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.


OBJECTIVE
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.
National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland; Cardiovascular Magnetic Resonance Unit, Royal Brompton and Harefield National Health Service Foundation Trust, London, United Kingdom; National Heart and Lung Institute, Imperial College London, London, United Kingdom. Electronic address: sonia.nielles-vallespin@nih.gov.
Sonia
S
Nielles-Vallespin
Cardiovascular Magnetic Resonance Unit, Royal Brompton and Harefield National Health Service Foundation Trust, London, United Kingdom; National Heart and Lung Institute, Imperial College London, London, United Kingdom; National Institute for Health Research Cardiovascular Biomedical Research Unit, Royal Brompton and Harefield National Health Service Foundation Trust, and Imperial College London, London, United Kingdom.
Zohya
Z
Khalique
Cardiovascular Magnetic Resonance Unit, Royal Brompton and Harefield National Health Service Foundation Trust, London, United Kingdom; National Heart and Lung Institute, Imperial College London, London, United Kingdom; National Institute for Health Research Cardiovascular Biomedical Research Unit, Royal Brompton and Harefield National Health Service Foundation Trust, and Imperial College London, London, United Kingdom.
Pedro F
PF
Ferreira
Cardiovascular Magnetic Resonance Unit, Royal Brompton and Harefield National Health Service Foundation Trust, London, United Kingdom; National Heart and Lung Institute, Imperial College London, London, United Kingdom; National Institute for Health Research Cardiovascular Biomedical Research Unit, Royal Brompton and Harefield National Health Service Foundation Trust, and Imperial College London, London, United Kingdom.
Ranil
R
de Silva
Cardiovascular Magnetic Resonance Unit, Royal Brompton and Harefield National Health Service Foundation Trust, London, United Kingdom; National Heart and Lung Institute, Imperial College London, London, United Kingdom; National Institute for Health Research Cardiovascular Biomedical Research Unit, Royal Brompton and Harefield National Health Service Foundation Trust, and Imperial College London, London, United Kingdom.
Andrew D
AD
Scott
Cardiovascular Magnetic Resonance Unit, Royal Brompton and Harefield National Health Service Foundation Trust, London, United Kingdom; National Heart and Lung Institute, Imperial College London, London, United Kingdom; National Institute for Health Research Cardiovascular Biomedical Research Unit, Royal Brompton and Harefield National Health Service Foundation Trust, and Imperial College London, London, United Kingdom.
Philip
P
Kilner
Cardiovascular Magnetic Resonance Unit, Royal Brompton and Harefield National Health Service Foundation Trust, London, United Kingdom; National Heart and Lung Institute, Imperial College London, London, United Kingdom.
Laura-Ann
LA
McGill
Cardiovascular Magnetic Resonance Unit, Royal Brompton and Harefield National Health Service Foundation Trust, London, United Kingdom; National Heart and Lung Institute, Imperial College London, London, United Kingdom.
Archontis
A
Giannakidis
Cardiovascular Magnetic Resonance Unit, Royal Brompton and Harefield National Health Service Foundation Trust, London, United Kingdom; National Heart and Lung Institute, Imperial College London, London, United Kingdom.
Peter D
PD
Gatehouse
Department of Radiological Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
Daniel
D
Ennis
Department of Radiological Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
Eric
E
Aliotta
Cardiovascular Magnetic Resonance Unit, Royal Brompton and Harefield National Health Service Foundation Trust, London, United Kingdom.
Majid
M
Al-Khalil
National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland.
Peter
P
Kellman
National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland.
Dumitru
D
Mazilu
National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland.
Robert S
RS
Balaban
Cardiovascular Magnetic Resonance Unit, Royal Brompton and Harefield National Health Service Foundation Trust, London, United Kingdom; National Heart and Lung Institute, Imperial College London, London, United Kingdom; National Institute for Health Research Cardiovascular Biomedical Research Unit, Royal Brompton and Harefield National Health Service Foundation Trust, and Imperial College London, London, United Kingdom.
David N
DN
Firmin
National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland.
Andrew E
AE
Arai
Cardiovascular Magnetic Resonance Unit, Royal Brompton and Harefield National Health Service Foundation Trust, London, United Kingdom; National Heart and Lung Institute, Imperial College London, London, United Kingdom; National Institute for Health Research Cardiovascular Biomedical Research Unit, Royal Brompton and Harefield National Health Service Foundation Trust, and Imperial College London, London, United Kingdom.
Dudley J
DJ
Pennell
D000328:Adult; D000368:Aged; D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000000981:diagnostic imaging* / Q000503:physiopathology; D002312:Cardiomyopathy, Hypertrophic / Q000000981:diagnostic imaging* / Q000503:physiopathology; D016022:Case-Control Studies; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D008875:Middle Aged; D055414:Myocardial Perfusion Imaging; D013552:Swine; D020257:Ventricular Remodeling / Q000502:physiology*
dilated cardiomyopathy; helical structure; hypertrophic cardiomyopathy; laminar structure; left ventricle; sheetlet structure