Quantitative analysis of cardiac tissue including fibroblasts using three-dimensional confocal microscopy and image reconstruction: towards a basis for electrophysiological modeling
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Quantitative analysis of cardiac tissue including fibroblasts using three-dimensional confocal microscopy and image reconstruction: towards a basis for electrophysiological modeling. / Schwab, Bettina C; Seemann, Gunnar; Lasher, Richard A; Torres, Natalia S; Wulfers, Eike M; Arp, Maren; Carruth, Eric D; Bridge, John H B; Sachse, Frank B.
in: IEEE T MED IMAGING, Jahrgang 32, Nr. 5, 05.2013, S. 862-872.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Quantitative analysis of cardiac tissue including fibroblasts using three-dimensional confocal microscopy and image reconstruction: towards a basis for electrophysiological modeling
AU - Schwab, Bettina C
AU - Seemann, Gunnar
AU - Lasher, Richard A
AU - Torres, Natalia S
AU - Wulfers, Eike M
AU - Arp, Maren
AU - Carruth, Eric D
AU - Bridge, John H B
AU - Sachse, Frank B
PY - 2013/5
Y1 - 2013/5
N2 - 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, 3-D 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 3-D 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±0.051 S/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.
AB - 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, 3-D 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 3-D 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±0.051 S/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.
KW - Animals
KW - Connexins/chemistry
KW - Electric Conductivity
KW - Electrophysiological Phenomena
KW - Fibroblasts/cytology
KW - Fluorescent Dyes/chemistry
KW - Gap Junctions/chemistry
KW - Heart/physiology
KW - Imaging, Three-Dimensional/methods
KW - Microscopy, Confocal/methods
KW - Models, Cardiovascular
KW - Myocardial Infarction/pathology
KW - Myocardium/chemistry
KW - Myocytes, Cardiac/cytology
KW - Rabbits
U2 - 10.1109/TMI.2013.2240693
DO - 10.1109/TMI.2013.2240693
M3 - SCORING: Journal article
C2 - 23340590
VL - 32
SP - 862
EP - 872
JO - IEEE T MED IMAGING
JF - IEEE T MED IMAGING
SN - 0278-0062
IS - 5
ER -
