H2O Positron Emission Tomography Research Articles

P5748Impact of specific crossing techniques in chronic total occlusion percutaneous coronary intervention on recovery of absolute myocardial perfusion

Abstract Background Multiple techniques in chronic coronary total occlusion (CTO) percutaneous coronary intervention (PCI) have been developed to cross CTOs. Purpose To compare recovery of quantitative myocardial blood flow (MBF) after different CTO PCI techniques. Methods Consecutive patients with [15O]H2O positron emission tomography perfusion imaging before and three months after successful CTO PCI were included. Change in quantitative hyperemic MBF, coronary flow reserve (CFR) and perfusion defect size were compared between antegrade wire escalation (AWE), retrograde wire escalation (RWE), antegrade dissection and reentry (ADR) and retrograde dissection and reentry (RDR), and further between specific subintimal crossing and reentry techniques. Results 193 patients were treated with AWE (N=90), RWE (N=24), ADR (N=35) and RDR (N=44). Significant improvements (all p<0.01) in hyperemic MBF (1.19±0.77, 0.94±0.65, 1.09±0.63, and 1.02±0.75 mL min–1 g–1, respectively), CFR (1.34±1.08, 1.14±1.09, 1.31±0.96, and 1.24±0.99, respectively), and perfusion defect size (3.17±2.13, 3.00±2.21, 2.74±2.09, and 2.93±1.92 segments, respectively) were comparable between the four approaches (p=0.40, p=0.84, and p=0.77, respectively). Recovery of hyperemic MBF was less pronounced after subintimal crossing with a knuckle-wire-technique compared to the use of CrossBoss in controlled ADR and RDR (p=0.02), and less after reentry with subintimal tracking and reentry (STAR) in ADR compared with controlled ADR (Stingray) or limited antegrade subintimal tracking (LAST) (p=0.02 and p<0.01). Conclusions Recovery of hyperemic MBF, CFR, and perfusion defect size was significant after CTO PCI and comparable between different crossing techniques. Improvement of hyperemic MBF was inferior after using the knuckle-wire subintimal crossing technique and STAR compared to other subintimal crossing and reentry techniques. Acknowledgement/Funding None

P964Relationships between extent of ischemic burden and changes in absolute myocardial perfusion after chronic total occlusion percutaneous coronary intervention

Abstract Background The patient benefits after chronic coronary total occlusion (CTO) percutaneous coronary intervention (PCI) are being questioned. Purpose The present study explored the relationships between baseline ischemic burden findings and subsequent changes in absolute myocardial perfusion after CTO PCI. Methods Consecutive patients underwent serial [15O]H2O positron emission tomography perfusion imaging prior and 3 months after successful CTO PCI. Change in perfusion defect size (in myocardial segments), quantitative (hyperemic) myocardial blood flow (MBF) and coronary flow reserve (CFR) in the CTO area were compared between patients with a limited (0–1 segment), moderate (2–3 segments) and large perfusion defect (≥4 segments). Results 193 patients were included, with 15, 61 and 117 patients having a limited, moderate and large perfusion defect at baseline. Hyperemic MBF and CFR were lower in a large perfusion defect compared to smaller defects (all comparisons p<0.01). The median decrease in defect size was 1 [0–1] vs 2 [1–3] vs 4 [2–5] in patients with a limited, moderate and large defect (all comparisons p<0.01), whereas hyperemic MBF and CFR improved significantly regardless of baseline defect size (between groups p=0.45 and p=0.55, respectively). Furthermore, when all 193 patients were divided in a low, median and high tertile based on hyperemic MBF and CFR at baseline, changes in hyperemic MBF and CFR after CTO PCI were comparable between patients in different tertiles (between groups p=0.75 and p=0.79, respectively) Conclusions Patients with a CTO and a larger perfusion defect have more severe hyperemic MBF and CFR levels. Major reductions in ischemic burden can be achieved by CTO PCI, with more defect size reduction in patients with a larger perfusion defect, whereas hyperemic MBF and CFR significantly improve irrespective of starting values before PCI. Acknowledgement/Funding None

1268A comparison between the diagnostic performance of quantitative flow ratio and non-invasive imaging modalities for diagnosing myocardial ischemia defined by FFR, a PACIFIC-trial interim analysis

Abstract Background Quantitative flow ratio (QFR) uses fast computational algorithms based on 3-dimensional quantitative coronary angiography and estimation of contrast flow velocity during invasive coronary angiography (ICA) to obtain QFR values equivalent to fractional flow reserve (FFR). Objective To compare the diagnostic performance of QFR with coronary computed tomography angiography (CCTA), single-photon emission tomography (SPECT), and positron emission tomography (PET) for diagnosing myocardial ischemia defined by FFR. Method QFR computation was attempted in 109 patients (286 vessels without a subtotal/total lesion) of the 208 patients included in the PACIFIC-trial. Patients underwent 256-slice CCTA, Tetrofosmin SPECT, and [15O]H2O PET prior to ICA in conjunction with 3 vessel FFR measurements. ICA images were obtained without the use of a dedicated QFR acquistion protocol. QFR was calculated using a fixed empiric hyperemic flow velocity (fQFR) as well as using a patient specific flow velocity based on contrast passage through the coronary (cQFR). All analysis were performed on a per vessel level. Results Fixed QFR computation succeeded in 152 (53%) vessels while cQFR analysis was successful in 140 (49%) vessels. A good correlation between FFR and fQFR/cQFR was observed (R=0.774, p<0.001/R=0.790, p<0.001). The diagnostic performance in terms of sensitivity, specificity, negative predictive value, positive predictive value, and accuracy is presented in table 1. In total, 133 vessels with matched FFR, fQFR, cQFR, CCTA, SPECT, and PET results were available for the comparative C-statistic analysis, figure 1. The diagnostic performance of fQFR and cQFR was comparable (p=0.451) and superior to CCTA (p=0.004/p=0.003), SPECT (p<0.001/p<0.001), and PET (p=0.008/p=0.006), figure 1. CCTA, and PET performed alike (p=0.568) and outperformed SPECT (p=0.023, p=0.002). Table 1 % (95% Confidence Interval) fQFR n=152 cQFR (n=140) CCTA (n=152) SPECT (n=150) PET (n=149) Sensitivity 76 (59–89) 71 (53–86) 70 (51–84) 30 (16–49) 76 (58–89) Specificity 94 (88–98) 93 (86–97) 73 (64–81) 96 (90–99) 80 (72–87) Negative Predictive Value 93 (88–96) 92 (86–95) 90 (84–94) 83 (79–86) 92 (86–96) Positive Predictive Value 79 (64–89) 74 (59–85) 42 (33–51) 67 (42–84) 52 (42–62) Accuracy 90 (84–94) 88 (81–93) 72 (65–79) 81 (74–87) 79 (72–85) Figure 1. Conclusion Fixed QFR and cQFR correlate well with FFR with a high diagnostic accuracy as result. QFR outperformed CCTA, SPECT, and PET for the diagnosis of myocardial ischemia on a per vessel basis with the important footnote that fQFR and cQFR could only be computed in 53%, and 49% of the vessels.

18F-FDG PET, the early phases and the delivery rate of 18F-AV45 PET as proxies of cerebral blood flow in Alzheimer's disease: Validation against 15O-H2O PET

IntroductionDual-biomarker positron emission tomography (PET), providing complementary information on cerebral blood flow and amyloid-β deposition, is of clinical interest for Alzheimer's disease (AD). The purpose of this study was to validate the perfusion components of early-phase 18F-florbetapir (eAV45), the 18F-AV45 delivery rate (R1), and 18F-FDG against 15O-H2O PET and assess how they change with disease severity. MethodsThis study included ten controls, 19 amnestic mild cognitive impairment, and 10 AD dementia subjects. Within-subject regional correlations between modalities, between-group regional and voxel-wise analyses of covariance per modality, and receiver operating characteristic analyses for discrimination between groups were performed. ResultsFDG standardized uptake value ratio, eAV45 (0–2 min) standardized uptake value ratio, and AV45-R1 were significantly associated with H2O PET (regional Pearson r = 0.54–0.82, 0.70–0.94, and 0.65–0.92, respectively; P < .001). All modalities confirmed reduced cerebral blood flow in the posterior cingulate of patients with amnestic mild cognitive impairment and AD dementia, which was associated with lower cognition (r = 0.36–0.65, P < .025) and could discriminate between patient and control groups (area under the curve > 0.80). However, eAV45 was less sensitive to reflect the disease severity than AV45-R1 or FDG. DiscussionR1 is preferable over eAV45 for accurate representation of brain perfusion in dual-biomarker PET for AD.

Myocardial blood flow and cardiac sympathetic innervation in young adults late after arterial switch operation for transposition of the great arteries

BackgroundThe arterial switch operation (ASO) for repair of transposition of the great arteries (TGA) requires transection of the great arterial trunks and re-implantation of the coronary arteries into the neoaortic root resulting in cardiac sympathetic denervation which may affect myocardial blood flow (MBF) regulation. The aims of the present study were to evaluate sympathetic (re-)innervation in young adults after ASO and its impact on MBF. MethodsTwelve patients (age 22.5 ± 2.6 years) after ASO for TGA in the neonatal period and ten healthy controls (age 22.0 ± 1.7 years) were included. Positron emission tomography (PET) was used for measuring cardiac sympathetic innervation with [11C]meta-hydroxyephedrine (mHED) and MBF with [15O]H2O PET at rest, during adenosine stimulation, and during sympathetic stimulation with cold pressor test. Cold pressor-induced MBF response capacity was calculated as maximal global MBF over peak rate-pressure product multiplied by 10′000. ResultsGlobal [11C]mHED uptake was significantly lower in patients compared to controls (7.0 ± 2.3 versus 11.8 ± 2.1%/min, p < 0.001). Global MBF was lower in patients compared to controls at rest and during adenosine-induced hyperemia (0.66 ± 0.08 versus 0.82 ± 0.15 ml/min/g, p = 0.005; 2.23 ± 1.19 versus 3.36 ± 1.04 ml/min/g, p = 0.030, respectively). Interestingly, MBF during cold pressor test did not differ between patients and controls (0.99 ± 0.20 versus 1.07 ± 0.16 ml/min/g, p = 0.330). However, cold pressor-induced MBF response capacity was significantly lower for patients as compared to controls (1.09 ± 0.35 versus 1.44 ± 0.39 ml/g/10,000 mmHg, p = 0.040). ConclusionsWith only partial sympathetic re-innervation of the coronary arteries, maximal dilator capacity of the coronary microvasculature and cold pressor-induced MBF response capacity remain substantially impaired in young adults after ASO compared to healthy controls.

Pancreatic perfusion and its response to glucose as measured by simultaneous PET/MRI

AimsPerfusion of the pancreas and the islets of Langerhans is sensitive to physiological stimuli and is dysregulated in metabolic disease. Pancreatic perfusion can be assessed by both positron emission tomography (PET) and magnetic resonance imaging (MRI), but the methods have not been directly compared or benchmarked against the gold-standard microsphere technique.MethodsPigs (n = 4) were examined by [15O]H2O PET and intravoxel incoherent motion (IVIM) MRI technique simultaneously using a hybrid PET/MRI scanner. The pancreatic perfusion was measured both at basal conditions and after intravenous (IV) administration of up to 0.5 g/kg glucose.ResultsPancreatic perfusion increased by 35%, 157%, and 29% after IV 0.5 g/kg glucose compared to during basal conditions, as assessed by [15O]H2O PET, IVIM MRI, and microspheres, respectively. There was a correlation between pancreatic perfusion as assessed by [15O]H2O PET and IVIM MRI (r = 0.81, R2 = 0.65, p < 0.01). The absolute quantification of pancreatic perfusion (ml/min/g) by [15O]H2O PET was within a 15% error of margin of the microsphere technique.ConclusionPancreatic perfusion by [15O]H2O PET was in agreement with the microsphere technique assessment. The IVIM MRI method has the potential to replace [15O]H2O PET if the pancreatic perfusion is sufficiently large, but not when absolute quantitation is required.

Continuous thermodilution to assess absolute flow and microvascular resistance: validation in humans using [15O]H2O positron emission tomography.

Continuous thermodilution is a novel technique to quantify absolute coronary flow and microvascular resistance (MVR). Notably, intracoronary infusion of saline elicits maximal hyperaemia, obviating the need for adenosine. The primary aim of this study was to validate continuous thermodilution in humans by comparing invasive measurements to [15O]H2O positron emission tomography (PET). As a secondary goal, absolute flow and MVR were compared between invasive measurements obtained with and without adenosine. Twenty-five patients underwent coronary computed tomography angiography (CCTA), [15O]H2O PET, and invasive assessment. Absolute coronary flow and MVR were measured in the left anterior descending and left circumflex artery using a dedicated infusion catheter and a temperature/pressure sensor-tipped guidewire. Invasive measurements were performed with and without adenosine. In order to compare invasive flow measurements with PET perfusion, subtending myocardial mass of the investigated vessels was derived from CCTA using the Voronoi algorithm. Invasive and non-invasive measurements of adenosine-induced hyperaemic flow and MVR showed strong correlation (r = 0.91; P < 0.001 for flow and r = 0.85; P < 0.001 for MVR) and good agreement [intraclass correlation coefficient (ICC) = 0.90; P < 0.001 for flow and ICC = 0.79; P < 0.001 for MVR]. Absolute flow and MVR also correlated well between measurements with and without adenosine (r = 0.97; P < 0.001 for flow and r = 0.98; P < 0.001 for MVR) and showed good agreement (ICC = 0.96; P < 0.001 for flow and ICC = 0.98; P < 0.001 for MVR). Continuous thermodilution is an accurate method to measure absolute coronary flow and MVR, which is evidenced by strong agreement with [15O]H2O PET derived flow and resistance. Absolute flow and MVR correlate highly between invasive measurements obtained with and without adenosine, which confirms that intracoronary infusion of room temperature saline elicits steady-state maximal hyperaemia.

Comparison of Coronary Computed Tomography Angiography, Fractional Flow Reserve, and Perfusion Imaging for Ischemia Diagnosis

BackgroundFractional flow reserve (FFR) computation from coronary computed tomography angiography (CTA) datasets (FFRCT) has emerged as a promising noninvasive test to assess hemodynamic severity of coronary artery disease (CAD), but has not yet been compared with traditional functional imaging. ObjectivesThe purpose of this study was to evaluate the diagnostic performance of FFRCT and compare it with coronary CTA, single-photon emission computed tomography (SPECT), and positron emission tomography (PET) for ischemia diagnosis. MethodsThis subanalysis involved 208 prospectively included patients with suspected stable CAD, who underwent 256-slice coronary CTA, 99mTc-tetrofosmin SPECT, [15O]H2O PET, and routine 3-vessel invasive FFR measurements. FFRCT values were retrospectively derived from the coronary CTA images. Images from each modality were interpreted by core laboratories, and their diagnostic performances were compared using invasively measured FFR ≤0.80 as the reference standard. ResultsIn total, 505 of 612 (83%) vessels could be evaluated with FFRCT. FFRCT showed a diagnostic accuracy, sensitivity, and specificity of 87%, 90%, and 86% on a per-vessel basis and 78%, 96%, and 63% on a per-patient basis, respectively. Area under the receiver-operating characteristic curve (AUC) for identification of ischemia-causing lesions was significantly greater for FFRCT (0.94 and 0.92) in comparison with coronary CTA (0.83 and 0.81; p < 0.01 for both) and SPECT (0.70 and 0.75; p < 0.01 for both), on a per-vessel and -patient level, respectively. FFRCT also outperformed PET on a per-vessel basis (AUC 0.87; p < 0.01), but not on a per-patient basis (AUC 0.91; p = 0.56). In the intention-to-diagnose analysis, PET showed the highest per-patient and -vessel AUC followed by FFRCT (0.86 vs. 0.83; p = 0.157; and 0.90 vs. 0.79; p = 0.005, respectively). ConclusionsIn this study, FFRCT showed higher diagnostic performance than standard coronary CTA, SPECT, and PET for vessel-specific ischemia, provided coronary CTA images were evaluable by FFRCT, whereas PET had a favorable performance in per-patient and intention-to-diagnose analysis. Still, in patients in whom 3-vessel FFRCT could be analyzed, FFRCT holds clinical potential to provide anatomic and hemodynamic significance of coronary lesions.

Impact of individualized segmentation on diagnostic performance of quantitative positron emission tomography for haemodynamically significant coronary artery disease.

Despite high variability in coronary anatomy, quantitative positron emission tomography (PET) perfusion in coronary territories is traditionally calculated according to the American Heart Association (AHA) 17-segments model. This study aimed to assess the impact of individualized segmentation of myocardial segments on the diagnostic accuracy of hyperaemic myocardial blood flow (MBF) values for haemodynamically significant coronary artery disease (CAD). Patients with suspected CAD (n = 204) underwent coronary computed tomography angiography (CCTA) and [15O]H2O PET followed by invasive coronary angiography with fractional flow reserve assessment of all major coronary arteries. Hyperaemic MBF per vascular territory was calculated using both standard segmentation according to the AHA model and individualized segmentation, in which CCTA was used to assign coronary arteries to PET perfusion territories. In 122 (59.8%) patients, one or more segments were redistributed after individualized segmentation. No differences in mean MBF values were seen between segmentation methods, except for a minor difference in hyperaemic MBF in the LCX territory (P = 0.001). These minor changes resulted in discordant PET-defined haemodynamically significant CAD between the two methods in only 5 (0.8%) vessels. The diagnostic value for detecting haemodynamically significant CAD did not differ between individualized and standard segmentation, with area under the curves of 0.79 and 0.78, respectively (P = 0.34). Individualized segmentation using CCTA-derived coronary anatomy led to redistribution of standard myocardial segments in 60% of patients. However, this had little impact on [15O]H2O PET MBF values and diagnostic value for detecting haemodynamically significant CAD did not change. Therefore, clinical impact of individualized segmentation seems limited.

Changes in cerebral oxygenation and cerebral blood flow during hemodialysis – A simultaneous near-infrared spectroscopy and positron emission tomography study

Near-infrared spectroscopy (NIRS) is used to monitor cerebral tissue oxygenation (rSO2) depending on cerebral blood flow (CBF), cerebral blood volume and blood oxygen content. We explored whether NIRS might be a more easy applicable proxy to [15O]H2O positron emission tomography (PET) for detecting CBF changes during hemodialysis. Furthermore, we compared potential determinants of rSO2 and CBF. In 12 patients aged ≥ 65 years, NIRS and PET were performed simultaneously: before (T1), early after start (T2), and at the end of hemodialysis (T3). Between T1 and T3, the relative change in frontal rSO2 (ΔrSO2) was −8 ± 9% (P = 0.001) and −5 ± 11% (P = 0.08), whereas the relative change in frontal gray matter CBF (ΔCBF) was −11 ± 18% (P = 0.009) and −12 ± 16% (P = 0.007) for the left and right hemisphere, respectively. ΔrSO2 and ΔCBF were weakly correlated for the left (ρ 0.31, P = 0.4), and moderately correlated for the right (ρ 0.69, P = 0.03) hemisphere. The Bland-Altman plot suggested underestimation of ΔCBF by NIRS. Divergent associations of pH, pCO2 and arterial oxygen content with rSO2 were found compared to corresponding associations with CBF. In conclusion, NIRS could be a proxy to PET to detect intradialytic CBF changes, although NIRS and PET capture different physiological parameters of the brain.

The effect of occipital nerve field stimulation on the descending pain pathway in patients with fibromyalgia: a water PET and EEG imaging study

BackgroundFibromyalgia is a chronic disorder characterized by widespread musculoskeletal pain accompanied by fatigue, sleep, memory, and mood problems. Recently, occipital nerve field stimulation (ONS) has been proposed as an effective potential treatment for fibromyalgia-related pain. The aim of this study is to unravel the neural mechanism behind occipital nerve stimulation’s ability to suppress pain in fibromyalgia patients.Materials and methodsSeven patients implanted with subcutaneous electrodes in the C2 dermatoma were enrolled for a Positron Emission Tomography (PET) H215O activation study. These seven patients were selected from a cohort of 40 patients who were part of a double blind, placebo-controlled study followed by an open label follow up at six months. The H215O PET scans were taken during both the “ON” (active stimulation) and “OFF” (stimulating device turned off) conditions. Electroencephalogram (EEG) data were also recorded for the implanted fibromyalgia patients during both the “ON” and “OFF” conditions.ResultsRelative to the “OFF” condition, ONS stimulation resulted in activation in the dorsal lateral prefrontal cortex, comprising the medial pain pathway, the ventral medial prefrontal cortex, and the bilateral anterior cingulate cortex as well as parahippocampal area, the latter two of which comprise the descending pain pathway. Relative deactivation was observed in the left somatosensory cortex, constituting the lateral pain pathway as well as other sensory areas such as the visual and auditory cortex. The EEG results also showed increased activity in the descending pain pathway. The pregenual anterior cingulate cortex extending into the ventral medial prefrontal cortex displayed this increase in the theta, alpha1, alpha2, beta1, and beta2 frequency bands.ConclusionPET shows that ONS exerts its effect via activation of the descending pain inhibitory pathway and the lateral pain pathway in fibromyalgia, while EEG shows activation of those cortical areas that could be responsible for descending inhibition system recruitment.Trial RegistrationThis study is registered with ClinicalTrials.gov, number NCT00917176 (June 10, 2009).

Abstract 16649: Recovery of Myocardial Perfusion After Percutaneous Coronary Intervention of Chronic Total Occlusions is Comparable to Non-Occlusive Lesions

Background: The benefits of chronic coronary total occlusion (CTO) percutaneous coronary intervention (PCI) are being questioned. The aim of this study was to assess the effects of CTO PCI on absolute myocardial perfusion, as compared to PCI of hemodynamically significant non-occlusive lesions. Methods: Consecutive patients with a preserved left ventricular ejection fraction (≥50%) and a CTO or non-CTO lesion, in whom [ 15 O]H 2 O positron emission tomography was performed prior and after successful PCI, were included. Change in quantitative (hyperemic) myocardial blood flow (MBF), coronary flow reserve (CFR) and perfusion defect size (in myocardial segments) were compared between CTOs and non-occlusive lesions. Results: Ninety-two patients with a CTO and 31 patients with a non-occlusive lesion were included. CTOs induced larger perfusion defect sizes (4.51±1.69 vs. 3.23±2.38 segments, p&lt;0.01) with lower hyperemic MBF (1.30±0.37 vs. 1.58±0.62 mL·min -1 ·g -1 , p&lt;0.01) and similarly impaired CFR (1.66±0.75 vs. 1.89±0.77, p=0.17) compared with non-occlusive lesions. After PCI both hyperemic MBF and CFR increased similarly between groups (p=0.57 and p=0.35) to normal ranges with higher hyperemic MBF values in non-CTO compared to CTO (2.89±0.94 vs. 2.48±0.73 mL·min -1 ·g -1 , p=0.03). Perfusion defect sizes decreased similarly after CTO PCI and non-CTO PCI (p=0.14), leading to small residual defect sizes in both groups (1.15±1.44 vs. 0.61±1.45 segments, p=0.054). Conclusions: Percutaneous revascularization of CTOs improves absolute myocardial perfusion similarly to PCI of hemodynamically significant non-occlusive lesions, leading to satisfying results. Myocardial perfusion findings are less favorable in patients with a CTO before and after PCI, suggesting a more advanced stage of coronary artery disease.

Hybrid coronary computed tomography angiography and positron emission tomography myocardial perfusion imaging in evaluation of recurrent symptoms after coronary artery bypass grafting.

Recurrent chest pain after coronary artery bypass grafting (CABG) poses a diagnostic challenge. We hypothesized that combining anatomy of bypass grafts and native coronary arteries with ischaemia detection by hybrid imaging could be used to gain valuable and complementary information in patients with recurrent symptoms after CABG. We analysed 36 consecutive patients (67 ± 9 years, 81% male) who had undergone hybrid imaging using coronary computed tomography angiography (CCTA) and [15O]H2O positron emission tomography (PET) myocardial perfusion imaging due to recurrent symptoms after CABG. Coronary tree and left ventricular myocardium were divided into three main territories, yielding a total of 108 coronary territories in 36 patients. The presence of obstructive (≥50%) stenosis and the patency of grafts were evaluated by CCTA, while myocardial ischaemia was assessed by quantitative adenosine-stress PET. Altogether 28 (78%) of the 36 study patients presented with matched PET/CCTA abnormalities. Forty-one coronary territories were supplied by non-obstructed bypass grafts or native coronary arteries (protected territory). However, 12 (29%) of these presented with a perfusion defect. In six cases, the perfusion defect involved myocardium distal to the graft-coronary anastomosis, as interpreted on the PET/CCTA fusion images. In turn, in 48 coronary territories the supplying artery was obstructed on CCTA (unprotected territory). Of these, 41 (85%, P < 0.001 vs. protected) presented with abnormal perfusion, involving myocardium distal to the anastomosis in 29 cases. Hybrid imaging provides complementary information on the presence and localization of atherosclerotic lesions and myocardial perfusion abnormalities in symptomatic patients with previous CABG.

Doppler Flow Velocity and Thermodilution to Assess Coronary Flow Reserve: A Head-to-Head Comparison With [15O]H2O PET

ObjectivesThis study sought to compare Doppler flow velocity reserve (CFRDoppl) and thermodilution-derived coronary flow reserve (CFRthermo) head-to-head with the gold standard for quantification of myocardial perfusion, [15O]H2O positron emission tomography (PET). BackgroundCoronary flow reserve (CFR) is an important parameter for assessing coronary vascular function. To date, 2 techniques are available for invasive assessment of CFR: Doppler flow velocity and thermodilution. Although these techniques have been compared with each other, neither has been compared with [15O]H2O PET perfusion imaging. MethodsCFR was assessed in 98 vessels of 40 consecutive stable patients with suspected coronary artery disease. Patients underwent [15O]H2O PET, followed by invasive angiography in conjunction with simultaneous measurements of fractional flow reserve, CFRDoppl, and CFRthermo. Both normal and obstructed arteries were included. ResultsThe quality of Doppler flow velocity traces was significantly lower than that of thermodilution curves (p < 0.001). A moderate correlation was observed between CFRDoppl and CFRthermo (r = 0.59; p < 0.001). CFRDoppl correlated well with PET-derived CFR (CFRPET) (r = 0.82; p < 0.001). In contrast, the correlation between CFRthermo and CFRPET was only modest (r = 0.55; p < 0.001). This difference in correlation with CFRPET was significant (t = 4.9; df = 95; p < 0.001). Bland-Altman analysis revealed a tendency of CFRthermo to overestimate flow reserve at higher values. ConclusionsCoronary flow reserve, determined using Doppler flow velocity, has superior agreement with [15O]H2O PET in comparison with CFRthermo.

Diagnostic value of longitudinal flow gradient for the presence of haemodynamically significant coronary artery disease.

The longitudinal myocardial blood flow (MBF) gradient derived from positron emission tomography (PET) has been proposed as an emerging non-invasive index of haemodynamically significant coronary artery disease (CAD). This study aimed to investigate the diagnostic value of longitudinal MBF gradient for the presence of haemodynamically significant CAD. A total of 204 patients (603 vessels) with suspected CAD underwent [15O]H2O PET followed by invasive coronary angiography with fractional flow reserve (FFR) of all major coronary arteries. Longitudinal base-to-apex MBF gradients were assessed by two methods, using MBF in apical and mid (Method 1) or in apical and basal (Method 2) myocardial segments to calculate the gradient. The hyperaemic longitudinal MBF gradient was only weakly correlated with FFR (Method 1: r = 0.12, P = 0.02; Method 2: r = 0.22, P < 0.001). The hyperaemic longitudinal MBF gradient (by both methods), had lower diagnostic value when compared with hyperaemic MBF for the presence of haemodynamically significant CAD, defined as an FFR ≤ 0.80. No significant correlations between longitudinal MBF gradients and FFR were noted in proximal lesions, whereas longitudinal MBF gradients and FFR were significantly correlated in non-proximal lesions (r = 0.57, P < 0.001). PET measured longitudinal flow parameters had lower diagnostic value when compared with hyperaemic MBF for the presence of haemodynamically significant CAD. Since lesion location was found to affect the correlation of PET measured longitudinal flow parameters and FFR, presence of a longitudinal flow gradient may be partly caused by normalization to a relatively normal perfused areas.

Quantification of O-(2-[18F]fluoroethyl)-L-tyrosine kinetics in glioma

BackgroundThis study identified the optimal tracer kinetic model for quantification of dynamic O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET) positron emission tomography (PET) studies in seven patients with diffuse glioma (four glioblastoma, three lower grade glioma). The performance of more simplified approaches was evaluated by comparison with the optimal compartment model. Additionally, the relationship with cerebral blood flow—determined by [15O]H2O PET—was investigated.ResultsThe optimal tracer kinetic model was the reversible two-tissue compartment model. Agreement analysis of binding potential estimates derived from reference tissue input models with the distribution volume ratio (DVR)-1 derived from the plasma input model showed no significant average difference and limits of agreement of − 0.39 and 0.37. Given the range of DVR-1 (− 0.25 to 1.5), these limits are wide. For the simplified methods, the 60–90 min tumour-to-blood ratio to parent plasma concentration yielded the highest correlation with volume of distribution VT as calculated by the plasma input model (r = 0.97). The 60–90 min standardized uptake value (SUV) showed better correlation with VT (r = 0.77) than SUV based on earlier intervals. The 60–90 min SUV ratio to contralateral healthy brain tissue showed moderate agreement with DVR with no significant average difference and limits of agreement of − 0.24 and 0.30. A significant but low correlation was found between VT and CBF in the tumour regions (r = 0.61, p = 0.007).ConclusionUptake of [18F]FET was best modelled by a reversible two-tissue compartment model. Reference tissue input models yielded estimates of binding potential which did not correspond well with plasma input-derived DVR-1. In comparison, SUV ratio to contralateral healthy brain tissue showed slightly better performance, if measured at the 60–90 min interval. SUV showed only moderate correlation with VT. VT shows correlation with CBF in tumour.

The renal blood flow reserve in healthy humans and patients with atherosclerotic renovascular disease measured by positron emission tomography using [15O]H2O

BackgroundMicrovascular function plays an important role in ARVD (atherosclerotic renovascular disease). RFR (renal flow reserve), the capacity of renal vasculature to dilate, is known to reflect renal microvascular function. In this pilot study, we assessed PET (positron emission tomography)-based RFR values of healthy persons and renal artery stenosis patients.Seventeen patients with ARVD and eight healthy subjects were included in the study. Intravenous enalapril 1 mg was used as a vasodilatant, and the maximum response (blood pressure and RFR) to it was measured at 40 min. Renal perfusion was measured by means of oxygen-15-labeled water PET. RFR was calculated as a difference of stress flow and basal flow and was expressed as percent [(stress blood flow − basal blood flow)/basal blood flow] × 100%.ResultsRFR of the healthy was 22%. RFR of the stenosed kidneys of bilateral stenosis patients (27%) was higher than that of the stenosed kidneys of unilateral stenosis patients (15%). RFR of the contralateral kidneys of unilateral stenosis patients was 21%. There was no difference of statistical significance between RFR values of ARVD subgroups or between ARVD subgroups and the healthy. In the stenosed kidneys of unilateral ARVD patients, stenosis grade of the renal artery correlated negatively with basal (p = 0.04) and stress flow (p = 0.02). Dispersion of RFR values was high.ConclusionsThis study is the first to report [15O]H2O PET-based RFR values of healthy subjects and ARVD patients in humans. The difference between RFR values of ARVD patients and the healthy did not reach statistical significance perhaps because of high dispersion of RFR values. [15O]H2O PET is a valuable non-invasive and quantitative method to evaluate renal blood flow though high dispersion makes imaging challenging. Larger studies are needed to get more information about [15O]H2O PET method in evaluation of renal blood flow.

Hemodialysis Induces an Acute Decline in Cerebral Blood Flow in Elderly Patients.

The initiation of hemodialysis is associated with an accelerated decline of cognitive function and an increased incidence of cerebrovascular accidents and white matter lesions. Investigators have hypothesized that the repetitive circulatory stress of hemodialysis induces ischemic cerebral injury, but the mechanism is unclear. We studied the acute effect of conventional hemodialysis on cerebral blood flow (CBF), measured by [15O]H2O positron emission tomography-computed tomography (PET-CT). During a single hemodialysis session, three [15O]H2O PET-CT scans were performed: before, early after the start of, and at the end of hemodialysis. We used linear mixed models to study global and regional CBF change during hemodialysis. Twelve patients aged ≥65 years (five women, seven men), with a median dialysis vintage of 46 months, completed the study. Mean (±SD) arterial BP declined from 101±11 mm Hg before hemodialysis to 93±17 mm Hg at the end of hemodialysis. From before the start to the end of hemodialysis, global CBF declined significantly by 10%±15%, from a mean of 34.5 to 30.5 ml/100g per minute (difference, -4.1 ml/100 g per minute; 95% confidence interval, -7.3 to -0.9 ml/100 g per minute; P=0.03). CBF decline (20%) was symptomatic in one patient. Regional CBF declined in all volumes of interest, including the frontal, parietal, temporal, and occipital lobes; cerebellum; and thalamus. Higher tympanic temperature, ultrafiltration volume, ultrafiltration rate, and pH significantly associated with lower CBF. Thus, conventional hemodialysis induces a significant reduction in global and regional CBF in elderly patients. Repetitive intradialytic decreases in CBF may be one mechanism by which hemodialysis induces cerebral ischemic injury.

Effect of Plaque Burden and Morphology on Myocardial Blood Flow and Fractional Flow Reserve

BackgroundAtherosclerotic plaque characteristics may affect downstream myocardial perfusion, as well as coronary lesion severity. ObjectivesThis study sought to evaluate the association between quantitative plaque burden and plaque morphology obtained using coronary computed tomography angiography (CTA) and quantitative myocardial perfusion obtained using [15O]H2O positron emission tomography (PET), as well as fractional flow reserve (FFR) derived invasively. MethodsTwo hundred eight patients (63% men; age 58 ± 8.7 years) with suspected coronary artery disease were prospectively included. All patients underwent 256-slice coronary CTA, [15O]H2O PET, and invasive FFR measurements. Coronary CTA-derived plaque burden and morphology were assessed using commercially available software and compared with PET perfusion and FFR. ResultsAtherosclerotic plaques were present in 179 patients (86%) and 415 of 610 (68%) evaluable coronary arteries. On a per-vessel basis, traditional coronary plaque burden indexes, such as plaque length and volume, minimal lumen area, and stenosis percentage, were significantly associated with impaired hyperemic myocardial blood flow (MBF) and FFR. In addition, morphological features, such as partially calcified plaques, positive remodeling (PR), and low attenuation plaque, displayed a negative impact on hyperemic MBF and FFR. Multivariable analysis revealed that the morphological feature of PR was independently related to impaired hyperemic MBF as well as an unfavorable FFR (p = 0.004 and p = 0.007, respectively), next to stenosis percentage (p = 0.001 and p < 0.001, respectively) and noncalcified plaque volume (p < 0.001 and p = 0.010, respectively). ConclusionsPR and noncalcified plaque volume are associated with detrimental downstream hyperemic myocardial perfusion and FFR, independent of lesion severity.

Diagnostic Value of Transluminal Attenuation Gradient for the Presence of Ischemia as Defined by Fractional Flow Reserve and Quantitative Positron Emission Tomography

ObjectivesThe aim of this study was to investigate the incremental diagnostic value of transluminal attenuation gradient (TAG), TAG with corrected contrast opacification (TAG-CCO), and transluminal diameter gradient (TDG) over coronary computed tomography angiography (CTA)–derived diameter stenosis alone for the identification of ischemia as defined by both the invasive reference standard fractional flow reserve (FFR) and the noninvasive reference standard quantitative positron emission tomography (PET). BackgroundIn addition to anatomic information obtained by coronary CTA, several functional CT parameters have been proposed to identify hemodynamically significant lesions more accurately, such as TAG, TAG-CCO, and more recently TDG. However, clinical validation studies have reported conflicting results, and a recent study has suggested that TAG may be affected by changes in vessel diameter. MethodsPatients with suspected coronary artery disease underwent coronary CTA and [15O]H2O PET followed by invasive coronary angiography with FFR of all major coronary arteries. TAG, TAG-CCO, and TDG were assessed, and the incremental diagnostic value of these parameters over coronary CTA–derived diameter stenosis alone for ischemia as defined by PET (hyperemic myocardial blood flow ≤2.30 ml/min/g) and FFR (≤0.80) was determined. ResultsA total of 557 (91.9%) coronary arteries of 201 patients were included for analysis. TAG, TAG-CCO, and TDG did not discriminate between vessels with or without ischemia as defined by either PET or FFR. Furthermore, these parameters did not have incremental diagnostic accuracy over coronary CTA alone for the presence of ischemia as defined by PET and FFR. There was a significant correlation between TDG and TAG (r = 0.47; p < 0.001) and between TDG and TAG-CCO (r = 0.37; p < 0.001). ConclusionsTAG, TAG-CCO, and TDG do not provide incremental diagnostic value over coronary CTA alone for the presence of ischemia as defined by [15O]H2O PET and/or FFR. The lack of diagnostic value of contrast enhancement–based flow estimations appears related to coronary luminal dimension variability.