Evaluation of simultaneous 201Tl/99mTc dual-isotope cardiac SPECT imaging with model-based crosstalk compensation using canine studies.

BACKGROUND: Simultaneous (201)Tl/(99m)Tc-sestamibi dual-isotope myocardial perfusion SPECT imaging can reduce imaging time and produce perfectly registered rest/stress images. However, crosstalk from (99m)Tc into (201)Tl images can significantly reduce (201)Tl image quality. We have developed a model-based compensation (MBC) method to compensate for this crosstalk. The method has previously been validated with phantom and simulation studies. In this study, we evaluated the MBC method using a canine model. METHODS: Left anterior descending or left circumflex coronary artery stenoses were created in 50 adult mongrel dogs weighing 20-30 kg. The dogs were injected with 111 MBq (3 mCi) of (201)Tl at rest, and a SPECT study acquired. Stress was induced by administering adenosine to the dog, followed by injection of 740 MBq (20 mCi) of (99m)Tc-sestamibi at peak stress. A second SPECT study was performed with data acquired in both (201)Tl and (99m)Tc energy windows to provide simultaneous dual-isotope projection data. The images were reconstructed using the ordered-subsets expectation-maximization reconstruction algorithm with compensation for attenuation, scatter, and detector response. For simultaneously acquired (201)Tl data, we also applied the MBC method to compensate for crosstalk contamination from (99m)Tc. RESULTS: Without compensation, (99m)Tc crosstalk increased the estimated (201)Tl activity concentration in the rest images and reduced defect contrast. After MBC, the (201)Tl images were in good agreement with the registered single-isotope images and ex vivo count data. The ischemic (IS) to non-ischemic (NIS) region (201)Tl activity concentration ratios were computed for single-isotope and dual-isotope studies. The correlation with ex vivo IS-NIS ratios was 0.815 after MBC, compared to the 0.495 from data without compensation. In addition, the regression line for the IS-NIS ratios with MBC was almost parallel to the line of identity with a slope of 0.93, compared to a slope of 0.45 without compensation. CONCLUSIONS: These results demonstrate that model-based crosstalk compensation can provide substantial reduction of crosstalk effects in simultaneously acquired myocardial perfusion SPECT images in living biological systems.

Adenovirus-mediated acidic fibroblast growth factor gene transfer induces angiogenesis in the nonischemic rabbit heart.

Most patients with severe coronary artery disease have normal baseline myocardial blood flow. Therefore, interventions aimed at inducing therapeutic angiogenesis in these patients should cause new blood vessel growth in the heart in the absence of chronic ischemia. It was examined whether adenovirus-mediated gene transfer of recombinant, secreted acidic fibroblast growth factor (sp+aFGF(1-154)), next to a major epicardial artery, may induce neovascularization and reduce the risk region for myocardial infarction upon coronary ligation near the injection site. Fifteen days prior to coronary artery occlusion, rabbits were treated with intramyocardial injections of AdCMV.sp+aFGF(1-154), the control vector AdCMV.NLSbetagal (1 x 10(9) plaque-forming units), or saline. Messenger RNA transcripts for aFGF(1-154) were present up to 12 days after injection in the tissues exposed to AdCMV.aFGF(1-154). Following coronary artery occlusion rabbits treated with AdCMV. sp+aFGF(1-154) showed a 50% reduction of the risk region for myocardial infarction (P < 0.01 vs control). Histologic analysis showed a twofold increase in length density of intramural coronary arterioles (P < 0.01 vs control) and a 17% increase in length density of the capillary network (P < 0.001) in the myocardium exposed to AdCMV.sp+aFGF(1-154). Thus, gene therapy with AdCMV. sp+aFGF(1-154) can induce angiogenesis in the absence of chronic ischemia. The newly formed collateral blood vessels provide an anatomical basis for the reduction in the risk region for myocardial infarction upon subsequent occlusion of the coronary artery in proximity of the site where angiogenesis was induced.

Preservation of canine myocardial high-energy phosphates during low-flow ischemia with modification of hemoglobin-oxygen affinity.

Conventional approaches for the treatment of myocardial ischemia increase coronary blood flow or reduce myocardial demand. To determine whether a rightward shift in the hemoglobin-oxygen saturation curve would reduce the metabolic and contractile effects of a myocardial oxygen-supply imbalance, we studied the impact of a potent synthetic allosteric modifier of hemoglobin-oxygen affinity, a 2-[4-[[(3,5-disubstituted anilino)carbonyl]methyl] phenoxy] -2-methylproprionic acid derivative (RSR13), during low-flow ischemia. Changes in myocardial high-energy phosphate levels and pH were studied by 31P nuclear magnetic resonance (NMR) spectroscopy in 12 open-chest dogs randomized to receive RSR13 or vehicle control during a reversible reduction of left anterior descending (LAD) coronary artery blood flow. Changes in cardiac metabolites and regional ventricular function studied by pressure segment-length relations were also investigated in additional animals before and after RSR13 administration during low-flow LAD ischemia. The intravenous administration of RSR13 before ischemia resulted in a substantial increase in the mean hemoglobin p50 and attenuated the decline in cardiac creatine phosphate/adenosine triphosphate (PCr/ATP), percent PCr, and pH during ischemia without a change in regional myocardial blood flow, heart rate, or systolic blood pressure. RSR13 given after the onset of low-flow ischemia also improved cardiac PCr/ATP ratios and regional function as measured by fractional shortening and regional work. Thus, synthetic allosteric reduction in hemoglobin-oxygen affinity may be a new and important therapeutic strategy to ameliorate the metabolic and functional consequences of cardiac ischemia.

Assessment of myocardial blood flow by real-time infrared imaging.

In order to evaluate the applicability of infrared imaging for the assessment of myocardial perfusion, 10 open-chested dogs were studied by a real-time infrared imaging system. The left anterior descending coronary artery was occluded for 90 min followed by 210 min of reperfusion. During the experiment, myocardial surface temperature was mapped by an infrared imaging system with a thermal resolution power of 0.1 degree C and correlated with regional myocardial blood flow measured using radiolabeled microspheres. Following the experiment, acute myocardial injury was evaluated using triphenyltetrazolium chloride staining. After 90 min of ischemia, there was a significant correlation between myocardial blood flow and myocardial surface temperature (R = 0.694, P less than 0.001). After reperfusion, temperature did not correlate with blood flow, but there was a significant correlation between temperature and ischemic myocardial injury (R = 0.551, P less than 0.05). Temperature changes during acute regional ischemia and reperfusion may be regulated by the changes in myocardial blood flow and myocardial metabolism. Temperature analysis using real-time infrared imaging may be a useful means for the evaluation of myocardial blood flow and myocardial injury during ischemia and reperfusion.

Intermittent coronary sinus occlusion in dogs: reduction of infarct size 10 days after reperfusion.

Intermittent balloon occlusion of the coronary sinus was applied to 11 open chest dogs subjected to 3 hours of ligation of the left anterior descending coronary artery followed by 8 to 12 days of reperfusion. Anticoagulants were not given during the reperfusion period. Risk region was assessed by planimetry of autoradiographs made from ventricular slices. Infarct size was equivalent when assessed by planimetry of ventricular slices before and after staining with triphenyltetrazolium chloride. In the seven survivors, 30 +/- 8% of the risk region was infarcted. Seven of 11 control dogs survived (p = NS); 75 +/- 4% of the risk region was infarcted in the control animals (p less than 0.01 versus treated survivors). Light microscopic inspection of specimens stained with hematoxylin-eosin confirmed the border between necrotic and preserved myocardium. Thrombus was observed in the coronary sinus in all survivors in the treatment group. These findings confirm earlier short-term studies that demonstrated a potent anti-ischemic effect of intermittent coronary sinus occlusion. At the same time, coronary sinus thrombosis warrants caution in the application of this technique to myocardial ischemia in humans.

Reversal of dysfunction in postischemic stunned myocardium by epinephrine and postextrasystolic potentiation.

After brief coronary occlusions, myocardium may become "stunned," exhibiting prolonged depression of function despite the absence of necrosis. Because of the accompanying decline in adenosine triphosphate and adenine nucleotide precursors, a deficiency of energy supply has been proposed as the basis for postischemic dysfunction. This study examined whether sufficient functional and metabolic reserve exists in stunned myocardium to sustain a prolonged, maximal inotropic response to epinephrine and postextrasystolic potentiation. In 11 open chest dogs, the left anterior descending coronary artery was occluded for 5 minutes, followed by 10 minutes of reflow, repeated 12 times, with a final 1 hour recovery period. Regional myocardial function was measured using pairs of ultrasonic dimension crystals implanted in ischemic and nonischemic zones. During repetitive reflows a progressive decrease in mean systolic segment shortening occurred: baseline 21.8%, 1st reflow 15.2%, 12th reflow 4.3%, 1 hour recovery 7.9%. Intravenous epinephrine, titrated to produce a maximal inotropic response, caused segment shortening to increase to 21.6% after 10 minutes and to 24.8% after 1 hour of infusion, despite a 20 mm Hg increase in systolic pressure. The same dose of epinephrine given before ischemia increased segment shortening to 30.5%. In six of the dogs, postextrasystolic potentiation before ischemia increased segment shortening from 21.8 to 31.1%, and after 1 hour of recovery from ischemia, from 7.9 to 24.8%. Lesser increases in segment shortening were also seen in nonischemic segments. The results indicate that stunned myocardium possesses considerable functional reserve. Deficient energy stores are therefore not likely to be the basis for depressed function seen at rest in stunned myocardium.