title: Dynamic permeability and quantitative susceptibility: related imaging biomarkers in cerebral cavernous malformations.
abstract: OBJECTIVE
  Hyperpermeability and iron deposition are 2 central pathophysiological phenomena in human cerebral cavernous malformation (CCM) disease. Here, we used 2 novel MRI techniques to establish a relationship between these phenomena.
  
  
  METHODS
  Subjects with CCM disease (4 sporadic and 17 familial) underwent MRI imaging using the dynamic contrast-enhanced quantitative perfusion and quantitative susceptibility mapping techniques that measure hemodynamic factors of vessel leak and iron deposition, respectively, previously demonstrated in CCM disease. Regions of interest encompassing the CCM lesions were analyzed using these techniques.
  
  
  RESULTS
  Susceptibility measured by quantitative susceptibility mapping was positively correlated with permeability of lesions measured using dynamic contrast-enhanced quantitative perfusion (r=0.49; P≤0.0001). The correlation was not affected by factors, including lesion volume, contrast agent, and the use of statin medication. Susceptibility was correlated with lesional blood volume (r=0.4; P=0.0001) but not with lesional blood flow.
  
  
  CONCLUSIONS
  The correlation between quantitative susceptibility mapping and dynamic contrast-enhanced quantitative perfusion suggests that the phenomena of permeability and iron deposition are related in CCM; hence, more leaky lesions also manifest a more cumulative iron burden. These techniques might be used as biomarkers to monitor the course of this disease and the effect of therapy.
authors.affiliation: From the Section of the Neurosurgery (A.G.M., H.T., R.S., L.L., L.Z., C.S., I.A.), Brain Research Imaging Center (X.G.), and Section of Neuroradiology, Department of Diagnostic Radiology (A.S., G.C.), The University of Chicago, IL; Department of Neurosurgery, West China Hospital of Sichuan University, Sichuan, China (L.L.); MedImageMetric LLC, New York, NY (T.L.); Department of Radiology, Weill Cornell Medical College, New York, NY (Y.W.); Department of Biomedical Engineering, Cornell University, Ithaca, NY (Y.W.); Department of Radiology, NorthShore University HealthSystem, Evanston, IL (R.R.E.); Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL (R.R.E.); Functional Imaging Unit, Department of Diagnostics, Glostrup Hospital, University of Copenhagen, Copenhagen, Denmark (H.B.W.L.); and Department of Circulation and Medical Imaging, The Norwegian University of Technology and Science, Trondheim, Norway (H.B.W.L.).
authors.forename: Abdul Ghani
authors.initials: AG
authors.lastname: Mikati
authors.forename: Huan
authors.initials: H
authors.lastname: Tan
authors.forename: Robert
authors.initials: R
authors.lastname: Shenkar
authors.forename: Luying
authors.initials: L
authors.lastname: Li
authors.forename: Lingjiao
authors.initials: L
authors.lastname: Zhang
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Guo
authors.forename: Henrik B W
authors.initials: HB
authors.lastname: Larsson
authors.forename: Changbin
authors.initials: C
authors.lastname: Shi
authors.forename: Tian
authors.initials: T
authors.lastname: Liu
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Akash
authors.initials: A
authors.lastname: Shah
authors.forename: Robert R
authors.initials: RR
authors.lastname: Edelman
authors.forename: Gregory
authors.initials: G
authors.lastname: Christoforidis
authors.forename: Issam
authors.initials: I
authors.lastname: Awad
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers; D001931:Brain Mapping; D002199:Capillary Permeability / Q000502:physiology*; D002648:Child; D003287:Contrast Media; D003627:Data Interpretation, Statistical; D005260:Female; D005682:Gadolinium; D020786:Hemangioma, Cavernous, Central Nervous System / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007501:Iron / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D015588:Observer Variation; D055815:Young Adult
chemical_list: D015415:Biomarkers; D003287:Contrast Media; D005682:Gadolinium; D007501:Iron
keywords: biomarkers; cerebral cavernous malformations; cerebrovascular disorders; hemangioma, cavernous; hemorrhagic stroke; magnetic resonance imaging; vascular permeability