H2O Positron Emission Tomography Research Articles

Myocardial Blood Flow in Newly Diagnosed Breast Cancer Patients at Rest and During Exercise

Heart depends critically on continuous supply of blood, but it is unknown whether cancer, without any treatments, affects myocardial blood flow (MBF) at rest or during exercise. This study therefore aimed at measuring MBF in cancer patients and control subjects and it was hypothesized that MBF is affected by cancer. The study included recently-diagnosed breast cancer patients (n=18) who had not started their oncologic treatments and age-matched female control participants (n=32). Controls were women referred to cardiac diagnostic testing but who were by this testing judged to be free of obstructive coronary artery disease. MBF was quantified with [15O]H2O positron emission tomography (PET) at rest in both groups and additionally during 10-min supine bicycling exercise in the breast cancer patients. Furthermore, cardiac morphological changes were analyzed with a breast cancer mice-model four weeks after the inoculation of 13TC mammary tumor cells. Respective mice without tumors served as controls. Resting heart rate (HR) and rate pressure product (RPP) correlated positively with resting MBF, but were similar in both groups resulting also in similar resting MBF in cancer patients and controls. MBF increased significantly from rest during exercise in breast cancer patients (p<0.0001) and exercising MBF correlated positively with the histologic grade of cancer (r=0.54, p=0.021). However, cancer grade did not associate with exercise intensity measures such as HR, RPP or HR percentage from age-predicted maximal HR. In the mouse model, the breast cancer did not affect heart weight, cardiomyocyte size, myocardial capillary density, or capillary-to-myocyte size ratio. In conclusion, resting MBF in humans or myocardial capillarity in mice appear not to be affected by breast cancer. However, the more severe is the histologic grade of cancer, the higher is the MBF during exercise in patients with breast cancer, independently of the intensity of the exercise suggesting dysregulation of myocardial blood supply with cancer. This novel finding requires further investigations. This study was financially supported by Academy of Finland and Hospital District of South-West Finland. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Microvascular resistance reserve before and after PCI: A serial FFR and [15O] H2O PET study

Background and aimsMicrovascular Resistance Reserve (MRR) has recently been introduced as a microvasculature-specific index and hypothesized to be independent of coronary stenosis. The aim of this study was to investigate the change of MRR after percutaneous coronary intervention (PCI). MethodsIn this post-hoc analysis from the PACIFC trials, symptomatic patients underwent [15O]H2O positron emission tomography (PET) and invasive fractional flow reserve (FFR) before and after revascularization. Coronary flow reserve (CFR) from PET and invasive FFR were used to calculate MRR. ResultsAmong 52 patients (87 % male, age 59.4 ± 9.4 years), 61 vessels with a median FFR of 0.71 (95 % confidence interval: 0.55 to 0.74) and a mean MRR of 3.80 ± 1.23 were included. Following PCI, FFR, hyperemic myocardial blood flow (hMBF) and CFR increased significantly (all p-values ≤0.001). MRR remained unchanged after PCI (3.80 ± 1.23 before PCI versus 3.60 ± 0.97 after PCI; p=0.23). In vessels with a pre-PCI, FFR ≤0.70 pre- and post-PCI MRR were 3.90 ± 1.30 and 3.73 ± 1.14 (p=0.56), respectively. Similar findings were observed for vessels with a FFR between 0.71 and 0.80 (pre-PCI MRR 3.70 ± 1.17 vs. post PCI MRR 3.48 ± 0.76, p=0.19). ConclusionsOur study indicates that MRR, assessed using a hybrid approach of PET and invasive FFR, is independent of the severity of epicardial stenosis. These findings suggest that MRR is a microvasculature-specific parameter.

Impact of sex on myocardial perfusion following percutaneous coronary intervention of chronic total coronary occlusions

ObjectivesWe sought to investigate the impact of sex on myocardial perfusion changes following chronic total coronary occlusion (CTO) percutaneous coronary intervention (PCI) as measured by [15O]H2O positron-emission tomography (PET) perfusion imaging. BackgroundCTO PCI has been associated with an increase in myocardial perfusion, yet females are less likely to undergo revascularization. As such, data on the impact of sex on myocardial perfusion following CTO PCI is scarce. MethodsA total of 212 patients were prospectively enrolled and underwent CTO PCI combined with [15O]H2O PET perfusion imaging prior to and 3 months after PCI. Hyperemic myocardial blood flow (hMBF, mL·min−1·g−1) and coronary flow reserve (CFR) allocated to the CTO territory were quantitatively assessed. ResultsThis study comprised 34 (16 %) females and 178 (84 %) males. HMBF at baseline did not differ between sexes. Females showed a higher increase in hMBF than males (Δ1.34 ± 0.67 vs. Δ1.06 ± 0.74, p = 0.044), whereas post-PCI hMBF was comparable (2.59 ± 0.85 in females vs. 2.28 ± 0.84 in males, p = 0.052). Female sex was independently associated with a higher increase in hMBF after correction for clinical covariates. CFR increase after revascularization was similar in females and males (Δ1.47 ± 0.99 vs. Δ1.30 ± 1.14, p = 0.711). ConclusionsThe present study demonstrates a greater recovery of stress perfusion in females compared to males as measured by serial [15O]H2O PET imaging. In addition, a comparable increase in CFR was found in females and males. These results emphasize the benefit of performing CTO PCI in both sexes. Clinical perspectiveWhat is new?•CTO PCI has been associated with an increase in myocardial perfusion, yet females are less likely to undergo revascularization.•We found a greater recovery of stress perfusion in females compared to males after CTO PCI as measured by serial [15O]H2O PET imaging, whereas coronary flow reserve was comparable between sexes.•The present study adds to the limited body of evidence on the impact of sex on myocardial perfusion following CTO PCI.What are the clinical implications?•Our findings suggest that recovery of myocardial perfusion following CTO PCI is achievable in both female and male patients.•These results underscore the need to adhere to current guidelines for optimal CTO management in both sexes.•Future studies with standardized preprocedural imaging are warranted to increase our understanding of the impact of sex on changes in myocardial perfusion following CTO PCI.

Guiding early revascularization using [15O]H2O PET myocardial perfusion imaging - Impact of atrial fibrillation.

Myocardial perfusion imaging (MPI) using [15O]H2O positron emission tomography (PET) is used to guide the selection of patients with angina for invasive angiography and possible revascularization. Our study evaluated whether atrial fibrillation (AF): 1) reduces global hyperemic myocardial blood flow (MBF) and 2) whether [15O]H2O PET MPI effectively guides revascularization procedures for patients with ongoing AF. We prospectively recruited 346 patients with angina and persistent or paroxysmal AF referred for baseline/hyperemic [15O]H2O PET MPI. The primary outcome was revascularization within 3 months of MPI. In the analyses, patients were divided into four groups based on whether they had ongoing AF or sinus rhythm (SR) and whether they had previously documented coronary artery disease (CAD) or not. Thus, four groups were compared: SR-noCAD, AF-noCAD, SR-CAD and AF-CAD. Hyperemic MBF was affected by both ongoing AF and prior CAD [MBF (mL/min/g): 2.82 (SR-noCAD) vs. 2.12 (AF-noCAD) vs. 2.22 (SR-CAD) vs. 1.80 (AF-CAD), two-way ANOVA p<0.0001]. In multiple linear regression ongoing AF was independently associated with reduced hyperemic MBF. Every 0.1 mL/min/g decrease in hyperemic MBF was associated with a 23% increase in odds of early revascularization. ROC-analysis of vessel specific hyperemic MBF to predict early revascularization yielded the following areas under the ROC curve (AUC): SR-noCAD: 0.95 (p<0.0001); AF-noCAD: 0.79 (p<0.0001); SR-CAD: 0.78 (p<0.0001); AF-CAD: 0.88 (p<0.0001). Ongoing AF is associated with 19-25 % reduced global hyperemic MBF as measured by [15O]H2O MPI PET. Regardless, vessel specific hyperemic MBF still predicts early revascularization in patients with AF.

Validation of resting full-cycle ratio and diastolic pressure ratio with [15O]H2O positron emission tomography myocardial perfusion

Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are invasive techniques used to evaluate the hemodynamic significance of coronary artery stenosis. These methods have been validated through perfusion imaging and clinical trials. New invasive pressure ratios that do not require hyperemia have recently emerged, and it is essential to confirm their diagnostic efficacy. The aim of this study was to validate the resting full-cycle ratio (RFR) and the diastolic pressure ratio (dPR), against [15O]H2O positron emission tomography (PET) imaging. A total of 129 symptomatic patients with an intermediate risk of coronary artery disease (CAD) were included. All patients underwent cardiac [15O]H2O PET with quantitative assessment of resting and hyperemic myocardial perfusion. Within a 2 week period, coronary angiography was performed. Intracoronary pressure measurements were obtained in 320 vessels and RFR, dPR, and FFR were computed. PET derived regional hyperemic myocardial blood flow (hMBF) and myocardial perfusion reserve (MPR) served as reference standards. In coronary arteries with stenoses (43%, 136 of 320), the overall diagnostic accuracies of RFR, dPR, and FFR did not differ when PET hyperemic MBF < 2.3 ml min−1 (69.9%, 70.6%, and 77.1%, respectively) and PET MPR < 2.5 (70.6%, 71.3%, and 66.9%, respectively) were considered as the reference for myocardial ischemia. Non-significant differences between the areas under the receiver operating characteristic (ROC) curve were found between the different indices. Furthermore, the integration of FFR with RFR (or dPR) does not enhance the diagnostic information already achieved by FFR in the characterization of ischemia via PET perfusion. In conclusion, the novel non-hyperemic pressure ratios, RFR and dPR, have a diagnostic performance comparable to FFR in assessing regional myocardial ischemia. These findings suggest that RFR and dPR may be considered as an FFR alternative for invasively guiding revascularization treatment in symptomatic patients with CAD.

Hemodynamic Failure Staging With Blood Oxygenation Level-Dependent Cerebrovascular Reactivity and Acetazolamide-Challenged (15O-)H2O-Positron Emission Tomography Across Individual Cerebrovascular Territories.

Staging of hemodynamic failure (HF) in symptomatic patients with cerebrovascular steno-occlusive disease is required to assess the risk of ischemic stroke. Since the gold standard positron emission tomography-based perfusion reserve is unsuitable as a routine clinical imaging tool, blood oxygenation level-dependent cerebrovascular reactivity (BOLD-CVR) with CO2 is a promising surrogate imaging approach. We investigated the accuracy of standardized BOLD-CVR to classify the extent of HF. Patients with symptomatic unilateral cerebrovascular steno-occlusive disease, who underwent both an acetazolamide challenge (15O-)H2O-positron emission tomography and BOLD-CVR examination, were included. HF staging of vascular territories was assessed using qualitative inspection of the positron emission tomography perfusion reserve images. The optimum BOLD-CVR cutoff points between HF stages 0-1-2 were determined by comparing the quantitative BOLD-CVR data to the qualitative (15O-)H2O-positron emission tomography classification using the 3-dimensional accuracy index to the randomly assigned training and test data sets with the following determination of a single cutoff for clinical application. In the 2-case scenario, classifying data points as HF 0 or 1-2 and HF 0-1 or 2, BOLD-CVR showed an accuracy of >0.7 for all vascular territories for HF 1 and HF 2 cutoff points. In particular, the middle cerebral artery territory had an accuracy of 0.79 for HF 1 and 0.83 for HF 2, whereas the anterior cerebral artery had an accuracy of 0.78 for HF 1 and 0.82 for HF 2. Standardized and clinically accessible BOLD-CVR examinations harbor sufficient data to provide specific cerebrovascular reactivity cutoff points for HF staging across individual vascular territories in symptomatic patients with unilateral cerebrovascular steno-occlusive disease.

Validation of the resting full-cycle ratio and diastolic pressure ratio through myocardial perfusion imaging with [15O]H2O positron emission tomography

Abstract Background Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are invasive techniques used to evaluate the hemodynamic significance of coronary artery stenosis. These methods have been validated through perfusion imaging techniques and clinical trials. However, new invasive pressure indices that do not require hyperemia have recently emerged, and it is essential to confirm their diagnostic efficacy. Purpose To validate the resting full-cycle ratio (RFR) and the diastolic pressure ratio (dPR), against [15O]H2O positron emission tomography (PET) imaging. Methods A total of 129 symptomatic patients with an intermediate risk of coronary artery disease (CAD) were included. All patients underwent cardiac [15O]H2O PET with quantitative assessment of myocardial perfusion, and within 2 weeks coronary angiography was performed. Intracoronary pressure measurements were obtained in 320 vessels and RFR, dPR, and FFR were computed. In the case of RFR and dPR, values ≤ 0.89, and for FFR, values ≤ 0.8 were classified as abnormal. PET myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) served as reference standards. The index tests and gold standard results were evaluated by blinded researchers. Results Figure 1 shows the diagnostic performance of each ratio in coronary arteries with stenoses (136 of 320 vessels, 38%). The overall diagnostic accuracies of RFR, dPR and FFR did not differ when PET MBF &amp;lt; 2.3 ml · min-1 and PET MPR &amp;lt; 2.5 were considered as the reference standard. No significant differences were observed in the areas under the receiver-operating-characteristic (ROC) curve among the indices (Figure 2). In addition, the indices demonstrated comparable performance when the analysis included all of the vessels. Conclusion The novel non-hyperemic pressure ratios, RFR and dPR, have a diagnostic performance that is comparable to FFR when using [15O]H2O PET to assess myocardial perfusion abnormalities. These findings suggest that RFR and dPR may be considered for clinical use in symptomatic patients with CAD.Figure 1Diagnostic performance;StenosisFigure 2ROC curve analysis;Stenosis

The integration of angio-IMR, QFR and FFR for the detection of ischemia

Abstract Background Fractional flow reserve (FFR) and quantitative flow ratio (QFR) are important tools to assess coronary-specific ischemia, but ischemia may be obscured in the presence of coronary microvascular dysfunction (CMD). Wire free angiography based index of microcirculatory resistance (angio-IMR) might aid in identifying ischemic territories with normal FFR or QFR. Purpose First we sought to validate angio-IMR against invasive resistance indices and [15O]H2O positron emission tomography (PET) derived resistance. Secondly, we investigated whether angio-IMR can help identifying ischemic vessels with normal FFR/QFR. Methods In this PACIFIC 1 and 2 sub study symptomatic patients underwent [15O]H2O PET and invasive coronary angiography with routine three vessel FFR. Invasive hyperemic microvascular resistance (HMR) and IMR were measured in a sub set of patients. A FFR/QFR ≤0.80 and hyperemic myocardial blood flow (hMBF) ≤2.3 ml/min/g were considered ischemic. Microvascular resistance on PET was defined as the ratio of mean distal coronary pressure to MBF. Angio-IMR, QFR and PET analyses were performed by core labs blinded to invasive angiography results. Results Among 259 patients (mean age 61 ± 9 years, 188 (73%) male) 494 vessels were included. Invasive IMR and or HMR were measured in 95 vessels. Angio-IMR did not correlate with invasive HMR/IMR for the right coronary artery (RCA) but correlated weakly with invasive HMR (r=0.39, p=0.03) and moderately (r=0.48, p&amp;lt;0.01) with invasive IMR for the left coronary artery (LCA). The RCA was excluded for further analysis. A very weak correlation between angio-IMR and PET resistance was observed (r=0.17, p&amp;lt;0.01). Territories with ischemia and a normal FFR showed a higher angio-IMR than ischemic territories with reduced FFR (31.3 ± 13.8 vs 22.2 ± 10.3, p&amp;lt;0.01). The same was observed after stratification by QFR/PET results (34.3 ± 15.5 vs 23.9 ± 9.9, p&amp;lt;0.01). Results remained consistent after stratification for diameter stenosis percentage. Conclusions A weak to moderate correlation was found between angio-IMR and invasive resistance indices for the LCA. In territories with an ischemic perfusion angio-IMR was higher in those with a normal FFR/QFR compared to patients with a reduced FFR/QFR. Integration of FFR/QFR and angio-IMR might lead to superior vessel-specific ischemia detection.

Adenosine-induced splenic switch-off on [15O]H2O PET perfusion for the assessment of vascular vasodilatation

BackgroundSplenic switch-off (SSO) is a marker of adequate adenosine-induced vasodilatation on cardiac magnetic resonance perfusion imaging. We evaluate the feasibility of quantitative assessment of SSO in myocardial positron emission tomography (PET) perfusion imaging using [15O]H2O.MethodsThirty patients underwent [15O]H2O PET perfusion with adenosine stress. Time-activity curves, as averaged standardized uptake values (SUVavg), were extracted from dynamic PET for spleen and liver. Maximum SUVavg, stress and rest spleen-to-liver ratio (SLR), and the splenic activity concentration ratio (SAR) were computed. Optimal cut-off values for SSO assessment were estimated from receiver operating characteristics (ROC) curve for maximum SUVavg and SLR. Also, differences between coronary artery disease, myocardial ischemia, beta-blockers, and diabetes were assessed. Data are presented as median [interquartile range].ResultsIn concordance with the SSO phenomenon, both the spleen maximum SUVavg and SLR were lower in adenosine stress when compared to rest perfusion (8.1 [6.5, 9.2] versus 16.4 [13.4, 19.0], p < 0.001) and (0.81 [0.63, 1.08] versus 1.86 [1.73, 2.06], p < 0.001), respectively. During adenosine stress, the SSO effect was most prominent 40–160 s after radiotracer injection. Cut-off values of 12.6 and 1.57 for maximum SUVavg and SLR, respectively, were found based on ROC analysis. No differences in SAR, SLRRest, or SLRStress were observed in patients with coronary artery disease, myocardial ischemia, or diabetes.ConclusionsSSO can be quantified from [15O]H2O PET perfusion and used as a marker for adequate adenosine-induced vasodilatation response. In contrary to other PET perfusion tracers, adenosine-induced SSO is time dependent with [15O]H2O.

Age-Dependent Changes in Regulation of Water Inflow Into the Vitreous Body.

Water inflow into the vitreous body regulated by retinal aquaporin-4 distributed within Müller cells has been observed in mice; however, the changes in this phenomenon with age remain unknown. This study aimed to evaluate whether intravenously injected H2O also flows into the vitreous body of human subjects and to investigate whether water dynamics in the human posterior eye change with age using [15O]H2O positron emission tomography (PET). Forty-six normal adult volunteers underwent [15O]H2O PET, and the standard uptake value (SUV) in the center of the vitreous body after 1000-MBq [15O]H2O administration was assessed. The SUV was fitted to an exponential curve, and y0, the steady state of the SUV, and b, the speed of increase in the SUV, were calculated. The results for patients ranging from in age from 20 to 39, 40 to 59, and 60 to 79 years were compared using analyses of variance followed by Games to Howell tests. For the parameter y0, statistical analysis revealed no statistically significant differences among the three groups. For parameter b, statistical analysis revealed statistically significant differences between the 20 to 39 and 60 to 79 age groups (P = 0.000), the 40 to 59 and 60 to 79 age groups (P = 0.025), and the 20 to 39 and 40 to 59 age groups (P = 0.037). The present study revealed that H2O injected into the vein flows into the human vitreous body and that the speed of increase in water flow into the vitreous body decreases with aging. This study suggests that water dynamics in the posterior eye, or the retinal glymphatic pathway, change significantly with aging.

Prognostic Value of Modified Coronary Flow Capacity Derived From [15O]H2O Positron Emission Tomography Perfusion Imaging.

Coronary flow capacity (CFC) is a measure that integrates hyperemic myocardial blood flow and coronary flow reserve to quantify the pathophysiological impact of coronary artery disease on vasodilator capacity. This study explores the prognostic value of modified CFC derived from [15O]H2O positron emission tomography perfusion imaging. Quantitative rest/stress perfusion measurements were obtained from 1300 patients with known or suspected coronary artery disease. Patients were classified as having myocardial steal (n=38), severely reduced CFC (n=141), moderately reduced CFC (n=394), minimally reduced CFC (n=245), or normal flow (n=482) using previously defined thresholds. The end point was a composite of death and nonfatal myocardial infarction. During a median follow-up of 5.5 (interquartile range, 3.7-7.8) years, the end point occurred in 153 (12%) patients. Myocardial steal (hazard ratio [HR], 6.70 [95% CI, 3.21-13.99]; P<0.001), severely reduced CFC (HR, 2.35 [95% CI, 1.16-4.78]; P=0.018), and moderately reduced CFC (HR, 1.95 [95% CI, 1.11-3.41]; P=0.020) were associated with worse prognosis compared with normal flow, after adjusting for clinical characteristics. Similarly, in the overall population, increased resting myocardial blood flow (HR, 3.05 [95% CI, 1.68-5.54]; P<0.001), decreased hyperemic myocardial blood flow (HR, 0.68 [95% CI, 0.52-0.90]; P=0.007) and decreased coronary flow reserve (HR, 0.55 [95% CI, 0.42-0.71]; P<0.001) were independently associated with adverse outcome. In a model adjusted for the combined use of perfusion metrics, modified CFC demonstrated independent prognostic value (overall P=0.017). [15O]H2O positron emission tomography-derived resting myocardial blood flow, hyperemic myocardial blood flow, coronary flow reserve, and CFC are prognostic factors for death and nonfatal myocardial infarction in patients with known or suspected coronary artery disease. Importantly, after adjustment for clinical characteristics and the combined use of [15O]H2O positron emission tomography perfusion metrics, modified CFC remained independently associated with adverse outcome.

Impact of cardiac history and myocardial scar on increase of myocardial perfusion after revascularization

PurposeWe sought to assess the impact of coronary revascularization on myocardial perfusion and fractional flow reserve (FFR) in patients without a cardiac history, with prior myocardial infarction (MI) or non-MI percutaneous coronary intervention (PCI). Furthermore, we studied the impact of scar tissue.MethodsSymptomatic patients underwent [15O]H2O positron emission tomography (PET) and FFR before and after revascularization. Patients with prior CAD, defined as prior MI or PCI, underwent scar quantification by magnetic resonance imaging late gadolinium enhancement.ResultsAmong 137 patients (87% male, age 62.2 ± 9.5 years) 84 (61%) had a prior MI or PCI. The increase in FFR and hyperemic myocardial blood flow (hMBF) was less in patients with prior MI or non-MI PCI compared to those without a cardiac history (FFR: 0.23 ± 0.14 vs. 0.20 ± 0.12 vs. 0.31 ± 0.18, p = 0.02; hMBF: 0.54 ± 0.75 vs. 0.62 ± 0.97 vs. 0.91 ± 0.96 ml/min/g, p = 0.04). Post-revascularization FFR and hMBF were similar across patients without a cardiac history or with prior MI or non-MI PCI. An increase in FFR was strongly associated to hMBF increase in patients without a cardiac history or with prior MI/non-MI PCI (r = 0.60 and r = 0.60, p < 0.01 for both). Similar results were found for coronary flow reserve. In patients with prior MI scar was negatively correlated to hMBF increase and independently predictive of an attenuated CFR increase.ConclusionsPost revascularization FFR and perfusion were similar among patients without a cardiac history, with prior MI or non-MI PCI. In patients with prior MI scar burden was associated to an attenuated perfusion increase.

A retrospective evaluation of Bayesian-penalized likelihood reconstruction for [15O]H2O myocardial perfusion imaging

BackgroundNew Block-Sequential-Regularized-Expectation-Maximization (BSREM) image reconstruction technique has been introduced for clinical use mainly for oncologic use. Accurate and quantitative image reconstruction is essential in myocardial perfusion imaging with positron emission tomography (PET) as it utilizes absolute quantitation of myocardial blood flow (MBF). The aim of the study was to evaluate BSREM reconstruction for quantitation in patients with suspected coronary artery disease (CAD). Methods and ResultsWe analyzed cardiac [15O]H2O PET studies of 177 patients evaluated for CAD. Differences between BSREM and Ordered-Subset-Expectation-Maximization with Time-Of-Flight (TOF) and Point-Spread-Function (PSF) modeling (OSEM-TOF-PSF) in terms of MBF, perfusable tissue fraction, and vascular volume fraction were measured. Classification of ischemia was assessed between the algorithms. OSEM-TOF-PSF and BSREM provided similar global stress MBF in patients with ischemia (1.84 ± 0.21 g⋅ml−1⋅min−1 vs 1.86 ± 0.21 g⋅ml−1⋅min−1) and no ischemia (3.26 ± 0.34 g⋅ml−1⋅min−1 vs 3.28 ± 0.34 g⋅ml−1⋅min−1). Global resting MBF was also similar (0.97 ± 0.12 g⋅ml−1⋅min−1 and 1.12 ± 0.06 g⋅ml−1⋅min−1). The largest mean relative difference in MBF values was 7%. Presence of myocardial ischemia was classified concordantly in 99% of patients using OSEM-TOF-PSF and BSREM reconstructions ConclusionOSEM-TOF-PSF and BSREM image reconstructions produce similar MBF values and diagnosis of myocardial ischemia in patients undergoing [15O]H2O PET due to suspected obstructive coronary artery disease

The Utility of Arterial Transit Time Measurement for Evaluating the Hemodynamic Perfusion State of Patients with Chronic Cerebrovascular Stenosis or Occlusive Disease: Correlative Study between MR Imaging and 15O-labeled H2O Positron Emission Tomography.

To verify whether arterial transit time (ATT) mapping can correct arterial spin labeling-cerebral blood flow (ASL-CBF) values and to verify whether ATT is a parameter that correlates with positron emission tomography (PET)-oxygen extraction fraction (OEF) and PET-mean transit time (MTT). Eleven patients with unilateral major cerebral artery stenosis or occlusion underwent MRI and PET in the chronic or asymptomatic phase. ASL-MRI acquisitions were conducted with each of two post-label delay (PLD) settings (0.7s and 2.0s) using a pseudo-continuous ASL pulse sequence and 3D-spin echo spiral readout with vascular crusher gradient. ATT maps were obtained using a low-resolution pre-scan approach with five PLD settings. Using the ASL perfusion images and ATT mapping, ATT-corrected ASL-CBF images were obtained. Four kinds of ASL-CBF methods (PLD 0.7s with or without ATT correction and PLD 2.0s with or without ATT correction) were compared to PET-CBF, using vascular territory ROIs. ATT and OEF were compared for all ROIs, unaffected side ROIs, and affected side ROIs, respectively. ATT and MTT were compared by the ratio of the affected side to the unaffected side. Transit time-based ROIs were used for the comparison with ATT. Comparing ASL-CBF and PET-CBF, the correlation was higher with ATT correction than without correction, and for a PLD of 2.0s compared with 0.7s. The best correlation was for PLD of 2.0s with ATT correction (R2 = 0.547). ROIs on the affected side showed a low but significant correlation between ATT and PET-OEF (R2 = 0.141). There was a low correlation between the ATT ratio and the MTT ratio (R2 = 0.133). Low-resolution ATT correction may increase the accuracy of ASL-CBF measurements in patients with unilateral major cerebral artery stenosis or occlusion. In addition, ATT itself might have a potential role in detecting compromised hemodynamic state.

Warranty period of coronary computed tomography angiography and [15O]H2O positron emission tomography in symptomatic patients.

Data on the warranty period of coronary computed tomography angiography (CTA) and combined coronary CTA/positron emission tomography (PET) are scarce. The present study aimed to determine the event-free (warranty) period after coronary CTA and the potential additional value of PET. Patients with suspected but not previously diagnosed coronary artery disease (CAD) who underwent coronary CTA and/or [15O]H2O PET were categorized based upon coronary CTA as no CAD, non-obstructive CAD, or obstructive CAD. A hyperaemic myocardial blood flow (MBF) ≤ 2.3 mL/min/g was considered abnormal. The warranty period was defined as the time for which the cumulative event rate of death and non-fatal myocardial infarction (MI) was below 5%. Of 2575 included patients (mean age 61.4 ± 9.9 years, 41% male), 1319 (51.2%) underwent coronary CTA only and 1237 (48.0%) underwent combined coronary CTA/PET. During a median follow-up of 7.0 years 163 deaths and 68 MIs occurred. The warranty period for patients with no CAD on coronary CTA was ≥10 years, whereas patients with non-obstructive CAD had a 5-year warranty period. Patients with obstructive CAD and normal hyperaemic MBF had a 2-year longer warranty period compared to patients with obstructive CAD and abnormal MBF (3 years vs. 1 year). As standalone imaging, the warranty period for normal coronary CTA is ≥10 years, whereas patients with non-obstructive CAD have a warranty period of 5 years. Normal PET yielded a 2-year longer warranty period in patients with obstructive CAD.

Validation of dynamic [18F]FE-PE2I PET for estimation of relative regional cerebral blood flow: a comparison with [15O]H2O PET

BackgroundDopamine transporter (DAT) imaging is used in the diagnostic work-up in suspected parkinsonian syndromes and dementia with Lewy bodies but cannot differentiate between these syndromes, and an extra brain imaging examination of the regional cerebral blood flow (rCBF) or glucose metabolism is often needed for differential diagnosis. The requirement of two different imaging examinations is resource-consuming and inconvenient for the patients. Therefore, imaging of both cortical blood flow and DAT imaging with the same radiotracer would be more convenient and cost-effective. The aim of this study was to test whether relative regional cerebral blood flow (rCBFR) can be measured with the DAT-specific positron emission tomography (PET) tracer [18F]FE-PE2I (FE-PE2I), by validation with cerebral perfusion measured with [15O]H2O PET (H2O).MethodsThe rCBFR was quantified by kinetic modeling for FE-PE2I (R1) and H2O (F). The R1 was calculated using the simplified reference tissue model, and F was calculated with a modified Koopman double-integration method. The linear relationship and intraclass correlation (ICC) between R1 and F were tested in image data derived from 29 patients with recent onset parkinsonism and 30 healthy controls.ResultsThere was a strong linear correlation across all subjects between R1 and F in the frontal, parietal, temporal, cingulate and occipital cortex as well as in the striatum (r ≥ 0.731–0.905, p < 0.001) with a good-to-excellent ICC, ranging from 0.727 to 0.943 (p < 0.001).ConclusionsOur results suggest that FE-PE2I may be used as a proxy for cerebral perfusion, thus potentially serving as a radiotracer for assessment of both DAT availability and rCBFR in one single dynamic scan. This could be valuable in the differential diagnosis of parkinsonian syndromes.Trial registration: EUDRA-CT 2015-003045-26. Registered 23 October 2015 https://www.clinicaltrialsregister.eu/ctr-search/search?query=2015-003045-26

Incorporating coronary artery calcium scoring in the prediction of obstructive coronary artery disease with myocardial ischemia: a study with sequential use of coronary computed tomography angiography and positron emission tomography imaging

BackgroundAdditional strategies are needed to refine the referral for diagnostic testing of symptomatic patients with suspected coronary artery disease (CAD). We aimed to compare various models to predict hemodynamically obstructive CAD. Methods and resultsSymptomatic patients with suspected CAD who underwent coronary artery calcium scoring (CACS) and sequential coronary computed tomography angiography (CCTA) and [15O]H2O positron emission tomography (PET) myocardial perfusion imaging were analyzed. Obstructive CAD was defined as a suspected coronary artery stenosis on CCTA with myocardial ischemia on PET (absolute stress myocardial perfusion ≤ 2.4 mL/g/min in ≥ 1 segment). Three models were developed to predict obstructive CAD-induced myocardial ischemia using logistic regression analysis: (1) basic model: including age, sex and cardiac symptoms, (2) risk factor model: adding number of risk factors to the basic model, and (3) CACS model: adding CACS to the risk factor model. Model performance was evaluated using discriminatory ability with area under the receiver-operating characteristic curves (AUC). A total of 647 patients (mean age 62 ± 9 years, 45% men) underwent CACS and sequential CCTA and PET myocardial perfusion imaging. Obstructive CAD with myocardial ischemia on PET was present in 151 (23%) patients. CACS was independently associated with myocardial ischemia (P < .001). AUC for the discrimination of ischemia for the CACS model was superior over the basic model and risk factor model (P < .001). ConclusionsAdding CACS to the model including age, sex, cardiac symptoms and number of risk factors increases the accuracy to predict obstructive CAD with myocardial ischemia on PET in symptomatic patients with suspected CAD.

Warranty period of normal CCTA and [15O]H2O PET in chest pain patients

Abstract Background Normal coronary computed tomography angiography (CTA) and positron emission tomography (PET) are associated with an excellent prognosis. Hitherto, data on the warranty period of normal coronary CTA and normal myocardial blood flow (MBF) by PET are scarce. Purpose To determine the event-free period after normal coronary CTA and PET results. In addition, to determine whether PET MBF imaging confers additional prognostic value beyond coronary anatomy in symptomatic patients. Methods Patients with suspected but not previously diagnosed coronary artery disease (CAD) who underwent coronary CTA or [15O]H2O PET were categorized based upon coronary CTA as no CAD, non-obstructive CAD or obstructive CAD. A hyperemic MBF &amp;lt;2.3 ml/min/g was considered abnormal and indicative for ischemia. A cumulative risk below 5% against death and myocardial infarction (MI) was used to define the warranty period. Results Of 2575 included patients (mean age 61.4±9.9 years, 41% male) 1319 (51.2%) underwent coronary CTA only, 1237 (48.0%) underwent both coronary CTA and PET and 19 (0.74%) patients underwent PET imaging only. During a median follow-up of 7.0 years 163 deaths and 68 MIs occurred. The warranty period for patients without any CAD was &amp;gt;10 years. Patients with non-obstructive CAD had a 5 year warranty period. In patients with no, non-obstructive or obstructive CAD on CTA, normal PET extended the warranty period with ≥2 years. The warranty period of patients with non-obstructive CAD or normal perfusion varied between 2.5 and &amp;gt;10 years for patients with or without clinical risk factors. Conclusions As standalone imaging, the warranty period for a normal coronary CTA is &amp;gt;10 years, whereas patients with non-obstructive CAD have a warranty period of 5 years. Independent of coronary anatomy normal perfusion imaging has additional prognostic value and extends the warranty period by ≥2 years. Funding Acknowledgement Type of funding sources: None.

Concordant low and discordant fractional flow reserve and instantaneous wave-free ratio measurements are associated with reduced myocardial perfusion

Abstract Background In patients undergoing invasive coronary angiography with functional lesion assessment, both fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) measurements can be used to guide coronary revascularization decision-making. The hemodynamic significance of lesions with discordant FFR and iFR measurements is debated. Purpose This study compared quantitative myocardial perfusion indices as assessed by [15O]H2O positron emission tomography (PET) perfusion imaging in vessels with concordant high, discordant and concordant low FFR/iFR measurements Methods This post-hoc analysis of the PACIFIC I and II studies included 198 patients suspected of obstructive coronary artery disease who had undergone [15O]H2O PET imaging and subsequent FFR/iFR interrogation in 468 vessels. Resting myocardial blood flow (MBF), hyperemic MBF and coronary flow reserve (CFR) were compared between 4 vessel subgroups: FFR+/iFR+ (n=79), FFR−/iFR+ (n=22), FFR+/iFR− (n=22) and FFR−/iFR− (n=345). Results Discordant FFR/iFR indices were found in 44 (9%) vessels. Hyperemic MBF was significantly lower for vessels with FFR+/iFR+ (2.09±0.67 mL min–1 g–1), FFR−/iFR+ (2.41±0.80 mL min–1 g–1) and FFR+/iFR− (2.40±0.69 mL min–1 g–1) compared to FFR−/iFR− vessels (2.91±0.84 mL min–1 g–1) (p&amp;lt;0.01, p=0.03 and p&amp;lt;0.01, respectively). Hyperemic MBF did not differ between vessels with FFR+/iFR+ compared to FFR−/iFR+ (p=0.38) and FFR+/iFR− (p=0.35) vessels. In addition, resting MBF was lower and CFR did not differ in the FFR+/iFR− versus the FFR−/iFR− group (resting MBF: 0.80±0.16 mL min–1 g–1 vs. 0.90±0.24 mL min–1 g–1, p=0.03 and CFR: 3.05±0.84 vs. 3.35±1.07, p=0.56). Finally, CFR was similar in FFR+/iFR+ and FFR−/iFR+ vessels (2.37±0.76 vs. 2.64±0.84, p=0.92). Conclusions We found lower baseline flow and similar flow reserve in FFR+/iFR− compared to FFR−/iFR− vessels. Importantly, [15O]H2O PET imaging demonstrated reduced hyperemic MBF in vessels with concordant low and discordant FFR and iFR measurements. Funding Acknowledgement Type of funding sources: None.

Prognostic value of coronary flow capacity derived from [15O]H2O positron emission tomography perfusion imaging

Abstract Background Coronary flow capacity (CFC) is a cross-modality framework integrating hyperemic myocardial blood flow (hMBF) and coronary flow reserve (CFR) to quantify the physiological impact of coronary atherosclerotic disease on vasodilator capacity. Purpose This study explores the prognostic value of CFC derived from [15O]H2O positron emission tomography (PET) perfusion imaging in addition to traditional perfusion metrics. Methods Quantitative perfusion measurements were obtained from 1300 patients with suspected or known coronary artery disease who underwent [15O]H2O PET imaging. Patients were classified as having myocardial steal, severely reduced CFC, moderately reduced CFC, minimally reduced CFC or normal flow using previously defined perfusion thresholds. The endpoint was a composite of death and non-fatal myocardial infarction (MI). Results The composite endpoint occurred in 153 (12%) patients during a median follow-up of 5.5 (interquartile range 3.7–7.8) years. Myocardial steal (HR 10.65, 95% CI 4.45–25.49, p&amp;lt;0.001), severely reduced CFC (HR 3.77, 95% CI 1.88–7.58, p&amp;lt;0.001), moderately reduced CFC (HR 2.03, 95% CI 1.25–3.29, p=0.004) and minimally reduced CFC (HR 1.72, 95% CI 1.05–2.81, p=0.030) were independently associated with worse outcome after adjusting for clinical risk factors. Similarly, increased resting MBF (HR 3.19, 95% CI 1.74–5.83, p&amp;lt;0.001), decreased hMBF (HR 0.72, 95% CI 0.57–0.90, p=0.004) and decreased CFR (HR 0.59, 95% CI 0.47–0.73, p&amp;lt;0.001) were significant prognostic factors for events. In a combined perfusion model, only resting MBF (p=0.018) and CFC (overall p=0.012) demonstrated independent prognostic value. Conclusions [15O]H2O PET-derived resting MBF, hMBF, CFR and CFC were prognostic factors for death and non-fatal MI. Notably, in a combined model including all perfusion metrics, only resting MBF and CFC were independently associated with adverse outcome. Funding Acknowledgement Type of funding sources: None.