Abdul Ghani Mikati1, Huan Tan, Robert Shenkar, Luying Li, Lingjiao Zhang, Xiaodong Guo, Henrik B W Larsson, Changbin Shi, Tian Liu, Yi Wang, Akash Shah, Robert R Edelman, Gregory Christoforidis, Issam Awad. 1. 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.).
Abstract
BACKGROUND AND PURPOSE: 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.
BACKGROUND AND PURPOSE: Hyperpermeability and iron deposition are 2 central pathophysiological phenomena in humancerebral 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.
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