Table 1

Potential cardiac applications of hyperpolarised magnetic resonance technology

Potential cardiac applicationBiochemical basisStrengthsWeaknessesAlternative approaches
Ischaemia testing in coronary artery diseaseHypoxia curtails Krebs cycle flux. Pyruvate metabolism switches from PDH to LDH—resulting [1- 13C]lactate can be imaged.By imaging [1-13C]lactate, the technique can measure the biochemical hallmark of ischaemia, not a surrogate marker.Sensitivity for low-grade ischaemia is yet to be seen; the models studied are reperfusion models. Extra – cardiac [1-13C]lactate makes cardiac imaging difficult.Conventional functional ischaemia testing:
(1) non-invasive: stress perfusion CMR, SPECT– MPI* and DSE; and
(2) invasive: FFR and iFR†
Viability testing in coronary artery diseaseViable myocardium must be respiring with flux through PDH. The CO2 produced equilibrates with HCO3 . H13CO3 production therefore defines viable myocardium.Unlike LGE, detection of H13CO3 delineates alive tissue with potential for recovery, potentially refining the group revascularised.Resolution – human cardiac imaging down to 8.8 × 8.8 × 10 mm is demonstrated. Reasonable SNR at higher resolution requires further technical development. This compares with 1.4 × 1.6 × 5 mm resolution for LGE.Conventional testing:
(1) CMR – LGE imaging and contractile reserve.
(2) SPECT – perfusion and contractile reserve.
(3) DSE – contractile reserve.
Heart failure (general considerations)Energy substrate handling changes with stepwise progression towards heart failure, initially with increased glucose usage. PDH in part regulates the balance between fatty acid and glucose metabolism.Serial 13C imaging and metabolic phenotyping of energy substrates in those at risk of developing heart failure may inform risk stratification and treatment regimens.Identification of shifts in substrate handling may simply reflect progression of heart failure and may not represent an opportunity for an intervention that alters progression.None comparable. Contemporary strategies of serial structural imaging with various modalities simply reports function only.
Heart failure (defining the aetiology)Insulin resistance and raised circulating fatty acids result in markedly reduced glucose oxidative ability in diabetic cardiomyopathy. Metabolic phenotyping may inform diagnosis in the failing heart.Characterising the metabolic hallmarks of cardiomyopathy may aid diagnosis in circumstances such as unexplained hypertrophy (HCM vs hypertensive vs storage disorders), and identify
those eligible for targeted
metabolic therapy
As for heart failure – general considerations.As yet metabolic phenotyping has not yet reached the clinic in this circumstance, however, 13C imaging would be a helpful adjunct to current imaging modalities.
DNP – the technique, compared with other metabolic imaging modalitiesThe magnetic energy (polarisation) and hence MR signal of the 13C tracer is increased up to 10 000 times. Achieved by transferring the high polarisation associated with free electrons at very low temperature by microwave irradiation.Allows in vivo real-time imaging of normal and abnormal metabolism, and the study of how this contributes to the disease phenotype.(1) Technically challenging: dissolution from 1K, pH neutralisation and radical removal must happen extremely fast for signal.
(2) Only fast metabolic reactions can be studied.
(3) Technical advances in coils and sequences needed to improve imaging resolution.
(4) Imaging fundamentally relies on tracer delivery.
Other metabolic imaging:
1) PET: only able to measure uptake of a radioactive tracer (eg, 18F– FDG) not its metabolic fate.
2) MRS: mostly limited to ex-vivo hearts due to the need for enriched 13C substrates and extended imaging times.
  • *Single photon emission computed tomography – myocardial perfusion imaging.

  • †Instantaneous wave free ratio – hyperaemia free intracoronary functional assessment.

  • CMR - Cardiovascular Magnetic Resonance; DNP, dynamic nuclear polarisation; DSE, Dobutamine stress echocardiography; FFR, Fractional flow reserve; iFR, instantaneous wave-free ratio - hyperaemia free intra-coronary functional assessment ; LDH, lactate dehydrogenase; LGE, late gadolinium enhancement; MRS, Magnetic resonance spectroscopy; PDH, pyruvate dehydrogenase; PET, Positron emission tomography; SPECT - MPI - Single photon emission computed tomography.