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Background: Quantitative stress cardiac magnetic resonance (CMR) can be performed using the dual-sequence (DS) technique or dual-bolus (DB) method. It is unknown if DS and DB produce similar results for myocardial blood flow (MBF) and myocardial perfusion reserve (MPR). The study objective is to investigate if there are any differences between DB- and DS-derived MBF and MPR., Methods: Retrospective observational study with 168 patients who underwent stress CMR. DB and DS methods were simultaneously performed on each patient on the same day. Global and segmental stress MBF and rest MBF values were collected., Results: Using Bland-Altman analysis, segmental and global stress MBF values were higher in DB than DS (0.22 ± 0.60 mL/g/min, p < 0.001 and 0.20 ± 0.48 mL/g/min, p = 0.005, respectively) with strong correlation (r = 0.81, p < 0.001 for segmental and r = 0.82, p < 0.001 for global). In rest MBF, segmental and global DB values were higher than by DS (0.15 ± 0.51 mL/g/min, p < 0.001 and 0.14 ± 0.36 mL/g/min, p = 0.011, respectively) with strong correlation (r = 0.81, p < 0.001 and r = 0.77, p < 0.001). Mean difference between MPR by DB and DS was -0.02 ± 0.68 mL/g/min (p = 0.758) for segmental values and -0.01 ± 0.49 mL/g/min (p = 0.773) for global values. MPR values correlated strongly as well in both segmental and global, both (r = 0.74, p < 0.001) and (r = 0.75, p < 0.001), respectively., Conclusion: There is a very good correlation between DB- and DS-derived MBF and MPR values. However, there are significant differences between DB- and DS-derived global stress and rest MBF. While MPR values did not show statistically significant differences between DB and DS methods., Competing Interests: Declaration of competing interests The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ming-Yen Ng reports a relationship with Bayer AG that includes funding grants and speaking and lecture fees. Ming-Yen Ng reports a relationship with GE Healthcare that includes funding grants and speaking and lecture fees. Ming-Yen Ng reports a relationship with Circle Cardiovascular Imaging Inc. that includes funding grants and speaking and lecture fees. Ming-Yen Ng reports a relationship with Boerhinger Ingelheim that includes speaking and lecture fees. Ming-Yen Ng reports a relationship with Lode B.V. that includes funding grants. Ming-Yen Ng reports a relationship with Arterys Inc. that includes funding grants. Ming-Yen Ng reports a relationship with TeraRecon Inc. that includes funding grants. Associate Editor of JCMR - Ming-Yen Ng and Amit Patel; Associate Editor of JCCT - Ming-Yen Ng. Haonan Wang and Martin Janich are employees of GE HealthCare. Amit Patel has received research grants from GE Healthcare and research support from CircleCVI, Neosoft, and Siemens Healthineers. Mitchel Benovoy is the Chief Executive Officer of Area19 Medical, the Chief Executive Officer of ViTAA Medical Solutions, and a Member of The Board of Advisors at Yunu, Inc. Andrew E Arai has received royalty payments from Circle CVI. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Aerobic exercise capacity is an independent predictor of mortality in dilated cardiomyopathy (DCM), but the central mechanisms contributing to exercise intolerance in DCM are unknown. The aim of this study was to characterize coronary microvascular function in DCM and determine if cardiovascular magnetic resonance (CMR) measures are associated with aerobic exercise capacity., Methods: Prospective case-control comparison of adults with DCM and matched controls. Adenosine-stress perfusion CMR to assess cardiac structure, function and automated inline myocardial blood flow quantification, and cardiopulmonary exercise testing to determine peak VO 2 was performed. Pre-specified multivariable linear regression, including key clinical and cardiac variables, was undertaken to identify independent associations with peak VO 2 ., Results: Sixty-six patients with DCM (mean age 61 years, 47 male) were propensity-matched to 66 controls (mean age 59 years, 47 male) based on age, sex, body mass index, and diabetes. DCM patients had markedly lower peak VO 2 (19.8 ± 5.5 versus 25.2 ± 7.3 mL/kg/min; P < 0.001). The DCM group had greater left ventricular (LV) volumes, lower systolic function, and more fibrosis compared to controls. In the DCM group, there was similar rest but lower stress myocardial blood flow (1.53 ± 0.49 versus 2.01 ± 0.60 mL/g/min; P < 0.001) and lower myocardial perfusion reserve (MPR) (2.69 ± 0.84 versus 3.15 ± 0.84; P = 0.002). Multivariable linear regression demonstrated that LV ejection fraction, extracellular volume fraction, and MPR, were independently associated with percentage-predicted peak VO 2 in DCM (R 2 = 0.531, P < 0.001)., Conclusion: In comparison to controls, DCM patients have lower stress myocardial blood flow and MPR. In DCM, MPR, LV ejection fraction, and fibrosis are independently associated with aerobic exercise capacity., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The author Gerry P. McCann is an Editorial Board Member for Journal of Cardiovascular Magnetic Resonance and was not involved in the editorial review or the decision to publish this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) assessment with non-invasive techniques represent an important tool to evaluate both coronary artery disease severity and extent. Currently, cardiac positron emission tomography-computed tomography (PET-CT) is the "gold standard" for the assessment of coronary function and provides accurate estimations of baseline and hyperemic MBF and MFR. Nevertheless, due to the high cost and complexity, PET-CT is not widely used in clinical practice. The introduction of cardiac-dedicated cadmium-zinc-telluride (CZT) cameras has renewed researchers' interest on MBF quantitation by single-photon emission computed tomography (SPECT). Indeed, many studies evaluated MPR and MBF measurements by dynamic CZT-SPECT in different cohorts of patients with suspected or overt coronary artery disease. As well, many others have compared the values obtained by CZT-SPECT to the ones by PET-CT, showing good correlations in detecting significant stenosis, although with different and non-standardized cut-off values. Nevertheless, the lack of standardized protocol for acquisition, reconstruction and elaboration makes more difficult to compare different studies and to further assess the real advantages of MBF quantitation by dynamic CZT-SPECT in clinical routine. Many are the issues involved in the bright and dark sides of dynamic CZT-SPECT. They include different type of CZT cameras, different execution protocols, different tracers with different myocardial extraction fraction and distribution, different software packages with different tools and algorithms, often requiring manual post-processing elaboration. This review article provides a clear summary of the state of the art on MBF and MPR evaluation by dynamic CZT-SPECT and outlines the major issues to solve to optimize this technique., Competing Interests: Disclosure of interest The authors declare that this work did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2023 Société française de radiologie. Published by Elsevier Masson SAS. All rights reserved.)

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., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aims: Recently developed in-line automated cardiovascular magnetic resonance (CMR) myocardial perfusion mapping has been shown to be reproducible and comparable with positron emission tomography (PET), and can be easily integrated into clinical workflows. Bringing quantitative myocardial perfusion CMR into routine clinical care requires knowledge of sex- and age-specific normal values in order to define thresholds for disease detection. This study aimed to establish sex- and age-specific normal values for stress and rest CMR myocardial blood flow (MBF) in healthy volunteers., Methods and Results: A total of 151 healthy volunteers recruited from two centres underwent adenosine stress and rest myocardial perfusion CMR. In-line automatic reconstruction and post processing of perfusion data were implemented within the Gadgetron software framework, creating pixel-wise perfusion maps. Rest and stress MBF were measured, deriving myocardial perfusion reserve (MPR) and were subdivided by sex and age. Mean MBF in all subjects was 0.62 ± 0.13 mL/g/min at rest and 2.24 ± 0.53 mL/g/min during stress. Mean MPR was 3.74 ± 1.00. Compared with males, females had higher rest (0.69 ± 0.13 vs. 0.58 ± 0.12 mL/g/min, P < 0.01) and stress MBF (2.41 ± 0.47 vs. 2.13 ± 0.54 mL/g/min, P = 0.001). Stress MBF and MPR showed significant negative correlations with increasing age (r = -0.43, P < 0.001 and r = -0.34, P < 0.001, respectively)., Conclusion: Fully automated in-line CMR myocardial perfusion mapping produces similar normal values to the published CMR and PET literature. There is a significant increase in rest and stress MBF, but not MPR, in females and a reduction of stress MBF and MPR with advancing age, advocating the use of sex- and age-specific reference ranges for diagnostic use., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Whether estimates of myocardial perfusion reserve (MPR) stemming from new-generation cadmium-zinc-telluride (CZT) cameras are accurate remains unclear., Methods: We queried our institutional database for patients undergoing MPR with CZT cameras. The primary goal was appraising the incremental diagnostic yield of MPR on top or at odds of maximal ischemia score (MIS)., Results: A total of 66 subjects were included. When distinguishing patients according to normal vs abnormal MPR (cut-off 2.1 mL/min/g) and normal vs abnormal MIS, 4 groups could be identified: 12 (18.1%) individuals with normal MPR and MIS, 12 (18.1%) with normal MPR and abnormal MIS, 16 (24.2%) with abnormal MPR and normal MIS, and 26 (39.4%) with abnormal MPR and MIS. MIS was significantly associated with several baseline features, whereas MPR did not. There was no significant association between MPR and MIS, nor with regional perfusion. Clinical outcomes were uncommon and not significantly associated with MPR or MIS, whereas angiographically significant coronary artery disease (CAD) was associated solely with MIS (P < 0.05), and not with MPR., Conclusions: There is limited agreement between CZT-derived MPR and baseline risk, perfusion and angiography results. Whether such discrepancies may still prove incrementally beneficial for the diagnosis or prognosis of CAD remains unclear.

Background: Quantification of myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) by cardiovascular magnetic resonance (CMR) perfusion requires sampling of the arterial input function (AIF). While variation in the AIF sampling location is known to impact quantification by CMR and positron emission tomography (PET) perfusion, there is no evidence to support the use of a specific location based on their diagnostic accuracy in the detection of coronary artery disease (CAD). This study aimed to evaluate the accuracy of stress MBF and MPR for different AIF sampling locations for the detection of abnormal myocardial perfusion with expert visual assessment as the reference., Methods: Twenty-five patients with suspected or known CAD underwent vasodilator stress-rest perfusion with a dual-sequence technique at 3T. A low-resolution slice was acquired in 3-chamber view to allow AIF sampling at five different locations: left atrium (LA), basal left ventricle (bLV), mid left ventricle (mLV), apical left ventricle (aLV) and aortic root (AoR). MBF and MPR were estimated at the segmental level using Fermi function-constrained deconvolution. Segments were scored as having normal or abnormal perfusion by visual assessment and the diagnostic accuracy of stress MBF and MPR for each location was evaluated using receiver operating characteristic curve analysis., Results: In both normal (300 out of 400, 75 %) and abnormal segments, rest MBF, stress MBF and MPR were significantly different across AIF sampling locations (p < 0.001). Stress MBF for the AoR (normal: 2.42 (2.15-2.84) mL/g/min; abnormal: 1.71 (1.28-1.98) mL/g/min) had the highest diagnostic accuracy (sensitivity 80 %, specificity 85 %, area under the curve 0.90; p < 0.001 versus stress MBF for all other locations including bLV: normal: 2.78 (2.39-3.14) mL/g/min; abnormal: 2.22 (1.83-2.48) mL/g/min; sensitivity 91 %, specificity 63 %, area under the curve 0.81) and performed better than MPR for the LV locations (p < 0.01). MPR for the AoR (normal: 2.43 (1.95-3.14); abnormal: 1.58 (1.34-1.90)) was not superior to MPR for the bLV (normal: 2.59 (2.04-3.20); abnormal: 1.69 (1.36-2.14); p = 0.717)., Conclusions: The AIF sampling location has a significant impact on MBF and MPR estimates by CMR perfusion, with AoR-based stress MBF comparing favorably to that for the current clinical reference bLV.

Purpose: Bolus-based dynamic contrast agent (CA) perfusion measurements of the heart are subject to systematic errors due to CA bolus dispersion in the coronary arteries. To better understand these effects on quantification of myocardial blood flow and myocardial perfusion reserve (MPR), an in-silico model of the coronary arteries down to the pre-arteriolar vessels has been developed., Methods: In this work, a computational fluid dynamics analysis is performed to investigate these errors on the basis of realistic 3D models of the left and right porcine coronary artery trees, including vessels at the pre-arteriolar level. Using advanced boundary conditions, simulations of blood flow and CA transport are conducted at rest and under stress. These are evaluated with regard to dispersion (assessed by the width of CA concentration time curves and associated vascular transport functions) and errors of myocardial blood flow and myocardial perfusion reserve quantification., Results: Contrast agent dispersion increases with traveled distance as well as vessel diameter, and decreases with higher flow velocities. Overall, the average myocardial blood flow errors are -28% ± 16% and -8.5% ± 3.3% at rest and stress, respectively, and the average myocardial perfusion reserve error is 26% ± 22%. The calculated values are different in the left and right coronary tree., Conclusion: Contrast agent dispersion is dependent on a complex interplay of several different factors characterizing the cardiovascular bed, including vessel size and integrated vascular length. Quantification errors evoked by the observed CA dispersion show nonnegligible distortion in dynamic CA bolus-based perfusion measurements. We expect future improvements of quantitative perfusion measurements to make the systematic errors described here more apparent., (© 2019 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

Background: We measured myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) by a dynamic low-dose CZT-SPECT protocol in patients with suspected or known coronary artery disease (CAD) and investigated the capability of dynamic data in predicting obstructive CAD. A total of 173 patients with suspected or known CAD underwent dynamic CZT-SPECT after the injection of 155 MBq and 370 MBq of 99m Tc-sestamibi for rest and stress imaging, respectively. Standard rest and stress imaging were performed at the end of each dynamic scan. A total perfusion defect (TPD) < 5% were considered normal. Obstructive CAD was defined as ≥ 70% stenosis at coronary angiography., Results: Global MPR was lower (p < 0.05) in patients with abnormal compared with those with normal MPI (2.40 ± 0.7 vs. 2.70 ± 0.8). A weak, albeit significant correlation between TPD and MPR (r = - 0.179, p < 0.05) was found. In 91 patients with available angiographic data, hyperemic MBF (2.59 ± 1.2 vs. 3.24 ± 1.1 ml/min/g) and MPR (1.96 ± 0.7 vs. 2.74 ± 0.9) were lower (both p < 0.05) in patients with obstructive CAD (n = 21) compared with those without (n = 70). At univariable analysis, TPD, hyperemic MBF, and MPR were significant predictors of obstructive CAD, whereas only MPR was independent predictor at multivariable analysis (p < 0.05). At per vessels analysis, regional hyperemic MBF (2.59 ± 1.2 vs. 3.24 ± 1.1 ml/min/g) and regional MPR (1.96 ± 0.7 vs. 2.74 ± 0.9) were lower in the 31 vessels with obstructive CAD compared with 242 vessels without (both p < 0.05)., Conclusions: In patients with suspected or known CAD, MPR assessed by low-dose dynamic CZT-SPECT showed a good correlation with myocardial perfusion imaging findings and it could be useful to predict obstructive CAD.

Purpose: Cardiac imaging with positron emission tomography/computed tomography (PET/CT) allows measurement of coronary artery calcium (CAC), stress-induced myocardial ischemia and myocardial perfusion reserve (MPR). We evaluated the prognostic role of the combined assessment of regional CAC score, ischemic total perfusion defect (ITPD) and MPR in predicting lesion-related outcome in patients with suspected coronary artery disease (CAD)., Methods: We studied 206 patients with suspected CAD referred to 82 Rb PET/CT cardiac imaging and available coronary angiographic data. The outcome end points were cardiac death, target vessel-related myocardial infarction or coronary revascularization., Results: Compared to vessels without event, those with event showed higher CAC score and ITPD, and lower hyperemic myocardial blood flow and MPR (all p < 0.001). At Cox regression multivariable analysis, significant CAD (≥50% stenosis) (p < 0.001), CAC score ≥ 300 (p < 0.01) and MPR <2 (p < 0.01) were independent predictors of events. The decision trees analysis for the identification of events produced five terminal nodes. The initial split was on CAC score values. For vessels with CAC <300 and MPR ≥2, no further split was performed, while vessels with CAC <300 and MPR <2 were further stratified by ITPD. For vessels with CAC ≥300 a further stratification was performed only by MPR. The worst prognosis was observed in vessels with CAC ≥300 and MPR <2 and in vessels with CAC <300, MPR <2 and ITPD ≥5%., Conclusion: The combination of CAC score and MPR is useful to predict the lesion-related outcome in the presence of significant CAD.

In this study, we sought to investigate the impact of baseline calibration, which is used in quantitative cardiac MRI perfusion analysis to correct for surface coil inhomogeneity and noise, on myocardial perfusion reserve index (MPRI) and its contribution to previously reported paradoxical low MPRI < 1.0 in patients with unobstructed coronary arteries. Semiquantitative perfusion analysis was performed in 20 patients with unobstructed coronary arteries undergoing stress/rest perfusion CMR and in ten patients undergoing paired rest perfusion CMR. The following baseline calibration settings were compared: (1) baseline division, (2) baseline subtraction and (3) no baseline calibration. In uncalibrated analysis, we observed ~ 20% segmental dispersion of signal intensity (SI)-over-time curves. Both baseline subtraction and baseline division reduced relative dispersion of t0-SI (p < 0.001), but only baseline division corrected for dispersion of peak-SI and maximum upslope also (p < 0.001). In the assessment of perfusion indices, however, baseline division resulted in paradoxical low MPRI (1.01 ± 0.23 vs. 1.63 ± 0.38, p < 0.001) and rest perfusion index (RPI 0.54 ± 0.07 vs. 0.94 ± 0.12, p < 0.001), respectively. This was due to a reversed ratio of blood-pool and myocardial baseline-SI before the second perfusion study caused by circulating contrast agent from the first injection. In conclusion, baseline division reliably corrects for inhomogeneity of the surface coil sensitivity profile facilitating comparisons of regional myocardial perfusion during hyperemia or at rest. However, in the assessment of MPRI, baseline division can lead to paradoxical low results (even MPRI < 1.0 in patients with unobstructed coronary arteries) potentially mimicking severely impaired perfusion reserve. Thus, in the assessment of MPRI we propose to waive baseline calibration.

Women with angina and no obstructive coronary artery disease (CAD) have worse cardiovascular prognosis than asymptomatic women. Limitation in myocardial perfusion caused by coronary microvascular dysfunction (CMD) is one of the proposed mechanisms contributing to the adverse prognosis. The aim of this study was to assess myocardial perfusion in symptomatic women with no obstructive CAD suspected for CMD compared with asymptomatic sex-matched controls using static CT perfusion (CTP). We performed a semi-quantitative assessment of the left ventricular myocardial perfusion and myocardial perfusion reserve (MPR), using static CTP with adenosine provocation, in 105 female patients with angina and no obstructive CAD (< 50% stenosis) and 33 sex-matched controls without a history of angina or ischemic heart disease.  Patients were on average 4 years older (p = 0.04) and had a higher burden of cardiovascular risk factors. While global perfusion during rest was comparable between the groups (age-adjusted p = 0.12), global perfusion during hyperemia was significantly reduced in patients compared with controls (163 ± 23 HU vs. 171 ± 25 HU; age-adjusted p = 0.023). The ability to increase myocardial perfusion during adenosine-induced vasodilation was significantly diminished in patients (MPR 148% vs. 158%; age-adjusted p < 0.001). This remained unchanged after adjustment for cardiovascular risk factors (p = 0.008). Women with angina and no obstructive CAD have reduced hyperemic myocardial perfusion and MPR compared with sex-matched controls. Impaired myocardial perfusion may be related to the presence of CMD in some of these women.

Aims: We evaluated the relationship between epicardial adipose tissue (EAT) and coronary vascular function assessed by rubidium-82 (82Rb) positron emission tomography/computed tomography (PET/CT) in patients with suspected coronary artery disease (CAD)., Methods and Results: The study population included 270 patients with suspected CAD and normal myocardial perfusion at stress-rest 82Rb PET/CT. Coronary artery calcium (CAC) score and EAT volume were measured. Absolute myocardial blood flow (MBF) was computed in mL/min/ from the dynamic rest and stress imaging. Myocardial perfusion reserve (MPR) was defined as the ratio of hyperaemic to baseline MBF and it was considered reduced when <2. MPR was normal in 177 (65%) patients and reduced in 93 (35%). Patients with impaired MPR were older (P < 0.001) and had higher CAC score values (P = 0.033), EAT thickness (P = 0.009), and EAT volume (P < 0.001). At univariable logistic regression analysis, age, heart rate reserve (HRR), CAC score, EAT thickness, and EAT volume resulted significant predictors of reduced MPR, but only age (P = 0.002), HRR (P = 0.021), and EAT volume (P = 0.043) were independently associated with reduced MPR, at multivariable analysis. In patients with CAC score 0 (n = 114), a significant relation between EAT volume and MPR (P = 0.014) was observed, while the relationship was not significant (P = 0.21) in patients with CAC score >0 (n = 156)., Conclusion: In patients with suspected CAD and normal myocardial perfusion, EAT volume predicts hyperaemic MBF and reduced MPR, confirming that visceral pericardium fat may influence coronary vascular function. Thus, EAT evaluation has a potential role in the early identification of coronary vascular dysfunction., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Background: Adenosine is used in stress perfusion cardiac imaging to reveal myocardial ischemia by its vasodilator effects. Caffeine is a competitive antagonist of adenosine. However, previous studies reported inconsistent results about the influence of caffeine on adenosine's vasodilator effect. This study assessed the impact of caffeine on the myocardial perfusion reserve index (MPRI) using adenosine stress cardiovascular magnetic resonance imaging (CMR). Moreover, we sought to evaluate if the splenic switch-off sign might be indicative of prior caffeine consumption., Methods: Semiquantitative perfusion analysis was performed in 25 patients who underwent: 1) caffeine-naïve adenosine stress CMR demonstrating myocardial ischemia and, 2) repeat adenosine stress CMR after intake of caffeine. MPRI (global; remote and ischemic segments), and splenic perfusion ratio (SPR) were assessed and compared between both exams., Results: Global MPRI after caffeine was lower vs. caffeine-naïve conditions (1.09 ± 0.19 vs. 1.24 ± 0.19; p <  0.01). MPRI in remote myocardium decreased by caffeine (1.24 ± 0.19 vs. 1.49 ± 0.19; p <  0.001) whereas MPRI in ischemic segments (0.89 ± 0.18 vs. 0.95 ± 0.23; p = 0.23) was similar, resulting in a lower MPRI ratio (=remote/ischemic segments) after caffeine consumption vs. caffeine-naïve conditions (1.41 ± 0.19 vs. 1.64 ± 0.35, p = 0.01). The SPR was unaffected by caffeine (SPR 0.38 ± 0.19 vs. 0.38 ± 0.18; p = 0.92)., Conclusion: Caffeine consumption prior to adenosine stress CMR results in a lower global MPRI, which is driven by the decreased MPRI in remote myocardium and underlines the need of abstinence from caffeine. The splenic switch-off sign is not affected by prior caffeine intake.

Purpose: Combined coronary CT angiography and CT perfusion (CTP) is a novel, non-invasive, 'one-stop' diagnostic tool to rule out ischaemia in patients suspected for coronary artery disease (CAD). However, the normal myocardial perfusion pattern by static CTP in humans is poorly described. We aimed to investigate global and regional myocardial perfusion during rest and adenosine-induced hyperaemia in asymptomatic women without history of coronary heart disease (CHD)., Methods: Using a 320-row CT scanner with a static protocol, semi-quantitative assessment of rest and stress CTP was performed in 34 asymptomatic middle-aged women without obstructive CAD (<50% stenosis) or history of CHD, and with normal exercise stress test and left ventricular (LV) function. Using a 16-segment model, we assessed global and regional values of LV myocardial perfusion reserve (MPR) and transmural perfusion ratio (TPR)., Results: Mean±SD age was 56 ± 13 years. Resting and hyperaemic myocardial perfusion was heterogeneously distributed throughout the LV myocardium. During hyperaemia, global MPR increased by median (IQR) 158% (144-176) with the highest increase in the right coronary artery territory (171%; P<0.02). Rest and stress segmental TPR values ranged between 0.93-1.26 and 0.99-1.13, respectively, with the lowest values detected in the inferoseptal segments. No differences in perfusion parameters were found between participants with normal epicardial arteries and participants with non-significant epicardial atheromatosis (all P>0.05). Global perfusion parameters were not associated with age or menopausal status (all P>0.05)., Conclusions: This descriptive study presents data on global and regional myocardial perfusion in a cohort of healthy middle-aged women., (© 2018 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.)

Background: Non-invasive assessment of myocardial ischaemia is a cornerstone of the diagnosis of coronary artery disease. Measurement of myocardial blood flow (MBF) using positron emission tomography (PET) is the current reference standard for non-invasive quantification of myocardial ischaemia. Dynamic myocardial perfusion cardiovascular magnetic resonance (CMR) offers an alternative to PET and a recently developed method with automated inline perfusion mapping has shown good correlation of MBF values between CMR and PET. This study assessed the repeatability of myocardial perfusion mapping by CMR in healthy subjects., Methods: Forty-two healthy subjects were recruited and underwent adenosine stress and rest perfusion CMR on two visits. Scans were repeated with a minimum interval of 7 days. Intrastudy rest and stress MBF repeatability were assessed with a 15-min interval between acquisitions. Interstudy rest and stress MBF and myocardial perfusion reserve (MPR) were measured for global myocardium and regionally for coronary territories and slices., Results: There was no significant difference in intrastudy repeated global rest MBF (0.65 ± 0.13 ml/g/min vs 0.62 ± 0.12 ml/g/min, p = 0.24, repeatability coefficient (RC) =24%) or stress (2.89 ± 0.56 ml/g/min vs 2.83 ± 0.64 ml/g/min, p = 0.41, RC = 29%) MBF. No significant difference was seen in interstudy repeatability for global rest MBF (0.64 ± 0.13 ml/g/min vs 0.64 ± 0.15 ml/g/min, p = 0.80, RC = 32%), stress MBF (2.71 ± 0.61 ml/g/min vs 2.55 ± 0.57 ml/g/min, p = 0.12, RC = 33%) or MPR (4.24 ± 0.69 vs 3.73 ± 0.76, p = 0.25, RC = 36%). Regional repeatability was good for stress (RC = 30-37%) and rest MBF (RC = 32-36%) but poorer for MPR (RC = 35-43%). Within subject coefficient of variation was 8% for rest and 11% for stress within the same study, and 11% for rest and 12% for stress between studies., Conclusions: Fully automated, inline, myocardial perfusion mapping by CMR shows good repeatability that is similar to the published PET literature. Both rest and stress MBF show better repeatability than MPR, particularly in regional analysis.

Background: Preliminary semi-quantitative cardiovascular magnetic resonance (CMR) perfusion studies have demonstrated reduced myocardial perfusion reserve (MPR) in patients with angina and risk factors for microvascular disease (MVD), however fully quantitative CMR has not been studied. The purpose of this study is to evaluate whether fully quantitative CMR identifies reduced MPR in this population, and to investigate the relationship between epicardial atherosclerosis, left ventricular hypertrophy (LVH), extracellular volume (ECV), and perfusion., Methods: Forty-six patients with typical angina and risk factors for MVD (females, or males with diabetes or metabolic syndrome) who had no obstructive coronary artery disease by coronary angiography and 20 healthy control subjects underwent regadenoson stress CMR perfusion imaging using a dual-sequence quantitative spiral pulse sequence to quantify MPR. Subjects also underwent T1 mapping to quantify ECV, and computed tomographic (CT) coronary calcium scoring to assess atherosclerosis burden., Results: In patients with risk factors for MVD, both MPR (2.21 [1.95,2.69] vs. 2.93 [2.763.19], p < 0.001) and stress myocardial perfusion (2.65 ± 0.62 ml/min/g, vs. 3.17 ± 0.49 ml/min/g p < 0.002) were reduced as compared to controls. These differences remained after adjusting for age, left ventricular (LV) mass, body mass index (BMI), and gender. There were no differences in native T1 or ECV between subjects and controls., Conclusions: Stress myocardial perfusion and MPR as measured by fully quantitative CMR perfusion imaging are reduced in subjects with risk factors for MVD with no obstructive CAD as compared to healthy controls. Neither myocardial hypertrophy nor fibrosis accounts for these differences.

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

Background: Impaired myocardial perfusion reserve (MPR) is prevalent in obesity and diabetes, even in the absence of obstructive coronary artery disease (CAD), and is prognostic of adverse events. We sought to establish the time course of reduced MPR and to investigate associated vascular and tissue properties in mice fed a high-fat diet (HFD), as they are an emerging model of human obesity, diabetes, and reduced MPR without obstructive CAD., Methods: C57Bl/6 mice fed a HFD or a low-fat diet (control) were imaged at 6, 12, 18 and 24 weeks post-diet. The cardiovascular magnetic resonance (CMR) protocol included multi-slice cine imaging to assess ejection fraction (EF), left-ventricular (LV) mass, LV wall thickness (LVWT), and LV volumes, and first-pass perfusion CMR to quantify MPR. Coronary vascular reactivity, aortic atherosclerosis, myocardial capillary density and tissue fibrosis were also assessed., Results: Body weight was increased in HFD mice at 6-24 weeks post-diet (p < 0.05 vs. control). MPR in HFD mice was reduced and LV mass and LVWT were increased in HFD mice at 18 and 24 weeks post-diet (p < 0.05 vs. control). Coronary arteriolar vascular reactivity to adenosine and acetylcholine were reduced in HFD mice (p < 0.05 vs. control). There were no significant differences in cardiac volumes, EF, or capillary density measurements between the two groups. Histology showed interstitial fibrosis in HFD and no aortic atherosclerosis in either group., Conclusions: C57Bl/6 mice fed a HFD for 18-24 weeks have progressively increased LV mass and impaired MPR with fibrosis, normal capillary density and no aortic plaque. These results establish C57Bl/6 mice fed a HFD for 18-24 weeks as a model of impaired MPR without obstructive CAD due to obesity and diabetes.

Unlabelled: Quantification of myocardial perfusion reserve (MPR) is an emerging topic in nuclear cardiology with an expected diagnostic and prognostic incremental value, especially for patients with severe coronary artery disease. The advent of new dedicated solid-state cameras has opened new perspectives for perfusion quantitation in SPECT. We appraised the feasibility of perfusion reserve estimation using a cadmium zinc telluride camera in a cohort of multivessel patients and its pertinence with respect to angiographic data., Methods: Twenty-three patients with known multivessel coronary artery disease were prospectively enrolled. Dynamic SPECT acquisitions using (99m)Tc-tetrofosmin at rest and after vasodilator stress were performed using a dedicated cadmium zinc telluride camera. Reconstructed frames were automatically segmented to extract the vascular input function and the myocardial uptake curve. One-compartment kinetic modeling was used to estimate global and regional uptake values, and then myocardial blood flow was derived using the Renkin-Crone equation. Global and regional MPR was assessed using flow difference (stress - rest) and flow ratio (stress/rest). All patients underwent control coronary angiography within 4 wk, which served as the reference for MPR index assessment. Relevant angiographic findings included maximal stenosis and (for a subgroup of 26 vessels) invasive measurement of fractional flow reserve (FFR). A stenosis was considered obstructive if greater than 50% and an FFR abnormal if lower than 0.8., Results: Global MPR correlated well with number of obstructed vessels (P < 0.001). After multivariate analysis, both regional flow ratio and flow difference were significantly associated with maximal stenosis (P < 0.001) and FFR (P < 0.001). Regional MPR indices were significantly different in obstructed and nonobstructed vessels (P < 0.001) and in vessels with normal and abnormal FFR (P < 0.001). With a cutoff of 2, the sensitivity, specificity, and accuracy of regional flow ratio were, respectively, 80%, 85%, and 81% for the detection of obstructed vessels and 89%, 82%, and 85% for the detection of abnormal FFR., Conclusion: Scintigraphic estimations of global and regional MPR in multivessel patients using a cadmium zinc telluride camera appear to correlate well with invasive angiographic findings, including maximal stenosis and FFR measurements., (© 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Purpose: To investigate and compare several quantification methods of myocardial perfusion measurements, paying special attention to the relation between the techniques and the required measurement duration., Methods: Seven patients underwent contrast-enhanced rest and stress cardiac perfusion measurements at 3T. Three slices were acquired in each patient and were divided into 16 segments, leading to 112 rest and stress data curves, which were analyzed using various tracer kinetic models as well as a model-free deconvolution. Plasma flow, plasma volume, and myocardial perfusion reserve were analyzed for the complete acquisition as well as for the first pass data only., Results: Deconvolution analysis yielded stable results for both rest and stress analysis, while Fermi and one compartment models agree well for first pass data (rest measurements only) and prolonged data acquisition (stress measurements only). More complex models do not yield satisfactory results for the short measurement times investigated in this study., Conclusions: When performing MRI-based quantification of myocardial perfusion, care must be taken that the method used is appropriate for the time frame under investigation. When a numerical deconvolution is used instead of tracer kinetic models, more stable results are obtained., (© 2014 Wiley Periodicals, Inc.)

Objectives: We compared the accuracy of quantified myocardial flow reserve and absolute stress myocardial blood flow (MBF) alone in the detection of coronary artery disease (CAD)., Background: Myocardial flow reserve, i.e. ratio of stress and rest flow, has been commonly used to detect CAD with many imaging modalities. However, it is not known whether absolute stress flow alone is sufficient for detection of significant CAD., Methods: We enrolled 104 patients with moderate (30-70%) pre-test likelihood of CAD without previous myocardial infarction. MBF was measured by positron emission tomography and O-15-water at rest and during the adenosine stress in the regions of the left anterior descending, left circumflex, and right coronary artery. All the patients underwent invasive coronary angiography including the measurement of fractional flow reserve when appropriate., Results: Quantified myocardial flow reserve (optimal cut-off value 2.5) detected significant coronary stenosis with sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 81, 87, 66 and 94%, respectively. When compared with flow reserve, absolute MBF at stress (optimal cut-off value of 2.4 mL/min/g) was more accurate in detecting significant coronary stenosis [area under the curve (AUC) 0.94 vs. 0.90, P = 0.02] with sensitivity, specificity, PPV, and NPV of 95% (P = 0.03 vs. flow reserve), 90, 73, and 98%, respectively. An absolute increase of MBF from rest to stress by <1.5 mL/g/min had also similar accuracy in detecting CAD (AUC: 0.95). The results were comparable in patients who did and did not receive i.v. beta-blockers prior imaging., Conclusions: Absolute stress perfusion alone was superior to perfusion reserve in the detection of haemodynamically significant CAD and allows shorter imaging protocols with smaller radiation dose., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Aortic valve replacement (AVR) leads to reverse cardiac remodeling in patients with aortic stenosis (AS). The aim of this secondary pooled analysis was to assess the degree and determinants of changes in myocardial perfusion post AVR, and its link with exercise capacity, in patients with severe AS. A total of 68 patients underwent same-day echocardiography and cardiac magnetic resonance imaging with adenosine stress pre and 6–12 months post-AVR. Of these, 50 had matched perfusion data available (age 67 ± 8 years, 86% male, aortic valve peak velocity 4.38 ± 0.63 m/s, aortic valve area index 0.45 ± 0.13cm2/m2). A subgroup of 34 patients underwent a symptom-limited cardiopulmonary exercise test (CPET) to assess maximal exercise capacity (peak VO2). Baseline and post-AVR parameters were compared and linear regression was used to determine associations between baseline variables and change in myocardial perfusion and exercise capacity. Following AVR, stress myocardial blood flow (MBF) increased from 1.56 ± 0.52 mL/min/g to 1.80 ± 0.62 mL/min/g (p < 0.001), with a corresponding 15% increase in myocardial perfusion reserve (MPR) (2.04 ± 0.57 to 2.34 ± 0.68; p = 0.004). Increasing severity of AS, presence of late gadolinium enhancement, lower baseline stress MBF and MPR were associated with a greater improvement in MPR post-AVR. On multivariable analysis low baseline MPR was independently associated with increased MPR post-AVR. There was no significant change in peak VO2 post-AVR, but a significant increase in exercise duration. Change in MPR was associated with change in peak VO2 post AVR (r = 0.346, p = 0.045). Those with the most impaired stress MBF and MPR at baseline demonstrate the greatest improvements in these parameters following AVR and the magnitude of change in MPR correlated with improvement in peak VO2, the gold standard measure of aerobic exercise capacity. [ABSTRACT FROM AUTHOR]

Purpose: We evaluated the feasibility of dynamic stress 201Tl/rest 99mTc-tetrofosmin SPECT imaging using a cardiac camera equipped with cadmium-zinc-telluride detectors for the quantification of myocardial perfusion reserve (MPR).Methods: Subjects with stable known or suspected coronary artery disease (CAD) who had undergone or were scheduled to undergo fractional flow reserve (FFR) measurement were prospectively enrolled. Dynamic stress 201Tl/rest 99mTc-tetrofosmin SPECT imaging was performed using a dedicated multiple pinhole SPECT camera with cadmium-zinc-telluride detectors. MPR was derived using Corridor4DM software.Results: A total of 34 subjects were enrolled (25 men and 9 women; mean age 60.4 years). FFR was measured in 65 coronary arteries with intermediate lesions. The average global MPR was 2.58 ± 1.03. Global MPR was associated with the extent of CAD (P = 0.028) and global summed stress score (r = −0.60, P < 0.001). Regional MPR showed a significant correlation with diameter stenosis (r = −0.57, P < 0.001), minimum lumen diameter (r = 0.50, P < 0.001), summed stress score (r = −0.52, P < 0.001) and FFR (r = 0.52, P < 0.001). The area under the receiver operating characteristic curve of MPR for the diagnosis of functionally significant stenosis (FFR ≤0.8) was 0.79 (P < 0.001). The sensitivity and specificity of regional MPR were 67% and 83%, respectively, using a cut-off value of 2.0.Conclusion: Dynamic stress 201Tl/rest 99mTc-tetrofosmin SPECT imaging and quantification of MPR is feasible in patients with stable CAD. The preliminary results of this study in a small number of patients require confirmation in a larger cohort to determine their implications for bolstering the role of SPECT imaging in the diagnosis and risk prediction of CAD. [ABSTRACT FROM AUTHOR]

Background Quantitative assessment of myocardial flow reserve (MFR) by single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is challenging but may facilitate evaluation of multi-vessel coronary artery disease (CAD). Methods We enrolled 153 patients with suspected or known CAD, referred for pharmacological stress MPI. They underwent a 99m Tc-perfusion stress/rest SPECT with an ultrafast cadmium-zinc-telluride (CZT) camera. Dynamic data were acquired and time-activity curves fitted to a 1-tissue compartment analysis with input function. K1 was assigned for stress and rest data. The MFR index (MFR i ) was calculated as K1 stress/K1 at-rest. The findings were validated by invasive coronary angiography in 69 consecutive patients. Results The global MFR i was 1.46 (1.16–1.76), 1.33 (1.12–1.54), and 1.18 (1.01–1.35), for 1-vessel disease (VD), 2-VD, and 3-VD, respectively. In the 3-VD, global MFR i was lower than that in 0-VD (1.63 [1.22–2.04], P < 0.0001) and 1-VD (P = 0.003). Multivariate logistic regression analysis for 3-VD showed significant associations with smoking history (odds ratio [OR]: 4.4 [0.4–8.4]), left ventricular ejection fraction (OR: 61.6 [57.5–66.0]), and global MFR i (OR: 119.6 [111.5–127.7], P = 0.002). A cut-off value of 1.3 yielded 93.3% sensitivity and 75.9% specificity for diagnosing 3-VD. Fractional flow reserve positively correlated with regional MFR i (r = 0.62, P = 0.008), and the SYNTAX score correlated negatively with global MFR i (r = 0.567, P = 0.0003). Conclusion We developed and validated a clinically available method for MFR quantification by dynamic 99m Tc-perfusion SPECT utilizing a CZT camera, which improves the detectability of multi-vessel CAD. [ABSTRACT FROM AUTHOR]

Coronary microvascular dysfunction (CMD) also known as syndrome X, is characterized by typical anginal symptoms, evidence of myocardial ischemia on non-invasive testing and normal to minimal coronary disease on coronary angiography. It has a female preponderance and has been detected in up to 50% of women presenting with chest pain symptoms. Definitive diagnosis of CMD is critical as recent evidence suggests that women with this condition are at increased risk of cardiovascular events in the future. Invasive coronary reactivity testing on coronary angiography is considered to be the 'gold standard' for diagnosis of CMD. Non-invasive imaging techniques such as PET and cardiac magnetic resonance hold promise for detection of CMD in the future. [ABSTRACT FROM AUTHOR]