Quantification Of Myocardial Blood Flow Research Articles

TAI-GAN: A Temporally and Anatomically Informed Generative Adversarial Network for early-to-late frame conversion in dynamic cardiac PET inter-frame motion correction

Inter-frame motion in dynamic cardiac positron emission tomography (PET) using rubidium-82 (82Rb) myocardial perfusion imaging impacts myocardial blood flow (MBF) quantification and the diagnosis accuracy of coronary artery diseases. However, the high cross-frame distribution variation due to rapid tracer kinetics poses a considerable challenge for inter-frame motion correction, especially for early frames where intensity-based image registration techniques often fail. To address this issue, we propose a novel method called Temporally and Anatomically Informed Generative Adversarial Network (TAI-GAN) that utilizes an all-to-one mapping to convert early frames into those with tracer distribution similar to the last reference frame. The TAI-GAN consists of a feature-wise linear modulation layer that encodes channel-wise parameters generated from temporal information and rough cardiac segmentation masks with local shifts that serve as anatomical information. Our proposed method was evaluated on a clinical 82Rb PET dataset, and the results show that our TAI-GAN can produce converted early frames with high image quality, comparable to the real reference frames. After TAI-GAN conversion, the motion estimation accuracy and subsequent myocardial blood flow (MBF) quantification with both conventional and deep learning-based motion correction methods were improved compared to using the original frames. The code is available at https://github.com/gxq1998/TAI-GAN.

Arterial Input Function (AIF) Correction Using AIF Plus Tissue Inputs with a Bi-LSTM Network.

Background: The arterial input function (AIF) is vital for myocardial blood flow quantification in cardiac MRI to indicate the input time-concentration curve of a contrast agent. Inaccurate AIFs can significantly affect perfusion quantification. Purpose: When only saturated and biased AIFs are measured, this work investigates multiple ways of leveraging tissue curve information, including using AIF + tissue curves as inputs and optimizing the loss function for deep neural network training. Methods: Simulated data were generated using a 12-parameter AIF mathematical model for the AIF. Tissue curves were created from true AIFs combined with compartment-model parameters from a random distribution. Using Bloch simulations, a dictionary was constructed for a saturation-recovery 3D radial stack-of-stars sequence, accounting for deviations such as flip angle, T2* effects, and residual longitudinal magnetization after the saturation. A preliminary simulation study established the optimal tissue curve number using a bidirectional long short-term memory (Bi-LSTM) network with just AIF loss. Further optimization of the loss function involves comparing just AIF loss, AIF with compartment-model-based parameter loss, and AIF with compartment-model tissue loss. The optimized network was examined with both simulation and hybrid data, which included in vivo 3D stack-of-star datasets for testing. The AIF peak value accuracy and ktrans results were assessed. Results: Increasing the number of tissue curves can be beneficial when added tissue curves can provide extra information. Using just the AIF loss outperforms the other two proposed losses, including adding either a compartment-model-based tissue loss or a compartment-model parameter loss to the AIF loss. With the simulated data, the Bi-LSTM network reduced the AIF peak error from -23.6 ± 24.4% of the AIF using the dictionary method to 0.2 ± 7.2% (AIF input only) and 0.3 ± 2.5% (AIF + ten tissue curve inputs) of the network AIF. The corresponding ktrans error was reduced from -13.5 ± 8.8% to -0.6 ± 6.6% and 0.3 ± 2.1%. With the hybrid data (simulated data for training; in vivo data for testing), the AIF peak error was 15.0 ± 5.3% and the corresponding ktrans error was 20.7 ± 11.6% for the AIF using the dictionary method. The hybrid data revealed that using the AIF + tissue inputs reduced errors, with peak error (1.3 ± 11.1%) and ktrans error (-2.4 ± 6.7%). Conclusions: Integrating tissue curves with AIF curves into network inputs improves the precision of AI-driven AIF corrections. This result was seen both with simulated data and with applying the network trained only on simulated data to a limited in vivo test dataset.

CME INSTRUCTIONS: Feasibility of myocardial blood flow quantification to detect flow-limited coronary artery disease with a one-day rest/stress continuous rapid imaging protocol on cardiac-dedicated CZT single photon emission computed tomography

CME INSTRUCTIONS: Feasibility of myocardial blood flow quantification to detect flow-limited coronary artery disease with a one-day rest/stress continuous rapid imaging protocol on cardiac-dedicated CZT single photon emission computed tomography

Myocardial blood flow quantification with SPECT

IntroductionThe addition of absolute myocardial blood flow (MBF) data improves the diagnostic and prognostic accuracy of relative perfusion imaging with nuclear medicine. Cardiac-specific gamma cameras allow measurement of MBF with SPECT. MethodsThis paper reviews the evidence supporting the use of SPECT to measure myocardial blood flow (MBF). Studies have evaluated SPECT MBF in large animal models and compared it in humans with invasive angiographic measurements and against the clinical standard of PET MBF. The repeatability of SPECT MBF has been determined in both single-site and multi-center trials. ResultsSPECT MBF has excellent correlation with microspheres in an animal model, with the number of stenoses and fractional flow reserve, and with PET-derived MBF. The inter-user coefficient of variability is ∼20% while the COV of test-retest MBF is ∼30%. SPECT MBF improves the sensitivity and specificity of the detection of multi-vessel disease over relative perfusion imaging and provides incremental value in predicting adverse cardiac events. ConclusionSPECT MBF is a promising technique for providing clinically valuable information in the assessment of coronary artery disease.

Feasibility of myocardial blood flow quantification to detect flow-limited coronary artery disease with a one-day rest/stress continuous rapid imaging protocol on cardiac-dedicated cadmium zinc telluride single photon emission computed tomography

BackgroundIt is clinically needed to explore a more efficient imaging protocol for single photon emission computed tomography (SPECT) myocardial blood flow (MBF) quantitation derived from cadmium zinc telluride (CZT) SPECT camera for the routine clinical utilization. MethodsOne hundred and twenty patients with matched clinical characteristics and angiographic findings who completed one-day rest/stress SPECT imaging with either the intermittently sequential imaging (ISI) protocol (two dynamic and two electrocardiography (ECG)-gated scans) or the continuous rapid imaging (CRI) protocol (two dynamic/ECG-gated scans) were included. MBF quantitation adopted residual activity correction (RAC) to correct for rest residual activity (RRA) in the stress dynamic SPECT scan for the detection of flow-limited coronary artery disease. ResultsThe CRI protocol reduced about 6.2 times shorter than the ISI protocol (25.5 min vs 157.6 min), but slightly higher than the RRA (26.7% ± 3.6% vs 22.3% ± 4.9%). With RAC, both protocols demonstrated close stress MBF (2.18 ± 1.13 vs 2.05 ± 1.10, P > 0.05) and myocardial flow reserve (MFR) (2.42 ± 1.05 vs 2.48 ± 1.11, P > 0.05) to deliver comparable diagnostic performance (sensitivity = 82.1%–92.3%, specificity = 81.2%–91.2%). Myocardial perfusion and left ventricular function overall showed no significant difference (all P > 0.26). ConclusionOne-day rest/stress SPECT with the CRI protocol and rest RAC is feasible to warrant the diagnostic performance of MBF quantitation with a shortened examination time and enhanced patient comfort. Further evaluation on the impact of extracardiac activity to regional MBF and perfusion pattern is required. Additional evaluation is needed in a patient population that is typical of those referred for SPECT MPI, including those with known or suspected coronary microvascular disease.

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

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

Comparison of Myocardial Blood Flow Quantification Models for Double ECG Gating Arterial Spin Labeling MRI: Reproducibility Assessment.

Arterial spin labeling (ASL) allows non-invasive quantification of myocardial blood flow (MBF). Double-ECG gating (DG) ASL is more robust to heart rate variability than single-ECG gating (SG), but its reproducibility requires further investigation. Moreover, the existence of multiple quantification models hinders its application. Frequency-offset-corrected-inversion (FOCI) pulses provide sharper edge profiles than hyperbolic-secant (HS), which could benefit myocardial ASL. To assess the performance of MBF quantification models for DG compared to SG ASL, to evaluate their reproducibility and to compare the effects of HS and FOCI pulses. Prospective. Sixteen subjects (27 ± 8 years). 1.5 T/DG and SG flow-sensitive alternating inversion recovery ASL. Three models for DG MBF quantification were compared using Monte Carlo simulations and in vivo experiments. Two models used a fitting approach (one using only a single label and control image pair per fit, the other using all available image pairs), while the third model used a T1 correction approach. Slice profile simulations were conducted for HS and FOCI pulses with varying B0 and B1. Temporal signal-to-noise ratio (tSNR) was computed for different acquisition/quantification strategies and inversion pulses. The number of images that minimized MBF error was investigated in the model with highest tSNR. Intra and intersession reproducibility were assessed in 10 subjects. Within-subject coefficient of variation, analysis of variance. P-value <0.05 was considered significant. MBF was not different across acquisition/quantification strategies (P = 0.27) nor pulses (P = 0.9). DG MBF quantification models exhibited significantly higher tSNR and superior reproducibility, particularly for the fitting model using multiple images (tSNR was 3.46 ± 2.18 in vivo and 3.32 ± 1.16 in simulations, respectively; wsCV = 16%). Reducing the number of ASL pairs to 13/15 did not increase MBF error (minimum = 0.22 mL/g/min). Reproducibility of MBF was better for DG than SG acquisitions, especially when employing a fitting model. 2 TECHNICAL EFFICACY: Stage 1.

Rationale and design of the RAPID-WATER-FLOW trial: Radiolabeled perfusion to identify coronary artery disease using water to evaluate responses of myocardial FLOW

ObjectivesThe objective of this study was to determine the diagnostic performance of 15O-water positron emission tomography (PET) myocardial perfusion imaging to detect coronary artery disease (CAD) using the truth-standard of invasive coronary angiography (ICA) with fractional flow reserve (FFR) or instantaneous wave-Free Ratio (iFR) or coronary computed tomography angiogram (CCTA). Background15O-water has a very high first-pass extraction that allows accurate quantification of myocardial blood flow and detection of flow-limiting CAD. However, the need for an on-site cyclotron and lack of automated production at the point of care and relatively complex image analysis protocol has limited its clinical use to date. MethodsThe RAPID WATER FLOW study is an open-label, multicenter, prospective investigation of the accuracy of 15O-water PET to detect obstructive angiographic and physiologically significant stenosis in patients with suspected CAD. The study will include the use of an automated system for producing, dosing, and injecting 15O-water and enrolling approximately 215 individuals with suspected CAD at approximately 10 study sites in North America and Europe. The primary endpoint of the study is the diagnostic sensitivity and specificity of the 15O-water PET study using the truth-standard of ICA with FFR or iFR to determine flow-limiting stenosis, or CCTA to rule out CAD and incorporating a quantitative analytic platform developed for the 15O-water PET acquisitions. Sensitivity and specificity are to be considered positive if the lower bound of the 95% confidence interval is superior to the threshold of 60% for both, consistent with prior registration studies.Subgroup analyses include assessments of diagnostic sensitivity, specificity, and accuracy in female, obese, and diabetic individuals, as well as in those with multivessel disease. All enrolled individuals will be followed for adverse and serious adverse events for up to 32 hours after the index PET scan.The study will have >90% power (one-sided test, α = 0.025) to test the hypothesis that sensitivity and specificity of 15O-water PET are both >60%. ConclusionsThe RAPID WATER FLOW study is a prospective, multicenter study to determine the diagnostic sensitivity and specificity of 15O-water PET as compared to ICA with FFR/iFR or CCTA. This study will introduce several novel aspects to imaging registration studies, including a more relevant truth standard incorporating invasive physiologic indexes, coronary CTA to qualify normal individuals for eligibility, and a more quantitative approach to image analysis than has been done in prior pivotal studies. Clinical trial registration informationClinical-Trials.gov (#NCT05134012).

Influence of different time framings, reconstruction algorithms and post-processing methods on the quantification of myocardial blood flow from 13 N-NH3 PET images.

The aim was to investigate to what extent the quantification of myocardial blood flow (MBF) from dynamic 13 N-NH3 positron emission tomography(PET) images is affected by time frame schemes, time-of-flight (ToF), reconstruction algorithms, blood pool volume of interest (VOI) locations and compartment models in patients with suspected chronic coronary syndrome. A standard MBF value was determined from 25 patients' rest/stress 13 N-NH3 PET/CT images reconstructed with ordered subset expectation maximization (OSEM), 5 s time frame for the first frames without ToF, subsequently analyzed using a basal VOI and the deGrado compartment model. MBFs calculated using 2or 10 s for the first frames, ToF, block-sequential regularized expectation maximization (BSREM), apical or large VOI, Hutchins or Krivokapich compartment models were compared to MBFstandard in Bland-Altman plots (bias ± SD). Good agreement in global rest/stress MBF (mL/min/g) was found when changing the time frame scheme or reconstruction algorithm (MBFstandard vs. MBF2s : -0.02 ± 0.06; MBF10s : 0.01 ± 0.07; MBFBSREM : 0.01 ± 0.07), while a lower level of agreement was found when altering the other factors (MBFstandard vs.MBFToF : -0.07 ± 0.10; MBFapical VOI : -0.27 ± 0.25; MBFlarge VOI : -0.11 ± 0.10; MBFHutchins : -0.08 ± 0.10; MBFKrivokapich : -0.47 ± 0.50). Quantification of MBF from 13 N-NH3 PET images is more affected by choice of compartment models, ToF and blood pool VOIs than by different time frame schemes and reconstruction algorithms.

Cardiac PET Myocardial Blood Flow Quantification Assessment of Early Cardiac Allograft Vasculopathy

BackgroundPositron emission tomography (PET) has demonstrated utility for diagnostic and prognostic assessment of cardiac allograft vasculopathy (CAV) but has not been evaluated in the first year after transplant. ObjectivesThe authors sought to evaluate CAV at 1 year by PET myocardial blood flow (MBF) quantification. MethodsAdults at 2 institutions enrolled between January 2018 and March 2021 underwent prospective 3-month (baseline) and 12-month (follow-up) post-transplant PET, endomyocardial biopsy, and intravascular ultrasound examination. Epicardial CAV was assessed by intravascular ultrasound percent intimal volume (PIV) and microvascular CAV by endomyocardial biopsy. ResultsA total of 136 PET studies from 74 patients were analyzed. At 12 months, median PIV increased 5.6% (95% CI: 3.6%-7.1%) with no change in microvascular CAV incidence (baseline: 31% vs follow-up: 38%; P = 0.406) and persistent microvascular disease in 13% of patients. Median capillary density increased 30 capillaries/mm2 (95% CI: −6 to 79 capillaries/mm2). PET myocardial flow reserve (2.5 ± 0.7 vs 2.9 ± 0.8; P = 0.001) and stress MBF (2.7 ± 0.6 vs 2.9 ± 0.6; P = 0.008) increased, and coronary vascular resistance (CVR) (49 ± 13 vs 47 ± 11; P = 0.214) was unchanged. At 12 months, PET and PIV had modest correlation (stress MBF: r = −0.35; CVR: r = 0.33), with lower stress MBF and higher CVR across increasing PIV tertiles (all P < 0.05). Receiver-operating characteristic curves for CAV defined by upper-tertile PIV showed areas under the curve of 0.74 for stress MBF and 0.73 for CVR. ConclusionsThe 1-year post-transplant PET MBF is associated with epicardial CAV, supporting potential use for early noninvasive CAV assessment. (Early Post Transplant Cardiac Allograft Vasculopahty [ECAV]; NCT03217786)

Dynamic CZT-SPECT: Characterizing the Lower Values of Myocardial Blood Flow and Reserve.

CZT-SPECT myocardial perfusion enables quantification of myocardial blood flow (MBF). Normal values and thresholds have been accurately defined in PET but remain unclear in SPECT. The aim of this study was to report normal MBF and myocardial flow reserve values in very low-risk patients referred for coronary artery disease screening with dynamic SPECT, in comparison with patients experiencing coronary artery disease. Eighty-four patients (31 male) were analyzed. The mean 10 years risk of fatal cardiovascular events score was 2.7% ± 1.4%. The mean global stress MBF and myocardial flow reserve were 1.6 ± 0.6 mL/min/g and 2.7 ± 0.7.

Improved reproducibility for myocardial ASL: Impact of physiological and acquisition parameters.

To investigate and mitigate the influence of physiological and acquisition-related parameters on myocardial blood flow (MBF) measurements obtained with myocardial Arterial Spin Labeling (myoASL). A Flow-sensitive Alternating Inversion Recovery (FAIR) myoASL sequence with bSSFP and spoiled GRE (spGRE) readout is investigated for MBF quantification. Bloch-equation simulations and phantom experiments were performed to evaluate how variations in acquisition flip angle (FA), acquisition matrix size (AMS), heart rate (HR) and blood relaxation time ( ) affect quantification of myoASL-MBF. In vivo myoASL-images were acquired in nine healthy subjects. A corrected MBF quantification approach was proposed based on subject-specific values and, for spGRE imaging, subtracting an additional saturation-prepared baseline from the original baseline signal. Simulated and phantom experiments showed a strong dependence on AMS and FA ( >0.73), which was eliminated in simulations and alleviated in phantom experiments using the proposed saturation-baseline correction in spGRE. Only a very mild HR dependence ( >0.59) was observed which was reduced when calculating MBF with individual . For corrected spGRE, in vivo mean global spGRE-MBF ranged from 0.54 to 2.59mL/g/min and was in agreement with previously reported values. Compared to uncorrected spGRE, the intra-subject variability within a measurement (0.60mL/g/min), between measurements (0.45mL/g/min), as well as the inter-subject variability (1.29mL/g/min) were improved by up to 40% and were comparable with conventional bSSFP. Our results show that physiological and acquisition-related factors can lead to spurious changes in myoASL-MBF if not accounted for. Using individual and a saturation-baseline can reduce these variations in spGRE and improve reproducibility of FAIR-myoASL against acquisition parameters.

New Non-Invasive Imaging Technologies in Cardiac Transplant Follow-Up: Acquired Evidence and Future Options.

Heart transplantation (HT) is the established treatment for end-stage heart failure, significantly enhancing patients' survival and quality of life. To ensure optimal outcomes, the routine monitoring of HT recipients is paramount. While existing guidelines offer guidance on a blend of invasive and non-invasive imaging techniques, certain aspects such as the timing of echocardiographic assessments and the role of echocardiography or cardiac magnetic resonance (CMR) as alternatives to serial endomyocardial biopsies (EMBs) for rejection monitoring are not specifically outlined in the guidelines. Furthermore, invasive coronary angiography (ICA) is still recommended as the gold-standard procedure, usually performed one year after surgery and every two years thereafter. This review focuses on recent advancements in non-invasive and contrast-saving imaging techniques that have been investigated for HT patients. The aim of the manuscript is to identify imaging modalities that may potentially replace or reduce the need for invasive procedures such as ICA and EMB, considering their respective advantages and disadvantages. We emphasize the transformative potential of non-invasive techniques in elevating patient care. Advanced echocardiography techniques, including strain imaging and tissue Doppler imaging, offer enhanced insights into cardiac function, while CMR, through its multi-parametric mapping techniques, such as T1 and T2 mapping, allows for the non-invasive assessment of inflammation and tissue characterization. Cardiac computed tomography (CCT), particularly with its ability to evaluate coronary artery disease and assess graft vasculopathy, emerges as an integral tool in the follow-up of HT patients. Recent studies have highlighted the potential of nuclear myocardial perfusion imaging, including myocardial blood flow quantification, as a non-invasive method for diagnosing and prognosticating CAV. These advanced imaging approaches hold promise in mitigating the need for invasive procedures like ICA and EMB when evaluating the benefits and limitations of each modality.

Prognostic value of myocardial flow reserve derived by quantitative SPECT for patients with intermediate coronary stenoses

BackgroundFunctional assessment of myocardial ischemia is critical for patients with intermediate coronary stenosis. As the diagnosis performance of absolute quantification of myocardial blood flow (MBF) and myocardial flow reserve (MFR) by single-photon emission tomography (SPECT) has been proven, its prognostic value in patients with intermediate coronary stenosis remains to be evaluated. MethodsPatients with one or more target lesions of ≥ 50% to ≤ 80% diameter stenoses on invasive coronary angiography were prospectively included in this study. All patients were scheduled for clinically indicated SPECT myocardial perfusion imaging (MPI) within 3 months and agreed to provide informed consent to participate in quantitative SPECT acquisitions to obtain MBF and MFR values. The primary endpoint was defined as a composite of the major adverse cardiac events (MACE): Cardiac death, myocardial infarction, late revascularization and heart failure or unstable angina-related rehospitalization. ResultsOne hundred and nineteen patients (mean age 57 ± 8 years, 62.2% men) were included in the analysis. The average lumen stenosis of patients was 67.0 ± 10.4%. Over a median follow-up duration of 1408 days (interquartile range 1297-1666 days), 18 patients (15.1%) had MACE. Patients with impaired MFR (MFR < 2) had a significantly higher incidence of events than those with preserved MFR (MFR ≥ 2) in Kaplan-Meier survival analysis (Log-rank = 8.105, P = 0.004), while no significant difference was found between patients with normal relative perfusion and those with relative perfusion abnormalities (log-rank = 0.098, P > 0.05). In a multivariate Cox hazards analysis, the SPECT-derived MFR remained an independent predictor of MACE (HR 0.352, 95% CI 0.145-0.854, P = 0.021). ConclusionsIn a cohort of patients with angiographic intermediate coronary lesions, SPECT-derived MFR was an independent predictor of prognosis.

Left-ventricular volumes and ejection fraction from cardiac ECG-gated 15O-water positron emission tomography compared to cardiac magnetic resonance imaging using simultaneous hybrid PET/MR

Background15O-water PET is the gold standard for noninvasive quantification of myocardial blood flow. In addition to evaluation of ischemia, the assessment of cardiac function and remodeling is important in all cardiac diseases. However, since 15O-water is freely diffusible and standard uptake images show little contrast between the myocardium and blood pool, the assessment of left-ventricular (LV) volumes and ejection fraction (EF) is challenging. Therefore, the aim of the present study was to investigate the feasibility of calculating LV volumes and EF from first-pass analysis of 15O-water PET, by comparison with cardiac magnetic resonance imaging (CMR) using a hybrid PET/MR scanner. MethodsTwenty-four patients with known or suspected CAD underwent a simultaneous ECG-gated cardiac PET/MR scan. The 15O-water first-pass images (0-50 seconds) were analyzed using the CarPET software and the CMR images were analyzed using the software Segment, for LV volumes and EF calculations. The LV volumes and EF were compared using correlation and Bland–Altman analysis. In addition, inter- and intra-observer variability of LV volumes and EF were assessed for both modalities. ResultsThe correlation between PET and CMR was strong for volumes (r > 0.84) and moderate for EF (r = 0.52), where the moderate correlation for EF was partly due to the small range of EF values. Agreement was high for all parameters, with a slight overestimation of PET values for end-diastolic volume but with no significant mean bias for other parameters. Inter- and intra-observer agreement of volumes was high and comparable between PET and CMR. For EF, inter-observer agreement was higher for PET and intra-observer agreement was higher for CMR. ConclusionLV volumes and EF can be calculated by first-pass analysis of a 15O-water PET scan with high accuracy and comparable precision as with CMR.

Quantification of myocardial blood flow using stress cardiac magnetic resonance for the detection of coronary artery disease

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): GE Healthcare. Background Myocardial blood flow (MBF) analysis using stress cardiac magnetic resonance (CMR) has been shown to detect obstructive coronary artery disease (CAD); however, evaluation of its diagnostic performance has primarily been limited to single-center studies. AQUA-MBF (Assessment of QUAntitative MBF using stress CMR) is an international study with the goal of assessing the diagnostic performance of stress MBF for the detection of CAD. In this study, we aim to determine how stress MBF assessment compared against visual analysis (VA) of stress CMR images for the detection of CAD. Methods. 144 individuals (89 (62%) men, age 62±16 years, 97 (68%) hypertension, 54 (38%) diabetes, 92 (64%) hyperlipidemia) from 9 centers who underwent dual sequence stress CMR (1.5T or 3.0T GE Healthcare) and also had either a coronary computed tomography angiography (CTA, n=31), invasive coronary angiogram (ICA, n=95), or low pre-test probability for CAD (n=18) were included. CAD was defined as the presence of: (1) a stenosis ≥50% in the left main coronary artery or ≥70% in the 1 major vessel based on ICA or CTA or (2) an invasive fractional flow reserve (FFR) ≤ 0.8. Absence of obstructive coronary disease (NOCAD) was defined as a no history of myocardial infarction and stenosis &amp;lt;50% by ICA or CTA, 50–70% stenosis with FFR&amp;gt;0.8, or a young individual with no cardiac risk factors. Myocardial perfusion imaging was performed during first pass perfusion of a gadolinium-based contrast agent following the administration of adenosine or regadenoson with a low-resolution image acquired to assess the arterial input function and 2–3 short axis slices acquired to assess myocardial perfusion. VA was performed by 2 experienced cardiologists who assigned a grade of 1–5 based on the probability a study was abnormal. Stress MBF values were determined for each of the 16 myocardial segments using Fermi deconvolution (CircleCVI). The global stress MBF was calculated as the average value of two segments with the lowest values from each of the three coronary artery territories. Unpaired t-test was used to compare stress MBF values between CAD vs NOCAD. Receiver-operating characteristics curves were used to determine diagnostic performance. Results. 60 patients had CAD (20: 1-vessel, 26: 2-vessel, and 14: 3-vessel) (Figure 1A) while 84 had NOCAD (Figure 1B). The global stress MBF in CAD was lower than in NOCAD (1.63±0.52ml/g/min vs 2.41±0.68ml/g/min, p&amp;lt;0.0001) (Figure 2A). Stress MBF had a higher AUC than VA (reader 1 – 0.83 vs 0.73, p = 0.07: reader 2–0.83 vs 0.71, p = 0.02). The optimal stress MBF cut-off value for detecting CAD was 2.05ml/g/min (Figure 2B). Conclusions. In this multicenter study, we show that global stress MBF reported as a single value can identify patients with CAD at least as accurately as VA performed by physicians experienced in the interpretation of stress CMR images.

Myocardial Flow Assessment After Heart Transplantation Using Dynamic Cadmium-Zinc-Telluride Single-Photon Emission Computed Tomography With 201Tl and 99mTc Tracers and Validated by 13N-NH3 Positron Emission Tomography.

Cardiac allograft vasculopathy (CAV) is an obliterative and diffuse form of vasculopathy and is the most common cause of long-term cardiovascular mortality in heart transplant patients. This study aimed to investigate the diagnostic performance of 99mTc and 201Tl tracers in the assessment of CAV using cadmium-zinc-telluride (CZT) single-photon emission computed tomography (SPECT) for myocardial blood flow (MBF) and myocardial flow reserve (MFR) quantification, which was further validated using 13 N-NH3 positron emission tomography (PET). Thirty-eight patients with prior heart transplantation who underwent CZT SPECT and 13 N-NH3 PET dynamic scans were included in this study. CZT SPECT with 99mTc-sestamibi was used in the first 19 patients and 201Tl-chloride for the remaining patients. To determine the diagnostic accuracy of angiographically defined moderate-to-severe CAV, the analysis included patients who underwent angiographic examinations within 1 year of their second scan. There were no significant differences in the patient characteristics between the 201Tl and 99mTc tracer groups. Both 201Tl and 99mTc CZT SPECT-derived stress MBF and MFR values globally and in 3 coronary territories showed good correlations with 13 N-NH3 PET. The 201Tl and 99mTc cohorts did not differ significantly in the correlation coefficients of CZT SPECT versus PET for MBF and MFR, except for stress MBF (201Tl:0.95 versus 99mTc:0.80, P=0.03). 201Tl and 99mTc CZT SPECT were satisfactory for detecting PET MFR <2.0 (201Tl area under the curve, 0.92 [0.71-0.99], 99mTc area under the curve, 0.87 [0.64-0.97]) and angiographically defined moderate-to-severe CAV, and CZT SPECT results were comparable to that of 13 N-NH3 PET (CZT area under the curve, 0.90 [0.70-0.99], PET area under the curve, 0.86 [0.64-0.97]). This small study suggests that CZT SPECT using 201Tl and 99mTc tracers showed comparable MBF and MFR, and the results correlated well with those of 13 N-NH3 PET. Hence, CZT SPECT with 201Tl or 99mTc tracers can be used to detect moderate-to-severe CAV in patients with prior heart transplantation. However, validation using larger studies is warranted.

Automated dynamic motion correction improves repeatability and reproducibility of myocardial blood flow quantification with rubidium-82 PET imaging

BackgroundPatient motion reduces the accuracy of PET myocardial blood flow (MBF) measurements. This study evaluated the effect of automatic motion correction on test-retest repeatability and inter-observer variability in a clinically relevant population. MethodsPatients with known or suspected CAD underwent repeat rest 82Rb PET scans within minutes as part of their scheduled rest-stress perfusion study. Two trained observers evaluated the presence of heart motion in each scan. Global LV and per-vessel MBF were computed from the dynamic rest images before and after automatic motion correction. Test-retest and inter-observer variability were assessed using intra-class correlation and Bland-Altman analysis. Results140 pairs of test-retest scans were included, with visual motion noted in 18%. Motion correction decreased the global MBF values by 3.5% (0.80 ± 0.24 vs 0.82 ± 0.25 mL⋅min−1⋅g−1; P < 0.001) suggesting that the blood input function was underestimated in cases with patient motion. Test-retest repeatability of global MBF improved by 9.7% (0.25 vs 0.28 mL⋅min−1⋅g−1; P < 0.001) and inter-observer repeatability was improved by 7.1% (0.073 vs 0.079 mL⋅min−1⋅g−1; P = 0.012). There was a marked impact on both test-retest repeatability as well as inter-observer repeatability in the LCX territory, with improvements of 16.5% (0.30 vs 0.36 mL⋅min−1⋅g−1; P < 0.0000) and 18.4% (0.13 vs 0.16 mL⋅min−1⋅g−1; P < 0.001), respectively. ConclusionAutomatic motion correction improved test-retest repeatability and reduced differences between observers.

Radionuclide Tracers for Myocardial Perfusion Imaging and Blood Flow Quantification

Myocardial perfusion imaging by nuclear cardiology is widely validated for the diagnosis, risk stratification, and management of patients with suspected or known coronary artery disease. Numerous radiopharmaceuticals are available for single-photon emission computed tomography and PET modalities. Each tracer shows advantages and limitations that should be taken into account in performing an imaging examination. This review aimed to summarize the state-of-the-art radiotracers used for myocardial perfusion imaging and blood flow quantification, highlighting the new technologic advances and promising possible applications.

Estimation of Microvascular Dysfunction by Using 13N-Ammonia Positron Emission Tomography with Quantitative Myocardial Blood Flow Analysis in Chronic Coronary Syndrome.

Although coronary artery disease (CAD) is characterized by epicardial atherosclerosis and microvascular disease, the importance of evaluating microvascular dysfunction has not been sufficiently recognized in clinical practice. We estimated microvascular disease severity by assessing hyperemic microvascular resistance (MVR), as determined by absolute quantification of myocardial blood flow (MBF) with 13N-ammonia positron emission tomography-myocardial perfusion imaging (PET-MPI). We retrospectively collected data for 23 CAD patients who underwent both stress/rest PET-MPI and invasive coronary angiography (CAG) with fractional flow reserve (FFR) measurement. Among 30 vessels for which FFR measurement was performed, 13 had a low FFR (FFR ≤0.75). For each patient, myocardial segments of a standard 17-segment model were assigned to the stenotic myocardial area perfused by the FFR-measured vessel and a reference normal-perfusion area based on PET-MPI and the coronary distribution on CAG. Hyperemic MVR was calculated by using the formula, hyperemic MVR = hyperemic mean blood pressure × FFR/hyperemic MBF of the stenotic vessel. A strong negative correlation was observed between hyperemic MVR and hyperemic MBF in the reference normal-perfusion area (R = -0.758, P<0.001). Microvascular disease severity in chronic CAD can be estimated by hyperemic MBF of the normal-perfusion area with 13N-ammonia PET-MPI.