Microstructural Infarct Border Zone Remodeling in the Post-infarct Swine Heart Measured by Diffusion Tensor MRI

Introduction: Computational models of the heart increasingly require detailed microstructural information to capture the impact of tissue remodeling on cardiac electromechanics in, for example, hearts with myocardial infarctions. Myocardial infarctions are surrounded by the infarct border zone (BZ), which is a site of electromechanical property transition. Magnetic resonance imaging (MRI) is an emerging method for characterizing microstructural remodeling and focal myocardial infarcts and the BZ can be identified with late gadolinium enhanced (LGE) MRI. Microstructural remodeling within the BZ, however, remains poorly characterized by MRI due, in part, to the fact that LGE and DT-MRI are not always available for the same heart. Diffusion tensor MRI (DT-MRI) can evaluate microstructural remodeling by quantifying the DT apparent diffusion coefficient (ADC, increased with decreased cellularity), fractional anisotropy (FA, decreased with increased fibrosis), and tissue mode (decreased with increased fiber disarray). The purpose of this work was to use LGE MRI in post-infarct porcine hearts (N = 7) to segment remote, BZ, and infarcted myocardium, thereby providing a basis to quantify microstructural remodeling in the BZ and infarcted regions using co-registered DT-MRI. Methods: Chronic porcine infarcts were created by balloon occlusion of the LCx. 6–8 weeks post-infarction, MRI contrast was administered, and the heart was potassium arrested, excised, and imaged with LGE MRI (0.33 × 0.33 × 0.33 mm) and co-registered DT-MRI (1 × 1 × 3 mm). Myocardium was segmented as remote, BZ, or infarct by LGE signal intensity thresholds. DT invariants were used to evaluate microstructural remodeling by quantifying ADC, FA, and tissue mode. Results: The BZ significantly remodeled compared to both infarct and remote myocardium. BZ demonstrated a significant decrease in cellularity (increased ADC), significant decrease in tissue organization (decreased FA), and a significant increase in fiber disarray (decreased tissue mode) relative to remote myocardium (all p < 0.05). Microstructural remodeling in the infarct was similar, but significantly larger in magnitude (all p < 0.05). Conclusion: DT-MRI can identify regions of significant microstructural remodeling in the BZ that are distinct from both remote and infarcted myocardium.

[1]  Daniel B. Ennis,et al.  Electrophysiology of Heart Failure Using a Rabbit Model: From the Failing Myocyte to Ventricular Fibrillation , 2016, PLoS Comput. Biol..

[2]  P Suetens,et al.  Remote myocardial dysfunction after acute anterior myocardial infarction: impact of left ventricular shape on regional function: a magnetic resonance myocardial tagging study. , 2000, Journal of the American College of Cardiology.

[3]  M. Weisfeldt,et al.  Cellular mechanisms of myocardial infarct expansion. , 1988, Circulation.

[4]  Pierre Croisille,et al.  Assessment of myocardial fibrosis with cardiovascular magnetic resonance. , 2011, Journal of the American College of Cardiology.

[5]  A. Garfinkel,et al.  Increased susceptibility of aged hearts to ventricular fibrillation during oxidative stress. , 2009, American journal of physiology. Heart and circulatory physiology.

[6]  R. Kim,et al.  Myocardial Gd-DTPA kinetics determine MRI contrast enhancement and reflect the extent and severity of myocardial injury after acute reperfused infarction. , 1996, Circulation.

[7]  Robin M Heidemann,et al.  High resolution diffusion‐weighted imaging using readout‐segmented echo‐planar imaging, parallel imaging and a two‐dimensional navigator‐based reacquisition , 2009, Magnetic resonance in medicine.

[8]  A. Becker,et al.  Remodeling after myocardial infarction in humans is not associated with interstitial fibrosis of noninfarcted myocardium. , 1997, Journal of the American College of Cardiology.

[9]  Stefan Skare,et al.  The presence of two local myocardial sheet populations confirmed by diffusion tensor MRI and histological validation , 2011, Journal of magnetic resonance imaging : JMRI.

[10]  Peter Kellman,et al.  Late Gadolinium-Enhancement Cardiac Magnetic Resonance Identifies Postinfarction Myocardial Fibrosis and the Border Zone at the Near Cellular Level in Ex Vivo Rat Heart , 2010, Circulation. Cardiovascular imaging.

[11]  Stanley E Lazic,et al.  The problem of pseudoreplication in neuroscientific studies: is it affecting your analysis? , 2010, BMC Neuroscience.

[12]  O. Simonetti,et al.  The use of contrast-enhanced magnetic resonance imaging to identify reversible myocardial dysfunction. , 2000, The New England journal of medicine.

[13]  S. Chugh,et al.  Isolated myocyte contractile function is normal in postinfarct remodeled rat heart with systolic dysfunction. , 1997, Circulation.

[14]  N. Sharpe,et al.  Left ventricular remodeling after myocardial infarction: pathophysiology and therapy. , 2000, Circulation.

[15]  Chao Zou,et al.  Transmural heterogeneity of left ventricular myocardium remodeling in postinfarct porcine model revealed by MR diffusion tensor imaging , 2011, Journal of magnetic resonance imaging : JMRI.

[16]  F. Marchlinski Ventricular Tachycardia Ablation Moving Beyond Treatment of Last Resort , 2008 .

[17]  M. Miragoli,et al.  Myofibroblasts Induce Ectopic Activity in Cardiac Tissue , 2007, Circulation research.

[18]  P. Ursell,et al.  Structural and Electrophysiological Changes in the Epicardial Border Zone of Canine Myocardial Infarcts during Infarct Healing , 1985, Circulation research.

[19]  Daniel B. Ennis,et al.  Simulation Methods and Validation Criteria for Modeling Cardiac Ventricular Electrophysiology , 2014, PloS one.

[20]  Capelle,et al.  Slow conduction in the infarcted human heart. 'Zigzag' course of activation. , 1993, Circulation.

[21]  J M de Bakker,et al.  Reentry as a cause of ventricular tachycardia in patients with chronic ischemic heart disease: electrophysiologic and anatomic correlation. , 1988, Circulation.

[22]  David O. Martin,et al.  Mode of initiation and ablation of ventricular fibrillation storms in patients with ischemic cardiomyopathy. , 2004, Journal of the American College of Cardiology.

[23]  Gordon L. Kindlmann,et al.  Linear Invariant Tensor Interpolation Applied to Cardiac Diffusion Tensor MRI , 2012, MICCAI.

[24]  J. Francis,et al.  The role of cardiovascular magnetic resonance imaging in heart failure. , 2009, Journal of the American College of Cardiology.

[25]  M. Allessie,et al.  Influences of anisotropic tissue structure on reentrant circuits in the epicardial border zone of subacute canine infarcts. , 1988, Circulation research.

[26]  David O. Martin,et al.  Relationship Between Successful Ablation Sites and the Scar Border Zone Defined by Substrate Mapping for Ventricular Tachycardia Post‐Myocardial Infarction , 2005, Journal of cardiovascular electrophysiology.

[27]  Henry R. Halperin,et al.  Magnetic Resonance–Based Anatomical Analysis of Scar-Related Ventricular Tachycardia: Implications for Catheter Ablation , 2007, Circulation research.

[28]  Daniel B. Ennis,et al.  Weighted component-based tensor distance applied to graph-based segmentation of cardiac DT-MRI , 2013, 2013 IEEE 10th International Symposium on Biomedical Imaging.

[29]  J. Milles,et al.  Automated segmentation of myocardial scar in late enhancement MRI using combined intensity and spatial information , 2010, Magnetic resonance in medicine.

[30]  B. Bulkley,et al.  Global cardiac remodeling after acute myocardial infarction: a study in the rat model. , 1985, Journal of the American College of Cardiology.

[31]  Anna Vilanova,et al.  Diffusion tensor imaging of left ventricular remodeling in response to myocardial infarction in the mouse , 2009, NMR in biomedicine.

[32]  P. LaViolette,et al.  Validation of functional diffusion maps (fDMs) as a biomarker for human glioma cellularity , 2010, Journal of magnetic resonance imaging : JMRI.

[33]  Sheng-Kwei Song,et al.  Remodeling of cardiac fiber structure after infarction in rats quantified with diffusion tensor MRI. , 2003, American journal of physiology. Heart and circulatory physiology.

[34]  P. Anversa,et al.  Left ventricular failure induced by myocardial infarction. I. Myocyte hypertrophy. , 1985, The American journal of physiology.

[35]  Daniel B Ennis,et al.  Visualization of tensor fields using superquadric glyphs , 2005, Magnetic resonance in medicine.

[36]  G. Kindlmann,et al.  Orthogonal tensor invariants and the analysis of diffusion tensor magnetic resonance images , 2006, Magnetic resonance in medicine.

[37]  Yin Wu,et al.  MR diffusion tensor imaging study of postinfarct myocardium structural remodeling in a porcine model , 2007, Magnetic resonance in medicine.

[38]  E. McVeigh,et al.  Electromechanical analysis of infarct border zone in chronic myocardial infarction. , 2005, American journal of physiology. Heart and circulatory physiology.

[39]  Eric Aliotta,et al.  Assessment of Myocardial Microstructural Dynamics by In Vivo Diffusion Tensor Cardiac Magnetic Resonance , 2017, Journal of the American College of Cardiology.

[40]  Holden H. Wu,et al.  Convex optimized diffusion encoding (CODE) gradient waveforms for minimum echo time and bulk motion–compensated diffusion‐weighted MRI , 2017, Magnetic resonance in medicine.