| Background:Autism,Asperger's Syndrome,Rett's syndrome and disorder-not otherwise specified(PDD-NOS)are a group of neurodevelopmental pathologies characterized by severe impairment in reciprocal social interactions and communication skills,and the presence of restricted,stereotypical behaviors.Impaired language function is frequently observed as the initial signs in people with autism.In recent years,the incidence of autism has kept on rising.Because of the serious effect to these patients and the high community and individual cost of ASDs,these disorders have received more and more attention in the global public health.Recently,the evaluation of the behavioral characteristics of children with ASD are based on several rating-scale instruments and qualitative analysis for the complexity of affecting factors.The mechanisms of ASD remain largely unknown.As a well-developed theory of ASD,Weak Central Coherence Theory,devised by Frith in 1994,was accepted in recent decades.The symptoms of ASD have been hypothesized to be caused by alterations in brain connectivity.White matter tracts form the structural foundation for brain connectivity by linking discrete grey matter regions into integrated neural circuits.Disruption of the long-range white matter tracts that mediate connectivity within systems may be an important pathogenic factor contributing to core social impairments in ASD.There is an already vast amount of studies on the arcuate fasciculus(AF),an important fiber pathway that connects the frontal expressive language area with the posterior temporoparietal receptive language areas and forms the substrate of the dorsal language pathway.Diffusion tensor imaging(DTI)is a noninvasive,exquisitely sensitive method to delineate WM tracts and providing indirect quantitative measures of WM integrity by measuring random motion or diffusion of water molecules in the underlying tissue microstructure.The tractography-based analysis method of language-related white matter tracts,such as arcuate fasciculus(AF),uncinate fasciculus(UF)and inferior fronto-occipital fasciculus(IFOF),are now widely recognised.WM tract reconstruction makes it possible to improve the precision of quantitative analysis.Although the research on language-related white matter tracts with DTI is abundant,the study especially on low age children is scant.Given the importance of early intervention in ASD,it is urgently needed to find efficient methods of early diagnosis.As an objective method,DTI may hold a very important position in assisting in clinic diagnosis of DSA.This study use DTI parameters to investigate the alterations of arcuate fasciculus in autism spectrum disorder toddlers with language delay.This study contains three parts:Part 1.The correlation of DTI parameters and assessment scores of toddlers with language delayObjective:To investigate the correlation of DTI parameters and assessment scores of 2-3-year-old toddlers with language delay using single-shot fast spin echo(SSFSE)MRI sequence.Material and Methods:There were 25 toddlers(14 men,11 women;mean age 2.39±0.14 years,rang 1.25-3.83 year)with language delay were included in this study.The assessment of language function was based on Expressive Language and Receptive Language subsets of the Chinese Version of the Psychoeducational Profile(C-PEP).For toddlers with language regression,the scores are subject to the time of MRI scan.Each subject was sedated using chloral hydrate(0.5 g in 10 ml)during MRI scanning with parental consent.All MRI scans were acquired with a 3.0 T Siemens TIM Trio scanner.MRI sequences included T2 Weighed imaging(T2WI),3-dimensional magnetization-prepared rapid acquisition gradient-echo(T1 3D MP-RAGE)and single-shot echo planar(SE-EPI).The imaging parameters were as follow,T2WI:TR = 3220 ms,TE = 99 ms,FOV = 250 mm,slices = 20,slice thickness = 5.0 mm.T1 3D MP-RAGE:TR = 1900 ms,TE = 2.5 ms,FOV = 250 mm,slices = 176,slice thickness = 1.0 mm,and bandwidth = 170.DTI:TR = 5500 ms,TE = 92 ms,FOV = 260 mm,matrix = 128 x 128,20 diffusion encoding directions,slice thickness = 3.0 mm,and variable b-values between 0 and 1000 s/mm2.For tractography,post-processing was performed using Neuro 3D in the Siemens Syngo Workstation.Tractography of the AF was performed by two raters.To access the fiber tracking of AF,a seed region of interest(ROI)was placed in the green triangular-shaped periventricular white matter on the encoded tensor map in the coronal plane.The target ROI was placed in the posterior temporal lobe,seen as a blue narrow strip structure lateral to the splenium of the corpus callosum.Then,fractional anisotropy(FA),average fiber length(AFL),tract volume(TV)and number of voxels(NV)were automatically calculated.Statistical analysis was performed using IBM SPSS v22 statistical software.Pearson correlation analysis was used to analyze the relation of DTI parameters and assessment scores of language,there was a significant difference when P<0.05.This study was approved by local institutional review board and informed consent was obtained.Results:After T2WI acquisition,one toddler diagnosed with gray matter heterotopias and another with leukomalacia were excluded.Finally,23 toddlers were included(13 men,10 women;mean age 2.33 ± 0.68 years,rang 1.25-3.83 year).The range of language scores were 16-56(EL)and 15-64(PL).The results of the Pearson correlation indicted that FA values were correlated positively and significantly with EL(r=0.647,P<0.05)and PL(r=0.590,P<0.05).NV and TV values were correlated negatively with EL(r=-0.692,P<0.001;r=-0.71,P<0.001)and PL(r=-0.482,P<0.05;r=-0.509,P<0.05).In addition,AFL values were not correlated significantly with EL or PL.Conclusion:The FA,NV and TV values of the AF were correlated with assessment scores of toddlers with language delay.Potentially,DTI parameters of anguage-related white matter tract would be one of the quantitative diagnosis of language disorders.Part 2.The value of DTI parameters to differentiate ASD toddlers with language delay from developmental language disorder(DLD)Objective:To evaluate the ability of DTI parameters of language-related white matter tract to different ASD from toddlers with from developmental language disorder.Material and Methods:There were 16 ASD toddlers with language delay and 18 DLD toddlers were included in this study.The diagnosis of those ASD toddlers were assessed by two experienced neuropsychologists using the Autism Behavior Checklist-ABC.All of them had a score of at least 30.The two groups were well matched with age,gender and handedness.The assessment of language function was based on Expressive Language and Receptive Language subsets of C-PEP.The mean IQs were obtained by the Wechsler Intelligence Scale for Children(WISC).Toddlers with hypoxic-ischaemic brain damage(HIBD),brain trauma and other congenital or acquired defects were excluded.MRI scans were acquired with a 3.0 T Siemens TIM Trio scanner.MRI sequences included T2WI,T1 3D MP-RAGE and DTI with the same parameters as previous part.Each toddlers were sedated using chloral hydrate(0.5 g in 10 ml)during MRI scanning.Tractography of the AF was performed by two senior radiologists using Neuro 3D in the Siemens Syngo Workstation.After fusing the images between T1 3D MP-RAGE and DTI,AF were tracked by placed seed ROI and target ROI in the coronal plane and transverse plane respectively as mentioned above.Similarly,FA,AFL,TV and NV values were automatically calculated.Pearson Chi-squared test and independent sample t-tests were used to compare gender,age,IQ and the scores of EL and PL respectively.Inter-group differences in the DTI parameters of AF were analyzed with analysis of variance(ANOVA),there was a significant difference when P<0.05.This study was approved by local institutional review board and informed consent was obtained.Results:After T2WI acquisition,one toddler diagnosed with ASD who had gray matter heterotopias and one toddler with hypoplasia of corpus callosum from the DLD group were excluded.In addition,one DLD toddler was excluded due to failure in fusing the images between T1 3D MP-RAGE and DTI.Finally,15 ASD toddlers(11 men,4 women;mean age 2.49±0.60 years,rang 1.42-3.25 year)and 16 TD toddlers(10 men,6 women;mean age 2.46±0.67 years,rang 1.25-3.83 year)were included.Pearson Chi-squared test and independent sample t-tests revealed that there were no significant differences in gender,age or PIQ between the two groups.However,DLD group had higher scores than ASD group in VIQ,EL and PL.The ANOVA showed that the ASD group had a significantly lower FA values(F =8.560,p<0.05),as well as significantly higher TV values(F = 8.158,p = 0.008)and NV values(F = 12.00,p = 0.002)compared to the DLD group.With age as the covariate,the analysis of covariance revealed different significance of TV(F=10.373,p =0.003)and NV(F=14.84,p=0.001).ANOVA for AFL revealed no significant differences between the two groups(F = 2.158,p>0.05).Conclusion:DTI parameters of FA were valuable to differentiate ASD with language delay from toddlers with DLD.DTI has the potential to be one of the objective and effective method in assisting early diagnosis,early intervention and improve the long-term outcomes of ASD. |
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