Magnetic resonance imaging and spectroscopy of the long-chain fatty acid β-oxidation deficient heart

Adrianus J. Bakermans PhD1, Jeannette C. Bleeker MD2,3, Paul de Heer MSc4, Aart J. Nederveen PhD1, Ronald J.A. Wanders PhD3, and Gepke Visser MD PhD2.

1Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;

2Paediatric Gastroenterology and Metabolic Diseases, Wilhelmina Children’s Hospital, UMC Utrecht, Utrecht, The Netherlands;

3Laboratory Genetic Metabolic Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;

4C.J. Gorter Center for High Field MR, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.

*E: a.j.bakermans@amc.uva.nl – T: 0031 20 566 47 91

Cardiomyopathy can be a serious clinical complication in inborn errors of long-chain fatty acid β-oxidation (lcFAO). Underlying disease mechanisms are poorly understood and quantitative assessments are lacking, hampering evidence-based treatment. Potential contributors to cardiomyopathy development include the toxic deposition of lipid intermediates and/or a disturbed energy homeostasis. Using in vivo magnetic resonance imaging (MRI) and spectroscopy (MRS), we previously quantified left-ventricular dysfunction and hypertrophy,

myocardial triglyceride accumulation and energy shortage in fasted long-chain acyl-CoA dehydrogenase knock- out mice.1,2

These MR methods are non-invasive and non-ionising, and – although technically challenging – can be exploited for investigations of the human heart. Our aim  is to  translate  our preclinical animal  studies into applications  for investigations of human lcFAO disorders.

Proton MRS (1H-MRS) and MRI data (figure) acquired in two lcFAO-deficient patients (very long-chain  acyl-CoA dehydrogenase deficiency, VLCADD) reveal elevated triglyceride levels and a higher left-ventricular mass, which is indicative of mild hypertrophy. Ejection fraction was normal, but may become compromised during metabolic stress situations such as exercise or fasting.

Ongoing work focusses on acquiring quantitative readouts of myocardial energy homeostasis (phosphocreatine, ATP) with phosphorus-31 MRS, and more detailed assessments of left-ventricular function (torsion, strain) through tagging MRI that may reveal subtle alterations prior to clinical symptoms of cardiomyopathy.

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