Patent Application
20230408616
Proton (1H) magnetic resonance (MR) single-voxel spectroscopy has been used to detect and quantify metabolites in vivo. In one specific example, single-voxel spectroscopy is used to detect and quantitate creatine and myocardial triglycerides within a particular voxel of the cardiac septum. Localization of the voxel is performed by applying either point-resolved spectroscopy (PRESS) or stimulated echo acquisition mode (STEAM) pulse sequences. Typically, two scans are performed, where the first scan measures the metabolite peak area and the second scan measures the water peak area. The triglycerides content is determined as the ratio of the metabolite peak area to the water peak area.
Accurate quantitation of metabolites in heart tissue is particularly challenging due to respiratory, cardiac, body and other motion, which causes movement of the voxel of interest. The effects of respiratory motion may be reduced by using a navigator to monitor respiration states and to perform gating based thereon. Similarly, cardiac motion can be mitigated by using ECG triggering to synchronize the localization and signal readout to a consistent phase of the cardiac cycle. However, signal loss is unavoidable as the heart is constantly moving during the cardiac cycle. Moreover, the degree of signal loss may vary depending on the trigger delay, which introduces additional uncertainty in the quantitation process.
The voxel of interest is typically placed on the septum to avoid signals from the blood pool. However, such techniques may be unreliable because the motion of the blood in the voxel is unpredictable and dependent on various factors, such as trigger time and function of the myocardium. Moreover, if the spectroscopy also includes the use of known motion-compensating methods, these methods may increase the signal from blood and cause further bias in the quantitation, particularly if the voxel partially includes the blood pool due to motion or inaccurate localization.
Improved single-voxel spectroscopy for quantitation of myocardial metabolites is desired.
The following description is provided to enable any person in the art to make and use the described embodiments. Various modifications will remain apparent to those in the art.
It would be desirable to provide a system and method for dark-blood and motion-compatible single-voxel MR spectroscopy suitable for quantitation of myocardial triglycerides or other metabolite content.
In some embodiments, single-voxel MR spectroscopy includes performing, using a magnetic resonance imaging (MRI) system, a dark-blood single-voxel spectroscopy pulse sequence to acquire MR data from a region of interest in a subject. The pulse sequence can include dual inversion preparation pulses applied in a first R-R interval followed by excitation pulses including a plurality of localization pulses for spectroscopy in a second successive R-R interval. The timing of the plurality of localization pulses may be configured to null blood signal, and a quantitation of metabolite content of the region of interest is generated based on the thusly-acquired MR data.
In some embodiments, single-voxel spectroscopy is used for imaging of other body parts where suppressing signal contribution from blood could also improve the accuracy of quantitation. Some embodiments may achieve accurate and reproducible quantitation of myocardial triglycerides content in combination with the second-order motion compensated localization. The plurality of localization pulses may comprise pulses conforming to point-resolved spectroscopy (PRESS) techniques, for example, for quantitating myocardial triglycerides. In some embodiments, the plurality of localization pulses may comprise pulses conforming to stimulated echo acquisition mode (STEAM) technique, for quantitating other metabolites, such as creatine. Some embodiments further utilize navigator pulses for respiratory motion control.
According to MR techniques, a substance (e.g., human tissue) is subjected to a main polarizing magnetic field (i.e., B0), causing the individual magnetic moments of the nuclear spins in the substance to process about the polarizing field in random order at their characteristic Larmor frequency, in an attempt to align with the field. A net magnetic moment Mz is produced in the direction of the polarizing field, and the randomly-oriented magnetic components in the perpendicular plane (the x-y plane) cancel out one another.
The substance is then subjected to an excitation field (i.e., B1) created by emission of a radiofrequency (RF) pulse, which is in the x-y plane and near the Larmor frequency, causing the net aligned magnetic moment Mz to rotate into the x-y plane so as to produce a net transverse magnetic moment Mt, which is rotating, or spinning, in the x-y plane at the Larmor frequency. The excitation field is terminated, and signals are emitted by the excited spins as they return to their pre-excitation field state. The emitted signals are detected, digitized and processed to reconstruct an image or a spectrum using one of many well-known MR techniques.
Gradient coils 6 produce magnetic field gradients Gx, Gy, and Gz which are used for position-encoding NMR signals. The magnetic field gradients Gx, Gy, and Gz distort the main magnetic field in a predictable way so that the Larmor frequency of nuclei within the main magnetic field varies as a function of position. Accordingly, an excitation field B1 which is near a particular Larmor frequency will tip the net aligned moment Mz of those nuclei located at field positions which correspond to the particular Larmor frequency, and signals will be emitted only by those nuclei after the excitation field B1 is terminated.
Gradient coils 6 may consist of three windings, for example, each of which is supplied with current by an amplifier 8a-8c in order to generate a linear gradient field in its respective Cartesian direction (i.e., x, y, or z). Each amplifier 8a-8c includes a digital-analog converter 9a-9c which is controlled by a sequence controller 10 to generate desired gradient pulses at prescribed times.
Sequence controller 10 also controls the generation of RF pulses by RF system 11 and RF power amplifier 12. RF system 11 and RF power amplifier 12 are responsive to a scan prescription and direction from sequence controller 10 to produce RF pulses of the desired frequency, phase, and pulse amplitude waveform. The generated RF pulses may be applied to the whole of RF coil 7 or to one or more local coils or coil arrays. RF coil 7 converts the RF pulses emitted by RF power amplifier 12, via multiplexer 13, into a magnetic alternating field to excite the nuclei and align the nuclear spins of the object to be examined or the region of the object to be examined. As mentioned above, RF pulses may be emitted in a magnetization preparation step to enhance or suppress certain signals.
The RF pulses are represented digitally as complex numbers. Sequence controller 10 supplies these numbers in real and imaginary parts to digital-analog converters 14a-14b in RF system 11 to create corresponding analog pulse sequences. Transmission channel 15 modulates the pulse sequences with a radio-frequency carrier signal having a base frequency corresponding to the resonance frequency of the nuclear spins in the volume to be imaged.
RF coil 7 both emits radio-frequency pulses as described above and scans the alternating field which is produced because of precessing nuclear spins, i.e., the nuclear spin echo signals. The received signals are received by multiplexer 13, amplified by RF amplifier 16 and demodulated in receiving channel 17 of RF system 11 in a phase-sensitive manner. Analog-digital converters 18a and 18b convert the demodulated signals into digitized real and imaginary components.
Electrocardiograph (“ECG”) monitor 19 acquires ECG signals from electrodes placed on patient 4 and respiratory monitor 20 acquires respiratory signals from a respiratory bellows or other respiratory monitoring device. Such physiological signals may be used by sequence controller 10 to synchronize, or “gate”, transmitted RF pulses of a spectroscopy pulse sequence based on the heartbeat and/or respiration of patient 4 as described herein.
Computing system 30 receives the digitized real and imaginary components from analog-digital converters 18a and 18b and may process the components according to known techniques. Such processing may, for example, include reconstructing two-dimensional or three-dimensional images by performing a Fourier transformation of raw k-space data, performing other image reconstruction techniques such as iterative or back-projection reconstruction techniques, applying filters to raw k-space data or to reconstructed images, generating functional magnetic resonance images, calculating motion or flow images, and generating a chemical shift vs. magnitude spectrum.
System 30 may comprise any general-purpose or dedicated computing system. Accordingly, system 30 includes one or more processing units 31 (e.g., processors, processor cores, execution threads, etc.) configured to execute processor-executable program code to cause system 30 to operate as described herein, and storage device 32 for storing the program code. Storage device 32 may comprise one or more fixed disks, solid-state random access memory, and/or removable media (e.g., a thumb drive) mounted in a corresponding interface (e.g., a USB port).
One or more processing units 31 may execute program code of control program 33 to provide instructions to sequence controller 10 via MR system interface 34. For example, sequence controller 10 may be instructed to initiate a desired pulse sequence of pulse sequences 35. In particular, sequence controller 10 may be instructed to control the switching of magnetic field gradients via amplifiers 8a-8c at appropriate times, the transmission of radio-frequency pulses having a specified phase and amplitude at specified times via RF system 11 and RF amplifier 12, and the readout of the resulting MR signals. The timing of the various pulses of a pulse sequence may be based on physiological data received by ECG monitor interface 36 and/or respiratory monitor 38.
Storage device 32 stores spectra 37 generated as described herein and MR images 39. Such spectra and images may be provided to terminal 40 via terminal interface 35 of system 30. Terminal interface 35 may also receive input from terminal 40, which may be used to provide commands to control program 33 to initiate single-voxel spectroscopy as described herein. Terminal 40 may comprise a display device and an input device coupled to system 30. In some embodiments, terminal 40 is a separate computing device such as, but not limited to, a desktop computer, a laptop computer, a tablet computer, and a smartphone.
Each element of system 1 may include other elements which are necessary for the operation thereof, as well as additional elements for providing functions other than those described herein. Storage device 22 may also store data and other program code for providing additional functionality and/or which are necessary for operation of system 20, such as device drivers, operating system files, etc.
In
In some embodiments, PRESS pulses 218 include three slice-selective RF pulses for localization. DIR pulses 216 may consist of a non-selective 180-degree RF pulse to invert all the magnetization and a selective 180-degree RF pulse applied immediately following the non-selective 180-degree RF pulse to restore the magnetization of the selected slice on the myocardium. The blood signal outside of the slice profile of the selective 180-degree RF pulse would then experience T1-relaxation and is nulled with the calculated timings when it arrives in the ventricles during the second heartbeat 208. In some embodiments, the RF pulses 216 are configured so that the selected slice includes the cardiac septum.
Application of pulses 216 is triggered by elapsing of time delay TDDIR 220 from R peak 206, and application of pulses 218 is triggered by elapsing of time delay TDPRESS 224 from R peak 208. TDDIR 220 and TDPRESS 224 are determined such that the magnetization Mz of septal myocardium (represented by curve 228) is substantially undisturbed while the magnetization Mz of blood pool (represented by curve 226) is substantially nulled (e.g., is substantially close to the zero magnitude line of magnetization Mz axis 214) with T1-relaxation at the end of DB delay 222 (i.e., before and/or during execution of pulses 218). TDDIR 220 and TDPRESS 224 may also or alternatively be determined such that the heart is in diastole during pulses 218. In some embodiments, TDDIR 220 and TDPRESS 224 may be determined based on the T1 of the blood and the heart rate.
In some embodiments, the determination assumes that pulses 216 and pulses 218 are applied during every other heartbeat and the signal of blood reaches a steady state of:
where RR indicates the average R-to-R interval 210 and is dependent on the heart rate of the subject. Therefore, to null the blood signal, DB delay 222 between DIR pulses 216 and PRESS pulses 218 is given by:
where T1 is the longitudinal relaxation time of blood and TDPRESS 224 is the trigger delay between the R peak of heartbeat 208 and commencement of PRESS pulses 218. TDPRESS may be defined as 250 ms to place PRESS pulses 218 at end-systole but embodiments are not limited thereto. Therefore, trigger delay TDDIR 220 before DIR pulses 216 is given by:
According, TDDIR 220 is dependent on measured heart rate.
Process 400 and all other processes mentioned herein may be embodied in executable program code read from one or more of non-transitory computer-readable media, such as a disk-based or solid-state hard drive, a DVD-ROM, a Flash drive, and a magnetic tape, and then stored in a compressed, uncompiled and/or encrypted format. In some embodiments, hard-wired circuitry may be used in place of, or in combination with, program code for implementation of processes according to some embodiments. Embodiments are therefore not limited to any specific combination of hardware and software.
An R-R interval of a subject is determined prior to process 400. The R-R interval may be determined by monitoring an ECG signal of the subject for a period of time after the subject is positioned in an MRI device. A value of T1 (i.e., the longitudinal relaxation time of blood) and TDPRESS (i.e., the delay between the detected R peak of a heartbeat and the commencement of single-voxel localization pulses are also determined prior to 400. The value of TDPRESS may be defined based on the R-R interval so that the single-voxel localization pulses occur during a desired phase of the cardiac cycle (e.g., end-systole), but embodiments are not limited thereto. The R-R interval, the T1 value and the TDPRESS value may be used as described above to determine a time delay between the R peak of a heartbeat and commencement of dual inversion recovery pulses (i.e., TDDIR).
At S410, double inversion recovery preparation pulses are applied to the subject during a first R-R interval. In one example of S410, an R peak of a heartbeat is detected and, after a period equal to TDDIR elapses, the double inversion recovery preparation pulses are applied as described above and/or as known in the art. Flow then pauses at S420 to detect a next R-R interval, for example by detecting a next R peak.
Once the next R peak is detected, process 400 waits at S430 for a delay time required to substantially null the signal from blood in the voxel of interest. This delay time is TDPRESS as described above. A plurality of pulses for single-voxel localization are applied during the next R-R interval and after the expiration of TDPRESS at S440. The plurality of pulses may comprise a PRESS module, a STEAM module, or any other suitable voxel-localization modules. MR data is acquired from the voxel as a result of the applied pulses at S450. The MR data includes digitized real and imaginary components as is known in the art.
Next, at S460, it is determined whether more data is to be acquired. In this regard, the MR data acquired at S450 typically consists of a subset of k-space lines. Accordingly, if all desired k-space lines have not yet been acquired, flow returns to S410 and continues as described above to acquire additional k-space lines at S450. Flow proceeds from S460 to S470 once all desired k-space lines have been acquired.
At S470, a quantity of one or more metabolites in the single voxel is determined based on the acquired MR data. S470 may comprise generating a spectrum of chemical shift versus magnitude based on the MR data and determining the one or more quantities as is known in the art. The determined one or more quantities may be presented to a user via a terminal such as terminal 40.
Some embodiments combine the above-described pulses with navigator pulses to enable free-breathing MR data acquisition.
More particularly,
Second navigator pulses 514b are applied in a next R-R interval, at a temporal position corresponding to a different phase of respiratory waveform 530. It will be assumed that this temporal position is determined to be suitable, and therefore DIR pulses 516 are applied once TDDIR 520 elapses after the occurrence of R peak 507 as shown in
PRESS pulses 517 are then applied in a next interval, after R peak 508 and elapsing of TDPRESS 524. In some embodiments, the application of the navigator pulses, double inversion recovery pulses and voxel-localization pulses may continue in this manner until all necessary MR data has been acquired.
Process 600 may be used to execute a sequence such as sequence 500 in some embodiments. As described above, values of TDDIR and TDPRESS are determined prior to process 600.
Navigator pulses are applied during an R-R interval at S610 and a navigator image is generated therefrom. The navigator image is reviewed at S620 to determine whether the navigator pulses were applied at the desired temporal position of respiration cycle (e.g., when the lung position corresponds to end-expiration). If not, flow returns to S610 where navigator pulses are applied during a next R-R interval and preferably during a different phase of the respiratory cycle.
If the temporal position of the navigator pulses is suitable, double inversion recovery preparation pulses are applied at S630. The double inversion recovery preparation pulses are applied during a same R-R interval as the prior-applied navigator pulses, and after the elapsing of TDDIR from the first R peak of that R-R interval.
S640 through S690 may proceed as described above with respect to S420 through S470. However, if it is determined at S680 that all desired k-space lines have not yet been acquired, flow returns to S610 to apply navigator pulses during a subsequent R-R interval and continues to acquire another set of k-space lines.
ECG axis 702 includes R peaks 706, 707, 708 and 709, RF axis 712, Mz axis 714, and respiratory motion waveform 730. In response to detection of R peak 706, double inversion recovery pulses 716 are applied after elapsing of TDDIR 720 as shown.
Navigator pulses 714a are then applied after detection of next R peak 707. As described above, it is determined whether the temporal position of pulses 714a is suitable in view of the phase of respiratory motion waveform 730 at this same temporal position. It will be assumed that the temporal position of pulses 714a is determined to be suitable, therefore PRESS pulses 717 are applied after elapsing of TDPRESS 724 from R peak 707. Application of navigator pulses in this embodiment should conclude in time to provide enough time for application of the PRESS pulses between the elapsing of TDPRESS and a next R peak.
Double inversion recovery pulses 718 applied in a next R-R interval, again after elapsing of TDDIR 726 from the first R peak 708 of the R-R interval. Navigator pulses 714b are then applied after detection of next R peak 709 at a temporal position which may correspond to a different phase of respiratory waveform 730. It will be assumed that this temporal position is determined to be unsuitable, and therefore PRESS pulses are not applied in the same R-R interval as pulses 714b. Accordingly, no MR data is acquired in this R-R interval. In some embodiments, the application of the navigator pulses, double inversion recovery pulses and voxel-localization pulses may continue in this manner until all necessary MR data has been acquired.
Process 800 may be used to execute a sequence such as sequence 700 in some embodiments, based on predetermined values of TDDIR and TDPRESS.
Double inversion recovery preparation pulses are applied at S810 during a first R-R interval and after the elapsing of TDDIR from the first R peak of the first R-R interval. Flow cycles at S820 until a next R peak (i.e., a first R peak of a next R-R interval) is detected.
Navigator pulses are applied during the second R-R interval at S830. The temporal position of the navigator pulses is compared with a respiration cycle at S840 to determine if the temporal position is suitable. If not, flow returns to S810 at which double inversion recovery preparation pulses are applied during a next R-R interval.
If the temporal position of the navigator pulses is determined to be suitable at S840, flow proceeds to S850 through S880 as described above with respect to S430 to S460. In some embodiments, flow may return from S870 to S810 and repeat until it is determined that sufficient MR data has been acquired, at which point flow continues to S880.
Executable program code for dark-blood single-voxel spectroscopy with double inversion recovery according to the above description may be stored on a form of non-transitory 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 program code, 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.
The foregoing diagrams represent logical architectures for describing processes according to some embodiments, and actual implementations may include more or different components arranged in other manners. Other topologies may be used in conjunction with other embodiments. Moreover, each component or device described herein may be implemented by any number of devices in communication via any number of other public and/or private networks. Two or more of such computing devices may be located remote from one another and may communicate with one another via any known manner of network(s) and/or a dedicated connection. Each component or device may comprise any number of hardware and/or software elements suitable to provide the functions described herein as well as any other functions. For example, any computing device used in an implementation of a system according to some embodiments may include a processor to execute program code such that the computing device operates as described herein.
Embodiments described herein are solely for the purpose of illustration. Those in the art will recognize other embodiments may be practiced with modifications and alterations to that described above.
This application claims priority to U.S. Provisional Patent Application No. 63/366,553, filed Jun. 17, 2022, the disclosure of which is incorporated herein by reference for all purposes.
| Number | Date | Country | |
|---|---|---|---|
| 63366553 | Jun 2022 | US |
