Manganese-enhanced T(1) mapping to quantify myocardial viability: validation with (18)F-fluorodeoxyglucose positron emission tomography

Gadolinium chelates are widely used in cardiovascular magnetic resonance imaging (MRI) as passive intravascular and extracellular space markers. Manganese, a biologically active paramagnetic calcium analogue, provides novel intracellular myocardial tissue characterisation. We previously showed manganese-enhanced MRI (MEMRI) more accurately quantifies myocardial infarction than gadolinium delayed-enhancement MRI (DEMRI). Here, we evaluated the potential of MEMRI to assess myocardial viability compared to gold-standard (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) viability. Coronary artery ligation surgery was performed in male Sprague-Dawley rats (n = 13) followed by dual MEMRI and (18)F-FDG PET imaging at 10–12 weeks. MEMRI was achieved with unchelated (EVP1001-1) or chelated (mangafodipir) manganese. T(1) mapping MRI was followed by (18)F-FDG micro-PET, with tissue taken for histological correlation. MEMRI and PET demonstrated good agreement with histology but native T(1) underestimated infarct size. Quantification of viability by MEMRI, PET and MTC were similar, irrespective of manganese agent. MEMRI showed superior agreement with PET than native T(1). MEMRI showed excellent agreement with PET and MTC viability. Myocardial MEMRI T(1) correlated with (18)F-FDG standard uptake values and influx constant but not native T(1). Our findings indicate that MEMRI identifies and quantifies myocardial viability and has major potential for clinical application in myocardial disease and regenerative therapies.