U.S. patent application number 09/774382 was filed with the patent office on 2001-06-14 for magnetic resonance imaging.
Invention is credited to Wald, Lawrence L..
Application Number | 20010003423 09/774382 |
Document ID | / |
Family ID | 21891847 |
Filed Date | 2001-06-14 |
United States Patent
Application |
20010003423 |
Kind Code |
A1 |
Wald, Lawrence L. |
June 14, 2001 |
Magnetic resonance imaging
Abstract
Methods for imaging the distribution of a marker compound in a
sample using magnetic resonance imaging.
Inventors: |
Wald, Lawrence L.;
(Cambridge, MA) |
Correspondence
Address: |
CLARK & ELBING LLP
176 FEDERAL STREET
BOSTON
MA
02110-2214
US
|
Family ID: |
21891847 |
Appl. No.: |
09/774382 |
Filed: |
January 30, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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09774382 |
Jan 30, 2001 |
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09036991 |
Mar 9, 1998 |
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6181134 |
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Current U.S.
Class: |
324/307 |
Current CPC
Class: |
G01R 33/485 20130101;
G01R 33/5607 20130101; G01R 33/4838 20130101 |
Class at
Publication: |
324/307 |
International
Class: |
G01V 003/00 |
Claims
What is claimed is:
1. A method for imaging the distribution of n-acetylaspartic acid
(NAA) in mammalian neuronal tissue, said method comprising: a)
exciting said neuronal tissue to generate magnetic resonance
signals, including signals corresponding to NAA; and b) suppressing
non-NAA magnetic resonance signals by a combination of band
selective inversion with gradient dephasing, and chemical shift
selective pre-excitation and dephasing.
2. A method of claim 1, wherein said suppressing step (b)
suppresses magnetic resonances down field from 2.5 ppm.
3. A method of claim 2, wherein said chemical shift selective
pre-excitation includes an excitation bandwidth of about 1.8 ppm to
2.5 ppm, said bandwidth including the water resonance.
4. A method of claim 2, wherein said band selective inversion
includes an excitation bandwidth of about 1.8 ppm to 2.5 ppm, and
said dephasing produces a suppression band which includes the water
resonance at about 4.7 ppm, the choline resonance at about 3.2 ppm,
and the phosphocreatine resonance at about 3.0 ppm.
5. A method of claim 1, further comprising, after the suppressing
step (b), the step (c) of encoding the NAA signal with readout and
phase encode gradients.
6. A method of claim 5, further comprising, after the encoding step
(c), the step (d) of reconstructing the image using two-dimensional
Fourier transformation to obtain a NAA weighted image.
7. A method of claim 5, wherein the encoding step (c) has a minimum
imaging time of 96 seconds for a spatial encoding matrix of at
least 256.times.64.
8. A method of claim 5, wherein the encoding step (c) has a minimum
imaging time of between 30 and 260 seconds for a spatial encoding
matrix of 256.times.256.
9. A method of claim 1, wherein said exciting step includes slice
selective spin-echo excitation.
10. A method of claim 1, wherein said exciting step (a) includes
volume selective double spin-echo excitation.
11. A method of claim 10, wherein said volume selective double
spin-echo excitation includes orthogonal slice selection pulses in
a double spin echo configuration
(90.degree.-180.degree.-180.degree.).
12. A method of claim 11, wherein said volume selective double
spin-echo excitation includes a STEAM localization configuration
(90.degree.-90.degree.-90.degree.).
13. A method for imaging the distribution of a marker compound
selected from n-acetyl aspartic acid, citrate, choline,
phosphocreatine, and lactate in mammalian tissue, said method
comprising: i) exciting said tissue to generate magnetic resonance
signals, including signals corresponding to said marker compound,
ii) suppressing non-marker compound magnetic resonance signals
using band selective inversion with gradient dephasing and chemical
shift selective pre-excitation, and iii) encoding the remaining
marker compound signal using conventional readout and phase
encoding gradients.
14. A method of claim 13, wherein said tissue is prostate tissue
and said marker is citrate.
15. A method of claim 13, wherein said marker is lactate, choline,
or phosphocreatine.
16. A method of claim 13, wherein said tissue is neuronal tissue
and said marker is n-acetyl aspartic acid, choline, or
phosphocreatine.
Description
BACKGROUND OF THE INVENTION
[0001] Neurodegenerative disorders include Alzheimer's disease,
amyotrophic lateral sclerosis (ALS), Parkinson's disease, and
multiple sclerosis. Selective neuronal loss or necrosis is also
associated with disorders such as schizophrenia, ischemia, cancer,
and stroke. Reduced levels of NAA are also associated with mesial
temporal lobe epilepsy.
[0002] A dicarboxylic acid found almost exclusively in neurons,
N-acetylaspartic acid (NAA) is endogenously localized in the
cytoplasm. Formed in the presence of acetyl CoA and a
membrane-bound enzyme from brain or spinal cord, NAA is the amino
acid or amino acid derivative found in highest concentration in the
brain, except for glutamic acid. NAA appears to be metabolically
inert in adults and may function as an anion or to effect
behavioral changes. The level of NAA correlates with neuronal
health. Mapping levels and distribution of NAA in a brain is a
noninvasive measure of neuronal density, which is useful in the
study, staging, and diagnosis of disorders relating to neuronal
injury, loss, or degeneration.
[0003] Conventional magnetic resonance spectroscopic imaging
(MRSI), or chemical shift imaging (CSI), has been used to map NAA.
See, for example, Brown et al., Proc. Natl. Acad. Sci. (USA)
79:3523-3526 (1982), and Maudsley et al., J. Magn. Reson.
51:147-152 (1983). Spatial and spectral information can be acquired
simultaneously by using a time-varying, periodic magnetic field
gradient wave form during the data acquisition (Echo Planar-CSI or
EPCSI). Mansfield, Magn. Reson. Med. 1:370-386 (1984). Other
approaches include acquiring data from different slices in the
brain, and using multiple echoes. Duyn et al., Radiology
188:277-282 (1993) and Spielman et al., J. Magn. Reson. Imaging
2:253-262, (1992).
[0004] These methods provide an NAA map of 16.times.16 or
32.times.32 pixels, the latter requiring about 17 minutes by
conventional CSI/MRSI techniques. A 256.times.64 image would take a
minimum of 4.5 hours. EP-CSI can acquire a 32.times.32.times.16
matrix in a 17 minute scan with degraded spectral resolution.
EP-CSI requires post-processing algorithms even more complicated
than conventional CSI/MRSI . The acquired data is manipulated and
reconstructed with the aid of custom software and a skilled
operator.
SUMMARY OF THE INVENTION
[0005] The invention features a method for imaging the distribution
of a marker compound in a sample, such as living tissue, using
magnetic resonance imagining. The method includes i) exciting the
tissue to generate magnetic resonance signals, including signals
corresponding to the marker compound and ii) suppressing non-marker
compound magnetic resonance signals using band selective inversion
with gradient dephasing and chemical shift selective
pre-excitation. The method can further include iii) encoding the
remaining marker compound signal using conventional readout and
phase encoding gradients. Examples of marker compounds include
n-acetyl aspartic acid, citrate, choline, phosphocreatine, and
lactate in mammalian tissue.
[0006] One aspect of the invention is a method for imaging the
distribution of n-acetylaspartic acid (NAA) in mammalian neuronal
tissue. This method includes the steps of (a) exciting the neuronal
tissue to generate magnetic resonance signals, including signals
corresponding to NAA; and (b) suppressing non-NAA magnetic
resonance signals by a combination of band selective inversion with
gradient dephasing, and chemical shift selective pre-excitation and
dephasing. The suppressing step (b) can suppress magnetic
resonances down field from 2.5 ppm. The chemical shift selective
pre-excitation can includes an excitation bandwidth of about 1.8
ppm to 2.5 ppm, where the bandwidth includes the water resonance.
The band selective inversion can include an excitation bandwidth of
about 1.8 ppm to 2.5 ppm. The dephasing can produce a suppression
band which includes the water resonance at about 4.7 ppm, the
choline resonance at about 3.2 ppm, and the phosphocreatine
resonance at about 3.0 ppm.
[0007] Embodiments of the invention can further include after the
suppressing step (b), the step (c) of encoding the NAA signal with
conventional readout and phase encode gradients. This step is an
encoding step, in other words, a data acquisition step. One aspect
of the invention further includes, after the encoding step (c), the
step (d) of reconstructing the image using two-dimensional Fourier
transformation to obtain a NAA weighted image. The encoding step
(c) has, for example a minimum imaging time of 96 seconds for a
spatial encoding matrix of at least 256.times.64; or a minimum
imaging time of between 30 and 260 seconds for a spatial encoding
matrix of 256.times.256. The exciting step (a) can include slice
selective spin-echo excitation. An example of slice selective
spin-echo excitation includes volume selective double spin-echo
excitation (which in turn can include orthogonal slice selection
pulses in a double spin echo configuration
(90.degree.-180.degree.-180.degree. or, alternatively, a STEAM
localization configuration (90.degree.-90.degree.-90.degree.).
[0008] The above methods can be used, for example, to measure
citrate in prostate tissue; lactate, choline, or phosphocreatine in
any tissue; or n-acetyl aspartic acid, choline, or phosphocreatine
in neuronal tissue.
[0009] Other features and advantages of the invention will be
apparent from the disclosure, figures, and claims below.
BRIEF DESCRIPTION OF THE DRAWINGS
[0010] FIG. 1 is a schematic pulse sequence for NAA weighted
imaging. The sequence consists of an asymmetric PRESS excitation
with CHESS and MEGA-BASING water suppression. Spatial encoding is
achieved with the x axis readout gradient and a y phase encode
gradient added to the crusher after the slice selective .pi./2
pulse.
[0011] FIGS. 2a-2c are images of a phantom sample obtained with the
NAA mapping sequence of FIG. 1. FIG. 2a is a water image showing
PRESS localized region and inner cylinder containing water and 12.5
mM of NAA and outer region with water only. FIG. 2b is a
256.times.128 NAA weighted image, 0.78 mL nominal voxel volume and
total acquisition time of 13 minutes, showing a signal only from
the NAA-containing region. FIG. 2c is an NAA weighted image low
pass filtered to 1 cm resolution.
[0012] FIGS. 3a-3e are images and spectra related to phantom data
acquired immediately after the pulse sequence of FIG. 1 using the
same PRESS and suppression parameters. FIG. 3a is a composite image
of a PRESS excitation region with a 16.times.16 CSI grid overlaid
on a convention water image. FIG. 3b is a subset of spectra from a
16.times.16 CSI acquisition, 3.1 mL nominal voxel volume. FIG. 3c
is an enlarged spectrum from the NAA containing region of the
phantom. FIG. 3d is an NAA map formed from the CSI acquisition of
FIG. 3b. FIG. 3e is an NAA map zero-filled.
[0013] FIGS. 4a and 4b are images obtained from a normal subject.
FIG. 4a is a water image acquired with the NAA mapping sequence of
FIG. 1 with no water suppression. FIG. 4b is an NAA weighted image
low pass filtered to 1 cm resolution, 256.times.128 matrix, 0.78 mL
voxel volume prior to filtering, 13 minute acquisition time.
[0014] FIGS. 5a-5f show spectroscopic data and images derived from
the same examination of FIG. 4. FIG. 5a is a PRESS localized
spectrum with CHESS and MEGA-BASING suppression centered on the
water region. FIG. 5b is a spectrum with MEGA-BASING suppression
placed to suppress choline (Cho) and phosphocreatine (Cre)
resonances. FIG. 5c is a conventional water image overlaid with a
16.times.16 CSI grid and PRESS excitation region. FIG. 5d is a
subset of spectra from the brain region of a 16.times.16 CSI
acquisition, 3.1 mL nominal voxel volume, 13 minute total
acquisition time. FIG. 5e is an NAA map formed from the CSI data.
FIG. 5f is the corresponding NAA map zero filled.
[0015] FIGS. 6a-6c are images obtained from a normal subject
acquired with the NAA mapping sequence with no water suppression.
FIG. 6a is the conventional image. FIG. 6b is an NAA weighted
image, 256.times.128 matrix, 0.78 mL voxel volume, 13 minute
acquisition time. FIG. 6c is an NAA weighted image low pass
filtered to 1 cm resolution.
[0016] FIGS. 7a-7e are spectra and images acquired from the same
examination as FIG. 6. FIG. 7a is a conventional water image
overlaid with a CSI grid and PRESS excitation region. FIG. 7b is a
subset of spectra from brain region of 16.times.16 CSI acquisition,
3.1 mL nominal voxel volume, 13 minute total acquisition time. FIG.
7c is a PRESS localized spectrum. FIG. 7d is an NAA map formed from
the CSI data. FIG. 7e is an NAA map zero filled.
[0017] FIG. 8 is an NAA weighted imaging sequence using 2 slice
selective pulses to limit the excitation in space to a slice. The
phase encode gradient is incorporated into the crusher gradient
following the .pi./2 rf pulse.
[0018] FIG. 9 is an NAA weighted imaging sequence using 3
orthogonal slice selective pulses to limit the excitation in space
to a rectangular prism (shoe box) shaped region and two additional
.pi. pulses which can be slice selective to produce two additional
echoes which are encoded with readout gradients. The additional
echoes can produce redundant information from the same slice as the
first echo to gain relaxation time information or increase
sensitivity. Alternatively, the additional echoes can be encoded
with additional phase encode gradients to decrease the minimum
imaging time.
[0019] FIG. 10 is an NAA weighted imaging sequence using 2 slice
selective pulses to limit the excitation in space to a slice as in
FIG. 2 but showing the use of 2 additional .pi. pulses and readout
gradients. Alternatively, the additional echoes can be encoded with
additional phase encode gradients to decrease the minimum imaging
time.
[0020] FIGS. 11a-11c are schemes for multi-slice NAA mapping. FIG.
11a is a block representation of a NAA weighted imaging sequence
having a length of 0.312 seconds. FIG. 11b is a scheme of blocks
repeated every TR seconds, in this case, TR=2.0 seconds, with a
different phase encode amplitude. Each phase encode step can be
similarly repeated to signal average for increased sensitivity.
FIG. 11c is a completed scheme for multi-slice NAA mapping showing
blocks applied to additional slice locations during the otherwise
unused time within the TR period. The series is repeated every TR
seconds using a different phase encode amplitude, or is repeated to
signal average for increased sensitivity.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
A. Definitions
[0021] Some terms are defined below and by their use herein.
[0022] Band Selective Inversion with Gradient Dephasing is a method
for suppressing unwanted spectral resonances (such as water) by
acting on these resonances with a chemical shift selective
(frequency selective) inversion pulse after the initial excitation
pulse of a sequence and subsequent dephasing of the effective
resonances with anti-symmetric gradient pulses. (Meicher et al.
1996, Star-Lack et al. 1997). The process of acting on the
undesired resonances with inversion pulses (also known as
refocusing pulses) while the magnetization is in the transverse
plane is advantageous, in part, because longitudinal relaxation
(T1) during and after the suppression process does not adversely
affect the degree of suppression.
[0023] Chemical Shift Selective Pre-Excitation is a method for
suppressing unwanted spectral resonances (such as water) by acting
on these resonances with one or more chemical shift selective
(frequency selective) excitation pulses before the initial
excitation pulse. (Haas et al. 1985). The transverse magnetization
created by each pre-excitation pulse is dephased by gradient pulses
immediately following the pre-excitation pulses. Typically, two
chemical shift selective 90.degree. RF pulses are used together
with a third chemical shift selective RF pulse of adjustable flip
angle. The flip angle of the last pulse is adjusted to partially
compensate for the T1 relaxation that occurs in the time interval
between the pre-excitation pulses and the excitation pulse.
[0024] Conventional Readout Gradient Encoding is a method for
encoding the MR signal to provide the spatial information necessary
for producing an image of the detected MR signal. Readout gradient
encoding is commonly used to encode one of the two spatial
dimensions in a 2 dimensional MR image. In the readout technique,
the MR signal is digitized while an magnetic field gradient is
applied to the object. This method is also referred to as frequency
encoding since the frequency of the resulting signal is a function
of the position from which the signal originated.
[0025] Excitation Bandwidth is the range of frequencies excited by
a radio frequency pulse.
[0026] Gradient Phase Encoding is a method for encoding the MR
signal to provide the spatial information necessary for producing
an image of the detected MR signal. Gradient phase encoding is
commonly used to encode one of the two spatial dimensions in a 2
dimensional MR image. In the phase encoding technique, a gradient
pulse is applied after the initial excitation of the MR signal. The
phase encode gradient causes the transverse magnetization to
develop a phase shift which is proportional to the position from
which the signal originated. Gradient phase encoding is commonly
used to encode the one spatial dimension of a 2 dimensional MR
image. Readout encoding is commonly used to encode the other. In
chemical shift imaging (CSI, also known as MR spectroscopic
imaging), phase encoding is used to encode the spatial information
in all of the spatial dimensions.
[0027] Marker compound is a compound or composition that has a
magnetic resonance signal. The signal may be narrow and sharp, such
as that of NAA, or it may be broader with multiple peaks, such as
that of glutamate. Markers include NAA, glutamate, citrate,
choline, and lactate. In some cases, the disclosed method can be
used even when a marker signal overlaps with another signal. For
example, the signals for choline and phosphocreatine are quite
close. However, the level of phosphocreatine, a marker for energy
metabolism, is generally stable whereas the level of choline, a
marker for cancer, can vary up to 5 times or 10 times normal.
Elevated choline is associated with the turnover of phospholipid
membranes resulting from rapid cell division, and thus is
associated with almost all types of cancer, including breast
cancer, lymphomas, and primary and metastatic brain tumors. Thus,
even the combined area under the choline/phosphocreatine signal
provides information correlated with the status of the patient.
Glutamate is a marker for metabolic disorders and excitotoxicity
disorders. Excessive glutamate release may result from a neuronal
lack of energy to contain glutamate (as in stroke), or the
excessive firing of glutamatergic neurons during a seizure (as in
epilepsy), or other mechanisms such as ALS. Citrate is a marker
found in the prostate and therefore useful for monitoring prostate
conditions, including prostate cancer. Lactate is a marker for
anaerobic energy metabolism and therefore useful for monitoring the
effects of ischemia or stroke.
[0028] Minimum imaging time is the minimum time required to form an
image with a given technique. The total imaging time can be a
multiple of the minimum imaging time since the spatial encoding
steps can be repeated and averaged to improve the signal to noise
ratio of the resulting image. A short minimum imaging time provides
increased flexibility in this trade-off between total imaging time
and signal to noise ratio.
[0029] Suppression Bandwidth is the range of frequencies in the
spectrum that is effectively suppressed by a suppression technique
such as chemical shift selective pre-excitation or band selective
inversion with gradient dephasing. The suppression bandwidth is
typically determined by the frequency bandwidth of the
radiofrequency pulse used in the suppression technique. Other
characteristics of the graph of degree of suppression as a function
of spectral frequency, such as the center frequency of the
suppression bandwidth and the transition bandwidth (width of the
transition between full suppression and negligible suppression),
are also determined by the characteristics of the radio frequency
pulse.
[0030] Water Resonance is the magnetic resonance spectral line that
arises from the protons in the water molecule. The position of this
resonance in the in vivo proton spectrum is at approximately 4.7
ppm and typically has a linewidth ranging from 0.05 ppm to 0.15
ppm.
B. NAA Imaging
[0031] According to the invention, in one embodiment, the NAA
resonance is isolated by suppressing the resonances of all other
compounds in the brain during data acquisition. According to the
invention, it is unnecessary to obtain spectral information. A
standard image can be formed using the standard read out gradient
and phase encoding gradient method. This is an NAA weighted image.
At least two frequency selective suppression techniques are used to
isolate the NAA resonances. For example, the pulse sequence can
include CHESS followed by BASING. Although CHESS is dependent upon
relaxation parameters, BASING is not. These suppression methods are
CHESS (Haase et al., Phys. Med. Biol. 30:341-344, (1985)) and
BASING (Star-Lack et al., Magn. Reson. Med. 38:311-321, (1997)).
These and other references cited herein are provided for the
reader's convenience and are hereby incorporated by reference in
their entirety.
[0032] The following method is an example of the invention. All of
the experiments were performed on a 1.5 Tesla clinical MR scanner
(General Electric Medical Systems, Milwaukee, Wis.) with 1.0 g/cm
maximum gradient strength. Radio-frequency excitation and detection
were performed with a clinical quadrature birdcage head coil. The
linear shim currents were optimized over the desired axial slice
with the field mapping sequence provided by General Electric. An
additional 15 dB of gain was added after the pre-amplifier to
increase the dynamic range of the NAA images.
[0033] The NAA mapping sequence, shown in FIG. 1, consists of CHESS
excitation and dephasing pulses followed by an asymmetric PRESS
sequence with the frequency selective MEGA-BASING .pi. pulses and
anti-symmetric crusher gradients following each of the slice
selective pulses. The MEGA-BASING .pi. pulses selectively crushed
resonances (such as water) within their excitation band. Resonances
outside of the MEGA-BASING excitation band were not dephased since
the net crusher gradient area was zero. All of the radiofrequency
pulses were designed using the Shinnar-LeRoux algorithm. Other
appropriate methods or types of pulses include sinc and windowed
sinc pulses, DANTE pulses, and preferably adiabatic inversion
pulses. The CHESS and MEGA-BASING excitation pulses were minimum
phase pulses with an excitation bandwidth of 125-160 Hz and 130 Hz
respectively. The excitation band of the CHESS pulses was centered
on the water resonance. The excitation band of the MEGA-BASING
pulses was set further up field (.about.40 Hz up field from water)
to suppress choline and creatine signals. The PRESS selected region
was chosen to fall entirely within the brain in order to reduce
contamination from subcutaneous lipids. In the human data, a single
out-of-voxel lipid suppression band was placed on the right side of
the head just outside of the PRESS region to further reduce lipid
signals.
[0034] The NAA images were acquired from an axial slice through the
brain or phantom with an imaging matrix of 256.times.64, field of
view (FOV) of 80 cm and 8 excitations (number of excitations,
"NEX") or a matrix of 256.times.128 with a FOV of 160 cm in the
readout direction and 80 cm in the phase encode direction and 4
NEX. A 2 cm slice thickness, with a nominal voxel volume of 0.78
ml, was used. The sequence used a TE of 144 ms, and a TR of 1.5 s
giving a total imaging time of 13 minutes. A readout bandwidth of
32 kHz was used yielding a data acquisition window length of 8 ms
for the 256 point acquisition.
[0035] Measurements were obtained from a phantom consisting of two
concentric cylinders with 8 cm and 23 cm diameters. The inner
cylinder contained a solution of NAA at approximately physiological
concentration (12.5 mM) and the outer cylinder contained water.
Both compartments were doped with 1 mL of gadodiamide solution
(Sanofi Winthrop Pharmaceuticals, New York, N.Y.) per liter. The
PRESS box was prescribed to completely excite a cross section of
the inner (NAA-containing) cylinder as well as a significant volume
of the water-only region.
[0036] The suppression of the undesired resonances was optimized by
monitoring the proton spectrum from the PRESS selected region
without the readout gradient using a spectral bandwidth of 2 kHz
and digitizing 1024 points in the time domain (512 ms acquisition
window). The flip angle of the last CHESS pulse was adjusted
interactively to minimize the amplitude of the water resonance with
CHESS alone. Then the MEGA-BASING pulses were applied and offset to
suppress the 3.2 ppm choline and 3.0 ppm creatine resonances. The
peak height of the NAA resonance was measured before and after
application of the MEGA-BASING pulses to insure that the creatine
and choline resonances were suppressed without significant
alteration of the NAA amplitude.
[0037] An averaged spectrum from the PRESS localized region was
obtained to assess the relative global contribution of the water,
NAA, creatine, choline, glutamate plus glutamine, and lipid
resonances to the PRESS localized spectrum. The relative
contributions of these resonances to the NAA weighted image was
determined by integrating the spectral regions of the PRESS
localized spectrum. First, the NAA methyl resonance was measured by
fitting the 2.0 ppm spectral peak to a Lorentzian function. This
function was subtracted from the spectrum and the residual spectrum
was integrated to determine the signal intensity in the water
region (5.5 ppm to 4.0 ppm) and metabolite region (4.0 ppm to 2.0
ppm). The metabolite region of the residual spectrum is expected to
contain contributions from creatine, choline, glutamate, glutamine,
and the aspartate resonances of NAA. The NAA phantom spectra
acquired with the MEGA-BASING sequence showed that the NAA
aspartate resonances at 2.5 ppm and 2.7 ppm contributed about 12%
of the total NAA signal.
[0038] To assess the relative contribution of water, creatine,
choline, NAA, and lipid to the NAA map, conventional CSI data were
acquired by removing the readout gradient. The spectroscopic
imaging data were acquired using PRESS and suppression parameters
that were identical to the NAA mapping sequence and 16.times.16
phase encoding, FOV=20 cm or 16 cm, 2 kHz spectral bandwidth, 1024
spectral points, 2 acquisitions per phase encode step, and a TR of
1.5 or 2.0 s, yielding a total acquisition time of 13 or 17
minutes, respectively. The spectroscopic image was formed using
exponential apodization in the time domain (2 Hz Lorentzian width)
and no apodization in kspace. The effective suppression of
resonances in the 6.0-2.5 ppm region yielded a MR signal dominated
by the 2.0 ppm NAA resonance with less than 5% decrease in the 2.0
ppm NAA resonance.
[0039] The SNR of the NAA weighted phantom images was compared to
that obtained from peak integration of the conventional
spectroscopic imaging data. The ratio of SNR values obtained by the
two methods was compared to that expected from the acquisition
parameters. Neglecting T.sub.2* decay, the SNR of an imaging
sequence is proportional to the voxel volume and the square root of
the total image acquisition time. For the NAA weighted imaging
sequence, the total image acquisition time is the product of the
number of excitation per phase encode step (NEX=4 or 8), the number
of phase encode steps (N.sub.pe=64 or 128), and the length of the
data acquisition window (t.sub.w=8 ms). For the spectroscopic
image, NEX=2 and N.sub.pe=16.times.16. Significant T.sub.2* decay
occurs during the 512 ms data acquisition window. Therefore, an
effective data acquisition window length which reflects T.sub.2*
losses, as well as the apodization function, was applied to the
data. Assuming an exponential apodization function with a decay
constant of T.sub.2*, the expected SNR reflects an effective
acquisition window of t.sub.eff=T.sub.2*/2.
[0040] Turning to the NAA weighted images of the phantom
measurement, FIG. 2 shows a signal only in the region of the
phantom containing NAA (inner cylinder). Water was suppressed in
the outer region to below the level of the noise. An artifact is
seen in the NAA map at the edge of the inner cylinder, presumably
due to unsuppressed water resulting from an air bubble induced
susceptibility shift. Integration of the water and NAA region of
the PRESS localized spectrum indicated that NAA contributed 92% of
the total spectral area, the remaining 8% contributed by water. The
conventional CSI acquisition (FIG. 3) confirms the water
suppression on a regional basis and demonstrates that the water
seen in the PRESS localized spectrum arises from a few voxels near
the interface between the two regions. Most of the water
contamination seen in the unlocalized spectrum arises from the
artifact.
[0041] The NAA weighted image had a SNR=5 compared to SNR=50 for
the spectroscopic image. The spectroscopic image is expected to
have a 12.6-fold higher SNR, based largely on the 4-fold larger
voxel volume of the chemical shift image, and also on the 10-fold
higher effective data acquisition window of the spectroscopic
acquisition.
[0042] A 256.times.128 NAA weighted image from the brain of a
normal adult subject was taken (FIG. 4a), and low pass filtered to
1 cm in-plane resolution. A lipid artifact is observed, localized
outside of the brain. For comparison, a water image was acquired
with the same PRESS localization, image matrix, and FOV as the NAA
weighted image (FIG. 4b). Spectroscopic imaging data was acquired
in the same examination (FIG. 5). The PRESS localized spectrum
illustrates complete suppression of the water resonance and
suppression of the choline and creatine resonances with less than
5% alteration of the NAA resonance (FIGS. 5a and 5b). The spectra
from the CSI array show complete suppression of the water resonance
throughout the PRESS localized region (FIGS. 5c and 5d). NAA maps
formed by integrating the NAA peak are shown in FIGS. 5e and
5f.
[0043] Results from a second normal adult subject are shown in
FIGS. 6a-6c and 7. The PRESS localized spectra show contributions
from the methyl group of NAA (2.0 ppm), creatine (3.0 ppm), lipids,
and the 3.0 ppm to 2.1 ppm resonances which contain the glutamate,
glutamine and aspartate resonances of NAA. The relative signal
contributions to the brain region of the NAA weighted images was
estimated based on the area of these resonances in the PRESS
localized spectrum. Since the lipid contribution measured in the
PRESS localized spectrum is expected to be spatially localized
outside the brain and contribute principally to the ring artifact
seen in the NAA weighted image, the lipid area was excluded from
the estimation of the relative contributions to the brain signal.
Integration of the water and metabolite regions after fitting and
subtraction of the methyl NAA resonance showed that NAA contributed
72% of the unlocalized spectrum while water contributed 2% and the
choline, creatine and glutamate plus glutamine resonances
contributed 26%. Thus, the principal contamination in the NAA
weighted brain image appears to arise from glutamate and glutamine.
Since glutamate and glutamine have a short effective T.sub.2
compared to NAA, the use of a longer echo time could also reduce
their contribution to the image.
C. Advantages
[0044] Conventional MR imaging (MRI) techniques can be used with
the methods of the invention without requiring spectral
information. The disclosed methods therefore provides several
advantages.
[0045] First, the minimum imaging time is reduced. For example, the
minimum image time for a 256.times.64 pixel NAA image is one
minute. An imaging time can be any multiple of this value.
[0046] Although a high readout bandwidth was used to demonstrate
the ability to acquire NAA weighted images with short data
acquisition window lengths, a single high bandwidth acquisition in
each TR period does not optimize the SNR of the measurement. Since
the SNR is proportional to the square root of the total sampling
time, a lower readout bandwidth would allow increased SNR.
[0047] Second, the available image matrix size is over 8 times
greater than the image matrix of previously known techniques. For
example, image matrices of 256.times.64, or 256.times.128, and even
256.times.256 have been produced.
[0048] Third, after the NAA resonance is isolated according to the
invention, conventional MR image reconstruction algorithms such as
those already found on commercial, clinical MR scanners are capable
of automatically reconstructing and displaying the NAA image. As a
practical matter, this reduces instrumentation costs and operator
time required to obtain a clinical image.
[0049] Fourth, the data acquisition window is no longer tied to the
spectral resolution. The resulting up to 50-fold shorter data
acquisition window, and the ability to trade SNR for bandwidth,
allows the immediate use of multi-echo and multi-slice acquisition
techniques, developed for conventional MRI, in NAA imaging. In
short, the disclosed method provides flexible ranges for imaging
time and image resolution. For example, T.sub.2 of NAA is
relatively long compared to T.sub.2* in vivo. It is estimated that
a train of 8 echoes could be acquired within T.sub.2 period of NAA
(.about.350 ms). The shorter data acquisition period also has the
potential to facilitate the acquisition of multiple interleaved
slices. With the parameters used in this study, the RF and gradient
pulses require the first 312 ms of the TR period suggesting that up
to 6 interleaved slices could be obtained with TR=2 s.
[0050] Finally, the use of a relatively short readout period is
expected to reduce motion sensitivity in the readout direction
compared to phase encoding techniques. Other embodiments and
advantages will be apparent from the examples, FIGS. 8-12
describing variations of the disclosed method, and the claims
below.
1TABLE 1 COMPARISON OF CHARACTERISTICS Disclosed Method CSI/MRSI
EP-CSI minimum imaging time for a 256 .times. 128 matrix 256
seconds 65,536 seconds not yet achieved and a TR of 2 seconds (4.27
min.) (18 hours) minimum imaging time for a matrix of at least 64
seconds 2,048 seconds 64 seconds 32 .times. 32 and a TR of 2
seconds reconstruction method for the NAA map of a 2 dimen. 3
dimensional FT, Re-gridding of the slice Fourier phasing and
filtering in non-rectilinear data transform. spectral domain, then
FT and spectral (FT) curvefit or integration processing as in of
the NAA region CSI/MRSI can reconstruction be done automatically
yes no no can reconstruction be done on a commercial yes no no MR
scanner minimum length of readout or data acquisition 8 ms >200
ms required for >200 ms required for window useable spectral
resol. useable spectral resol., limited by gradient perform, to 200
ms Number of echoes that can be acquired before 8 1 1 NAA decays by
one T2 = 350 ms time constant. Assuming first echo is formed at
time TE = 144 ms, the minimum readout or data acquisition window
length is used and 10 ms is needed for the pulses to generate each
additional echo. Number of slices that can be acquired within a 6 3
3 TR = 2 seconds period assuming an echo time of TE = 144 ms is
used and that the pulses prior to the echo require 312 ms. After
the echo, the minimum readout or data acquisition window length is
used. spectral resolution not good, but requires long poor, due to
the applicable data acquisition difficulty of window maintaining
oscillating read gradient for 200 ms and eddy current
EXAMPLES
Example 1
Double Stop-bands
[0051] The disclosed method can be adapted to produce two
suppression bands with bandwidths from 1 to 2.5 ppm in the band
selective inversion with gradient dephasing. This is a 2 stop-band
BASING method, in contrast to the 1 stop-band BASING method
described above. Two stop-bands allow imaging of a marker compound
where there is at least one interfering resonance upfield from the
resonance of the marker compound, and at least one interfering
resonance downfield from the marker compound resonance. The double
stop band method is generally described in the original BASING
paper. Star-Lack et al., Magn. Reson. Med. 38:311-321, (1997),
hereby incorporated by reference.
[0052] For NAA imaging, two stop-bands can suppress lipid
resonances (upfield from NAA) as well as the water resonance
(downfield from NAA), preferably with high field strength imagers
(3T or 4T). In one example relating to NAA, the first suppression
band includes water, choline and phosphocreatine resonances, while
the second band includes lipid resonances near 1.5 ppm but does not
include the NAA resonance at 2.0 ppm. In another example relating
to non-neuronal tissue, the first suppression band includes the
water resonance but not the choline or phosphocreatine or citrate
resonances at about 3.2 ppm, 3.0 ppm, and 2.7 ppm. The second band
includes lipid resonances near 1.5 ppm and the NAA resonance at 2.0
ppm. This allows imaging of the choline marker or citrate marker in
non-neuronal tissue such as breast or prostate cancers.
Example 2
Choline/phosphocreatine in Neuronal and Non-neuronal Tissue
[0053] Two stop-bands allow choline imaging in neuronal tissue
since such imaging requires the suppression of both the water
resonance (downfield from choline) and also the NAA resonance
(upfield from choline).
[0054] In choline imaging of non-neuronal tissue (such as a cancer
of the lymph nodes or breast), one stop band would suppress water
(downfield from choline) and the other stop band would suppress
lipid (upfield from choline). The tissue is tumor embedded in
normal tissue such as breast cancer lesions in normal breast tissue
or associated lymph nodes. The first suppression band includes the
water resonance, and the second suppression band includes the lipid
resonances near 1.5 ppm. In one embodiment, the second suppression
band does not include the choline and phosphocreatine resonances at
3.2 ppm and 3.0 ppm. The remaining marker compound resonances are
attributed to choline and phosphocreatine, which often overlap and
are difficult to separate by this method. Since the phosphocreatine
level is generally stable, changes in the combined choline and
phosphocreatine resonances are attributed to changes in choline
levels.
Example 3
Multiple Spin Echoes
[0055] The disclosed method can be adapted to include additional
180.degree. RF refocusing pulses to generate additional spin echos.
For example, each spin echo is encoded with a readout gradient to
acquire the same image at different echo times to infer regional
information about the variation of the NAA signal with echo time by
measuring the T2 relaxation time. Alternatively, each spin echo is
encoded with a readout gradient to provide multiple maps of NAA
which are averaged together to improve sensitivity.
[0056] In another example, each spin echo is encoded with a readout
and phase encode gradient to allow multiple phase encode steps to
be measured per excitation step. This decreases the minimum image
acquisition time, and increases the image sensitivity at a given
total imaging time (see FIGS. 9 and 10).
[0057] As described above, the disclosed method acquires a single
echo per excitation sequence, requiring 312 ms for the application
of the preexcitation and suppression, volume selective excitation,
inversion and dephasing suppression, and readout gradient (of 8 ms
length) encoding and a 1.5 second or 2 second recovery period. With
these same parameters, and a requirement of 10 ms to add each
additional 180 degree refocusing pulse and associated crusher
gradients (which include the phase encode gradient if desired),
each additional echo requires 18 ms of additional time at the end
of the excitation sequence. Since the NAA signal decays with a
characteristic decay time T2 (approximately 300 ms), it is
preferable to limit the number of spin echos to that which can be
acquired in the 300 ms following the initial excitation pulse. For
example, in this case, the first spin echo is formed 144 ms after
the excitation pulse, indicating that an additional 156 ms remains
of the 300 ms NAA decay duration. Up to 8 additional echos can be
collected during this time, for a total of between 2 and 9 echoes.
Any number of echoes can be used, although even numbers (e.g., 2,
4, 6, or preferably 8) are preferred. This method is especially
useful for applications requiring high sensitivity and disorders
where a measure of the NAA T2 relaxation time would be valuable for
mapping relaxation time changes or for characterizing NAA T2
relaxation time for use with methods that calibrate the molar
concentration of NAA in the brain.
Example 4
Multiple Spatial Slices
[0058] In this aspect, marker compound images, such as NAA images,
are acquired from multiple slices in the same imaging acquisition.
This is achieved by applying pre-excitation suppression, slice
selective excitation, suppression by band selective inversion with
gradient dephasing, and readout gradient encoding to additional
spatial slices in the order described through the subject's body
during the recovery time between successive phase encode steps
(see, e.g., FIG. 11). The spatial slices are defined by the slice
selective excitation or the volume selective excitation step.
Therefore, to avoid interference between the excitations, the
spatial slices preferably do not overlap spatially. The spatial
slices can be acquired in two or more interleaved acquisitions to
allow contiguous slices to be obtained with minimal interference
between adjacent slices.
[0059] In practice, for example, the method above requires 312 ms
for the application of the pre-excitation and suppression, volume
selective excitation, inversion and dephasing suppression, and
readout gradient encoding techniques and a 1.5 second to 2 second
recovery period. With these parameters, data from up to 5
additional slices is acquired in the 2 second recovery period. The
data from the separate spatial slices is stored and reconstructed
to produce NAA maps from each of the 6 slices. This technique is
useful for applications where more than one slice through the
anatomy of interest is needed to visualize the pathology of the
organ.
Example 5
Clinical Method
[0060] One aspect of the invention features a slice selective spin
echo excitation where additional slices are excited and encoded
during the otherwise unused time period of the sequence. Three or
more chemical shift selective pre-excitation pulses and associated
crusher gradients are used to suppress the resonances downfield
from NAA. The pre-excitation pulses have a flip angle of .pi./2
with the flip angle of the last pre-excitation pulse being adjusted
to maximize the suppression of the water resonance. The center of
the excitation bands of the pre-excitation pulses are centered near
the water resonance. The slice selective spin echo or double spin
echo excitation utilizes an echo time of 100 ms to 300 ms to
minimize lipid signal contributions and provide time for the band
selective inversion pulses and their associated gradient dephasing
pulses. The pre-excitation and band selective inversion pulses are
shaped RF pulses designed to provide sharp transition bandwidths
and low in-band and out-of-band ripple. The band selective
inversion pulses are 20 ms to 50 ms in length. The center of the
inversion band is initially placed on the water resonance and
adjusted so that the brain phosphocreatine and choline resonances
at 3.2 ppm and 3.0 ppm are suppressed without affecting the NAA
resonance. The band selective inversion pulses must have a
bandwidth of at least 1.7 ppm to ensure suppression of the 4.7 ppm
water resonance in addition to the phosphocreatine and choline
resonances at 3.2 ppm and 3.0 ppm. The resulting magnetic resonance
signal arises predominantly from NAA and is encoded with 64 to 256
phase encode steps and 128 to 256 points in readout direction. The
readout bandwidth is 16 kHz. The excitations are averaged 2 to 8
times to increase the sensitivity of the NAA map. The phase encode
and averaging steps are repeated at a repetition time (TR) of 1.5
seconds to 3 seconds. The number of excitations averaged for a
given number of phase encode steps and TR is chosen to give a total
imaging time of 8 to 20 minutes.
OTHER EMBODIMENTS
[0061] Based on the disclosure, the essential features and
advantages of the present invention can be ascertained. Other
embodiments of the invention, which are within the spirit and scope
of the claims, can be easily developed or adapted to various usages
and conditions.
* * * * *