Quantification of regional myocardial mean intracellular water lifetime: A nonhuman primate study in myocardial stress

Heart failure with preserved ejection fraction (HFpEF) is typically associated with early metabolic remodeling. Noninvasive imaging biomarkers that reflect these changes will be crucial in determining responses to early drug interventions in these patients. Mean intracellular water lifetime (τ i ) has been shown to be partially inversely related to Na, K‐ATPase transporter activity and may thus provide insight into the metabolic status in HFpEF patients. Here, we aim to perform regional quantification of τ i using dynamic contrast‐enhanced (DCE) magnetic resonance imaging (MRI) in the nonhuman primate (NHP) heart and evaluate its region‐specific variations under conditions of myocardial stress in the context of perturbed myocardial function. Cardiac stress was induced in seven naïve cynomolgus macaques using a dobutamine stepwise infusion protocol. All animals underwent 3 T cardiac dual‐bolus DCE and tagging MRI experiments. The shutter‐speed model was employed to quantify regional τ i from the DCE‐MR images. Additionally, τ i values were correlated with myocardial strains. During cardiac stress, there was a significant decrease in global τ i (192.9 ± 76.3 ms vs 321.6 ± 70 ms at rest, P < 0.05) in the left ventricle, together with an increase in global peak circumferential strain (−15.4% ± 2.7% vs −10.1% ± 2.9% at rest, P < 0.05). Specifically, slice‐level analysis further revealed that a greater significant decrease in mean τ i was observed in the apical region (Δτ I = 182.4 ms) compared with the basal (Δτ i = 113.2 ms) and midventricular regions (Δτ i = 108.4 ms). Regional analysis revealed that there was a greater significant decrease in mean τ i in the anterior (Δτ i = 243.9 ms) and antero‐lateral (Δτ i = 177.2 ms) regions. In the inferior and infero‐septal regions, although a decrease in τ i was observed, it was not significant. Whole heart regional quantification of τ i is feasible using DCE‐MRI. τ i is sensitive to regional changes in metabolic state during cardiac stress, and its value correlates with strain.