Objective To compare myocardial blood flow (MBF) and myocardial flow reserve (MFR) estimates from 82Rb PET data using ten software packages (SPs): Carimas, Corridor4DM, FlowQuant, HOQUTO, ImagenQ, MunichHeart, PMOD, QPET, syngo MBF, and UW-QPP. Background It is unknown how MBF and MFR values from existing SPs agree for 82Rb PET. Methods Rest and stress 82Rb PET scans of 48 patients with suspected or known coronary artery disease (CAD) were analyzed in 10 centers. Each center used one of the 10 SPs to analyze global and regional MBF using the different kinetic models implemented. Values were considered to agree if they simultaneously had an intraclass correlation coefficient (ICC) > 0.75 and a difference < 20% of the median across all programs. Results The most common model evaluated was the one-tissue compartment model (1TCM) by Lortie et al. (2007). MBF values from seven of the eight software packages implementing this model agreed best (Carimas, Corridor4DM, FlowQuant, PMOD, QPET, syngoMBF, and UW-QPP). Values from two other models (El Fakhri et al. in Corridor4DM and Alessio et al. in UW-QPP) also agreed well, with occasional differences. The MBF results from other models (Sitek et al. 1TCM in Corridor4DM, Katoh et al. 1TCM in HOQUTO, Herrero et al. 2TCM in PMOD, Yoshida et al. retention in ImagenQ, and Lautamäki et al. retention in MunichHeart) were less in agreement with Lortie 1TCM values. Conclusions SPs using the same kinetic model, as described in Lortie et al. (2007), provided consistent results in measuring global and regional MBF values, suggesting they may be used interchangeably to process data acquired with a common imaging protocol.

OBJECTIVE-Insulin stimulates brain glucose metabolism, but this effect of insulin is already maximal at fasting concentrations in healthy subjects. It is not known whether insulin is able to stimulate glucose metabolism above fasting concentrations in patients with impaired glucose tolerance.RESEARCH DESIGN AND METHODS-We studied the effects of insulin on brain glucose metabolism and cerebral blood flow in 13 patients with impaired glucose tolerance and nine healthy subjects using positron emission tomography (PET). All subjects underwent PET with both [18 F]fluorodeoxyglucose (for brain glucose metabolism) and [15 O]H 2 O (for cerebral blood flow) in two separate conditions (in the fasting state and during a euglycemic-hyperinsulinemic clamp). Arterial blood samples were acquired during the PET scans to allow fully quantitative modeling.RESULTS-The hyperinsulinemic clamp increased brain glucose metabolism only in patients with impaired glucose tolerance (whole brain: +18%, P = 0.001) but not in healthy subjects (whole brain: +3.9%, P = 0.373). The hyperinsulinemic clamp did not alter cerebral blood flow in either group.CONCLUSIONS-We found that insulin stimulates brain glucose metabolism at physiological postprandial levels in patients with impaired glucose tolerance but not in healthy subjects. These results suggest that insulin stimulation of brain glucose metabolism is maximal at fasting concentrations in healthy subjects but not in patients with impaired glucose tolerance.

The results demonstrate high reproducibility of myocardial perfusion quantitation with (15)O-labelled water PET using Carimas. The results support the feasibility of robust analysis and good clinical accuracy.

Evidence from both animal and human studies suggests that adenosine plays a role in the regulation of exercise hyperemia in skeletal muscle. We tested whether adenosine also plays a role in the regulation of blood flow (BF) distribution and heterogeneity among and within quadriceps femoris (QF) muscles during exercise, measured using positron emission tomography. In six healthy young women, BF was measured at rest and then during three incremental low and moderate intermittent isometric one-legged knee-extension exercise intensities without and with theophylline-induced nonselective adenosine receptor blockade. BF heterogeneity within muscles was calculated from 16-mm(3) voxels in BF images and heterogeneity among the muscles from the mean values of the four QF compartments. Mean BF in the whole QF and its four parts increased, and heterogeneity decreased with workload both without and with theophylline (P < 0.001). Adenosine receptor blockade did not have any effect on mean bulk BF or BF heterogeneity among the QF muscles, yet blockade increased within-muscle BF heterogeneity in all four QF muscles (P = 0.03). Taken together, these results show that BF becomes less heterogeneous with increasing exercise intensity in the QF muscle group. Adenosine seems to play a role in muscle BF heterogeneity even in the absence of changes in bulk BF at low and moderate one-leg intermittent isometric exercise intensities.

Positron emission tomography (PET) enables quantitative measurements of myocardial blood flow (MBF) and myocardial flow reserve (MFR). Recent developments and improved availability of PET technology have resulted in growing interest in translation of quantitative flow analysis from mainly a research tool to routine clinical practice. Quantitative PET measurements of absolute MBF and MFR have potential to improve accuracy of myocardial perfusion imaging in diagnosis of multivessel coronary artery disease as well as definition of the extent and functional importance of stenoses. This article reviews recent advances and experience in the quantitative myocardial perfusion imaging together with issues that need to be resolved for quantitative analysis to become clinical reality.

Proper muscle activation is a key feature of survival in different tasks in daily life as well as sports performance, but can be impaired in elderly and in diseases. Therefore it is also clinically important to better understand the phenomenon that can be elucidated in humans non-invasively by positron emission tomography (PET) with measurements of spatial heterogeneity of glucose uptake within and among muscles during exercise. We studied six healthy young men during 35 minutes of cycling at relative intensities of 30% (low), 55% (moderate), and 75% (high) of maximal oxygen consumption on three separate days. Glucose uptake in the quadriceps femoris muscle group (QF), the main force producing muscle group in recreational cycling, and its four individual muscles, was directly measured using PET and 18F-fluoro-deoxy-glucose. Within-muscle heterogeneity was determined by calculating the coefficient of variance (CV) of glucose uptake in PET image voxels within the muscle of interest, and among-muscles heterogeneity of glucose uptake in QF was expressed as CV of the mean glucose uptake values of its separate muscles. With increasing intensity, within-muscle heterogeneity decreased in the entire QF as well as within its all four individual parts. Among-muscles glucose uptake heterogeneity also decreased with increasing intensity. However, mean glucose uptake was consistently lower and heterogeneity higher in rectus femoris muscle that is known to consist of the highest percentage of fast twitch type II fibers, compared to the other three QF muscles. In conclusion, these results show that in addition to increased contribution of distinct muscle parts, with increases in exercise intensity there is also an enhanced recruitment of muscle fibers within all of the four heads of QF, despite established differences in muscle-part specific fiber type distributions. Glucose uptake heterogeneity may serve as a useful non-invasive tool to elucidate muscle activation in aging and diseased populations.

For global and regional MBF, Carimas and Cardiac VUer showed excellent agreement and intra-observer reproducibility. These results confirm that, for patients with intermediate likelihood of CAD, these validated SP are interchangeable and can be utilized for routine clinical practice of (15)O-water cardiac PET.

Previous human studies have shown divergent results concerning the effects of exercise training on myocardial blood flow (MBF) at rest or during adenosine-induced hyperaemia in humans. We studied whether these responses are related to alterations in adenosine A 2A receptor (A 2A R) density in the left-ventricular (LV) myocardium, size and work output of the athlete's heart, or to fitness level. MBF at baseline and during intravenous adenosine infusion, and A 2A R density at baseline were measured using positron emission tomography, and by a novel A 2A R tracer in 10 healthy male endurance athletes (ET) and 10 healthy untrained (UT) men. Structural LV parameters were measured with echocardiography. LV mass index was 71% higher in ET than UT (193 ± 18 g m −2 versus 114 ± 13 g m −2 , respectively). MBF per gram of tissue was significantly lower in the ET than UT at baseline, but this was only partly explained by reduced LV work load since MBF corrected for LV work was higher in ET than UT, as well as total MBF. The MBF during adenosine-induced hyperaemia was reduced in ET compared to UT, and the fitter the athlete was, the lower was adenosine-induced MBF. A 2A R density was not different between the groups and was not coupled to resting or adenosine-mediated MBF. The novel findings of the present study show that the adaptations in the heart of highly trained endurance athletes lead to relative myocardial 'overperfusion' at rest. On the other hand hyperaemic perfusion is reduced, but is not explained by A 2A R density.