Studies On The Diffusion Anisotropy Of White Matter Fibers And Its Clinical Significance Of Leukoaraiosis

Research backgroundLeuko-araiosis(LA) was discovered by CT scanning and was proposed for the first time as a neurological imaging term in 1987.In recent years,along with the wide application of CT and MRI in the clinical medicine,LA was more and more examined in middle aged and elder people,including the normal persons without any clinical symptoms and those with nervous system diseases.Therefore,the imaging and clinical studies on LA have attracted great interest.However,CT and MRI have limitation in their study of cerebral white matter structure,as they could not show the microstructure of white matter,small lesions and LA patients' pathological changes in normal appearing white matter(NAWM).This leads to confusion among LA studies:LA's diagnosis and grading are inconsistent,the incidence reported in the literature is quite different,the pathogenesis,risk factors and clinical significance are uncertain,the relationship between LA and cerebrovascular diseases and that between LA and cognitive dysfunction are considerably disputed.This situation is caused by the lag of neuropathological researches and nerve imaging.Diffusion Tensor MR Imaging(DTI) is a newly developed technology,which offers a better way to explore cerebral white matter damage.In this thesis,we explore the relationship between LA and cerebrovascular diseases,and that between LA and cognitive dysfunction by DTI and clinical studies. Objective and SignificanceTo explore diffusion anisotropy of the white matter fibers in normal subjects' brain tissues and the relations between the diffusion anisotropy and age,providing theoretical basis for LA and the influence of age factors;To investigate the diffusion anisotropy characteristics of LA lesions amd NAWM and explore the diagnosis significance of DTI on LA;To explore the relations between LA and cerebral vascular diseases and provide the valuable gists for clinical diagnosis and prevention of LA by retrospectively analyzing the case history and MRI examination.To investigate the diffusion anisotropy of Lacunar infarction(LI) and LA and explore their differential diagnosis value;To explore the relationships between severe grades of LA and the cognitive impairment by using the mini-mental state examination (MMSE).To further explore the relationships between the diffusion anisotropy and the cognitive impairment of LA by DTI examination.Part?The characteristics of the diffusion anisotropy of the leukoaraiosis suffers' white matter fibersMaterials and MethodsDTI of the cerebral white matter of normal adults Subjects were chosen randomly from those normal people who received head imaging in Southern Hospital from April 2007 to Mar.2008.Qualifying standards:no symptoms or only slight dizziness or headache clinically;no history of nervous system diseases or brain injuries;no cognitive dysfunction;no positive physical signs by nervous system examination;and no abnormal observations confirmed by MRI.16 people respectively in the age group of 25 to 35 years,of 45 to 55,and of 65 above,were chosen at random from those meeting the standards listed above.DTI of LA Subjects were chosen from those who received head MRI in Southern Hospital from April 2007 to Mar.2008 and were divided into the LA group and control group.28 cases LA diagnosed with LA by two experienced physicians were included in the LA group;20 healthy people,with no symptoms or only slight dizziness or headache clinically,no history of nervous system diseases or brain injuries,no cognitive dysfunction,no positive physical signs by nervous system examination and no abnormal observations confirmed by MRI,were chosen as the control group.The subjects in the two groups were age-matched.Methods and Data AnalysisAll participants received a MRI examination.With the application of SE sequence,T1WI(TR 2632ms,TI 850ms,TE 23.3ms),T2WI(TR 5100ms,TE 137.9ms),cross-section scanning was made for each subjects,and,when necessary, sagittal and coronal scannings were conducted.In DTI examination,conventional T1WI,T2WI and FLAIR crsoss-section scannings were conducted.DTI was conducted in the form of single shot echo planar imaging(SE-EPI) cross-section scanning,with the diffusion sensitivity gradient directions being 25.The datum were input into the GE workshop and then processed with the software "Functool" to produce the mean diffusivity(MD) image and fractional anisotropy(FA) image.The genu and splenium of the corpus callosum,the anterior and posterior limb of internal capsule,the frontal lobe white matter,semi-oval center, head of caudate nucleus and thalamus were chosen as the regions of interest(ROI),of which the FA values of the brain tissues in different positions were determined.For LA patients,FA and MD in lesions and NAWM around the anterior and posterior horn of the lateral ventricle and the semi-oval center were measured.Results1.For normal adults,there is no significant difference in the FA values of the corresponding positions in the left and right cerebral hemispheres(P?0.05).The order of FA values is:The splenium(genu) of the corpus callosum?the posterior limb of internal capsule?the anterior limb of internal capsule?semi-oval center?the frontal lobe white matter?thalamus?head of caudate nucleus(P?0.05).But there is no significant difference in the FA values between the splenium and genu of the corpus callosum.2.For all the three age groups,the FA values of the genu of the corpus callosum, the semi-oval center and the frontal lobe white matter decrease with the age increase (P?0.05).Compared between the elderly group and the youth group,the elderly group and the middle-age group,the FA value of the splenium of the corpus callosum decreases with the age increase(P?0.05).Compared with the elderly group and the youth group,the FA value of the anterior limb of internal capsule decreases with the age increase(P?0.05).3.Around the anterior and posterior horn of the lateral ventricle and the semi-oval center,The order of MD value is:MD(LA lesions)?MD(LA NAWM)?MD(control group),(P?0.05).While the order of FA values is:FA(LA lesions)?FA(LA NAWM)?MD(control group),(P?0.05).4.With the increase in the severe grades,the MD values increase and the FA values decrease,(P?0.05).Conclusions1.The FA value can reflect the difference in the structure and spreading of the nerve fiber bundles at different locations of the cerebral white matter.DTI could be employed to quantitatively evaluate the microstructure of the cerebral white matter.2.The FA value can provide the micro-structural information on brain tissue retrogradation in the early stage,thus providing a new pathway for diagnosis of cerebral white matter degeneration.3.DTI is more sensitive than the conventional MRI in monitoring pathological changes in the cerebral white matter,DTI is capable of spotting LA in its early stage. Part?The relationship between LA and cerebrovascular diseases and the differential diagnosis between LA and lacunar infarction Materials and MethodsRetrospective study of leukoaraiosis and cerebrovascular diseases A total of 277 patients diagnosed with cerebrovascular diseases by CT or MRI were collected from Jan.2003 to Aug.2007 in Southern Hospital and 198 patients diagnosed as LA were also collected.The diagnoses of cerebral hemorrhage and cerebral infarction conformed by the standards issued at the fourth national conference on cerebrovascular diseases in 1995.DTI study of LA and lacunar infarction Subjects were randomly chosen form the patients who received MRI scan from Apr.2007 to Feb.2008 in Southern Hospital.28 patiants in LA group were diagnosed with MRI by two experienced doctors.11 patients in LI group who were diagnosed according to the standards established at the fourth national conference on cerebrovascular diseases.These patients developed signs and symptoms of acute cerebral ischemia or nerve systems in 24 hours and went to our hospital for treatment.20 healthy people,with no clinical symptoms,or minor ones such as headache and dizziness,no history of nerve system diseases,no cognitive dysfunction,no obvious nerve system signs,no abnormalities found after MRI examination,were divided into control group.The subjects in the there groups were age-matched.Methods and data analysisAll participants received a MRI examination.With the application of SE sequence,T1WI(TR 2632ms,TI 850ms,TE 23.3ms),T2WI(TR 5100ms,TE 137.9ms),cross-section scanning was made for each subjects,and,when necessary, sagittal and coronal scanning were conducted.In DTI examination,conventional T1WI,T2WI and FLAIR crsoss-section scannings were conducted.DTI was conducted in the form of single shot echo planar imaging(SE-EPI) cross-section scanning,with the diffusion sensitivity gradient directions being 25.The datum were input into the GE workshop and then processed with the software "Functool" to produce the mean diffusivity(MD) image and fractional anisotropy(FA) image.ROIs were placed at the lesions of LA,the infarction centers of LI and its healthy opposite site respectively.FA and MD were measured.Results1.The incidences of LA among 277 patients with cerebrovascular diseases in terms of age were as follows:20.8%(16/77) for patients under 60;34.1%(29/85) for patients from 61 to 70;63.3%(50/79) for patients from 71 to 80 and 94.4%(34/36) for patients above 81,(P?0.05).2.The incidences of LA in different types of cerebrovascular diseases were as follows:30.3%(10/33) with mild LA for patients with cerebral hemorrhage; 40.2%(72/129) with severer LA for patients with cortical infarction and subcortical infarction and 72.3%(47/65) with severest LA for patients with lacunar infarction, (P?0.05).3.Among 198 LA patients with LA,5.1%(10/198) were accompanied with cerebral hemorrhage;60.1%(119/198) with ischemic cerebrovascular diseases, (P?0.05).4.The average MD value of the infarction centers of LI is lower than that of the control group;while the MD value of the LA lesions is higher than that of the control group.The FA values both in infarction centers LI and LA lesions are lower than that of the control group,(P?0.05).Conclusions1.Between two risk factors of age and the cerebrovascular diseases,the former has greater correlations with LA than the latter. 2.Cerebrovascular diseases also have correlations with LA,among which ischemic cerebrovascular diseases,especially lacunar infarction is closely related toLA.3.It is suggested that cerebral infarction should not be regarded as a premonitor of LA,on the contrary,LA maybe develops before cerebral infarction and LA may be the omen of the occurrence of cerebral infarction.4.There is a diagnostic difference in DTI parameters between LA and acute cerebral infarction,which provide the basis for the differential diagnose between the two diseases.PART?Preliminary study on the relationship between LA and cognitive dysfunctionMaterials and methodesTotal 49 cases were involved in this study,including hospitalized patients diagnosed with LA in the Department of Neurology and people for medical check-up in Southern Hospital from Apr.2007 to Mar.2008.LA was divided into three grades according to the standards proposed by Wahlund.Control group:18 people with no obvious clinical symptom or with slight dizziness and headache,negative history for neural system diseases,no cognitive dysfunction,no brain trauma,no positive sign in neurological examination,no abnormities MRI examination.All patients were matched according to age and education.MethodsThe mini-mental state examination(MMSE) were performed to evaluate the patients' status of cognitive function.LA patients were checked with diffusion tensor MR imaging(DTI) and the FA and MD values in NAWM were measured.Results1.The cognitive function of LA patients decreases with the decrease of the MMSE scores,compared LA-1 with LA-3 group,LA-1 and control group,LA-2 and control group,LA-3 and control group respectively,(P?0.05).2.On the item of time orientation,place orientation and mental arithmetic,the scores of LA patients are lower than that of control group,(P?0.05).On the item of memory,language and comprehensive abilities,there is no significant difference between LA and control group.3.The FA value and MD value correlated with cognitive function(the correlation coefficient is from 0.5 to 0.8,p?0.05 ) in LA-1,LA-2 and all 31 patients group respectively,among which,FA value has positive correlation and MD value has negative correlation with cognitive function.Conclusions1.The DTI parameters of LA NAWM region have significant correlation with cognitive function of LA patients.2.DTI is far more sensitive in studying LA patients' cognitive dysfunction than that of MRI.