Quantitative analysis of cardiac tissue including fibroblasts using three-dimensional confocal microscopy and image reconstruction: Towards a basis for electrophysiological modeling

B.C. Schwab, Gunnar Seemann, Richard A. Lasher, Natalia S. Torres, Eike M. Wülfers, Maren Arp, Eric D. Carruth, John H.B. Bridge, Frank B. Sachse

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    Abstract

    Electrophysiological modeling of cardiac tissue is commonly based on functional and structural properties measured in experiments. Our knowledge of these properties is incomplete, in particular their remodeling in disease. Here, we introduce a methodology for quantitative tissue characterization based on fluorescent labeling, three-dimensional scanning confocal microscopy, image processing and reconstruction of tissue micro-structure at sub-micrometer resolution. We applied this methodology to normal rabbit ventricular tissue and tissue from hearts with myocardial infarction. Our analysis revealed that the volume fraction of fibroblasts increased from 4.83±0.42% (mean±standard deviation) in normal tissue up to 6.51±0.38% in myocardium from infarcted hearts. The myocyte volume fraction decreased from 76.20±9.89% in normal to 73.48±8.02% adjacent to the infarct. Numerical field calculations on three-dimensional reconstructions of the extracellular space yielded an extracellular longitudinal conductivity of 0.264±0.082 S/m with an anisotropy ratio of 2.095±1.11 in normal tissue. Adjacent to the infarct, the longitudinal conductivity increased up to 0.400±0.051S/m, but the anisotropy ratio decreased to 1.295±0.09. Our study indicates an increased density of gap junctions proximal to both fibroblasts and myocytes in infarcted versus normal tissue, supporting previous hypotheses of electrical coupling of fibroblasts and myocytes in infarcted hearts. We suggest that the presented methodology provides an important contribution to modeling normal and diseased tissue. Applications of the methodology include the clinical characterization of disease-associated remodeling.
    Original languageUndefined
    Pages (from-to)862-872
    Number of pages11
    JournalIEEE transactions on medical imaging
    Volume32
    Issue number5
    DOIs
    Publication statusPublished - May 2013

    Keywords

    • METIS-296318
    • IR-85839
    • Confocal imaging
    • Gap junctions
    • Myocardial infarction
    • Fibroblasts
    • Parameter estimation
    • EWI-23109

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