In-vivo Magnetic Resonance Imaging of GABA and Glutamate

TL;DR

This paper introduces a novel spectrally-edited MRI technique called overlap-resolved CEST (orCEST) that improves specificity in mapping brain metabolites, successfully separating Glutamate and GABA signals in vivo, and demonstrating changes under water deprivation.

Contribution

The paper presents the first application of the orCEST method to distinguish GABA and Glutamate in vivo, overcoming spectral overlap limitations in CEST MRI.

Findings

Successfully separated GABA and Glutamate signals in rat brains.

Detected neurotransmitter level changes due to water deprivation.

Validated the effectiveness of orCEST in neuroscience applications.

Abstract

Chemical Exchange Saturation Transfer (CEST) Magnetic Resonance Imaging (MRI) is a molecular imaging methodology capable of mapping brain metabolites with relatively high spatial resolution. Specificity is the main goal of such experiments; yet CEST is confounded by spectral overlap between different molecular species. Here, we overcome this major limitation using a general framework termed overlap-resolved CEST (orCEST) - a kind of spectrally-edited experiment restoring specificity. First, we present evidence revealing that CEST experiments targeting the central nervous system's primary excitatory neurotransmitter, Glutamate (GluCEST) - is significantly contaminated by gamma-aminobutyric acid (GABA) - the primary inhibitory neurotransmitter in the CNS. Then, we harness the novel orCEST methodology to separate Glutamate and - for the first time - GABA signals, thus delivering the desired specificity. In-vivo orCEST experiments resolved the rat brain's primary neurotransmitters and revealed changes in Glutamate and GABA levels upon water deprivation in thirst-related areas. orCEST's features bode well for many applications in neuroscience and biomedicine.