Abstract TP12: Changes in Plasma Metabolites Reflect Lesional Iron Content and Permeability Imaging as Monitoring Biomarkers of Hemorrhage in Cavernous Angiomas

Background: Increase in mean lesional iron content (≥6%) measurement by QSM and vascular permeability (≥ 40%) assessed by DCEQP MRI have been associated with new bleeding in cavernous angiomas (CA), and are used as monitoring biomarkers in clinical trial of pharmacotherapy in CAs with symptomatic hemorrhage (SH). Plasma metabolites have been associated with CA in unsupervised discovery, and linked mechanistically to the permissive microbiome and angiogenic and inflammatory mechanisms in CAs. To date, their levels change has not been compared to lesional QSM and DCEQP change during prospective monitoring.

Methods: Fifty-nine paired plasma samples and MRI sequences were simultaneously acquired in 46 subjects at beginning and end of 1-year epochs in prospective follow-up of cases with CA enrolled in clinical trial after SH. Plasma levels of 14 metabolites previously associated with CA were assayed by liquid-chromatography mass spectrometry, and their changes were compared to changes in mean lesional QSM and DCEQP during the same epochs. Univariate correlations were followed by multivariate analyses combining multiple metabolites levels to minimize Akaike Information Criterion (AIC) or increase R ² . Accuracy (AUC on receiver operating curves) and sum of squared error (SSE) are reported for associations achieving statistical significance with FDR correction.

Results: Aceltyl.L.carnitine absolute change was correlated with QSM absolute change (p=0.01). Highest accuracy for lesional ΔθΣμ ινχρεασε ≥6% was reported for the absolute change of Arachidonic Acid + LPE.18.0 (AUC 99.7%; SD 0.003; p0.01). Relative change of Arachidonic Acid + Hypoxanthine + Piperine, and absolute change of LPE.18.0 + Pipecolic Acid + Piperine had the highest accuracy (AUC 99.1%; SD 0.008 and 98.0%; 0.013) for lesional DCEQP increase of ≥40%. Relative change in Phenylacetylglutamine and LPE.18.0+Piperine reported the lowest SSE (9.77; 438.33) with respective QSM and DCEQP relative change

Conclusion: Changes in circulating metabolites accurately reflect changes in lesional iron content and permeability in CASH during yearly follow-up. Results are a proof of concept that blood tests could replace more complex and costly imaging biomarkers in monitoring CA hemorrhage.