Multiparametric CEST MRI for Time-Associated Characterization of Acute Ischemic Stroke: NOE (−3.5 ppm) Signal as a Potential Imaging Biomarker

This study investigated time-dependent group-level changes in chemical exchange saturation transfer (CEST) signals in a mouse model and explored utility in identifying stroke onset time. Multiparametric magnetic resonance imaging (diffusion weighted imaging, arterial spin labeling, and CEST) was conducted on 12 normal and 26 ischemic mice. Imaging findings were validated by immunohistochemical analysis. CEST parameters in infarct and penumbra were compared between strokes within 4.5 h and over 4.5 h. Correlations, regression, and receiver operating characteristic curves evaluated performance. Infarct guanidine, magnetization transfer (MT), nuclear Overhauser enhancement (NOE) (−3.5 ppm), and NOE (−1.6 ppm) significantly differed between groups and associated with onset time ( P  < .01). MT, NOE (−3.5 ppm), NOE (−1.6 ppm) showed significant associations with onset time in univariate logistic regression ( P  < .05). The NOE (−3.5 ppm) achieved an area under the curve of 0.848 (95% CI: 0.655-1.000), outperforming apparent diffusion coefficient ( z  = −2.397, P  = .017) and cerebral blood flow ( z  = −2.271, P  = .0271). NOE (−3.5 ppm) signals and lipid peroxidation both declined progressively with ischemic duration. These findings indicate that NOE (−3.5 ppm) signal attenuation parallels lipid peroxidation and may indicate progressive membrane lipid loss in ischemia.