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Published on: October 17, 2025
Applying harmonic optical microscopy for spatial alignment of atrial collagen fibers
Yu-Wei Chiu1, Men Tzung Lo, Ming-Rung Tsai
1Division of Cardiology, Department of Internal Medicine, Far-Eastern Memorial Hospital, Taipei, Taiwan.
Background:
Atrial fibrosis creates a vulnerable tissue for atrial fibrillation (AF), but the spatial disarray of collagen fibers underlying atrial fibrosis is not fully elucidated.
Objective:
This study hypothesizes that harmonics optical microscopy can illuminate the spatial mal-alignment of collagen fibers in AF via a layer-by-layer approach.
Patients And Methods:
Atrial tissues taken from patients who underwent open-heart surgery were examined by harmonics optical microscopy. Using the two-dimensional Fourier transformation method, a spectral-energy description of image texture was constituted and its entropy was used to quantify the mal-alignment of collagen fibers. The amount of collagen fiber was derived from its area ratio to total atrial tissue in each image. Serum C-terminal pro-collagen pro-peptide (CICP), pro-matrix metalloproteinase-1 (pro-MMP-1), and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) were also evaluated.
Results:
46 patients were evaluated, including 20 with normal sinus rhythm and 26 with AF. The entropy of spectral-energy distribution of collagen alignment was significantly higher in AF than that in sinus rhythm (3.97 ± 0.33 vs. 2.80 ± 0.18, p<0.005). This difference was more significant in the permanent AF group. The amount of collagen was also significantly higher in AF patients (0.39 ± 0.13 vs. 0.18 ± 0.06, p<0.005) but serum markers of cardiac fibrosis were not significantly different between the two groups.
Conclusions:
Harmonics optical microscopy can quantify the spatial mal-alignment of collagen fibers in AF. The entropy of spectral-energy distribution of collagen alignment is a potential tool for research in atrial remodeling.

