Skip to main content

Resolving the Three-Dimensional Histology of the Heart

  • Conference paper
Computational Methods in Systems Biology (CMSB 2012)

Abstract

Cardiac histo-anatomical structure is a key determinant in all aspects of cardiac function. While some characteristics of micro- and macrostructure can be quantified using non-invasive imaging methods, histology is still the modality that provides the best combination of resolution and identification of cellular/sub-cellular substrate identities. The main limitation of histology is that it does not provide inherently consistent three-dimensional (3D) volume representations. This paper presents methods developed within our group to reconstruct 3D histological datasets. It includes the use of high-resolution MRI and block-face images to provide supporting volumetric datasets to guide spatial reintegration of 2D histological section data, and presents recent developments in sample preparation, data acquisition, and image processing.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Plank, G., Burton, R.A.B., Hales, P., Bishop, M., Mansoori, T., Bernabeu, M.O., Garny, A., Prassl, A.J., Bollensdorff, C., Mason, F., Mahmood, F., Rodriguez, B., Grau, V., Schneider, J.E., Gavaghan, D., Kohl, P.: Generation of histo-anatomically respresentative models of the individual heart: tools and applications. Phil Trans R Soc A 367(1896), 2257–2292 (2009)

    Article  MATH  Google Scholar 

  2. Kanai, A., Salama, G.: Optical mapping reveals that repolarization heart spreads anisotropically and is guided by fiber orientation in guinea pig hearts. Circ Res. 77, 784–802 (1995)

    Article  Google Scholar 

  3. Vetter, F.J., Simons, S.B., Mironov, S., Hyatt, C.J., Pertsov, A.M.: Epicardial fiber organization in swine right ventricle and its impact on propagation. Circ Res. 96, 244–251 (2005)

    Article  Google Scholar 

  4. Chen, P.S., Cha, Y.M., Peters, B.B., Chen, L.S.: Effects of myocardial fiber orientation on the electrical induction of ventricular fibrillation. Am J Physiol. 264, H1760–H1773 (1993)

    Google Scholar 

  5. De Bakker, J.M., Stein, M., van Rijen, H.V.: Three-dimensional anatomic structure as substrate for ventricular tachycardia/ventricular fibrillation. Heart Rhythm 2, 777–779 (2005)

    Article  Google Scholar 

  6. Eason, J., Schmidt, J., Dabasinskas, A., Siekas, G., Aguel, F., Trayanova, N.: Influence of anisotropy on local and global measures of potential gradient in computer models of defibrillation. Ann. Biomed. Eng. 26, 840–849 (1998)

    Article  Google Scholar 

  7. Hooks, D.A., Tomlinson, K.A., Marsden, S.G., LeGrice, I.J., Smaill, B.H., Pullan, A.J., Hunter, P.J.: Cardiac microstructure: implications for electrical propagation and defibrillation in the heart. Circ. Res. 91, 331–338 (2002)

    Article  Google Scholar 

  8. Waldman, L.K., Nosan, D., Villarreal, F., Covell, J.W.: Relation between transmural deformation and local myofiber direction in canine left ventricle. Circ. Res. 63, 550–562 (1988)

    Article  Google Scholar 

  9. Ashikaga, H., Coppola, B.A., Yamazaki, K.G., Villarreal, F.J., Omens, J.H., Covell, J.W.: Changes in regional myocardial volume during the cardiac cycle: implications for transmural blood flow and cardiac structure. Am. J. Physiol. 295, 610–618 (2008)

    Google Scholar 

  10. Iribe, G., Ward, C.W., Camelliti, P., Bollensdorff, C., Mason, F., Burton, R.A.B., Garny, A., Morphew, M., Hoenger, A., Lederer, W.J., Kohl, P.: Axial stretch of rat single ventricular cardiomyocytes causes an acute and transient increase in Ca2 +  spark rate. Circ. Res. 104, 787–795 (2009)

    Article  Google Scholar 

  11. Kohl, P., Bollensdorff, C., Garny, A.: Effects of mechanosensitive ion channels on ventricular electrophysiology: experimental and theoretical models. Exp. Physiol. 91, 307–321 (2006)

    Article  Google Scholar 

  12. Ozgen, N., Rosen, M.R.: Cardiac memory: a work in progress. Heart Rhythm 6, 564–570 (2009)

    Article  Google Scholar 

  13. Choy, J.S., Kassab, G.S.: Wall thickness of coronary vessels varies transmurally in the LV but not the RV: implications for local stress distribution. Am. J. Physiol. 297, H750–H758 (2009)

    Article  Google Scholar 

  14. Cheng, A., Nguyen, T.C., Malinowski, M., Langer, F., Liang, D., Daughters, G.T., Ingels, N.B., Miller Jr., D.C.: Passive ventricular constraint prevents transmural shear strain progression in left ventricle remodeling. Circulation 114, 79–86 (2006)

    Article  Google Scholar 

  15. Hunter, P., Coveney, P.V., de Bono, B., Diaz, V., Fenner, J., Frangi, A.F., Harris, P., Hose, R., Kohl, P., Lawford, P., McCormack, K., Mendes, M., Omholt, S., Quarteroni, A., Skår, J., Tegner, J., Randall Thomas, S., Tollis, I., Tsamardinos, I., van Beek, J.H., Viceconti, M.: A vision and strategy for the virtual physiological human in 2010 and beyond. Philos. Transact. A Math. Phys. Eng. Sci. 368(1920), 2595–2614 (2010)

    Article  Google Scholar 

  16. Kohl, P., Crampin, E.J., Quinn, T.A., Noble, D.: Systems biology: an approach. Clin. Pharmacol. Ther. 88, 25–33 (2010)

    Article  Google Scholar 

  17. Moreno, J.D., Zhu, Z.I., Yang, P.C., Bankston, J.R., Jeng, M.T., Kang, C., Wang, L., Bayer, J.D., Christini, D.J., Trayanova, N.A., Ripplinger, C.M., Kass, R.S., Clancy, C.E.: A computational model to predict the effects of class I anti-arrhythmic drugs on ventricular rhythms. Sci. Transl. Med. 3, 83–98 (2011)

    Article  Google Scholar 

  18. Rodriguez, B., Burrage, K., Gavaghan, D., Grau, V., Kohl, P., Noble, D.: The systems biology approach to drug development: application to toxicity assessment of cardiac drugs. Clin. Pharmacol. Ther. 88, 130–134 (2010)

    Article  Google Scholar 

  19. Mirams, G.R., Davies, M.R., Cui, Y., Kohl, P., Noble, D.: Application of cardiac electrophysiology simulations to pro-arrhythmic safety testing. Br. J. Pharmacol. (2012) (Epub ahead of print; doi: 10.1111/j.1476-5381.2012.02020)

    Google Scholar 

  20. Streeter Jr., D.D., Bassett, D.L.: An engineering analysis of myocardial fiber orientation in pig’s left ventricle in systole. Anat. Rec. 155, 503–511 (1966)

    Article  Google Scholar 

  21. Dandel, M., Lehmkuhl, H., Knosalla, C., Suramelashvili, N., Hetzer, R.: Strain and strain rate imaging by echocardiography - basic concepts and clinical applicability. Curr. Cardiol. Rev. 5, 133–148 (2009)

    Article  Google Scholar 

  22. Zerhouni, E.A., Parish, D.M., Rogers, W.J., Yang, A., Shapiro, E.P.: Human heart: tagging with MR imaging - a method for noninvasive assessment of myocardial motion. Radiology 169, 59–63 (1988)

    Article  Google Scholar 

  23. Pelc, N.J., Drangova, M., Pelc, L.R., Zhu, Y., Noll, D.C., Bowman, B.S., Herfkens, R.J.: Tracking of cyclic motion with phase-contrast cine MR velocity data. J. Magn. Reson. Imaging 5, 339–345 (1995)

    Article  Google Scholar 

  24. Gilbert, S.H., Benoist, D., Benson, A.P., White, E., Tanner, S.F., Holden, A.V., Dobrzynski, H., Bernus, O., Radjenovic, A.: Visualization and quantification of whole rat heart laminar structure using high-spatial resolution contrast-enhanced MRI. Am. J. Physiol. 302, H287–H298 (2012)

    Google Scholar 

  25. Palm, C., Penney, G.P., Crum, W.R., Schnabel, J.A., Pietrzyk, U., Hawkes, D.J.: Fusion of rat brain histology and MRI using weighted multi-image mutual information. In: Medical Imaging 2008: Image Processing, Pts. 1-3, vol. 6914, pp. M9140–M9140 (2008)

    Google Scholar 

  26. Yelnik, J., Bardinet, E., Dormont, D., Malandain, G., Ourselin, S., Tandé, D., Karachi, C., Ayache, N., Cornu, P., Agid, Y.: A three-dimensional, histological and deformable atlas of the human basal ganglia. I. Atlas construction based on immunohistochemical and MRI data. NeuroImage 34, 618–638 (2007)

    Article  Google Scholar 

  27. Schormann, T., Zilles, K.: Three-dimensional Linear and Nonlinear Transformations: An Integration of Light Microscopical and MRI Data. Human Brain Mapping, 339 (1998)

    Google Scholar 

  28. Eickhoff, S.B., Heim, S., Zilles, K., Amunts, K.: A systems perspective on the effective connectivity of overt speech production. Philos. Transact. A Math. Phys. Eng. Sci. 367(1896), 2399–2421 (2009)

    Article  Google Scholar 

  29. Breen, M.S., Lazebnik, R.S., Wilson, D.L.: Three-dimensional registration of magnetic resonance image data to histological sections with model-based evaluation. Ann. Biomed. Eng. 33, 1100–1112 (2005)

    Article  Google Scholar 

  30. Ko, Y.-S., Yeh, H.-I., Ko, Y.-L., Hsu, Y.-C., Chen, C.-F., Wu, S., Lee, Y.-S., Severs, N.J.: Three-dimensional reconstruction of the rabbit atrioventricular conduction axis by combining histological, desmin, and connexin mapping data. Circulation 109, 1172–1179 (2004)

    Article  Google Scholar 

  31. Rutherford, S.L., Trew, M.L., Sands, G.B., Legrice, I.J., Smaill, B.H.: High-resolution 3-dimensional reconstruction of the infarct border zone. Circ. Res. (2012) (Epub ahead of print: doi: 10.1161/CIRCRESAHA.111.260943)

    Google Scholar 

  32. Goodyer, C., Hodrien, J., Wood, J., Kohl, P., Brodlie, K.: Using high-resolution displays for high-resolution cardiac data. Philos. Transact. A Math. Phys. Eng. Sci. 367(1898), 2667–2677 (2009)

    Article  Google Scholar 

  33. Burton, R.A.B., Plank, G., Schneider, J.E., Grau, V., Ahamer, H., Keeling, S.L., Lee, J., Smith, N.P., Gavaghan, D., Trayanova, N., Kohl, P.: Three-dimensional models of individual cardiac histo-anatomy: tools and challenges. Ann. NY. Acad. Sci. 1080, 301–319 (2006)

    Article  Google Scholar 

  34. Schneider, J.E., Bose, J., Bamforth, S., Gruber, A.D., Broadbent, C., Clarke, K., Neubauer, S., Lengeling, A., Bhattacharya, S.: Identification of cardiac malformations in mice lacking PTDSR using a novel high-throughput magnetic resonance imaging technique. BMC. Dev. Biol. 4, 16 (2004)

    Article  Google Scholar 

  35. Mansoori, T., Plank, G., Burton, R.A.B., Schneider, J.E., Kohl, P., Gavaghan, D., Grau, V.: Building detailed cardiac models by combination of histoanatomical and high-resolution MRI images. In: IEEE International Symposium on Biomedical Imaging (ISBI), pp. 572–575 (2007)

    Google Scholar 

  36. Brennan, T., Fink, M., Rodriguez, B.: Multiscale modelling of drug-induced effects on cardiac electrophysiological activity. Eur. J. Pharm. Sci. 36, 62–77 (2009)

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Gibb, M. et al. (2012). Resolving the Three-Dimensional Histology of the Heart. In: Gilbert, D., Heiner, M. (eds) Computational Methods in Systems Biology. CMSB 2012. Lecture Notes in Computer Science(), vol 7605. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-33636-2_2

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-33636-2_2

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-33635-5

  • Online ISBN: 978-3-642-33636-2

  • eBook Packages: Computer ScienceComputer Science (R0)

Publish with us

Policies and ethics