Mitigating bias in deep learning for diagnosis of coronary artery disease from myocardial perfusion SPECT images.

PURPOSE: Artificial intelligence (AI) has high diagnostic accuracy for coronary artery disease (CAD) from myocardial perfusion imaging (MPI). However, when trained using high-risk populations (such as patients with correlating invasive testing), the disease probability can be overestimated due to selection bias. We evaluated different strategies for training AI models to improve the calibration (accurate estimate of disease probability), using external testing. METHODS: Deep learning was trained using 828 patients from 3 sites, with MPI and invasive angiography within 6 months. Perfusion was assessed using upright (U-TPD) and supine total perfusion deficit (S-TPD). AI training without data augmentation (model 1) was compared to training with augmentation (increased sampling) of patients without obstructive CAD (model 2), and patients without CAD and TPD < 2% (model 3). All models were tested in an external population of patients with invasive angiography within 6 months (n = 332) or low likelihood of CAD (n = 179). RESULTS: Model 3 achieved the best calibration (Brier score 0.104 vs 0.121, p < 0.01). Improvement in calibration was particularly evident in women (Brier score 0.084 vs 0.124, p < 0.01). In external testing (n = 511), the area under the receiver operating characteristic curve (AUC) was higher for model 3 (0.930), compared to U-TPD (AUC 0.897) and S-TPD (AUC 0.900, p < 0.01 for both). CONCLUSION: Training AI models with augmentation of low-risk patients can improve calibration of AI models developed to identify patients with CAD, allowing more accurate assignment of disease probability. This is particularly important in lower-risk populations and in women, where overestimation of disease probability could significantly influence down-stream patient management.

Unsupervised learning to characterize patients with known coronary artery disease undergoing myocardial perfusion imaging.

PURPOSE: Patients with known coronary artery disease (CAD) comprise a heterogenous population with varied clinical and imaging characteristics. Unsupervised machine learning can identify new risk phenotypes in an unbiased fashion. We use cluster analysis to risk-stratify patients with known CAD undergoing single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). METHODS: From 37,298 patients in the REFINE SPECT registry, we identified 9221 patients with known coronary artery disease. Unsupervised machine learning was performed using clinical (23), acquisition (17), and image analysis (24) parameters from 4774 patients (internal cohort) and validated with 4447 patients (external cohort). Risk stratification for all-cause mortality was compared to stress total perfusion deficit (< 5%, 5-10%, ≥10%). RESULTS: Three clusters were identified, with patients in Cluster 3 having a higher body mass index, more diabetes mellitus and hypertension, and less likely to be male, have dyslipidemia, or undergo exercise stress imaging (p < 0.001 for all). In the external cohort, during median follow-up of 2.6 [0.14, 3.3] years, all-cause mortality occurred in 312 patients (7%). Cluster analysis provided better risk stratification for all-cause mortality (Cluster 3: hazard ratio (HR) 5.9, 95% confidence interval (CI) 4.0, 8.6, p < 0.001; Cluster 2: HR 3.3, 95% CI 2.5, 4.5, p < 0.001; Cluster 1, reference) compared to stress total perfusion deficit (≥10%: HR 1.9, 95% CI 1.5, 2.5 p < 0.001; < 5%: reference). CONCLUSIONS: Our unsupervised cluster analysis in patients with known CAD undergoing SPECT MPI identified three distinct phenotypic clusters and predicted all-cause mortality better than ischemia alone.

Accurate and efficient rapid acquisition early post-injection stress-first CZT SPECT myocardial perfusion imaging with tetrofosmin and attenuation correction.

INTRODUCTION: Myocardial perfusion imaging (MPI) protocols have not changed significantly despite advances in instrumentation and software. We compared an early post-injection, stress-first SPECT protocol to standard delayed imaging. METHODS: 95 patients referred for SPECT MPI were imaged upright and supine on a Spectrum Dynamics D-SPECT CZT system with CT attenuation correction. Patients received injection of 99mTc tetrofosmin at peak of regadenoson stress and were imaged. Early post-stress (mean 17 ± 2 minutes) and Standard 1-h delay (mean 61 ± 13 min). Three blinded readers evaluated images for overall interpretation, perceived need for rest imaging, image quality, and reader confidence. Laboratory efficiency was also evaluated. RESULTS: Blinded readers had the same response for the need for rest in 77.9% of studies. Studies also had the same interpretation in 89.5% of studies. Reader confidence was high (86.0% (Early) and 90.3% (Standard p = 0.52. Image quality was good or excellent in 87.4% Early vs 96.8% Standard (p = 0.09). Time between patient check-in and end of stress imaging was 104 ± (Standard) to 60 ± 18 minutes (Early) (p < 0.001). CONCLUSION: Early post-injection stress-only imaging using CZT SPECT/CT appears promising with Tc-99m tetrofosmin with similar image quality, reader confidence, diagnosis, and need for a rest scan.

Coronary vascular dysfunction is associated with increased risk of death in patients with peripheral artery disease.

BACKGROUND: Peripheral artery disease (PAD) and coronary vascular dysfunction are common in patients with cardiometabolic disease. Neither the prevalence of coronary vascular dysfunction among patients with PAD nor the prognostic impact with these two conditions present together has been well studied. METHODS: Consecutive patients who underwent PET MPI were analyzed for presence of coronary vascular dysfunction [myocardial blood flow reserve (MBFR) < 2]. Cox regression was used to examine the association of reduced MBFR with mortality in patients with PAD, as well as the association of comorbid MBFR < 2 and PAD with all-cause death. RESULTS: Among 13,940 patients, 1936 (14%) had PAD, 7782 (56%) had MBFR < 2 and 1346 (10%) had both PAD and MBFR < 2. Reduced MBFR was very common (69.5%) and was associated with increased risk of all-cause death (HR 1.69, 95%CI 1.32, 2.16, p < 0.01) in patients with PAD. Patients with both PAD and MBFR < 2, and those with either PAD or reduced MBFR had increased risk of death compared to those with neither condition: PAD + MBFR < 2 [(HR 95%CI), 2.30; 1.97-2.68], PAD + MBFR ≥ 2 (1.37; (1.08-1.72), PAD - MBFR < 2 (1.98; 1.75-2.25), p < 0.001 for all). CONCLUSION: Coronary vascular dysfunction was common in patients with PAD and was associated with increased risk of death.

Hot spot imaging in cardiovascular diseases: an information statement from SNMMI, ASNC, and EANM.

This information statement from the Society of Nuclear Medicine and Molecular Imaging, American Society of Nuclear Cardiology, and European Association of Nuclear Medicine describes the performance, interpretation, and reporting of hot spot imaging in nuclear cardiology. The field of nuclear cardiology has historically focused on cold spot imaging for the interpretation of myocardial ischemia and infarction. Hot spot imaging has been an important part of nuclear medicine, particularly for oncology or infection indications, and the use of hot spot imaging in nuclear cardiology continues to expand. This document focuses on image acquisition and processing, methods of quantification, indications, protocols, and reporting of hot spot imaging. Indications discussed include myocardial viability, myocardial inflammation, device or valve infection, large vessel vasculitis, valve calcification and vulnerable plaques, and cardiac amyloidosis. This document contextualizes the foundations of image quantification and highlights reporting in each indication for the cardiac nuclear imager.

Reasons for discordance between positron emission tomography (PET) myocardial perfusion imaging (MPI) results and subsequent management.

BACKGROUND: Referral patterns to coronary angiography following positron emission tomography (PET) myocardial perfusion imaging (MPI) and reasons for non-referral following abnormal PET MPI are largely unknown. METHODS: Referral rates to coronary angiography within 90 days post PET MPI were determined. A random subset of 100 patients with severe (≥ 10%) ischemia on MPI between 2014-16 who were not referred for angiography were examined to better understand reasons as to why patients with high-risk MPI findings did not undergo coronary angiography. RESULTS: Among 19,282 unique patients, overall rate of 90-day coronary angiography was 18.5% (3574/19282). Among patients with severe ischemia, 64.1% (1930/3011) underwent angiography within 90 days; the rate was lower in those with mild-moderate (20.6% [1010/4898]) and no ischemia (5.6% [634/11373]). In the random sample of 100 patients, the most common physician reasons for non-referral were uncertainty regarding whether the test results were responsible for the patient's presenting symptoms, renal failure, and patient age, frailty, or cognitive status, while patient preference for medical management was by far the most common patient reason. CONCLUSION: Referral rates for coronary angiography after PET correlate with severity of ischemia. However, there appear to be opportunities to reconsider testing for instances when results will not change clinical management.

Machine learning to predict abnormal myocardial perfusion from pre-test features.

BACKGROUND: Accurately predicting which patients will have abnormal perfusion on MPI based on pre-test clinical information may help physicians make test selection decisions. We developed and validated a machine learning (ML) model for predicting abnormal perfusion using pre-test features. METHODS: We included consecutive patients who underwent SPECT MPI, with 20,418 patients from a multi-center (5 sites) international registry in the training population and 9019 patients (from 2 separate sites) in the external testing population. The ML (extreme gradient boosting) model utilized 30 pre-test features to predict the presence of abnormal myocardial perfusion by expert visual interpretation. RESULTS: In external testing, the ML model had higher prediction performance for abnormal perfusion (area under receiver-operating characteristic curve [AUC] 0.762, 95% CI 0.750-0.774) compared to the clinical CAD consortium (AUC 0.689) basic CAD consortium (AUC 0.657), and updated Diamond-Forrester models (AUC 0.658, p < 0.001 for all). Calibration (validation of the continuous risk prediction) was superior for the ML model (Brier score 0.149) compared to the other models (Brier score 0.165 to 0.198, all p < 0.001). CONCLUSION: ML can predict abnormal myocardial perfusion using readily available pre-test information. This model could be used to help guide physician decisions regarding non-invasive test selection.

Prevalence and predictors of automatically quantified myocardial ischemia within a multicenter international registry.

BACKGROUND: The utility of cardiac stress testing depends on the prevalence of myocardial ischemia within candidate populations. However, a comprehensive assessment of the factors influencing frequency of myocardial ischemia within contemporary populations referred for stress testing has not been performed. METHODS: We assessed 19,690 patients undergoing nuclear stress testing from a multicenter registry. The chi-square test was used to assess the relative importance of features for predicting myocardial ischemia. RESULTS: In the overall cohort, LVEF, male gender, and rest total perfusion deficit (TPD) were the top three predictors of ischemia, followed by CAD status, age, typical angina, and CAD risk factors. Myocardial ischemia was observed in 13.6 % of patients with LVEF > 55 %, in 26.2 % of patients with LVEF 45 %-54 %, and in 48.3% among patients with LVEF < 45 % (P < 0.001). A similar pattern was noted for rest TPD (P < 0.001). Men had a threefold higher frequency of ischemia versus women (25.8 % vs. 8.4%, P < 0.001). Although the relative ranking of ischemia predictors varied among centers, LVEF and/or rest TPD were among the two most potent predictors of myocardial ischemia within each center. CONCLUSION: The prevalence of myocardial ischemia varied markedly according to clinical and imaging characteristics. LVEF and rest TPD are robust predictors of myocardial ischemia.

Automated quantitative analysis of CZT SPECT stratifies cardiovascular risk in the obese population: Analysis of the REFINE SPECT registry.

BACKGROUND: Obese patients constitute a substantial proportion of patients referred for SPECT myocardial perfusion imaging (MPI), presenting a challenge of increased soft tissue attenuation. We investigated whether automated quantitative perfusion analysis can stratify risk among different obesity categories and whether two-view acquisition adds to prognostic assessment. METHODS: Participants were categorized according to body mass index (BMI). SPECT MPI was assessed visually and quantified automatically; combined total perfusion deficit (TPD) was evaluated. Kaplan-Meier and Cox proportional hazard analyses were used to assess major adverse cardiac event (MACE) risk. Prognostic accuracy for MACE was also compared. RESULTS: Patients were classified according to BMI: BMI < 30, 30 ≤ BMI < 35, BMI ≥ 35. In adjusted analysis, each category of increasing stress TPD was associated with increased MACE risk, except for 1% ≤ TPD < 5% and 5% ≤ TPD < 10% in patients with BMI ≥ 35. Compared to visual analysis, single-position stress TPD had higher prognostic accuracy in patients with BMI < 30 (AUC .652 vs .631, P < .001) and 30 ≤ BMI < 35 (AUC .660 vs .636, P = .027). Combined TPD had better discrimination than visual analysis in patients with BMI ≥ 35 (AUC .662 vs .615, P = .003). CONCLUSIONS: Automated quantitative methods for SPECT MPI interpretation provide robust risk stratification in the obese population. Combined stress TPD provides additional prognostic accuracy in patients with more significant obesity.

Diagnostic safety of a machine learning-based automatic patient selection algorithm for stress-only myocardial perfusion SPECT.

BACKGROUND: Stress-only myocardial perfusion imaging (MPI) markedly reduces radiation dose, scanning time, and cost. We developed an automated clinical algorithm to safely cancel unnecessary rest imaging with high sensitivity for obstructive coronary artery disease (CAD). METHODS AND RESULTS: Patients without known CAD undergoing both MPI and invasive coronary angiography from REFINE SPECT were studied. A machine learning score (MLS) for prediction of obstructive CAD was generated using stress-only MPI and pre-test clinical variables. An MLS threshold with a pre-defined sensitivity of 95% was applied to the automated patient selection algorithm. Obstructive CAD was present in 1309/2079 (63%) patients. MLS had higher area under the receiver operator characteristic curve (AUC) for prediction of CAD than reader diagnosis and TPD (0.84 vs 0.70 vs 0.78, P < .01). An MLS threshold of 0.29 had superior sensitivity than reader diagnosis and TPD for obstructive CAD (95% vs 87% vs 87%, P < .01) and high-risk CAD, defined as stenosis of the left main, proximal left anterior descending, or triple-vessel CAD (sensitivity 96% vs 89% vs 90%, P < .01). CONCLUSIONS: The MLS is highly sensitive for prediction of both obstructive and high-risk CAD from stress-only MPI and can be applied to a stress-first protocol for automatic cancellation of unnecessary rest imaging.

Comparison of diabetes to other prognostic predictors among patients referred for cardiac stress testing: A contemporary analysis from the REFINE SPECT Registry.

BACKGROUND: Diabetes mellitus (DM) is increasingly prevalent among contemporary populations referred for cardiac stress testing, but its potency as a predictor for major adverse cardiovascular events (MACE) vs other clinical variables is not well delineated. METHODS AND RESULTS: From 19,658 patients who underwent SPECT-MPI, we identified 3122 patients with DM without known coronary artery disease (CAD) (DM+/CAD-) and 3564 without DM with known CAD (DM-/CAD+). Propensity score matching was used to control for the differences in characteristics between DM+/CAD- and DM-/CAD+ groups. There was comparable MACE in the matched DM+/CAD- and DM-/CAD+ groups (HR 1.15, 95% CI 0.97-1.37). By Chi-square analysis, type of stress (exercise or pharmacologic), total perfusion deficit (TPD), and left ventricular function were the most potent predictors of MACE, followed by CAD and DM status. The combined consideration of mode of stress, TPD, and DM provided synergistic stratification, an 8.87-fold (HR 8.87, 95% CI 7.27-10.82) increase in MACE among pharmacologically stressed patients with DM and TPD > 10% (vs non-ischemic, exercised stressed patients without DM). CONCLUSIONS: Propensity-matched patients with DM and no known CAD have similar MACE risk compared to patients with known CAD and no DM. DM is synergistic with mode of stress testing and TPD in predicting the risk of cardiac stress test patients.

The Potential of F-18 Flurpiridaz PET/CT Myocardial Perfusion Imaging for Precision Imaging.

PURPOSE OF THE REVIEW: Myocardial perfusion imaging (MPI) with single photon emission computed tomography (SPECT) has been the main method for assessing patients with known or suspected coronary artery disease (CAD) for decades. Based on a strong and growing evidence base, positron emission tomography (PET) MPI is increasingly favored when it is available. However, currently available PET perfusion tracers have limitations that have hampered broad utilization. RECENT FINDINGS: F-18 flurpiridaz is a novel PET MPI agent that is nearing completion of studies necessary to obtain regulatory approval. It has unique capabilities that will facilitate further expansion of PET MPI utilization. In addition, it has characteristics that may define it as the best MPI agent to date, in terms of the potential to equalize accuracy independent of patient size, gender, complexity, or ability to perform exercise stress. The combination of excellent image quality and accurate absolute blood flow quantification hold the potential of its being an ideal precision tool for non-invasive assessment of myocardial blood flow and entire spectrum of ischemic heart disease.

Stress myocardial perfusion imaging in patients presenting with syncope: Comparison of PET vs. SPECT.

BACKGROUND: The role of myocardial perfusion imaging (MPI) in patients with suspected coronary artery disease (CAD) presenting with syncope is controversial. We aimed to determine diagnostic yield of MPI for evaluation of syncope in patients without known CAD, as a function of pre-test patient risk and test modality (PET vs SPECT). METHODS: Between 1/2010 and 12/2016, 1324 consecutive patients presenting with syncope without known CAD underwent MPI with PET (n = 640) or SPECT (n = 684). Rates of abnormal MPI (summed difference score (SDS) > 2 or left ventricular ejection fraction (LVEF) reserve ≤ 0 for PET and SDS > 2 or post-stress LVEF ≤ 45% for SPECT) were determined among patients stratified by pre-test risk. In patients who were referred for coronary angiography, diagnostic yield of obstructive CAD was calculated in the overall cohort as well as in a propensity-matched cohort compared to patients without syncope. RESULTS: Abnormal MPI was noted in 36.5% (201/551) of patients who had PET compared with 13.0% (87/671) who had SPECT (P < 0.001), which is largely related to higher comorbidity burden and greater pre-test CAD risk in the PET population. Among patients who had an abnormal MPI, 8.5% (47/551) with PET and 0.7% (5/671) with SPECT were found to have obstructive CAD if referred for coronary angiography. Patients at intermediate-high pre-test risk had a higher proportion of abnormal MPIs and obstructive CAD as compared to those at low risk in both the PET and SPECT cohorts. The rate of abnormal testing and diagnostic yield of PET MPI was similar and proportionate to pre-test likelihood among matched patients with and without syncope. CONCLUSIONS: Among patients referred for PET MPI with syncope at an intermediate-high pre-test CAD risk, 1 in 3 had an abnormal MPI and 1 in 10 had obstructive CAD. The value of MPI was related to pre-test risk as opposed to the presence of syncope, and MPI testing with PET or SPECT in the low-risk population was low value.

Assessing myocardial perfusion in suspected coronary artery disease: rationale and design of the second phase 3, open-label multi-center study of flurpiridaz (F-18) injection for positron emission tomography (PET) imaging.

BACKGROUND: Positron emission tomography (PET) myocardial perfusion imaging (MPI) with the novel radiopharmaceutical Fluorine-18 Flurpiridaz has been shown in Phase 1, 2, and first Phase 3 clinical studies to be safe and effective in diagnosing coronary artery disease (CAD). We describe the methodology of the second FDA-mandated phase 3 prospective, open-label, international, multi-center trial of F-18 Flurpiridaz PET MPI. METHODS: The primary study end point is to assess the diagnostic efficacy of F-18 Flurpiridaz PET MPI in the detection of significant CAD [≥ 50% by quantitative invasive coronary angiography (ICA)] in patients with suspected CAD. The secondary endpoints are to evaluate the diagnostic efficacy of F-18 Flurpiridaz PET MPI compared to Tc-99 m-labeled SPECT MPI in the detection of CAD in all patients and in the following subgroups: (1) females; (2) patients with body mass index ≥ 30 kg/m2; and (3) diabetic patients. This trial's design differs from the first phase 3 trial in that (1) comparison to SPECT is now a secondary end point; (2) patients with known CAD are excluded; and (3) both SPECT and PET MPI are performed before ICA. CONCLUSIONS: This second phase 3 study will provide additional evidence on the diagnostic efficacy of F-18 Flurpiridaz PET MPI in the detection of significant CAD. TRIAL REGISTRATION NUMBER: NCT03354273.

Myocardial blood flow reserve assessed by positron emission tomography myocardial perfusion imaging identifies patients with a survival benefit from early revascularization.

AIMS: Positron emission tomography (PET) myocardial perfusion imaging (MPI) can non-invasively measure myocardial blood flow reserve (MBFR). We aimed to examine whether MBFR identifies patients with a survival benefit after revascularization, helping to guide post-test management. METHODS AND RESULTS: We examined all-cause mortality in 12 594 consecutive patients undergoing Rb82 rest/stress PET MPI from January 2010 to December 2016, after excluding those with cardiomyopathy, prior coronary artery bypass surgery (CABG), and missing MBFR. Myocardial blood flow reserve was calculated as the ratio of stress to rest absolute myocardial blood flow. A Cox model adjusted for patient and test characteristics, early revascularization (percutaneous coronary intervention or CABG ≤90 days of MPI), and the interaction between MBFR and early revascularization was developed to identify predictors of all-cause mortality. After a median follow-up of 3.2 years, 897 patients (7.1%) underwent early revascularization and 1699 patients (13.5%) died. Ischaemia was present in 4051 (32.3%) patients, with 1413 (11.2%) having ≥10% ischaemia. Mean MBFR was 2.0 ± 1.3, with MBFR <1.8 in 4836 (38.5%). After multivariable adjustment, every 0.1 unit decrease in MBFR was associated with 9% greater hazard of all-cause death (hazard ratio 1.09, 95% confidence interval 1.08-1.10; P < 0.001). There was a significant interaction between MBFR and early revascularization (P < 0.001); such that patients with MBFR ≤1.8 had a survival benefit with early revascularization, regardless of type of revascularization or level of ischaemia. CONCLUSION: Myocardial blood flow reserve on PET MPI is associated with all-cause mortality and can identify patients who receive a survival benefit with early revascularization compared to medical therapy. This may be used to guide revascularization, and prospective validation is needed.

Technetium pyrophosphate nuclear scintigraphy for cardiac amyloidosis: Imaging at 1 vs 3 hours and planar vs SPECT/CT.

BACKGROUND: Multi-societal consensus recommendations endorse both planar and single photon emission tomographic (SPECT) image acquisitions for the evaluation of cardiac amyloidosis. However, the correlation between planar and SPECT findings and the optimal timing of image acquisitions remain uncertain. METHODS: This is an analysis of 109 consecutive patients who underwent technetium pyrophosphate nuclear scintigraphy for the evaluation of cardiac amyloidosis. Patients were imaged at 1 and 3 hours after radiotracer injection using both planar and SPECT/CT, and the correlations between imaging protocols were compared. RESULTS: In the overall cohort (median age 77 years, 75% male), 33 patients had radiotracer localized to the myocardium on SPECT/CT images. There was strong correlation between 1- and 3-hour planar heart-to-contralateral lung ratios (mean difference 0.07, r = 0.94). However, there was discordance between planar image interpretation (based upon semiquantitative score and H/CL ratio) and myocardial localization of radiotracer on SPECT/CT in 17 patients (16%). The pattern of SPECT/CT uptake was identical at 1 and 3 hours in all cases (32 diffuse, 1 focal). CONCLUSION: These data support the recommendation that SPECT/CT should be obtained in addition to planar images when performing nuclear scintigraphy for the detection of cardiac amyloidosis. A 1-hour planar and SPECT/CT protocol appears optimal.

Drivers of radiation dose reduction with myocardial perfusion imaging: A large health system experience.

BACKGROUND: Despite increasing emphasis on reducing radiation exposure from myocardial perfusion imaging (MPI), the use of radiation-sparing practices (RSP) at nuclear laboratories remains limited. Defining real-world impact of RSPs on effective radiation dose (E) can potentially further motivate their adoption. METHODS: MPI studies performed between 1/2010 and 12/2016 within a single health system were included. Mean E was compared between sites with 'basic' RSP (defined as elimination of thallium-based protocols and use of stress-only (SO) imaging on conventional single photon emission computed tomography (SPECT) cameras) and those with 'advanced' capabilities (sites that additionally used solid-state detector (SSD) SPECT cameras, advanced post-processing software (APPS) or positron emission tomography (PET) imaging), after matching patients by age, gender, and weight. Contributions of individual RSP to E reduction were determined using multiple linear regression after adjusting for factors affecting tracer dose. RESULTS: Among 55,930 MPI studies performed, the use of advanced RSP was associated with significantly lower mean E compared to basic RSP (7 ± 5.6 mSv and 16 ± 5.4 mSv, respectively; P < 0.001), with a greater likelihood of achieving E < 9 mSv (65.7% vs. 10.8%, respectively; OR 15.8 [95% CI 14 to 17.8]; P < 0.0001). Main driver of E reduction was SO-SSD SPECT (mean reduction = 11.5 mSv), followed by use of SO-SPECT + APPS (mean reduction = 10.1 mSv), ;ET (mean reduction = 9.7 mSv); and elimination of thallium protocols (mean reduction = 9.1 mSv); P < 0.0001 for all comparisons. CONCLUSION: In a natural experiment with implementation of radiation-saving practices at a large health system, stress-only protocols used in conjunction with modern SPECT technologies, the use of PET and elimination of thallium-based protocols were associated with greatest reductions in radiation dose. Availability of several approaches to dose reduction within a health system can facilitate achievement of targeted radiation benchmarks in a greater number of performed studies.

Rationale and design of the REgistry of Fast Myocardial Perfusion Imaging with NExt generation SPECT (REFINE SPECT).

BACKGROUND: We aim to establish a multicenter registry collecting clinical, imaging, and follow-up data for patients who undergo myocardial perfusion imaging (MPI) with the latest generation SPECT scanners. METHODS: REFINE SPECT (REgistry of Fast Myocardial Perfusion Imaging with NExt generation SPECT) uses a collaborative design with multicenter contribution of clinical data and images into a comprehensive clinical-imaging database. All images are processed by quantitative software. Over 290 individual imaging variables are automatically extracted from each image dataset and merged with clinical variables. In the prognostic cohort, patient follow-up is performed for major adverse cardiac events. In the diagnostic cohort (patients with correlating invasive angiography), angiography and revascularization results within 6 months are obtained. RESULTS: To date, collected prognostic data include scans from 20,418 patients in 5 centers (57% male, 64.0 ± 12.1 years) who underwent exercise (48%) or pharmacologic stress (52%). Diagnostic data include 2079 patients in 9 centers (67% male, 64.7 ± 11.2 years) who underwent exercise (39%) or pharmacologic stress (61%). CONCLUSION: The REFINE SPECT registry will provide a resource for collaborative projects related to the latest generation SPECT-MPI. It will aid in the development of new artificial intelligence tools for automated diagnosis and prediction of prognostic outcomes.

Upper reference limits of transient ischemic dilation ratio for different protocols on new-generation cadmium zinc telluride cameras: A report from REFINE SPECT registry.

BACKGROUND: Upper reference limits for transient ischemic dilation (TID) have not been rigorously established for cadmium-zinc-telluride (CZT) camera systems. We aimed to derive TID limits for common myocardial perfusion imaging protocols utilizing a large, multicenter registry (REFINE SPECT). METHODS: One thousand six hundred and seventy-two patients with low likelihood of coronary artery disease with normal perfusion findings were identified. Images were processed with Quantitative Perfusion SPECT software (Cedars-Sinai Medical Center, Los Angeles, CA). Non-attenuation-corrected, camera-, radiotracer-, and stress protocol-specific TID limits in supine position were derived from 97.5th percentile and mean + 2 standard deviations (SD). Reference limits were compared for different solid-state cameras (D-SPECT vs. Discovery), radiotracers (technetium-99m-sestamibi vs. tetrofosmin), different types of stress (exercise vs. four different vasodilator-based protocols), and different vasodilator-based protocols. RESULTS: TID measurements did not follow Gaussian distribution in six out of eight subgroups. TID limits ranged from 1.18 to 1.52 (97.5th percentile) and 1.18 to 1.39 (mean + 2SD). No difference was noted between D-SPECT and Discovery cameras (P = 0.71) while differences between exercise and vasodilator-based protocols (adenosine, regadenoson, or regadenoson-walk) were noted (all P < 0.05). CONCLUSIONS: We used a multicenter registry to establish camera-, radiotracer-, and protocol-specific upper reference limits of TID for supine position on CZT camera systems. Reference limits did not differ between D-SPECT and Discovery camera.

Reliability of the 123I-mIBG heart/mediastinum ratio: Results of a multicenter test-retest reproducibility study.

A quantitative measurement, the Heart-to-Mediastinum (H/M) ratio of counts derived from a planar acquisition approximately 4 hours after injection of 123I-mIBG, is a strong predictor of outcomes in patients with stable class II-III heart failure and LVEF ≤ 35%. This study assessed the test-retest reproducibility of the H/M ratio in such patients. 47 subjects with class II-III systolic heart failure and LVEF ≤ 35% were tested at two time intervals separated by 5 to 14 days. Subjects were imaged twice on the same camera using the same radionuclide dose. Images were sent to a core analysis lab, where three nuclear technologists independently determined the H/M ratios. The primary endpoint was test-retest H/M ratio reproducibility calculated as the absolute difference in mean value determined by the three readers. Mean subject age was 65 ± 12 years, 85% were male, and mean BMI was 29 ± 6 kg/m2. Mean injected activity was 10.18 ± 0.43 mCi for first dose and 10.09 ± 0.52 mCi for the second dose. The mean and SD values for first and repeat studies were almost identical: the 95% confidence interval of the mean test-retest difference was 0.055 to 0.076. Bland-Altman plots showed no systematic effect of the H/M ratio on the magnitude of the difference between replicate measurements. Inter-reader measurements were nearly identical. There were no serious adverse events despite exposure to 123I-mIBG on 2 occasions in a short time period. The Heart-to-Mediastinum ratio of 123I-mIBG is a consistent and highly reproducible measurement in stable Class II to III heart failure patients.