Multi-parameter in vivo cardiac magnetic resonance imaging demonstrates normal perfusion reserve despite severely attenuated beta-adrenergic functional response in neuronal nitric oxide synthase knockout mice.

AIMS: The role of neuronal nitric oxide synthase (nNOS) in regulating contractile function remains controversial, and in regulating myocardial perfusion is uninvestigated. We used magnetic resonance imaging (MRI) to phenotype nNOS(-/-) and wild-type (WT) mice regarding left ventricular (LV) structure, baseline function, beta-adrenergic responsiveness, and perfusion reserve. METHODS AND RESULTS: Cine MRI showed higher LV mass to end-diastolic volume ratio (2.3 +/- 0.2 mg/microL nNOS(-/-) vs. 1.7 +/- 0.1 mg/microL WT; P=0.032) and LV ejection fraction (64.9 +/- 2.1% nNOS(-/-) vs. 55.8 +/- 1.1% WT; P = 0.003) in nNOS(-/-). Myocardial tagging demonstrated similar baseline systolic circumferential strain (Ecc) in nNOS(-/-) and WT. With dobutamine, the normal change in Ecc was nearly absent in nNOS(-/-) (-0.5 +/- 0.3% nNOS(-/-) vs. -2.2 +/- 0.3% WT; P = 0.001), and the systolic strain rate (dEcc/dt) response to dobutamine seen in WT was reduced in nNOS(-/-) (-29 +/- 13%/s nNOS(-/-) vs. -106+/-16%/s WT; P = 0.001). Diastolic strain rate increased significantly with dobutamine only in WT. Arterial spin labelling showed that baseline perfusion and perfusion reserve with either dobutamine or an adenosine receptor agonist are normal in nNOS(-/-). CONCLUSION: MRI provides non-invasive in vivo evidence that nNOS does not play a role in basal contractile function or myocardial perfusion, but is required for increasing cardiac inotropy and lusitropy upon beta-adrenergic stimulation.

Black blood gradient echo cine magnetic resonance imaging of the mouse heart.

A black blood gradient echo sequence for multiphase cardiac MRI of the mouse heart was implemented on a 4.7-T scanner and compared to a conventional bright blood sequence. Black blood was achieved using the double inversion recovery technique. Ten mice were imaged using both the bright and the black blood sequences, and 2 of the mice were additionally imaged using bright and black blood sequences modified to perform myocardial tagging. Manual planimetry of the images was performed by two independent observers to detect the endocardial and epicardial borders and subsequently to compute chamber volumes and myocardial mass. Weight of the excised left ventricle was used as a gold standard for myocardial mass. Bland-Altman analysis demonstrated reduced interobserver variability for the measurement of cardiac volumes using the black blood sequence compared to the bright blood sequence (95% confidence interval was -0.89-0.73 microL for black blood versus -1.86-1.28 microL for bright blood). Also, Bland-Altman analysis showed that the black blood sequence provides improved accuracy for the measurement of myocardial mass compared to the bright blood sequence (average difference between MRI versus weight was 0.9 microg for black blood and -11.2 microg for bright blood, P < 0.01). For myocardial tagging, qualitative assessment demonstrated improved endocardial border definition using the black blood sequence. Black blood cine MRI in mice provides reduced interobserver variability and improved accuracy for the measurement of myocardial volumes and mass compared to the conventional bright blood technique.