U.S. patent application number 11/024185 was filed with the patent office on 2005-06-09 for pulse imaging sequences and methods for t1p-weighted mri.
Invention is credited to Borthakur, Ari, Charagundla, Sridhar R., Reddy, Ravinder, Shapiro, Eric M..
Application Number | 20050122102 11/024185 |
Document ID | / |
Family ID | 29553327 |
Filed Date | 2005-06-09 |
United States Patent
Application |
20050122102 |
Kind Code |
A1 |
Reddy, Ravinder ; et
al. |
June 9, 2005 |
Pulse imaging sequences and methods for T1p-weighted MRI
Abstract
Provided are pulse imaging sequences and methods for 2D
mulfi-slice T.sub.1p-weighted and 3D T.sub.1p-weighted magnetic
resonance imaging (MRI). Further provided is a self-compensating
spin-locking sequence for correcting and reducing artifacts in
T.sub.1p-weighted imaging. Also provided is a sequence combining 3D
T.sub.1p-weighted MRI with a self-compensating spin-locking pulse
for facilitating T.sub.1p-weighted imaging with surface coils.
Inventors: |
Reddy, Ravinder;
(Phoenixville, PA) ; Charagundla, Sridhar R.;
(Morton, PA) ; Borthakur, Ari; (Philadelphia,
PA) ; Shapiro, Eric M.; (Washington, DC) |
Correspondence
Address: |
DRINKER BIDDLE & REATH
ATTN: INTELLECTUAL PROPERTY GROUP
ONE LOGAN SQUARE
18TH AND CHERRY STREETS
PHILADELPHIA
PA
19103-6996
US
|
Family ID: |
29553327 |
Appl. No.: |
11/024185 |
Filed: |
December 28, 2004 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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11024185 |
Dec 28, 2004 |
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10389502 |
Mar 14, 2003 |
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6836114 |
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60364878 |
Mar 15, 2002 |
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Current U.S.
Class: |
324/307 ;
324/309 |
Current CPC
Class: |
G01R 33/50 20130101;
G01R 33/4835 20130101 |
Class at
Publication: |
324/307 ;
324/309 |
International
Class: |
G01V 003/00 |
Goverment Interests
[0002] This work was supported in part by National Institutes of
Health Research Resource Grant RR02305 and by the Arthritis
Foundation and National Institutes of Arthritis and Musculoskeletal
and Skin Diseases (NLAMS-NIH grants RO145252, RO145404 and
R21-EB00480. The government may have certain rights in this
invention.
Claims
What is claimed is:
1. A 2D multi-slice T.sub.1p-weighted pulse sequence for magnetic
resonance imaging, comprising in sequential order: a first radio
frequency pulse for selectively exciting a band of spins; a second
radio frequency pulse, wherein the second pulse is a spin-locking
pulse divided into at least two segments, wherein the spin-locking
segments have 90 .degree. alternating phase shift for spin-locking
in a transverse plane of the spins; a third radio frequency
slice-selective pulse, phase-shifted 180.degree. from the first
radio frequency pulse, which restores spin-locked magnetization to
a longitudinal axis for imaging with any pulse sequence; and a
strong crusher gradient applied to destroy residual transverse
magnetization.
2. The pulse sequence of claim 1, wherein each of the first and
third radio frequency pulses is a .pi./2 pulse.
3. A method of 2D multi-slice T.sub.1p-weighted imaging using the
sequence of claim 1, comprising: applying a first radio frequency
pulse for selectively exciting a band of spins; applying a
spin-locking pulse, wherein the spin-locking pulse further
comprises at least two segments with 90 .degree. alternating phase
shift for spin-locking in a transverse plane of the spins; applying
a third radio frequency slice-selective pulse, phase-shifted 180
.degree. from the first radio frequency pulse which restores
spin-locked magnetization to a longitudinal axis for imaging with
any pulse sequence; and applying a strong crusher gradient applied
to destroy residual transverse magnetization.
4. The method of claim 3, wherein applying each of the first and
third radio frequency pulses further comprises applying a .pi./2
pulse.
5. A self-compensating spin-locking pulse sequence for correcting
artifacts in T.sub.1p-weighted magnetic resonance imaging,
comprising in sequential order: a first radio frequency pulse for a
selected .theta. that nutates magnetization into a transverse
plane; a spin-locking pulse, wherein the spin-locking pulse further
comprises at least two segments that are 90 .degree. phase-shifted
and have an amplitude B.sub.s1, applied for time period TSL; a
second radio frequency pulse for a selected .theta. applied,
phase-shifted by 180.degree. to return a T.sub.1p-relaxed
magnetization to a longitudinal axis for imaging; and a crusher
gradient to dephase residual transverse magnetization.
6. The sequence of claim 5, wherein each of the first and second
radio frequency pulses for a selected .theta. is a .pi./2
pulse.
7. A method of correcting artifacts in T.sub.1p-weighted imaging
with the self compensating spin-locking pulse of claim 5,
comprising applying a three-pulse preparatory cluster to an imaging
sequence.
8. The method of claim 7, further comprising applying the
three-pulse preparatory cluster pre-appended to a spin-echo-based
imaging sequence.
9. The method of claim 7, further comprising applying the
three-pulse preparatory cluster pre-appended to a gradient
echo-based imaging sequence.
10. The method of claim 7, wherein applying the three-pulse
preparatory cluster further comprises: applying a first radio
frequency pulse for a selected 0 that nutates magnetization into a
transverse plane; applying a spin-locking pulse, wherein the
spin-locking pulse further comprises at least two segments that are
90.degree. phase-shifted and have an amplitude B.sub.s1, applied
for time period TSL; applying a second radio frequency pulse for a
selected .theta. phase-shifted by 180.degree. to return a
T.sub.1p-relaxed magentization to a longitudinal axis for imaging;
and applying a crusher gradient to dephase residual longitudinal
magnetization.
11. The method of claim 10, wherein B.sub.s1 is a fraction of a
maximum available radio frequency field B.sub.1.
12. The method of claim 10, wherein each of the first and second
radio frequency pulses is a .pi./2 hard pulse.
13. A 3D T.sub.1p-weighted pulse sequence for magnetic resonance
imaging, comprising a pulse cluster pre-encoded with a gradient
echo sequence, wherein the pulse cluster further comprises in
sequential order: a first .pi./2 hard pulse; a spin-locking pulse
having amplitude B.sub.1; a second .pi./2 hard pulse phase shifted
180.degree. from the first hard pulse; and a strong crusher
gradient applied before a ax pulse to destroy residual
magnetization in a transverse plane and inhibit the formation of
unwanted coherences.
14. The pulse sequence of claim 13, wherein the spin-locking pulse
further comprises two or more segments with alternating phases.
15. The pulse sequence of claim 14, wherein spin-locking pulse
segments are +90.degree. and -90.degree. phase-shifted from the
phase of the first .pi./2 pulse.
16. A method of providing 3D T.sub.1p-weighted magnetic resonance
imaging using the sequence of claim 13, comprising applying a pulse
cluster pre-encoded with a gradient echo sequence, wherein applying
a pulse cluster further comprises; applying a first .pi./2 hard
pulse; applying a spin-locking pulse having amplitude B.sub.1;
applying a second .pi./2 hard pulse phase shifted 180.degree. from
the first hard pulse; and applying a strong crusher gradient before
a a pulse to destroy residual magnetization in a transverse plane
and inhibit the formation of unwanted coherences.
17. The method of claim 16, wherein the step of applying a
spin-locking pulse further comprises applying a spin-locking pulse
having at least two segments, wherein the at least two spin-locking
segments have alternating phases for spin-locking in a transverse
plane.
18. A method of obtaining 3D T.sub.1p-weighted images with a coil,
comprising applying a pulse cluster pre-encoded with a gradient
echo sequence, wherein applying a pulse cluster further comprises;
applying a first .pi./2 hard pulse; applying a spin-locking pulse
having amplitude B.sub.1 and having at least two segments, wherein
the spin-locking segments have alternating phases for spin-locking
in a transverse plane of the spins; applying a second .pi./2 hard
pulse, phase shifted 180.degree. from the first hard pulse; and
applying a strong crusher gradient before a a pulse to destroy
residual magnetization in the transverse plane and inhibit the
formation of unwanted coherences.
19. The method of claim 18, wherein the coil is a surface coil.
20. The method of claim 18, wherein the coil is a volume radio
frequency coil.
21. The method of claim 18, wherein applying spin-locking segments
further comprises applying spin-locking segments +90.degree. and
-90.degree. phase shifted from the first hard pulse.
Description
REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to U.S. Provisional
Application No. 60/364,878 filed Mar. 15, 2002, herein incorporated
by reference in its entirety.
FIELD OF THE INVENTION
[0003] This invention relates generally to the field of magnetic
resonance imaging (MRI). Specifically, the invention relates to
spin-locking and T.sub.1p-weighted MRI pulse sequences.
BACKGROUND OF THE INVENTION
[0004] Magnetic resonance imaging (MRI) has become the modality of
choice for imaging joints due to its excellent definition of
ligaments, cartilage, bone, muscle, fat and superior soft tissue
contrast (Smith, Magn. Reson. Imaging Clin. N. Am. 3:229-248
(1995); Sofka, et al., Radiology 5:217-226 (2001)). For two
decades, proton magnetic resonance imaging (MRI) has shown its
efficacy in the noninvasive analysis of soft tissues, particularly
in the diagnosis of tendinomuscular and osteoarticular diseases
(Peterfy, et al., Radiol. Clin. North Am. 34:195 (1996); Peterfy,
Magn. Reson, Imaging Clin. N. Amer. 8:409-430 (2000)).
[0005] Articular cartilage is a connective tissue consisting of
relatively few cells and a highly charged and hydrated
extracellular matrix (ECM). The constituents of the ECM are
proteoglycans (PG), collagen, and non-collagenous proteins and
water (Grushko, et al., Conn. Tiss. Res. 19:149-176 (1989);
Lohmander, J. Anatomy 184:477-492 (1994); Mankin, et al., J. Bone
Joint Surg-Am. 53:523-537 (1971)). Despite its remarkable
durability, degeneration of articular cartilage can result from
either noninflammatory processes, such as osteoarthritis (OA), or
inflammatory processes, such as rheumatoid arthritis (RA). The
early stage of OA is associated with loss of PG and changes in
water content (Grushko, et al., 1989; Lohmander, 1994). Recent
developments in chondroprotective therapies, cartilage grafting,
gene therapy and tissue engineering have increased the demand for
accurate and non-invasive techniques that will enable the detection
of the early biochemical changes of cartilage degeneration in
vivo.
[0006] Conventional proton MR techniques have been able to provide
information about late stages of degeneration in which structural
defects are present (Recht, et al., Am. J. Roent. 163:283-290
(1994); Peterfy, et al., Radiol. Clin. North Am. 32:291-311
(1994)). Recently, delayed gadolinium (Gd)-enhanced proton MRI of
cartilage (dGEMIC) (Bashir, et al., Magn. Reson. Med. 36:665-673
(1996); Burstein, et al., Magn. Reson. Med. 45:36-41 (2001);
Mlynarik, et al., J. Magn. Reson. Imaging 10:497-502 (1999)),
positively charged nitroxide based techniques (Lattanzio, et al.,
25:1024 (2000), and sodium MRI (Reddy, et al., Magn. Reson. Med.
39:697-701 (1998); Shapiro, et al., J. Magn. Reson.142:24-31;
Shapiro, et al., Magn. Reson. Med. 47:284-291 (2002)) have been
employed to measure PG changes in cartilage both in vivo and in
vitro. However, these techniques have some practical limitations.
In dGEMRIC, long waiting period between contrast agent injection
and imaging and variation in intra tissue Gd-relaxivity may
contribute to the errors in PG quantitation, thereby reducing the
accuracy of this technique in the detection of OA. Although sodium
MR imaging has high specificity towards proteoglycans, it has an
inherently low sensitivity and requires special radio-frequency
hardware modifications before it can be used with a routine
clinical imaging unit.
[0007] Spin lattice relaxation time in the rotating frame
(T.sub.1p) has been shown to be sensitive to changes in PG content
of cartilage (Duvvuri, et al., Magn. Reson. Med. 38:863-867 (1997);
Akella, et al., Magn. Reson. Med. 46:419-423 (2001)). It is well
suited for probing macromolecular slow motions at high static
fields without modifying MR system hardware (Sepponen, et al., J.
Computer Assisted Tomography 9:1007-1011 (1985); Santyr, et al.,
Magn. Reson. Med. 12:25-37 (1989)).
[0008] T.sub.1p provides an alternative contrast compared to
conventional MRI methods. Since the first description by Redfield
(Phys. Rev. 98:1787 (1955)), spin-locking technique has been used
extensively, to investigate the low frequency interactions between
the macromolecules and bulk water. Several authors have
investigated the T.sub.1p dispersion characteristics of biological
tissues, including brain (Aronen, et al, Magn. Reson. Imag.
17:1001-1010 (1999); Rizi, et al., J. Magn Reson Imaging
8:1090-1096 (1998)), tumors (Aronen, et al., Magn. Reson. Imag.
17:1001-1010 (1999); Markkola, et al., Radiology 200:369-375
(1996)), and articular cartilage (Mlynarik, et al., 1999; Akella,
et al., 2001; Duvvuri, et al., 1997; Duvvuri, et al., Radiology
220:822-826 (2001)). These studies have demonstrated the potential
value of T.sub.1p-weighting in evaluating various
physiologic/pathologic states.
[0009] Although recent studies have demonstrated the potential role
of T.sub.1p-weighted MRI in measuring cartilage degeneration, they
all have been restricted to single slice imaging, and hence, are
impractical for the imaging of a typical anatomic volume. The use
of single slice techniques results from the problem in making the
spin-locking pulse slice selective. A 2D multi-slice T.sub.1p MRI
sequence has not been implemented since the use of a nonselective
spin-lock (SL) pulse poses a challenge to slice-selective imaging.
Multi-slice imaging requires the application of multiple radio
frequency (RF) pulse trains within a sequence repetition time (TR)
to excite several slices in a time efficient manner. Currently,
T.sub.1p pulse sequences employ a non-selective RF pulse to
spin-lock the magnetization in the transverse plane following the
application of a non-selective .pi./2 pulse. As a result, using
this method, the spin-lock pulse excites signals from the entire
sample during each application, but the subsequent imaging sequence
acquires data from only a single slice, wasting the information
from the remainder of the volume. Accordingly, a need has remained
until the present invention for a method to perform multi-slice
T.sub.1p-weighted MRI.
[0010] Furthermore, in addition to the improved ability to image
anatomic regions through 2D multi slice imaging, a 3D image
provides even better contrast and faster acquisition than a 2D
image. Even though a 3D, gradient-echo readout of a
T.sub.1p-weighted MR signal has been used (Aronen, et al., 1999),
that sequence was implemented on a low field magnet (0.1T) with a
combination of adiabatic pulses, and RF spoiling alone was employed
to destroy unwanted transverse coherence. The use of adiabatic
pulses has certain drawbacks. Their long pulse lengths result in
substantial decay of magnetization during the pulse period. These
pulses cannot be easily calibrated on a clinical scanner, are more
RF power intensive and may introduce specific absorption rate (SAR)
issues. Moreover, any residual transverse magnetization resulting
from incomplete restoration of the T.sub.1p-prepared magnetization
to the longitudinal axis by the second adiabatic pulse will result
in unwanted image artifacts.
[0011] The need has remained for a MR pulse sequence capable of
performing 3D T.sub.1p-weighted MRI imaging on a high field
clinical scanner. However, when using high field clinical scanners
(greater than or equal to 1.5T), the SAR by the pulse sequence is
significant, and imaging parameters must be chosen such that the
energy deposition does not exceed the established SAR guidelines.
Hence, determining the optimal sequence parameters has been
necessary, so that the energy deposition by the radio frequency
pulses in the sequence, measured as the SAR, does not exceed safety
guidelines for imaging human subjects.
[0012] Additionally, significant artifacts arise in
T.sub.1p-weighted imaging when mutation angles suffer small
deviations from their expected values. These artifacts vary with
spin-locking time and amplitude, severely limiting attempts to
perform quantitative imaging or measurement of T.sub.1p relaxation
times. As a result, a need has also remained for a
"self-compensating" spin-locking pulse that dramatically reduces
artifacts and provides a more robust implementation of T.sub.1p
imaging despite spatial variations in mutation angles.
[0013] Finally, T.sub.1p-weighted MRI in volume coils has been
employed to improve tissue contrast (Markkola, et al., J. Magn.
Reson. Imaging 7:873-879 (1997); Santyr, Magn. Reson. Imaging Clin.
N. Am. 2:673-690 (1994)). However, the use of surface coils is
attractive due to their signal-to-noise ratio (SNR)
characteristics, especially when used on extremities. Inhomogeneous
B.sub.1 profiles of surface coils produce undesired image artifacts
that prevent conventional T.sub.1p-weighted imaging. Accordingly, a
need has remained for combining 3D T.sub.1p-weighted MRI and a self
compensating spin-lock pulse to obtain artifact-free 3D
T.sub.1p-weighted MRI using surface coils.
SUMMARY OF THE INVENTION
[0014] The present invention provides novel T.sub.1p-weighted
imaging pulse sequences for 2D multi-slice and 3D T.sub.1p MR
imaging. Also provided is a pulse sequence for correction of
artifacts with a self-compensating spin-locking pulse.
[0015] In one aspect of the present invention, a 2D multi slice
T.sub.1p-weighted MR imaging pulse sequence is provided. The pulse
sequence comprises a first .pi./2 pulse for selectively exciting a
band of spins that are spin-locked in the transverse plane by the
application of a train of spin-locking pulses with alternating
phase (.+-.90.degree. phase-shifted from the phase of the first
.pi./2 pulse), a second slice-selective .pi./2 pulse which restores
the spin-locked magnetization to the longitudinal axis for imaging
with any pulse sequence, and a strong "crusher" gradient applied to
destroy any residual transverse magnetization. Also provided is a
method for obtaining 2D multi-slice T.sub.1p-weighted MR images
[0016] In another aspect of the invention, a self-compensating
spin-locking pulse sequence for correcting artifacts in
T.sub.1p-weighted imaging is provided. A preferred embodiment of
the self-compensating spin-locking pulse comprises a four-pulse
preparatory cluster, further comprising a .pi./2 pulse (P.sub.1)
which nutates magnetization into the transverse plane, followed by
a spin-locking pulse (SL) with phase-shift of 90.degree. and
amplitude B.sub.s1, which is applied for some time TSL/2, then an
SL pulse with phase-shift of -90.degree. and amplitude B.sub.s1,
and a final .pi./2 pulse (P.sub.2) which is applied, phase-shifted
by 180.degree. to return the T.sub.1p-relaxed magnetization to the
longitudinal axis for imaging. B.sub.s1 is some fraction of the
maximum available RF field B.sub.1. A crusher gradient is then
applied to dephase any residual longitudinal magnetization.
Additionally, a method of correcting for artifacts in
T.sub.1p-weighted MR imaging is provided.
[0017] In yet another aspect of the invention there is provided a
3D T.sub.1p-weighted pulse sequence for MR imaging. A preferred
embodiment of the 3D T.sub.1p-weighted pulse sequence comprises: a
first .pi./2 hard pulse; a spin-lock pulse having amplitude
B.sub.1; a second .pi./2 hard pulse phase-shifted 180 degrees from
the first hard pulse; and a strong "crusher" gradient applied
before the a pulse to destroy any residual magnetization in the
transverse plane and prevent the formation of unwanted coherences.
A method of obtaining 3D T.sub.1p-weighted MR images is also
provided. In yet another embodiment a method of obtaining 3D
T.sub.1p-weighted MR images with a surface coil is provided.
[0018] Additional objects, advantages and novel features of the
invention will be set forth in part in the description, examples
and figures which follow, and in part will become apparent to those
skilled in the art on examination of the following, or may be
learned by practice of the invention.
DESCRIPTION OF THE DRAWINGS
[0019] The foregoing summary, as well as the following detailed
description of the invention, will be better understood when read
in conjunction with the appended drawings. For the purpose of
illustrating the invention, there are shown in the drawings,
certain embodiment(s) which are presently preferred. It should be
understood, however, that the invention is not limited to the
precise arrangements and instrumentalities shown.
[0020] FIG. 1 depicts a preferred embodiment of a timing diagram of
a pulse sequence for 2D multi-slice T.sub.1p-weighted MRI.
[0021] FIGS. 2A-D show MR images for two tubes across five slices.
FIG. 2A show results from a conventional spin-echo multi-slice
sequence. FIG. 2B shows the poor quality results due to saturation
of the magnetization of multi-slice imaging without phase
alternating the spin-lock pulses. FIG. 2C shows the correction for
the image signal loss by phase alternating the spin-lock pulses.
FIG. 2D shows increasing the TR from 500 ms in images FIG. 2A-2C to
5 seconds produces a high signal intensity image comparable to the
original spin-echo image.
[0022] FIG. 3 shows a preferred embodiment of a 3D T.sub.1p MRI
pulse sequence.
[0023] FIG. 4 shows a preferred embodiment of a 3D
T.sub.1p-weighted pulse sequence for obtaining 3D T.sub.1p-weighted
MR images with a surface coil.
[0024] FIG. 5A shows a T.sub.2 weighted image of a coronal slice.
FIG. 5B shows a T.sub.1p-weighted image of the coronal slice of
FIG. 5A.
[0025] FIG. 6A shows a T.sub.2 relaxation map of a coronal slice.
FIG. 6B shows a T.sub.1p-weighted relaxation of map of the slice of
FIG. 6A.
[0026] FIG. 7A shows an in vivo T.sub.1p-weighted MR image of the
brain of a healthy volunteer.
[0027] FIG. 7B shows the T.sub.2 map and FIG. 7C shows the T.sub.1p
map, respectively, of the image of FIG. 7A.
[0028] FIG. 8 shows images obtained with a conventional
spin-locking pulse compared to images obtained with a
self-compensating spin-locking pulse for a range of flip
angles.
[0029] FIGS. 9A-D show the temperature change in a series of
"post-test" images of a knee. FIG. 9A shows the position of an
agarose gel phantom within a coil and the overlaid sketch shows the
typical position of the knee inside the coil. FIGS. 9B-D show the
measured increase in temperature, with varying TRs, in the phantom
after the 3D sequence from FIG. 9A. FIG. 9B shows the image with a
of TR of 138 ms, FIG. 9C is with a TR of 100 ms and FIG. 9D is with
a TR of 75 ms.
[0030] FIGS. 10A-C show representative slices from a 3D data
set.
[0031] FIG. 11 shows additional axial images of a healthy knee
obtained with a 3D T.sub.1p-weighted imaging sequence of the
present invention.
[0032] FIGS. 12A and 12B show in vivo T.sub.1p relaxation maps of
human patellar cartilage. FIG. 12A shows a T.sub.1p relaxation map
of a healthy knee. FIG. 12B shows a T.sub.1p relaxation map of a
subject with clinical symptoms of osteoarthritis.
[0033] FIGS. 13A-D show the comparison of T.sub.2 and T.sub.1p maps
of control and 40% of PG depleted bovine patellae. FIG. 13A is a
control T.sub.2 map. FIG. 13B is a control T.sub.1p map. FIG. 13C
is a 40% PG depleted T.sub.2 map. FIG. 13D is a 40% PG depleted
T.sub.1p map.
[0034] FIGS. 14A-D show T.sub.1p-weighted MR images of an agarose
gel phantom obtained with self-compensating or conventional methods
with a surface coil. FIGS. 14A and 14B show images obtained with
the self-compensating method with an SL pulse divided into four
segments and two segments, respectively. FIGS. 14C and D show
images obtained with the conventional method, with one SL pulse and
the SL pulse turned off, respectively.
[0035] FIG. 15A shows in vivo T.sub.1p-weighted axial MR image of a
human knee joint obtained with a surface coil using the
conventional pulse sequence. FIG. 15B shows the same image using
the self-compensating pulse sequence.
DESCRIPTION OF PREFERRED EMBODIMENTS OF THE INVENTION
[0036] The present invention provides novel T.sub.1p-weighted MR
imaging sequences and methods for use thereof. The novel sequences
provide better imaging delineation and improved methods for in vivo
use. These pulse sequences provide 2D multi slice T.sub.1p-weighted
MRI and 3D T.sub.1p-weighted MRI for high field magnets.
[0037] The T.sub.1p images show better contrast and higher
signal-to-noise ratio (SNR) than T2 weighted images. The improved
SNR is due to the effect of spin locking. In T.sub.2-weighted
images, spins dephase through diffusion through inhomogeneities and
susceptibility variations caused by internal and applied gradients.
In T.sub.1p-weighted images, spin-locking reduces diffusion losses
and susceptibility artifacts and gives T.sub.1p contrast
(Engelhardt, et al., Magnetic Resonance in Medicine 35:781-786
(1996)). Also spin locking minimizes the dipolar couplings and
chemical exchange that lead to decrease in T.sub.2 relaxation
times. The higher SNR and improved contrast between cartilage and
surrounding fat of T.sub.1p imaging provides better definition of
lesions and accurate quantification of small changes in cartilage
degeneration. Thus, T.sub.1p relaxation mapping can be used to
quantify the early degenerative changes in cartilage in vivo.
[0038] 2D Multi-Slice Tirweighted Pulse Sequence
[0039] In one embodiment of the present invention, a novel imaging
pulse sequence to perform multi-slice T.sub.1p-weighted MRI is
provided. The pulse sequence for 2D multi-slice T.sub.1p-weighted
MRI is shown in FIG. 1. The first .pi./2 pulse selectively excites
a band of spins that are spin-locked in the transverse plane by the
application of a pulse train, e.g., two pulses as shown in FIG. 1,
spin-lock (SL) pulses with alternating phase (.+-.900 phase-shifted
from the phase of the first .pi./2 pulse). During the application
of such a pulse train, only the spins that were excited by the
.pi./2 pulse will be spin-locked and off-axis spins will nutate
back-and-forth and not achieve any spin-locking. The second
slice-selective .pi./2 pulse then restores the spin-locked
magnetization to the longitudinal axis for imaging with any pulse
sequence, e.g., a spin-echo readout train. A strong "crusher"
gradient (indicated as a filled square block in FIG. 1) is applied
to destroy any residual transverse magnetization. The images thus
obtained are T.sub.1p-weighted but also contain some degree of
T.sub.1 weighting, which can be reduced by increasing the TR of the
pulse sequence.
[0040] A critical element of the 2D multi-slice pulse sequence is
the phase alternating spin-lock pulses. As discussed previously,
multiple radio frequency (RF) pulse trains are required to excite
multiple slices. However, at the same time, a non-selective
spin-lock pulse excites and saturates the signal from the entire
sample, and thereby wipes out the signal from all but a single
slice. Hence, the sequence of the present invention provides a
phase alternating spin-locking pulse. In the embodiment of FIG. 1,
the second half of the spin-locking pulse is phase-shifted by 90
degrees with respect to the first half. However, any number of
spin-locking pulses may be used so long as the number of phase
alternating pulses are balanced.
[0041] The pulse sequence as shown in FIG. 1 was implemented on a
4.7T horizontal-bore MRI scanner controlled via a Varian console.
Two 5 cm-long water-filled tubes were imaged with a 3 cm-diameter
quadrature birdcage coil. The imaging parameters were: FOV=2
cm.times.2 cm, five slices with thickness=1 mm, TE=15 ms were
obtained with varying TR (500 ms and 5s), TSL (1 pulse 5 ms long
and two phase-alternated pulses each 2.5 ms long). For comparison,
a 2D multi-slice spin-echo data set with identical imaging
parameters (but no T.sub.1p-preparation pulses) and a TR=500 ms was
also obtained.
[0042] Results from the conventional spin-echo multi-slice sequence
(FIG. 2A) show the two tubes across the five slices. The two tubes
were displaced from each other along their long axes so that only
one tube was visible in the first slice. As shown in FIG. 2B,
without phase alternating the SL pulses, multi-slice imaging
results in a poor quality image due to saturation of the
magnetization. However, as shown in FIG. 2C phase alternating the
SL pulses corrects for the image signal loss. At the same time, the
signal is lower than that of the spin-echo images due to the loss
of any steady-state signal from transverse coherence in the
spin-locked images due to the presence of a crusher gradient. As a
result, increasing the IR from 500 ms in images FIGS. 2A-C to 5
seconds in image FIG. 2D produces a high signal intensity image,
comparable to the original spin-echo image. The distorted signal
seen in the center of the tubes in images 4 and 5 in rows FIGS.
2B-D are due to a B.sub.0 inhomogeneity produced by an air bubble
at the end of the tubes resulting in an improper spin-lock
magnetization.
[0043] Self-Compensating Spin-Locking Pulse Sequence
[0044] As described above, in order to accomplish the 2D
T.sub.1p-weighted multi slice imaging, the pulse sequence required
a phase alternating spin-lock pulse. However, as shown above, in
addition to allowing the readout of multi-slice signals, the phase
alternating spin-lock pulses also provide a "self-compensating"
spin-locking pulse, which dramatically reduces the image artifacts
and provides a more robust implementation of T.sub.1p imaging,
despite spatial variations in RF field B.sub.1. Artifacts in
T.sub.1p-weighted imaging are created by B.sub.0 inhomogeneity and
by variations in the RF field (inhomogeneous B.sub.1). The
self-compensating pulse of the present invention corrects for
artifacts created from both sources.
[0045] In an alternative embodiment as described above, and as
shown in FIG. 1, the self-compensating spin-locking pulse comprises
a four-pulse preparatory pulse cluster pre-appended to a fast
spin-echo (FSE) imaging sequence. FIG. 1 shows the
self-compensating spin-locking pulse split into two halves, or two
pulses, of opposed phase. However, the pulse can be divided into an
arbitrary number of smaller pulses, as long as the positively and
negatively phased portions of the pulse are balanced. Additionally,
although FIG. 1 shows a first and second .pi./2 slice selective
pulse, in an alternate embodiment of the four-pulse preparatory
cluster of the self-compensating spin-locking pulse, hard .pi./2
pulses may replace the slice selective pulses. Additionally, in
alternate embodiments, any arbitrary flip angle .theta. pulse may
replace the .pi./2 pulse.
[0046] In an alternative embodiment, the four-pulse preparatory
cluster comprises a hard .pi./2 pulse (P.sub.1) which nutates
magnetization into the transverse plane. This is followed by a
spin-locking (SL) pulse with phase-shift of 90.degree. and
amplitude B.sub.s1, which is applied for some time TSL/2, then an
SL pulse with phase shift of -90.degree. and amplitude B.sub.s1,
and a final hard .pi./2 pulse (P.sub.2). P.sub.2 is applied,
phase-shifted by 180.degree. to return the T.sub.1p-relaxed
magentization to the longitudinal axis for imaging. B.sub.s1 is
some fraction of the maximum available RF field B.sub.1. A crusher
gradient is then applied to dephase any residual longitudinal
magnetization. Where there is variation of B.sub.1, P.sub.1 and
P.sub.2 perform some arbitrary flip angle .theta..
[0047] Additionally, T.sub.1p weighted imaging with a
self-compensating spin-locking pulse allows the use of a surface
coil, despite large spatial variations in B.sub.1. Use of this
pulse sequence generates relatively artifact-free images,
facilitating quantitative T.sub.1p imaging while exploiting the
sensitivity and convenience of surface coils. The self-compensating
spin-locking pulse corrects for artifacts and yields homogeneous
images, despite large variations in flip angle. In addition, with
manipulation of the preparatory pulse cluster, the same imaging
sequence can be utilized for B.sub.1 mapping, as well as data
acquisition.
[0048] 3D T1p-Weighted Pulse Sequence
[0049] In another embodiment of the present invention, a 3D
T.sub.1p-weighted pulse sequence is provided. This pulse sequence
combines superior contrast with high signal to noise
characteristics offered by the T.sub.1p pulse-cluster utilizing
hard .pi./2 pulses with the speed and fat-suppression capability of
a 3D spoiled gradient echo (SPGR) sequence. The calculated SAR of
the 3D T.sub.1p-weighted sequence determines optimal imaging
parameters for T.sub.1p-weighted images in vivo. Furthermore, the
temperature increase in a CoCl.sub.2-doped agarose gel phantom
resulting from the use of these imaging parameters, shows that the
sequence can be safely performed in vivo.
[0050] As previously described, there are at least two advantages
of a 3D T.sub.1p-weighted technique, when compared with 2D
T.sub.1p-weighted. First, the 3D T.sub.1p MRI allows rapid
acquisition of the entire anatomic region, in contrast to the
single section 2D technique. Second, 3D T.sub.1p-weighted MRI
generates better demarcation between cartilage and bone marrow
(fat) and fluid by suppressing the fluid and fat signals when
compared with 2D T.sub.1p-weighted techniques. The main reason for
this fat-suppression is that in the 2D T.sub.1p-weighted technique,
the three pulse cluster is pre-encoded with a fast-spin-echo (FSE)
imaging sequence, whereas in 3D T.sub.1p-weighted MRI, the pulse
cluster is pre-encoded with a gradient echo (GRE) sequence. In 2D
T.sub.1p-weighted sequence (FSE readout) the four 1800 refocusing
pulses (ETL=4) have a decoupling effect (elimination of J-coupling
modulation effects), resulting in a higher fat signal in contrast
to 3D T.sub.1p-weighted sequence (GRE readout).
[0051] The 3D T.sub.1p MRI pulse sequence is shown in FIG. 3. The
first three RF pulses prepare the T.sub.1p-weighted magnetization.
The amplitude of the SL pulse, B.sub.1, is typically given as the
nutation frequency (.gamma.B.sub.1, where .gamma. is the
gyromagnetic constant of .sup.1H nuclei in Hz/T). A strong
"crusher" gradient (indicated by the solid block) is applied before
the a pulse to destroy any residual magnetization in the transverse
plane, and to "inhibit," meaning a statistically significant
reduction up to the point of preventing, the formation of unwanted
coherences. The signal is spatially encoded in a 3D fashion
following the .alpha. pulse. The steady-state signal expression is
simply solved from the Bloch equation (Aronen, et al., 1999): 1 S (
TSL ) - TSL T 1 p ( 1 - e - ( TR - TSL ) T 1 ) 1 - - TSL T 1 P - (
TR - TSL ) T 1 cos sin ( Equation 1 )
[0052] where TR is the time between subsequent a imaging pulses,
TSL is the length of the SL pulse and T.sub.1 is the spin-lattice
relaxation time constant of the tissue of interest.
[0053] The optimal imaging parameters were determined from the SAR
calculation. The SAR was calculated from the electric field
generated by a typical quadrature coil on a simulated head of known
tissue electrical properties and material density (Collins, et al.,
Magn. Reson. Med. 40:847-856 (1998)). The SAR, of a single pulse of
flip angle .alpha. and duration .tau. (in ms), is calculated with
Equation 2: 2 SAR ( , ) = f ( 3 ) 2 ( 90 .degree. ) 2 SAR ( 90
.degree. , 3 ) ( Equation 2 )
[0054] where f is a shape factor, equaling 1 for a hard pulse, or
equaling the width of the central lobe at the zero crossing point
for a sinc pulse. The minimum TR for the pulse sequence was
determined from Equation 3: 3 TR = n = 1 N SAR ( 1 , 1 ) x 1 SAR
FDA ( Equation 3 )
[0055] where SAR(.alpha..sub.1.tau..sub.1) was calculated from
Equation 2 for all four pulses in the sequence and SAR.sub.FDA is
the FDA suggested maximum SAR level.
[0056] Pulse Sequence for 3D T1p-Weighted MRI with a Surface
Coil
[0057] In yet another embodiment of the present invention, the 3D
T1p-weighted MRI is combined with the self compensating spin-lock
pulse, thereby creating a 3D pulse sequence that facilitates
T.sub.1p-weighted MRI with surface coils. In this sequence, the SL
pulse is divided into multiple, even-numbered segments of equal
duration with alternating phases. By combining a self-compensating
spin-lock pulse with a 3D imaging sequence, an artifact-free
T.sub.1p-weighted MR image with a surface coil is obtained. This
sequence can also be used with volume radio frequency coils to
obtain artifact free 3D T.sub.1p-weighted images.
[0058] The 3D T.sub.1p MRI pulse sequence of this embodiment is
shown in FIG. 4. The spin-lock pulse is either a single pulse with
a constant phase and duration TSL ("conventional"), or it is
divided into even number of segments with alternating phase and
equal durations ("self-compensating"). A strong crusher gradient,
shown as solid block in the slice gradient axis, is applied to
destroy any residual magnetization in the transverse plane. This
sequence provides a method to obtain artifact-free
T.sub.1p-weighted MRI with surface coils.
EXAMPLES
[0059] The present invention is further described in the following
examples in which experiments were conducted to validate the pulse
sequences and show particular applications for the pulse sequences.
These examples are provided for purposes of illustration to those
skilled in the art, and are not intended to be limiting unless
otherwise specified. Moreover, these examples are not to be
construed as limiting the scope of the appended claims. Thus, the
invention should in no way be construed as being limited to the
following examples, but rather, should be construed to encompass
any and all variations which become evident as a result of the
teaching provided herein.
Example 1
[0060] Qualitative Validation
[0061] To confirm that images using T.sub.1p-weighted pulse
sequences provide improved contrast between cartilage and
surrounding fat over images using T.sub.2 weighted sequences,
T.sub.1p relaxation maps were computed and compared to T.sub.2
relaxation maps for a human wrist cartilage. Additionally, the
T.sub.1p times dependence on spin-locking amplitude ("T.sub.1p
dispersion") was computed to show changes in T.sub.1p associated
with pathology.
[0062] T.sub.2 and T.sub.1p experiments were performed on a 1.5
Tesla GE Signa clinical MR system (SIGNA, GEMS, Milwaukee, Wis.) on
wrist joints of five healthy volunteers with no known history of
arthritis or pain (5 male with mean age 30 years). The radio
frequency (RF) coil was placed to the side of the volunteer and
strapped to the bed to minimize the errors due to motion. A one
inch thick foam was placed in between the volunteer's body and coil
to avoid signal interference from the body. The wrist was placed in
a custom built, 9.5 cm inner diameter, quadrature birdcage coil
tuned to a proton frequency of 63.75 MHz. Coronal plane provided
the clearest definition of important structures in the wrist joint.
Single slice T.sub.1, measurements were performed with a 2D fast
spin echo (FSE) sequence pre-encoded with a three pulse cluster
consisting of two 90 degree hard pulses separated by a low power
pulse for spin-locking.
[0063] Imaging parameters were: TR/Eff. TE (effective echo
time)=3000 ms/15 ms; ETL=4; FOV=8 cm.times.8 cm; slice thickness=3
mm; data matrix=256.times.128 and spin-lock frequency (.omega.)
varied from 0-600 Hz, TSL (length of the spin-lock pulse) varied
from I ms to 38 ms (5 steps) and scan time for each TSL is 102
seconds. A fat suppressed single slice multi-echo spin-echo pulse
sequence was used for T.sub.2 mapping with the same FOV and
location and echo times (TE) of 15, 30, 45 and 60 ms. The total
scan time for multiecho spin-echo sequence was 7 minutes.
[0064] The image data was processed offline on an SGI workstation
with custom built routines written in IDL language (RSI Tech.,
Boulder, Colo.). T.sub.1p relaxation maps were computed by fitting
the image pixel intensity as a function of TSL to the Equation
4.
M.sub.y(TSL)=M.sub.oe.sup.-(TSL/T1p)+K (Equation 4)
[0065] where M.sub.y, M.sub.o and K are the components of
transverse magnetization, equilibrium magnetization and a constant,
respectively. Regions of interest (ROI) were manually selected by a
single observer from various locations of the wrist to measure the
T.sub.1p and T.sub.2 relaxation times and overall trend of the
T.sub.2 and T.sub.1p relaxation values is similar, irrespective of
the size of the ROI. The calculated T.sub.1p and T.sub.2 values are
an average of several pixels from an ROI. The elliptical ROIs had a
long axis of approximately 15 pixels. Contrast was calculated from
the following formula: (S.sub.S-S.sub.M)/S.sub.S, where S.sub.S and
S.sub.M were the signal intensities of a region of interest in
cartilage and bone marrow, respectively. Signal to noise ratio
(SNR) was calculated by dividing the signal intensity of the
cartilage with signal intensity in the noise region. Statistical
analysis was performed with 2-tailed students' t-test from the
department of statistics, UCLA
(http:calculators.stat.ucla.edu).
[0066] Several ROIs within the wrist joint were manually selected
in different locations from each map. Average T.sub.1p at 500 Hz
and T.sub.2 relaxation values for all the volunteers from various
locations were obtained. The variation of T.sub.1p from the
selected locations as a function of .omega..sub.1 was plotted and
an exponential increase of T.sub.1p relaxation values was observed
up to a .omega..sub.1 of 500 Hz. This data shows that there is
T.sub.1p dispersion in the range of sol studied.
T.sub.1p-relaxation shows different dispersive characteristics in
various locations of the wrist joint. T.sub.1p values are 32-63%
higher than T.sub.2 relaxation values at the selected locations.
Based on the Collins model, the amount of SAR was calculated with
the coil at 63.75 MHz for the parameters used in the T.sub.1p
sequence. The calculated SAR was 0.8 W/Kg which is far below the
maximum FDA allowable limit of 12 W/kg.
[0067] A typical coronal slice of the T.sub.2 weighted image (FIG.
5A) and the corresponding T.sub.1p-weighted image at a
.omega..sub.1 of 500 Hz (FIG. 5B) are displayed in FIG. 5. The
Figures show the higher SNR and better contrast between cartilage
and surrounding carpal bones with reasonable fat signal suppression
in the T.sub.1p-weighted image when compared to the
T.sub.2-weighted image. The improved SNR (20-35%) and contrast
(33-38%) at selected locations on the T.sub.1p-weighted images with
respect to T.sub.2-weighted images allowed easy delineation of the
cartilage from the surrounding fat.
[0068] FIG. 6A is a T.sub.2-weighted relaxation map constructed
from a series of T.sub.2-weighted images, while 6B is
T.sub.1p-weighted relaxation map constructed from a series of
T.sub.1p-weighted images in which each pixel in the maps represents
a relaxation value. These maps clearly show the articular cartilage
surrounding the major bones of the wrist. From the relaxation maps,
it was observed that T.sub.1p relaxation times are greater than
T.sub.2 relaxation times at every location in all the individuals.
The variation of T.sub.1p in selected locations plotted as a
function of .omega..sub.1 shows an exponential increase of T.sub.1p
relaxation values up to a .omega..sub.1 of 500 Hz. Thus, there is
T.sub.1p dispersion in the range of col. T.sub.1p-relaxation shows
different dispersive characteristics in selected locations of the
wrist joints.
Example 2
[0069] Qualitative Validation
[0070] To confirm the improved contrast of T.sub.1p MR images over
T.sub.2 MR images for delineating tumors and gliomas, T.sub.1p maps
and T.sub.2 maps of the brain were computed and compared.
Additionally, the T.sub.1p times dependence on spin-locking
amplitude ("T.sub.1p dispersion") was computed to show changes in
T.sub.1p associated with pathology.
[0071] The T.sub.1p and T.sub.2 maps of the brain were calculated
from MR images from four healthy male volunteers (ages 30-40 years)
on a 1.5T GE Signa scanner using the standard head-coil. A 2D
single-slice spin-echo-based T.sub.1p imaging sequence was used. In
this pulse sequence, a .pi./2 (.phi.=00)-spin-lock
(.phi.=90.degree.)-.pi./2 (.phi.=180.degree.) pulse-cluster was
preencoded to a fast-spin-echo (FSE) sequence. Imaging parameters
were TE/TR =17/4000 ms, FOV=24 cm.times.24 cm, slice thickness=3 mm
with 256.times.128 matrix size and 8 echoes per TR. The total
imaging time was 1 minute. The pulse-width of each hard 90.degree.
pulse was 200 .mu.s. T.sub.1p maps were generated from
T.sub.1p-weighted images by varying TSL between 15-100 ms with a
fixed SL amplitude (B.sub.1) of 500 Hz. T.sub.1p dispersion data
was obtained on one individual by obtaining T.sub.1p maps for five
different B.sub.1 values ranging from 62 to 500 Hz. T.sub.1p maps
were generated for each pixel by fitting the signal from each TSL
to an exponential decaying curve. T.sub.2-weighted images with a
multi-echo, spin-echo sequence with echo times (TE=30, 60, 90, 120
ms) were used to generate T.sub.2 maps by fitting pixel intensities
to an exponential decaying curve as well. Regions of interest of
10.times.10 pixels were selected in each map by a single user to
measure average T.sub.1p and T.sub.2 of cerebrospinal fluid (CSF)
in the ventricles, superficial white matter (WM) and cortical gray
matter (GM). The average T.sub.1p and T.sub.2 values from the four
healthy volunteers were obtained where the variation in CSF values
is due to partial voluming of choroids plexus and peri-ventricular
brain tissue. Average T.sub.1p values for gray matter, white matter
and cerebrospinal fluid were 85.+-.3,99.+-.1 and 1496.+-.213 ms at
a spin-locking field of 500 Hz, respectively.
[0072] FIG. 7A shows an in vivo T.sub.1p-weighted MR image of the
brain of a healthy volunteer. FIGS. 7B and 7C show the
corresponding T.sub.2 map and T.sub.1p map, respectively. As shown
in FIG. 7, the T.sub.1p map has a greater dynamic range of than the
T.sub.2 map. The reported T.sub.1p and T.sub.2 values were averaged
in 10.times.10 pixels in three regions indicated: gray matter (GM),
white matter (WM) and cerebrospinal fluid (CSF). T.sub.1p
dispersion was observed in the human brain in vivo. Average
T.sub.1p values for GM, WM and CSF were 32%, 29% and 319%,
respectively, higher than corresponding T.sub.2 values. In part,
this difference is due to relative insensitivity of T.sub.1p to
diffusion, leading to an improved signal-to-noise ratio.
Example 3
[0073] Self-Compensating Spin-Locking Pulse Validation
[0074] To analyze artifacts in T.sub.1p imaging, and establish
their relationship to B.sub.1 inhomogeneity, and to determine and
validate the dependence of these artifacts on spin-locking time and
B.sub.1, the following study was conducted. In the course of the
study a novel self-compensating spin-locking pulse was developed to
reduce these artifacts.
[0075] In MR imaging applications, every coil has some degree of
B.sub.1 inhomogeneity. Where there are variations in the amplitude,
B.sub.1, the first and second RF pulses in the MR imaging pulse
sequence perform some arbitrary flip angle, .theta.. Also, even if
the spin-locking amplitude is small, it is applied for a
comparatively long time, resulting in large rotations. Areas with a
large B.sub.1 gradient exhibit large spatial variations in flip
angle and rotation, resulting in pronounced artifacts. Given that
image artifacts arise from a rotation which occurs during the
spin-locking pulse, phase-shifting the second half of the
spin-locking pulse by 180.degree. with respect to the first half,
exactly cancels this rotation and reduces such artifacts, without
requiring knowledge of regional B.sub.1.
[0076] In this study, simulations were performed using the
Interactive Data Language (IDL, RSI, Boulder, Colo.) programming
environment on a Silicon Graphics workstation (Mountain View,
Calif.). Artificial B.sub.1 maps were generated with linear
gradient and Gaussian shapes, using dimensionalities identical to
experimentally obtained images, and a range of B.sub.1 values also
similar to those obtained experimentally. Artifacts were calculated
using Equation 5:
M.sub.x=0,
M.sub.y=0,
M.sub.2=sin.sup.2.theta..multidot.e.sup.-TSL/T1p+cos.sup.2.theta.cos.alpha-
..multidot.e.sup.-TSL/T2p (Equation 5)
[0077] where .theta.=.gamma.B.sub.1.tau., and
.alpha.=.omega..sub.1y, TSL=P.sub..gamma.B.sub.1 TSL, where B.sub.1
is the maximum RF amplitude achievable at a given point, .tau. is
the normal .pi./2 pulse width, P is a parameter indicating the
spin-lock amplitude expressed as a fraction of the maximum B.sub.1,
i.e., B.sub.s1=P.times.B.sub.1, and TSL is the spin-locking time.
The conventional and self-compensating spin-locking pulse sequences
were created by modifying the General Electric (Milwaukee, Wis.)
fast spin-echo pulse sequence, utilizing the EPIC programming
language. MR images of a water phantom were obtained on a 4T whole
body GE Signa scanner using a solenoid coil tuned to the .sup.1H
200 Larmor frequency (170 MHz). Imaging was performed using a TR of
2 seconds, effective TE of 17 ms, field of view of 8 cm, slice
thickness of 3 mm, bandwidth of 15 kHz, and acquisition matrix of
256.times.128. Initially, calibration of the hard pulses was
performed by turning off the spin-locking pulse and P.sub.2, while
retaining P.sub.1. The transmit gain (TG) was then titrated until
the signal was minimized, implying that P.sub.1 was a .pi./2 pulse.
TG was fixed at this value.
[0078] Images to calculate the B.sub.1 map of the solenoid coil
were then obtained. A baseline image was first obtained with both
hard pulses (P.sub.1 and P.sub.2) activated. Since P.sub.1 and
P.sub.2 were 180.degree. apart in phase, they canceled each other
out. The crusher gradient had no effect, and the resulting image
represented maximum signal intensity (effectively, a flip angle of
zero for P.sub.1 and P.sub.2). The P.sub.2 hard pulse was then
turned off, and images were acquired with varying amplitudes of
P.sub.1. As the amplitude of P.sub.1 approached .pi./2, the crusher
gradient destroyed more magnetization, and the image signal
intensity was reduced. In other words, for a flip angle .theta.,
induced by P.sub.1, image signal intensity followed cos
(.theta.).
[0079] A total of five P.sub.1 amplitudes were utilized, varying
from 31 to 92% of the maximum amplitude. The arc-cosine of image
signal intensity was plotted as a function of the amplitude of
P.sub.1 for each pixel, and the slope of a linear fit yielded a
value for B.sub.1 at each pixel. Hard pulses P.sub.1, P.sub.2, and
a standard spin-locking pulse were then activated. The amplitudes
of P.sub.1 and P.sub.2 were simultaneously varied to generate
artifacts. Images were obtained with a variety of hard pulse
amplitudes, spin-locking pulse amplitudes, and spin-locking times.
Using the experimentally determined B.sub.1 map, artifacts were
simulated using Equation 5, and the results were compared to the
experimentally obtained image artifacts.
[0080] Finally, the standard spin-locking pulse was exchanged for a
"self-compensating" spin-locking pulse for fixed TSL and B.sub.1,
and the amplitudes of P.sub.1 and P.sub.2 were again simultaneously
varied. Artifacts obtained with the standard spin-locking pulse
were compared to those obtained with the "self-compensating"
spin-locking pulse. Artifacts were quantified by computing the
standard deviation of signal intensity divided by the mean signal
intensity, i.e., percent variation, within a central region of
interest.
[0081] The images obtained with the conventional spin-locking pulse
and the respective images obtained with a self-compensating
spin-locking pulse for a range of flip angles are shown in FIG. 8.
In FIG. 8, images in the top row were obtained with a conventional
spin-locking pulse, while the images in the bottom row were
obtained with a self-compensating spin-locking pulse, for the range
of flip angles shown. Use of the self-compensating spin-locking
pulse resulted in remarkably consistent images, despite large
changes in the flip angles, P.sub.1 and P.sub.2. The variation in
image signal intensity was plotted as a function of nominal flip
angle for images acquired with the conventional and
self-compensating spin-locking pulses. The variation in signal
intensity is strongly dependent on flip angle when the conventional
spin-locking pulse is used, and it was found that the
self-compensating spin-locking pulse dramatically reduces this
dependence, resulting in homogeneous images despite a poorly
calibrated flip angle.
[0082] Thus, use of the self-compensating spin-locking pulse
facilitates quantitative T.sub.1p imaging despite variations in
B.sub.1. However, it should be noted that the second half of the
spin-locking pulse will not exactly compensate for the first half
if there is significant motion of spins over a gradient of B.sub.1.
Also, while the artifacts arising from spatial variation in B.sub.1
are corrected, a variation in B.sub.1 affects spin-locking
amplitude, which translates into an effect on measured T.sub.1p
times. Therefore, T.sub.1p values and T.sub.1p relaxation time maps
measured in the presence of an inhomogeneous B.sub.1 field must
take this into consideration, since spatial variations in T.sub.1p
may actually be due to spatial variations in B.sub.1 rather than
properties of the sample itself.
[0083] In this study, the self-compensating spin-locking pulse was
split into two halves of opposed phase. However, in principle, the
pulse can be divided into any arbitrary number of smaller pulses,
as long as the positively and negatively phased portions of the
pulse are balanced. Additionally, T.sub.1p-weighted imaging with a
self-compensating spin-locking pulse allowed for the use of a
surface coil. This study showed that despite large spatial
variations in B.sub.1, use of this pulse sequence appears to
generate relatively artifact-free images, facilitating quantitative
T.sub.1p imaging while exploiting the sensitivity and convenience
of surface coils. Also, with appropriate manipulation of the
preparatory pulse cluster, the same imaging sequence can be
utilized for B.sub.1 mapping, as well as for data acquisition.
Example 4
[0084] 3D T.sub.1p-Weighted Pulse Sequence Validation
[0085] The following study was performed to validate the 3D
T.sub.1p-weighted pulse sequence. The MRI experiments were
performed on a 1.5T GE clinical MRI system.
[0086] Specimen Imaging
[0087] The T.sub.1p values measured with the 3D T.sub.1p-weighted
sequence were confirmed to be the same as those obtained from a
previously validated 2D T.sub.1p imaging sequence. 3D and 2D
T.sub.1p maps were generated of an intact bovine patella specimen
obtained from a local slaughterhouse (Beirig Bros.; Vineland, N.J.)
within hours of sacrifice using a custom-built, 15 cm-diameter,
quadrature birdcage knee-coil. Care was taken to prevent motion of
the patella from mechanical vibrations of the gradients during
imaging. A groove was cut along the length of the articular surface
with a saw and the specimen was wedged onto a plastic divider. The
imaging parameters were TE/TR=2.2/200 ms resulting in a total
imaging time of 7 minutes for 16 slices of FOV=10 cm.times.10 cm,
1.5 mm slice thickness with 256.times.128 matrix size, and
.alpha.=35.degree.. Single-slice 2D images were obtained with
TE/TR=17/3000 ms, and echo train length of 4 echoes resulting in an
imaging time of 1.6 minutes for a single 3 mm slice with a FOV=10
cm.times.10 cm and the same pixel size as the 3D sequence. In both
3D and 2D sequences, the pulse-width of each hard 90.degree. pulse
was 200 .mu.s, and the B.sub.1 of the SL pulse was fixed at 500 Hz
and the TSL time was varied from 25-165 ms in eight increments.
[0088] The T.sub.1p-weighted images were processed offline on a G4
Titanium computer (Apple Computer; Cupertino, Calif.) with custom
software written in IDL (RSI; Boulder, Colo.) data processing
language.
[0089] The images were used to generate T.sub.1p maps by fitting
each pixel to Equation 1, (or e.sup.-TSL/T1p for the 2D FSE data),
with a least-squares algorithm and assuming T.sub.1=1 second for
articular cartilage (Borthakur, et al., Osteoarthritis Cartilage
8:288-293 (2000)). As discussed below, this assumption results in
only a small error in the calculated T.sub.1p values. The accuracy
of the fits was determined from a sum of the difference squared
between the data points and the fit.
[0090] The maps calculated from the 2D and 3D T.sub.1p sequences
resulted in similar calculated T.sub.1p values in the cartilage. In
a specific region investigated, the average T.sub.1p calculated
from the 3D and 2D sequences were 84.+-.2 ms and 80.+-.3 ms,
respectively. The error between the data points and the fit was
less than 1.times.10.sup.-5 confirming that the fit was very
accurate. T.sub.1p values calculated by the two sequences were very
similar, hence the 3D sequence is a reliable imaging alternative to
the 2D method.
[0091] Temperature Mapping
[0092] The RF energy deposited by a coil during MR imaging results
in focal temperature increases (Chen, et al., Magn. Reson. Med.
29:386-390 (1993)). One method of temperature mapping uses
CoCl.sub.2-doped agarose gel phantom (Shapiro, 2002). In this
technique, MR images of the phantom are acquired before and after
running a "test" pulse sequence. The phase difference between these
pre and post images, resulting from the temperature-dependent
chemical shift of the water peak, can be used to generate
phase-difference maps (.DELTA..phi.) that can be directly converted
to temperature maps (.DELTA.T) by the following equation (MacFall,
et al., Med. Phys. 23:1775-1782 (1996)): 4 T = 360 B o K TE (
Equation 6 )
[0093] where B.sub.0 is the magnetic field strength (1.5T), TE is
the echo time of the imaging sequence (20 ms, in this experiment)
and K is the "temperature sensitivity," i.e., the chemical shift of
the water in the CoCl.sub.2-doped phantom. K was previously
measured as -0.041 ppm/.degree. C., which is four times greater
than that of distilled water (-0.011 ppm/.degree. C.). The factor
of 360 accounts for the phase degrees in every cycle.
[0094] Using this technique, the temperature increase was
determined that was generated by the 3D T1p pulse sequence in a
cylindrical 160 mM COCl.sub.2-doped 4% (w/v) agarose gel phantom
with dimensions that mimic a typical knee-joint (10 cm diameter and
10 cm long) weighing 5 kg. The phantom was placed in a MRI scanner
room overnight to equilibrate with the ambient temperature. Phase
difference maps were generated for every slice from two image sets
obtained with a 2D multi-slice gradient echo sequence with FOV=16
cm.times.16 cm, slice thickness=3 mm, TE/TR=20/34 ms and with
256.times.128 pixels. With this sequence, a "pre-test" data set of
six slices was obtained in under 30 seconds. Following this, the
"test" 3D T.sub.1p sequence was run with a TR calculated from
Equation 3 for the maximum values of the parameters, fixed B.sub.1
(400 Hz) and TSL (45 ms), for use in vivo. Then, a "post-test" 2D
multi-slice experiment was performed.
[0095] The 3D sequence was run twice more with reduced TRs (100 ms
and 75 ms) and two more "post-test" data sets were acquired after
each 3D test. The maximum meter reading from a power monitor,
attached to the RF output from the MRI scanner, was recorded during
each 3D scan. Using Equation 6, the three post-test data sets were
used to generate temperature maps using a pixel-by-pixel
determination of the phase difference between the post-test data
sets and the pre-test data set. The temperature maps were acquired
without waiting for the phantom to cool to room temperature. As a
result, the measured increase in temperature in the second and
third temperature maps was cumulative.
[0096] The power meter readings and imaging times were used to
calculate the expected temperature rise by assuming that all the
power was converted to heat in the phantom, and the specific heat
of the 4% agarose gel phantom was that of pure water (4.18J/g/K) in
each experiment.
[0097] FIG. 9A shows the position of the agarose gel phantom within
the coil and the overlaid sketch shows the typical position of the
knee inside the coil. In order to expedite T.sub.1p MRI in vivo,
the B.sub.1 of the SL pulse was decreased to 400 Hz and the TSL was
kept at 45 ms. This resulted in a calculated SAR of 1.62 J/kg,
which implied a minimum TR of 138 ms which met the FDA mandated
safety guidelines. With these parameters, the measured increase in
temperature in the phantom after the 3D sequence was only
0.015.degree. C. (FIG. 9B). As a test, the 3D sequence was run with
a higher duty cycle, and the cumulative temperature rose to only
0.029.degree. C. (FIGS. 9C and D). No significant "hot spots" were
observed in any of the images. Accordingly, this example shows that
the imaging parameters did not result in any significant
temperature change, and therefore are safe for use in imaging
humans in vivo.
[0098] Furthermore, calculated .DELTA.T yielded results greater
that what was actually measured in the phantoms, suggesting that
only a fraction of the power put into the coil was heating the
phantom. This was not a surprising result, since there could be
other mechanisms of energy dissipation during the experiments that
were not accounted for in the calculated .DELTA.T. Additionally,
since the electric conductivity of the phantom is greater than
human tissue (Gabriel, et al., Phys. Med. Biol. 41:2251-2269
(1996)), and the fact that tissue contains vessels and blood flow
to facilitate heat dissipation, these experiments actually
overestimate the temperature rise.
[0099] In Vivo Imaging
[0100] After determining the safe limits of the imaging parameters,
both through the calculation of SAR and temperature mapping, a 3D
T.sub.1p-weighted, sagittal MR data set was obtained of the knee
joint of a 30-year old healthy volunteer. To ensure that SAR limits
are not exceeded, imaging parameters were set at B.sub.1=400 Hz,
TSL=45 ms, and TR=2.2/140 ms. Other parameters were TE=2.2 ms
FOV=10 cm.times.10 cm, slice thickness of 1.5 mm, such that a data
set of 16 slices was obtained under 5 minutes.
[0101] Using the 3D sequence described above, the T.sub.1p-weighted
images were obtained of the human knee joint. FIGS. 10A-C show
representative slices from a 3D data set of 16 slices that were
acquired in less than 5 minutes with high SNR (29:1, measured in
the cartilage). In these images, the cartilage between the patella
and the distal femur is clearly seen. Due to the T.sub.1-weighting
in the short TR gradient-echo readout, superior contrast between
cartilage and other tissues is achieved. Images provided excellent
delineation of patellar cartilage and suppression of signal from
fatty marrow and surrounding tissues.
[0102] FIG. 11 shows additional axial images of a healthy volunteer
knee (30 year male, with no known abnormalities of knee) obtained
with a 3D-T.sub.1p, weighted imaging sequence (five slices from a
16 slice data set). The arrow indicates cartilage. This figure
shows an excellent contrast between cartilage and other tissues.
For FIG. 11, the in plane resolution of these images is .about.390
.mu.m with slice thickness of 3 mm.
[0103] Additionally, FIGS. 12A and B show in vivo T.sub.1p
relaxation maps of human patellar cartilage. These are maps of one
slice from a 3D data set of 16 slices. FIG. 12A shows a T.sub.1p
relaxation map of a healthy volunteer (30 year male, with no known
abnormalities of knee). The average T.sub.1p relaxation in this
healthy tissue is 50.+-.5ms. For FIG. 12A the in plane resolution
in this map is 390 .mu.m with a slice thickness of 3 mm. FIG. 12B
shows a T.sub.1p relaxation map of a subject with clinical symptoms
of osteoarthritis (40 yr female, absence of cartilage abnormalities
on radiographs). The Rheumatologist and Orthopedist diagnosed the
subject with osteoarthritis and the subject is on medication for
about a year. For FIG. 12B, the in plane resolution in this map is
312 .mu.m with a slice thickness of 1.5 mm. There is a substantial
increase in T.sub.1p relaxation numbers in the ROI shown (T.sub.1p
values are .about.36% higher compared to the healthy tissue). This
clearly demonstrates the feasibility of quantifying the degree of
abnormality in cartilage.
[0104] Finally, FIGS. 13A-D show the comparison of T.sub.2, and
T.sub.1p maps of control and 40% of PG depleted bovine patellae. As
shown, FIG. 13A is a control T.sub.2 map, FIG. 13B is a control
T.sub.1p map, FIG. 13C is a 40% PG depleted T.sub.2 map and FIG.
13D is a 40 % PG depleted T.sub.1p map. The color bar scale shows
the relaxation numbers from 0 to 256 ms
Example 5
[0105] Pulse Sequence for 3D T.sub.1p-Weighted MRI with a Surface
Coil
[0106] In order to obtain artifact-free T1p-weighted MRI using
surface coils, the following study was performed to validate
combining a 3D T.sub.1p-weighted pulse sequence for MR imaging with
a self-compensating spin-locking pulse sequence.
[0107] On a 4T GE clinical MRI system, T.sub.1p-weighted images of
a cylindrical (7 cm outer-diameter) agarose gel phantom and a knee
joint of a 30-year old healthy volunteer were obtained with a
custom-built surface coil (7 cm inner-diameter). MRI parameters
were TE/TR=2.2/140 ms, FOV=10 cm.times.10 cm, 3 mm slice thickness
with 256.times.128 matrix size and .alpha.=30.degree.. Total
imaging time was 4.7 minutes for a data set of 16 slices. The
pulse-width of each nominal hard 90.degree. pulse was 200 .mu.s,
and the amplitude of the SL pulse was 500 Hz. In one set of
experiments, the SL pulse was divided into even segments of equal
duration, with the phase of each segment alternating between
.+-.90.degree., i.e., "self-compensating" SL pulse. In a second set
of experiments, a "conventional" single SL pulse with
.phi.=90.degree. was used.
[0108] FIGS. 14A-D shows T.sub.1p-weighted MR images of an agarose
gel phantom obtained with the "self-compensating" (FIGS. 14A and
14B) or the "conventional" (FIGS. 14C and 14D) methods. In FIG.
14A, the SL pulse is divided into 4 segments of 1 ms each (i.e.,
TSL=4 ms), and in FIG. 14B, two segments of 4 ms each (ie., TSL=8
ms). These, and two more images obtained at longer TSL times, were
used to generate a T.sub.1p map. For comparison, the image in FIG.
14C was obtained with one SL pulse of 4 ms duration (TSL=4 ms). The
image in FIG. 14D was obtained with the SL pulse turned off, but
the 4 ms delay was maintained between the 90.degree. pulses. FIGS.
15A and B show in vivo T.sub.1p-weighted axial MR images of the
human knee joint obtained with a surface coil, with the
conventional (FIG. 15A), and self-compensating (FIG. 15B) pulse
sequences. (The arrows in FIG. 15B indicate the plane of the
surface coil). Reduction of artifacts in the cartilage and inside
the patella in the image in FIG. 15B are obvious.
[0109] The disclosures of each patent, patent application and
publication cited or described in this document are hereby
incorporated herein by reference, in their entirety.
[0110] While the foregoing specification has been described with
regard to certain preferred embodiments, and many details have been
set forth for the purpose of illustration, it will be apparent to
those skilled in the art without departing from the spirit and
scope of the invention, that the invention may be subject to
various modifications and additional embodiments, and that certain
of the details described herein can be varied considerably without
departing from the basic principles of the invention. Such
modifications and additional embodiments are also intended to fall
within the scope of the appended claims.
* * * * *