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Updated: May 5, 2026
Induction and Micro-CT Imaging of Cerebral Cavernous Malformations in Mouse Model
Published on: September 4, 2017
Circulating molecules reflect imaging biomarkers of hemorrhage in cerebral cavernous malformations
Stephanie F Hage1, Dehua E Bi2, Serena Kinkade1
1Neurovascular Surgery Program, Department of Neurological Surgery, University of Chicago Medicine and Biological Sciences, Chicago, IL, USA.
Abstract:
Increases in mean lesional iron content by quantitative susceptibility mapping (QSM) by ≥6% and/or vascular permeability by dynamic contrast enhanced quantitative perfusion (DCEQP) by ≥40% on MRI have been associated with new symptomatic hemorrhage (SH) in cerebral cavernous malformations (CCMs). It is not known if plasma biomarkers can reflect these changes within the lesion proper. This cohort study enrolled 46 CCM patients with SH in the prior year. Plasma samples, QSM and DCEQP were simultaneously acquired at the beginning and end of 60 one-year epochs of prospective follow-up. Plasma levels of 16 proteins and 12 metabolites linked to CCM hemorrhage were assessed by enzyme-linked immunosorbent assay and liquid-chromatography mass spectrometry, respectively. A weighted model combining the percent changes in plasma levels in roundabout guidance receptor-4, cluster of differentiation 14, thrombomodulin and acetyl-L-carnitine reflected a mean increase in QSM ≥ 6% (97.2% and 100% specificity/sensitivity, p = 3.1 × 10-13). A weighted combination of percent changes in plasma levels of endoglin, pipecolic acid, arachidonic acid and hypoxanthine correlated with an increase in mean DCEQP ≥40% (99.6% specificity and 100% sensitivity, p = 4.1 × 10-17). This is a first report linking with great accuracy changes of circulating molecules to imaging changes reflecting new SH during prospective follow-up of CCMs.
Insights
Plasma biomarkers can now predict MRI-detected changes associated with symptomatic hemorrhage (SH) in cerebral cavernous malformations (CCMs). This breakthrough links circulating molecules to imaging markers, improving SH risk assessment in CCM patients.
Area of Science:
- Neuroimaging
- Biomarker Discovery
- Vascular Biology
Background:
- Cerebral cavernous malformations (CCMs) are associated with symptomatic hemorrhage (SH).
- MRI metrics like quantitative susceptibility mapping (QSM) and dynamic contrast-enhanced quantitative perfusion (DCEQP) detect lesion changes linked to SH.
- The relationship between plasma biomarkers and these in-lesion MRI changes in CCMs remains unclear.
Purpose of the Study:
- To investigate if plasma biomarkers can reflect MRI-detected changes in lesional iron content and vascular permeability in CCM patients.
- To establish correlations between changes in specific plasma biomarkers and quantitative MRI metrics associated with SH risk.
Main Methods:
- A cohort of 46 CCM patients with prior SH was prospectively followed for one year.
- Simultaneous plasma sampling and MRI (QSM and DCEQP) were performed at baseline and follow-up.
- Plasma levels of 16 proteins and 12 metabolites were analyzed using ELISA and liquid chromatography-mass spectrometry.
Main Results:
- A weighted model of four plasma biomarkers (roundabout guidance receptor-4, CD14, thrombomodulin, acetyl-L-carnitine) accurately predicted increases in QSM (≥6%) with high sensitivity and specificity.
- Another weighted model of four different plasma biomarkers (endoglin, pipecolic acid, arachidonic acid, hypoxanthine) correlated with increased DCEQP (≥40%) with exceptional accuracy.
- These findings represent the first accurate linkage of circulating molecular changes to imaging indicators of new SH in CCMs during follow-up.
Conclusions:
- Specific combinations of plasma biomarkers can serve as accurate, non-invasive indicators of MRI-detectable lesion changes associated with SH risk in CCM patients.
- This study establishes a novel link between systemic molecular changes and localized vascular pathology in CCMs.
- These findings may pave the way for improved monitoring and risk stratification of SH in individuals with CCMs.
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