title: Vascular permeability and iron deposition biomarkers in longitudinal follow-up of cerebral cavernous malformations.
abstract: OBJECTIVE Vascular permeability and iron leakage are central features of cerebral cavernous malformation (CCM) pathogenesis. The authors aimed to correlate prospective clinical behavior of CCM lesions with longitudinal changes in biomarkers of dynamic contrast-enhanced quantitative permeability (DCEQP) and quantitative susceptibility mapping (QSM) assessed by MRI. METHODS Forty-six patients with CCMs underwent 2 or more permeability and/or susceptibility studies in conjunction with baseline and follow-up imaging and clinical surveillance during a mean 12.05 months of follow-up (range 2.4-31.27 months). Based on clinical and imaging features, cases/lesions were classified as stable, unstable, or recovering. Associated and predictive changes in quantitative permeability and susceptibility were investigated. RESULTS Lesional mean permeability and QSM values were not significantly different in stable versus unstable lesions at baseline. Mean lesional permeability in unstable CCMs with lesional bleeding or growth increased significantly (+85.9% change; p = 0.005), while mean permeability in stable and recovering lesions did not significantly change. Mean lesional QSM values significantly increased in unstable lesions (+44.1% change; p = 0.01), decreased slightly with statistical significance in stable lesions (-3.2% change; p = 0.003), and did not significantly change in recovering lesions. Familial cases developing new lesions during the follow-up period showed a higher background brain permeability at baseline (p = 0.001), as well as higher regional permeability (p = 0.003) in the area that would later develop a new lesion as compared with the homologous contralateral brain region. CONCLUSIONS In vivo assessment of vascular permeability and iron deposition on MRI can serve as objective and quantifiable biomarkers of disease activity in CCMs. This may be applied in natural history studies and may help calibrate clinical trials. The 2 techniques are likely applicable in other disorders of vascular integrity and iron leakage such as aging, hemorrhagic microangiopathy, and traumatic brain injury.
authors: Neurovascular Surgery Program, Section of Neurosurgery, The University of Chicago Medicine, Chicago, Illinois.
authors: Romuald
authors: R
authors: Girard
authors: Neurovascular Surgery Program, Section of Neurosurgery, The University of Chicago Medicine, Chicago, Illinois.
authors: Maged D
authors: MD
authors: Fam
authors: Neurovascular Surgery Program, Section of Neurosurgery, The University of Chicago Medicine, Chicago, Illinois.
authors: Hussein A
authors: HA
authors: Zeineddine
authors: Neurovascular Surgery Program, Section of Neurosurgery, The University of Chicago Medicine, Chicago, Illinois.
authors: Huan
authors: H
authors: Tan
authors: Neurovascular Surgery Program, Section of Neurosurgery, The University of Chicago Medicine, Chicago, Illinois.
authors: Abdul Ghani
authors: AG
authors: Mikati
authors: Neurovascular Surgery Program, Section of Neurosurgery, The University of Chicago Medicine, Chicago, Illinois.
authors: Changbin
authors: C
authors: Shi
authors: Neurovascular Surgery Program, Section of Neurosurgery, The University of Chicago Medicine, Chicago, Illinois.
authors: Michael
authors: M
authors: Jesselson
authors: Neurovascular Surgery Program, Section of Neurosurgery, The University of Chicago Medicine, Chicago, Illinois.
authors: Robert
authors: R
authors: Shenkar
authors: Neurovascular Surgery Program, Section of Neurosurgery, The University of Chicago Medicine, Chicago, Illinois.
authors: Meijing
authors: M
authors: Wu
authors: Neurovascular Surgery Program, Section of Neurosurgery, The University of Chicago Medicine, Chicago, Illinois.
authors: Ying
authors: Y
authors: Cao
authors: Neurovascular Surgery Program, Section of Neurosurgery, The University of Chicago Medicine, Chicago, Illinois.
authors: Nicholas
authors: N
authors: Hobson
authors: Functional Imaging Unit, Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet Glostrup Institute of Clinical Medicine, The Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.|Department of Circulation and Medical Imaging, The Norwegian University of Technology and Science, Trondheim, Norway; and.
authors: Henrik B W
authors: HBW
authors: Larsson
authors: Department of Radiology, University of Chicago Medicine, Illinois.
authors: Gregory A
authors: GA
authors: Christoforidis
authors: Neurovascular Surgery Program, Section of Neurosurgery, The University of Chicago Medicine, Chicago, Illinois.
authors: Issam A
authors: IA
authors: Awad
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism*; D002199:Capillary Permeability; D016022:Case-Control Studies; D005500:Follow-Up Studies; D020786:Hemangioma, Cavernous, Central Nervous System / Q000000981:diagnostic imaging / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D015415:Biomarkers; D007501:Iron
keywords: AUC = area under the curve; CCM = cerebral cavernous malformation; DCEQP = dynamic contrast-enhanced quantitative permeability; IRB = institutional review board; QSM = quantitative susceptibility mapping; ROC = receiver operating characteristic; ROCK = RhoA kinase; ROI = region of interest; SWI = susceptibility-weighted imaging; WMF = white matter far from the lesion; WMN = white matter near the lesion; biomarker; cerebral cavernous malformation; df = degrees of freedom; dynamic contrast-enhanced quantitative permeability; iron; quantitative susceptibility mapping; vascular disorders