Monitoring the Neurotransmitter Response to Glycemic Changes Using an Advanced Magnetic Resonance Spectroscopy Protocol at 7T

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The primary excitatory and inhibitory neurotransmitters glutamate (Glu) and gamma-aminobutyric acid (GABA) are thought to be involved in the response of the brain to changes in glycemia. Therefore, their reliable measurement is critical for understanding the dynamics of these responses. The concentrations of Glu and GABA, as well as glucose (Glc) in brain tissue, can be measured in vivo using proton ( 1H) magnetic resonance spectroscopy (MRS). Advanced MRS methodology at ultrahigh field allows reliable monitoring of these metabolites under changing metabolic states. However, the long acquisition times needed for these experiments while maintaining blood Glc levels at predetermined targets present many challenges. We present an advanced MRS acquisition protocol that combines commercial 7T hardware (Siemens Scanner and Nova Medical head coil), BaTiO 3 dielectric padding, optical motion tracking, and dynamic frequency and B 0 shim updates to ensure the acquisition of reproducibly high-quality data. Data were acquired with a semi-LASER sequence [repetition time/echo time (TR/TE) = 5,000/26 ms] from volumes of interest (VOIs) in the prefrontal cortex (PFC) and hypothalamus (HTL). Five healthy volunteers were scanned to evaluate the effect of the BaTiO 3 pads on B 1 + distribution. Use of BaTiO 3 padding resulted in a 60% gain in signal-to-noise ratio in the PFC VOI over the acquisition without the pad. The protocol was tested in six patients with type 1 diabetes during a clamp study where euglycemic (~100 mg/dL) and hypoglycemic (~50 mg/dL) blood Glc levels were maintained in the scanner. The new protocol allowed retention of all HTL data compared with our prior experience of having to exclude approximately half of the HTL data in similar clamp experiments in the 7T scanner due to subject motion. The advanced MRS protocol showed excellent data quality (reliable quantification of 11-12 metabolites) and stability ( p > 0.05 for both signal-to-noise ratio and water linewidths) between euglycemia and hypoglycemia. Decreased brain Glc levels under hypoglycemia were reliably detected in both VOIs. In addition, mean Glu level trended lower at hypoglycemia than euglycemia for both VOIs, consistent with prior observations in the occipital cortex. This protocol will allow robust mechanistic investigations of the primary neurotransmitters, Glu and GABA, under changing glycemic conditions.

Original languageEnglish (US)
Article number698675
JournalFrontiers in Neurology
StatePublished - Aug 18 2021

Bibliographical note

Funding Information:
This work was supported by the National Institute of Neurological Disorders and Stroke (NINDS) Grant R01 NS035192. The Center for Magnetic Resonance Research (CMRR) was supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB) Grant P41 EB027061 and NINDS Grant P30 NS076408. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.

Publisher Copyright:
© Copyright © 2021 Park, Deelchand, Joers, Kumar, Alvear, Moheet, Seaquist and Öz.


  • brain metabolism
  • dielectric pad
  • magnetic resonance spectography
  • prospective motion correction
  • ultrahighfield MRI


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