title: Mapping the alterations in glutamate with GluCEST MRI in a mouse model of dopamine deficiency.
abstract: Glutamate chemical exchange saturation transfer (GluCEST) MRI was used to measure metabolic changes in mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) by mapping regional cerebral glutamate. The GluCEST contrast following MPTP treatment was correlated with1H-MR spectroscopy, motor function, and immunohistochemical measures. The GluCEST contrast was found to be significantly higher in the striatum and motor cortex of mice treated with MPTP than in controls (p < 0.001), which was confirmed by localized1H-MR spectroscopy. Elevated striatal GluCEST was positively associated with local astrogliosis measured by immunohistochemistry for glial fibrillary acidic protein. Additionally, a negative correlation was found between motor function, measured by the four-limb grip strength test, and GluCEST of the striatum (R = -0.705, p < 0.001) and the motor cortex (R = -0.617, p < 0.01), suggesting a role of elevated glutamate in the abnormal cerebral motor function regulation. The GluCEST contrast and glial fibrillary acidic protein immunostaining were unaltered in the thalamus indicating glutamate elevation was localized to the striatum and the motor cortex. These findings suggest that in addition to measuring spatial changes in glutamate, GluCEST may serve as an in vivo biomarker of metabolic and functional changes that may be applied to the assessment of a broad range of neuropathologies. Read the Editorial Highlight for this article on page 346.
authors.affiliation: Center for Magnetic Resonance and Optical Imaging (CMROI), Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Puneet
authors.initials: P
authors.lastname: Bagga
authors.affiliation: Center for Magnetic Resonance and Optical Imaging (CMROI), Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Rachelle
authors.initials: R
authors.lastname: Crescenzi
authors.affiliation: Center for Magnetic Resonance and Optical Imaging (CMROI), Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Guruprasad
authors.initials: G
authors.lastname: Krishnamoorthy
authors.affiliation: Center for Magnetic Resonance and Optical Imaging (CMROI), Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Verma
authors.affiliation: Center for Magnetic Resonance and Optical Imaging (CMROI), Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Ravi Prakash Reddy
authors.initials: RP
authors.lastname: Nanga
authors.affiliation: Center for Magnetic Resonance and Optical Imaging (CMROI), Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Damodar
authors.initials: D
authors.lastname: Reddy
authors.affiliation: Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Joel
authors.initials: J
authors.lastname: Greenberg
authors.affiliation: Center for Functional Neuroimaging, Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: John A
authors.initials: JA
authors.lastname: Detre
authors.affiliation: Center for Magnetic Resonance and Optical Imaging (CMROI), Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Hari
authors.initials: H
authors.lastname: Hariharan
authors.affiliation: Center for Magnetic Resonance and Optical Imaging (CMROI), Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania. krr@upenn.edu.
authors.forename: Ravinder
authors.initials: R
authors.lastname: Reddy
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D004298:Dopamine / Q000172:deficiency*; D015259:Dopamine Agents / Q000633:toxicity; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000473:pathology; D018698:Glutamic Acid / Q000378:metabolism*; D018737:Hand Strength; D020267:MPTP Poisoning / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism
chemical_list: D015259:Dopamine Agents; D005904:Glial Fibrillary Acidic Protein; C493465:Slc17a7 protein, mouse; D050598:Vesicular Glutamate Transport Protein 1; C528900:glial fibrillary astrocytic protein, mouse; D018698:Glutamic Acid; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine
keywords: 
  CEST
  ; 
  GFAP
  ; 
  MRI
  ; astrogliosis; brain; glutamate; tyrosine hydroxylase