Reduced Fractional Anisotropy on Diffusion Tensor Magnetic Resonance Imaging After Hypoxic-Ischemic Encephalopathy Phil Ward, Serena Counsell, Joanna Allsop, Frances Cowan, Yuji Shen, David Edwards and Mary Rutherford Pediatrics 2006;117;e619 ; originally published online March 1, 2006; DOI: 10.1542/peds.2005-0545

Department of Paediatrics, MRC Clinical Sciences Centre, Imperial College Faculty of Medicine, Hammersmith Hospital, London, England.
PEDIATRICS (Impact Factor: 5.47). 05/2006; 117(4):e619-30. DOI: 10.1542/peds.2005-0545
Source: PubMed


Apparent diffusion coefficients (ADC) that are measured by diffusion-weighted imaging are reduced in severe white matter (WM) and in some severe basal ganglia and thalamic (BGT) injury in infants who present with hypoxic-ischemic encephalopathy (HIE). However, ADC values may pseudonormalize or even be high during this time in some less severe but clinically significant injuries. We hypothesized that fractional anisotropy (FA), a measure of the directional diffusivity of water made using diffusion tensor imaging, may be abnormal in these less severe injuries; therefore, the objective of this study was to use diffusion tensor imaging to measure ADC and FA in infants with moderate and severe hypoxic-ischemic brain injury.
Twenty infants with HIE and 7 normal control infants were studied. All infants were born at >36 weeks' gestational age, and MRI scans were obtained within 3 weeks of delivery. Data were examined for normality, and comparisons were made using analysis of variance or Kruskal-Wallis as appropriate.
During the first week, FA values were decreased with both severe and moderate WM and BGT injury as assessed by conventional imaging, whereas ADC values were reduced only in severe WM injury and some severe BGT injury. Abnormal ADC values pseudonormalized during the second week, whereas FA values continued to decrease.
FA is reduced in moderate brain injury after HIE. A low FA may reflect a breakdown in WM organization. Moderate BGT injury may result in atrophy but not overt infarction; it is possible that delayed apoptosis is more marked than immediate necrosis, and this may account for normal early ADC values. The accompanying low FA within some severe and all moderate gray matter lesions, which is associated with significant later impairment, may help to confirm clinically significant abnormality in infants with normal ADC values.

Download full-text


Available from: David Edwards, Oct 12, 2015
52 Reads
  • Source
    • "We showed that global HI induced a marked loss of preOLs, which was paralleled by hypomyelination of the preterm brain. In line with clinical evidence [37], FA values obtained with diffusion tensor imaging (DTI) were decreased following global HI indicating HI-induced breakdown of white matter organization. Intravenous administration of MSC prevented the loss of preOLs after global HI and reduced histological white matter injury, which was confirmed with DTI. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Hypoxic-ischemic encephalopathy (HIE) in preterm infants is a severe disease for which no curative treatment is available. Cerebral inflammation and invasion of activated peripheral immune cells have been shown to play a pivotal role in the etiology of white matter injury, which is the clinical hallmark of HIE in preterm infants. The objective of this study was to assess the neuroprotective and anti-inflammatory effects of intravenously delivered mesenchymal stem cells (MSC) in an ovine model of HIE. In this translational animal model, global hypoxia-ischemia (HI) was induced in instrumented preterm sheep by transient umbilical cord occlusion, which closely mimics the clinical insult. Intravenous administration of 2 x 10(6) MSC/kg reduced microglial proliferation, diminished loss of oligodendrocytes and reduced demyelination, as determined by histology and Diffusion Tensor Imaging (DTI), in the preterm brain after global HI. These anti-inflammatory and neuroprotective effects of MSC were paralleled by reduced electrographic seizure activity in the ischemic preterm brain. Furthermore, we showed that MSC induced persistent peripheral T-cell tolerance in vivo and reduced invasion of T-cells into the preterm brain following global HI. These findings show in a preclinical animal model that intravenously administered MSC reduced cerebral inflammation, protected against white matter injury and established functional improvement in the preterm brain following global HI. Moreover, we provide evidence that induction of T-cell tolerance by MSC might play an important role in the neuroprotective effects of MSC in HIE. This is the first study to describe a marked neuroprotective effect of MSC in a translational animal model of HIE.
    PLoS ONE 08/2013; 8(8):e73031. DOI:10.1371/journal.pone.0073031 · 3.23 Impact Factor
  • Source
    • "AS patients did not present with mean and axial diffusivity abnormalities (except from the fornix). Moreover, hypoxia usually presents with cerebellar white matter abnormalities [20] that were not found in AS patients. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Alström Syndrome (AS) is a rare ciliopathy characterized by cone-rod retinal dystrophy, sensorineural hearing loss, obesity, type 2 diabetes mellitus and cardiomyopathy. Most patients do not present with neurological issues and demonstrate normal intelligence, although delayed psychomotor development and psychiatric disorders have been reported. To date, brain Magnetic Resonance Imaging (MRI) abnormalities in AS have not been explored. We investigated structural brain changes in 12 genetically proven AS patients (mean-age 22 years; range: 6-45, 6 females) and 19 matched healthy and positive controls (mean-age 23 years; range: 6-43; 12 females) using conventional MRI, Voxel-Based Morphometry (VBM) and Diffusion Tensor Imaging (DTI). 6/12 AS patients presented with brain abnormalities such as ventricular enlargement (4/12), periventricular white matter abnormalities (3/12) and lacune-like lesions (1/12); all patients older than 30 years had vascular-like lesions. VBM detected grey and white matter volume reduction in AS patients, especially in the posterior regions. DTI revealed significant fractional anisotropy decrease and radial diffusivity increase in the supratentorial white matter, also diffusely involving those regions that appeared normal on conventional imaging. On the contrary, axial and mean diffusivity did not differ from controls except in the fornix. Brain involvement in Alström syndrome is not uncommon. Early vascular-like lesions, gray and white matter atrophy, mostly involving the posterior regions, and diffuse supratentorial white matter derangement suggest a role of cilia in endothelial cell and oligodendrocyte function.
    Orphanet Journal of Rare Diseases 02/2013; 8(1):24. DOI:10.1186/1750-1172-8-24 · 3.36 Impact Factor
  • Source
    • "FA measures tissue organization, and can detect pathological tissue (Basser and Pierpaoli, 1996); the procedures do not differentiate the stage of tissue injury (Neil et al., 1998; Basser and Jones, 2002; Beaulieu, 2002). Axonal loss and demyelination are reflected by decreased FA values in chronic stages of tissue injury (Trip et al., 2006; Li et al., 2011), and both acute (Ward et al., 2006; Shereen et al., 2011) and subacute (between acute and chronic) stages after hypoxia are also associated with reduced FA values (Ward et al., 2006). However, MD procedures distinguish acute from chronic stages after hypoxia/ischemia, with decreased values in acute stages, values similar to those of normal conditions in subacute stages, and increased values in chronic stages (Matsumoto et al., 1995; Ahlhelm et al., 2002). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Obstructive sleep apnea (OSA) is a common and progressive disorder accompanied by severe cardiovascular and neuropsychological sequelae, presumably induced by brain injury resulting from the intermittent hypoxia and cardiovascular processes accompanying the syndrome. However, whether the predominant brain tissue pathology is acute or chronic in newly-diagnosed, untreated OSA subjects is unclear; this assessment is essential for revealing pathological processes. Diffusion tensor imaging (DTI)-based mean diffusivity (MD) procedures can detect and differentiate acute from chronic pathology and may be useful to reveal processes in the condition. We collected four DTI series from 23 newly-diagnosed, treatment-naïve OSA and 23 control subjects, using a 3.0-Tesla magnetic resonance imaging scanner. Mean diffusivity maps were calculated from each series, realigned, averaged, normalized to a common space, and smoothed. Global brain MD values for each subject were calculated using normalized MD maps and a global brain mask. Mean global brain MD values and smoothed MD maps were compared between groups by using analysis of covariance (covariate: age). Mean global brain MD values were significantly reduced in OSA compared with controls (P = 0.01). Multiple brain sites in OSA, including medullary, cerebellar, basal ganglia, prefrontal and frontal, limbic, insular, cingulum bundle, external capsule, corpus callosum, temporal, occipital, and corona radiata regions showed reduced regional MD values compared with controls. The results suggest that global brain MD values are significantly reduced in OSA, with certain regional sites especially affected, presumably a consequence of axonal, glial, and other cell changes in those areas. The findings likely represent acute pathological processes in newly-diagnosed OSA subjects.
    Journal of Neuroscience Research 10/2012; 90(10):2043-52. DOI:10.1002/jnr.23083 · 2.59 Impact Factor
Show more