Segmental Myocardial Blood Flow Research Articles

Coronary sinus reducer for the treatment of refractory angina (ORBITA-COSMIC): a randomised, placebo-controlled trial

The coronary sinus reducer (CSR) is proposed to reduce angina in patients with stable coronary artery disease by improving myocardial perfusion. We aimed to measure its efficacy, compared with placebo, on myocardial ischaemia reduction and symptom improvement. ORBITA-COSMIC was a double-blind, randomised, placebo-controlled trial conducted at six UK hospitals. Patients aged 18 years or older with angina, stable coronary artery disease, ischaemia, and no further options for treatment were eligible. All patients completed a quantitative adenosine-stress perfusion cardiac magnetic resonance scan, symptom and quality-of-life questionnaires, and a treadmill exercise test before entering a 2-week symptom assessment phase, in which patients reported their angina symptoms using a smartphone application (ORBITA-app). Patients were randomly assigned (1:1) to receive either CSR or placebo. Both participants and investigators were masked to study assignment. After the CSR implantation or placebo procedure, patients entered a 6-month blinded follow-up phase in which they reported their daily symptoms in the ORBITA-app. At 6 months, all assessments were repeated. The primary outcome was myocardial blood flow in segments designated ischaemic at enrolment during the adenosine-stress perfusion cardiac magnetic resonance scan. The primary symptom outcome was the number of daily angina episodes. Analysis was done by intention-to-treat and followed Bayesian methodology. The study is registered with ClinicalTrials.gov, NCT04892537, and completed. Between May 26, 2021, and June 28, 2023, 61 patients were enrolled, of whom 51 (44 [86%] male; seven [14%] female) were randomly assigned to either the CSR group (n=25) or the placebo group (n=26). Of these, 50 patients were included in the intention-to-treat analysis (24 in the CSR group and 26 in the placebo group). 454 (57%) of 800 imaged cardiac segments were ischaemic at enrolment, with a median stress myocardial blood flow of 1·08 mL/min per g (IQR 0·77-1·41). Myocardial blood flow in ischaemic segments did not improve with CSR compared with placebo (difference 0·06 mL/min per g [95% CrI -0·09 to 0·20]; Pr(Benefit)=78·8%). The number of daily angina episodes was reduced with CSR compared with placebo (OR 1·40 [95% CrI 1·08 to 1·83]; Pr(Benefit)=99·4%). There were two CSR embolisation events in the CSR group, and no acute coronary syndrome events or deaths in either group. ORBITA-COSMIC found no evidence that the CSR improved transmural myocardial perfusion, but the CSR did improve angina compared with placebo. These findings provide evidence for the use of CSR as a further antianginal option for patients with stable coronary artery disease. Medical Research Council, Imperial College Healthcare Charity, National Institute for Health and Care Research Imperial Biomedical Research Centre, St Mary's Coronary Flow Trust, British Heart Foundation.

Normal values of myocardial blood flow measured with dynamic myocardial CT perfusion.

Dynamic myocardial CT perfusion (DM-CTP) can, in combination with coronary CT angiography (CCTA), provide anatomical and functional evaluation of coronary artery disease (CAD). However, normal values of myocardial blood flow (MBF) are needed to identify impaired myocardial blood supply in patients with suspected CAD.We aimed to establish normal values for MBF measured using DM-CTP, to assess the effects of age and sex, and to assess regional distribution of MBF. A total of 82 healthy individuals (46 women) aged 45-78 years with normal coronary arteries by CCTA underwent either rest and adenosine stress DM-CTP (n = 30) or adenosine induced stress DM-CTP only (n = 52). Global and segmental MBF were assessed. Global MBF at rest and during stress were 0.93 ± 0.42 mL/min/g and 3.58 ± 1.14 mL/min/g respectively. MBF was not different between the sexes (P = 0.88 at rest and P = 0.61 during stress) and no correlation was observed between MBF and age (P = 0.08 at rest and P = 0.82 during stress). Among the 16 myocardial segments, significant inter-segmental differences were found (P < 0.01), which was not related to age, sex or coronary dominance. Myocardial blood flow assessed by DM-CTP in healthy individuals with normal coronary arteries displays significant intersegmental heterogeneity which does not seem to be affected by age, sex or coronary dominance. Normal values of myocardial blood flow may be helpful in the clinical evaluation of suspected myocardial ischemia using DM-CTP.

Long-term impact of myocardial inflammation on quantitative myocardial perfusion—a descriptive PET/MR myocarditis study

PurposeWhether myocardial inflammation causes long-term sequelae potentially affecting myocardial blood flow (MBF) is unknown. We aimed to assess the effect of myocardial inflammation on quantitative MBF parameters, as assessed by 13N-ammonia positron emission tomography myocardial perfusion imaging (PET-MPI) late after myocarditis.MethodsFifty patients with a history of myocarditis underwent cardiac magnetic resonance (CMR) imaging at diagnosis and PET/MR imaging at follow-up at least 6 months later. Segmental MBF, myocardial flow reserve (MFR), and 13N-ammonia washout were obtained from PET, and segments with reduced 13N-ammonia retention, resembling scar, were recorded. Based on CMR, segments were classified as remote (n = 469), healed (inflammation at baseline but no late gadolinium enhancement [LGE] at follow-up, n = 118), and scarred (LGE at follow-up, n = 72). Additionally, apparently healed segments but with scar at PET were classified as PET discordant (n = 18).ResultsCompared to remote segments, healed segments showed higher stress MBF (2.71 mL*min−1*g−1 [IQR 2.18–3.08] vs. 2.20 mL*min−1*g−1 [1.75–2.68], p < 0.0001), MFR (3.78 [2.83–4.79] vs. 3.36 [2.60–4.03], p < 0.0001), and washout (rest 0.24/min [0.18–0.31] and stress 0.53/min [0.40–0.67] vs. 0.22/min [0.16–0.27] and 0.46/min [0.32–0.63], p = 0.010 and p = 0.021, respectively). While PET discordant segments did not differ from healed segments regarding MBF and MFR, washout was higher by ~ 30% (p < 0.014). Finally, 10 (20%) patients were diagnosed by PET-MPI as presenting with a myocardial scar but without a corresponding LGE.ConclusionIn patients with a history of myocarditis, quantitative measurements of myocardial perfusion as obtained from PET-MPI remain altered in areas initially affected by inflammation.Graphical abstractCMR = cardiac magnetic resonance; PET = positron emission tomography; LGE = late gadolinium enhancement

Impact of myocardial inflammation on quantitative myocardial perfusion at long-term follow-up - a descriptive hybrid PET/MR myocarditis study

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swiss National Science Foundation (SNSF). Background Whether myocardial inflammation causes long-term sequelae potentially affecting myocardial blood flow (MBF) is unknown. Objectives To assess the effect of myocardial inflammation on quantitative MBF parameters, as assessed by 13N-ammonia positron emission tomography myocardial perfusion imaging (PET-MPI) late after myocarditis. Methods Fifty patients with a history of myocarditis underwent cardiac magnetic resonance (CMR) imaging at diagnosis and PET/MR imaging at follow-up at least 6 months later. Segmental MBF, myocardial flow reserve (MFR), and 13N-ammonia washout were obtained from PET, and segments with reduced 13N-ammonia retention, resembling scar, were recorded. Based on CMR, segments were classified as remote (n=469), healed (inflammation at baseline but no late gadolinium enhancement [LGE] at follow-up, n=118), and scarred (LGE at follow-up, n=72). Additionally, apparently healed segments but with scar at PET were classified as PET discordant (n=18). Results Compared to remote segments, healed segments showed higher stress MBF (2.71mL*min-1*g-1 [IQR 2.18–3.08] vs. 2.20 mL*min-1*g-1 [1.75–2.68], p&amp;lt;0.0001), MFR (3.78 [2.83–4.79] vs. 3.36 [2.60–4.03], p&amp;lt;0.0001) and washout (rest 0.24/min [0.18–0.31] and stress 0.53/min [0.40–0.67] vs. 0.22/min [0.16–0.27] and 0.46/min [0.32–0.63], p = 0.010 and p = 0.021, respectively). While PET discordant segments did not differ from healed segments regarding MBF and MFR, washout was higher by ∼30% (p&amp;lt;0.014). Finally, 10 (20%) patients were diagnosed by PET-MPI as presenting with myocardial scar but without corresponding LGE. Conclusions In patients with a history of myocarditis, quantitative measurements of myocardial perfusion as obtained from PET-MPI remain altered in areas initially affected by inflammation.

Abstract 14447: Multi-Center Evaluation of Stress Myocardial Blood Flow by Cardiac Magnetic Resonance in Known and Suspected Ischemic Heart Disease: Preliminary Findings From the AQUA-MBF Initiative

Introduction: Quantitative myocardial blood flow (MBF) analysis using stress cardiac magnetic resonance (CMR) has been shown to detect obstructive coronary artery disease (CAD) and coronary microvascular dysfunction (CMD) in several mostly small, single-center studies. The AQUA-MBF ( A ssessment of QUA ntitative MBF ) study is a multicenter initiative involving 16 centers. Hypothesis: The goal of this sub-study is to determine if MBF can differentiate CAD, CMD, and normal volunteers in this multicenter setting. Methods: We present data from 53 subjects (15 with CAD, 20 at risk for CMD and 18 controls) who underwent vasodilator stress CMR (Figure) using 1.5T and 3.0T MR scanners (General Electric). At risk for CMD was defined as having diabetes and 2 other risk factors in absence of ≥50% stenosis based on coronary CT. CAD was defined as the presence of stenosis ≥70% based on invasive coronary angiography. Stress perfusion images were acquired using the dual sequence technique. Stress MBF was measured in each of the 16 AHA segments using Fermi deconvolution (Circle Cvi42). In the CAD group, each segment was further classified as having late gadolinium enhancement (LGE), supplied by CAD, or a normal remote territory. The means of the 5 groups were compared using one-way analysis of variance. Results: The segmental stress MBF (ml/g/min) for the 5 groups are shown in figure. Compared to the normal group, segmental stress MBF in 4 disease groups were significantly lower (p&lt;0.001). Segmental MBF in those at risk for CMD was lower than normal segments and greater than CAD segments (p&lt;0.001). LGE and CAD segments had the lowest stress MBF but similar to each other (p=0.9). Conclusions: In this multicenter study, we show that quantification of MBF using the dual sequence stress perfusion CMR technique can differentiate diseased from healthy myocardium and also between obstructive CAD and those at risk for CMD.

Therapeutic Hypothermia Reduces Peritoneal Dialysis Induced Myocardial Blood Flow Heterogeneity and Arrhythmia.

Background: Moderate therapeutic hypothermia (TH) is a well-recognized cardio-protective strategy. The instillation of fluid into the peritoneum provides an opportunity to deliver moderate hypothermia as primary prevention against cardiovascular events. We aimed to to investigate both cardiac perfusion consequences (overall blood flow and detailed assessment of perfusion heterogeneity) and subsequently simulate the associated arrhythmic risk for patients undergoing peritoneal dialysis (PD) induced TH.Methods: Patients underwent high resolution myocardial perfusion scanning using high resolution 256 slice CT scanning, at rest and with adenosine stress. The first visit using the patient's usual PD regimen, on the second visit the same regime was utilized but with cooled peritoneal dialysate at 32°C. Myocardial blood flow (MBF) was quantified from generated perfusion maps, reconstructed in 3D. MBF heterogeneity was assessed by fractal dimension (FD) measurement on the 3D left ventricular reconstruction. Arrhythmogenicity was quantified from a sophisticated computational simulation using a multi-scale human 3D ventricle wedge electrophysiological computational model.Results: We studied 7 PD patients, mean age of 60 ± 7 and mean vintage dialysis of 23.6 ± 17.6 months. There were no significant different in overall segmental MBF between normothermic condition (NT) and TH. MBF heterogeneity was significantly decreased (−14%, p = 0.03) at rest and after stress (−14%, p = 0.03) when cooling was applied. Computational simulation showed that TH allowed a normalization of action potential, QT duration and T wave.Conclusion: TH-PD results in moderate hypothermia leading to a reduction in perfusion heterogeneity and simulated risk of non-terminating malignant ventricular arrhythmias.

Impact of the Choice of Native T1 in Pixelwise Myocardial Blood Flow Quantification.

BackgroundQuantification of myocardial blood flow (MBF) from dynamic contrast‐enhanced (DCE) MRI can be performed using a signal intensity model that incorporates T1 values of blood and myocardium.PurposeTo assess the impact of T1 values on pixelwise MBF quantification, specifically to evaluate the influence of 1) study population‐averaged vs. subject‐specific, 2) diastolic vs. systolic, and 3) regional vs. global myocardial T1 values.Study TypeProspective.SubjectsFifteen patients with chronic coronary heart disease.Field Strength/Sequence3T; modified Look–Locker inversion recovery for T1 mapping and saturation recovery gradient echo for DCE imaging, both acquired in a mid‐ventricular short‐axis slice in systole and diastole.AssessmentMBF was estimated using Fermi modeling and signal intensity nonlinearity correction with different T1 values: study population‐averaged blood and myocardial, subject‐specific systolic and diastolic, and segmental T1 values. Myocardial segments with perfusion deficits were identified visually from DCE series.Statistical TestsThe relationships between MBF parameters derived by different methods were analyzed by Bland–Altman analysis; corresponding mean values were compared by t‐test.ResultsUsing subject‐specific diastolic T1 values, global diastolic MBF was 0.61 ± 0.13 mL/(min·g). It did not differ from global MBF derived from the study population‐averaged T1 (P = 0.88), but the standard deviation of differences was large (0.07 mL/(min·g), 11% of mean MBF). Global diastolic and systolic MBF did not differ (P = 0.12), whereas global diastolic MBF using systolic (0.62 ± 0.13 mL/(min·g)) and diastolic T1 values differed (P < 0.05). If regional instead of global T1 values were used, segmental MBF was lower in segments with perfusion deficits (bias = −0.03 mL/(min·g), −7% of mean MBF, P < 0.05) but higher in segments without perfusion deficits (bias = 0.01 mL/(min·g), 1% of mean MBF, P < 0.05).Data ConclusionWhereas cardiac phase‐specific T1 values have a minor impact on MBF estimates, subject‐specific and myocardial segment‐specific T1 values substantially affect MBF quantification.Level of Evidence3Technical Efficacy Stage3

Myocardial blood flow analysis of stress dynamic myocardial CT perfusion for hemodynamically significant coronary artery disease diagnosis: The clinical value of relative parameter optimization

BackgroundThe methods for calculating the optimal myocardial blood flow (MBF) relative parameters in stress dynamic myocardial CT perfusion (CTP) in the detection of hemodynamically significant coronary artery disease (CAD) are non-uniform and lack standards. MethodsA total of 86 patients who were prospectively recruited underwent APT stress dynamic myocardial CTP. The relative MBF perfusion parameters were calculated as av_Ratio, Q3av_Ratio and hi_Ratio according to the three types of reference MBF values, respectively: (1) average segmental MBF value, (2) the third quartile of the average segmental MBF value, and (3) highest segmental MBF value. All the data were derived from both the endocardial and transmural layers of the myocardium. Invasive coronary angiography and fractional flow reserve (ICA/FFR) were used as the reference standards for myocardial ischemia evaluation. ResultsA total of 151 vessels of 60 patients (43 men and 17 women; 61.38 ± 8.01 years) were enrolled in the analysis. The performance of the endocardial layer was superior to that of the transmural layer (all P < 0.05). The hi_Ratio of the endocardial myocardium (AUC = 0.906, 95% CI: 0.857–0.954), for which the highest segmental value was selected as the reference MBF, was superior to both av_Ratio and Q3av_Ratio for ischemia detection (AUC, 0.906 vs.0.879, P < 0.05; 0.906 vs.0.891, P = 0.18), and the sensitivity, specificity, PPV, NPV and diagnostic accuracy were 74.1%, 93.6%, 87.8%, 85.3% and 86.1%, respectively. The cutoff value of hi_Ratio was 0.675. ConclusionsThe relative MBF parameter of the endocardial myocardium using the highest segmental MBF value as a reference provided optimal diagnostic accuracy for the detection of hemodynamically significant CAD.

Acute Microvascular Impairment Post-Reperfused STEMI Is Reversible and Has Additional Clinical Predictive Value: A CMR OxAMI Study

ObjectivesThis study sought to investigate the clinical utility and the predictive relevance of absolute rest myocardial blood flow (MBF) by cardiac magnetic resonance (CMR) in acute myocardial infarction. BackgroundMicrovascular obstruction (MVO) remains one of the worst prognostic factors in patients with reperfused ST-segment elevation myocardial infarction (STEMI). Clinical trials have focused on cardioprotective strategies to maintain microvascular functionality, but there is a need for a noninvasive test to determine their efficacy. MethodsA total of 64 STEMI patients post–primary percutaneous coronary intervention underwent 3-T CMR scans acutely and at 6 months (6M). The protocol included cine function, T2-weighted edema imaging, pre-contrast T1 mapping, rest first-pass perfusion, and late gadolinium enhancement imaging. Segmental MBF, corrected for rate pressure product (MBFcor), was quantified in remote, edematous, and infarcted myocardium. ResultsAcute MBFcor was significantly reduced in infarcted myocardium compared with remote MBF (MBFinfarct 0.76 ± 0.20 ml/min/g vs. MBFremote 1.02 ± 0.21 ml/min/g, p < 0.001), but it significantly increased at 6M (MBFinfarct 0.76 ± 0.20 ml/min/g acute vs. 0.85 ± 0.22 ml/min/g at 6M, p < 0.001). On a segmental basis, acute MBFcor had incremental prognostic value for infarct size at 6M (odds of no LGE at 6M increased by 1.4:1 [p < 0.001] for each 0.1 ml/min/g increase of acute MBFcor) and functional recovery (odds of wall thickening >45% at 6M increased by 1.38:1 [p < 0.001] for each 0.1 ml/min/g increase of acute MBFcor). In subjects with coronary flow reserve >2 or index of myocardial resistance <40, acute MBF was associated with long-term functional recovery and was an independent predictor of infarct size reduction. ConclusionsAcute MBF by CMR could represent a novel quantitative imaging biomarker of microvascular reversibility, and it could be used to identify patients who may benefit from more intensive or novel therapies.

Cardiac PET/CT with Rb-82: optimization of image acquisition and reconstruction parameters

BackgroundOur aim was to characterize the influence of time-of-flight (TOF) and point spread function (PSF) recovery corrections, as well as ordered subset expectation maximization (OSEM) reconstruction parameters, in 82Rb PET/CT quantification of myocardial blood flow (MBF) and myocardial flow reserve (MFR).Rest and stress list-mode dynamic 82Rb PET acquisition data from 10 patients without myocardial flow defects and 10 patients with myocardial blood flow defects were reconstructed retrospectively. OSEM reconstructions were performed with Gaussian filters of 4, 6, and 8 mm, different iterations, and subset numbers (2 × 24; 2 × 16; 3 × 16; 4 × 16). Rest and stress global, regional, and segmental MBF and MFR were computed from time activity curves with FlowQuant© software. Left ventricular segmentation using the 17-segment American Heart Association model was obtained.ResultsWhole left ventricle (LV) MBF at rest and stress were 0.97 ± 0.30 and 2.30 ± 1.00 mL/min/g, respectively, and MFR was 2.40 ± 1.13. Concordance was excellent and all reconstruction parameters had no significant impact on MBF, except for the exclusion of TOF which led to significantly decreased concordance in rest and stress MBF in patients with or without perfusion defects on a coronary artery basis and in MFR in patients with perfusion defects.ConclusionsChanges in reconstruction parameters in perfusion 82Rb PET/CT studies influence quantitative MBF analysis. The inclusion of TOF information in the tomographic reconstructions had significant impact in MBF quantification.

Assessment of segmental myocardial blood flow and myocardial perfusion reserve by adenosine-stress myocardial arterial spin labeling perfusion imaging.

To determine the feasibility of measuring increases in myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) on a per-segment basis using arterial spin labeled (ASL) magnetic resonance imaging (MRI) with adenosine vasodilator stress in normal human myocardium. Myocardial ASL scans at rest and during adenosine infusion were incorporated into a routine 3T MR adenosine-induced vasodilator stress protocol and were performed in 10 healthy human volunteers. Myocardial ASL was performed using single-gated flow-sensitive alternating inversion recovery (FAIR) tagging and balanced steady-state free precession (bSSFP) imaging at 3T. A T2 -prep blood oxygen level-dependent (BOLD) SSFP sequence was used to concurrently assess segmental myocardial oxygenation with BOLD signal intensity (SI) percent change in the same subjects. There was a statistically significant difference between MBF measured by ASL at rest (1.75 ± 0.86 ml/g/min) compared to adenosine stress (4.58 ± 2.14 ml/g/min) for all wall segments (P < 0.0001), yielding a per-segment MPR of 3.02 ± 1.51. When wall segments were divided into specific segmental myocardial perfusion territories (ie, anteroseptal, anterior, anterolateral, inferolateral, inferior, and inferoseptal), the differences between rest and stress regional MBF for each territory remained consistently statistically significant (P < 0.001) after correcting for multiple comparisons. This study demonstrates the feasibility of measuring MBF and MPR on a segmental basis by single-gated cardiac ASL in normal volunteers. Second, this study demonstrates the feasibility of performing the ASL sequence and T2 -prepared SSFP BOLD imaging during a single adenosine infusion. 2 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:413-420.

Abstract 13031: A Randomized Trial Comparing the Effects of Ticagrelor versus Clopidogrel on Myocardial Perfusion in Patients With Coronary Artery Disease

Introduction: Ticagrelor is a reversible P2Y12 receptor antagonist used in patients with acute coronary syndrome (ACS). In the PLATO trial, treatment with ticagrelor reduced mortality compared to clopidogrel, to which pleotropic mechanisms may have contributed. In this study, we compared the effects of ticagrelor versus clopidogrel in patients with stable coronary artery disease on myocardial blood flow (MBF) at rest and during intermediate and high dose adenosine infusion. Methods: Patients (n=22) were randomized using a double-blind crossover design to ticagrelor 90 mg orally twice a day for 10 days and clopidogrel 75 mg orally once a day for 10 days, with a washout period of at least 5 days between the treatments. MBF was measured using Rb-82 PET-CT at baseline and at intermediate (80 mcg/kg/min) and high dose adenosine (140 mcg/kg/min). Results: Global MBF was significantly greater with ticagrelor versus clopidogrel at intermediate dose adenosine (1.28±0.55 versus 1.13±0.47, p=0.002), and not different at baseline (0.65±0.19 versus 0.60±0.15, p=0.4254) nor at high dose adenosine (1.64±0.40 versus 1.61±0.19, p=0.5302). In abnormal segments with low MBF reserve (&lt;2.5), MBF was significantly greater with ticagrelor compared to clopidogrel at intermediate and high dose of adenosine (p&lt;0.0001), with no difference at baseline. For segments with high MBF reserve (≥2.5 and &lt; 3.5), segmental MBF was significantly greater with ticagrelor compared to clopidogrel at baseline (p&lt;0.001) and at intermediate adenosine dose (p&lt;0.0001). Conclusions: Global stress MBF was greater with ticagrelor compared to clopidogrel during intermediate dose adenosine infusion. Regional MBF in segments with reduced MBF reserve was greater with ticagrelor compared to clopidogrel during intermediate and high dose adenosine. This suggests that ticagrelor may potentiate adenosine-induced myocardial blood coronary flow increases in patients with stable CAD compared to clopidogrel; an effect that may explain the observed incremental mortality benefit observed with ticagrelor.

Effect of tracer arrival time on the estimation of the myocardial perfusion in DCE-CMR

Background An accurate segmental myocardial blood flow (MBF) quantification can be performed by means of signal deconvolution techniques. The accuracy of MBF estimates relies on the precise identification of the tracer arrival time in the myocardium (tOnset). Voxelwise MBF quantification is likel yt o be more subject to such error than segmental MBF analysis due to the lower signal-to-noise ratio of myocardial signal intensity curves. Automated tOnset detection methods would be therefore warranted. The aim of this study was to assess the importance to of tOnset identification on voxelwise MBF quantification and to describe an automated algorithm to detect the optimal tOnset which minimizes the error in MBF estimates. Methods Perfusion data were obtained from an hardware perfusion phantom (validated MBF 5 ml/g/min) and from patients during adenosine-induced hyperaemia (140µg/ kg/min) using 0.075mmol/kg Gadobutrol (Gadovist, Schering, Germany) injected at 4ml/minute followed by a 20 ml saline flush. A pre-bolus technique was used for quantification.

Myocardial Perfusion Imaging After Coronary Artery Bypass Surgery Using Cardiovascular Magnetic Resonance

Background— Absolute quantification of perfusion with cardiovascular magnetic resonance has not previously been applied in patients with coronary artery bypass grafting (CABG). Owing to increased contrast bolus dispersion due to the greater distance of travel through a bypass graft, this approach may result in systematic underestimation of myocardial blood flow (MBF). As resting MBF remains normal in segments supplied by noncritical coronary stenosis (&lt;85%), measurement of perfusion in such territories may be utilized to reveal systematic error in the quantification of MBF. The objective of this study was to test whether absolute quantification of perfusion with cardiovascular magnetic resonance systematically underestimates MBF in segments subtended by bypass grafts. Methods and Results— The study population comprised 28 patients undergoing elective CABG for treatment of multivessel coronary artery disease. Eligible patients had angiographic evidence of at least 1 myocardial segment subtended by a noncritically stenosed coronary artery (&lt;85%). Subjects were studied at 1.5 T, with evaluation of resting MBF using model-independent deconvolution. Analyses were confined to myocardial segments subtended by native coronary arteries with &lt;85% stenosis at baseline, and MBF was compared in grafted and ungrafted segments before and after revascularization. A total of 249 segments were subtended by coronary arteries with &lt;85% stenosis at baseline. After revascularization, there was no significant difference in MBF in ungrafted (0.82±0.19 mL/min/g) versus grafted segments (0.82±0.15 mL/min/g, P =0.57). In the latter, MBF after revascularization did not change significantly from baseline (0.86±0.20 mL/min/g, P =0.82). Conclusions— Model-independent deconvolution analysis does not systematically underestimate blood flow in graft-subtended territories, justifying the use of this methodology to evaluate myocardial perfusion in patients with CABG.

Automatic generation of absolute myocardial blood flow images using [15O]H2O and a clinical PET/CT scanner

PurposeParametric imaging of absolute myocardial blood flow (MBF) using [15O]H2O enables determination of MBF with high spatial resolution. The aim of this study was to develop a method for generating reproducible, high-quality and quantitative parametric MBF images with minimal user intervention.MethodsNineteen patients referred for evaluation of MBF underwent rest and adenosine stress [15O]H2O positron emission tomography (PET) scans. Ascending aorta and right ventricular (RV) cavity volumes of interest (VOIs) were used as input functions. Implementation of a basis function method (BFM) of the single-tissue model with an additional correction for RV spillover was used to generate parametric images. The average segmental MBF derived from parametric images was compared with MBF obtained using nonlinear least-squares regression (NLR) of VOI data. Four segmentation algorithms were evaluated for automatic extraction of input functions. Segmental MBF obtained using these input functions was compared with MBF obtained using manually defined input functions.ResultsThe average parametric MBF showed a high agreement with NLR-derived MBF [intraclass correlation coefficient (ICC) = 0.984]. For each segmentation algorithm there was at least one implementation that yielded high agreement (ICC > 0.9) with manually obtained input functions, although MBF calculated using each algorithm was at least 10% higher. Cluster analysis with six clusters yielded the highest agreement (ICC = 0.977), together with good segmentation reproducibility (coefficient of variation of MBF <5%).ConclusionParametric MBF images of diagnostic quality can be generated automatically using cluster analysis and a implementation of a BFM of the single-tissue model with additional RV spillover correction.Electronic supplementary materialThe online version of this article (doi:10.1007/s00259-011-1730-3) contains supplementary material, which is available to authorized users.

Incremental Diagnostic Value of Regional Myocardial Blood Flow Quantification Over Relative Perfusion Imaging With Generator-Produced Rubidium-82 PET

Myocardial blood flow (MBF) can be measured with positron emission tomography (PET) and its quantification should provide diagnostic information beyond that obtained through standard visual analysis. However, this possibility has not been fully studied with PET and generator-produced rubidium-82 (⁸²Rb). We evaluated regional MBF in segments with and without ischemia using ⁸²Rb PET in patients with coronary artery disease (CAD). Rest and stress ⁸²Rb PET and coronary angiography were performed for 12 patients with CAD. Based on angiography and relative ⁸²Rb perfusion images, segments were classified into 4 groups (Group A: myocardial ischemia with >70% diameter stenosis; Group B: no ischemia with stenosis; Group C: no ischemia without stenosis; Group D: ischemia without stenosis). Rest MBF was similar among the 4 groups. Groups A and B showed reduced hyperemic MBF compared with Group C (P < 0.05 vs. Group C) [Group A (n=16) 1.28 ± 0.58 ml·min⁻¹·g⁻¹; Group B (n=11) 1.72 ± 0.64 ml·min⁻¹·g⁻¹; Group C (n=9) 2.60 ± 1.09 ml·min⁻¹·g⁻¹; Group D (n=2) 2.33 ml·min⁻¹·g⁻¹]. Coronary flow reserves were inversely correlated with percent diameter stenosis (r=0.76, P < 0.0001). Segments with ischemia and coronary stenosis had reduced hyperemic MBF. Segments with coronary stenosis without ischemia also had reduced hyperemic MBF compared with non-stenotic segments. MBF quantification using ⁸²Rb PET may provide additional diagnostic information.

Coronary calcium score scans for attenuation correction of quantitative PET/CT 13N-ammonia myocardial perfusion imaging

The aim of this study was to evaluate whether ECG-triggered coronary calcium scoring (CCS) scans can be used for attenuation correction (AC) to quantify myocardial blood flow (MBF) and coronary flow reserve (CFR) assessed by PET/CT with (13)N-ammonia. Thirty-five consecutive patients underwent a (13)N-ammonia PET/CT scan at rest and during standard adenosine stress. MBF values were calculated using AC maps obtained from the ECG-triggered CCS scan during inspiration and validated against MBF values calculated using standard non-gated transmission scans for AC. CFR was calculated as the ratio of hyperaemic over resting MBF. In all 35 consecutive patients intraobserver variability was assessed by blinded repeat analysis for both AC methods. There was an excellent correlation between CT AC and CCS for global MBF values at rest (n = 35, r = 0.94, p < 0.001) and during stress (n = 35, r = 0.97, p < 0.001) with narrow Bland-Altman (BA) limits of agreement (-0.21 to 0.10 ml/min per g and -0.41 to 0.30 ml/min per g) as well as for global CFR (n = 35, r = 0.96, p < 0.001, BA -0.27 to 0.34). The excellent correlation was preserved on the segmental MBF analysis for both rest and stress (n = 1190, r = 0.93, p < 0.001, BA -0.60 to 0.50) and for CFR (n = 595, r = 0.87, p < 0.001, BA -0.71 to 0.74). In addition, reproducibility proved excellent for global CFR by CT AC (n = 35, r = 0.91, p < 0.001, BA -0.42-0.58) and CCS scans (n = 35, r = 0.94, p < 0.001, BA -0.34-0.45). Use of attenuation maps from CCS scans allows accurate quantitative MBF and CFR assessment with (13)N-ammonia PET/CT.

Left Ventricular Dysfunction Secondary to Ischemia in Women with Angina and Normal Coronary Angiograms

Microvascular disease is proposed as a cause of segmental myocardial blood flow abnormalities and heterogeneous myocardial perfusion in cardiac syndrome X. To assess if myocardial ischemia can be evidenced through both perfusion abnormalities and poststress left ventricular ejection fraction (LVEF) reduction by gated single photon emission tomography (SPECT) myocardial scintigraphy in women with syndrome X in a similar way to those with epicardial coronary lesions. Three groups of postmenopausal women were studied: group I, 20 women with angina, perfusion defects, and normal coronary angiography; group II, 20 women with epicardial coronary lesions (> or =50% of coronary lumen reduction); group III, 15 volunteers without signs or symptoms of ischemia (control group). Each underwent technetium-99m ((99m)TC) methoxyisobutylisonitrile gated SPECT myocardial scintigraphy (protocol: exercise-stress-rest), brachial artery endothelial function measured by ultrasonography, and lipidogram. Groups I and III patients had a higher body mass index (BMI). There were more smokers in groups I and II. Very low density lipoprotein cholesterol (VLDL-C) and triglycerides were higher in group II patients. The brachial artery vasodilator responsiveness after 5 minutes of ischemia was similarly lower in patients of groups I and II compared with those of group III (3% vs. 6.5%, respectively; p = 0.03 group III vs. group I and group II). Mean DeltaLVEF (LVEF poststress minus LVEF at rest) was -3.86%, -2.90%, and 4.18% in groups I, II, and III, respectively (p = NS between I and II, p = 0.005 between II and III, and p = 0.003 between I and III). In 43% of group I patients and in 10 of 18 group III patients with perfusion defects, there was a poststress LVEF reduction >5%. Stress-induced ischemia is associated with poststress LVEF reduction as a probable manifestation of myocardial stunning in postmenopausal women with typical angina and normal coronary angiography.

Hemodialysis-Induced Cardiac Dysfunction Is Associated with an Acute Reduction in Global and Segmental Myocardial Blood Flow

Hemodialysis is associated with hemodynamic instability, acute cardiac ischemia, and the development of regional wall motion abnormalities (RWMAs). This study used serial intradialytic H(2)(15)O positron emission tomography scanning to confirm that the development of dialysis-induced RWMAs was associated with reduction in myocardial blood flow (MBF). Four prevalent hemodialysis patients without angiographically significant coronary artery disease had measurements of MBF during standard hemodialysis and biofeedback dialysis. All patients underwent serial measurements of MBF using positron emission tomography. Concurrent echocardiography was used to assess left ventricular function and the development of RWMAs. Hemodynamic variables were measured using continuous pulse wave analysis. Mean prehemodialysis MBF was within the normal range. Global MBF was acutely reduced during hemodialysis. Segmental MBF was reduced to a significantly greater extent in areas that developed RWMAs compared with those that did not. Not all regions with reduced MBF were functionally affected, but a reduction in myocardial blood flow of >30% from baseline was significantly associated with the development of RWMAs. No significant differences in hemodynamic tolerability, RWMA development, or MBF between dialysis modalities were observed. Hemodialysis is associated with repetitive myocardial ischemia, which, in the absence of coronary artery disease, may be due to coronary microvascular dysfunction. Stress-induced segmental left ventricular dysfunction correlates with matched reduction in MBF. Functional poststress recovery is consistent with myocardial stunning induced by hemodialysis. This process may be important in the development of heart failure in long-term hemodialysis patients.

Abstract 3357: Haemodialysis Induced Contractile Dysfunction is Associated with Acute and Reversible Reduction in Global and Segmental Myocardial Blood Flow

Hemodialysis (HD) is associated with acute cardiac ischemia, as evidenced by the development of regional wall motion abnormalities (RWMAs). Repetitive acute myocardial ischemia may lead to the development of chronic left ventricular (LV) dysfunction. This study utilised serial H 2 15 O PET scans to confirm that the development of HD-induced RWMAs was associated with reduction in myocardial blood flow (MBF). Four prevalent HD patients without angiographically significant coronary artery disease (CAD) had measurements of MBF during standard HD and biofeedback dialysis (BFD). All patients underwent serial measurements of MBF using PET. Echocardiography was used concurrently to assess LV function. Hemodynamic variables were measured using continuous pulse wave analysis. Mean pre-HD MBF was within the normal range. Global MBF was acutely reduced during HD (see figure ) (P&lt;0.002). Segmental MBF was significantly reduced in areas that developed RWMAs compared to those that did not (P&lt;0.001). Not all regions with reduced MBF were functionally affected but a reduction in MBF of &gt;30% from baseline was associated with the development of RWMAs (P&lt;0.01). No significant differences in haemodynamic tolerability, RWMA development or MBF between dialysis modality were observed. HD is associated with repetitive myocardial ischemia which in absence of significant CAD may be due to coronary microvascular dysfunction. Stress induced, segmental LV dysfunction correlates with a matched reduction in MBF. Functional post-stress recovery is consistent with myocardial stunning induced by HD. This process may be an important component in the development of heart failure in chronic HD patients.