In vivo mouse myocardial (31)P MRS using three-dimensional image-selected in vivo spectroscopy (3D ISIS): technical considerations and biochemical validations.
(31)P MRS provides a unique non-invasive window into myocardial energy homeostasis. Mouse models of cardiac disease are widely used in preclinical studies, but the application of (31)P MRS in the in vivo mouse heart has been limited. The small-sized, fast-beating mouse heart imposes challenges regarding localized signal acquisition devoid of contamination with signal originating from surrounding tissues. Here, we report the implementation and validation of three-dimensional image-selected in vivo spectroscopy (3D ISIS) for localized (31)P MRS of the in vivo mouse heart at 9.4 T. Cardiac (31)P MR spectra were acquired in vivo in healthy mice (n = 9) and in transverse aortic constricted (TAC) mice (n = 8) using respiratory-gated, cardiac-triggered 3D ISIS. Localization and potential signal contamination were assessed with (31)P MRS experiments in the anterior myocardial wall, liver, skeletal muscle and blood. For healthy hearts, results were validated against ex vivo biochemical assays. Effects of isoflurane anesthesia were assessed by measuring in vivo hemodynamics and blood gases. The myocardial energy status, assessed via the phosphocreatine (PCr) to adenosine 5'-triphosphate (ATP) ratio, was approximately 25% lower in TAC mice compared with controls (0.76 ± 0.13 versus 1.00 ± 0.15; P < 0.01). Localization with one-dimensional (1D) ISIS resulted in two-fold higher PCr/ATP ratios than measured with 3D ISIS, because of the high PCr levels of chest skeletal muscle that contaminate the 1D ISIS measurements. Ex vivo determinations of the myocardial PCr/ATP ratio (0.94 ± 0.24; n = 8) confirmed the in vivo observations in control mice. Heart rate (497 ± 76 beats/min), mean arterial pressure (90 ± 3.3 mmHg) and blood oxygen saturation (96.2 ± 0.6%) during the experimental conditions of in vivo (31)P MRS were within the normal physiological range. Our results show that respiratory-gated, cardiac-triggered 3D ISIS allows for non-invasive assessments of in vivo mouse myocardial energy homeostasis with (31)P MRS under physiological conditions.
Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands.|Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Adrianus J
AJ
Bakermans
Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands.
Desiree
D
Abdurrachim
Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands.
Bastiaan J
BJ
van Nierop
Laboratory of Experimental Intensive Care and Anesthesiology, Department of Anesthesiology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Anneke
A
Koeman
Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands.
Inge
I
van der Kroon
Experimental Cardiology, Heart Failure Research Center, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Antonius
A
Baartscheer
Experimental Cardiology, Heart Failure Research Center, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Cees A
CA
Schumacher
Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands.|Biomedical Engineering and Physics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Gustav J
GJ
Strijkers
Laboratory Genetic Metabolic Diseases, Department of Clinical Chemistry, and Department of Pediatrics, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Sander M
SM
Houten
Laboratory of Experimental Intensive Care and Anesthesiology, Department of Anesthesiology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Coert J
CJ
Zuurbier
Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands.
Klaas
K
Nicolay
Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands.
Jeanine J
JJ
Prompers
D000255:Adenosine Triphosphate / Q000032:analysis*; D000769:Anesthesia, Inhalation; D018685:Anesthetics, Inhalation; D000818:Animals; D001011:Aorta; D004734:Energy Metabolism; D006439:Hemodynamics; D006706:Homeostasis; D021621:Imaging, Three-Dimensional / Q000379:methods*; D007530:Isoflurane; D008026:Ligation; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000737:chemistry* / Q000378:metabolism; D010100:Oxygen / Q000097:blood; D010725:Phosphocreatine / Q000032:analysis*; D010759:Phosphorus Isotopes; D018487:Ventricular Dysfunction, Left / Q000378:metabolism / Q000473:pathology
D018685:Anesthetics, Inhalation; D010759:Phosphorus Isotopes; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D007530:Isoflurane; D010100:Oxygen
31P MRS; ISIS; energy metabolism; heart; mouse; transverse aortic constriction (TAC)