Michel Cogneau

Direct comparison of [13N]ammonia and [15O]water estimates of perfusion with quantification of regional myocardial blood flow by microspheres.

BackgroundBoth [13N ammonia and [15Olwater have been used to quantify myocardial blood flow with positron emission tomography using appropriate tracer kinetic models. A direct comparison of the two tracers with radioactive microspheres has not been performed in the same experimental preparation. Methods and ResultsThe two tracers have been tested for myocardial blood flow quantification in closed-chest dogs with circumflex coronary stenosis or permanent occlusion at rest and during adenosine-induced hyperemia. [13N]ammonia- and [15Olwater-derived myocardial blood flow values have been compared with radiolabeled microspheres. Validation studies consisted of simultaneous measurements of blood flow with positron emission tomography and microspheres over a wide range of flow values. Blood pool and regional tissue activity curves were fitted with a three-compartment model for [13Nlammonia with and without arterial metabolite correction and with a single-tissue-compartment model for [11Ojwater. A correction for finite-resolution effect before the fit was also applied. In large regions of interest (5 cm3), a good correlation between the microsphere method and [13NJ ammonia (with metabolite correction) was obtained (y=3+0.78x, r=0.94). The correlation with microspheres was slightly better with [15O1water (y=-3+0.89x, r=0.97). Similar correlations were achieved in smaller regions of interest (1 cm3) as well as in akinetic segments and in central infarct regions.Conclsions. Positron emission tomography with appropriate tracer kinetic models using [13NIammonia and [15Ojwater provides an accurate quantitative method for measuring regional myocardial blood flow over a wide range of flow values in normally contracting or akinetic canine myocardium in the absence and in the presence of infarction.

Regional oxidative metabolism in patients after recovery from reperfused anterior myocardial infarction. Relation to regional blood flow and glucose uptake.

BackgroundEnhanced uptake of the glucose analogue 18F-fluorodeoxyglucose (FDG) in relation to flow has been proposed as an accurate method of identifying viable myocardium. The evaluation of myocardial oxidative metabolism could be an alternate way to identify reversible injury. The aim of the present study was to investigate in patients with reperfused anterior infarction whether differences in regional oxidative metabolism exist among regions with and without flow-metabolism mismatch. Methods and Resuts.Fifteen patients with reperfused anterior myocardial infarction were studied between 2 weeks and 3 months after the acute event. Regional myocardial blood flow (13N-ammonia; three-compartment model), oxidative metabolism (11C-acetate; monoexponential clearance), and glucose uptake (FDG, linear graphic analysis) were evaluated with dynamic positron emission tomography. Flow-metabolism patterns were used to differentiate reversibly (FDG/flow >1.2) from irreversibly injured myocardium (FDG/flow < 1.2) using circumferential profile technique. Relative 13N-ammonia uptake was reduced in 71 of 90 anterior and/or septal segments, including 24 with (seven patients) and 38 without (eight patients) flow-metabolism mismatch. Acetate clearance (k), reflecting oxidative metabolism, was reduced by 51% in the center of the infarct area versus remote segments (27±12 versus 55±13 min−1. 10−3, p < 0.001). Compared with infarct segments without flow-metabolism mismatch, segments exhibiting increased glucose uptake relative to flow had faster acetate clearance (35±14 versus 23±9 min−1.10−3, p < 0.01). Similarly, myocardial blood flow was better preserved in segments with flow-metabolism mismatch (54±13 versus 45±8 ml/min/100 g, p < 0.0l) compared with segments without mismatch. However, at similar levels of hypoperfusion, there was no significant difference in acetate clearance among segments with and those without flow-metabolism mismatch: 37±14 versus 41±15 min−1.10−3, respectively. A positive correlation (r = 0.89, p < 0.001) was found between absolute myocardial blood flow and acetate clearance, regardless of the flow-metabolism pattern. ConclusionsIn patients with reperfused myocardial infarction studied between 2 weeks and 3 months after the acute event, regional oxidative metabolism is reduced in proportion to residual myocardial blood flow and does not differ significantly among similarly hypoperfused segments with and without flow-metabolism mismatch.

Assessment of Bone-marrow Blood-flow Using Positron Emission Tomography - No Relationship With Bone-marrow Cellularity

Bone marrow blood flow has been assessed using positron emission tomography and the 15O‐labelled carbon dioxide steady‐state technique. The measurements were performed at the site of the posterior iliac crest. The bone marrow blood flow was 10.0 ml/min/100 cm3±3.0 (SD) in normal volunteers. It was markedly increased in patients with polycythaemia vera (26.9±4.6), chronic granulocytic leukaemia (25.2 ± 3.9) and myelofibrosis (35.1 ± 7.3). However, bone marrow blood flow did not differ from normal in patients with aplastic anaemia, chronic haemolysis or chronic lymphocytic leukaemia. There was no relationship between bone marrow cellularity and bone marrow blood flow. The data show that bone marrow blood flow is markedly elevated in polycythaemia vera, myelofibrosis and chronic granulocytic leukaemia and suggest that bone marrow cellularity is not a major factor in regulating bone marrow blood flow.

Brain glucose utilization in childhood Huntington's disease studied with positron emission tomography (PET).

Brain glucose metabolism was measured in two children with early-onset Huntingtons disease, using positron emission tomography with fluorodeoxyglucose (FDG) as the tracer. A marked (48%) hypometabolism was found at the level of the caudate nuclei, but other areas of the brain, particularly the cerebral cortex, were not significantly affected. Despite its different clinical presentation, Huntingtons disease in children is characterized by brain metabolic alterations similar to those found in adult patients.

Magnesium Uptake by Intestinal Brush-Border Membranes of Spontaneously Hypertensive Rats

Abstract Magnesium uptake by intestinal brush-border membranes (BBM) was studied in duodenal and jejunal vesicles of the spontaneously hypertensive rat (SHR) and normotensive control, the Wistar-Kyoto (WKY) rat. In the duodenum, no statistical difference was evidenced between the two types of rats. By contrast, initial rates of magnesium uptake in jejunal vesicles were lower in SHR (5.4 ±2.1 nmol/mg protein × 10 sec) in comparison to WKY rats (11.0 ± 2.5 nmol/mg protein × 10 sec) at a magnesium concentration of 1 mM (P < 0.01). In jejunal BBM, kinetic analysis of magnesium uptake showed three components in WKY rats, with one being diffusional. In SHR, only two components were seen, with the diffusional one being absent. The two saturable components showed V max of 6.5 ± 1.3 and 26.2 ± 6.0 nmol/mg protein × 10 sec and apparent Km of 0.22 ± 0.12 mM and 1.9 ± 0.4 mM in WKY rats, and V max of 10.9 ± 3.5 and 14.8 ± 5.9 nmol/mg protein × 10 sec and apparent Km of 0.43 ± 0.23 mM and 1.3 ± 0.2 mM in SHR. Only the component with the lowest apparent affinity appeared statistically different in SHR as compared with WKY rats for both V max and apparent Km (P < 0.05). Time course evolution of magnesium uptake in jejunal BBM indicated, by extrapolation at zero time, that 2.5 and 5.1 nmol magnesium/mg protein in SHR and WKY rats, respectively, would be in the bound state. The study of the influence of medium osmolarity on 60-min magnesium uptakes was also indicative of a smaller binding compartment in jejunal BBM of SHR (3.70 and 8.26 nmol/mg protein in SHR and WKY rats, respectively); at the four osmolarities assayed, the 60-min uptakes were significantly lower in SHR as compared with WKY rats (P < 0.01). From 60-min glucose uptakes, a smaller volume of jejunal BBM vesicles was determined for SHR as compared with WKY rats (0.34 ± 0.06 and 0.63 ±0.17 μl/mg of protein in SHR and WKY rats respectively, P < 0.05), this volume being significantly augmented by the presence of 1 m/W MgCI2 (0.48 ± 0.05 and 1.27 ± 0.02 μl/mg of protein in SHR and WKY rats respectively, P < 0.01). These results suggest that magnesium uptake and binding by jejunal BBM are altered in SHR in comparison to WKY rats, implying a possible role of the small intestine in the abnormalities of magnesium metabolism in genetic hypertension.

Clinical Applications of PET: Studies of Brain Glucose Metabolism in Pediatric Neurology

So far, positron emission tomography (PET) has not been applied extensively in pediatric neurology, possibly due to difficulties inherent in radioisotope analyses in children. This situation is subject to change, however, with the continuous improvement in the sensitivity of PET cameras. In this chapter, data from the literature and our recent experiences with the use of FDG in children are summarized. Studies with other tracers are reviewed elsewhere (Phelps and Mazziotta, 1985; Perlman et al., 1985) and will not be considered.