Evaluating iron deposition in gray matter nuclei of patients with unilateral middle cerebral artery stenosis using quantitative susceptibility mapping

Abstract

Iron mediated oxidative stress is involved in the process of brain injury after long-term ischemia. While increased iron deposition in the affected brain regions was observed in animal models of ischemic stroke, potential changes in the brain iron content in clinical patients with cerebral ischemia remain unclear. Quantitative susceptibility mapping (QSM), a non-invasive magnetic resonance imaging technique, can be used to evaluate iron content in the gray matter (GM) nuclei reliably. In this study, we aimed to quantitatively evaluate iron content changes in GM nuclei of patients with long-term unilateral middle cerebral artery (MCA) stenosis/occlusion-related cerebral ischemia using QSM. Forty-six unilateral MCA stenosis/occlusion patients and 38 age-, sex- and education-matched healthy controls underwent QSM. Clinical variables of history of hypertension, diabetes, hyperlipidemia, hyperhomocysteinemia, smoking, and drinking in all patients were evaluated. The iron-related susceptibility of GM nucleus subregions, including the bilateral caudate nucleus (CN), putamen (PU), globus pallidus (GP), thalamus, substantia nigra (SN), red nucleus, and dentate nucleus, was assessed. Susceptibility was compared between the bilateral GM nuclei in patients and controls. Receiver operating characteristic curve analysis was used to evaluate the efficacy of QSM susceptibility in distinguishing patients with unilateral MCA stenosis/occlusion from healthy controls. Multiple linear regression analysis was used to evaluate the relationship between ipsilateral susceptibility levels and clinical variables. Except for the CN, the susceptibility in most bilateral GM nucleus subregions was comparable in healthy controls, whereas for patients with unilateral MCA stenosis/occlusion, the ipsilateral PU, GP, and SN exhibited significantly higher susceptibility than the contralateral side (all P < 0.05). Compared with controls, susceptibility of the ipsilateral PU, GP, and SN and of contralateral PU in patients were significantly increased (all P < 0.05). The area under the curve (AUC) was greater for the ipsilateral PU than for the GP and SN (AUC = 0.773, 0.662 and 0.681; all P < 0.05). Multiple linear regression analysis showed that the increased susceptibility of the ipsilateral PU was significantly associated with hypertension, of the ipsilateral GP associated with smoking, and of the ipsilateral SN associated with diabetes (all P < 0.05). Our findings provide support for abnormal iron accumulation in the GM nuclei after chronic MCA stenosis/occlusion and its correlation with some cerebrovascular disease risk factors. Therefore, iron deposition in the GM nuclei, as measured by QSM, may be a potential biomarker for long-term cerebral ischemia.

Keywords: Cerebral ischemia; Gray matter nuclei; Iron deposition; Middle cerebral artery stenosis or occlusion; Quantitative susceptibility mapping.