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Simple and accurate assessment of forward cardiac output by use of 1-[11C]acetate PET verified in a pig model
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
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2003 (English)In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 44, no 7, 1176-1183 p.Article in journal (Refereed) Published
Abstract [en]

Dynamic 1-(11)C-acetate PET (AC-PET) allows quantification of myocardial blood flow and oxidative metabolism. We wanted to determine the accuracy of AC-PET in measuring cardiac output (CO) using first-pass analysis and the indicator dilution principle. Further, we wanted to investigate the pulmonary uptake of acetate in relation to left atrial filling pressures and ventricular function.

METHODS: Twenty-four steady-state experiments were performed in 5 domestic pigs. Pulmonary capillary wedge pressure (PCWP) and CO by thermodilution (CO(thermo)) were recorded invasively simultaneous with AC-PET scans at baseline (n = 9), dobutamine infusion (n = 6), high-dose metoprolol and morphine (n = 6), and angiotensinamide infusion (n = 3). 1-(11)C-Acetate was injected as a rapid manual bolus. Regions of interest (ROIs) were placed in the right (RV) and left (LV) heart cavities. Time-activity curves were constructed and the area under the curve (AUC) was integrated from beginning the scan to the time of visually determined recirculation by simple arithmetic. CO by PET (CO(PET)) was calculated as injected dose/AUC. Image handling and curve analysis were repeated by a blinded observer. Total pulmonary extravascular retention of (11)C, expressed as percentage of injected dose (lung-uptake %ID), was measured using a combination of transmission, (15)O-carbon monoxide, and AC-PET scans.

RESULTS: CO(thermo) ranged from 2.1 to 8.2 L/min. CO(PET) determined from both LV and RV was linearly related to CO(thermo) with slopes close to 1 (LV, r = 0.98; RV, r = 0.96; both P < 0.001). Interobserver reproducibility was r = 0.98, P < 0.001. The PCWP range was 6-14 mm Hg and the lung-uptake %ID was 2.7-8.5 %ID. When normalized to baseline, lung-uptake %ID was correlated with PCWP (r = 0.56, P = 0.01) and linearly correlated with LV input resistance (PCWP divided by CO(thermo); r = 0.91, P < 0.001). When both lung-uptake %ID and stroke volume were normalized to baseline, a piecewise linear relation was found (r = 0.95, P < 0.001).

CONCLUSION: Our results suggest that measurements of CO by AC-PET are feasible and accurate. Using RV ROIs might favor CO measurements by any injectable PET tracer. The lung-uptake %ID might be useful in evaluation of pulmonary congestion, but further studies are needed.

Place, publisher, year, edition, pages
2003. Vol. 44, no 7, 1176-1183 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-92350PubMedID: 12843234OAI: oai:DiVA.org:uu-92350DiVA: diva2:165392
Available from: 2004-11-15 Created: 2004-11-15 Last updated: 2013-07-02Bibliographically approved
In thesis
1. PET in Heart Failure - Methods and Applications
Open this publication in new window or tab >>PET in Heart Failure - Methods and Applications
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
PET vid hjärtsvikt - metoder och tillämpningar
Abstract [en]

Positron Emission Tomography (PET) permits regional myocardial perfusion, fibrosis and oxidative metabolism to be non-invasively quantified with radioactive tracers such as [15O]-water and [1-11C]-acetate. PET is an established research tool in congestive heart failure (CHF), a major cause of morbidity and mortality. However, as CHF is a syndrome that eventually affects all aspects of cardiac and systemic hemodynamic function, more clinically relevant information from a single PET scan is desirable. The aim of this thesis therefore was to develop and implement some new concepts in cardiac PET.

A new method for the measurement of cardiac output with any tracer was validated in animal experiments and CHF patients. The early pulmonary retention of [1-11C]-acetate was inversely related to left ventricular (LV) function in animals and was directly proportional to lung water content and severity of LV diastolic dysfunction in patients.

Eight patients with acute myocardial infarction were followed with serial PET from 3 hours to 3 weeks after trombolytic treatment. PET revealed that myocardial perfusion and the extraction and utilization of fuel substrates all decreased closer to the infarct centre. The rate of oxygen utilization within the infarct at 3 h predicted degree of myocardial fibrosis, pulmonary oedema and tissue viability at 3 weeks.

Seventeen patients with CHF due to chronic ischemic cardiomyopathy and severely reduced LV function were evaluated with [1-11C]-acetate PET before and after coronary artery bypass surgery. There was a dramatic improvement in physical performance and symptoms, which was not correlated to the standard LV ejection indices. PET revealed that functional improvement was associated with improved LV loading conditions, reversed remodeling and homogenization of oxidative metabolism rather than increased output.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2004. 53 p.
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1387
Keyword
Medicine, congestive heart failure, myocardial ischemia, positron emission tomography, left ventricular dysfunction, tracer kinetic models, Medicin
National Category
Dermatology and Venereal Diseases
Identifiers
urn:nbn:se:uu:diva-4654 (URN)91-554-6085-2 (ISBN)
Public defence
2004-12-09, Akademiska sjukhuset, Robergsalen, Ingång 40, 4tr, Akademiska Sjukhuset, Uppsala, 13:15
Opponent
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Available from: 2004-11-15 Created: 2004-11-15Bibliographically approved

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Sörensen, JensStåhle, ElisabethLångström, BengtWikström, GerhardHedenstierna, Göran

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