1H Echo Planar Spectroscopic Imaging of 2-hydroxyglutarate in Gliomas at 7T in vivo
Zhongxu An1, Sandeep Ganji1, Vivek Tiwari1, Marco C. Pinho1,2, Edward Pan3,4,5, Bruce E. Mickey3,5,6, Elizabeth A. Maher3,4,6,7, and Changho Choi1,2,3

1Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, United States, 2Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, United States, 3Harold C. Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, United States, 4Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, United States, 5Department of Neurological Surgery, University of Texas Southwestern Medical Center, Dallas, TX, United States, 6Annette Strauss Center for Neuro-Oncology, University of Texas Southwestern Medical Center, Dallas, TX, United States, 7Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, United States

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 tumors1,2. 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 2HG3,4,5. 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 4T6,7. A recent study showed linear dependence of SNR and linewidth on field strength8. 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 method9. Since the published data processing methods10,11 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)ms12 in glioma patients. To avoid the chemical shift artifact in the re-gridding process8, 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 software13, 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 method9, 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 noise14. 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 studies15. 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 T2w-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 7T8, 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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Figures

Fig 1. Scan Parameters of in vivo 1H Echo Planar Spectroscopic Imaging at 7T

Fig 2. (a) The proposed read-out gradient-alternated scheme. The polarities of read-out gradients were reversed for odd- and even-number acquisitions. (b) Even-echo data of two acquisitions were swapped to increase spectral width.

Fig 3. (a) MR images of a normal subject. (b) EPSI-STEAM spectra of VOI. (c) 6 major metabolite maps. (d) Representative spectra of EPSI-STEAM TE=(16,30)ms from white-matter and gray-matter dominant regions, shown with LCModel fit and individual metabolite spectra.

Fig 4. (a) T2w-FLAIR images of a IDH-mutated glioma patient. Tumor was identified in left-frontal cortex region. (b) EPSI-PRESS spectra of VOI. (c) 2HG with 6 other major metabolite maps. (d) Representative spectra of EPSI-PRESS TE=(58,20)ms from tumor and contralateral region. Dotted pink lines were drawn at 2.25ppm.

Fig 5. (a) T2w-FLAIR images of a IDH-mutated glioma patient. Tumor were identified in left-frontal temporal region. (b) EPSI-PRESS spectra of VOI. (c) 2HG with 6 other major metabolite maps. (d) Representative spectra of EPSI-PRESS TE=(58,20)ms from tumor region. Dotted pink lines were drawn at 2.25ppm.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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