H2O Positron Emission Tomography Research Articles

Abstract 10176: Absolute Perfusion Increase in Remote Myocardium Following Chronic Total Coronary Occlusion Percutaneous Coronary Intervention

Introduction: Successful revascularization of a chronic total coronary occlusion (CTO) impacts coronary physiology of the remote myocardial territory. This study evaluated the impact of CTO percutaneous coronary intervention (PCI) on absolute perfusion in remote myocardium. Methods: A total of 164 patients underwent serial [ 15 O]H 2 O positron emission tomography (PET) perfusion imaging at baseline and 3 months after successful CTO PCI to evaluate changes in hyperemic myocardial blood flow (hMBF) and coronary flow reserve (CFR) in remote myocardium subtended by non-target collateral donor coronary arteries. Results: Absolute perfusion indices in the CTO and remote myocardium showed a positive linear correlation before (hMBF: r=0.75, p<0.01; CFR: r=0.77, p<0.01) and after (hMBF: r=0.87, p<0.01; CFR: r=0.81, p<0.01) CTO PCI. An increase in absolute myocardial perfusion (hMBF: 2.29±0.67 to 2.48±0.75 mL·min -1 ·g -1 , p<0.01; CFR: 2.48±0.76 to 2.74±0.85, p<0.01) was observed in the remote myocardial territory between baseline and follow-up. Improvements in remote myocardial perfusion were largest in patients with higher increases in hMBF (β 0.55, 95% CI: 0.46-0.64, p<0.01) and CFR (β 0.52, 95% CI: 0.43-0.61, p<0.01) in the CTO territory, independent of clinical, angiographic and procedural characteristics. Furthermore, lower baseline (hMBF: p<0.01; CFR: p<0.01) and higher post-PCI perfusion (hMBF: p<0.01; CFR: p<0.01) in both the remote and CTO territory were associated with larger perfusion increases in remote myocardium. Conclusions: Baseline and post-PCI perfusion indices in remote and CTO myocardium were positively correlated. An overall increase in remote myocardial perfusion was observed following CTO PCI and the absolute perfusion increase in the CTO territory was an independent predictor of remote myocardial perfusion improvement. Successful CTO PCI impacts coronary hemodynamics in the closely interlinked CTO and remote myocardium.

Machine learning from quantitative coronary computed tomography angiography predicts ischemia and impaired myocardial blood flow

Abstract Background Atherosclerotic plaque characteristics influence the hemodynamic consequences of coronary lesions. This study sought to assess the performance of a machine learning (ML) score integrating coronary computed tomography angiography (CCTA)-based quantitative plaque features for the prediction of ischemia by invasive fractional flow reserve (FFR) and impaired myocardial blood flow (MBF) by [15O]H2O positron emission tomography (PET). Methods This post-hoc analysis of the PACIFIC (Prospective Comparison of Cardiac PET/CT, SPECT/CT Perfusion Imaging and CT Coronary Angiography With Invasive Coronary Angiography) trial included 208 patients with suspected coronary artery disease who underwent CCTA, [15O]H2O PET, and 3-vessel invasive FFR. Plaque quantification from CCTA was performed using semiautomated software. A boosted ensemble ML algorithm (XGBoost) trained on data from the NXT (Analysis of Coronary Blood Flow using CT Angiography: Next Steps) trial was used to develop a ML score for the prediction of per-vessel ischemia (invasive FFR ≤0.80). The performance of the ML score was evaluated in 551 vessels from the PACIFIC trial for external validation. Thereafter, we assessed the discriminative ability of the ML score for per-vessel impaired hyperemic MBF (≤2.30 mL/min/g). Results In total, 138 (25.0%) vessels had ischemia and 195 (35.4%) vessels had impaired hyperemic MBF. CCTA-derived quantitative percent diameter stenosis and low-density noncalcified plaque (LDNCP) volume were higher in ischemic vessels compared with non-ischemic vessels (60.8% vs. 19.9%; and 42.3 mm3 vs. 9.1 mm3; both p<0.001). The ML score demonstrated a significantly higher area under the receiver-operating characteristic curve (AUC) for predicting ischemia (0.92, 95% confidence interval [CI] 0.89–0.94) compared with visual stenosis grade (0.84, 95% CI 0.80–0.87; p<0.001). Overall, quantitative percent diameter stenosis and LDNCP volume had greatest feature importance for ML, followed by percent area stenosis, minimum luminal diameter, and contrast density drop (Figure 1). An individualized explanation of ML ischemia prediction is shown in Figure 2. When applied for impaired MBF discrimination, the ML score exhibited an AUC of 0.82 (95% CI 0.78–0.85) and was superior to visual stenosis grade (AUC 0.76, 95% CI 0.72–0.80; p=0.03). Conclusions An externally validated ML score integrating CCTA-based quantitative plaque features accurately predicts FFR-defined ischemia and abnormal MBF by PET, outperforming standard visual CCTA interpretation. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Heart, Lung, and Blood Institute, United States Performance of the ML scoreIndividual explanation of ML prediction

The effect of chronic total coronary occlusion percutaneous coronary intervention on absolute perfusion in remote myocardium

Abstract Background Successful revascularization of a chronic total coronary occlusion (CTO) impacts coronary physiology of the remote myocardial territory. Purpose This study evaluated the effect of CTO percutaneous coronary intervention (PCI) on changes in absolute perfusion in remote myocardium as assessed by serial [15O]H2O positron emission tomography (PET) perfusion imaging. Methods A total of 164 patients underwent [15O]H2O PET imaging at baseline and 3 months after successful single-vessel revascularization of a CTO to evaluate changes in hyperemic myocardial blood flow (hMBF) and coronary flow reserve (CFR) in the remote myocardial territory supplied by both non-target coronary arteries. Results Remote hMBF and CFR improved (2.29±0.67 to 2.48±0.75 mL min–1 g–1 and 2.48±0.76 to 2.74±0.85, respectively) after CTO revascularization (p<0.01 for both). Absolute perfusion indices in the CTO vessel and the remote myocardium showed a positive linear correlation, both before (r=0.75, p<0.01 and r=0.77, p<0.01 for hMBF and CFR, respectively) and after (hMBF: r=0.87, p<0.01 and CFR: r=0.81, p<0.01) CTO PCI. Absolute increases in remote myocardial perfusion were largest in patients with a higher increase in hMBF (βeta [β] 0.56; 95% CI: 0.47–0.65; p<0.01) and CFR (β 0.51 (0.42–0.60); p<0.01) in the CTO territory, independent of clinical, angiographic and procedural characteristics. Furthermore, baseline (hMBF: β −0.24 (−0.39, −0.08); p<0.01 and CFR: β −0.26 (−0.41, −0.11); p<0.01) and post-PCI perfusion (hMBF: β 0.36; (0.27, 0.46); p<0.01 and CFR: β 0.30 (0.21, 0.40); p<0.01) in the CTO vessel were independently associated with the increase in remote myocardial perfusion after CTO PCI. Conclusions An overall increase in remote myocardial perfusion was observed following CTO PCI. Absolute perfusion indices in the remote myocardium showed a positive linear correlation with perfusion in the CTO vessel, before and after CTO revascularization. Importantly, baseline, post-PCI and the absolute increase in perfusion in the CTO territory were independently associated with increases in remote myocardial perfusion after revascularization. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2

A 7-year warranty period for chest pain patients with a non-ischaemic [15O]H2O positron emission tomography: a follow-up of 273 individuals

Abstract Funding Acknowledgements Type of funding sources: None. Background A normal perfusion scan is associated with a favourable outcome. The aim of the present study is to determine the warranty period of normal hyperemic myocardial blood flow (MBF) derived with quantitative [15O]H2O positron emission tomography (PET) in symptomatic individuals with cardiovascular risk factors. Methods A total of 539 patients referred for baseline adenosine [15O]H2O PET MBF imaging because of suspected coronary artery disease (CAD) were investigated. A PET scan was considered normal if the hyperemic MBF was > 2.3 ml/min/g. The warranty period was predefined as < 2% annual event rate. The primary endpoint was a composite of late revascularizations, myocardial infarction and all-cause mortality. Results In a total of 273 patients (mean age 57.2 ± 9.1; 34.4% male) with a normal PET scan, 19 events occurred during a median follow-up of 6.8 years (interquartile range 4.9-7.7). Events included 10 late revascularizations, 2 myocardial infarctions and 7 deaths. The annual event rate exceeded 2% in the 8th year of follow-up, resulting in a warranty period of 7 years (see Figure 1). Conclusion In patients referred for suspected CAD a normal hyperemic perfusion derived by [15O]H2O PET confers a 7-year warranty period against late revascularization, myocardial infarction and all-cause mortality.

Deep-learning-based attenuation correction in dynamic [15O]H2O studies using PET/MRI in healthy volunteers

Quantitative [15O]H2O positron emission tomography (PET) is the accepted reference method for regional cerebral blood flow (rCBF) quantification. To perform reliable quantitative [15O]H2O-PET studies in PET/MRI scanners, MRI-based attenuation-correction (MRAC) is required. Our aim was to compare two MRAC methods (RESOLUTE and DeepUTE) based on ultrashort echo-time with computed tomography-based reference standard AC (CTAC) in dynamic and static [15O]H2O-PET. We compared rCBF from quantitative perfusion maps and activity concentration distribution from static images between AC methods in 25 resting [15O]H2O-PET scans from 14 healthy men at whole-brain, regions of interest and voxel-wise levels. Average whole-brain CBF was 39.9 ± 6.0, 39.0 ± 5.8 and 40.0 ± 5.6 ml/100 g/min for CTAC, RESOLUTE and DeepUTE corrected studies respectively. RESOLUTE underestimated whole-brain CBF by 2.1 ± 1.50% and rCBF in all regions of interest (range −2.4%– −1%) compared to CTAC. DeepUTE showed significant rCBF overestimation only in the occipital lobe (0.6 ± 1.1%). Both MRAC methods showed excellent correlation on rCBF and activity concentration with CTAC, with slopes of linear regression lines between 0.97 and 1.01 and R2 over 0.99. In conclusion, RESOLUTE and DeepUTE provide AC information comparable to CTAC in dynamic [15O]H2O-PET but RESOLUTE is associated with a small but systematic underestimation.

Machine Learning From Quantitative Coronary Computed Tomography Angiography Predicts Ischemia And Impaired Myocardial Blood Flow

Introduction: Atherosclerotic plaque characteristics may influence the hemodynamic consequences of coronary lesions. This study sought to assess the performance of a machine learning (ML) score integrating coronary computed tomography angiography (CCTA)-based quantitative plaque features for the prediction of ischemia by invasive fractional flow reserve (FFR) and impaired myocardial blood flow (MBF) by [15O]H2O positron emission tomography (PET).

Ischemic Burden Reduction and Long-Term Clinical Outcomes After Chronic Total Occlusion Percutaneous Coronary Intervention

The authors sought to evaluate the impact of ischemic burden reduction after chronic total occlusion (CTO) percutaneous coronary intervention (PCI) on long-term prognosis and cardiac symptom relief. The clinical benefit of CTO PCI is questioned. In a high-volume CTO PCI center, 212 patients prospectively underwent quantitative [15O]H2O positron emission tomography perfusion imaging before and three months after successful CTO PCI between 2013-2019. Perfusion defects (PD) (in segments) and hyperemic myocardial blood flow (hMBF) (in ml · min-1 · g-1) allocated to CTO areas were related to prognostic outcomes using unadjusted (Kaplan-Meier curves, log-rank test) and risk-adjusted (multivariable Cox regression) analyses. The prognostic endpoint was a composite of all-cause death and nonfatal myocardial infarction. After a median [interquartile range] of 2.8 years [1.8 to 4.3 years], event-free survival was superior in patients with≥3 versus<3 segment PD reduction (p<0.01; risk-adjusted p=0.04; hazard ratio [HR]: 0.34 [95% confidence interval (CI): 0.13 to 0.93]) and with hMBF increase above (Δ≥1.11ml · min-1 · g-1) versus below the population median (p<0.01; risk-adjusted p<0.01; HR: 0.16 [95%CI: 0.05 to 0.54]) after CTO PCI. Furthermore, event-free survival was superior in patients without versus any residual PD (p<0.01; risk-adjusted p=0.02; HR: 0.22 [95%CI: 0.06 to 0.76]) or with a residual hMBF level >2.3 versus≤2.3ml · min-1 · g-1 (p<0.01; risk-adjusted p=0.03; HR: 0.25 [95%CI: 0.07 to 0.91]) at follow-up positron emission tomography. Patients with residual hMBF >2.3ml · min-1 · g-1 were more frequently free of angina and dyspnea on exertion at long-term follow-up (p=0.04). Patients with extensive ischemic burden reduction and no residual ischemia after CTO PCI had lower rates of all-cause death and nonfatal myocardial infarction. Long-term cardiac symptom relief was associated with normalization of hMBF levels after CTO PCI.

Secretin activates brown fat and induces satiation.

Brown adipose tissue (BAT) thermogenesis is activated by feeding. Recently, we revealed a secretin-mediated gut-BAT-brain axis, which stimulates satiation in mice, but the purpose of meal-induced BAT activation in humans has been unclear. In this placebo-controlled, randomized crossover study, we investigated the effects of intravenous secretin on BAT metabolism (measured with [18F]FDG and [15O]H2O positron emission tomography) and appetite (measured with functional magnetic resonance imaging) in healthy, normal weight men (GUTBAT trial no. NCT03290846). Participants were blinded to the intervention. Secretin increased BAT glucose uptake (primary endpoint) compared to placebo by 57% (median (interquartile range, IQR), 0.82 (0.77) versus 0.59 (0.53) μmol per 100 g per min, 95% confidence interval (CI) (0.09, 0.89), P = 0.002, effect size r = 0.570), while BAT perfusion remained unchanged (mean (s.d.) 4.73 (1.82) versus 6.14 (3.05) ml per 100 g per min, 95%CI (-2.91, 0.07), P = 0.063, effect size d = -0.549) (n = 15). Whole body energy expenditure increased by 2% (P = 0.011) (n = 15). Secretin attenuated blood-oxygen level-dependent activity (primary endpoint) in brain reward circuits during food cue tasks (significance level false discovery rate corrected at P = 0.05) (n = 14). Caloric intake did not significantly change, but motivation to refeed after a meal was delayed by 39 min (P = 0.039) (n = 14). No adverse effects were detected. Here we show in humans that secretin activates BAT, reduces central responses to appetizing food and delays the motivation to refeed after a meal. This suggests that meal-induced, secretin-mediated BAT activation is relevant in the control of food intake in humans. As obesity is increasing worldwide, this appetite regulating axis offers new possibilities for clinical research in treating obesity.

Comparison between cardiac magnetic resonance stress T1 mapping and [15O]H2O positron emission tomography in patients with suspected obstructive coronary artery disease.

To compare cardiac magnetic resonance (CMR) measurement of T1 reactivity (ΔT1) with [15O]H2O positron emission tomography (PET) measurements of quantitative myocardial perfusion. Forty-three patients with suspected obstructed coronary artery disease underwent [15O]H2O PET and CMR at 1.5-T, including rest and adenosine stress T1 mapping (ShMOLLI) and late gadolinium enhancement to rule out presence of scar tissue. ΔT1 was determined for the three main vascular territories and compared with [15O]H2O PET-derived regional stress myocardial blood flow (MBF) and myocardial flow reserve (MFR). ΔT1 showed a significant but poor correlation with stress MBF (R2 = 0.04, P = 0.03) and MFR (R2 = 0.07, P = 0.004). Vascular territories with impaired stress MBF (i.e. ≤2.30 mL/min/g) demonstrated attenuated ΔT1 compared with vascular territories with preserved stress MBF (2.9 ± 2.2% vs. 4.1 ± 2.2%, P = 0.008). In contrast, ΔT1 did not differ between vascular territories with impaired (i.e. <2.50) and preserved MFR (3.2 ± 2.6% vs. 4.0 ± 2.1%, P = 0.25). Receiver operating curve analysis of ΔT1 resulted in an area under the curve of 0.66 [95% confidence interval (CI): 0.57-0.75, P = 0.009] for diagnosing impaired stress MBF and 0.62 (95% CI: 0.53-0.71, P = 0.07) for diagnosing impaired MFR. CMR stress T1 mapping has poor agreement with [15O]H2O PET measurements of absolute myocardial perfusion. Stress T1 and ΔT1 are lower in vascular territories with reduced stress MBF but have poor accuracy for detecting impaired myocardial perfusion.

Prognostic Value of RCA Pericoronary Adipose Tissue CT-Attenuation Beyond High-Risk Plaques, Plaque Volume, and Ischemia

ObjectivesThis study was designed to assess the prognostic value of pericoronary adipose tissue computed tomography attenuation (PCATa) beyond quantitative coronary computed tomography angiography (CCTA)–derived plaque volume and positron emission tomography (PET) determined ischemia. BackgroundInflammation plays a crucial role in atherosclerosis. PCATa has been shown to assess coronary-specific inflammation and is of prognostic value in patients with suspected coronary artery disease (CAD). MethodsA total of 539 patients who underwent CCTA and [15O]H2O PET perfusion imaging because of suspected CAD were included. Imaging assessment included coronary artery calcium score (CACS), presence of obstructive CAD (≥50% stenosis) and high-risk plaques (HRPs), total plaque volume (TPV), calcified/noncalcified plaque volume (CPV/NCPV), PCATa, and myocardial ischemia. The endpoint was a composite of death and nonfatal myocardial infarction. Prognostic thresholds were determined for quantitative CCTA variables. ResultsDuring a median follow-up of 5.0 (interquartile range: 4.7 to 5.0) years, 33 events occurred. CACS >59 Agatston units, obstructive CAD, HRPs, TPV >220 mm3, CPV >110 mm3, NCPV >85 mm3, and myocardial ischemia were associated with shorter time to the endpoint with unadjusted hazard ratios (HRs) of 4.17 (95% confidence interval [CI]: 1.80 to 9.64), 4.88 (95% CI: 1.88 to 12.65), 3.41 (95% CI: 1.72 to 6.75), 7.91 (95% CI: 3.05 to 20.49), 5.82 (95% CI: 2.40 to 14.10), 8.07 (95% CI: 3.33 to 19.55), and 4.25 (95% CI: 1.84 to 9.78), respectively (p < 0.05 for all). Right coronary artery (RCA) PCATa above scanner specific thresholds was associated with worse prognosis (unadjusted HR: 2.84; 95% CI: 1.44 to 5.63; p = 0.003), whereas left anterior descending artery and circumflex artery PCATa were not related to outcome. RCA PCATa above scanner specific thresholds retained is prognostic value adjusted for imaging variables and clinical characteristics associated with the endpoint (adjusted HR: 2.45; 95% CI: 1.23 to 4.93; p = 0.011). ConclusionsParameters associated with atherosclerotic burden and ischemia were more strongly associated with outcome than RCA PCATa. Nonetheless, RCA PCATa was of prognostic value beyond clinical characteristics, CACS, obstructive CAD, HRPs, TPV, CPV, NCPV, and ischemia.

Impact of coronary revascularization on regional artery-specific coronary flow capacity: a serial [15O]H2O positron emission tomography perfusion imaging study

Abstract Funding Acknowledgements Type of funding sources: None. Background. Coronary flow capacity (CFC) combines absolute hyperemic myocardial blood flow (hMBF) and coronary flow reserve (CFR) in a graphical representation of the severity of myocardial perfusion impairment. Studies evaluating the impact of coronary revascularization on CFC as assessed by [15O]H2O positron emission tomography (PET) are lacking. Purpose. The present study explored the impact of coronary revascularization on regional, artery-specific CFC as assessed by [15O]H2O PET. Methods. A total of 315 patients (mean age 62 ± 10 years) underwent absolute myocardial perfusion imaging at baseline and directly after either percutaneous or surgical coronary revascularization (at 110 ± 50 days). Revascularized perfusion regions were stratified in 3 CFC groups at baseline: severely reduced CFC (defined as myocardial ischemia), moderately reduced CFC and normal CFC. Results. Baseline CFC was severely reduced in 262 vessels (70%), moderately reduced in 95 vessels (25%) and normal in 17 vessels (5%). Regional, artery-specific CFC, hMBF and CFR improved after successful revascularization (P &amp;lt; 0.01). In 127/262 regions, CFC increased from severely reduced to moderately reduced and in 29/262 to normal flow after revascularization (p &amp;lt; 0.01 for both). Additionally, 28/95 revascularized regions increased from moderately reduced to normal flow (P = 0.18). Changes in hMBF (severe vs. moderate vs. normal: 0.84 ± 0.73; 0.41 ± 0.60 and 0.35 ± 0.84 mL·min-1·g-1 ) and CFR (0.92 ± 0.83; 0.49 ± 1.00 and -0.39 ± 1.15) were significantly different comparing baseline CFC groups (both p &amp;lt; 0.01). Furthermore, mixed-model analysis including traditional CAD risk factors revealed that baseline CFC and gender were independent predictors of changes in CFC, hMBF and CFR between baseline and follow-up. Conclusions. Successful revascularization demonstrated a significant and positive impact on regional, artery-specific CFC, hMBF and CFR. Improvements were largest among lower baseline CFC groups. Furthermore, baseline CFC was an independent predictor of change in CFC, hMBF and CFR. These results suggest that the assessment of flow capacity by [15O]H2O PET prior to revascularization may aid in the selection of regions in which absolute myocardial perfusion is most likely to improve. Abstract Figure 1.

Contralateral improvement of cerebrovascular reactivity and TIA frequency after unilateral revascularization surgery in moyamoya vasculopathy

ObjectiveMoyamoya vasculopathy is a rare, often bilateral disease characterized by progressive stenosis and occlusion of the distal internal carotid artery, leading to a progressive deterioration of cerebrovascular reactivity (CVR) and increased risk of transient ischemic attacks (TIAs), infarction and hemorrhage. Surgical revascularization is a widely accepted symptomatic treatment, often performed bilaterally in one or two stages. To possibly further optimize treatment strategy, we investigated the effect of unilateral revascularization surgery on the CVR of, and TIA frequency originating from, the contralateral hemisphere. MethodsFrom our database of 143 moyamoya vasculopathy patients we selected those with bilateral disease, who underwent hemodynamic imaging ([15O]H2O positron emission tomography (PET)-CT with acetazolamide challenge) before and 14 months (median) after unilateral revascularization. We evaluated CVR in three regions per hemisphere, and averaged these per hemisphere for statistical comparison. Conservatively treated patients were showed as a comparison group. To examine TIA frequency, we selected patients who presented with TIAs that (also) originated from the contralateral – not to be operated – hemisphere. We scored changes in CVR and TIA frequency of the ipsilateral and contralateral hemisphere over time. ResultsSeven surgical and seven conservative patients were included for CVR comparison. Of the 20 scored contralateral regions in the surgical group, 15 showed improved CVR after unilateral revascularization, while 5 remained stable. The averaged scores improved significantly for both hemispheres. In conservatively treated patients, however, only 3 of the 20 scored regions improved in the least-affected (contralateral) hemispheres, and 9 deteriorated. From the 6 patients with contralateral TIAs at presentation, 4 had a decreased TIA frequency originating from the contralateral hemisphere after unilateral surgery, while 2 patients remained stable. ConclusionBoth CVR and TIA frequency in the contralateral hemisphere can improve after unilateral revascularization surgery in bilateral MMV.

Defining the prognostic value of [15O]H2O positron emission tomography-derived myocardial ischaemic burden.

Myocardial ischaemic burden (IB) is used for the risk stratification of patients with coronary artery disease (CAD). This study sought to define a prognostic threshold for quantitative [15O]H2O positron emission tomography (PET)-derived IB. A total of 623 patients with suspected or known CAD who underwent [15O]H2O PET perfusion imaging were included. The endpoint was a composite of death and non-fatal myocardial infarction (MI). A hyperaemic myocardial blood flow (hMBF) and myocardial flow reserve (MFR)-derived IB were determined. During a median follow-up time of 6.7 years, 62 patients experienced an endpoint. A hMBF IB of 24% and MFR IB of 28% were identified as prognostic thresholds. Patients with a high hMBF or MFR IB (above threshold) had worse outcome compared to patients with a low hMBF IB [annualized event rates (AER): 2.8% vs. 0.6%, P < 0.001] or low MFR IB [AER: 2.4% vs. 0.6%, P < 0.001]. Patients with a concordant high IB had the worst outcome (AER: 3.1%), whereas patients with a concordant low or discordant IB result had similar and low AERs of 0.5% and 0.9% (P = 0.953), respectively. Both thresholds were of prognostic value beyond clinical characteristics, however, only the hMBF IB threshold remained predictive when adjusted for clinical characteristics and combined use of the hMBF and MFR thresholds. A hMBF IB ≥24% was a stronger predictor of adverse outcome than an MFR IB ≥28%. Nevertheless, classifying patients according to concordance of IB result allowed for the identification of low- and high-risk patients.

Defining the prognostic value of [15O]H2O positron emission tomography derived myocardial ischemic burden

Abstract Background A myocardial ischemic burden (IB) of 10% is used to denote high-risk patients with coronary artery disease (CAD). This threshold has primarily been assessed by single-photon emission computed tomography. Differences in the pharmacokinetics of the utilized traces, higher resolution of positron emission tomography (PET), and lastly differences in assessment of IB might lead to a higher prognostic threshold for quantitative PET. Purpose To determine a [15O]H2O PET derived IB to identify low (annualized event rate (AER) &amp;lt;1.0%) and high (AER ≥3%) risk CAD patients. Methods 623 patients who underwent [15O]H2O PET because of suspected CAD and in whom follow-up was obtained were included. The IB was defined as the percentage of myocardium with a hyperemic blood flow (hMBF) ≤2.3 ml/min/g and by a coronary flow reserve (CFR) of ≤2.5. The endpoint was a composite of death and non-fatal myocardial infarction (MI). Time-dependent ROC curves were constructed for the prediction of the endpoint within the first 5-years, based on these curves thresholds were selected for which specificity was maximized and sensitivity was at least 80%. Patients were classified as having a high IB if their respective IBs were above the prognostic thresholds and as having a low IB if not. Results During a median follow-up of 6.7 years, 34 (6%) patients died and 28 (4%) experienced a MI resulting in 62 (10%) endpoints. An IB of 24% and 28% for hMBF and CFR, respectively, was found to be the optimal threshold to define prognosis. Patients with a high hMBF or high CFR IB had worse outcome compared to patients with a low IB (log-rank p&amp;lt;0.001 for both), with AERs of 0.6% vs. 2.8%, and 0.6% vs. 2.4% (p&amp;lt;0.001 for both), respectively. Patients with a concordantly high hMBF and CFR derived IB had the worst outcome (AER: 3.1%), whereas patients with a concordantly low or discordant IB result had a similarly low event rate of 0.5% and 0.9% (p=0.953), respectively (log-rank p=0.445). A concordantly high hMBF and CFR IB was an independent predictor of adverse outcome beyond clinical characteristics (adjusted hazard ratio: 3.52, p&amp;lt;0.001). Conclusion An IB of 24% and 28% for hMBF and CFR was found to be the optimal prognostic threshold. Both measurements can be used to determine patients outcome. However combining hMBF and CFR IB results leads to a further refinement of risk-stratification allowing for the identification of low (concordant low or discordant IB result) and high (concordant high IB result) risk CAD patients. Funding Acknowledgement Type of funding source: None

Ischemic burden reduction after chronic total occlusion percutaneous coronary intervention related to patient prognosis

Abstract Background Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) leads to major reductions in ischemic burden. However, to date, studies investigating if more ischemia reduction after CTO PCI translates into an improved patient prognosis, are lacking. Purpose To evaluate if change in absolute myocardial perfusion after CTO PCI is related to patient prognosis. Methods Between 2013–2019, 219 prospectively recruited patients with a CTO underwent quantitative [15O]H2O positron emission tomography perfusion imaging before and 3 months after successful CTO PCI in a single high-volume CTO PCI center (175 procedures/year). Changes in perfusion defect size (in myocardial segments) and hyperemic myocardial blood flow (MBF, in mL min–1 g–1) within the CTO territory after PCI were related to the combined endpoint of death or myocardial infarction (MI). Kaplan-Meier curves (log-rank test) and multivariable Cox regression (including covariates age, gender, prior MI, and left ventricular function) were used to analyze unadjusted and risk-adjusted event-free survivals with HR [95% CI]. Results Out of 213 (97%) patients with a median follow-up of 3.2 [2.1–4.7] years, 22 (10%) patients experienced the composite of death (19, 9%) or MI (5, 2%). Event-free survival was significantly improved in patients with a perfusion defect size reduction of ≥3 segments (N=132, 62%) after CTO PCI compared to &amp;lt;3 segments (p=0.01, risk-adjusted: p=0.02 with HR 0.36 [0.15–0.87]), as well in patients with increase in hyperemic MBF above the median of the population (delta &amp;gt;1.13 mL min–1 g–1) as compared to below the median (p&amp;lt;0.01, risk-adjusted: p=0.01 with HR 0.27 [0.10–0.75]). After PCI, patients with ≥1 segment residual perfusion defect size in the CTO territory at follow-up (N=114, 54%) had a significantly worse event-free survival compared to patients with no residual defect size (p&amp;lt;0.01, risk-adjusted: p=0.01 with HR 4.12 [1.35–12.59]), whereas patients with a residual hyperemic MBF &amp;gt;2.30 mL min–1 g–1 (N=105, 49%) showed a better event-free survival compared to patients with lower residual hyperemic MBF levels (p=0.02, risk-adjusted: p=0.04 with HR 0.33 [0.12–0.95]). Conclusions Patients with more ischemic burden reduction and less residual ischemia following CTO PCI showed a major improved survival free of death or MI. A limitation was the low absolute number of events that prohibited more extensive risk-adjustment of the analyses. Funding Acknowledgement Type of funding source: None

Synthesis and evaluation of N-isopropyl-p-[11C]methylamphetamine as a novel cerebral blood flow tracer for positron emission tomography

IntroductionIncreases in fasting plasma glucose (PG) levels lead to a decrease in 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) uptake in the normal brain, especially in the precuneus, resulting in an Alzheimer’s disease (AD)-like uptake pattern. Therefore, patients with higher PG levels, such as those with diabetes, can be erroneously diagnosed with AD when positron emission tomography (PET) imaging is done using [18F]FDG, due to reduced uptake of [18F]FDG in the precuneus. To help avoid an erroneous diagnosis of AD due to differences in glucose metabolism, evaluating cerebral blood flow (CBF) in the brain is useful. However, current techniques such as single photon emission computed tomography (SPECT) and [15O]H2O PET have limitations regarding early diagnosis of AD because the images they produce are of low resolution. Here, we developed a novel CBF PET tracer that may be more useful than [18F]FDG for diagnosis of AD.MethodsWe synthesized and evaluated N-isopropyl-p-[11C]methylamphetamine ([11C]4) as a carbon-11-labeled analogue of the standard CBF SPECT tracer N-isopropyl-p-[123I]iodoamphetamine. Fundamental biological evaluations such as biodistribution, peripheral metabolism in mice, and brain kinetics of [11C]4 in non-human primates with PET with successive measurement of [15O]H2O were performed.Results[11C]4 was synthesized by methylation of the corresponding tributyltin precursor (2) with [11C]MeI in a palladium-promoted Stille cross-coupling reaction. The brain uptake of [11C]4 in mice peaked at 5–15 min after injection and then promptly decreased. Most radioactivity in the brain was detected in the unchanged form, although in the periphery, [11C]4 was rapidly metabolized to hydrophilic components. Acetazolamide (AZM) treatment significantly increased the brain uptake of [11C]4 without affecting the blood levels of radioactivity in mice. Preliminary kinetics analysis showed that the K1 of [11C]4 reflected regional CBF in a vehicle-treated monkey, but that the K1 did not reflect CBF in higher flow regions after AZM loading.Conclusion[11C]4 is a potential novel CBF PET tracer. Further validation studies are needed before [11C]4 can be used in humans.

Quantification of [18F]afatinib using PET/CT in NSCLC patients: a feasibility study

IntroductionOnly a subgroup of non-small cell lung cancer (NSCLC) patients benefit from treatment using epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) such as afatinib. Tumour uptake of [18F]afatinib using positron emission tomography (PET) may identify those patients that respond to afatinib therapy. Therefore, the aim of this study was to find the optimal tracer kinetic model for quantification of [18F]afatinib uptake in NSCLC tumours.Methods[18F]Afatinib PET scans were performed in 10 NSCLC patients. The first patient was scanned for the purpose of dosimetry. Subsequent patients underwent a 20-min dynamic [15O]H2O PET scan (370 MBq) followed by a dynamic [18F]afatinib PET scan (342 ± 24 MBq) of 60 or 90 min. Using the Akaike information criterion (AIC), three pharmacokinetic plasma input models were evaluated with both metabolite-corrected sampler-based input and image-derived (IDIF) input functions in combination with discrete blood samples. Correlation analysis of arterial on-line sampling versus IDIF was performed. In addition, perfusion dependency and simplified measures were assessed.ResultsTen patients were included. The injected activity of [18F]afatinib was 341 ± 37 MBq. Fifteen tumours could be identified in the field of view of the scanner. Based on AIC, tumour kinetics were best described using an irreversible two-tissue compartment model and a metabolite-corrected sampler-based input function (Akaike 50%). Correlation of plasma-based input functions with metabolite-corrected IDIF was very strong (r2 = 0.93). The preferred simplified uptake parameter was the tumour-to-blood ratio over the 60- to 90-min time interval (TBR60–90). Tumour uptake of [18F]afatinib was independent of perfusion.ConclusionThe preferred pharmacokinetic model for quantifying [18F]afatinib uptake in NSCLC tumours was the 2T3K_vb model. TBR60–90 showed excellent correlation with this model and is the best candidate simplified method.Trial registrationhttps://eudract.ema.europa.eu/ nr 2012-002849-38

Coronary computed tomography angiography and [15O]H2O positron emission tomography perfusion imaging for the assessment of coronary artery disease.

Determining the anatomic severity and extent of coronary artery disease (CAD) by means of coronary computed tomography angiography (CCTA) and its effect on perfusion using myocardial perfusion imaging (MPI) form the pillars of the non-invasive imaging assessment of CAD. This review will 1) focus on CCTA and [15O]H2O positron emission tomography MPI as stand-alone imaging modalities and their combined use for detecting CAD, 2) highlight some of the lessons learned from the PACIFIC trial (Comparison of Coronary CT Angiography, SPECT, PET, and Hybrid Imaging for Diagnosis of Ischemic Heart Disease Determined by Fractional Flow Reserve (FFR) (NCT01521468)), and 3) discuss the use of [15O]H2O PET MPI in the clinical work-up of patients with a chronic coronary total occlusion (CTO).

Ischaemic burden and changes in absolute myocardial perfusion after chronic total occlusion percutaneous coronary intervention.

The aim of this study was to explore the relationships between ischaemic burden and changes in absolute myocardial perfusion following chronic coronary total occlusion (CTO) percutaneous coronary intervention (PCI). A total of 193 consecutive patients underwent [15O]H2O positron emission tomography prior to and three months after successful CTO PCI. Change in perfusion defect size, quantitative hyperaemic myocardial blood flow (MBF) and coronary flow reserve (CFR) within the CTO area were compared among patients with limited (0-1 segment, N=15), moderate (2-3 segments, N=61) and large (≥4 segments, N=117) perfusion defects. Median reductions in defect size were 1 [0-1], 2 [1-3], and 4 [2-5] segments in patients with a limited, moderate and large defect (all comparisons p<0.01). Hyperaemic MBF and CFR improved significantly regardless of baseline defect size (overall between groups p=0.45 and p=0.55). After stratification of patients to a low, intermediate or high tertile according to baseline hyperaemic MBF or CFR levels, changes in hyperaemic MBF and CFR after CTO PCI were comparable between tertiles (overall p=0.75 and p=0.79). Major reductions in ischaemic burden can be achieved following CTO PCI, with more defect size reduction in patients with a larger perfusion defect, whereas hyperaemic MBF and CFR improve significantly irrespective of their baseline values or perfusion defect size.

Comparison Between the Performance of Quantitative Flow Ratio and Perfusion Imaging for Diagnosing Myocardial Ischemia

ObjectivesThis study compared the performance of the quantitative flow ratio (QFR) with single-photon emission computed tomography (SPECT) and positron emission tomography (PET) myocardial perfusion imaging (MPI) for the diagnosis of fractional flow reserve (FFR)−defined coronary artery disease (CAD). BackgroundQFR estimates FFR solely based on cine contrast images acquired during invasive coronary angiography (ICA). Head-to-head studies comparing QFR with noninvasive MPI are lacking. MethodsA total of 208 (624 vessels) patients underwent technetium-99m tetrofosmin SPECT and [15O]H2O PET imaging before ICA in conjunction with FFR measurements. ICA was obtained without using a dedicated QFR acquisition protocol, and QFR computation was attempted in all vessels interrogated by FFR (552 vessels). ResultsQFR computation succeeded in 286 (52%) vessels. QFR correlated well with invasive FFR overall (R = 0.79; p < 0.001) and in the subset of vessels with an intermediate (30% to 90%) diameter stenosis (R = 0.76; p < 0.001). Overall, per-vessel analysis demonstrated QFR to exhibit a superior sensitivity (70%) in comparison with SPECT (29%; p < 0.001), whereas it was similar to PET (75%; p = 1.000). Specificity of QFR (93%) was higher than PET (79%; p < 0.001) and not different from SPECT (96%; p = 1.000). As such, the accuracy of QFR (88%) was superior to both SPECT (82%; p = 0.010) and PET (78%; p = 0.004). Lastly, the area under the receiver operating characteristics curve of QFR, in the overall sample (0.94) and among vessels with an intermediate lesion (0.90) was higher than SPECT (0.63 and 0.61; p < 0.001 for both) and PET (0.82; p < 0.001 and 0.77; p = 0.002), respectively. ConclusionsIn this head-to-head comparative study, QFR exhibited a higher diagnostic value for detecting FFR-defined significant CAD compared with perfusion imaging by SPECT or PET.