| Background and ObjectiveLeukemia is one of the most common primary malignant tumor in children and adolescents, and acute lymphocytic leukemia(ALL) the most common observed type. At present,there are over five million leukemia patients in our country,of which accounted for about 50% in children, leukemia is among our children malignant tumor incidence forefront, incidence of children under the age of 15 is about 4 over one hundred thousand, accounted for 35% of all of the malignant tumor in children, incidence of a disease in recent years, rising at a rate of 5% every five years.Childhood leukemia has two characteristics:First, high degree of malignancy, rapid progression of the disease, a serious threat to life and health in children; the second is sensitive to chemotherapy, leukemic cell is easy to kill.The survival rate of children with leukemia has effectively improve by methotrexate given intravenously (IV-MTX), but leukoencephalopathy (LE) induced by chemotherapy seriously affect brain structure and intellectual development in children with leukemia. Therefore, it is very important to timely treat LE in ALL children.In recent years, Radiological imaging studies have shifted from a morphological diagnostic to combination of form and function, some new functional imaging technology is gradually used for clinical. They are not only from the morphology,and more from function of nervous cell to further deep research brain structure and function changes in ALL children after treatment.Magnetic resonance spectroscopy (MRS) is a non-invasive techology to study of metabolism, biochemical changes and quantitative analysis of chemical in living tissue. At present, MRS is the most commonly used in hydrogen spectroscopy (1H) and phosphorus (31P), in recent years, the most extensive application of’HMRS, because of the highest concentration of the hydrogen proton in the organism. The N-acetylaspartate (NAA), choline (Cho), creatine (Cr) and other brain metabolites can be measured by 1HMRS.NAA is a biomaker of neuron, which can reflect the content and function of neuron. Cho include choline, acetylcholine and phosphatidylcholine. Cr include creatine, creatine phosphate, and a small amount of GABA, which is often used as a reference because of its content stability.Diffusion-weighted MR imaging(DWI) is a techology to reflect the molecular motion in cell,which can measure the microscopic random motion of water molecules in vivo. The characteristics of water molecule motion can be indicated by apparent diffusion coefficient (ADC).Diffusion tensor imaging (DTI) is a 3D imaging technology based on DWI.Diffusion anisotropy of water molecules can be quantified in multiple directions by using diffusion sensitive gradient.It can reveal the relationship between white matter fibers and continuity, so as to reflect the subtle structure of tissues in vivo. Apparent diffusion coefficient (ADC) and anisotropic water diffusion (FA) can be measured by DTI. ADC can reflect the average diffuse distance of water molecules in region of interest area, and FA is to measure the diffuse direction of water molecules.Some researches demonstrated that there was serious IQ impairment in ALL children with LE induced by MTX chemotherapy the studys of functional magnetic resonance imaging(FMRI)in ALL children focused on one aspect of MRI, and after a long time at CR. To our knowledge, at present,there was no study on the correlation between MRS values and IQ in ALL children after chemotherapy.The study of single-voxel 1HMRS on local sites found that ALL children with CR had NAA/Cr, NAA/Cho decreased, while Cho/Cr increased.The DTI study found that specific locations of the brain atrophy, FA value decreased, but no significant change in the ADC value. The studies of correlation between DTI parameters and IQ focus on adult with childhood ALL. So they could not accurately reflect the correlation in the first week at CR. At the same time, according to clinical risk, ALL is divided into standard risk (SR), intermediate risk (IR) and high risk (HR), these different groups treated with different drug dose, method and therapy time.There are no knowledge about the brain structure and function change induced by different chemotherapy in ALL children.there are many aspects of LE in ALL children need to be resolved. 1,The dynamic evolution process of brain metabolites and diffusion of water molecules at short time after CR; 2 The correlation between brain metabolites, ADC value, fractional anisotropy value(FA),etc and IQ in ALL children after CR; 3,Which imaging technique is earlier and more sensitive to observe the LE in ALL patients caused by chemotherapy;4, The difference of brain metabolites, ADC value and FA value in ALL children by different chemotherapy.This study combined the 1HMRS, DTI and intelligence(IQ) score to measure the changes of metabolites in the brain (NAA, Cho, Cr,etc) ADC values, FA values, and IQ score in ALL chidren before therapy and complete remission(CR) after chemotherapy,Effects of Ⅳ-MTX on the structure, metabolism and function of brain in ALL children were analyzed by FMRI and intelligence. To provide theoretical basis for LE induced by IV-MTX chemotherapy, and to provide clinical treatment decisions for the prevention of LE.Part1 Analyses of brain in children with acute lymphoblastic leukemia by using proton magnetic resonance spectroscopyPurpose:To investigate the value of proton magnetic resonancespectroscopy(1H MRS) in the pediatric patients with acute lymphoblastic leukemia (ALL).Methods:30 pediatric patients(2-14year) with ALL and 30 pediatric volunteers (2-14year) were examined with 1H MRS,the MRS values[N-acetylasparate(NAA)、Choline(Cho)、Creatine(Cr)、Lactate(Lac)、NAA/Cr、 NAA/Cho、Cho/Cr] were observed.T paired test was used to compare MRS values measured in ALL patients before start of treatment and after treatment at CR.Two independent-sample t test was used to compare MRS values between patients and control subjects.ANOVA was used to compare MRS values between SR,IR and HR in ALL children after CR, at first, analysis of variance Levene homogeneity before ANOVA.Significance was accepted at the p<0.05 level.Result:NAA/Cho、NAA/Cr in complete remission(CR) ALL patients were diminished,Cho/Cr were increased, as compared with ALL patients before therapy and normal volunteers.There were no statistical significance of NAA/Cho、NAA/Cr and Cho/Cr in frontal lobe, genu of Corpus callosum and internal capsule between SR group,and IR group,and HR group in ALL patients after CR.Conclusion:1H MRS can accurately measure the changes of brain metabolites in ALL patients before treatment and after complete remission. There were no differences of the changes of brain metabolites in ALL patients with different therapy after CR.Part2 Analyses of brain in children with acute Iymphoblasticleukemia by using Diffuse tensor MR imagingPurpose:To investigate the value of Diffuse tensor MR imaging(DTI) in the pediatric patients with acute lymphoblastic leukemia (ALL).Methods:30 pediatric patients (2-14year) with ALL and 30 pediatric volunteers (2-14year) were examined with DTI,the ADC value and FA value were observed.T paired test was used to compare ADC value and FA value measured in ALL patients before start of treatment and after treatment at CR.Two independent-sample t test was used to compare ADC value and FA value between patients and control subjects. ANOVA was used to compare DTI values between SR,IR and HR in ALL children after CR, at first, analysis of variance Levene homogeneity before ANOVA.Significance was accepted at the p<0.05 level.Result:2 (6.7%) HR group patients after CR had hyperintensity in deep white matter on DWI images.7(23.3%) patients after CR showed Brain atrophy, include cerebral fissure widened, reduced brain volume, ventricular dilatation.There was no statistical significance of ADC and FA, as compared with ALL patients before therapy and normal volunteers.FA values in complete remission(CR) ALL patients were decreased, There was statistical significance of ADC in frontal lobe and splenium of corpus callosum,but others ADC values were no different.There was statistical significance of FA in frontal lobe and genu of corpus callosum,others had no statistical significance, as compared with ALL patients before therapy and after complete remission.There were no statistical significance of ADC and FA in frontal lobe, genu and splenium of corpus callosum,and internal capsule between SR group,and IR group,and HR group in ALL patients after CR.There were no differences of white matter bundles in ALL patients between before treatment and after CR by 3D CDTI technology.Conclusion:DTI can accurately measure the changes of ADC value and FA value in ALL patients before treatment and after complete remission. There were no differences of the changes of ADC and FA in ALL patients with different therapy after CR.Part3 Analyses of the changes of intelligence in acute lymphoblastic leukemia children and the correlation between the changes of intelligence and fMRI valuesPurpose:To investigate the changes of Intelligence in the acute lymphoblastic leukemia (ALL) children before treatment and after complete remission by using Intelligence Scale for Children. To study the correlation between the changes of intelligence and fMRI values.Methods:30 pediatric patients (2-14year)with ALL and 30 pediatric volunteers (2-14year) were assessed by The Wechsler Preschool and Primary Scale of Intelligence (WPPSI-Ⅲ2002) and Wechsler Intelligence Scale for Children (WISC-IV 2003).The total intelligence quotient(IQ), verbal comprehension, perceptual reasoning,working memory and processing speed were ossessed. T paired test was used to compare MRS values measured in ALL patients before start of treatment and after treatment at CR.Two independent-sample t test was used to compare MRS values between patients and control subjects.Pearman regression analysis was used to analye the correlation between the changes of intelligence and fMRI values.Significance was accepted at the p<0.05 level.Result:There were no differences of intelligence between ALL patients before treatment and normal contral. The total intelligence quotient(IQ) were decreased in ALL children after CR. As compared with ALL patients before therapy and normal volunteers, in> 6 years group,the total IQ, perceptual reasoning,working memory and processing speed had statistical significance,but verbal comprehension had no statistical significance, in< 6 years group, all total intelligence quotient(IQ) had statistical significance.The differences of intelligence were positively correlated with anisotropy fractional (FA) value and the ratio of NAA/Cr and NAA/Cho in some location.In>6 years group,the locations were frontal lobe. The difference of intelligence was negative correlated with Cho/Cr in genu of internal capsule, in<6 years group, the location was fontal lobe. In two groups, the locations of positive correlation with FA value were frontal lobe,genu and splenium of corpus callosum.The others IQs were not correlated with the others values of DTI and MRS.Conclusion：Ⅳ-MTX chemotherapy can affect intelligence in initial ALL children.MRS may earlier found LE induced by chemotherapy in ALL children; NAA and FA could be a more sensitive indicator to reflect LE in ALL patients after chemotherapy. |
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