Gaurav Verma1, Seena Dehkharghani2, Leeor Alon3, and Priti Balchandani1
1Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States, 2Radiology and Neurology, New York University, New York, NY, United States, 3Radiology, New York University, New York, NY, United States
Synopsis
A spectrally-interleaved semi-adiabatic magnetic resonance
spectroscopic imaging sequence was developed to simultaneously acquire water
and metabolite resonances within the same repetition time. A water interleave
enables eddy current correction, absolute quantification through water
reference and thermometry using empirically-derived formulae based on chemical
shifts of temperature-sensitive water and temperature-insensitive metabolites.
The sequence successfully acquired both 1-minute single voxel and 4-minute multi-voxel
acquisitions in phantom and in vivo,
producing temperature estimates of 21.2 °C, and 35.7 °C, respectively. LCModel fitting
of metabolites provided reliable fitting of multiple metabolite peaks including
separation of glutamate and glutamine.
Introduction
Magnetic resonance spectroscopic imaging at ultrahigh field receives
dual benefits of proportionally higher signal-to-noise ratio and spectral
separation. However, scanning at ultrahigh field poses technical challenges,
such as B1-inhomogeneity, for which B1-insensitive
adiabatic refocusing pulses have emerged as popular solutions. Metabolites at
ultrahigh field tend to experience faster t2* relaxation but slower
t1 relaxation, such that maximizing signal requires significant “dead
time” between readouts and following excitations. Spectral interleaving
capitalizes on this available time by applying two sets of narrow-band
excitations at non-overlapping frequency ranges during the same repetition. i.e.,
interleaving a frequency band exciting brain metabolites followed by a second
band nutating the water signal. This approach can serve two important
applications: 1) It can provide a reference unsuppressed water signal useful
for eddy current correction or absolute quantification of metabolite signal by
fitting programs such as LCModel. 2) The frequency shift between temperature-insensitive
metabolite resonances (e.g. the methyl resonance of neuronal N-acetylaspartate (NAA)
c.a. 2.02 ppm) and the temperature-sensitive resonance of hydrogen bound water can
be used to perform non-invasive thermometry.
Among adiabatic pulse sequences, SASSI is uniquely suited
for interleaving because the spatial-spectral pulses are spectrally-selective and achieve
significantly lower specific absorption rates (SAR) than other approaches like
semi-LASER. The SASSI sequence can maintain a repetition time under two seconds
and remain well within SAR limits even with the inclusion of a second
interleaved frequency band, which can be a limiting factor at ultrahigh field.
This study presents an interleaved spectroscopy sequence implementing low-SAR
adiabatic pulses to acquire metabolite and unsuppressed (partially-excited) water
signal in a single repetition.Materials & Methods
Figure 1 shows the interleaved SASSI pulse sequence diagram,
which is capable of being run both as a single voxel sequence (SVS) and
chemical shift imaging (CSI). The sequence implemented narrow-band adiabatic
refocusing pulses generated through the adiabatic Shinnar-Le Roux algorithm.
The pulses (spatial/spectral responses shown in figure 2) had 8 ms duration,
660 Hz bandwidth (2.2 ppm at 7T) such that one interleave ran from 1.9 to 4.1
ppm to capture metabolites while the other ran from 4.5 ppm to 6.7 ppm to
capture water. The center frequency of the spectral interleaves are
user-selectable using the delta frequency field built into the sequence special
card, though these ranges should be spaced at least 0.2 ppm apart to account
for pulse transition bands. The water interleave was run at low flip angle (5
degrees, modulating the amplitude of the excitation pulse) for faster t1
relaxation. The sequence was applied in a brain phantom and in the occipital
lobe of a healthy volunteer (female, age 25) with scan parameters as follows: TE/TR
= 31ms/2000ms, two interleaved acquisitions of 4000 Hz bandwidth, 2048 complex
points and 512ms duration each. The SVS had 32 averages for a 1-minute scan
time, voxel size = 2.5x2.5x2.5 cm3. The CSI sequence had 4x4 spatial
resolution, 8x8 cm2 field of view and 2 cm slice thickness and 8
averages for a 4-minute scan time.
Acquired data were post-processed through a custom
Matlab-based reconstruction algorithm, which performed coil combination,
averaging, Fourier transform and baseline correction. The resulting data was processed
using the LCModel prior-knowledge based fitting algorithm using the interleaved
unsuppressed water signal to perform absolute metabolite quantification.Results
Figure 3 shows a CSI with interleaved spectra from the brain
phantom. Interleave 1, covering metabolites over the range of 1.9 to 4.1 ppm,
is shown in red, while interleave 2, covering only water over the range of 4.5
to 6.7 ppm, is shown in blue. Figure 4 shows the same type of CSI grid as well
as a single voxel acquisition from the occipital lobe of a healthy volunteer.
Metabolite peaks due to NAA, creatine (Cr), choline (Cho), myo-Inositol (mI),
and the combination of glutamate and glutamine (Glx) are labeled in the single
voxel scan, though the same peaks are also detectable within the CSI grid. The Glx
component peaks of glutamate and glutamine were partially separable in the SVS
acquisition, and LCModel fitting of this spectrum showed high-confidence fits for
both individual metabolites. Figure 5 shows the LCModel processing of the human
SVS study, showing reliable quantification of several metabolites. Across all
phantom and human studies SAR values measured by the scanner remained under 20%
of the maximum limit.
Chemical shifts for NAA were referenced to 2.02 in phantom and
2.02 in vivo, whereas water chemical
shift was 4.85 and 4.70, respectively. Using thermometry formulae derived by
Covaciu et. al. 2010, [temperature = -97.134*(δWater-δNAA)+296.068],
the midline temperature estimate was calculated as 35.7 °C for human and 21.2 °C
for phantom studies.Discussion
The SASSI sequence achieves sufficient spectral selectivity
that metabolite and water signal can be acquired in interleaved acquisitions in vivo. Combined with the SNR and
spectral selectivity advantages at ultrahigh field, this sequence can capture
subtle chemical shift changes between the water and temperature-independent
references signals concurrently and free of potential confounds related to
interscan motion or frequency offsets in MR thermometry applications. Future
development of the sequence will implement an echo-planar spectroscopic imaging
(EPSI) version of the sequence for faster spatial acquisition to enable
potential 3D spectroscopic imaging applications in a reasonable scan time.Acknowledgements
The authors would like to acknowledge funding from NIH R01 MH109544. The authors would also like to thank Mackenzie Langan for her contributions to this work.References
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