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Background: Cerebral cavernous angioma (CA) is a capillary vasculopathy affecting more than a million Americans with a small fraction of cases demonstrating lesional bleed or growth with major clinical sequelae. Perfusion and permeability are fundamental features of CA pathophysiology, but their role as prognostic biomarkers is unclear., Purpose: To investigate whether perfusion or permeability lesional descriptors derived from dynamic contrast-enhanced quantitative perfusion (DCEQP) magnetic resonance imaging (MRI) can predict subsequent lesional bleed/growth in the year following imaging., Study Type: Single-site case-controlled study., Subjects: Two hundred and five consecutively enrolled patients (63.4% female)., Field Strength/sequence: Three-Tesla/T 1 -mapping with contrast-enhanced dynamic two-dimensional (2D) spoiled gradient recalled acquisition (SPGR) sequences., Assessment: Prognostic associations with bleed/growth (present or absent) in the following year were assessed in 745 CA lesions evaluated by DCEQP in the 205 patients in relation to lesional descriptors calculated from permeability and perfusion maps. A subgroup of 30 cases also underwent peripheral blood collection at the time of DCEQP scans and assays of plasma levels of soluble CD14, IL-1β, VEGF, and soluble ROBO4 proteins, whose weighted combination had been previously reported in association with future CA bleeding., Statistical Tests: Mann-Whitney U-test for univariate analyses. Logistic regression models minimizing the Bayesian information criterion (BIC), testing sensitivity and specificity (receiver operating characteristic curves) of weighted combinations of parameters., Results: The best prognostic biomarker for lesional bleed or growth included brainstem lesion location, mean lesional permeability, and low-value perfusion cluster mean (BIC = 201.5, sensitivity = 77%, specificity = 72%, P < 0.05). Adding a previously published prognostic plasma protein biomarker improved the performance of the imaging model (sensitivity = 100%, specificity = 88%, P < 0.05)., Data Conclusion: A combination of MRI-based descriptors reflecting higher lesional permeability and lower perfusion cluster may potentially predict future bleed/growth in CAs. The sensitivity and specificity of the prognostic imaging biomarker can be enhanced when combined with brainstem lesion location and a plasma protein biomarker of CA hemorrhage., Level of Evidence: 2 TECHNICAL EFFICACY: Stage 5., (© 2021 International Society for Magnetic Resonance in Medicine.)

Background: Quantitative susceptibility mapping (QSM) and dynamic contrast-enhanced quantitative permeability (DCEQP) on magnetic resonance (MR) have been shown to correlate with neurovascular disease progression as markers of vascular leakage and hemosiderin deposition. Applying these techniques as monitoring biomarkers in clinical trials will be necessary; however, their validation across multiple MR platforms and institutions has not been rigorously verified., Purpose: To validate quantitative measurement of MR biomarkers on multiple instruments at different institutions., Study Type: Phantom validation between platforms and institutions., Phantom Model: T 1 /susceptibility phantom, two-compartment dynamic flow phantom., Field Strength/sequence: 3T/QSM, T 1 mapping, dynamic 2D SPGR., Assessment: Philips Ingenia, Siemens Prisma, and Siemens Skyra at three different institutions were assessed. A QSM phantom with concentrations of gadolinium, corresponding to magnetic susceptibilities of 0, 0.1, 0.2, 0.4, and 0.8 ppm was assayed. DCEQP was assessed by measuring a MultiHance bolus as the consistency of the width ratio of the curves at the input and outputs over a range of flow ratios between outputs., Statistical Tests: Each biomarker was assessed by measures of accuracy (Pearson correlation), precision (paired t-test between repeated measurements), and reproducibility (analysis of covariance [ANCOVA] between instruments)., Results: QSM accuracy of r 2  > 0.997 on all three platforms was measured. Precision (P = 0.66 Achieva, P = 0.76 Prisma, P = 0.69 Skyra) and reproducibility (P = 0.89) were good. T 1 mapping of accuracy was r 2  > 0.98. No significant difference between width ratio regression slopes at site 2 (P = 0.669) or site 3 (P = 0.305), and no significant difference between width ratio regression slopes between sites was detected by ANCOVA (P = 0.48)., Data Conclusion: The phantom performed as expected and determined that MR measures of QSM and DCEQP are accurate and consistent across repeated measurements and between platforms., Level of Evidence: 1 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:1192-1199., (© 2019 International Society for Magnetic Resonance in Medicine.)