Mapping iron in human heart tissue with synchrotron x-ray fluorescence microscopy and cardiovascular magnetic resonance

BACKGROUND: MRI assessment of cardiac iron is particularly important for assessing transfusion-dependent anaemia patients. However, comparing the iron distribution from histology or bulk samples to MRI is not ideal. Non-destructive, high-resolution imaging of post-mortem samples offers the ability to examine iron distributions across large samples at resolutions closer to those used in MRI. The aim of this ex vivo case study was to compare synchrotron X-ray fluorescence microscopy (XFM) elemental iron maps with magnetic resonance transverse relaxation rate maps of cardiac tissue samples from an iron-loaded patient. METHODS: Two 5 mm thick slices of formalin fixed cardiac tissue from a Diamond Blackfan anaemia patient were imaged in a 1.5 T MR scanner. R2 and R2* transverse relaxation rate maps were generated for both slices using RF pulse recalled spin echo and gradient echo acquisition sequences. The tissue samples were then imaged at the Australian Synchrotron on the X-ray Fluorescence Microscopy beamline using a focussed incident X-ray beam of 18.74 keV and the Maia 384 detector. The event data were analyzed to produce elemental iron maps (uncalibrated) at 25 to 60 microns image resolution. RESULTS: The R2 and R2* maps and profiles for both samples showed very similar macro-scale spatial patterns compared to the XFM iron distribution. Iron appeared to preferentially load into the lateral epicardium wall and there was a strong gradient of decreasing iron, R2 and R2* from the epicardium to the endocardium in the lateral wall of the left ventricle and to a lesser extent in the septum. On co-registered images XFM iron was more strongly correlated to R2* (r = 0.86) than R2 (r = 0.79). There was a strong linear relationship between R2* and R2 (r = 0.87). CONCLUSIONS: The close qualitative and quantitative agreement between the synchrotron XFM iron maps and MR relaxometry maps indicates that iron is a significant determinant of R2 and R2* in these ex vivo samples. The R2 and R2* maps of human heart tissue give information on the spatial distribution of tissue iron deposits.