J Magn Reson Imaging. 2026 Jul 2. doi: 10.1002/jmri.70431. Online ahead of print.
ABSTRACT
BACKGROUND: Susceptibility alterations in deep gray matter (DGM) nuclei after acute ischemic stroke (AIS) may relate to impaired functional independence. However, conventional quantitative susceptibility mapping (QSM) cannot separate paramagnetic iron-related from diamagnetic myelin-related sources, potentially obscuring relevant pathophysiological alterations.
PURPOSE: To apply χ-separation to disentangle paramagnetic susceptibility (χpara) and diamagnetic susceptibility (χdia) in DGM nuclei after AIS and assess associations with 3-month functional independence.
STUDY TYPE: Prospective.
POPULATION: 82 AIS patients (52 M/30 F) and 82 healthy controls (49 M/33 F).
FIELD STRENGTH/SEQUENCE: 3 T; 3D multi-echo gradient-echo sequence for QSM and χ-separation reconstruction.
ASSESSMENT: χpara and χdia were measured in the caudate, putamen, globus pallidus, substantia nigra, red nucleus, thalamus, and dentate nucleus. Contralesional nuclei were analyzed in patients. Group differences and 3-month outcome associations were assessed. Functional independence was defined as modified Rankin Scale score 0-2, and poor outcome as 3-6.
STATISTICAL TESTS: Linear mixed-effects models, analysis of covariance, logistic regression, receiver operating characteristic analysis; p < 0.05 was significant.
RESULTS: Compared with healthy controls, patients showed higher χpara in all seven nuclei, including the dentate nucleus (84.065 ± 15.086 vs. 76.172 ± 11.387 ppb) and thalamus (30.633 [28.036, 34.454] vs. 28.867 [26.749, 31.804] ppb), and higher χdia in the caudate, putamen, red nucleus, thalamus, and dentate nucleus (dentate nucleus: -18.916 ± 6.496 vs. -22.220 ± 5.002 ppb). Poor 3-month outcome was independently associated with higher dentate nucleus χpara (OR, 1.07; 95% CI, 1.03-1.11), higher dentate nucleus χdia (OR, 1.14; 95% CI, 1.04-1.26), and higher thalamus χpara (OR, 1.22; 95% CI, 1.08-1.38). The combined model, incorporating conventional model factors (age, sex, stroke subtype, NIHSS score, and infarct volume) and χ-separation metrics, outperformed the conventional model (AUC, 0.862 vs. 0.757).
DATA CONCLUSION: χ-separation revealed iron- and myelin-related susceptibility alterations in contralesional DGM nuclei after AIS. Susceptibility metrics in the dentate nucleus and thalamus were associated with poor 3-month functional outcome.
EVIDENCE LEVEL: 2.
TECHNICAL EFFICACY: Stage 1.
PMID:42393438 | DOI:10.1002/jmri.70431
