Brain Glymphatic/Lymphatic Imaging by MRI and PET
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REVIEW
Brain Glymphatic/Lymphatic Imaging by MRI and PET Dong Soo Lee 1,2 & Minseok Suh 1,2 & Azmal Sarker 2 & Yoori Choi 1,2 Received: 2 June 2020 / Revised: 9 August 2020 / Accepted: 19 August 2020 # Korean Society of Nuclear Medicine 2020
Abstract Since glymphatic was proposed and meningeal lymphatic was discovered, MRI andeven PET were introduced to investigate brain parenchymal interstitial fluid (ISF),cerebrospinal fluid (CSF), and lymphatic outflow in rodents and humans. Previousfindings by ex vivo fluorescent microscopic, and in vivo two-photon imaging in rodentswere reproduced using intrathecal contrast (gadobutrol and the similar)-enhanced MRIin rodents and further in humans. On dynamic MRI of meningeal lymphatics, in contrastto rodents, humans use mainly dorsal meningeal lymphatic pathways of ISF-CSFlymphaticefflux. In mice, ISF-CSF exchange was examined thoroughly using an intracisterninjection of fluorescent tracers during sleep, aging, and neurodegenerationyielding many details. CSF to lymphatic efflux is across arachnoid barrier cells over thedorsal dura in rodents and in humans. Meningeal lymphatic efflux to cervical lymphnodes and systemic circulation is also well delineated especially in humans onintrathecal contrast MRI. Sleep- or anesthesia-related changes of glymphatic-lymphaticflow and the coupling of ISFCSF-lymphatic drainage are major confounders ininterpreting brain glymphatic/lymphatic outflow in rodents. PET imaging in humansshould be interpreted based on human anatomy and physiology, different in someaspects, using MRI recently. Based on the summary in this review, we propose noninvasiveand longer-term intrathecal SPECT/PET or MRI studies to unravel the roles of brain glymphatic/lymphatic in diseases. Keywords Interstitial fluid . Cerebrospinal fluid . Glymphatic . Meningeal lymphatic . Imaging.
Introduction Brain glymphatic was proposed in 2012 by Iliff and colleagues to explain waste clearance from the brain parenchyma [1]. In 2015, Louveau and colleagues found the existence of meningeal lymphatics and suggested that meningeal lymphatic can clear wastes from the brain [2]. Afterward, there had been many efforts to link glymphatic clearance [3–12] and lymphatic drainage in small animals and humans [12–17]. Now, interstitial fluid (ISF) is drained to cerebrospinal fluid (CSF) [1, 3] (Fig. 1), and further drainage of CSF to meningeal lymphatics are well-established [12, 13, 22] (Fig. 2). CSF is considered to drain via dorsal lymphatic vessels; basal * Dong Soo Lee [email protected] 1
Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
2
Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Medicine or College of Pharmacy, Seoul National University, Seoul 03080, Republic of Korea
lymphatic vessels [2, 4, 12–14, 17, 25–27], along the nerve sheaths of olfactory and other cranial nerves [27–31]; and spinal meningeal lymphatics [28, 32–34] (Fig. 3). Deep
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