R De Silva

Noninvasive quantification of regional myocardial blood flow in coronary artery disease with oxygen-15-labeled carbon dioxide inhalation and positron emission tomography

BackgroundOxygen-15-labeled water is a diffusible, metabolically inert myocardial blood flow tracer with a short half-life (2 minutes) that can be used quantitatively with positron emission tomography (PET). The purpose of this study was to validate a new technique to quantify myocardial blood flow (MBF) in animals and to assess its application in patients. Methods and ResultsThe technique involves the administration of 150-labeled carbon dioxide (C1502) and rapid dynamic scanning. Arterial and myocardial time activity curves were fitted to a single tissue compartment tracer kinetic model to estimate MBF in each myocardial region. Validation studies consisted of 52 simultaneous measurements ofMBF with PET and y-labeled microspheres in nine closed-chest dogs over a flow range of 0.5-6.1 ml/g/min. A good correlation between the two methods was obtained (y = 0.36 + 1.0x, r = 0.91). Human studies consisted of 11 normal volunteers and eight patients with chronic stable angina and single-vessel disease, before and after intravenous dipyridamole infusion. In the normal group, MBF was homogeneous throughout the left ventricle both at rest and after administration of dipyridamole (0.88 ± 0.08 ml/g/min and 3.52 ± + 1.12 ml/g/min, respectively; p≤0.001). In patients, resting MBF was similar in the distribution of the normal and stenotic arteries (1.03 ± 0.23 and 0.93 ± 0.21 ml/g/min, respectively). After dipyridamole infusion, MBF in normally perfused areas increased to 2.86 ± 0.83 ml/g/min, whereas in the regions supplied by stenotic arteries it increased to only 1.32 ± 0.27 ml/g/min (p<0.001). ConclusionsPET with C1502 inhalation provides an accurate noninvasive quantitative method for measuring regional myocardial blood flow in patients. (Circulation 1991;83:875–885)

A new strategy for the assessment of viable myocardium and regional myocardial blood flow using 15O-water and dynamic positron emission tomography.

BackgroundWe have developed a new measure of myocardial viability, the water-perfusable tissue index (PTI), which is calculated from transmission, C1550, and H215O positron emission tomography (PET) data sets. It is defined as the proportion of the total anatomical tissue within a given region of interest (ROI) that is capable of rapidly exchanging water and has units g (perfusable tissue)/g (total anatomical tissue). The aim of this study was to assess the prognostic value of PMI in predicting improvement in regional wall motion after successful thrombolysis for acute myocardial infarction (AMI) and to measure the myocardial blood flow to the perfusable tissue (MBFp, ml/min/g [perfusable tissue]). Furthermore, PTI was compared with 18FDG metabolic imaging in patients with old myocardial infarction (OMI). Methods and ResultsPET scans were performed in healthy volunteers (group 1, n = 8), patients with OMI (group 2, n = 15), and in patients who were successfully thrombolysed after an AMI (group 3, n = 11). Systolic wall thickening was measured by two-dimensional echocardiography within 2–4 days of AMI and after 4 months to assess contractile recovery. In the healthy volunteers, MBFp was 0.95±0.13 ml/min/g (perfusable tissue). PTI in these regions was 1.08±0.07 g (perfusable tissue)/g (total anatomical tissue), which was consistent with all normal myocardium being perfusable by water. In the OMI group, the ratio of the relative 18FDG activity to the relative MBFp defect (metabolism-flow ratio) was calculated for each asynergic segment. Regions in which the metabolism-flow ratio was ≥1.20 were considered reversibly injured, whereas those in which the ratio was < 1.20 were deemed irreversibly injured. PTI in the former group of regions (n = 9) was 0.75±0.14 g (perfusable tissue)/g (total anatomical tissue) and was significantly higher than in irreversibly injured regions (n = 6) (0.53±0.12 g [perfusable tissue]/g [total anatomical tissue], p<0.01). Values of MBFp were similar in these segments. Seven of 12 segments in the AMI patients showed improved systolic wall thickening on follow-up. PTI in these recovery segments was 0.88±0.10 g (perfusable tissue)/g (total anatomical tissue) (p = NS versus control). PTI in the nonrecovery regions was 0.53±0.11 g (perfusable tissue)/g (total anatomical tissue), which was similar to the segments in group 2 in which 18FDG uptake was absent. MBFp was similar in both the recovery and nonrecovery segments in the subacute phase. ConclusionsThese data indicate that PTI may be a good prognostic indicator for the recovery of contractile function after successful thrombolysis and show that myocardial viability may be assessed by PET without metabolic imaging.

Preoperative prediction of the outcome of coronary revascularization using positron emission tomography.

BackgroundPrevious assessments of myocardial viability using positron emission tomography (PET) relied on demonstration of glucose metabolism in hypoperfused asynergic segments using the glucose analogue [18F]2-fluoro-2-deoxyglucose (FDG). Recently, it was shown that myocardial viability could be assessed by calculating the water-perfusable tissue index (PTI) for the asynergic region. PTI represents the proportion of the myocardium that is capable of rapid transsarcolemmal exchange of water and thus perfusable by water. The aim of the present study was to assess myocardial viability by PET using PTI in patients undergoing coronary revascularization. Methods and ResultsTwelve patients with chronic coronary artery disease and previous myocardial infarction were studied. Analysis of transmission (tissue density) and 15O-labeled carbon monoxide (blood pool), and 150-labeled water (myocardial blood flow [MBF]) emission PET data enabled the simultaneous quantification of MBF (ml · min−1 · g perfusable tissue−1) and PTI (gram of perfusable tissue per gram of total anatomic tissue). In addition, PET imaging with FDG after 75-g oral glucose load was performed in eight patients. Preoperative echocardiography identified 33 hypocontractile and 26 control segments. Follow-up echocardiography performed 3 to 5 months later demonstrated 26 of 33 segments with improved wall motion (recovery) and seven of 33 segments without improvement (nonrecovery). MBF in the control segments (0.97 ± 0.22 ml · min−1 · g perfusable tissue−1) was significantly higher (p < 0.001) than in both the recovery (0.73 ± 0.18 ml min−1 g perfusable tissue−1) and the nonrecovery (0.45 ± 0.11 ml min−1 · g perfusable tissue−1) segments. PTI in the recovery regions (0.99 ± 0.15) was≥0.7 in all cases and slightly less than in control regions (1.10 ± 0.15, p < 0.02). FDG uptake in these regions was 92 ± 17% (n=13) of the uptake in control segments with normal wall motion. In the nonrecovery group, PTI was 0.62 ± 0.06 (p < 0.02 versus control and recovery) and always < 0.7. In the one patient in whom a comparison with metabolic imaging was made, FDG uptake was 46% of the uptake in a reference region with normal wall motion. ConclusionsThese data showed that contractile recovery occurred only in segments where PTI was ≥0.7, suggesting that ≥70% of myocardial tissue in a given asynergic segment should be perfusable by water to enable contractile recovery. There was good agreement between the PTI and FDG methods for predicting improvements in regional wall motion after revascularization. Although further studies should be performed in a larger patient group, the preliminary results are promising and suggest that PTI may be a good predictor of contractile recovery after coronary revascularization.

Measurement of regional myocardial blood flow using C15O2 and positron emission tomography: comparison of tracer models

Eight different modifications of the same single tissue compartment model to measure myocardial blood flow, based on inhalation of 15O-labelled CO2 and positron emission tomography, were assessed in both dogs and human normal volunteers. Several models provided results with the same degree of accuracy in dogs. However, a number of these models gave poorer results in humans. It was established that the model containing components for blood flow, fraction of water exchanging tissue and spill-over arterial blood volume provided the most accurate and reproducible results. This model contains inherent corrections for the limited spatial resolution of positron emission tomographs. For ease of computation, linearisation of the operational (fitting) equation was tested, but found not to be satisfactory. The left atrium was slightly better than the left ventricle for determining the arterial input function. Inclusion of the blood volume term in the fitting procedure was significantly better than subtracting blood volume prior to analysis, both in terms of accuracy and precision.