Arkadiusz Sitek

Improved Cardiac Risk Assessment With Noninvasive Measures of Coronary Flow Reserve

Background— Impaired vasodilator function is an early manifestation of coronary artery disease and may precede angiographic stenosis. It is unknown whether noninvasive assessment of coronary vasodilator function in patients with suspected or known coronary artery disease carries incremental prognostic significance. Methods and Results— A total of 2783 consecutive patients referred for rest/stress positron emission tomography were followed up for a median of 1.4 years (interquartile range, 0.7–3.2 years). The extent and severity of perfusion abnormalities were quantified by visual evaluation of myocardial perfusion images. Rest and stress myocardial blood flows were calculated with factor analysis and a 2-compartment kinetic model and were used to compute coronary flow reserve (coronary flow reserve equals stress divided by rest myocardial blood flow). The primary end point was cardiac death. Overall 3-year cardiac mortality was 8.0%. The lowest tertile of coronary flow reserve (<1.5) was associated with a 5.6-fold increase in the risk of cardiac death (95% confidence interval, 2.5–12.4; P<0.0001) compared with the highest tertile. Incorporation of coronary flow reserve into cardiac death risk assessment models resulted in an increase in the c index from 0.82 (95% confidence interval, 0.78–0.86) to 0.84 (95% confidence interval, 0.80–0.87; P=0.02) and in a net reclassification improvement of 0.098 (95% confidence interval, 0.025–0.180). Addition of coronary flow reserve resulted in correct reclassification of 34.8% of intermediate-risk patients (net reclassification improvement=0.487; 95% confidence interval, 0.262–0.731). Corresponding improvements in risk assessment for mortality from any cause were also demonstrated. Conclusion— Noninvasive quantitative assessment of coronary vasodilator function with positron emission tomography is a powerful, independent predictor of cardiac mortality in patients with known or suspected coronary artery disease and provides meaningful incremental risk stratification over clinical and gated myocardial perfusion imaging variables.

Clinical Myocardial Perfusion PET/CT

The field of nuclear cardiology is witnessing growing interest in the use of cardiac PET for the evaluation of patients with coronary artery disease (CAD). The available evidence suggests that myocardial perfusion PET provides an accurate means for diagnosing obstructive CAD, which appears superior to SPECT especially in the obese and in those undergoing pharmacologic stress. The ability to record changes in left ventricular function from rest to peak stress and to quantify myocardial perfusion (in mL/min/g of tissue) provides an added advantage over SPECT for evaluating multivessel CAD. There is growing and consistent evidence that gated myocardial perfusion PET also provides clinically useful risk stratification. Although the introduction of hybrid PET/CT technology offers the exciting possibility of assessing the extent of anatomic CAD (CT coronary angiography) and its functional consequences (ischemic burden) in the same setting, there are technical challenges in the implementation of CT-based transmission imaging for attenuation correction. Nonetheless, this integrated platform for assessing anatomy and biology offers a great potential for translating advances in molecularly targeted imaging into humans.

Reproducibility and Accuracy of Quantitative Myocardial Blood Flow Assessment with 82Rb PET: Comparison with 13N-Ammonia PET

82Rb cardiac PET allows the assessment of myocardial perfusion with a column generator in clinics that lack a cyclotron. There is evidence that the quantitation of myocardial blood flow (MBF) and coronary flow reserve (CFR) with dynamic 82Rb PET is feasible. The objectives of this study were to determine the accuracy and reproducibility of MBF estimates from dynamic 82Rb PET by using our methodology for generalized factor analysis (generalized factor analysis of dynamic sequences [GFADS]) and compartment analysis. Methods: Reproducibility was evaluated in 22 subjects undergoing dynamic rest and dipyridamole stress 82Rb PET studies at a 2-wk interval. The inter- and intraobserver variability of MBF quantitation with dynamic 82Rb PET was assessed with 4 repeated estimations by each of 4 observers. Accuracy was evaluated in 20 subjects undergoing dynamic rest and dipyridamole stress PET studies with 82Rb and 13N-ammonia, respectively. The left ventricular and right ventricular blood pool and left ventricular tissue time–activity curves were estimated by GFADS. MBF was estimated by fitting the blood pool and tissue time–activity curves to a 2-compartment kinetic model for 82Rb and to a 3-compartment model for 13N-ammonia. CFR was estimated as the ratio of peak MBF to baseline MBF. Results: The reproducibility of the MBF estimates in repeated 82Rb studies was very good at rest and during peak stress (R2= 0.935), as was the reproducibility of the CFR estimates (R2 = 0.841). The slope of the correlation line was very close to one for the estimation of MBF (0.986) and CFR (0.960) in repeated 82Rb studies. The intraobserver reliability was less than 3% for the estimation of MBF at rest and during peak stress as well as for the estimation of CFR. The interobserver reliabilities were 0.950 at rest and 0.975 at peak stress. The correlation between myocardial flow estimates obtained at rest and those obtained during peak stress in 82Rb and 13N-ammonia studies was very good (R2 = 0.857). Bland–Altman plots comparing CFR estimated with 82Rb and CFR estimated with 13N-ammonia revealed an underestimation of CFR with 82Rb compared with 13N-ammonia; the underestimation was within ±1.96 SD. Conclusion: MBF quantitation with GFADS and dynamic 82Rb PET demonstrated excellent reproducibility as well as intra- and interobserver reliability. The accuracy of the absolute quantitation of MBF with factor and compartment analyses and dynamic 82Rb PET was very good, compared with that achieved with 13N-ammonia, for MBF of up to 2.5 mL/g/min.

Reconstruction and visualization of fiber and laminar structure in the normal human heart from ex vivo diffusion tensor magnetic resonance imaging (DTMRI) data.

Objective:The human heart is composed of a helical network of muscle fibers organized to form sheets that are separated by cleavage planes responsible for the orthotropic mechanical properties of cardiac muscle. The purpose of this study is the reconstruction and visualization of these structures in 3 dimensions. Methods:Anisotropic least square filtering followed by fiber and sheet tracking techniques were applied to diffusion tensor magnetic resonance imaging data of the excised human heart. Fibers were reconstructed using the first eigenvectors of the diffusion tensors. The sheets were reconstructed using the second and third eigenvectors and visualized as surfaces. Results:The fibers are shown to lie in sheets that have transmural structure, which correspond to histologic studies published in the literature. Quantitative measurements show that the sheets as appose to the fibers are organized into laminar orientations without dominant populations. Conclusions:A visualization algorithm was developed to demonstrate the complex 3-dimensional orientation of the fibers and sheets in human myocardium.

Reproducibility and Accuracy of Quantitative Myocardial Blood Flow Assessment with 82 Rb PET: Comparison with 13 N-Ammonia PET

82Rb cardiac PET allows the assessment of myocardial perfusion with a column generator in clinics that lack a cyclotron. There is evidence that the quantitation of myocardial blood flow (MBF) and coronary flow reserve (CFR) with dynamic 82Rb PET is feasible. The objectives of this study were to determine the accuracy and reproducibility of MBF estimates from dynamic 82Rb PET by using our methodology for generalized factor analysis (generalized factor analysis of dynamic sequences [GFADS]) and compartment analysis. Methods: Reproducibility was evaluated in 22 subjects undergoing dynamic rest and dipyridamole stress 82Rb PET studies at a 2-wk interval. The inter- and intraobserver variability of MBF quantitation with dynamic 82Rb PET was assessed with 4 repeated estimations by each of 4 observers. Accuracy was evaluated in 20 subjects undergoing dynamic rest and dipyridamole stress PET studies with 82Rb and 13N-ammonia, respectively. The left ventricular and right ventricular blood pool and left ventricular tissue time–activity curves were estimated by GFADS. MBF was estimated by fitting the blood pool and tissue time–activity curves to a 2-compartment kinetic model for 82Rb and to a 3-compartment model for 13N-ammonia. CFR was estimated as the ratio of peak MBF to baseline MBF. Results: The reproducibility of the MBF estimates in repeated 82Rb studies was very good at rest and during peak stress (R2= 0.935), as was the reproducibility of the CFR estimates (R2 = 0.841). The slope of the correlation line was very close to one for the estimation of MBF (0.986) and CFR (0.960) in repeated 82Rb studies. The intraobserver reliability was less than 3% for the estimation of MBF at rest and during peak stress as well as for the estimation of CFR. The interobserver reliabilities were 0.950 at rest and 0.975 at peak stress. The correlation between myocardial flow estimates obtained at rest and those obtained during peak stress in 82Rb and 13N-ammonia studies was very good (R2 = 0.857). Bland–Altman plots comparing CFR estimated with 82Rb and CFR estimated with 13N-ammonia revealed an underestimation of CFR with 82Rb compared with 13N-ammonia; the underestimation was within ±1.96 SD. Conclusion: MBF quantitation with GFADS and dynamic 82Rb PET demonstrated excellent reproducibility as well as intra- and interobserver reliability. The accuracy of the absolute quantitation of MBF with factor and compartment analyses and dynamic 82Rb PET was very good, compared with that achieved with 13N-ammonia, for MBF of up to 2.5 mL/g/min.

Quantification of Myocardial Perfusion Reserve Using Dynamic SPECT Imaging in Humans: A Feasibility Study

Myocardial perfusion imaging (MPI) is well established in the diagnosis and workup of patients with known or suspected coronary artery disease (CAD); however, it can underestimate the extent of obstructive CAD. Quantification of myocardial perfusion reserve with PET can assist in the diagnosis of multivessel CAD. We evaluated the feasibility of dynamic tomographic SPECT imaging and quantification of a retention index to describe global and regional myocardial perfusion reserve using a dedicated solid-state cardiac camera. Methods: Ninety-five consecutive patients (64 men and 31 women; median age, 67 y) underwent dynamic SPECT imaging with 99mTc-sestamibi at rest and at peak vasodilator stress, followed by standard gated MPI. The dynamic images were reconstructed into 60–70 frames, 3–6 s/frame, using ordered-subsets expectation maximization with 4 iterations and 32 subsets. Factor analysis was used to estimate blood-pool time–activity curves, used as input functions in a 2-compartment kinetic model. K1 values (99mTc-sestamibi uptake) were calculated for the stress and rest images, and K2 values (99mTc-sestamibi washout) were set to zero. Myocardial perfusion reserve (MPR) index was calculated as the ratio of the stress and rest K1 values. Standard MPI was evaluated semiquantitatively, and total perfusion deficit (TPD) of at least 5% was defined as abnormal. Results: Global MPR index was higher in patients with normal MPI (n = 51) than in patients with abnormal MPI (1.61 [interquartile range (IQR), 1.33–2.03] vs. 1.27 [IQR, 1.12–1.61], P = 0.0002). By multivariable regression analysis, global MPR index was associated with global stress TPD, age, and smoking. Regional MPR index was associated with the same variables and with regional stress TPD. Sixteen patients undergoing invasive coronary angiography had 20 vessels with stenosis of at least 50%. The MPR index was 1.11 (IQR, 1.01–1.21) versus 1.30 (IQR, 1.12–1.67) in territories supplied by obstructed and nonobstructed arteries, respectively (P = 0.02). MPR index showed a stepwise reduction with increasing extent of obstructive CAD (P = 0.02). Conclusion: Dynamic tomographic imaging and quantification of a retention index describing global and regional perfusion reserve are feasible using a solid-state camera. Preliminary results show that the MPR index is lower in patients with perfusion defects and in regions supplied by obstructed coronary arteries. Further studies are needed to establish the clinical role of this technique as an aid to semiquantitative analysis of MPI.

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.

Quantitative relationship between the extent and morphology of coronary atherosclerotic plaque and downstream myocardial perfusion.

OBJECTIVES The purpose of this study was to quantify the effects of coronary atherosclerosis morphology and extent on myocardial flow reserve (MFR). BACKGROUND Although the relationship between coronary stenosis and myocardial perfusion is well established, little is known about the contribution of other anatomic descriptors of atherosclerosis burden to this relationship. METHODS We evaluated the relationship between atherosclerosis plaque burden, morphology, and composition and regional MFR (MFR(regional)) in 73 consecutive patients undergoing Rubidium-82 positron emission tomography and coronary computed tomography angiography for the evaluation of known or suspected coronary artery disease. RESULTS Atherosclerosis was seen in 51 of 73 patients and in 107 of 209 assessable coronary arteries. On a per-vessel basis, the percentage diameter stenosis (p = 0.02) or summed stenosis score (p = 0.002), integrating stenoses in series, was the best predictor of MFR(regional). Importantly, MFR(regional) varied widely within each coronary stenosis category, even in vessels with nonobstructive plaques (n = 169), 38% of which had abnormal MFR(regional) (<2.0). Total plaque length, composition, and remodeling index were not associated with lower MFR. On a per-patient basis, the modified Duke CAD (coronary artery disease) index (p = 0.04) and the number of segments with mixed plaque (p = 0.01) were the best predictors of low MFR(global). CONCLUSIONS Computed tomography angiography descriptors of atherosclerosis had only a modest effect on downstream MFR. On a per-patient basis, the extent and severity of atherosclerosis as assessed by the modified Duke CAD index and the number of coronary segments with mixed plaque were associated with decreased MFR.

Tomographic reconstruction using an adaptive tetrahedral mesh defined by a point cloud

Medical images in nuclear medicine are commonly represented in three dimensions as a stack of two-dimensional images that are reconstructed from tomographic projections. Although natural and straightforward, this may not be an optimal visual representation for performing various diagnostic tasks. A method for three-dimensional (3-D) tomographic reconstruction is developed using a point cloud image representation. A point cloud is a set of points (nodes) in space, where each node of the point cloud is characterized by its position and intensity. The density of the nodes determines the local resolution allowing for the modeling of different parts of the image with different resolution. The reconstructed volume, which in general could be of any resolution, size, shape, and topology, is represented by a set of nonoverlapping tetrahedra defined by the nodes. The intensity at any point within the volume is defined by linearly interpolating inside a tetrahedron from the values at the four nodes that define the tetrahedron. This approach creates a continuous piecewise linear intensity over the reconstruction domain. The reconstruction provides a distinct multiresolution representation, which is designed to accurately and efficiently represent the 3-D image. The method is applicable to the acquisition of any tomographic geometry, such as parallel-, fan-, and cone-beam; and the reconstruction procedure can also model the physics of the image detection process. An efficient method for evaluating the system projection matrix is presented. The system matrix is used in an iterative algorithm to reconstruct both the intensity and location of the distribution of points in the point cloud. Examples of the reconstruction of projection data generated by computer simulations and projection data experimentally acquired using a Jaszczak cardiac torso phantom are presented. This work creates a framework for voxel-less multiresolution representation of images in nuclear medicine

Factor analysis with a priori knowledge - application in dynamic cardiac SPECT

Two factor analysis of dynamic structures (FADS) methods for the extraction of time-activity curves (TACs) from cardiac dynamic SPECT data sequences were investigated. One method was based on a least squares (LS) approach which was subject to positivity constraints. The other method was the well known apex-seeking (AS) method. A post-processing step utilizing a priori information was employed to correct for the non-uniqueness of the FADS solution. These methods were used to extract 99mTc-teboroxime TACs from computer simulations and from experimental canine and patient studies. In computer simulations, the LS and AS methods, which are completely different algorithms, yielded very similar and accurate results after application of the correction for non-uniqueness. FADS-obtained blood curves correlated well with curves derived from region of interest (ROI) measurements in the experimental studies. The results indicate that the factor analysis techniques can be used for semi-automatic estimation of activity curves derived from cardiac dynamic SPECT images, and that they can be used for separation of physiologically different regions in dynamic cardiac SPECT studies.