Prenatal stress and limbic-prefrontal white matter microstructure in children aged 6–9 years: a preliminary diffusion tensor imaging study

Objectives. Maternal prenatal stress is associated with elevated risk of adverse behavioural outcomes in offspring. This association may involve developmental disruption to limbic-prefrontal white matter circuitry, of which the uncinate fasciculus is the major tract. One potential candidate for modulating brain development is maternal prenatal stress. We provide the first prospective study of prenatal stress and white matter microstructure in children. Methods. A total of 22 healthy children (mean age 7 years) of mothers recruited in pregnancy underwent diffusion tensor magnetic resonance imaging. We examined correlations between prenatal stressful life events and white matter microstructural organisation indices (fractional anisotropy (FA) and perpendicular diffusivity (D_perp)) of the uncinate fasciculus and a “control” tract. Results. Maternal prenatal stressful life events were correlated positively with right uncinate fasciculus FA, and negatively with right uncinate fasciculus D_perp in their child, with a similar trend with left uncinate fasciculus D_perp. Prenatal stress was not associated with control tract properties; sociodemographic/obstetric variables were not associated with FA/D_perp of either tract. Conclusions. Variation in maternal prenatal stress may be associated with differences in the development of white matter within brain networks underlying child social behaviour.     

Ex vivo diffusion tensor imaging and neuropathological correlation in a murine model of hypoxia–ischemia-induced thrombotic stroke

Diffusion tensor imaging (DTI) is a powerful method to visualize white matter, but its use in patients with acute stroke remains limited because of the lack of corresponding histologic information. In this study, we addressed this issue using a hypoxia–ischemia (HI)-induced thrombotic model of stroke in adult mice. At 6, 15, and 24 hours after injury, animals were divided into three groups for (1) in vivo T2- and diffusion-weighted magnetic resonance imaging, followed by histochemistry, (2) ex vivo DTI and electron microscopy, and (3) additional biochemical or immunochemical assays. The temporal changes of diffusion anisotropy and histopathology were compared in the fimbria, internal capsule, and external capsule. We found that HI caused a rapid reduction of axial and radial diffusivities in all three axonal bundles. A large decrease in fractional anisotropy, but not in axial diffusivity per se, was associated with structural breakdown of axons. Furthermore, the decrease in radial diffusivity correlated with swelling of myelin sheaths and compression of the axoplasma. The gray matter of the hippocampus also exhibited a high level of diffusion anisotropy, and its reduction signified dendritic degeneration. Taken together, these results suggest that cross-evaluation of multiple DTI parameters may provide a fuller picture of axonal and dendritic injury in acute ischemic stroke.     

Age-related changes of lateral ventricular width and periventricular white matter in the human brain： a diffusion tensor imaging study

<正>Introduction Aging is the accumulation of multidimensional deterioration of processing of biological,psychological,and social changes with expansion over time(Bowen and Atwood,2004;Grady,2012).Aging-related changes are typically accompanied by decline in cognitive function,urinary control,sensory-motor function,and gait ability(Bradley et al.,1991;Bowen and Atwood,2004;Hedden and Gabrieli,2004;Grady,2012;Moran et al.,     

Head injury or head motion? Assessment and quantification of motion artifacts in diffusion tensor imaging studies

The relationship between head motion and diffusion values such as fractional anisotropy (FA) and mean diffusivity (MD) is currently not well understood. Simulation studies suggest that head motion may introduce either a positive or negative bias, but this has not been quantified in clinical studies. Moreover, alternative measures for removing bias as result of head motion, such as the removal of problematic gradients, has been suggested but not carefully evaluated. The current study examined the impact of head motion on FA and MD across three common pipelines (tract-based spatial statistics, voxelwise, and region of interest analyses) and determined the impact of removing diffusion weighted images. Our findings from a large cohort of healthy controls indicate that while head motion was associated with a positive bias for both FA and MD, the effect was greater for MD. The positive bias was observed across all three analysis pipelines and was present following established protocols for data processing, suggesting that current techniques (i.e., correction of both image and gradient table) for removing motion bias are likely insufficient. However, the removal of images with gross artifacts did not fundamentally change the relationship between motion and DTI scalar values. In addition, Monte Carlo simulations suggested that the random removal of images increases the bias and reduces the precision of both FA and MD. Finally, we provide an example of how head motion can be quantified across different neuropsychiatric populations, which should be implemented as part of any diffusion tensor imaging quality assurance protocol.     

Advanced MR diffusion imaging and chemotherapy‐related changes in cerebral white matter microstructure of survivors of childhood bone and soft tissue sarcoma?

With the increase of survival rates of pediatric cancer patients, the number of children facing potential cognitive sequelae has grown. Previous adult studies suggest that white matter (WM) microstructural changes may contribute to cognitive impairment. This study aims to investigate WM microstructure in childhood bone and soft tissue sarcoma. Differences in (micro‐)structure can be investigated using diffusion MRI (dMRI). The typically used diffusion tensor model (DTI) assumes Gaussian diffusion, and lacks information about fiber populations. In this study, we compare WM structure of childhood bone and soft tissue sarcoma survivors (n = 34) and matched controls (n = 34), combining typical and advanced voxel‐based models (DTI and NODDI model, respectively), as well as recently developed fixel‐based models (for estimations of intra‐voxel differences, apparent fiber density [AFD] and fiber cross‐section [FC]). Parameters with significant findings were compared between treatments, and correlated with subscales of the WAIS‐IV intelligence test, age at diagnosis, age at assessment and time since diagnosis. We encountered extensive regions showing lower fractional anisotropy, overlapping with both significant NODDI parameters and fixel‐based parameters. In contrast to these diffuse differences, the fixel‐based measure of AFD was reduced in the cingulum and corpus callosum only. Furthermore, AFD of the corpus callosum was significantly predicted by chemotherapy treatment and correlated positively with time since diagnosis, visual puzzles and similarities task scores. This study suggests altered WM structure of childhood bone and soft tissue sarcoma survivors. We conclude global chemotherapy‐related changes, with particular vulnerability of centrally located WM bundles. Finally, such differences could potentially recover after treatment.     

Traumatic brain injury and the frontal lobes: What can we gain with diffusion tensor imaging?

Traumatic brain injury (TBI) is a leading cause of death in the young population and long-term disability in relation to pervasive cognitive-behavioural disturbances that follow frontal lobe damage. To date, emphasis has been placed primarily on the clinical correlates of frontal cortex damage, whilst identification of the contribution of subjacent white matter lesion is less clear. Our poor understanding of white matter pathology in TBI is primarily due to the low sensitivity of conventional neuroimaging to identify pathological changes in less severe traumatic injury and the lack of methods to localise white matter pathology onto individual frontal lobe connections. In this paper we focus on the potential contribution of diffusion tensor imaging (DTI) to TBI. Our review of the current literature supports the conclusion that DTI is particularly sensitive to changes in the microstructure of frontal white matter, thus providing a valuable biomarker of the severity of traumatic injury and prognostic indicator of recovery of function. Furthermore we propose an atlas approach to TBI to map white matter lesions onto individual tracts. In the cases presented here we showed a direct correspondence between the clinical manifestations of the patients and the damage to specific white matter tracts. We are confident that in the near future the application of DTI to TBI will improve our understanding of the complex and heterogeneous clinical symptomatology which follows a TBI, especially mild and moderate head injury, which still represents 70-80% of all clinical population.     

Children with cerebral palsy and periventricular white matter injury: Does gestational age affect functional outcome?

This study aimed to determine differences in functional profiles and movement disorder patterns in children aged 4–12 years with cerebral palsy (CP) and periventricular white matter injury (PWMI) born >34 weeks gestation compared with those born earlier. Eligible children born between 1999 and 2006 were recruited through the Victorian CP register. Functional profiles were determined using the Gross Motor Function Classification System (GMFCS), Manual Abilities Classification System (MACS), Communication Function Classification System (CFCS), Functional Mobility Scale (FMS) and Bimanual Fine Motor Function (BFMF). Movement disorder and topography were classified using the Surveillance of Cerebral Palsy in Europe (SCPE) classification. 49 children born >34 weeks (65% males, mean age 8y 9mo [standard deviation (SD) 2y 2mo]) and 60 children born ≤34 weeks (62% males, mean age 8y 2mo [SD 2y 2mo]) were recruited. There was evidence of differences between the groups for the GMFCS (p = 0.003), FMS 5, 50 and 500 (p = 0.003, 0.002 and 0.012), MACS (p = 0.04) and CFCS (p = 0.035), with a greater number of children born ≤34 weeks more severely impaired compared with children born later. Children with CP and PWMI born >34 weeks gestation had milder limitations in gross motor function, mobility, manual ability and communication compared with those born earlier.     

Long-term diffusion impairment of cerebral white matter in a degenerative disease of the central and peripheral nervous system: reflection of chronic excitotoxicity?

The authors report an abnormal prolonged restricted magnetic resonance imaging (MRI) proton diffusion that persisted for more than 2 years in a 6.5-year-old boy with a progressive neurological disease characterized by developmental retardation, peripheral polyneuropathy, and bilateral optical nerve atrophy. The long-term restricted magnetic resonance imaging proton diffusion observed in diffusion-weighted magnetic resonance images indicates chronic metabolic tissue impairment in the affected white matter, whereas measurable lactate accumulation in proton magnetic resonance spectroscopy was absent, and no respiratory complex abnormality was found in muscle tissue. These findings are suggestive of a chronically disturbed regulation of energy supply triggering a "slow onset" excitotoxicity, causing chronic hypoxia and leading to slow cell death as has been postulated in certain neurodegenerative processes.     

MRI and diffusion tensor imaging in assessing correlation of activation of cortical motor function and manifestations of corticospinal tract with muscle strength in patients with ischemic stroke

IN T R O D U C T IO N Ischem ic stroke is often follow ed by the abnorm alities ofneurons and corticospinaltract,w hich lead to corresponding clinicalsym ptom s and signs. R ecently, w ith the continuous perfection ofhigh-field M R Iin- strum ent, itis po…     

Microstructural white matter alterations in Alzheimer’s disease and amnestic mild cognitive impairment and its diagnostic value based on diffusion kurtosis imaging: a tract-based spatial statistics study

Brain Imaging and Behavior - This prospective study aimed to explore the white matter microstructural alterations in Alzheimer’s disease (AD) and amnestic mild cognitive impairment (aMCI)...     

2001–2011: a decade of the LADIS (Leukoaraiosis And DISability) Study: what have we learned about white matter changes and small-vessel disease?

Over the last 20 years, evidence about the clinical correlates of cerebral white matter changes (WMC; also called leukoaraiosis) has been accumulating. WMC are now listed among the neuroimaging expressions of cerebral small-vessel disease and are no longer considered an innocuous finding because they are associated, in cross-sectional surveys, with various disturbances and, in follow-up studies, with poor prognosis. The Leukoaraiosis And DISability (LADIS) study has contributed substantially to this body of knowledge. LADIS is a European multicenter collaboration that was started in 2001 with the aim of assessing the independent role of WMC in predicting disability in subjects aged 65-84. The main results of the LADIS study have been released in 2009 with the demonstration that severe WMC more than double the risk of transition from an autonomous to a dependent status after 3 years of follow-up. The LADIS study has also contributed more focused substudies assessing the possible role of WMC in the decline of cognitive and motor performances, depressive symptoms associated with aging and cerebrovascular diseases, urinary disturbances, and also the role of other brain lesions (lacunar infarcts, cerebral atrophy, and corpus callosum morphology). The LADIS study provides a good example of harmonization of instruments (MRI protocol, clinical, neuropsychological, and functional scales) within an international collaboration. Currently, the LADIS study is providing data about the natural history of WMC. In this paper, we review the background and the main results of the LADIS study. This review puts forward some considerations for future studies in the field.     

Nucleated red blood cell counts: An early predictor of brain injury and 2-year outcome in neonates with hypoxic–ischemic encephalopathy in the era of cooling-based treatment

Background: Raised nucleated red blood cell (NRBC) counts in neonates may indicate in utero hypoxia and brain damage. Objective: The study aimed to examine the use of NRBC counts as a predictor of brain injury and neurodevelopmental outcomes in neonates with hypoxic–ischemic encephalopathy (HIE) treated under current cooling-based strategy. Methods: Forty-three neonates with asphyxia between 2004 and 2010 were retrospectively investigated. Twenty neonates with moderate/severe HIE underwent hypothermia (HT), and 23 with mild HIE were treated in normothermia (NT). Neonates were divided into groups according to the presence of cerebral parenchymal lesions on magnetic resonance imaging (MRI) at 2 weeks after birth. All patients were followed-up neurologically for ?24 months. NRBC counts during the first 3 days were compared between groups. Results: Eleven HT (HT-N) and 21 NT (NT-N) neonates had normal MRI, and 9 HT (HT-L) and 2 NT (NT-L) neonates had parenchymal lesions. NRBC counts, both absolute and /100 white blood cells (WBC) counts, during the first 3 days in HT-L and NT-L were significantly higher than those in HT-N and NT-N, particularly within 6 hours after birth (HT-N: 502 [0–3060]/mm³ vs HT-L: 2765 [496–6192]; 0 [0–3417] vs NT-L: 4384 [3978–4789], median [range]). Neonates with /100 white blood cells ?6/mm³ and absolute NRBC counts ?1324/mm³ within 6 hours of birth had high risks of abnormal MRIs and 2-year outcomes. Conclusions: NRBC counts can predict brain injury and neurological outcomes in cooled and non-cooled asphyxiated neonates.     

Immunohistochemical and ultrastructural evidence for the pathogenesis of white matter degeneration in patients with panencephalopathic-type Creutzfeldt–Jakob disease: Inducible nitric oxide synthase overexpression in bizarre astrocytes

Excessive production of nitric oxide (NO) due to the overinduction of inducible nitric oxide synthase (iNOS) has a severe cytotoxic effect, which may relate to the pathogenesis of neurodegenerative disorders. In this study, we report the novel finding that iNOS is overinduced in a large number of bizarre astrocytes in the white matter of patients with panencephalopathic (PE)-type Creutzfeldt–Jakob disease (CJD). This study was carried out on brain tissue from seven patients with PE-type CJD. As controls, 12 normal individuals and nine patients with cerebral infarction were examined. We identified a large number of bizarre astrocytes in the degenerative cerebral white matter in PE-type CJD. Using immunohistochemistry, only bizarre astrocytes in PE-type CJD showed strong immunoreactivity for both iNOS and superoxide dismutase 1 (SOD1). Ultrastructural examination demonstrated that these bizarre astrocytes contained many free polyribosome-like granules. No significant iNOS immunoreactivity was observed in either the astrocytes of patients with cerebral infarcts or in the normal controls. This study suggests that the iNOS-overexpressing astrocytes, especially iNOS-overexpressing bizarre astrocytes, could play an important role in the development of white matter lesions in PE-type CJD. Our data also suggest that the bizarre astrocytes could be protecting themselves from the cytotoxicity of NO by producing SOD1. These immunohistochemical findings are supported by the ultrastructural observation of numerous polyribosome granules restricted to the cytoplasm of these bizarre astrocytes.     

Blood–brain barrier dysfunction following traumatic brain injury: correlation of Ktrans (DCE-MRI) and SUVR (99mTc-DTPA SPECT) but not serum S100B

Abstract

Objective:

Damage to the blood–brain barrier (BBB) is an important secondary mechanism that occurs following traumatic brain injury (TBI) and may provide a potential therapeutic target to improve patient outcome. For such a progress to be realised, an accurate assessment of BBB compromise needs to be established.

Methods:

Fourteen patients with TBI were prospectively recruited. Post-traumatic BBB dysfunction was assessed using dynamic contrast-enhanced MRI (DCE-MRI), single-photon emission computerised tomography (SPECT) and serum S100B levels.

Results:

A statistically significant correlation between standardised uptake value ratio (SUVR) calculated from 99mTc-DTPA SPECT and K^trans (a volume transfer constant) from DCE-MRI was found for those eight patients who had concurrent scans. The positive correlation persisted when the data were corrected for patient age, number of days following trauma and both parameters combined. We found no statistically significant correlation between either of the imaging modalities and concurrent serum S100B levels.

Discussion:

The correlation of SPECT with DCE-MRI suggests that either scan may be used to assess post-traumatic BBB damage. We could not support serum S100B to be an accurate measure of BBB damage when sampled a number of days following injury but the small number of patients, the heterogeneity in TBI patients and the delay following injury makes any firm conclusions regarding S100B and BBB difficult.