Quantification of myocardial blood flow (MBF) with ^82 Rb PET/CT requires accurate delineation of the left ventricle (LV). Manual or semi-automated contouring remains time-consuming and error-prone, particularly in hypoperfused myocardium. We developed and validated a fully automatic LV segmentation pipeline using nnU-Net applied to ^82 Rb PET/CT. A manual, multimodal segmentation protocol integrating dynamic PET and CT was established in a single-center cohort of 40 non-gated PET/CT series (20 patients, rest stress), including challenging cases with extensive necrosis (median 21

BACKGROUND:Quantification of myocardial blood flow (MBF) with [Formula: see text]Rb PET/CT requires accurate delineation of the left ventricle (LV). Manual or semi-automated contouring remains time-consuming and error-prone, particularly in hypoperfused myocardium. We developed and validated a fully automatic LV segmentation pipeline using nnU-Net applied to [Formula: see text]Rb PET/CT. A manual, multimodal segmentation protocol integrating dynamic PET and CT was established in a single-center cohort of 40 non-gated PET/CT series (20 patients, rest & stress), including challenging cases with extensive necrosis (median 21%). The resulting ground truth masks were used for five-fold cross-validation, and semi-supervised learning incorporated 805 additional unlabeled dynamic PET series (504 patients). Model performance was compared with an optimized semi-automatic thresholding baseline (35% [Formula: see text]). RESULTS:The nnU-Net significantly outperformed the baseline, achieving a mean Dice of 87.8[85.6, 89.2]% vs 75.1[72.9, 76.9]%, recall 89.1[86.1, 91.4]% vs 82.6[79.1, 85.4]%, and precision 88.1[84.2, 90.4]% vs 70.2[67.2, 73.0]%. The improvement was most pronounced in hypoperfused regions, where recall increased by 20-30% compared to thresholding. Semi-supervised learning modestly enhanced model robustness across both rest and stress acquisitions. CONCLUSIONS:A deep-learning-based approach enables fully automatic LV segmentation in [Formula: see text]Rb PET/CT with near-expert accuracy. This framework eliminates manual interaction, supports large-scale MBF quantification, and paves the way for reproducible, high-throughput cardiac PET analysis in clinical and research workflows.

Background:Quantitative myocardial blood flow (MBF) and myocardial flow reserve (MFR) provide incremental diagnostic and prognostic value in cardiac PET, but their widespread use is limited by the technical demands of dynamic imaging protocols. We evaluated the feasibility of using artificial intelligence (AI) to predict MBF and MFR from static and gated PET images, without the need for dynamic acquisition. Methods:A machine learning (XGBoost) model was trained on 82Rb PET multi-center dataset using static perfusion imaging, injected dose, hemodynamic measures, clinical data and CT-derived features (including body composition) from the hybrid CT attenuation scan. Model performance was evaluated externally in an independent cohort. Results:In total, 10,566 (derivation-cohort) and 7,842 (external-cohort) patients were included in this multi-center study. On the external-cohort, AI approach achieved an Area under the curve (AUC) of 0.92 (0.92-0.93) for abnormal stress MBF and 0.91 (0.90-0.92) for abnormal MFR; Intra-class correlation (ICC) 0.80 (0.78-0.82) and 0.78 (0.76-0.79), respectively. AI MFR closely mirrored the prognostic performance of measured MFR, showing nearly identical Kaplan-Meier risk stratification (both p<0.0001) and maintaining strong, and independently significant associations with all-cause mortality (HR 3.4 [2.8-4.2] vs. 4.6 [3.6-5.8]; both p<0.001), and demonstrated similar added value to perfusion for mortality prediction. Conclusion:AI-predicted virtual stress MBF and MFR assessment using static and gated PET data is feasible and generalizable across cohorts. By removing the dependency on dynamic acquisitions, this approach has the potential to broaden the clinical adoption of flow quantification.

Segmenting the left atrial wall from late gadolinium enhancement magnetic resonance images (MRI) is challenging due to the wall's thin geometry, low contrast, and the scarcity of expert annotations. We propose a Model-Agnostic Meta-Learning (MAML) framework for K-shot (K = 5, 10, 20) 3D left atrial wall segmentation that is meta-trained on the wall task together with auxiliary left atrial and right atrial cavity tasks and uses a boundary-aware composite loss to emphasize thin-structure accuracy. We evaluated MAML segmentation performance on a hold-out test set and assessed robustness under an unseen synthetic shift and on a distinct local cohort. On the hold-out test set, MAML appeared to improve segmentation performance compared to the supervised fine-tuning model, achieving a Dice score (DSC) of 0.64 vs. 0.52 and HD95 of 5.70 vs. 7.60 mm at 5-shot, and approached the fully supervised reference at 20-shot (0.69 vs. 0.71 DSC). Under unseen shift, performance degraded but remained robust: at 5-shot, MAML attained 0.59 DSC and 5.99 mm HD95 on the unseen domain shift and 0.57 DSC and 6.01 mm HD95 on the local cohort, with consistent gains as K increased. These results suggest that more accurate and reliable thin-wall boundaries are achievable in low-shot adaptation, potentially enabling clinical translation with minimal additional labeling for the assessment of atrial remodeling.

11C-acetate PET is used to measure biventricular oxygen myocardial consumption rate (MVO2) and myocardial blood flow (MBF) changes associated with right ventricular (RV) remodelling. We studied PET reproducibility and repeatability for such RV assessments. 10 pulmonary hypertension (PH) patients underwent 11C-acetate PET. Five of these patients also had a repeat scan after 26 ± 2 weeks. A one-tissue compartment model was used to measure the myocardial tissue-activity washout rate (k2 [1/min] for MVO2 estimation) and the blood-to-tissue activity flux (K1 [1/min] for MBF calculation). Values were measured by 2 blinded observers and analyzed by ANOVA and Bland–Altman tests. The interquartile ranges (IQR), within-subject coefficients of variation (wCV), and intraclass correlation coefficients (ICC) were reported. All patients had stable PH with the clinical assessments showed comparable biventricular function and size between baseline and follow-up. The k2-derived MVO2 and K1-derived MBF values were consistently higher in the LV than RV. The high inter- and intra-observer reproducibility (for biventricular MVO2 and MBF) was indicated by low IQR (≤ 7.6

Background: Atrial fibrillation (AF) is the most common arrhythmia, associated with increased risks of stroke, heart failure, and mortality. Structural and autonomic remodeling contribute to its pathophysiology, with evidence suggesting that sympathetic denervation may promote a pro-arrhythmic substrate. 11C-Hydroxyephedrine (HED) PET enables noninvasive assessment of cardiac sympathetic innervation in AF. Objective: To evaluate cardiac sympathetic innervation using HED PET imaging in healthy controls vs. patients with persistent AF, and its relationship to catheter ablation (CA) outcomes. Methods: This prospective study enrolled patients with symptomatic persistent AF accepted for clinically indicated CA. Patients were recruited between 2016–2018 at a tertiary center. All underwent HED hybrid PET/CT imaging prior to CA aimed at pulmonary vein isolation. Clinical endpoint was freedom from AF recurrence >30 seconds. Patients had 14-day Holter monitoring at 3, 6, and 12 months, and as needed for symptoms. Image analysis was independently performed by two readers using HERMIA software. Regions of interest were drawn on transaxial, sagittal, and coronal views to capture the left atrial (LA) myocardium and blood pool activity. Minimum, maximum, and range (max–min) of standardized uptake value (SUV) and tissue-to-blood ratio (TBR) in the LA were recorded. Group comparisons used Mann–Whitney U and Kruskal–Wallis tests. Results: Thirty-six patients with AF and 7 healthy controls were included (9 females; 61±9 years old). In the AF group (mean LA size 45±8 mm), 26 remained AF-free and 10 had recurrence. Mean AF-free duration was 23±7 months (AF-free) vs. 6±2 months (AF-recur). Mean LA TBR minimum was 0.92±0.15 (controls), 0.66±0.22 (AF-free), and 0.67±0.25 (AF-recur) (p=0.017; Fig. 1). Compared to controls, TBR minimum was lower in AF-free (p=0.007), AF-recur (p=0.022), and all AF patients (p=0.005). TBR range was 1.86±0.28 (controls), 2.88±0.97 (AF-free), and 0.99±1.24 (AF-recur) (p=0.013; Fig. 2); it was elevated in AF-free (p=0.002) and all AF (p=0.003) but did not meet statistical significance for AF-recur (p=0.070). Conclusion: Patients with persistent AF exhibit marked sympathetic denervation (low TBR minimum) and regional heterogeneity (high TBR range) on HED PET, suggestive of autonomic imbalance and atrial vulnerability. These patterns may contribute to AF recurrence and warrant further study to assess their role in ablation outcomes.

Background The role of advanced (cardiac magnetic resonance [CMR] or positron emission tomography [PET]) vs single-photon emission computerized tomography (SPECT) ischemia imaging to guide management remains unclear in patients with ischemic heart failure (IHF). The primary aim was to determine the effect of imaging modality on a composite cardiovascular endpoint and cardiac death in patients with IHF who require ischemia assessment. Methods Patients with IHF were randomized to advanced or SPECT imaging. A parallel registry also was performed. The primary endpoint was the composite of cardiac death, infarction, arrest, and cardiac rehospitalization. The key secondary endpoint was cardiac death. Results Patients in the randomized population (advanced imaging [PET or CMR; n = 64] or SPECT [n = 56]) had a cumulative incidence rate (CIR) for the primary endpoint of 33.1% and 33.0%, respectively (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.49, 1.80, P = 0.853). CIRs for cardiac death were 13.8% and 25.1%, respectively (HR 0.62, 95% CI 0.25, 1.80, P = 0.296).In the parallel registry (n = 336 advanced; n = 216 SPECT), the primary endpoint CIRs were 31.2% and 35.3%, respectively (HR 0.81, 95% CI 0.56, 1.19, P = 0.284). CIRs for cardiac death were 11.0% and 16.6%, respectively (HR 0.53, 95% CI 0.27, 1.04, P = 0.066). Patients were followed for a median (interquartile range) of 24.1 (11.6, 27.5) months.Pooled analysis from the randomized and registry populations revealed a significant benefit of advanced imaging for reduction of cardiac death (HR 0.56, 95% CI 0.33, 0.96, P = 0.04) with minimal heterogeneity (I2 = 0%). Conclusion Among IHF patients assessed for ischemia, advanced imaging (PET or CMR) was not associated with reduced composite cardiac events, compared to SPECT. Clinical Trial Registration NCT01288560.

Background The REgistry of Flow and Perfusion Imaging for Artificial Intelligence with positron emission tomography (REFINE PET) was established to collect multicenter PET and associated computed tomography (CT) images, together with clinical data and outcomes, into a comprehensive research resource. REFINE-PET will enable validation and development of both standard and novel cardiac PET/CT processing methods. Methods REFINE-PET is a multicenter, international registry that contains both clinical and imaging data. The PET scans were processed using QPET software (Cedars-Sinai Medical Center, Los Angeles, CA), while the CT scans were processed using deep learning (DL) to detect coronary artery calcium (CAC). Patients were followed up for the occurrence of major adverse cardiovascular events (MACE), which include death, myocardial infarction, unstable angina, and late revascularization (>90 days from PET). Results The REFINE-PET registry currently contains data for 35595 patients from 14 sites, with additional patient data and sites anticipated. Comprehensive clinical data (including demographics, medical history, and stress test results) were integrated with more than 2100 imaging variables across 34 categories. The registry is poised to address a broad range of clinical questions, supported by correlating invasive angiography (within 6 months of PET myocardial perfusion imaging [MPI]) in 5955 patients and a total of 9278 major adverse cardiovascular events during a median follow-up of 4.2 years. Conclusions The REFINE-PET registry leverages the integration of clinical, multimodality imaging, and novel quantitative and AI tools to advance the role of PET/CT MPI in diagnosis and risk stratification.

The image quality and quantitative accuracy of 82Rb myocardial perfusion imaging (MPI) using PET is challenged by the extensive positron range (PR) effects, with the PR of 82Rb being about 7 mm in soft tissues. This study explored the feasibility of applying postacquisition PR correction (PRC) to routine 82Rb PET/CT MPI acquisitions and assessed its impact on diagnostic accuracy and image quality. Methods: We implemented a PRC method adjusted to 82Rb into a vendor-provided reconstruction toolbox, using tissue-specific corrections for soft tissue, bone, and air/lungs. The PRC was evaluated in 2 cohorts: the first comprised 25 healthy volunteers who underwent repeated 82Rb MPI within 2 wk, and the second included 66 patients with known or suspected coronary artery disease. We measured the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) for the volunteer cohort. In the patient cohort, the impact of PRC was evaluated as changes in the area under the receiver operating characteristic curve (AUC), using fractional flow reserve as the gold standard (values < 80% were considered significantly reduced). We calculated AUCs for stress and ischemic total perfusion deficits. Results: In the volunteer cohort, PRC-based reconstructions (standard reconstruction [STD] + PRC) demonstrated significantly improved SNR and CNR compared with STD, with median increases of 22% and 47% for SNR and CNR, respectively (P < 0.05). For the patient cohort, comparable AUCs were reported for STD- versus PRC-based reconstructions (stress total perfusion deficits, 0.84 vs. 0.83 [P = 0.49]; ischemic total perfusion deficits, 0.87 vs. 0.87 [P = 0.80]). Conclusion: PRC significantly enhances SNR and CNR compared with STD without affecting the diagnostic accuracy of the scans. Given the significantly improved image quality, PRC may be recommended for MPI using 82Rb PET/CT clinical-routine-assessment interpretation of TPD.

BACKGROUND:The longitudinal myocardial blood flow (MBF) gradient, reflecting the basal-to-apical decline in stress MBF, has been proposed as a non-invasive marker for obstructive coronary artery disease (CAD). However, its clinical utility in Rubidium-82 (82Rb) positron emission tomography (PET) remains unestablished. METHODS:This single-center retrospective study included consecutive patients who underwent rest/dipyridamole-stress 82Rb PET myocardial perfusion imaging and invasive coronary angiography within 90 days from January 2012 to December 2019. Stress MBF and longitudinal gradients (basal-to-apical differences) were quantified in left anterior descending (LAD), left circumflex (LCX), and right coronary artery (RCA) territories. Coronary territories were stratified by coronary artery calcification (CAC) and perfusion defects (PD) into groups A (CAC-, PD-), B (CAC+, PD-), and C (PD+). Associations with CAD burden and diagnostic performance for obstructive CAD (≥50% angiographic stenosis) were evaluated using receiver operating characteristic analysis. RESULTS:Of 1,516 patients screened, 396 (median age: 68 years; 30.6% female) were included, contributing 1,077 coronary territories (LAD: 391; LCX: 377; RCA: 309). In LAD territory, longitudinal MBF gradients increased with CAD burden (P < 0.001) and improved diagnostic accuracy beyond relative perfusion and stress MBF (AUC 0.774 vs 0.743, P = 0.002). Conversely, gradients in LCX and RCA territories decreased with increasing CAD burden (both P < 0.001) and did not improve diagnostic performance (LCX: AUC 0.704 vs 0.715, P = 0.267; RCA: AUC 0.727 vs 0.723, P = 0.698). CONCLUSIONS:Longitudinal stress MBF gradients derived from 82Rb PET may enhance diagnostic accuracy for obstructive CAD in the LAD territory. No additional diagnostic value was observed in LCX or RCA territories.

Background:Patients who have recurrent ventricular tachycardia (VT) despite receiving antiarrhythmic drugs (AADs), implantable cardioverter defibrillator placement, and catheter ablation (CA) are at significant risk of morbidity and mortality. Methods:We offered completely noninvasive cardiac radio-ablation (CRA) on a "compassionate use" basis for patients who were unable or unwilling to undergo CA for recurrent VT despite their having received treatment with AADs and placement of an implantable cardioverter defibrillator. All patients who were referred to the CRA program were entered into a prospective registry and followed indefinitely thereafter. Results:A total of 20 patients were referred for CRA, and 10 elected to undergo the treatment as outpatients. Ten patients declined CRA therapy, owing to fear of complications and/or logistic concerns relating to attending multiple hospital visits; they received escalated drug therapy. All patients who were referred to and were agreeable to CRA received CRA. No patients were excluded or were denied CRA by clinicians for any reason, and all patients were followed clinically. The VT burden decreased significantly, by > 90% (both anti-tachycardia pacing and shocks), and 1 patient died of a cardiovascular cause at 1 year following a single CRA treatment of 25 Gy. One patient experienced steroid-responsive pneumonitis as an adverse event post-CRA (common terminology criteria for adverse events [CTCAE] grade 2). For the 10 patients who declined CRA, no appreciable reduction in VT occurred, despite their receipt of increasing dosages of AADs, and 5 patients died of cardiovascular causes within 1 year. Conclusions:Noninvasive stereotactic CRA is well tolerated with good short-term efficacy for recurrent VT on a "compassionate use" basis. Prospective randomized controlled trials to determine the relative efficacy of CA vs CRA for VT are urgently required.