Assessment of Myocardial Microstructural Dynamics by In Vivo Diffusion Tensor Cardiac Magnetic Resonance

BACKGROUND Cardiomyocytes are organized in microstructures termed sheetlets that reorientate during left ventricular thickening. Diffusion tensor cardiac magnetic resonance (DT-CMR) may enable noninvasive interrogation of in vivo cardiac microstructural dynamics. Dilated cardiomyopathy (DCM) is a condition of abnormal myocardium with unknown sheetlet function. OBJECTIVES This study sought to validate in vivo DT-CMR measures of cardiac microstructure against histology, characterize microstructural dynamics during left ventricular wall thickening, and apply the technique in hypertrophic cardiomyopathy (HCM) and DCM. METHODS In vivo DT-CMR was acquired throughout the cardiac cycle in healthy swine, followed by in situ and ex vivo DT-CMR, then validated against histology. In vivo DT-CMR was performed in 19 control subjects, 19 DCM, and 13 HCM patients. RESULTS In swine, a DT-CMR index of sheetlet reorientation (E2A) changed substantially (E2A mobility ∼46°). E2A changes correlated with wall thickness changes (in vivo r2 = 0.75; in situ r2 = 0.89), were consistently observed under all experimental conditions, and accorded closely with histological analyses in both relaxed and contracted states. The potential contribution of cyclical strain effects to in vivo E2A was ∼17%. In healthy human control subjects, E2A increased from diastole (18°) to systole (65°; p < 0.001; E2A mobility = 45°). HCM patients showed significantly greater E2A in diastole than control subjects did (48°; p < 0.001) with impaired E2A mobility (23°; p < 0.001). In DCM, E2A was similar to control subjects in diastole, but systolic values were markedly lower (40°; p < 0.001) with impaired E2A mobility (20°; p < 0.001). CONCLUSIONS Myocardial microstructure dynamics can be characterized by in vivo DT-CMR. Sheetlet function was abnormal in DCM with altered systolic conformation and reduced mobility, contrasting with HCM, which showed reduced mobility with altered diastolic conformation. These novel insights significantly improve understanding of contractile dysfunction at a level of noninvasive interrogation not previously available in humans.

[1]  K K Kwong,et al.  Anisotropy of water diffusion in the myocardium of the rat. , 1994, Circulation research.

[2]  B Maisch,et al.  Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the Definition and Classification of cardiomyopathies. , 1996, Circulation.

[3]  A. McCulloch,et al.  Relating myocardial laminar architecture to shear strain and muscle fiber orientation. , 2001, American journal of physiology. Heart and circulatory physiology.

[4]  L. Younes,et al.  Ex vivo 3D diffusion tensor imaging and quantification of cardiac laminar structure , 2005, Magnetic resonance in medicine.

[5]  Peter Kohl,et al.  Histo-anatomical structure of the living isolated rat heart in two contraction states assessed by diffusion tensor MRI , 2012, Progress in biophysics and molecular biology.

[6]  Thorsten Feiweier,et al.  In vivo diffusion tensor MRI of the human heart: Reproducibility of breath‐hold and navigator‐based approaches , 2013, Magnetic resonance in medicine.

[7]  David Atkinson,et al.  Dual-Phase Cardiac Diffusion Tensor Imaging with Strain Correction , 2014, PLoS ONE.

[8]  W D Spotnitz,et al.  Cellular basis for volume related wall thickness changes in the rat left ventricle. , 1974, Journal of molecular and cellular cardiology.

[9]  Sheng-Kwei Song,et al.  Regional ventricular wall thickening reflects changes in cardiac fiber and sheet structure during contraction: quantification with diffusion tensor MRI. , 2005, American journal of physiology. Heart and circulatory physiology.

[10]  Y. Saeki,et al.  Excitation-contraction coupling in mammalian cardiac muscle during Ba2+-induced contracture. , 1981, The American journal of physiology.

[11]  D. Pennell,et al.  Reproducibility of in-vivo diffusion tensor cardiovascular magnetic resonance in hypertrophic cardiomyopathy , 2012, Journal of Cardiovascular Magnetic Resonance.

[12]  Timothy G Reese,et al.  Cardiac diffusion MRI without motion effects , 2002, Magnetic resonance in medicine.

[13]  Timothy G Reese,et al.  Imaging myocardial fiber disarray and intramural strain hypokinesis in hypertrophic cardiomyopathy with MRI , 2006, Journal of magnetic resonance imaging : JMRI.

[14]  Denis Noble,et al.  A theory of biological relativity: no privileged level of causation , 2012, Interface Focus.

[15]  J. Nyengaard,et al.  The Three‐Dimensional Arrangement of the Myocytes Aggregated Together Within the Mammalian Ventricular Myocardium , 2009, Anatomical record.

[16]  Aart J. Nederveen,et al.  Diffusion Tensor MRI of the Heart – In Vivo Imaging of Myocardial Fiber Architecture , 2014, Current Cardiovascular Imaging Reports.

[17]  John Forder,et al.  Histological validation of myocardial microstructure obtained from diffusion tensor magnetic resonance imaging. , 1998, American journal of physiology. Heart and circulatory physiology.

[18]  I. Efimov,et al.  Focal but reversible diastolic sheet dysfunction reflects regional calcium mishandling in dystrophic mdx mouse hearts. , 2012, American journal of physiology. Heart and circulatory physiology.

[19]  R H Hruban,et al.  Underlying causes and long-term survival in patients with initially unexplained cardiomyopathy. , 2000, The New England journal of medicine.

[20]  V. Wedeen,et al.  Measuring Diffusion in the Presence of Material Strain , 1996, Journal of magnetic resonance. Series B.

[21]  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.

[22]  J. Ross,et al.  Fiber Orientation in the Canine Left Ventricle during Diastole and Systole , 1969, Circulation research.

[23]  J. Zhang,et al.  Reconstruction of Cardiac Ventricular Geometry and Fiber Orientation Using Magnetic Resonance Imaging , 2000, Annals of Biomedical Engineering.

[24]  P. Basser,et al.  MR diffusion tensor spectroscopy and imaging. , 1994, Biophysical journal.

[25]  Leon Axel,et al.  Probing dynamic myocardial microstructure with cardiac magnetic resonance diffusion tensor imaging , 2014, Journal of Cardiovascular Magnetic Resonance.

[26]  D. L. Bassett,et al.  An engineering analysis of myocardial fiber orientation in pig's left ventricle in systole , 1966 .

[27]  Timothy G Reese,et al.  Combined diffusion and strain MRI reveals structure and function of human myocardial laminar sheets in vivo , 2003, Magnetic resonance in medicine.

[28]  S. Colan,et al.  Comparison of Echocardiographic and Cardiac Magnetic Resonance Imaging in Hypertrophic Cardiomyopathy Sarcomere Mutation Carriers Without Left Ventricular Hypertrophy , 2013, Circulation. Cardiovascular genetics.

[29]  Bruce H Smaill,et al.  Automated imaging of extended tissue volumes using confocal microscopy , 2005, Microscopy research and technique.

[30]  Tevfik F Ismail,et al.  In vivo cardiovascular magnetic resonance diffusion tensor imaging shows evidence of abnormal myocardial laminar orientations and mobility in hypertrophic cardiomyopathy , 2014, Journal of Cardiovascular Magnetic Resonance.

[31]  Andrew D McCulloch,et al.  Laminar fiber architecture and three-dimensional systolic mechanics in canine ventricular myocardium. , 1999, American journal of physiology. Heart and circulatory physiology.

[32]  J. Downey,et al.  Barium contracture: a model for systole. , 1980, The American journal of physiology.

[33]  R. Dinsmore,et al.  Imaging myocardial fiber architecture in vivo with magnetic resonance , 1995, Magnetic resonance in medicine.

[34]  J W Covell,et al.  Transverse shear along myocardial cleavage planes provides a mechanism for normal systolic wall thickening. , 1995, Circulation research.

[35]  L. Younes,et al.  Evidence of Structural Remodeling in the Dyssynchronous Failing Heart , 2005, Circulation research.

[36]  F. Rutten,et al.  2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). , 2014, European heart journal.

[37]  Henggui Zhang,et al.  Left ventricular ejection fraction is determined by both global myocardial strain and wall thickness , 2015, International journal of cardiology. Heart & vasculature.

[38]  P. Basser Inferring microstructural features and the physiological state of tissues from diffusion‐weighted images , 1995, NMR in biomedicine.

[39]  V. Wedeen,et al.  Cardiac diffusion tensor MRI in vivo without strain correction , 1999, Magnetic resonance in medicine.

[40]  C H Lorenz,et al.  Differentiation of Heart Failure Related to Dilated Cardiomyopathy and Coronary Artery Disease Using Gadolinium‐Enhanced Cardiovascular Magnetic Resonance , 2003, Circulation.

[41]  M. Sheppard,et al.  Prognostic significance of myocardial fibrosis in hypertrophic cardiomyopathy using cardiovascular magnetic resonance , 2010 .

[42]  Kevin D Costa,et al.  Contribution of laminar myofiber architecture to load-dependent changes in mechanics of LV myocardium. , 2002, American journal of physiology. Heart and circulatory physiology.

[43]  Hiroshi Ashikaga,et al.  Direct measurement of transmural laminar architecture in the anterolateral wall of the ovine left ventricle: new implications for wall thickening mechanics. , 2005, American journal of physiology. Heart and circulatory physiology.

[44]  R R Edelman,et al.  In vivo measurement of water diffusion in the human heart , 1994, Magnetic resonance in medicine.

[45]  Eloisa Arbustini,et al.  Classification of the cardiomyopathies: a position statement from the European Society Of Cardiology Working Group on Myocardial and Pericardial Diseases. , 2007, European heart journal.

[46]  P. Sengupta,et al.  Myocardial mechanics in cardiomyopathies. , 2014, Progress in cardiovascular diseases.

[47]  D. Pennell,et al.  Optimal diffusion weighting for in vivo cardiac diffusion tensor imaging , 2015, Magnetic resonance in medicine.

[48]  Peter Boesiger,et al.  Diffusion imaging of the in vivo heart using spin echoes–considerations on bulk motion sensitivity , 2007, Magnetic resonance in medicine.

[49]  Tevfik F Ismail,et al.  Association of fibrosis with mortality and sudden cardiac death in patients with nonischemic dilated cardiomyopathy. , 2013, JAMA.