Regional Myocardial Blood Flow Research Articles

Prognostic value of [15O]H2O positron emission tomography-derived global and regional myocardial perfusion.

To evaluate the prognostic value of global and regional quantitative [15O]H2O positron emission tomography (PET) perfusion. In this retrospective study, 648 patients with suspected or known coronary artery disease (CAD) who underwent [15O]H2O PET were followed for the occurrence of death and myocardial infarction (MI). Global and regional hyperaemic myocardial blood flow (hMBF) and coronary flow reserve (CFR) were obtained from [15O]H2O PET. During median follow-up of 6.9 (5.0-7.9) years, 64 (9.9%) patients experienced the composite of death (36-5.6%) and MI (28-4.3%). Impaired global hMBF (<2.65 mL/min/g) and CFR (<2.88) were both significant prognostic factors for death/MI after adjusting for clinical characteristics (both P < 0.001). However, after adjusting for clinical parameters and the combined use of hMBF and CFR, only hMBF remained an independent prognostic factor (P = 0.04). For regional perfusion, both impaired hMBF (<2.10 mL/min/g) and CFR (<2.07) demonstrated prognostic value for events (both P < 0.001). Similarly, after adjusting for clinical characteristics and combined use of hMBF and CFR, only hMBF had independent prognostic value (P = 0.04). The combination of global and regional perfusion did not improve prognostic performance over either global (P = 0.55) or regional perfusion (P = 0.37) alone. Global and regional hMBF and CFR were all prognostic factors for death and MI. However, for both global and regional perfusion, hMBF remained the only independent prognostic factor after adjusting for the combined use of hMBF and CFR. Additionally, integrating global and regional perfusion did not increase prognostic performance compared to either regional or global perfusion alone.

Larger infarct size but equal protection by ischemic conditioning in septum and anterior free wall of pigs with LAD occlusion.

The ischemic area at risk (AAR) is one major determinant of infarct size (IS). In patients, the largest AAR is seen with a proximal occlusion of the left anterior descending (LAD) coronary artery, which serves parts of the septum and of the anterior free wall. It is not clear, whether regional differences in the perfusion territories also impact on IS and the magnitude of cardioprotection by ischemic conditioning. We have retrospectively analyzed 132 experiments in pigs, which have a similar LAD perfusion territory as humans. The LAD was occluded for 60 min with subsequent 180 min reperfusion. Cardioprotection by either local ischemic pre‐ or postconditioning or remote ischemic pre‐ or perconditioning was induced in 93 pigs. The AAR was demarcated by blue dye staining, and IS was assessed by triphenyltetrazolium chloride (TTC) staining. Using digital planimetry, the AAR was separated into sections unequivocally located in the septum (AARS) or the anterior free wall (AARAFW). Relative IS was calculated for AARS or AARAFW. AARAFW was larger than AARS (51 ± 9% vs. 34 ± 8% of total AAR; mean ± SD, P < 0.001). Regional myocardial blood flow (microspheres) was not different between septum and anterior free wall. IS without ischemic conditioning tended to be larger in AARS than in AARAFW (50 ± 17% vs. 44 ± 19%; % of AARAWF or AARS, respectively; P = 0.075). Also, with robust IS reduction by ischemic conditioning, the difference in relative IS remained (AARS: 27 ± 16%; AARAFW: 21 ± 16%; P = 0.01). There is a somewhat greater susceptibility for infarction in septal than anterior free wall myocardium. However, ischemic conditioning still reduces IS in both septal and anterior free wall myocardium.

New 99mTc Radiotracers for Myocardial Perfusion Imaging by SPECT.

Myocardial Perfusion Imaging (MPI) with radiotracers is an integral component in evaluation of the patients with known or suspected coronary artery diseases (CAD). 99mTc-Sestamibi and 99mTc-Tetrofosmin are commercial radiopharmaceuticals for MPI by single photon-emission computed tomography (SPECT). Despite their widespread clinical applications, they do not meet the requirements of an ideal perfusion imaging agent due to their inability to linearly track the regional myocardial blood flow rate at >2.5 mL/min/g. With tremendous development of CZT-based SPECT cameras over the past several years, the nuclear cardiology community has been calling for better perfusion radiotracers with improved extraction and biodistribution properties. This review will summarize recent research efforts on new cationic and neutral 99mTc radiotracers for SPECT MPI. The goal of these efforts is to develop a 99mTc radiotracer that can be used to detect perfusion defects at rest or under stress, determine the regional myocardial blood flow, and measure the perfusion and left ventricular function. The advantage of cationic radiotracers (e.g. 99mTc-Sestamibi) is their long myocardial retention because of the positive molecular charge and fast liver clearance kinetics. 99mTc-Teboroxime derivatives have a high initial heart uptake (high first-pass extraction fraction) due to their neutrality. 99mTc- 3SPboroxime is the most promising radiotracer for future clinical translation considering its initial heart uptake, myocardial retention time, liver clearance kinetics, heart/liver ratios and SPECT image quality. 99mTc-3SPboroximine is an excellent example of perfusion radiotracers, the heart uptake of which is largely relies on the regional blood flow. It is possible to use 99mTc-3SPboroximine for detection of perfusion defect(s), accurate quantification and determination of regional blood flow rate. Development of such a 99mTc radiotracer is of great clinical benefit for accurate diagnosis of CAD and assessing the risk of future hard events (e.g. heart attack and sudden death) in cardiac patients.

Improved regional myocardial blood flow and flow reserve after coronary revascularization as assessed by serial 15O-water positron emission tomography/computed tomography.

Myocardial perfusion imaging without and with quantitative myocardial blood flow (MBF) and myocardial flow reserve (MFR) plays an important role in the diagnosis and risk stratification of patients with stable coronary artery disease (CAD). We aimed to quantify the effects of coronary revascularization on regional stress MBF and MFR and to determine whether the presence of subendocardial infarction was associated with these changes. Forty-seven patients with stable CAD were prospectively enrolled. They underwent 15O-water positron emission tomography at baseline and 6 months after optimal medical therapy alone (n = 16), percutaneous coronary intervention (PCI) (n = 18), or coronary artery bypass grafting (CABG) (n = 13). Stenosis of ≥50% diameter was detected in 98/141 vessels (70%). The regional MFR was significantly increased from baseline to follow-up [1.84 (interquartile range, IQR 1.28-2.17) vs. 2.12 (IQR 1.69-2.63), P < 0.001] in vessel territories following PCI or CABG due to an increase in the stress MBF [1.33 (IQR 0.97-1.67) mL/g/min vs. 1.64 (IQR 1.38-2.17) mL/g/min, P < 0.001], whereas there was no significant change in the regional stress MBF or MFR in vessel territories without revascularization. A multilevel mixed-effects models adjusted for baseline characteristics, subendocardial infarction assessed by cardiovascular magnetic resonance imaging, and intra-patient correlation showed that the degree of angiographic improvement after coronary revascularization was significantly associated with increased regional stress MBF and MFR (P < 0.05 for all). Coronary revascularization improved the regional stress MBF and MFR in patients with stable CAD. The magnitude of these changes was associated with the extent of revascularization independent of subendocardial infarction.

A combined static-dynamic single-dose imaging protocol to compare quantitative dynamic SPECT with static conventional SPECT

BackgroundSPECT myocardial perfusion imaging (MPI) is a clinical mainstay that is typically performed with static imaging protocols and visually or semi-quantitatively assessed for perfusion defects based upon the relative intensity of myocardial regions. Dynamic cardiac SPECT presents a new imaging technique based on time-varying information of radiotracer distribution, which permits the evaluation of regional myocardial blood flow (MBF) and coronary flow reserve (CFR). In this work, a preliminary feasibility study was conducted in a small patient sample designed to implement a unique combined static-dynamic single-dose one-day visit imaging protocol to compare quantitative dynamic SPECT with static conventional SPECT for improving the diagnosis of coronary artery disease (CAD). MethodsFifteen patients (11 males, four females, mean age 71 ± 9 years) were enrolled for a combined dynamic and static SPECT (Infinia Hawkeye 4, GE Healthcare) imaging protocol with a single dose of 99mTc-tetrofosmin administered at rest and a single dose administered at stress in a one-day visit. Out of 15 patients, eleven had selective coronary angiography (SCA), 8 within 6 months and the rest within 24 months of SPECT imaging, without intervening symptoms or interventions. The extent and severity of perfusion defects in each myocardial region was graded visually. Dynamically acquired data were also used to estimate the MBF and CFR. Both visually graded images and estimated CFR were tested against SCA as a reference to evaluate the validity of the methods. ResultsOverall, conventional static SPECT was normal in ten patients and abnormal in five patients, dynamic SPECT was normal in 12 patients and abnormal in three patients, and CFR from dynamic SPECT was normal in nine patients and abnormal in six patients. Among those 11 patients with SCA, conventional SPECT was normal in 5, 3 with documented CAD on SCA with an overall accuracy of 64%, sensitivity of 40% and specificity of 83%. Dynamic SPECT image analysis also produced a similar accuracy, sensitivity, and specificity. CFR was normal in 6, each with CAD on SCA with an overall accuracy of 91%, sensitivity of 80%, and specificity of 100%. The mean CFR was significantly lower for SCA detected abnormal than for normal patients (3.86±1.06 vs 1.94±0. 0.67, P < 0.001). ConclusionsThe visually assessed image findings in static and dynamic SPECT are subjective, and may not reflect direct physiologic measures of coronary lesion based on SCA. The CFR measured with dynamic SPECT is fully objective, with better sensitivity and specificity, available only with the data generated from the dynamic SPECT method.

Role of autonomic dysfunction in the regulation of myocardial blood flow in systemic sclerosis evaluated by cardiac magnetic resonance.

Autonomic dysfunction (AD) is an early feature of systemic sclerosis (SSc). A regular endothelial function is a prerequisite for normal response of the myocardial blood flow (MBF) to cold pressure test (CPT). The aim of the study was to evaluate the relation between MBF and AD at rest and after CPT in asymptomatic SSc patients. Twenty SSc patients and 10 age-, sex- and body mass index-matched healthy controls underwent cardiac magnetic resonance at rest and after CPT. All subjects underwent 24hours ambulatory 3-channel electrocardiogram Holter to evaluate AD by heart rate variability. We did not observe any significant difference in MBF (mL/g/min) at rest and after CPT between SSc patients and healthy controls. Delta of MBF (difference between MBF after CPT and rest MBF) was lower (P=0.039) in SSc patients than healthy controls (0.28 [0.04-0.40] vs 0.33 [0.24-0.54]). The low frequency/high frequency (LF/HF) was higher (P=0.002) in SSc patients than healthy controls (3 [1.7-6] vs 1.8 [1.1-2.8]). The high frequencies (HF), modulated mainly by paraympathetic system, was lower (P = 0.003) in SSc patients than healthy controls (30 [16-42] vs 36.5 [24-44]). Sympathetic hyperactivity, due to reduction of parasympathetic activity (HF), is present in SSc patients. A negative correlation was observed between Delta of MBF and LF/HF (r = -0.572, P = 0.0031). AD, characterized by sympathovagal imbalance due to a reduced parasympathetic tone with high LF/HF ratio, could be responsible for the reduced myocardial vasodilatory response after CPT.

Cardiac Autonomic Function Is Associated With Myocardial Flow Reserve in Type 1 Diabetes.

The link between cardiac autonomic neuropathy and risk of cardiovascular disease is highlighted as an area in which research is needed. This study was undertaken to evaluate the association between measures of cardiac autonomic function and cardiac vascular function in type 1 diabetes using new and sensitive methods. This was a cross-sectional study in patients with type 1 diabetes, stratified by normoalbuminuria (n = 30) and macroalbuminuria (n = 30), and in healthy control subjects (n = 30). Cardiac autonomic function was evaluated using heart rate variability (HRV) indices, cardiovascular autonomic reflex tests (CARTs), and cardiac 123I-metaiodobenzylguanidine (MIBG) imaging. Cardiac vascular function was assessed as myocardial flow reserve (MFR) measured by cardiac 82Rb-positron emission tomography/computed tomography. The measures of cardiac autonomic function (except low frequency-to-high frequency ratio and the Valsalva test ratio) were positively correlated to MFR in unadjusted analysis. All the HRV indices lost significance after adjustment for age and heart rate. After further adjustment for relevant cardiovascular risk factors, the late heart-to-mediastinum ratio directly measuring the function of adrenergic receptors and sympathetic integrity (from the MIBG scintigraphy) and the 30-to-15 ratio (a CART), remained positively associated with MFR (P ≤ 0.04). Cardiac autonomic dysfunction, including loss of cardiac sympathetic integrity in type 1 diabetes, is associated with and may contribute to impaired myocardial blood flow regulation.

The impact of revascularization on myocardial blood flow as assessed by positron emission tomography

PurposeRevascularization aims to improve myocardial perfusion. However, changes in regional artery-specific quantitative perfusion after revascularization have not been systematically investigated. It is unclear whether artery-specific thresholds for coronary flow capacity (CFC) and/or relative perfusion predict improved stress perfusion after revascularization. We sought to determine the impact of revascularization based on predefined, artery-specific, severity size thresholds for CFC and/or relative perfusion defects.MethodsFifty patients underwent PET imaging before revascularization and then prospectively within 90 days after revascularization. Changes in regional myocardial blood flow (MBF) were stratified based on baseline perfusion abnormalities, baseline reduced CFC, and whether revascularization was performed in that region.ResultsFollowing angiographic stenosis-directed revascularization, in regions with relative perfusion abnormalities and decreased CFC, stress MBF (sMBF) increased by 0.51 cm3/min/g (59%) from baseline (p < 0.001). In regions without baseline perfusion abnormalities and yet decreased CFC, sMBF increased by 0.35 cm3/min/g (40%) from baseline (p < 0.001). In regions without perfusion abnormalities and normal CFC, sMBF did not increase significantly (+0.07 cm3/min/g, p = 0.56). Patients in whom revascularization was concordant with abnormal PET findings showed increased whole-heart sMBF (+0.22 cm3/min/g, p < 0.001), but in patients in whom revascularization was targeted only to regions without perfusion abnormalities or low CFC, sMBF did not change significantly (−0.06 cm3/min/g, p = 0.38).ConclusionRevascularization targeted to regions with reduced CFC and relative perfusion abnormalities on baseline PET yielded significant improvements in sMBF. When revascularization was performed in regions without reduced CFC, sMBF did not improve.

Complement- and endothelial activation after out-of-hospital cardiac arrest is associated with poor cerebral outcome

Acetate has a pivotal role in the intermediary metabolism of living cells. Glucose, fatty acids and other carbon sources for oxidation are converted to acetate before entering the mitochondrial tricarboxylic acid cycle. 11C-acetate PET is an established technique in cardiac imaging since decades and allows accurate estimates of both regional myocardial blood flow (MBF) and oxygen consumption (MVO2) to be obtained simultaneously from a single scan of less than 30 min duration. Image acquisition is based on dynamic imaging and analysis requires kinetic modeling approaches for optimal results. These requirements, as well as the need for an on-site cyclotron for carbon-11 production, so far limited the clinical use to advanced PET facilities. In recent years, myocardial 11C-acetate PET has seen a renewed interest in heart failure research into myocardial external efficiency (MEE). MEE is defined as the ratio of the energy associated with external pressure-volume work (cardiac output x systemic blood pressure, converted to Joule) and chemical energy consumed (MVO2 x left ventricular mass (LVM), converted to Joule). Cardiac output and LVM can be measured by echocardiography, magnetic resonance imaging or directly from the 11C-acetate PET scan, and hence provides a fully non-invasive approach to detailing important aspects of the inner workings of the heart. MEE is increasingly used to evaluate new therapies in heart failure and has been validated for that purpose. MEE has a high reproducibility and might potentially also be of use for early diagnosis of heart failure before symptoms develop.This chapter describes scanning parameters with image analysis and summarizes the clinical utility of MBF, MVO2 and MEE measurements obtained from 11C-acetate PET.

Perspectives of quantitative assessment of myocardial blood flow

Positron emission tomography (PET) is an excellent imaging technique for quantitative analysis with high-quality images. Myocardial perfusion imaging (MPI) using PET has high diagnostic accuracy and prognostic value. In addition, PET MPI can be used to quantitate regional myocardial blood flow (MBF) and myocardial flow reserve (MFR: hyperemic MBF/MBF at rest). Reduced MFR was often seen in coronary artery disease and also microvascular dysfunction with various coronary risk factors. On the other hand, such MFR reduction may be improved with various medical treatments with and without coronary interventions. PET perfusion study permits improvement in MFR under various medical treatments and/or modification of risk factors. MBF response to cold pressor test has recently been used to estimate coronary endothelial function which is considered as earlier process of atherosclerosis. Thus, MPI using PET holds a promise for wide clinical applications for risk analysis and patient management in cardiovascular diseases.

15O-H2O PET/CT as a tool for the quantitative assessment of early post-radiotherapy changes of heart perfusion in breast carcinoma patients.

Studies examining radiation-induced heart toxicity in breast cancer patients are inconclusive. The aim of this study was to prospectively and quantitatively asses myocardial blood flow (MBF) with, for the first time, 15O-H2O PET/CT as a marker of heart damage in irradiated breast cancer patients. 15 breast cancer patients receiving intact breast or chest wall irradiation were included in the analysis (six with right-sided and nine with left-sided breast cancer). They underwent 15O-H2O PET/CT before radiotherapy (RT) and 2 and 8 months after RT. MBF was quantitatively assessed at rest and under stress conditions in 17 heart segments distinguished according to the American Ultrasound Association classification. Regional MBF values were derived in each of the coronary artery territories. MBF decreased in 53% and increased in 33% of cases 2 months after RT in both left-sided and right-sided breast cancer patients. Stress testing was more sensitive than at-rest testing, demonstrating decreased perfusion in the segments supplied by the left anterior descending coronaryartery (LAD) [5.41 ± 1.74 vs 4.52 ± 1.82 ml (g*min)-1; p = 0.018], which persisted at 6 months [5.41 ± 1.74 vs 4.40 ± 1.38 ml(g*min)-1; p = 0.032] and a decrease in global heart perfusion [5.14 ± 1.49 vs 4.46 ± 1.73 ml(g*min)-1; p = 0.036]. A minimal radiation dose applied to the LAD correlated with MBF changes observed 2 months after RT (r = -0.57; p = 0.032). Radiological findings were not correlated with clinical symptoms of heart toxicity. 15O-H2O PET/CT is safe and effective for the early detection and quantitative analysis of subclinical post-RT changes in heart perfusion in breast cancer patients. The LV segments supplied by the LAD are the main site of MBF changes. A minimum radiation dose deposited in the LAD may be a predictor of radiation-induced heart toxicity. Advances in knowledge: This is the first time that 15O-H2O PET/CT has been used to assess MBF after RT and the first granular description of the distribution of blood flow changes after breast cancer RT.

Myocardial blood flow and myocardial flow reserve values in 13N\u2013ammonia myocardial perfusion PET/CT using a time-efficient protocol in patients without coronary artery disease

BackgroundCardiac imaging by means of myocardial Positron Emission Tomography/Computed Tomography (PET/CT) is being used increasingly to assess coronary artery disease, to guide revascularization decisions with more accuracy, and it allows robust quantitative analysis of both regional myocardial blood flow (MBF) and myocardial flow reserve (MFR).Recently, a more time-efficient protocol has been developed in combination with a residual activity correction algorithm in which a stress acquisition is performed directly after completion of the rest acquisition to subtract remaining myocardial radioactivity.The objective of this study is to define flow values of myocardial blood flow (MBF) and Myocardial Flow Reserve (MFR) with 13N–ammonia (13NH3) myocardial perfusion PET/CT on patients without coronary artery disease using a time-efficient protocol, since reference values for this particular type of study are lacking in literature. In addition, we aim to determine the effect of the residual activity correction algorithm in this time-efficient protocol.ResultsA mean MBF in rest of 1.02 ± 0.22 ml/g/min, a mean MBF in stress of 2.54 ± 0.41 ml/g/min with a mean MFR of 2.60 ± 0.61 were measured. Female patients had a significant higher MBF in rest and stress, but lower MFR; a small but significant negative correlation was measured between age and MBF in stress and MFR. Residual activity correction had a significant effect resulting in a difference in global stress MBF before and after correction of 0.39 ± 0.13 ml/g/min.ConclusionsThis study established flow values for 13NH3 myocardial PET/CT with a time-efficient protocol, and established that MBF in stress corrected for residual activity is comparable with known reference values in normal studies without temporal overlap. Further validation of the technique could be of value, e.g. by comparison to standard imaging without temporal overlap, or validation against catheterization results.

Reflection of Cardioprotection by Remote Ischemic Perconditioning in Attenuated ST-Segment Elevation During Ongoing Coronary Occlusion in Pigs: Evidence for Cardioprotection From Ischemic Injury.

Reduction of infarct size by remote ischemic perconditioning (perRIC) is evident only after several hours reperfusion. To develop a potential real-time estimate of cardioprotection by perRIC, we have analyzed the time course of ST-segment elevation. Anesthetized open-chest pigs were subjected to 60-minute coronary occlusion and 180-minute reperfusion (placebo; n=19). PerRIC (n=18; 4×5 min/5 min hindlimb occlusion/reperfusion) was induced 20 minutes after coronary occlusion. Regional myocardial blood flow was measured with microspheres, areas of no-reflow with thioflavin-S, area at risk with blue dye, and infarct size with triphenyl tetrazolium chloride staining. Phosphorylation of protein kinase B α/β/γ, extracellular signal-regulated kinase 1/2, and signal transducer and activator of transcription 3 was determined by Western blot. ST-segment elevation was analyzed in a V2-like ECG-lead at baseline, 5- and 55-minute coronary occlusion, and 10-, 30-, 60-, and 120-minute reperfusion. Transmural blood flow at 5-minute coronary occlusion was not different between perRIC (0.029±0.015 mL/min per gram; mean±SD) and placebo (0.024±0.018 mL/min per gram) as was area at risk (perRIC: 24±6% of the left ventricle; placebo: 21±4%). Areas of no-reflow tended to be smaller with perRIC (9±12% of area at risk versus 15±14% with placebo; P=0.13). Infarct size with perRIC was 23±12% of area at risk versus 40±11% with placebo (P<0.001). PerRIC increased phosphorylation of signal transducer and activator of transcription 3 at 120-minute reperfusion by 196±142% versus 109±120% with placebo (P=0.047). The time courses of ST-segment elevation in perRIC and placebo protocols, respectively, were different (P=0.017). With similar ST-segment elevation at 5-minute coronary occlusion (perRIC 282±34 µV; placebo 259±28 µV), partial recovery of ST-segment elevation between 5- and 55-minute coronary occlusion was more pronounced with perRIC than placebo (by 111±84 versus 15±94 µV; P=0.028). Infarct size reduction by perRIC is reflected in the ST-segment elevation during coronary occlusion in pigs, supporting the notion of protection from ischemic injury.

Stress Myocardial Blood Flow Heterogeneity Is a Positron Emission Tomography Biomarker of Ventricular Arrhythmias in Patients With Hypertrophic Cardiomyopathy

Patients with hypertrophic cardiomyopathy (HC) are at increased risk of sudden cardiac death. Abnormalities in myocardial blood flow (MBF) detected by positron emission tomography (PET) are common in HC, but a PET marker that identifies patients at risk of sudden cardiac death is lacking. We hypothesized that disparities in regional myocardial perfusion detected by PET would identify patients with HC at risk of ventricular arrhythmias. To test this hypothesis, we quantified global and regional MBFs by 13NH3-PET at rest and at stress, and developed a heterogeneity index to assess MBF heterogeneity in 133 symptomatic patients with HC. The MBF heterogeneity index was computed by dividing the highest by the lowest regional MBF value, at rest and after vasodilator stress, in each patient. High stress MBF heterogeneity was defined as an index of ≧1.85. Patients with HC were stratified by the presence or the absence of ventricular arrhythmias, defined as sustained ventricular tachycardia (VT) and/or nonsustained VT, during follow-up. We found that global and regional MBFs at rest and stress were similar in patients with HC with or without ventricular arrhythmias. Variability in regional stress MBF was observed in both groups, but the stress MBF heterogeneity index was significantly higher in patients with HC who developed ventricular arrhythmias (1.82 ± 0.77 vs 1.49 ± 0.25, p <0.001). A stress MBF heterogeneity index of ≧1.85 was an independent predictor of both sustained VT (hazard ratio 16.1, 95% confidence interval 3.2 to 80.3) and all-VT (sustained-VT + nonsustained VT: hazard ratio 3.7, 95% confidence interval 1.4 to 9.7). High heterogeneity of stress MBF, reflected by an MBF heterogeneity index of ≥1.85, is a PET biomarker for ventricular arrhythmias in symptomatic patients with HC.

Non-contrast assessment of microvascular integrity using arterial spin labeled cardiovascular magnetic resonance in a porcine model of acute myocardial infarction

BackgroundFollowing acute myocardial infarction (AMI), microvascular integrity and function may be compromised as a result of microvascular obstruction (MVO) and vasodilator dysfunction. It has been observed that both infarcted and remote myocardial territories may exhibit impaired myocardial blood flow (MBF) patterns associated with an abnormal vasodilator response. Arterial spin labeled (ASL) CMR is a novel non-contrast technique that can quantitatively measure MBF. This study investigates the feasibility of ASL-CMR to assess MVO and vasodilator response in swine.MethodsThirty-one swine were included in this study. Resting ASL-CMR was performed on 24 healthy swine (baseline group). A subset of 13 swine from the baseline group underwent stress ASL-CMR to assess vasodilator response. Fifteen swine were subjected to a 90-min left anterior descending (LAD) coronary artery occlusion followed by reperfusion. Resting ASL-CMR was performed post-AMI at 1–2 days (N = 9, of which 6 were from the baseline group), 1–2 weeks (N = 8, of which 4 were from the day 1–2 group), and 4 weeks (N = 4, of which 2 were from the week 1–2 group). Resting first-pass CMR and late gadolinium enhancement (LGE) were performed post-AMI for reference.ResultsAt rest, regional MBF and physiological noise measured from ASL-CMR were 1.08 ± 0.62 and 0.15 ± 0.10 ml/g/min, respectively. Regional MBF increased to 1.47 ± 0.62 ml/g/min with dipyridamole vasodilation (P < 0.001). Significant reduction in MBF was found in the infarcted region 1–2 days, 1–2 weeks, and 4 weeks post-AMI compared to baseline (P < 0.03). This was consistent with perfusion deficit seen on first-pass CMR and with MVO seen on LGE. There were no significant differences between measured MBF in the remote regions pre and post-AMI (P > 0.60).ConclusionsASL-CMR can assess vasodilator response in healthy swine and detect significant reduction in regional MBF at rest following AMI. ASL-CMR is an alternative to gadolinium-based techniques for assessment of MVO and microvascular integrity within infarcted, as well as salvageable and remote myocardium. This has the potential to provide early indications of adverse remodeling processes post-ischemia.

An Open Benchmark Challenge for Motion Correction of Myocardial Perfusion MRI.

Cardiac magnetic resonance perfusion examinations enable noninvasive quantification of myocardial blood flow. However, motion between frames due to breathing must be corrected for quantitative analysis. Although several methods have been proposed, there is a lack of widely available benchmarks to compare different algorithms. We sought to compare many algorithms from several groups in an open benchmark challenge. Nine clinical studies from two different centers comprising normal and diseased myocardium at both rest and stress were made available for this study. The primary validation measure was regional myocardial blood flow based on the transfer coefficient (Ktrans), which was computed using a compartment model and the myocardial perfusion reserve (MPR) index. The ground truth was calculated using contours drawn manually on all frames by a single observer, and visually inspected by a second observer. Six groups participated and 19 different motion correction algorithms were compared. Each method used one of three different motion models: rigid, global affine, or local deformation. The similarity metric also varied with methods employing either sum-of-squared differences, mutual information, or cross correlation. There were no significant differences in Ktrans or MPR compared across different motion models or similarity metrics. Compared with the ground truth, only Ktrans for the sum-of-squared differences metric, and for local deformation motion models, had significant bias. In conclusion, the open benchmark enabled evaluation of clinical perfusion indices over a wide range of methods. In particular, there was no benefit of nonrigid registration techniques over the other methods evaluated in this study. The benchmark data and results are available from the Cardiac Atlas Project ( www.cardiacatlas.org).

Noninvasive PET quantitative myocardial blood flow with regadenoson for assessing cardiac allograft vasculopathy in orthotopic heart transplantation patients

BackgroundRisk stratification and early detection of cardiac allograft vasculopathy (CAV) is essential in orthotopic heart transplantation (OHT) patients. This study assesses the changes in myocardial blood flow (MBF) noninvasively in OHT patients using quantitative cardiac PET with regadenoson. MethodsTwelve patients (Group 1) (8 males, 4 females, mean age 55 ± 7 years) with no history of post OHT myocardial ischemia were enrolled 5.4 ± 2.0 years after OHT. Fifteen patients (Group 2) (9 males, 6 females, mean age 71 ± 9 years) with intermediate pretest probability but not documented evidence for coronary artery disease (CAD) were also included to serve as control. Global and regional MBFs were assessed using dynamic 13N-NH3 PET at rest and during regadenoson-induced hyperemia. The coronary flow reserve (CFR) was also calculated as the ratio of hyperemic to resting MBF. ResultsMean regadenoson-induced rate-pressure products were similar in both groups, while there was an increase in resting rate-pressure product in Group 1 patients. Both mean and median values of resting MBF were higher in Group 1 than Group 2 patients (1.33 ± 0.31 and 1.01 ± 0.21 mL/min/g for Groups 1 and 2, respectively, P < .001), while mean hyperemic MBF values were similar in both Groups (2.68 ± 0.84 and 2.64 ± 0.94 mL/min/g, P = NS) but median hyperemic MBF values were lower in Group 1 than Group 2 patients (2.0 vs. 2.60 mL/min/g, P = .018). Both mean and median CFR values demonstrated a significant reduction for Group 1 compared to Group 2 patients (2.07 ± 0.74 vs 2.63 ± 0.48, P = .025). ConclusionsThis study suggests that the MBF in OHT patients may be abnormal at resting state with diminished CFR. This hints that the epicardial and microvascular coronary subsystem may be exacerbated after OHT leading to the gradual progression of CAV.

Rapid computation of single PET scan rest-stress myocardial blood flow parametric images by table look up.

We have recently reported a method for measuring rest-stress myocardial blood flow (MBF) using a single, relatively short, PET scan session. The method requires two IV tracer injections, one to initiate rest imaging and one at peak stress. We previously validated absolute flow quantitation in ml/min/cc for standard bull's eye, segmental analysis. In this work, we extend the method for fast computation of rest-stress MBF parametric images. We provide an analytic solution to the single-scan rest-stress flow model which is then solved using a two-dimensional table lookup method (LM). Simulations were performed to compare the accuracy and precision of the lookup method with the original nonlinear method (NLM). Then the method was applied to 16 single scan rest/stress measurements made in 12 pigs: seven studied after infarction of the left anterior descending artery (LAD) territory, and nine imaged in the native state. Parametric maps of rest and stress MBF as well as maps of left (fLV ) and right (fRV ) ventricular spill-over fractions were generated. Regions of interest (ROIs) for 17 myocardial segments were defined in bull's eye fashion on the parametric maps. The mean of each ROI was then compared to the rest (K1r ) and stress (K1s ) MBF estimates obtained from fitting the 17 regional TACs with the NLM. In simulation, the LM performed as well as the NLM in terms of precision and accuracy. The simulation did not show that bias was introduced by the use of a predefined two-dimensional lookup table. In experimental data, parametric maps demonstrated good statistical quality and the LM was computationally much more efficient than the original NLM. Very good agreement was obtained between the mean MBF calculated on the parametric maps for each of the 17 ROIs and the regional MBF values estimated by the NLM (K1mapLM =1.019×K1ROINLM +0.019, R2 =0.986; mean difference=0.034±0.036mL/min/cc). We developed a table lookup method for fast computation of parametric imaging of rest and stress MBF. Our results show the feasibility of obtaining good quality MBF maps using modest computational resources, thus demonstrating that the method can be applied in a clinical environment to obtain full quantitative MBF information.

Positron Emission Tomography-Determined Hyperemic Flow, Myocardial Flow Reserve, and Flow Gradient-Quo Vadis?

Positron emission tomography/computed tomography (PET/CT) applied with positron-emitting flow tracers such as 13N-ammonia and 82Rubidium enables the quantification of both myocardial perfusion and myocardial blood flow (MBF) in milliliters per gram per minute for coronary artery disease (CAD) detection and characterization. The detection of a regional myocardial perfusion defect during vasomotor stress commonly identifies the culprit lesion or most severe epicardial narrowing, whereas adding regional hyperemic MBFs, myocardial flow reserve (MFR), and/or longitudinal flow decrease may also signify less severe but flow-limiting stenosis in multivessel CAD. The addition of regional hyperemic flow parameters, therefore, may afford a comprehensive identification and characterization of flow-limiting effects of multivessel CAD. The non-specific origin of decreases in hyperemic MBFs and MFR, however, prompts an evaluation and interpretation of regional flow in the appropriate context with the presence of obstructive CAD. Conversely, initial results of the assessment of a longitudinal hyperemic flow gradient suggest this novel flow parameter to be specifically related to increases in CAD caused epicardial resistance. The concurrent assessment of myocardial perfusion and several hyperemic flow parameters with PET/CT may indeed open novel avenues of precision medicine to guide coronary revascularization procedures that may potentially lead to a further improvement in cardiovascular outcomes in CAD patients.

The effect of coronary revascularization on regional myocardial blood flow as assessed by stress positron emission tomography

ObjectivesWe examined whether regional improvement in stress myocardial blood flow (sMBF) following angiography-guided coronary revascularization depends on the existence of a perfusion defect on positron emission tomography (PET). BackgroundPercent stenosis on coronary angiography often is the main factor when deciding whether to perform revascularization, but it does not reliably relate to maximum sMBF. PET is a validated method of assessing sMBF. Methods19 patients (79% M, 65 ± 12 years) underwent PET stress before and after revascularization (17 PCI, 2 CABG). Pre- and post-revascularization sMBF for each left ventricular quadrant (anterior, septal, lateral, and inferior) was stratified by the presence or absence of a baseline perfusion defect on PET and whether that region was revascularized. ResultsIntervention was performed on 40 of 76 quadrants. When a baseline perfusion defect existed in a region that was revascularized (n = 26), post-revascularization flow increased by 0.6 ± 0.7 cc/min/g (1.2 ± 0.4 vs 1.7 ± 0.8, P < 0.001). When no defect existed but revascularization was performed (n = 14), sMBF did not change significantly (1.7 ± 0.3 vs 1.5 ± 0.4 cc/min/g, P = 0.16). In regions without a defect that were not revascularized (n = 29), sMBF did not significantly change (2.0 ± 0.6 vs 1.9 ± 0.7, P = 0.7). ConclusionsWhen a stress-induced perfusion defect exists on PET, revascularization improves sMBF in that region. When there is no such defect, sMBF shows no net change, whether or not intervention is performed in that area. PET stress may be useful for identifying areas of myocardium that could benefit from revascularization, and also areas in which intervention is unlikely to yield improvement in myocardial blood flow.