Validation of [1-11C]acetate as a tracer for noninvasive assessment of oxidative metabolism with positron emission tomography in normal, ischemic, postischemic, and hyperemic canine myocardium.

Armbrecht, Juergen; Buxton, Denis B.; Schelbert, H R

doi:10.1161/01.cir.81.5.1594

Cited by 156 publications

(74 citation statements)

References 25 publications

(3 reference statements)

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“…22 Myocardial sectors defined by the polar map were then transferred to the whole dynamic sequence, and time-activity curves were obtained. The early phase of 11 C acetate washout was fitted monoexponentially to obtain the constant k(mono) as a previously validated measure of oxidative metabolism, 15 expressed in another polar map. The average of k(mono) for the whole map was calculated to define global myocardial oxygen consumption.…”

Section: Petmentioning

confidence: 99%

“…Clearance kinetics of 11 C acetate were used to quantify tricarboxylic acid cycle flux, which is directly related to overall myocardial oxidative metabolism. 15 By a combination with noninvasive measures of cardiac function, a previously validated estimate of myocardial efficiency was derived. 13 Additionally, the norepinephrine analogue 11 C HED was used in transplant recipients to quantify presence and extent of sympathetic reinnervation.…”

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confidence: 99%

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Myocardial Efficiency and Sympathetic Reinnervation After Orthotopic Heart Transplantation

et al. 2001

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Background-The lack of cardiac catecholamine uptake and storage caused by sympathetic denervation may influence performance of the transplanted heart. Reinnervation, occurring late after transplantation, may partially resolve these effects. In this study, oxidative metabolism and its relation to cardiac work were compared in allografts and normal and failing hearts, and the effects of sympathetic reinnervation were evaluated. Methods and Results-Twenty-seven nonrejecting, symptom-free transplant recipients, 11 healthy control subjects, and 10 patients with severe dilated cardiomyopathy underwent PET with 11 C acetate for assessment of oxidative metabolism by the clearance constant k(mono) and radionuclide angiography or MRI for measurement of ventricular function, geometry, and work. Efficiency was estimated noninvasively by a work-metabolic index [WMIϭ(stroke volumeϫheart rateϫsystolic pressure)/k(mono)]. In 14 of 27 transplants, presence of regional reinnervation was identified with PET and the catecholamine analogue 11 C hydroxyephedrine (extent, 24Ϯ14% of left ventricle). The WMI was comparable in normal subjects and reinnervated and denervated transplants (6.2Ϯ2.3 versus 4.9Ϯ2.0 versus 4.9Ϯ1.2 ⅐ 10 6 mm Hg · mL; PϭNS) and significantly lower in cardiomyopathy patients (3.0Ϯ1.3 ⅐ 10 6 mm Hg ⅐ mL; PϽ0.001). For normal subjects and transplant recipients, the WMI was significantly correlated with afterload (peripheral vascular resistance; rϭϪ0.65, PϽ0.01), preload (end-diastolic volume; rϭ0.78, PϽ0.01), and stroke volume (rϭ0.81, PϽ0.01) but not with hydroxyephedrine retention (transplants only; rϭ0.09, PϭNS). Conclusions-After transplantation, cardiac efficiency is improved compared with failing hearts and comparable to normal hearts. Differences between denervated and reinnervated allografts were not surveyed. Additionally, the dependency on loading conditions and contractility was preserved, suggesting that normal regulatory interactions for efficiency are intact and that sympathetic tone does not play a role under resting conditions.

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Section: Petmentioning

confidence: 99%

mentioning

confidence: 99%

Myocardial Efficiency and Sympathetic Reinnervation After Orthotopic Heart Transplantation

et al. 2001

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“…These results can for the large part be attributed to the following factors. First, based on previous investigations, 19 Methods 1 and 3 assume that release of 11 Clabelled metabolites, such as amino acids, TCA cycle intermediates and 11 CO 2 , during the initial myocardial uptake phase is minimal. However, it has been shown that, within the first 2 and 4 minutes, nearly 14% and 42% of radioactivity, respectively, can be ascribed to 11 C-labelled metabolites.…”

Section: Journal Of Nuclear Cardiologymentioning

confidence: 99%

“…Second, several studies have shown that myocardial extraction of [ 11 C]acetate is incomplete, decreasing with increasing myocardial perfusion. 8,9,19 Recent data suggest that the extraction fraction of [ 11 C]acetate ranges from 90% to 80% within the flow range of .5-1.0 mL/ minute/g. 8,9 Therefore, K 1 , being the product of flow and extraction fraction, will always be lower than MBF.…”

Section: Journal Of Nuclear Cardiologymentioning

confidence: 99%

Potential of [11C]acetate for measuring myocardial blood flow: Studies in normal subjects and patients with hypertrophic cardiomyopathy

Timmer

Lubberink

Germans

et al. 2010

Journal of Nuclear Cardiology

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Background. Measuring the rate of clearance of carbon-11 labelled acetate from myocardium using positron emission tomography (PET) is an accepted technique for noninvasively assessing myocardial oxygen consumption. Initial myocardial uptake of [ 11 C]acetate, however, is related to myocardial blood flow (MBF) and several tracer kinetic models for quantifying MBF using [11 C]acetate have been proposed. The objective of this study was to assess these models.Methods. (J Nucl Cardiol 2010;17:264-75.)

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“…In a canine model with coronary artery stenosis, for the normal myocardial territory, when a vasodilator (e.g., adenosine or dipyridamole) is applied, regional blood flow will increase without a significant change in MVO 2 (24). According to Eq.…”

Section: Theory Of the Measurement Of Mpr With Bold Imagingmentioning

confidence: 99%

Assessment of myocardial oxygen extraction fraction and perfusion reserve with BOLD imaging in a canine model with coronary artery stenosis

Zhang

Gropler

et al. 2007

Magnetic Resonance Imaging

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Purpose:To determine the feasibility of T 2 -weighted BOLD imaging for estimating regional myocardial oxygen extraction fraction (OEF) and approximating perfusion reserve (MPR) simultaneously in a canine model with moderate coronary artery stenosis. Materials and Methods:Eight mongrel dogs with moderate coronary artery stenosis underwent BOLD imaging at rest and during dipyridamole-induced hyperemia, using a turbo spin echo (TSE) sequence. Based on a two-compartment model, myocardial OEF hyperemia was calculated with the corresponding T 2 . MPR could be approximated based on Fick's law. Results:During responsive hyperemia, a regional hypointensity was observed in the abnormally perfused myocardium, reflecting a relatively smaller myocardial T 2 increase (3.06% Ϯ 2.74%, in contrast to 10.19% Ϯ 4.12% in the normal region). The average OEFs in the normally and abnormally perfused myocardial territories were 0.21 Ϯ 0.11 and 0.43 Ϯ 0.12, respectively. For the MPR approximated from the BOLD imaging, a strong correlation (R ϭ 0.9) in the normal myocardium and a good correlation (R ϭ 0.6) distal to the stenosis were obtained compared to microsphere results. Conclusion:In a canine model with moderate coronary artery stenosis, TSE-based BOLD imaging can quantitatively estimate the regional OEF hyperemia and approximate the MPR, and can distinguish segments perfused by defected coronary artery. CORONARY ARTERY DISEASE (CAD) manifests as an imbalance between myocardial oxygen supply and demand. The myocardial oxygen extraction fraction (OEF) and myocardial perfusion reserve (MPR, the ratio of peak myocardial blood flow to the baseline) are two important physiological indices of CAD and can provide early information for detecting ischemic heart disease. First-pass magnetic resonance imaging (MRI) can quantify MPR by bolus-tracking kinetics of the injected contrast agent (1-3) with a relatively high signal-tonoise ratio (SNR) and high sensitivity (4). However, this approach cannot provide information about the myocardial oxygenation, and requires at least two contrastagent injections to measure the myocardial blood flow at rest and during pharmacologic stress. Alternatively, MR blood oxygen level-dependent (BOLD) imaging may serve as a non-contrast-agent approach to determine myocardial oxygenation (5-7) and to estimate MPR at the same time (8). Briefly speaking, alterations of oxygen content in the capillaries and venous vessels result in different signal intensities in T* 2 -or T 2 -weighted MRI (known as the BOLD effect) because of the local magnetic field inhomogeneities in and around the vessel caused by paramagnetic deoxyhemoglobin in the vessels. Though T* 2 -weighted imaging has a larger signal response to changes in blood oxygenation than T 2 -weighted imaging (9), cardiac motion and the substantial field inhomogeneity between the heart and lung interface may cause artifacts in T* 2 -weighted gradient-echo-based BOLD images (10 -13), inhibiting accurate data interpretation in the myocardium. The T 2 -prepared steady-...

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Validation of [1-11C]acetate as a tracer for noninvasive assessment of oxidative metabolism with positron emission tomography in normal, ischemic, postischemic, and hyperemic canine myocardium.

Abstract: Extraction and clearance kinetics of

Cited by 156 publications

References 25 publications

Myocardial Efficiency and Sympathetic Reinnervation After Orthotopic Heart Transplantation

Myocardial Efficiency and Sympathetic Reinnervation After Orthotopic Heart Transplantation

Potential of [11C]acetate for measuring myocardial blood flow: Studies in normal subjects and patients with hypertrophic cardiomyopathy

Assessment of myocardial oxygen extraction fraction and perfusion reserve with BOLD imaging in a canine model with coronary artery stenosis

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