Skip to main content Accessibility help

Quantification of Cardiomyocyte Alignment from Three-Dimensional (3D) Confocal Microscopy of Engineered Tissue

  • William J. Kowalski (a1) (a2), Fangping Yuan (a1) (a2), Takeichiro Nakane (a1) (a3) (a4), Hidetoshi Masumoto (a1) (a3) (a4), Marc Dwenger (a1) (a5), Fei Ye (a1) (a2), Joseph P. Tinney (a1) (a2) and Bradley B. Keller (a1) (a2) (a5)...


Biological tissues have complex, three-dimensional (3D) organizations of cells and matrix factors that provide the architecture necessary to meet morphogenic and functional demands. Disordered cell alignment is associated with congenital heart disease, cardiomyopathy, and neurodegenerative diseases and repairing or replacing these tissues using engineered constructs may improve regenerative capacity. However, optimizing cell alignment within engineered tissues requires quantitative 3D data on cell orientations and both efficient and validated processing algorithms. We developed an automated method to measure local 3D orientations based on structure tensor analysis and incorporated an adaptive subregion size to account for multiple scales. Our method calculates the statistical concentration parameter, κ, to quantify alignment, as well as the traditional orientational order parameter. We validated our method using synthetic images and accurately measured principal axis and concentration. We then applied our method to confocal stacks of cleared, whole-mount engineered cardiac tissues generated from human-induced pluripotent stem cells or embryonic chick cardiac cells and quantified cardiomyocyte alignment. We found significant differences in alignment based on cellular composition and tissue geometry. These results from our synthetic images and confocal data demonstrate the efficiency and accuracy of our method to measure alignment in 3D tissues.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Quantification of Cardiomyocyte Alignment from Three-Dimensional (3D) Confocal Microscopy of Engineered Tissue
      Available formats

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Quantification of Cardiomyocyte Alignment from Three-Dimensional (3D) Confocal Microscopy of Engineered Tissue
      Available formats

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Quantification of Cardiomyocyte Alignment from Three-Dimensional (3D) Confocal Microscopy of Engineered Tissue
      Available formats


Corresponding author

* Corresponding author.


Hide All
Akdis, D., Brunckhorst, C., Duru, F. & Saguner, A.M. (2016). Arrhythmogenic cardiomyopathy: Electrical and structural phenotypes. Arrhythm Electrophysiol Rev 5(2), 90101.
Altendorf, H., Decenciere, E., Jeulin, D., De Sa Peixoto, P., Deniset-Besseau, A., Angelini, E., Mosser, G. & Schanne-Klein, M.C. (2012). Imaging and 3D morphological analysis of collagen fibrils. J Microsc 247(2), 161175.
Altendorf, H. & Jeulin, D. (2009). 3D directional mathematical morphology for analysis of fiber orientations. Image Anal Stereol 28, 143153.
Ashikaga, H., Van Der Spoel, T.I., Coppola, B.A. & Omens, J.H. (2009). Transmural myocardial mechanics during isovolumic contraction. JACC Cardiovasc Imaging 2(2), 202211.
Avila, F.J. & Bueno, J.M. (2015). Analysis and quantification of collagen organization with the structure tensor in second harmonic microscopy images of ocular tissues. Appl Opt 54(33), 98489854.
Banglmaier, R.F., Sander, E.A. & Vandevord, P.J. (2015). Induction and quantification of collagen fiber alignment in a three-dimensional hydroxyapatite-collagen composite scaffold. Acta Biomater 17, 2635.
Barocas, V.H., Girton, T.S. & Tranquillo, R.T. (1998). Engineered alignment in media equivalents: Magnetic prealignment and mandrel compaction. J Biomech Eng 120(5), 660666.
Baumgartner, S., Halbach, M., Krausgrill, B., Maass, M., Srinivasan, S.P., Sahito, R.G., Peinkofer, G., Nguemo, F., Muller-Ehmsen, J. & Hescheler, J. (2015). Electrophysiological and morphological maturation of murine fetal cardiomyocytes during electrical stimulation in vitro. J Cardiovasc Pharmacol Ther 20(1), 104112.
Bayan, C., Levitt, J.M., Miller, E., Kaplan, D. & Georgakoudi, I. (2009). Fully automated, quantitative, noninvasive assessment of collagen fiber content and organization in thick collagen gels. J Appl Phys 105(10), 102042.
Bernus, O., Radjenovic, A., Trew, M.L., Legrice, I.J., Sands, G.B., Magee, D.R., Smaill, B.H. & Gilbert, S.H. (2015). 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. J Cardiovasc Magn Reson 17, 31.
Bian, W., Jackman, C.P. & Bursac, N. (2014). Controlling the structural and functional anisotropy of engineered cardiac tissues. Biofabrication 6(2), 024109.
Biot, E., Crowell, E., Hofte, H., Maurin, Y., Vernhettes, S. & Andrey, P. (2008). A new filter for spot extraction in n-dimensional biological imaging. In 5th IEEE International Symposium on Biomedical Imaging: From Nano to Macro, pp. 975–978. Paris, France: IEEE.
Black, L.D. 3rd, Meyers, J.D., Weinbaum, J.S., Shvelidze, Y.A. & Tranquillo, R.T. (2009). Cell-induced alignment augments twitch force in fibrin gel-based engineered myocardium via gap junction modification. Tissue Eng Part A 15(10), 30993108.
Bolli, R., Chugh, A.R., D’amario, D., Loughran, J.H., Stoddard, M.F., Ikram, S., Beache, G.M., Wagner, S.G., Leri, A., Hosoda, T., Sanada, F., Elmore, J.B., Goichberg, P., Cappetta, D., Solankhi, N.K., Fahsah, I., Rokosh, D.G., Slaughter, M.S., Kajstura, J. & Anversa, P. (2011). Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): Initial results of a randomised phase 1 trial. Lancet 378(9806), 18471857.
Bray, M.A., Adams, W.J., Geisse, N.A., Feinberg, A.W., Sheehy, S.P. & Parker, K.K. (2010). Nuclear morphology and deformation in engineered cardiac myocytes and tissues. Biomaterials 31(19), 51435150.
Bredfeldt, J.S., Liu, Y., Conklin, M.W., Keely, P.J., Mackie, T.R. & Eliceiri, K.W. (2014a). Automated quantification of aligned collagen for human breast carcinoma prognosis. J Pathol Inform 5(1), 28.
Bredfeldt, J.S., Liu, Y., Pehlke, C.A., Conklin, M.W., Szulczewski, J.M., Inman, D.R., Keely, P.J., Nowak, R.D., Mackie, T.R. & Eliceiri, K.W. (2014b). Computational segmentation of collagen fibers from second-harmonic generation images of breast cancer. J Biomed Opt 19(1), 16007.
Burggren, W.W. & Reyna, K.S. (2011). Developmental trajectories, critical windows and phenotypic alteration during cardio-respiratory development. Respir Physiol Neurobiol 178(1), 1321.
Carrier, L., Bonne, G., Bahrend, E., Yu, B., Richard, P., Niel, F., Hainque, B., Cruaud, C., Gary, F., Labeit, S., Bouhour, J.B., Dubourg, O., Desnos, M., Hagege, A.A., Trent, R.J., Komajda, M., Fiszman, M. & Schwartz, K. (1997). Organization and sequence of human cardiac myosin binding protein C gene (MYBPC3) and identification of mutations predicted to produce truncated proteins in familial hypertrophic cardiomyopathy. Circ Res 80(3), 427434.
Chaudhuri, B.B., Kundu, P. & Sarkar, N. (1993). Detection and gradation of oriented texture. Pattern Recogn Lett 14(2), 147153.
Chaudhuri, S., Nguyen, H., Rangayyan, R.M., Walsh, S. & Frank, C.B. (1987). A Fourier domain directional filtering method for analysis of collagen alignment in ligaments. IEEE Trans Biomed Eng 34(7), 509518.
Chen, Y.H., Wei, D., Newstadt, G., Degraef, M., Simmons, J. & Hero, A. (2015). Parameter estimation in spherical symmetry groups. IEEE Signal Proc Let 22(8), 11521155.
Clause, K.C., Tinney, J.P., Liu, L.J., Keller, B.B. & Tobita, K. (2009). Engineered early embryonic cardiac tissue increases cardiomyocyte proliferation by cyclic mechanical stretch via p38-MAP kinase phosphorylation. Tissue Eng Part A 15(6), 13731380.
Clendenon, S.G., Young, P.A., Ferkowicz, M., Phillips, C. & Dunn, K.W. (2011). Deep tissue fluorescent imaging in scattering specimens using confocal microscopy. Microsc Microanal 17(4), 614617.
Costa, K.D., Lee, E.J. & Holmes, J.W. (2003). Creating alignment and anisotropy in engineered heart tissue: Role of boundary conditions in a model three-dimensional culture system. Tissue Eng 9(4), 567577.
Costa, K.D., Takayama, Y., Mcculloch, A.D. & Covell, J.W. (1999). Laminar fiber architecture and three-dimensional systolic mechanics in canine ventricular myocardium. Am J Physiol 276(2 Pt 2), H595H607.
Daniels, F., Ter Haar Romeny, B.M., Rubbens, M.P. & Van Assen, H.C. (2006). Quantification of collagen orientation in 3D engineered tissue. In 3rd Kuala Lumpur International Conference on Biomedical Engineering 2006, Ibrahim, F., Azuan Abu Osman, N., Usman, J. & Adib Kadri, N. (Eds.), pp. 282–286. Kuala Lumpur, Malaysia: Springer.
Dhein, S., Seidel, T., Salameh, A., Jozwiak, J., Hagen, A., Kostelka, M., Hindricks, G. & Mohr, F.W. (2014). Remodeling of cardiac passive electrical properties and susceptibility to ventricular and atrial arrhythmias. Front Physiol 5, 424.
Diaspro, A., Federici, F. & Robello, M. (2002). Influence of refractive-index mismatch in high-resolution three-dimensional confocal microscopy. Appl Opt 41(4), 685690.
Drew, N.K., Eagleson, M.A., Baldo, D.B. Jr., Parker, K.K. & Grosberg, A. (2015). Metrics for assessing cytoskeletal orientational correlations and consistency. PLoS Comput Biol 11(4), e1004190.
Elbischger, P.H., Bischof, H., Regitnig, P. & Holzapfel, G.A. (2004). Automatic analysis of collagen fiber orientation in the outermost layer of human arteries. Pattern Anal Appl 7(3), 269284.
Eriksson, T., Kroon, M. & Holzapfel, G.A. (2009). Influence of medial collagen organization and axial in situ stretch on saccular cerebral aneurysm growth. J Biomech Eng 131(10), 101010.
Feinberg, A.W., Alford, P.W., Jin, H., Ripplinger, C.M., Werdich, A.A., Sheehy, S.P., Grosberg, A. & Parker, K.K. (2012). Controlling the contractile strength of engineered cardiac muscle by hierarchal tissue architecture. Biomaterials 33(23), 57325741.
Finsterer, J. & Stollberger, C. (2016). Arrhythmogenic right ventricular dysplasia in neuromuscular disorders. Clin Med Insights Cardiol 10, 173180.
Fisher, N.I. (1986). Robust-tests for comparing the dispersions of several Fisher or Watson distributions on the sphere. Geophys J Int 85(3), 563572.
Fisher, N.I. (1995). Statistical Analysis of Circular Data. Cambridge: Cambridge University Press.
Fisher, N.I., Lewis, T. & Embleton, B.J.J. (1987). Statistical Analysis of Spherical Data. Cambridge: Cambridge University Press.
Fisher, S.A., Doree, C., Mathur, A. & Martin-Rendon, E. (2015). Meta-analysis of cell therapy trials for patients with heart failure. Circ Res 116(8), 13611377.
Frangi, A., Niessen, W.J., Vincken, K.L. & Viergever, M.A. (1998). Multiscale vessel enhancement filtering. In Medical Image Computing and Computer-Assisted Intervention — MICCAI’98, Wells, W.M., Colchester, A. & Delp, S. (Eds.), pp. 130137. Cambridge, MA: Springer.
Fujimoto, K.L., Clause, K.C., Liu, L.J., Tinney, J.P., Verma, S., Wagner, W.R., Keller, B.B. & Tobita, K. (2011). Engineered fetal cardiac graft preserves its cardiomyocyte proliferation within postinfarcted myocardium and sustains cardiac function. Tissue Eng Part A 17(5–6), 585596.
Galbraith, C.G., Skalak, R. & Chien, S. (1998). Shear stress induces spatial reorganization of the endothelial cell cytoskeleton. Cell Motil Cytoskeleton 40(4), 317330.
Garcia, D. (2010). Robust smoothing of gridded data in one and higher dimensions with missing values. Comput Stat Data Anal 54(4), 11671178.
Garcia, D. (2011). A fast all-in-one method for automated post-processing of PIV data. Exp Fluids 50(5), 12471259.
Gasser, T.C., Gallinetti, S., Xing, X., Forsell, C., Swedenborg, J. & Roy, J. (2012). Spatial orientation of collagen fibers in the abdominal aortic aneurysm’s wall and its relation to wall mechanics. Acta Biomater 8(8), 30913103.
Gasser, T.C., Ogden, R.W. & Holzapfel, G.A. (2006). Hyperelastic modelling of arterial layers with distributed collagen fibre orientations. J R Soc Interface 3(6), 1535.
Gilbert, S.H., Benoist, D., Benson, A.P., White, E., Tanner, S.F., Holden, A.V., Dobrzynski, H., Bernus, O. & Radjenovic, A. (2012). Visualization and quantification of whole rat heart laminar structure using high-spatial resolution contrast-enhanced MRI. Am J Physiol Heart Circ Physiol 302(1), H287H298.
Gilbert, S.H., Benson, A.P., Li, P. & Holden, A.V. (2007). Regional localisation of left ventricular sheet structure: Integration with current models of cardiac fibre, sheet and band structure. Eur J Cardiothorac Surg 32(2), 231249.
Godier-Furnemont, A.F., Tiburcy, M., Wagner, E., Dewenter, M., Lammle, S., El-Armouche, A., Lehnart, S.E., Vunjak-Novakovic, G. & Zimmermann, W.H. (2015). Physiologic force-frequency response in engineered heart muscle by electromechanical stimulation. Biomaterials 60, 8291.
Grosberg, A., Alford, P.W., Mccain, M.L. & Parker, K.K. (2011). Ensembles of engineered cardiac tissues for physiological and pharmacological study: Heart on a chip. Lab Chip 11(24), 41654173.
Gunther, M.I., Gunther, M., Schneiders, M., Rupp, R. & Blesch, A. (2015). AngleJ: A new tool for the automated measurement of neurite growth orientation in tissue sections. J Neurosci Methods 251, 143150.
Hahn, A., Lauriol, J., Thul, J., Behnke-Hall, K., Logeswaran, T., Schanzer, A., Bogurcu, N., Garvalov, B.K., Zenker, M., Gelb, B.D., Von Gerlach, S., Kandolf, R., Kontaridis, M.I. & Schranz, D. (2015). Rapidly progressive hypertrophic cardiomyopathy in an infant with Noonan syndrome with multiple lentigines: Palliative treatment with a rapamycin analog. Am J Med Genet A 167A(4), 744751.
Hill, M.R., Simon, M.A., Valdez-Jasso, D., Zhang, W., Champion, H.C. & Sacks, M.S. (2014). Structural and mechanical adaptations of right ventricle free wall myocardium to pressure overload. Ann Biomed Eng 42(12), 24512465.
Hirschy, A., Schatzmann, F., Ehler, E. & Perriard, J.C. (2006). Establishment of cardiac cytoarchitecture in the developing mouse heart. Dev Biol 289(2), 430441.
Hirt, M.N., Boeddinghaus, J., Mitchell, A., Schaaf, S., Bornchen, C., Muller, C., Schulz, H., Hubner, N., Stenzig, J., Stoehr, A., Neuber, C., Eder, A., Luther, P.K., Hansen, A. & Eschenhagen, T. (2014). Functional improvement and maturation of rat and human engineered heart tissue by chronic electrical stimulation. J Mol Cell Cardiol 74, 151161.
Hong, L., Wan, Y.F. & Jain, A. (1998). Fingerprint image enhancement: Algorithm and performance evaluation. IEEE Trans Pattern Anal 20(8), 777789.
Hooks, D.A., Trew, M.L., Caldwell, B.J., Sands, G.B., Legrice, I.J. & Smaill, B.H. (2007). Laminar arrangement of ventricular myocytes influences electrical behavior of the heart. Circ Res 101(10), e103e112.
Hsu, E.W., Muzikant, A.L., Matulevicius, S.A., Penland, R.C. & Henriquez, C.S. (1998). Magnetic resonance myocardial fiber-orientation mapping with direct histological correlation. Am J Physiol 274(5 Pt 2), H1627H1634.
Huang, Y.C., Khait, L. & Birla, R.K. (2007). Contractile three-dimensional bioengineered heart muscle for myocardial regeneration. J Biomed Mater Res A 80(3), 719731.
Jouk, P.S., Usson, Y., Michalowicz, G. & Grossi, L. (2000). Three-dimensional cartography of the pattern of the myofibres in the second trimester fetal human heart. Anat Embryol (Berl) 202(2), 103118.
Kadish, A., Shinnar, M., Moore, E.N., Levine, J.H., Balke, C.W. & Spear, J.F. (1988). Interaction of fiber orientation and direction of impulse propagation with anatomic barriers in anisotropic canine myocardium. Circulation 78(6), 14781494.
Karlon, W.J., Hsu, P.P., Li, S., Chien, S., Mcculloch, A.D. & Omens, J.H. (1999). Measurement of orientation and distribution of cellular alignment and cytoskeletal organization. Ann Biomed Eng 27(6), 712720.
Karpawich, P.P., Justice, C.D., Cavitt, D.L. & Chang, C.H. (1990). Developmental sequelae of fixed-rate ventricular pacing in the immature canine heart: An electrophysiologic, hemodynamic, and histopathologic evaluation. Am Heart J 119(5), 10771083.
Kaunas, R., Nguyen, P., Usami, S. & Chien, S. (2005). Cooperative effects of Rho and mechanical stretch on stress fiber organization. Proc Natl Acad Sci U S A 102(44), 1589515900.
Kerschnitzki, M., Kollmannsberger, P., Burghammer, M., Duda, G.N., Weinkamer, R., Wagermaier, W. & Fratzl, P. (2013). Architecture of the osteocyte network correlates with bone material quality. J Bone Miner Res 28(8), 18371845.
Kersh, M.E., Zysset, P.K., Pahr, D.H., Wolfram, U., Larsson, D. & Pandy, M.G. (2013). Measurement of structural anisotropy in femoral trabecular bone using clinical-resolution CT images. J Biomech 46(15), 26592666.
Khan, M., Xu, Y., Hua, S., Johnson, J., Belevych, A., Janssen, P.M., Gyorke, S., Guan, J. & Angelos, M.G. (2015). Evaluation of changes in morphology and function of human induced pluripotent stem cell derived cardiomyocytes (HiPSC-CMs) cultured on an aligned-nanofiber cardiac patch. PLoS One 10(5), e0126338.
Kofron, C.M., Liu, Y.T., Lopez-Fagundo, C.Y., Mitchel, J.A. & Hoffman-Kim, D. (2010). Neurite outgrowth at the biomimetic interface. Ann Biomed Eng 38(6), 22102225.
Kolesova, H., Capek, M., Radochova, B., Janacek, J. & Sedmera, D. (2016). Comparison of different tissue clearing methods and 3D imaging techniques for visualization of GFP-expressing mouse embryos and embryonic hearts. Histochem Cell Biol 146(2), 141152.
Krag, T.O., Pinos, T., Nielsen, T.L., Brull, A., Andreu, A.L. & Vissing, J. (2016). Differential muscle involvement in mice and humans affected by McArdle disease. J Neuropathol Exp Neurol 75(5), 441454.
Larsson, D., Luisier, B., Kersh, M.E., Dall’ara, E., Zysset, P.K., Pandy, M.G. & Pahr, D.H. (2014). Assessment of transverse isotropy in clinical-level CT images of trabecular bone using the gradient structure tensor. Ann Biomed Eng 42(5), 950959.
Lee, E.J., Holmes, J.W. & Costa, K.D. (2008). Remodeling of engineered tissue anisotropy in response to altered loading conditions. Ann Biomed Eng 36(8), 13221334.
Li, J., Mkrtschjan, M.A., Lin, Y.H. & Russell, B. (2016). Variation in stiffness regulates cardiac myocyte hypertrophy via signaling pathways. Can J Physiol Pharmacol 94(11), 11781186.
Linkert, M., Rueden, C.T., Allan, C., Burel, J.M., Moore, W., Patterson, A., Loranger, B., Moore, J., Neves, C., Macdonald, D., Tarkowska, A., Sticco, C., Hill, E., Rossner, M., Eliceiri, K.W. & Swedlow, J.R. (2010). Metadata matters: Access to image data in the real world. J Cell Biol 189(5), 777782.
Lux, M., Andree, B., Horvath, T., Nosko, A., Manikowski, D., Hilfiker-Kleiner, D., Haverich, A. & Hilfiker, A. (2016). In vitro maturation of large-scale cardiac patches based on a perfusable starter matrix by cyclic mechanical stimulation. Acta Biomater 30, 177187.
Mahoney, M.J., Chen, R.R., Tan, J. & Saltzman, W.M. (2005). The influence of microchannels on neurite growth and architecture. Biomaterials 26(7), 771778.
Mannhardt, I., Breckwoldt, K., Letuffe-Breniere, D., Schaaf, S., Schulz, H., Neuber, C., Benzin, A., Werner, T., Eder, A., Schulze, T., Klampe, B., Christ, T., Hirt, M.N., Huebner, N., Moretti, A., Eschenhagen, T. & Hansen, A. (2016). Human engineered heart tissue: Analysis of contractile force. Stem Cell Rep 7(1), 2942.
Mao, H., Gribble, M., Pertsov, A.M. & Shi, P. (2013). Embryonic heart morphogenesis from confocal microscopy imaging and automatic segmentation. Comput Math Methods Med 2013, 293069.
Masumoto, H., Ikuno, T., Takeda, M., Fukushima, H., Marui, A., Katayama, S., Shimizu, T., Ikeda, T., Okano, T., Sakata, R. & Yamashita, J.K. (2014). Human iPS cell-engineered cardiac tissue sheets with cardiomyocytes and vascular cells for cardiac regeneration. Sci Rep 4, 6716.
Masumoto, H., Nakane, T., Tinney, J.P., Yuan, F., Ye, F., Kowalski, W.J., Minakata, K., Sakata, R., Yamashita, J.K. & Keller, B.B. (2016). The myocardial regenerative potential of three-dimensional engineered cardiac tissues composed of multiple human iPS cell-derived cardiovascular cell lineages. Sci Rep 6, 29933.
Matsuda, T., Takahashi, K., Nariai, T., Ito, T., Takatani, T., Fujio, Y. & Azuma, J. (2005). N-cadherin-mediated cell adhesion determines the plasticity for cell alignment in response to mechanical stretch in cultured cardiomyocytes. Biochem Biophys Res Commun 326(1), 228232.
Maxwell, J.T., Wagner, M.B. & Davis, M.E. (2016). Electrically induced calcium handling in cardiac progenitor cells. Stem Cells Int 2016, 8917380.
Mekkaoui, C., Porayette, P., Jackowski, M.P., Kostis, W.J., Dai, G., Sanders, S. & Sosnovik, D.E. (2013). Diffusion MRI tractography of the developing human fetal heart. PLoS One 8(8), e72795.
Miller, C.E., Thompson, R.P., Bigelow, M.R., Gittinger, G., Trusk, T.C. & Sedmera, D. (2005). Confocal imaging of the embryonic heart: How deep? Microsc Microanal 11(3), 216223.
Mitchel, J.A., Martin, I.S. & Hoffman-Kim, D. (2013). Neurient: An algorithm for automatic tracing of confluent neuronal images to determine alignment. J Neurosci Methods 214(2), 210222.
Mozaffarian, D., Benjamin, E.J., Go, A.S., Arnett, D.K., Blaha, M.J., Cushman, M., Das, S.R., De Ferranti, S., Despres, J.P., Fullerton, H.J., Howard, V.J., Huffman, M.D., Isasi, C.R., Jimenez, M.C., Judd, S.E., Kissela, B.M., Lichtman, J.H., Lisabeth, L.D., Liu, S., Mackey, R.H., Magid, D.J., Mcguire, D.K., Mohler, E.R. 3rd, Moy, C.S., Muntner, P., Mussolino, M.E., Nasir, K., Neumar, R.W., Nichol, G., Palaniappan, L., Pandey, D.K., Reeves, M.J., Rodriguez, C.J., Rosamond, W., Sorlie, P.D., Stein, J., Towfighi, A., Turan, T.N., Virani, S.S., Woo, D., Yeh, R.W., Turner, M.B., American Heart Association Statistics Committee & Stroke Statistics Subcommittee. (2016). Heart disease and stroke statistics-2016 update: A report from the American Heart Association. Circulation 133(4), e38e360.
Muthappan, P. & Calkins, H. (2008). Arrhythmogenic right ventricular dysplasia. Prog Cardiovasc Dis 51(1), 3143.
Nectow, A.R., Kilmer, M.E. & Kaplan, D.L. (2014). Quantifying cellular alignment on anisotropic biomaterial platforms. J Biomed Mater Res A 102(2), 420428.
Nguyen, H., Badie, N., Mcspadden, L., Pedrotty, D. & Bursac, N. (2014). Quantifying electrical interactions between cardiomyocytes and other cells in micropatterned cell pairs. Methods Mol Biol 1181, 249262.
Nguyen, M.D., Tinney, J.P., Yuan, F.P., Roussel, T.J., El-Baz, A., Giridharan, G., Keller, B.B. & Sethu, P. (2013). Cardiac cell culture model as a left ventricle mimic for cardiac tissue generation. Anal Chem 85(18), 87738779.
Nunes, S.S., Miklas, J.W., Liu, J., Aschar-Sobbi, R., Xiao, Y., Zhang, B., Jiang, J., Masse, S., Gagliardi, M., Hsieh, A., Thavandiran, N., Laflamme, M.A., Nanthakumar, K., Gross, G.J., Backx, P.H., Keller, G. & Radisic, M. (2013). Biowire: A platform for maturation of human pluripotent stem cell-derived cardiomyocytes. Nat Methods 10(8), 781787.
Omens, J.H., May, K.D. & Mcculloch, A.D. (1991). Transmural distribution of three-dimensional strain in the isolated arrested canine left ventricle. Am J Physiol 261(3 Pt 2), H918H928.
Panfilov, A.V. & Keener, J.P. (1993). Generation of reentry in anisotropic myocardium. J Cardiovasc Electrophysiol 4(4), 412421.
Petroll, W.M., Cavanagh, H.D., Barry, P., Andrews, P. & Jester, J.V. (1993). Quantitative analysis of stress fiber orientation during corneal wound contraction. J Cell Sci 104(Pt 2), 353363.
Portera-Cailliau, C., Weimer, R.M., De Paola, V., Caroni, P. & Svoboda, K. (2005). Diverse modes of axon elaboration in the developing neocortex. PLoS Biol 3(8), e272.
Punske, B.B., Taccardi, B., Steadman, B., Ershler, P.R., England, A., Valencik, M.L., Mcdonald, J.A. & Litwin, S.E. (2005). Effect of fiber orientation on propagation: Electrical mapping of genetically altered mouse hearts. J Electrocardiol 38(4 Suppl), 4044.
Puspoki, Z., Storath, M., Sage, D. & Unser, M. (2016). Transforms and operators for directional bioimage analysis: A survey. Adv Anat Embryol Cell Biol 219, 6993.
Radisic, M., Park, H., Shing, H., Consi, T., Schoen, F.J., Langer, R., Freed, L.E. & Vunjak-Novakovic, G. (2004). Functional assembly of engineered myocardium by electrical stimulation of cardiac myocytes cultured on scaffolds. Proc Natl Acad Sci U S A 101(52), 1812918134.
Reckova, M., Rosengarten, C., Dealmeida, A., Stanley, C.P., Wessels, A., Gourdie, R.G., Thompson, R.P. & Sedmera, D. (2003). Hemodynamics is a key epigenetic factor in development of the cardiac conduction system. Circ Res 93(1), 7785.
Reuze, P., Coatrieux, J.L., Luo, L.M. & Dillenseger, J.L. (1993). A 3-D moment based approach for blood vessel detection and quantification in MRA. Technol Health Care 1(2), 181188.
Ribeiro, A.J., Ang, Y.S., Fu, J.D., Rivas, R.N., Mohamed, T.M., Higgs, G.C., Srivastava, D. & Pruitt, B.L. (2015). Contractility of single cardiomyocytes differentiated from pluripotent stem cells depends on physiological shape and substrate stiffness. Proc Natl Acad Sci U S A 112(41), 1270512710.
Ripplinger, C.M., Li, W., Hadley, J., Chen, J., Rothenberg, F., Lombardi, R., Wickline, S.A., Marian, A.J. & Efimov, I.R. (2007). Enhanced transmural fiber rotation and connexin 43 heterogeneity are associated with an increased upper limit of vulnerability in a transgenic rabbit model of human hypertrophic cardiomyopathy. Circ Res 101(10), 10491057.
Robb, K., Wirjadi, O. & Schladitz, K. (2007). Fiber orientation estimation from 3D image data: Practical algorithms, visualization, and interpretation. In 7th International Conference on Hybrid Intelligent Systems (HIS 2007), pp. 320–325. Kaiserlautern, Germany: IEEE.
Roberts, W.C. & Ferrans, V.J. (1975). Pathologic anatomy of the cardiomyopathies. Idiopathic dilated and hypertrophic types, infiltrative types, and endomyocardial disease with and without eosinophilia. Hum Pathol 6(3), 287342.
Rutherford, S.L., Trew, M.L., Sands, G.B., Legrice, I.J. & Smaill, B.H. (2012). High-resolution 3-dimensional reconstruction of the infarct border zone: Impact of structural remodeling on electrical activation. Circ Res 111(3), 301311.
Sanganalmath, S.K. & Bolli, R. (2013). Cell therapy for heart failure: A comprehensive overview of experimental and clinical studies, current challenges, and future directions. Circ Res 113(6), 810834.
Sankova, B., Machalek, J. & Sedmera, D. (2010). Effects of mechanical loading on early conduction system differentiation in the chick. Am J Physiol Heart Circ Physiol 298(5), H1571H1576.
Sarkar, N.C., Tilkar, M., Jain, S., Mondal, S., Sarkar, P. & Modi, N. (2016). Evaluation of long term effect of RV apical pacing on global LV function by echocardiography. J Clin Diagn Res 10(3), OC03OC06.
Saxena, S. & Caroni, P. (2007). Mechanisms of axon degeneration: From development to disease. Prog Neurobiol 83(3), 174191.
Schena, G. & Favretto, S. (2007). Pore space network characterization with sub-voxel definition. Transport Porous Med 70(2), 181190.
Schmitt, B., Fedarava, K., Falkenberg, J., Rothaus, K., Bodhey, N.K., Reischauer, C., Kozerke, S., Schnackenburg, B., Westermann, D., Lunkenheimer, P.P., Anderson, R.H., Berger, F. & Kuehne, T. (2009). Three-dimensional alignment of the aggregated myocytes in the normal and hypertrophic murine heart. J Appl Physiol 107(3), 921927.
Scientific Computing and Imaging Institute (2015). “Seg3D” Volumetric Image Segmentation and Visualization. Salt Lake City, UT: Scientific Computing and Imaging Institute (SCI).
Sedmera, D., Grobety, M., Reymond, C., Baehler, P., Kucera, P. & Kappenberger, L. (1999). Pacing-induced ventricular remodeling in the chick embryonic heart. Pediatr Res 45(6), 845852.
Sedmera, D., Pexieder, T., Vuillemin, M., Thompson, R.P. & Anderson, R.H. (2000). Developmental patterning of the myocardium. Anat Rec 258(4), 319337.
Singh, P., Negi, P., Laezza, F., Papadakis, M. & Labate, D. (2016). Multiscale analysis of neurite orientation and spatial organization in neuronal images. Neuroinformatics 14(4), 465477.
Smith, R.M., Matiukas, A., Zemlin, C.W. & Pertsov, A.M. (2008). Nondestructive optical determination of fiber organization in intact myocardial wall. Microsc Res Tech 71(7), 510516.
Sosnovik, D.E., Wang, R., Dai, G., Wang, T., Aikawa, E., Novikov, M., Rosenzweig, A., Gilbert, R.J. & Wedeen, V.J. (2009). Diffusion spectrum MRI tractography reveals the presence of a complex network of residual myofibers in infarcted myocardium. Circ Cardiovasc Imaging 2(3), 206212.
Stoppel, W.L., Kaplan, D.L. & Black, L.D. 3rd (2016). Electrical and mechanical stimulation of cardiac cells and tissue constructs. Adv Drug Deliv Rev 96, 135155.
Streeter, D.D. Jr., Spotnitz, H.M., Patel, D.P., Ross, J. Jr. & Sonnenblick, E.H. (1969). Fiber orientation in the canine left ventricle during diastole and systole. Circ Res 24(3), 339347.
Sun, M., Bloom, A.B. & Zaman, M.H. (2015). Rapid quantification of 3D collagen fiber alignment and fiber intersection correlations with high sensitivity. PLoS One 10(7), e0131814.
Tabor, Z. & Rokita, E. (2007). Quantifying anisotropy of trabecular bone from gray-level images. Bone 40(4), 966972.
Tearney, G.J., Brezinski, M.E., Southern, J.F., Bouma, B.E., Hee, M.R. & Fujimoto, J.G. (1995). Determination of the refractive index of highly scattering human tissue by optical coherence tomography. Opt Lett 20(21), 2258.
Tobita, K., Garrison, J.B., Liu, L.J., Tinney, J.P. & Keller, B.B. (2005). Three-dimensional myofiber architecture of the embryonic left ventricle during normal development and altered mechanical loads. Anat Rec A Discov Mol Cell Evol Biol 283(1), 193201.
Tobita, K., Liu, L.J., Janczewski, A.M., Tinney, J.P., Nonemaker, J.M., Augustine, S., Stolz, D.B., Shroff, S.G. & Keller, B.B. (2006). Engineered early embryonic cardiac tissue retains proliferative and contractile properties of developing embryonic myocardium. Am J Physiol Heart Circ Physiol 291(4), H1829H1837.
Tower, T.T. & Tranquillo, R.T. (2001). Alignment maps of tissues: I. Microscopic elliptical polarimetry. Biophys J 81(5), 29542963.
Tsang, K.M.C., Annabi, N., Ercole, F., Zhou, K., Karst, D.J., Li, F.Y., Haynes, J.M., Evans, R.A., Thissen, H., Khademhosseini, A. & Forsythe, J.S. (2015). Facile one-step micropatterning using photodegradable gelatin hydrogels for improved cardiomyocyte organization and alignment. Adv Funct Mater 25(6), 977986.
Tulloch, N.L., Muskheli, V., Razumova, M.V., Korte, F.S., Regnier, M., Hauch, K.D., Pabon, L., Reinecke, H. & Murry, C.E. (2011). Growth of engineered human myocardium with mechanical loading and vascular coculture. Circ Res 109(1), 4759.
Vader, D., Kabla, A., Weitz, D. & Mahadevan, L. (2009). Strain-induced alignment in collagen gels. PLoS One 4(6), e5902.
Valderrabano, M., Lee, M.H., Ohara, T., Lai, A.C., Fishbein, M.C., Lin, S.F., Karagueuzian, H.S. & Chen, P.S. (2001). Dynamics of intramural and transmural reentry during ventricular fibrillation in isolated swine ventricles. Circ Res 88(8), 839848.
Waldman, L.K., Nosan, D., Villarreal, F. & Covell, J.W. (1988). Relation between transmural deformation and local myofiber direction in canine left ventricle. Circ Res 63(3), 550562.
Wang, Y., Zhang, K., Wasala, N.B., Duan, D. & Yao, G. (2015). Optical polarization tractography revealed significant fiber disarray in skeletal muscles of a mouse model for Duchenne muscular dystrophy. Biomed Opt Express 6(2), 347352.
Weickert, J. (1998). Anisotropic Diffusion in Image Processing. Stuttgart: B. G. Teubner.
Wickline, S.A., Verdonk, E.D., Wong, A.K., Shepard, R.K. & Miller, J.G. (1992). Structural remodeling of human myocardial tissue after infarction. Quantification with ultrasonic backscatter. Circulation 85(1), 259268.
Wilson, J.S., Baek, S. & Humphrey, J.D. (2012). Importance of initial aortic properties on the evolving regional anisotropy, stiffness and wall thickness of human abdominal aortic aneurysms. J R Soc Interface 9(74), 20472058.
Wirjadi, O., Schladitz, K., Rack, A. & Breuel, T. (2009). Applications of anisotropic image filters for computing 2D and 3D-fiber orientations. In 10th European Congress of Stereology and Image Analysis, Capasso, V. (Ed.), pp. 107112. Milan, Italy: Esculapio.
Wu, J., Rajwa, B., Filmer, D.L., Hoffmann, C.M., Yuan, B., Chiang, C., Sturgis, J. & Robinson, J.P. (2003). Automated quantification and reconstruction of collagen matrix from 3D confocal datasets. J Microsc 210(Pt 2), 158165.
Xu, F., Beyazoglu, T., Hefner, E., Gurkan, U.A. & Demirci, U. (2011). Automated and adaptable quantification of cellular alignment from microscopic images for tissue engineering applications. Tissue Eng Part C Methods 17(6), 641649.
Ye, F., Yuan, F., Li, X., Cooper, N., Tinney, J.P. & Keller, B.B. (2013). Gene expression profiles in engineered cardiac tissues respond to mechanical loading and inhibition of tyrosine kinases. Physiol Rep 1(5), e00078.
Zhang, J., Klos, M., Wilson, G.F., Herman, A.M., Lian, X., Raval, K.K., Barron, M.R., Hou, L., Soerens, A.G., Yu, J., Palecek, S.P., Lyons, G.E., Thomson, J.A., Herron, T.J., Jalife, J. & Kamp, T.J. (2012). Extracellular matrix promotes highly efficient cardiac differentiation of human pluripotent stem cells: The matrix sandwich method. Circ Res 111(9), 11251136.
Zhao, J., Butters, T.D., Zhang, H., Pullan, A.J., Legrice, I.J., Sands, G.B. & Smaill, B.H. (2012a). An image-based model of atrial muscular architecture: Effects of structural anisotropy on electrical activation. Circ Arrhythm Electrophysiol 5(2), 361370.
Zhao, J., Krueger, M.W., Seemann, G., Meng, S., Zhang, H., Dossel, O., Legrice, I.J. & Smaill, B.H. (2012b). Myofiber orientation and electrical activation in human and sheep atrial models. Conf Proc IEEE Eng Med Biol Soc 2012, 63656368.
Zimmermann, W.H., Fink, C., Kralisch, D., Remmers, U., Weil, J. & Eschenhagen, T. (2000). Three-dimensional engineered heart tissue from neonatal rat cardiac myocytes. Biotechnol Bioeng 68(1), 106114.
Zimmermann, W.H., Schneiderbanger, K., Schubert, P., Didie, M., Munzel, F., Heubach, J.F., Kostin, S., Neuhuber, W.L. & Eschenhagen, T. (2002). Tissue engineering of a differentiated cardiac muscle construct. Circ Res 90(2), 223230.



Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed