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BackgroundHigh levels of ketone bodies are associated with improved survival as observed with regular exercise, caloric restriction, and—most recently—treatment with sodium–glucose linked transporter 2 inhibitor antidiabetic drugs. In heart failure, indices of ketone body metabolism are upregulated, which may improve energy efficiency and increase blood flow in skeletal muscle and the kidneys. Nevertheless, it is uncertain how ketone bodies affect myocardial glucose uptake and blood flow in humans. Our study was therefore designed to test whether ketone body administration in humans reduces myocardial glucose uptake (MGU) and increases myocardial blood flow.Methods and ResultsEight healthy subjects, median aged 60 were randomly studied twice: (1) During 390 minutes infusion of Na‐3‐hydroxybutyrate (KETONE) or (2) during 390 minutes infusion of saline (SALINE), together with a concomitant low‐dose hyperinsulinemic–euglycemic clamp to inhibit endogenous ketogenesis. Myocardial blood flow was measured by 15O‐H2O positron emission tomography/computed tomography, myocardial fatty acid metabolism by 11C‐palmitate positron emission tomography/computed tomography and MGU by 18F‐fluorodeoxyglucose positron emission tomography/computed tomography. Similar euglycemia, hyperinsulinemia, and suppressed free fatty acids levels were recorded on both study days; Na‐3‐hydroxybutyrate infusion increased circulating Na‐3‐hydroxybutyrate levels from zero to 3.8±0.5 mmol/L. MGU was halved by hyperketonemia (MGU [nmol/g per minute]: 304±97 [SALINE] versus 156±62 [KETONE], P<0.01), whereas no effects were observed on palmitate uptake oxidation or esterification. Hyperketonemia increased heart rate by ≈25% and myocardial blood flow by 75%.ConclusionsKetone bodies displace MGU and increase myocardial blood flow in healthy humans; these novel observations suggest that ketone bodies are important cardiac fuels and vasodilators, which may have therapeutic potentials.

PurposeParametric imaging of absolute myocardial blood flow (MBF) using [15O]H2O enables determination of MBF with high spatial resolution. The aim of this study was to develop a method for generating reproducible, high-quality and quantitative parametric MBF images with minimal user intervention.MethodsNineteen patients referred for evaluation of MBF underwent rest and adenosine stress [15O]H2O positron emission tomography (PET) scans. Ascending aorta and right ventricular (RV) cavity volumes of interest (VOIs) were used as input functions. Implementation of a basis function method (BFM) of the single-tissue model with an additional correction for RV spillover was used to generate parametric images. The average segmental MBF derived from parametric images was compared with MBF obtained using nonlinear least-squares regression (NLR) of VOI data. Four segmentation algorithms were evaluated for automatic extraction of input functions. Segmental MBF obtained using these input functions was compared with MBF obtained using manually defined input functions.ResultsThe average parametric MBF showed a high agreement with NLR-derived MBF [intraclass correlation coefficient (ICC) = 0.984]. For each segmentation algorithm there was at least one implementation that yielded high agreement (ICC > 0.9) with manually obtained input functions, although MBF calculated using each algorithm was at least 10% higher. Cluster analysis with six clusters yielded the highest agreement (ICC = 0.977), together with good segmentation reproducibility (coefficient of variation of MBF <5%).ConclusionParametric MBF images of diagnostic quality can be generated automatically using cluster analysis and a implementation of a BFM of the single-tissue model with additional RV spillover correction.Electronic supplementary materialThe online version of this article (doi:10.1007/s00259-011-1730-3) contains supplementary material, which is available to authorized users.

We provide direct evidence that sarcomere mutations perturb the energetic cost of cardiac contraction. Gene-specific severity of cardiac abnormalities may underlie differences in disease onset and suggests that early initiation of metabolic treatment may be beneficial, in particular, in MYH7 mutation carriers.

Quantification of tumor perfusion using radioactive water (H 2 15 O) and PET is a promising method for monitoring treatment with antiangiogenic agents. However, use of dynamic H 2 15 O scans together with a fully 3-dimensional clinical PET/CT scanner needs to be validated. The purpose of the present study was to assess validity and reproducibility of dynamic H 2 15 O PET/CT scans for measuring tumor perfusion and validate the quantitative accuracy of parametric perfusion images. Methods: Eleven patients with non-small cell lung cancer were included in this study. Patients underwent 2 dynamic H 2 15 O (370 MBq) PET scans on the same day. During the first scan, arterial blood was withdrawn continuously. Input functions were derived from blood sampler data and the ascending aorta as seen in the images themselves (image-derived input function [IDIF]). Parametric perfusion images were computed using a basis function implementation of the standard single-tissuecompartment model. Volumes of interest (VOIs) were delineated on low-dose CT (LD-CT) and parametric perfusion images. Results: VOIs could be accurately delineated on both LD-CT and parametric perfusion images. These parametric perfusion images had excellent image quality and quantitative accuracy when compared with perfusion values determined by nonlinear regression. Good correlation between perfusion values derived from the blood sampler input function and IDIF was found (Pearson correlation coefficient, r 5 0.964; P , 0.001). Test-retest variability of tumor perfusion was 16% and 20% when delineated on LD-CT and parametric perfusion images, respectively. Conclusion: The use of ascending aorta IDIFs is an accurate alternative to arterial blood sampling for quantification of tumor perfusion. Image quality obtained with a clinical PET/CT scanner enables generation of accurate parametric perfusion images. VOIs delineated on LD-CT have the highest reproducibility, and changes of more than 16% in tumor perfusion are likely to represent treatment effects.