System and Method for Concurrent X-Nuclei and H-Nuclei Magnetic Resonance Imaging

A method for generating magnetic resonance (MR) images of a kidney region or a brain of a subject using multinuclear magnetic resonance imaging MRI includes performing, using an MRI system, an Na-nuclei pulse sequence module to acquire a portion of a first set of MR data from the kidney or brain region of the subject and performing, using the MRI system, an H-nuclei pulse sequence module to acquire a portion of a second set of MR data from the kidney or brain region of the subject. The Na-nuclei pulse sequence module and the H-nuclei pulse sequence module may be repeated in an interleaved manner until acquisition of the first set of MR data and the second set of MR data are complete. The method further includes generating at least one Na-based image using the first set of MR data, generating at least one H-based image using the second set of MR data and displaying one or more of the at least one Na-based image and the at least one H-based image on a display.

BACKGROUND

Magnetic resonance imaging (MRI) is clinically performed on hydrogen (H) nuclei as it is the most abundant element in the human body in the form of water. However, other nuclei are also visible with MRI. These are referred to as X-nuclei, where X can stand for several different elements. Potentially useful elements (X) for medical imaging are sodium (Na), fluorine (F) and phosphorous (P), each of which play key roles in biochemistry. However, the relative low abundance of X-nuclei compared to hydrogen nuclei makes them difficult to see above the background noise. While hydrogen protons have a concentration of about 110 M in the body, the next most abundant, sodium (Na), is in the tens of mM, i.e., a factor of 10,000 lower. To achieve adequate signal levels for X-nuclei, such as sodium, necessitates low spatial resolution and long measurement times by averaging many times. Averaging increases the signal linearly while noise adds as the square root, leading to an overall improvement in signal to noise ratio (SNR) as the square root of number of averages. The square root increase in SNR with linear increase in scan time is particularly challenging when trying to overcome a factor of 10000. In principle, to match the SNR of a 1-minute hydrogen proton scan would require the sodium scan to last for 190 years. This is, however, unfeasible and researchers have spent considerable effort in optimizations to claw back numerous small factors of 2-4 by reductions in spatial resolution and others forms of averaging (low bandwidth, multiple echo combination, steady state imaging with short repetition times), as well as hardware improvements. Typical X-nucleus scan times, incorporating all these compromises, are on the order of 30 minutes, which is comparable to the time for a clinical MRI examination of hydrogen.

X-nucleus imaging is never done in isolation but always in conjunction with proton imaging so the total time can add up to an hour. A recent study (Zidan Yu, Guillaume Madelin, Daniel K. Sodickson, Martijn A. Cloos, “Simultaneous proton magnetic resonance fingerprinting and sodium MRI,” Mag. Reson. in Med. 2019) described perfectly synchronous hydrogen and X-nucleus imaging, in which identical instructions were sent to both imaging nuclei. This is efficient but of limited clinical value since it requires the same pattern of instructions (or “sequence” in MRI terminology) to be transmitted to the H- and X-nuclei. Clinical imaging uses many different sequences that are sensitive to different lesion types so it would be clinically a non-starter to limit the H-imaging component this way.

SUMMARY

In accordance with an embodiment, a method for generating magnetic resonance (MR) images of a kidney region of a subject using multinuclear magnetic resonance imaging (MRI) includes performing, using an MRI system, a Na-nuclei pulse sequence module to acquire a portion of a first set of MR data from the kidney region of the subject and performing, using the MRI system, an H-nuclei pulse sequence module to acquire a portion of a second set of MR data from the kidney region of the subject. The Na-nuclei pulse sequence module and the H-nuclei pulse sequence module may be repeated in an interleaved manner until acquisition of the first set of MR data and the second set of MR data are complete. The method further includes generating at least one Na-based image using the first set of MR data, generating at least one H-based image using the second set of MR data and displaying one or more of the at least one Na-based image and the at least one H-based image on a display.

In accordance with another embodiment, a method for generating magnetic resonance (MR) images of a brain of a subject using multinuclear magnetic resonance imaging (MRI) includes performing a Na-nuclei pulse sequence module to acquire a portion of a first set of MR data from the brain of the subject and performing an H-nuclei pulse sequence module to acquire a portion of a second set of MR data from the brain of the subject. The Na-nuclei pulse sequence module and the H-nuclei pulse sequence module may be repeated in an interleaved manner until acquisition of the first set of MR data and the second set of MR data are complete. The method further includes generating at least one Na-based image using the first set of MR data, generating at least one H-base image using the second set of MR data and displaying one or more of the at least one Na-based image and the at least one H-based image.

In accordance with another embodiment, a method for generating magnetic resonance (MR) images of a brain of a subject using multinuclear magnetic resonance imaging (MRI) includes performing a Na-nuclei pulse sequence module to acquire a portion of a first set of MR data from the brain of the subject and performing an H-nuclei pulse sequence module to acquire a portion of a second set of MR data from the brain of the subject, wherein the H-nuclei pulse sequence module includes a preparation module. The Na-nuclei pulse sequence module and the H-nuclei pulse sequence module may be repeated in an interleaved manner until acquisition of the first set of MR data and the second set of MR data are complete. The method further includes generating at least one Na-based image using the first set of MR data, generating at least one H-base image using the second set of MR data and displaying one or more of the at least one Na-based image and the at least one H-based image.

DETAILED DESCRIPTION

FIG.1shows an example of an MRI system100that may be used to perform the methods described herein. MRI system100includes an operator workstation102, which may include a display104, one or more input devices106(e.g., a keyboard, a mouse), and a processor108. The processor108may include a commercially available programmable machine running a commercially available operating system. The operator workstation102provides an operator interface that facilitates entering scan parameters into the MRI system100. The operator workstation102may be coupled to different servers, including, for example, a pulse sequence server110, a data acquisition server112, a data processing server114, and a data store server116. The operator workstation102and the servers110,112,114, and116may be connected via a communication system140, which may include wired or wireless network connections.

The pulse sequence server110functions in response to instructions provided by the operator workstation102to operate a gradient system118and a radiofrequency (“RF”) system120. Gradient waveforms for performing a prescribed scan are produced and applied to the gradient system118, which then excites gradient coils in an assembly122to produce the magnetic field gradients Gx, Gy, and Gzthat are used for spatially encoding magnetic resonance signals. The gradient coil assembly122forms part of a magnet assembly124that includes a polarizing magnet126and a whole-body RF coil128.

RF waveforms are applied by the RF system120to the RF coil128, or a separate local coil to perform the prescribed magnetic resonance pulse sequence. Responsive magnetic resonance signals detected by the RF coil128, or a separate local coil, are received by the RF system120. The responsive magnetic resonance signals may be amplified, demodulated, filtered, and digitized under direction of commands produced by the pulse sequence server110. The RF system120includes an RF transmitter for producing a wide variety of RF pulses used in MRI pulse sequences. The RF transmitter is responsive to the prescribed scan and direction from the pulse sequence server110to produce RF pulses of the desired frequency, phase, and pulse amplitude waveform. The generated RF pulses may be applied to the whole-body RF coil128or to one or more local coils or coil arrays.

The pulse sequence server110may receive patient data from a physiological acquisition controller130. By way of example, the physiological acquisition controller130may receive signals from a number of different sensors connected to the patient, including electrocardiograph (“ECG”) signals from electrodes, or respiratory signals from a respiratory bellows or other respiratory monitoring devices. These signals may be used by the pulse sequence server110to synchronize, or “gate,” the performance of the scan with the subject's heart beat or respiration.

The pulse sequence server110may also connect to a scan room interface circuit132that receives signals from various sensors associated with the condition of the patient and the magnet system. Through the scan room interface circuit132, a patient positioning system134can receive commands to move the patient to desired positions during the scan.

The digitized magnetic resonance signal samples produced by the RF system120are received by the data acquisition server112. The data acquisition server112operates in response to instructions downloaded from the operator workstation102to receive the real-time magnetic resonance data and provide buffer storage, so that data is not lost by data overrun. In some scans, the data acquisition server112passes the acquired magnetic resonance data to the data processor server114. In scans that require information derived from acquired magnetic resonance data to control the further performance of the scan, the data acquisition server112may be programmed to produce such information and convey it to the pulse sequence server110. For example, during pre-scans, magnetic resonance data may be acquired and used to calibrate the pulse sequence performed by the pulse sequence server110. As another example, navigator signals may be acquired and used to adjust the operating parameters of the RF system120or the gradient system118, or to control the view order in which k-space is sampled. In still another example, the data acquisition server112may also process magnetic resonance signals used to detect the arrival of a contrast agent in a magnetic resonance angiography (“MRA”) scan. For example, the data acquisition server112may acquire magnetic resonance data and processes it in real-time to produce information that is used to control the scan.

The data processing server114receives magnetic resonance data from the data acquisition server112and processes the magnetic resonance data in accordance with instructions provided by the operator workstation102. Such processing may include, for example, reconstructing two-dimensional or three-dimensional images by performing a Fourier transformation of raw k-space data, performing other image reconstruction algorithms (e.g., iterative or backprojection reconstruction algorithms), applying filters to raw k-space data or to reconstructed images, generating functional magnetic resonance images, or calculating motion or flow images.

Images reconstructed by the data processing server114are conveyed back to the operator workstation102for storage. Real-time images may be stored in a data base memory cache, from which they may be output to operator display104or a display136. Batch mode images or selected real time images may be stored in a host database on disc storage138. When such images have been reconstructed and transferred to storage, the data processing server114may notify the data store server116on the operator workstation102. The operator workstation102may be used by an operator to archive the images, produce films, or send the images via a network to other facilities.

The MRI system100may also include one or more networked workstations142. For example, a networked workstation142may include a display144, one or more input devices146(e.g., a keyboard, a mouse), and a processor148. The networked workstation142may be located within the same facility as the operator workstation102, or in a different facility, such as a different healthcare institution or clinic.

The networked workstation142may gain remote access to the data processing server114or data store server116via the communication system140. Accordingly, multiple networked workstations142may have access to the data processing server114and the data store server116. In this manner, magnetic resonance data, reconstructed images, or other data may be exchanged between the data processing server114or the data store server116and the networked workstations142, such that the data or images may be remotely processed by a networked workstation142.

The present disclosure describes an approach to imaging H-nuclei and X-nuclei at the same time. The described embodiments for multinuclear MRI imaging methods involve various ways of interleaving the sets of instructions (or modules or sequence building blocks (SBB)) that are used on the H-nuclei and the X-nuclei during a scan. Interleaving the H-nuclei pulse sequence modules (or SBBs) and the X-nuclei pulse sequence modules (or SBBs) retains the flexibility to perform independent sequences on each nucleus using the MRI scanner. As used herein, the terms H-SBB, H-nuclei module, or H-nuclei pulse sequence module refer to a unit of a hydrogen imaging sequence and the terms X-SBB, X-nuclei module, or X-nuclei pulse sequence module refer to a unit of the X-nucleus imaging sequence. In an embodiment, the present disclosure describes methods for interleaved and simultaneous Na+and H+acquisition (where the X-nuclei is Na). In particular, Na-nuclei and H-nuclei modules (or SBBs) are designed that can be put together to build a single multinuclear pulse sequence and, for example, cut sequence time by approximately 50%. In various embodiments, the multinuclear sequence with interleaved X-nuclei and H-nuclei modules (or SBBs) may be used in various imaging applications, such as evaluating renal impairment, stroke, epilepsy, and brain tumors. While the following description will refer to embodiments where sodium (Na) is the X-nuclei, it should be understood that the methods described herein may be used for imaging other X-nuclei, such as fluorine (F) and phosphorous (P), in multinuclear MRI imaging.

FIG.2illustrates a method for multinuclear MR imaging in accordance with an embodiment. At block202, an X-nuclei pulse sequence module (or SBB) may be performed using an MRI system (e.g., MRI system100described above with respect toFIG.1) to acquire a portion of a first set of MR data from a region of interest in a subject. For example, in the following description, the X-nuclei is sodium (Na-nuclei). The first set of MR data may be acquired using a first RF coil that is tuned to the X-nuclei. The Na-nuclei pulse sequence module (or SBB) may take various forms, for example, as shown inFIGS.3-6. InFIG.3, an example Na-Density Adapted GRE (DAR) sequence building block or module (Na+-SBBDAR)300is shown. InFIG.3, a 90° excitation RF pulse302is followed by a gradient echo readout304. In the example module300, the readout trajectory is center out. In some embodiments, the gradients of the density-adapted radial projection can be designed such that the outer k-space has a constant sampling density in each spherical shell. InFIG.4, an example Na-Double Half-Echo (DHE) sequence building block or module (Na+-SBBDHE)400is shown. InFIG.5, an example X- (e.g., Na) Ernst Angle (EA), spoiled, sequence building block or module (X-SBBEA)500is shown. InFIG.5, a 30° excitation RF pulse502is followed by a gradient echo readout504. In the example module500, the readout trajectory is center out. The RF pulse502and gradient echo readout504can be repeatedly applied. To ensure no transverse component of the magnetization at the beginning of the cycles, spoiling can be implemented with an additional spoiler gradient after readout module504, or changing phase of the RF pulse module from acquisition to acquisition. InFIG.6, an example X-Balanced Steady-State Free Precession (bSSFP) sequence building block or module (Z-SBBSS) is shown. InFIG.6, a 60° excitation RF pulse602is followed by a gradient echo readout604. In the example module600, the readout trajectory is center out. The RF pulse602and gradient echo readout604can be repeatedly applied. Compared to module504shown inFIG.5, module604can include a refocusing gradient after readout to ensure zero gradient-induced dephasing over the repetition time interval.

Returning toFIG.2, at block204an H-nuclei pulse sequence module (or SBB) may be performed using the MRI system (e.g., MRI system100described above with respect toFIG.1) to acquire a portion of a second set of MR data from the region of interest in the subject. The second set of MR data may be acquired using a second RF coil that is tuned to the H-nuclei. The MRI system (e.g., MRI system100described above with respect toFIG.1) is configured to switch between the first RF coil tuned to the X-nuclei and the second RF coil tuned to the H-nuclei. The H-nuclei pulse sequence module (or SBB) may take various forms, for example, as shown inFIGS.7-12. InFIG.7, an example H+—Turbo Spin Echo (TSE) sequence building block or module (H+—SBBTTSE)700is shown. In this example, an excitation RF pulse704and a refocusing RF pulse706are played out consecutively, followed by a readout of multiple k-space lines, represented by the RF pulse708, phase encoding gradient702, and readout ADC710. InFIG.8, an example H-Phase Contrast (PC) MRI sequence building block or module (H+-SBBPC)800is shown. In the flow component802, an excitation RF pulse806is played out with the slice-selection gradient808, followed by phase-encoding gradient810, readout gradient812, and readout ADC814. Compared to normal gradient echo sequences, the gradient modules808,810, and812can be characterized by an additional gradient lobe added prior to signal readout to compensate for motion-induced dephasing of the time of echo. In the flow-encoding module804, similarly, an excitation RF pulse816is played out with the slice-selection gradient818, followed by phase-encoding gradient820, readout gradient822, and readout ADC824. Compared to the flow-compensated module802, the gradient modules818,820, and822can be characterized by an additional pair of bipolar gradients (shown with dashed lines) to induce a phase shift in moving spins.

InFIG.9, an example H-Gradient Echo (GE) Echo Planar Imaging (EPI) sequence building block or module (H+-SBBGE-EPI)900is shown. In this example, a 90° RF binomial water excitation pulse902is played out with the slice-selection gradient, followed by an EPI readout with phase-encoding gradient910, readout gradient906, and readout ADC914. In addition, a phase correction acquisition can be performed immediately before the readout. Spoiler gradients904,908, and912in three gradient directions are applied at the end of each repetition time interval, before the next excitation pulse. InFIG.10, an example H-Diffusion Weighted (DW) EPI sequence building block or module (H+-SBBDw-EpI)1000is shown. In this example, a 90° excitation pulse1002is followed by the diffusion gradients1008, which is played before and after a refocusing RF pulse1004. InFIG.11, an example H-Spin and Gradient Echo (SAGE) EPI sequence building block or module (H +SBBsAGE-EpI)1100is shown. In this example, a 90° RF binomial water excitation pulse1102is played out with the slice-selection gradients1118, followed by the EPI readout at the first echo time (TE1) with phase-encoding gradients1116, readout gradients1106, and readout ADC1120. After that, a second EPI readout at the second echo time (TE2) is performed with phase-encoding gradients1116, readout gradients1108, and readout ADC1122. Following the second EPI readout, a 180° refocusing pulse is executed before the acquisition of the EPI readout of the third echo time (TE3), with phase-encoding gradients1116, readout gradients1110, and readout ADC1124. Lastly, the EPI is acquired at the fourth echo time1126. Similar to EPI module900, a phase correction acquisition is performed immediately before the readout of the first EPI. Spoiler gradient1114is applied at the end of each repetition time interval, before the next excitation pulse. InFIG.12, an example Chemical Exchange Saturation Transfer (CEST) preparation (H+-SBBCEST-Prep) and EPI (H+-SBBEPT) sequence building block or module1200is shown. In this example, CEST preparation can be performed with a train of non-selective gaussian saturation pulses1202. The CEST preparation (H+-SBBCEST-Prep) is followed by the EPI (H+-SBBEPI) module as described above, with excitation pulse1204, phase correction acquisition1206, and EPI readout1208.

Returning toFIG.2, at block206the H-nuclei (e.g., Na-nuclei) pulse sequence module and the H-nuclei pulse sequence module are repeatedly performed using the MRI system in an interleaved manner. In other words, the Na-nuclei pulse sequence module and the H-nuclei pulse sequence module are interleaved during the scan to acquire both the first set of MR data and the second set of MR data. As mentioned above, the MRI system (e.g., MRI system100described above with respect toFIG.1) is configured to switch between a first RF coil tuned to the X-nuclei and a second RF coil tuned to the H-nuclei. Various examples of interleaved acquisition strategies for X-nuclei and H-nuclei for multinuclear MRI are shown inFIGS.13-15. InFIG.13, the interleaved acquisition strategy1300includes an X-SBB module1302that is fit into multi-slice H-SBB modules1304. In an embodiment, the H-SBB1304may be any proton sequence, or part of a sequence including a single excitation event from a multishot sequence or multiple excitations (shots) from one or more sequences. In the acquisition strategy1300ofFIG.13, the interleaved X-SBB1302and H-SBB1304may be repeated for N shots. InFIG.14, the interleaved acquisition strategy1400includes an X-SBB module1402that is fit into multi-slice H-SBB modules1404. In an embodiment, the H-SBB1404may be any proton sequence, or part of a sequence including a single excitation event from a multishot sequence or multiple excitations (shots) from one or more sequences. In the acquisition strategy1400ofFIG.14, the interleaved X-SBB1402and H-SBB1404may be repeated Nshot/4. InFIG.15, the interleaved acquisition strategy1500includes RF preparatory modules (H-SBBPrep)1502, for example, chemical exchange saturation transfer (CEST), magnetization transfer (MT), inversion recovery (IR), or saturation recovery (SR). In the acquisition strategy1500ofFIG.15, the alternating between the X-SBB1504and the H-SBB1506in an interleaved manner may be repeated for N shots.

Referring again toFIG.2, at block208the X-nuclei pulse sequence module and the H-nuclei pulse sequence module are repeatedly performed in an interleaved manner until the acquisition of first set of MR data and the second set of MR data are complete. If the acquisition of the first set of MR data and the second set of MR data are not complete at block208, the process returns to block206. If the acquisition of the first set of MR data and the second set of MR data are complete at block208, at least one X-nuclei (e.g., Na) based image of the region of interest is generated using the first set of MR data at block210. In an embodiment where the X-nuclei pulse sequence module is a Na-nuclei pulse sequence module, the Na-based image may be, for example, a static sodium image or a sodium TSC variation map may be generated using the first set of MR data. At block212, at least one H-nuclei based image of the region of interest is generated using the second set of MR data. For example, a T2-weighted image, a diffusion weighted image, a perfusion weighted image, fMRI image, and etc. may be generated using the second set of MR data. At block214, one or more of the at least one X-nuclei based image and the at least one H-nuclei based image may be displayed on a display (e.g., display104,136or144shown inFIG.1).

As mentioned above, the multinuclear sequence with interleaved X-nuclei and H-nuclei modules (or SBBs) may be used in various imaging applications, such as evaluating renal impairment, stroke, epilepsy, and brain tumors.FIG.16illustrates a method for multinuclear turbo spin echo MR imaging for generating images of a kidney region of a subject for use in evaluating renal impairment of the subject in accordance with an embodiment. InFIG.16, the X-nuclei is sodium (Na). In this embodiment, an Na+Density-Adapted GRE, Na+-SBBDAR, module (e.g., Na+-SBBDARmodule300shown inFIG.3) is interleaved with an H+turbo spin echo, H+-SBBTSE, module (e.g., H+-SBBTSEmodule700shown inFIG.7) to acquire a set of MR data to generate Na-nuclei based image(s) and to acquire a set of MR data to generate H-nuclei based MR image(s), respectively, of a kidney region of a subject. At block1602, an Na-nuclei pulse sequence module (i.e., an Na+-SBBDAR module) may be performed in a first repetition time (TR) using an MRI system (e.g., MRI system100described above with respect toFIG.1) to acquire a portion of a first set of MR data from a kidney region in a subject. In some embodiments, the acquired portion of the first MR data set may be a line of k-space. The portion of the first set of MR data may be acquired using a first RF coil that is tuned to the Na-nuclei. At block1604, an H-nuclei pulse sequence module (i.e., a H+-SBBTSEmodule) may be performed in the first repetition time using the MRI system (e.g., MRI system100described above with respect toFIG.1) to acquire a portion of a second set of MR data from the kidney region in the subject. In some embodiments, the portion of the second set of MR data is a shot, plurality or group of k-space lines. The portion of the second set of MR data may be acquired using a second RF coil that is tuned to the H-nuclei.

At block1606, the Na+-SBBDARmodule and the H+-SBBTSEmodule are repeatedly performed using the MRI system in an interleaved manner. Accordingly, each repetition time (TR) can include performing one Na+-SBBDARmodule to acquire a portion of the first set of MR data followed by performing an H+-SBBTSEmodule to acquire a portion of the second set of MR data. As mentioned, in some embodiments, each TR produces a single line of k-space from the Na+-SBBDARmodule and each TR acquires a shot, group or plurality of k-space lines from the H+-SBBTSEmodule. Accordingly, each TR can be used to cycle through single lines of —space for the first set of MR data acquired using the Na+-SBBDARmodule and each TR can be used to cycle through shots or groups of k-space lines using the H+-SBBTSEmodule. At block1608, the Na+-SBBDARmodule and the H+-SBBTSEmodule are repeatedly performed in an interleaved manner until the acquisition of first set of MR data and the acquisition of the second set of MR data are complete. If the acquisition of the first set of MR data and the second set of MR data are not complete at block1608, the process returns to block1606. If the acquisition of the first set of MR data and the second set of MR data are complete at block1608, at the end of the acquisition the acquired k-space lines from all TRs (which cycle through k-space) for the first set of MR data may be constructed into at least one Na-nuclei based image, for example, a single static sodium image of the kidney region at block1610and the acquired data for the second set of MR data may be constructed into at least one H-nuclei based image, for example, a T2-weighted image of the kidney region at block1612. At block1614, one or more of the at least one Na-nuclei based image and the at least one H-nuclei based image may be displayed on a display (e.g., display104,136or144shown inFIG.1). The at least one Na-nuclei based image (e.g., a static sodium image) and the at least one H-nuclei based image (e.g., a T2-weighted image) of the kidney region may be used to evaluate renal impairment of the subject.

FIG.17illustrates a method for multinuclear EPI MR imaging for generating images of a brain of a subject in accordance with an embodiment. InFIG.17, the X-nuclei is sodium (Na). In some embodiments, the multinuclear EPI MR imaging acquisition may be configured for diffusion MRI and used to evaluate stroke in a subject. In some embodiments, the multinuclear EPI MR imaging acquisition may be configured for dynamic susceptibility contrast (DSC) Perfusion MRI and used to evaluate stroke in a subject. At block1702, an Na-nuclei pulse sequence module may be performed in a first repetition time (TR) to acquire a portion of a first set of MR data from a brain region in a subject and, at block1704, an H-nuclei pulse sequence module may be performed in the first repetition time to acquire a portion of a second set of MR data from the brain region in the subject. The Na-nuclei pulse sequence module and H-nuclei pulse sequence module may be performed using an MRI system (e.g., MRI system100described above with respect toFIG.1).

In some embodiments, for diffusion MRI, an Na+Density-Adapted GRE, Na+-SBBDAR, module (e.g., Na+-SBBDARmodule300shown inFIG.3) is interleaved with an H+-Diffusion Weighted (DW) EPI, H+-SBBDW-EPI, module (e.g., H+-SBBDW-EPImodule1000shown inFIG.10) to acquire a set of MR data to generate Na-nuclei based image(s) and to acquire a set of MR data to generate H-nuclei based MR image(s), respectively, of the brain region of the subject. In some embodiments, the portion of the first MR data set acquired using the Na+-SBBDARmodule may be a line of k-space. The portion of the first set of MR data may be acquired using a first RF coil that is tuned to the Na-nuclei. In some embodiments, the portion of the second set of MR data acquired using the H+-SBBDW-EPImodule is data for a DW direction or b-value. The portion of the second set of MR data may be acquired using a second RF coil that is tuned to the H-nuclei.

In some embodiments, for DSC perfusion MRI, an Na+Density-Adapted GRE, Na+-SBBDAR, module (e.g., Na+-SBBDARmodule300shown inFIG.3) is interleaved with an H+-Gradient Echo (GE) Echo Planar Imaging (EPI), H+-SBBGE-EPI, module (e.g., H+-SBBGE-EPImodule900shown inFIG.9) to acquire a set of MR data to generate Na-nuclei based image(s) and to acquire a set of MR data to generate H-nuclei based MR image(s), respectively, of a brain region of the subject. In some embodiments, the portion of the first MR data set acquired using the Na+-SBBDARmodule may be a line of k-space. The portion of the first set of MR data may be acquired using a first RF coil that is tuned to the Na-nuclei. In some embodiments, the portion of the second set of MR data acquired using the H+-SBBGE-EPImodule is data for a dynamic time point. Data may be acquired for dynamic time points before and after the injection of a contrast agent in the subject. The portion of the second set of MR data may be acquired using a second RF coil that is tuned to the H-nuclei.

In some embodiments, for evaluating epilepsy, an Na+Density-Adapted GRE, Na+-SBBDAR, module (e.g., Na+-SBBDARmodule300shown inFIG.3) is interleaved with an H+-Gradient Echo (GE) Echo Planar Imaging (EPI). H+-SBBGE-EPI, module (e.g., H+-SBBGE-EPIin module900shown inFIG.9) to acquire a set of MR data to generate Na-nuclei based image(s) and to acquire a set of MR data to generate H-nuclei based MR image(s), respectively, of the brain region of the subject. In some embodiments, the portion of the first MR data set acquired using the Na+-SBBDARmodule may be a line of k-space. In some embodiments, each TR may use a sliding window to acquire dynamic sodium MR data. The portion of the first set of MR data may be acquired using a first RF coil that is tuned to the Na-nuclei. In some embodiments, the portion of the second set of MR data acquired using the H +-SBBGE-EPImodule is data for a dynamic time point. The portion of the second set of MR data may be acquired using a second RF coil that is tuned to the H-nuclei.

At block1706, the Na-nuclei module and the H-nuclei module are repeatedly performed using the MRI system in an interleaved manner. Accordingly, each repetition time (TR) can include performing one Na-nuclei module to acquire a portion of the first set of MR data followed by performing an H-nucleimodule to acquire a portion of the second set of MR data. In some embodiments, for diffusion MRI, each repetition time (TR) can include performing one Na+-SBBDARmodule to acquire the portion of the first set of MR data followed by performing an H+-SBBDW-EPImodule to acquire the portion of the second set of MR data. As mentioned above, for diffusion MRI, each TR can produce a single line of k-space from the Na+-SBBDARmodule and each TR can acquire data for a DW direction or b-value from the H+-SBBDW-EPImodule. Accordingly, each TR can be used to cycle through single lines of —space for the first set of MR data acquired using the Na+-SBBDARmodule and each TR can be used to cycle through data for DW directions or b-values using the H+-SBBDW-EPImodule.

In some embodiments, for DSC perfusion MRI, each repetition time (TR) can include performing one Na+-SBBDARmodule to acquire the portion of the first set of MR data followed by performing an H+-SBBGE-EPImodule to acquire the portion of the second set of MR data. As mentioned above, for DSC perfusion MRI, each TR can produce a single line of k-space from the Na+-SBBDARmodule and each TR can acquire data for a dynamic time point from the H+-SBBDW-EPImodule. Accordingly, each TR can be used to cycle through single lines of —space for the first set of MR data acquired using the Na+-SBBDARmodule and each TR can be used to cycle through data for dynamics time points using the H+-SBBGE-EPImodule. As mentioned above, data may be acquired for dynamic time points before and after the injection of a contrast agent in the subject.

In some embodiments, for evaluating epilepsy, each repetition time (TR) can include performing one Na+-SBBDARmodule to acquire the portion of the first set of MR data followed by performing an H+-SBBGE-EPImodule to acquire the portion of the second set of MR data. As mentioned above, for DSC perfusion MRI, each TR can produce a single line of k-space from the Na+-SBBDARmodule and each TR can acquire data for a dynamic time point from the H+-SBBDW-EPImodule. Accordingly, each TR can be used to cycle through single lines of —space for the first set of MR data acquired using the Na+-SBBDARmodule and each TR can be used to cycle through data for dynamics time points using the H+SBBGE-EPTmodule.

At block1708, the Na-nuclei module and the H-nuclei module are repeatedly performed in an interleaved manner until the acquisition of first set of MR data and the acquisition of the second set of MR data are complete. If the acquisition of the first set of MR data and the second set of MR data are not complete at block1708, the process returns to block1706. If the acquisition of the first set of MR data and the second set of MR data are complete at block1708, the first set of MR data may be constructed into at least one Na-nuclei based image at block1710and the acquired data for the second set of MR data may be constructed into at least one H-nuclei based image at block1712. In some embodiments, for diffusion MRI, at the end of the acquisition the acquired k-space lines from all TRs (which cycle through k-space) for the first set of MR data may be constructed into at least one Na-nuclei based image, for example, a single static sodium image of the brain and the acquired data for all DW directions or b-values from all TRs may be constructed into, for example, a diffusion-weighted image of the brain. In some embodiments, for DSC perfusion MRI, at the end of the acquisition the acquired k-space lines from all TRs (which cycle through k-space) for the first set of MR data may be constructed into at least one Na-nuclei based image, for example, a single static sodium image of the brain and the acquired data for all data from a dynamic time points from all TRs may be constructed into, for example, a T2*-weighted image of the brain. In some embodiments, the generated T2*-weighted images may be used as a dynamic time series of the brain at the end of the acquisition. In some embodiments, for evaluation of epilepsy, at the end of the acquisition the acquired k-space lines from all TRs (which cycle through k-space) for the first set of MR data may be constructed into at least one Na-nuclei based image, for example, a single static sodium image of the brain and the acquired data for all data from a dynamic time points from all TRs may be constructed into, for example, an fMRI image of the brain. In some embodiments, each TR uses a sliding window to acquire dynamic sodium MR data to generate, for example, a sodium TSC variation map.

At block1714, one or more of the at least one Na-nuclei based image and the at least one H-nuclei based image may be displayed on a display (e.g., display104,136or144shown inFIG.1). In some embodiments, for diffusion MRI, the at least one Na-nuclei based image (e.g., a static sodium image) and the at least one H-nuclei based image (e.g., a diffusion-weighted image) of the brain region may be used to evaluate stroke in the subject. In some embodiments, for DSC perfusion MRI, the at least one Na-nuclei based image (e.g., a static sodium image) and the at least one H-nuclei based image (e.g., a T2*-weighted image) of the brain region may be used to evaluate stroke in the subject. In some embodiments, the at least one Na-nuclei based image (e.g., a static or dynamic sodium image) and the at least one H-nuclei based image (e.g., an fMRI image) of the brain region may be used to evaluate stroke in the subject.

FIG.18illustrates a method for multinuclear CEST-SAGE-EPI MR imaging for generating images of a brain in a subject for use in metabolic imaging of brain tumors in the subject in accordance with an embodiment. InFIG.18, the X-nuclei is sodium (Na). In some embodiments, an Na+Density-Adapted GRE, Na+-SBBDAR, module (e.g., Na+-SBBDARmodule300shown inFIG.3) is interleaved with an H+-SBBCEST-SAGE-EPImodule (e.g., the combination of modules1100and1200shown inFIGS.11and12, respectively) to acquire a set of MR data to generate Na-nuclei based image(s) and to acquire a set of MR data to generate H-nuclei based MR image(s), respectively, of a brain of a subject. In some embodiments, the Na-nuclei based image may be, for example, a static sodium image of the brain and the H-nuclei based image may be, for example, a metabolic-weighted image. In some embodiments, the multinuclear CEST-SAGE-EPI MR sequence (i.e., a multinuclear Na+H+metabolic MR sequence) may be configured to be sensitive to Na+concentration, tissue pH, and O2utilization and may be used to acquire Na+-, pH-, and O2-weighted images. For acquisition of Na+-, pH-, and O2-weighted images, the H+SBBCEST-SAGE-EPImodule may be a fast anime proton CEST-SAGE-EPI acquisition. The interleaved Na+-SBBDARmodule and H+SBBCEST-SAGE-EPImodule may be used to obtain a set of pH- and O2-sensitive images at the same time as a line of k-space is acquired for Na+images. For example, the H+- SBBCEST-SAGE-EPImodule can be performed during the “dead time” TR or relaxation time required for the Na+nuclei to return to equilibrium. Conventional methods for acquiring Na+, pH-, and O2-weighted images collect the images sequentially resulting in a total scan time of approximately 30-60 min. Advantageously, in some embodiments, interleaving Na+and H+-CEST-SAGE-EPI acquisitions can allow Na+-, pH-, and O2image contrasts to be constructed in approximately 15 minutes, making it clinically and economically feasible.

At block1802, an Na-nuclei pulse sequence module (e.g., a Na+-SBBDARmodule) may be performed in a first repetition time (TR) using an MRI system (e.g., MRI system100described above with respect toFIG.1) to acquire a portion of a first set of MR data from a brain region in a subject. In some embodiments, the acquired portion of the first MR data set using the Na+-SBBDARmodule may be a line of k-space. The portion of the first set of MR data may be acquired using a first RF coil that is tuned to the Na-nuclei. At block1804, an H-nuclei pulse sequence module (i.e., a H+-SBBCEST-SAGE-EPImodule) including a preparation module may be performed in the first repetition time using the MRI system (e.g., MRI system100described above with respect toFIG.1) to acquire a portion of a second set of MR data from the brain region in the subject. In some embodiments, the H+-SBBCEST-SAGE-EPImodule incudes a H+-SBBCEST-Preppreparation module and a H+-SBBSAGE-EPImodule (for example, the combination of modules shown inFIGS.11and12). In some embodiments, the portion of the second set of MR data using the H+-SBBCEST-SAGE-EPImodule is data for a CEST z-spectral point. The portion of the second set of MR data may be acquired using a second RF coil that is tuned to the H-nuclei.

At block1806, the Na+-SBB module and the H+-SBBCEST-SAGE-EPImodule are repeatedly performed using the MRI system in an interleaved manner. Accordingly, each repetition time (TR) can include performing one Na+-SBBDARmodule to acquire a portion of the first set of MR data followed by performing an H+SBBCEST-SAGE-EPImodule to acquire a portion of the second set of MR data. As mentioned, in some embodiments, each TR produces a single line of k-space from the Na+-SBB module and each TR acquires a CEST z-spectral point from the H+-SBBCEST-SAGE-EPImodule. Accordingly, each TR can be used to cycle through single lines of —space for the first set of MR data acquired using the Na+-SBB module and each TR can be used to cycle through data for CEST z-spectral points (or the CEST z-spectrum) using the H+-SBBCEST-SAGE-EPImodule. In some embodiments for acquisition of Na+, pH-, and O2-weighted images, during each effective repetition time (TReff) or epoch, the technique will cycle through lines of k-space for the Na+nuclei while cycling through z-spectral RF offset frequencies for the H+nuclei.

At block1808, the Na+-SBB module and the H+-SBBCEST-SAGE-EPImodule are repeatedly performed in an interleaved manner until the acquisition of first set of MR data and the acquisition of the second set of MR data are complete. If the acquisition of the first set of MR data and the second set of MR data are not complete at block1808, the process returns to block1806. If the acquisition of the first set of MR data and the second set of MR data are complete at block1808, at the end of the acquisition the acquired k-space lines from all TRs (which cycle through k-space) for the first set of MR data may be constructed into at least one Na-nuclei based image, for example, single static sodium image of the brain at block1810and the acquired data for the second set of MR data may be constructed into at least one H-nuclei based image, for example, a metabolic-weighted image of the brain at block1812. In some embodiments, the at Na-nuclei based image(s) can include a static Na+image (NaT) and the H-nuclei image(s) can include pH- and O2-weighted images (e.g., MTRasymat 3 ppm and R2′, respectively). In some embodiments, an AGI may be constructed and fused with the NaT image, resulting in estimates of:

where rCBV is relative cerebral blood volume. Accordingly, the disclosed acquisition technique can allow for the construction of Na+-. pH-, and O2-weighted MR images simultaneously. In some embodiments, advantageously the Na+. pH-, and O2-weighted MR images can be constructed with no added contrast or risk to patients. Known methods may be used to generate or calculate the various types of Na-nuclei and H-nuclei images (e.g., static sodium image, pH-weighted image, O2-weighted image, etc.) from the acquired MR data.

At block1814, one or more of the at least one Na-nuclei based image and the at least one H-nuclei based image may be displayed on a display (e.g., display104,136or144shown inFIG.1). The at least one Na-nuclei based image (e.g., a static sodium image) and the at least one H-nuclei based image (e.g., a metabolic-weighted image) of the kidney region may be used to evaluate brain tumor of the subject

Computer-executable instructions for multinuclear MRI using interleaved X-nuclei and H-nuclei modules (or SBBs) according to the above-described methods may be stored on a form of computer readable media. Computer readable media includes volatile and nonvolatile, 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. Computer readable media 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 disk ROM (CD-ROM), digital volatile disks (DVD) or other optical storage, magnetic cassettes, magnetic tape, magnetic disk storage or other magnetic storage devices, or any other medium which can be used to store the desired instructions and which may be accessed by a system (e.g., a computer), including by internet or other computer network form of access.