About

Rene R. S. Packard is an Associate Professor-in-residence in the Departments of Medicine and Physiology at the University of California, Los Angeles (UCLA). His educational background includes a PhD in Molecular, Cellular, and Integrative Physiology from UCLA, completed in 2016, and an MD from the Faculty of Medicine at the University of Geneva in 2004. His training also encompasses advanced cardiac imaging and internal medicine from programs at UCLA Medical Center, Case Western Reserve University, and Harvard Medical School. Dr. Packard's research focuses on cardiovascular imaging, particularly the development and application of positron emission tomography (PET) techniques for diagnosing and managing coronary artery disease. His work involves establishing and improving radiotracers, quantitative image analysis methods, and clinical guidelines for cardiac PET imaging. He has contributed to the understanding of myocardial blood flow metrics, the clinical promise of PET imaging, and the expansion of radiotracer repertoire. His research also extends to exploring high-risk atherosclerotic features, extracardiac findings in imaging, and the integration of artificial intelligence in cardiovascular diagnostics. Dr. Packard has received multiple awards and honors for his contributions to cardiovascular research and imaging.

Research topics

• Artificial Intelligence
• Machine Learning
• Computer Science
• Internal medicine
• Medicine
• Cardiology
• Radiology
• Surgery
• Nuclear medicine
• Computer vision

Selected publications

• Protocol optimization for 18F-flurpiridaz positron emission tomography myocardial perfusion imaging to enhance clinical workflow

  Journal of Nuclear Cardiology · 2026-04-01

  articleSenior author
  PublisherDOI

• The REgistry of Flow and Perfusion Imaging for Artificial INtelligEnce with PET (REFINE PET): Rationale and Design

  medRxiv · 2025-07-11 · 1 citations

  preprintOpen access

  Rationale: The REgistry of Flow and Perfusion Imaging for Artificial INtelligEnce with PET (REFINE PET) was established to aggregate PET and associated computed tomography (CT) images with clinical data from hospitals around the world into one comprehensive research resource. 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 35,588 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 2200 imaging variables across 42 categories. The registry is poised to address a broad range of clinical questions, supported by correlating invasive angiography (within 6 months of MPI) in 5972 patients and a total of 9252 major adverse cardiovascular events during a median follow-up of 4.2 years. Conclusion: 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.

  PublisherOA PDFDOI

• AI-Derived Splenic Response in Cardiac PET Predicts Mortality: A Multi-Site Study

  medRxiv · 2025-06-28 · 2 citations

  preprintOpen access

  Abstract Background Inadequate pharmacologic stress may limit the diagnostic and prognostic accuracy of myocardial perfusion imaging (MPI). The splenic ratio (SR), a measure of stress adequacy, has emerged as a potential imaging biomarker. Objectives To evaluate the prognostic value of artificial intelligence (AI)-derived SR in a large multicenter 82 Rb-PET cohort undergoing regadenoson stress testing. Methods We retrospectively analyzed 10,913 patients from three sites in the REFINE PET registry with clinically indicated MPI and linked clinical outcomes. SR was calculated using fully automated algorithms as the ratio of splenic uptake at stress versus rest. Patients were stratified by SR into high (≥90th percentile) and low (<90th percentile) groups. The primary outcome was major adverse cardiovascular events (MACE). Survival analysis was conducted using Kaplan-Meier and Cox proportional hazards models adjusted for clinical and imaging covariates, including myocardial flow reserve (MFR ≥2 vs. <2). Results The cohort had a median age of 68 years, with 57% male patients. Common risk factors included hypertension (84%), dyslipidemia (76%), diabetes (33%), and prior coronary artery disease (31%). Median follow-up was 4.6 years. Patients with high SR (n=1,091) had an increased risk of MACE (HR 1.18, 95% CI 1.06–1.31, p=0.002). Among patients with preserved MFR (≥2; n=7,310), high SR remained independently associated with MACE (HR 1.44, 95% CI 1.24–1.67, p<0.0001). Conclusions Elevated AI-derived SR was independently associated with adverse cardiovascular outcomes, including among patients with preserved MFR. These findings support SR as a novel, automated imaging biomarker for risk stratification in 82 Rb PET MPI. Condensed Abstract AI-derived splenic ratio (SR), a marker of pharmacologic stress adequacy, was independently associated with increased cardiovascular risk in a large 82 Rb PET cohort, even among patients with preserved myocardial flow reserve (MFR). High SR identified individuals with elevated MACE risk despite normal perfusion and flow findings, suggesting unrecognized physiologic vulnerability. Incorporating automated SR into PET MPI interpretation may enhance risk stratification and identify patients who could benefit from intensified preventive care, particularly when traditional imaging markers appear reassuring. These findings support SR as a clinically meaningful, easily integrated biomarker in stress PET imaging.

  PublisherOA PDFDOI

• SNMMI/EANM/ASNC/ACNM Procedure Standard/Practice Guideline for ¹⁸F-Flurpiridaz PET Myocardial Perfusion Imaging and Blood Flow Quantitation

  Journal of Nuclear Medicine · 2025-09-18 · 1 citations

  article1st authorCorresponding
  PublisherDOI

• Age- and Sex-Adjusted Myocardial Flow Reserve Percentiles for Personalized Cardiovascular Risk Assessment

  medRxiv · 2025-12-31 · 1 citations

  articleOpen access

  Introduction: Positron emission tomography (PET) myocardial flow reserve (MFR) is a robust indicator of coronary vascular health and a strong predictor of cardiovascular risk. Clinical guidelines typically use fixed MFR thresholds (e.g., <2.0) to stratify risk, yet this approach overlooks individual variation, particularly by age and sex. We aimed to establish age- and sex-adjusted MFR percentiles and to evaluate their prognostic and predictive performance for cardiovascular risk assessment, in comparison with conventional fixed-threshold MFR approach. Methods: Using data from the REFINE PET registry (24,820 patients from 12 sites), we measured PET MFR and derived age- and sex-adjusted MFR reference percentiles using quantile regression in patients without known coronary artery disease. All patients were categorized into percentile-based quartile groups. The primary outcome for prognostic and prediction analyses was major adverse cardiovascular events (MACE), defined as all-cause mortality, myocardial infarction, or heart-failure hospitalization. Time-to-event associations were evaluated using covariate-adjusted survival models, with cumulative incidence and hazard ratios (HR) estimated at 1 and 5 years in the derivation dataset, an independent but similar validation dataset A, and a high-risk validation dataset B. Predictive performance for MACE was assessed using discrimination, calibration, and reclassification metrics, comparing percentile-based models with models using a fixed MFR threshold (<2.0). Results: Among participants (mean age 66.5 years; median follow-up 3.6 years), age- and sex-adjusted MFR quartile groups were strong independent predictors of MACE, with adjusted HR increasing stepwise across quartile groups at both early and later follow-up. At 1 year, HR (95% CI) comparing the lowest to the highest quartile group were 4.06 (3.41-4.82) in the derivation cohort, 3.31 (2.32-4.71) in validation cohort A, and 2.35 (2.05-2.70) in validation cohort B. At 5 years, the corresponding HR were 2.18 (1.86-2.56), 1.77 (1.31-2.40), and 1.59 (1.36-1.86). Percentile-based models demonstrated consistently higher discrimination, better calibration, and greater net reclassification for MACE at both time points compared with fixed-threshold MFR models. Although 67.2% of patients had preserved MFR (>2.0), cardiovascular risk increased steadily across MFR percentiles even within this range.Several limitations should be considered. First, the study population may not represent the broader, non-referral population or specialized groups such as cardiac transplant patients. Second, although missing data was minimal overall, information on abnormal renal function was missing for a substantial proportion of participants and therefore could not be fully adjusted for in the multivariable models. Third, perfusion and flow measurements were fully automatically processed using standard quantitative software, which may differ from semi-automatic measurements, though the increasing adoption of AI-based tools and validated software is likely to standardize automated processing soon. Finally, the proportion of non-White participants was 15-20%, which is lower than that of the overall U.S. population, but may be appropriate given that the study included patients from North and Central America and Europe. Conclusion: Age- and sex-adjusted MFR percentiles provide a reliable, clinically actionable measure of vascular health, improving cardiovascular risk stratification by better capturing age- and sex-related heterogeneity in vascular risk. Compared with traditional fixed-threshold approaches, MFR percentiles demonstrate improved predictive performance for cardiovascular risk assessment across diverse patient populations.

  PublisherOA PDFDOI

• Phase III Prospective Multicenter Study Assessing Diagnostic Efficacy of a18F-labeled Myocardial Perfusion Tracer [18F]SYN2. SAFER 3.

  Journal of Nuclear Cardiology · 2025-08-01

  article
  PublisherDOI

• Established and Emerging Fluorine-18–Labeled Cardiac PET Radiotracers

  JACC. Cardiovascular imaging · 2025-05-28 · 12 citations

  review1st authorCorresponding
  PublisherDOI

• Abstract 4367053: ¹⁸ F-FDG PET/CT Evaluation of Incidental Extracardiac CT Findings on ⁸² Rb-Chloride PET Myocardial Perfusion Imaging

  Circulation · 2025-11-03

  articleSenior author

  Background: Positron emission tomography (PET) combined with computed tomography (CT) is a valuable strategy for myocardial perfusion imaging (MPI) in ischemic heart disease evaluation. CT attenuation correction (CTAC) enhances the diagnostic performance of PET and provides further characterization of the coronary vasculature. CTAC performed as part of MPI, however, frequently reveals incidental extracardiac findings whose clinical significance remains underexplored. Research Question: This study aimed to assess the prevalence of incidental extracardiac lesions on 82 Rb-chloride PET/CT MPI and investigate whether subsequent 18 F-FDG (fluorodeoxyglucose) uptake patterns identify clinically actionable lesions, particularly those suggesting occult malignancy. Methods: This retrospective study included 468 patients from the West Los Angeles Veterans Affairs Medical Center who underwent 18 F-FDG PET/CT within six months of 82 Rb-chloride PET/CT MPI between January 2017 and July 2022. From this cohort, 162 patients who underwent 82 Rb-chloride PET/CT MPI first and had no prior malignancy history were identified as the target cohort. Positive predictive values and chi-squared analyses evaluated the association between extracardiac lesions identified on CTAC and subsequent 18 F-FDG uptake. Results: A total of 209 extracardiac findings were noted on CTAC in the target cohort, with 108 demonstrating positive 18 F-FDG uptake. Pulmonary nodules were the most commonly identified extracardiac finding on CTAC and comprised 30% of all incidental lesions. Pulmonary nodule size was significantly associated with 18 F-FDG uptake, particularly in smokers (chi-squared value = 26.4, P &lt; 0.001). In non-smokers, while isolated pulmonary nodules had no association with 18 F-FDG uptake, those accompanied by lymphadenopathy exhibited a trend towards significant association with 18 F-FDG uptake (chi-squared value = 10.9, P = 0.052). Conclusions: Extracardiac findings observed on CTAC during 82 Rb-chloride PET MPI in patients without a history of cancer are associated with subsequent 18 F-FDG uptake on PET/CT. This association is influenced by pulmonary nodule size, with a stronger relationship observed in patients with a history of smoking. These findings underscore the importance of integrating extracardiac lesion evaluation with patient demographics into routine cardiovascular imaging workflows to identify patients at highest risk for indolent malignancy.

  PublisherDOI

• The clinical promise of 18F-flurpiridaz PET imaging heralds a new frontier in the diagnosis and management of coronary artery disease

  Nature Cardiovascular Research · 2025-01-17 · 8 citations

  article1st authorCorresponding
  PublisherDOI

• Personalized Risk Prediction with Age- and Sex-Specific Myocardial Flow Reserve Percentiles

  Journal of Nuclear Cardiology · 2025-08-01

  article
  PublisherDOI

Recent grants

• Dissecting mechanisms of anthracycline-induced cardiotoxicity

  NIH · $390k · 2022–2024

• Integrating 3-D Intravascular Sensors with Fractional Flow Reserve for Lipid-Rich Plaques

  NIH · 2020–2023

Frequent coauthors

• Tzung K. Hsiai

  University of California, Los Angeles

  76 shared

• Peter Libby

  Universidade de São Paulo

  48 shared

• Yuan Luo

  Chinese Academy of Sciences

  48 shared

• Yichen Ding

  Yunnan Normal University

  36 shared

• Natalia Neverova

  30 shared

• Junjie Chen

  Southern Medical University

  28 shared

• Ronald P. Karlsberg

  Cardiovascular Research Foundation

  27 shared

• Kevin Croce

  Harvard University

  26 shared

Awards & honors

• David Geffen School of Medicine Dean's Seed Grant, UCLA, 202…
• Lauren B. Leichtman and Arthur E. Levine Cardiovascular Disc…
• Basic Cardiovascular Sciences Early Career Mentorship Progra…
• 1st Place, Cardiovascular Council Young Investigator Award,…
• Kenneth Brown Award, American Society of Nuclear Cardiology,…