The effects of HIV-1 infection on subcortical brain structures in children receiving ART : a structural MRI study

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dc.contributor.advisorMeintjes, Ernesta Men_ZA
dc.contributor.advisorWarton, Christopheren_ZA
dc.contributor.authorRandall, Steven Ronalden_ZA
dc.date.accessioned2016-06-02T08:46:17Z
dc.date.available2016-06-02T08:46:17Z
dc.date.issued2015en_ZA
dc.description.abstractINTRODUCTION This project investigated volumetric differences in certain subcortical structures as measured on high-resolution structural Magnetic Resonance Imaging (MRI) scans traced manually. The sample comprised 79 5-year old children, 52 with HIV and 27 uninfected controls. Infected children were all stable on antiretroviral therapy (ART) and were from the Children with HIV early antiretroviral (CHER) cohort who have been followed since birth. The study aimed to investigate the long-term effects of HIV and ART on the developing brain. While high-resolution structural data has been analysed using automated FreeSurfer to determine volume and cortical thickness, manual tracing remains the gold standard. Thus, manual tracing was used to validate automated measures and investigate subtle group differences in selected regions of interest. METHODS Extensive clinical data were available for all participants in the study. MR images were AC-PC transformed and converted to analyse format. Structures were traced using MultiTracer software. Structures selected included the caudate, nucleus accumbens (NA), putamen (Pu), globus pallidus (GP) and corpus callosum (CC). Four of these structures occur bilaterally. Tracing was performed in 79 subjects. Three subjects were excluded due to poor quality images or pathology; 5 HIV-1 infected children were excluded as they were not randomized between treatment groups. Certain subjects were retraced for inter and intrarater reliabilities. The effect and association of ethnicity, age, birthweight and sex as possible confounders were investigated. As the groups were not well matched for ethnicity, all Cape Coloured children were excluded from further analyses. Analysis of variance was used to test the effect on structure size between HIV-1 infected children and controls, as well as between 3 treatment arms (ART deferred until clinical criteria were met, early ART for 40 weeks, early ART for 96 weeks) and uninfected controls. Analysis of covariance was used to control for the possible confounding effects of sex and age. Each structure was tested for possible association with clinical variables (CD4, CD8, CD4/CD8 ratio and CD4%) both at enrolment and time of scanning. Linear regressions were modelled using clinical variables that showed significant correlation with structure size whilst controlling for covariates. Congruence between automated FreeSurfer and manual segmentation were evaluated via Bland-Altman, Pearson r and Cronbach's alpha.en_ZA
dc.identifier.apacitationRandall, S. R. (2015). <i>The effects of HIV-1 infection on subcortical brain structures in children receiving ART : a structural MRI study</i>. (Thesis). University of Cape Town ,Faculty of Health Sciences ,Division of Anatomical Pathology. Retrieved from http://hdl.handle.net/11427/19894en_ZA
dc.identifier.chicagocitationRandall, Steven Ronald. <i>"The effects of HIV-1 infection on subcortical brain structures in children receiving ART : a structural MRI study."</i> Thesis., University of Cape Town ,Faculty of Health Sciences ,Division of Anatomical Pathology, 2015. http://hdl.handle.net/11427/19894en_ZA
dc.identifier.citationRandall, S. 2015. The effects of HIV-1 infection on subcortical brain structures in children receiving ART : a structural MRI study. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Randall, Steven Ronald AB - INTRODUCTION This project investigated volumetric differences in certain subcortical structures as measured on high-resolution structural Magnetic Resonance Imaging (MRI) scans traced manually. The sample comprised 79 5-year old children, 52 with HIV and 27 uninfected controls. Infected children were all stable on antiretroviral therapy (ART) and were from the Children with HIV early antiretroviral (CHER) cohort who have been followed since birth. The study aimed to investigate the long-term effects of HIV and ART on the developing brain. While high-resolution structural data has been analysed using automated FreeSurfer to determine volume and cortical thickness, manual tracing remains the gold standard. Thus, manual tracing was used to validate automated measures and investigate subtle group differences in selected regions of interest. METHODS Extensive clinical data were available for all participants in the study. MR images were AC-PC transformed and converted to analyse format. Structures were traced using MultiTracer software. Structures selected included the caudate, nucleus accumbens (NA), putamen (Pu), globus pallidus (GP) and corpus callosum (CC). Four of these structures occur bilaterally. Tracing was performed in 79 subjects. Three subjects were excluded due to poor quality images or pathology; 5 HIV-1 infected children were excluded as they were not randomized between treatment groups. Certain subjects were retraced for inter and intrarater reliabilities. The effect and association of ethnicity, age, birthweight and sex as possible confounders were investigated. As the groups were not well matched for ethnicity, all Cape Coloured children were excluded from further analyses. Analysis of variance was used to test the effect on structure size between HIV-1 infected children and controls, as well as between 3 treatment arms (ART deferred until clinical criteria were met, early ART for 40 weeks, early ART for 96 weeks) and uninfected controls. Analysis of covariance was used to control for the possible confounding effects of sex and age. Each structure was tested for possible association with clinical variables (CD4, CD8, CD4/CD8 ratio and CD4%) both at enrolment and time of scanning. Linear regressions were modelled using clinical variables that showed significant correlation with structure size whilst controlling for covariates. Congruence between automated FreeSurfer and manual segmentation were evaluated via Bland-Altman, Pearson r and Cronbach's alpha. DA - 2015 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2015 T1 - The effects of HIV-1 infection on subcortical brain structures in children receiving ART : a structural MRI study TI - The effects of HIV-1 infection on subcortical brain structures in children receiving ART : a structural MRI study UR - http://hdl.handle.net/11427/19894 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/19894
dc.identifier.vancouvercitationRandall SR. The effects of HIV-1 infection on subcortical brain structures in children receiving ART : a structural MRI study. [Thesis]. University of Cape Town ,Faculty of Health Sciences ,Division of Anatomical Pathology, 2015 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/19894en_ZA
dc.language.isoengen_ZA
dc.publisher.departmentDivision of Anatomical Pathologyen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.subject.otherAnatomyen_ZA
dc.titleThe effects of HIV-1 infection on subcortical brain structures in children receiving ART : a structural MRI studyen_ZA
dc.typeMaster Thesis
dc.type.qualificationlevelMasters
dc.type.qualificationnameMSc (Med)en_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceThesisen_ZA
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