Hyperpolarized 13C Pyruvate-MRI and FDG-PET in a Single Exam for the Prognosis of Ischemic Cardiomyopathy

Обзор

This prospective, non-blinded, single-center, translational research study aims to validate a multimodal advanced imaging exam for cardiac viability. The protocol utilizes three distinct imaging modalities: Single Photon Emission Computed Tomography Myocardial Perfusion Imaging (SPECT MPI), 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), and Hyperpolarized Carbon-13 (HP-13C) Pyruvate Magnetic Resonance Imaging (MRI). Under this protocol, the SPECT MPI and FDG-PET exams will be used in combination to comprehensively assess myocardial viability. Concurrently, the HP-13C Pyruvate MRI will be utilized to provide additional insights into myocardial metabolism. The study will evaluate healthy volunteers to establish baseline parameters and patients with ischemic cardiomyopathy (ICM) before and after surgical revascularization.

Подробное описание

schemic cardiomyopathy (ICM), characterized by compromised blood flow to the heart muscle, demands innovative solutions to accurately assess myocardial viability and metabolic function. While myocardial viability assessment is a widely practiced concept for selecting patients for revascularization, current imaging techniques often require separate sessions and lack holistic functional data.

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This project introduces a novel hybrid multimodal imaging method designed to holistically understand the interplay between metabolism and perfusion in ischemic cardiomyopathy. To achieve this, the study deliberately partitions imaging objectives:

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Myocardial Viability: SPECT MPI and 18F-FDG PET will be used together to assess myocardial viability. FDG-PET exploits the preferential uptake of glucose by metabolically active cells to identify viable myocardial tissue within ischemic regions.

Myocardial Metabolism: HP-13C-MRI provides additional, distinct insights into myocardial metabolism. By tracking the conversion of hyperpolarized 13C-pyruvate into metabolic intermediates like bicarbonate and lactate, this technique allows for the real-time quantification of alterations in cardiac substrate utilization and oxidative metabolism.

The study will enroll a total of 15 human subjects divided into two primary groups:

Healthy Participants (n=6): Individuals with normal left ventricular ejection fraction (LVEF \> 0.50) to establish baseline imaging parameters.

ICM Participants (n=9): Patients with advanced ischemic cardiomyopathy and low LVEF (≤ 40%) scheduled for standard-of-care CABG surgery.

Due to current technical constraints regarding multi-nuclear support on hybrid PET-MRI scanners, the imaging modalities will be acquired on separate days within a 3-month period. The ICM cohort will be evaluated at two critical time points: preoperatively before CABG surgery, and longitudinally at one follow-up point 3-6 months post-surgery. Ultimately, this multimodal approach seeks to provide a non-invasive, highly accurate evaluation of disease severity, progression, and postoperative myocardial response to surgical revascularization.

Study Objectives

Primary Objective:

To evaluate myocardial metabolism, viability, and mechanical function in preoperative ICM patients with low LVEF (≤ 40%) scheduled for Coronary Artery Bypass Graft (CABG) using a combined assessment of HP-13C-MRI, FDG-PET, and SPECT MPI. This aims to correlate metabolic and viability data with clinical indicators, providing insights into abnormal cardiac metabolism.

Secondary Objectives:

Secondary Objective 1: To establish baseline metabolic, viability, and mechanical function parameters in healthy subjects with normal LVEF (\> 0.50) using the combined HP-13C-MRI, FDG-PET, and SPECT MPI approach, serving as a comparative foundation.

Secondary Objective 2: To longitudinally assess changes in myocardial metabolism, viability, and mechanical function in the ICM patient cohort at 3-6 months post-surgical revascularization (CABG). This aims to elucidate the impact of surgical revascularization on postoperative myocardial changes.

Вмешательства

• Диагностический тест Hyperpolarized 13C Pyruvate Magnetic Resonance Imaging (HP-13C MRI)
  HP-13C MRI is a metabolic imaging technique that enables real-time assessment of myocardial substrate utilization by tracking the conversion of hyperpolarized \[1-13C\] pyruvate to metabolic intermediates such as bicarbonate and lactate. This imaging modality provides insights into oxidative metabolism and mitochondrial function, facilitating the identification of metabolically active and ischemic myocardial regions in patients with ischemic cardiomyopathy.
• Диагностический тест [¹⁸F]Fluorodeoxyglucose Positron Emission Tomography (FDG-PET)
  FDG-PET is a molecular imaging technique used to assess myocardial viability by quantifying glucose uptake in cardiac tissue. This method differentiates viable myocardium, which retains metabolic activity, from non-viable scar tissue. FDG-PET is widely used in ischemic cardiomyopathy for viability assessment to guide revascularization decisions.
• Диагностический тест SPECT MPI (Single Photon Emission Computed Tomography Myocardial Perfusion Imaging)
  This procedure involves a Rest and a Stress SPECT Myocardial Perfusion Imaging Study. It uses myocardial perfusion imaging (MPI) with a radioactive tracer to compare pictures of the heart at rest and during stress, induced either by treadmill exercise or the medication Regadenoson.

Первичные конечные точки

• Assessment of Myocardial Metabolism and Viability via HP-13C MRI, FDG-PET, and SPECT MPI [Срок оценки: Baseline imaging at enrollment (pre-CABG)]

Вторичные конечные точки (3)

• Comparison of Myocardial Metabolic Profiles and Viability in Ischemic Cardiomyopathy Patients vs. Healthy Subjects [Срок оценки: Baseline imaging at enrollment across separate imaging visits (SPECT MPI, FDG-PET, and HP-13C MRI on different days).]
• Longitudinal Changes in Myocardial Metabolism Post-CABG [Срок оценки: Follow-up imaging at a single time point 3-6 months post-CABG.]
• Correlation of Preoperative Multimodal Imaging with Post-Surgical Exam [Срок оценки: Measured at baseline (pre-CABG) and at the 3-6 months post-CABG follow-up.]

Критерии участия

Study Population Description The study population will consist of 12 to 15 human subjects divided into two main groups. The first group includes 6 healthy individuals with a normal left ventricular ejection fraction (LVEF > 0.50). The second group comprises 9 patients with advanced ischemic cardiomyopathy (ICM) and a low LVEF (< 0.40) who are scheduled for standard-of-care Coronary Artery Bypass Graft (CABG) surgery. The study team will aim to recruit a mixed-sex, age-matched population with equal numbers for all metabolic imaging studies.

Ischemic Cardiomyopathy (ICM) Patient Cohort

Критерии включения

Male or Female, age 18-80 years. Patient scheduled for Coronary Artery Bypass Surgery as standard of care therapy per clinical guidelines.

Presence of 1 or more stenotic coronary artery vessels. Left Ventricular Ejection Fraction (LVEF) ≤ 40%, or clinical indication for myocardial viability assessment.

Able to tolerate FDG PET/MRI protocol and preparation (e.g., fasting state, glucose regulation).

Medication use within 24 hours of the scan is allowed and will be reported. Negative pregnancy test for females of childbearing age (on the day of scanning).

No known contraindications to 3T MRI, SPECT MPI, or FDG PET.

Критерии исключения

Male or female, age < 18 or > 80 years of age. Patients not scheduled for CABG or those without confirmed coronary artery disease (CAD).

History of prior myocardial infarction with transmural scar > 50% (based on prior imaging or clinical history).

Patient not eligible for 3T MRI (Any condition or device precluding safe MRI e.g., pacemakers, defibrillators, metal implants), SPECT (significant arrhythmias or hemodynamic instability), or FDG-PET (e.g., severely impaired glucose metabolism).

Positive pregnancy test or females currently breastfeeding (on the day of scanning).

Severe renal impairment (GFR < 30 mL/min) or contraindication to FDG PET tracer.

History of uncontrolled diabetes mellitus (HbA1c > 9%) or inability to achieve stable glucose levels for FDG PET preparation.

Healthy Volunteer Cohort

Критерии включения

Male or Female, age 18-80 years. No history of coronary artery disease or diabetes. Eligible for 3T MRI, SPECT, and FDG-PET. Negative pregnancy test for females of childbearing age (on the day of scanning).

Критерии исключения

History of coronary artery disease, diabetes, or other medical conditions deemed exclusionary by the study team.

Positive pregnancy test or females currently breastfeeding (on the day of scanning).

Contraindications to MRI (e.g., metallic implants, claustrophobia), SPECT MPI, or FDG-PET.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

США · 1 центр

• University of Texas Southwestern Medical Center — Dallas

Идентификаторы

NCT: NCT06814587 · STU-2024-0809

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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