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Published on: September 4, 2017
Dynamic permeability and quantitative susceptibility: related imaging biomarkers in cerebral cavernous malformations
Abdul Ghani Mikati1, Huan Tan, Robert Shenkar
1From 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.).
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.
Insights
In cerebral cavernous malformation (CCM) disease, increased vessel leakiness and iron buildup are linked. Novel MRI techniques show that more permeable CCM lesions have greater iron accumulation, suggesting potential biomarkers for disease monitoring.
Area of Science:
- Neuroimaging
- Vascular Malformations
- Biomarkers
Background:
- Cerebral cavernous malformation (CCM) disease involves hyperpermeability and iron deposition.
- Understanding the relationship between these phenomena is crucial for disease management.
Purpose of the Study:
- To investigate the relationship between hyperpermeability and iron deposition in CCM disease.
- To utilize novel MRI techniques for assessing these pathophysiological features.
Main Methods:
- Employed dynamic contrast-enhanced quantitative perfusion (DCE-QP) MRI to measure lesion permeability.
- Utilized quantitative susceptibility mapping (QSM) MRI to quantify iron deposition.
- Analyzed regions of interest in CCM lesions from 21 patients (4 sporadic, 17 familial).
Main Results:
- A significant positive correlation was found between QSM-measured susceptibility (iron deposition) and DCE-QP-measured permeability (r=0.49, P≤0.0001).
- This correlation remained consistent regardless of lesion volume, contrast agent, or statin use.
- Susceptibility also correlated with lesional blood volume (r=0.4, P=0.0001) but not lesional blood flow.
Conclusions:
- Permeability and iron deposition are interconnected in CCM disease, with leakier lesions exhibiting higher cumulative iron burden.
- DCE-QP and QSM show promise as imaging biomarkers for monitoring CCM disease progression and therapeutic response.
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