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Title: Transmural Remodeling of Cardiac Microstructure in Aged Spontaneously Hypertensive Rats by Diffusion Tensor MRI

Abstract

The long-standing high blood pressure (also known as hypertension) overworks the heart. Microstructural remodeling is a key factor of hypertensive heart disease progression. Diffusion tensor magnetic resonance imaging (DT-MRI) is a powerful tool for the rapid noninvasive nondestructive delineation of the cardiomyocyte organization. The spontaneously hypertensive rat (SHR) is a well-established model of genetic hypertension. The goal of this study was to employ high-resolution DT-MRI and the SHR animal model to assess the transmural layer-specific remodeling of myocardial microstructure associated with hypertension. Ex vivo experiments were performed on excised formalin-fixed hearts of aged SHRs (n = 4) and age-matched controls (n = 4). The DT-MRI-derived fractional anisotropy (FA), longitudinal diffusivity (λ L ), transversal diffusivity (λ T ), and mean diffusivity (MD) served as the readout parameters investigated at three transmural zones (i.e., endocardium, mesocardium, and epicardium). The helix angles (HAs) of the aggregated cardiomyocytes and the orientation of laminar sheetlets were also studied. Compared with controls, the SHRs exhibited decreased epicardial FA, while FA changes in the other two transmural regions were insignificant. No substantial differences were observed in the diffusivity parameters and the transmural course of HAs between the two groups. A consistent distribution pattern of laminar sheetletmore » orientation was not identified for either group. Our findings are in line with the known cellular microstructure from early painstaking histological studies. Biophysical explanations of the study outcomes are provided. In conclusion, our experimental findings indicate that the epicardial microstructure is more vulnerable to high blood pressure leading to more pronounced changes in this region during remodeling. DT-MRI is well-suited for elucidating these alterations. The revealed transmural nonuniformity of myocardial reorganization may shed light on the mechanisms of the microstructure-function relationship in hypertension progression. Our results provide insights into the management of patients with systemic arterial hypertension, thus prevent the progression toward heart failure. The findings of this study should be acknowledged by electromechanical models of the heart that simulate the specific cardiac pathology.« less

Authors:
 [1];  [2]
  1. Nottingam Trent Univ. (United Kingdom); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Imperial College, London (United Kingdom)
  2. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Univ. of California, San Francisco, CA (United States)
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institutes of Health (NIH)
OSTI Identifier:
1619156
Grant/Contract Number:  
AC02-05CH11231; R01 EB007219
Resource Type:
Accepted Manuscript
Journal Name:
Frontiers in Physiology
Additional Journal Information:
Journal Volume: 11; Journal ID: ISSN 1664-042X
Publisher:
Frontiers
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; myocardium; microstructure; remodeling; left ventricle; diffusion tensor MRI; hypertension

Citation Formats

Giannakidis, Archontis, and Gullberg, Grant T. Transmural Remodeling of Cardiac Microstructure in Aged Spontaneously Hypertensive Rats by Diffusion Tensor MRI. United States: N. p., 2020. Web. https://doi.org/10.3389/fphys.2020.00265.
Giannakidis, Archontis, & Gullberg, Grant T. Transmural Remodeling of Cardiac Microstructure in Aged Spontaneously Hypertensive Rats by Diffusion Tensor MRI. United States. https://doi.org/10.3389/fphys.2020.00265
Giannakidis, Archontis, and Gullberg, Grant T. Tue . "Transmural Remodeling of Cardiac Microstructure in Aged Spontaneously Hypertensive Rats by Diffusion Tensor MRI". United States. https://doi.org/10.3389/fphys.2020.00265. https://www.osti.gov/servlets/purl/1619156.
@article{osti_1619156,
title = {Transmural Remodeling of Cardiac Microstructure in Aged Spontaneously Hypertensive Rats by Diffusion Tensor MRI},
author = {Giannakidis, Archontis and Gullberg, Grant T.},
abstractNote = {The long-standing high blood pressure (also known as hypertension) overworks the heart. Microstructural remodeling is a key factor of hypertensive heart disease progression. Diffusion tensor magnetic resonance imaging (DT-MRI) is a powerful tool for the rapid noninvasive nondestructive delineation of the cardiomyocyte organization. The spontaneously hypertensive rat (SHR) is a well-established model of genetic hypertension. The goal of this study was to employ high-resolution DT-MRI and the SHR animal model to assess the transmural layer-specific remodeling of myocardial microstructure associated with hypertension. Ex vivo experiments were performed on excised formalin-fixed hearts of aged SHRs (n = 4) and age-matched controls (n = 4). The DT-MRI-derived fractional anisotropy (FA), longitudinal diffusivity (λ L ), transversal diffusivity (λ T ), and mean diffusivity (MD) served as the readout parameters investigated at three transmural zones (i.e., endocardium, mesocardium, and epicardium). The helix angles (HAs) of the aggregated cardiomyocytes and the orientation of laminar sheetlets were also studied. Compared with controls, the SHRs exhibited decreased epicardial FA, while FA changes in the other two transmural regions were insignificant. No substantial differences were observed in the diffusivity parameters and the transmural course of HAs between the two groups. A consistent distribution pattern of laminar sheetlet orientation was not identified for either group. Our findings are in line with the known cellular microstructure from early painstaking histological studies. Biophysical explanations of the study outcomes are provided. In conclusion, our experimental findings indicate that the epicardial microstructure is more vulnerable to high blood pressure leading to more pronounced changes in this region during remodeling. DT-MRI is well-suited for elucidating these alterations. The revealed transmural nonuniformity of myocardial reorganization may shed light on the mechanisms of the microstructure-function relationship in hypertension progression. Our results provide insights into the management of patients with systemic arterial hypertension, thus prevent the progression toward heart failure. The findings of this study should be acknowledged by electromechanical models of the heart that simulate the specific cardiac pathology.},
doi = {10.3389/fphys.2020.00265},
journal = {Frontiers in Physiology},
number = ,
volume = 11,
place = {United States},
year = {2020},
month = {3}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Figures / Tables:

FIGURE 1 FIGURE 1: Determination of the region of interest (ROI). The left ventricular wall was segmented semi-automatically in the B0 dataset (left image). Extra care was taken to exclude papillary muscles. The three transmural sectors (endocardium in cyan, mesocardium in yellow, epicardium in brown) were defined evenly spanning the left ventricularmore » wall (right image).« less

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Works referenced in this record:

Mechanical adaptation to chronic pressure overload
journal, April 1988


Animal models of hypertension: An overview
journal, September 2005

  • Lerman, Lilach O.; Chade, Alejandro R.; Sica, Vincenzo
  • Journal of Laboratory and Clinical Medicine, Vol. 146, Issue 3
  • DOI: 10.1016/j.lab.2005.05.005

Progressive changes in T 1 , T 2 and left-ventricular histo-architecture in the fixed and embedded rat heart: STRUCTURAL CHANGES IN FIXED, EMBEDDED RAT MYOCARDIUM
journal, December 2010

  • Hales, Patrick W.; Burton, Rebecca A. B.; Bollensdorff, Christian
  • NMR in Biomedicine, Vol. 24, Issue 7
  • DOI: 10.1002/nbm.1629

Q-ball imaging
journal, January 2004

  • Tuch, David S.
  • Magnetic Resonance in Medicine, Vol. 52, Issue 6
  • DOI: 10.1002/mrm.20279

Electrophysiological Modeling of Cardiac Ventricular Function: From Cell to Organ
journal, August 2000


Progression of myocardial remodeling and mechanical dysfunction in the spontaneously hypertensive rat
journal, December 2012

  • LeGrice, Ian J.; Pope, Adèle J.; Sands, Gregory B.
  • American Journal of Physiology-Heart and Circulatory Physiology, Vol. 303, Issue 11
  • DOI: 10.1152/ajpheart.00748.2011

Imaging myocardial fiber disarray and intramural strain hypokinesis in hypertrophic cardiomyopathy with MRI
journal, January 2005

  • Tseng, Wen-Yih I.; Dou, Jiangang; Reese, Timothy G.
  • Journal of Magnetic Resonance Imaging, Vol. 23, Issue 1
  • DOI: 10.1002/jmri.20473

On the averaging of cardiac diffusion tensor MRI data: the effect of distance function selection
journal, October 2016


Resolving the natural myocardial remodelling brought upon by cardiac contraction; a porcine ex-vivo cardiovascular magnetic resonance study of the left and right ventricle
journal, July 2019

  • Omann, Camilla; Agger, Peter; Bøgh, Nikolaj
  • Journal of Cardiovascular Magnetic Resonance, Vol. 21, Issue 1
  • DOI: 10.1186/s12968-019-0547-2

Molecular adaptation to pressure overload in human and rat hearts
journal, December 1989


Comparison of diffusion tensor imaging by cardiovascular magnetic resonance and gadolinium enhanced 3D image intensity approaches to investigation of structural anisotropy in explanted rat hearts
journal, April 2015

  • Bernus, Olivier; Radjenovic, Aleksandra; Trew, Mark L.
  • Journal of Cardiovascular Magnetic Resonance, Vol. 17, Issue 1
  • DOI: 10.1186/s12968-015-0129-x

A Translational Approach to Hypertensive Heart Disease
journal, January 2010


Quantitative comparison of myocardial fiber structure between mice, rabbit, and sheep using diffusion tensor cardiovascular magnetic resonance
journal, November 2011

  • Healy, Lindsey J.; Jiang, Yi; Hsu, Edward W.
  • Journal of Cardiovascular Magnetic Resonance, Vol. 13, Issue 1
  • DOI: 10.1186/1532-429X-13-74

Wall stress induced arrhythmia is enhanced by low potassium and early left ventricular hypertrophy in the working rat heart
journal, April 1995


Apoptosis in hypertensive heart disease: a clinical approach
journal, January 2006


In vivo cardiovascular magnetic resonance diffusion tensor imaging shows evidence of abnormal myocardial laminar orientations and mobility in hypertrophic cardiomyopathy
journal, November 2014

  • Ferreira, Pedro F.; Kilner, Philip J.; McGill, Laura-Ann
  • Journal of Cardiovascular Magnetic Resonance, Vol. 16, Issue 1
  • DOI: 10.1186/s12968-014-0087-8

Image‐based models of cardiac structure in health and disease
journal, June 2010

  • Vadakkumpadan, Fijoy; Arevalo, Hermenegild; Prassl, Anton J.
  • Wiley Interdisciplinary Reviews: Systems Biology and Medicine, Vol. 2, Issue 4
  • DOI: 10.1002/wsbm.76

Pitfalls of invasive blood pressure monitoring using the caudal ventral artery in rats
journal, February 2017

  • Ohta, Hiroki; Ohki, Takao; Kanaoka, Yuji
  • Scientific Reports, Vol. 7, Issue 1
  • DOI: 10.1038/srep41907

Resolving Fine Cardiac Structures in Rats with High-Resolution Diffusion Tensor Imaging
journal, July 2016

  • Teh, Irvin; McClymont, Darryl; Burton, Rebecca A. B.
  • Scientific Reports, Vol. 6, Issue 1
  • DOI: 10.1038/srep30573

Morphometric analysis of cardiac hypertrophy during development, maturation, and senescence in spontaneously hypertensive rats.
journal, April 1987

  • Engelmann, G. L.; Vitullo, J. C.; Gerrity, R. G.
  • Circulation Research, Vol. 60, Issue 4
  • DOI: 10.1161/01.RES.60.4.487

Spread of excitation in 3-D models of the anisotropic cardiac tissue. II. Effects of fiber architecture and ventricular geometry
journal, January 1998


Magnetic resonance myocardial fiber-orientation mapping with direct histological correlation
journal, May 1998

  • Hsu, E. W.; Muzikant, A. L.; Matulevicius, S. A.
  • American Journal of Physiology-Heart and Circulatory Physiology, Vol. 274, Issue 5
  • DOI: 10.1152/ajpheart.1998.274.5.H1627

Validation of diffusion tensor MRI measurements of cardiac microstructure with structure tensor synchrotron radiation imaging
journal, March 2017

  • Teh, Irvin; McClymont, Darryl; Zdora, Marie-Christine
  • Journal of Cardiovascular Magnetic Resonance, Vol. 19, Issue 1
  • DOI: 10.1186/s12968-017-0342-x

Image-driven constitutive modeling of myocardial fibrosis
journal, May 2016

  • Wang, Vicky Y.; Niestrawska, Justyna A.; Wilson, Alexander J.
  • International Journal for Computational Methods in Engineering Science and Mechanics, Vol. 17, Issue 3
  • DOI: 10.1080/15502287.2015.1082675

Development of a Strain of Spontaneously Hypertensive Rats
journal, January 1963

  • Okamoto, Kozo; Aoki, Kyuzo
  • Japanese Circulation Journal, Vol. 27, Issue 3
  • DOI: 10.1253/jcj.27.282

Bipolar stimulation of a three-dimensional bidomain incorporating rotational anisotropy
journal, April 1998

  • Muzikant, A. L.; Henriquez, C. S.
  • IEEE Transactions on Biomedical Engineering, Vol. 45, Issue 4
  • DOI: 10.1109/10.664201

Mechano-electric interactions in heterogeneous myocardium: development of fundamental experimental and theoretical models
journal, May 2003

  • Markhasin, V. S.; Solovyova, O.; Katsnelson, L. B.
  • Progress in Biophysics and Molecular Biology, Vol. 82, Issue 1-3
  • DOI: 10.1016/S0079-6107(03)00017-8

A model of the mechanics of the left ventricle
journal, May 1979

  • Arts, Theo; Reneman, Robert S.; Veenstra, Peter C.
  • Annals of Biomedical Engineering, Vol. 7, Issue 3-4
  • DOI: 10.1007/BF02364118

Sex and gender differences in control of blood pressure
journal, June 2013

  • Maranon, Rodrigo; Reckelhoff, Jane F.
  • Clinical Science, Vol. 125, Issue 7
  • DOI: 10.1042/CS20130140

A Comparative Study of Acquisition Schemes for Diffusion Tensor Imaging Using MRI
journal, March 1999

  • Papadakis, Nikolaos G.; Xing, Da; Huang, Christopher L. -H.
  • Journal of Magnetic Resonance, Vol. 137, Issue 1
  • DOI: 10.1006/jmre.1998.1673

MR diffusion tensor spectroscopy and imaging
journal, January 1994


Increased Systolic Performance With Diastolic Dysfunction in Adult Spontaneously Hypertensive Rats
journal, February 2003


Patient-specific electromechanical models of the heart for the prediction of pacing acute effects in CRT: A preliminary clinical validation
journal, January 2012


Histological validation of myocardial microstructure obtained from diffusion tensor magnetic resonance imaging
journal, December 1998

  • Scollan, D. F.; Holmes, Alex; Winslow, Raimond
  • American Journal of Physiology-Heart and Circulatory Physiology, Vol. 275, Issue 6
  • DOI: 10.1152/ajpheart.1998.275.6.H2308

Visualization and quantification of whole rat heart laminar structure using high-spatial resolution contrast-enhanced MRI
journal, January 2012

  • Gilbert, Stephen H.; Benoist, David; Benson, Alan P.
  • American Journal of Physiology-Heart and Circulatory Physiology, Vol. 302, Issue 1
  • DOI: 10.1152/ajpheart.00824.2011

Histo-anatomical structure of the living isolated rat heart in two contraction states assessed by diffusion tensor MRI
journal, October 2012

  • Hales, Patrick W.; Schneider, Jürgen E.; Burton, Rebecca A. B.
  • Progress in Biophysics and Molecular Biology, Vol. 110, Issue 2-3
  • DOI: 10.1016/j.pbiomolbio.2012.07.014

Physiologic Versus Pathologic Hypertrophy and the Pressure-Overloaded Myocardium
journal, January 1987


Imaging myocardial fiber architecturein vivo with magnetic resonance
journal, December 1995

  • Reese, Timothy G.; Weisskoff, Robert M.; Smith, R. Neil
  • Magnetic Resonance in Medicine, Vol. 34, Issue 6
  • DOI: 10.1002/mrm.1910340603

Assessment of Myocardial Microstructural Dynamics by In Vivo Diffusion Tensor Cardiac Magnetic Resonance
journal, February 2017

  • Nielles-Vallespin, Sonia; Khalique, Zohya; Ferreira, Pedro F.
  • Journal of the American College of Cardiology, Vol. 69, Issue 6
  • DOI: 10.1016/j.jacc.2016.11.051

Ultrastructural Changes in Hypertrophied Myocardium of Spontaneously Hypertensive Rats
journal, January 1976

  • Kawamura, Keishiro; Kashii, Chujiro; Imamura, Kikuko
  • Japanese Circulation Journal, Vol. 40, Issue 10
  • DOI: 10.1253/jcj.40.1119