Abstract
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 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) viability. Coronary artery ligation surgery was performed in male Sprague-Dawley rats (n = 13) followed by dual MEMRI and 18F-FDG PET imaging at 10–12 weeks. MEMRI was achieved with unchelated (EVP1001-1) or chelated (mangafodipir) manganese. T1 mapping MRI was followed by 18F-FDG micro-PET, with tissue taken for histological correlation. MEMRI and PET demonstrated good agreement with histology but native T1 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 T1. MEMRI showed excellent agreement with PET and MTC viability. Myocardial MEMRI T1 correlated with 18F-FDG standard uptake values and influx constant but not native T1. Our findings indicate that MEMRI identifies and quantifies myocardial viability and has major potential for clinical application in myocardial disease and regenerative therapies.
Highlights
Gadolinium chelates are widely used in cardiovascular magnetic resonance imaging (MRI) as passive intravascular and extracellular space markers
Quantification of viable myocardium was similar whether determined by positron emission tomography (PET), manganese-enhanced MRI (MEMRI) T1 or Masson’s trichrome (MTC) (Figs. 2 and 3), irrespective of manganese contrast agent
Viability quantification by native T1 mapping was lower than MEMRI T1 mapping (P < 0.01), PET (P < 0.01) or MTC (P = 0.03)
Summary
Gadolinium chelates are widely used in cardiovascular magnetic resonance imaging (MRI) as passive intravascular and extracellular space markers. We previously showed manganese-enhanced MRI (MEMRI) more accurately quantifies myocardial infarction than gadolinium delayed-enhancement MRI (DEMRI). Magnetic resonance imaging with gadolinium delayed-enhancement (DEMRI) has an increasingly important role in assessing myocardial viability by quantifying transmurality of scar[1,2]. Manganese is a paramagnetic calcium analogue which is biologically active It combines T1 shortening properties with intracellular uptake defining myocardium with functional calcium-handling[6]. This technique has potential to add important functional assessment to current imaging with gadolinium delayed-enhancement which principally defines structure of pathology. Manganese-based contrast media can be administered in chelated (e.g. mangafodipir, manganese dipyridoxyl diphosphate, Mn-DPDP), or non-chelated (e.g. EVP1001-1, manganese gluconate with calcium gluconate) formulations Both formulations demonstrate robust safety profiles in clinical studies whilst retaining favourable imaging properties. Our previous preclinical work demonstrated both these agents can be used to achieve MEMRI T1 mapping, which quantifies infarct size more accurately than DEMRI and DEMRI T1 mapping, and has potential to track and quantify altered calcium-handling in remodelling myocardium[11]
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