A magnetic gradient system comprising a plurality of magnetic gradient coils configured to apply at least one magnetic gradient field to the polarization magnetic field. A radio frequency (RF) system configured to apply an RF field to the subject and configured to receive magnetic resonance signals from the subject using a coil array; as well as Computer system, the computer system being programmed to: At least two images of the region of interest of the subject were acquired using magnetic resonance (MR) data, with each image prepared using a different T2. The at least two images are generated using the corresponding MR data; as well as By comparing the at least two images, an image with a signal representing water exchange is generated.

25. A magnetic resonance imaging (MRI) system, comprising: A magnet system configured to generate a polarized magnetic field around at least a portion of the subject; A magnetic gradient system comprising a plurality of magnetic gradient coils configured to apply at least one magnetic gradient field to the polarization magnetic field. A radio frequency (RF) system configured to apply an RF field to the subject and configured to receive magnetic resonance signals from the subject using a coil array; as well as Computer system, the computer system being programmed to: Magnetic resonance (MR) data of at least two images of the region of interest of the subject were acquired, with different application timings prepared for T2 for each image; The at least two images are generated using the corresponding MR data; as well as By comparing the at least two images, an image with a signal representing water exchange is generated.

26. A method for velocity-selective arterial spin-labeling magnetic resonance imaging of tissue perfusion in a region of interest in a subject, comprising: At least two images of the region of interest of the subject were acquired using a magnetic resonance imaging (MRI) system, with different application timings prepared for velocity selectivity for each image; The at least two images are generated using the corresponding MR data; as well as By comparing the at least two images, an image with a signal representing perfusion is generated.

27. The method of claim 26, wherein acquiring MR data from at least two images of the region of interest of the subject comprises: MR data of a first image of the region of interest of the subject is acquired using a first pulse sequence selectively prepared at a rate applied at a first moment; as well as MR data of a second image of the region of interest of the subject are acquired using a second pulse sequence selectively prepared at a second time, wherein the second time is different from the first time.

28. The method of claim 27, wherein the first pulse sequence further comprises at least one inversion recovery (IR) pulse, and the first time precedes the at least one IR pulse.

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

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

Images