Hyperpolarized MRSI in Ischemic Heart Disease: A Metabolic Investigation of the Heart Muscle

Condition(s) studied

Investigational drug(s) / intervention(s)

13C-enriched pyruvate: Before starting the hyperpolarization injection procedure, the patient will be scanned using the standard MR imaging defined in the clinical protocol and 13C prescriptions and a pre-scan will be completed. The clinical investigator will mount the administration syringe in the MR compatible power-injector with pre-adjusted injection volume calculated according to body weight (0.43 ml /kg bw). This setting is checked by the scanning operator and clinical investigator. The injection valve is set for agent delivery, and agent injected at a rate of 5 ml/s. The timings are monitored using a stopwatch on the SPINLAB. Following injection of hyperpolarized \[1-13C\]-Pyruvate , 20 ml of sterile saline in a separate syringe, already attached to the patient line, will be used to flush the IV line at the same injection rate (5 ml/s).

Study summary

This study aims to investigate the potential of using hyperpolarized \[1-13C\]-pyruvate magnetic resonance imaging (MRI) to assess metabolic alterations in patients with ischemic heart disease (IHD). Altered myocardial metabolism is recognized as a crucial factor in heart failure and IHD, and modulating cardiac metabolism offers a new approach to treatment. However, current diagnostic modalities use ionizing radiation and have shown limited prognostic value.

Hyperpolarization through dynamic nuclear polarization (DNP) enables highly sensitive in vivo detection of metabolic processes. Hyperpolarized \[1-13C\]-pyruvate allows visualization of glycolysis-related metabolism, providing insights into the breakdown of glucose and its derivatives. By using this technique, the study aims to differentiate viable from non-viable myocardium in patients with IHD.

The objectives include implementing hyperpolarized \[1-13C\]-pyruvate cardiac MRI to image metabolic flux in the human heart and investigating the potential of this method to distinguish viable from non-viable myocardium in patients with IHD. The study endpoints involve assessing metabolic flux through the pyruvate dehydrogenase complex (PDC) and analyzing ratios of different metabolites, which can indicate the extent of pyruvate oxidation and lactate production.

A cross-sectional study design involving patients with CHF and ischemic heart disease will be used. Patients will undergo hyperpolarized \[1-13C\]-pyruvate MRI, PET imaging, late gadolinium enhancement (LGE) MRI, and cardiac magnetic resonance imaging (CMR). The study will compare \[1-13C\]-pyruvate MRI findings with PET results, allowing for a correlation between metabolic data and traditional imaging techniques. This innovative approach could provide valuable insights into the metabolic changes associated with ischemic heart disease

Eligibility

Primary outcome measure(s)

• Quantitative numerical data given as metabolite ratios — 45 minutes
  \[13C\]-bicarbonate/\[1-13C\]-pyruvate ratio, b) \[1-13C\]-lactate / \[1-13C\]-pyruvate ratio and \[1-13C\]-lactate / \[1-13C\]-bicarbonate ratio. The latter gives ratio indices of PDC-mediated pyruvate oxidation and lactate production via lactate dehydrogenase.

Trial sites (1)

Other trials for the same condition