Assessment of tissue permeability by early CT perfusion as a surrogate parameter for early brain injury after subarachnoid hemorrhage

Restricted access

OBJECTIVE

The severity of early brain injury (EBI) after aneurysmal subarachnoid hemorrhage (aSAH) correlates with delayed cerebral ischemia (DCI) and outcome. A disruption of the blood-brain barrier is part of EBI pathophysiology. The aim of this study was to assess tissue permeability (PMB) by CT perfusion (CTP) in the acute phase after aSAH and its impact on DCI and outcome.

METHODS

CTP was performed on day 3 after aSAH. Qualitative and quantitative analyses of all CTP parameters, including PMB, were performed. The areas with increased PMB were documented. The value of an early PMB increase as a predictor of DCI and outcome according to the modified Rankin Scale (mRS) grade 3 to 24 months after aSAH was assessed. Possible associations of increased PMB with the Subarachnoid Hemorrhage Early Brain Edema Score (SEBES) and with early perfusion deficits, as radiographic EBI markers, were evaluated.

RESULTS

A total of 69 patients were enrolled in the study. An increased PMB on early CTP was detected in 10.1% (7/69) of all patients. A favorable outcome (mRS grade ≤ 2) occurred in 40.6% (28/69) of all patients. DCI was detected in 25% (17/69) of all patients. An increased PMB was a predictor of DCI (logistic regression, p = 0.03) but not of outcome (logistic regression, p = 0.40). The detection of increased PMB predicted DCI with a sensitivity of 25%, a specificity of 94%, a positive predictive value of 57%, and a negative predictive value of 79% (chi-square test p = 0.03). Early perfusion deficits were seen in 68.1% (47/69) of the patients, a finding that correlated with DCI (p = 0.005) but not with the outcome. No correlation was found between the SEBES and increased PMB.

CONCLUSIONS

Changes in PMB can be detected by early CTP after aSAH, which correlates with DCI. Future studies are needed to evaluate the time course of PMB changes and their interaction with therapeutic measures.

ABBREVIATIONS aSAH = aneurysmal subarachnoid hemorrhage; BBB = blood-brain barrier; BFV = blood flow velocity; CTP = CT perfusion; DCI = delayed cerebral ischemia; EBI = early brain injury; mRS = modified Rankin Scale; NPV = negative predictive value; PMB = permeability; PPV = positive predictive value; SEBES = Subarachnoid Hemorrhage Early Brain Edema Score; VOI = volume of interest.

Article Information

Correspondence Vesna Malinova: Georg-August-University, Göttingen, Germany. vesna.malinova@gmail.com.

INCLUDE WHEN CITING Published online August 23, 2019; DOI: 10.3171/2019.5.JNS19765.

M.N.P. and D.M. contributed equally to this work and share senior authorship.

Disclosures Dr. Psychogios reports receiving speaker honoraria from Siemens.

© AANS, except where prohibited by US copyright law.

Headings

Figures

  • View in gallery

    An area with a focal increase in PMB (VOI marked with outer border of squares). Figure is available in color online only.

  • View in gallery

    Incidence of DCI dependent on the presence of increased PMB. Figure is available in color online only.

References

  • 1

    Ahn SHSavarraj JPPervez MJones WPark JJeon SB: The subarachnoid hemorrhage early brain edema score predicts delayed cerebral ischemia and clinical outcomes. Neurosurgery 83:1371452018

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Al-Mufti FAmuluru KSmith BDamodara NEl-Ghanem MSingh IP: Emerging markers of early brain injury and delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage. World Neurosurg 107:1481592017

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3

    Choi HABajgur SSJones WHSavarraj JPKo SBEdwards NJ: Quantification of cerebral edema after subarachnoid hemorrhage. Neurocrit Care 25:64702016

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Dolatowski KMalinova VFrölich AMSchramm RHaberland UKlotz E: Volume perfusion CT (VPCT) for the differential diagnosis of patients with suspected cerebral vasospasm: qualitative and quantitative analysis of 3D parameter maps. Eur J Radiol 83:188118892014

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Duan YXu HLi RZheng KHu ZWu N: Computed tomography perfusion deficits during the baseline period in aneurysmal subarachnoid hemorrhage are predictive of delayed cerebral ischemia. J Stroke Cerebrovasc Dis 26:1621682017

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Etminan NBeseoglu KHeiroth HJTurowski BSteiger HJHänggi D: Early perfusion computerized tomography imaging as a radiographic surrogate for delayed cerebral ischemia and functional outcome after subarachnoid hemorrhage. Stroke 44:126012662013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Frontera JAClaassen JSchmidt JMWartenberg KETemes RConnolly ES Jr: Prediction of symptomatic vasospasm after subarachnoid hemorrhage: the modified Fisher scale. Neurosurgery 59:21272006

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Frontera JAProvencio JJSehba FAMcIntyre TMNowacki ASGordon E: The role of platelet activation and inflammation in early brain injury following subarachnoid hemorrhage. Neurocrit Care 26:48572017

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Fujii MYan JRolland WBSoejima YCaner BZhang JH: Early brain injury, an evolving frontier in subarachnoid hemorrhage research. Transl Stroke Res 4:4324462013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Germanò Ad’Avella DImperatore CCaruso GTomasello F: Time-course of blood-brain barrier permeability changes after experimental subarachnoid haemorrhage. Acta Neurochir (Wien) 142:5755812000

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Grasso GAlafaci CMacdonald RL: Management of aneurysmal subarachnoid hemorrhage: state of the art and future perspectives. Surg Neurol Int 8:112017 (Erratum in Surg Neurol Int 8:71 2017)

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Hänggi DEtminan NAldrich FSteiger HJMayer SADiringer MN: Randomized, open-label, phase 1/2a study to determine the maximum tolerated dose of intraventricular sustained release nimodipine for subarachnoid hemorrhage (NEWTON [Nimodipine Microparticles to Enhance Recovery While Reducing Toxicity After Subarachnoid Hemorrhage]). Stroke 48:1451512017

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Heye AKCulling RDValdés Hernández MDCThrippleton MJWardlaw JM: Assessment of blood-brain barrier disruption using dynamic contrast-enhanced MRI. A systematic review. Neuroimage Clin 6:2622742014

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Horsch ADBennink Evan Seeters TKappelle LJvan der Graaf YMali WPTM: Computed tomography perfusion derived blood brain barrier permeability does not yet improve prediction of hemorrhagic transformation. Cerebrovasc Dis 45:26322018

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Johshita HKassell NFSasaki TOgawa H: Impaired capillary perfusion and brain edema following experimental subarachnoid hemorrhage: a morphometric study. J Neurosurg 73:4104171990

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Kassner AMerali Z: Assessment of blood-brain barrier disruption in stroke. Stroke 46:331033152015

  • 17

    Kusaka GIshikawa MNanda AGranger DNZhang JH: Signaling pathways for early brain injury after subarachnoid hemorrhage. J Cereb Blood Flow Metab 24:9169252004

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Li ZLiang GMa TLi JWang PLiu L: Blood-brain barrier permeability change and regulation mechanism after subarachnoid hemorrhage. Metab Brain Dis 30:5976032015

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Macdonald RLHigashida RTKeller EMayer SAMolyneux ARaabe A: Clazosentan, an endothelin receptor antagonist, in patients with aneurysmal subarachnoid haemorrhage undergoing surgical clipping: a randomised, double-blind, placebo-controlled phase 3 trial (CONSCIOUS-2). Lancet Neurol 10:6186252011

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Malinova VDolatowski KSchramm PMoerer ORohde VMielke D: Early whole-brain CT perfusion for detection of patients at risk for delayed cerebral ischemia after subarachnoid hemorrhage. J Neurosurg 125:1281362016

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Michinaga SKoyama Y: Protection of the blood brain barrier as a therapeutic strategy for brain damage. Biol Pharm Bull 40:5695752017

  • 22

    Murphy AManoel ALBurgers KKouzmina ELee TMacdonald RL: Early CT perfusion changes and blood-brain barrier permeability after aneurysmal subarachnoid hemorrhage. Neuroradiology 57:7677732015

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Nagaraja TNKnight RAEwing JRKarki KNagesh VFenstermacher JD: Multiparametric magnetic resonance imaging and repeated measurements of blood-brain barrier permeability to contrast agents. Methods Mol Biol 686:1932122011

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Naraoka MMatsuda NShimamura NAsano KOhkuma H: The role of arterioles and the microcirculation in the development of vasospasm after aneurysmal SAH. BioMed Res Int 2014:2537462014

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    Rowland MJHadjipavlou GKelly MWestbrook JPattinson KT: Delayed cerebral ischaemia after subarachnoid haemorrhage: looking beyond vasospasm. Br J Anaesth 109:3153292012

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26

    Sanelli PCAnumula NJohnson CEComunale JPTsiouris AJRiina H: Evaluating CT perfusion using outcome measures of delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage. AJNR Am J Neuroradiol 34:2922982013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27

    Sehba FAPluta RMZhang JH: Metamorphosis of subarachnoid hemorrhage research: from delayed vasospasm to early brain injury. Mol Neurobiol 43:27402011

  • 28

    Sasaki TKassell NFYamashita MFujiwara SZuccarello M: Barrier disruption in the major cerebral arteries following experimental subarachnoid hemorrhage. J Neurosurg 63:4334401985

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29

    van Swieten JCKoudstaal PJVisser MCSchouten HJAvan Gijn J: Interobserver agreement for the assessment of handicap in stroke patients. Stroke 19:6046071988

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 30

    Villringer KSanz Cuesta BEOstwaldt ACGrittner UBrunecker PKhalil AA: DCE-MRI blood-brain barrier assessment in acute ischemic stroke. Neurology 88:4334402017

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31

    Williams JR: The Declaration of Helsinki and public health. Bull World Health Organ 86:6506522008

  • 32

    Xu HLi RDuan YWang JLiu SZhang Y: Quantitative assessment on blood-brain barrier permeability of acute spontaneous intracerebral hemorrhage in basal ganglia: a CT perfusion study. Neuroradiology 59:6776842017

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation

TrendMD

Metrics

Metrics

All Time Past Year Past 30 Days
Abstract Views 397 397 355
Full Text Views 55 55 44
PDF Downloads 43 43 37
EPUB Downloads 0 0 0

PubMed

Google Scholar