title: Resolving myoarchitectural disarray in the mouse ventricular wall with diffusion spectrum magnetic resonance imaging.
abstract: The myoarchitecture of the ventricular wall provides a structural template dictating tissue-scale patterns of mechanical function. We studied whether myofiber tract imaging performed with MR diffusion spectrum imaging (DSI) tractography has the capacity to resolve abnormalities of ventricular myoarchitecture in a model of congenital hypertrophic cardiomyopathy (HCM) associated with the ablation of myosin binding protein-C (MyBP-C). Homozygous MyBP-C knockout mice were generated by deletion of exons 3-10 from the endogenous MyBP-C gene. Fiber alignment in the left ventricular wall of wild type mice was depicted through DSI tractography (and confirmed by multi-slice two-photon microscopy) as a set of helical structures whose angles display a continuous transition from negative in the subepicardium to positive in the subendocardium. In contrast, the hearts obtained from the MyBP-C knockouts displayed substantial myoarchitectural disarray, characterized by a loss of voxel-to-voxel orientational coherence for fibers principally located in the mid-myocardium-subendocardium and impairment of the transmural progression of helix angles. These results substantiate the use of DSI tractography in determining myoarchitectural disarray in models of cardiomyopathy and suggest a biological association between myofilament expression, cardiac fiber alignment, and torsional rotation in the setting of congenital HCM.
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, USA.
authors.forename: Teresa T
authors.initials: TT
authors.lastname: Wang
authors.forename: Hyuk Sang
authors.initials: HS
authors.lastname: Kwon
authors.forename: Guangping
authors.initials: G
authors.lastname: Dai
authors.forename: Ruopeng
authors.initials: R
authors.lastname: Wang
authors.forename: Srboljub M
authors.initials: SM
authors.lastname: Mijailovich
authors.forename: Richard L
authors.initials: RL
authors.lastname: Moss
authors.forename: Peter T C
authors.initials: PT
authors.lastname: So
authors.forename: Van J
authors.initials: VJ
authors.lastname: Wedeen
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Gilbert
mesh_terms: D008841:Actin Cytoskeleton / Q000648:ultrastructure; D000818:Animals; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics / Q000473:pathology*; D002352:Carrier Proteins / Q000235:genetics; D038524:Diffusion Magnetic Resonance Imaging; D056324:Diffusion Tensor Imaging / Q000379:methods*; D006352:Heart Ventricles / Q000648:ultrastructure*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000648:ultrastructure*; D000099163:Myosin Binding Protein C
chemical_list: D002352:Carrier Proteins; D000099163:Myosin Binding Protein C
references.citation: Circ Cardiovasc Imaging. 2009 May;2(3):206-12
references.pmid: 19808594
references.citation: Circ Res. 2004 May 28;94(10):1279-89
references.pmid: 15166115
references.citation: Neuroimage. 2003 Jul;19(3):482-95
references.pmid: 12880782
references.citation: Circ Res. 2004 Oct 29;95(9):930-6
references.pmid: 15472117
references.citation: NMR Biomed. 2009 Feb;22(2):182-90
references.pmid: 18780284
references.citation: Annu Rev Biomed Eng. 2003;5:147-77
references.pmid: 14527312
references.citation: J Magn Reson Imaging. 2006 Jan;23(1):1-8
references.pmid: 16331592
references.citation: J Mol Biol. 2007 Mar 16;367(1):36-41
references.pmid: 17254601
references.citation: J Mol Biol. 2008 Dec 5;384(1):60-72
references.pmid: 18817784
references.citation: Circ Res. 2002 Mar 22;90(5):594-601
references.pmid: 11909824
references.citation: Appl Opt. 1999 Oct 1;38(28):6004-9
references.pmid: 18324120
references.citation: J Biomed Opt. 2008 Nov-Dec;13(6):064005
references.pmid: 19123652
references.citation: Circ Res. 1981 Oct;49(4):829-42
references.pmid: 7023741
references.citation: J Physiol. 2000 Oct 1;528 Pt 1:151-6
references.pmid: 11018113
references.citation: Circ Res. 1999 May 28;84(10):1117-26
references.pmid: 10347086
references.citation: Magn Reson Imaging. 1996;14(7-8):701-9
references.pmid: 8970070
references.citation: Circ Res. 2006 May 12;98(9):1212-8
references.pmid: 16574907
references.citation: Circ Res. 1969 Mar;24(3):339-47
references.pmid: 5766515
references.citation: Circ Res. 2003 Oct 17;93(8):752-8
references.pmid: 14500336
references.citation: Circ Res. 2007 Oct 26;101(9):928-38
references.pmid: 17823372
references.citation: Circ Res. 1973 Dec;33(6):639-55
references.pmid: 4762006
references.citation: Radiology. 2000 Jul;216(1):128-39
references.pmid: 10887238
references.citation: Biophys J. 2008 Jul;95(2):720-8
references.pmid: 18375505
references.citation: Circ Res. 1995 Jul;77(1):182-93
references.pmid: 7788876
references.citation: Circ Res. 2004 May 14;94(9):1249-55
references.pmid: 15059932
references.citation: Anat Rec A Discov Mol Cell Evol Biol. 2006 Nov;288(11):1173-82
references.pmid: 17031810
references.citation: J Biomed Opt. 2007 Jan-Feb;12(1):014015
references.pmid: 17343490
references.citation: Cell Struct Funct. 1997 Feb;22(1):123-9
references.pmid: 9113398
references.citation: Anat Rec A Discov Mol Cell Evol Biol. 2004 Jan;276(1):43-57
references.pmid: 14699633
references.citation: Dev Biol. 2004 Oct 15;274(2):225-32
references.pmid: 15385154
references.citation: Eur J Cardiothorac Surg. 2005 Feb;27(2):191-201
references.pmid: 15691670
references.citation: Biophys J. 2006 Aug 1;91(3):1014-22
references.pmid: 16679361
references.citation: Am J Physiol. 1981 Jun;240(6):H920-6
references.pmid: 7246754
references.citation: Semin Cell Dev Biol. 2007 Feb;18(1):84-9
references.pmid: 17267246
references.citation: Magn Reson Med. 2003 Jul;50(1):107-13
references.pmid: 12815685
references.citation: Br Heart J. 1981 Mar;45(3):248-63
references.pmid: 7008815
references.citation: Biophys J. 2006 Jun 1;90(11):4119-27
references.pmid: 16513777