Dynamic Contrast-enhanced Magnetic Resonance Imaging Of Meningeal Lymphatic Drainage In Patients With Idiopathic Parkinson’s Disease

Background:In 2015,the first discovery of meningeal lymphatic vessels(mLVs)overturned the recognition that the brain is an immune-exempt organ.There is a lymphoid-meningeal lymphatic system that is different from the periphery,which combines soluble proteins and metabolites in brain.Such macromolecular substances are cleared to deep cervical lymph nodes(dcLNs),which are involved in removing waste,regulating the flow of cerebrospinal fluid(CSF)and maintaining the balance in the brain.Animal studies have found that the lymphatic outflow of CSF in elderly mice is significantly reduced compared with that in younger mice,indicating that the altered or impaired drainage of mLVs plays a role in age-related neurological diseases.Ligation of dcLNs in a transgenic mouse model of Alzheimer’s disease blocked the drainage of mLVs and increased the deposition of amyloid in the meninges.Similarly,blocking meningeal lymphatic drainage by ligating dcLNs can aggravate Parkinson-like pathology in mice.So far,no direct evidence has been obtained from patients with neurodegenerative diseases to support the findings in animal models.Therefore,the function of meningeal lymphatic drainage to dcLNs is qualified with a non-invasive dynamic method.It may be helpful to understand the role of meningeal lymphatic drainage to dcLNs in neurological diseases.Objective:Using dynamic contrast-enhanced magnetic resonance technology(DCE-MRI)to quantitatively analyze dcLNs perfusion,evaluate the drainage function of mLVs in patients with idiopathic Parkinson’s disease(iPD),and explore the clinical value of DCE-MRI parameters in the differential diagnosis of iPD and multiple system atrophy(MSA)and Progressive Supranuclear palsy-Richardson’s syndrome(PSP-RS).Method:114 patients who met the criteria were recruited from the Henan Parkinson’s disease database,including 50 iPD,28 MSA,and 36 PSP-RS.In addition,50 healthy subjects were recruited from the Physical Examination Center of the First Affiliated Hospital of Zhengzhou University from September 2018 to October 2020.We collected the general clinical data of all subjects and assess the severity of iPD patients by the Hoehn-Yahr staging(H-Y staging)scale.All subjects conducted cervical vascular ultrasound and DCE-MRI scan,and examined blood pressure and heart rate before and after DCE-MRI.We manually select the region of interest(ROI),draw time-intensity curves(TIC),and measure DCE-MRI parameters:Time to peak(TTP),Area under the curve(AUC)and wash-in rate.Besides,we compared the parameters as follow:the differences of blood pressure and heart rate before and after DCE-MRI examination,the difference of neck vascular ultrasound examination indexs and the difference of DCE-MRI parameters among NC,iPD,MSA and PSP-RS group.Spearman correlation analysis was used to compare the correlation between DCE-MRI parameters and H-Y scale in the iPD group.We draw receiver operating characteristic curve(ROC),and then analyze the sensitivity and specificity of each parameter of DCE-MRI to the differential diagnosis of iPD.Results:1.There was no statistically significant difference in blood pressure and heart rate before and after DCE-MRI in the NC group,iPD group,MSA group and PSP-RS group.2.There was no significant differences in blood flow velocity and vessel diameter of external and internal carotid arteries among NC group,iPD group,MSA group and PSP-RS group.3.Compared with the NC group,MSA group and PSP-RS group,the average TTP value of bilateral dcLNs in the iPD group was significantly longer(P<0.0001),and the average AUC value was significantly higher than that of the MSA group and PSP-RS group(P<0.0001).The average wash-in rate of dcLNs in the iPD group was significantly reduced(P<0.0001).There was no significant difference in DCE-MRI parameters of dcLNs among NC group,MSA group and PSP-RS group.4.The average TTP value and average AUC value of bilateral dcLNs in the iPD group were significantly positively correlated with H-Y scale(r=0.8782,P<0.0001;r=0.5252,P<0.0001),and the average wash-in rate value was negatively correlated with HY scale(r=0.4334,P=0.0017).5.ROC curve showed that TTP value,AUC value and wash-in rate value of DCE-MRI parameters of bilateral dcLNs had high sensitivity(98.00%;70%;92%)and specificity(95.3 1%;90.63%;89.06%)for the differential diagnosis of iPD.Conclusions:1.In iPD patients,bilateral dcLNs perfusion is reduced,and meningeal lymphatic drainage are impaired.2.DCE-MRI parameters of bilateral dcLNs in iPD patients were correlated with H-Y stage,and meningeal lymphatic drainage disorder was correlated with disease severity.3.The DCE-MRI parameters of bilateral dcLNs are helpful for the differential diagnosis of iPD from MSA and PSP-RS.