The Technology And Clinical Application Of Arterial Spin Labeling And Double Inversion Recovery In Cerebral Small Vessel Disease

Cerebral small vessel disease(CSVD)is the fifth leading cause of dementia worldwide.The common neuroimaging finding of CSVD include:recent small subcortical infarction,lacunes,white matter hyperintensities,perivascular spaces,microbleeds and brain atrophy.Recently,there is a growing recognition on that cerebrovascular disease is associated with the cognitive decline even the occurrence of cerebral infarction.Therefore,CSVD begun to draw more attention.WMHs used to define as "normal" appearance of aging.In a Meta analyses consist of 22 researches,WMHs is obviously related to the cognation,and will double the risk of dementia and triple the risk of stroke.Many studies define WMHs as a biomarker of brain degeneration.According to the Wardlaw et al,WMHs are defined as abnormal signal of white matter(WM)with different volume with following characteristics:hyperintensity on T2-weighted images such as fluid-attenuated invasion recovery,no cavitation(signal different from CSF).At the same time,lesions in the subcortical grey matter(GM)or brainstem are not included in this category.If the lesions in deep GM and the brainstem are all included,the term should be subcortical hyper intensities.It is hard to simply describe the pathology and cause of WHMs.However,lots of researches indicates that the pathology of WMHs including:discontinuous edema,gliosis,the loss of white matter fiber and demyelination.The loss of neuroglial,vacuolization,activation of microglia and endothelial cells and the deposition of some kinds of protein are all related to the cause of WMHs.For the detection of WMHs,Double Inversion Recovery(DIR)of Magnetic Resonance Imaging(MRI)has lots of advantages.First of all,with two reverse pulse,the signal of white matter can be suppressed,resulting in higher contrast compare to the single reverse pulse.Additionally,DIR is a 3 dimensional(3D)sequence with higher resolution compare to the 2 dimensional(2D)T2-weighted-Fluid-Attenuated Inversion Recovery(FLAIR).DIR has advantages in detecting small lesions and distinguish whether the lesion located in the WM or GM.Besides,perfusion parameters like cerebral blood flow(CBF)is also very important to evaluate CSVD.And CBF can reflect the metabolism and function changes of human brain.Lots of ways can be used to evaluate the brain perfusion as follow:Positron Emission Tomography(PET),Computed Tomography scan(CT)perfusion,Dynamic contrast-enhanced(DCE),Arterial spin labeling(ASL)and so on.ASL is a non-invasive technique to label the blood by radiofrequency pulse to get the hemodynamic information.The CBF and bolus arrival time(BAT)are detected in this research.With the characteristic of non-invasive,replicability and no need of contrast agent,ASL is highly recommend for clinical use.There exist many kinds of ASL sequences,for example:Pulsed Arterial Spin Labeling(PASL),Continuous Arterial Spin Labeling(CASL),Pseudo-Continuous Arterial Spin Labeling(pCASL)and so on.In this study,we use the multi-inversion-time pulsed ASL(mTI PASL)sequence,with 16 different post label delay time and fitting method to get more accurate perfusion value.MTI ASL avoid the influence of post label delay time to CBF and can achieve the BAT at the same time.BAT is less focused compare to CBF,in this study BAT has obvious relationship with the associated symptom of diabetes.Many risk factors(including:aging,diabetes,hypertension,hyperlipidemia and Alzheimer's disease)are closely related to CSVD.Type 2 diabetes is the most common metabolic disease in China.According to a recent study with sample of 46239 adults,the prevalences of total diabetes and prediabetes were 9.7%and 15.5%respectively.Diabetes has become a major public health problem in China.Many previous researches all demonstrate that diabetes can cause both microvascular and macrovascular disease.Among these,the diabetes related microvascular disease can cause many complications(Diabetic retinopathy and so on).These complications is the main cause of decline in the living standard and shortened expectation of life.And the diabetic retinopathy is recommended to be an important indicator for CSVD.In this study,we use more accurate methods to analyses the MRI imaging characters of CSVD based on the disease like type 2 diabetes,hypertension and hyperlipidemia.This study contains two parts,as follow:1.Cerebral Hemodynamic of Type 2 Diabetes Revealed by Multi-TI ASL;2.T2-weighted-Fluid-Attenuated Inversion Recovery and Double inversion recovery sequences imaging the characteristics of White matter hyperintensity and their relationship with the clinical feature.Part ?Cerebral Hemodynamic of Type 2 Diabetes Revealed by Multi-TI ASLPurposeThe purpose of this study was to characterize cerebral hemodynamic changes of type 2 diabetes using a multi-inversion-time(mTI)3D GRASE pulsed ASL(PASL)sequence to simultaneously measure CBF and bolus arrival time(BAT).BackgroundDiabetes has been reported to affect the microvasculature and lead to cerebral small vessel disease(CSVD).Past studies using arterial spin labeling(ASL)at single post-labeling delay reported reduced cerebral blood flow(CBF)in patients with type 2 diabetes.Materials and MethodsThirty-six patients with type 2 diabetes(43 to 71 years,17 male)and 36 gender-and age-matched control subjects underwent MRI scans at 3T.Mean CBF/BAT values were computed for gray and white matter(GM and WM)of each subject,while a voxel-wise analysis was performed for comparison of regional CBF and BAT between the two groups.ResultsMean CBF of the WM but not GM of the diabetes group was significantly lower than that of the control group(p<0.0001).Regional CBF decreases were detected in the left middle occipital gyrus(p=0.0075),but failed to reach significance after correction of partial volume effects.BAT increases were observed in the right calcimine fissure(p<0.0001),left middle occipital gyrus(p<0.0001)and right middle occipital gyrus(p=0.0011).Within the group of diabetic patients,BAT in the right middle occipital gyrus was positively correlated with the disease duration(r=0.501,p=0.002),BAT in the left middle occipital gyrus was negatively correlated with the binocular visual acuity(r=-0.408,p=0.014).Conclusions Significant differences in CBF and BAT were observed in patients with diabetes,which may be related to impaired vision and risk of CSVD of type 2 diabetes.Part ? T2-weighted-Fluid-Attenuated Inversion Recovery and Double Inversion Recovery Sequences Imaging the Characteristics of White Matter Hyperintensities and the Relationship of the Imaging Data and Clinical Data PurposeThe purpose of this study is to detect and analyze the White Matter Hyperintensities(WMHs)in the patients with Cerebral Small Vessel Disease(CSVD)(e.g.diabetes,hypertension and hyperlipidemia)by Double Inversion Recovery(DIR)and Fluid Attenuated Inversion Recovery(FLAIR)sequences.And explore the relationship of WMHs and clinical feature.BackgroundRecently,CSVD and its correlation with the clinical feature draw more and more attention.The related WMHs are one of the main manifestation of CSVD on MRI.Compare to FLAIR,DIR provide better contrast to noise ratio(CNR)and higher resolution.Manual and automatic segmentation of WMHs benefit the study of WMHs.Materials and Methods36 type 2 diabetes patients and 36 age-and gender-matched control subjects were recruited,DIR,FLAIR and T1-MPRAGE data were collected on the MAGNETOM Skyra 3T scanner(Siemens,Erlangen,Germany).24 patients with CSVD(including diabetes,hypertension,hyperlipidemia and so on)were recruited,FLAIR and T1-MPRAGE data were collected on the MAGNETOM Prisma 3T scanner(Siemens,Erlangen,Germany).Clinical data including age,gender,blood sugar,blood lipid,blood pressure,cognition score and so on were collected.The number of WMHs between diabetes group and control group were counted and compared.WMHs were segmented manual and automatic by ITK-SNAP and the method from DeCarli et al.The volume of the WMHs were calculated with ITK-SNAP and Matlab.The correlation of the volume of WMHs and clinical data were calculated.The T1 images were segmented into white matter(WM),grey matter(GM)and cerebrospinal fluid(CSF).ResultsCompare to the control group,type 2 diabetic patients had more WMHs than the control group(p=0.0039).Compare to the registration method by Advanced NormalizationTools(ANTS)and Statistical Parametric Mapping(SPM),the modified Elastix registration method have the advantages of saving time,and better performance.We get good automatic segmentation method by improving the registration and segmentation.Compare to the manual segmentation results,the automatic segmentation results have some overestimate and under estimate.The correlation between the results are still good(p<0.01).Some significant correlations were founded in between the clinical data and the imaging data.There is a clear positive correlation between:Age and pulse pressure(r=0.77);Sex and volume of the GM(r=0.58);Sex and the whole brain volume(r=0.67);Diastolic blood pressure and cholesterol(r=0.63);Diastolic blood pressure and Low density lipoprotein(r=0.68).There is a clear negative correlation between:Age and volume of the GM(r=-0.63);Age and volume of the WM(r=-0.73);Age and whole brain volume(r=-0.59);Sex and pulse pressure(r=-0.55);Sex and NIH Flanker Scale(r=-0.55);Pulse pressure and volume of WM(r=-0.56);Pulse pressure and the whole brain volume(r=-0.67)and so on.ConclusionsMore WMHs were observed in patients with diabetes,which may be related the risk of CSVD of type 2 diabetes.The manual segmentation method and the automatic segmentation method have good correlations.Some correlations between clinical data and the imaging data was founded.