title: In vivo cardiac 1H-MRS in the mouse.
abstract: The mouse is the predominant animal model to study the effect of gene manipulations. Imaging techniques to define functional effects on the heart caused by genomic alterations are becoming increasingly routine in mice, yet methods for in vivo investigation of metabolic phenotypes in the mouse heart are lacking. In this work, cardiac 1H-MRS was developed and applied in mouse hearts in vivo using a single-voxel technique (PRESS). In normal C57Bl/6J mice, stability and reproducibility achieved by dedicated cardiac and respiratory gating was demonstrated by measuring amplitude and zero-order phase changes of the unsuppressed water signal. Various cardiac metabolites, such as creatine, taurine, carnitine, or intramyocardial lipids were successfully detected and quantified relative to the total water content in voxels as small as 2 microl, positioned in the interventricular septum. The method was applied to a murine model of guanidinoacetate N-methyltransferase (GAMT) deficiency, which is characterized by substantially decreased myocardial creatine levels. Creatine deficiency was confirmed noninvasively in myocardium of anesthetized GAMT-/- mice. This is the first study to report the application of cardiac 1H-MRS in mice in vivo.
authors.affiliation: Department of Cardiovascular Medicine, University of Oxford, UK. jurgen.schneider@cardiov.ox.ac.uk
authors.forename: Jürgen E
authors.initials: JE
authors.lastname: Schneider
authors.forename: Damian J
authors.initials: DJ
authors.lastname: Tyler
authors.forename: Michiel
authors.initials: M
authors.lastname: ten Hove
authors.forename: A Elizabeth
authors.initials: AE
authors.lastname: Sang
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Cassidy
authors.forename: Alexandra
authors.initials: A
authors.lastname: Fischer
authors.forename: Julie
authors.initials: J
authors.lastname: Wallis
authors.forename: Liam M
authors.initials: LM
authors.lastname: Sebag-Montefiore
authors.forename: Hugh
authors.initials: H
authors.lastname: Watkins
authors.forename: Dirk
authors.initials: D
authors.lastname: Isbrandt
authors.forename: Kieran
authors.initials: K
authors.lastname: Clarke
authors.forename: Stefan
authors.initials: S
authors.lastname: Neubauer
mesh_terms: D000818:Animals; D002331:Carnitine / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D005240:Feasibility Studies; D005989:Glycerides / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism*; D013654:Taurine / Q000378:metabolism
chemical_list: D005989:Glycerides; D013654:Taurine; D003401:Creatine; D002331:Carnitine