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INTRODUCTION: Cerebral palsy (CP) is the most common physical disability of childhood worldwide. Historically the diagnosis was made between 12 and 24 months, meaning data about effective early interventions to improve motor outcomes are scant. In high-income countries, two in three children will walk. This evaluator-blinded randomised controlled trial will investigate the efficacy of an early and sustained Goals-Activity-Motor Enrichment approach to improve motor and cognitive skills in infants with suspected or confirmed CP. METHODS AND ANALYSIS: Participants will be recruited from neonatal intensive care units and the community in Australia across four states. To be eligible for inclusion infants will be aged 3-6.5 months corrected for prematurity and have a diagnosis of CP or 'high risk of CP' according to the International Clinical Practice Guideline criteria. Eligible participants whose caregivers consent will be randomly allocated to receive usual care or weekly sessions at home from a GAME-trained study physiotherapist or occupational therapist, paired with a daily home programme, until age 2. The study requires 150 participants per group to detect a 0.5 SD difference in motor skills at 2 years of age, measured by the Peabody Developmental Motor Scales-2. Secondary outcomes include gross motor function, cognition, functional independence, social-emotional development and quality of life. A within-trial economic evaluation is also planned. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Sydney Children's Hospital Network Human Ethics Committee in April 2017 (ref number HREC/17/SCHN/37). Outcomes will be disseminated through peer-reviewed journal publications, presentations at international conferences and consumer websites. TRIAL REGISTRATION NUMBER: ACTRN12617000006347.

Background: Fetal growth restriction (FGR) is a serious pregnancy complication associated with increased risk of adverse neurodevelopment and neuromorbidity. Current imaging techniques, including conventional magnetic resonance imaging (MRI), are not sensitive enough to detect subtle structural abnormalities in the FGR brain. We examined whether advanced MRI analysis techniques have the capacity to detect brain injury (particularly white matter injury) caused by chronic hypoxia-induced fetal growth restriction in newborn preterm lambs. Method(s): Surgery was undertaken in twin bearing pregnant ewes at 88-90 days gestation (term = 150 days) to induce FGR in one fetus. At 127 days gestation (~32 weeks human brain development), FGR and control (appropriate for gestational age, AGA) lambs were delivered by caesarean section, intubated and ventilated. Conventional and advanced brain imaging was conducted within the first two hours of life using a 3T MRI scanner. T1-weighted (T1w) and T2-weighted (T2w) structural imaging, magnetic resonance spectroscopy (MRS), and diffusion MRI (dMRI) data were acquired. Diffusion tensor imaging (DTI) modelling and analysis of dMRI data included the following regions of interest (ROIs): subcortical white matter, periventricular white matter, cerebellum, hippocampus, corpus callosum and thalamus. Fixel-based analysis of 3-tissue constrained spherical deconvolution (CSD) of the dMRI data was performed and compared between FGR and AGA lambs. Lambs were euthanised immediately after the scans and brain histology performed in the regions of interest to correlate with imaging. Result(s): FGR and AGA lamb (body weight, mean (SD): 2.2(0.5) vs. 3.3(0.3) kg, p = .002) MRI brain scans were analysed. There were no statistically significant differences observed between the groups in conventional T1w, T2w or MRS brain data. Mean, axial and radial diffusivity, and fractional anisotropy indices obtained from DTI modelling also did not show any statistical

BACKGROUND: Fetal growth restriction (FGR) is a serious pregnancy complication associated with increased risk of adverse neurodevelopment and neuromorbidity. Current imaging techniques, including conventional magnetic resonance imaging (MRI), are not sensitive enough to detect subtle structural abnormalities in the FGR brain. We examined whether advanced MRI analysis techniques have the capacity to detect brain injury (particularly white matter injury) caused by chronic hypoxia-induced fetal growth restriction in newborn preterm lambs. METHODS: Surgery was undertaken in twin bearing pregnant ewes at 88-90 days gestation (term = 150 days) to induce FGR in one fetus. At 127 days gestation (~32 weeks human brain development), FGR and control (appropriate for gestational age, AGA) lambs were delivered by caesarean section, intubated and ventilated. Conventional and advanced brain imaging was conducted within the first two hours of life using a 3T MRI scanner. T1-weighted (T1w) and T2-weighted (T2w) structural imaging, magnetic resonance spectroscopy (MRS), and diffusion MRI (dMRI) data were acquired. Diffusion tensor imaging (DTI) modelling and analysis of dMRI data included the following regions of interest (ROIs): subcortical white matter, periventricular white matter, cerebellum, hippocampus, corpus callosum and thalamus. Fixel-based analysis of 3-tissue constrained spherical deconvolution (CSD) of the dMRI data was performed and compared between FGR and AGA lambs. Lambs were euthanised immediately after the scans and brain histology performed in the regions of interest to correlate with imaging. RESULTS: FGR and AGA lamb (body weight, mean (SD): 2.2(0.5) vs. 3.3(0.3) kg, p = .002) MRI brain scans were analysed. There were no statistically significant differences observed between the groups in conventional T1w, T2w or MRS brain data. Mean, axial and radial diffusivity, and fractional anisotropy indices obtained from DTI modelling also did not show any statistically s

Aim: This study aimed to examine associations between structural MRI and concurrent motor, neurological and neurobehavioral measures at 30–32 weeks postmenstrual age (PMA; ‘Early’), and at term equivalent age (‘Term’). Method: In this prospective cohort study, infants underwent Early MRI (n = 119; 73 male; median 32 weeks 1 day PMA) and Term MRI (n = 102; 61 male; median 40 weeks 4 days PMA) at 3 T. Structural images were scored generating white matter (WM), cortical gray matter, deep gray matter, cerebellar and global brain abnormality scores. Clinical measures were General Movements Assessment (GMs), Hammersmith Neonatal Neurological Examination (HNNE) and NICU Neonatal Neurobehavioral Scale (NNNS). The Premie-Neuro was administered Early and the Test of Infant Motor Performance (TIMP) and a visual assessment at Term. Results: Early MRI cerebellar scores were strongly associated with neurological components of HNNE (reflexes), NNNS (Hypertonicity), the Premie-Neuro neurological subscale (regression coefficient β = −0.06; 95% confidence interval CI = −0.09, −0.04; p < .001) and cramped-synchronized GMs (β = 1.10; 95%CI = 0.57, 1.63; p < .001). Term MRI WM and global scores were strongly associated with the TIMP (WM β = −1.02; 95%CI = −1.67, −0.36; p = .002; global β = −1.59; 95%CI = −2.62, −0.56; p = .001). Interpretation: Brain structure on Early and Term MRI was associated with concurrent motor, neurological and neurobehavioral function in very preterm infants.

© Crown 2018. This study examined postmenstrual age (PMA) estimation (in weeks) from brain diffusion MRI of very preterm born infants (born <31weeks gestational age), with an objective to investigate how differences in estimated brain age and PMA were associated with the risk of Cerebral Palsy disorders (CP). Infants were scanned up to 2 times, between 29 and 46 weeks (w) PMA. We applied a deep learning 2D convolutional neural network (CNN) regression model to estimate PMA from local image patches extracted from the diffusion MRI dataset. These were combined to form a global prediction for each MRI scan. We found that CNN can reliably estimate PMA (Pearson’s r = 0.6, p < 0.05) from MRIs before 36 weeks of age (‘Early’ scans). These results revealed that the local fractional anisotropy (FA) measures of these very early scans preserved age specific information. Most interestingly, infants who were later diagnosed with CP were more likely to have an estimated younger brain age from ‘Early’ scans, the estimated age deviations were significantly different (Regression coefficient: -2.16, p < 0.05, corrected for actual age) compared to those infants who were not diagnosed with CP.

Background: Of children with hemiplegic cerebral palsy, 75% have impaired somatosensory function, which contributes to learned non-use of the affected upper limb. Currently, motor learning approaches are used to improve upper-limb motor skills in these children, but few studies have examined the effect of any intervention to ameliorate somatosensory impairments. Recently, Sense© training was piloted with a paediatric sample, seven children with hemiplegic cerebral palsy, demonstrating statistically and clinically significant change in limb position sense, goal performance and bimanual hand-use. This paper describes a protocol for a Randomised Controlled Trial of Sense© for Kids training, hypothesising that its receipt will improve somatosensory discrimination ability more than placebo (dose-matched Goal Directed Therapy via Home Program). Secondary hypotheses include that it will alter brain activation in somatosensory processing regions, white-matter characteristics of the thalamocortical tracts and improve bimanual function, activity and participation more than Goal Directed Training via Home Program. Methods and design: This is a single blind, randomised matched-pair, placebo-controlled trial. Participants will be aged 6-15years with a confirmed description of hemiplegic cerebral palsy and somatosensory discrimination impairment, as measured by the sense©_assess Kids. Participants will be randomly allocated to receive 3h a week for 6weeks of either Sense© for Kids or Goal Directed Therapy via Home Program. Children will be matched on age and severity of somatosensory discrimination impairment. The primary outcome will be somatosensory discrimination ability, measured by sense©_assess Kids score. Secondary outcomes will include degree of brain activation in response to a somatosensory task measured by functional MRI, changes in the white matter of the thalamocortical tract measured by diffusion MRI, bimanual motor function, activity and participation. Discussion

To characterise brain lesions in dyskinetic cerebral palsy (DCP) using the semi-quantitative scale for structural MRI (sqMRI) and to investigate their relationship with motor, communication and cognitive function. Materials and methods: Thirty-nine participants (19 females, median age 21y) with DCP were assessed in terms of motor function, communication and a variety of cognitive domains. Whole-head magnetic resonance imaging (MRI) was performed including T1-MPRAGE, T2 turbo spin echo (axial plane), and fluid attenuated inversion recovery images (FLAIR). A child neurologist visually assessed images for brain lesions and scored these using the sqMRI. Ordinal, Poisson and binomial negative regression models identified which brain lesions accounted for clinical outcomes. Results: Brain lesions were most frequently located in the ventral posterior lateral thalamus and the frontal lobe. Gross (B = 0.180, p <.001; B = 0.658, p <.001) and fine (B = 0.136, p =.003; B = 0.540, p <.001) motor function were associated with global sqMRI score and parietal involvement. Communication functioning was associated with putamen involvement (B = 0.747, p <.028). Intellectual functioning was associated with global sqMRI score and posterior thalamus involvement (B = -0.018, p <.001; B = -0.192, p <.001). Selective attention was associated with global sqMRI score (B = -0.035, p <.001), parietal (B = -0.063, p =.023), and corpus callosum involvement (B = -0.448, p <.001). Visuospatial and visuoperceptive abilities were associated with global sqMRI score (B = -0.078, p =.007) and medial dorsal thalamus involvement (B = -0.139, p <.012), respectively. Conclusions: Key clinical outcomes in DCP are associated with specific observable brain lesions as indexed by a simple lesion scoring system that relies only on standard clinical MRI.

Preterm birth causes significant disruption in ongoing brain development, frequently resulting in adverse neurodevelopmental outcomes. Brain imaging using diffusion MRI may provide valuable insight into microstructural properties of the developing brain. The aim of this study was to establish whether the recently introduced fixel-based analysis method, with its associated measures of fibre density (FD), fibre bundle cross-section (FC), and fibre density and bundle cross-section (FDC), is suitable for the investigation of the preterm infant brain at term equivalent age. High-angular resolution diffusion weighted images (HARDI) of 55 preterm-born infants and 20 term-born infants, scanned around term-equivalent age, were included in this study (3 T, 64 directions, b = 2000 s/mm2). Postmenstrual age at the time of MRI, and intracranial volume (FC and FDC only), were identified as confounding variables. Gestational age at birth was correlated with all fixel measures in the splenium of the corpus callosum. Compared to term-born infants, preterm infants showed reduced FD, FC, and FDC in a number of regions, including the corpus callosum, anterior commissure, cortico-spinal tract, optic radiations, and cingulum. Preterm infants with minimal macroscopic brain abnormality showed more extensive reductions than preterm infants without any macroscopic brain abnormality; however, little differences were observed between preterm infants with no and with minimal brain abnormality. FC showed significant reductions in preterm versus term infants outside regions identified with FD and FDC, highlighting the complementary role of these measures. Fixel-based analysis identified both microstructural and macrostructural abnormalities in preterm born infants, providing a more complete picture of early brain development than previous diffusion tensor imaging (DTI) based approaches.

© 2017 IEEE. Spatio-temporal atlas is a useful tool in imaging studies of neurodevelopment, which characterizes the growth of brain, and allows the monitoring of its development. The imaging of preterm and term born infants provides opportunities to develop a series of spatio-temporal atlases that track the changes during the particular period of neurodevelopment between. The aim of this paper is to develop a spatio-temporal atlas of diffusion MRI for neonatal brains between 32 to 42 weeks postmenstrual age (PMA). We subdivided the cohort consisting of preterm- and term-born infants according to their PMA at the MRI scan based on a kernel ridge regression, and generated the atlases based on Fibre Orientation Distribution (FOD) reconstruction of the diffusion data.

Aim: To examine the diagnostic ability of early magnetic resonance imaging (MRI; < 36wks postmenstrual age) to detect later adverse motor outcomes or cerebral palsy (CP) in infants born preterm. Method: Studies of infants born preterm with MRI earlier than 36 weeks postmenstrual age and quantitative motor data or a diagnosis of CP at or beyond 1 year corrected age were identified. Study details were extracted and meta-analyses performed where possible. Quality of included studies was evaluated with the QUADAS-2 (a revised tool for the quality assessment of diagnostic accuracy studies). Results: Thirty-one articles met the inclusion criteria, five of which reported diagnostic accuracy and five reported data sufficient for calculation of diagnostic accuracy. Early structural MRI global scores detected a later diagnosis of CP with a pooled sensitivity of 100% (95% confidence interval [CI] 86-100) and a specificity of 93% (95% CI 59-100). Global structural MRI scores determined adverse motor outcomes with a pooled sensitivity of 89% (95% CI 44-100) and a specificity of 98% (95% CI 90-100). White matter scores determined adverse motor outcomes with a pooled sensitivity of 33% (95% CI 20-48) and a specificity of 83% (95% CI 78-88). Interpretation: Early structural MRI has reasonable sensitivity and specificity to determine adverse motor outcomes and CP in infants born preterm. Greater reporting of diagnostic accuracy in studies examining relationships with motor outcomes and CP is required to facilitate clinical utility of early MRI. What this paper adds: Early magnetic resonance imaging (MRI) has reasonable sensitivity and specificity to determine later adverse motor outcomes and cerebral palsy (CP). Detection of infants who progressed to CP was stronger than motor outcomes. Global MRI scores determined adverse motor outcomes more accurately than white matter scores. Few studies report diagnostic accuracy of early MRI findings. Diagnostic accuracy is required to draw

Objectives Congenital hemiplegia is the most common form of cerebral palsy (CP). Children with unilateral CP show signs of upper limb asymmetry by 8 months corrected age (ca) but are frequently not referred to therapy until after 12 months ca. This study compares the efficacy of infant-friendly modified constraint-induced movement therapy (Baby mCIMT) to infant friendly bimanual therapy (Baby BIM) on upper limb, cognitive and neuroplasticity outcomes in a multisite randomised comparison trial. Methods and analysis 150 infants (75 in each group), aged between 3 and 6 months ca, with asymmetric brain injury and clinical signs of upper extremity asymmetry will be recruited. Children will be randomised centrally to receive equal doses of either Baby mCIMT or Baby BIM. Baby mCIMT comprises restraint of the unimpaired hand using a simple restraint (eg, glove, sock), combined with intensive parent implemented practice focusing on active use of the impaired hand in a play-based context. In contrast, Baby BIM promotes active play requiring both hands in a play-based context. Both interventions will be delivered by parents at home with monthly home visits and interim telecommunication support by study therapists. Assessments will be conducted at study entry; at 6, 12 months ca immediately postintervention (primary outcome) and 24 months ca (retention). The primary outcome will be the Mini-Assisting Hand Assessment. Secondary outcomes include the Bayley Scale for Infant and Toddler Development (cognitive and motor domains) and the Hand Assessment of Infants. A subset of children will undertake MRI scans at 24 months ca to evaluate brain lesion severity and brain (re)organisation after intervention. Ethics and dissemination Full ethical approvals for this study have been obtained from the relevant sites. The findings will be disseminated in peer-reviewed publications. Trial registration number Australian and New Zealand Clinical Trials Registry: ACTRN12615000180516, Pre results

Background and Purpose: The diagnostic and prognostic potential of brain MR imaging before term-equivalent age is limited until valid MR imaging scoring systems are available. This study aimed to validate an MR imaging scoring system of brain injury and impaired growth for use at 29 to 35 weeks postmenstrual age in infants born at < 31 weeks gestational age. Materials and Methods: Eighty-three infants in a prospective cohort study underwent early 3T MR imaging between 29 and 35 weeks' postmenstrual age (mean, 32 +2 ± 1 +3 weeks; 49 males, born at median gestation of 28 +4 weeks; range, 23 +6 -30 +6 weeks; mean birthweight, 1068±312 g). Seventy-seven infants had a secondMRscan at term-equivalent age (mean, 40 +6 ±1 +3 weeks). Structural images were scored using a modified scoring system which generated WM, cortical gray matter, deep gray matter, cerebellar, and global scores. Outcome at 12-months corrected age (mean, 12 months 4 days ± 1 +2 weeks) consisted of the Bayley Scales of Infant and Toddler Development, 3rd ed. (Bayley III), and the Neuro-Sensory Motor Developmental Assessment. Results: Early MR imaging global, WM, and deep gray matter scores were negatively associated with Bayley III motor (regression coefficient for global score ß =-1.31; 95% CI,-2.39 to-0.23; P = .02), cognitive (ß =-1.52; 95% CI,-2.39 to-0.65; P < .01) and the Neuro-Sensory Motor Developmental Assessment outcomes (ß =-1.73; 95% CI,-3.19 to-0.28; P = .02). Early MR imaging cerebellar scores were negatively associated with the Neuro-Sensory Motor Developmental Assessment (ß =-5.99; 95% CI,-11.82 to-0.16; P = .04). Results were reconfirmed at term-equivalent-age MR imaging. Conclusions: This clinically accessible MR imaging scoring system is valid for use at 29 to 35 weeks postmenstrual age in infants born very preterm. It enables identification of infants at risk of adverse outcomes before the current standard of term-equivalent age.

Background: Dyskinetic cerebral palsy (CP) is one of the most disabling motor types of CP and has been classically associated with injury to the basal ganglia and thalamus. Although cognitive dysfunction is common in CP, there is a paucity of published quantitative analyses investigating the relationship between white matter (WM) microstructure and cognition in this CP type. Aims: This study aims (1) to compare brain WM microstructure between people with dyskinetic CP and healthy controls, (2) to identify brain regions where WM microstructure is related to intelligence and (3) to identify brain regions where WM microstructure is related to executive function in people with dyskinetic CP and (4) to identify brain regions where the correlations are different between controls and people with CP in IQ and executive functions. Patients and methods: Thirty-three participants with dyskinetic CP (mean ± SD age: 24.42 ± 12.61, 15 female) were age and sex matched with 33 controls. Participants underwent a comprehensive neuropsychological battery to assess intelligence quotient (IQ) and four executive function domains (attentional control, cognitive flexibility, goal setting and information processing). Diffusion weighted MRI scans were acquired at 3T. Voxel-based whole brain groupwise analyses were used to compare fractional anisotropy (FA) and of the CP group to the matched controls using a general lineal model. Further general linear models were used to identify regions where white matter FA correlated with IQ and each of the executive function domains. Results: White matter FA was significantly reduced in the CP group in all cerebral lobes, predominantly in regions connected with the parietal and to a lesser extent the temporal lobes. There was no significant correlation between IQ or any of the four executive function domains and WM microstructure in the control group. In participants with CP, lower IQ was associated with lower FA in all cerebral lobes, predominantly in l

Aims: To investigate the extent of white matter damage in children with unilateral cerebral palsy (UCP) caused by periventricular white matter lesions comparing between unilateral and bilateral lesions; and to investigate a relationship between white matter microstructure and hand function. Methods and procedures: Diffusion MRI images from 46 children with UCP and 18 children with typical development (CTD) were included. Subjects were grouped by side of hemiparesis and unilateral or bilateral lesions. A voxel-wise white matter analysis was performed to identify regions where fractional anisotropy (FA) was significantly different between UCP groups and CTD; and where FA correlated with either dominant or impaired hand function (using Jebsen Taylor Hand Function Test). Outcomes and results: Children with unilateral lesions had reduced FA in the corticospinal tract of the affected hemisphere. Children with bilateral lesions had widespread reduced FA extending into all lobes. In children with left hemiparesis, impaired hand function correlated with FA in the contralateral corticospinal tract. Dominant hand function correlated with FA in the posterior thalamic radiations as well as multiple other regions in both left and right hemiparesis groups. Conclusions and implications: Periventricular white matter lesions consist of focal and diffuse components. Focal lesions may cause direct motor fibre insult resulting in motor impairment. Diffuse white matter injury is heterogeneous, and may contribute to more global dysfunction.What this paper adds. •Focal white matter alterations are observed in the corticospinal tract in UCP with unilateral white matter lesions•Diffuse white matter alterations throughout all cerebral lobes are observed in UCP with bilateral white matter lesions•Fractional anisotropy in the posterior thalamic radiations correlates with dominant hand function.

© 2016 Lai et al.Background: Preterm infants follow an altered neurodevelopmental trajectory compared to their term born peers as a result of the influence of early birth, and the altered environment. Infant massage in the preterm infant has shown positive effects on weight gain and reduced length of hospital stay. There is however, limited current evidence of improved neurodevelopment or improved attachment, maternal mood or anxiety.The aim of this study is to investigate the effects of infant massage performed by the mother in very preterm (VPT) infants.Effects on the infant will be assessed at the electrophysiological, neuroradiological and clinical levels. Effects on maternal mood, anxiety and mother-infant attachment will also be measured. Methods/Design: A randomised controlled trial to investigate the effect of massage therapy in VPT infants. Sixty VPT infants, born at 28 to 32weeks and 6days gestational age, who are stable, off supplemental oxygen therapy and have normal cranial ultrasounds will be recruited and randomised to an intervention (infant massage) group or a control (standard care) group. Ten healthy term born infants will be recruited as a reference comparison group. The intervention group will receive standardised massage therapy administered by the mother from recruitment, until term equivalent age (TEA). The control group will receive care as usual (CAU). Infants and their mothers will be assessed at baseline, TEA, 12months and 24months corrected age (CA), with a battery of clinical, neuroimaging and electrophysiological measures, as well as structured questionnaires, psychoanalytic observations and neurodevelopmental assessments. Discussion: Optimising preterm infant neurodevelopment is a key aim of neonatal research, which could substantially improve long-term outcomes and reduce the socio-economic impact of VPT birth. This study has the potential to give insights into the mother-baby relationship and any positive effects of infant massageon

In this work we investigate the structural connectivity of the anterior cingulate cortex (ACC) and its link with impaired executive function in children with unilateral cerebral palsy (UCP) due to periventricular white matter lesions.Fifty two children with UCP and 17 children with typical development participated in the study, and underwent diffusion and structural MRI. Five brain regions were identified for their high connectivity with the ACC using diffusion MRI fibre tractography: the superior frontal gyrus, medial orbitofrontal cortex, rostral middle frontal gyrus, precuneus and isthmus cingulate. Structural connectivity was assessed in pathways connecting these regions to the ACC using three diffusion MRI derived measures: fractional anisotropy (FA), mean diffusivity (MD) and apparent fibre density (AFD), and compared between participant groups. Furthermore we investigated correlations of these measures with executive function as assessed by the Flanker task.The ACC–precuneus tract had significantly different MD (p < 0.0001) and AFD (p = 0.0072) between groups, with post-hoc analysis showing significantly increased MD in the right hemisphere of children with left hemiparesis compared with controls. The ACC–superior frontal gyrus tract had significantly different FA (p = 0.0049) and MD (p = 0.0031) between groups. AFD in this tract (contralateral to side of hemiparesis; right hemisphere in controls) showed a significant relationship with Flanker task performance (p = 0.0045, β = −0.5856), suggesting that reduced connectivity correlates with executive dysfunction.Reduced structural integrity of ACC tracts appears to be important in UCP, in particular the connection to the superior frontal gyrus. Although damage to this area is heterogeneous it may be important in early identification of children with impaired executive function.

© 2015 Published by Elsevier Inc.. Aim To provide first evidence of construct validity of a semi-quantitative scale for brain structural MRI (sqMRI scale) in children with unilateral cerebral palsy (UCP) secondary to periventricular white matter (PWM) lesions, by examining the relationship with hand sensorimotor function and whole brain structural connectivity. Methods Cross-sectional study of 50 children with UCP due to PWM lesions using 3 T (MRI), diffusion MRI and assessment of hand sensorimotor function. We explored the relationship of lobar, hemispheric and global scores on the sqMRI scale, with fractional anisotropy (FA), as a measure of brain white matter microstructure, and with hand sensorimotor measures (Assisting Hand Assessment, AHA; Jebsen-Taylor Test for Hand Function, JTTHF; Melbourne Assessment of Unilateral Upper Limb Function, MUUL; stereognosis; 2-point discrimination). Results Lobar and hemispheric scores on the sqMRI scale contralateral to the clinical side of hemiplegia correlated with sensorimotor paretic hand function measures and FA of a number of brain structural connections, including connections of brain areas involved in motor control (postcentral, precentral and paracentral gyri in the parietal lobe). More severe lesions correlated with lower sensorimotor performance, with the posterior limb of internal capsule score being the strongest contributor to impaired hand function. Conclusion The sqMRI scale demonstrates first evidence of construct validity against impaired motor and sensory function measures and brain structural connectivity in a cohort of children with UCP due to PWM lesions. More severe lesions correlated with poorer paretic hand sensorimotor function and impaired structural connectivity in the hemisphere contralateral to the clinical side of hemiplegia. The quantitative structural MRI scoring may be a useful clinical tool for studying brain structure-function relationships but requires further validation in other populatio

Background. Crossed cerebellar diaschisis is the disruption of functional connectivity between cerebrum and cerebellum after hemispheric unilateral brain lesions. In adults and to a lesser extent in children, crossed cerebellar diaschisis has been largely investigated by functional connectivity and demonstrated to influence paretic hand function. Objective. We aim to demonstrate a disruption in structural corticopontocerebellar (CPC) connectivity in children with congenital brain lesions and examine its correlation with paretic hand motor function. Methods. Thirty-six children (Manual Ability Classification System: I, n = 21; II, n = 15) with unilateral brain lesions and 18 controls were analyzed in a case-control study, and diffusion magnetic resonance imaging data were acquired at 3T. High angular resolution diffusion imaging probabilistic tractography was employed for the region of interest-based reconstruction of CPC tracts. To identify statistical differences in structural cerebrocerebellar connectivity between case and control groups, an asymmetry index based on the number of streamlines of CPC tracts was used. In the case group, the correlation between asymmetry index and hand function measures was also determined. Results. Projections through the middle cerebellar peduncle to the contralateral cerebral cortex showed greater asymmetry in children with congenital unilateral brain lesion compared to controls (P =.03), thus indicating a disruption of structural cerebrocerebellar connectivity. The degree of asymmetry index showed a correlation (P <.03; r = -0.31) with impaired hand abilities in bimanual tasks. Conclusions. Disruption of structural cerebrocerebellar connectivity is present in patients with congenital unilateral brain injury and might be related to impaired hand function in bimanual skills, with potential implication in tailoring early intervention strategies.

© 2015 George et al. Background: More than 50 percent of all infants born very preterm will experience significant motor and cognitive impairment. Provision of early intervention is dependent upon accurate, early identification of infants at risk of adverse outcomes. Magnetic resonance imaging at term equivalent age combined with General Movements assessment at 12 weeks corrected age is currently the most accurate method for early prediction of cerebral palsy at 12 months corrected age. To date no studies have compared the use of earlier magnetic resonance imaging combined with neuromotor and neurobehavioural assessments (at 30 weeks postmenstrual age) to predict later motor and neurodevelopmental outcomes including cerebral palsy (at 12-24 months corrected age). This study aims to investigate i) the relationship between earlier brain imaging and neuromotor/neurobehavioural assessments at 30 and 40 weeks postmenstrual age, and ii) their ability to predict motor and neurodevelopmental outcomes at 3 and 12 months corrected age. Methods/design: This prospective cohort study will recruit 80 preterm infants born =30 week's gestation and a reference group of 20 healthy term born infants from the Royal Brisbane & Women's Hospital in Brisbane, Australia. Infants will undergo brain magnetic resonance imaging at approximately 30 and 40 weeks postmenstrual age to develop our understanding of very early brain structure at 30 weeks and maturation that occurs between 30 and 40 weeks postmenstrual age. A combination of neurological (Hammersmith Neonatal Neurologic Examination), neuromotor (General Movements, Test of Infant Motor Performance), neurobehavioural (NICU Network Neurobehavioural Scale, Premie-Neuro) and visual assessments will be performed at 30 and 40 weeks postmenstrual age to improve our understanding of the relationship between brain structure and function. These data will be compared to motor assessments at 12 weeks corrected age and motor and neurodevelopmental ou

Background: Cerebral palsy (CP) is a term to describe the spectrum of disorders of impaired motor and sensory function caused by a brain lesion occurring early during development. Diffusion MRI and tractography have been shown to be useful in the study of white matter (WM) microstructure in tracts likely to be impacted by the static brain lesion. Aim: The purpose of this study was to identify WM pathways with altered connectivity in children with unilateral CP caused by periventricular white matter lesions using a whole-brain connectivity approach. Methods: Data of 50 children with unilateral CP caused by periventricular white matter lesions (5–17 years; manual ability classification system [MACS] I = 25/II = 25) and 17 children with typical development (CTD; 7–16 years) were analysed. Structural and High Angular Resolution Diffusion weighted Images (HARDI; 64 directions, b = 3000 s/mm2) were acquired at 3 T. Connectomes were calculated using whole-brain probabilistic tractography in combination with structural parcellation of the cortex and subcortical structures. Connections with altered fractional anisotropy (FA) in children with unilateral CP compared to CTD were identified using network-based statistics (NBS). The relationship between FA and performance of the impaired hand in bimanual tasks (Assisting Hand Assessment—AHA) was assessed in connections that showed significant differences in FA compared to CTD.Results: FA was reduced in children with unilateral CP compared to CTD. Seven pathways, including the corticospinal, thalamocortical, and fronto-parietal association pathways were identified simultaneously in children with left and right unilateral CP. There was a positive relationship between performance of the impaired hand in bimanual tasks and FA within the cortico-spinal and thalamo-cortical pathways (r2 = 0.16–0.44; p < 0.05). Conclusion: This study shows that network-based analysis of structural connectivity can identify alterations in FA in unilatera

There is reduced integrity of corticospinal projections that traverse the posterior limb of the internal capsule (PLIC) in children with unilateral cerebral palsy (CP). It remains unclear whether there are changes in integrity of other projections traversing the PLIC. Forty children with congenital hemiparesis and 15 typically developing children underwent structural and diffusion-weighted MRI. All children with congenital hemiparesis showed lesions to the periventricular white matter. Structural images were parcellated into 34 cortical regions per hemisphere and posterior limb of the internal capsule was identified. PLIC connections to each cortical region were extracted using probabilistic tractography. Differences between hemispheres for each cortical projection (asymmetry index (AI)) and tract microstructure (fractional anisotropy (FA), mean diffusivity (MD)) were assessed. The results showed that 17 children (42.5%) with congenital hemiparesis showed bilateral lesions on structural MRI. Projections to the primary motor cortex (precentral gyrus and paracentral lobule) showed greater asymmetry in unilateral CP group compared to typically developing children and indicate reduced projections on the hemisphere contralateral to the impaired limb (i.e., contralateral hemisphere). Reduced FA and increased MD were also observed for connections with the primary motor cortex, primary sensory cortex (postcentral gyrus) and precuneus on the contralateral hemisphere in children with congenital hemiparesis. Similar changes were observed between children with unilateral and bilateral lesions on structural MRI. Notably, microstructural changes were associated with deficits in both sensory and motor function. The findings further unravel the underlying neuroanatomical correlates of sensorimotor deficits in children with congenital hemiparesis. © 2013 Elsevier Ltd.

Aim: Preterm birth is associated with an increased risk of adverse neurodevelopmental outcomes. Diffusion magnetic resonance imaging (dMRI) combined with tractography can be used to assess non-invasively white matter microstructure and brain development in preterm infants. Our aim was to conduct a systematic review of the current evidence obtained from tractography studies of preterm infants in whom MRI was performed up to term-equivalent age. Method: Databases were searched for dMRI tractography studies of preterm infants. Results: Twenty-two studies were assessed. The most frequently assessed tracts included the corticospinal tract, the corpus callosum, and the optic radiations. The superior longitudinal fasciculus, and the anterior and superior thalamic radiations were investigated less frequently. A clear relationship exists between diffusion metrics and postmenstrual age at the time of scanning, although the evidence of an effect of gestational age at birth and white matter injury is conflicting. Sex and laterality may play an important role in the relationship between diffusion metrics, early clinical assessment, and outcomes. Interpretation: Studies involving infants of all gestational ages are required to elucidate the relationship between gestational age and diffusion metrics, and to establish the utility of tractography as a predictive tool. There is a need for more robust acquisition and analysis methods to improve the accuracy of assessing development of white matter pathways. © 2013 Mac Keith Press.

© 2014 Mac Keith Press. Aim: The aim of this study was to quantify grey matter changes in children with unilateral cerebral palsy (UCP), differentiating between cortical or deep grey matter (CDGM) lesions, periventricular white matter (PWM) lesions, and unilateral and bilateral lesions. Method: In a cross-sectional study we obtained high resolution structural magnetic resonance images from 72 children (41 males, 31 females, mean age 10y 9mo [SD 3y 1mo], range 5y 1mo-17y 1mo) with UCP (33 left, 39 right hemiplegia; Manual Ability Classification System level I n=29, II n=43; Gross Motor Function Classification System level I n=46, II n=26), and 19 children with typical development (CTD; eight males, 11 females, mean age 11y 2mo [SD 2y 7mo], range 7y 8mo-16y 4mo). Images were classified by lesion type and analyzed using voxel-based morphometry (VBM) and subcortical volumetric analysis. Results: Deep grey matter volumes were not significantly different between children with CDGM and PWM lesions, with the thalamus, putamen, and globus pallidus being reduced unilaterally in both groups compared with CTD (p=0.001). Children with CDGM lesions additionally showed widespread cortical changes involving all lobes using VBM (p<0.01). Children with bilateral lesions had reduced thalamus and putamen volumes bilaterally (p<0.001). The thalamic volume was reduced bilaterally in children with unilateral lesions (p=0.004). Interpretation: Lesions to the PWM cause secondary changes to the deep grey matter structures similar to primary changes seen in CDGM lesions. Despite having a unilateral phenotype, grey matter changes are observed bilaterally, even in children with unilateral lesions.

Preservation of thalamocortical projections to the sensorimotor cortex is related to improved hand function in children with cerebral palsy (CP). Whether CP is associated with altered microstructure of these sensorimotor projections or other thalamocortical pathways remains unclear. Forty-two children with congenital hemiplegia and fifteen typically developing children (TDC) underwent structural and diffusion-weighted imaging (high-angular-resolution diffusion imaging) using a 3T MRI. Structural T1-images were parcellated into 34 cortical regions and the thalamus per hemisphere. Thalamocortical projections were extracted using probabilistic tractography and the top tan cortical regions with the greatest number of thalamocortical streamlines for the TDC group were selected for further analysis. The thalamus was parcellated based on its cortical connections. Differences between hemispheres for thalamocortical streamline numbers to each cortical region [asymmetry index (AI)], tract volume and tract microstructure [weighted mean fractional anisotropy (FA) and mean diffusivity (MD)] were calculated. Correlations between these measures (AI, FA and MD) and sensorimotor function were performed. Thalamocortical projections showed topographical organisation based on cortical connectivity. Projections to paracentral lobule, pre-central and post-central gyri showed greater AI in CP group, which indicates reduced streamlines on the ipsilesioned hemisphere. Reduced FA, reduced tract volume and increased MD were also found for these thalamocortical projections on the ipsilesioned hemisphere in children with CP. Changes in AI and tract microstructure of these projections were associated with poorer sensorimotor function. The findings suggest CP is associated with reorganisation of thalamocortical projections to the sensorimotor cortex. Integrity in these projections may underpin deficits in sensorimotor function.

Brain injury and subsequent plasticity of sensory and corticospinal pathways play an integral role in determining paretic hand function in congenital hemiplegia. There is limited knowledge regarding the relationship between the disruption of sensorimotor thalamic pathways projecting into the primary motor cortex and motor control. This study sought to investigate the relationship between the structural connectivity of motor networks that anatomically link the brain stem with the precentral and postcentral gyri with paretic motor sensory function by using an automated analysis strategy. Magnetic resonance imaging structural connectivity was measured by using high-angular-resolution diffusion imaging, probabilistic tractography, and the anatomic parcellation of high-resolution structural images in 16 children with congenital unilateral periventricular white-matter damage. Connectivity of the corticospinal and corticothalamic pathways was determined by using an asymmetry index based on the number of streamlines contained within these projections and compared with measures of paretic hand function and bimanual coordination. For cortical development, the volume of the ipsilesional precentral gyrus was significantly reduced. For connectivity measures, the numbers of streamlines in corticospinal tracts and corticothalamic pathways within the ipsilesional hemisphere were decreased compared with the contralesional side. The sensorimotor thalamic projections were more significantly correlated with paretic hand functions than were the corticospinal tracts. These data support the concept that preservation of sensorimotor thalamic pathways that directly project into the primary motor cortex has more influence on motor function control of the paretic hand than does preservation of corticospinal tracts. © 2011, Mary Ann Liebert, Inc. All rights reserved.