Browsing by Author "Meintjes, Ernesta"

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    A vector based approach for high frequency prospective correction of rigid body motion in Magnetic Resonance Imaging (MRI)
    (2019) Van Niekerk, Adam Marthinus Johannes; Meintjes, Ernesta; van der Kouwe, Andre
    Magnetic Resonance Imaging (MRI) is remarkable in that it is possible to obtain image resolutions much smaller than the wavelength of the radiated signal. This is achieved through the use of specialised gradient coils that linearly manipulate the magnitude of the magnetic field within the imaging volume. The instantaneous signal received from the subject represents a periodically varying map based on the duration and magnitude (moment) of the previously applied gradient fields. Representing an object as the sum of periodic maps is difficult and as a result many unique gradient moments are required to form an image. When the subject moves the periodic maps are no longer coherent and the constructive/destructive interference becomes invalid. The artefacts are dependent on how and when motion occurred, and manifest as ghosting, ringing and blurring of the image. This thesis describes a novel approach to measuring and correcting for motion as the data are acquired. A small device was constructed that combines observations from a magnetometer (static magnetic field [z]) and an accelerometer (earth’s gravitational field [y]) with an angular rate sensor to determine its orientation with respect to the imaging coordinate frame (VectOrient). It was precise enough to track the subject’s heart beat and breathing and accurate to within one degree. A gradient field probe was then designed for position encoding. The probe measured the rate of change of the gradient magnetic fields using three mutually orthogonal pickup coils. Assuming linear gradients and using Maxwell’s equations, with negligible rates of change of curl and divergence, it was possible to accurately model the three dimensional vector fields that the gradients produce, eliminating the need for a laborious manual calibration. Sub-microsecond synchronisation was achieved by detecting radio frequency pulses in the imaging sequence with a small resonant circuit. This combined with a 2.4 GHz radio link enabled the probe to be wireless. Finally, the pickup coil observations were combined with the vector based orientation estimates and the gradient field model to achieve efficient multidimensional position, orientation and inter-gradient-delay encoding with a 880 µs pulse sequence insert. The Wireless Radio frequency triggered Acquisition Device (WRAD) tracks involuntary and deliberate subject motion, improving image quality without scanner specific calibration.
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    Active shape model segmentation of Brain structures in MR images of subjects with fetal alcohol spectrum disorder
    (2010) Eicher, Anton; Marais, Patrick; Meintjes, Ernesta
    Fetal Alcohol Spectrum Disorder (FASD) is the most common form of preventable mental retardation worldwide. This condition affects children whose mothers excessively consume alcohol whilst pregnant. FASD can be identified by physical and mental defects, such as stunted growth, facial deformities, cognitive impairment, and behavioural abnormalities. Magnetic Resonance Imaging provides a non-invasive means to study the neural correlates of FASD. One such approach aims to detect brain abnormalities through an assessment of volume and shape of sub-cortical structures on high-resolution MR images.
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    Assessing strain in arrhythmogenic right ventricular cardiomyopathy using cine DENSE MRI
    (BioMed Central Ltd, 2009) Ongori, Joash; Hendricks, Neil; Spottiswoode, Bruce; Meintjes, Ernesta; Epstein, Frederick; Mayosi, Bongani
    The kinematics of the right ventricle (RV) are not well understood due to its thin wall and asymmetric geometry. Cine displacement encoding with stimulated echoes (cine DENSE), which measures intramyocardial displacement and strain, has been adapted for RV analysis with encouraging preliminary results in normal subjects. This preliminary study evaluates cine DENSE MRI for detecting decreased myocardial strain in arrhythmogenic right ventricular cardiomyopathy (ARVC). ARVC is a unique heart muscle disease affecting predominantly the RV. The pathological hallmark of fibro-fatty replacement of the myocardium may result in localised aneurysms and wall motion abnormalities, detectable by cardiac magnetic resonance imaging.
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    Calculating 3D intramyocardial strain tensors in a single slice of myocardium using MRI
    (2006) Hess, Aaron; Meintjes, Ernesta
    Strain is a measure of cardiac deformation and provides information on the mechanical and functional properties of the heart. As this deformation occurs in three dimensions (3D), a 3D measure of strain is appropriate, however, currently the procedures for measuring 3D intramyocardial strain fields are limited to a handful of techniques. The only widely accepted method being the use of tagging in orthogonal image planes that requires the imaging of the entire myocardial volume, followed by lengthy and time consuming post processing. A method to combine cine displacement encoding with stimulated echoes (cine-DENSE) and cine strain encoded MRI (cine-SENC) for the formulation of the complete 3D strain tensor field for a single slice of myocardium is proposed.
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    Characterization of the facial phenotype associated with fetal alcohol syndrome using stereo-photogrammetry and geometric morphometrics
    (2009) Mutsvangwa, Tinashe E M; Douglas, Tania S; Meintjes, Ernesta
    Fetal Alcohol Syndrome (FAS) is a clinical condition caused by excessive pre-natal alcohol exposure and is regarded as a leading identifiable and preventable cause of mental retardation in the Western world. The highest prevalence of FAS was reported in the wine-growing regions of South Africa but data for the rest of the country is not available. Required, therefore, are large-scale screening and surveillance programmes to be conducted in South Africa in order for the epidemiology of the disease to be understood. Efforts to this end have been stymied by the cost and labour-intensive nature of collecting the facial anthropometric data useful in FAS diagnosis. Stereo-photogrammetry provides a low cost, easy to use and non-invasive alternative to traditional facial anthropometry. The design and implementation of a landmark-based stereo-photogrammetry system to obtain 3D facial information for fetal alcohol syndrome diagnosis (FAS) is described. The system consists of three high resolution digital cameras resting on a purpose-built stand and a control frame which surrounds the subject's head during imaging. Reliability and assessments of accuracy for the stereo-photogrammetric tool are presented using 275 inter-landmark distance comparisons between the system and direct anthropometry using a doll. These showed the system to be highly reliable and precise.
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    Comparison of Magnetic Resonance Spectroscopy (MRS) data in children with and without HIV at 11-12 years
    (2020) Graham, Amy; Robertson, Frances; Meintjes, Ernesta
    Although HIV and antiretroviral drugs have been shown to cause damage in the brain, the long-term impacts of perinatal infection, early treatment and exposure in children at 11 years, remain unclear. The effects of HIV and antiretroviral therapy (ART), whilst indistinguishable, can be investigated at a chemical level through proton magnetic resonance spectroscopy (1H-MRS). Previous studies in children have largely focused on individual metabolite changes. However, several adult studies have now advanced beyond this to address patterns of metabolic activity that are altered with HIV infection. Using a 3T Skyra scanner, 136 children (76 HIV+, 30 HEU, 30 HU; 71 males) between the ages of 11.0- 12.5 years, and from a similar socioeconomic background, were scanned. In this study metabolite concentrations were quantified within the basal ganglia (BG), midfrontal gray matter (MFGM) and peritrigonal white matter (PWM). We utilised linear regression to investigate individual metabolite differences, comparing HIV-infected (HIV+) children from the Children with HIV Early Antiretroviral Therapy (CHER) trial, and HIV-exposed-uninfected (HEU) children, to HIV-unexposed (HU) children. Pearson's correlation analysis, factor analysis and logistic regression were then used to study alterations in metabolic patterns between HIV+ and HIV-uninfected (HIV-) children. Analysis of the data was carried out in R. We found elevated total choline in the BG (p = 0.03) and MFGM (p < 0.001) of HIV+ children, as well as reduced PWM total NAA (p = 0.03) and total creatine (p = 0.01). Altered metabolite concentrations were further observed in HEU children. Additionally, we identified a cross-regional coupling of choline which distinguishes HIV+ from HIV- children (p < 0.001). These findings indicate that multiregional inflammation and PWM axonal damage are occurring in HIV+ children at 11 years. Ultimately, the consequences of perinatal HIV acquisition, in spite of early treatment, continue to be seen at 11 years, as do the impacts of exposure.
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    A control system approach to subject specific prospective respiratory motion correction in cardiac MRI
    (2012) Burger, Ian H; Meintjes, Ernesta
    Respiratory motion of the heart is a problem for high-resolution cardiac MRI. Diaphragmatic navigator gating with a 5mm acceptance window is most commonly used to address this but has an inherently low respiratory efficiency that is further compromised by respiratory drift. A novel method is presented that uses data from multiple navigators prior to the imaging segment as input for a control system to predict the diaphragm position throughout the imaging segment and correct the slice position in real time.
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    Development of a Prospectively Motion Corrected Free-breathing FLASH Sequence.
    (2023) Harris, Graeme; Meintjes, Ernesta; Jermy Stephen
    Respiratory motion of the heart is a fundamental challenge to cardiac MR imaging (CMR). This motion is frequently compensated for with breath-holding and acceptance-window methods. In situations where breath-holding is not viable, navigated free-breathing with an acceptance window can be used. This method results in inefficient acquisitions, creating longer scan times. This dissertation outlines the implementation of an adaptive predictor-observer control system in a FLASH sequence. The control system predicts the position of the diaphragm throughout the imaging segments based on multiple diaphragm position measurements acquired during the nonimaging segments. The position of the imaging slice is then prospectively adjusted using a linear scaling factor to perform slice following of the heart. Typically, a generalized scaling factor of 0.6 is used but this does not compensate for the variation amongst subjects nor the 3D nature of the heart. The performance of the control system was tested on phantoms and in 8 healthy volunteers. All imaging was performed on a 3T Skyra (Siemens AG, Erlangen). Initial phantom testing was performed utilizing a motion rig that simulates tidal breathing motion. Five sets of ECG-triggered FLASH acquisitions were performed in each healthy volunteer: (i) breath-holds (BH), (ii) free-breathing with no motion correction, (iii) freebreathing navigated-FLASH with a 4mm acceptance window (gated), (iv) free-breathing navigated-FLASH adapted to utilize the control system, and (v) a set of low-resolution cine FLASH images (TR=86ms, 50 images). The log data from the acquisitions with the control system adapted sequence were then analysed to measure the accuracy of the control system's predictions. Images acquired with the standard BH sequence were compared to those from the control system adapted sequence, the acceptance window sequence, and the uncorrected free-breathing sequence. Finally, the set of cine images were segmented at the lung-liver interface and around the heart. The edge of the lungliver interface and an edge of the heart were tracked to calculate the proportional change of the diaphragm's position to the heart's position, for each subject. The error between the control system's predicted position of the diaphragm and estimated actual position was within the 4mm acceptance window used by the gated sequence. The root mean squared error (RMSE) was below 3mm for many of the acquisitions and below 4mm for all except three acquisitions. The resultant images show improved quality using the control system compared with no correction and similar quality when compared to the gated acquisition, although artifacts due to the expansion and contraction of the chest wall remained. Tracking the edge of the lung-liver interface and the heart yielded variable tracking factors across subjects (0.58 to 1.02). Although the slice following of the control system is accurate, tracking during nonlinear sections of the breathing cycle remains challenging. There remains a risk of large tracking inaccuracy if errors in median calculation occur. The linear tracking factors relating diaphragm positions to the heart positions are constant for each subject but vary greatly between each subject, indicating the need for further research into subject specific tracking factors for each individual acquisition. The control system adapted acquisition can provide similar image quality to the gated acquisition, for certain tracking factors, whilst maintaining 100% imaging efficiency through the respiratory cycle.
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    Development of an interactive image-guided neurosurgical system
    (2004) Watson, Megan J; Meintjes, Ernesta
    The aim of this project is to develop an interactive image-guided neurosurgical system. Three technologies for three-dimensional (3D) measurement were investigated and the method of choice developed.
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    Differences in callosal and subcortical volumes and associated neurobehavioural deficits in children with prenatal alcohol exposure
    (2019) Biffen, Stevie Crystal; Meintjes, Ernesta; Warton, Christopher
    Certain high-risk communities in the Western Cape Province of South Africa where heavy maternal prenatal alcohol consumption is perpetuated by historical and societal challenges, have some of the highest prevalence rates of fetal alcohol syndrome (FAS) in the world. FAS has lifelong behavioural and cognitive consequences. Neuroimaging research aims to link deficits in brain structure and function to behavioural outcomes. Manual tracing is considered the gold standard of neuroanatomical volumetric analysis. Combined with neurobehavioural testing it can provide links between structure and function, but is time consuming and labour intensive. Automated segmentation programmes, such as FreeSurfer, are a faster alternative. The challenge is creating automated programmes that can provide results that are comparable to manual tracing, especially in a clinical sample. The aims of this thesis were to investigate (1) the effects of prenatal alcohol exposure (PAE) on the sizes of the caudate nucleus, nucleus accumbens, hippocampus and corpus callosum (CC) and potential relations of regional volumes with IQ and verbal learning, (2) to compare the performance of manual and automated segmentation methods in identifying alcohol-related changes in brain morphometry, and (3) to examine the effects of PAE on inter-hemispheric transfer during adolescence and potential relations of CC size with inter-hemispheric transfer deficits. Participants for this project were recruited from the Cape Town Longitudinal Cohort for whom alcohol exposure data were gathered prospectively from the mothers during pregnancy using the timeline follow-back approach. Participants had been diagnosed previously by two expert dysmorphologists as either control, non-syndromal heavily exposed (HE), partial FAS (PFAS) or FAS. High-resolution T1-weighted images were acquired using a sequence optimized for morphometric neuroanatomical analysis on a Siemens 3T Allegra MRI scanner for 71 right-handed children (9 FAS, 19 PFAS, 24 HE and 19 non-exposed controls) from this cohort at ages 9-11 years. Bilateral caudate nuclei, nucleus accumbens and hippocampi and the CC were manually traced using Multitracer. FreeSurfer was used for automated segmentation. All structures were segmented with both FreeSurfer versions 5.1 and 6.0 to compare progress within development of automated segmentation algorithms. Associations of volumes from manual tracing with IQ and performance on the California Verbal Learning Test-Children’s Version (CVLT-C) were also examined. Inter-hemispheric transfer was assessed using a finger localization task (FLT) administered to 74 participants (12 FAS, 16 PFAS, 14 HE, and 32 controls) from the same cohort at ages 16-17 years. Of these, 34 participants had completed MRI at 9-11 years. Higher levels of PAE were associated with reductions in CC area, as well as bilateral volume reductions in caudate nuclei and hippocampi, effects that remained significant after controlling for alcohol-related reductions in TIV (total intracranial volume). Amongst dysmorphic children (FAS/PFAS), poorer performance on the CVLT-C was related to larger hippocampi and smaller CC. Smaller CC was also associated with lower IQ and partially mediated the effect of PAE on IQ. Manual and automated comparisons showed good agreement in the caudate nuclei, which are simpler to segment, moderate to good agreement in the smaller, more complex nucleus accumbens and hippocampi, and poor agreement in the CC. The latter is not surprising, however, in view of the fact that manual tracing measured the average area of the CC on a mid-sagittal slice, while FreeSurfer measures CC volume over a number of contiguous slices. After controlling for confounders and adjustment for smaller TIV, the latest FreeSurfer version 6.0 provided evidence of alcohol-related volumetric brain reductions comparable to manual segmentation. Only the most severely affected children with FAS demonstrated inter-hemispheric transfer deficits, with the number of transfer-related errors tending to increase with decreasing CC volume among children with PAE. This study confirms and extends evidence of PAE-related decreases in subcortical and CC size and that callosal volume partially mediates alcohol-related impairment in IQ. Although FreeSurfer v 6.0 achieves automated segmentations that are comparable to manual tracing, even in a paediatric clinical sample, performance is more reliable in some structures than others. Improvement and standardization of CC segmentation is especially important given the vulnerability of the CC and its critical role in domains affected by PAE, including verbal learning, IQ and inter-hemispheric transfer of information.
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    DTI-based tractographic analysis of white matter alterations in HIV infected children
    (2019) Madzime, Joanah; Jankiewicz, Marcin; Holmes, Martha; Meintjes, Ernesta
    Despite early combination antiretroviral therapy (cART) administration, children born with human immunodeficiency virus (HIV) continue to demonstrate neurodevelopmental abnormalities. Often, there is a link between structural and functional abnormalities. Previously, we found HIV-associated changes in white matter and functional networks in a cohort of 7-year-old HIV infected (HIV+) children who intiatied early cART compared to uninfected controls. To explore possible relationships between these alterations, we used tractography to identify HIV-related abnormalities within structural connections located in functional resting state networks. Within HIV+ children (n=61), we identified white matter (WM) tracts with lower mean fractional anisotropy (FA) and/or higher mean diffusivity (MD) located in several functional networks, including the somatosensory, auditory, salience, default mode network (DMN), motor and basal ganglia networks compared to uninfected controls (n=46). Among the uninfected controls, children born to HIV+ mothers (exposed uninfected, HEU) (n=19) showed WM alterations (higher FA) compared to HIV unexposed uninfected children (HUU) (n=27) within tracts in the posterior DMN, visual (occipital lobe and lingual gyrus), salience and motor networks. The observed WM alterations in HIV+ children point to demyelination/dysmyelination within six networks. Four of these networks – the basal ganglia, default mode, salience and somatosensory – were all found to have altered functional connectivity in a previous study; therefore, these results point to damage or developmental delay in white matter may be related to or responsible for the HIV-associated functional abnormalities. The observed WM alterations in the HEU children suggest that even exposure to HIV and/or antiretroviral therapy (ART) also has long-term effects on axonal integrity in the developing brain.
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    Effects of prenatal alcohol exposure on cerebellar volume in children an MRI study
    (2012) Boonzaier, Natalie Rosella; Meintjes, Ernesta; Warton, Christopher
    Years of research have demonstrated that prenatal exposure to alcohol contributes to a range of effects in exposed children. These include problems in attention and hyperactivity, deficits in memory and learning, and problems with social, as well as emotional development. Past research has demonstrated that the cerebellum is a significant target of the teratogenic effects of alcohol. The aim of this study was to determine whether prenatal exposure to alcohol has specific effects on the volumes of specific lobules of the cerebellum. Lobule tracing was performed manually, with Multitracer, using a refined methodology. Lobule volumes (normalized for total cerebellar cortical volume) were analysed as functions of diagnosis as well as alcohol exposure. Lobules IX and X were affected when analysing normalized volumes as a function of diagnosis, with the fetal alcohol syndrome diagnostic group being most specifically affected. Significant differences between sex groups were found only for right lobules I-V and left lobule VIII, and hemisphere differences were found in lobule X. When analysing normalized lobule volume as a function of alcohol exposure, in the left hemisphere, lobules I-V showed positive correlations with alcohol exposure, suggesting that this region is relatively spared. Lobule IX and the vermis of the right hemisphere showed negative correlations with alcohol exposure. The strongest negative correlations were found for measures of absolute alcohol per day averaged across the period of pregnancy as opposed to at time of conception. Overall findings suggest that prenatal alcohol exposure causes disproportionate reductions in volume in specific lobules of the cerebellums of children with fetal alcohol spectrum disorders.
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    Elliptical Subject Specific model for respiratory motion
    (Biomed Central Ltd, 2012) Burger, Ian; Meintjes, Ernesta; Keegan, Jennifer; Firmin, David
    Respiratory motion of the heart poses a problem for high resolution cardiac MR imaging. Prospective slice following uses the navigator position immediately prior to the imaging segment to correct the slice positions throughout the segment [1]. The navigator is typically placed over the right hemi-diaphragm and a fixed correction factor is used to adjust for the difference to the motion of the heart. The relationship between the motion of the heart and the superior-inferior motion of the diaphragm is approximately linear although highly subject specific, with an element of hysteresis [2]. We investigated a more complex model to incorporate non rigid transformation of the heart as well as hysteresis.
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    Exploring the relationship between multimodal magnetic resonance neuroimaging and cognitive outcomes in children: applying machine learning algorithms to brain MRI features to predict cognitive scores and performance categories of children living with and without HIV
    (2025) Khobo, Isaac; Robertson, Frances; Meintjes, Ernesta
    Background: A constantly growing body of literature shows that children from low- socioeconomic status (SES) backgrounds are at risk of cognitive developmental delays, poor health outcomes, and cognitive difficulties which lead to high rates of school drop-outs and struggles in other areas of life. In sub-Saharan Africa, where the human immu- nodeficiency virus (HIV) is the most prevalent, low-SES households and communities are disproportionately affected by the disease and its effects on neurodevelopment. The ability to predict cognitive abilities or deficits from neuroimaging or other methods could make it easier to identify at-risk children who may benefit the most from targeted inter-ventions. This is of relevance in low-SES populations with relatively high rates of child-hood HIV that may affect neurodevelopment. Magnetic resonance (MR) imaging (MRI) is a versatile tool that can be used to measure a broad range of brain tissue properties giving rise to cognitive functions. For example, structural MRI (sMRI) can quantify brain volumes and other morphometrics, diffusion tensor imaging (DTI) can estimate the amount of nerve fibre damage, and proton MR spectroscopy (1H-MRS) can charac- terise the biochemical profile of grey and white matter (GM, WM).Research aims : The aims of this study were: First, collect evidence for what is known about the relationship between cognitive performance assessed by a comprehensive set of cognitive test batteries and brain changes measured with neuroimaging in children, adolescents, and youth living with HIV. Second, compare the predictive performance of penalised linear models (PLMs), support vector machines/regression (SVM/R), and de-cision tree ensembles (DTEs) in predicting continuous scores on cognitive tests, as well as categories of cognitive performance from multimodal neuroimaging in a cohort com-prising both children living with and without HIV. Third, determine whether multimodal MRI offers any predictive advantage compared to predicting future performance using cognitive scores at a younger age. Methods and materials : To address these aims, we first conducted a systematic liter-ature review and secondly a multimodal MRI neuroimaging and cognitive testing study of 132 children from low-SES backgrounds. For the review, we searched PubMed, Scopus, Web of Science, CINAHL, APA Psych Info & Psych Articles, and Academic Search Premier for studies published between 1 January 2006 and 31 October 2022. Inclusion criteria were studies that investigated a relationship between neuroimaging brain measures and cognitive test scores and included children (0–14 years), adolescents (15–18), and youth (19–26) living with HIV. For the neuroimaging and cognitive study, structural MRI, DTI, and 1H-MRS were ac-quired at ages 7 and 9 years. Cognitive performance was assessed using the Kaufman assessment battery for children, Beery-Buktenica developmental test of visual-motor in- tegrations, test of variables of attention, Purdue pegboard test, the Peabody picture vocabulary test, and semantic fluency test at both ages. PLMs, SVMs/R, and DTEs prediction models were implemented with Bayesian optimization and assessed with 10-fold cross validation (CV) and compared for their ability to predict continuous scores (regression) or categories of cognitive performance (classification). Poorer and better cognitive performance categories were identified with a hierarchical clustering algorithm. Regression performance was assessed via 10-fold CV errors, coefficient of determination (R2), and Pearson's r between predicted and actual values. For the classification models, 10-fold CV sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were obtained.Results : Evidence from the literature suggests that HIV may lead to alterations in the brain's structure, function, neurometabolism, and WM microstructure. Individual brain measures are linked to outcomes of short-term memory, processing speed, working memory, problem solving, and general intelligence quotients in children, adolescents, and youth living with and without. We could not find any studies linking multimodal MRI to cognitive performance in this population of young people. PLMs, SVMs/SVR, and DTEs performed poorly for the regression problem; the predic-tive models led to small training and fitting errors but high generalised CV errors. How-ever, using either multimodal MRI data or cognitive scores at age 7, we could predict auditory working memory (R2 = 0.45, r = 0.75), short-term memory (R2 = 0.43, r =0.62), visual-motor integration (R2 = 0.26, r = 0.39), and executive reasoning (R2 = 0.33, r = 0.27) scores at age 9 with moderate to strong Pearson's r. Classification of children into poorer or better performance categories was more successful than regression of the individual scores, with 0.75–0.81 AUC, 70–77% accuracies, 70–81% specificities, 71–79% sensitivities using historic multimodal MRI and cognitive scores. Historic multimodal MRI (AUC = 0.80, accuracy = 76%) was marginally better than cognitive scores (AUC= 0.75, accuracy = 70%) in classifying future overall cognitive performance.Conclusion: There were multimodal brain measures relevant in the prediction models, these included creatine and glutamate concentrations in midfrontal gray matter region, thalamus volume, diffusivity in the cingulum WM tract, cingulate gyrus area, and gyri-fication index of the parietal lobe. This suggests that multiple MRI modalities and fea-tures should be considered simultaneously to establish correlates of overall cognitive performance. The neural correlates we find could potentially be used to identify bi-omarkers of cognitive impairment, understand the developmental nature of cognitive plasticity, and enable the development of targeted interventions that can modulate brain networks associated with cognitive functions.
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    Implementation of anatomical navigators for real time motion correction in diffusion tensor imaging
    (2012) Alhamud, Alkathafi Ali; Van der Kouwe, Andre; Meintjes, Ernesta
    Prospective motion correction methods using an optical system, diffusion-weighted prospective acquisition correction, or a free induction decay navigator have recently been applied to correct for motion in diffusion tensor imaging. These methods have some limitations and drawbacks. This article describes a novel technique using a three-dimensional-echo planar imaging navigator, of which the contrast is independent of the b-value, to perform prospective motion correction in diffusion weighted images, without having to reacquire volumes during which motion occurred, unless motion exceeded some preset thresholds. Water phantom and human brain data were acquired using the standard and navigated diffusion sequences, and the mean and whole brain histogram of the fractional anisotropy and mean diffusivity were analyzed.
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    Investigating brain metabolite levels in adolescents living with HIV using atlas-based magnetic resonance spectroscopic imaging (MRSI)
    (2024) Maharaj, Sonam; Robertson, Frances; Meintjes, Ernesta
    Deficiencies in brain function and structure have been linked to perinatally acquired HIV (PHIV) despite the introduction of antiretroviral therapy (ART). Current studies are predominantly based on single voxel magnetic resonance spectroscopy (MRS) in younger children, with inconsistent findings. We aimed to develop atlas-based pipelines for analysing MRSI data to examine whether there are differences in brain metabolite levels between adolescents with PHIV and uninfected controls. The study participants were 165 adolescents, of whom 86 were adolescents living with HIV from the CHER trial and 79 were age- and sociodemographically- matched uninfected controls. They were scanned on a Siemens 3T Skyra scanner with the scanning protocol including a high-resolution T1- weighted structural MRI using a multi-echo magnetization-prepared rapid acquisition gradient echo (MEMPRAGE) sequence and volumetric MRSI using spiral-encoded localized adiabatic selective refocusing (LASER) CSI. LCModel was utilized to achieve spec
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    Investigating the effects of living with HIV on neural circuits involved in reward processing in adolescents
    (2024) Mac Arthur, Anika; Meintjes, Ernesta; Robertson, Frances
    The CHER (Children with HIV Early Antiretroviral) trial found that early ART (12- weeks) reduced mortality and morbidity in children with perinatal HIV (CPHIV). Despite early ART, CPHIV from the CHER trial demonstrate neuroimaging alterations, but little is known about the effects of PHIV and long-term ART on the adolescent brain. Adolescence is a time of increased vulnerability to risk-taking behaviour. Here, neural circuits involved in reward processing during adolescence are investigated using functional MRI (fMRI). FMRI scans acquired during a Reward Magnitude Task were available for 106 socio economically matched adolescents (66 children perinatally infected with HIV (CPHIV), 40 controls living without HIV; age 150.4 years). Data were preprocessed using fMRIPrep. Differences in brain activation for anticipation, monetary wins vs losses, and reward/loss outcome magnitudes were compared between CPHIV and controls using FSL FEAT. Z-statistic images were thresholded at Z>3.1 and a cluster significance threshold of p=0.05. Across all subjects, there were robust responses to reward processing (win>loss) in the striatum (38,610mm3 ; peak MNI -10.1; 9.1; 0.7) and in the (ventromedial) prefrontal cortex (11,280mm3 ; peak MNI -5.3; 25.9; 41.5). There were no regions where activation increases, for any of our contrasts, were greater in CPHIV than controls, but CPHIV showed smaller activation increases than controls during anticipation and reward processing. We specifically saw smaller activation increases during processing of larger wins in 2 distinct small left superior frontal clusters as well as in the left paracingulate gyrus. Similar to findings from the Human Connectome Project in Development, the task reliably activated striatal and medial frontal regions involved in decision-making and reward seeking/processing. While we found no differences between CPHIV and controls within this reward processing network, CPHIV showed smaller activation differences in our contrasts in the left superior frontal cortex – a region involved in the working memory component of executive function. Notably, impaired working memory processing and storage, especially in the visual domain, has been reported previously in children living with HIV. The current finding suggests that HIV-related brain response abnormalities in working memory regions may impact reward processing.
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    An investigation of the integrity of two components of the cerebellar neurocircuitry involved in classical eyeblink conditioning in children prenatally exposed to alcohol: a magnetic resonance spectroscopy and functional magnetic resonance imaging study
    (2014) Du Plessis, Lindie; Meintjes, Ernesta
    Impairment in classical eyeblink conditioning (EBC) has previously been reported in children with fetal alcohol spectrum disorders (FASD) (Jacobson et al., 2008). The deep cerebellar nuclei and cerebellar cortex are critical elements of the cerebellar-brainstem circuitry that mediates EBC (Green et al., 2002a; Yeo and Hardiman, 1992; Perret et al., 1993). In this study, we used magnetic resonance spectroscopy (MRS) and functional MRI (fMRI) to assess the effects of prenatal alcohol exposure on brain metabolism in the cerebellar deep nuclei and brain function in the cerebellar cortex, respectively. We found that higher levels of prenatal alcohol exposure were associated with lower levels of both N-Acetylaspartate (NAA) and choline-containing metabolites, and with higher levels of glutamate plus glutamine (Glx), suggesting a disruption of the glutamate-glutamine cycling involved in glutamatergic excitatory neurotransmission. Since the interpositus nucleus is one of the most crucial structures in the acquisition of the EBC response, abnormal metabolism in this region could be responsible for altered synaptic plasticity in children with FASD. Of the four cerebellar regions that were identified as being activated more by control children during rhythmic vs. non-rhythmic finger tapping, smaller differences in BOLD (blood oxygenation level dependent) activation were observed in children with FASD in two, namely vermis IV-V and right Crus I. Increasing levels of prenatal alcohol exposure were, however, associated with smaller differences in activation in all four regions, all of which have previously been linked to timed responses. In the paced/unpaced finger tapping fMRI study, we found four regions where increased BOLD activation during unpaced tapping compared to rest was associated with improved ability to maintain rhythm as evidenced by lower intertapping variability - right VIIIa and b, left VIIIa and right VI. These regions have previously been implicated in motor control with additional evidence of timing in lobule VI. In three of the regions, all except right VIIIa, increasing alcohol exposure was related to smaller increases in activation during unpaced tapping, with the strongest relations seen in the dosage dependent variable. Interestingly, the location of the activation in right VI is similar to a region that has been implicated in studies of EBC (Blaxton et al., 1996; Cheng et al., 2008). Our results point to altered metabolic levels in the deep nuclei and reduced functioning of several cerebellar cortical regions in children with FASD, highlighting the extensive damage caused by prenatal alcohol exposure. Although we did not find associations of EBC performance with either metabolite levels or activity in these regions, suggesting that damage to these areas are not primarily responsible for the observed EBC deficit, the extent of this damage could play a role in the impaired EBC performance seen in these children.
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    Longitudinal analysis of Brain Metabolite levels for HIV infected Children from ages five to eleven
    (2020) Van Biljon, Noëlle; Little, Francesca; Meintjes, Ernesta; Holmes, Martha; Robertson, Frances
    HIV infected (HIV+) children initiate antiretroviral therapy (ART) early in life and remain on it lifelong. However, the long-term impact of ART and HIV on the maturing brain is not well documented and longitudinal neuroimaging studies are rare, especially in developing countries most heavily impacted by HIV/AIDS where access to imaging resources are limited. We have examined HIV related changes in metabolite level trajectories from 5-11 years in three brain regions using Magnetic Resonance Spectroscopy (MRS). We used univariate linear mixed effect models to identify independent profiles of the metabolites measured in each region of the brain. To explore the metabolite trends in a multivariate setting we generated multilevel mixed effects models, and correlated response models. There was an element of confounding introduced through the change of MRI scanner during the follow-up period and we compare different methods to resolve this issue. Consequently, we did observe differences in metabolite profiles from HIV+ children compared to HIV uninfected (HIV-) controls. This suggests that while these children are on ART treatment, there is still some underlying effect on their neurochemistry which sets their development apart from the normal healthy profiles we expect.
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    Open Access
    Preliminary evidence that prenatal maternal choline supplementation protects the white matter microstructure of infants born to heavy-drinking women
    (2024) Maiphetlho, Oreneile; Meintjes, Ernesta; Warton Fleur
    Prenatal alcohol exposure (PAE) is the most widespread preventable cause of neurocognitive and neurodevelopmental disabilities worldwide, known collectively as fetal alcohol spectrum disorders. It has been shown in a small double-blind, randomized choline supplementation trial that prenatal maternal choline supplementation reduces PAE-related postnatal growth restrictions, cognitive deficits, and regional brain volume reductions in infants born to heavydrinking women. The impact of prenatal maternal choline supplementation on white matter (WM) microstructure – an area particularly vulnerable to PAE – has not been assessed. This project used diffusion tensor imaging (DTI) in 43 neonates born to heavy-drinking mothers enrolled in that choline supplementation trial to examine the effects of prenatal maternal choline supplementation on the microstructure of WM connecting select subcortical regions. Given that pre-myelination (at 30-40 weeks gestational age (GA)) and maturation of the axonal cytoskeleton are categorised by stable fractional anisotropy (FA), decreasing axial diffusivity (AD) and radial diffusivity (RD), we hypothesised that neonates with PAE whose mothers had received choline would demonstrate lower AD and RD than those in the placebo arm, and that lower AD and RD would be associated with better cognitive performance. T1-weighted structural magnetic resonance (sMR) and diffusion tensor (DT) imaging (DTI) data were acquired for each neonate between 1-7 weeks postpartum on a 3T Siemens Allegra. Previously, 17 subcortical brain regions (ROIs) had been manually traced on sMR images in Freeview. After DTI pre-processing, the manually traced ROIs were transformed into the DTI space and used as seeds for full probabilistic tractography. FA, AD and RD were extracted for each identified connection. Visual recognition memory scores on the Fagen test of Infant Intelligence (FTII) assessed at 12 months were also available for 34 participants. We examined differences in the DTI measures between the choline and placebo groups, as well as associations of DTI measures with choline dose and FTII scores using robust linear regression. Choline dose was approximated in 2 ways: (1) using maternal treatment adherence (in % packets consumed), with choline dose set to zero for infants in the placebo arm, and (2) computing the total choline (in grams) consumed by the mothers throughout participation in the study (enrolment through to delivery). A total of 22 neonates (14 choline; 11 boys; mean GA (SD) = 41.8 (2.0) weeks) provided usable, non-biased DTI data and FTII scores were available for 14 of these neonates (8 choline). We examined treatment effects in 15 WM connections that were present in a least 85 % of the neonates. Three neonates in the choline arm whose mothers had low treatment adherence (< 50 %) were excluded from the group difference analyses. Additionally, one choline-treated participant whose average AD value introduced bias was excluded from all analyses that included the DTI measures. After controlling for confounders, FA in the WM connection between the caudate and pallidum on the left was lower in the choline group (p = 0.023) and on the right was inversely associated with choline dose – both in % packets consumed (β (ε) = -0.55 (0.20); p = 0.016) and in grams (β (ε) = -0.51 (0.20); p = 0.024). Moreover, increasing choline dose – in % packets consumed and in grams – was associated with lower AD in 2 WM connections: between the right caudate and right putamen, and right putamen and right pallidum (|β|'s > 0.40; p's < 0.05). Finally, better visual recognition memory on the FTII was associated with lower RD (β (ε) = -0.62 (0.27); p = 0.038) in the connection between the left and right thalami, and with higher RD (β (ε) = 0.54 (0.18); p = 0.009) in the WM connection between the right caudate and right putamen. Although choline-related decreases in FA were observed in the connection between the right caudate and right pallidum, the choline-related decreases in AD in the caudate, putamen and pallidum on the right aligned with our hypothesis. Studies of participants with Williams syndrome and attention-deficit/hyperactivity disorder have speculated that the lower FA observed in their control groups may be accredited to higher levels of axonal branching. Given that choline promotes axonal growth and branching in rodent models, the lower FA observed here may be indicative of choline-related increases in axonal branching in the caudate to pallidum connections. Studies of postnatal WM development have found that AD and RD decrease during the first postnatal year. Given that AD provides information on axonal integrity and organization, the age-related decreases for AD have been accredited to increases in axonal growth. Human studies have demonstrated increases in fibre cross-sections in the first 6 months of life and animal studies have shown the importance of choline in axonal growth and elongation. Thus, the choline-related reductions in AD in connections between the caudate, putamen and pallidum on the right suggest accelerated brain development through the promotion of axonal growth in these WM connections. Axonal pruning may also contribute to decreases in AD. Growth-related increases in axonal diameter may explain the association of higher RD seen in the same connection, right caudate to right putamen, with better visual recognition memory. The negative association between visual recognition memory and RD in the connection between the left and right thalami aligns with our hypothesis and several studies conducted in infants, children and adults. These results provide preliminary evidence that choline is associated with the microstructural properties of subcortical WM connections, specifically between the caudate, putamen and pallidum, which are regions known to be affected by PAE. These findings need to be replication in a larger sample and with unexposed controls. Further research is required to examine the impact of prenatal maternal choline supplementation on cortical WM.