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Feasibility of Partial 3D GluCEST in Healthy Human Adults at 7.0T
Ravi Prakash Reddy Nanga1, Abigail T. J. Cember1, Deepa Thakuri1, Dushyant Kumar1, Neil E. Wilson1, Hari Hariharan1, Mark Elliott1, Cynthia Neill Epperson2, and Ravinder Reddy1

1Radiology, University of Pennsylvania, Philadelphia, PA, United States, 2Psychiatry, University of Colorado, Aurora, CO, United States

Synopsis

GluCEST imaging at 7.0T has been promising in clinical applications as demonstrated in small subset of temporal lobe epilepsy subjects and in early psychosis. However, these studies employed 2D GluCEST limiting to single slice and limited coverage of anatomy of interest. Here, we tried to implement the partial 3D GluCEST in order to capture the glutamate contrast from the entire hippocampus as opposed to single slice in the same amount of time.

Introduction

Glutamate is an important excitatory neurotransmitter and has been implicated in many neurological conditions and disorders (1-3), and its excitotoxicity hypotheses had gained more importance in the last few decades. Chemical Exchange Saturation Transfer (CEST) imaging of glutamate (GluCEST) is an emerging technique and its applications in vivo, in preclinical models, and in human studies such as temporal lobe epilepsy and in early psychosis are promising (4-11). One of the limitations with the 2D study is its inability to capture the entire anatomy of interest and partial volume effects in the single slice. So, in this study we tried to explore the feasibility of entire hippocampus imaging with partial 3D GluCEST with an aim to do acquisition within the same time frame as for single slice 2D GluCEST.

Methods

All of the human studies were conducted under an approved Institutional Review Board study protocol. Five volunteers (4M, 1F) aged between 25-67 years participated in the study. The study protocol consisted of the following steps: a localizer, MPRAGE and T2-weighted imaging followed by 3D GluCEST. 3D GluCEST was performed on oblique slab covering the entire hippocampus in 7.0T Siemens scanner with a 32 channel phased array head coil using Siemens turbo flash sequence with a saturation preparation segment followed by a turbo flash read out (12) on an axial slice with the following parameters: number of slices = 12, slice thickness = 2mm, in-plane resolution = 1x1mm2, matrix size = 240x180, GRE readout TR/TE = 3.5/1.79ms, averages = 1, shot TR = 6000ms, dummy shots = 2, shots per slice = 3, PAT mode = GRAPPA, Acceleration factor PE = 2, Reference lines PE = 24, Elliptical scanning = on, Reordering = combined slice and phase encode spiral, and a saturation pulse of B1rms = 3.06μT with 800ms long saturation pulse train consisting of a series of 99ms Hanning windowed saturation pulses with a 1ms inter pulse delay (100ms pulse train). CEST images were acquired from ±1.8 to ±4.2ppm (water set at 0ppm) with a step-size of 0.3ppm and also at ±20 & 100ppm. To compute B0 maps water saturation shift referencing (WASSR) images (13) were collected from ±0 to ±1ppm (step-size 0.1ppm) with a saturation pulse of B1rms = 0.29μT with 200ms duration and imaging parameters identical to those used for CEST as described above. MP2RAGE which is a 2D multi-slice Siemens product sequence was used with the same spatial parameters as described for CEST to generate a T1 map which was further used for segmentation of gray and white matter for in vivo data. A relative B1 map was generated using square preparation pulses with flip-angles of 20°, 40° and 80°. The total acquisition time for the CEST images, and B0 and B1 field maps was approximately 10 min for each imaging session. GluCEST contrast map for the imaging slice were generated using in-house MATLAB routines, as described by Cai, K., et al (4).

Phantom: 10 mM Glutamate phantom was prepared at pH 7. For phantom in addition to the 3D GluCEST, 2D GluCEST was also performed with same parameters as above with the exception of being a single slice with a thickness of 4mm and the averages set to 2.

Results & Discussion

Due to fold over artifacts in the first and last slices in the 3D data set, they were removed from analysis and the data presented are from rest of the slices.

For phantom as shown in Figure 1, the GluCEST contrast from the 2D slice was 4.7 ± 0.4% and the corresponding slices from 3D are 6th & 7th slice and the GluCEST contrast were 4.69 ± 0.4% & 4.64 ± 0.6%, respectively, while the mean GluCEST from all the slices were 4.55 ± 0.08% (range 4.43 - 4.69). Therefore, the contrast loss from 3D GluCEST is negligible when compared to 2D.

One set of representative GluCEST maps from all the slices covering the hippocampus region is shown in Figure 2 with the corresponding region of interest (i.e hippocampus) overlayed as shown in Figure 3. Mean GluCEST from the 3D scan of all the human volunteers from the slices corresponding to right and left hippocampus are 11.21 ± 0.7% (range 10.61% to 12.39%) and 11.56 ± 0.5% (range 10.83% to 12.05%), respectively.

Conclusions

In this study, we showed the feasibility of partial 3D GluCEST in phantoms and in humans with the acquisition time being same as that of 2D GluCEST.

Acknowledgements

This project was supported by the National Institute of Biomedical Imaging and Bioengineering of the National Institute of Health through grant number p41-EB015893 and by the National Institute of Drug Abuse of the National Institutes of Health under award Number R01DA037289.

References

1. Jolles J. Cognitive, emotional and behavioral dysfunctions in aging and dementia. In: Progress of brain research. Aging of the brain and Alzheimer’s disease. Elsevier Science Publishers, Amsterdam 1986;70:15-39.

2. Blandini F, Greenamyre JT. Protective and symptomatic strategies for therapy of Parkinson’s disease. Drugs Today (Barc) 1999;35(6):473-483.

3. Michaelis ML. Drugs targeting Alzheimer’s disease:some things old and some things new. J Pharmacol Exp Ther 2003;304(3):897-904.

4. Cai K, Haris M, Singh A, et al. Magnetic resonance imaging of glutamate. Nat Med. 2012;18(2):302-6.

5. Haris M, Nath K, Cai K, et al. Imaging of glutamate neurotransmitter alterations in Alzheimer's disease. NMR Biomed. 2013;26(4):386-91.

6. Crescenzi R, DeBrosse C, Nanga RPR, et al. In vivo measurement of glutamate loss is associated with synapse loss in a mouse model of tauopathy. Neuroimage. 2014;101:185-92.

7. Davis KA, Nanga RPR, Das S, et al. Glutamate imaging (GluCEST) lateralizes epileptic foci in nonlesional temporal lobe epilepsy. Sci Transl Med. 2015;7(309):309ra161.

8. Pepin J, Francelle L, Carrillo-de Sauvage MA, et al. In vivo imaging of brain glutamate defects in a knock-in mouse model of Huntington's disease. Neuroimage. 2016;139:53-64.

9. Bagga P, Crescenzi R, Krishnamoorthy G, et al. Mapping the alterations in glutamate with GluCEST MRI in a mouse model of dopamine deficiency. J Neurochem. 2016;139(3):432-439.

10. Crescenzi R, DeBrosse C, Nanga RPR, et al. Longitudinal imaging reveals subhippocampal dynamics in glutamate levels associated with histopathologic events in a mouse model of tauopathy and healthy mice. Hippocampus. 2017;27(3):285-302.

11. Roalf DR, Nanga RPR, Rupert PE, et al. Glutamate imaging (GluCEST) reveals lower brain GluCEST contrast in patients on the psychosis spectrum. Mol Psychiatry. 2017;22(9):1298-1305.

12. Krishnamoorthy G, Nanga RPR, Bagga P, et al. High quality three-dimensional gagCEST imaging of in vivo human knee cartilage at 7 Tesla. Magn Reson Med. 2017, 77(5):1866-1873.

13. Kim, M., Gillen, J., Landman, B.A., et al. Water saturation shift referencing (WASSR) for chemical exchange saturation transfer (CEST) experiments. Magn Reson Med. 2009, 61(6):1441-1450.

Figures

Figure 1. GluCEST map from the 2D acquisition in shown in the top panel while the bottom panel shows all the slices from the 3D acquisition with 6th and 7th slice corresponding to the 2D GluCEST slice.

Figure 2: One of the representative GluCEST maps for all the slices from the entire slab covering the hippocampus region in an oblique plane from a healthy volunteer is shown above.

Figure 3: Global CEST maps from the slices covering the hippocampus is shown in the top panel while the hippocampi region of interests (ROIs) drawn from the corresponding slice is shown in the bottom panel from one of the healthy volunteer. ROIs drawn on the slices covering the hippocampi were averaged for the mean GluCEST values for right and left hippocampus.

Proc. Intl. Soc. Mag. Reson. Med. 27 (2019)
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