3D quantitative myocardial perfusion imaging with hyperpolarized HP001(bis-1,1-(hydroxymethyl)-[1-13C]cyclopropane-d8): Application of gradient echo and balanced SSFP sequences.

PURPOSE: This study aims to show the viability of conducting three-dimensional (3D) myocardial perfusion quantification covering the entire heart using both GRE and bSSFP sequences with hyperpolarized HP001. METHODS: A GRE sequence and a bSSFP sequence, both with a stack-of-spirals readout, were designed and applied to three pigs. The images were reconstructed using 13 $$ {}^{13} $$ C coil sensitivity maps measured in a phantom experiment. Perfusion was quantified using a constrained decomposition method, and the estimated rest/stress perfusion values from 13 $$ {}^{13} $$ C GRE/bSSFP and Dynamic contrast-enhanced MRI (DCE-MRI) were individually analyzed through histograms and the mean perfusion values were compared with reference values obtained from PET( 15 $$ {}^{15} $$ O-water). The Myocardial Perfusion Reserve Index (MPRI) was estimated for 13 $$ {}^{13} $$ C GRE/bSSFP and DCE-MRI and compared with the reference values. RESULTS: Perfusion values, estimated by both DCE and 13 $$ {}^{13} $$ C MRI, were found to be lower than reference values. However, DCE-MRI's estimated perfusion values were closer to the reference values than those obtained from 13 $$ {}^{13} $$ C MRI. In the case of MPRI estimation, the 13 $$ {}^{13} $$ C estimated MPRI values (GRE/bSSFP: 2.3/2.0) more closely align with the literature value (around 3) than the DCE estimated MPRI value (1.6). CONCLUSION: This study demonstrated the feasibility of 3D whole-heart myocardial perfusion quantification using hyperpolarized HP001 with both GRE and bSSFP sequences. The 13 $$ {}^{13} $$ C perfusion measurements underestimated perfusion values compared to the 15 $$ {}^{15} $$ O PET literature value, while the 13 $$ {}^{13} $$ C estimated MPRI value aligned better with the literature. This preliminary result indicates 13 $$ {}^{13} $$ C imaging may more accurately estimate MPRI values compared to DCE-MRI.

Early left ventricular microvascular dysfunction in diabetic pigs: a longitudinal quantitative myocardial perfusion CMR study.

BACKGROUND: Microvascular pathology is one of the main characteristics of diabetic cardiomyopathy; however, the early longitudinal course of diabetic microvascular dysfunction remains uncertain. This study aimed to investigate the early dynamic changes in left ventricular (LV) microvascular function in diabetic pig model using the cardiac magnetic resonance (CMR)-derived quantitative perfusion technique. METHODS: Twelve pigs with streptozotocin-induced diabetes mellitus (DM) were included in this study, and longitudinal CMR scanning was performed before and 2, 6, 10, and 16 months after diabetic modeling. CMR-derived semiquantitative parameters (upslope, maximal signal intensity, perfusion index, and myocardial perfusion reserve index [MPRI]) and fully quantitative perfusion parameters (myocardial blood flow [MBF] and myocardial perfusion reserve [MPR]) were analyzed to evaluate longitudinal changes in LV myocardial microvascular function. Pearson correlation was used to analyze the relationship between LV structure and function and myocardial perfusion function. RESULTS: With the progression of DM duration, the upslope at rest showed a gradually increasing trend (P = 0.029); however, the upslope at stress and MBF did not change significantly (P > 0.05). Regarding perfusion reserve function, both MPRI and MPR showed a decreasing trend with the progression of disease duration (MPRI, P = 0.001; MPR, P = 0.042), with high consistency (r = 0.551, P < 0.001). Furthermore, LV MPR is moderately associated with LV longitudinal strain (r = - 0.353, P = 0.022), LV remodeling index (r = - 0.312, P = 0.033), fasting blood glucose (r = - 0.313, P = 0.043), and HbA1c (r = - 0.309, P = 0.046). Microscopically, pathological results showed that collagen volume fraction increased gradually, whereas no significant decrease in microvascular density was observed with the progression of DM duration. CONCLUSIONS: Myocardial microvascular reserve function decreased gradually in the early stage of DM, which is related to both structural (but not reduced microvascular density) and functional abnormalities of microvessels, and is associated with increased blood glucose, reduced LV deformation, and myocardial remodeling.

Coronary Microvascular Dysfunction and Diffuse Myocardial Fibrosis in Patients With Type 2 Diabetes Using Quantitative Perfusion MRI.

BACKGROUND: Imaging techniques that quantitatively and automatically measure changes in the myocardial microcirculation in patients with diabetes are lacking. PURPOSE: To detect diabetic myocardial microvascular complications using a novel automatic quantitative perfusion MRI technique, and to explore the relationship between myocardial microcirculation dysfunction and fibrosis. STUDY TYPE: Prospective. SUBJECTS: 101 patients with type 2 diabetes mellitus (T2DM) (53 without and 48 with complications), 20 healthy volunteers. FIELD STRENGTH/SEQUENCE: 3.0T; modified Look-Locker inversion-recovery sequence; saturation recovery sequence and dual-bolus technique; segmented fast low-angle shot sequence. ASSESSMENT: All participants underwent MRI to determine the rest myocardial blood flow (MBF), stress MBF, myocardial perfusion reserve (MPR), and extracellular volume (ECV), which represents the extent of myocardial fibrosis. STATISTICAL TESTS: Kolmogorov-Smirnov test, Shapiro-Wilk test, Kruskal-Wallis H test, Mann-Whitney U test, chi-square test, Spearman correlation coefficient, multivariable linear regression analysis. P < 0.05 was considered statistically significant. RESULTS: The rest MBF was not significantly different between the T2DM without complications group (1.1, IQR: 0.9-1.3) and the control group (1.1, 1.0-1.3) (P = 1.000), but it was significantly lower in the T2DM with complications group (0.8, 0.6-1.0) than in both other groups. The stress MBF and MPR were significantly lower in the T2DM without complications group (1.9, 1.5-2.3, and 1.7, 1.4-2.1, respectively) than in the control group (3.0, 2.6-3.5, and 2.7, 2.4-3.1, respectively), and were also significantly lower in the T2DM with complications group (1.1, 0.9-1.4, and 1.4, 1.2-1.8, respectively) than in the T2DM without complications group. A decrease in MBF and MPR were significantly associated with an increase in the ECV. DATA CONCLUSION: Quantitative perfusion MRI can evaluate myocardial microcirculation dysfunction. In T2DM, there was a significant decrease in both MBF and MPR compared to healthy controls, with the decrease being significantly different between T2DM with and without complications groups. The decrease of MBF was significantly associated with the development of myocardial fibrosis, as determined by ECV. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.

Myocardial perfusion imaging with retrospective gating and integrated correction of attenuation, scatter, respiration, motion, and arrhythmia.

BACKGROUND: Absolute quantitative myocardial perfusion SPECT requires addressing of aleatory and epistemic uncertainties in conjunction with providing image quality sufficient for lesion detection and characterization. Iterative reconstruction methods enable the mitigation of the root causes of image degradation. This study aimed to determine the feasibility of a new SPECT/CT method with integrated corrections attempting to enable absolute quantitative cardiac imaging (xSPECT Cardiac; xSC). METHODS: We compared images of prototype xSC and conventional SPECT (Flash3DTM) acquired at rest from 56 patients aged 71 ± 12 y with suspected coronary heart disease. The xSC prototype comprised list-mode acquisitions with continuous rotation and subsequent iterative reconstructions with retrospective electrocardiography (ECG) gating. Besides accurate image formation modeling, patient-specific CT-based attenuation and energy window-based scatter correction, additionally we applied mitigation for patient and organ motion between views (inter-view), and within views (intra-view) for both the gated and ungated reconstruction. We then assessed image quality, semiquantitative regional values, and left ventricular function in the images. RESULTS: The quality of all xSC images was acceptable for clinical purposes. A polar map showed more uniform distribution for xSC compared with Flash3D, while lower apical count and higher defect contrast of myocardial infarction (p = 0.0004) were observed on xSC images. Wall motion, 16-gate volume curve, and ejection fraction were at least acceptable, with indication of improvements. The clinical prospectively gated method rejected beats ≥20% in 6 patients, whereas retrospective gating used an average of 98% beats, excluding 2% of beats. We used the list-mode data to create a product equivalent prospectively gated dataset. The dataset showed that the xSC method generated 18% higher count data and images with less noise, with comparable functional variables of volume and LVEF (p = ns). CONCLUSIONS: Quantitative myocardial perfusion imaging with the list-mode-based prototype xSPECT Cardiac is feasible, resulting in images of at least acceptable image quality.

Comparison of the prognostic value of impaired stress myocardial blood flow, myocardial flow reserve, and myocardial flow capacity on low-dose Rubidium-82 SiPM PET/CT.

BACKGROUND: The most reliable quantitative variable on Rubidium-82 (82Rb) cardiac PET/CT for predicting major adverse cardiovascular events (MACE) has not been characterized with low-dose silicon photomultipliers (SiPM) technology, which allows halving injected activity and radiation dose delivering less than 1.0 mSv in a 70-kg individual. METHODS AND RESULTS: We prospectively enrolled 234 consecutive participants with suspected myocardial ischemia. Participants underwent 82Rb cardiac SiPM PET/CT (5 MBq/kg) and were followed up for MACE over 652 days (interquartile range 559-751 days). For each participant, global stress myocardial blood flow (stress MBF), global myocardial flow reserve (MFR), and regional severely reduced myocardial flow capacity (MFCsevere) were measured. The Youden index was used to select optimal thresholds. In multivariate analysis after adjustments for clinical risk factors, reduced global stress MBF < 1.94 ml/min/g, reduced global MFR < 1.98, and regional MFCsevere > 3.2% of left ventricle emerged all as independent predictors of MACE (HR 4.5, 3.1, and 3.67, respectively, p < 0.001). However, only reduced global stress MBF remained an independent prognostic factor for MACE after adjusting for clinical risk factors and the combined use of global stress MBF, global MFR, and regional MFCsevere impairments (HR 2.81, p = 0.027). CONCLUSION: Using the latest SiPM PET technology with low-dose 82Rb halving the standard activity to deliver < 1 mSv for a 70-kg patient, impaired global stress MBF, global MFR, and regional MFC were powerful predictors of cardiovascular events, outperforming traditional cardiovascular risk factors. However, only reduced global stress MBF independently predicted MACE, being superior to global MFR and regional MFC impairments.

Comparison between quantitative cardiac magnetic resonance perfusion imaging and [15O]H2O positron emission tomography.

PURPOSE: To compare cardiac magnetic resonance imaging (CMR) with [15O]H2O positron emission tomography (PET) for quantification of absolute myocardial blood flow (MBF) and myocardial flow reserve (MFR) in patients with coronary artery disease (CAD). METHODS: Fifty-nine patients with stable CAD underwent CMR and [15O]H2O PET. The CMR imaging protocol included late gadolinium enhancement to rule out presence of scar tissue and perfusion imaging using a dual sequence, single bolus technique. Absolute MBF was determined for the three main vascular territories at rest and during vasodilator stress. RESULTS: CMR measurements of regional stress MBF and MFR showed only moderate correlation to those obtained using PET (r = 0.39; P < 0.001 for stress MBF and r = 0.36; P < 0.001 for MFR). Bland-Altman analysis revealed a significant bias of 0.2 ± 1.0 mL/min/g for stress MBF and - 0.5 ± 1.2 for MFR. CMR-derived stress MBF and MFR demonstrated area under the curves of respectively 0.72 (95% CI: 0.65 to 0.79) and 0.76 (95% CI: 0.69 to 0.83) and had optimal cutoff values of 2.35 mL/min/g and 2.25 for detecting abnormal myocardial perfusion, defined as [15O]H2O PET-derived stress MBF ≤ 2.3 mL/min/g and MFR ≤ 2.5. Using these cutoff values, CMR and PET were concordant in 137 (77%) vascular territories for stress MBF and 135 (80%) vascular territories for MFR. CONCLUSION: CMR measurements of stress MBF and MFR showed modest agreement to those obtained with [15O]H2O PET. Nevertheless, stress MBF and MFR were concordant between CMR and [15O]H2O PET in 77% and 80% of vascular territories, respectively.

Deep-Learning-Based Preprocessing for Quantitative Myocardial Perfusion MRI.

BACKGROUND: Quantitative myocardial perfusion cardiac MRI can provide a fast and robust assessment of myocardial perfusion status for the noninvasive diagnosis of myocardial ischemia while being more objective than visual assessment. However, it currently has limited use in clinical practice due to the challenging postprocessing required, particularly the segmentation. PURPOSE: To evaluate the efficacy of an automated deep learning (DL) pipeline for image processing prior to quantitative analysis. STUDY TYPE: Retrospective. POPULATION: In all, 175 (350 MRI scans; 1050 image series) clinical patients under both rest and stress conditions (135/10/30 training/validation/test). FIELD STRENGTH/SEQUENCE: 3.0T/2D multislice saturation recovery T1 -weighted gradient echo sequence. ASSESSMENT: Accuracy was assessed, as compared to the manual operator, through the mean square error of the distance between landmarks and the Dice similarity coefficient of the segmentation and bounding box detection. Quantitative perfusion maps obtained using the automated DL-based processing were compared to the results obtained with the manually processed images. STATISTICAL TESTS: Bland-Altman plots and intraclass correlation coefficient (ICC) were used to assess the myocardial blood flow (MBF) obtained using the automated DL pipeline, as compared to values obtained by a manual operator. RESULTS: The mean (SD) error in the detection of the time of peak signal enhancement in the left ventricle was 1.49 (1.4) timeframes. The mean (SD) Dice similarity coefficients for the bounding box and myocardial segmentation were 0.93 (0.03) and 0.80 (0.06), respectively. The mean (SD) error in the RV insertion point was 2.8 (1.8) mm. The Bland-Altman plots showed a bias of 2.6% of the mean MBF between the automated and manually processed MBF values on a per-myocardial segment basis. The ICC was 0.89, 95% confidence interval = [0.87, 0.90]. DATA CONCLUSION: We showed high accuracy, compared to manual processing, for the DL-based processing of myocardial perfusion data leading to quantitative values that are similar to those achieved with manual processing. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2020;51:1689-1696.

Pitfalls in quantitative myocardial PET perfusion II: Arterial input function.

RATIONALE: We aimed to define the impact of variable arterial input function on myocardial perfusion severity that may misguide interventional decisions and relates to limited capacity of 3D PET for high-count arterial input function of standard bolus R-82. METHODS: We used GE Discovery-ST 16 slice PET-CT, serial 2D and 3D acquisitions of variable Rb-82 dose in a dynamic circulating arterial function model, static resolution and uniformity phantoms, and in patients with dipyridamole stress to quantify per-pixel rest and stress cc·min-1·g-1, CFR and CFC with (+) and (-) 10% simulated change in arterial input. RESULTS: For intermediate, border zone severity of stress perfusion, CFR and CFC comprising 7% of 3987 cases, simulated arterial input variability of ± 10% may cause over or underestimation of perfusion severity altering interventional decisions. In phantom tests, current 3D PET has capacity for quantifying high activity of arterial input and high-count per-pixel values of perfusion metrics per artery or branches. CONCLUSIONS: Accurate, reproducible arterial input function is essential for at least 7% of patients at thresholds of perfusion severity for optimally guiding interventions and providing high-activity regional per-pixel perfusion metrics by 3D PET for displaying complex quantitative perfusion readily understood ("owned") by interventionalists to guide procedures.

Pitfalls in quantitative myocardial PET perfusion I: Myocardial partial volume correction.

BACKGROUND: PET quantitative myocardial perfusion requires correction for partial volume loss due to one-dimensional LV wall thickness smaller than scanner resolution. METHODS: We aimed to assess accuracy of risk stratification for death, MI, or revascularization after PET using partial volume corrections derived from two-dimensional ACR and three-dimensional NEMA phantoms for 3987 diagnostic rest-stress perfusion PETs and 187 MACE events. NEMA, ACR, and Tree phantoms were imaged with Rb-82 or F-18 for size-dependent partial volume loss. Perfusion and Coronary Flow Capacity were recalculated using different ACR- and NEMA-derived partial volume corrections compared by Kolmogorov-Smirnov statistics to standard perfusion metrics with established correlations with MACE. RESULTS: Partial volume corrections based on two-dimensional ACR rods (two equal radii) and three-dimensional NEMA spheres (three equal radii) over estimate partial volume corrections, quantitative perfusion, and Coronary Flow Capacity by 50% to 150% over perfusion metrics with one-dimensional partial volume correction, thereby substantially impairing correct risk stratification. CONCLUSIONS: ACR (2-dimensional) and NEMA (3-dimensional) phantoms overestimate partial volume corrections for 1-dimensional LV wall thickness and myocardial perfusion that are corrected with a simple equation that correlates with MACE for optimal risk stratification applicable to most PET-CT scanners for quantifying myocardial perfusion.

A model-based reconstruction technique for quantitative myocardial perfusion imaging.

PURPOSE: To reduce saturation effects in the arterial input function (AIF) estimation of quantitative myocardial first-pass saturation recovery perfusion imaging by employing a model-based reconstruction. THEORY AND METHODS: Imaging was performed with a saturation recovery prepared radial FLASH sequence. A model-based reconstruction was applied for reconstruction. By exploiting prior knowledge about the relaxation process, an image series with different saturation recovery times was reconstructed. By evaluating images with an effective saturation time of approximately 3 ms, saturation effects in the AIF determination were reduced. In a volunteer study, this approach was compared with a standard prebolus technique. RESULTS: In comparison to the low-dose injection of a prebolus acquisition, saturation effects were further reduced in the AIFs determined using the model-based approach. These effects, which were clearly visible for all six volunteers, were reflected in a statistically significant difference of up to 20% in the absolute perfusion values. CONCLUSION: The application of model-based reconstruction algorithms in quantitative myocardial perfusion imaging promises a significant improvement of the AIF determination. In addition to greatly reducing saturation effects that occur even for the prebolus methods, only a single bolus has to be applied. Magn Reson Med 76:880-887, 2016. © 2015 Wiley Periodicals, Inc.

Quantitative Coronary Physiology for Clinical Management: the Imaging Standard.

Pressure derived FFR and coronary flow capacity by PET define a physiologic severity-risk-benefit continuum wherein probability of benefit from revascularization over risk of the procedure and risk of residual global diffuse disease guides personalized, informed, evidenced based, interventional decisions. For the many variations in PET or MRI protocols for quantifying myocardial perfusion to define physiologic severity, the simple standard performance test combining measurement accuracy and clinical coronary pathophysiology to assure correct clinical decisions is the capacity to measure (i) rest perfusion of 0.2 cm(3)/min/gm in transmural scar in at least five patients to test low perfusion accuracy (ii) regional and global CFR of 4.0 or stress perfusion of 2.9 cm(3)/min/gm on two sequential rest-stress PET perfusion studies in the same subject with ±15 % variability for at least 15 young healthy volunteers with no risk factors, no smoking, no obesity, and no measureable blood caffeine levels.

Myocardial Blood Flow Quantified Using Stress Cardiac Magnetic Resonance After Mild COVID-19 Infection.

BACKGROUND: Severe COVID-19 infection is known to alter myocardial perfusion through its effects on the endothelium and microvasculature. However, the majority of patients with COVID-19 infection experience only mild symptoms, and it is unknown if their myocardial perfusion is altered after infection. OBJECTIVES: The authors aimed to determine if there are abnormalities in myocardial blood flow (MBF), as measured by stress cardiac magnetic resonance (CMR), in individuals after a mild COVID-19 infection. METHODS: We conducted a prospective, comparative study of individuals who had a prior mild COVID-19 infection (n = 30) and matched controls (n = 26) using stress CMR. Stress and rest myocardial blood flow (sMBF, rMBF) were quantified using the dual sequence technique. Myocardial perfusion reserve was calculated as sMBF/rMBF. Unpaired t-tests were used to test differences between the groups. RESULTS: The median time interval between COVID-19 infection and CMR was 5.6 (IQR: 4-8) months. No patients with the COVID-19 infection required hospitalization. Symptoms including chest pain, shortness of breath, syncope, and palpitations were more commonly present in the group with prior COVID-19 infection than in the control group (57% vs 7%, P < 0.001). No significant differences in rMBF (1.08 ± 0.27 mL/g/min vs 0.97 ± 0.29 mL/g/min, P = 0.16), sMBF (3.08 ± 0.79 mL/g/min vs 3.06 ± 0.89 mL/g/min, P = 0.91), or myocardial perfusion reserve (2.95 ± 0.90 vs 3.39 ± 1.25, P = 0.13) were observed between the groups. CONCLUSIONS: This study suggests that there are no significant abnormalities in rest or stress myocardial perfusion, and thus microvascular function, in individuals after mild COVID-19 infection.

AI-AIF: artificial intelligence-based arterial input function for quantitative stress perfusion cardiac magnetic resonance.

Aims: One of the major challenges in the quantification of myocardial blood flow (MBF) from stress perfusion cardiac magnetic resonance (CMR) is the estimation of the arterial input function (AIF). This is due to the non-linear relationship between the concentration of gadolinium and the MR signal, which leads to signal saturation. In this work, we show that a deep learning model can be trained to predict the unsaturated AIF from standard images, using the reference dual-sequence acquisition AIFs (DS-AIFs) for training. Methods and results: A 1D U-Net was trained, to take the saturated AIF from the standard images as input and predict the unsaturated AIF, using the data from 201 patients from centre 1 and a test set comprised of both an independent cohort of consecutive patients from centre 1 and an external cohort of patients from centre 2 (n = 44). Fully-automated MBF was compared between the DS-AIF and AI-AIF methods using the Mann-Whitney U test and Bland-Altman analysis. There was no statistical difference between the MBF quantified with the DS-AIF [2.77 mL/min/g (1.08)] and predicted with the AI-AIF (2.79 mL/min/g (1.08), P = 0.33. Bland-Altman analysis shows minimal bias between the DS-AIF and AI-AIF methods for quantitative MBF (bias of -0.11 mL/min/g). Additionally, the MBF diagnosis classification of the AI-AIF matched the DS-AIF in 669/704 (95%) of myocardial segments. Conclusion: Quantification of stress perfusion CMR is feasible with a single-sequence acquisition and a single contrast injection using an AI-based correction of the AIF.

Long-Term Prognostic Value of 82Rb PET/CT-Determined Myocardial Perfusion and Flow Reserve in Cancer Patients.

Myocardial flow reserve (MFR), derived from quantitative measurements of myocardial blood flow during PET imaging, provides prognostic information on patients with coronary artery disease (CAD), but it is not known if this also applies to cancer patients with a competing risk for mortality. Methods: To determine the prognostic value of MFR in patients with cancer, we designed a retrospective cohort study comprising 221 patients with known or suspected CAD (median age, 71 y; range, 41-92 y) enrolled between June 2009 and January 2011. Most patients were referred for perioperative risk assessment. Patients underwent measurement of myocardial blood flow at rest and during pharmacologic stress, using quantitative 82Rb PET imaging. They were divided into early-stage versus advanced-stage cancer groups based on cancer histopathology and clinical state and were further stratified by myocardial perfusion summed stress score, summed difference score, and calculated MFR. Overall survival (OS) was assessed using the Kaplan-Meier estimator, and Cox proportional-hazards regression helped identify independent predictors for OS. Results: During a follow-up of 85.6 mo, 120 deaths occurred. MFR, summed difference score, and cancer stage were significantly associated with OS. In the age-adjusted Cox hazard multivariable analysis, MFR and cancer stage remained independent prognostic factors. MFR combined with cancer stage enhanced OS discrimination. The groups had significantly different outcomes (P < 0.001), with 5-y OS of 88% (MFR ≥ 1.97 and early-stage), 53% (MFR < 1.97 and early-stage), 33% (MFR ≥ 1.97 and advanced-stage), and 13% (MFR < 1.97 and advanced-stage). Conclusion: Independent of cancer stage, MFR derived from quantitative PET was prognostic of OS in our cohort of cancer patients with known or suspected CAD. Combining these 2 parameters enhanced discrimination of OS, suggesting that MFR improves risk stratification and may serve as a treatment target to increase survival in cancer patients.

Abnormal left ventricular subendocardial perfusion and diastolic function in women with obesity and heart failure and preserved ejection fraction.

PURPOSE: - Coronary microvascular dysfunction (CMD) is common in patients with heart failure with preserved ejection fraction (HFpEF) and obesity. Stress cardiovascular magnetic resonance (CMR) has been proposed as a non-invasive tool for detection of CMD. The aim of this study was to determine relationship between CMD and diastolic function in patients with HFpEF using a novel CMR technique. METHODS: - Patients with obesity and HFpEF without epicardial coronary artery disease (CAD) underwent Doppler echocardiography to measure diastolic function, followed by vasodilator stress CMR, using a single bolus, dual sequence, quantitative myocardial perfusion mapping to measure myocardial blood flow (MBF) at rest and at peak hyperemia. With this, myocardial perfusion reserve (MPR), global stress endocardial-to-epicardial (endo:epi) perfusion ratio, and total ischemic burden (IB, defined as myocardial segments with MBF < 1.94 mL/min/g) were calculated. Results are reported as median and interquartile range. RESULTS: - Nineteen subjects were enrolled (100% female, 42% Black). Median age was 64 [56-72] years. Global stress MBF was 2.43 ml/min/g [2.16-2.78] and global myocardial perfusion reserve (MPR) was 2.34 [2.07-2.88]. All had an abnormal subendocardial perfusion with an endo:epi of less than 1 (0.87 [0.81-0.90]). Regional myocardial hypoperfusion was detected in 14 (74%) patients with an IB of 6% [0-34.4]. Endo:epi ratio significantly correlated with IB (R=-0.510, p = 0.026) and measures of diastolic function (R = 0.531, p = 0.019 and R=-0.544, p = 0.014 for e' and E/e' respectively). CONCLUSION: - Using a novel quantitative stress CMR myocardial perfusion mapping technique, women with obesity and HFpEF were found to have patterns of abnormal subendocardial perfusion which significantly correlated with measures of diastolic dysfunction.

The impact of coronary revascularization on vessel-specific coronary flow capacity and long-term outcomes: a serial [15O]H2O positron emission tomography perfusion imaging study.

AIMS: Coronary flow capacity (CFC) integrates quantitative hyperaemic myocardial blood flow (hMBF) and coronary flow reserve (CFR) to comprehensively assess physiological severity of coronary artery disease (CAD). This study evaluated the effects of revascularization on CFC as assessed by serial [15O]H2O positron emission tomography (PET) perfusion imaging. METHODS AND RESULTS: A total of 314 patients with stable CAD underwent [15O]H2O PET imaging at baseline and after myocardial revascularization to assess changes in hMBF, CFR, and CFC in 415 revascularized vessels. Using thresholds for ischaemia and normal perfusion, vessels were stratified in five CFC categories: myocardial steal, severely reduced CFC, moderately reduced CFC, minimally reduced CFC, and normal flow. Additionally, the association between CFC increase and the composite endpoint of death and non-fatal myocardial infarction (MI) was studied. Vessel-specific CFC improved after revascularization (P < 0.01). Furthermore, baseline CFC was an independent predictor of CFC increase (P < 0.01). The largest changes in ΔhMBF (0.90 ± 0.74, 0.93 ± 0.65, 0.79 ± 0.74, 0.48 ± 0.61, and 0.29 ± 0.66 mL/min/g) and ΔCFR (1.01 ± 0.88, 0.99 ± 0.69, 0.87 ± 0.88, 0.66 ± 0.91, and -0.01 ± 1.06) were observed in vessels with lower baseline CFC (P < 0.01 for both). During a median follow-up of 3.5 (95% CI 3.1-3.9) years, an increase in CFC was independently associated with lower rates of death and non-fatal MI (HR 0.43, 95% CI 0.19-0.98, P = 0.04). CONCLUSION: Successful revascularization results in an increase in CFC. Furthermore, baseline CFC was an independent predictor of change in hMBF, CFR, and subsequently CFC. In addition, an increase in CFC was associated with a favourable outcome in terms of death and non-fatal MI.

Mortality Prediction by Quantitative PET Perfusion Expressed as Coronary Flow Capacity With and Without Revascularization.

OBJECTIVES: This study sought to determine the relationship between the severity of reduced quantitative perfusion parameters and mortality with and without revascularization. BACKGROUND: The physiological mechanisms for differential mortality risk of coronary flow reserve (CFR) and coronary flow capacity (CFC) before and after revascularization are unknown. METHODS: Global and regional rest-stress (ml/min/g), CFR, their regional per-pixel combination as CFC, and relative stress in ml/min/g were measured as percent of LV in all serial routine 5,274 diagnostic PET scans with systematic follow-up over 10 years (mean 4.2 ± 2.5 years) for all-cause mortality with and without revascularization. RESULTS: Severely reduced CFR of 1.0 to 1.5 and stress perfusion ≤1.0 cc/min/g incurred increasing size-dependent risks that were additive because regional severely reduced CFC (CFCsevere) was associated with the highest major adverse cardiac event rate of 80% (p < 0.0001 vs. either alone) and a mortality risk of 14% (vs. 2.3% for no CFCsevere; p = 0.001). Small regions of CFCsevere ≤0.5% predicted high risk (p < 0.0001 vs. no CFCsevere) related to a wave front of border zones at risk around the small most severe center. By receiver-operating characteristic analysis, relative stress topogram maps of stress (ml/min/g) as a fraction of LV defined these border zones at risk or for mildly reduced CFC (area under the curve [AUC]: 0.69) with a reduced relative tomographic subendocardial-to-subepicardial ratio. CFCsevere incurred the highest mortality risk that was reduced by revascularization (p = 0.005 vs. no revascularization) for artery-specific stenosis not defined by global CFR or stress perfusion alone. CONCLUSIONS: CFC is associated with the size-dependent highest mortality risk resulting from the additive risk of CFR and stress (ml/min/g) that is significantly reduced after revascularization, a finding not seen for global CFR. Small regions of CFCsevere ≤0.5% of LV also carry a high risk because of the surrounding border zones at risk defined by relative stress perfusion and a reduced relative subendocardial-to-subepicardial ratio.

Cardiac Magnetic Resonance for Evaluating Nonculprit Lesions After Myocardial Infarction: Comparison With Fractional Flow Reserve.

OBJECTIVES: This study sought to determine the agreement between cardiac magnetic resonance (CMR) imaging and invasive measurements of fractional flow reserve (FFR) in the evaluation of nonculprit lesions after ST-segment elevation myocardial infarction (STEMI). In addition, we investigated whether fully quantitative analysis of myocardial perfusion is superior to semiquantitative and visual analysis. BACKGROUND: The agreement between CMR and FFR in the evaluation of nonculprit lesions in patients with STEMI with multivessel disease is unknown. METHODS: Seventy-seven patients with STEMI with at least 1 intermediate (diameter stenosis 50% to 90%) nonculprit lesion underwent CMR and invasive coronary angiography in conjunction with FFR measurements at 1 month after primary intervention. The imaging protocol included stress and rest perfusion, cine imaging, and late gadolinium enhancement. Fully quantitative, semiquantitative, and visual analysis of myocardial perfusion were compared against a reference of FFR. Hemodynamically obstructive was defined as FFR ≤0.80. RESULTS: Hemodynamically obstructive nonculprit lesions were present in 31 (40%) patients. Visual analysis displayed an area under the curve (AUC) of 0.74 (95% confidence interval [CI]: 0.62 to 0.83), with a sensitivity of 73% and a specificity of 70%. For semiquantitative analysis, the relative upslope of the stress signal intensity time curve and the relative upslope derived myocardial flow reserve had respective AUCs of 0.66 (95% CI: 0.54 to 0.77) and 0.71 (95% CI: 0.59 to 0.81). Fully quantitative analysis did not augment diagnostic performance (all p > 0.05). Stress myocardial blood flow displayed an AUC of 0.76 (95% CI: 0.64 to 0.85), with a sensitivity of 69% and a specificity of 77%. Similarly, MFR displayed an AUC of 0.82 (95% CI: 0.71 to 0.90), with a sensitivity of 82% and a specificity of 71%. CONCLUSIONS: CMR and FFR have moderate-good agreement in the evaluation of nonculprit lesions in patients with STEMI with multivessel disease. Fully quantitative, semiquantitative, and visual analysis yield similar diagnostic performance.

Regional, Artery-Specific Thresholds of Quantitative Myocardial Perfusion by PET Associated with Reduced Myocardial Infarction and Death After Revascularization in Stable Coronary Artery Disease.

Because randomized coronary revascularization trials in stable coronary artery disease (CAD) have shown no reduced myocardial infarction (MI) or mortality, the threshold of quantitative myocardial perfusion severity was analyzed for association with reduced death, MI, or stroke after revascularization within 90 d after PET. Methods: In a prospective long-term cohort of stable CAD, regional, artery-specific, quantitative myocardial perfusion by PET, coronary revascularization within 90 d after PET, and all-cause death, MI, and stroke (DMS) at 9-y follow-up (mean ± SD, 3.0 ± 2.3 y) were analyzed by multivariate Cox regression models and propensity analysis. Results: For 3,774 sequential rest-stress PET scans, regional, artery-specific, severely reduced coronary flow capacity (CFC) (coronary flow reserve ≤ 1.27 and stress perfusion ≤ 0.83 cc/min/g) associated with 60% increased hazard ratio for major adverse cardiovascular events and 30% increased hazard of DMS that was significantly reduced by 54% associated with revascularization within 90 d after PET (P = 0.0369), compared with moderate or mild CFC, coronary flow reserve, other PET metrics or medical treatment alone. Depending on severity threshold for statistical certainty, up to 19% of this clinical cohort had CFC severity associated with reduced DMS after revascularization. Conclusion: CFC by PET provides objective, regional, artery-specific, size-severity physiologic quantification of CAD severity associated with high risk of DMS that is significantly reduced after revascularization within 90 d after PET, an association not seen for moderate to mild perfusion abnormalities or medical treatment alone.

Quantitative myocardial perfusion positron emission tomography and caffeine revisited with new insights on major adverse cardiovascular events and coronary flow capacity.

AIMS: To evaluate effects of caffeine on quantitative myocardial perfusion by positron emission tomography (PET) and associated major adverse cardiovascular events (MACE). METHODS AND RESULTS: Serum caffeine was measured for all 6087 PETs with 328 positive results (5.4%). Paired caffeine positive/negative PETs (84 patients for dipyridamole with median caffeine 1.6 mg/L, and additional 25 volunteers for regadenoson with median caffeine 7.4 mg/L) were compared for quantitative perfusion. Multivariate regression analysis for associations among caffeine, clinical/imaging variables, predicted caffeine probability was performed. MACEs were followed up to 9 years after PETs. For caffeine vs. no caffeine, respectively, stress flow was 1.74 ± 0.55 vs. 2.14 ± 0.53 for dipyridamole and 1.82 ± 0.61 vs. 2.33 ± 0.49 mL/min/g for regadenoson, and coronary flow reserve (CFR) was 2.26 ± 0.67 vs. 2.67 ± 0.72 for dipyridamole and 1.84 ± 0.33 vs. 2.31 ± 0.41 for regadenoson (all P < 0.001). Subjects were reclassified from high-risk CFR ≤2.0 with caffeine to low-risk CFR >2.0 without caffeine in 66.7% and 80% of dipyridamole and regadenoson caffeine-no-caffeine pairs, respectively. While relative images showed no differences, caffeine significantly altered coronary flow capacity (CFC) to false negative and false positive severity in 2.1% and 5.5% of the 328 caffeine positives, respectively (0.1% and 0.3% of 6087 PETs) but without change in severity guided management in most patients (92.4% of 328 caffeine or 99.6% of total 6087 PETs). CONCLUSION: Even low serum caffeine levels reduce quantitative perfusion during vasodilatory stress with false positive or false negative results minimized by empathic instruction, CFC analysis or repeat PET after strict caffeine abstention for definitive individualized risk stratification and management.