Synopsis
2-hydroxyglutarate (2HG) is the first imaging biomarker for
IDH-mutated gliomas. High-spatial resolution spectroscopic imaging of 2HG is clinically
important. We propose a new EPSI read-out scheme to overcome the conventional
limitation of EPSI spectral bandwidth at high field. With SNR and linewidth benefit
at 7T, we demonstrated the in vivo feasibility of this new EPSI method in mapping
of 2HG and other important brain metabolites in normal subject and glioma
patients at 7T.PURPOSE
Mutations in isocitrate
dehydrogenase (IDH) 1 and 2 in gliomas are associated with longer survival and
better response to therapy than IDH wild-type tumors
1,2. Elevated in
IDH-mutated gliomas, 2-hydroxyglutarate (2HG) is well established as a
biomarker for diagnosis and prognosis in brain tumors. Recently, single voxel
1H MRS has been proposed for in vivo
detection of 2HG
3,4,5. There is a high interest in high-spatial
resolution spectroscopic imaging of 2HG and other important metabolites in
brain tumors.
1H Echo Planar Spectroscopic Imaging (EPSI) is an
effective tool for high-resolution imaging of brain metabolites at 3T and 4T
6,7.
A recent study showed linear dependence of SNR and linewidth on field strength
8.
Hence, 7T EPSI may be advantageous for mapping low concentration metabolites.
However, application of EPSI at 7T is strongly restricted due to small spectral
width, which occurs in the conventional odd-even-echo reconstruction method
9.
Since the published data processing methods
10,11 for expanding EPSI spectral width are complicated
and time consuming, a simple EPSI method with high spatial resolution may be highly
beneficial for clinical application. Here we report a novel EPSI approach, a
read-out gradient-alternated scheme, that can reliably measure the distribution
of 2HG and other important metabolites at 7T with high spatial resolution,
doubled spectral width, and low read-out gradient strength.
METHODS
The new EPSI method was
tested in 1 normal adult subject and 2 IDH-mutated glioma patients. The volume
prescription for EPSI acquisition was obtained with water-suppressed short-TE
STEAM in normal subject, and with a previously-reported 2HG-optimized PRESS (TE1,TE2)=(58,20)ms
12
in glioma patients. To avoid the chemical shift artifact in the re-gridding
process
8, data were acquired only during the plateau of read-out
gradient. Other scan parameters were as shown in Fig. 1. Data were acquired
with a 32-channel head coil in a 7T whole-body scanner (Philips Medical
Systems). A read-out gradient-alternated scheme was used for acquisition (Fig.
2a) and data were re-ordered during the first step of post-processing (Fig.
2b). The k-space data were zero-filled to 40x34 and 66x60, resulting in 0.25mL
and 0.13mL voxel sizes in normal and glioma subjects, respectively. Data in the
time domain were zero-filled to 4096 points. 1-Hz and 3-Hz exponential functions
were applied to the time-domain data from normal and glioma subjects,
respectively. Water-unsuppressed data were used for eddy-current compensation
and multi-channel combination. Spectral fitting was performed, with LCModel software
13,
using in-house calculated basis spectra of 15 metabolites. Metabolites were
quantified with reference to creatine in normal gray-matter region at 8mM.
RESULTS
and DISCUSSION
As shown in Fig. 2a,
the polarities of echo-planar readout gradients for even- and odd-number
acquisitions were opposite to each other. During data reconstruction, even-echo
data from the two acquisitions were swapped to maintain the same acquisition
gradient polarity in the time-domain data (Fig. 2b). This newly-proposed method
resulted in two-fold greater spectral bandwidth than conventional odd-even-echo
data processing method
9, while preserving the SNR (data not shown). In
addition, low read-out gradient strength and ramp-up rate (7.5-9.5mT/m and
90mT/m/ms, respectively), were used at 7T, which reduced gradient-caused
artifact and acoustic noise
14. Figure 3 shows EPSI spectra (voxel
size 0.13mL) from the cortex region of normal subjects together with 6
metabolite maps and representative spectra. Metabolite distributions were in good
agreement with prior MRSI studies
15. The EPSI spectra from a glioma
patient are shown in Fig. 4. A 2HG signal was clearly discernible at 2.25ppm in
the spectra from tumor, while 2HG signal was null in the contralateral data (Fig.
4d). Metabolite maps showed that high 2HG, high total choline (tCho) and low
NAA (Fig 4c) correlated with T
2w-FLAIR high-intensity region. Fig. 5
shows the EPSI data from a subject with tumor in the temporal region, which is
often challenging for MRS imaging. The overall baseline of spectra was quite
flat, and metabolite signals were well defined in all spectra without
substantial artifacts. In the tumor region, 2HG distribution was heterogeneous between
0mM and 5mM, while tCho and NAA distributions were quite uniform (~1.4mM and
~2.5mM, respectively).
CONCLUSION
We report a novel gradient-alternated
EPSI readout scheme, together with the post-processing at 7T. This method
doubles the EPSI spectral width, compared with the conventional method. With SNR
benefit at 7T
8, we demonstrated the capability of this new EPSI
method for mapping 2HG and other important metabolites in gliomas with high spatial
resolution, reasonable spectral width, and low gradient strength. In
conclusion, 2HG and other brain metabolites can be reliably mapped with our
proposed EPSI method at 7T. The method may provide an effective tool for
studying potential alterations in metabolite levels in brain tumors and
neuro-psychiatric diseases.
Acknowledgements
This work was supported by Cancer Prevention Research Institute of Texas grant RP140021-P04 and RP130427 and a US National Institutes of Health grant CA184584.References
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