7T IMAGES PERIVASCULAR SPACES: Anatomy, Pathology and 7T Imaging

Anne G. Osborn, M.D.

TERMINOLOGY PERIVASCULAR SPACES Anatomic Classification • Type I • Synonyms • Along LSAs • Perivascular spaces (PVS) • Through anterior perforated substance • Intramural periarterial drainage • (around anterior commissure) • Virchow-Robin spaces (VRSs) • Most common location visible on MR • Paravascular spaces • Type II • Perivascular vs. paravascular? PVSs! • Along perforating medullary • Through cortical gray matter, subcortical WM II • Definitions • Over high convexities • Pial-lined (not arachnoid) • Type III • Accompany vessels • Along penetrating collicular arteries • Entering (penetrating arteries) or • Pontomesencephalic junction • Leaving brain (draining ) • , thalami I • Filled with interstitial fluid (ISF) • Caveat • Not CSF! • “Can be seen throughout brain wherever vessels are present” I • Don’t connect with the subarachnoid space Kwee et al: Virchow-Robin spaces at MR imaging. Radiographics 27: 1071-86, 2007

LOCATION OF PVSs ROLE OF PVSs Post-mortem air (clostridium) in PVSs Key Component of Brain “Glymphatics” • Glymphatics • Brain-wide pathway (the brain’s “garbage truck”) • Facilitates fluid (CSF-ISF) exchange • Occurs within brain parenchyma • Probably mediated by AQP4 channels • Clears solutes from brain • ISF drainage via PVSs • Into paravascular, perineural spaces • Increases during sleep • Clears interstitial solutes (e.g., β-amyloid etc) • IV GBCAs normally enter brain along cortical PVSs

Rasmussen MK et al: The glymphatic pathway in neurological disorders. Lancet Neurol 17: 1016-24, 2018 Naganawa S et al: Glymphatic system: Review of challenges visualizing structure and function with imaging using MRI. Magn Reson Med Sci 2020 Nov 27 ePub ahead of print Deike-Hofmann K et al: Glymphatic pathway of gadolinium-based contrast agents through the brain: Overlooked and misinterpreted. Invest Radiol 54: 229-237, 2019

Page 1 PERIVASCULAR SPACES AT 1.5T PERIVASCULAR SPACES AT 3T • Imaging appearance • ~100% of normal cases • Round/ovoid/linear/tubular • Smooth, not irregular • Most (not all!) are ≤2 mm • Often appear in variably-sized clusters • Asymmetry common • Signal intensity • Follows CSF on all sequences • 75% suppress completely on FLAIR • ~25% have hyperintense rim 60yF, neurologically normal • ~ 5-10% hyperintense WM • No enhancement (except central vessel) 1.5T

PERIVASCULAR SPACES AT 7T ENLARGED PERIVASCULAR SPACES

• Common • Rare but important • Normal variant • Giant PVSs • Aging brain • “Tumefactive” PVSs • Less common • Cryptococcosis • État criblé • Mucopolysaccharidoses

Rudie JD et al: Neuroimaging of dilated perivascular spaces: From benign and pathologic causes to mimics. J Neuroimaging 28: 139-149, 2018

Note: Even at 7T, PVSs are not visible as they pass through cortex!!!

PROMINENT PVSs ÉTAT CRIBLÉ Multiple Bilateral Prominent Basal Ganglia PVSs • Can be normal… 80yM, normal cognition • But just what is “normal”? • Reported associations • Age, • Cerebral small vessel • Traumatic brain injury • MCI, • Sleep deprivation

Smeijer D et al: Enlarged perivascular spaces and dementia: A systematic review. J Alzheimer’s Disease 72 (2019) 247-256 (meta-analysis; no independent association of ePVSs with dementia) Zhang H et al: Lacune and large perivascular space: Two kinds of cavities are of different risk factors and risk. Cerebrovasc Dis 2020;49(5):522-530 92yF, cognitively normal Iavierre-Petit C et al: Neuropathologic and cognitive correlates of enlarged perivascular spaces in a community-based cohort of older adults. Stroke 2020 Sep; 51(9)::2825-2833

Page 2 “TUMEFACTIVE” PVSs UNILATERAL TYPE II ENLARGED PVSs Location-based Classification • Type I 54yF, neurologically normal • Along LSAs, basal ganglia • Usually asymptomatic • Adjacent brain normal • Type II • Perforating medullary arteries, WM • Rarely symptomatic, no follow-up needed • T2/FLAIR abnormalities parenchyma in ~1/3 35yM, headaches, • Type III neurologically normal • Mesencephalothalamic and other (pons, dentate) • 75% symptomatic (, etc) • 95% no signal abnormality • Needs follow-up

Kwee RM, Kwee TC: Tumefactive Virchow-Robin spaces. Eur J Radiol 111: 21-33, 2019

GIANT TYPE II TUMEFACTIVE PVSs TYPE II “TUMEFACTIVE” PVSs Can be very asymmetric, mimic watershed infarct on NECT 67y M headeaches, no focal neurological abnormalities

Focal mass effect with expanded gyri, sparing cortex

“TUMEFACTIVE” PVSs TYPE III MESENCEPHALOTHALAMIC Type III (mesencephalic) 41yM headache, disequilibrium, memory and cognitive sx

Salzman KL et al: Giant tumefactive perivascular spaces. AJNR 26: 298-305, 2005 Kwee RM, Kwee TC: Tumefactive Virchow-Robin spaces. Eur J Radiol 111: 21-33, 2019 Thirumurthi T et al: Giant perivascular space: a rare cause of acute neurosurgical emergency. Br J Neurosurg 2020 Sept 22;1-5

Page 3 GIANT TYPE III TUMEFACTIVE PVSs TYPE III TUMEFACTIVE PVSs 40yM with headaches, stable x 4 years “Other” (pons, dentate)

41yM double vision, facial numbness,

TYPE III TUMEFACTIVE PVSs AND…. The largest, weirdest of them all! Dentate, protrude into CPA cistern

Biopsy-proven!!! Unusual type 1

72yF bilateral hearing loss

TH ?4 (“OPERCULAR”) SUBTYPE? PVS TYPES SUMMARY A new “leave me alone” lesion • Distinct subtype of PVSs • Location, size • Anterior Type I = basal ganglia Type II = WM along along LSAs (USUALLY perforating medullary • Frontal operculum asymptomatic) arteries (usually • 3.5-24 mm (median = 8 mm) asymptomatic) • Imaging • Surrounding ↑ T2/FLAIR • Nearly 90% • Can wax, wane Type III = midbrain Type IV (provisional) along collicular opercular/anterior • Close contact with MCA arteries + “other” temporal lobe (usually • “Knuckle” of MCA (dentate, etc), only asymptomatic) • Can be misdiagnosed as type that is often • Cystic , neuroglial cyst symptomatic

McArdle DJT et al: Opercular perivascular cysts: A proposed new subtype of dilated perivascular spaces. Eur J Radiol 124 (2020) 1008838

Page 4 PATHOLOGIC PVSs MUCOPOLYSACCHARIDOSES

• Glycosaminoglycans • Congenital • Incomplete degradation of GAGs • Mucopolysaccharidoses • Progressive accumulation in • PVSs • PVSs as route of acquired pathologic processes • • CVJ ligaments • Infections (pyogenic meningitis, cryptococcosis, TB etc) • Imaging • Vasculitis (including “tumefactive” vasculitis) • Prototypes MPS 1H, 2 • Macrocephaly, frontal bossing • Neurosarcoidosis • Enlarged PVSs • Nonifectious inflammation (CLIPPERS etc) • “Cribriform” posterior WM, • “Hurler holes” T2 hyperintense, suppress on FLAIR! • (intravascular lymphoma, GBM etc) • Variable patchy T2/FLAIR WM around “holes”

ENHANCING PVSs CRYPTOCOCCOSIS Linear, “dotted line” or punctate enhancement

• Common • Rare but important • Meningitis (pyogenic, TB) • CLIPPERS • Vasculitis • Inflammatory amyloid • Less common • Lymphomatoid granulomatosis • Neurosarcoid • Fulminant • Intravascular lymphoma • Meningioangiomatosis • Glioblastoma • IgG4-RD • LCH

Courtesy N. Omar, MD

MENINGITIS VASCULITIS Along Penetrating Arteries/PVSs

Inflammation + necrosis 29yM biopsy-proven granulomatous PACNS

Page 5 NEUROSARCOIDOSIS INTRAVASCULAR LYMPHOMA

Dura-arachnoid → pia → PVSs

Penetrating arteries

INTRAVASCULAR LYMPHOMA DIFFUSELY INFILTRATING GBM 61yM with DLBCL 66yF, survived 9 months after diagnosis

SUMMARY

• PVSs • Universally seen in 7T • Type III (mesencephalothalamic) most common symptomatic • Enhancing PVSs? Think • Infection or granulomatous disease (e.g., sarcoid) • Vasculitis • Neoplasm (intravascular lymphoma, GBM) • Fulminant demyelinating disease

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