Quantitative Myocardial Blood Flow Research Articles

Comparison between N13NH3-PET and 99mTc-Tetrofosmin-CZT SPECT in the evaluation of absolute myocardial blood flow and flow reserve

BackgroundPET/CT is the standard for quantitative assessments of myocardial blood flow (MBF), but it requires short-lived-tracers, costly, and not widely available. SPECT with Cadmium Zinc Telluride (CZT) detectors allows dynamic acquisition and quantitation of MBF. The study aims were to compare MBF measurements by 99mTc-tetrofosmin-CZT to N13NH3 PET/CT after regadenoson-induced coronary hyperemia and to evaluate the effect of attenuation correction (AC). Methods54 patients were evaluated at rest and during vasodilation by 99mTc-tetrofosmin-CZT and N13NH3 PET/CT within 2 weeks. MBF and MBF reserve (MFR) were measured by CZT with or without AC (NAC). ResultsThe global rest MBF was 0.76 ± 0.19 mL/min/gr by PET and 0.76 ± 0.24 by AC-CZT (P = NS) and 1.14 ± 0.4 by NAC-CZT (P < 0.001 vs PET and AC-CZT). Stress MBF was higher when measured by PET than AC-CZT (1.87 ± 0.45 vs 1.62 ± 0.68 mL/min/gr, P < 0.0008), but lower than NAC-CZT (2.36 ± 1.1, P < 0.0003). The MBF reserve ratio (MFR) was higher by PET than AC-CZT (2.52 ± 0.56 vs 2.22 ± 1 (P < 0.009) and NAC-CZT (2.18 ± 1.0, P < 0.004). Linear regression was better between PET (MFR and stress MBF) and AC-CZT than between PET and NAC-CZT. ROC curve analysis showed the significant ability of AC-CZT to predict MFR < 2 and stress MBF < 1.7 (AUC = 0.75 and 0.82 respectively) and to differentiate between normal and CAD patients (AUC = 0.747 and 0.892 for MFR and stress MBF, respectively). ConclusionsOur data show a reasonable correlation between MBF and MFR measured by N13NH3-PET and 99mTc-Tetrofosmin-CZT SPECT. NAC-CZT overestimates MBF. AC is recommended when using CZT for measuring MBF.

Routine clinical use of 15O-water cardiac PET: Initial experience with a novel automated solution

Abstract Funding Acknowledgements Type of funding sources: None. Introduction While considered the gold standard for cardiac perfusion imaging and myocardial blood flow quantitation, the use of 15O-water has been largely restricted to research purposes. The practical hurdles associated with the ultra-short half-life of the tracer and the lack of dedicated software have hampered the routine clinical use of 15O-water and novel solutions have been sought to obviate the issues limiting its use. An innovative bedside 15O-water generator designed for simple push button operation and high patient through-put has been developed and recently installed at our institution and utilized clinically under a magistral exception. The system also includes an infusion device and a dedicated display and analysis software. We report the initial experience utilizing such solution for routine clinical use of 15O-water. Methods The first routine human myocardial perfusion imaging tests with PET 15O-water were conducted at our institution in December 2020. The 15O-water was produced and infused using the bed-side water generator. The activity per scan was 400 MBq in 20-35 mL of saline infused at a speed of 1-2 mL/s. Each exam consisted of a low-dose CT followed by a 4 min rest dynamic PET scan and, finally, a 4 min stress dynamic PET scan. Pharmacological stress was induced using a 6 min infusion of adenosine (0.14 mg/kg/min) starting 2 min prior to the stress PET scan. The exam time (time from initiation of the low dose CT to the end of the stress PET scan) was monitored. Images were analyzed using the dedicated software. Results Since its implementation on December 7, 2020 and as of February 23, 2021, all patients referred to the hospital for cardiac perfusion imaging have been studied with this approach. Over this period of time, a total of 295 patients have been imaged with an average of 6 patients per day (a total of 50 scan days, 3-8 patients per day). The median total exam time was 22 min (85% of the exams were within 25 min and 95% below 30 min). Conclusion Routine clinical use of 15O-water PET has been practically implemented utilizing a novel bedside generator and infusion solution. The system has proven to be reliable and efficient. This initial experience suggests that a very high patient throughput is achievable with improved resource utilization. The expected high diagnostic accuracy of the test is being evaluated with the dedicated imaging software.

Myocardial blood flow values based on 15O-water PET are insensitive to image reconstruction settings

Abstract Funding Acknowledgements Type of funding sources: None. Background For 15O-water PET, a cutoff hyperemic myocardial blood flow (MBF) value of 2.3 mL/g/min for significant ischemia has been established (1). For other tracers, different studies show a wide range of proposed cutoff values. The use of uniform absolute cutoff values for pathological hyperemic MBF or flow reserve in clinical decision making requires robust quantification of MBF, with comparable values across scanners, centres, and reconstruction methods. Purpose The aim of the present work was to assess the effect of different reconstruction methods on quantitative MBF values based on 15O-water PET. Methods 20 patients referred for assessment of ischemia underwent 4 min dynamic stress PET scans starting simultaneously with automated bolus injection of 400 MBq 15O-water on a digital PET/CT scanner. Images were reconstructed using 17 different reconstruction methods, with the clinical reconstruction used as reference: time-of-flight (TOF) ordered subsets expectation maximization (OSEM) with 3 iterations and 16 subsets, including point spread function recovery (PSF) and a 5 mm gaussian post-filter. Parameters that were varied were number of iterations (1-6), filter (3, 5 or 8 mm), exclusion of TOF and PSF, and using regularized reconstruction with 7 different values of the regularization parameter beta. Images were analyzed fully automatically using aQuant software, resulting in parametric MBF images and polar maps as well as regional MBF values. Correlation and agreement of MBF values based on each reconstruction were compared using regression and Bland-Altman analysis as well as Wilcoxon tests. Results Whole left ventricle MBF values ranged from 1.1 to 3.9 mL/g/min. Visually, there were only small differences in MBF images or polar maps between methods (Figure 1). Correlation between whole left ventricle MBF values based on the various reconstruction algorithms was high (r &amp;gt; 0.99). At the regional level, correlation coefficients were always &amp;gt; 0.94 (Figure 2). No significant bias was found between any of the reconstruction methods and the standard method (p &amp;gt; 0.65). Regression slopes relative to the standard method ranged from 0.993 to 1.080. Changes in reconstruction settings did not alter diagnosis in any patient. Conclusion Changes in reconstruction settings such as filter size, number of iterations, inclusion of time-of-flight or resolution recovery, and regularization, have negligible impact on MBF values based on 15O-water PET analyzed using the automated software. This is likely due to the fact that MBF is determined by the clearance rate of 15O-water rather than its uptake rate such as for other PET tracers, in addition to the used segmentation routines. These results also indicate that quantitative MBF measurements using 15O-water are likely to be robust across different types of PET scanners and hospitals, which is highly important for reliable clinical use of cut-off values for ischemia.

Myocardial perfusion after COVID-19 infection: No persisting impaired myocardial blood flow in surviving patients

Funding AcknowledgementsType of funding sources: None.Background Acute myocardial damage is common in hospitalized patients with severe COVID-19, with evidence of myocardial infarction and myocarditis demonstrated on cardiovascular magnetic resonance (CMR). Post-mortem studies have also implicated microvascular thrombosis, which may cause persistent microvascular disease. Purpose To determine the long-term coronary sequelae in recovered COVID-19 using multiparametric CMR including state-of-the-art inline quantitative stress myocardial blood flow (sMBF) mapping to assess global and regional sMBF.Methods Prospective, multicentre observational study of recovered COVID-19 patients scanned at three London CMR units. Results were compared to a propensity-matched, pre-COVID chest pain cohort (104 patients referred for perfusion CMR, with subsequently demonstrated unobstructed coronary arteries) and 27 healthy volunteers (HV). Perfusion image analysis was performed using a novel artificial intelligence approach deriving global and regional stress and rest MBF with a cut-off of >2.25mL/g/min signifying normal sMBF and <1.82mL/g/min abnormal sMBF (Kotecha JCVI 2019). Results 104 recovered, post-COVID patients (median age 62 years, 76% male; 89[87%] hospitalised, 41/89[46%] requiring ICU) underwent adenosine-stress perfusion CMR at a median 131(IQR 43-179) days from COVID-19 diagnosis. Median LVEF was 67% (IQR 60-71%; 12 (11.5%) with impaired LVEF), 51 patients (49%) had late gadolinium enhancement (LGE); 18% infarct-pattern and 33% non-ischaemic LGE. Global stress MBF in post-COVID patients was no different to age-, sex- and co-morbidities-matched controls (2.57 ± 0.77 vs. 2.40 ± 0.75 ml/g/min, p = 0.11, Figure 1), though lower than HV (3.00 ± 0.76 ml/g/min, p = 0.001). Post-COVID, multivariate predictors of low sMBF were male sex (OR 0.57, 95%CI 0.41-0.80, p = 0.001) and hypertension (OR 0.67, 95%CI 0.51-0.88, p = 0.004), but not COVID-19 disease severity (ICU admission) or presence of scar (ischemic/non-ischemic). 21/42 with reduced sMBF (<2.25mL/g/min) had regional perfusion defects consistent with epicardial coronary disease.Conclusions COVID-19 survivors do not demonstrate evidence of reduced global MBF by CMR compared to risk factor matched controls. Stress perfusion CMR identifies etiology of acute myocardial damage (infarction/myocarditis) and presence of occult coronary ischemia. Figure.

Ischemia and No Obstructive Coronary Artery Disease and Pulmonary Hypertension in a 16-Year-Old Girl with Unquenched Hyperthyroidism of Graves' Disease.

A combination of myocardial and pulmonary hypertension was reported in a neonate with Graves’ disease.1 However, neither ischemia and no obstructive coronary artery (INOCA) nor pulmonary hypertension was invasively investigated by single-photon emission computed tomography (SPECT) or right heart catheterization in pediatric patients with Graves’ disease. We reported a 16-year-old girl with unnoticed/untreated Graves’ disease, presenting with exertional dyspnea and cyanosis, undergoing chest radiogram, echocardiography with Doppler, right heart catheterization, coronary angiography, 201thallium-SPECT, and 99mtechnetium-sestamibi dynamic SPECT with myocardial blood flow quantitation, INOCA and pulmonary hypertension due to coronary and pulmonary microvascular dysfunction was diagnosed. We highlight using dynamic SPECT with myocardial blood flow quantitation and right heart catheterization to track down microvascular dysfunction as a culprit of concurrence of INOCA and pulmonary hypertension in patients with Graves’ disease and unquenched hyperthyroidism. The pathogenesis of pulmonary hypertension and INOCA will be discussed.

The Importance of Time-of-Flight Reconstruction and Point Spread Modeling in the Measurement of Myocardial Blood Flow Parameters

Absolute quantitation of myocardial blood flow has been recognized as one of the most important advances in nuclear cardiology. The addition of absolute myocardial blood flow quantitation has had a significant impact on the determination of normalcy, artifact/defect differentiation, and the true extent of coronary artery disease in patients with known or suspected coronary disease. Time-of-flight reconstruction and point spread function modeling of the potential to greatly improve resolution and signal to background. This combined with absolute blood flow measurements could improve the reliability of regional blood flow estimates and overall image quality. Recent publications have demonstrated that time-of-flight reconstruction can have an impact on the amount of spillover between the blood pool ROI and the myocardial regions. This may necessitate changes to kinetic models; however, these changes if implemented correctly may result in improved accuracy and reproducibility of blood flow estimates. This may also have the benefit of assessing blood flow in the microvasculature using newer F-18 labeled blood flow tracers. Time of flight and point spread function modeling represent significant improvements in the accuracy and quality of reconstructed myocardial perfusion PET images. This may also have significant implications for the reliability of blood flow estimates. To achieve these benefits, attention must be given to blood flow models to ensure that they have been correctly optimized for the scanner-specific time-of-flight reconstruction properties.

Effects of two patient-specific dosing protocols on measurement of myocardial blood flow with 3D 82Rb cardiac PET

Clinical measurement of myocardial blood flow (MBF) has emerged as an important component of routine PET-CT assessment of myocardial perfusion in patients with known or suspected coronary artery disease. Although multiple society guidelines recommend patient-specific dosing, there is a lack of studies evaluating the efficacy of patient-specific dosing for quantitative MBF accuracy. Two patient-specific dosing protocols (weight- and BMI-adjusted) were retrospectively evaluated in 435 consecutive clinical patients referred for PET myocardial perfusion assessment. MBF was estimated at rest and after regadenoson-induced hyperemia. The effect of dosing protocol on dose reduction, PET scanner saturation, relative perfusion, and image quality was compared. The effect of PET saturation on the accuracy of MBF and myocardial flow reserve (MFR) in remote myocardium was assessed with multivariable linear regression. BMI-adjusted dosing was associated with lower administered 82Rb activities (1036.0 ± 274 vs. 1147 ± 274MBq, p = 0.003) and lower PET scanner saturation incidence (28 vs. 38%, p = 0.006) and severity (median saturation severity index 0.219 ± 0.33 vs. 0.397 ± 0.59%, p = 0.018) compared to weight-adjusted dosing. PET saturation that occurred with either dosing protocol was moderate and resulted in modest remote MBF and MFR biases ranging from 2 to 9% after adjusting for patient age, sex, BMI, rate-pressure product, and LV ejection fraction. No adverse effects of BMI dose adjustment were observed in relative perfusion assessment or image quality. Patient-specific dosing according to BMI is an effective method for guideline-directed dose reduction while maintaining image quality and accuracy for routine MBF and MFR quantification.

Impaired Coronary Vasodilator Reserve and Adverse Prognosis in Patients With Systemic Inflammatory Disorders

ObjectivesThe purpose of this study was to evaluate the prognostic value of quantitative myocardial blood flow (MBF) and myocardial flow reserve (MFR), reflecting the integrated effects of diffuse atherosclerosis and microvascular dysfunction in patients with systemic inflammatory disorders. BackgroundRheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and psoriasis (PsO) are common inflammatory conditions with excess cardiovascular (CV) risk compared to the general population. Systemic inflammation perturbs endothelial function and has been linked to coronary vasomotor dysfunction. However, the prognostic significance of this vascular dysfunction is not known. MethodsThis was a retrospective study of patients with RA, SLE, and PsO undergoing clinically indicated rest and stress myocardial perfusion positron emission tomography (PET). Patients with an abnormal myocardial perfusion study or left ventricular dysfunction were excluded. MFR was calculated as the ratio of myocardial blood flow (MBF, ml/min/g) at peak stress compared to that at rest. ResultsAmong the 198 patients (median age: 65 years; 80% female), 20.7% had SLE, 31.8% had PsO, and 47.5% had RA. There were no differences in mean MFR between these conditions. Over a median follow-up of 7.8 years, there were 51 deaths and 63 major adverse cardiovascular events (MACE). Patients in the lowest tertile (MFR <1.65) had higher all-cause mortality than the highest tertile, which remained significant after adjusting for age, sex, and the pre-test clinical risk score (hazard ratio [HR]: 2.4; 95% confidence interval [CI]: 1.05 to 5.4; p = 0.038). Similarly, compared to the highest MFR tertile, those in the lowest tertile had a lower MACE-free survival after adjusting for age, sex, and the pre-test clinical risk score (HR: 3.6; 95% CI: 1.7 to 7.6; p = 0.001). ConclusionsIn patients with systemic inflammatory disorders, impaired coronary vasodilator reserve was associated with worse cardiovascular outcomes and all-cause mortality.

Diagnostic efficiency of quantification of myocardial blood flow and coronary flow reserve with CZT dynamic SPECT imaging for patients with suspected coronary artery disease: a comparative study with traditional semi-quantitative evaluation.

Myocardial blood flow (MBF) quantitation with cadmium-zinc-telluride (CZT) dynamic single-photon emission computed tomography (SPECT) is being increasingly investigated toward clinical utilization. In this prospective study, forty-nine patients with suspected or known coronary artery disease (CAD) underwent a rest/adenosine triphosphate (ATP) stress dynamic and routine gated myocardial perfusion imaging (MPI) by CZT SPECT and then received coronary angiography (CAG). Quantitative diagnosis from the dynamic SPECT and a flow diagram was automatically obtained by the dedicated software and compared with the result of semi-quantitative analysis with gated MPI using the angiographic stenosis as the reference standard. When stenosis ≥50% was considered at the participant level, the sensitivity (SN), specificity (SP), positive predictive value (PPV), negative predictive value (NPV) and accuracy (AC) of the quantitative diagnosis were higher than semi-quantitative method as (84.4% vs. 65.6%, 88.2% vs. 70.6%, 93.1% vs. 80.8%, 75.0% vs. 52.2%, 85.7% vs. 67.3%) (all P<0.05). The receiver operating characteristic (ROC) curve analysis generated the optimal critical value as 1.86 and 1.61 mL/min/g for stress MBF (sMBF) and MFR, respectively. The diagnosis performance of the quantitative diagnosis was higher than semi-quantitative method as (78.9% vs. 68.4%, 63.3% vs. 60.0%, 57.7% vs. 52.0%, 82.6% vs. 75.0%, 69.4% vs. 63.3%) for the criteria of ≥75% stenosis on CAG (all P<0.05) with optimal critical values as 1.71 and 1.15 mL/min/g. There was no significant difference between sMBF and MFR. The diagnostic efficiency by using the quantitative method of CZT dynamic SPECT imaging is superior to traditional semi-quantitative gated MPI for the diagnosis of CAD, which improved the diagnostic specificity and accuracy when the critical was stenosis ≥50%.

Role of quantitative myocardial blood flow and 13N-ammonia washout for viability assessment in ischemic cardiomyopathy

ObjectivePositron emission tomography (PET) integrating assessment of perfusion with 13N-ammonia (NH3) and viability with 18F-fluorodeoxyglucose (FDG) has high accuracy to identify viable, hibernating myocardium. We tested whether quantification of myocardial blood flow (MBF) and washout (k2) can predict myocardial viability using FDG as standard of reference. MethodsIn 180 consecutive patients with ischemic cardiomyopathy, myocardium was categorized on a segment-level into normal, ischemic, hibernating, and scar. From dynamic images, stress MBF, rest MBF, and k2 were derived and myocardial flow reserve (MFR) and volume of distribution (VD) were calculated. ResultsAcross myocardial tissues, all parameters differed significantly. The area under the curve (AUC) was 0.564 (95% CI 0.527-0.601), 0.635 (0.599-0.671), 0.553 (0.516-0.591), 0.520 (0.482-0.559), and 0.560 (0.522-0.597) for stress MBF, rest MBF, MFR, k2, and VD. The generalized linear mixed model correctly classified 81% of scar as viable, hibernating myocardium. If the threshold of rest MBF to predict viability was set to 0.45 mL·min−1·g−1, sensitivity and specificity were 96% and 12%, respectively. ConclusionQuantitative NH3 PET parameters have low to moderate diagnostic performance to predict viability in ischemic cardiomyopathy. However, if rest MBF falls below 0.45 mL·min−1·g−1, viability testing by FDG-PET may be safely deferred.

Automated Segmental Analysis of Fully Quantitative Myocardial Blood Flow Maps by First-Pass Perfusion Cardiovascular Magnetic Resonance.

First pass gadolinium-enhanced cardiovascular magnetic resonance (CMR) perfusion imaging allows fully quantitative pixel-wise myocardial blood flow (MBF) assessment, with proven diagnostic value for coronary artery disease. Segmental analysis requires manual segmentation of the myocardium. This work presents a fully automatic method of segmenting the left ventricular myocardium from MBF pixel maps, validated on a retrospective dataset of 247 clinical CMR perfusion studies, each including rest and stress images of three slice locations, performed on a 1.5T scanner. Pixel-wise MBF maps were segmented using an automated pipeline including region growing, edge detection, principal component analysis, and active contours to segment the myocardium, detect key landmarks, and divide the myocardium into sectors appropriate for analysis. Automated segmentation results were compared against a manually defined reference standard using three quantitative metrics: Dice coefficient, Cohen Kappa and myocardial border distance. Sector-wise average MBF and myocardial perfusion reserve (MPR) were compared using Pearson’s correlation coefficient and Bland-Altman Plots. The proposed method segmented stress and rest MBF maps of 243 studies automatically. Automated and manual myocardial segmentation had an average (± standard deviation) Dice coefficient of 0.86 ± 0.06, Cohen Kappa of 0.86 ± 0.06, and Euclidian distances of 1.47 ± 0.73 mm and 1.02 ± 0.51 mm for the epicardial and endocardial border, respectively. Automated and manual sector-wise MBF and MPR values correlated with Pearson’s coefficient of 0.97 and 0.92, respectively, while Bland-Altman analysis showed bias of 0.01 and 0.07 ml/g/min. The validated method has been integrated with our fully automated MBF pixel mapping pipeline to aid quantitative assessment of myocardial perfusion CMR.

Myocardial blood flow quantitation in patients with congestive heart failure: head-to-head comparison between rapid-rotating gantry SPECT and CZT SPECT

PurposeRecently, the feasibility of myocardial blood flow (MBF) quantitation using rapid-rotating gantry (RRG) and cadmium–zinc–telluride (CZT) SPECT cameras has been demonstrated. We compared MBF quantitation using these two camera systems. MethodsTwenty patients with congestive heart failure (CHF) and 20 patients without CHF (non-CHF) were included. On two consecutive days, dynamic SPECT imaging was performed after a bolus injection of 20 mCi of 99mTc-Sestamibi (MIBI) with RRG-SPECT and list-mode acquisition with CZT-SPECT. All dynamic SPECT images were reconstructed with full physical corrections, corrections for ventricular spillover and partial volume effect, using one-tissue kinetic modeling. Resting MBF converted from K1 was then corrected for MIBI extraction fraction and adjusted for rate-pressure product. ResultsIn both patient groups, there was no significant difference between resting MBF values measured with RRG-SPECT and CZT-SPECT systems (P = 0.06, P = 0.2 respectively). For CHF patients, linear regression (LR) was y(RRG) = 1.0412x (CZT) (r = 0.97) with a small systemic difference (Δ = 0.03 mL·min−1·g−1, 95% CI − 0.11 to 0.20) by Bland–Altman analysis. For non-CHF patients, LR was y(RRG) = 1.025x (CZT) (r = 0.89) with also small systemic difference (ΔT= 0.02 mL·min−1·g−1, 95% CI − 0.14 to 0.19) in BA analysis. ConclusionPhysical corrections along with other image corrections can provide comparable MBF quantitations in both CHF and non-CHF patients, regardless of the type of SPECT systems used.

High-Resolution Cardiac Magnetic Resonance Imaging Techniques for the Identification of Coronary Microvascular Dysfunction

ObjectivesThis study assessed the ability to identify coronary microvascular dysfunction (CMD) in patients with angina and nonobstructive coronary artery disease (NOCAD) using high-resolution cardiac magnetic resonance (CMR) and hypothesized that quantitative perfusion techniques would have greater accuracy than visual analysis. BackgroundHalf of all patients with angina are found to have NOCAD, while the presence of CMD portends greater morbidity and mortality, it now represents a modifiable therapeutic target. Diagnosis currently requires invasive assessment of coronary blood flow during angiography. With greater reliance on computed tomography coronary angiography as a first-line tool to investigate angina, noninvasive tests for diagnosing CMD warrant validation. MethodsConsecutive patients with angina and NOCAD were enrolled. Intracoronary pressure and flow measurements were acquired during rest and vasodilator-mediated hyperemia. CMR (3-T) was performed and analyzed by visual and quantitative techniques, including calculation of myocardial blood flow (MBF) during hyperemia (stress MBF), transmural myocardial perfusion reserve (MPR: MBFHYPEREMIA / MBFREST), and subendocardial MPR (MPRENDO). CMD was defined dichotomously as an invasive coronary flow reserve <2.5, with CMR readers blinded to this classification. ResultsA total of 75 patients were enrolled (57 ± 10 years of age, 81% women). Among the quantitative perfusion indices, MPRENDO and MPR had the highest accuracy (area under the curve [AUC]: 0.90 and 0.88) with high sensitivity and specificity, respectively, both superior to visual assessment (both p < 0.001). Visual assessment identified CMD with 58% accuracy (41% sensitivity and 83% specificity). Quantitative stress MBF performed similarly to visual analysis (AUC: 0.64 vs. 0.60; p = 0.69). ConclusionsHigh-resolution CMR has good accuracy at detecting CMD but only when analyzed quantitatively. Although omission of rest imaging and stress-only protocols make for quicker scans, this is at the cost of accuracy compared with integrating rest and stress perfusion. Quantitative perfusion CMR has an increasingly important role in the management of patients frequently encountered with angina and NOCAD.

Related risk factors of PET/CT detected coronary microvascular disease in patients with chest pain and no obstructive coronary artery disease

Objective: To explore the related factors of the coronary microvascular disease (CMD) diagnosed with positron emission tomography(PET)/CT in patients with chest pain and without obstructive coronary artery disease (NOCA). Methods: This study was a single-center retrospective cross-sectional study. Consecutive patients with chest pain and NOCA on coronary angiography, who underwent PET/CT quantitative myocardial blood flow measurements at TEDA International Cardiovascular Hospital from August 2018 to January 2019, were enrolled for this study. The diagnostic criteria for NOCA was the absence of coronary artery diameter stenosis ≥50% on coronary angiography. Clinical data, global left ventricular myocardial blood flow on stress and rest, and the coronary flow reserve (CFR) were analyzed. Patients were divided into two groups according to CFR. Patients with CFR<2 were defined as CMD group, and the rest were classified as control group. Pearson correlation analysis and Logistics regression analysis were used for exploring the risk factors of the CMD. Results: A total of 66 patients, with an mean age of (56.7±9.6) years, were included in the study, including 41 females (62%). There were 20 patients with CMD (30%). Body mass index (BMI) was significantly higher in CND group than in control group ((28.1±3.6) kg/m2 vs. (25.6±3.5) kg/m2, P=0.01). Total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) were also significantly higher in CMD group than in control group ((4.89±1.03) mmol/L vs. (4.30±1.02) mmol/L and (3.23±0.81) mmol/L vs. (2.71±0.95) mmol/L respectively, P=0.038). Pearson correlation analysis showed that CFR was moderately correlated with BMI (r=-0.45, P<0.001), and was weakly correlated with TC and LDL-C (r=-0.271 and r=-0.280, respectively, P<0.05). Multivariate logistic regression analysis showed that BMI (the risk of CMD increased by 1.528 times for every 5 kg/m2 increase in BMI, 95%CI 1.083-5.897, P<0.05) was an independent risk factor of CMD after adjusted by gender, hypertension, diabetic mellites and LDL-C. Conclusion: For patients with NOCA and chest pain, high BMI is independent risk factor of CMD diagnosed by PET/CT.

Prevalence of microvascular dysfunction and association with clinical outcomes in heart failure with preserved ejection fraction

Abstract Introduction Heart failure with preserved ejection fraction (HFpEF) accounts for approximately 50% of symptomatic heart failure. A recently proposed paradigm for the pathophysiology of HFpEF postulates a central inflammatory aetiology with coronary microvascular function at its core. However, the pathophysiological and clinical significance of microvascular dysfunction in HFpEF remains uncertain. Purpose Utilising cardiovascular magnetic resonance (CMR), we sought to (1) quantify coronary microvascular function, (2) evaluate the impact of microvascular dysfunction and fibrosis on long-term clinical outcomes and (3) examine the relationship between myocardial perfusion and fibrosis. Methods In a prospective, observational study, 147 subjects (104 HFpEF without a prior history or CMR evidence of coronary artery disease, and 43 asymptomatic controls) underwent multiparametric CMR, comprising left ventricular volumetric assessment, absolute quantitation of myocardial blood flow [MBF] during adenosine stress (140mcg/kg/min) and at rest, and evaluation of diffuse myocardial fibrosis (extracellular volume [ECV]). The primary endpoint was the composite of death or hospitalisation with heart failure. Results 104 HFpEF patients (mean age 73±9 years, mean ejection fraction 56%) and 43 controls (mean age 73±5 years, mean ejection fraction 58%) were studied. There was no significant difference in resting MBF (1.10±0.42ml/min/g in HFpEF subjects vs 1.00±0.38 ml/min/g in controls, p=0.23), though hyperaemic MBF was lower in HFpEF subjects (1.66±0.68 ml/min/g vs 1.97±0.59 ml/min/g, p=0.01). Myocardial perfusion reserve [MPR] was also lower in HFpEF subjects (1.73±0.75 vs 2.22±0.76; p&amp;lt;0.01). Microvascular dysfunction (defined as MPR&amp;lt;2.0) was present in 70% of HFpEF patients (versus 33% of controls, p&amp;lt;0.01). During median follow-up of 3.4 years, there were 46 composite events. MPR was predictive of clinical outcome (one unit increase – hazard ratio [HR] 0.57; 95% CI 0.35–0.92; p=0.02), as was ECV (one standard deviation [SD] increase – HR 1.65; 95% CI 1.14–2.39; p=0.01). However, there was no significant linear correlation between MPR and diffuse fibrosis (r&amp;lt;0.01, p=0.99). Conclusion Microvascular dysfunction is highly prevalent in HFpEF and is associated with adverse clinical outcomes. The lack of correlation between abnormal myocardial perfusion and fibrosis challenges the assertion of a direct causal link between these entities. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): NIHR, BHF

The detection of multivessel coronary artery disease: the value of quantitative myocardial blood flow and coronary flow reserve assessment

Abstract Background/Introduction The recent Cadmium-Zinc-Telluride (CZT) camera for MPS allows evaluating absolute MBF and CFR, possibly increasing the accuracy in detecting of multivessel CAD. Purpose To evaluate the accuracy of myocardial blood flow (MBF) and coronary flow reserve (CFR) quantitation performed by myocardial perfusion scintigraphy (MPS) for the detection of multivessel coronary artery disease (CAD). Methods Fifty-two patients with suspected or known CAD were enrolled in the study. All patients underwent CZT MPS, with the evaluation of MBF and CFR, followed by invasive coronary angiography. According to MPS and coronary angiography results, patients were divided into three groups. 1) non-obstructive CAD and normal MPS scan (control group) (n=7), 2) one vessel disease (1VD) (n=16), with significant coronary stenosis (≥70%) in one major epicardial coronary artery, 3) multivessel disease (MVD) group (n=29), with two or more major epicardial coronary arteries with (≥70%) stenoses or with ≥50% LMA stenosis. Results Absolute MBF and CFR were significantly reduced in patients with MVD as compared to those with 1VD [0.93 (IQR 0.76; 1.39) vs 1.94 (1.37; 2.21) ml/min/g, p=0.00012] and [1.4 (IQR 1.02; 1.85) vs 2.3 (1.8; 2.67), p=0.0004], respectively. The Syntax score correlated with global stress MBF (ρ=−0.64; p&amp;lt;0.0001) and CFR (ρ=−0.53; p=0.0003). ROC analysis showed higher sensitivity and specificity for stress MBF (85.2% and 81%), and CFR (88.9% and 80%) compared with semiquantitative MPS stress evaluation (69% and 69%). Multivariate regression analysis showed that only stress MBF [OR (95% CI) 0.59 (0.42–0.82); p&amp;lt;0.0003] was an independent predictor of MVD. Conclusion The use of absolute myocardial blood flow analysis with the CZT camera may identify high risk patients, such as those with multivessel disease. This approach could be used in clinical practice, increasing the accuracy in the evaluation of patients with known or suspected coronary artery disease. Funding Acknowledgement Type of funding source: None

Stress myocardial perfusion with qualitative magnetic resonance and quantitative dynamic computed tomography: comparison of diagnostic performance and incremental value over coronary computed tomography angiography.

Assessment of haemodynamically significant coronary artery disease (CAD) using cardiovascular magnetic resonance (CMR) imaging perfusion or dynamic stress myocardial perfusion imaging by computed tomography (CT perfusion) may aid patient selection for invasive coronary angiography (ICA). We evaluated the diagnostic performance and incremental value of qualitative CMR perfusion and quantitative CT perfusion complementary to cardiac computed tomography angiography (CCTA) for the diagnosis of haemodynamically significant CAD using fractional flow reserve (FFR) and quantitative coronary angiography (QCA) as reference standard. CCTA, qualitative visual CMR perfusion, visual CT perfusion, and quantitative relative myocardial blood flow (CT-MBF) were performed in patients with stable angina pectoris. FFR was measured in coronary vessels with stenosis visually estimated between 30% and 90% diameter reduction on ICA. Haemodynamically significant CAD was defined as FFR <0.80, or QCA ≥80% in those cases where FFR could not be performed. A total of 218 vessels from 93 patients were assessed. An optimal cut-off of 0.72 for relative CT-MBF was determined. The diagnostic performances (area under the receiver-operating characteristics curves, 95% CI) of visual CMR perfusion (0.84, 0.77-0.90) and relative CT-MBF (0.86, 0.81-0.92) were comparable and outperformed visual CT perfusion (0.64, 0.57-0.71). In combination with CCTA ≥50%, CCTA + visual CMR perfusion (0.91, 0.86-0.96), CCTA + relative CT-MBF (0.92, 0.88-0.96), and CCTA + visual CT perfusion (0.82, 0.75-0.90) improved discrimination compared with CCTA alone (all P < 0.05). Visual CMR perfusion and relative CT-MBF outperformed visual CT perfusion and provided incremental discrimination compared with CCTA alone for the diagnosis of haemodynamically significant CAD.

Emerging F-18-Labelled PET Myocardial Perfusion Tracers.

PET myocardial perfusion imaging (MPI) is an established modality for the evaluation of ischemic heart disease and quantitation of myocardial blood flow (MBF). New F-18-labelled radiopharmaceuticals have been recently developed to overcome some of the limitations of currently used tracers such as the need of an on-site cyclotron. The characteristics of the new tracers and the clinical results obtained so far will be reviewed. Most of the interest in the field of 18F-labelled radiotracers for PET MPI has been concentrated on MC-1 inhibitors, the prototype of which is 18F-flurpiridaz. It was shown in experimental and clinical reports that these radiotracers allow good quality rest/stress MPI studies and a reliable quantitation of MBF. Recent evidence suggests that PET MPI with 18F-flurpiridaz may provide a superior diagnostic accuracy for obstructive CAD even if a large comparative clinical trial with SPECT is still ongoing.

Ischaemic burden and changes in absolute myocardial perfusion after chronic total occlusion percutaneous coronary intervention.

The aim of this study was to explore the relationships between ischaemic burden and changes in absolute myocardial perfusion following chronic coronary total occlusion (CTO) percutaneous coronary intervention (PCI). A total of 193 consecutive patients underwent [15O]H2O positron emission tomography prior to and three months after successful CTO PCI. Change in perfusion defect size, quantitative hyperaemic myocardial blood flow (MBF) and coronary flow reserve (CFR) within the CTO area were compared among patients with limited (0-1 segment, N=15), moderate (2-3 segments, N=61) and large (≥4 segments, N=117) perfusion defects. Median reductions in defect size were 1 [0-1], 2 [1-3], and 4 [2-5] segments in patients with a limited, moderate and large defect (all comparisons p<0.01). Hyperaemic MBF and CFR improved significantly regardless of baseline defect size (overall between groups p=0.45 and p=0.55). After stratification of patients to a low, intermediate or high tertile according to baseline hyperaemic MBF or CFR levels, changes in hyperaemic MBF and CFR after CTO PCI were comparable between tertiles (overall p=0.75 and p=0.79). Major reductions in ischaemic burden can be achieved following CTO PCI, with more defect size reduction in patients with a larger perfusion defect, whereas hyperaemic MBF and CFR improve significantly irrespective of their baseline values or perfusion defect size.

Noninvasive estimation of quantitative myocardial blood flow with Tc-99m MIBI by a compartment model analysis in rat

BackgroundWe aimed to investigate the use of dynamic cardiac planar images to estimate myocardial blood flow (MBF) by a compartment model analysis using time-to-peak (TP) map and compared it by the microsphere technique in rat. Positron emission tomography is considered the gold standard method, but is not available everywhere. By contrast, although myocardial perfusion imaging (MPI) with single-photon tracers is more widely available, it may be difficult to obtain adequate region of interest (ROI) settings. We proposed using the TP map to set the ROI, and hypothesized that this method could facilitate the measurement of absolute MBF by MPI in rat. MethodsTwenty-one normal rats were studied. Dynamic planar images with Tc-99m MIBI were obtained, and input function and cardiac ROIs were set using the obtained TP map. MBF was estimated by a one-compartment model analysis with the Renkin-Crone model and by the microsphere technique. ResultsThe MBFs from these two methods were significantly correlated. A negative proportional bias was observed, but no significant difference was observed between the mean MBFs calculated with each method. ConclusionsMBF estimation by a compartment model analysis using TP map could facilitate absolute MBF measurement in rats.