Investigation of dynamic SPECT measurements of the arterial input function in human subjects using simulation, phantom and human studies.

Computer simulations, a phantom study and a human study were performed to determine whether a slowly rotating single-photon computed emission tomography (SPECT) system could provide accurate arterial input functions for quantification of myocardial perfusion imaging using kinetic models. The errors induced by data inconsistency associated with imaging with slow camera rotation during tracer injection were evaluated with an approach called SPECT/P (dynamic SPECT from positron emission tomography (PET)) and SPECT/D (dynamic SPECT from database of SPECT phantom projections). SPECT/P simulated SPECT-like dynamic projections using reprojections of reconstructed dynamic (94)Tc-methoxyisobutylisonitrile ((94)Tc-MIBI) PET images acquired in three human subjects (1 min infusion). This approach was used to evaluate the accuracy of estimating myocardial wash-in rate parameters K(1) for rotation speeds providing 180° of projection data every 27 or 54 s. Blood input and myocardium tissue time-activity curves (TACs) were estimated using spatiotemporal splines. These were fit to a one-compartment perfusion model to obtain wash-in rate parameters K(1). For the second method (SPECT/D), an anthropomorphic cardiac torso phantom was used to create real SPECT dynamic projection data of a tracer distribution derived from (94)Tc-MIBI PET scans in the blood pool, myocardium, liver and background. This method introduced attenuation, collimation and scatter into the modeling of dynamic SPECT projections. Both approaches were used to evaluate the accuracy of estimating myocardial wash-in parameters for rotation speeds providing 180° of projection data every 27 and 54 s. Dynamic cardiac SPECT was also performed in a human subject at rest using a hybrid SPECT/CT scanner. Dynamic measurements of (99m)Tc-tetrofosmin in the myocardium were obtained using an infusion time of 2 min. Blood input, myocardium tissue and liver TACs were estimated using the same spatiotemporal splines. The spatiotemporal maximum-likelihood expectation-maximization (4D ML-EM) reconstructions gave more accurate reconstructions than did standard frame-by-frame static 3D ML-EM reconstructions. The SPECT/P results showed that 4D ML-EM reconstruction gave higher and more accurate estimates of K(1) than did 3D ML-EM, yielding anywhere from a 44% underestimation to 24% overestimation for the three patients. The SPECT/D results showed that 4D ML-EM reconstruction gave an overestimation of 28% and 3D ML-EM gave an underestimation of 1% for K(1). For the patient study the 4D ML-EM reconstruction provided continuous images as a function of time of the concentration in both ventricular cavities and myocardium during the 2 min infusion. It is demonstrated that a 2 min infusion with a two-headed SPECT system rotating 180° every 54 s can produce measurements of blood pool and myocardial TACs, though the SPECT simulation studies showed that one must sample at least every 30 s to capture a 1 min infusion input function.

Myocardial uptake of 7'-(Z)-[(123)I]iodorotenone during vasodilator stress in dogs with critical coronary stenoses.

BACKGROUND: There is a well-recognized need for a new generation of single photon emission computed tomography (SPECT) perfusion tracers with improved myocardial extraction over a wide flow range. Radiotracers that target complex I of the mitochondrial electron transport chain have been proposed as a new class of myocardial perfusion imaging agents. 7-(Z)-[(125)I]iodorotenone ((125)I-ZIROT) has demonstrated superior myocardial extraction and retention characteristics in rats and in isolated perfused rabbit hearts. We sought to fully characterize the biodistribution and myocardial extraction versus flow relationship of (123)I-ZIROT in an intact large-animal model. METHODS AND RESULTS: The (123)I-ZIROT was administered during adenosine A(2A) agonist-induced hyperemia in 5 anesthetized dogs with critical left anterior descending (LAD) stenoses. When left circumflex (LCx) flow was maximal, (123)I-ZIROT and microspheres were coinjected and the dogs were euthanized 5 minutes later. (123)I-ZIROT biodistribution was evaluated in 2 additional dogs by in vivo planar imaging. At (123)I-ZIROT injection, transmural LAD flow was unchanged from baseline (mean±SEM, 0.90±0.22 versus 0.87±0.11 mL/[min · g]; P=0.92), whereas LCx zone flow increased significantly (mean±SEM, 3.25±0.51 versus 1.00±0.17 mL/[min · g]; P<0.05). Myocardial (123)I-ZIROT extraction tracked regional myocardial flow better than either thallium-201 or (99m)Tc-sestamibi from previous studies using a similar model. Furthermore, the (123)I-ZIROT LAD/LCx activity ratios by ex vivo imaging or well counting (mean±SEM, 0.42±0.08 and 0.45±0.1, respectively) only slightly underestimated the LAD/LCx microsphere flow ratio (0.32±0.09). CONCLUSIONS: The ability of (123)I-ZIROT to more linearly track blood flow over a wide range makes it a promising new SPECT myocardial perfusion imaging agent with potential for improved coronary artery disease detection and better quantitative estimation of the severity of flow impairment.

Longitudinal Evaluation of Fatty Acid Metabolism in Normal and Spontaneously Hypertensive Rat Hearts with Dynamic MicroSPECT Imaging.

The goal of this project is to develop radionuclide molecular imaging technologies using a clinical pinhole SPECT/CT scanner to quantify changes in cardiac metabolism using the spontaneously hypertensive rat (SHR) as a model of hypertensive-related pathophysiology. This paper quantitatively compares fatty acid metabolism in hearts of SHR and Wistar-Kyoto normal rats as a function of age and thereby tracks physiological changes associated with the onset and progression of heart failure in the SHR model. The fatty acid analog, (123)I-labeled BMIPP, was used in longitudinal metabolic pinhole SPECT imaging studies performed every seven months for 21 months. The uniqueness of this project is the development of techniques for estimating the blood input function from projection data acquired by a slowly rotating camera that is imaging fast circulation and the quantification of the kinetics of (123)I-BMIPP by fitting compartmental models to the blood and tissue time-activity curves.

Dynamic single photon emission computed tomography--basic principles and cardiac applications.

The very nature of nuclear medicine, the visual representation of injected radiopharmaceuticals, implies imaging of dynamic processes such as the uptake and wash-out of radiotracers from body organs. For years, nuclear medicine has been touted as the modality of choice for evaluating function in health and disease. This evaluation is greatly enhanced using single photon emission computed tomography (SPECT), which permits three-dimensional (3D) visualization of tracer distributions in the body. However, to fully realize the potential of the technique requires the imaging of in vivo dynamic processes of flow and metabolism. Tissue motion and deformation must also be addressed. Absolute quantification of these dynamic processes in the body has the potential to improve diagnosis. This paper presents a review of advancements toward the realization of the potential of dynamic SPECT imaging and a brief history of the development of the instrumentation. A major portion of the paper is devoted to the review of special data processing methods that have been developed for extracting kinetics from dynamic cardiac SPECT data acquired using rotating detector heads that move as radiopharmaceuticals exchange between biological compartments. Recent developments in multi-resolution spatiotemporal methods enable one to estimate kinetic parameters of compartment models of dynamic processes using data acquired from a single camera head with slow gantry rotation. The estimation of kinetic parameters directly from projection measurements improves bias and variance over the conventional method of first reconstructing 3D dynamic images, generating time-activity curves from selected regions of interest and then estimating the kinetic parameters from the generated time-activity curves. Although the potential applications of SPECT for imaging dynamic processes have not been fully realized in the clinic, it is hoped that this review illuminates the potential of SPECT for dynamic imaging, especially in light of new developments that enable measurement of dynamic processes directly from projection measurements.

Measuring regional changes in the diastolic deformation of the left ventricle of SHR rats using microPET technology and hyperelastic warping.

The objective of this research was to assess applicability of a technique known as hyperelastic warping for the measurement of local strains in the left ventricle (LV) directly from microPET image data sets. The technique uses differences in image intensities between template (reference) and target (loaded) image data sets to generate a body force that deforms a finite element (FE) representation of the template so that it registers with the target images. For validation, the template image was defined as the end-systolic microPET image data set from a Wistar Kyoto (WKY) rat. The target image was created by mapping the template image using the deformation results obtained from a FE model of diastolic filling. Regression analysis revealed highly significant correlations between the simulated forward FE solution and image derived warping predictions for fiber stretch (R (2) = 0.96), circumferential strain (R (2) = 0.96), radial strain (R (2) = 0.93), and longitudinal strain (R (2) = 0.76) (p < 0.001 for all cases). The technology was applied to microPET image data of two spontaneously hypertensive rats (SHR) and a WKY control. Regional analysis revealed that, the lateral freewall in the SHR subjects showed the greatest deformation compared with the other wall segments. This work indicates that warping can accurately predict the strain distributions during diastole from the analysis of microPET data sets.

Method of generating multiple sets of experimental phantom data.

UNLABELLED: Currently, 2 types of phantoms (physical and computer generated) are used for testing and comparing tomographic reconstruction methods. Data from physical phantoms include all physical effects associated with the detection of radiation. However, with physical phantoms it is difficult to control the number of detected counts, simulate the dynamics of uptake and washout, or create multiple noise realizations of an acquisition. Computer-generated phantoms can overcome some of the disadvantages of physical phantoms, but simulation of all factors affecting the detection of radiation is extremely complex and in some cases impossible. To overcome the problems with both types of phantoms, we developed a physical and computer-generated hybrid phantom that allows the creation of multiple noise realizations of tomographic datasets of the dynamic uptake governed by kinetic models. METHODS: The method is phantom and camera specific. We applied it to an anthropomorphic torso phantom with a cardiac insert, using a SPECT system with attenuation correction. First, real data were acquired. For each compartment (heart, blood pool, liver, and background) of the physical phantom, large numbers of short tomographic projections were acquired separately for each angle. Sinograms were built from a database of projections by summing the projections of each compartment of the phantom. The amount of activity in each phantom compartment was regulated by the number of added projections. Sinograms corresponding to various projection times, configurations and numbers of detector heads, numbers of noise realizations, numbers of phantom compartments, and compartment-specific time-activity curves in MBq/cm3 were assembled from the database. RESULTS: The acquisition produced a database of 120 projection angles ranging over 360 degrees . For each angle, 300 projections of 0.5 s each were stored in 128 x 128 matrices for easy access. The acquired database was successful in the generation of static and dynamic sinograms for which the myocardial uptake and washout was governed by a compartment kinetic model. CONCLUSION: A method has been developed that allows creation of sinograms of physical phantoms with the capacity to control the number of noise realizations, the level of noise, the dynamics of uptake in the phantom compartments, and the acquisition parameters and acquisition modes.

Kinetic analysis of 18F-fluorodihydrorotenone as a deposited myocardial flow tracer: comparison to 201Tl.

UNLABELLED: The goals of this investigation were to assess the accuracy of (18)F-fluorodihydrorotenone ((18)F-FDHR) as a new deposited myocardial flow tracer and to compare the results to those for (201)Tl. METHODS: The kinetics of these flow tracers in 22 isolated, erythrocyte- and albumin-perfused rabbit hearts were evaluated over a flow range encountered in patients. The 2 flow tracers plus a vascular reference tracer ((131)I-albumin) were introduced as a bolus through a port just above the aortic cannula. Myocardial extraction, retention, washout, and uptake parameters were computed from the venous outflow curves with the multiple-indicator dilution technique and spectral analysis. RESULTS: The mean +/- SD initial extraction fractions for (18)F-FDHR (0.85 +/- 0.07) and (201)Tl (0.87 +/- 0.05) were not significantly different, although the initial extraction fraction for (18)F-FDHR declined with flow (P < 0.0001), whereas the initial extraction fraction for (201)Tl did not. The washout of (201)Tl was faster (P < 0.001) and more affected by flow (P < 0.05) than was the washout of (18)F-FDHR. Except for the initial extraction fraction, (18)F-FDHR retention was higher (P < 0.001) and less affected by flow (P < 0.05) than was (201)Tl retention. Reflecting its superior retention, the net uptake of (18)F-FDHR was better correlated with flow than was that of (201)Tl at both 1 and 15 min after tracer introduction (P < 0.0001 for both comparisons). CONCLUSION: The superior correlation of (18)F-FDHR uptake with flow indicates that it is a better flow tracer than (201)Tl in the isolated rabbit heart. Compared with the other currently available positron-emitting flow tracers ((82)Rb, (13)N-ammonia, and (15)O-water), (18)F-FDHR has the potential of providing excellent image resolution without the need for an on-site cyclotron.

Flow heterogeneity following global no-flow ischemia in isolated rabbit heart.

The purpose of this study was to evaluate flow heterogeneity and impaired reflow during reperfusion after 60-min global no-flow ischemia in the isolated rabbit heart. Radiolabeled microspheres were used to measure relative flow in small left ventricular (LV) segments in five ischemia + reperfused hearts and in five nonischemic controls. Relative flow heterogeneity was expressed as relative dispersion (RD) and computed as standard deviation/mean. In postischemic vs. preischemic hearts, RD was increased for the whole LV (0.92 +/- 0.41 vs. 0.37 +/- 0.07, P < 0.05) as well as the subendocardium (Endo) and subepicardium considered separately (1.28 +/- 0.74 vs. 0.30 +/- 0.09 and 0.69 +/- 0.22 vs. 0.38 +/- 0.08; P < 0.05 for both comparisons, respectively) during early reperfusion. During late reperfusion, the increased RD for the whole LV and Endo remained significant (0.70 +/- 0.22 vs. 0.37 +/- 0.07 and 1.06 +/- 0.55 vs. 0.30 +/- 0.09; P < 0.05 for both comparisons, respectively). In addition to the increase in postischemic flow heterogeneity, there were some regions demonstrating severely impaired reflow, indicating that regional ischemia can persist despite restoration of normal global flow. Also, the relationship between regional and global flow was altered by the increased postischemic flow heterogeneity, substantially reducing the significance of measured global LV reflow. These observations emphasize the need to quantify regional flow during reperfusion after sustained no-flow ischemia in the isolated rabbit heart.