Clinical trial NCT06814587: Hyperpolarized 13C Pyruvate-MRI and FDG-PET in a Single Exam for the Prognosis of Ischemic Cardiomyopathy
Official title: Hyperpolarized 13C Pyruvate-MRI and FDG-PET in a Single Exam for the Prognosis of Ischemic Cardiomyopathy
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Coronary Artery Disease
Coronary Artery Bypass Graft (CABG)
Keywords: Coronary Artery Disease
Hyperpolarized 13C Pyruvate-MRI
FDG-PET
PET-MRI
Myocardial Viability
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
Collaborators: name: American Heart Association
First posted: 2025-02-07
Enrollment: 12
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This study includes patients with ischemic cardiomyopathy undergoing CABG and healthy controls to establish metabolic reference values.

Brief summary: The goal of this clinical trial is to evaluate a novel imaging approach that combines hyperpolarized 13C pyruvate magnetic resonance imaging (HP-13C-MRI) and \[¹⁸F\]Fluorodeoxyglucose positron emission tomography (FDG-PET) in a single exam to improve the prognostic assessment of ischemic cardiomyopathy. The main questions this study aims to answer are:

Primary Hypothesis: Can the simultaneous acquisition of HP-13C-MRI and FDG-PET data improve the metabolic, viability, and mechanical function assessment in ischemic cardiomyopathy? Primary Outcome Measure: To determine whether the combined HP-13C-MRI/FDG-PET approach provides better prognostic value for ischemic cardiomyopathy compared to current separate imaging modalities.

Secondary Outcome Measures:

Baseline metabolic and viability profiles in healthy individuals. Correlation of metabolic imaging with clinical outcomes in preoperative patients with low left ventricular ejection fraction (LVEF).

Longitudinal changes in myocardial metabolism post-surgery. Study Design: This is a prospective, non-blinded, single-center study utilizing a hybrid PET-MR scanner for simultaneous imaging.

Participants will be divided into three groups:

Healthy subjects (n=6) with normal LVEF for baseline reference. Preoperative patients (n=6) with low LVEF due to ischemic cardiomyopathy undergoing coronary artery bypass grafting (CABG).

Post-CABG patients (n=6 at 4-6 months, n=6 at 10-12 months) to evaluate post-surgical changes.

Procedures:

Undergo HP-13C-MRI and FDG-PET imaging in a single session. Blood samples for metabolic biomarkers (lactate, pyruvate, triglycerides, insulin, glucose).

Standard clinical cardiac imaging (Echocardiography, SPECT Myocardial Perfusion Imaging).

Detailed description: 1. Study Rationale and Significance 1.1. Ischemic Cardiomyopathy and the Need for Advanced Imaging Approaches Ischemic cardiomyopathy (ICM) is a progressive disorder characterized by myocardial dysfunction due to reduced coronary perfusion, most commonly caused by underlying coronary artery disease (CAD) or previous myocardial infarction (MI). The prognosis of ICM remains poor, with high rates of morbidity and mortality despite advances in pharmacologic, interventional, and surgical therapies. A major clinical challenge in managing ICM is the accurate and comprehensive assessment of myocardial viability and metabolic function to guide appropriate revascularization strategies. Traditional imaging techniques, including late gadolinium-enhanced cardiac magnetic resonance imaging (LGE-CMR), single-photon emission computed tomography (SPECT), and dobutamine stress echocardiography, provide structural and functional insights but are limited in their ability to dynamically assess metabolic alterations that precede irreversible myocardial damage.

   1.2. Limitations of Current Imaging Modalities in Assessing Viability and Metabolism Existing non-invasive imaging approaches for myocardial viability assessment rely primarily on anatomical markers of fibrosis, contractile reserve, or static glucose metabolism, requiring multiple imaging sessions with different modalities. These approaches pose several limitations, including discordant results between imaging techniques, increased patient burden due to multiple appointments, and delays in treatment decisions. More importantly, the lack of an integrated imaging strategy limits the ability to assess real-time metabolic adaptations that can predict myocardial recovery potential post-revascularization.

   1.3. The Rationale for a Combined HP-13C MRI and FDG-PET Imaging Approach The proposed study seeks to overcome these limitations by employing a novel integrated metabolic imaging method combining hyperpolarized 13C-pyruvate magnetic resonance imaging (HP-13C-MRI) and \[¹⁸F\]Fluorodeoxyglucose positron emission tomography (FDG-PET) in a single examination. HP-13C-MRI provides real-time metabolic flux information, allowing direct visualization of substrate utilization and oxidative metabolism, while FDG-PET enables quantification of glucose uptake and viability assessment. By simultaneously acquiring metabolic, viability, and mechanical function data, this hybrid approach has the potential to transform the diagnostic paradigm for ischemic cardiomyopathy.
2. Study Objectives and Hypotheses 2.1. Primary Objective The primary objective of this study is to determine whether simultaneous HP-13C-MRI and FDG-PET imaging can improve the assessment of myocardial viability and metabolic function in ischemic cardiomyopathy compared to current standard imaging approaches.

   2.2. Secondary Objectives

   The secondary objectives include:

   2.2.1. Establishing baseline myocardial metabolism, viability, and mechanical function parameters in healthy subjects using combined HP-13C-MRI and FDG-PET to serve as a reference for subsequent patient cohorts.

   2.2.2. Evaluating metabolic abnormalities in preoperative patients with ischemic cardiomyopathy and low left ventricular ejection fraction (LVEF) to correlate metabolic activity with clinical disease severity and revascularization outcomes.

   2.2.3. Conducting a longitudinal assessment of myocardial metabolism and function following surgical revascularization to determine the predictive value of baseline metabolic imaging for post-surgical myocardial recovery.

   2.3. Primary Hypothesis It is hypothesized that the simultaneous acquisition of metabolic and viability data via HP-13C-MRI and FDG-PET in a single imaging session will provide superior diagnostic accuracy and prognostic value for ischemic cardiomyopathy compared to standard imaging techniques performed separately.

   2.4. Secondary Hypotheses 2.4.1. In healthy individuals with normal myocardial function, HP-13C-MRI and FDG-PET will establish normal metabolic flux patterns, which will differ significantly from those observed in patients with ischemic cardiomyopathy.

   2.4.2. In preoperative patients with ischemic cardiomyopathy, metabolic derangements detected via HP-13C-MRI will correlate with regional glucose uptake on FDG-PET and provide insights into myocardial segments with reversible dysfunction.

   2.4.3. Post-CABG follow-up imaging will demonstrate metabolic improvement in viable myocardial segments, confirming the potential of preoperative metabolic imaging as a predictive tool for post-revascularization myocardial recovery.
3. Study Design and Methodology 3.1. Study Type and Design This is a prospective, single-center, non-blinded translational research study employing a hybrid PET-MR scanner for simultaneous imaging.

   3.2. Study Population and Group Allocation

   A total of 12 human subjects will be enrolled, stratified into three groups:

   3.2.1. Healthy control group (n=6) consisting of individuals with normal LVEF (\>50%) to establish baseline metabolic and viability reference values.

   3.2.2. Pre-CABG ischemic cardiomyopathy group (n=6) consisting of patients with reduced LVEF (\<35%) undergoing planned coronary artery bypass grafting (CABG).

   3.2.3. Post-CABG follow-up group (n=6 at 4-6 months, n=6 at 10-12 months) consisting of the same pre-CABG cohort undergoing post-surgical follow-up imaging to assess metabolic recovery.

   3.3. Study Procedures 3.3.1. All participants will undergo one or two imaging sessions involving HP-13C-MRI and FDG-PET in a single session using a hybrid PET-MR scanner.

   3.3.2. Participants will undergo blood sampling before and after imaging to measure key metabolic biomarkers, including lactate, pyruvate, triglycerides, insulin, and glucose.

   3.3.3. Clinical cardiac imaging data, including echocardiography, SPECT myocardial perfusion imaging, and invasive coronary angiography, will be collected for correlation with metabolic imaging findings.

   3.4. Imaging Protocol 3.4.1. Hyperpolarized 13C Pyruvate MRI Acquisition 3.4.1.1. Hyperpolarized \[1-13C\] pyruvate will be dynamically injected, and real-time conversion to metabolic intermediates (bicarbonate and lactate) will be measured.

   3.4.1.2. Cardiac-gated 13C imaging sequences will be used to quantify myocardial metabolic flux, focusing on segmental variations in oxidative metabolism.

   3.4.2. FDG-PET Acquisition 3.4.2.1. FDG uptake will be measured to assess myocardial viability and regional glucose metabolism.

   3.4.2.2. Metabolic activity will be compared across ischemic and non-ischemic myocardial regions.
4. Data Analysis and Statistical Considerations 4.1. Primary Statistical Analysis 4.1.1. HP-13C MRI and FDG-PET data will be analyzed using MATLAB-based reconstruction and analysis pipelines.

   4.1.2. Quantitative metabolic parameters, including bicarbonate-to-lactate ratio and myocardial FDG uptake, will be compared across study groups.

   4.1.3. Statistical significance will be determined using an unpaired t-test (α=0.05, one-tailed) for two-group comparisons and ANOVA/2-way ANOVA for multi-group comparisons.

   4.2. Sample Size Justification 4.2.1. The sample size of 12 subjects (24 imaging sessions) is based on feasibility and prior studies demonstrating significant metabolic differences with HP-13C MRI in small cohorts.

   4.2.2. Power calculations suggest that this sample size will be sufficient to detect clinically relevant differences in myocardial metabolic parameters with an estimated effect size of 1.0 and 80% power at α=0.05.
5. Safety and Risk Considerations 5.1. Radiation Exposure 5.1.1. The combined HP-13C MRI and FDG-PET protocol will result in a radiation exposure of \~10.5 mSv, within acceptable diagnostic limits.

5.1.2. Radiation exposure will be monitored to comply with institutional and regulatory guidelines.

5.2. Adverse Event Monitoring 5.2.1. Subjects will be closely monitored during imaging, with continuous ECG and blood pressure monitoring.

5.2.2. Any adverse events will be reported and managed according to institutional safety protocols.

Eligibility criteria: Inclusion Criteria:

Participants must meet all of the following criteria:

* Age between 20-80 years
* Eligible for MRI, PET, and contrast agents (based on institutional screening protocols)
* Scheduled for CABG (for ischemic cardiomyopathy patients)
* Left ventricular ejection fraction (LVEF) ≤ 40% or clinical indication for myocardial viability assessment
* No history of coronary artery disease or diabetes (for healthy controls)
* Negative pregnancy test (for female participants of childbearing potential)

Exclusion Criteria:

Participants will be excluded if they meet any of the following criteria:

* Age \<20 or \>80 years
* Prior extensive myocardial infarction (defined as \>50% transmural scar on viability imaging)
* Contraindications to MRI, PET, or contrast agents (including severe claustrophobia or allergy)
* Pregnant or breastfeeding women
* Severe renal impairment (GFR \<30 mL/min/1.73m²)
* Uncontrolled diabetes (HbA1c \>9%)

Primary outcomes:
measure: Myocardial Metabolic and Viability Assessment via HP-13C MRI and FDG-PET
timeFrame: Baseline imaging at enrollment (pre-CABG, within 30 days before surgery)
Secondary outcomes:
measure: Comparison of Myocardial Metabolic Profiles in Healthy vs. Ischemic Cardiomyopathy Patients
timeFrame: Baseline imaging at enrollment (single session within 14 days of consent)
measure: Longitudinal Changes in Myocardial Metabolism Post-CABG
timeFrame: Follow-up imaging at 4-6 months (±2 weeks) and 10-12 months (±2 weeks) post-CABG.
measure: Correlation of Preoperative Metabolic Imaging with Post-Surgical Cardiac Function
timeFrame: LVEF and cardiac function measured at baseline (pre-CABG, within 30 days before surgery), 4-6 months (±2 weeks) post-CABG, and 10-12 months (±2 weeks) post-CABG.
Other outcomes:
measure: Feasibility and Reproducibility of Combined HP-13C MRI and FDG-PET in a Single Imaging Session
timeFrame: Assessed at each imaging session (baseline imaging within 14 days of consent, follow-up imaging at 4-6 months and 10-12 months post-CABG).
Locations:
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
Study officials:
affiliation: UT Southwestern Medical Center
name: Gaurav Sharma, PhD, MBA
role: PRINCIPAL_INVESTIGATOR
References: