Quantitative MRI biomarkers to characterize regional left ventricular perfusion and function in nonhuman primates during dobutamine-induced stress: A reproducibility and reliability study

Sampath, Smita; Parimal, Annamalai Sarayu; Dai, Feng; Chang, Miko May Lee; Baumgartner, Richard N.; Klimas, Michael; Jacobsen, Katja Kemp; Manigbas, Elaine; Gsell, Willy; Evelhoch, Jeffrey L.; Chin, Chih‐Liang

doi:10.1002/jmri.25379

Cited by 4 publications

(6 citation statements)

References 47 publications

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“…Interestingly, a significant increase in K trans was not observed in most regions during stress, although the trend/mean indicates that K trans increases during stress. The global mean perfusion reserve, calculated as the ratio of the global K trans under stress over that at rest, was found to be ~ 1.3, which was lower than our previously reported mean value of 1.6 calculated using the ratio of myocardial blood flow at stress over that at rest in the same cohort of animals . As K trans can be expressed as the product of myocardial blood flow (MBF) and extraction fraction (E), the fact that we see a lower increase in K trans than expected may indicate that E actually decreases.…”

Section: Discussioncontrasting

confidence: 88%

“…The global mean perfusion reserve, calculated as the ratio of the global K trans under stress over that at rest, was found to be~1.3, which was lower than our previously reported mean value of 1.6 calculated using the ratio of myocardial blood flow at stress over that at rest in the same cohort of animals. 33 As K trans can be expressed as the product of myocardial blood flow (MBF) and extraction fraction (E), the fact that we see a lower increase in K trans than expected may indicate that E actually decreases. According to the Renkin Crone equation, E = 1 -exp(-PS/MBF), where PS is the permeability surface area product.…”

Section: Discussionmentioning

confidence: 64%

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

Sampath¹,

Parimal²,

Huang

et al. 2020

NMR in Biomedicine

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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 (τi) 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 τi 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 τi from the DCE‐MR images. Additionally, τi values were correlated with myocardial strains. During cardiac stress, there was a significant decrease in global τi (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 τi was observed in the apical region (ΔτI = 182.4 ms) compared with the basal (Δτi = 113.2 ms) and midventricular regions (Δτi = 108.4 ms). Regional analysis revealed that there was a greater significant decrease in mean τi in the anterior (Δτi = 243.9 ms) and antero‐lateral (Δτi = 177.2 ms) regions. In the inferior and infero‐septal regions, although a decrease in τi was observed, it was not significant. Whole heart regional quantification of τi is feasible using DCE‐MRI. τi is sensitive to regional changes in metabolic state during cardiac stress, and its value correlates with strain.

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Section: Discussioncontrasting

confidence: 88%

Section: Discussionmentioning

confidence: 64%

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

Sampath¹,

Parimal²,

Huang

et al. 2020

NMR in Biomedicine

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“…In a previous study from our group, we were able to show the positive additional role of LV strain analysis during dobutamine stress in a group of patients with coronary artery disease [18]. A good reproducibility and a low inter-observer variability of dobutamine stress Echo and CMR has been previously observed in human [21,26] and animal studies [15]. However, only few studies concentrated on the reproducibility of LV strain in hyper-and hypo-contractility model.…”

Section: Discussionmentioning

confidence: 62%

“…Large animals, such as Landrace pigs, are instead more suited to investigate myocardial function under various pharmacological interventions given a cardiac anatomy and physiology closer to humans. There is only one study in the literature that has assessed the reproducibility of myocardial deformation parameters in large animals (macaque) [15] and no studies have performed such an analysis in pigs. Accordingly, we performed this preliminary study to evaluate inter-and intraobserver reproducibility of CMR-FT derived strain measurements in a porcine model of pharmacologically induced hyper-and hypo-contractility.…”

Section: Introductionmentioning

confidence: 99%

Cardiovascular magnetic resonance feature tracking in pigs: a reproducibility and sample size calculation study

Faragli

Tanacli

Kolp

et al. 2020

Int J Cardiovasc Imaging

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Cardiovascular magnetic resonance feature tracking (CMR-FT) is a novel technique for non-invasive assessment of myocardial motion and deformation. Although CMR-FT is standardized in humans, literature on comparative analysis from animal models is scarce. In this study, we measured the reproducibility of global strain under various inotropic states and the sample size needed to test its relative changes in pigs. Ten anesthetized healthy Landrace pigs were investigated. After baseline (BL), two further steps were performed: (I) dobutamine-induced hyper-contractility (Dob) and (II) verapamil-induced hypocontractility (Ver). Global longitudinal (GLS), circumferential (GCS) and radial strain (GRS) were assessed. This study shows a good to excellent inter- and intra-observer reproducibility of CMR-FT in pigs under various inotropic states. The highest inter-observer reproducibility was observed for GLS at both BL (ICC 0.88) and Ver (ICC 0.79). According to the sample size calculation for GLS, a small number of animals could be used for future trials.

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“…Biomarkers, such as peak circumferential strain, average diastolic strain rate, contractile reserve, and myocardial blood flow were reported to be robust with good interobserver and intra-observer reproducibility and test-retest reliability during pharmacologically induced stress in healthy male (7-10 years old) macaques. 113 Currently, it is unclear what tissue changes contribute to the ventricular dysfunction. Whether the LV extracellular space expansion, previously seen in the fetal heart, persists into adulthood or occurs in the RV has not yet been determined.…”

Section: Future Applications Of Cmr In the Study Of Cardiac Programmingmentioning

confidence: 99%

Cardiac magnetic resonance imaging: insights into developmental programming and its consequences for aging

Clarke

Kuo

et al. 2020

J Dev Orig Health Dis

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Cardiovascular diseases (CVD) are important consequences of adverse perinatal conditions such as fetal hypoxia and maternal malnutrition. Cardiac magnetic resonance imaging (CMR) can produce a wealth of physiological information related to the development of the heart. This review outlines the current state of CMR technologies and describes the physiological biomarkers that can be measured. These phenotypes include impaired ventricular and atrial function, maladaptive ventricular remodeling, and the proliferation of myocardial steatosis and fibrosis. The discussion outlines the applications of CMR to understanding the developmental pathways leading to impaired cardiac function. The use of CMR, both in animal models of developmental programming and in human studies, is described. Specific examples are given in a baboon model of intrauterine growth restriction (IUGR). CMR offers great potential as a tool for understanding the sequence of dysfunctional adaptations of developmental origin that can affect the human cardiovascular system.

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Quantitative MRI biomarkers to characterize regional left ventricular perfusion and function in nonhuman primates during dobutamine-induced stress: A reproducibility and reliability study

Abstract: 1 J. Magn. Reson. Imaging 2017;45:556-569.

Cited by 4 publications

References 47 publications

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

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

Cardiovascular magnetic resonance feature tracking in pigs: a reproducibility and sample size calculation study

Cardiac magnetic resonance imaging: insights into developmental programming and its consequences for aging

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