Positron Emission Tomography Perfusion Imaging Research Articles

Diagnostic Performance of Quantitative Perfusion Cardiac Magnetic Resonance Imaging in Patients with Prior Coronary Artery Disease.

The diagnostic performance of quantitative perfusion cardiac magnetic resonance (QP-CMR) imaging has scarcely been evaluated in patients with a history of coronary artery disease (CAD) and new onset chest pain. The present study compared the diagnostic performance of automated QP-CMR for detection of fractional flow reserve (FFR) defined hemodynamically significant CAD with visual assessment of first-pass stress perfusion CMR (v-CMR) and quantitative [15O]H2O positron emission tomography (PET) imaging in a true head-to-head fashion in patients with prior CAD. This PACIFIC-2 substudy included 145 symptomatic chronic coronary symptom patients with prior myocardial infarction (MI) and/or percutaneous coronary intervention (PCI). All patients underwent dual-sequence, single bolus perfusion CMR and [15O]H2O PET perfusion imaging followed by invasive coronary angiography with three-vessel FFR. Hemodynamically significant CAD was defined as an FFR ≤0.80. QP-CMR, v-CMR and PET exhibited a sensitivity of 66%, 67%, and 80%, respectively, whereas specificity was 60%, 62%, and 63%. Sensitivity of QP-CMR was lower than PET (P=0.015), whereas specificity of QP-CMR and PET was comparable. Diagnostic accuracy and area under the curve (AUC) of QP-CMR (64% and 0.66) was comparable to both v-CMR (66% [P=NS] and 0.67 (P=NS]) and PET (74% [P=NS] and 0.78 [P=NS]). In patients with prior MI and/or PCI, the diagnostic performance of QP-CMR was comparable to visual assessment of first-pass stress perfusion CMR and quantitative [15O]H2O PET for the detection of hemodynamically significant CAD as defined by FFR.

Impact of sex on myocardial perfusion following percutaneous coronary intervention of chronic total coronary occlusions

ObjectivesWe sought to investigate the impact of sex on myocardial perfusion changes following chronic total coronary occlusion (CTO) percutaneous coronary intervention (PCI) as measured by [15O]H2O positron-emission tomography (PET) perfusion imaging. BackgroundCTO PCI has been associated with an increase in myocardial perfusion, yet females are less likely to undergo revascularization. As such, data on the impact of sex on myocardial perfusion following CTO PCI is scarce. MethodsA total of 212 patients were prospectively enrolled and underwent CTO PCI combined with [15O]H2O PET perfusion imaging prior to and 3 months after PCI. Hyperemic myocardial blood flow (hMBF, mL·min−1·g−1) and coronary flow reserve (CFR) allocated to the CTO territory were quantitatively assessed. ResultsThis study comprised 34 (16 %) females and 178 (84 %) males. HMBF at baseline did not differ between sexes. Females showed a higher increase in hMBF than males (Δ1.34 ± 0.67 vs. Δ1.06 ± 0.74, p = 0.044), whereas post-PCI hMBF was comparable (2.59 ± 0.85 in females vs. 2.28 ± 0.84 in males, p = 0.052). Female sex was independently associated with a higher increase in hMBF after correction for clinical covariates. CFR increase after revascularization was similar in females and males (Δ1.47 ± 0.99 vs. Δ1.30 ± 1.14, p = 0.711). ConclusionsThe present study demonstrates a greater recovery of stress perfusion in females compared to males as measured by serial [15O]H2O PET imaging. In addition, a comparable increase in CFR was found in females and males. These results emphasize the benefit of performing CTO PCI in both sexes. Clinical perspectiveWhat is new?•CTO PCI has been associated with an increase in myocardial perfusion, yet females are less likely to undergo revascularization.•We found a greater recovery of stress perfusion in females compared to males after CTO PCI as measured by serial [15O]H2O PET imaging, whereas coronary flow reserve was comparable between sexes.•The present study adds to the limited body of evidence on the impact of sex on myocardial perfusion following CTO PCI.What are the clinical implications?•Our findings suggest that recovery of myocardial perfusion following CTO PCI is achievable in both female and male patients.•These results underscore the need to adhere to current guidelines for optimal CTO management in both sexes.•Future studies with standardized preprocedural imaging are warranted to increase our understanding of the impact of sex on changes in myocardial perfusion following CTO PCI.

PET-determined myocardial perfusion and flow in coronary artery disease characterization

Positron emission tomography (PET) myocardial perfusion imaging in conjunction with tracer-kinetic modeling enables the concurrent assessment of myocardial perfusion and regional myocardial blood flow (MBF) of the left ventricle in absolute terms in milliliters per gram per minute (mL/g/min). The non-invasive quantification of MBF during pharmacologically induced hyperemia, at rest, and corresponding myocardial flow reserve (MFR) opens a new avenue for the identification and characterization of classical or endogen type of coronary microvascular dysfunction (CMD) as functional substrate for microvascular angina in patients with non-obstructive coronary artery disease (CAD) and/or no CAD at all. Further, PET-MBF quantification expands the scope of conventional myocardial perfusion imaging from the identification of advanced, and flow-limiting, epicardial CAD to early stages of atherosclerosis and/or CMD. Adding MBF assessment to myocardial perfusion may also reliably unravel diffuse ischemia owing to significant left main stenosis and/or multivessel CAD, commonly confirmed by peak stress transient ischemic cavity dilation of the left ventricle during maximal vasomotor stress compared to rest on gated PET images. Owing to high spatial and contrast resolution in conjunction with photon-attenuation free myocardial perfusion PET images, PET is preferentially used for CAD detection in advanced obesity and women with pronounced breast habitus. With increasing clinical use of cardiac PET perfusion and MBF assessment, individualized, and image-guided cardiovascular treatment decisions in CAD patients is likely to ensue, while its translation into improved cardiovascular outcome remains to be investigated.

The PREMISE database of 20 Macaca fascicularis PET/MRI brain images available for research

Non-human primate studies are unique in translational research, especially in neurosciences where neuroimaging approaches are the preferred methods used for cross-species comparative neurosciences. In this regard, neuroimaging database development and sharing are encouraged to increase the number of subjects available to the community, while limiting the number of animals used in research. Here we present a simultaneous positron emission tomography (PET)/magnetic resonance (MR) dataset of 20 Macaca fascicularis images structured according to the Brain Imaging Data Structure standards. This database contains multiple MR imaging sequences (anatomical, diffusion and perfusion imaging notably), as well as PET perfusion and inflammation imaging using respectively [15O]H2O and [11C]PK11195 radiotracers. We describe the pipeline method to assemble baseline data from various cohorts and qualitatively assess all the data using signal-to-noise and contrast-to-noise ratios as well as the median of intensity and the pseudo-noise-equivalent-count rate (dynamic and at maximum) for PET data. Our study provides a detailed example for quality control integration in preclinical and translational PET/MR studies with the aim of increasing reproducibility. The PREMISE database is stored and available through the PRIME-DE consortium repository.

Incremental value of a CCTA-derived AI-based ischemia algorithm over standard CCTA interpretation for coronary ischemia in patients with suspected coronary artery disease

Abstract Background Coronary computed tomography angiography (CCTA) is a widely used non-invasive test to diagnose coronary artery stenosis in patients with suspected coronary artery disease (CAD). Positive predictive value for ischemia has been suboptimal using clinical reading. A novel AI-based ischemia algorithm applying machine learning that considers an array of atherosclerotic and vascular morphology features from CCTA images has been suggested to improve the diagnostic performance for ischemia. Purpose This study aims to evaluate the incremental diagnostic performance of CCTA derived AI-based ischemia algorithm in evaluating myocardial ischemia. Methods Patients with suspected CAD referred for CCTA at Turku University Hospital from February 2007 to December 2016 were analysed. The AI-based ischemia algorithm was calculated by analysts blinded for patient characteristics and clinical outcomes using typically-acquired CCTA images. In diagnostic reading significant stenosis defined by a stenosis > 50% on CCTA. The reference standard was ischemia detected by stress 15O-H2O positron emission tomography (PET). Results A total of 1445 patients (mean age 63 ± 9 years, 46% male) were included in this analysis. Myocardial ischemia by PET was detected in 384 (27%) patients while the other patients had either normal PET or had non-obstructive CAD by CCTA. A positive AI-based ischemia algorithm was found in 431 (30%) patients. The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the AI-based ischemia algorithm for the assessment of myocardial ischemia were 83%, 74%, 86%, 66%, and 90%, respectively. Compared with diagnostic reading of CCTA (area under the receiver operating characteristic curve [AUC], 0.853; 95%CI 0.832-0.874), the model including clinical reading and AI-based ischemia algorithm demonstrated superior discrimination of myocardial ischemia (AUC 0.883; 95%CI 0.863-0.904, p-value <0.001). (Figure) Conclusions A novel AI-based ischemia algorithm derived from CCTA improves diagnostic accuracy compared with clinical reading of CCTA in assessing myocardial ischemia by PET perfusion imaging in patients with suspected CAD.Figure

Incremental prognostic value of downstream positron emission tomography perfusion imaging after coronary computed tomography angiography: a study using machine learning.

To evaluate the incremental value of positron emission tomography (PET) myocardial perfusion imaging (MPI) over coronary computed tomography angiography (CCTA) in predicting short- and long-term outcome using machine learning (ML) approaches. A total of 2411 patients with clinically suspected coronary artery disease (CAD) underwent CCTA, out of whom 891 patients were admitted to downstream PET MPI for haemodynamic evaluation of obstructive coronary stenosis. Two sets of Extreme Gradient Boosting (XGBoost) ML models were trained, one with all the clinical and imaging variables (including PET) and the other with only clinical and CCTA-based variables. Difference in the performance of the two sets was analysed by means of area under the receiver operating characteristic curve (AUC). After the removal of incomplete data entries, 2284 patients remained for further analysis. During the 8-year follow-up, 210 adverse events occurred including 59 myocardial infarctions, 35 unstable angina pectoris, and 116 deaths. The PET MPI data improved the outcome prediction over CCTA during the first 4 years of the observation time and the highest AUC was at the observation time of Year 1 (0.82, 95% confidence interval 0.804-0.827). After that, there was no significant incremental prognostic value by PET MPI. PET MPI variables improve the prediction of adverse events beyond CCTA imaging alone for the first 4 years of follow-up. This illustrates the complementary nature of anatomic and functional information in predicting the outcome of patients with suspected CAD.

Prognostic Value of Modified Coronary Flow Capacity Derived From [15O]H2O Positron Emission Tomography Perfusion Imaging.

Coronary flow capacity (CFC) is a measure that integrates hyperemic myocardial blood flow and coronary flow reserve to quantify the pathophysiological impact of coronary artery disease on vasodilator capacity. This study explores the prognostic value of modified CFC derived from [15O]H2O positron emission tomography perfusion imaging. Quantitative rest/stress perfusion measurements were obtained from 1300 patients with known or suspected coronary artery disease. Patients were classified as having myocardial steal (n=38), severely reduced CFC (n=141), moderately reduced CFC (n=394), minimally reduced CFC (n=245), or normal flow (n=482) using previously defined thresholds. The end point was a composite of death and nonfatal myocardial infarction. During a median follow-up of 5.5 (interquartile range, 3.7-7.8) years, the end point occurred in 153 (12%) patients. Myocardial steal (hazard ratio [HR], 6.70 [95% CI, 3.21-13.99]; P<0.001), severely reduced CFC (HR, 2.35 [95% CI, 1.16-4.78]; P=0.018), and moderately reduced CFC (HR, 1.95 [95% CI, 1.11-3.41]; P=0.020) were associated with worse prognosis compared with normal flow, after adjusting for clinical characteristics. Similarly, in the overall population, increased resting myocardial blood flow (HR, 3.05 [95% CI, 1.68-5.54]; P<0.001), decreased hyperemic myocardial blood flow (HR, 0.68 [95% CI, 0.52-0.90]; P=0.007) and decreased coronary flow reserve (HR, 0.55 [95% CI, 0.42-0.71]; P<0.001) were independently associated with adverse outcome. In a model adjusted for the combined use of perfusion metrics, modified CFC demonstrated independent prognostic value (overall P=0.017). [15O]H2O positron emission tomography-derived resting myocardial blood flow, hyperemic myocardial blood flow, coronary flow reserve, and CFC are prognostic factors for death and nonfatal myocardial infarction in patients with known or suspected coronary artery disease. Importantly, after adjustment for clinical characteristics and the combined use of [15O]H2O positron emission tomography perfusion metrics, modified CFC remained independently associated with adverse outcome.

The incremental value of PET perfusion imaging over coronary CT angiography in predicting outcome. A study using machine learning

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Academy of Finland, Turku University Hospital Background Coronary computed tomography angiography (CTA) and myocardial perfusion imaging (MPI) are powerful non-invasive tools to evaluate the patients with suspected coronary artery disease (CAD). Purpose The goal of this study was to evaluate the incremental value of these imaging methods in predicting short- and long-term cardiac events using machine learning (ML) approaches. Methods 2411 patients with clinically suspected CAD underwent coronary CTA and subsequent positron emission tomography (PET) MPI. Following our local routine, if obstructive CAD cannot be ruled-out by coronary CTA, PET MPI using 15O-water is performed. The incremental prognostic value of PET imaging was tested using several ML models of which XGBoost models consistently outperformed others and were chosen for further analyses. XGBoost models were trained by using clinical data from medical records and coronary imaging findings: one set of models used all the available variables, while a second set of models used only clinical and CTA-based variables. Differences in the performances of the models were then used to assess the incremental value of PET perfusion variables in outcome prediction. Results After the removal of incomplete data entries, data from 2284 patients was retained for further analysis. During 8-year follow-up period 210 patients had a major cardiac event (these endpoints correspond to 59 myocardial infarctions, 35 unstable angina pectoris, and 116 deaths). The PET perfusion imaging data improved the predictive power of CTA during the first 4 years of observation time. After that, no significant difference in the predictive power was observed between the considered sets of XGBoost models, which either included or did not include PET perfusion data in the input variables. The highest area under the receiver operating characteristic curve (AUC) was at the observation time of 2 years (0.81, 95% CI 0.805–0.823) when PET data were included. The corresponding AUC when PET data were not included was at the observation time of 2 years (0.79, 95% CI 0.785–0.802). Conclusions Based on ML approach PET perfusion imaging improves the power in predicting cardiac events over anatomical CTA imaging for the first 4 years. The results illustrate the differences and complementary nature of anatomic and perfusion information in predicting outcome of patients with suspected CAD.

Prognostic value of combined coronary CT angiography and myocardial perfusion imaging in women and men

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): State Research Funding for Turku University Hospital. Background Combined anatomical and functional imaging enables detection of non-obstructive and obstructive coronary artery disease (CAD) as well as myocardial ischemia, and also provides prognostic information. Purpose We evaluated sex differences in disease phenotype and adverse outcomes by using non-invasive combined anatomical and functional imaging in symptomatic patients with suspected CAD. Methods We retrospectively evaluated patients undergone coronary computed tomography angiography (CTA) for suspected CAD. According to local routine, patients with suspected obstructive stenosis on CTA were referred to downstream 15O-water positron emission tomography (PET) myocardial perfusion imaging to assess stress myocardial blood flow (MBF; ≤2.3 mL/g/min considered abnormal). A composite adverse endpoint was recorded, including all-cause death, myocardial infarction, and unstable angina pectoris. Results A total of 1948 patients (59% women) underwent coronary CTA of whom 657 (34%) patients underwent downstream PET perfusion imaging. During a mean follow-up of 6.8 years, 182 adverse events occurred. Women more often had normal coronary arteries (42% vs. 22%, p&amp;lt;0.001) and less often abnormal stress MBF (9% vs. 28%, p&amp;lt;0.001), as compared with men. The annual adverse event rate was lower in women versus men (1.2% vs. 1.7%, p = 0.02). Both in women and men, coronary calcification, non-obstructive CAD, and abnormal stress MBF were independent predictors of events. Abnormal stress MBF was associated with 5.0 and 5.6-fold adverse event rates in women and men, respectively. There was no statistical interaction between sex and coronary calcification, non-obstructive CAD, or abnormal stress MBF in terms of predicting adverse outcome. Conclusion Among patients evaluated for chronic chest pain, women have lower prevalence of ischemic CAD and lower rate of future adverse events. Combined coronary CTA and PET myocardial perfusion imaging predicts outcomes equally in women and men.

Plaque volume, composition, and fraction versus ischemia and outcomes in patients with coronary artery disease

BackgroundThe various plaque components have been associated with ischemia and outcomes in patients with coronary artery disease (CAD). The main goal of this analysis was to test the hypothesis that, at patient level, the fraction of non-calcified plaque volume (PV) of total PV is associated with ischemia and outcomes in patients with CAD. This ratio could be a simple and clinically useful parameter, if predicting outcomes. MethodsConsecutive patients with suspected CAD undergoing coronary computed tomography angiography with selective positron emission tomography perfusion imaging were selected. Plaque components were quantitatively analyzed at patient level. The fraction of various plaque components were expressed as percentage of total PV and examined among patients with non-obstructive CAD, suspected stenosis with normal perfusion, and those with reduced myocardial perfusion. Clinical outcomes included all-cause mortality and myocardial infarction. ResultsIn total, 494 patients (age 63 ​± ​9 years, 55% male) were included. Total PV and all plaque components were significantly larger in patients with reduced myocardial perfusion compared to patients with normal perfusion and those with non-obstructive CAD. During follow-up 35 events occurred. Patients with any plaque component ​≥ ​median showed worse outcomes (log-rank p ​< ​0.001 for all). In addition, low-attenuation plaque ​≥ ​median was associated with worse outcomes independent of total PV (adjusted HR: 2.754, 95% CI: 1.022–7.0419, p ​= ​0.045). The fractions of the various plaque components were not associated with outcomes. ConclusionLarger total PV or any plaque component at patient level are associated with abnormal myocardial perfusion and adverse events. The various plaque components as fraction of total PV lack additional prognostic value.

A simplified method to correct saturation of arterial input function for cardiac magnetic resonance first-pass perfusion imaging: validation with simultaneously acquired PET

BackgroundFirst-pass perfusion imaging in magnetic resonance imaging (MRI) is an established method to measure myocardial blood flow (MBF). An obstacle for accurate quantification of MBF is the saturation of blood pool signal intensity used for arterial input function (AIF). The objective of this project was to validate a new simplified method for AIF estimation obtained from single-bolus and single sequence perfusion measurements. The reference MBF was measured simultaneously on 13N-ammonia positron emission tomography (PET). MethodsSixteen patients with clinically confirmed myocardial ischemia were imaged in a clinical whole-body PET-MRI system. PET perfusion imaging was performed in a 10-min acquisition after the injection of 10 mCi of 13N-ammonia. The MRI perfusion acquisition started simultaneously with the start of the PET acquisition after the injection of a 0.075 mmol/kg gadolinium contrast agent. Cardiac stress imaging was initiated after the administration of regadenoson 20 s prior to PET-MRI scanning. The saturation part of the MRI AIF data was modeled as a gamma variate curve, which was then estimated for a true AIF by minimizing a cost function according to various boundary conditions. A standard AHA 16-segment model was used for comparative analysis of absolute MBF from PET and MRI. ResultsOverall, there were 256 segments in 16 patients, mean resting perfusion for PET was 1.06 ± 0.34 ml/min/g and 1.04 ± 0.30 ml/min/g for MRI (P = 0.05), whereas mean stress perfusion for PET was 2.00 ± 0.74 ml/min/g and 2.12 ± 0.76 ml/min/g for MRI (P < 0.01). Linear regression analysis in MBF revealed strong correlation (r = 0.91, slope = 0.96, P < 0.001) between PET and MRI. Myocardial perfusion reserve, calculated from the ratio of stress MBF over resting MBF, also showed a strong correlation between MRI and PET measurements (r = 0.82, slope = 0.81, P < 0.001). ConclusionThe results demonstrated the feasibility of the simplified AIF estimation method for the accurate quantification of MBF by MRI with single sequence and single contrast injection. The MRI MBF correlated strongly with PET MBF obtained simultaneously. This post-processing technique will allow easy transformation of clinical perfusion imaging data into quantitative information.

68Ga-FAPI PET visualize heart failure: from mechanism to clinic.

Heart failure (HF) is a chronic progressive clinical syndrome associated with structural and/or functional heart abnormalities. Active fibroblasts and ventricular remodelling play an essential role in HF progression. 68Ga-labelled fibroblast activation protein (FAP) inhibitor (68Ga-FAPI) binds to FAP. This study aimed to examine the feasibility of using 68Ga-FAPI positron emission tomography (PET)/computed tomography (CT) to visualize changes in cardiac fibrosis and function over time in the HF setting. After establishing an isoproterenol (ISO)-induced HF rat model (14 consecutive days of intraperitoneal ISO injections), echocardiography and 68Ga-FAPI PET/CT were performed weekly in experimental and control groups. Rat hearts were examined weekly for biodistribution analysis; autoradiography; and haematoxylin and eosin, FAP immunofluorescence and Masson's trichrome staining analysis. Rat blood was sampled weekly for enzyme-linked immunosorbent assay analysis of various plasma indicators. A preliminary clinical study was also performed in seven HF patients who underwent both 13N-amino (NH3) perfusion and 68Ga-FAPI cardiac PET imaging. In the animal experiments, myocardial 68Ga-FAPI uptake, expression of FAP and myocardial contractility peaked on day 7 after the initial ISO injection. Only slight fibrotic changes were observed on histopathological examination. 68Ga-FAPI uptake and ventricular wall motion decreased over time as cardiac fibrosis and degree of myocardial injury gradually increased. In the human HF patient study, 68Ga-FAPI PET imaging identified varying degrees of 68Ga-FAPI uptake in the myocardium that did not precisely match with 13N-NH3 myocardial perfusion. As HF progresses, 68Ga-FAPI uptake is high in the early stages and then gradually decreases. Although preliminary, our findings suggest that 68Ga-FAPI PET can be used to demonstrate active myocardial fibrosis. Active myocardial FAP expression is followed by myocardial remodelling and fibrosis. Detection of early active FAP expression may assist treatment decision making in HF patients. NCT04982458.

Prior SARS-CoV-2 Infection Is Associated With Coronary Vasomotor Dysfunction as Assessed by Coronary Flow Reserve From Cardiac Positron Emission Tomography.

Background Cardiovascular complications from COVID-19 contribute to its high morbidity and mortality. The effect of COVID-19 infection on the coronary vasculature is not known. The objective of this study was to investigate the prevalence of coronary vasomotor dysfunction identified by coronary flow reserve from cardiac positron emission tomography in patients with previous COVID-19 infection. Methods and Results All patients who had polymerase chain reaction-confirmed SARS-CoV-2 infection referred for myocardial stress perfusion positron emission tomography imaging at Brigham and Women's Hospital from April 2020 to July 2021 were compared with a matched control group without prior SARS-CoV-2 infection imaged in the same period. The main outcome was the prevalence of coronary vasomotor dysfunction. Myocardial perfusion and myocardial blood flow reserve were quantified using N13-ammonia positron emission tomography imaging. Thirty-four patients with prior COVID-19 were identified and compared with 103 matched controls. The median time from polymerase chain reaction-confirmed SARS-CoV-2 to cardiac positron emission tomography was 4.6 months (interquartile range,1.2-5.6 months). There were 16 out of 34 (47%) patients previously hospitalized for COVID-19 infection. Baseline cardiac risk factors were common, and 18 (53%) patients in the COVID-19 group had abnormal myocardial perfusion. Myocardial blood flow reserve was abnormal (<2) in 44.0% of the patients with COVID-19 compared with 11.7% of matched controls (P<0.001). The mean myocardial blood flow reserve was 19.4% lower in patients with COVID-19 compared with control patients (2.00±0.45 versus 2.48±0.47, P<0.001). Conclusions Myocardial blood flow reserve was impaired in patients with prior COVID-19 infection compared with cardiovascular risk factor-matched controls, suggesting a relationship between SARS-CoV-2 infection and coronary vascular health. These data highlight the need to assess long-term consequences of COVID-19 on vascular health in future prospective studies.

Time-resolved fluorescence based direct two-site apoA-I immunoassays and their clinical application in patients with suspected obstructive coronary artery disease.

ObjectiveHigh-density lipoprotein (HDL) is a heterogeneous group of subpopulations differing in protein/lipid composition and in their anti-atherogenic function. There is a lack of assays that can target the functionality of HDL particles related to atherosclerosis. The objective of this study was to construct two-site apolipoprotein A-I (apoA-I) assays and to evaluate their clinical performance in patients with suspected obstructive coronary artery disease (CAD).Approach and resultsDirect two-site apoA-I assays (named 109–121 and 110–525) were developed to identify the presence of apoA-I in the HDL of patients with CAD using apoA-I antibodies as a single-chain variable fragment fused with alkaline phosphatase. ApoA-I109−121 and apoA-I110−525 were measured in 197 patients undergoing coronary computed tomography angiography (CTA) and myocardial positron emission tomography perfusion imaging due to suspected obstructive CAD. Among patients not using lipid-lowering medication (LLM, n = 125), the level of apoA-I110−525 was higher in the presence than in the absence of coronary atherosclerosis [21.88 (15.89–27.44) mg/dl vs. 17.66 (13.38–24.48) mg/dl, P = 0.01)], whereas there was no difference in apoA-I109−121, HDL cholesterol, and apoA-I determined using a polyclonal apoA-I antibody. The levels of apoA-I109−121 and apoA-I110−525 were similar in the presence or absence of obstructive CAD. Among patients not using LLM, apoA-I110−525 adjusted for age and sex identified individuals with coronary atherosclerosis with a similar accuracy to traditional risk factors [area under the curve [AUC] (95% CI): 0.75(0.66–0.84) 0.71 (0.62–0.81)]. However, a combination of apoA-I110−525 with risk factors did not improve the accuracy [AUC (95% CI): 0.73 (0.64–0.82)].ConclusionDirect two-site apoA-I assays recognizing heterogeneity in reactivity with apoA-I could provide a potential approach to identify individuals at a risk of coronary atherosclerosis. However, their clinical value remains to be studied in larger cohorts.

Prognostic value of coronary flow capacity derived from [15O]H2O positron emission tomography perfusion imaging

Abstract Background Coronary flow capacity (CFC) is a cross-modality framework integrating hyperemic myocardial blood flow (hMBF) and coronary flow reserve (CFR) to quantify the physiological impact of coronary atherosclerotic disease on vasodilator capacity. Purpose This study explores the prognostic value of CFC derived from [15O]H2O positron emission tomography (PET) perfusion imaging in addition to traditional perfusion metrics. Methods Quantitative perfusion measurements were obtained from 1300 patients with suspected or known coronary artery disease who underwent [15O]H2O PET imaging. Patients were classified as having myocardial steal, severely reduced CFC, moderately reduced CFC, minimally reduced CFC or normal flow using previously defined perfusion thresholds. The endpoint was a composite of death and non-fatal myocardial infarction (MI). Results The composite endpoint occurred in 153 (12%) patients during a median follow-up of 5.5 (interquartile range 3.7–7.8) years. Myocardial steal (HR 10.65, 95% CI 4.45–25.49, p&amp;lt;0.001), severely reduced CFC (HR 3.77, 95% CI 1.88–7.58, p&amp;lt;0.001), moderately reduced CFC (HR 2.03, 95% CI 1.25–3.29, p=0.004) and minimally reduced CFC (HR 1.72, 95% CI 1.05–2.81, p=0.030) were independently associated with worse outcome after adjusting for clinical risk factors. Similarly, increased resting MBF (HR 3.19, 95% CI 1.74–5.83, p&amp;lt;0.001), decreased hMBF (HR 0.72, 95% CI 0.57–0.90, p=0.004) and decreased CFR (HR 0.59, 95% CI 0.47–0.73, p&amp;lt;0.001) were significant prognostic factors for events. In a combined perfusion model, only resting MBF (p=0.018) and CFC (overall p=0.012) demonstrated independent prognostic value. Conclusions [15O]H2O PET-derived resting MBF, hMBF, CFR and CFC were prognostic factors for death and non-fatal MI. Notably, in a combined model including all perfusion metrics, only resting MBF and CFC were independently associated with adverse outcome. Funding Acknowledgement Type of funding sources: None.

The use of lipid-lowering medication after diagnostic imaging procedures in patients with chest pain

Abstract Background Coronary CT angiography (CTA) combined with myocardial perfusion imaging accurately detects both non-obstructive and obstructive coronary artery disease (CAD). Lipid-lowering therapy is known to effectively reduce cardiovascular events, but the impact of non-invasive imaging findings on the usage of lipid-lowering therapy remains largely unknown. Purpose To assess the use of lipid-lowering medication in patients referred to coronary CTA and subsequent positron emission tomography (PET) myocardial perfusion imaging due to suspected obstructive CAD. Methods We retrospectively analyzed data on purchases of lipid-lowering drugs obtained from the Finnish national registry for a time period starting 1 year before and ending 2 years after the date of diagnostic imaging. This time period was divided into six 6-month intervals, for each of which the presence of any statin and/or ezetimibe purchase was recorded. According to the local routine, patients with suspected obstructive (≥50%) stenosis on coronary CTA entered downstream 15O-water PET myocardial perfusion imaging during adenosine stress to assess the hemodynamic significance of the coronary stenosis. The use of medication was compared among patients with normal coronary arteries, non-obstructive CAD, and obstructive CAD. Results During 2008–2016, a total of 1973 patients (41% male, median age 63 years) underwent coronary CTA and 33% of these had PET perfusion imaging. There were 9081 purchases of lipid-lowering drugs during the 3-year observation period. There were 676 (34%) patients with normal coronary arteries, 640 (32%) patients with non-obstructive atherosclerosis on CTA, 325 (16%) patients with suspected obstructive stenosis on CTA but normal PET perfusion, and 332 (17%) patients with obstructive stenosis and abnormal hyperemic PET perfusion. The proportion of patients buying lipid-lowering drugs was 24%, 51%, 72%, and 91%, respectively, as assessed within the 6-month interval following the CTA/PET imaging. After diagnostic testing, proportion of patients purchasing lipid-lowering medications increased in all groups except those with normal coronary arteries (Figure 1). However, there was a marked decrease in all patient groups in proportion of patients using lipid-lowering medication towards the end of the 2-year follow-up period. Conclusions In a real-world cohort of symptomatic patients with chest pain undergoing diagnostic imaging for suspected CAD, subsequent purchases of lipid-lowering drugs increase in relation to the severity of imaging findings. Although majority of patients with obstructive CAD initially purchased lipid-lowering medication, our results indicate a marked decrease in the use of these preventive medications towards the end of 2-year follow-up period. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): State Research Funding of Turku University Hospital; the Academy of Finland; Finnish Foundation for Cardiovascular Research.

Comparison of second-line on-site computed quantitative flow ratio from coronary computed tomography angiography to PET perfusion imaging for detecting obstructive coronary artery disease

Abstract Introduction In patients with suspected obstructive coronary artery disease (CAD) on coronary computed tomography (CTA), guidelines endorse second-line selective testing for hemodynamic evaluation of suspected CAD. A variety of non-invasive modalities are available, and myocardial perfusion imaging with Rubidium-82 positron emission tomography (PET) is an established method with high diagnostic performance. Recently, an on-site method estimating computed tomography-derived quantitative flow ratio (CT-QFR) showed promising results for discriminating obstructive CAD. However, no study has compared the diagnostic performances of PET and CT-QFR. Purpose To assess a possible non-inferiority of CT-QFR compared to PET in patients with suspected obstructive CAD at CTA using invasive coronary angiography (ICA) with fractional flow reserve (FFR) as reference. Methods Patients (n=1732, 57% males, age 59±9.5) referred on a clinical indication with symptoms suggestive of obstructive CAD underwent routine CTA. Patients with ≥50% diameter stenosis (DS) on CTA were referred for PET and subsequent ICA with FFR. CT-QFR was analyzed post-hoc blinded to PET and ICA results. Abnormal CT-QFR was defined as CT-QFR ≤0.80 in any vessel with a diameter ≥1.5mm. An independent core-lab evaluated PET scans as abnormal/normal with optional analyst-dependent application of pre-specified criteria; summed stress score of ≥4 in ≥2 contiguous segments, vessel-specific myocardial blood flow (MBF) &amp;lt;2.00 ml/g/min, global myocardial blood flow reserve ≤1.8, and/or transient ischemic dilatation ratio &amp;gt;1.13. Obstructive CAD was defined as ICA with FFR ≤0.80 or high-grade stenosis (≥90% DS). Results In total, 445/1732 patients (25%) had suspected obstructive CAD on CTA of whom 400/445 patients (90%) underwent subsequent PET and ICA. CT-QFR was successfully analysed in 383/400 (96%) patients classifying 174/383 (45%) patients as having disease. In comparison, PET classified 130/383 (34%) patients as having disease. In total, obstructive CAD by ICA with FFR was identified in 162 (42%) patients. There was no significant difference in area under the receiver-operating characteristic curves for CT-QFR compared to the best performing PET metric (lowest vessel-specific MBF); 0.84 (95% CI 0.80–0.89) vs. 0.81 (0.77–0.85), p=0.19)) (Fig. 1). Overall diagnostic accuracy of CT-QFR versus PET was similar (78% (95% CI 74–82) vs. 77% (72–81), p=0.70. Sensitivities for CT-QFR and PET were 78% (71–84) and 63% (55–70), p&amp;lt;0.01, respectively, and specificities 78% (72–84) and 87% (82–91), p=0.01, respectively (Fig. 2). Three-vessel or left main disease on ICA was correctly identified in 30/31 patients by both CT-QFR and PET. Conclusion In patients with suspected obstructive CAD by CTA, second-line CT-QFR was non-inferior to PET for discriminating obstructive CAD by invasive FFR; Although diagnostic accuracy was similar, CT-QFR demonstrated higher sensitivity while PET showed higher specificity Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Aarhus University PhD fellowshipRegion Mid Health Research Foundation

TCT-264 Prognostic Value of Coronary Flow Capacity Derived From [15O]H2O Positron Emission Tomography Perfusion Imaging

TCT-264 Prognostic Value of Coronary Flow Capacity Derived From [15O]H2O Positron Emission Tomography Perfusion Imaging

Decoding the Heterogeneity of Malignant Gliomas by PET and MRI for Spatial Habitat Analysis of Hypoxia, Perfusion, and Diffusion Imaging: A Preliminary Study

BackgroundTumor heterogeneity poses major clinical challenges in high-grade gliomas (HGGs). Quantitative radiomic analysis with spatial tumor habitat clustering represents an innovative, non-invasive approach to represent and quantify tumor microenvironment heterogeneity. To date, habitat imaging has been applied mainly on conventional magnetic resonance imaging (MRI), although virtually extendible to any imaging modality, including advanced MRI techniques such as perfusion and diffusion MRI as well as positron emission tomography (PET) imaging.ObjectivesThis study aims to evaluate an innovative PET and MRI approach for assessing hypoxia, perfusion, and tissue diffusion in HGGs and derive a combined map for clustering of intra-tumor heterogeneity.Materials and MethodsSeventeen patients harboring HGGs underwent a pre-operative acquisition of MR perfusion (PWI), Diffusion (dMRI) and 18F-labeled fluoroazomycinarabinoside (18F-FAZA) PET imaging to evaluate tumor vascularization, cellularity, and hypoxia, respectively. Tumor volumes were segmented on fluid-attenuated inversion recovery (FLAIR) and T1 post-contrast images, and voxel-wise clustering of each quantitative imaging map identified eight combined PET and physiologic MRI habitats. Habitats’ spatial distribution, quantitative features and histopathological characteristics were analyzed.ResultsA highly reproducible distribution pattern of the clusters was observed among different cases, particularly with respect to morphological landmarks as the necrotic core, contrast-enhancing vital tumor, and peritumoral infiltration and edema, providing valuable supplementary information to conventional imaging. A preliminary analysis, performed on stereotactic bioptic samples where exact intracranial coordinates were available, identified a reliable correlation between the expected microenvironment of the different spatial habitats and the actual histopathological features. A trend toward a higher representation of the most aggressive clusters in WHO (World Health Organization) grade IV compared to WHO III was observed.ConclusionPreliminary findings demonstrated high reproducibility of the PET and MRI hypoxia, perfusion, and tissue diffusion spatial habitat maps and correlation with disease-specific histopathological features.

The Application of Conditional Probability to Harmonize Nuclear Cardiology Test Results.

Both exercise single photon emission computed tomography (SPECT) imaging and myocardial perfusion imaging with positron emission tomography produce multiple outcome variables. These include the stress electrocardiogram (ECG), visual perfusion assessment and quantitative myocardial blood flow. Bayes' analysis using conditional probability allows the distillation of multiple test results into a single probability of disease for individual patients. This paper examines the application of conditional probability analysis to two noninvasive modalities that generate multiple outcome results: exercise ECG combined with SPECT imaging and vasodilator RB-82 positron emission tomography perfusion imaging combined with quantitative measure of absolute myocardial blood flow. In this manner, a single probability of disease incorporating all the available data is generated for an individual patient.