Quantitative longitudinal investigation of non-alcoholic steatohepatitis in mice by photoacoustic microscopy

Non-alcoholic steatohepatitis (NASH) is a prevalent chronic liver disease characterized by significant alterations in liver microvascular structures, leading to microcirculatory dysfunction and potentially contributing to various extrahepatic complications. In this study, we propose a longitudinal i...

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Main Authors: Jianshuang Wei, Ren Zhang, Mingchen Jiang, Lulu Gao, Ximiao Yu, XiuLi Liu, Yanfeng Dai, Qingming Luo, Zhihong Zhang, Xiaoquan Yang
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:Photoacoustics
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Online Access:http://www.sciencedirect.com/science/article/pii/S2213597925000643
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author Jianshuang Wei
Ren Zhang
Mingchen Jiang
Lulu Gao
Ximiao Yu
XiuLi Liu
Yanfeng Dai
Qingming Luo
Zhihong Zhang
Xiaoquan Yang
author_facet Jianshuang Wei
Ren Zhang
Mingchen Jiang
Lulu Gao
Ximiao Yu
XiuLi Liu
Yanfeng Dai
Qingming Luo
Zhihong Zhang
Xiaoquan Yang
author_sort Jianshuang Wei
collection DOAJ
description Non-alcoholic steatohepatitis (NASH) is a prevalent chronic liver disease characterized by significant alterations in liver microvascular structures, leading to microcirculatory dysfunction and potentially contributing to various extrahepatic complications. In this study, we propose a longitudinal investigative pipeline based on liver photoacoustic microscopy (LPAM), integrating optical-resolution photoacoustic microscopy (OR-PAM), a modular liver window (MLW), a custom 3D-printed liver imaging mount (LIM), and a dedicated vessel-sinusoid separation and analysis method. This pipeline enabled continuous monitoring and quantitative assessment of microvascular changes in a NASH mouse model over a six-week period. As NASH progressed, vessel density decreased by 64.18 %, and hepatic sinusoid vessel coverage was reduced by 77.38 %. Furthermore, hepatic sinusoidal volume, length, radius, tortuosity, and density declined by 87.29 %, 83.92 %, 21.86 %, 71.57 %, and 86.81 %, Analysis of hepatic sinusoidal branches revealed a 51.80 % decrease in the fractal dimension of composite branches and a 54.90 % increase in that of dead-end branches. These findings suggest that lipid accumulation and inflammatory responses contribute to the progressive deterioration of hepatic microvascular structures, thereby exacerbating vascular damage. LPAM offers a high-resolution, label-free imaging approach for dynamic monitoring of NASH-associated microvascular alterations. This study advances our understanding of hepatic microcirculatory changes in NASH and provides valuable insights for both basic research and clinical management.
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spelling doaj-art-bfbc6e47302b4e51befae7505b36da722025-08-20T03:32:02ZengElsevierPhotoacoustics2213-59792025-08-014410074110.1016/j.pacs.2025.100741Quantitative longitudinal investigation of non-alcoholic steatohepatitis in mice by photoacoustic microscopyJianshuang Wei0Ren Zhang1Mingchen Jiang2Lulu Gao3Ximiao Yu4XiuLi Liu5Yanfeng Dai6Qingming Luo7Zhihong Zhang8Xiaoquan Yang9MOE Key Laboratory for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan 430074, ChinaMOE Key Laboratory for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan 430074, ChinaMOE Key Laboratory for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan 430074, ChinaMOE Key Laboratory for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan 430074, ChinaMOE Key Laboratory for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan 430074, ChinaMOE Key Laboratory for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan 430074, ChinaState Key Laboratory of Digital Medical Engineering, Key Laboratory of Biomedical Engineering of Hainan Province, School of Biomedical Engineering, Hainan University, Haikou 570228, ChinaState Key Laboratory of Digital Medical Engineering, Key Laboratory of Biomedical Engineering of Hainan Province, School of Biomedical Engineering, Hainan University, Haikou 570228, China; Corresponding author.MOE Key Laboratory for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan 430074, China; State Key Laboratory of Digital Medical Engineering, Key Laboratory of Biomedical Engineering of Hainan Province, School of Biomedical Engineering, Hainan University, Haikou 570228, China; Corresponding authors at: MOE Key Laboratory for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan 430074, China.MOE Key Laboratory for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan 430074, China; State Key Laboratory of Digital Medical Engineering, Key Laboratory of Biomedical Engineering of Hainan Province, School of Biomedical Engineering, Hainan University, Haikou 570228, China; Corresponding authors at: MOE Key Laboratory for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan 430074, China.Non-alcoholic steatohepatitis (NASH) is a prevalent chronic liver disease characterized by significant alterations in liver microvascular structures, leading to microcirculatory dysfunction and potentially contributing to various extrahepatic complications. In this study, we propose a longitudinal investigative pipeline based on liver photoacoustic microscopy (LPAM), integrating optical-resolution photoacoustic microscopy (OR-PAM), a modular liver window (MLW), a custom 3D-printed liver imaging mount (LIM), and a dedicated vessel-sinusoid separation and analysis method. This pipeline enabled continuous monitoring and quantitative assessment of microvascular changes in a NASH mouse model over a six-week period. As NASH progressed, vessel density decreased by 64.18 %, and hepatic sinusoid vessel coverage was reduced by 77.38 %. Furthermore, hepatic sinusoidal volume, length, radius, tortuosity, and density declined by 87.29 %, 83.92 %, 21.86 %, 71.57 %, and 86.81 %, Analysis of hepatic sinusoidal branches revealed a 51.80 % decrease in the fractal dimension of composite branches and a 54.90 % increase in that of dead-end branches. These findings suggest that lipid accumulation and inflammatory responses contribute to the progressive deterioration of hepatic microvascular structures, thereby exacerbating vascular damage. LPAM offers a high-resolution, label-free imaging approach for dynamic monitoring of NASH-associated microvascular alterations. This study advances our understanding of hepatic microcirculatory changes in NASH and provides valuable insights for both basic research and clinical management.http://www.sciencedirect.com/science/article/pii/S2213597925000643Photoacoustic microscopyNon-alcoholic steatohepatitisLongitudinal investigationThree-dimensional quantification
spellingShingle Jianshuang Wei
Ren Zhang
Mingchen Jiang
Lulu Gao
Ximiao Yu
XiuLi Liu
Yanfeng Dai
Qingming Luo
Zhihong Zhang
Xiaoquan Yang
Quantitative longitudinal investigation of non-alcoholic steatohepatitis in mice by photoacoustic microscopy
Photoacoustics
Photoacoustic microscopy
Non-alcoholic steatohepatitis
Longitudinal investigation
Three-dimensional quantification
title Quantitative longitudinal investigation of non-alcoholic steatohepatitis in mice by photoacoustic microscopy
title_full Quantitative longitudinal investigation of non-alcoholic steatohepatitis in mice by photoacoustic microscopy
title_fullStr Quantitative longitudinal investigation of non-alcoholic steatohepatitis in mice by photoacoustic microscopy
title_full_unstemmed Quantitative longitudinal investigation of non-alcoholic steatohepatitis in mice by photoacoustic microscopy
title_short Quantitative longitudinal investigation of non-alcoholic steatohepatitis in mice by photoacoustic microscopy
title_sort quantitative longitudinal investigation of non alcoholic steatohepatitis in mice by photoacoustic microscopy
topic Photoacoustic microscopy
Non-alcoholic steatohepatitis
Longitudinal investigation
Three-dimensional quantification
url http://www.sciencedirect.com/science/article/pii/S2213597925000643
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