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ORIGINAL RESEARCH article
Front. Cardiovasc. Med.
Sec. Cardiovascular Imaging
Volume 11 - 2024 |
doi: 10.3389/fcvm.2024.1433227
Imaging human coronary cholesterol/urate crystals with crosspolarized micro-optical coherence tomography
Provisionally accepted
Kensuke Nishimiya
1,2
Gargi Sharma
2
Kanwarpal Singh
2*
Osman O. Ahsen
2*
Joseph Gardecki
2
Guillermo J. Tearney
2,3*- 1 Tohoku University, Sendai, Japan
- 2 Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States
- 3 Harvard Medical School, Boston, Massachusetts, United States
Introduction: Birefringent crystals such as monosodium-urate (MSU) and cholesterol crystals (CC) likely contribute to the progression of coronary artery disease (CAD) due to their potential to exacerbate inflammation through inflammatory cytokine activation. Here, we present cross-polarized micro-optical coherence tomography (CP-µOCT) for visualizing individual birefringent crystals in human coronary arteries.Human cadaver coronary arteries with a history of CAD with or without gout were dissected for CP-µOCT imaging. Specimens were processed for histological identification of birefringence under polarization light microscopy (PLM). CP-µOCT visualized needle-crystals that appeared as long projections in orthogonal planes, and PLM confirmed that CP-µOCT-delineated needle-crystals demonstrated negative birefringence. The needle-crystals were dissolved after immersion in uricase (p<0.05), and thus were MSU. CP-µOCT was three-dimensionally volumerendered for counting MSU and CCs in 79 regions of interest sized [750 (x)x 500 (y)x 400 (z) µm].Crystal counts were normalized by the total coronary length utilized. The relationship between CP-µOCT-delineated MSU counts and those seen in corresponding histology, and the difference in coronary MSU amongst gout vs. non-gout patients was analyzed. CP-µOCT-delineated MSU counts were significantly correlated with MSU counted by PLM-based histology (R=0.98, p<0.01), and with histology-derived intimal thickening (R=0.51, p<0.01). MSU and CCs were both significantly greater in gout patients compared with non-gout patients (p<0.05).Discussion: These results demonstrate a significant increase in CP-µOCT-delineated crystals in gout vs. non-gout patients, suggesting that this technology can be used to improve our understanding of crystal-driven coronary pathogenesis.
Keywords: Optical Coherence Tomography, Coronary Artery Disease, cholesterol crystals, Gout, Uric Acid, Inflammation
Received: 24 May 2024; Accepted: 07 Oct 2024.
Copyright: © 2024 Nishimiya, Sharma, Singh, Ahsen, Gardecki and Tearney. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Kanwarpal Singh, Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, 02114, Massachusetts, United States
Osman O. Ahsen, Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, 02114, Massachusetts, United States
Guillermo J. Tearney, Harvard Medical School, Boston, 02115, Massachusetts, United States
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