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

https://doi.org/10.1016/j.jacc.2016.11.051Get rights and content
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Abstract

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.

Key Words

dilated cardiomyopathy
helical structure
hypertrophic cardiomyopathy
laminar structure
left ventricle
sheetlet structure

Abbreviations and Acronyms

CMR
cardiac magnetic resonance
DCM
dilated cardiomyopathy
DT
diffusion tensor
E1A
primary diffusion tensor eigenvector angle
E1AR
E1 angle range
E2A
secondary diffusion tensor eigenvector angle
EF
ejection fraction
HA
helix angle
HAR
helix angle range
HCM
hypertrophic cardiomyopathy
IQR
interquartile range
LV
left ventricle
SA
sheetlet angle
WT
wall thickness

Cited by (0)

This work was supported by the National Heart, Lung, and Blood Institute, National Institutes of Health, Division of Intramural Research, Department of Health and Human Services (HL004607-14CPB); the British Heart Foundation; and the National Institute of Health Research Cardiovascular Biomedical Research Unit at the Royal Brompton Hospital and Imperial College, London. Dr. Gatehouse has a departmental research agreement and collaborates on other work with Siemens. Dr. Ennis has received research support from Siemens Medical Solutions. Dr. Arai is a principal investigator on a U.S. government Cooperative Research and Development Agreement with Siemens Medical Solutions (HL-CR-05-004); and has a research agreement with Bayer. Dr. Pennell is a shareholder and Director of Cardiovascular Imaging Solutions; and has received research support from Siemens. Royal Brompton Hospital has research collaboration agreements with Siemens AG Medical Solutions. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Nielles-Vallespin, Khalique, and Ferreira contributed equally to this work and are joint first authors. Drs. Firmin, Arai, and Pennell contributed equally to this work and are joint senior authors.

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Published by Elsevier on behalf of the American College of Cardiology Foundation.