Clinical evaluation of carbon-11-phenylephrine: MAO-sensitive marker of cardiac sympathetic neurons.

UNLABELLED: The sympathomimetic drug phenylephrine recently has been labeled with 11C for use in PET studies of cardiac sympathetic innervation. Previous reports using isolated perfused rat heart models indicate that phenylephrine is metabolized by intraneuronal monoamine oxidase (MAO). This report compares the imaging characteristics, neuronal selectivity and kinetics of (-)-[11C]phenylephrine (PHEN) to the structurally similar but MAO-resistant analog (-)-[11C]-meta-hydroxyephedrine (HED), an established heart neuronal marker. METHODS: Fourteen healthy volunteers were studied with PET and PHEN. Ten had paired studies with HED; four of the 10 were scanned a second time with each tracer after oral administration of desipramine, a selective neuronal transport blocker. Hemodynamic and electrocardiographic responses were monitored. Blood levels of intact radiotracer and radiolabeled metabolites were determined from venous blood samples taken during the PET study. Myocardial retention indices for both tracers were calculated. RESULTS: No hemodynamic or electrocardiographic effects were observed with either tracer. PHEN showed reduced myocardial retention at 50 min compared to HED; however, image quality and uniformity of distribution were comparable. PHEN cleared from myocardium with a mean half-time of 59 +/- 5 min, while myocardial levels of HED remained constant. PHEN metabolites appeared in the blood approximately three times faster than HED metabolites. Desipramine pretreatment markedly reduced (> 60%) myocardial retention of both PHEN and HED. CONCLUSION: PHEN provides PET images of human heart comparable in quality and uniformity to HED. Like HED, PHEN localizes in the sympathetic nerves of the heart. However, the more rapid efflux of PHEN, that is likely mediated by MAO, may provide information on the functional status of cardiac sympathetic neurons unobtainable with HED.

Carbon-11-acetate PET imaging in renal disease.

UNLABELLED: The purpose of this study was to investigate the use of [1-11C]acetate as a metabolic tracer for renal imaging in human subjects. METHODS: Eighteen patients underwent dynamic PET imaging of the kidneys after intravenous bolus injection of 10-20 mCi [1-11C]acetate. Time-activity curves of renal parenchyma tracer activity were fitted to a two-compartment model using direct arterial blood sampling for the arterial input function. RESULTS: Renal uptake of [1-11C]acetate is prompt and high target-to-background ratios are achieved even in the presence of markedly reduced renal function. Carbon-11-acetate is cleared from the renal parenchyma without any urinary excretion and the rate of clearance is comparable to myocardial clearance rates. Among normal subjects, K1, ranged from 0.653 to 1.37 ml/min-g, and was reduced to as low as 0.363 ml/min-g in severe renal disease (serum creatinine greater than 5 mg/dl), while k2 ranged from 0.114 to 0.166 min-1 among normal subjects and was reduced to as low as 0.053 min-1 in severe renal disease. Kinetic parameters K1 and k2 were both reduced in the presence of intrinsic renal disease or significant renal artery stenosis. Renal cell carcinoma demonstrated similar uptake of [1-11C]acetate, but substantially reduced the rate of clearance compared to normal and diseased non-neoplastic renal tissue, allowing for ready differentiation of renal cell carcinoma from non-neoplastic renal tissue on images acquired beyond 10 min of tracer administration. CONCLUSION: Carbon-11-acetate is a promising physiologic tracer for the study of renal disease.

Compartmental analysis of technetium-99m-teboroxime kinetics employing fast dynamic SPECT at rest and stress.

UNLABELLED: We have examined the feasibility of compartmental analysis of 99mTc-teboroxime kinetics in measuring physiological changes in response to adenosine-induced coronary vasodilation. To evaluate the effect of tracer recirculation on 99mTc-teboroxime kinetics in the myocardium, we also compared compartmental analysis with washout analysis (monoexponential fitting), which does not account for this effect. METHODS: Eight healthy male volunteers were imaged using fast dynamic SPECT protocols (5 sec per tomographic image) at rest and during adenosine infusion. A two-compartment model was used and compartmental parameters K1 and k2 (characterizing the diffusion of 99mTc-teboroxime from the blood to the myocardium and from the myocardium to the blood, respectively) were fitted from myocardial time-activity curves and left ventricular input functions. RESULTS: Both K1 and washout estimates for the whole left ventricular myocardium changed significantly in response to coronary vasodilation. Mean stress-to-rest (S/R) ratios were almost two times higher for K1 (S/R = 2.7 +/- 1.1) than for washout estimates (S/R = 1.5 +/- 0.3). Estimation of K1 for all local regions, except the septal wall, is feasible because variations in K1 estimates for all local regions, except the septum during stress, are comparable with those for the global region. CONCLUSIONS: We conclude that quantitative compartmental analysis of 99mTc-teboroxime kinetics provides a sensitive indicator for changes in response to adenosine-induced coronary vasodilation.

Model-based estimation for dynamic cardiac studies using ECT.

The authors develop a strategy for joint estimation of physiological parameters and myocardial boundaries using ECT (emission computed tomography). They construct an observation model to relate parameters of interest to the projection data and to account for limited ECT system resolution and measurement noise. The authors then use a maximum likelihood (ML) estimator to jointly estimate all the parameters directly from the projection data without reconstruction of intermediate images. They also simulate myocardial perfusion studies based on a simplified heart model to evaluate the performance of the model-based joint ML estimator and compare this performance to the Cramer-Rao lower bound. Finally, the authors discuss model assumptions and potential uses of the joint estimation strategy.

Model-based estimation with boundary side information or boundary regularization [cardiac emission CT].

The authors have previously developed a model-based strategy for joint estimation of myocardial perfusion and boundaries using ECT (emission computed tomography). They have also reported difficulties with boundary estimation in low contrast and low count rate situations. Here they propose using boundary side information (obtainable from high resolution MRI and CT images) or boundary regularization to improve both perfusion and boundary estimation in these situations. To fuse boundary side information into the emission measurements, the authors formulate a joint log-likelihood function to include auxiliary boundary measurements as well as ECT projection measurements. In addition, they introduce registration parameters to align auxiliary boundary measurements with ECT measurements and jointly estimate these parameters with other parameters of interest from the composite measurements. In simulated PET O-15 water myocardial perfusion studies using a simplified model, the authors show that the joint estimation improves perfusion estimation performance and gives boundary alignment accuracy of <0.5 mm even at 0.2 million counts. They implement boundary regularization through formulating a penalized log-likelihood function. They also demonstrate in simulations that simultaneous regularization of the epicardial boundary and myocardial thickness gives comparable perfusion estimation accuracy with the use of boundary side information.

Preconditioning methods for improved convergence rates in iterative reconstructions.

Because of the characteristics of the tomographic inversion problem, iterative reconstruction techniques often suffer from poor convergence rates-especially at high spatial frequencies. By using preconditioning methods, the convergence properties of most iterative methods can be greatly enhanced without changing their ultimate solution. To increase reconstruction speed, spatially invariant preconditioning filters that can be designed using the tomographic system response and implemented using 2-D frequency-domain filtering techniques have been applied. In a sample application, reconstructions from noiseless, simulated projection data, were performed using preconditioned and conventional steepest-descent algorithms. The preconditioned methods demonstrated residuals that were up to a factor of 30 lower than the assisted algorithms at the same iteration. Applications of these methods to regularized reconstructions from projection data containing Poisson noise showed similar, although not as dramatic, behavior.

Myocardial clearance kinetics of technetium-99m-SQ30217: a marker of regional myocardial blood flow.

SQ30217 is a new, technetium-99m-(99mTc) labeled perfusion agent introduced for cardiac imaging. To evaluate the myocardial tracer kinetics, 99mTc-SQ30217, was injected intracoronarily in open-chested dogs under baseline conditions and after administration of intravenous (i.v.) dipyridamole. Myocardial first-pass retention fraction averaged 0.90 +/- 0.04. Clearance of the tracer occurred in a biexponential manner. Sixty-seven percent of retained activity cleared with a half-time of 2.3 +/- 0.6 min, while the residual activity demonstrated slow clearance. The clearance rate of the rapid phase correlated with myocardial blood flow (r = 0.72, p less than 0.001). Myocardial SQ30217 clearance rate following i.v. injection as determined by dynamic imaging with tomography (SPRINT) averaged 21 +/- 4 min and increased to 13 +/- 4 min following dipyridamole. Thus, 99mTc-SQ30217 is a promising flow tracer with high initial myocardial retention and rapid tissue clearance, which allow repeated flow determinations within short time intervals using advanced SPECT technology.