Abstract

Research on microcirculatory alterations in human heart disease is essential to understand the genesis of myocardial contractile dysfunction and its evolution towards heart failure. The use of contrast agents in magnetic resonance imaging is an important tool in medical diagnostics related to this dysfunction. Contrast agents significantly improve the imaging by enhancing the nuclear magnetic relaxation rates of water protons in the tissues where they are distributed. Gadolinium complexes are widely employed in clinical practice due to their high magnetic moment and relatively long electronic relaxation time. In this study, the behavior of gadolinium ion as a contrast agent was investigated by two complementary methods, relaxometry and secondary ion mass spectrometry. The study examined the distribution of blood flow within the microvascular network in ex vivo Langendorff isolated rat heart models, perfused with Omniscan® contrast agent. The combined use of secondary ion mass spectrometry and relaxometry allowed for both a qualitative mapping of agent distribution as well as the quantification of gadolinium ion concentration and persistence. This combination of a chemical mapping and temporal analysis of the molar concentration of gadolinium ion in heart tissue allows for new insights on the biomolecular mechanisms underlying the microcirculatory alterations in heart disease.

Highlights

  • Coronary microcirculation plays an important role in human pathology

  • Research on the biomolecular mechanisms that lead to microcirculatory alterations related to human cardiopathies is essential to understand the genesis of myocardial contractile dysfunction and coronary atherosclerotic disease

  • Fast field cycling relaxometry experiments on homogenized rat heart tissue perfused with Omniscan were performed to check the presence of gadolinium in the heart tissue and to confirm its persistence

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Summary

Introduction

Coronary microcirculation plays an important role in human pathology. Research on the biomolecular mechanisms that lead to microcirculatory alterations related to human cardiopathies is essential to understand the genesis of myocardial contractile dysfunction and coronary atherosclerotic disease. The synergic use of mass spectrometry and relaxometric experiments allows for both mapping and quantification of the intracellular content of flow tracers Such information presents multiple advantages to improving our understanding of the physio-pathological mechanisms that lie at the base of an improved prevention and treatment. The simultaneous application of relaxometry and ToF-SIMS for the study of the microperfusion of the heart was explored in terms of both quantification (relaxometry) and blood flow mapping at high resolution (microns) of coronary micro-circulation

Fast Field Cycling Relaxometry Fast field cycling relaxometry
Optical Analysis
Sample Preparation
ToF-SIMS Measurements
Relaxation Rate Measurements
Statistical Data Treatment
Conclusions
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