Application Of Quantitative Magnetic Resonance Imaging In Aging And Alzheimer’s Disease

PART 1 Investigation of Age-Related White Matter Changes in Healthy Adults Brain using Synthetic MRI:a Preliminary StudyObjective:To explore the relaxometry and volumetric characteristics of the white matter at different ages using synthetic MRI.Materials and methods:A total of 107 healthy volunteers in Beijing Hospital from November 2017 to August 2018 were enrolled in this study.According to the age,they were divided in to 20-39 years group(29 persons),40-59years group(31 persons),60-79 years group(30 persons),and ≥80 years(17 persons).All participants underwent brain synthetic MRI.Volumetric characteristics including white matter volume and white matter fraction,the T1 and T2 values of white matter were also obtained.Nonlinear regression analysis was conducted between these parameters and age.ANOVA test was performed to assess the difference among different age groups.Pearson correlation coefficient between WMV and the T1 and T2 values were also calculated.Results:The white matter volume(male and female separately),white matter fraction,T1 and T2 values of white matter followed a second order polynomial relationship with age[R2=0.67(male)、0.42(female)、0.44、0.52、0.25,P<0.001],the white matter volume of male had the best goodness of fit,during 40-59 years old,the white matter volume was highest,and T1 and T2 values were lowest.Significant differences were observed in white matter volume(male and female separately),white matter fraction,T1 and T2 values of the white matter among four age groups[the white matter volumes of males=(608±48)ml,(615±54)ml,(558±82)ml and(463±46)ml,respectively,F=19.49,P<0.001,and the white matter volumes of females=(538±54)ml,(546±52)ml and(471±66)ml,respectively(the number of females ≥80 years old was too small to calculate),F=8.70,P=0.001,white matter volume fraction=0.44 ± 0.02,0.47±0.02,0.43±0.03 and 0.40±0.02,respectively,F=23.18,P<0.001,T1 values of white matter=(728 ± 10)ms,(721 ± 11)ms,(740±16)ms and(757±13)ms,respectively,F=35.04,P<0.001,and T2 values of white matter=(71.4 ± 1.2)ms,(70.6 ± 2.1)ms,(72.2± 2.5)ms and(73.4±2.4)ms,respectively,F=7.10,P<0.001(in the order of aging)].The white matter volume of male and female was linearly correlated negatively with the T1 value[r=-0.69(male),-0.73(female),P<0.001]and T2 value[r=-0.50(male),-0.49(female),P<0.001]of white matter.Conclusion:Through the MRI quantitative parameters of white matter from synthetic MRI,this study found that the white matter volume,white matter fraction,T1 and T2 values of white matter showed second order polynomial relationship with age,as the highest white matter volume in 40-59 years of age.The study also provided reference data for brain volume and relaxation time in healthy adults at different ages.Part 2 Application of Synthetic MRI in Alzheimer’s DiseaseObjective:To investigate the changes of white matter volume and relaxometry in Alzheimer’s disease(AD)using synthetic MRI.Materials and methods:From July 2018 to December 2019,18 AD patients and 18 healthy controls matched by gender and age were collected.Brain synthetic MRI was performed on GE 3.0T machine.The volume quantitative parameters included in this study were white matter volume,white matter fraction,and brain parenchyma volume.We chose 12 regions of interest(ROIs)of the white matter including bilateral frontal lobe,parietal lobe,temporal lobe,occipital lobe,genu and splenium of corpus callosum,and posterior limbs of internal capsule,and get their T1 values,T2 values and proton density(PD)values.The data were analyzed by IBM SPSS 19.0,the differences of the MRI quantitative parameters were calculated by independent sample t-test.Pearson correlation coefficients were calculated between T1 value,T2 value and PD value of ROIs and MMSE in AD group.The performance of MRI parameters was assessed using the receiver operating characteristic(ROC)curve analysis,and calculated the area under the curve(AUC).Results:There was no difference of white matter volume,white matter fraction,and brain parenchyma volume between AD group and healthy control group[white matter volume=(444.68 ± 59.69)ml vs(470.78±89.19)ml,t=-1.05,P=0.30,white matter fraction=0.41±0.24 vs 0.41±0.34,t=-0.62,P=0.54,brain parenchymal volume=(1094.17±115.94)ml vs(1137.15±147.64)ml,t=-0.99,P=0.32].There were statistically significant differences in T1 values of right occipital and left parietal white matter ROI between AD group and healthy control group[T1 values=(797.55±66.44)ms vs(753.48±40.85)ms,(829.79±65.36)ms vs(787.73±36.45)ms,t=2.49,2.41,P=0.02 and 0.02.respectively].Differences of T2 values in right occipital white matter,left parietal white matter and right temporal white matter were statistically significant[T2 values=(87.04±11.26)ms vs(79.12±5.44)ms,(86.71±10.71)ms vs(78.75±5.44)ms,(79.98±8.48)ms vs(74.01±7.52)ms,t=2.55,2.84 and 2.30,P=0.02,0.01 and 0.03,respectively].T1 and T2 values in AD group were higher than those in healthy control group.There was no significant difference of T1 and T2 values of other 9 ROIs,and PD values of 12 ROIs between AD group and healthy control group.There was no significant correlation between T1 value,T2 value and PD value of 12 ROIs and MMSE score.The ROC curve revealed the T1 values of right occipital lobe and left parietal lobe ROIs,and T2 values of right occipital lobe,left parietal lobe and right temporal lobe ROIs had diagnostic efficacy to predict AD(P<0.05),AUC=0.69-0.74.Conclusion:Synthetic MRI can provide multiple quantitative magnetic resonance parameters at one time,such as brain volume and relaxation time.This study found the increased T1 and T2 values of ROIs in right occipital lobe and left parietal lobe,T2 value of right temporal lobe.Synthetic MRI may help to diagnosis of AD.Part 3 Application of Quantitative MRI in Alzheimer’s Disease and Mild Cognitive ImpairmentObjective:Combining amide proton transfer(APT)MRI and T1 mapping MRI,explore the APT parameters and T1 values changes in Alzheimer’s disease(AD)and mild cognitive impairment(MCI).Materials and methods:From September 2020 to January 2022,29 patients with AD,19 patients with MCI and 20 sex and age-matched healthy controls were collected.3D APT,3D T1WI and T1mapping sequences were performed on Siemens 3.0T MRI machine.The post processing of MRI imaging were written on Matlab platform which can calculate the 30 brain subregions MRI quantitative parameters including gray matter and white matter of bilateral cerebral lobes and bilateral hippocampus.Multiple MRI quantitative parameters are magnetization transfer ratio asymmetry metric(MTRasym),chemical exchange saturation transfer ration normalized with the reference value(CESTRnr),and magnetisation transfer ratio relaxation due to exchange(MTRRex),apparent exchange-dependent relaxation(AREX)at 3.5ppm,and T1 value.The data were analyzed by IBM SPSS 19.0,and the differences among three groups were compared by ANOVA test,the brain subregions with differences were further tested by t-test(Bonferroni correction).Pearson correlation analysis was conducted between MRI quantitative parameters and mini-mental state examination(MMSE)and montreal cognitive assessment(MoCA)scores in AD and MCI group.Receiver operating characteristic(ROC)curve was used to test the efficiency of MRI parameters of AD,and calculated the area under the curve(AUC),the multivariate logistic regression model was used to combine the multiple MRI parameters.Results:The MTRasym values of left frontal gray matter and white matter were significantly different among the three groups[MTRasym(%)=1.43±0.40 vs 1.13 ±0.38 vs 1.27±0.26,0.96±0.40 vs 0.73±0.28 vs 0.72±0.22(AD vs MCI vs Healthy controls),F=4.18,4.19,P=0.02,0.019,respectively].CESTRnr values of left hippocampus,right hippocampus,left frontal gray matter and left frontal white matter had significant differences among the three groups[CESTRnr(%)=3.44±0.87 vs 3.72±0.80 vs 4.04±0.46,3.33±0.99 vs 3.75±0.63 vs 3.89±0.58,2.78±0.76 vs 2.22±0.76 vs 2.51±0.48,2.27±0.85 vs 1.78±0.70 vs 1.76±0.54(AD vs MCI vs Healthy controls),F=3.85,3.25,3.74,and 3.30,P=0.026,0.035,0.029 and 0.026,respectively].The MTRRex values of left hippocampus,right hippocampus,left frontal gray matter,left frontal white matter and right insular lobe were significantly different among the three groups[MTRRex(%)=7.18±2.36 vs 8.32±2.13 vs 9.46±1.32,7.02±2.87 vs 8.52±1.89 vs 9.09±1.66,5.57±1.56 vs 4.49±1.58 vs 5.09±1.02,5.52±1.96 vs 4.42±1.81 vs 4.3 9±1.39,5.46±1.75 vs 6.03±1.41 vs 6.74±1.99(AD vs MCI vs Healthy controls),F=7.44,5.30,3.24,3.30,and 3.18,P=0.001,0.007,0.046,0.043 and 0.048,respectively].The AREX values of left hippocampus,right hippocampus,left occipital gray matter and right insular lobe were significantly different among the three groups[AREX(%)=5.08±1.96 vs 6.11 ±1.76 vs 7.21 ± 1.25,5.10±2.49 vs 6.39±1.63 vs 7.08±1.49,5.34±0.82 vs 5.68±0.97 vs 6.18±1.09,3.56±1.31 vs 4.13±1.21 vs 4.68±1.48(AD vs MCI vs Healthy controls),F=9.08,6.10,4.66,and 4.27,P=0.001,0.004,0.013 and 0.018,respectively].T1 values of bilateral cerebral lobe white matter and hippocampus were different among three groups(P<0.05).Positive correlations were found between the APT MRI parameters and MMSE and MoCA scales in AD and MRI group.No correlation between T1 value and clinical scale was found.ROC curve analysis showed MRI quantitative parameters had certain diagnostic efficacy for AD(AUC=0.66-0.81).Multivariate logistic regression analysis showed that MTRasym of left frontal white matter and AREX of the left hippocampus had the best diagnosis efficient(P=0.001,0.018,respectively,AUC=0.89)in the differentiation between AD and healthy controls.Conclusion:The different MRI quantitative parameters can reflect different pathological changes in AD.For APT MRI,the main different brain subregion between AD and MCI was left frontal gray matter,while the main different brain subregions between AD and healthy control group were bilateral hippocampus and left frontal white matter.The T1 values of bilateral hippocampal and white matter subregions in AD group were higher than MCI group and healthy control group.Multiple APT MRI parameters were correlated positively with MMSE and MoCA.Therefore,quantitative MRI may be a powerful tool for the diagnosis,differential diagnosis of AD,and monitoring the AD course.