15O-water Positron Emission Tomography Research Articles

Quantitation of mitral regurgitation using positron emission tomography

BackgroundCardiac positron emission tomography (PET) offers non-invasive assessment of perfusion and left ventricular (LV) function from a single dynamic scan. However, no prior assessment of mitral regurgitation severity by PET has been presented. Application of indicator dilution techniques and gated image analyses to PET data enables calculation of forward stroke volume and total LV stroke volume. We aimed to evaluate a combination of these methods for measurement of regurgitant volume (RegVol) and fraction (RegF) using dynamic 15O-water and 11C-acetate PET in comparison to cardiovascular magnetic resonance (CMR).ResultsTwenty-one patients with severe primary mitral valve regurgitation underwent same-day dynamic PET examinations (15O-water and 11C-acetate) and CMR. PET data were reconstructed into dynamic series with short time frames during the first pass, gated 15O-water blood pool images, and gated 11C-acetate myocardial uptake images. PET-based RegVol and RegF correlated strongly with CMR (RegVol: 15O-water r = 0.94, 11C-acetate r = 0.91 and RegF: 15O-water r = 0.88, 11C-acetate r = 0.84, p < 0.001). A systematic underestimation (bias) was found for PET (RegVol: 15O-water − 11 ± 13 mL, p = 0.002, 11C-acetate − 28 ± 16 mL, p < 0.001 and RegF: 15O-water − 4 ± 6%, p = 0.01, 11C-acetate − 10 ± 7%, p < 0.001). PET measurements in patients were compared to healthy volunteers (n = 18). Mean RegVol and RegF was significantly lower in healthy volunteers compared to patients for both tracers. The accuracy of diagnosing moderately elevated regurgitant volume (> 30mL) was 95% for 15O-water and 92% for 11C-acetate.ConclusionsLV regurgitation severity quantified using cardiac PET correlated with CMR and showed high accuracy for discriminating patients from healthy volunteers.

Improvement in the estimation of perfusable tissue fraction and myocardial flow reserve in the ischemic myocardial lesions using ECG-gated dynamic myocardial PET with 15O-water.

Perfusable tissue fraction (PTF) and myocardial flow reserve (MFR) from 15O-water dynamic positron emission tomography (PET) are parameters of myocardial viability. However, myocardial motion causes errors in these values. We aimed to develop accurate estimation of PTF and MFR in ischemic lesions using an electro-cardiogram (ECG)-gated dynamic myocardial PET with 15O-water. Twenty-seven patients with ischemic heart disease were enrolled. All patients underwent percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). List mode 3D PET data and ECG signals were acquired using Philips Gemini TF64 instrument. For each scan, 500MBq of 15O-water was infused slowly for 2min, and the dynamic data were scanned for 6min. Both non-gated dynamic images and ECG-gated diastolic dynamic images were reconstructed. On the myocardial PET images of each patient, the entire myocardial region of interest (ROI) was set and divided into 17 segments. Myocardial blood flow in the resting state (rest MBF), hyperemic state (stress MBF), PTF, and MFR in each segment were estimated from both non-gated and ECG-gated dynamic PET images. Coronary arteriograms were obtained for all patients. In total, 128 normal segments without stenosis and 50 ischemic segments with > 90% stenosis were evaluated. In the ischemic myocardial segments, the PTF with ECG-gated PET was estimated as significantly lower than that with non-gated PET (0.63 ± 0.09 vs. 0.72 ± 0.08 [mL/mL], p < 0.001). The ECG-gated PET estimated a significantly lower PTF in the ischemic segments than in the normal segments (0.63 ± 0.09 vs. 0.67 ± 0.07 [mL/mL], p < 0.01). In the normal segments, the ECG-gated PET detected no significant difference in MFR compared with those from the non-gated PET (2.15 ± 0.76 vs. 2.24 ± 0.79, p = 0.28). However, in the ischemic myocardial segments, the MFR with ECG-gated PET was estimated as significantly lower than that with the non-gated PET (1.23 ± 0.29 vs. 1.69 ± 0.71, p < 0.001). The ECG-gated PET presented a significantly higher inter-observer reproducibility of PTF and rest MBF than the non-gated PET (p < 0.01). Neither stress MBF nor MFR yielded significant differences in inter-observer reproducibility between the ECG-gated and non-gated PET. The ECG-gated dynamic 15O-water PET suppressed the myocardial motion effect and resulted in a lower PTF and MFR in ischemic myocardial lesions than the non-gated PET. The ECG-gated PET seemed to be better than the conventional non-gated dynamic PET for the detection of ischemic myocardial lesion.

Turning brain MRI into diagnostic PET: 15O-water PET CBF synthesis from multi-contrast MRI via attention-based encoder–decoder networks

Accurate quantification of cerebral blood flow (CBF) is essential for the diagnosis and assessment of a wide range of neurological diseases. Positron emission tomography (PET) with radiolabeled water (15O-water) is the gold-standard for the measurement of CBF in humans, however, it is not widely available due to its prohibitive costs and the use of short-lived radiopharmaceutical tracers that require onsite cyclotron production. Magnetic resonance imaging (MRI), in contrast, is more accessible and does not involve ionizing radiation. This study presents a convolutional encoder–decoder network with attention mechanisms to predict the gold-standard 15O-water PET CBF from multi-contrast MRI scans, thus eliminating the need for radioactive tracers. The model was trained and validated using 5-fold cross-validation in a group of 126 subjects consisting of healthy controls and cerebrovascular disease patients, all of whom underwent simultaneous 15O-water PET/MRI. The results demonstrate that the model can successfully synthesize high-quality PET CBF measurements (with an average SSIM of 0.924 and PSNR of 38.8 dB) and is more accurate compared to concurrent and previous PET synthesis methods. We also demonstrate the clinical significance of the proposed algorithm by evaluating the agreement for identifying the vascular territories with impaired CBF. Such methods may enable more widespread and accurate CBF evaluation in larger cohorts who cannot undergo PET imaging due to radiation concerns, lack of access, or logistic challenges.

Rationale and design of the RAPID-WATER-FLOW trial: Radiolabeled perfusion to identify coronary artery disease using water to evaluate responses of myocardial FLOW

ObjectivesThe objective of this study was to determine the diagnostic performance of 15O-water positron emission tomography (PET) myocardial perfusion imaging to detect coronary artery disease (CAD) using the truth-standard of invasive coronary angiography (ICA) with fractional flow reserve (FFR) or instantaneous wave-Free Ratio (iFR) or coronary computed tomography angiogram (CCTA). Background15O-water has a very high first-pass extraction that allows accurate quantification of myocardial blood flow and detection of flow-limiting CAD. However, the need for an on-site cyclotron and lack of automated production at the point of care and relatively complex image analysis protocol has limited its clinical use to date. MethodsThe RAPID WATER FLOW study is an open-label, multicenter, prospective investigation of the accuracy of 15O-water PET to detect obstructive angiographic and physiologically significant stenosis in patients with suspected CAD. The study will include the use of an automated system for producing, dosing, and injecting 15O-water and enrolling approximately 215 individuals with suspected CAD at approximately 10 study sites in North America and Europe. The primary endpoint of the study is the diagnostic sensitivity and specificity of the 15O-water PET study using the truth-standard of ICA with FFR or iFR to determine flow-limiting stenosis, or CCTA to rule out CAD and incorporating a quantitative analytic platform developed for the 15O-water PET acquisitions. Sensitivity and specificity are to be considered positive if the lower bound of the 95% confidence interval is superior to the threshold of 60% for both, consistent with prior registration studies.Subgroup analyses include assessments of diagnostic sensitivity, specificity, and accuracy in female, obese, and diabetic individuals, as well as in those with multivessel disease. All enrolled individuals will be followed for adverse and serious adverse events for up to 32 hours after the index PET scan.The study will have >90% power (one-sided test, α = 0.025) to test the hypothesis that sensitivity and specificity of 15O-water PET are both >60%. ConclusionsThe RAPID WATER FLOW study is a prospective, multicenter study to determine the diagnostic sensitivity and specificity of 15O-water PET as compared to ICA with FFR/iFR or CCTA. This study will introduce several novel aspects to imaging registration studies, including a more relevant truth standard incorporating invasive physiologic indexes, coronary CTA to qualify normal individuals for eligibility, and a more quantitative approach to image analysis than has been done in prior pivotal studies. Clinical trial registration informationClinical-Trials.gov (#NCT05134012).

Left-ventricular volumes and ejection fraction from cardiac ECG-gated 15O-water positron emission tomography compared to cardiac magnetic resonance imaging using simultaneous hybrid PET/MR

Background15O-water PET is the gold standard for noninvasive quantification of myocardial blood flow. In addition to evaluation of ischemia, the assessment of cardiac function and remodeling is important in all cardiac diseases. However, since 15O-water is freely diffusible and standard uptake images show little contrast between the myocardium and blood pool, the assessment of left-ventricular (LV) volumes and ejection fraction (EF) is challenging. Therefore, the aim of the present study was to investigate the feasibility of calculating LV volumes and EF from first-pass analysis of 15O-water PET, by comparison with cardiac magnetic resonance imaging (CMR) using a hybrid PET/MR scanner. MethodsTwenty-four patients with known or suspected CAD underwent a simultaneous ECG-gated cardiac PET/MR scan. The 15O-water first-pass images (0-50 seconds) were analyzed using the CarPET software and the CMR images were analyzed using the software Segment, for LV volumes and EF calculations. The LV volumes and EF were compared using correlation and Bland–Altman analysis. In addition, inter- and intra-observer variability of LV volumes and EF were assessed for both modalities. ResultsThe correlation between PET and CMR was strong for volumes (r > 0.84) and moderate for EF (r = 0.52), where the moderate correlation for EF was partly due to the small range of EF values. Agreement was high for all parameters, with a slight overestimation of PET values for end-diastolic volume but with no significant mean bias for other parameters. Inter- and intra-observer agreement of volumes was high and comparable between PET and CMR. For EF, inter-observer agreement was higher for PET and intra-observer agreement was higher for CMR. ConclusionLV volumes and EF can be calculated by first-pass analysis of a 15O-water PET scan with high accuracy and comparable precision as with CMR.

Prognostic value of combined coronary CT angiography and myocardial perfusion imaging in women and men

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): State Research Funding for Turku University Hospital. Background Combined anatomical and functional imaging enables detection of non-obstructive and obstructive coronary artery disease (CAD) as well as myocardial ischemia, and also provides prognostic information. Purpose We evaluated sex differences in disease phenotype and adverse outcomes by using non-invasive combined anatomical and functional imaging in symptomatic patients with suspected CAD. Methods We retrospectively evaluated patients undergone coronary computed tomography angiography (CTA) for suspected CAD. According to local routine, patients with suspected obstructive stenosis on CTA were referred to downstream 15O-water positron emission tomography (PET) myocardial perfusion imaging to assess stress myocardial blood flow (MBF; ≤2.3 mL/g/min considered abnormal). A composite adverse endpoint was recorded, including all-cause death, myocardial infarction, and unstable angina pectoris. Results A total of 1948 patients (59% women) underwent coronary CTA of whom 657 (34%) patients underwent downstream PET perfusion imaging. During a mean follow-up of 6.8 years, 182 adverse events occurred. Women more often had normal coronary arteries (42% vs. 22%, p&amp;lt;0.001) and less often abnormal stress MBF (9% vs. 28%, p&amp;lt;0.001), as compared with men. The annual adverse event rate was lower in women versus men (1.2% vs. 1.7%, p = 0.02). Both in women and men, coronary calcification, non-obstructive CAD, and abnormal stress MBF were independent predictors of events. Abnormal stress MBF was associated with 5.0 and 5.6-fold adverse event rates in women and men, respectively. There was no statistical interaction between sex and coronary calcification, non-obstructive CAD, or abnormal stress MBF in terms of predicting adverse outcome. Conclusion Among patients evaluated for chronic chest pain, women have lower prevalence of ischemic CAD and lower rate of future adverse events. Combined coronary CTA and PET myocardial perfusion imaging predicts outcomes equally in women and men.

Hybrid CTA/PET imaging of coronary artery disease in non-diabetic, prediabetic and diabetic patients evaluated for chest pain

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Academy of Finland Finnish foundation for cardiovascular research. Background Patients with prediabetes or diabetes are at increased risk of developing cardiovascular disease and cardiac events. First-line coronary computed tomography angiography (CTA) followed by selective use of positron emission tomography (PET) myocardial perfusion imaging is a feasible strategy to diagnose and risk-stratify patients with suspected coronary artery disease (CAD). Purpose To study whether prediabetes or diabetes affects the relationship between imaging-defined CAD and patient outcome. Methods We retrospectively identified consecutive symptomatic patients who underwent coronary CTA for suspected CAD. In patients with suspected obstructive CAD on CTA, myocardial ischemia was routinely evaluated by 15O-water PET myocardial perfusion imaging. The relationship of CAD phenotype and long-term outcome was investigated according to patient’s diabetic status. A composite outcome included all-cause mortality, myocardial infarction (MI), and unstable angina pectoris. Results A total of 1743 patients were included: 1214 (70%) non-diabetic, 259 (15%) prediabetic, and 270 (16%) type 2 diabetic patients. During 6.43 years of follow-up, 164 (9%) adverse events occurred, including 106 deaths, 41 MIs and 17 episodes of unstable angina. The prevalence of normal coronary arteries on CTA was highest in the non-diabetic patients (39%). The prevalence of hemodynamically significant CAD (i.e., obstructive stenosis and abnormal perfusion) increased from 14% in non-diabetic patients to 20% in prediabetic and to 27% in diabetic patients. The lowest event rate was seen in patients with normal coronary arteries (annual event rate 0.2%) and highest in patients with concomitant type 2 diabetes and hemodynamically significant CAD (annual event rate 4.7%). However, neither prediabetes nor diabetes were independent predictors of the composite adverse outcome after adjustment for the clinical risk factors and imaging findings. Conclusions Coronary CTA followed by selective downstream use of PET myocardial perfusion imaging predicts long-term outcome similarly in type 2 diabetic, prediabetic, and non-diabetic patients.

The impact of diabetes on the relationship of coronary artery disease and outcome: a study using multimodality imaging

BackgroundPatients with prediabetes or diabetes are at increased risk of developing cardiovascular disease and adverse outcomes. First-line coronary computed tomography angiography (CTA) followed by selective use of positron emission tomography (PET) myocardial perfusion imaging is a feasible strategy to diagnose and risk-stratify patients with suspected coronary artery disease (CAD). The aim of the present study was to study whether diabetes changes the relationship of CAD and long-term outcome.MethodsWe retrospectively identified consecutive symptomatic patients who underwent coronary CTA for suspected CAD. In patients with suspected obstructive CAD on CTA, myocardial ischemia was evaluated by 15O-water PET myocardial perfusion imaging. The relationship of the phenotype of CAD and long-term outcome in patients with no diabetes, prediabetes, or type 2 diabetes was investigated. A composite endpoint included all-cause mortality, myocardial infarction (MI), and unstable angina pectoris (UAP).ResultsA total of 1743 patients were included: 1214 (70%) non-diabetic, 259 (15%) prediabetic, and 270 (16%) type 2 diabetic patients. During 6.43 years of median follow-up, 164 adverse events occurred (106 deaths, 41 MIs, 17 UAPs). The prevalence of normal coronary arteries on CTA was highest in the non-diabetic patients (39%). The prevalence of hemodynamically significant CAD (abnormal perfusion) increased from 14% in non-diabetic patients to 20% in prediabetic and 27% in diabetic patients. The event rate was lowest in patients with normal coronary arteries and highest in patients with concomitant type 2 diabetes and hemodynamically significant CAD (annual event rate 0.2% vs. 4.7%). However, neither prediabetes nor diabetes were independent predictors of the composite adverse outcome after adjustment for the clinical risk factors and imaging findings.ConclusionsCoronary CTA followed by selective downstream use of PET myocardial perfusion imaging predicts long-term outcome similarly in non-diabetic and diabetic patients.

Prognostic value of combined coronary CT angiography and myocardial perfusion imaging in women and men.

Combined anatomical and functional imaging enables detection of non-obstructive and obstructive coronary artery disease (CAD) as well as myocardial ischaemia. We evaluated sex differences in disease profile and outcomes after combined computed tomography angiography (CTA) and positron emission tomography (PET) perfusion imaging in patients with suspected obstructive CAD. We retrospectively evaluated 1948 patients (59% women) referred for coronary CTA due to suspected CAD during the years 2008-2016. Patients with a suspected obstructive lesion on coronary CTA (n = 657) underwent 15O-water PET to assess stress myocardial blood flow (MBF). During a mean follow-up of 6.8 years, 182 adverse events (all-cause death, myocardial infarction, or unstable angina) occurred. Women had more often normal coronary arteries (42% vs. 22%, P < 0.001) and less often abnormal stress MBF (9% vs. 28%, P < 0.001) than men. The annual adverse event rate was lower in women vs. men (1.2% vs. 1.7%, P = 0.02). Both in women and men, coronary calcification, non-obstructive CAD, and abnormal stress MBF were independent predictors of events. Abnormal stress MBF was associated with 5.0- and 5.6-fold adverse event rates in women and men, respectively. There was no interaction between sex and coronary calcification, non-obstructive CAD, or abnormal stress MBF in terms of predicting adverse events. Among patients evaluated for chronic chest pain, women have a lower prevalence of ischaemic CAD and a lower rate of adverse events. Combined coronary CTA and PET myocardial perfusion imaging predict outcomes equally in women and men.

Influence of image reconstruction on quantitative cardiac 15O-water positron emission tomography

BackgroundThe impact on quantitative 15O-water PET/CT of a wide range of different reconstruction settings, including regularized reconstruction by block-sequential regularized expectation maximization (BSREM), was investigated. MethodsTwenty clinical stress scans from patients referred for assessment of myocardial ischemia were included. Patients underwent a 4-min dynamic stress PET scan with 15O-water on a digital PET/CT scanner. Twenty-two reconstructions were generated from each scan and a clinical reconstruction was used as reference. Varied parameters were number of iterations, filter, exclusion of time-of-flight and point-spread function, and regularization parameter with BSREM. Analyses were performed in aQuant utilizing two different methods and resulting regional myocardial blood flow (MBF), perfusable tissue fraction (PTF), and transmural MBF (MBFt) values were evaluated. ResultsAcross the two analyses, correlations toward the reference reconstruction were strong for all parameters (ρ ≥ 0.83). Using automated analysis and the diagnostic threshold of hyperemic MBF at 2.3 mL⋅g−1⋅min−1, diagnosis was unchanged irrespective of reconstruction method in all patients except for one, where only four of the most extreme reconstruction methods resulted in a change of diagnosis. ConclusionThe low sensitivity of MBF values to reconstruction method and, as previously shown, scanner type and PET/CT misalignment, confirms that diagnostic hyperemic MBF cutoff values can be consistently used for 15O-water.

Molecular imaging of alphaVbeta3 integrin for evaluation of myocardial injury after acute myocardial infarction

Abstract Background 68Ga-NODAGA-RGD is a positron emission tomography (PET) tracer targeting αvβ3 integrin that is upregulated during angiogenesis. αvβ3 integrin expression increases early after acute myocardial infarction (AMI), and has been proposed as a marker of myocardial repair. Purpose We prospectively evaluated the uptake of 68Ga-NODAGA-RGD and its association to left ventricular function after human AMI. Methods Thirty patients underwent PET at 7.7±3.8 days after primary percutaneous coronary intervention for ST-elevation AMI. Resting myocardial perfusion was evaluated using 15O-water PET followed by evaluation of 68Ga-NODAGA-RGD uptake 60–75 minutes after injection of 179 MBq of tracer. Left ventricular function was evaluated by transthoracic echocardiography on the day of PET, and at 6-month follow-up. The definition of the ischemic area at risk and remote myocardial segments was based on the culprit coronary arterial segments in invasive angiography. 68Ga-NODAGA-RGD images were co-registered with perfusion images and uptake was measured as the standardized uptake value in the segment with the highest uptake (SUVmax) in ischemic area at risk, and the mean standardized uptake value (SUVmean) in remote segments. In addition, we calculated 68Ga-NODAGA-RGD uptake corrected to the mean myocardial blood flow (MBF) in the area at risk (SUVmax/MBFmean) to account for reduced distribution of tracer in non-viable tissue. Results Mean age of patients was 64±9 years, and 90% were males. Uptake of 68Ga-NODAGA-RGD was low in the remote myocardium, but focally increased in the ischemic area at risk (Figure 1). SUVmax in the ischemic area at risk was higher than SUVmean of the remote myocardium (0.73±0.16 vs. 0.51±0.11, p&amp;lt;0.001). 68Ga-NODAGA-RGD SUVmax did not correlate with MBF in the area at risk. Univariable predictors of 68Ga-NODAGA-RGD SUVmax in the area at risk included peak Troponin T (p&amp;lt;0.001), peak pro-BNP (p&amp;lt;0.001), low global longitudinal strain (p=0.01), and low regional longitudinal strain in the area at risk (p=0.02). In multivariable analysis, peak pro-BNP independently predicted SUVmax in the area at risk (p&amp;lt;0.001). At follow-up, left ventricular ejection fraction increased by 1.6±6.9% and global longitudinal strain by 0.5±3.2%. In univariable analysis, SUVmax and SUVmax/MBFmean in the area at risk predicted improvement of global longitudinal strain at 6 months after AMI (p=0.04 and p&amp;lt;0.001, respectively). Conclusion 68Ga-NODAGA-RGD uptake shows increased αvβ3 integrin expression in the ischemic area at risk early after reperfused AMI that is associated with the extent of myocardial injury, both regional and global systolic dysfunction, and increased left ventricular filling pressure. Increased 68Ga-NODAGA-RGD uptake in ischemic myocardium at risk predicts left ventricular function improvement at 6 months after AMI. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Academy of Finland, Finnish Foundation for Cardiovascular Research

The use of lipid-lowering medication after diagnostic imaging procedures in patients with chest pain

Abstract Background Coronary CT angiography (CTA) combined with myocardial perfusion imaging accurately detects both non-obstructive and obstructive coronary artery disease (CAD). Lipid-lowering therapy is known to effectively reduce cardiovascular events, but the impact of non-invasive imaging findings on the usage of lipid-lowering therapy remains largely unknown. Purpose To assess the use of lipid-lowering medication in patients referred to coronary CTA and subsequent positron emission tomography (PET) myocardial perfusion imaging due to suspected obstructive CAD. Methods We retrospectively analyzed data on purchases of lipid-lowering drugs obtained from the Finnish national registry for a time period starting 1 year before and ending 2 years after the date of diagnostic imaging. This time period was divided into six 6-month intervals, for each of which the presence of any statin and/or ezetimibe purchase was recorded. According to the local routine, patients with suspected obstructive (≥50%) stenosis on coronary CTA entered downstream 15O-water PET myocardial perfusion imaging during adenosine stress to assess the hemodynamic significance of the coronary stenosis. The use of medication was compared among patients with normal coronary arteries, non-obstructive CAD, and obstructive CAD. Results During 2008–2016, a total of 1973 patients (41% male, median age 63 years) underwent coronary CTA and 33% of these had PET perfusion imaging. There were 9081 purchases of lipid-lowering drugs during the 3-year observation period. There were 676 (34%) patients with normal coronary arteries, 640 (32%) patients with non-obstructive atherosclerosis on CTA, 325 (16%) patients with suspected obstructive stenosis on CTA but normal PET perfusion, and 332 (17%) patients with obstructive stenosis and abnormal hyperemic PET perfusion. The proportion of patients buying lipid-lowering drugs was 24%, 51%, 72%, and 91%, respectively, as assessed within the 6-month interval following the CTA/PET imaging. After diagnostic testing, proportion of patients purchasing lipid-lowering medications increased in all groups except those with normal coronary arteries (Figure 1). However, there was a marked decrease in all patient groups in proportion of patients using lipid-lowering medication towards the end of the 2-year follow-up period. Conclusions In a real-world cohort of symptomatic patients with chest pain undergoing diagnostic imaging for suspected CAD, subsequent purchases of lipid-lowering drugs increase in relation to the severity of imaging findings. Although majority of patients with obstructive CAD initially purchased lipid-lowering medication, our results indicate a marked decrease in the use of these preventive medications towards the end of 2-year follow-up period. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): State Research Funding of Turku University Hospital; the Academy of Finland; Finnish Foundation for Cardiovascular Research.

Diagnosis of left ventricular hypertrophy using non-ECG-gated 15O-water PET

AimTo develop a method for diagnosing left ventricular (LV) hypertrophy from cardiac perfusion 15O-water positron emission tomography (PET). MethodsWe retrospectively pooled data from 139 subjects in four research cohorts. LV remodeling patterns ranged from normal to severe eccentric and concentric hypertrophy. 15O-water PET scans (n = 197) were performed with three different PET devices. A low-end scanner (66 scans) was used for method development, and remaining scans with newer devices for a blinded evaluation. Dynamic data were converted into parametric images of perfusable tissue fraction for semi-automatic delineation of the LV wall and calculation of LV mass (LVM) and septal wall thickness (WT). LVM and WT from PET were compared to cardiac magnetic resonance (CMR, n = 47) and WT to 2D-echocardiography (2DE, n = 36). PET accuracy was tested using linear regression, Bland–Altman plots, and ROC curves. Observer reproducibility were evaluated using intraclass correlation coefficients. ResultsHigh correlations were found in the blinded analyses (r ≥ 0.87, P < 0.0001 for all). AUC for detecting increased LVM and WT (> 12 mm and > 15 mm) was ≥ 0.95 (P < 0.0001 for all). Reproducibility was excellent (ICC ≥ 0.93, P < 0.0001). Conclusion15O-water PET might detect LV hypertrophy with high accuracy and precision.

Influence of patient motion on quantitative accuracy in cardiac 15O-water positron emission tomography

BackgroundPatient motion is a common problem during cardiac PET. The purpose of the present study was to investigate to what extent motions influence the quantitative accuracy of cardiac 15O-water PET/CT and to develop a method for automated motion detection. MethodFrequency and magnitude of motion was assessed visually using data from 50 clinical 15O-water PET/CT scans. Simulations of 4 types of motions with amplitude of 5 to 20 mm were performed based on data from 10 scans. An automated motion detection algorithm was evaluated on clinical and simulated motion data. MBF and PTF of all simulated scans were compared to the original scan used as reference. ResultsPatient motion was detected in 68% of clinical cases by visual inspection. All observed motions were small with amplitudes less than half the LV wall thickness. A clear pattern of motion influence was seen in the simulations with a decrease of myocardial blood flow (MBF) in the region of myocardium to where the motion was directed. The perfusable tissue fraction (PTF) trended in the opposite direction. Global absolute average deviation of MBF was 3.1% ± 1.8% and 7.3% ± 6.3% for motions with maximum amplitudes of 5 and 20 mm, respectively. Automated motion detection showed a sensitivity of 90% for simulated motions ≥ 10 mm but struggled with the smaller (≤ 5 mm) simulated (sensitivity 45%) and clinical motions (accuracy 48%). ConclusionPatient motion can impair the quantitative accuracy of MBF. However, at typically occurring levels of patient motion, effects are similar to or only slightly larger than inter-observer variability, and downstream clinical effects are likely negligible.

Effect of hematocrit on cerebral blood flow measured by pseudo-continuous arterial spin labeling MRI: A comparative study with 15O-water positron emission tomography

IntroductionIn cerebral blood flow (CBF) quantification with pseudo-continuous arterial spin labeling (pCASL) MRI, arterial blood T1 (T1a) is usually fixed to a typical value (e.g., 1650 ms). However, individual T1a depends strongly on hematocrit (Hct) level. To investigate the utility of Hct-based T1a as an alternative to the fixed T1a method, we performed a comparative study with 15O-water positron emission tomography (PET). MethodsFor patients with unilateral occlusion or stenosis of major arteries, hemispheric CBF on the healthy side was measured using pCASL and 15O-water PET. The pCASL CBFs were calculated with both (a) fixed T1a (1650 ms) and (b) individual T1a estimated from blood-sampled Hct (Hct-based T1a). Correlation coefficients of Hct–CBF were calculated and compared between pCASL and PET. ResultsIn pCASL, CBF with fixed T1a showed a strong negative correlation with Hct (r = −0.568), which was reduced with individual Hct-based T1a (r = −0.341 to −0.190), consistent with the Hct–CBF relation measured with PET (r = −0.349). Discussion and conclusionWe demonstrated that Hct-based T1a resulted in smaller inter-individual variations in pCASL CBF and an inverse Hct–CBF relationship more similar to that of PET. Care must be taken in the interpretation of pCASL CBF imaging in relation to Hct level even in subjects without anemia. Further comparative studies are needed to investigate whether advanced techniques improve pCASL CBF quantification at the individual level.

Extensive and balanced reduction of myocardial blood flow in patients with suspected obstructive coronary artery disease: 15O-water PET study

BackgroundDetection of obstructive coronary artery disease (CAD) by stress myocardial perfusion imaging (MPI) is conventionally based on relative differences in perfusion. This may lead to either underestimation of the extent of myocardial ischemia, or the ischemia might be completely missed in case of balanced perfusion reduction. Using absolute quantification of myocardial blood flow (MBF) by positron emission tomography (PET), we evaluated how common are extensive and balanced myocardial perfusion abnormalities in symptomatic patients with suspected obstructive CAD. Methods and resultsAmong 758 consecutive symptomatic patients undergone coronary computed tomography angiography (CTA), 286 patients subsequently underwent quantitative 15O-water adenosine-stress PET MPI to assess the hemodynamic significance of suspected obstructive stenosis. Out of these, 46 (16%) patients had reduced (≤2.3 ml/g/min) absolute stress MBF in all three standard coronary territories (LAD, LCX, RCA). Subsequently, relative stress MBF in each coronary territory was calculated, considering a territory with the highest absolute stress MBF as a reference region. Among the 46 patients, 72% had significant regional heterogeneity in myocardial perfusion (defined as having ≥1 territory with relative stress MBF <80%) while the remaining 28% (4.5% of the whole MPI cohort) showed balanced perfusion reduction (all relative MBF values ≥80%). ConclusionsAmong symptomatic patients with suspected obstructive stenosis on coronary CTA, quantitative PET revealed that 16% of patients had reduced stress MBF involving all three coronary artery territories, of whom approximately one third showed balanced reduction. Thus, in 4.5% of the patients the perfusion abnormalities could have been missed by conventional relative MPI analysis.

Evaluation of Arterial Spin Labeling MRI-Comparison with 15O-Water PET on an Integrated PET/MR Scanner.

Cerebral blood flow (CBF) measurements are of high clinical value and can be acquired non-invasively with no radiation exposure using pseudo-continuous arterial spin labeling (ASL). The aim of this study was to evaluate accordance in resting state CBF between ASL (CBFASL) and 15O-water positron emission tomography (PET) (CBFPET) acquired simultaneously on an integrated 3T PET/MR system. The data comprised ASL and dynamic 15O-water PET data with arterial blood sampling of eighteen subjects (eight patients with focal epilepsy and ten healthy controls, age 21 to 61 years). 15O-water PET parametric CBF images were generated using a basis function implementation of the single tissue compartment model. Cortical and subcortical regions were automatically segmented using Freesurfer. Average CBFASL and CBFPET in grey matter were 60 ± 20 and 75 ± 22 mL/100 g/min respectively, with a relatively high correlation (r = 0.78, p < 0.001). Bland-Altman analysis revealed poor agreement (bias = −15 mL/100 g/min, lower and upper limits of agreements = −16 and 45 mL/100 g/min, respectively) with a negative relationship. Accounting for the negative relationship, the width of the limits of agreement could be narrowed from 61 mL/100 g/min to 35 mL/100 g/min using regression-based limits of agreements. Although a high correlation between CBFASL and CBFPET was found, the agreement in absolute CBF values was not sufficient for ASL to be used interchangeably with 15O-water PET.

Greater reductions in blood flow after anti-angiogenic treatment in non-small cell lung cancer patients are associated with shorter progression-free survival

To evaluate tumor blood flow using 15O-water positron emission tomography (PET) in patients with non-small cell lung cancer (NSCLC) before and after chemotherapy with bevacizumab, and to investigate the effects of bevacizumab on tumor blood flow changes and progression-free survival (PFS). Twelve patients with NSCLC were enrolled. Six patients underwent chemotherapy with bevacizumab and the other six without bevacizumab. 15O-water dynamic PET scans were performed within 1 week before the start of chemotherapy and within 1 week after the first day of chemotherapy. Tumor blood flow was analyzed quantitatively using a single one-tissue compartment model with the correction of pulmonary circulation blood volume and arterial blood volume via an image-derived input function. In the bevacizumab group, mean tumor blood flow was statistically significantly reduced post-chemotherapy (pre-chemotherapy 0.27 ± 0.14 mL/cm3/min, post-chemotherapy 0.18 ± 0.12 mL/cm3/min). In the no bevacizumab group, there was no significant difference between mean tumor perfusion pre-chemotherapy (0.42 ± 0.42 mL/cm3/min) and post-chemotherapy (0.40 ± 0.27 mL/cm3/min). In the bevacizumab group, there was a positive correlation between the blood flow ratio (tumor blood flow post-chemotherapy/tumor blood flow pre-chemotherapy) and PFS (correlation coefficient 0.94). Mean tumor blood flow decreases after bevacizumab administration and was positively correlated with longer PFS.

Cerebral blood flow measurements with 15O-water PET using a non-invasive machine-learning-derived arterial input function

Cerebral blood flow (CBF) can be measured with dynamic positron emission tomography (PET) of 15O-labeled water by using tracer kinetic modelling. However, for quantification of regional CBF, an arterial input function (AIF), obtained from arterial blood sampling, is required. In this work we evaluated a novel, non-invasive approach for input function prediction based on machine learning (MLIF), against AIF for CBF PET measurements in human subjects. Twenty-five subjects underwent two 10 min dynamic 15O-water brain PET scans with continuous arterial blood sampling, before (baseline) and following acetazolamide medication. Three different image-derived time-activity curves were automatically segmented from the carotid arteries and used as input into a Gaussian process-based AIF prediction model, considering both baseline and acetazolamide scans as training data. The MLIF approach was evaluated by comparing AIF and MLIF curves, as well as whole-brain grey matter CBF values estimated by kinetic modelling derived with either AIF or MLIF. The results showed that AIF and MLIF curves were similar and that corresponding CBF values were highly correlated and successfully differentiated before and after acetazolamide medication. In conclusion, our non-invasive MLIF method shows potential to replace the AIF obtained from blood sampling for CBF measurements using 15O-water PET and kinetic modelling.

15O-Water Positron Emission Tomography of Myocardial Ischemia in Patients Referred for Percutaneous Coronary Intervention

The diagnostic accuracy of non-invasive diagnostic methods for detecting coronary artery disease has increased in recent years. This study aimed to assess the diagnostic performance of 15O-water positron emission tomography (PET) in terms of stress myocardial blood flow (MBF) and myocardial flow reserve (MFR) in patients with single-vessel disease referred for percutaneous coronary intervention (PCI), using fractional flow reserve (FFR) value of ≤0.80 as the reference for a significant stenosis. We also assessed the influence of the index of microcirculatory resistance (IMR) on the diagnostic performance of PET. 15O-water PET FFR and IMR were measured before PCI in 26 patients with single-vessel disease. Stress MBF < 2.5 ml/min/g (95% confidence interval [CI]) had sensitivity 78% (95% CI: 52%–94%), specificity 50% (95% CI: 16%–84%), positive predictive value (PPV) 78% (95% CI: 63%–88%), negative predictive value (NPV) 50% (95% CI: 25%–75%), and accuracy 69% (95% CI: 48%–86%). MFR < 2.5 had sensitivity 72% (95% CI: 47%–90%), specificity 75% (95% CI: 35%–97%), PPV 87% (95% CI: 65%–96%), NPV 55% (95% CI: 34%–74%), and accuracy 73% (95% CI: 52%–88%). In patients with IMR > 24, stress MBF correlated with FFR (r = 0.651; p = 0.016) whereas stress MBF did not correlate with FFR in patients with IMR < 24. In conclusion, stress MBF and MFR had modest diagnostic performance compared to invasive FFR measurements in patients with single-vessel disease.