Gadolinium-enhanced magnetic resonance imaging for detection and quantification of fibrosis in human myocardium in vitro

Abstract

Background: The availability of a non-invasive test to detect and quantify interstitial and replacement fibrosis would be a useful advance for evaluation of cardiac therapies that could prevent fibrosis progression. There is an established role for magnetic resonance imaging (MRI) in the assessment of replacement fibrosis (when fibrosis replaces myocytes), but the potential for assessment of interstitial fibrosis (when amount of fibrosis increases between myocytes) has not been evaluated.

Methods: A novel in vitro MRI technique was developed for comparison of gadodiamide contrast distribution volume as a measure of both kinds of myocardial fibrosis, with histologically determined myocardial collagen volume fraction, the current gold standard for quantification of myocardial fibrosis. Eight samples of human myocardium were obtained postmortem and a fast spin-echo sequence (3 Tesla) with non-slice selective inversion pulse performed before and after immersion in a gadodiamide saline solution for determination of the gadodiamide partition coefficient. T1 values were calculated from the inversion recovery signal curves. The same samples were fixed in formalin, and collagen volume fraction was determined by the picrosirius red method using a semi-automated, polarized, digital microscopy system.

Results: Both gadodiamide distribution volumes as well as CVF values were significantly different in normal myocardium versus interstitial fibrosis (P = 0.001), and normal versus replacement fibrosis (P = 0.015). Moreover, there was a significant positive correlation between the two methods, across all three histological categories of myocardial fibrosis (r = 0.73; P = 0.017).

Conclusion: These findings indicate an expanded potential for gadodiamide enhanced MRI as a novel, non-invasive alternative to histological evaluation, for the quantification of both interstitial and replacement myocardial fibrosis.