Dynamically Acquired 1H MRS for Detection of 13C Labeled Cerebral Glucose Metabolism In-vivo

Poster No:

2001 

Submission Type:

Abstract Submission 

Authors:

Masoumeh Dehghani1,2, Pedro Rosa-Neto3,4, Pierre Etienn5, Steven Zhang6, Chathura Kumaragamage7, Jamie Near1,2

Institutions:

1Centre d'Imagerie Cérébrale, Douglas Mental Health University, Montreal, Quebec, Canada, 2Dept of Psychiatry, McGill University, Montreal, Quebec, Canada, 3Translational Neuroimaging Laboratory, Douglas Research Institute, Montreal, Quebec, Canada, 4Dept of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada, 5Clinical Research Division, Montreal, Quebec, Canada, 6Dept of Neuroscience, McGill University, Montreal, Quebec, Canada, 7Dept of Radiology and Biomedical Imaging, Yale University, New Haven, CT, US

First Author:

Masoumeh Dehghani  
Centre d'Imagerie Cérébrale, Douglas Mental Health University|Dept of Psychiatry, McGill University
Montreal, Quebec, Canada|Montreal, Quebec, Canada

Co-Author(s):

Pedro Rosa-Neto  
Translational Neuroimaging Laboratory, Douglas Research Institute|Dept of Neurology and Neurosurgery, McGill University
Montreal, Quebec, Canada|Montreal, Quebec, Canada
Pierre Etienn  
Clinical Research Division
Montreal, Quebec, Canada
Steven Zhang  
Dept of Neuroscience, McGill University
Montreal, Quebec, Canada
Chathura Kumaragamage  
Dept of Radiology and Biomedical Imaging, Yale University
New Haven, CT, US
Jamie Near, Ph.D.  
Centre d'Imagerie Cérébrale, Douglas Mental Health University|Dept of Psychiatry, McGill University
Montreal, Quebec, Canada|Montreal, Quebec, Canada

Introduction:

NMR spectroscopy has been used to probe metabolic pathways in vivo following infusion of specific 13C‐enriched substrates. In the current study, we investigate the ability of the short TE SPECIAL sequence and the MEGA-PRESS J-editing sequence, without a 13C radiofrequency channel, to detect 13C labeled glucose metabolism in the brain, and we demonstrate for the first time its application in human participants.

Methods:

All experiments were performed on a Siemens 3T clinical MR scanner with a commercial body transmit-volume coil and 32-channel-receive array. B0 field inhomogeneities were minimized over volumes of interest (VOIs) by GRE-shim. 1H MRS data were acquired prior to and following the bolus infusion of 99% [1-13C] glucose in two healthy volunteers as described in a previous study (1). In the first subject, localized water suppressed 1H spectra were acquired using the SPECIAL sequence (2) (TR/TE = 2400/8.5 ms) from two VOIs measuring 4 x 3 x 2.5 cm3: one in the anterior and one in the posterior cingulate cortex(Fig 1.a). In the second subject, 1H spectra were acquired using the MEGA-PRESS editing sequence(3) (TR/TE = 3000/68 ms) from a VOI measuring 5 x 4.5 x 3.5 cm3 positioned over the precuneus/posterior cingulate (Fig 2.a). MEGA-PRESS involved two interleaved datasets of edit-on and edit-off to selectively refocus the evolution of J-coupling to the GABA spins at 3 ppm(3). Spectral pre-processing steps for both sequences included phase and frequency correction, averaging and subtraction of SPECIAL/MEGA-PRESS sub-spectra were performed in MATLAB using the FID-A toolkit(4). Labelling timeseries spectra were obtained by subtracting the processed pre-infusion spectrum from each subsequent timepoint's processed post-infusion spectrum. Using simulated basis spectra to model signal changes in both 12C-bonded and 13C-coupled resonances(5), the acquired spectra were fitted in LCModel to obtain labeling time courses for glutamate(Glu) and GABA. The fractional enrichments of Glu and GABA were calculated by comparing the post-infusion labelling time-series to the Glu and GABA concentrations estimated from the pre-infusion baseline scan.

Results:

Subtracting edit-off subspectra from edit-on subspectra in MEGA-PRESS removes overlying creatine signals from the edited spectrum, revealing the GABA signal in the difference spectrum. Fig 1.b and Fig 2.b shows the time-series of labeled-difference spectra acquired using SPECIAL and MEGA-PRESS sequences during and after 13C glucose infusion, respectively. The presence of the 13C label was clearly detectable in both labeled difference spectra, owing to the pronounced effect of heteronuclear (13C-1H) scalar coupling on the observed 1H spectra. The LCModel fit of post-infusion labeled-difference spectra, along with the fit residuals and the estimated fit components for Glu labeled at positions C4, C3, C2 and GABA labeled at positions C2 and C3 are shown in Fig 1.c and 2.c. The FE of Glu-C4 and Glu-C3 estimated using SPECIAL sequence was similar in both regions ACC and PCC, 11-13 % and 3-5%, respectively. At the end of the acquisition using MEGA-PRESS, the FEs of total labeled Glu and GABA were 27 % and 8 %, respectively.
Supporting Image: Figure1.jpg
Supporting Image: Figure2.jpg
 

Conclusions:

In the present study, we demonstrate the use of SPECIAL sequence and MEGA-PRESS editing sequence to follow the fate of 13C label from infused [1-13C] glucose in the human brain, in the absence of complicated hardware and heteronuclear decoupling RF pulses. This technique allows to detect the labeling of two major neurotransmitters, GABA and Glu signals. The changes in signal amplitudes of the Glu and GABA peaks in the labeled-difference time-series might give insight into the GABAergic and glutamatergic neurotransmitter cycling flux in the brain. These preliminary results suggest that both SPECIAL and MEGA-PRESS editing sequence has the potential to clearly detect the conversion of 13C labeled glucose into downstream cerebral metabolic products.

Modeling and Analysis Methods:

Methods Development 2

Novel Imaging Acquisition Methods:

MR Spectroscopy 1

Physiology, Metabolism and Neurotransmission :

Physiology, Metabolism and Neurotransmission Other

Keywords:

Data analysis
Development
GABA
Glutamate
Magnetic Resonance Spectroscopy (MRS)
Modeling
MR SPECTROSCOPY
MRI PHYSICS
Neurotransmitter
Other - glucose metabolism

1|2Indicates the priority used for review

My abstract is being submitted as a Software Demonstration.

No

Please indicate below if your study was a "resting state" or "task-activation” study.

Other

Healthy subjects only or patients (note that patient studies may also involve healthy subjects):

Healthy subjects

Was any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.

Yes

Was any animal research approved by the relevant IACUC or other animal research panel? NOTE: Any animal studies without IACUC approval will be automatically rejected.

Not applicable

Please indicate which methods were used in your research:

Other, Please specify  -   MRS

For human MRI, what field strength scanner do you use?

3.0T

Which processing packages did you use for your study?

Other, Please list  -   FID-A and LCModel

Provide references using author date format

1. Moreno A, Blüml S, Hwang J-H, Ross BD. (2001), 'Alternative 1-13C glucose infusion protocols for clinical 13C MRS examinations of the brain'. Magnetic Resonance in Medicine. vol 46, no. 1, pp. 39-48.
2. Mekle R, Mlynárik V, Gambarota G, Hergt M, Krueger G, Gruetter R. (2009), 'MR spectroscopy of the human brain with enhanced signal intensity at ultrashort echo times on a clinical platform at 3T and 7T'. Magnetic Resonance in Medicine, vol. 61, no 6, pp. 1279-1285.
3. Near J, Evans CJ, Puts NAJ, Barker PB, Edden RAE. ( 2013), 'J-difference editing of GABA: simulated and experimental multiplet patterns', Magnetic Resonance in Medicine, vol 70, no 5. pp. 1183-91.
4. Simpson R, Devenyi GA, Jezzard P, Hennessy TJ, Near J. ( 2017), 'Advanced processing and simulation of MRS data using the FID appliance (FID-A)-An open source, MATLAB-based toolkit'. Magnetic Resonance in Medicine, vol 77, no 1, pp 23-33.
5. Boumezbeur F, Besret L, Valette J, et al. (2004), 'NMR measurement of brain oxidative metabolism in monkeys using 13C-labeled glucose without a 13C radiofrequency channel'. Magnetic Resonance in Medicine, vol 52, no 1, pp. 33-40.