 Germany
ABSTRACT
The aim of this study was to validate Quantitative Gated SPECT (QGS) and 4D-MSPECT for assessing left ventricular end-diastolic and systolic volumes (EDV and ESV, respectively) and left ventricular ejection fraction (LVEF) from gated 18F-FDG PET. Methods: Forty-four patients with severe coronary artery disease were examined with gated 18F-FDG PET (8 gates per cardiac cycle). EDV, ESV, and LVEF were calculated from gated 18F-FDG PET using QGS and 4D-MSPECT. Within 2 d (median), cardiovascular cine MRI (cMRI) (20 gates per cardiac cycle) was done as a reference. Results: QGS failed to accurately detect myocardial borders in 1 patient; 4D-MSPECT, in 2 patients. For the remaining 42 patients, correlation between the results of gated 18F-FDG PET and cMRI was high for EDV (R = 0.94 for QGS and 0.94 for 4D-MSPECT), ESV (R = 0.95 for QGS and 0.95 for 4D-MSPECT), and LVEF (R = 0.94 for QGS and 0.90 for 4D-MSPECT). QGS significantly (P < 0.0001) underestimated LVEF, whereas no other parameter differed significantly between gated 18F-FDG PET and cMRI for either algorithm. Conclusion: Despite small systematic differences that, among other aspects, limit interchangeability, agreement between gated 18F-FDG PET and cMRI is good across a wide range of clinically relevant volumes and LVEF values assessed by QGS and 4D-MSPECT.
Key Words: gated 18F-FDG PET cardiovascular MRI Quantitative Gated SPECT 4D-MSPECT
Left ventricular cardiac volumes and left ventricular ejection fraction (LVEF) are reliable prognostic parameters for patients with coronary artery disease (CAD) (1,2). 18F-FDG PET is widely used for identifying impaired but viable myocardium in patients with severe CAD (3).
Gated data acquisition in myocardial perfusion SPECT allows analysis of wall motion and calculation of end-diastolic and end-systolic volumes (EDV and ESV, respectively) and LVEF (46). The clinical relevance of wall motion analysis has been proven (7), and in a recent metaanalysis, volumetric analysis by gated SPECT was validated using cardiovascular cine MRI (cMRI) (8).
Given that 18F-FDG PET has a higher spatial resolution than does perfusion SPECT and that dysfunctional but viable myocardium often shows preserved 18F-FDG uptake but reduced perfusion tracer uptake, gated 18F-FDG PET seems to be better suited than gated SPECT for calculating these parametersespecially in patients with severe CAD who are referred for myocardial viability diagnosticseven if the image quality of myocardial 18F-FDG PET is more variable and dependent on physiologic parameters such as glucose and insulin levels than is the image quality of perfusion SPECT.
In a pilot study (9), we evaluated the use of Quantitative Gated SPECT (QGS; Cedars-Sinai Medical Center) for gated 18F-FDG PET data after transformation into a SPECT-like format with a voxel size of 5.8 mm in side length. This new study was done on a larger patient cohort to validate the QGS and 4D-MSPECT (University of Michigan) algorithms for quantifying EDV, ESV, and LVEF using original (i.e., untransformed) gated 18F-FDG PET data and to elucidate the characteristic differences between the 2 algorithms.
The method of reference chosen was cMRI because it allows an accurate (10), reproducible (11,12), and clinically relevant assessment of cardiac volumes and function with high temporal and spatial resolution. It is therefore best suited for a comparison with gated 18F-FDG PET. Earlier studies evaluating QGS for gated 18F-FDG PET used radionuclide angiography (13,14) as a reference method, and 2 studies with cine ventriculography (15,16) as a reference method used commercially unavailable algorithms to derive the global function from gated 18F-FDG PET. However, none of these studies used as a reference a 3-dimensional dataset without any assumptions about left ventricular geometry.
MATERIALS AND METHODS
Patients
We examined 44 patients (37 male, 7 female; mean age, 65 ± 8 y; range, 4881 y) who had severe CAD and were scheduled for routine 18F-FDG PET to assess myocardial viability. Of these, 36 had a history of at least 1 previous myocardial infarction, 15 had 1-vessel disease, 9 had 2-vessel disease, and 20 had 3-vessel disease. Diabetes mellitus had previously been diagnosed in 13 patients. The mean fasting glucose level was 131 ± 61 mg/dL (range, 81430 mg/dL). All patients gave informed consent for cMRI. The local ethics committee approved the study.
PET Methodology
PET scans were obtained on an ECAT EXACT 922/47 scanner (Siemens-CTI). All patients received 250 mg of acipimox 2 h before administration of 18F-FDG. One hour before injection of 18F-FDG, nondiabetic patients received an oral glucose load of 50 g to stimulate endogenous insulin secretion. Instead of receiving glucose, diabetics received insulin (330 IU) intravenously 510 min before administration of 18F-FDG. Gated acquisition was done 60 min after intravenous administration of 283 ± 38 MBq of 18F-FDG, dividing the cardiac cycle into 8 equal intervals. The acquisition time was 30 min for emission (2-dimensional mode) and 15 min for transmission (68Ge/68Ga rod sources). After attenuation and scatter correction of the gated 18F-FDG PET sinograms, reconstruction using filtered backprojection in a 128 x 128 matrix was done for all gates (Hanning filter; cutoff frequency, 0.4 Nyquist). A zoom factor of 1.525 was applied to obtain transverse images with an isotropic voxel size of 3.38 mm per side. The isotropic datasets were transferred to a Siemens e.soft workstation (Siemens Gammasonics Inc.), where they were reoriented on the transverse planes, with reorientation parallel first to the septum and then to the inferior wall. The resulting reoriented datasets were stored for analysis.
Quantification Using QGS and 4D-MSPECT
The reoriented datasets were loaded into fully automated QGS (4,5), which first determined the maximal-count midmyocardial surface. Next, rays were subtended normally to it and count profiles were extracted for each ray. Endocardial and epicardial boundaries were then estimated using an asymmetric gaussian fit of the count profiles.
Unlike QGS, the semiautomated 4D-MSPECT software (6) processes data on the basis of a 2-dimensional gradient image from which the initial estimates of the ventricle are made. Thereafter, a series of 1- and 2-dimensional weighted splines are used to refine the endocardial and epicardial surface estimates. In 10 patients, 4D-MSPECT did not adequately detect the estimated basal plane, and the basal planes were therefore adjusted using the interactive quality assurance module.
QGS failed to accurately detect myocardial borders in 1 patient, and 4D-MSPECT, in 2; thus, the algorithms together provided the EDV, ESV, and LVEF values for 42 patients in common.
cMRI Methodology and Data Analysis
Within a median of 2 d, all patients underwent cMRI on a 1.5-T Gyroscan ACS-NT (Philips Medical Systems) using a balanced fast-field echo sequence also known as true fast imaging with steady-state precession (12). Integrated SENSE (SENSitivity Encoding) technology allowed superior image quality because of the shorter acquisition time and the higher contrast-to-noise ratio. Patients were imaged in end-expiration using a dedicated cardiac synergy coil and breath-hold technique, with repetition and echo times of 3.1 and 1.5 msec, respectively, a flip angle of 65°, and a matrix of 256 x 256 (field of view, 350400 mm). Twenty phases were obtained per cardiac cycle. The 10- to 15-min scanning protocol included the vertical and horizontal long axes of the left ventricle, on which the planning of the short axis was then based. From base to apex, the whole left ventricle was acquired with slices of 8-mm thickness, resulting in full-volume datasets for all patients.
Left ventricular function was assessed by determining the EDV, ESV, and subsequent LVEF using the cardiac analysis software package provided by the manufacturer. The examiner did not know the results of the gated 18F-FDG PET analysis. After the cardiac base and apex were determined, the first gate in each series was defined as the end-diastolic phase, and the image with the smallest ventricular volume was defined as the end-systolic phase. The endocardial borders of both heart phases were traced manually, with the trabeculation and the papillary muscles segmented as part of the myocardium. Both EDV and ESV were then automatically computed by summing the cross-sectional areas contained by the endocardial borders of all analyzed short-axis slices (10,11). The LVEF, expressed as a percentage, was calculated as the stroke volume divided by the EDV.
Statistical Analysis
Statistical analysis was done using SPSS 10 (SPSS Inc.) and Origin 6.1 G (OriginLab Corp.) software. The data are shown as mean ± SD. The mean values of EDV, ESV,