PET MPI Research Articles

Real-world evidence study on the impact of SPECT MPI, PET MPI, cCTA and stress echocardiography on downstream healthcare utilisation in patients with coronary artery disease in the US.

Coronary artery disease (CAD) is associated with a large clinical and economic burden. However, consensus on the optimal approach to CAD diagnosis is lacking. This study sought to compare downstream healthcare resource utilisation following different cardiac imaging modalities, to inform test selection for CAD diagnosis. Claims and electronic health records data from the Decision Resources Group Real-World Evidence US Data Repository were analysed for 2.5 million US patients who underwent single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI), positron emission tomography myocardial perfusion imaging (PET MPI), coronary computed tomography angiography (cCTA), or stress echocardiography between January 2016 and March 2018. Patients were stratified into nine cohorts based on suspected or existing CAD diagnosis, pre-test risk, and prior events or interventions. Downstream healthcare utilisation, including additional diagnostic imaging, coronary angiography, and cardiac-related health system encounters, was compared by cohort and index imaging modality. Among patients with suspected CAD diagnosed within 3 months of the index test, PET MPI was associated with lower downstream utilisation; 25-37% of patients who underwent PET MPI required additional downstream healthcare resources compared with 40-49% of patients who received SPECT MPI, 35-41% of patients who underwent cCTA, and 44-47% of patients who received stress echocardiography. Patients who underwent PET MPI experienced fewer acute cardiac events (5.3-9.4%) and generally had lower rates of healthcare encounters (0.8-4.1%) and invasive coronary angiography (ICA, 15.4-24.2%) than those who underwent other modalities. SPECT MPI was associated with more downstream ICA (31.3-38.2%) and a higher rate of cardiac events (9.5-13.2%) compared with PET MPI (5.3-9.4%) and cCTA (6.9-9.9%). Across all cohorts, additional diagnostic imaging was 1.6 to 4.7 times more frequent with cCTA compared with PET MPI. Choice of imaging modality for CAD diagnosis impacts downstream healthcare utilisation. PET MPI was associated with lower utilisation across multiple metrics compared with other imaging modalities studied.

How to differentiate obstructive from non-obstructive CAD with quantitative PET MPI using coronary flow capacity

How to differentiate obstructive from non-obstructive CAD with quantitative PET MPI using coronary flow capacity

Automated quantitation of 18F-flurpiridaz PET MPI and its diagnostic performance of coronary artery disease

Automated quantitation of 18F-flurpiridaz PET MPI and its diagnostic performance of coronary artery disease

Quantitative and qualitative comparison of Rubidium-82 and Oxygen-15 water cardiac PET

BackgroundDifferences in tracer characteristics may influence the interpretation of positron emission tomography myocardial perfusion imaging (MPI). We compare the reading of MPIs with a low-extraction retention tracer (82Rb) and a high-extraction non-retention tracer (15O-water) in a selected cohort of patients with known coronary artery disease (CAD). MethodsThirty-nine patients with known CAD referred to 82Rb MPI due to angina underwent rest and stress imaging with both tracers and experienced MPI readers provided blinded consensus reads of all studies. In addition, a comparison of regional and global quantitative measures of perfusion was performed. ResultsThe results showed 74 % agreement in the reading of 82Rb and 15O-water MPI for regional reversible ischemia and global disease, and 82 % agreement for regional irreversible ischemia. The 15O-water MPI identified more cases of global disease (n = 12 (15O-water) vs n = 4 (82Rb), p = 0.03), whereas differences in reversible ischemia (n = 22 vs n = 16, p = 0.11) and, irreversible ischemia (n = 8 vs n = 11, p = 0.45) were not significant. The correlation between myocardial blood flow measured using the two tracers was similar to previous studies (R2 = 0.78) with wide limits of agreement (−0.93 to 0.84 ml/g/min). ConclusionsAgreement between consensus readings of 82Rb and 15O-water MPI was good in patients with known CAD. In this limited size study, no significant differences in the identification of reversible and irreversible ischemia found, whereas 15O-water MPI had a higher positive rate for suspected global disease.

Cost-effectiveness of sequential CAC-first imaging approach for detection of coronary artery disease in comparison to SPECT-first imaging

Abstract Background Prior guidelines recommended a functional first-line test as in patients with suspected CAD. More recently the high NPV of a coronary artery calcium score (CACS) of zero has put focus on CACS-first strategy in selected patients. However, it is unknown if a CACS-first strategy followed by additional Coronary CT angiography (CCTA) or PET MPI if CACS > 0 is a cost-effective alternative. Purpose Our aim was to retrospectively compare the costs-effectiveness of sequential CACS-first imaging to SPECT-first imaging. Methods 2152 patients with CACS-first strategy were retrospectively 1:1 propensity matched with a cohort of SPECT-first strategy resulting in a total of 4304 patients. Referral to invasive coronary angiography (ICA), percentage of patients with diagnosed obstructive CAD, revascularization or all-cause death during 1 year follow-up were compared between both groups. In addition, the non-invasive and invasive diagnostic costs within the first year to detect obstructive CAD were also compared. Results 30.0% (N=646) in the CACS-first group had CAC zero and 51.% (N=1086) had normal stress-SPECY only. Downstream referral to ICA <90 days was lower in the CAC group ( 8.4% vs 11.5%, p=0.001), while obstructive CAD on ICA within 90 days was comparable (60.2% vs 62.5%, p=0.705) between the CACS-first and SPECT-first. Number of revascularizations (6.3% vs 7.9%, p=0.044) was lower in the CACS-first group, while death (0.5% vs 0.3%, p=0.331) was comparable between the CACS-first and SPECT-first group within the first year, respectively. The average costs spent on both non-invasive (€407 vs. €674, p<0.001) and invasive diagnostic imaging (€587 vs. €888, p<0.001) was lower when offering CACS-first instead of a MPI SPECT first protocol, respectively. Conclusion Sequential CAC-first protocol is a more cost-effective than a SPECT-first protocol in patients suspected of having CAD and reduces the referral for ICA while more patients underwent revascularization in the SPECT-first group without impact on prognosis. We therefore recommend the use of a CAC-first CT protocol in these patients.

The second phase-3 multi-center trial of flurpiridaz F-18 PET myocardial perfusion imaging for coronary artery disease evaluation

Abstract Background/Introduction Flurpiridaz F-18 (flurpiridaz) is a novel PET myocardial perfusion imaging tracer with outstanding imaging characteristics. Purpose To further assess the diagnostic efficacy and safety of flurpiridaz PET for the detection and evaluation of coronary artery disease (CAD) defined as >50% stenosis by quantitative invasive coronary angiography (ICA) in a multi-center prospective international clinical trial. The primary end point was to assess the diagnostic efficacy (sensitivity and specificity) of flurpiridaz PET MPI for the detection of CAD. The secondary end points were to compare the diagnostic performance of flurpiridaz PET vs. Tc-99m SPECT in the detection of CAD in all patients and in the clinically important subgroups of women, obese [body mass index (BMI) ≥30 kg/m2], and diabetics. Also, PET and Tc-99m SPECT were compared for defect severity/extent, image quality, confidence of interpretation and radiation dose to patients. The safety of flurpiridaz PET was also evaluated. Methods 730 patients with suspected CAD from 48 clinical sites in US, Canada and Europe were enrolled. Patients underwent 1-day rest/stress (pharmacological or exercise) flurpiridaz PET and 1- or 2-day rest-stress Tc-99m labeled SPECT before ICA. PET and SPECT images were read by 3 experts blinded to clinical and ICA data. ICA was quantified by a core laboratory expert blinded to clinical and image data. Results 578 patients (age, 63.7±9.5 years) were evaluable. Flurpiridaz PET met the prespecified primary endpoint of the study; sensitivity and specificity were significantly higher than the prespecified threshold value by two of the three readers. The secondary endpoints were also met in the overall population, in women, in obese patients, and in diabetics. Flurpiridaz PET ROC area under the curves were significantly higher than SPECT in the overall population (0.80 vs 0.68, p<0.0001), in women (0.84 vs 0.70, p<0.01), and in obese patients (0.79 vs 0.67, p<0.001), but not in diabetics (0.76 vs 0.69, p=0.088). Flurpiridaz PET was also superior to SPECT for assessment of defect extent/severity (p<0.0001). Image quality (% excellent or good) of flurpiridaz PET was significantly better than SPECT for rest images (93% vs 72%, p<0.0001), pharmacological stress images (96% vs 78%, p<0.0001), and treadmill exercise images (97% vs 87%, p<0.05). Radiation exposure, evaluated in 604 dosed patients, was less for PET than same-day rest/stress SPECT using either Tetrofosmin or Sestamibi with 6.25 mSv for flurpiridaz PET, 9.86 mSv for 99mTc-tetrofosmin SPECT and 12.41 mSv for 99mTc-sestamibi SPECT. Conclusion This second flurpiridaz PET myocardial perfusion imaging multicenter international trial demonstrates that flurpiridaz has promise as a new tracer for detection and evaluation of coronary artery disease. This is particularly so in women and patients with BMI≥30.

Longitudinal Change and Predictors of Myocardial Flow Reserve by Positron Emission Tomography for the Evaluation of Cardiac Allograft Vasculopathy Following Heart Transplantation

Background: PET myocardial flow reserve (MFR) is a noninvasive method to detect cardiac allograft vasculopathy in heart transplant (HT) recipients. There is limited data on longitudinal change and predictors of MFR following HT. Methods: We conducted a retrospective analysis of HT recipients undergoing PET MPI at an academic center. Multivariable linear and Cox regression models were constructed to identify longitudinal trends, predictors, and prognostic value of MFR after HT. Results: 183 HT recipients underwent 658 PET studies. Average MFR was 2.34 ± 0.70. MFR initially increased in the first three years following HT (+0.12 per year, P = 0.01) before beginning to decline at an annual rate of -0.06 per year (P <0.001). MFR declines preceding acute rejection and improves after treatment. Treatment with mTOR inhibitors (37.2%) slowed the rate of annual MFR decline (P = 0.03). Higher-intensity statin therapy was associated with improved MFR. Longer time post-transplant (p <0.001), hypertension (P <0.001), chronic kidney disease (P < 0.001), diabetes mellitus (P = 0.038), antibody-mediated rejection (P = 0.040), and cytomegalovirus infection (P = 0.034) were associated with reduced MFR. Reduced MFR (HR: 7.6, 95% CI: 4.4-13.4, P <0.001) and PET-defined ischemia (HR: 2.3, 95% CI: 1.4-3.9, P <0.001) was associated with a higher risk of the composite outcome of mortality, retransplantation, heart failure hospitalization, acute coronary syndrome, or revascularization. Conclusion: MFR declines after the third post-transplant year and is prognostic for cardiovascular events. Cardiometabolic risk factor modification and treatment with higher-intensity statin therapy and MTI are associated with a higher MFR.

Prevalence and Prognostic Importance of Abnormal Positron Emission Tomography Among Asymptomatic Patients With Diabetes Mellitus

BackgroundIschemia and reduced global myocardial blood flow reserve (MBFR) are associated with high cardiovascular risk among symptomatic patients with diabetes mellitus (DM). ObjectivesThis study aimed to assess the prevalence and prognostic importance of silent ischemia and reduced MBFR among asymptomatic patients with DM. MethodsThis study included 2,730 consecutive patients with DM, without known coronary artery disease (CAD) or cardiomyopathy, who underwent rubidium-82 rest/stress positron emission tomography (PET) myocardial perfusion imaging (MPI) from 2010 to 2016. These patients were followed up for all-cause mortality (n = 461) for a median follow-up of 3 years. Patients were considered asymptomatic if neither chest pain nor dyspnea was elicited. Rates of ischemia, reduced MBFR, and coronary microvascular dysfunction on PET were assessed in both groups. Cox regression was used to define the independent association of abnormal MPI markers with mortality. ResultsOne-quarter of patients with DM (23.7%; n = 647) were asymptomatic; ischemia was present in 30.5% (n = 197), reduced MBFR in 62.3% (n = 361), and coronary microvascular dysfunction in 32.7% (n = 200). In adjusted analyses, reduced MBFR (HR per 0.1 unit decrease in MBFR: 1.08 [95% CI: 1.03-1.12]; P = 0.001) and reduced ejection fraction (HR per 5% decrease: 1.10 [95% CI: 1.01-1.18]; P = 0.02) were independently prognostic of mortality among asymptomatic patients, but ischemia was not. This was comparable to DM patients with symptoms. Insulin use and older age were significant predictors of reduced MBFR among asymptomatic patients with DM. ConclusionsIn both symptomatic and asymptomatic patients with DM, impairment in MBFR is common and associated with greater mortality risk.

Improved diagnostic accuracy for coronary artery disease detection with quantitative 3D 82Rb PET myocardial perfusion imaging.

To establish requirements for normal databases for quantitative rubidium-82 (82Rb) PET MPI analysis with contemporary 3D PET/CT technology and reconstruction methods for maximizing diagnostic accuracy of total perfusion deficit (TPD), a combined metric of defect extent and severity, versus invasive coronary angiography. In total, 1571 patients with 82Rb PET/CT MPI on a 3D scanner and stress static images reconstructed with and without time-of-flight (TOF) modeling were identified. An additional eighty low pre-test probability of disease (PTP) patients reported as normal were used to form separate sex-stratified and sex-independent iterative and TOF normal databases. 3D normal databases were applied to matched patient reconstructions to quantify TPD. Per-patient and per-vessel performance of 3D versus 2D PET normal databases was assessed with receiver operator characteristic curve analysis. Diagnostic accuracy was evaluated at optimal thresholds established from PTP patients. Results were compared against logistic regression modeling of TPD adjusted for clinical variables, and standard clinical interpretation. TPD diagnostic accuracy was significantly higher using 3D PET normal databases (per-patient: 80.1% for 3D databases, versus 74.9% and 77.7% for 2D database applied to iterative and TOF images respectively, p < 0.05). Differences in male and female normal distributions for 3D attenuation-corrected reconstructions were not clinically meaningful; therefore, sex-independent databases were used. Logistic regression modeling including TPD demonstrated improved performance over clinical reads. Normal databases tailored to 3D PET images provide significantly improved diagnostic accuracy for PET MPI evaluation with automated quantitative TPD. Clinical application of these techniques should be considered to support accurate image interpretation.

Detection and correction of patient motion in dynamic 15O-water PET MPI

BackgroundPatient motion constitutes a limitation to 15O-water cardiac PET imaging. We examined the ability of image readers to detect and correct patient motion using simulated motion data and clinical patient scans.MethodsSimulated data consisting of 16 motions applied to 10 motion-free scans were motion corrected using two approaches, pre-analysis and post-analysis for motion identification. Both approaches employed a manual frame-by-frame correction method. In addition, a clinical cohort was analyzed for assessment of prevalence and effect of motion and motion correction.ResultsMotion correction was performed on 94% (pre-analysis) and 64% (post-analysis) of the scans. Large motion artifacts were corrected in 91% (pre-analysis) and 74% (post-analysis) of scans. Artifacts in MBF were reduced in 56% (pre-analysis) and 58% (post-analysis) of the scans. The prevalence of motion in the clinical patient cohort (n = 762) was 10%. Motion correction altered exam interpretation in only 10 (1.3%) clinical patient exams.ConclusionFrame-by-frame motion correction after visual inspection is useful in reducing motion artifacts in cardiac 15O-water PET. Reviewing the initial results (parametric images and polar maps) as part of the motion correction process, reduced erroneous corrections in motion-free scans. In a large clinical cohort, the impact of motion correction was limited to few patients.

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

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. 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. 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). Coronary vascular dysfunction was common in patients with PAD and was associated with increased risk of death.

Positron emission tomography myocardial perfusion imaging (PET MPI) findings predictive of post-liver transplant major adverse cardiac events.

Positron emission tomography myocardial perfusion imaging (PET MPI) is a noninvasive diagnostic test capable of detecting coronary artery disease, structural heart disease, and myocardial flow reserve (MFR). We aimed to determine the prognostic utility of PET MPI to predict post-liver transplant (LT) major adverse cardiac events (MACE). Among the 215 LT candidates that completed PET MPI between 2015 and 2020, 84 underwent LT and had 4 biomarker variables of clinical interest on pre-LT PET MPI (summed stress and difference scores, resting left ventricular ejection fraction, global MFR). Post-LT MACE were defined as acute coronary syndrome, heart failure, sustained arrhythmia, or cardiac arrest within the first 12 months post-LT. Cox regression models were constructed to determine associations between PET MPI variable/s and post-LT MACE. The median LT recipient age was 58 years, 71% were male, 49% had NAFLD, 63% reported prior smoking, 51% had hypertension, and 38% had diabetes mellitus. A total of 20 MACE occurred in 16 patients (19%) at a median of 61.5 days post-LT. One-year survival of MACE patients was significantly lower than those without MACE (54% vs. 98%, p =0.001). On multivariate analysis, reduced global MFR ≤1.38 was associated with a higher risk of MACE [HR=3.42 (1.23-9.47), p =0.019], and every % reduction in left ventricular ejection fraction was associated with an 8.6% higher risk of MACE [HR=0.92 (0.86-0.98), p =0.012]. Nearly 20% of LT recipients experienced MACE within the first 12 months of LT. Reduced global MFR and reduced resting left ventricular ejection fraction on PET MPI among LT candidates were associated with increased risk of post-LT MACE. Awareness of these PET-MPI parameters may help improve cardiac risk stratification of LT candidates if confirmed in future studies.

Splenic switch-off as a novel marker for adenosine response in nitrogen-13 ammonia PET myocardial perfusion imaging: Cross-validation against CMR using a hybrid PET/MR device

BackgroundNo methodology is available to distinguish truly reduced myocardial flow reserve (MFR) in positron emission tomography myocardial perfusion imaging (PET MPI) from seemingly impaired MFR due to inadequate adenosine response. The adenosine-induced splenic switch-off (SSO) sign has been proposed as a potential marker for adequate adenosine response in cardiac magnetic resonance (CMR). We assessed the feasibility of detecting SSO in nitrogen-13 ammonia PET MPI using SSO in CMR as the standard of reference. Methods and ResultsFifty patients underwent simultaneous CMR and PET MPI on a hybrid PET/MR device with co-injection of a gadolinium-based contrast agent and nitrogen-13 ammonia during rest and adenosine-induced stress. In CMR, SSO was assessed visually (positive vs negative SSO) and quantitatively by calculating the ratio of the peak signal intensity of the spleen during stress over rest (SIR). In PET MPI, the splenic signal activity ratio (SAR) was calculated as the maximal standard uptake value of the spleen during stress over rest. The median SIR was significantly lower in patients with positive versus negative SSO in CMR (0.57 [IQR 0.49 to 0.62] vs 0.89 [IQR 0.76 to 0.98]; P < .001). Similarly, median SAR in PET MPI was significantly lower in patients with positive versus negative SSO (0.40 [IQR 0.32 to 0.45] vs 0.80 [IQR 0.47 to 0.98]; P < .001). ConclusionSimilarly to CMR, SSO can be detected in nitrogen-13 ammonia PET MPI. This might help distinguish adenosine non-responders from patients with truly impaired MFR due to microvascular dysfunction or multivessel coronary artery disease.

Performance of cardiac PET/CT with and without phase analysis for detection of scar in cardiac sarcoidosis: Comparison to cardiac magnetic resonance imaging

BackgroundThe presence of myocardial scar in CS patients results in poor prognosis and worse outcomes. 18F-fluorodeoxyglucose (18F-FDG) PET/CT excels at visualizing inflammation but is suboptimal at detecting scar. We evaluated PET/CT sensitivity to detect scar and investigated the incremental diagnostic value of automated PET-derived data. Methods176 patients who underwent cardiac magnetic resonance (CMR) and N-13 ammonia/18F-FDG cardiac PET/CT for suspected CS within 3 months were enrolled. Scar was defined as late gadolinium enhancement (LGE) on CMR without concordant 18F-FDG uptake on 18F-FDG PET/CT. Accuracy of cardiac PET/CT at detecting scar (perfusion defect without concordant 18F-FDG uptake) was assessed before and after addition of automated PET-derived data. ResultsSensitivity of PET/CT for scar detection was 45.3% (specificity 88.9%). Addition of PET-derived LV volumes and function in a logistic regression model improved sensitivity to 57.0% (specificity: 80.0%, AUC 0.72). Addition of phase analysis maximum segmental onset of myocardial contraction > 61 improved AUC to 0.75, correctly relabeling 16.3% of patients as scar (net reclassification index 8.2%). ConclusionSensitivity of gated PET MPI alone for scar detection in CS is suboptimal. Adding PET-derived volumes/function and phase analysis data results in improved detection and characterization of scar.

Nuclear Cardiology in Women and Underrepresented Minority Populations.

To outline sex-specific features of coronary artery disease (CAD) that should be considered in the assessment of women, including those from ethnic minority populations with suspected stable ischemic heart disease (IHD). Second, to determine the latest nuclear imaging tools available to assess microvascular CAD. Latest studies indicate that women are more likely to have ischemia with no obstructive coronary arteries (INOCA) and paradoxically have worse outcomes. Therefore, the evaluation of women with suspected IHD should include assessing microvascular and epicardial coronary circulation. The prevalence of CAD is increasing in younger women due to the increased cardiovascular disease (CVD) risk burden. CAD is often underrecognized in these patients. There is increasing recognition that INOCA is not benign and should be accurately diagnosed and managed. Nuclear imaging assesses the full spectrum of CAD from microvascular CAD to multivessel obstructive epicardial CAD. Further research on myocardial blood flow (MBF) assessment with PET MPI is needed.

Artificial intelligence approach improves ischaemia prediction beyond the known pretest probability scores

Abstract Background Pre-test probability (PTP) assessment is crucial in the assessment of patients with suspected ischaemia/coronary artery disease. Presently there is no established role for artificial intelligence in estimating PTP. Purpose Comparison of a recently developed memetic pattern based algorithm (MPA) with the diagnostic power of established scores in predicting ischaemia on positron emission tomography myocardial perfusion imaging (PET MPI). Methods Consecutive patients undergoing Rubidium PET MPI for routine clinical evaluation of ischaemia were included. The PTP for each patient was estimated by MPA, the Diamond and Forrester scores (DFS), the PTP models from the European Society of Cardiology Guidelines from 2013 (ESC 2013) and 2019 (ESC 2019) and the Framingham scores (FRS). The PET MPI studies were assessed for the presence of ischaemia. Ischaemia was defined as a summed difference score (SDS) ≥2. Results The mean age of the 531 patients was 66±11 years, 34% were female, and 50% had known prior coronary artery disease; 208 patients had evidence of ischaemia. No ischaemia was found in 323 patients. The areas under the curve (AUC) are shown in the figure. The artificial intelligence based MPA provided an AUC of 0.76, PTP (ESC 2013) AUC of 0.67, PTP (ESC 2019) AUC 0.67, DFS AUC 0.56, FRS 0.68. Conclusion The MPA outperforms the established scores for PTP assessment of the ESC, DFS and FRS in prediction of ischaemia on PET MPI. It has the potential to improve the accuracy of the established diagnostic algorithm for CAD and ischaemia. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The study was in part funded by the Swiss Heart Foundation.

Internal validation of myocardial flow reserve PET imaging using stress/rest myocardial activity ratios with Rb-82 and N-13-ammonia

BackgroundMyocardial flow reserve (MFR) measurement provides incremental diagnostic and prognostic information. The objective of the current study was to investigate the application of a simplified model for the estimation of MFR using only the stress/rest myocardial activity ratio (MAR) in patients undergoing rest–stress cardiac PET MPI. Methods and resultsRest and dipyridamole stress dynamic PET imaging was performed in consecutive patients using 82Rb or 13NH3 (n = 250 each). Reference standard MFR was quantified using a standard one-tissue compartment model. Stress/rest myocardial activity ratio (MAR) was calculated using the LV-mean activity from 2 to 6 minutes post-injection. Simplified estimates of MFR (MFREST) were then calculated using an inverse power function. For 13NH3, there was good correlation between MFR and MFREST values (R = 0.63), with similar results for 82Rb (R = 0.73). There was no bias in the MFREST values with either tracer. The overall diagnostic performance of MFREST for detection of MFR < 2 was good with ROC area under the curve (AUC) = 83.2 ± 1.2% for 13NH3 and AUC = 90.4 ± 0.7% for 82Rb. ConclusionMFR was estimated with good accuracy using 82Rb and 13NH3 with a simplified method that relies only on stress/rest activity ratios. This novel approach does not require dynamic imaging or tracer kinetic modeling. It may be useful for routine quality assurance of PET MFR measurements, or in scanners where full dynamic imaging and tracer kinetic modeling is not feasible for technical or logistical reasons.

Splenic switch off as a novel marker for adenosine response in 13N-ammonia PET myocardial perfusion imaging – a pilot study

Abstract Background Positron emission tomography myocardial perfusion imaging (PET MPI) is a robust and excellent tool for assessing ischemia. So far, however, no methodology has been established to distinguish truly reduced MFR due to microvascular dysfunction or three-vessel coronary disease (CAD) from seemingly impaired MFR due to inadequate adenosine response. Conversely, for cardiac stress magnetic resonance (CMR) the adenosine induced splenic switch-off (SSO) sign has been proposed as a potential marker for adequate adenosine response. Purpose We assessed the feasibility of detecting SSO in adenosine stress 13N-ammonia PET MPI using SSO in CMR as the standard of reference. Methods 50 patients underwent simultaneous PET MPI and CMR on a hybrid PET/MR device with co-injection of 13N-ammonia and a gadolinium-based contrast agent during rest and adenosine-induced stress. In CMR, SSO was assessed qualitatively and quantitatively by calculating the ratio of the peak signal intensity of the spleen during stress over rest (SIR). Similarly, in PET MPI the splenic signal activity ratio (SAR) was calculated as the proportion of the maximal standard uptake value of the spleen in stress and rest. Additionally, MFR was quantified in PET MPI. Results Visual SSO in CMR was present in 37 (74%) patients, whereas 13 patients had no SSO. The median SIR in CMR was significantly lower in patients with visual SSO compared to patients without visual SSO (0.57 [IQR 0.49–0.62] vs. 0.89 [IQR 0.76–0.98]; p&amp;lt;0.001). Similarly, median SAR in PET was significantly lower in patients with visual SSO in CMR compared to patients without visual SSO (0.4 [IQR 0.32–0.45] vs. 0.8 [IQR 0.47–0.98]; p&amp;lt;0.001). SIR correlated significantly with SAR (r=0.4, p&amp;lt;0.05). Mean MFR was significantly higher in patients with visual SSO compared to patients without visual SSO (3.38±0.86 vs. 2.53±0.84; p&amp;lt;0.05). Conclusion Similarly to CMR, SSO can be detected in 13N-ammonia PET MPI. This might help distinguish adenosine non-responders from patients with truly impaired MFR due to microvascular dysfunction or multivessel CAD. Figure 1. Splenic switch off (*) illustrated on transaxial 13N-ammonia PET MPI stress (A) compared to rest perfusion images (B) and similarly in stress (C) and rest (D) short axis CMR (**) in the same patient during adenosine induced stress and co-injection of 13N-ammonia and a gadolinium based contrast agent, acquired on a hybrid PET/MR device. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Swiss National Science Foundation (SNSF)

RELATIVE PROGNOSTIC SIGNIFICANCE OF POSITRON EMISSION TOMOGRAPHY (PET) MYOCARDIAL PERFUSION IMAGING (MPI) MARKERS IN ISCHEMIC AND NON-ISCHEMIC CARDIOMYOPATHY

Rubidium-82 PET MPI measures of rest and peak stress perfusion, myocardial flow reserve (MFR), and changes in ejection fraction (LVEF). We compared the relative association of MFR, perfusion defects, and LVEF reserve with prognosis in ICM and NICM. Between 2010-2016, 1,679 consecutive patients with

Benefits of adding coronary calcium score scan to stress myocardial perfusion positron emission tomography imaging.

There have been little and conflicting data regarding the relationship between coronary artery calcification score (CACS) and myocardial ischemia on positron emission tomography myocardial perfusion imaging (PET MPI). The aims of this study were to investigate the relationship between myocardial ischemia on PET MPI and CACS, the frequency and severity of CACS in patients with normal PET MPI, and to determine the optimal CACS cutoff point for abnormal PET. This retrospective study included 363 patients who underwent same-setting stress PET perfusion imaging and CACS scan because of clinically suspected coronary artery disease (CAD). Fifty-five (55%) of the 363 patients had abnormal PET perfusion. There was an association between sex, diabetes mellitus (DM), smoking, and CACS and PET perfusion abnormities with P = 0.003, 0.05, 0.005, and 0.001, respectively. However, there was no association between PET perfusion abnormalities with age, body mass index, hypertension, and hypercholesterolemia. There was association between CACS and age, sex, and DM with P = 0.000, 0.014, and 0.052, respectively, and stepwise increase in the frequency of myocardial ischemia and CACS groups. Receiver-operating characteristic analysis showed that a CACS ≥304 is the optimal cutoff for predicting perfusion abnormalities with sensitivity of 64% and specificity of 69%. In conclusion, the frequency of CAC in patients with normal PET MPI is 49%, it is highly recommended to combine CACS with PET MPI in patients without a history of CAD. PET MPI identifies myocardial ischemia and defines the need for coronary revascularization, but CAC reflects the anatomic burden of coronary atherosclerosis. Combining CACS to PET MPI allows better risk stratification and identifies high-risk patients with PET, and it may change future follow-up recommendations. CACS scan is readily available and easily acquired with modern PET-computed tomography (CT) and single-photon emission CT (SPECT)-CT with modest radiation exposure.