A comprehensive analysis of metabolic changes in the salvaged penumbra

Abstract

Introduction: We aimed to assess metabolite profiles in peri-infarct tissue with magnetic resonance spectroscopy (MRS) and correlate these with early and late clinical recovery.

Methods: One hundred ten anterior circulation ischemic stroke patients presenting to hospital within 4.5 h of symptom onset and treated with intravenous thrombolysis were studied. Patients underwent computer tomography perfusion (CTP) scanning and subsequently 3-T magnetic resonance imaging (MRI) 24 h after stroke onset, including single-voxel, short-echo-time (30 ms) MRS, and diffusion- and perfusion-weighted imaging (DWI and PWI). MRS voxels were placed in the peri-infarct region in reperfused penumbral tissue. A control voxel was placed in the contralateral homologous area.

Results: The concentrations of total creatine (5.39 vs 5.85 mM, p = 0.044) and N-acetylaspartic acid (NAA, 6.34 vs 7.13 mM ± 1.57, p < 0.001) were reduced in peri-infarct tissue compared to the matching contralateral region. Baseline National Institutes of Health Stroke Score was correlated with glutamate concentration in the reperfused penumbra at 24 h (r (2) = 0.167, p = 0.017). Higher total creatine was associated with better neurological outcome at 24 h (r (2) = 0.242, p = 0.004). Lower peri-infarct glutamate was a stronger predictor of worse 3-month clinical outcome (area under the curve (AUC) 0.89, p < 0.001) than DWI volume (AUC = 0.79, p < 0.001).

Conclusion: Decreased glutamate, creatine, and NAA concentrations are associated with poor neurological outcome at 24 h and greater disability at 3 months. The significant metabolic variation in salvaged tissue may potentially explain some of the variability seen in stroke recovery despite apparently successful reperfusion.

Keywords: Clinical outcome; Glutamate; Ischemic stroke; Penumbra; Spectroscopy.