TARGET AUDIENCE

MR scientists, MR technologists, clinicians, and scientists interested in assessing cardiac metabolism.

OUTCOME/OBJECTIVES

Explain the current development in cardiac metabolic imaging using multinuclear MR spectroscopy, including ¹H, ³¹P and hyperpolarized ¹³C-MRS.

OVERVIEW

The heart requires a vast amount of energy, in the form of adenosine triphosphate (ATP), to maintain its regular pumping function suppling the body with oxygenated blood. As such, most diseases that affect the heart have a metabolic component. This can be structural in origin, e.g. in ischemic heart disease where the obstruction of blood flow limits the supply of fuel and oxygen to myocardial tissue driving anaerobic metabolism. Alternatively, this can be metabolic in origin, e.g. in diabetic cardiomyopathy where there is a functional consequence to the altered metabolism that is inherent in the diabetic heart. As such, the ability to directly assess metabolic derangements offers the potential for improved diagnosis, prognosis and monitoring of disease progression and treatment response. Metabolic assessment can also yield improved understanding of the mechanisms underlying cardiovascular diseases and aid the development of novel therapeutics through basic and clinical research.
Magnetic resonance spectroscopy (MRS) is a method for non-invasively probing metabolism with an extensive range of compounds it can detect. In the heart the major nuclei studied by MRS include proton (¹H), phosphorus (31P), and carbon (13C). 1H-MRS is a prime tool for quantification of cardiac lipid deposition^{1, 2} and the assessment of creatine content³, as such it is very indicative of deterioration of cardiac function due to fat deposition and decrease in creatine concentration. Other metabolites of cardiac ¹H-MR spectra, e.g., choline could also be measured and potentially of interest. ³¹P-MRS is a technique for direct assessment of cardiac energy metabolism since ATP releases energy through its hydrolysis to ADP and inorganic phosphate (Pi) and it’s homeostasis is secured through oxidative-phosphorylation and in case of rapid nee creatine kinase system from phosphocreatine (PCr). The PCr/ATP is a good surrogate marker of energy state of the heart shown to change in most major cardiac disorders and its comorbidities, e.g. obesity and diabetes mellitus^4-6. ³¹P-MRS also provides a tool for investigation of the kinetics of ATP production and hydrolysis⁷ and to measure pH⁸. ¹³C-MRS acquired at thermal equilibrium allow for stable-isotope tracer studies focusing on substrate turnover in the myocardium. Recently hyperpolarized magnetic resonance (HP-MRI) was introduced to introduce an SNR increase of ¹³C-enriched tracers by more than 10,000-fold⁹. This allows the use of hyperpolarized pyruvate infusion to study glycolysis rates in the cardiac muscle, which significantly changes in failing heart¹⁰.
The session will start with a summary of the particular challenges that cardiac MRS brings, in particular low sensitivity, cardiac and breathing motion and blood contamination before giving an update of the currently used and new techniques emerging from the different sites undertaking cardiac MRS. It will then continue with an overview of the application of the techniques in obesity, diabetes and cardiac disorders.
Following the talk, attendees should be able to understand what cardiac MRS offers, what the main challenges are and how to overcome them.

Acknowledgements

The Sir Henry Dale Fellowship from the Wellcome Trust [098436/Z/12/B] supports LV. The support of the Slovak Grant Agencies VEGA [2/0003/20] and APVV [#15–0029] is also gratefully acknowledged.

References

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6. Rider OJ, et al. Int J Cardiovasc Imaging. 2013,29:1043-1050.
7. Robitaille PM, et al. Magn Reson Med. 1990,15:8-24.
8. Valkovič L, et al. J Cardiovasc Magn Reson. 2019,21:19.
9. Ardenkjaer-Larsen JH, et al. Proc Natl Acad Sci U S A. 2003,100:10158-10163.
10. Rider OJ, et al. Circ Res. 2020.