Measurement Of Myocardial Blood Flow Research Articles

Effect of hypoglycaemia on measures of myocardial blood flow and myocardial injury in adults with and without type 1 diabetes: A prospective, randomised, open-label, blinded endpoint, cross-over study.

AimsThis study examined the effect of experimentally‐induced hypoglycaemia on measures of myocardial blood flow and myocardial injury in adults with, and without, type 1 diabetes.MethodsIn a prospective, randomised, open‐label, blinded, endpoint cross‐over study, 17 young adults with type 1 diabetes with no cardiovascular risk factors, and 10 healthy non‐diabetic volunteers, underwent hyperinsulinaemic‐euglycaemic (blood glucose 4.5–5.5 mmol/L) and hypoglycaemic (2.2–2.5 mmol/L) clamps. Myocardial blood flow was assessed using transthoracic echocardiography Doppler coronary flow reserve (CFR) and myocardial injury using plasma high‐sensitivity cardiac troponin I (hs‐cTnI) concentration.ResultsDuring hypoglycaemia, coronary flow reserve trended non‐significantly lower in those with type 1 diabetes than in the non‐diabetic participants (3.54 ± 0.47 vs. 3.89 ± 0.89). A generalised linear mixed‐model analysis examined diabetes status and euglycaemia or hypoglycaemia as factors affecting CFR. No statistically significant difference in CFR was observed for diabetes status (p = .23) or between euglycaemia and hypoglycaemia (p = .31). No changes in hs‐cTnI occurred during hypoglycaemia or in the recovery period (p = .86).ConclusionsA small change in CFR was not statistically significant in this study, implying hypoglycaemia may require more than coronary vasomotor dysfunction to cause harm. Further larger studies are required to investigate this putative problem.

Practical Guide for Interpreting and Reporting Cardiac PET Measurements of Myocardial Blood Flow: An Information Statement from the American Society of Nuclear Cardiology, and the Society of Nuclear Medicine and Molecular Imaging.

One of the most exciting and useful advances in nuclear cardiology is the opportunity to measure myocardial blood flow (MBF) routinely as part of myocardial perfusion imaging (MPI) with positron emission tomography (PET). Incorporating MBF into the MPI evaluation improves diagnosis and assessment of

Coronary microvascular function is impaired in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare inherited disease caused by NOTCH3 gene mutations. Although the main clinical features reflect brain injury, CADASIL is a systemic microangiopathy, and cardiac involvement has been observed but not systematically assessed. We aimed to study the prevalence and severity of coronary microvascular dysfunction (CMD) in CADASIL patients. Seventeen patients with genetically confirmed CADASIL, aged <60years (mean age 40±9years), with ≤1 cardiovascular risk factor underwent neurological and neuropsychological evaluation, 3T brain magnetic resonance imaging (MRI), 12-lead electrocardiography (ECG), standard echocardiography, and measurement of myocardial blood flow at rest (resting MBF) and of maximal myocardial blood flow following Regadenoson infusion (Reg-MBF) by 13 NH3 positron emission tomography (PET). Coronary flow reserve (CFR) was defined as Reg-MBF/resting MBF. PET results were compared to those of 15 healthy controls who were age and sex matched. Twelve patients (71%) presented migraine, none (53%) had psychiatric disturbances, and one (6%) had a previous stroke. None had cognitive impairment or ECG or echocardiography abnormalities. Both Reg-MBF and CFR were blunted in CADASIL patients compared with controls (Reg-MBF 2.46±0.54 vs. 3.09±0.44ml/g/min, respectively; p<0.01; CFR 2.74±0.36 vs. 3.28±0.66, respectively, p<0.01). No correlations were found between Reg-MBF values and neuropsychological performance or cerebral lesion burden on MRI. CADASIL patients exhibit blunted CFR due to CMD, which can be severe and is independent of the severity of brain lesion load and cognitive performances. CADASIL is a systemic microcirculation disease, and active surveillance of cardiac symptoms should be considered in these patients.

Beneficial effects of exercise training on physical performance in patients with vasospastic angina

AimsIn vasospastic angina (VSA), coronary vasomotion abnormalities could develop not only in epicardial coronary arteries but also in coronary microvessels, where calcium channel blockers (CCBs) have limited efficacy. However, efficacy of exercise training for VSA remains to be elucidated. We thus aimed to examine whether vasodilator capacity of coronary microvessels is impaired in VSA patients, and if so, whether exercise exerts beneficial effects on the top of CCBs. MethodsWe performed 2 clinical protocols. In the protocol 1, we measured myocardial blood flow (MBF) using adenosine-stress dynamic computed tomography perfusion (CTP) in 38 consecutive VSA patients and 17 non-VSA controls. In the protocol 2, we conducted randomized controlled trial, where 20 VSA patients were randomly assigned to either 3-month exercise training group (Exercise group) or Non-Exercise group (n= 10 each). ResultsIn the protocol 1, MBF on CTP was significantly decreased in the VSA group compared with the Non-VSA group (138 ± 6 vs 166 ± 10 ml/100 g/min, P = 0.02). In the protocol 2, exercise capacity was significantly increased in the Exercise group than in the Non-Exercise group (11.5 ± 0.5 to 15.4 ± 1.8 vs 12.6 ± 0.7 to 14.0 ± 0.8 ml/min/kg, P < 0.01). MBF was also significantly improved after 3 months only in the Exercise group (Exercise group, 145 ± 12 to 172 ± 8 ml/100 g/min, P < 0.04; Non-Exercise group, 143 ± 14 to 167 ± 8 ml/100 g/min, P = 0.11), although there were no significant between-group differences. ConclusionsThese results provide the first evidence that, in VSA patients, exercise training on the top of CCBs treatment may be useful to improve physical performance, although its effect on MBF may be minimal.

Related risk factors of PET/CT detected coronary microvascular disease in patients with chest pain and no obstructive coronary artery disease

Objective: To explore the related factors of the coronary microvascular disease (CMD) diagnosed with positron emission tomography(PET)/CT in patients with chest pain and without obstructive coronary artery disease (NOCA). Methods: This study was a single-center retrospective cross-sectional study. Consecutive patients with chest pain and NOCA on coronary angiography, who underwent PET/CT quantitative myocardial blood flow measurements at TEDA International Cardiovascular Hospital from August 2018 to January 2019, were enrolled for this study. The diagnostic criteria for NOCA was the absence of coronary artery diameter stenosis ≥50% on coronary angiography. Clinical data, global left ventricular myocardial blood flow on stress and rest, and the coronary flow reserve (CFR) were analyzed. Patients were divided into two groups according to CFR. Patients with CFR<2 were defined as CMD group, and the rest were classified as control group. Pearson correlation analysis and Logistics regression analysis were used for exploring the risk factors of the CMD. Results: A total of 66 patients, with an mean age of (56.7±9.6) years, were included in the study, including 41 females (62%). There were 20 patients with CMD (30%). Body mass index (BMI) was significantly higher in CND group than in control group ((28.1±3.6) kg/m2 vs. (25.6±3.5) kg/m2, P=0.01). Total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) were also significantly higher in CMD group than in control group ((4.89±1.03) mmol/L vs. (4.30±1.02) mmol/L and (3.23±0.81) mmol/L vs. (2.71±0.95) mmol/L respectively, P=0.038). Pearson correlation analysis showed that CFR was moderately correlated with BMI (r=-0.45, P<0.001), and was weakly correlated with TC and LDL-C (r=-0.271 and r=-0.280, respectively, P<0.05). Multivariate logistic regression analysis showed that BMI (the risk of CMD increased by 1.528 times for every 5 kg/m2 increase in BMI, 95%CI 1.083-5.897, P<0.05) was an independent risk factor of CMD after adjusted by gender, hypertension, diabetic mellites and LDL-C. Conclusion: For patients with NOCA and chest pain, high BMI is independent risk factor of CMD diagnosed by PET/CT.

Coronary microvascular function is impaired in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)

Abstract Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL; OMIM 125310) is a rare inherited disease, caused by NOTCH3 gene mutations. Main clinical manifestations of CADASIL include recurrent subcortical ischemic events, migraine, cognitive impairment and psychiatric disturbances. CADASIL is a systemic microangiopathy and cardiac involvement has been observed in a series of Dutch patients, presenting higher frequency of myocardial infarction compared to non-mutated relatives and general population. In particular, electron microscopic examination of myocardial tissue of a study participant demonstrated CADASIL characteristics. We sought to investigate the relationship between CADASIL and microvascular dysfunction (MVD). Seventeen patients with genetically-confirmed CADASIL, aged &amp;lt;60 years, with ≤1 cardiovascular risk factor (current smoke, diabetes, hypertension, dyslipidemia), recent (&amp;lt;3 months) neurological evaluation with neuropsychological tests and 3 Tesla brain magnetic resonance imaging (MRI) underwent 12-lead ECG, echocardiography, and measurement of maximal myocardial blood flow following Regadenoson infusion (Reg-MBF) by 13NH3positron emission tomography (PET), to investigate the presence of coronary microvascular dysfunction (CMD). Coronary flow reserve (CFR) was defined as Reg-MBF/resting MBF. PET results were compared to those of 15 healthy controls matched for age and sex recruited among a historical cohort of healthy patients. The study was approved by the institutional review board and all the subjects gave informed consent. Mean age was 40±9 years (range 28–57 years); 6 patients (35%) were male. One was a current smoker and 3 ex-smokers; 1 patient was on aspirin, 1 on acetazolamide and 2 on escitalopram, none was taking statins. 12 patients (71%) presented with migraine, 9 (53%) had psychiatric disturbances and 1 (6%) had a previous stroke. Brain MRI showed mild-moderate and severe leukoencephalopathy in 11 (65%) and 5 (29%) patients respectively, lacunes were present in 14 patients and microbleeds in 1; one patient had normal findings. Both Reg-MBF and CFR were blunted in CADASIL patients compared with controls (Reg-MBF 2.46±0.54 versus 3.09±0.44 ml/gr/min respectively, p&amp;lt;0.001; CFR 2.74±0.36 vs. 3.28±0.66, respectively, p&amp;lt;0.01). In 3 male patients (17%), CFR reduction was severe (&amp;lt;2). Segmental Reg-MBF analysis of left ventricular flow showed diffuse hypoperfusion, excluding preferential regional involvement. No correlations were found between Reg-MBF values and neuropsychological performance or cerebral lesion burden, suggesting that neurological and cardiac involvement might be independent in CADASIL. These data represent the first documentation of coronary microvascular involvement in a group of young and mildly symptomatic CADASIL patients, confirming the systemic nature of the disease. This proof of concept study expands our understanding of genetically-driven CMD. Funding Acknowledgement Type of funding source: None

Sub-endocardial and sub-epicardial measurement of myocardial blood flow using 13NH3 PET in man

BackgroundThis study examined whether measuring myocardial blood flow (MBF) in the sub-endocardial (SEN) and sub-epicardial (SEP) layers of the left ventricular myocardium using 13NH3 positron emission tomography (PET) and an automated procedure gives reasonable results in patients with known or suspected coronary artery disease (CAD). MethodsResting and stress 13NH3 dynamic PET were performed in 70 patients. Using ≥ 70% diameter stenosis in invasive coronary angiography (ICA) to identify significant CAD, we examined the diagnostic value of SEN- and SEP-MBF, and coronary flow reserve (CFR) vs. the corresponding conventional data averaged on the whole wall thickness. ResultsICA demonstrated 36 patients with significant CAD. Their global stress average [1.61 (1.26, 1.87) mL·min−1·g−1], SEN [1.39 (1.2, 1.59) mL·min−1·g−1] and SEP [1.22 (0.96, 1.44) mL·min−1·g−1] MBF were significantly lower than in the 34 no-CAD patients: 2.05 (1.76, 2.52), 1.72 (1.53, 1.89) and 1.46 (1.23, 1.89) mL·min−1·g−1, respectively, all P < .005. In the 60 CAD vs. the 150 non-CAD territories, stress average MBF was 1.52 (1.10, 1.83) vs. 2.06 (1.69, 2.48) mL·min−1·g−1, SEN-MBF 1.33 (1.02, 1.58) vs. 1.66 (1.35, 1.93) mL·min−1·g−1, and SEP-MBF 1.07 (0.80, 1.29) vs. 1.40 (1.12, 1.69) mL·min−1·g−1, respectively, all P < .05. Using receiver operating characteristics analysis for the presence of significant CAD, the areas under the curve (AUC) were all significant (P < .0001 vs. AUC = 0.5) and similar: stress average MBF = 0.79, SEN-MBF = 0.75, and SEP-MBF = 0.73. AUC was 0.77 for the average CFR, 0.75 for SEN, and 0.70 for SEP CFR. The stress transmural perfusion gradient (TPG) AUC (0.51) was not significant. However, stress TPG was significantly lower in segments subtended by totally occluded arteries vs. those subtended by sub-total stenoses: 1.10 (0.86, 1.33) vs. 1.24 (0.98, 1.56), respectively, P < .005. ConclusionAutomatic assessment of SEN- and SEP-MBF (and CFR) using 13NH3 PET gives reasonable results that are in good agreement with the conventional average whole wall thickness data. Further studies are needed to examine the utility of layer measurements such as in patients with hibernating myocardium or microvascular disease.

Assessment of Multivessel Coronary Artery Disease Using Cardiovascular Magnetic Resonance Pixelwise Quantitative Perfusion Mapping

ObjectivesThe authors sought to compare the diagnostic accuracy of quantitative perfusion maps to visual assessment (VA) of first-pass perfusion images for the detection of multivessel coronary artery disease (MVCAD). BackgroundVA of first-pass stress perfusion cardiac magnetic resonance (CMR) may underestimate ischemia in MVCAD. Pixelwise perfusion mapping allows quantitative measurement of regional myocardial blood flow, which may improve ischemia detection in MVCAD. MethodsOne hundred fifty-one subjects recruited at 2 centers underwent stress perfusion CMR with myocardial perfusion mapping, and invasive coronary angiography with coronary physiology assessment. Ischemic burden was assessed by VA of first-pass images and by quantitative measurement of stress myocardial blood flow using perfusion maps. ResultsIn patients with MVCAD (2-vessel [2VD] or 3-vessel disease [3VD]; n = 95), perfusion mapping identified significantly more segments with perfusion defects (median segments per patient 12 [interquartile range (IQR): 9 to 16] by mapping vs. 8 [IQR: 5 to 9.5] by VA; p < 0.001). Ischemic burden (IB) measured using mapping was higher in MVCAD compared with IB measured using VA (3VD mapping 100 % (75% to 100%) vs. first-pass 56% (38% to 81%) ; 2VD mapping 63% (50% to 75%) vs. first-pass 41% (31% to 50%); both p < 0.001), but there was no difference in single-vessel disease (mapping 25% (13% to 44%) vs. 25% (13% to 31%). Perfusion mapping was superior to VA for the correct identification of extent of coronary disease (78% vs. 58%; p < 0.001) due to better identification of 3VD (87% vs. 40%) and 2VD (71% vs. 48%). ConclusionsVA of first-pass stress perfusion underestimates ischemic burden in MVCAD. Pixelwise quantitative perfusion mapping increases the accuracy of CMR in correctly identifying extent of coronary disease. This has important implications for assessment of ischemia and therapeutic decision-making.

Comparison of two dipyridamole infusion protocols for myocardial perfusion imaging in subjects with low likelihood of significant obstructive coronary artery disease

BackgroundMyocardial perfusion imaging (MPI) with positron emission tomography allows accurate measurements of myocardial blood flow (MBF). Stress MBF thresholds have been proposed to provide diagnostic and prognostic information in different pathology. Most studies relying on dipyridamole use a 5-minute infusion protocol, while current guidelines recommend a 4-minute infusion. The purpose of this study is to compare the effects of different dipyridamole infusion times on stress MBF. MethodsThe charts of 2,207 patients who underwent rubidium-82 MPI were retrospectively reviewed and 147 subjects with low likelihood of significant coronary artery disease (CAD) defined as calcium score = 0, body mass index < 45 kg·m−2, and summed stress score ≤ 3 were included. Of those, 65 were imaged with a 4-minute dipyridamole infusion (0.56 mg·kg−1) protocol and 82 with a 5-minute protocol (0.70 mg·kg−1). ResultsStress MBF (3.23±0.76 vs 3.02±0.71 mL·min−1·g−1, P = 0.09), myocardial flow reserve (2.70±0.67 vs 2.85±0.74, P = 0.20), and coronary vascular resistance index (30±10 vs 31±9 mmHg × g × min·mL−1, P = 0.38) were not significantly different between the two protocols. The 5-minute protocol was associated with higher prevalence of symptoms (92.7% vs 81.5%, P = 0.04) and greater decrease in systolic blood pressure (− 9 vs − 6 mmHg, P = 0.03). ConclusionsThe 4-minute and 5-minute dipyridamole infusion protocols produce comparable myocardial flow response, hemodynamic changes, and symptoms, in subjects with low likelihood of significant obstructive CAD.

Noninvasive estimation of quantitative myocardial blood flow with Tc-99m MIBI by a compartment model analysis in rat

BackgroundWe aimed to investigate the use of dynamic cardiac planar images to estimate myocardial blood flow (MBF) by a compartment model analysis using time-to-peak (TP) map and compared it by the microsphere technique in rat. Positron emission tomography is considered the gold standard method, but is not available everywhere. By contrast, although myocardial perfusion imaging (MPI) with single-photon tracers is more widely available, it may be difficult to obtain adequate region of interest (ROI) settings. We proposed using the TP map to set the ROI, and hypothesized that this method could facilitate the measurement of absolute MBF by MPI in rat. MethodsTwenty-one normal rats were studied. Dynamic planar images with Tc-99m MIBI were obtained, and input function and cardiac ROIs were set using the obtained TP map. MBF was estimated by a one-compartment model analysis with the Renkin-Crone model and by the microsphere technique. ResultsThe MBFs from these two methods were significantly correlated. A negative proportional bias was observed, but no significant difference was observed between the mean MBFs calculated with each method. ConclusionsMBF estimation by a compartment model analysis using TP map could facilitate absolute MBF measurement in rats.

Quantitative assessment of myocardial blood flow and extracellular volume fraction using 68Ga-DOTA-PET: A feasibility and validation study in large animals

BackgroundHere we evaluated the feasibility of PET with Gallium-68 (68Ga)-labeled DOTA for non-invasive assessment of myocardial blood flow (MBF) and extracellular volume fraction (ECV) in a pig model of myocardial infarction. We also aimed to validate MBF measurements using microspheres as a gold standard in healthy pigs. Methods8 healthy pigs underwent three sequential 68Ga-DOTA-PET/CT scans at rest and during pharmacological stress with simultaneous injection of fluorescent microspheres to validate MBF measurements. Myocardial infarction was induced in 5 additional pigs, which underwent 68Ga-DOTA-PET/CT examinations 7-days after reperfusion. Dynamic PET images were reconstructed and fitted to obtain MBF and ECV parametric maps. ResultsMBF assessed with 68Ga-DOTA-PET showed good correlation (y = 0.96x + 0.11, r = 0.91) with that measured with microspheres. MBF values obtained with 68Ga-DOTA-PET in the infarcted area (LAD, left anterior descendant) were significantly reduced in comparison to remote ones LCX (left circumflex artery, P < 0.0001) and RCA (right coronary artery, P < 0.0001). ECV increased in the infarcted area (P < 0.0001). Conclusion68Ga-DOTA-PET allowed non-invasive assessment of MBF and ECV in pigs with myocardial infarction and under rest-stress conditions. This technique could provide wide access to quantitative measurement of both MBF and ECV with PET imaging.

A rapid protocol to evaluate coronary flow reserve with myocardial scintigraphy: A prospective study using Regadenoson

Cardiac positron emission tomography (PET) is superior to single-photon emission computed tomography (SPECT) thanks to its quantitative analysis capabilities, especially for measuring myocardial blood flow (MBF) and myocardial flow reserve (MFR). The recent development of new cadmium zinc telluride (CZT) gamma cameras has enabled dynamic acquisition, allowing measurement of MBF and MFR. This prospective study aimed to determine the fastest protocol, to analyse MBF and perfusion imaging. Methods and resultsFrom February to June 2018, 10 patients were referred to our centre and prospectively enrolled in our study to evaluate the MBF and MFR, with 5 different reconstruction list-mod. The primary endpoint was to assess the reproducibility of the different reconstruction, and time of acquisition. The secondary endpoint was the evaluation of the image quality of the MPI. The 6-min tests highlighted no significant difference in the flow measurement and MFR (P=0,15). Differences become significant by decreasing acquisition time. The image quality did not differ significantly (P=0.6). ConclusionWe determined a fast (12mn acquisition) reliable and reproducible protocol to evaluate MBF and MFR without any loss of MPI information.

Study of the Effect of Reconstruction Parameters for Myocardial Perfusion Imaging in PET With a Novel Flow Phantom

Myocardial perfusion imaging (MPI) with positron emission tomography (PET) allows quantitative temporal measurements of the radioactive tracer distribution in tissue. The quantification for myocardial blood flow (MBF) is conducted with kinetic modelling of the image-derived time-activity curves (TACs) allowing derivation for MBF in units of mL/min per gram of tissue. The ordered-subset expectation maximization (OSEM) reconstruction algorithm with time-of-flight (TOF) and point spread function (PSF) modelling is now routinely employed in cardiac imaging. However, the varying counting statistics of the MPI measurements conducted with short-lived tracers present a challenge for the PET image reconstruction methods. Thus, the effect of the reconstruction methods on the flow quantification needs to be evaluated in a standardized manner. Recently, a novel PET flow phantom modelling the MBF has been developed for investigation of the standardization of the MBF measurements. In this study, the effect of the reconstruction parameters on the image-derived flow values against a known reference flow of the flow phantom was studied with [15O]H2O. The effects were studied by comparison of TACs and relative errors of the image-derived flow values with respect to the phantom-derived reference flow value using 5 repeated PET scans with fixed acquisition parameters using a digital Discovery MI PET/CT system. The reconstruction methods applied were OSEM using both TOF and PSF (OSEM-TOF-PSF) with several matrix sizes (128x128, 192x192, 256x256, 384x384), Gaussian filter sizes (4 mm, 8mm) and OSEM without TOF and PSF (OSEM), with TOF (OSEM-TOF) and with PSF (OSEM-PSF) in addition to recently introduced regularized reconstruction method based on Bayesian-penalized maximum likelihood (Q.Clear). Between repeated measurements, the image-derived flow values showed high repeatability with a SD less than 2 mL/min as well as high accuracy with the maximum error of 7 % with respect to the reference flow for all reconstructions. Overall, reconstruction settings had only a small impact on the resulting flow values. In conclusion, due to the small differences detected, any of the implemented reconstruction algorithms on the system can be applied in MPI studies for accurate flow quantification.

3D PET/CT 82Rb PET myocardial blood flow quantification: comparison of half-dose and full-dose protocols.

Quantification of myocardial blood flow (MBF) has become central in the clinical application of Rubidium-82 (82Rb) PET myocardial perfusion scans. Current recommendations suggest injections of 1100-1500MBq of 82Rb in bolus form, which poses a potential risk of PET system saturation on most 3D PET/CT systems currently being used. We aimed to evaluate the frequency and impact of PET system saturation and to test the potential use of a half-dose acquisition protocol. This study comprised 20 patients who underwent repeated rest scans in a single imaging session, one employing a full-dose (FD), and the other scan a half-dose (HfD) protocol. Datasets were evaluated for saturation based on visual assessments of input functions and sinograms. We compared FD and HfD MBF measurements using Bland-Altman plots, coefficients of variation (CV), and paired t tests. A correction factor permitting serial analyses using FD/HfD imaging protocols was obtained using only the datasets without saturation. A dose reduction of 47% was reported for the HfD protocol (FD, 1247 ± 196MBq; HfD, 662 ± 115MBq). Saturation effects were observed in 4/20 (20%) FD scans, with none observed in the 20 HfD scans. Assessment of MBFs for FD and HfD protocols revealed bias in the MBF assessments of 0.09ml/g/min (global MBF, FD = 1.03 ± 0.29 vs HfD = 0.94 ± 0.22ml/g/min (p = 0.001)). Exclusion of patients with visually identified saturation effects (N = 4) reduced the bias to 0.05ml/g/min (global MBF, FD = 0.97 ± 0.28 vs HfD = 0.92 ± 0.23ml/g/min (p = 0.02)). From the datasets without saturation effect, it was possible to generate a bias-correction: Corrected MBFHfD = 1.09*MBFHfD-0.03ml/g/min. MBFFD and MBFHfD did not differ following the bias correction (MBFFD = 0.97 ± 0.28, MBFHfD,corrected = 0.98 ± 0.25ml/g/min, p = 0.77). Saturation effects can be problematic in 82Rb MBF studies using the recommended FD protocols for 3D PET/CT scanners. The use of HfD protocol eliminates the risks of saturation and should be used instead of clinical protocols to avoid erroneous results.

Reduced myocardial blood flow reserve in kidney transplant candidates may hamper risk stratification.

Vasodilator nuclear stress testing is frequently ordered for risk stratification prior to kidney transplantation. Since 82Rb-positron emission tomography-computed tomography can measure myocardial blood flow (MBF), the response to vasodilator stress can be verified rendering the results of the scan more reliable. We reviewed the MBF response to dipyridamole infusion in 328 patients with end-stage kidney disease (ESKD) prior to transplant (188 hemodialysis-HD, 120 peritoneal dialysis-PD, and 20 pre-dialysis patients-CKD5) and in 100 controls with normal kidney function. A stress/rest MBF ratio ≥ 2 was considered an adequate response to dipyridamole. Coronary artery calcium (CAC) was measured on CT. Inadequate MBF response was seen in 36%-HD, 21%-PD, 45%-CKD5 vs. 23%-controls (p = 0.006). Univariable predictors of poor MBF response in ESKD patients were age, diabetes mellitus, and CAC (all p < 0.03) while serum hemoglobin was borderline significant (p = 0.052). Multivariable predictors of a poor MBF response were age (p = 0.002) and lower serum hemoglobin (p = 0.014). Ischemia was identified in 8% of ESKD patients and 24% of controls (p < 0.001). ESKD patients are less likely to respond appropriately to vasodilator stress compared to patients with normal renal function and had a lower incidence of ischemia despite a high pre-test probability of disease. Physicians performing vasodilator stress without MBF measurement should be aware of the high probability of a false negative response.

Myocardial Perfusion Imaging Using Positron Emission Tomography.

Coronary artery disease (CAD), also known as ischemic heart disease, is a major cause of morbidity and mortality worldwide, and timely noninvasive diagnosis of clinical and subclinical CAD is imperative to mitigate its burden on individual patients and populations. Positron emission tomography (PET) is a versatile tool that can perform relative myocardial perfusion imaging (MPI) with high accuracy; furthermore, it provides valuable information about the coronary microvasculature using rest and stress myocardial blood flow (MBF) and coronary flow reserve (CFR) measurements. Several radiotracers are approved by the US Food and Drug Administration to help with MPI, MBF, and CFR evaluation. A large body of evidence indicates that evaluation of the coronary microcirculation using MBF and CFR provides strong diagnostic and prognostic data in a multitude of patient populations. This review describes the technical aspects of PET compared to other modalities and discusses its clinical uses for diagnosis and prognosis of coronary arterial epicardial and microcirculatory disease.

Test-Retest Precision of Myocardial Blood Flow Measurements With 99mTc-Tetrofosmin and Solid-State Detector Single Photon Emission Computed Tomography.

Measurement of myocardial blood flow (MBF) with single photon emission computed tomography (SPECT) is feasible using cardiac cameras with solid-state detectors. SPECT MBF has been shown to be accurate when compared with positron emission tomography MBF measured in the same patients. However, the value of a test result applied to an individual patient depends strongly on the precision or repeatability of the test. The purpose of our study is to measure the precision of SPECT MBF measurements using 99mTc-tetrofosmin and a solid-state cardiac camera. SPECT MBF was measured in 30 patients and repeated at a mean interval of 18 days. MBF was evaluated from images with and without attenuation correction based on a separately acquired CT scan. The dynamic images were processed independently by 2 operators using in-house kinetic analysis software that applied a 1-tissue-compartment model. The K1 rate constant was converted to MBF using previously determined extraction fraction corrections. Correction for patient body motion was applied manually. The average coefficient of variation (COV) in the differences between the 2 MBF measurements was between 28% and 31%. The interobserver COV was between 11% and 15%. Myocardial flow reserve is the ratio of MBF measured at stress and rest, and the COV is correspondingly higher. The COV for the difference in repeated myocardial flow reserve was 33% to 38%, whereas the interobserver COV was 13% to 22%. The COV for the difference in SPECT MBF measurements obtained on separate days is 28% to 31%. The corresponding COV for myocardial flow reserve is 33% to 38%.

Microvascular Angina Diagnosed by Absolute PET Myocardial Blood Flow Quantification.

The aim of this review is to provide an update on the use of positron emission tomography (PET) with myocardial blood flow (MBF) quantification for the diagnosis and management of patients with microvascular disease. It is now recognized that a large proportion of patients with classical angina and non-obstructive epicardial disease are suffering from microvascular angina. Microvascular angina shares several key features with epicardial coronary disease, including many risk factors. Clinical criteria for the diagnosis of microvascular angina were recently proposed and PET imaging is called to play a central role in evaluation of these patients. Indeed, PET allows non-invasive measurements of MBF and flow reserve, which are altered in microvascular dysfunction. Furthermore, PET with flow quantification provides independent prognostic information and has the potential to monitor response to therapy in microvascular disease. PET with MBF quantification allows detection of microvascular dysfunction and plays a key role in the investigation of patients with suspected microvascular angina.

Preclinical Validation of a Single-Scan Rest/Stress Imaging Technique for 13N-Ammonia Positron Emission Tomography Cardiac Perfusion Studies.

We previously proposed a technique for quantitative measurement of rest and stress absolute myocardial blood flow (MBF) using a 2-injection single-scan imaging session. Recently, we validated the method in a pig model for the long-lived radiotracer 18F-Flurpiridaz with adenosine as a pharmacological stressor. The aim of the present work is to validate our technique for 13NH3. Nine studies were performed in 6 pigs; 5 studies were done in the native state and 4 after infarction of the left anterior descending artery. Each study consisted of 3 dynamic scans: a 2-injection rest-rest single-scan acquisition (scan A), a 2-injection rest/stress single-scan acquisition (scan B), and a conventional 1-injection stress acquisition (scan C). Variable doses of adenosine combined with dobutamine were administered to induce a wide range of MBF. The 2-injection single-scan measurements were fitted with our nonstationary kinetic model (MGH2). In 4 studies, 13NH3 injections were paired with microsphere injections. MBF estimates obtained with our method were compared with those obtained with the standard method and with microspheres. We used a model-based method to generate separate rest and stress perfusion images. In the absence of stress (scan A), the MBF values estimated by MGH2 were nearly the same for the 2-radiotracer injections (mean difference: 0.067±0.070 mL·min-1·cc-1, limits of agreement: [-0.070 to 0.204] mL·min-1·cc-1), showing good repeatability. Bland-Altman analyses demonstrated very good agreement with the conventional method for both rest (mean difference: -0.034±0.035 mL·min-1·cc-1, limits of agreement: [-0.103 to 0.035] mL·min-1·cc-1) and stress (mean difference: 0.057±0.361 mL·min-1·cc-1, limits of agreement: [-0.651 to 0.765] mL·min-1·cc-1) MBF measurements. Positron emission tomography and microsphere MBF measurements correlated closely. Very good quality perfusion images were obtained. This study provides in vivo validation of our single-scan rest-stress method for 13NH3 measurements. The 13NH3 rest/stress myocardial perfusion imaging procedure can be compressed into a single positron emission tomography scan session lasting less than 15 minutes.

P361 Assessment of accuracy and reproducibility of coronary flow reserve measured by SPECT in patients with known or suspected coronary artery disease

Abstract Funding Acknowledgements Spectrum Dynamics Background Traditional relative assessment of regional myocardial perfusion by single photon emission computed tomography (SPECT) has limited ability to identify multivessel coronary artery disease, as well as diffuse atherosclerosis and coronary microvascular dysfunction. Current gamma cameras with cadmium-zinc-telluride (CZT) detectors have higher temporal resolution and sensitivity and allow the acquisition of multi-frame images and quantification of absolute myocardial blood flow (MBF) and coronary flow reserve (CFR Purpose The aim of this study was to assess the accuracy and reproducibility of quantitative measurements of MBF and CFR obtained with a CZT SPECT system compared to PET in a cohort of patients with known or suspected coronary artery disease. Methods Accuracy was assessed in 22 patients who underwent dynamic rest/stress 99mTc-sestamibi-SPECT and 13N-ammonia PET myocardial perfusion imaging within two weeks of each other. Fourteen patients comprised the reproducibility cohort and underwent two dynamic 99mTc-sestamibi SPECT scans within two weeks. A rest/pharmacological stress single-day SPECT protocol was performed, using a 1:3 dose ratio. SPECT image reconstruction was performed using a spline-fitting method and SPECT MBF was quantified using a net retention kinetic model in commercially available software. Rest MBF and CFR were adjusted for heart-rate pressure product. Results Global MBF at rest and stress showed a good correlation between SPECT and PET (r = 0.814, p &amp;lt; 0.001). For global rest MBF the mean difference between the two techniques was -0.25 ± 0.24 ml/min/g, while for stress MBF mean difference was -0.21 ± 0.40 ml/min/g. We also observed a significant correlation between global SPECT and PET CFR measurements (r = 0.745, p &amp;lt; 0.001), with no significant difference between the two (mean difference: 0.16 ± 0.50). Regarding the reproducibility cohort, the correlation between global CFR measured by two SPECT scans was also significant (r = 0.616, p = 0.019), with a mean difference of 0.14 ±0.51. The mean difference between scans for rest MBF (-0.05 ± 0.19) and stress MBF (0.01 ± 0.42) were also not significant. Conclusion MBF and CFR quantification is feasible using a CZT gamma camera and provides accurate and reproducible results that correlate with 13N-ammonia PET. This may be of special relevance in sites where PET is not available, enabling MBF and CFR quantification with CZT SPECT cameras. Abstract P361 Figure.