High-resolution 3-D T1*-mapping and quantitative image analysis of GRAY ZONE in chronic fibrosis

The substrate of potentially lethal cardiac arrhythmias often resides in the gray zone (GZ), a mixture of viable myocytes and collagen strands found between healthy myocardium and infarct core (IC). The specific aims of this paper are to demonstrate correspondence between regions delineated in T1* (apparent T1) maps and tissue characteristics seen in histopathology and to determine the MR imaging resolution needed to adequately identify GZ-associated substrate in chronic infarct. For this, a novel 3-D multicontrast late enhancement (MCLE) MR method was used to image ex vivo swine hearts with chronic infarction, at high resolution ( 0.6×0.6×1.25 mm). Pixel-wise classified tissue maps were calculated using steady-state and T1* images as input to a fuzzy-clustering algorithm. Quantitative histology based on collagen stains was performed in n = 10 selected slabs and showed very good correlations between histologically-determined areas of heterogeneous and dense fibrosis, and the corresponding GZ ( R2 = 0.96) and IC ( R2 = 0.97 ) in tissue classified maps. Furthermore, in n = 24 slabs, we performed volumetric measurements of GZ and IC, at the original and decreased image resolutions. Our results demonstrated that the IC volume remained relatively unchanged across all resolutions, whereas the GZ volume progressively increased with diminished image resolution, with changes reaching significance at 1×1×5 mm resolution (p < 0.05 ) but not at 1×1×2.5 mm, suggesting that this resolution may be sufficient to adequately identify the GZ from MCLE images, enabling an effective MR probing of remodeled myocardium in late infarct. Future work will focus on translating these findings to optimizing the current in vivo MCLE imaging of the GZ.