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Nuclear Medicine and Molecular Imaging
Published in: Nuclear Medicine and Molecular Imaging 5/2020

01-10-2020 | Magnetic Resonance Imaging | Review

Brain Glymphatic/Lymphatic Imaging by MRI and PET

Authors: Dong Soo Lee, Minseok Suh, Azmal Sarker, Yoori Choi

Published in: Nuclear Medicine and Molecular Imaging | Issue 5/2020

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Abstract

Since glymphatic was proposed and meningeal lymphatic was discovered, MRI and even PET were introduced to investigate brain parenchymal interstitial fluid (ISF), cerebrospinal fluid (CSF), and lymphatic outflow in rodents and humans. Previous findings by ex vivo fluorescent microscopic, and in vivo two-photon imaging in rodents were reproduced using intrathecal contrast (gadobutrol and the similar)-enhanced MRI in rodents and further in humans. On dynamic MRI of meningeal lymphatics, in contrast to rodents, humans use mainly dorsal meningeal lymphatic pathways of ISF-CSF-lymphatic efflux. In mice, ISF-CSF exchange was examined thoroughly using an intra-cistern injection of fluorescent tracers during sleep, aging, and neurodegeneration yielding many details. CSF to lymphatic efflux is across arachnoid barrier cells over the dorsal dura in rodents and in humans. Meningeal lymphatic efflux to cervical lymph nodes and systemic circulation is also well-delineated especially in humans onintrathecal contrast MRI. Sleep- or anesthesia-related changes of glymphatic-lymphatic flow and the coupling of ISF-CSF-lymphatic drainage are major confounders ininterpreting brain glymphatic/lymphatic outflow in rodents. PET imaging in humans should be interpreted based on human anatomy and physiology, different in some aspects, using MRI recently. Based on the summary in this review, we propose non-invasive and longer-term intrathecal SPECT/PET or MRI studies to unravel the roles of brain glymphatic/lymphatic in diseases.
Literature
1.
Iliff JJ, Wang M, Liao Y, Plogg BA, Peng W, Gundersen GA, et al. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid. β Sci Transl Med. 2012;4:147ra111.
2.
Louveau A, Smirnov I, Keyes TJ, Eccles JD, Rouhani SJ, Peske JD, et al. Structural and functional features of central nervous system lymphatic vessels. Nature. 2015;523:337–41.PubMedPubMedCentral
3.
Iliff JJ, Wang M, Zeppenfeld DM, Venkataraman A, Plog BA, Liao Y, et al. Cerebral arterial pulsation drives paravascular CSF-interstitial fluid exchange in the murine brain. J Neurosci. 2013;33:18190–9.PubMedPubMedCentral
4.
Aspelund A, Antila S, Proulx ST, Karlsen TV, Karaman S, Detmar M, et al. A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules. J Exp Med. 2015;212:991–9.PubMedPubMedCentral
5.
Smith AJ, Yao X, Dix JA, Jin BJ, Verkman AS. Test of the ‘glymphatic’ hypothesis demonstrates diffusive and aquaporin-4-independent solute transport in rodent brain parenchyma. Elife. 2017;6:e27679.
6.
Lei Y, Han H, Yuan F, Javeed A, Zhao Y. The brain interstitial system: anatomy, modeling, in vivo measurement, and applications. Prog Neurobiol. 2017;157:230–46.PubMed
7.
Mestre H, Hablitz LM, Xavier ALR, Feng W, Zou W, Pu T, et al. Aquaporin-4-dependent glymphatic solute transport in the rodent brain. Elife. 2018;7:e40070.
8.
Nakada T, Kwee IL. Fluid dynamics inside the brain barrier: current concept of interstitial flow, glymphatic flow, and cerebrospinal fluid circulation in the brain. Neuroscientist. 2019;25:155–66.PubMed
9.
Iliff J, Simon M. CrossTalk proposal: the glymphatic system supports convective exchange of cerebrospinal fluid and brain interstitial fluid that is mediated by perivascular aquaporin-4. J Physiol. 2019;597:4417–9.PubMedPubMedCentral
10.
Smith AJ, Verkman AS. CrossTalk opposing view: going against the flow: interstitial solute transport in brain is diffusive and aquaporin-4 independent. J Physiol. 2019;597:4421–4.PubMedPubMedCentral
11.
12.
Louveau A, Plog BA, Antila S, Alitalo K, Nedergaard M, Kipnis J. Understanding the functions and relationships of the glymphatic system and meningeal lymphatics. J Clin Invest. 2017;127:3210–9.PubMedPubMedCentral
13.
14.
Antila S, Karaman S, Nurmi H, Airavaara M, Voutilainen MH, Mathivet T, et al. Development and plasticity of meningeal lymphatic vessels. J Exp Med. 2017;214:3645–67.PubMedPubMedCentral
15.
Da Mesquita S, Louveau A, Vaccari A, Smirnov I, Cornelison RC, Kingsmore KM, et al. Functional aspects of meningeal lymphatics in ageing and Alzheimer’s disease. Nature. 2018;560:185–91.PubMedPubMedCentral
16.
Frederick N, Louveau A. Meningeal lymphatics, immunity and neuroinflammation. Curr Opin Neurobiol. 2020;62:41–7.PubMed
17.
Da Mesquita S, Fu Z, Kipnis J. The meningeal lymphatic system: a new player in neurophysiology. Neuron. 2018;100:375–88.PubMedPubMedCentral
18.
Xie L, Kang H, Xu Q, Chen MJ, Liao Y, Thiyagarajan M, et al. Sleep drives metabolite clearance from the adult brain. Science (80- ). 2013;342:373–7.
19.
Kress BT, Iliff JJ, Xia M, Wang M, Wei HS, Zeppenfeld D, et al. Impairment of paravascular clearance pathways in the aging brain. Ann Neurol. 2014;76:845–61.PubMedPubMedCentral
20.
Mastorakos P, McGavern D. The anatomy and immunology of vasculature in the central nervous system. Sci Immunol 2019;4:eaav0492.
21.
Coles JA, Myburgh E, Brewer JM, McMenamin PG. Where are we? The anatomy of the murine cortical meninges revisited for intravital imaging, immunology, and clearance of waste from the brain. Prog Neurobiol. 2017;156:107–48.PubMed
22.
Zhou Y, Cai J, Zhang W, Gong X, Yan S, Zhang K, et al. Impairment of the glymphatic pathway and putative meningeal lymphatic vessels in the aging human. Ann Neurol. 2020;87:357–69.PubMed
23.
Castro Dias M, Mapunda JA, Vladymyrov M, Engelhardt B. Structure and junctional complexes of endothelial, epithelial and glial brain barriers. Int J Mol Sci. 2019;20:5372.
24.
Ringstad G, Eide PK. Cerebrospinal fluid tracer efflux to parasagittal dura in humans. Nat Commun. 2020;11:1–9.
25.
Goodman JR, Adham ZO, Woltjer RL, Lund AW, Iliff JJ. Characterization of dural sinus-associated lymphatic vasculature in human Alzheimer’s dementia subjects. Brain Behav Immun. 2018;73:34–40.PubMedPubMedCentral
26.
Dupont G, Schmidt C, Yilmaz E, Oskouian RJ, Macchi V, de Caro R, et al. Our current understanding of the lymphatics of the brain and spinal cord. Clin Anat. 2019;32:117–21.PubMed
27.
Ahn JH, Cho H, Kim JH, Kim SH, Ham JS, Park I, et al. Meningeal lymphatic vessels at the skull base drain cerebrospinal fluid. Nature. 2019;572:62–6.PubMed
28.
Lüdemann W, von Rautenfeld DB, Samii M, Brinker T. Ultrastructure of the cerebrospinal fluid outflow along the optic nerve into the lymphatic system. Childs Nerv Syst. 2005;21:96–103.PubMed
29.
Walter BA, Valera VA, Takahashi S, Ushiki T. The olfactory route for cerebrospinal fluid drainage into the peripheral lymphatic system. Neuropathol Appl Neurobiol. 2006;32:388–96.PubMed
30.
Ma Q, Ineichen BV, Detmar M, Proulx ST. Outflow of cerebrospinal fluid is predominantly through lymphatic vessels and is reduced in aged mice. Nat Commun. 2017;8:1434.
31.
Wang X, Lou N, Eberhardt A, Yang Y, Kusk P, Xu Q, et al. An ocular glymphatic clearance system removes β-amyloid from the rodent eye. Sci Transl Med. 2020;12:eaaw3210.
32.
Miura M, Kato S, Von Lüdinghausen M. Lymphatic drainage of the cerebrospinal fluid from monkey spinal meninges with special reference to the distribution of the epidural lymphatics. Arch Histol Cytol. 1998;61:277–86.PubMed
33.
Clapham R, O’sullivan E, Weller RO, Carare RO. Cervical lymph nodes are found in direct relationship with the internal carotid artery: significance for the lymphatic drainage of the brain. Clin Anat 2009;23:43–47.
34.
Jacob L, Boisserand LSB, Geraldo LHM, de Brito Neto J, Mathivet T, Antila S, et al. Anatomy and function of the vertebral column lymphatic network in mice. Nat Commun. 2019;10:4594.
35.
Kuo PH, Stuehm C, Squire S, Johnson K. Meningeal lymphatic vessel flow runs countercurrent to venous flow in the superior sagittal sinus of the human brain. Tomography. 2018;4:99–104.PubMedPubMedCentral
36.
Maloveska M, Danko J, Petrovova E, Kresakova L, Vdoviakova K, Michalicova A, et al. Dynamics of Evans blue clearance from cerebrospinal fluid into meningeal lymphatic vessels and deep cervical lymph nodes. Neurol Res. 2018;40:372–80.PubMed
37.
Bradbury MW, Cole DF. The role of the lymphatic system in drainage of cerebrospinal fluid and aqueous humour. J Physiol. 1980;299:353–65.PubMedPubMedCentral
38.
Boulton M, Flessner M, Armstrong D, Hay J, Johnston M. Determination of volumetric cerebrospinal fluid absorption into extracranial lymphatics in sheep. Am J Physiol - Regul Integr Comp Physiol. 1998;274:R88–96.
39.
Eide PK, Vatnehol SAS, Emblem KE, Ringstad G. Magnetic resonance imaging provides evidence of glymphatic drainage from human brain to cervical lymph nodes. Sci Rep. 2018;8:7194.
40.
Ma Q, Ries M, Decker Y, Müller A, Riner C, Bücker A, et al. Rapid lymphatic efflux limits cerebrospinal fluid flow to the brain. Acta Neuropathol. 2019;137:151–65.PubMed
41.
Koh Chang-Soon Nuclear Medicine. Korea; 2008.
42.
Grubb S, Lauritzen M. Deep sleep drives brain fluid oscillations. Science. 2019;366:572–3.
43.
Iadecola C. The neurovascular unit coming of age: a journey through neurovascular coupling in health and disease. Neuron. 2017;96:17–42.PubMedPubMedCentral
44.
Matsumae M, Kuroda K, Yatsushiro S, Hirayama A, Hayashi N, Takizawa K, et al. Changing the currently held concept of cerebrospinal fluid dynamics based on shared findings of cerebrospinal fluid motion in the cranial cavity using various types of magnetic resonance imaging techniques. Neurol Med Chir (Tokyo). 2019;59:133–46.
45.
Hirayama A, Matsumae M, Yatsushiro S, Abdulla A, Atsumi H, Kuroda K. Visualization of pulsatile CSF motion around membrane-like structures with both 4D velocity mapping and time-SLIP technique. Magn Reson Med Sci. 2015;14:263–73.PubMed
46.
Fultz NE, Bonmassar G, Setsompop K, Stickgold RA, Rosen BR, Polimeni JR, et al. Coupled electrophysiological, hemodynamic, and cerebrospinal fluid oscillations in human sleep. Science (80- ). 2019;366:628–31.
47.
Matsumae M, Hirayama A, Atsumi H, Yatsushiro S, Kuroda K. Velocity and pressure gradients of cerebrospinal fluid assessed with magnetic resonance imaging-clinical article. J Neurosurg. 2014;120:218–27.PubMed
48.
Murtha LA, Yang Q, Parsons MW, Levi CR, Beard DJ, Spratt NJ, et al. Cerebrospinal fluid is drained primarily via the spinal canal and olfactory route in young and aged spontaneously hypertensive rats. Fluids Barriers CNS. 2014;11:12.PubMedPubMedCentral
49.
Iliff JJ, Lee H, Yu M, Feng T, Logan J, Nedergaard M, et al. Brain-wide pathway for waste clearance captured by contrast-enhanced MRI. J Clin Invest. 2013;123:1299–309.PubMedPubMedCentral
50.
Absinta M, Ha SK, Nair G, Sati P, Luciano NJ, Palisoc M, et al. Human and nonhuman primate meninges harbor lymphatic vessels that can be visualized noninvasively by MRI. Elife. 2017;6:e29738.
51.
Watts R, Steinklein JM, Waldman L, Zhou X, Filippi CG. Measuring glymphatic flow in man using quantitative contrast-enhanced MRI. Am J Neuroradiol. 2019;40:648–51.PubMed
52.
Suzuki K, Yamada K, Nakada K, Suzuki Y, Watanabe M, Kwee IL, et al. MRI characteristics of the glia limitans externa: a 7T study. Magn Reson Imaging. 2017;44:140–5.PubMed
53.
Gakuba C, Gaberel T, Goursaud S, Bourges J, D Palma C, Quenault A, et al. General anesthesia inhibits the activity of the “glymphatic system” Theranostics 2018;8:710–722.
54.
Benveniste H, Heerdt PM, Fontes M, Rothman DL, Volkow ND. Glymphatic system function in relation to anesthesia and sleep states. Anesth Analg. 2019;128:747–58.PubMed
55.
Benveniste H, Lee H, Ding F, Sun Q, Al-Bizri E, Makaryus R, et al. Anesthesia with dexmedetomidine and low-dose isoflurane increases solute transport via the glymphatic pathway in rat brain when compared with high-dose isoflurane. Anesthesiology. 2017;127:976–88.PubMedPubMedCentral
56.
Benveniste H, Liu X, Koundal S, Sanggaard S, Lee H, Wardlaw J. The Glymphatic system and waste clearance with brain aging: a review. Gerontology. 2019;65:106–19.PubMed
57.
Lundgaard I, Lu ML, Yang E, Peng W, Mestre H, Hitomi E, et al. Glymphatic clearance controls state-dependent changes in brain lactate concentration. J Cereb Blood Flow Metab. 2017;37:2112–24.PubMed
58.
Lundgaard I, Wang W, Eberhardt A, Vinitsky HS, Reeves BC, Peng S, et al. Beneficial effects of low alcohol exposure, but adverse effects of high alcohol intake on glymphatic function. Sci Rep 2018;8:2246.
59.
Taoka T, Jost G, Frenzel T, Naganawa S, Pietsch H. Impact of the glymphatic system on the kinetic and distribution of gadodiamide in the rat brain. Investig Radiol. 2018;53:529–34.
60.
Taoka T, Naganawa S. Glymphatic imaging using MRI. J Magn Reson Imaging. 2020;51:11–24.PubMed
61.
De Leon MJ, Li Y, Okamura N, Tsui WH, Saint-Louis LA, Glodzik L, et al. Cerebrospinal fluid clearance in Alzheimer disease measured with dynamic PET. J Nucl Med. 2017;58:1471–6.PubMedPubMedCentral
62.
Schubert JJ, Veronese M, Marchitelli L, Bodini B, Tonietto M, Stankoff B, et al. Dynamic 11C-PIB PET shows cerebrospinal fluid flow alterations in Alzheimer disease and multiple sclerosis. J Nucl Med. 2019;60:1452–60.PubMedPubMedCentral
63.
Smith AJ, Verkman AS. The “glymphatic” mechanism for solute clearance in Alzheimer’s disease: game changer or unproven speculation? FASEB J. 2018;32:543–51.PubMed
64.
Asgari M, De Zélicourt D, Kurtcuoglu V. Glymphatic solute transport does not require bulk flow. Sci Rep. 2016;6:38635.
65.
Kounda S, Elkin R, Nadeem S, Xue Y, Constantinou S, Sanggaard S, et al. Optimal mass transport with Lagrangian workflow reveals advective and diffusion driven solute transport in the glymphatic system. Sci Rep 2020;10:1990.
66.
Cai X, Qiao J, Kulkarni P, Harding IC, Ebong E, Ferris CF. Imaging the effect of the circadian light–dark cycle on the glymphatic system in awake rats. Proc Natl Acad Sci U S A. 2020;117:668–76.PubMed
67.
Hablitz LM, Vinitsky HS, Sun Q, Stæger FF, Sigurdsson B, Mortensen KN, et al. Increased glymphatic influx is correlated with high EEG delta power and low heart rate in mice under anesthesia. Sci Adv. 2019;5:eaav5447.
68.
Achariyar TM, Li B, Peng W, Verghese PB, Shi Y, McConnell E, et al. Glymphatic distribution of CSF-derived apoE into brain is isoform specific and suppressed during sleep deprivation. Mol Neurodegener 2016;11:74.
69.
70.
Gandhi GK, Cruz NF, Ball KK, Dienel GA. Astrocytes are poised for lactate trafficking and release from activated brain and for supply of glucose to neurons. J Neurochem. 2009;111:522–36.PubMedPubMedCentral
71.
Verkhratsky A, Nedergaard M. Physiology of astroglia. Physiol Rev. 2018;98:239–389.PubMed
72.
Brown RE, Basheer R, McKenna JT, Strecker RE, McCarley RW. Control of sleep and wakefulness. Physiol Rev. 2012;92:1087–187.PubMedPubMedCentral
73.
Cordone S, Annarumma L, Rossini PM, De Gennaro L. Sleep and β-amyloid deposition in Alzheimer disease: insights on mechanisms and possible innovative treatments. Front Pharmacol 2019;10:659.
74.
Ooms S, Overeem S, Besse K, Rikkert MO, Verbeek M, Claassen JAHR. Effect of 1 night of total sleep deprivation on cerebrospinal fluid β-amyloid 42 in healthy middle-aged men a randomized clinical trial. JAMA Neurol. 2014;71:971–7.PubMed
75.
Shokri-Kojori E, Wang GJ, Wiers CE, Demiral SB, Guo M, Kim SW, et al. β-Amyloid accumulation in the human brain after one night of sleep deprivation. Proc Natl Acad Sci U S A. 2018;115:4483–8.PubMedPubMedCentral
76.
Leenaars CHC, Savelyev SA, Van der Mierden S, Joosten RNJMA, Dematteis M, Porkka-Heiskanen T, et al. Intracerebral adenosine during sleep deprivation: a meta-analysis and new experimental data. J Circadian Rhythms. 2018;16:1–11.
77.
Kang JE, Lim MM, Bateman RJ, Lee JJ, Smyth LP, Cirrito JR, et al. Amyloid-β dynamics are regulated by orexin and the sleep-wake cycle. Science. 2009;326(80):1005–7.PubMedPubMedCentral
78.
Holth JK, Fritschi SK, Wang C, Pedersen NP, Cirrito JR, Mahan TE, et al. The sleep-wake cycle regulates brain interstitial fluid tau in mice and CSF tau in humans. Science. 2019;363(80):80–884.
79.
Noble W, Spires-Jones TL. Sleep well to slow Alzheimer’s progression? Sleep disruption promotes the spread of damaging tau pathology in Alzheimer’s disease. Science. 2019;363(80):813–4.PubMed
80.
81.
82.
Ribeiro-Rodrigues TM, Martins-Marques T, Morel S, Kwak BR, Girão H. Role of connexin 43 in different forms of intercellular communication-gap junctions, extracellular vesicles and tunnelling nanotubes. J Cell Sci. 2017;130:3619–30.PubMed
83.
Azevedo FAC, Carvalho LRB, Grinberg LT, Farfel JM, Ferretti REL, Leite REP, et al. Equal numbers of neuronal and nonneuronal cells make the human brain an isometrically scaled-up primate brain. J Comp Neurol. 2009;513:532–41.PubMed
84.
von Bartheld CS, Bahney J, Herculano-Houzel S. The search for true numbers of neurons and glial cells in the human brain: a review of 150 years of cell counting. J Comp Neurol. 2016;524:3865–95.
85.
Triacca V, Güç E, Kilarski WW, Pisano M, Swartz MA. Transcellular pathways in lymphatic endothelial cells regulate changes in solute transport by fluid stress. Circ Res. 2017;120:1440–52.PubMed
86.
Berridge CW, Schmeichel BE, España RA. Noradrenergic modulation of wakefulness/arousal. Sleep Med Rev. 2012;16:187–97.PubMedPubMedCentral
87.
Greene RW, Bjorness TE, Suzuki A. The adenosine-mediated, neuronal-glial, homeostatic sleep response. Curr Opin Neurobiol. 2017;44:236–42.PubMedPubMedCentral
88.
Hauglund NL, Pavan C, Nedergaard M. Cleaning the sleeping brain–the potential restorative function of the glymphatic system. Curr Opin Physiol. 2020;15:1–6.
89.
90.
Zuroff L, Daley D, Black KL, Koronyo-Hamaoui M. Clearance of cerebral Aβ in Alzheimer’s disease: reassessing the role of microglia and monocytes. Cell Mol Life Sci. 2017;74:2167–201.PubMedPubMedCentral
91.
Yamazaki Y, Zhao N, Caulfield TR, Liu CC, Bu G. Apolipoprotein E and Alzheimer disease: pathobiology and targeting strategies. Nat Rev Neurol. 2019;15:501–18.PubMedPubMedCentral
92.
Shi Y, Holtzman DM. Interplay between innate immunity and Alzheimer disease: APOE and TREM2 in the spotlight. Nat Rev Immunol. 2018;18:759–72.PubMedPubMedCentral
93.
Yeh FL, Hansen DV, Sheng M. TREM2, microglia, and neurodegenerative diseases. Trends Mol Med. 2017;23:512–33.PubMed
94.
95.
Mathys H, Davila-Velderrain J, Peng Z, Gao F, Mohammadi S, Young JZ, et al. Single-cell transcriptomic analysis of Alzheimer’s disease. Nature. 2019;570:332–7.PubMedPubMedCentral
96.
Guo JL, Lee VMY. Cell-to-cell transmission of pathogenic proteins in neurodegenerative diseases. Nat Med. 2014;20:130–8.PubMedPubMedCentral
97.
Peng C, Trojanowski JQ, Lee VMY. Protein transmission in neurodegenerative disease. Nat Rev Neurol. 2020;16:199–212.PubMed
98.
Vaquer-Alicea J, Diamond MI. Propagation of protein aggregation in neurodegenerative diseases. Annu Rev Biochem. 2019;88:785–810.PubMed
99.
Chen XQ, Mobley WC. Alzheimer disease pathogenesis: insights from molecular and cellular biology studies of oligomeric Aβ and tau species. Front Neurosci 2019;13:659.
100.
Canter RG, Penney J, Tsai LH. The road to restoring neural circuits for the treatment of Alzheimer’s disease. Nature. 2016;539:187–96.PubMed
101.
Španić E, Langer Horvat L, Hof PR, Šimić G. Role of microglial cells in Alzheimer’s disease tau propagation. Front Aging Neurosci. 2019;11:271.PubMedPubMedCentral
102.
Liddelow SA, Guttenplan KA, Clarke LE, Bennett FC, Bohlen CJ, Schirmer L, et al. Neurotoxic reactive astrocytes are induced by activated microglia. Nature. 2017;541:481–7.PubMedPubMedCentral
103.
Rothhammer V, Borucki DM, Tjon EC, Takenaka MC, Chao CC, Ardura-Fabregat A, et al. Microglial control of astrocytes in response to microbial metabolites. Nature. 2018;557:724–8.PubMedPubMedCentral
104.
Zott B, Simon MM, Hong W, Unger F, Chen-Engerer HJ, Frosch MP, et al. A vicious cycle of β amyloid−dependent neuronal hyperactivation. Science. 2019;365(80):559–65.PubMedPubMedCentral
105.
Busche MA, Wegmann S, Dujardin S, Commins C, Schiantarelli J, Klickstein N, et al. Tau impairs neural circuits, dominating amyloid-β effects, in Alzheimer models in vivo. Nat Neurosci. 2019;22:57–64.PubMed
106.
Götz J, Bodea LG, Goedert M. Rodent models for Alzheimer disease. Nat Rev Neurosci. 2018;19:583–98.PubMed
107.
van der Kant R, Goldstein LSB, Ossenkoppele R. Amyloid-β-independent regulators of tau pathology in Alzheimer disease. Nat Rev Neurosci. 2020;21:21–35.PubMed
108.
Hardy J, De Strooper B. Alzheimer’s disease: where next for anti-amyloid therapies? Brain. 2017;140:853–5.PubMed
109.
Gauthier S, Alam J, Fillit H, Iwatsubo T, Liu-Seifert H, Sabbagh M, et al. Combination therapy for Alzheimer’s disease: perspectives of the EU/US CTAD Task Force. J Prev Alzheimer’s Dis. 2019;6:164–8.
110.
Vander Zanden CM, Chi EY. Passive immunotherapies targeting amyloid beta and tau oligomers in Alzheimer’s disease. J Pharm Sci. 2020;109:68–73.PubMed
111.
Liu CC, Hu J, Zhao N, Wang J, Wang N, Cirrito JR, et al. Astrocytic LRP1 mediates brain Aβ clearance and impacts amyloid deposition. J Neurosci. 2017;37:4023–31.PubMedPubMedCentral
112.
Lee Y, Choi Y, Park E-J, Kwon S, Kim H, Lee JY, et al. Improvement of glymphatic-lymphatic drainage of beta-amyloid by focused ultrasound in Alzheimer’s disease model. bioRxiv 2020; Sci Rep in revision.
113.
Patel TK, Habimana-Griffin L, Gao X, Xu B, Achilefu S, Alitalo K, et al. Dural lymphatics regulate clearance of extracellular tau from the CNS. Mol Neurodegener. 2019;14:11.PubMedPubMedCentral
114.
Dupont G, Iwanaga J, Yilmaz E, Tubbs RS. Connections between amyloid beta and the meningeal lymphatics as a possible route for clearance and therapeutics. Lymphat Res Biol. 2020;18:2–6.PubMed
115.
Louveau A, Da Mesquita S, Kipnis J. Lymphatics in neurological disorders: a neuro-Lympho-vascular component of multiple sclerosis and Alzheimer’s disease? Neuron. 2016;91:957–73.PubMedPubMedCentral
116.
Romanova L, Philips H, Calip G, Hauser K, Peterson D, Lazarov O, et al. Energy-dependent transport at dural lymphatic vessels is necessary for Aβ brain clearance in Alzheimer’s disease. bioRxiv. 2019;427617.
117.
Yoffey JM, Drinker CK. The lymphatic pathway from the nose and pharynx: the absorption of dyes. J Exp Med. 1938;68:1–12.
118.
Larsen S, Landolt H, Berger W, Nedergaard M, Knudsen G, Holst S. Haplotype of the astrocytic water channel AQP4 modulates slow wave energy in human NREM sleep. PLoS Biology. 2020;18.5:e3000623.
119.
Jordão JF, Thévenot E, Markham-Coultes K, Scarcelli T, Weng YQ, Xhima K, et al. Amyloid-β plaque reduction, endogenous antibody delivery and glial activation by brain-targeted, transcranial focused ultrasound. Exp Neurol. 2013;248:16–29.PubMedPubMedCentral
120.
Burgess A, Dubey S, Yeung S, Hough O, Eterman N, Aubert I, et al. Alzheimer disease in a mouse model: Mr imaging-guided focused ultrasound targeted to the hippocampus opens the blood-brain barrier and improves pathologic abnormalities and behavior. Radiology. 2014;273:736–45.PubMedPubMedCentral
121.
Leinenga G, Götz J. Scanning ultrasound removes amyloid-b and restores memory in an Alzheimer’s disease mouse model. Sci Transl Med. 2015;7. 278:278ra33-278ra33.
122.
Poon CT, Shah K, Lin C, Tse R, Kim KK, Mooney S, et al. Time course of focused ultrasound effects on β-amyloid plaque pathology in the TgCRND8 mouse model of Alzheimer’s disease. Sci Rep. 2018;8:1–11.
123.
Karakatsani ME, Kugelman T, Ji R, Murillo M, Wang S, Niimi Y, et al. Unilateral focused ultrasound-induced blood-brain barrier opening reduces phosphorylated tau from the rTg4510 mouse model. Theranostics. 2019;9:5396–411.PubMedPubMedCentral
124.
Pandit R, Leinenga G, Götz J. Repeated ultrasound treatment of tau transgenic mice clears neuronal tau by autophagy and improves behavioral functions. Theranostics. 2019;9:3754–67.PubMedPubMedCentral
125.
Meng Y, Abrahao A, Heyn CC, Bethune AJ, Huang Y, Pople CB, et al. Glymphatics visualization after focused ultrasound-induced blood–brain barrier opening in humans. Ann Neurol. 2019;86:975–80.PubMed
126.
xu LD, He X, Wu D, Zhang Q, Yang C, yin LF, et al. Continuous theta burst stimulation facilitates the clearance efficiency of the glymphatic pathway in a mouse model of sleep deprivation. Neurosci Lett. 2017;653:189–94.PubMed
127.
Zeppenfeld DM, Simon M, Haswell JD, D’Abreo D, Murchison C, Quinn JF, et al. Association of perivascular localization of aquaporin-4 with cognition and Alzheimer disease in aging brains. JAMA Neurol. 2017;74:91–9.PubMed
128.
Gate D, Saligrama N, Leventhal O, Yang AC, Unger MS, Middeldorp J, et al. Clonally expanded CD8 T cells patrol the cerebrospinal fluid in Alzheimer’s disease. Nature. 2020;577:399–404.PubMedPubMedCentral
129.
Pan WR, Suami H, Taylor GI. Lymphatic drainage of the superficial tissues of the head and neck: anatomical study and clinical implications. Plast Reconstr Surg. 2008;121:1614–24.PubMed
130.
131.
Sakka L, Coll G, Chazal J. Anatomy and physiology of cerebrospinal fluid. Eur Ann Otorhinolaryngol Head Neck Dis. 2011;128:309–16.PubMed
132.
Herisson F, Frodermann V, Courties G, Rohde D, Sun Y, Vandoorne K, et al. Direct vascular channels connect skull bone marrow and the brain surface enabling myeloid cell migration. Nat Neurosci. 2018;21:1209–17.PubMedPubMedCentral
133.
Paasonen J, Stenroos P, Salo RA, Kiviniemi V, Gröhn O. Functional connectivity under six anesthesia protocols and the awake condition in rat brain. Neuroimage. 2018;172:9–20.PubMed
134.
Ringstad G, Vatnehol SAS, Eide PK. Glymphatic MRI in idiopathic normal pressure hydrocephalus. Brain. 2017;140:2691–705.PubMedPubMedCentral
Metadata
Title
Brain Glymphatic/Lymphatic Imaging by MRI and PET
Authors
Dong Soo Lee
Minseok Suh
Azmal Sarker
Yoori Choi
Publication date
01-10-2020
Publisher
Springer Singapore
Published in
Nuclear Medicine and Molecular Imaging / Issue 5/2020
Print ISSN: 1869-3474
Electronic ISSN: 1869-3482
DOI
https://doi.org/10.1007/s13139-020-00665-4

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