Association of Iron and Myelin Alterations in the Contralesional Dentate Nucleus and Thalamus With Functional Outcome in Acute Ischemic Stroke: A Susceptibility Source Separation Study

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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 ( χ para ) and diamagnetic susceptibility ( χ dia ) 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 χ para and χ dia 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 χ para 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 χ dia 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 χ para (OR, 1.07; 95% CI, 1.03–1.11), higher dentate nucleus χ dia (OR, 1.14; 95% CI, 1.04–1.26), and higher thalamus χ para (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.

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