Fixel-based analysis of the preterm brain: Disentangling bundle-specific white matter microstructural and macrostructural changes in relation to clinical risk factors

Diffusion MRI (dMRI) studies using the tensor model have identified abnormal white matter development associated with perinatal risk factors in preterm infants studied at term equivalent age (TEA). However, this model is an oversimplification of the underlying neuroanatomy. Fixel-based analysis (FBA) is a novel quantitative framework, which identifies microstructural and macrostructural changes in individual fibre populations within voxels containing crossing fibres. The aim of this study was to apply FBA to investigate the relationship between fixel-based measures of apparent fibre density (FD), fibre bundle cross-section (FC), and fibre density and cross-section (FDC) and perinatal risk factors in preterm infants at TEA. We studied 50 infants (28 male) born at 24.0-32.9 (median 30.4) weeks gestational age (GA) and imaged at 38.6-47.1 (median 42.1) weeks postmenstrual age (PMA). dMRI data were acquired in non-collinear directions with b-value 2500 s/mm2 on a 3 Tesla system sited on the neonatal intensive care unit. FBA was performed to assess the relationship between FD, FC, FDC and PMA at scan, GA at birth, days on mechanical ventilation, days on total parenteral nutrition (TPN), birthweight z-score, and sex. FBA reveals fibre population-specific alterations in FD, FC and FDC associated with clinical risk factors. FD was positively correlated with GA at birth and was negatively correlated with number of days requiring ventilation. FC was positively correlated with GA at birth, birthweight z-scores and was higher in males. FC was negatively correlated with number of days on ventilation and days on TPN. FDC was positively correlated with GA at birth and birthweight z-scores, negatively correlated with days on ventilation and days on TPN and higher in males. We demonstrate that these relationships are fibre-specific even within regions of crossing fibres. These results show that aberrant white matter development involves both microstructural changes and macrostructural alterations

Reduced structural connectivity in non-motor networks in children born preterm and the influence of early postnatal human cytomegalovirus infection.

INTRODUCTION Preterm birth is increasingly recognized to cause lifelong functional deficits, which often show no correlate in conventional MRI. In addition, early postnatal infection with human cytomegalovirus (hCMV) is being discussed as a possible cause for further impairments. In the present work, we used fixel-based analysis of diffusion-weighted MRI to assess long-term white matter alterations associated with preterm birth and/or early postnatal hCMV infection. MATERIALS AND METHODS 36 former preterms (PT, median age 14.8 years, median gestational age 28 weeks) and 18 healthy term-born controls (HC, median age 11.1 years) underwent high angular resolution DWI scans (1.5 T, b = 2 000 s/mm2, 60 directions) as well as clinical assessment. All subjects showed normal conventional MRI and normal motor function. Early postnatal hCMV infection status (CMV+ and CMV-) had been determined from repeated screening, ruling out congenital infections. Whole-brain analysis was performed, yielding fixel-wise metrics for fiber density (FD), fiber cross-section (FC), and fiber density and cross-section (FDC). Group differences were identified in a whole-brain analysis, followed by an analysis of tract-averaged metrics within a priori selected tracts associated with cognitive function. Both analyses were repeated while differentiating for postnatal hCMV infection status. RESULTS PT showed significant reductions of fixel metrics bilaterally in the cingulum, the genu corporis callosum and forceps minor, the capsula externa, and cerebellar and pontine structures. After including intracranial volume as a covariate, reductions remained significant in the cingulum. The tract-specific investigation revealed further reductions bilaterally in the superior longitudinal fasciculus and the uncinate fasciculus. When differentiating for hCMV infection status, no significant differences were found between CMV+ and CMV-. However, comparing CMV+ against HC, fixel metric reductions were of higher magnitude and of larger spatial extent than in CMV- against HC. CONCLUSION Preterm birth can lead to long-lasting alterations of WM micro- and macrostructure, not visible on conventional MRI. Alterations are located predominantly in WM structures associated with cognitive function, likely underlying the cognitive deficits observed in our cohort. These observed structural alterations were more pronounced in preterms who suffered from early postnatal hCMV infection, in line with previous studies suggesting an additive effect

Programming the brain: common outcomes and gaps in knowledge from animal studies of IUGR

Available online 7 June 2016Abstract not availableDamien S. Hunter, Susan J. Hazel, Karen L. Kinda, Julie A. Owens, Julia B. Pitcher, Kathryn L. Gatfor

Measuring cortical connectivity in Alzheimer's disease as a brain neural network pathology: Toward clinical applications

Objectives: The objective was to review the literature on diffusion tensor imaging as well as resting-state functional magnetic resonance imaging and electroencephalography (EEG) to unveil neuroanatomical and neurophysiological substrates of Alzheimer’s disease (AD) as a brain neural network pathology affecting structural and functional cortical connectivity underlying human cognition. Methods: We reviewed papers registered in PubMed and other scientific repositories on the use of these techniques in amnesic mild cognitive impairment (MCI) and clinically mild AD dementia patients compared to cognitively intact elderly individuals (Controls). Results: Hundreds of peer-reviewed (cross-sectional and longitudinal) papers have shown in patients with MCI and mild AD compared to Controls (1) impairment of callosal (splenium), thalamic, and anterior–posterior white matter bundles; (2) reduced correlation of resting state blood oxygen level-dependent activity across several intrinsic brain circuits including default mode and attention-related networks; and (3) abnormal power and functional coupling of resting state cortical EEG rhythms. Clinical applications of these measures are still limited. Conclusions: Structural and functional (in vivo) cortical connectivity measures represent a reliable marker of cerebral reserve capacity and should be used to predict and monitor the evolution of AD and its relative impact on cognitive domains in pre-clinical, prodromal, and dementia stages of AD. (JINS, 2016, 22, 138–163

Whole-Brain DTI Assessment of White Matter Damage in Children with Bilateral Cerebral Palsy: Evidence of Involvement beyond the Primary Target of the Anoxic Insult

BACKGROUND AND PURPOSE: Cerebral palsy is frequently associated with both motor and nonmotor symptoms. DTI can characterize the damage at the level of motor tracts but provides less consistent results in nonmotor areas. We used a standardized pipeline of analysis to describe and quantify the pattern of DTI white matter abnormalities of the whole brain in a group of children with chronic bilateral cerebral palsy and periventricular leukomalacia. We also explored potential correlations between DTI and clinical scale metrics. MATERIALS AND METHODS: Twenty-five patients (mean age, 11.8 years) and 25 healthy children (mean age, 11.8 years) were studied at 3T with a 2-mm isotropic DTI sequence. Differences between patients and controls were assessed both voxelwise and in ROIs obtained from an existing DTI atlas. Clinical metrics included the Gross Motor Function Classification System, the Manual Ability Classification System, and intelligence quotient. RESULTS: The voxel-level and ROI-level analyses demonstrated highly significant ( P CONCLUSIONS: We demonstrated the involvement of several motor and nonmotor areas in the chronic damage associated with periventricular leukomalacia and showed new correlations between motor skills and DTI metrics

Development of brain structures following perinatal cerebral lesions suggests the involvement of the cerebellum in the working memory network

openCrossed cerebro-cerebellar diaschisis in very preterm born individuals, following perinatal cerebral lesions, reveals functional connectivity between some cerebral areas involved in working memory (WM) and yet undefined cerebellar regions: this may support the role of the latter in the WM network. The cerebellum has long been associated with motor control and coordination. In the last two decades, researchers have studied its involvement in a broad range of cognitive functions, such as visuospatial attention and WM. In this overview, I define the brain regions activated by the WM network and their development in term- and very preterm- infants compared, according to the most recent studies. These findings could contribute to support the involvement of the cerebellum in non-motor functions, specifically in WM.Crossed cerebro-cerebellar diaschisis in very preterm born individuals, following perinatal cerebral lesions, reveals functional connectivity between some cerebral areas involved in working memory (WM) and yet undefined cerebellar regions: this may support the role of the latter in the WM network. The cerebellum has long been associated with motor control and coordination. In the last two decades, researchers have studied its involvement in a broad range of cognitive functions, such as visuospatial attention and WM. In this overview, I define the brain regions activated by the WM network and their development in term- and very preterm- infants compared, according to the most recent studies. These findings could contribute to support the involvement of the cerebellum in non-motor functions, specifically in WM

Papez Circuit Observed by in vivo Human Brain With 7.0T MRI Super-Resolution Track Density Imaging and Track Tracing

The Papez circuit has been considered as an important anatomical substrate involved in emotional experience. However, the circuit remains difficult to elucidate in the human brain due to the resolution limit of current neuroimaging modalities. In this article, for the first time, we report the direct visualization of the Papez circuit with 7-Tesla super-resolution magnetic resonance tractography. Two healthy, young male subjects (aged 30 and 35 years) were recruited as volunteers following the guidelines of the institutional review board (IRB). Track density imaging (TDI) generation with track tracing was performed using MRtrix software package. With these tools, we were able to visualize the entire Papez circuit. We believe this is the first study to visualize the complete loop of the Papez circuit, including the perforant path (PP), thalamocortical fibers of the anterior nucleus (AN), and mammillothalamic tract (MTT), which were hitherto difficult to visualize by conventional imaging techniques

Diffusion tensor imaging in frontostriatal tracts is associated with executive functioning in very preterm children at 9 years of age

Background Very preterm birth can disturb brain maturation and subject these high-risk children to neurocognitive difficulties later. Objective The aim of the study was to evaluate the impact of prematurity on microstructure of frontostriatal tracts in children with no severe neurologic impairment, and to study whether the diffusion tensor imaging metrics of frontostriatal tracts correlate to executive functioning. Materials and methods The prospective cohort study comprised 54 very preterm children (mean gestational age 28.8 weeks) and 20 age- and gender-matched term children. None of the children had severe neurologic impairment. The children underwent diffusion tensor imaging and neuropsychological assessments at a mean age of 9 years. We measured quantitative diffusion tensor imaging metrics of frontostriatal tracts using probabilistic tractography. We also administered five subtests from the Developmental Neuropsychological Assessment, Second Edition, to evaluate executive functioning. Results Very preterm children had significantly higher fractional anisotropy and axial diffusivity values (PPeer reviewe