Metabolomics Predicts Neuroimaging Characteristics of Transient Ischemic Attack Patients

• Published in: EBioMedicine 2016-12, Vol.14, p.131-138
• Main Authors: Purroy, Francisco, Cambray, Serafi, Mauri-Capdevila, Gerard, Jové, Mariona, Sanahuja, Jordi, Farré, Joan, Benabdelhak, Ikram, Molina-Seguin, Jessica, Colàs-Campàs, Laura, Begue, Robert, Gil, M. Isabel, Pamplona, Reinald, Portero-Otín, Manuel
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Biomarkers; Brain - metabolism; Brain - pathology; Cluster Analysis; Diffusion Magnetic Resonance Imaging; Female; Humans; Ischemic Attack, Transient - diagnostic imaging; Ischemic Attack, Transient - drug therapy; Ischemic Attack, Transient - etiology; Ischemic Attack, Transient - metabolism; Male; Metabolome; Metabolomics; Metabolomics - methods; Middle Aged; Neuroimaging - methods; Prognosis; Research Paper; Risk Factors; TIA
• ISSN: 2352-3964; 2352-3964
• DOI: 10.1016/j.ebiom.2016.11.010

Neuroimaging is essential for the diagnosis and prognosis of transient ischemic attack (TIA). The discovery of a plasmatic biomarker related to neuroimaging findings is of enormous interest because, despite its relevance, magnetic resonance diffusion weighted imaging (DWI) is not always available in all hospitals that attend to TIA patients. Metabolomic analyses were performed by liquid chromatography coupled to mass spectrometry in order to establish the metabolomic patterns of positive DWI, DWI patterns and acute ischemic lesion volumes. We used these methods with an initial TIA cohort of 129 patients and validated them with a 2nd independent cohort of 152 patients. Positive DWI was observed in 115 (40.9%) subjects and scattered pearls in one arterial territory was the most frequent lesion pattern (35.7%). The median acute ischemic lesion volume was 0.33 (0.15–1.90)cm3. We detected a specific metabolomic profile common to both cohorts for positive DWI (11 molecules including creatinine, threoninyl-threonine, N-acetyl-glucosamine, lyso phosphatidic acid and cholesterol-related molecules) and ischemic lesion volume (10 molecules including lysophosphatidylcholine, hypoxanthine/threonate, and leucines). Moreover lysophospholipids and creatinine clearly differed the subcortical DWI pattern from other patterns. There are specific metabolomic profiles associated with representative neuroimaging features in TIA patients. Our findings could allow the development of serum biomarkers related to acute ischemic lesions and specific acute ischemic patterns. •Metabolomics could identify plasmatic biomarkers related to acute ischemia and neuroimaging features among TIA patients•Creatinine, lysophosphatidic acid, N-acetyl-glucosamine and Threonil-Threonine are potential Biomarkers for DWI positive•Leucine levels correlate with Ischemic Volume•Metabolomics identify specific ischemic DWI patterns among TIA patients. We used the metabolomic approach on two independent TIA cohorts (129 and 152 patients) to identify patients with positive DWI and also to obtain metabolomic profiles for specific acute ischemic patterns. We found that DWI positive patients showed a specific metabolomic profile in both cohorts. What is more, we also found a set of metabolites related to acute ischemic volume and also a specific metabolomic signature to determinate DWI patterns. These findings will help to develop specific tools for ischemia detection in TIA patients that are not able to undergo