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  3. High-frequency ultrasound imaging for monitoring the function of meningeal lymphatic system in mice

High-frequency ultrasound imaging for monitoring the function of meningeal lymphatic system in mice

  • Ultrasonics. 2023 Feb 8;131:106949. doi: 10.1016/j.ultras.2023.106949.
Onanong Mee-Inta 1,  Chin-Fang Hsieh 2,  De-Quan Chen 2,  Ching-Hsiang Fan 3,  Yu-Yi Chiang 2,  Chan-Chuan Liu 4,  Chun-I Sze 5,  Po-Wu Gean 6,  Ping-Ching Wu 7,  Mon-Shieh Yang 8,  Po-Sheng Huang 9,  Pin Chieh Wu 9,  Yu-Min Kuo 10,  Chih-Chung Huang 11
Affiliations

Affiliations

  • 1 Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
  • 2 Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan.
  • 3 Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan; Medical Device Innovation Center, National Cheng Kung University, Tainan, Taiwan.
  • 4 Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan.
  • 5 Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
  • 6 Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
  • 7 Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan; Medical Device Innovation Center, National Cheng Kung University, Tainan, Taiwan; Institute of Oral Medicine and Department of Stomatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University Tainan, Taiwan; Center of Applied Nanomedicine, National Cheng Kung University, Tainan, Taiwan.
  • 8 College of Science, National Cheng Kung University, Tainan, Taiwan.
  • 9 Department of Photonics, National Cheng Kung University, Tainan, Taiwan.
  • 10 Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, Taiwan. Electronic address: kuoym@mail.ncku.edu.tw.
  • 11 Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan; Medical Device Innovation Center, National Cheng Kung University, Tainan, Taiwan. Electronic address: cchuang@mail.ncku.edu.tw.
PMID: 36773481 DOI: 10.1016/j.ultras.2023.106949
Abstract

The meningeal lymphatic system drains the cerebrospinal fluid from the subarachnoid space to the cervical lymphatic system, primarily to the deep cervical lymph nodes. Perturbations of the meningeal lymphatic system have been linked to various neurologic disorders. A method to specifically monitor the flow of meningeal lymphatic system in real time is unavailable. In the present study, we adopted the high-frequency ultrasound (HFUS) with 1,1'diocatadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI)-loaded microbubble and FePt@PLGA nanoparticle contrast agents to evaluate the flow of the meningeal lymphatic system in 2-month-old mice. Statistical analysis was performed to identify changes of HFUS signals among the microbubbles, FePt@PLGA nanoparticles, and saline control groups. Approximately 15 min from the start of intracerebroventricular injection of contrast agents, their signals were evident at the deep cervical lymph nodes and lasted for at least 60 min. These signals were validated on the basis of the presence of DiI and Fe signals in the deep cervical lymph nodes. Ligation of afferent lymphatic vessels to the deep cervical lymph nodes eliminated the HFUS signals. Moreover, ablation of lymphatic vessels near the confluence of sinuses decreased the HFUS signals in the deep cervical lymph nodes. Glioma-bearing mice that exhibited reduced lymphatic vessel immunostaining signals near the confluence of sinuses had lowered HFUS signals in the deep cervical lymph nodes within 60 min. The proposed method provides a minimally invasive approach to monitor the qualities of the meningeal lymphatic system in real time as well as the progression of the meningeal lymphatic system in various brain disease animal models.

Keywords

FePt@PLGA nanoparticle; High-frequency ultrasound imaging; Meningeal lymphatic system; Microbubble.

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