Regional high iron deposition on quantitative susceptibility mapping correlates with cognitive decline in type 2 diabetes mellitus

Abstract

ObjectiveTo quantitatively evaluate the iron deposition and volume changes in deep gray nuclei according to threshold-method of quantitative susceptibility mapping (QSM) acquired by strategically acquired gradient echo (STAGE) sequence, and to analyze the correlation between the magnetic susceptibility values (MSV) and cognitive scores in type 2 diabetes mellitus (T2DM) patients.MethodsTwenty-nine patients with T2DM and 24 healthy controls (HC) matched by age and gender were recruited in this prospective study. QSM images were used to evaluate whole-structural volumes (Vwh), regional magnetic susceptibility values (MSVRII), and volumes (VRII) in high-iron regions in nine gray nuclei. All QSM data were compared between groups. Receiver operating characteristic (ROC) analysis was used to assess the discriminating ability between groups. The predictive model from single and combined QSM parameters was also established using logistic regression analysis. The correlation between MSVRII and cognitive scores was further analyzed. Multiple comparisons of all statistical values were corrected by false discovery rate (FDR). A statistically significant P-value was set at 0.05.ResultsCompared with HC group, the MSVRII of all gray matter nuclei in T2DM were increased by 5.1–14.8%, with significant differences found in bilateral head of caudate nucleus (HCN), right putamen (PUT), right globus pallidus (GP), and left dentate nucleus (DN) (P < 0.05). The Vwh of most gray nucleus in T2DM group were decreased by 1.5–16.9% except bilateral subthalamic nucleus (STN). Significant differences were found in bilateral HCN, bilateral red nucleus (RN), and bilateral substantia nigra (SN) (P < 0.05). VRII was increased in bilateral GP, bilateral PUT (P < 0.05). VRII/Vwh was also increased in bilateral GP, bilateral PUT, bilateral SN, left HCN and right STN (P < 0.05). Compared with the single QSM parameter, the combined parameter showed the largest area under curve (AUC) of 0.86, with a sensitivity of 87.5% and specificity of 75.9%. The MSVRII in the right GP was strongly associated with List A Long-delay free recall (List A LDFR) scores (r = −0.590, P = 0.009).ConclusionIn T2DM patients, excessive and heterogeneous iron deposition as well as volume loss occurs in deep gray nuclei. The MSV in high iron regions can better evaluate the distribution of iron, which is related to the decline of cognitive function.

Deep gray matters iron deposition is positively associated with white matter hyperintensity in hypertension

“…We found that the susceptibilities measured by RII analysis differed in more deep gray matters than RI analysis between hypertensive patients and healthy controls or m-s WMH and n-m WMH, suggesting that RII analysis may be an appropriate method to detect changes in iron content. Previous studies on Parkinson's disease and type 2 diabetes mellitus (T2DM) 18,32 have also shown that RII analysis is more sensitive for distinguishing patients from healthy volunteers.…”

“…(1) removing interference from diamagnetic substances; and (2) better reflecting small-scale iron accumulation within the ROI or the uneven distribution of iron. 18 There were relatively few studies on the relationship between iron deposition and WMH, and the results were inconsistent. One group used an R2* technology and found a positive correlation between iron deposition in GP and WMH volume of healthy adults.…”

“…We found that the susceptibilities measured by RII analysis differed in more deep gray matters than RI analysis between hypertensive patients and healthy controls or m‐s WMH and n‐m WMH, suggesting that RII analysis may be an appropriate method to detect changes in iron content. Previous studies on Parkinson's disease and type 2 diabetes mellitus (T2DM) 18,32 have also shown that RII analysis is more sensitive for distinguishing patients from healthy volunteers. Therefore, we speculate that RII analysis can reveal the correlation between iron deposition and WMH more sensitively, mainly due to: (1) removing interference from diamagnetic substances; and (2) better reflecting small‐scale iron accumulation within the ROI or the uneven distribution of iron 18 …”

“…Previous studies on Parkinson's disease and type 2 diabetes mellitus (T2DM) 18,32 have also shown that RII analysis is more sensitive for distinguishing patients from healthy volunteers. Therefore, we speculate that RII analysis can reveal the correlation between iron deposition and WMH more sensitively, mainly due to: (1) removing interference from diamagnetic substances; and (2) better reflecting small‐scale iron accumulation within the ROI or the uneven distribution of iron 18 …”

“…Using a high‐iron content region (RII) analysis can eliminate the impact of diamagnetic substances such as calcifications and sphingomyelins on iron assessment. In addition, RI analysis calculates the average susceptibilities of the brain region and cannot reveal the uneven distribution of iron 18 . Studies in healthy volunteers have demonstrated that the RII analysis is more robust and sensitive to reveal the linear relationship between iron and age 19,20 .…”