Magnetic Resonance Imaging of Contracting Ultrathin Cardiac Tissue.
Objective
Integrating cardiac-tissue patches into the beating heart and evaluating the long-term effects of such integration on cardiac contractility are two challenges in an emerging field of regenerative medicine. This pilot study presents tools for the imaging of contracting multicellular cardiac tissue constructs (MTCs) in vitro and demonstrates the feasibility of tracking the early development of strand geometry and contractions in ultrathin strands and layers of cardiac tissue using CINE MRI.


Approach
Cultured, ultrathin (~50-100-micron) MTCs of rat neonatal cardiomyocytes were plated in rectangular cell chambers (4.5 × 2.0 cm) with and without ultrathin, carbon EP electrodes embedded in the floor of the cell chamber. Two-dimensional, steady-state free precession (SSFP) CINE MRI, cell microscopy, and tissue photography were performed on Days 5-9 of cell development. Potential confounders and MRI artifacts were evaluated using non-contracting cardiac tissues and cell-free chambers filled with the cell-culture medium.


Main results
Synchronized contractions formed by Day 7; individual contracting tissue strands became identifiable by Day 9. The global patterns and details of the strand geometry and movement patterns in the SSFP images were in excellent agreement with microscopic and photographic images. No synchronized movement was identifiable by either microscopy or CINE MRI in the non-contracting MTCs or the cell-free medium. The EP recordings revealed well-defined depolarization and repolarization waveforms; the imaging artifacts generated by the carbon electrodes were small.


Significance
This pilot study demonstrates the feasibility of imaging cardiac-strand patterns and contractile activity in ultrathin, two-dimensional cardiac tissue in commonly used clinical scanners.
['Shusterman|Vladimir|V|', 'Nagpal|Prashant|P|', 'Thedens|Daniel|D|', 'Zhu|Xiaodong|X|', 'Matasic|Daniel S|DS|', 'Yoon|Jin-Young|JY|', 'Morgan|Gina|G|', 'Hoffman|Stacy|S|', 'London|Barry|B|']
magnetic resonance imaging electrophysiological monitoring engineered heart muscle