Amide I kurtosis maps cardiac amyloid in human tissue by ultrabroadband multiplex coherent anti-Stokes Raman scattering (CARS) microscopy
- 1Graduate School of Science and Technology, Keio University
Abstract
Cardiac amyloidosis is caused by deposits of misfolded proteins in the heart and can lead to heart failure. Histological confirmation typically involves staining tissue sections with Congo red and examining them under polarized light for apple-green birefringence; however, achieving an interpretable, label-free, and observer-independent assessment remains challenging. Here we show that Pearson kurtosis of channel intensities within the amide I window provides an interpretable, fitting-free contrast for cardiac amyloid in unstained human cardiac tissue sections from ten participants imaged by ultrabroadband multiplex coherent anti-Stokes Raman scattering (CARS). In a discovery participant, high-kurtosis regions corresponded with Congo red-positive tissue in two CARS-histology pairs of adjacent sections (descriptive spatial AUCs, 0.79 and 0.73). Across 15 fields from nine additional participants, field-level kurtosis values did not overlap between severe-deposition and Congo red-negative tissue fields. Among the descriptors examined, kurtosis showed the largest standardized participant-level separation. Exploratory multivariate curve resolution yielded a deposit-associated component with aromatic-residue features shared with reagent transthyretin. In one field from the discovery participant, the second harmonic generation (SHG) signal, acquired simultaneously with CARS, showed a broadly inverse spatial pattern relative to the amide I kurtosis map, revealing distinct tissue-architectural contrast. Together, these findings support a potential label-free approach to detecting cardiac amyloid deposits that combines amide I kurtosis derived from broadband CARS with SHG-derived architectural contrast.
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BibTeX
@misc{ota2026amide,
title = {{Amide I kurtosis maps cardiac amyloid in human tissue by ultrabroadband multiplex coherent anti-Stokes Raman scattering (CARS) microscopy}},
author = {K. Ota and T.-H. Chen and T. Yamaguchi and T. Otsubo and Y. Murakami and M. Masaki and P. Leproux and R. Suzuki and K. Node and H. Kano},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.07.757266},
url = {https://www.biorxiv.org/content/10.64898/2026.10.07.757266v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Amide I kurtosis maps cardiac amyloid in human tissue by ultrabroadband multiplex coherent anti-Stokes Raman scattering (CARS) microscopy
AU - K. Ota
AU - T.-H. Chen
AU - T. Yamaguchi
AU - T. Otsubo
AU - Y. Murakami
AU - M. Masaki
AU - P. Leproux
AU - R. Suzuki
AU - K. Node
AU - H. Kano
PY - 2026
DA - 2026/10/07
PB - bioRxiv
DO - 10.64898/2026.10.07.757266
UR - https://www.biorxiv.org/content/10.64898/2026.10.07.757266v1
AB - Cardiac amyloidosis is caused by deposits of misfolded proteins in the heart and can lead to heart failure. Histological confirmation typically involves staining tissue sections with Congo red and examining them under polarized light for apple-green birefringence; however, achieving an interpretable, label-free, and observer-independent assessment remains challenging. Here we show that Pearson kurtosis of channel intensities within the amide I window provides an interpretable, fitting-free contrast for cardiac amyloid in unstained human cardiac tissue sections from ten participants imaged by ultrabroadband multiplex coherent anti-Stokes Raman scattering (CARS). In a discovery participant, high-kurtosis regions corresponded with Congo red-positive tissue in two CARS-histology pairs of adjacent sections (descriptive spatial AUCs, 0.79 and 0.73). Across 15 fields from nine additional participants, field-level kurtosis values did not overlap between severe-deposition and Congo red-negative tissue fields. Among the descriptors examined, kurtosis showed the largest standardized participant-level separation. Exploratory multivariate curve resolution yielded a deposit-associated component with aromatic-residue features shared with reagent transthyretin. In one field from the discovery participant, the second harmonic generation (SHG) signal, acquired simultaneously with CARS, showed a broadly inverse spatial pattern relative to the amide I kurtosis map, revealing distinct tissue-architectural contrast. Together, these findings support a potential label-free approach to detecting cardiac amyloid deposits that combines amide I kurtosis derived from broadband CARS with SHG-derived architectural contrast.
ER -