June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
In vivo contrast-enhanced MRI of cerebrospinal fluid dynamics in mouse optic nerve
Author Affiliations & Notes
  • Muneeb A Faiq
    Department of Ophthalmology, New York University School of Medicine, New York, New York, United States
  • Anoop Sainulabdeen
    Department of Ophthalmology, New York University School of Medicine, New York, New York, United States
  • Carlos Parra
    Department of Ophthalmology, New York University School of Medicine, New York, New York, United States
  • Xinlei Wang
    Department of Ophthalmology, New York University School of Medicine, New York, New York, United States
  • Choong H Lee
    Department of Radiology, New York University School of Medicine, New York, New York, United States
  • Jiangyang Zhang
    Department of Radiology, New York University School of Medicine, New York, New York, United States
  • Crystal Liu
    Department of Ophthalmology, New York University School of Medicine, New York, New York, United States
  • Wenyu Deng
    Department of Ophthalmology, New York University School of Medicine, New York, New York, United States
  • Gadi Wollstein
    Department of Ophthalmology, New York University School of Medicine, New York, New York, United States
  • Joel S Schuman
    Department of Ophthalmology, New York University School of Medicine, New York, New York, United States
    Department of Biomedical Engineering, NYU Tandon School of Engineering, NY, New York, United States
  • Kevin C Chan
    Department of Ophthalmology, New York University School of Medicine, New York, New York, United States
    Department of Radiology, New York University School of Medicine, New York, New York, United States
  • Footnotes
    Commercial Relationships   Muneeb Faiq, None; Anoop Sainulabdeen, None; Carlos Parra, None; Xinlei Wang, None; Choong Lee, None; Jiangyang Zhang, None; Crystal Liu, None; Wenyu Deng, None; Gadi Wollstein, None; Joel Schuman, Zeiss, Inc (P); Kevin Chan, None
  • Footnotes
    Support  This work was supported in part by the National Institutes of Health R01-EY028125 (Bethesda, Maryland); BrightFocus Foundation G2013077, G2016030 and G20190103 (Clarksburg, Maryland); and an Unrestricted Grant from Research to Prevent Blindness to NYU Langone Health Department of Ophthalmology.
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 2767. doi:
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    • Get Citation

      Muneeb A Faiq, Anoop Sainulabdeen, Carlos Parra, Xinlei Wang, Choong H Lee, Jiangyang Zhang, Crystal Liu, Wenyu Deng, Gadi Wollstein, Joel S Schuman, Kevin C Chan; In vivo contrast-enhanced MRI of cerebrospinal fluid dynamics in mouse optic nerve. Invest. Ophthalmol. Vis. Sci. 2020;61(7):2767.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : The glymphatic system has been postulated to play a crucial role in the central nervous system via metabolic waste removal from brain tissues by the cerebrospinal fluid (CSF). However, it remains unclear whether there is a direct glymphatic pathway in the visual pathway, partly due to limited in vivo methods for assessing the physiology of CSF dynamics in the optic nerve (ON). Contrast-enhanced MRI has been shown to be capable of monitoring the dynamics of glymphatic system in the brain using paramagnetic contrast agents. Investigating the same in and around the ON might give insights into the mechanisms of vision-related diseases such as glaucoma.

Methods : In the present study, we infused a small molecular weight gadolinium-DTPA contrast agent intrathecally into the lumbar region (L4-L5) of 3 healthy adult C57BL/6J mice and imaged its flow, accumulation and clearance in the brain and the optic nerve over time using a 7-Tesla MRI scanner under isoflurane anesthesia. Contrast dynamics was monitored using a 3D T1-weighted imaging sequence at an isotropic resolution of 78x78x78 µm3. Each scan lasted 10 min and a total of 12 continuous scans were acquired. These scans included 3 baseline acquisitions followed by 30 min of gadolinium contrast infusion using an automated pump while the scanning continued until the 12th time point. The intensity-time curves of the ON parenchyma, ON subarachnoid space (SAS), olfactory bulb, lateral ventricles and muscle tissues were generated and compared quantitatively. Data are represented as mean±SEM.

Results : The ON parenchyma, ON-SAS, olfactory bulb and lateral ventricles showed a gradual increase in contrast enhancement (Figures 1 and 2A) with peak intensities at 92.03±16.21% (p<0.05), 440.50±39.41% (p<0.01), 210.54±20.69% (p<0.01) and 196.63±38.63% (p<0.05) respectively relative to baseline (Figure 2B). Peak intensity occurred first in the olfactory bulb followed by ON-SAS, ON parenchyma and finally the lateral ventricles (Figure 2B). No apparent contrast uptake was observed in the nearby muscle tissues.

Conclusions : This study illustrates direct communications between CSF and ON parenchyma and supports the evidence of the glymphatic system in the ON. In vivo imaging of CSF dynamics in and around the ON may open up new avenues for understanding ON function in health and disease with the possibility of devising novel drug delivery routes and therapeutic targets.

This is a 2020 ARVO Annual Meeting abstract.

 

 

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