Manoj Kumar Sarma1,2, Andres Saucedo3, and M. Albert Albert Thomas3
1Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, TX, United States, 2Radiology, UT Southwestern Medical Center, Dallas, TX, United States, 3Radiology, UCLA School of Medicine, Los Angeles, CA, United States
Synopsis
Diffusion-weighted spectroscopy
(DW-MRS) is an excellent tool to explore the compartment specific assessment of
tissue microstructure. Although there has been growing interest in DW-MRS for
clinical applications, most of the studies involving human brain metabolites so
far have used single-voxel methods, which limit its
application to specific white matter tracts or arbitrarily selected regions of
interest. There has been only a few attempts to evaluate the diffusion
properties of brain metabolites with DW-MRSI. Here,
we propose an echo planar-based diffusion-weighted spectroscopic imaging using
semi-LASER localization and bipolar diffusion gradients. Initial results show
good spectral quality and spatial localization.
Introduction:
Diffusion-weighted spectroscopy (DW-MRS) is an excellent
tool to explore the diffusion properties of intracellular metabolites1,2
allowing compartment specific assessment of tissue microstructure. Combined
with other imaging modalities such as DW-MRI, DW‐MRS has been shown to
differentiate between axonal degeneration, glial activation, and demyelination3-5.
Although there has been growing interest in DW‐MRS for clinical applications6-9,
most of the studies involving human brain metabolite so far used single voxel
methods, which limit its application to specific
white matter tracts or arbitrarily selected regions of interest. There have
been only few attempts to obtain maps of the diffusion properties of
brain metabolites with DW-MRSI10-12.
One of the reasons for this is the intrinsic low signal-to-noise ratio (SNR) of
metabolites, especially at high diffusion-weightings; coupled with signal
losses related to B1 field inhomogeneities and chemical shift
displacement error. DW-MRS with semi-LASER localization and adiabatic selective refocusing pulses has been shown to minimize
these signal losses and a recent study evaluated the feasibility of this
method in a clinical setting13. In this study, we develop and evaluate
the feasibility of an echo planar-based diffusion-weighted spectroscopic
imaging using semi‐LASER localization (DW-sL-EPSI) at 3T, which uses pairs of
bipolar diffusion gradients to measure the apparent diffusion coefficient (ADC)
of metabolites.Materials and Methods:
Figure 1 shows the schematic diagram of
the DW-sL-EPSI sequence with diffusion sensitizing gradients (DSG) added in a bipolar
configuration. A slice‐selective 90° pulse was used for excitation followed by
two pairs of slice-selective adiabatic refocusing hyperbolic secant (HS) pulses.
Eight bipolar diffusion-weighted gradients where applied around the four HS
refocusing pulses in the three orthogonal directions simultaneously with 26.8
ms duration (δ),
and 71 ms diffusion time (Δ). The bipolar gradient scheme helps to
minimize eddy currents as well as cross terms between the diffusion
gradients and gradients rising from inhomogeneities of the B0
field. Spatial-spectral encoding was performed using a series of EPI readout
modules. Outer volume suppression and water
suppression via WET were implemented using the standard pulse sequence
components available.
To examine the efficiency and reliability, brain
phantom data were collected using the DW-sL-EPSI on a 3T Prisma MRI scanner
equipped with a 16-channel head ‘receive’ coil. Following parameters were used:
TE=120 ms, TR=2.5 ms, 1.5x1.5x2 cm3 voxel for VOI localization, 512
bipolar echo pairs, FOV = 16x16 cm2, 12 averages, spectral width 1190
Hz respectively. A non-water-suppressed scan with one average was also recorded
for eddy current correction and estimation of coil sensitivities. For both water-suppressed
and non-suppressed data, each gradient lobe was applied in 3 orthogonal
gradient directions at 2 and 21 mT/m resulting in b = 36 and 3996 s/mm2.
A non-zero b-value for the low b acquisition was used to assist suppressing
unwanted echo pathways. The signal processing of DW-sL-EPSI data and spectral quantification
based on peak integral was performed using a custom MATLAB (the Mathworks,
Inc., Natick, MA) program. Metabolite and water ADCs were estimated from mono-exponential fits.Results and Discussion:
Figure 2(A) shows the T1-weighted localization image with
VOI represented by a solid rectangle. Figure 2(B) and (C) shows the spectra
obtained from the 3x3 voxel within the VOI. Even at high b-value of 3996 s/mm2,
the quality of the MR spectra was sufficient to quantify the metabolites. There
was no noticeable difference in the metabolite line shape, and the quality of
the spectrum was sufficiently restored. Typical ADC maps for Glx (Glutamate +
Glutamine) from a phantom measurement is shown in Figure 3(a). Metabolite ADC
map was roughly homogeneous showing less variation in ADC estimation inside the
VOI. Table 1 shows ADC values for – four metabolites, total N-Acetylaspartate
(tNAA), total choline (tCho), creatine (Cr) and Glx – calculated from the
DW-EPSI phantom experiments which ensured the accuracy of the DW-sL-EPSI
results. The ADC values were consistent with previous studies6,10,14.
This demonstrates feasibility of implementing DW-sL-EPSI with bipolar DSG and
semi-LASER localization at 3T. As DSGs are applied only in a single direction,
the present work does not provide rotationally invariant estimates of ADCs.
Still, the DW-sL-EPSI results are in agreement with previous studies. One of
the limitations of the current implementation is the long scan time that could
limit clinical investigations. This can be overcome using accelerated imaging
technique such as non-uniform sampling combined with compressed sensing and
machine learning15,16. Conclusion:
Combining semi-LASER localization, echo planar readout
and bipolar DSG, we have demonstrated the pilot feasibility
of DW-sL-EPSI. While these initial results are promising, further optimization and validation with a
large pool of human subjects is needed. Future work will address robust
sampling and acceleration techniques. Acknowledgements
This research was supported by grants from 1) NIH/NHLBBI (5R01HL135562-03),
and 2) a Breakthrough Step I grant from the US Congressionally Directed Medical
Research Program (CDMRP)/ Breast Cancer Research Program (BCRP) (W81XWH-16-1-0524).References
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