Molecular Imaging of the heart by mass spectrometry

BACKGROUND Cardiovascular diseases are the world’s number one death cause, accounting for 17.1 million deaths a year. There is still much unknown about cardiovascular diseases and their physiological underlying mechanism. Understanding the nature of complex biological processes occurring in both healthy and diseased heart tissue requires identifying the compounds involved and determining where they are located. Summary METHODS We have investigated a complementary mass spectrometry imaging (MSI) approach using matrix-assisted laser desorption/ionization (MALDI) and secondary ion mass spectrometry (SIMS) on the major areas of rat heart: the pericardium, the myocardium, the endocardium, and the great vessels to study the native distribution and identity of atomics, lipids, peptides and proteins in rat heart sections. 40 layers of horizontal tissue slices were acquired and reconstructed into a 3 D dataset. RESULTS Surface rastering of heart tissue sections generated multiple secondary ions in a mass range up to 1500 m/z. In the negative spectra we identified cholesterol related ions that show high intensity in both atrias, the aorta, the pulmonary artery and the outline both ventricles. The m/z 105 (choline) signal localizes in both atrias, aorta, pulmonary artery, in the atrioventricular valves and semilunar valves but is not present in ventricles surface. DAG species with probable identifications as Oleic, Linoleic [OL]+ at m/z 602 and [OO]+ (Oleic, Oleic) at m/z 604, can be detected. The images of 3D reconstruction show a highly complementary localization between Na+, K+, ion at m/z 145 and ion at m/z 667. Na+ is localized to tissue regions corresponding to atrias, while K+ is strongly localized to tissue regions corresponding to ventricles surface.The ion at m/z 667 localized very precisely within the aortic wall and the ion at m/z 145 is primarily located to the atria regions. CONCLUSIONS To promote further research with cardiovascular disease, we report the identification of characteristic molecules that map the spatial organization in a rat heart’s structure. A series of images obtained from successive sections of animal heart could, in principle, be used to produce a molecular atlas. Such tissue atlases (based optical images) are widely used for anatomical and physiological reference. The specific aim of this project is to optimize the data obtained from Heart SIMS a analysis and the 3-D reconstructive techniques developed to aid in investigating and visualizing differential molecular localizations in heart rat structures. The results reported here represent the first 3D molecular reconstruction of rat heart by SIMS imaging.