Stress Myocardial Blood Flow Values Research Articles

Machine and deep learning models for accurate detection of ischemia and scar with myocardial blood flow positron emission tomography imaging

BackgroundQuantification of myocardial blood flow (MBF) is used for the noninvasive diagnosis of patients with coronary artery disease (CAD). This study compared traditional statistics, machine learning, and deep learning techniques in their ability to diagnose disease using only the rest and stress MBF values. MethodsThis study included 3245 rest and stress rubidium-82 positron emission tomography (PET) studies and matching diagnostic labels from perfusion reports. Standard logistic regression, lasso logistic regression, support vector machine, random forest, multilayer perceptron, and dense U-Net were compared for per-patient detection and per-vessel localization of scars and ischemia. ResultsReceiver-operator characteristic area under the curve (AUC) of machine learning models was significantly higher than those of traditional statistics models for per-patient detection of disease (0.92–0.95 vs. 0.87) but not for per-vessel localization of ischemia or scar. Random forest showed the highest AUC = 0.95 among the different models compared. On the final hold-out set for generalizability, random forest showed an AUC of 0.92 for detection and 0.89 for localization of perfusion abnormalities. ConclusionsFor per-vessel localization, simple models trained on segmental data performed similarly to a convolutional neural network trained on polar-map data, highlighting the need to justify the use of complex predictive algorithms through comparison with simpler methods.

Comparison of dual-bolus versus dual-sequence techniques for determining myocardial blood flow and myocardial perfusion reserve by cardiac magnetic resonance stress perfusion: From the Automated Quantitative analysis of myocardial perfusion cardiac Magnetic Resonance Consortium

BackgroundQuantitative stress cardiac magnetic resonance (CMR) can be performed using the dual sequence (DS) technique or dual bolus (DB) method. It is unknown if DS and DB produce similar results for myocardial blood flow (MBF) and myocardial perfusion reserve (MPR). The study objective is to investigate if there are any differences between DB and DS derived MBF and MPR. MethodsRetrospective observational study with 168 patients underwent stress CMR. Dual bolus and dual sequence methods were simultaneously performed on each patient on the same day. Global and segmental stress MBF and rest MBF values were collected. ResultsUsing Bland-Altman analysis, segmental and global stress MBF values were higher in DB than DS (0.22 + 0.60ml/g/min, p<0.001 and 0.20 + 0.48ml/g/min, p=0.005 respectively) with strong correlation (r = 0.81, p < 0.001 for segmental and r = 0.82, p < 0.001 for global). In rest MBF, segmental and global DB values were higher than by DS (0.15 + 0.51ml/g/min, p<0.001 and 0.14 + 0.36ml/g/min, p=0.011 respectively) with strong correlation (r = 0.81, p < 0.001 and r = 0.77, p < 0.001). Mean difference between MPR by DB and DS was -0.02 + 0.68ml/g/min (p=0.758) for segmental values and -0.01 + 0.49ml/g/min (p=0.773) for global values. MPR values correlated strongly as well in both segmental and global, both (r = 0.74, p < 0.001) and (r = 0.75, p < 0.001) respectively. ConclusionsThere is very good correlation between DB and DS derived MBF and MPR values. However, there are significant differences between DB and DS derived global stress and rest MBF. Whilst MPR values did not show statistically significant differences between DB and DS methods.

Abstract 15103: Stratifying Coronary Artery Disease (CAD) GWAS Loci Using Cardiac Perfusion Positron Emission Tomography to Identify Loci for Coronary Microvascular Disease

Introduction: Coronary Microvascular Disease (CMVD), defined as disease of the coronary pre-arterioles, arterioles, and capillaries, accounts for 30-50% of the burden of Ischemic Heart Disease (IHD). CAD GWAS studies have identified more than 235 loci, however, the populations enrolled represent heterogeneous IHD with inclusion criteria that include ischemia without confirmation of obstructive CAD (Ischemia with non-obstructed Coronary Arteries). Hypothesis: We hypothesize that CAD GWAS studies are really IHD GWAS studies and a subset of patients enrolled have CMVD as the etiology of their ischemia. Thus several CAD GWAS loci may be CMVD loci. Here we use quantitative measures of myocardial blood flow (MBF) and MBF reserve (MBFR) from cardiac Perfusion PET studies to stratify known CAD loci for CMVD. Methods: We performed a genomic association study for 235 known CAD loci in 383 samples of European (EUR) and 539 samples of African ancestry (AFR) in the Penn Medicine Biobank using clinical Rubidium-82 PET using REGENIE software. Models were adjusted for age, sex, age 2 , age x sex, 5 principal components, and batch corresponding to phenotype extraction. We examined regions within 250kb of known CAD loci for association with PET-derived MBF and MBFR. Bonferroni corrected P-value &lt; 2.13e-4 was considered significant. Results: We found 40 loci in patients of AFR ancestry and 11 CAD loci in patients of EUR ancestry that were significantly associated with MBFR, including several genes which are known to play a role in microvasculature function and angiogenesis (VEGFa, FLT1, and FGF1). Stress MBF values have been shown to reflect epicardial CAD. We found 28 loci in patients of AFR ancestry and 12 loci in patients of EUR ancestry which were significantly associated with stress MBF and are mostly distinct from loci associated with MBFR. One notable exception is PRDM16 which was highly significant in both phenotypes. Conclusions: Our study sub-stratified variants previously associated with CAD to identify those that may be involved in CMVD. Several genes known to be involved in microvasculature function (VEGFa, FLT1, and FGF1) were putative CMVD genes. PRDM16 was associated with stress MBF and MBFR. This work prioritizes CAD loci for further study of mechanisms of CMVD.

Quantitative myocardial blood flow as a prognostic marker for cardiovascular outcomes in patients with Type 2 Diabetes Mellitus: a multicentre study

Abstract Introduction: Patients with Type 2 Diabetes Mellitus (T2DM) are at increased risk of cardiovascular disease, including epicardial coronary heart disease, silent myocardial infarction (MI), and coronary microvascular dysfunction (CMD) [1]. All of these can be assessed and quantified using cardiac magnetic resonance (CMR), including most recently quantitative myocardial blood flow (MBF). We aimed to determine the prognostic relevance of MBF in patients with T2DM and test the hypothesis that impaired stress MBF and myocardial perfusion reserve (MPR) have independent prognostic value over standard clinical and imaging parameters. Methods A 4-centre study of patients with T2DM who underwent quantitative perfusion assessment using CMR. Diagnosis of T2DM was based on Hba1c &amp;gt;48mmol/l or a known diagnosis of T2DM. Image analysis was performed automatically using an artificial intelligence approach deriving global MBF and MPR [2]. Cox proportional hazard models adjusting for comorbidities and CMR parameters sought associations between stress MBF and MPR with death and major adverse cardiovascular events (MACE), including MI, non-fatal stroke, heart failure hospitalisation and death. Results A total of 630 patients with T2DM were included with a median follow-up of 722 days (interquartile range 493) days. There were 27 (4.3%) deaths and 76 MACE events in 62 (12.1%) patients. Patient data was represented into groups depending on threshold stress MBF values of 1.94ml/g/min and MPR thresholds of 1.96 using validated data from invasive coronary physiology [3]. Patient demographics and CMR data are seen in table 1. Kaplan-Meier curves are seen in figure 1. Stress MBF was associated with mortality and MACE after adjusting for age, LV ejection fraction and HbA1c. The stress MBF adjusted hazard ratios for all cause death and death and MACE were 0.35 (95% CI, 0.13–0.95, P=0.04) and 0.54 (95% CI, 0.30–0.96, P=0.04), respectively. MPR was not significantly associated with death and MACE after adjusting for age, LV ejection fraction and HbA1c; hazard ratio for all cause death and death and MACE was 0.83 (95% CI, 0.41–1.69, P=0.60) and 0.81 (95% CI, 0.53–1.23, p=0.32) respectively. Conclusion In patients with T2DM, reduced stress MBF measured automatically inline using artificial intelligence quantification of cardiovascular magnetic resonance perfusion mapping provides a strong, independent predictor of adverse cardiovascular outcome. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): 1. REC ID 14/EE/0007 (Barts Heart Centre funding). 2. For PREDICT (Leicester data) ethical approval was provided by the UK Health Research Authority Research Ethics Committee (reference 17/WM/0192). 3. MATCH Study, Leeds - British Heart Foundation - 17/YH/0300. 4. LEAN-DM, Leeds - British Heart Foundation - 18/YH/01685. CEED, Leeds: British Heart Foundation - REC reference - 18/YH/0190

Characteristics of anginal patients with high resting myocardial blood flow measured with N-13 ammonia PET/CT.

We hypothesized that anginal patients with low coronary flow reserve (CFR) could have variable clinical features according to resting myocardial blood flow (MBF). Therefore, we analyzed the clinical and imaging characteristics according to resting MBF in anginal patients. We enrolled 70 patients who underwent N-13 ammonia PET-computed tomography (CT) for evaluation of angina. Resting and stress MBF values were obtained and resting MBF was corrected with rate-pressure product to exclude the effect of heart rate and blood pressure on resting MBF. Clinical and imaging characteristics were compared on the basis of MBF and CFR. Among patients with CFR less than 2.0, those with high resting MBF (≥1.0 ml/min/g) had significantly fewer number of smokers, were younger, had lower Agatston calcium scores, and had less coronary stenosis compared with those with low resting MBF (<1.0 ml/min/g). In contrast, there was no significant difference in clinical or imaging findings according to resting MBF when compared among all patients or within those with CFR greater than or equal to 2.0. The subgroup analysis of patients with CFR less than 2.0 revealed lower Agatston calcium score and less coronary stenosis in patients with high resting MBF regardless of stress MBF. High resting MBF is associated with a lower rate of smoking, younger age, less coronary calcium burden, and less coronary stenosis compared with low resting MBF in anginal patients with low CFR. Moreover, in these patients, favorable angiographic features were mainly associated with high resting MBF, irrespective of stress MBF. Therefore, resting MBF should be reviewed to validate the clinical significance of low CFR measured by N-13 ammonia PET/CT especially in anginal patients showing low CFR.

DYNAMIC CT MYOCARDIAL PERFUSION MEASUREMENTS OF RESTING AND HYPEREMIC BLOOD FLOW IN HEALTHY SUBJECTS

Compared to PET & MRI, there is a paucity of literature on normal myocardial blood flow (MBF) values measured by dynamic CT. Our aim was to 1) describe rest & stress MBF values in a healthy population using 128-slice dual source CT myocardial perfusion imaging (CTMPI), 2) compare MBF values of the

Absolute myocardial flow quantification with 82Rb PET/CT: comparison of different software packages and methods

In clinical cardiac (82)Rb PET, globally impaired coronary flow reserve (CFR) is a relevant marker for predicting short-term cardiovascular events. However, there are limited data on the impact of different software and methods for estimation of myocardial blood flow (MBF) and CFR. Our objective was to compare quantitative results obtained from previously validated software tools. We retrospectively analyzed cardiac (82)Rb PET/CT data from 25 subjects (group 1, 62 ± 11 years) with low-to-intermediate probability of coronary artery disease (CAD) and 26 patients (group 2, 57 ± 10 years; P=0.07) with known CAD. Resting and vasodilator-stress MBF and CFR were derived using three software applications: (1) Corridor4DM (4DM) based on factor analysis (FA) and kinetic modeling, (2) 4DM based on region-of-interest (ROI) and kinetic modeling, (3) MunichHeart (MH), which uses a simplified ROI-based retention model approach, and (4) FlowQuant (FQ) based on ROI and compartmental modeling with constant distribution volume. Resting and stress MBF values (in milliliters per minute per gram) derived using the different methods were significantly different: using 4DM-FA, 4DM-ROI, FQ, and MH resting MBF values were 1.47 ± 0.59, 1.16 ± 0.51, 0.91 ± 0.39, and 0.90 ± 0.44, respectively (P<0.001), and stress MBF values were 3.05 ± 1.66, 2.26 ± 1.01, 1.90 ± 0.82, and 1.83 ± 0.81, respectively (P<0.001). However, there were no statistically significant differences among the CFR values (2.15 ± 1.08, 2.05 ± 0.83, 2.23 ± 0.89, and 2.21 ± 0.90, respectively; P=0.17). Regional MBF and CFR according to vascular territories showed similar results. Linear correlation coefficient for global CFR varied between 0.71 (MH vs. 4DM-ROI) and 0.90 (FQ vs. 4DM-ROI). Using a cut-off value of 2.0 for abnormal CFR, the agreement among the software programs ranged between 76 % (MH vs. FQ) and 90 % (FQ vs. 4DM-ROI). Interobserver agreement was in general excellent with all software packages. Quantitative assessment of resting and stress MBF with (82)Rb PET is dependent on the software and methods used, whereas CFR appears to be more comparable. Follow-up and treatment assessment should be done with the same software and method.

Low-Dose Quantitative Myocardial Blood Flow Imaging Using 15O-Water and PET Without Attenuation Correction

Misalignment between PET and low-dose CT (LD-CT) can cause severe artifacts in cardiac PET/CT because of attenuation-correction errors, even when using slow or cine LD-CT. Myocardial blood flow (MBF), as measured by (15)O-water, can be determined from the rate of (15)O-water washout from myocardial tissue, which is independent of tissue attenuation. The purpose of the present study was to assess the accuracy of these MBF measurements in the absence of attenuation correction. Twenty-five patients referred for evaluation of myocardial perfusion underwent 6-min rest and adenosine stress PET scans after the administration of 370 MBq of (15)O-water; both scans were followed by slow LD-CT. Data were acquired on a PET/CT scanner and reconstructed by a 3-dimensional row-action maximum likelihood algorithm both with (CTAC) and without (NAC) attenuation correction. An ascending aorta volume of interest was used as input function. MBF and coronary flow reserve (CFR) were calculated for 17 myocardial segments using nonlinear regression of the standard single-tissue-compartment model with corrections for left and right ventricular spillover and perfusable tissue fraction. High correlation (r(2) = 0.99 and 0.97, with slopes of 0.96 and 0.91 for rest and stress, respectively) and excellent agreement (intraclass correlation coefficient [ICC], 1.00 and 0.98) between NAC- and CTAC-based MBF values were found. Absolute rest and stress MBF values were 3% and 8%, respectively, lower for NAC scans. The correlation coefficient between all NAC and CTAC CFR values was 0.95 (ICC, 0.95; slope, 0.92) and 0.97 (ICC, 0.99; slope, 1.01) when only CFR values below 2 were considered. Deviations between CTAC and NAC values were smallest for basal segments and increased toward the apex. MBF and CFR can be measured accurately using (15)O-water and PET without correcting for attenuation, reducing the effective dose to the patient to 0.8 mSv for a complete rest-stress protocol. This dose is an order of magnitude lower than typical values for (82)Rb, (99m)Tc-methoxyisobutylisonitrile, or CT perfusion scans.