Patent application title: ARTERIAL SPIN-LABELED (ASL) MULTIPLEXED ECHO PLANAR IMAGING (M-EPI)
David Feinberg (Sebastapol, CA, US)
IPC8 Class: AA61B5026FI
Class name: Detecting nuclear, electromagnetic, or ultrasonic radiation magnetic resonance imaging or spectroscopy of fluid flow
Publication date: 2013-04-04
Patent application number: 20130085379
An MRI system and method for imaging perfusion in an arterial spin
labeled (ASL) process in which multiplexed echo-planar imaging (M-EPI) is
used rather than conventional EPI, to thereby speed up imaging and
generate sets of images that show different phases of perfusion and
provide additional benefits. A single multiband RF excitation pulse can
be used to excite multiple slices for imaging, or a time sequence of
multiband pulses can be used to further increase the number of slices.
1. A magnetic resonance imaging (MRI) method of imaging perfusion in a
patient using arterial spin labeling (ASL) and multiplexed echo planar
imaging (M-EPI) comprising: positioning a patient in an MRI scanner;
applying arterial spin labeling to a selected portion of the patient's
anatomy; applying a first multiband RF excitation pulse that essentially
simultaneously excites multiple selected slices of the patient's anatomy;
applying magnetic gradients to the patient; essentially simultaneously
acquiring a first set of magnetic resonance (MR) signals generated for
the multiple selected slices in response to the first multiband RF
excitation pulse in an M-EPI process; said acquiring being selectively
timed relative to arterial, capillary and/or venous perfusion in the
patient related to the applying of arterial labeling; and
computer-processing the first set of MR signals to generate a first set
of ASL perfusion images of the slices and display the imaged on a
2. The method of claim 1 further including: applying a second multiband RF excitation pulse after applying the first one, to thereby again excite the multiple selected slices but in a subsequent phase of said perfusion, and essentially simultaneously acquiring a second set of MR signals generated for the multiple selected slices in response to the second multiband RF excitation pulse; wherein the computer system is further configured to computer-process the second set of MR signals to generate a second set of ASL perfusion images of the slices, and wherein the first and second set of images show respective different phases of the perfusion.
3. The method of claim 2 further including applying additional multiband RF excitation pulses in a time succession after the first and second RF excitation pulses to excite the slices at respective different times, acquiring additional sets of MR signals essentially simultaneously for said slices at times related to the respective additional RF excitation pulses, and including said additional sets of MR signals in said computer-processing to thereby generate additional sets of slice images showing respective additional phases of the perfusion.
4. A magnetic resonance imaging (MRI) system for imaging perfusion in a patient using arterial spin labeling (ASL) and multiplexed echo planar imaging (M-EPI) comprising: an MRI scanner having an imaging volume for a patient; an arterial spin labeling source configured to apply ASL pulses to the patient in the imaging volume; RF coils configured to selectively apply a first multiband RF excitation pulse that essentially simultaneously excites multiple selected slices of the patient in the imaging volume; magnetic gradient coils configured to apply magnetic gradients to the patient in the imaging volume; MR signal acquisition coils configured to essentially simultaneously acquire magnetic resonance (MR) signals generated for the multiple selected slices in response to the first multiband RF excitation pulse in an M-EPI process; said acquiring being selectively timed relative to arterial, capillary and/or venous perfusion in the patient related to the applying of arterial labeling; and a computer system configured to computer-processing the MR signals to generate a first set of ASL perfusion images of the slices.
5. The system of claim 4 in which: the RF coils are further configured to apply a second multiband RF excitation pulse after applying the first one, to thereby again excite the multiple selected slices but in a subsequent phase of said perfusion, the MR signal acquisition coils are further configured to essentially simultaneously acquire a second set of magnetic resonance (MR) signals generated for the multiple selected slices in response to the second multiband RF excitation pulse; and the computer system is further configured to computer-process the second set of MR signals to thereby generate a second set of ASL perfusion images of the slices, wherein the first and second set of images show respective phases of the perfusion.
6. The system of claim 5 in which: the RF coils are further configured to apply a sequence of additional multiband RF excitation pulses after applying the first and second RF excitation pulses, to thereby excite the multiple selected slices in respective subsequent phase of said perfusion; the MR signal acquisition coils are further configured to essentially simultaneously acquire additional sets of MR signals generated for the multiple selected slices in response to the respective additional multiband RF excitation pulses; and the computer system is further configured to computer-process the additional sets of MR signals to thereby generate additional sets of ASL perfusion images of the slices that show additional respective phases of the perfusion.
CROSS-REFERENCE TO RELATED APPLICATIONS AND INCORPORATION BY REFERENCE
 This patent application is a continuation-in-part of (a) PCT International Application No. PCT/US11/57161, filed Oct. 20, 2011, which claims the benefit of U.S. Provisional Application No. 61/394,929, filed Oct. 20, 2010, and (b) U.S. patent application Ser. No. 13/632,941, filed Oct. 1, 2012, which is a continuation of U.S. patent application Ser. No. 13/397,634, filed Feb. 15, 2012, which claims the benefit of U.S. Provisional Application Nos. 61/443,215, filed Feb. 15, 2011, 61/444,031, filed Feb. 17, 2011, and 61/444,039, filed Feb. 17, 2011. This patent specification incorporates by reference the entire contents of each of these applications, including their drawings and the appendices attached thereto.
 This patent specification is in the field of magnetic resonance imaging (MRI). More specifically it pertains to imaging tissue perfusion with MRI.
BACKGROUND AND SUMMARY OF THE DISCLOSURE
 Arterial spin labeling (ASL) is a technique for imaging tissue perfusion with MRI. It is generally limited by signal-to-noise ratio (SNR) due to the small (e.g., 3%) fraction of blood in tissue volumes so the MR signal is proportionately small. Another limitation is that tissue blood is moving through different vascular compartments including arterial, capillary and venous compartments, so the time window of imaging can be constrained to a few hundred milliseconds for the capillary compartment. ASL labels the blood with an inversion pulse, followed by a delay and then readout of image slices. The is repeated with and without inversion labeling so that differences between the two acquired signals would tend to null the static signal whereas the inversion labeled blood would be separated and remain in the image. Echo planar imaging (EPI) has been used as a readout image for the ASL perfusion technique but is limited in the number of slices that can be imaged due to the normal physiological time course of labeled blood moving through the different vascular compartments. For that reason repeated ASL labeling inversion pulses may be utilized to acquire many images and slices, consistent with physiological time constraints. ASL with conventional multi-slice 2D EPI has not been able to satisfactorily image perfusion in the entire brain because of timing limitations. 3D imaging techniques, including 3D GRASE, have therefore been developed as an alternative to 2D EPI. However, 2D images have certain desirable characteristics compared with 3D images, and it would be desirable to find an effective way to accurately record perfusion in 2D images.
 In order to retain the benefits of 2D perfusion images, it has been discovered that it is not only practical but also brings about surprising benefits to replace conventional EPI in ASL techniques with multiplexed EPI that uses multiband (MB) RF excitation pulses. The technique of using MB RF excitation pulses in EPI imaging can be called M-EPI in this patent specification. ASL perfusion imaging with M-EPI can be several times faster than ASL with conventional EPI because M-EPI records images for several 2D slices essentially simultaneously, and the location of the blood is the same for all images, whereas this is not true in conventional, time sequential acquisition of multiple EPI images. Further improvements can be achieved by using a time sequence of multiband excitation pulses, so that the number of slices that are imaged in a single pulse sequence is the product of the number of slices for each multiband RF pulses times the number of multiband RF pulses in a single pulses sequence. For example, this product can be 2×2, 2×8, 3×8, etc., where the first number is the number of slices per multiband RF pulse and the second is the number of multiband pulses used in time succession in a single pulse sequence. Of note, a single multiband RF pulse can be used so the number of slices M=MB where MB is the number of simultaneously excited slices using a single multiband RF pulse. See said U.S. patent application Ser. No. 13/397,634, filed Feb. 15, 2012 (including its Appendices A-C). The technique of using a sequence of RF excitation pulses to image multiple 2D slices in a single pulse sequence can be called simultaneous image refocusing (SIR) or simultaneous echo refocusing (SER).
 The replacement of EPI with M-EPI in ASL imaging has several advantages. For example, the complex interdependence of slice saturation effects on arterial input functions and recorded MR signal is greatly improved as far fewer time sequential echo trains are utilized. The time sequential echo trains can be reduced by a factor of N (the number of simultaneously images slices) in M-EPI compared with conventional EPI. With ASL using M-EPI combined with SIR, the entire brain can be scanned in, e.g., in 400 ms or less time with 30 to 60 images, as determined by N images=SIR×MB factors. If SIR=1, then N=MB alone, and this is one example included in the scope of the new process described in this patent specification. Ultimately, all slices can be acquired in a single echo train if the SIR and/or MB factors are large enough for the product to create enough slices to cover the entire brain or at least the portion of interest. It can be very important to cover the entire brain or organ, or at least the portion of interest, with slices to record the entire state of perfusion. This has not been possible for the entire brain with ASL based on conventional EPI due to the limited time window for measuring the hemodynamic perfusion effects because it was not believed possible to acquire enough conventional EPI images to cover the entire brain. Equally limiting to ASL using conventional EPI in this relationship to hemodynamics, is that the EPI images are time sequential and so even during a limited total scan time to make 10 images within an acceptable time window, each image is at a different temporal delay with respect to the initial blood labeling inversion pulse, so that each image actually has a different inflow time and this gives error in calculating their combined measurement of perfusion in the brain.
 Another benefit of using ASL with M-EPI, is that the time to scan the brain can be reduced to such a great amount, for example in the range of 6 to 30 times faster than with EPI, that multiple measurements of MR signals can be made after the labeling inversion pulse. This can result in a series of inflow time-dependent measurements which can sample the blood as it moves through different vascular compartments. The MR signal data can be combined to improve SNR or accuracy and used to model the different transit times for useful hemodynamic parameters to describe disease states within the brain or other organ. Many different variants of ASL labeling schemes can be combined with M-EPI and/or SIR.
 Note that ASL imaging techniques typically utilize two identical acquisitions differing in one being a Labeling sequence (L) in which the blood is labeled and a control sequence (C) in which the blood is not labeled but all other parameters are unchanged so that L-C gives a measure of blood labeled with subtraction of other sources of signal that are constant in the two sequence acquisitions.
BRIEF DESCRIPTION OF THE DRAWING
 FIG. 1 illustrates MR signal acquisition in arterial spin labeling (ASL) using conventional echo-planar imaging (EPI).
 FIGS. 2a and 2b illustrate a comparison between ASL using conventional multi-slice EPI (FIG. 2a) and ALS using a multi-band RF excitation pulse to carry out M-EPI in which MR signals for multiple slices are acquired essentially simultaneously.
 FIG. 3 illustrates a similar comparison related to phases of perfusion in tissue and changes in the value of an ASL signal with time. The upper portion of FIG. 4 illustrates the case of using ASL with conventional EPI to acquire MR signals for multiple slices while the lower portion illustrates the case of using a single multiband RF excitation signal to essentially concurrently acquire MR signals for the same number of multiple slices. In each case, acquisition time is related to changes in perfusion with time.
 FIG. 4 illustrates ALS using a time sequence of multiband RF excitation pulses to acquire, in time sequence, blocks of MR signals where each block is for multiple, essentially simultaneously acquired slices but different blocks correspond to different perfusion phases.
 FIG. 5(A) illustrates the use of EPI limited by time of physiological phase which limits number of ASL images.
 FIG. 5(B) illustrates the use of M-EPI that increases the number of obtainable images within the same time window to achieve much greater coverage of the entire brain.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
 FIG. 1 illustrates conventional multi-slice 2D EPI in which several slice images are acquired one after the other in time. The different blood inflow times in consecutively acquired slice images limit the accuracy of blood flow quantization. Different vascular compartments are filled at different times, resulting in undesirable coupling to spatial slice position.
 FIGS. 2a and 2b illustrate important differences between ASL multi-slice EPI imaging and ASL multiplexed EPI imaging. The example of FIG. 2a illustrates that MR signals for multiple 2D slice images are obtained in time sequence over a time span that is much longer than that seen in FIG. 2b, where MR signals for the same number of multiple 2D slice images are obtained using M-EPI essentially simultaneously.
 FIG. 3 illustrates some important consequences of differences between ASL using conventional EPI and the new approach of using ASL with M-EPI. With the old approach, the acquisition time of MR signals for the illustrated multiple images (top part of FIG. 3) extends over an excessively long portion of the delay time inherent in perfusion through different vascular compartments (arteries and capillaries). However, with the new approach of ASL using M-EPI (with or without using SIR as well), the time to acquire the same number of slice images is much shorter and can reflect perfusion parameters and their relationships much more accurately. While an example of 36 slice images is shown in FIG. 3 for the case of the prior technique of ASL using conventional EPI, in fact typically only 8 to 10 slice images were acquired in practice to give a reasonable estimate of perfusion parameters but for less than the entire brain or organ of interest. Using selected timing the images for ASL with M-EPI can be acquired for the intra-capillary phase (as illustrated in FIG. 3, middle portion), or for the intra-arterial phase, or for some other phase.
 FIG. 4 illustrates one of the important benefits of the new ASL with M-EPI approach, in which perfusion parameters for the entire brain or organ of interest can be obtained so rapidly that scans of the organ can be taken repeatedly to thereby view dynamic changes and exchanges of blood between arterial, capillary and venous compartments. As seen in FIG. 4, MR signals are taken in 14 time-sequential blocks, where the MR signals for 36 slices are essentially simultaneously acquired in each block. Because the blocks are sequential in time, each block can result in images for 36 slices that show a respective phase of perfusion. FIG. 4 illustrates a case in which imaging starts as intra-capillary perfusion accelerates, but the MR signal acquisition can be timed to cover any desired phase in arterial, capillary or venous perfusion.
 FIGS. 5(A) and 5(B) illustrate an important difference between previously known ASL EPI imaging and the use of M-EPI to obtain additional slices to cover a larger region of the brain than would be achievable using current EPI imaging.
 In FIG. 5(A), which illustrates the previously known process, the time duration is limited to the window of time in which blood is primarily within the vascular compartment. Using EPI, typically N=8 images can be acquired in this time window which can then only cover N×slice thickness for the extent of slices covering the brain.
 FIG. 5(B) illustrates that the use of M-EPI can increase the extent of slice coverage to equal N×M where M is the number of simultaneously acquired slices. In other words, M-EPI gives much greater slice coverage, even possibly whole brain coverage within the physiological limited time window of choosing a particular vascular compartment such as capillary perfusion phase. Current ASL EPI techniques are limited to a few slices due to the limited time window so this would greatly improve the utility of the technique.
 ASL M-EPI imaging as described in this patent specification may be performed with or without SIR. Expressed more generally, an MRI system using the teachings of this patent specification can generate ALS MR signals for multiple slices using any one of (a) RF excitation pulses that are multiband pulses to essentially simultaneously excite plural slices of the patient's anatomy, (b) a time sequence of two or more multiband RF excitation pulses each of which essentially simultaneously excites multiple slices and the time sequence of which excites a number of slices equal to the product of the bands in each multiband pulse times the number of multiband pulses in the sequence, and (c) a time sequence of RF excitation pulses that are not multiband pulses. Different MRI scanner hardware may have different RF coils and gradients so that it may be desirable to perform M-EPI in these more limited ways, in which ASL M-EPI (without SIR) would still have advantage of a reduced scan time.
 An explanation and illustrations of M-EPI and SIR pulse sequences, and MRI scanners using them, can be found in the PCT application and the U.S. application that re incorporated by reference in this patent specification. In addition, the following papers may provide useful background and are hereby incorporated by reference:
 1. Barbier E L, et al., Perfusion Imaging Using Dynamic Arterial Spin Labeling (DASL), Magnetic Resonance in Medicine 45:1021-1021 (2001);
 2. Wang Y, Regional reproducibility of pulsed arterial spin labeling perfusion imaging at 3T, NeuroImage 54 (2011) 1188-1195;
 3. Wang J, Reduced susceptibility effects in perfusion fMRI with single-shot spin-echo EPI acquisitions at 1.4 Tesla, Magnetic Resonance Imaging 22 (2004) 1-7; and
 4. Donahue M J, et al., Cerebral blood flow, blood volume, and oxygen metabolism dynamics in human visual and motor cortex as measured by whole-brain multi-modal magnetic resonance imaging, Journal of Cerebral Blood Flow & Metabolism (2009) 29, 1856-1866.
Patent applications by David Feinberg, Sebastapol, CA US
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