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Imaging the Perivascular Space as a Potential Biomarker of Neurovascular and Neurodegenerative Diseases

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Abstract

Although the brain lacks conventional lymphatic vessels found in peripheral tissue, evidence suggests that the space surrounding the vasculature serves a similar role in the clearance of fluid and metabolic waste from the brain. With aging, neurodegeneration, and cerebrovascular disease, these microscopic perivascular spaces can become enlarged, allowing for visualization and quantification on structural MRI. The purpose of this review is to: (i) describe some of the recent pre-clinical findings from basic science that shed light on the potential neurophysiological mechanisms driving glymphatic and perivascular waste clearance, (ii) review some of the pathobiological etiologies that may lead to MRI-visible enlarged perivascular spaces (ePVS), (iii) describe the possible clinical implications of ePVS, (iv) evaluate existing qualitative and quantitative techniques used for measuring ePVS burden, and (v) propose future avenues of research that may improve our understanding of this potential clinical neuroimaging biomarker for fluid and metabolic waste clearance dysfunction in neurodegenerative and neurovascular diseases.

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References

  • Adachi M, Hosoya T, Haku T, Yamaguchi K (1998) Dilated Virchow–Robin spaces: MRI pathological study. Neuroradiology 40:27–31

    Article  CAS  PubMed  Google Scholar 

  • Adams HH, Cavalieri M, Verhaaren BF et al (2013) Rating method for dilated Virchow–Robin spaces on magnetic resonance imaging. Stroke 44:1732–1735

    Article  CAS  PubMed  Google Scholar 

  • Aribisala BS, Wiseman S, Morris Z et al (2014) Circulating inflammatory markers are associated with magnetic resonance imaging-visible perivascular spaces but not directly with white matter hyperintensities. Stroke 45:605–607. doi:10.1161/STROKEAHA.113.004059

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Aspelund A, Antila S, Proulx ST et al (2015) A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules. J Exp Med 212:991–999

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bateman RJ, Munsell LY, Morris JC et al (2006) Human amyloid-beta synthesis and clearance rates as measured in cerebrospinal fluid in vivo. Nat Med 12:856–861

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Beckmann N, Schuler A, Mueggler T et al (2003) Age-dependent cerebrovascular abnormalities and blood flow disturbances in APP23 mice modeling Alzheimer’s disease. J Neurosci 23:8453–8459

    CAS  PubMed  Google Scholar 

  • Berezuk C, Ramirez J, Gao F et al (2015) Virchow–Robin spaces: correlations with polysomnography-derived sleep parameters. Sleep 38:853–858

    PubMed  PubMed Central  Google Scholar 

  • Black SE, Gao FQ, Bilbao J (2009) Understanding white matter disease: imaging-pathological correlations in vascular cognitive impairment. Stroke 40:S48–S52

    Article  PubMed  Google Scholar 

  • Bokura H, Kobayashi S, Yamaguchi S (1998) Distinguishing silent lacunar infarction from enlarged Virchow–Robin spaces: a magnetic resonance imaging and pathological study. J Neurol 245:116–122

    Article  CAS  PubMed  Google Scholar 

  • Braffman BH, Zimmerman RA, Trojanowski JQ et al (1988) Brain MR: pathologic correlation with gross and histopathology. 1. Lacunar infarction and Virchow–Robin spaces. AJR Am J Roentgenol 151:551–558

    Article  CAS  PubMed  Google Scholar 

  • Bucchieri F, Farina F, Zummo G, Cappello F (2015) Lymphatic vessels of the dura mater: a new discovery? J Anat 227:702–703

    Article  PubMed  Google Scholar 

  • Carare RO, Bernardes-Silva M, Newman TA et al (2008) 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 34:131–144

    Article  CAS  PubMed  Google Scholar 

  • Charidimou A, Meegahage R, Fox Z et al (2013) Enlarged perivascular spaces as a marker of underlying arteriopathy in intracerebral haemorrhage: a multicentre MRI cohort study. J Neurol Neurosurg Psychiatry 84:624–629

    Article  PubMed  PubMed Central  Google Scholar 

  • Charidimou A, Jaunmuktane Z, Baron JC et al (2014) White matter perivascular spaces: an MRI marker in pathology-proven cerebral amyloid angiopathy? Neurology 82:57–62. doi:10.1212/01.wnl.0000438225.02729.04

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Charidimou A, Hong YT, Jager HR et al (2015) White matter perivascular spaces on magnetic resonance imaging: marker of cerebrovascular amyloid burden? Stroke 46:1707–1709. doi:10.1161/STROKEAHA.115.009090

    Article  PubMed  Google Scholar 

  • Chen W, Song X, Zhang Y (2011) Assessment of the Virchow–Robin Spaces in Alzheimer disease, mild cognitive impairment, and normal aging, using high-field MR imaging. AJNR Am J Neuroradiol 32:1490–1495

    Article  CAS  PubMed  Google Scholar 

  • Chen A, Akinyemi RO, Hase Y et al (2016) Frontal white matter hyperintensities, clasmatodendrosis and gliovascular abnormalities in ageing and post-stroke dementia. Brain 139:242–258

    Article  PubMed  Google Scholar 

  • Cohen RM, Rezai-Zadeh K, Weitz TM et al (2013) A transgenic Alzheimer rat with plaques, tau pathology, behavioral impairment, oligomeric Aβ, and frank neuronal loss. J Neurosci 33:6245–6256

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Crossgrove JS, Li GJ, Zheng W (2005) The choroid plexus removes beta-amyloid from brain cerebrospinal fluid. Exp Biol Med (Maywood) 230:771–776

    CAS  Google Scholar 

  • Cueni LN, Detmar M (2008) The lymphatic system in health and disease. Lymphat Res Biol 6:109–122. doi:10.1089/lrb.2008.1008

    Article  PubMed  PubMed Central  Google Scholar 

  • Cumurciuc R, Guichard JP, Reizine D et al (2006) Dilation of Virchow–Robin spaces in CADASIL. Eur J Neurol 13:187–190

    Article  CAS  PubMed  Google Scholar 

  • Dorr A, Sahota B, Chinta LV et al (2012) Amyloid-beta-dependent compromise of microvascular structure and function in a model of Alzheimer’s disease. Brain 135:3039–3050

    Article  PubMed  Google Scholar 

  • Doubal FN, MacLullich AM, Ferguson KJ et al (2010) Enlarged perivascular spaces on MRI are a feature of cerebral small vessel disease. Stroke 41:450–454

    Article  PubMed  Google Scholar 

  • Echeverria V, Ducatenzeiler A, Alhonen L et al (2004) Rat transgenic models with a phenotype of intracellular Abeta accumulation in hippocampus and cortex. J Alzheimers Dis 6:209–219

    CAS  PubMed  Google Scholar 

  • Gao FQ, Swartz RH, Scheltens P et al (2011) Complexity of MRI white matter hyperintensity assessments in relation to cognition in aging and dementia from the Sunnybrook Dementia Study. J Alzheimers Dis 26(Suppl 3):379–388

    PubMed  Google Scholar 

  • Gao F, Keith J, Noor R et al (2014) Collagenosis of the deep medullary veins correlates with periventricular white matter changes in Alzheimer’s disease. Alzheimer’s Dement 10:P424

    Article  Google Scholar 

  • González-Marrero I, Giménez-Llort L, Johanson CE et al (2015) Choroid plexus dysfunction impairs beta-amyloid clearance in a triple transgenic mouse model of Alzheimer’s disease. Front Cell Neurosci 9:17

    Article  PubMed  PubMed Central  Google Scholar 

  • Gouw AA, Seewann A, van der Flier WM et al (2011) Heterogeneity of small vessel disease: a systematic review of MRI and histopathology correlations. J Neurol Neurosurg Psychiatry 82:126–135

    Article  PubMed  Google Scholar 

  • Groeschel S, Chong WK, Surtees R, Hanefeld F (2006) Virchow–Robin spaces on magnetic resonance images: normative data, their dilatation, and a review of the literature. Neuroradiology 48:745–754

    Article  PubMed  Google Scholar 

  • Hawkes CA, Hartig W, Kacza J et al (2011) Perivascular drainage of solutes is impaired in the ageing mouse brain and in the presence of cerebral amyloid angiopathy. Acta Neuropathol 121:431–443

    Article  PubMed  Google Scholar 

  • Hawkes CA, Sullivan PM, Hands S et al (2012) Disruption of arterial perivascular drainage of amyloid-β from the brains of mice expressing the human APOE ε4 allele. PLoS One 7:e41636

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hawkes CA, Jayakody N, Johnston DA et al (2014) Failure of perivascular drainage of β-amyloid in cerebral amyloid angiopathy. Brain Pathol 24:396–403

    Article  CAS  PubMed  Google Scholar 

  • Heier LA, Bauer CJ, Schwartz L et al (1989) Large Virchow–Robin spaces: MR-clinical correlation. Am J Neuroradiol 10:929–936

    CAS  PubMed  Google Scholar 

  • Hernandez MD, Piper RJ, Wang X et al (2013) Towards the automatic computational assessment of enlarged perivascular spaces on brain magnetic resonance images: A systematic review. J Magn Reson Imaging 38(4):774–785

    Article  Google Scholar 

  • Hladky SB, Barrand MA (2014) Mechanisms of fluid movement into, through and out of the brain: evaluation of the evidence. Fluids Barriers CNS 11:26

    Article  PubMed  PubMed Central  Google Scholar 

  • Huang Y, Potter R, Sigurdson W et al (2012) Effects of age and amyloid deposition on Aβ dynamics in the human central nervous system. Arch Neurol 69:51–58

    Article  PubMed  PubMed Central  Google Scholar 

  • Iliff JJ, Nedergaard M (2013) Is there a cerebral lymphatic system? Stroke 44:S93–S95. doi:10.1161/STROKEAHA.112.678698

    Article  PubMed  PubMed Central  Google Scholar 

  • Iliff JJ, Wang M, Liao Y et al (2012) A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid beta. Sci Transl Med 4:147ra111

    PubMed  PubMed Central  Google Scholar 

  • Iliff JJ, Wang M, Zeppenfeld DM et al (2013) Cerebral arterial pulsation drives paravascular CSF-interstitial fluid exchange in the murine brain. J Neurosci 33:18190–18199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jessen NA, Munk ASF, Lundgaard I, Nedergaard M (2015) The glymphatic system: a beginner’s guide. Neurochem Res 40(12):2583–2599

    Article  CAS  PubMed  Google Scholar 

  • Johnston M, Zakharov A, Papaiconomou C et al (2004) Evidence of connections between cerebrospinal fluid and nasal lymphatic vessels in humans, non-human primates and other mammalian species. Cerebrospinal Fluid Res 1:2

    Article  PubMed  PubMed Central  Google Scholar 

  • Johnston M, Armstrong D, Koh L (2007) Possible role of the cavernous sinus veins in cerebrospinal fluid absorption. Cerebrospinal Fluid Res 4:3. doi:10.1186/1743-8454-4-3

    Article  PubMed  PubMed Central  Google Scholar 

  • Kalaria RN (2002) Small vessel disease and Alzheimer’s dementia: pathological considerations. Cerebrovasc Dis 13(Suppl 2):48–52

    Article  CAS  PubMed  Google Scholar 

  • Kang J-E, Lim MM, Bateman RJ et al (2009) Amyloid-beta dynamics are regulated by orexin and the sleep-wake cycle. Science 326:1005–1007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kress BT, Iliff JJ, Xia M et al (2014) Impairment of paravascular clearance pathways in the aging brain. Ann Neurol 76:845–861

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lai AY, Dorr A, Thomason LAM et al (2015) Venular degeneration leads to vascular dysfunction in a transgenic model of Alzheimer’s disease. Brain 138:1046–1058

    Article  PubMed  Google Scholar 

  • Liao S, Padera TP (2013) Lymphatic function and immune regulation in health and disease. Lymphat Res Biol 11:136–143. doi:10.1089/lrb.2013.0012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lim ASP, Yu L, Schneider JA, et al (2016) Sleep fragmentation, cerebral arteriolosclerosis, and brain infarct pathology in community-dwelling older people. Stroke STROKEAHA.115.011608

  • Louveau A, Smirnov I, Keyes TJ et al (2015) Structural and functional features of central nervous system lymphatic vessels. Nature 523:337–341. doi:10.1038/nature14432

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lucey BP, Bateman RJ (2014) Amyloid-β diurnal pattern: possible role of sleep in Alzheimer’s disease pathogenesis. Neurobiol Aging 35S2:S29–S34. doi: 10.1016/j.neurobiolaging.2014.03.035

  • MacLullich AM, Wardlaw JM, Ferguson KJ et al (2004) Enlarged perivascular spaces are associated with cognitive function in healthy elderly men. J Neurol Neurosurg Psychiatry 75:1519–1523

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maia LF, Kaeser SA, Reichwald J et al (2013) Changes in amyloid-β and Tau in the cerebrospinal fluid of transgenic mice overexpressing amyloid precursor protein. Sci Transl Med 5:194re2

    PubMed  Google Scholar 

  • Mantyla R, Erkinjuntti T, Salonen O et al (1997) Variable agreement between visual rating scales for white matter hyperintensities on MRI. Comparison of 13 rating scales in a poststroke cohort. Stroke 28:1614–1623

    Article  CAS  PubMed  Google Scholar 

  • Martinez-Ramirez S, Pontes-Neto OM, Dumas AP et al (2013) Topography of dilated perivascular spaces in subjects from a memory clinic cohort. Neurology 80:1551–1556

    Article  PubMed  PubMed Central  Google Scholar 

  • Meyer EP, Ulmann-Schuler A, Staufenbiel M, Krucker T (2008) Altered morphology and 3D architecture of brain vasculature in a mouse model for Alzheimer’s disease. Proc Natl Acad Sci USA 105:3587–3592

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mezey É, Palkovits M (2015) Neuroanatomy: forgotten findings of brain lymphatics. Nature 524:415

    Article  CAS  PubMed  Google Scholar 

  • Michaud J-P, Bellavance M-A, Préfontaine P, Rivest S (2013) Real-time in vivo imaging reveals the ability of monocytes to clear vascular amyloid beta. Cell Rep 5:646–653

    Article  CAS  PubMed  Google Scholar 

  • Mills S, Cain J, Purandare N, Jackson A (2007) Biomarkers of cerebrovascular disease in dementia. Br J Radiol 80 Spec No:S128–S145

  • Moody DM, Brown WR, Challa VR, Anderson RL (1995) Periventricular venous collagenosis: association with leukoaraiosis. Radiology 194:469–476

    Article  CAS  PubMed  Google Scholar 

  • Nedergaard M (2013) Garbage truck of the brain. Science (80-) 340:1529–1530. doi:10.1126/science.1240514

    Article  CAS  Google Scholar 

  • Pantoni L (2010) Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol 9:689–701

    Article  PubMed  Google Scholar 

  • Papisov MI, Belov VV, Gannon KS (2013) Physiology of the intrathecal bolus: the leptomeningeal route for macromolecule and particle delivery to CNS. Mol Pharm 10:1522–1532

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Patankar TF, Mitra D, Varma A et al (2005) Dilatation of the Virchow–Robin space is a sensitive indicator of cerebral microvascular disease: study in elderly patients with dementia. Am J Neuroradiol 26:1512–1520

    PubMed  Google Scholar 

  • Poirier J, Derouesne C (1984) Cerebral lacunae. A proposed new classification. Clin Neuropathol 3:266

    CAS  PubMed  Google Scholar 

  • Potter GM, Doubal FN, Jackson CA et al (2013) Enlarged perivascular spaces and cerebral small vessel disease. Int J Stroke 10(3):376–381

    Article  PubMed  PubMed Central  Google Scholar 

  • Potter GM, Chappell FM, Morris Z, Wardlaw JM (2015) Cerebral perivascular spaces visible on magnetic resonance imaging: development of a qualitative rating scale and its observer reliability. Cerebrovasc Dis 39:224–231

    Article  PubMed  PubMed Central  Google Scholar 

  • Preston SD, Steart PV, Wilkinson A et al (2003) Capillary and arterial cerebral amyloid angiopathy in Alzheimer’s disease: defining the perivascular route for the elimination of amyloid beta from the human brain. Neuropathol Appl Neurobiol 29:106–117

    Article  CAS  PubMed  Google Scholar 

  • Ramirez J, Berezuk C, McNeely AA et al (2015) Visible Virchow–Robin spaces on magnetic resonance imaging of Alzheimer’s disease patients and normal elderly from the sunnybrook dementia study. J Alzheimers Dis 43:415–424

    PubMed  Google Scholar 

  • Redzic ZB, Segal MB (2004) The structure of the choroid plexus and the physiology of the choroid plexus epithelium. Adv Drug Deliv Rev 56:1695–1716

    Article  CAS  PubMed  Google Scholar 

  • Rennels ML, Gregory TF, Blaumanis OR et al (1985) Evidence for a “paravascular” fluid circulation in the mammalian central nervous system, provided by the rapid distribution of tracer protein throughout the brain from the subarachnoid space. Brain Res 326:47–63

    Article  CAS  PubMed  Google Scholar 

  • Roh JH, Huang Y, Bero AW et al (2012) Disruption of the sleep-wake cycle and diurnal fluctuation of β-amyloid in mice with Alzheimer’s disease pathology. Sci Transl Med 4:150ra122

    PubMed  PubMed Central  Google Scholar 

  • Roher AE, Esh C, Kokjohn TA et al (2003) Circle of willis atherosclerosis is a risk factor for sporadic Alzheimer’s disease. Arterioscler Thromb Vasc Biol 23:2055–2062

    Article  CAS  PubMed  Google Scholar 

  • Rothman SM, Herdener N, Frankola KA et al (2013) Chronic mild sleep restriction accentuates contextual memory impairments, and accumulations of cortical Aβ and pTau in a mouse model of Alzheimer’s disease. Brain Res 1529:200–208

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rouhl RP, van Oostenbrugge RJ, Knottnerus IL et al (2008) Virchow–Robin spaces relate to cerebral small vessel disease severity. J Neurol 255:692–696

    Article  CAS  PubMed  Google Scholar 

  • Ruiz-Opazo N, Kosik KS, Lopez LV et al (2014) Attenuated hippocampus-dependent learning and memory decline in transgenic TgAPPswe Fischer-344 rats. Mol Med 10:36–44

    Google Scholar 

  • Santos-Galindo M, Acaz-Fonseca E, Bellini MJ, Garcia-Segura LM (2011) Sex differences in the inflammatory response of primary astrocytes to lipopolysaccharide. Biol Sex Differ 2:7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schley D, Carare-Nnadi R, Please CP et al (2006) Mechanisms to explain the reverse perivascular transport of solutes out of the brain. J Theor Biol 238:962–974

    Article  CAS  PubMed  Google Scholar 

  • Selvarajah J, Scott M, Stivaros S et al (2009) Potential surrogate markers of cerebral microvascular angiopathy in asymptomatic subjects at risk of stroke. EurRadiol 19:1011–1018

    Google Scholar 

  • Szentistványi I, Patlak CS, Ellis RA, Cserr HF (1984) Drainage of interstitial fluid from different regions of rat brain. Am J Physiol 246:F835–F844

    PubMed  Google Scholar 

  • Tarasoff-Conway JM, Carare RO, Osorio RS et al (2015) Clearance systems in the brain-implications for Alzheimer disease. Nat Rev Neurol 11:457–470

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thore CR, Anstrom JA, Moody DM et al (2007) Morphometric analysis of arteriolar tortuosity in human cerebral white matter of preterm, young, and aged subjects. J Neuropathol Exp Neurol 66:337–345

    Article  PubMed  Google Scholar 

  • Udaka F, Sawada H, Kameyama M (2002) White matter lesions and dementia: MRI-pathological correlation. Ann N Y Acad Sci 977:411–415

    Article  PubMed  Google Scholar 

  • van den Heuvel DM, ten Dam V, de Craen AJ et al (2006) Measuring longitudinal white matter changes: comparison of a visual rating scale with a volumetric measurement. AJNR Am J Neuroradiol 27:875–878

    PubMed  Google Scholar 

  • van Veluw SJ, Biessels GJ, Bouvy WH et al (2015) Cerebral amyloid angiopathy severity is linked to dilation of juxtacortical perivascular spaces. J. Cereb, Blood Flow Metab

    Google Scholar 

  • Wang Z, Ying Z, Bosy-Westphal A et al (2012) Evaluation of specific metabolic rates of major organs and tissues: comparison between nonobese and obese women. Obes (Silver Spring) 20:95–100. doi:10.1016/j.biotechadv.2011.08.021.Secreted

    Article  CAS  Google Scholar 

  • Wang X, Valdés Hernández MDC, Doubal F et al (2016) Development and initial evaluation of a semi-automatic approach to assess perivascular spaces on conventional magnetic resonance images. J Neurosci Methods 257:34–44

    Article  PubMed  PubMed Central  Google Scholar 

  • Wardlaw JM, Smith EE, Biessels GJ et al (2013) Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol 12:822–838

    Article  PubMed  PubMed Central  Google Scholar 

  • Weller RO, Subash M, Preston SD et al (2008) Perivascular drainage of amyloid-beta peptides from the brain and its failure in cerebral amyloid angiopathy and Alzheimer’s disease. Brain Pathol 18:253–266

    Article  CAS  PubMed  Google Scholar 

  • Weller RO, Boche D, Nicoll JA (2009a) Microvasculature changes and cerebral amyloid angiopathy in Alzheimer’s disease and their potential impact on therapy. Acta Neuropathol 118:87–102

    Article  CAS  PubMed  Google Scholar 

  • Weller RO, Djuanda E, Yow H-Y, Carare RO (2009b) Lymphatic drainage of the brain and the pathophysiology of neurological disease. Acta Neuropathol 117:1–14

    Article  CAS  PubMed  Google Scholar 

  • Weller RO, Hawkes CA, Kalaria RN et al (2015) White matter changes in dementia: role of impaired drainage of interstitial fluid. Brain Pathol 25:63–78

    Article  PubMed  Google Scholar 

  • Wuerfel J, Haertle M, Waiczies H et al (2008) Perivascular spaces—MRI marker of inflammatory activity in the brain? Brain 131:2332–2340

    Article  PubMed  Google Scholar 

  • Xie L, Kang H, Xu Q et al (2013) Sleep drives metabolite clearance from the adult brain. Science 342:373–377

    Article  CAS  PubMed  Google Scholar 

  • Yaffe K, Laffan AM, Harrison SL et al (2011) Sleep-disordered breathing, hypoxia, and risk of mild cognitive impairment and dementia in older women. JAMA 306:613–619

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang ET, Inman CB, Weller RO (1990) Interrelationships of the pia mater and the perivascular (Virchow–Robin) spaces in the human cerebrum. J Anat 170:111–123

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhu YC, Tzourio C, Soumare A et al (2010) Severity of dilated Virchow–Robin spaces is associated with age, blood pressure, and MRI markers of small vessel disease: a population-based study. Stroke 41:2483–2490

    Article  PubMed  Google Scholar 

  • Zhu YC, Dufouil C, Mazoyer B et al (2011) Frequency and location of dilated Virchow–Robin spaces in elderly people: a population-based 3D MR imaging study. AJNR Am J Neuroradiol 32:709–713

    Article  PubMed  Google Scholar 

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Acknowledgments

The authors gratefully acknowledge financial support from the Canadian Institutes of Health Research (MOP#13129; MOP#142367), the Alzheimer Society of Canada and Alzheimer Association (US), the Heart and Stroke Foundation Canadian Partnership for Stroke Recovery (HSFCPSR), Hurvitz Brain Sciences Research program at Sunnybrook Research Institute, and the Linda C. Campbell Foundation. JR receives partial funding support from the Canadian Vascular Network. JR, CB, AAM, and FQG receive salary support from HSFCPSR and SEB from the Sunnybrook Research Institute, Brill Chair in Neurology Department of Medicine, Sunnybrook Health Sciences Centre and University of Toronto, Department of Medicine (Neurology) Sunnybrook Health Sciences Centre, and the Toronto Dementia Research Alliance.

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    Authors and Affiliations

    1. LC Campbell Cognitive Neurology Research Unit, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Toronto, ON, Canada, M4N 3M5

      Joel Ramirez, Courtney Berezuk, Alicia A. McNeely, Fuqiang Gao & Sandra E. Black

    2. Heart & Stroke Foundation Canadian Partnership for Stroke Recovery, Sunnybrook Health Sciences Centre (SHSC), Toronto, ON, Canada

      Joel Ramirez, Courtney Berezuk, Alicia A. McNeely, Fuqiang Gao & Sandra E. Black

    3. Department of Medicine, Neurology (SHSC), Institute of Medical Science, University of Toronto, Toronto, ON, Canada

      Sandra E. Black

    4. Department of Biological Sciences, Sunnybrook Research Institute, Toronto, ON, Canada

      JoAnne McLaurin

    5. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada

      JoAnne McLaurin

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    Correspondence to Joel Ramirez.

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    Joel Ramirez and Courtney Berezuk have contributed equally to this work.

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    Ramirez, J., Berezuk, C., McNeely, A.A. et al. Imaging the Perivascular Space as a Potential Biomarker of Neurovascular and Neurodegenerative Diseases. Cell Mol Neurobiol 36, 289–299 (2016). https://doi.org/10.1007/s10571-016-0343-6

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