In-vivo Magnetic Resonance Imaging of GABA and Glutamate

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.