| Studyl A Quantitative Imaging Study of 3D-ASL perfusion in diabetes-associated cognitive dysfunction of type 2 diabetes mellitus without hypertensionObjective:To evaluate the feasibility of three dimensional arterial spin labeling(3D-ASL)in early identifying the occurrence and progression of Diabetes-associated cognitive dysfunction(DACD)of type 2 diabetes mellitus(T2DM)patients without hypertension.Methods:15 patients with mild cognitive impairment(MCI+)in T2DM without hypertension,17 patients without mild cognitive impairment(MCI-)in T2DM without hypertension and 19 normal control(NC)subjects matched with T2DM patients in terms of age,gender,education level and blood lipid were included.All subjects underwent cognitive function scales,3D-T1WI and 3D-ASL scanning.Regional CBF(rCBF)and cognitive score were compared among the three groups,and the correlation between rCBF of different brain regions and cognitive score in MCI+ and MCI-groups was analyzed.Results:Compared with MCI-group,rCBF in bilateral superior temporal gyrus and insular region in MCI+group decreased significantly(P<0.05);Compared with NC group,rCBF in left cingulate gyrus decreased in MCI group(P<0.0001).The scores of Montreal cognitive assessment(MoCA)in MCI+group were positively correlated with the rCBF of left superior temporal gyrus(rho=0.563,P=0.000),left insula(rho=0.502,P=0.002),right insula and superior temporal gyrus(rho=0.826,P=0.000);The scores of Wechsler intelligence Scale-digital span test(WMS-DST)were positively correlated with the rCBF of left superior temporal gyrus(rho-0.383,P=0.023),right insular lobe and superior temporal gyrus(rho=0.705,P=0.000);The total score of WMS-DST was positively correlated with rCBF in left superior temporal gyrus(rho=0.515,P=0.002),left insula(rho=0.488,P=0.003),right insula and superior temporal gyrus(rho=0.707,P=0.000);The score of semantic verbal fluency(SVF)was positively correlated with rCBF in left superior temporal gyrus(rho=0.403,P=0.016),right insula and superior temporal gyrus(rho=0.622,P=0.000).In univariate logistic regression model,age and duration of diabetes are risk factors for MCI in T2DM.The increased rCBF in the left superior temporal gyrus,left insula and hypercholesterolemia is a protective factor for MCI in T2DM without hypertension.In the multivariate logistic regression model,age is an independent risk factor for MCI in T2DM patients without hypertension.Conclusion:Magnetic resonance 3D-ASL technology can sensitively detect abnormal cerebral perfusion in T2DM patients in early time.The decrease of rCBF in the left cingulate gyrus may occur early in the course of T2DM without hypertension.The increased rCBF in the left superior temporal gyrus,left insula is a protective factor for MCI in T2DM without hypertension.3D-ASL technology has important clinical application prospects in T2DM cognitive neuroscience.Study 2 Three-dimensional-arterial spin labeling perfusion correlation with diabetes-associated cognitive dysfunction and vascular endothelial growth factor in type 2 diabetes mellitus ratObjective:To assess the correlation between CBF(measured by 3D-ASL)and VEGF expression and DACD in a rat model of T2DM.Methods:Forty eight Sprague-dawley male rats were divided into control and T2DM groups.The T2DM group was established by feeding rats a high-fat diet and glucose to induce impaired glucose tolerance and then injecting them with streptozotocin to induce T2DM.Cognitive function was assessed using the Morris water maze experiment.The CBF changes were measured by 3D-ASL magnetic resonance imaging.VEGF expression was determined using immunofluorescence.Results:The escape latency time significantly reduced 15 wk after streptozotocin injection in the T2DM group.The total distance traveled was longer in the T2DM group;also,the platform was crossed fewer times.The percentage of distance in the target zone significantly decreased.CBF decreased in the bilateral hippocampus in the T2DM group.No difference was found between the right CBF value and the left CBF value in the T2DM group.The VEGF expression level in the hippocampus was lower in the T2DM group and correlated with the CBF value.The escape latency negatively correlated with the CBF value.The number of rats crossing the platform positively correlated with the CBF value.Conclusion:Low CBF in the hippocampus and decreased VEGF expression might be crucial in DACD.CBF measured by 3D-ASL might serve as a noninvasive imaging biomarker for diabetes-associated cognitive dysfunction of T2DM.Study 3 A Quantitative Imaging Study of Amide proton transfer-weighted imaging in diabetes-associated cognitive dysfunction of type 2 diabetes mellitusObjective:To evaluate the feasibility of identifying the occurrence and development of diabetes-associated cognitive dysfunction(DACD)of type 2 diabetes mellitus using APTw SI(%).Methods:28 patients with mild cognitive impairment(MCI+)in T2DM,8 patients without mild cognitive impairment(MCI-)in T2DM and 11 normal control(NC)subjects matched with T2DM patients in terms of age,gender,education level and blood lipid were included.APTw was performed in patients with T2DM and evaluated by the multiple field cognitive function scale.Fasting blood glucose,glycosylated hemoglobin,triglyceride and total cholesterol were measured.Data were analysed using ANOVA and student-t test.The APTw SI(%)of the head,body and tail of the hippocampus were obtained in workstation.APTw SI(%)of different parts of bilateral hippocampus in three groups and the APTw SI(%)of the head,body and tail of the hippocampus were analysed.The correlation of APTw SI and multiple field cognitive function scale was analyzed by Pearson analysis correlation in MCI+group.Results:The APTw SI(%)of left hippocampal head,left hippocampal body and right hippocampal tail were statistically different among three groups(P<0.05).The APTw SI(%)of the head,body and tail of the hippocampus were statistically significant(P<0.05)in MCI+group.SVF score was positively correlated with APTw SI(%)in left hippocampal head of MCI+group(rho=0.414,P=0.044),TMT-A score was negatively correlated with APTw SI(%)in left hippocampal tail of MCI+group(rho=-0.333,P=0.021),AVLT-H(delaye memory)scores was negatively correlated with APTw SI(%)in left hippocampal tail of MCI+group(rho=-0.376,P=0.000).Conclusion:Findings suggestive of the progression of MCI were found from the APTw SI in different regions of hippocampus.APTw technique may be a noninvasive and potential imaging biomarkers for the occurrence and progress of DACD of T2DM in molecular imaging level.APTw technique has tremendous potential to assist with early diagnosis and improve intervention programs in DACD.Study 4 A Quantitative Imaging Study of Amide proton transfer weighted imaging in diabetes-associated cognitive dysfunction in type 2 diabetes mellitus ratObjective:To assess the correlation between APTw SI(%),Tau expression and DACD in a rat model of T2DM.To evaluate the feasibility of APTw technique in reflecting the pathological changes of brain tissue,cognitive impairment in T2DM and to explore the pathophysiological mechanism of cognitive function changes in T2DM.Methods:Forty eight Sprague-dawley male rats were divided into control and T2DM groups.The T2DM group was established by feeding rats a high-fat diet and glucose to induce impaired glucose tolerance and then injecting them with streptozotocin to induce T2DM.Cognitive function was assessed using the Morris water maze experiment.The APTw SI(%)was measured by APTw technique.Tau expression was determined using immunofluorescence and Immunohistochemistry.The difference of APTw SI(%)between the two groups was compared by independent sample t-test.Finally,Pearson and Spearman correlation analysis were used to study the relationship between hippocampal APTw SI(%),tau protein expression and cognitive function.Results:The escape latency time significantly reduced in the T2DM group.The total distance traveled was longer in the T2DM group.The platform was crossed fewer times in T2DM group.The percentage of distance in the target zone significantly decreased.The APTw SI(%)in bilateral hippocampus in T2DM group was significantly higher than that in NC group(P<0.05).Compared with NC group,the expression of t-Tau and p-Tau ser199 increased in T2DM group(P<0.05).The expression of t-Tau protein was positively correlated with escape latency time(rho=0.425,P=0.0486).The expression of t-Tau protein was negatively correlated with the percentage of distance in the target zone(rho=-0.6748,P=0.0227).There was a positive correlation between APTw SI(%)and t-Tau protein expression.There was a negative correlation between APTw SI value(%)and the percentage of distance in the target zone(rho=-0.3986,P=0.0108).APTw SI value(%)is negatively correlated with platform crossings times.Conclusion:T2DM may result in increase the expression of t-Tau and p-Tau ser199 protein in hippocampus.The increase of t-Tau protein is closely related to the cognitive function of T2DM rats.The increase of t-Tau protein may be the cause of DACD.APTw SI(%)is closely related to t-Tau protein.Animal experiments further proved that MRI APTw technology can be used as an imaging biomarker for the pathological changes of brain parenchyma and cognitive function in T2DM. |
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