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The purpose of this study was to appraise the value of PET in the assessment of the effect of supposedly proangiogenic new therapies such as gene therapy with vascular endothelial growth factor (VEGF) gene and endomyocardial laser therapy. Methods: Thirty-five patients with end-stage coronary artery disease and class III (Canadian Cardiovascular Society) angina were included. Myocardial ischemia was evaluated with dipyridamole PET scanning and exercise tolerance with bicycle ergometry. Ten patients were treated with naked plasmid DNA encoding for human VEGF(165) (VEGF) and 12 patients were treated with laser therapy (direct myocardial revascularization [DMR]) using an electromechanical mapping system. Thirteen patients were treated with standard medical therapy (control). Results: In both active treatment groups, angina was reduced in most subjects, except in 2 VEGF and 5 DMR patients. In the control group, no improvement in anginal classification was found, except in 3 subjects. On the PET scan, solely in the VEGF group, the stress perfusion was significantly improved (from 57 +/- 33 to 81 +/- 55 mL/min/100 g; P = 0.031). Furthermore, in the VEGF group, the number of ischemic segments was reduced from 274 +/- 41 to 234 +/- 48 segments (P = 0.004) but not in the DMR group (from 209 +/- 43 to 215 +/- 52 segments) or in the control group (from 218 +/- 18 to 213 +/- 28 segments). Bicycle exercise duration showed slight nonsignificant changes in the VEGF group (from 3.6 +/- 2.0 to 4.6 +/- 2.1 min), in the DMR group (from 5.1 +/- 1.5 to 4.7 +/- 1.3 min), and in the control group (from 3.3 +/- 1.8 to 3.5 +/- 2.3 min). Conclusion: PET showed that intramyocardial gene therapy with the human VEGF(165) gene in contrast to laser DMR treatment effectively reduces myocardial ischemia.

Quantification of myocardial beta-adrenoceptor density (B-max) is of interest in cardiac diseases in which altered function of the sympathetic nervous system is thought to play a pathophysiological role. PET provides an unrivaled means of taking regional measurements of cardiac microcirculatory function, tissue metabolism and autonomic nervous system activity. Measurements in small regional areas may be biased because of increased noise levels. This study examined the parametric polar map approach for the regional quantification of B-max. Methods: Dynamic PE-T with parametric polar map imaging was performed in 10 healthy volunteers and 4 patients with hypertrophic cardiomyopathy using (S)-[C-11]-(4-(3-tertiarybutylamino-2-hydroxypropoxy)-benzidimazole-2)-on hydrochloride (CGP)-12177 and a double-injection protocol. Time-activity curves were corrected for partial volume, spill-over and wall motion effects. The mean B-max of the left ventricle was calculated in two ways. First, the average time-activity curve of all segments, having the highest achievable signal-to-noise ratio, was used to calculate B-max(mTAC) (the myocardial beta-adrenoceptor density of the left ventricle calculated using the average time-activity curve). The bias in B-max(mTAC) introduced by noise is minimal. Second, an estimate of whole-heart receptor density was calculated using the polar map method by averaging the values of B-max obtained for 576 individual segments. In these calculations, three different filters (3 x 5, 3 x 9 and 3 x 13 segments) were used to smooth the time-activity curves before calculating B-max. Mean values of whole-left-ventricular receptor density obtained by averaging regional values using the different filters (B-max(PMF1/2/3)) were compared with B-max(mTAC) to assess bias introduced by the polar map approach. Segments with a calculated B-max outside the range 0.1-50 pmol/g were considered unreliable and were excluded from the analysis. Results: The differences between the two methods of calculating B-max were small (7.8%, 4.8% and 3.2%, with the three filters, respectively). Reliable results were obtained in >95% of the segments and in 9 volunteers and all 4 patients. Conclusion: When using PET for the quantification of beta-adrenoceptor density, the regional variation in B-max can be reliably assessed using the parametric polar map approach.

Heterogeneity of left ventricular myocardial perfusion is an important clinical characteristic. Different aspects of this heterogeneity were analyzed. Methods: The coefficient of variation (v), characterizing heterogeneity, was modeled as a function of the number of segments (n), characterizing spatial resolution of the measurement, using two independent pairs of mutually dependent parameters: the first pair describes v as a power function of n, and the second pair adds a correction for n small. n was Varied by joining equal numbers of neighboring segments. Local similarity of the perfusion was characterized by the correlation between the perfusions of neighboring segments, Genesis of the perfusion distribution was modeled by repeated asymmetric subdivision of the perfusion into a volume among two equal subvolumes. These analyses were applied to study the differences between 16 syndrome X patients and 16 age- and sex-matched healthy volunteers using N-13-ammonia parametric PET perfusion data with a spatial resolution of 480 segments. Results: The heterogeneity of patients is higher for the whole range of spatial resolutions considered (2 less than or equal to n less than or equal to 480; for n = 480, v = 0.22 +/- 0.03 and 0.18 +/- 0.02; p 0.1), For both groups of subjects there is a significant positive local correlation for distances up to 30 segments. This correlation is a formal description of the patchy nature of the perfusion distribution. Conclusion: When comparing values of v, these should be based on the same value of n. The model makes it possible to calculate v for all values of n 480. Mean perfusion together with the two pairs of parameters are necessary and sufficient to describe all aspects of the perfusion distribution. For n small, heterogeneity estimation is less reliable. Patients have a higher heterogeneity because their perfusion distribution is more asymmetrical from the third to the seventh generation of subdivision (8 less than or equal to n less than or equal to 128). Therefore, a spatial resolution of n greater than or equal to 128 is recommended for parametric imaging of perfusion with PET. Patients have only a very slightly more patchy distribution than volunteers. The differences in perfusion between areas with low perfusion and areas with high perfusion is larger in patients.

Most efficacy studies of cardiac PET in demonstrating myocardial ischemia and viability have been performed using one or more transversal static images of the heart. In contrast, in this paper we describe a method of functional imaging of the complete left ventricular myocardium for perfusion with nitrogen-13-ammonia, both at rest and during a dipyridamol stress test, and of glucose metabolism with F-18-fluorodeoxyglucose ((18)FDG). Methods: This was performed by using the data of each of 48 radial segments of 10 short-axis images as tissue data and LV cavity data of three basal planes as blood pool data. The study describes the results of 19 normal volunteers and 36 patients with coronary artery disease. From the data of the normal volunteers a 95% normal confidence interval was calculated for each imaging modality. These intervals were then used to describe the patient data as normal, ischemic or infarcted. Results: The results of analysis of the parametric images was compared with the results of static analysis of the same patient data and found to be less dependant on the detection threshold used. Conclusion: The described method enables the routine application of functional PET imaging of the total myocardium by the semi-automatic construction of parametric flow and metabolism polar maps. It thus provides an increased performance in the diagnosis, quantification and localization of myocardial ischemia and viability over conventional PET imaging.