Multicenter Evaluation of the Feasibility of Clinical Implementation of SPECT Myocardial Blood Flow Measurement: Intersite Variability and Imaging Time.

BACKGROUND: Single-center studies have shown that single photon emission computed tomography myocardial blood flow (MBF) measurement is accurate compared with MBF measured with microspheres in a porcine model, positron emission tomography, and angiography. Clinical implementation requires consistency across multiple sites. The study goal is to determine the intersite processing repeatability of single photon emission computed tomography MBF and the additional camera time required. METHODS: Five sites (Canada, Italy, Japan, Germany, and Singapore) each acquired 25 to 35 MBF studies at rest and with pharmacological stress using technetium-99m-tetrofosmin on a pinhole-collimated cadmium-zinc-telluride-based cardiac single photon emission computed tomography camera with standardized list-mode imaging and processing protocols. Patients had intermediate to high pretest probability of coronary artery disease. MBF was measured locally and at a core laboratory using commercially available software. The time a room was occupied for an MBF study was compared with that for a standard rest/stress myocardial perfusion study. RESULTS: With motion correction, the overall correlation in MBF between core laboratory and local site was 0.93 (range, 0.87-0.97) at rest, 0.90 (range, 0.84-0.96) at stress, and 0.84 (range, 0.70-0.92) for myocardial flow reserve. The local-to-core difference in global MBF (bias-MBF) was 5.4% (-3.8% to 14.8%; median [interquartile range]) at rest and 5.4% (-6.2% to 19.4%) at stress. Between the 5 sites, bias-MBF ranged from -1.6% to 11.0% at rest and from -1.9% to 16.3% at stress; the interquartile range in bias-MBF was between 9.3% (4.8%-14.0%) and 22.3% (-10.3% to 12.0%) at rest and between 17.0% (-11.3% to 5.6%) and 33.3% (-10.4% to 22.9%) at stress and was not significantly different between most sites. Both bias and interquartile range were like previously reported interobserver variability and less than the SD of the test-retest difference of 30%. The overall difference in myocardial flow reserve was 1.52% (-10.6% to 11.3%). There were no significant differences between with and without motion correction. The average additional acquisition time varied between sites from 44 to 79 minutes. CONCLUSIONS: The average bias-MBF and bias-MFR values were small with standard deviations substantially less than the test-retest variability. This demonstrates that MBF can be measured consistently across multiple sites and further supports that this technique can be reliably implemented. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03427749.

Improved precision of SPECT myocardial blood flow using a net tracer retention model.

BACKGROUND: Noninvasive quantification of absolute myocardial blood flow (MBF) and myocardial flow reserve (MFR) provides incremental benefit to relative myocardial perfusion imaging (MPI) to diagnose and manage heart disease. MBF can be measured with single-photon emission computed tomography (SPECT) but the uncertainty in the measured values is high. Standardization and optimization of protocols for SPECT MBF measurements will improve the consistency of this technique. One element of the processing protocol is the choice of kinetic model used to analyze the dynamic image series. PURPOSE: This study evaluates if a net tracer retention model (RET) will provide a better fit to the acquired data and greater test-retest precision than a one-compartment model (1CM) for SPECT MBF, with (+MC) and without (-MC) manual motion correction. METHODS: Data from previously acquired rest-stress MBF studies (31 SPECT-PET and 30 SPECT-SPECT) were reprocessed ± MC. Rate constants (K1) were extracted using 1CM and RET, +/-MC, and compared pairwise with standard PET MBF measurements using cross-validation to obtain calibration parameters for converting SPECT rate constants to MBF and to assess the goodness-of-fit of the calibration curves. Precision (coefficient of variation of test re-test relative differences, COV) of flow measurements was computed for 1CM and RET ± MC using data from the repeated SPECT MBF studies. RESULTS: Both the RET model and MC improved the goodness-of-fit of the SPECT MBF calibration curves to PET. All models produced minimal bias compared with PET (mean bias < 0.6%). The SPECT-SPECT MBF COV significantly improved from 34% (1CM+MC) to 28% (RET+MC, P = 0.008). CONCLUSION: The RET+MC model provides a better calibration of SPECT to PET and blood flow measurements with better precision than the 1CM, without loss of accuracy.

Patient-specific SPECT imaging protocols to standardize image noise.

BACKGROUND: In addition to acquired photon counts, image noise depends on the image reconstruction algorithm. This work develops patient-specific activity or acquisition time protocols to standardize the average noise in a reconstructed image for different patients, cameras, and reconstruction algorithms. METHODS: Image noise was calculated for images from 43 patients acquired on both a conventional and a multiple-pinhole cardiac SPECT camera. Functions were found to relate image noise to radiotracer activity, scan time, and body mass and were validated by normalizing the image noise in a test set of 58 patients. RESULTS: There was a 3.6-fold difference in photon sensitivity between the two cameras but a 16-fold difference in activity-scan time was necessary to match the noise levels. Image noise doubled from 45 to 128 kg for the conventional camera (12.8 minutes) and tripled for the multiple-pinhole camera (5 minutes) for 350 MBq (9.5 mCi) 99mTc-tetrofosmin. It was 16.3% and 6.1% respectively for an average sized patient. CONCLUSIONS: A linear scaling of activity with respect to the patient weight normalizes image noise but the scaling factors depend on the choice of camera and image reconstruction parameters. Therefore, equivalent numbers of acquired photon counts are not sufficient to guarantee equivalent image noise.

Noise heterogeneity in attenuation-corrected cardiac SPECT images increases perfusion value uncertainty near the base of the heart.

BACKGROUND: Dedicated cardiac SPECT cameras which employ multi-pinhole detectors have variable photon sensitivity within the camera's field-of-view such that a lower number of photon counts is typically detected from the base of the heart than from the apex. Consequently, the noise in a reconstructed image is expected to be higher at the base than at the apex of the heart. METHODS: Patient emission images were resampled to create statistical replicates which were reconstructed with and without attenuation correction. Noise images were computed using one standard deviation of the replicated images. These were evaluated for 93 patients with normal study results, each imaged with both a dual-headed parallel-hole camera and a multi-pinhole camera. Statistics for a normal database (NDB) of images from the 93 patients were also calculated. RESULTS: Image noise (1.7-fold) and NDB uncertainty (1.3-fold) increase significantly from the apex-to-the base of the heart in attenuation-corrected multi-pinhole SPECT images. The differences for non-attenuation-corrected images or those acquired with a parallel-hole camera were not significant. CONCLUSIONS: For best interpretation of attenuation-corrected images acquired with multi-pinhole cameras, knowledge of NDB uncertainty gradients should be taken into consideration.

Correction to: Patient-specific SPECT imaging protocols to standardize image noise.

The originally published version of this article contained typographical errors in the units of photon sensitivity. The units of counts · MBq-1 · min-1 and kcounts · mCi-1 · min-1 were mistakenly recorded as counts · MBq · min and kcounts · mCi · min respectively. The original article has been corrected.

Patient-specific estimation of spatially variant image noise for a pinhole cardiac SPECT camera.

PURPOSE: New single photon emission computed tomography (SPECT) cameras using fixed pinhole collimation are increasingly popular. Pinhole collimators are known to have variable sensitivity with distance and angle from the pinhole aperture. It follows that pinhole SPECT systems will also have spatially variant sensitivity and hence spatially variant image noise. The objective of this study was to develop and validate a rapid method for analytically estimating a map of the noise magnitude in a reconstructed image using data from a single clinical acquisition. METHODS: The projected voxel (PV) noise estimation method uses a modified forward projector with attenuation effects to estimate the number of photons detected from each voxel in the field-of-view. We approximate the noise for each voxel as the standard deviation of a Poisson distribution with a mean equal to the number of detected photons. An empirical formula is used to address scaling discrepancies caused by image reconstruction. Calibration coefficients are determined for the PV method by comparing it with noise measured from a nonparametrically bootstrapped set of images of a spherical uniformly filled Tc-99m water phantom. Validation studies compare PV noise estimates with bootstrapped measured noise for 31 patient images (5 min, 340 MBq, 99m Tc-tetrofosmin rest study). RESULTS: Bland-Altman analysis shows R2 correlations ≥70% between the PV-estimated and -measured image noise. For the 31 patient cardiac images, the PV noise estimate has an average bias of 0.1% compared to bootstrapped noise and have a coefficient of variation (CV) ≤ 17%. The bootstrap approach to noise measurement requires 5 h of computation for each image, whereas the PV noise estimate requires only 64 s. In cardiac images, image noise due to attenuation and camera sensitivity varies on average from 4% at the apex to 9% in the basal posterior region of the heart. The standard deviation between 15 healthy patient study images (including physiological variability in the population) ranges from 6% to 16.5% over the length of the heart. CONCLUSIONS: The PV method provides a rapid estimate for spatially variant patient-specific image noise magnitude in a pinhole-collimated dedicated cardiac SPECT camera with a bias of -0.3% and better than 83% precision.