Document resource
Introduction Acute ischemic stroke (AIS) is a time-critical emergency in which speed of diagnosis directly determines neurological and procedural outcomes. Current diagnostic pathways rely on clinical assessment and neuroimaging, tools that require specialist interpretation, dedicated infrastructure, and transfer to capable centers, all of which introduce delays that cost salvageable brain tissue. Real-time breath metabolic analysis represents a promising, underexplored alternative, requiring no specialist infrastructure and yielding results within seconds of sampling. Volatile organic compounds (VOC) in exhaled breath may provide rapid, accessible indicators of AIS, capturing systemic and cerebral metabolic and inflammatory signatures. This study characterizes the perioperative VOC breath signature of AIS patients undergoing thrombectomy as a first step toward identifying breath-based biomarkers for rapid stroke diagnosis and triage.Methods This prospective pilot study enrolled seven AIS patients undergoing mechanical thrombectomy. Exhaled breath was collected immediately before and within 48 hours after the procedure and analyzed using a Syft Voice200 Ultra selected ion flow tube mass spectrometer, performing full-spectrum VOC profiling across 1,067 metabolite channels. Pre- versus post-procedural profiles were compared using within-patient log 2fold-change analysis and paired Wilcoxon signed-rank testing, with channels assessed for directional consistency across all patients to identify robust candidate biomarkers.Results Twenty-four VOC channels demonstrated perfectly consistent directional change across all seven patients following thrombectomy (p = 0.016 per channel), with 22 decreasing and 2 increasing post-procedure (figure1). Among identifiable compounds, heptanal and octanal, established markers of lipid peroxidation and oxidative stress, decreased uniformly post-procedure, consistent with metabolic changes accompanying cerebral reperfusion. Hexanal, a related aldehyde, increased consistently, potentially reflecting acute reperfusion-associated oxidative injury. Two novel high-molecular-weight compounds detected reproducibly across independent reagent ion series showed the largest magnitude changes post-procedure (median log 2FC -1.95 and -6.45 respectively). No channels survived correction for multiple comparisons, consistent with the pilot sample size.Conclusion Exhaled breath analysis in AIS patients reveals a reproducible, patient-consistent perioperative VOC signature centered on lipid peroxidation-associated aldehydes and novel uncharacterized volatile compounds. These findings demonstrate the feasibility of breath-based metabolomic profiling in the acute stroke setting and support the existence of a VOC signature reflective of ischemic cerebral metabolism. Prospective validation in a larger cohort is needed to determine whether such a signature is of sufficient diagnostic specificity to support rapid, pre-imaging triage of AIS patients.Disclosures W. Chung: None. D. Yeung: None. E. Gross: None. N. Telischak: None.Abstract E-313 Figure 1