Volume 33, Issue 1 pp. 102-108

CLINICAL INVESTIGATIVE STUDY

High-resolution MRI to noninvasively characterize drainage around the carotid artery into the cervical lymph nodes

Zafer Keser,

Zafer Keser

orcid.org/0000-0001-6415-0874

Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA

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Garrett Smith,

Garrett Smith

Department of Radiology, College of Medicine, University of Florida, Gainesville, Florida, USA

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Emin Cagil,

Emin Cagil

Department of Neurosurgery, Ankara Numune Training and Research Hospital, Ankara, Turkey

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Fatih Tufan,

Fatih Tufan

Geriatrician (PP), Silivrikapi Mh. Hisaralti Cd, Istanbul, Turkey

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Onder Albayram,

Onder Albayram

Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, South Carolina, USA

Department of Neuroscience, Medical University of South Carolina, Charleston, South Carolina, USA

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Mehmet Sait Albayram,

Corresponding Author

Mehmet Sait Albayram

[email protected]

Department of Radiology, College of Medicine, University of Florida, Gainesville, Florida, USA

Correspondence

Mehmet Sait Albayram, Department of Radiology, College of Medicine, University of Florida, PO Box 100374, Gainesville, FL 32610, USA.

Email: [email protected]

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Zafer Keser,

Zafer Keser

orcid.org/0000-0001-6415-0874

Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA

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Garrett Smith,

Garrett Smith

Department of Radiology, College of Medicine, University of Florida, Gainesville, Florida, USA

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Emin Cagil,

Emin Cagil

Department of Neurosurgery, Ankara Numune Training and Research Hospital, Ankara, Turkey

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Fatih Tufan,

Fatih Tufan

Geriatrician (PP), Silivrikapi Mh. Hisaralti Cd, Istanbul, Turkey

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Onder Albayram,

Onder Albayram

Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, South Carolina, USA

Department of Neuroscience, Medical University of South Carolina, Charleston, South Carolina, USA

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Mehmet Sait Albayram,

Corresponding Author

Mehmet Sait Albayram

[email protected]

Department of Radiology, College of Medicine, University of Florida, Gainesville, Florida, USA

Correspondence

Mehmet Sait Albayram, Department of Radiology, College of Medicine, University of Florida, PO Box 100374, Gainesville, FL 32610, USA.

Email: [email protected]

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First published: 02 October 2022

https://doi.org/10.1111/jon.13056

Citations: 1

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Abstract

Background and Purpose

Previous studies have proposed multiple parallel channels for waste clearance from the brain, though many gaps remain in our understanding of these systems. In this study, we examined periarterial fluid drainage around intracranial and extracranial segments of the internal carotid arteries (ICAs) from the brain into the cervical lymph nodes using a noninvasive and clinical-based method.

Methods

Eighty-one subjects (45 females, aged 15-80 years old) with nonlesioned epilepsy underwent high-resolution 3-dimensional T2-weighted fluid-attenuated inversion recovery (FLAIR) MRI. We utilized a noninvasive and clinical-based method with a manual semiautomated approach to characterize the periarterial lymphatic system's maximum thickness and signal intensities along the ICAs using high-resolution 3-dimensional FLAIR imaging. We conducted group comparisons and correlation analyses to investigate sex- and age-based trends. Results were corrected with Bonferroni's test for multiple comparisons, and we performed power analysis for sample size calculations.

Results

Using high-resolution FLAIR images, we show evidence that fluid drainage emerges around the ICA petrous segment and joins lymphatic flow from cranial nerves in the upper neck, with this flow ultimately draining into the cervical lymph nodes bilaterally. Lymphatic signal at the petrous segment level was significantly thinner in females compared to males bilaterally (w = 413, p = .0001 on the right, w = 356, p < .0001 on the left). Lymphatic drainage around the petrous segments of the ICAs bilaterally was thicker with age in males but not in females.

Conclusions

We describe the in vivo high-resolution imaging characteristics of periarterial fluid drainage along the vessel walls of ICAs. This represents a potentially major channel for brain waste clearance. We also report interesting sex- and age-based trends in these structures within our cohort.

REFERENCES

1Klostranec JM, Vucevic D, Bhatia KD, et al. Current concepts in intracranial interstitial fluid transport and the glymphatic system: part II-imaging techniques and clinical applications. Radiology 2021; 301: 516-32.
10.1148/radiol.2021204088
PubMed Web of Science® Google Scholar
2Carare RO, Aldea R, Agarwal N, et al. Clearance of interstitial fluid (ISF) and CSF (CLIC) group-part of vascular Professional Interest Area (PIA): cerebrovascular disease and the failure of elimination of amyloid-β from the brain and retina with age and Alzheimer's disease-opportunities for therapy. Alzheimers Dement 2020; 12:e12053.
10.1002/dad2.12053
Web of Science® Google Scholar
3Mato M, Ookawara S. Influences of age and vasopressin on the uptake capacity of fluorescent granular perithelial cells (FGP) of small cerebral vessels of the rat. Am J Anat 1981; 162: 45-53.
10.1002/aja.1001620105
CAS PubMed Web of Science® Google Scholar
4Bulat M, Klarica M. Recent insights into a new hydrodynamics of the cerebrospinal fluid. Brain Res Rev 2011; 65: 99-112.
10.1016/j.brainresrev.2010.08.002
PubMed Web of Science® Google Scholar
5Gouveia-Freitas K, Bastos-Leite AJ. Perivascular spaces and brain waste clearance systems: relevance for neurodegenerative and cerebrovascular pathology. Neuroradiology 2021; 63: 1581-97.
10.1007/s00234-021-02718-7
PubMed Web of Science® Google Scholar
6Weller RO, Subash M, Preston SD, et al. Perivascular drainage of amyloid-beta peptides from the brain and its failure in cerebral amyloid angiopathy and Alzheimer's disease. Brain Pathol 2008; 18: 253-66.
10.1111/j.1750-3639.2008.00133.x
CAS PubMed Web of Science® Google Scholar
7Mestre H, Kostrikov S, Mehta RI, et al. Perivascular spaces, glymphatic dysfunction, and small vessel disease. Clin Sci 2017; 131: 2257-74.
10.1042/CS20160381
CAS PubMed Web of Science® Google Scholar
8Agarwal N, Carare RO. Cerebral vessels: an overview of anatomy, physiology, and role in the drainage of fluids and solutes. Front Neurol 2020; 11:611485.
10.3389/fneur.2020.611485
PubMed Web of Science® Google Scholar
9Diem AK, Macgregor Sharp M, Gatherer M, et al. Arterial pulsations cannot drive intramural periarterial drainage: significance for Aβ drainage. Front Neurosci 2017; 11: 475.
10.3389/fnins.2017.00475
PubMed Web of Science® Google Scholar
10Diem AK, Carare RO, Weller RO, et al. A control mechanism for intra-mural peri-arterial drainage via astrocytes: how neuronal activity could improve waste clearance from the brain. PLoS ONE 2018; 13:e0205276.
10.1371/journal.pone.0205276
PubMed Web of Science® Google Scholar
11Aldea R, Weller RO, Wilcock DM, et al. Cerebrovascular smooth muscle cells as the drivers of intramural periarterial drainage of the brain. Front Aging Neurosci 2019; 11: 1.
10.3389/fnagi.2019.00001
CAS PubMed Web of Science® Google Scholar
12Kutkut I, Meens MJ, Mckee TA, et al. Lymphatic vessels: an emerging actor in atherosclerotic plaque development. Eur J Clin Invest 2015; 45: 100-8.
10.1111/eci.12372
PubMed Web of Science® Google Scholar
13Ueno M, Chiba Y, Murakami R, et al. Disturbance of intracerebral fluid clearance and blood-brain barrier in vascular cognitive impairment. Int J Mol Sci 2019; 20: 2600.
10.3390/ijms20102600
CAS PubMed Web of Science® Google Scholar
14Macgregor Sharp M, Saito S, Keable A, et al. Demonstrating a reduced capacity for removal of fluid from cerebral white matter and hypoxia in areas of white matter hyperintensity associated with age and dementia. Acta Neuropathol Commun 2020; 8: 131.
10.1186/s40478-020-01009-1
CAS PubMed Web of Science® Google Scholar
15Weller RO, Galea I, Carare RO, et al. Pathophysiology of the lymphatic drainage of the central nervous system: implications for pathogenesis and therapy of multiple sclerosis. Pathophysiology 2010; 17: 295-306.
10.1016/j.pathophys.2009.10.007
CAS PubMed Google Scholar
16Varatharaj A, Carare RO, Weller RO, et al. Gadolinium enhancement of cranial nerves: implications for interstitial fluid drainage from brainstem into cranial nerves in humans. Proc Natl Acad Sci USA 2021; 118:e2106331118.
10.1073/pnas.2106331118
CAS PubMed Web of Science® Google Scholar
17Albayram MS, Smith G, Tufan F, et al. Non-invasive MR imaging of human brain lymphatic networks with connections to cervical lymph nodes. Nat Commun 2022; 13: 203.
10.1038/s41467-021-27887-0
CAS PubMed Web of Science® Google Scholar
18Aspelund A, Antila S, Proulx ST, et al. A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules. J Exp Med 2015; 212: 991-9.
10.1084/jem.20142290
CAS PubMed Web of Science® Google Scholar
19Chen X, Liu X, Koundal S, et al. Cerebral amyloid angiopathy is associated with glymphatic transport reduction and time-delayed solute drainage along the neck arteries. Nature Aging 2022; 2: 214-23.
10.1038/s43587-022-00181-4
PubMed Google Scholar
20Clapham R, O'Sullivan E, Weller RO, et al. Cervical lymph nodes are found in direct relationship with the internal carotid artery: significance for the lymphatic drainage of the brain. Clin Anat 2010; 23: 43-7.
10.1002/ca.20887
CAS PubMed Web of Science® Google Scholar
21Zolla V, Nizamutdinova IT, Scharf B, et al. Aging-related anatomical and biochemical changes in lymphatic collectors impair lymph transport, fluid homeostasis, and pathogen clearance. Aging Cell 2015; 14: 582-94.
10.1111/acel.12330
CAS PubMed Web of Science® Google Scholar
22Gashev AA, Chatterjee V. Aged lymphatic contractility: recent answers and new questions. Lymphat Res Biol 2013; 11: 2-13.
10.1089/lrb.2013.0003
PubMed Web of Science® Google Scholar
23Carare RO, Bernardes-Silva M, Newman TA, et al. Solutes, but not cells, drain from the brain parenchyma along basement membranes of capillaries and arteries: significance for cerebral amyloid angiopathy and neuroimmunology. Neuropathol Appl Neurobiol 2008; 34: 131-44.
10.1111/j.1365-2990.2007.00926.x
CAS PubMed Web of Science® Google Scholar
24Arbel-Ornath M, Hudry E, Eikermann-Haerter K, et al. Interstitial fluid drainage is impaired in ischemic stroke and Alzheimer's disease mouse models. Acta Neuropathol 2013; 126: 353-64.
10.1007/s00401-013-1145-2
CAS PubMed Web of Science® Google Scholar
25Eide PK, Ringstad G. MRI with intrathecal MRI gadolinium contrast medium administration: a possible method to assess glymphatic function in human brain. Acta Radiol Open 2015; 4:2058460115609635.
10.1177/2058460115609635
Web of Science® Google Scholar
26Deike-Hofmann K, Reuter J, Haase R, et al. Glymphatic pathway of gadolinium-based contrast agents through the brain: overlooked and misinterpreted. Invest Radiol 2019; 54: 229-37.
10.1097/RLI.0000000000000533
CAS PubMed Web of Science® Google Scholar
27Jacob L, De Brito Neto J, Lenck S, et al. Conserved meningeal lymphatic drainage circuits in mice and humans. J Exp Med 2022; 219:e20220035.
10.1084/jem.20220035
CAS PubMed Web of Science® Google Scholar
28Taoka T, Masutani Y, Kawai H, et al. Evaluation of glymphatic system activity with the diffusion MR technique: diffusion tensor image analysis along the perivascular space (DTI-ALPS) in Alzheimer's disease cases. Jpn J Radiol 2017; 35: 172-8.
10.1007/s11604-017-0617-z
PubMed Web of Science® Google Scholar
29Wong SM, Backes WH, Drenthen GS, et al. Spectral diffusion analysis of intravoxel incoherent motion MRI in cerebral small vessel disease. J Magn Reson Imaging 2020; 51: 1170-80.
10.1002/jmri.26920
PubMed Web of Science® Google Scholar
30Ahn JH, Cho H, Kim J-H, et al. Meningeal lymphatic vessels at the skull base drain cerebrospinal fluid. Nature 2019; 572: 62-66.
10.1038/s41586-019-1419-5
CAS PubMed Web of Science® Google Scholar
31Johnston M, Armstrong D, Koh L. Possible role of the cavernous sinus veins in cerebrospinal fluid absorption. Cerebrospinal Fluid Res 2007; 4: 3.
10.1186/1743-8454-4-3
PubMed Google Scholar

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Volume33, Issue1

January/February 2023

Pages 102-108

High-resolution MRI to noninvasively characterize drainage around the carotid artery into the cervical lymph nodes

Abstract

Background and Purpose

Methods

Results

Conclusions

REFERENCES

Citing Literature

References

Information

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High-resolution MRI to noninvasively characterize drainage around the carotid artery into the cervical lymph nodes

Abstract

Background and Purpose

Methods

Results

Conclusions

REFERENCES

Citing Literature

References

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