Diffusion Tensor Imaging Predicts Long-Term Motor Functional Outcome in Patients with Acute Supratentorial Intracranial Hemorrhage

Background: Neonatal white matter injury (NWMI) is the leading cause of cerebral palsy in prematurely born children. In order to develop a test bed for therapeutics, we recently reported a mouse model of NWMI by using a modified Rice-Vannucci model of neonatal ischemia on postnatal day 5 (P5) in CD-1 mice. We have previously shown that these mice illustrate initial neuroinflammation and oligodendroglial differentiation arrest followed by long-term dysmyelination, periventricular astrogliosis and axonal injury, resembling human NWMI. The objective of this study was to determine the sex-dependent long-term effects of neonatal brain injury on neurobehavioral and advanced in vivo neuroimaging indices in this mouse model, and to correlate these variables with histopathology. Methods: After right common artery ligation on P5, in vivo T2-weighted imaging and diffusion tensor imaging (DTI) were performed on ligated and control animals at 4 and 8 weeks. Common sets of regions of interest were used to compare fractional anisotropy (FA) values between ischemic and control mice. Behavioral testing (open field, startle response and grip strength) was performed at adult age. Finally, the animals were sacrificed for immunohistochemical (IHC) assessment of major white matter tracts. Results: DTI revealed significant sex-dependent changes in FA values ipsi- and contralateral to the ligation. Behavioral testing showed decreased reaction to acoustic stimuli in males but not females. Similarly, increased number of rearings and lack of novelty-induced habituation in the open field were encountered only in the male subgroup. Several regional correlations were found between FA values and these behavioral alterations. IHC studies revealed degeneration of mature oligodendrocytes and damage of white matter tracts in ligated animals, as previously reported in this model, and showed regional correlation with in vivo FA values and behavioral alterations. Conclusions: Our findings suggest structural sex-dependent long-term abnormalities after neonatal ischemia. These changes lead to behavioral deficits resembling common problems of patients with cerebral palsy.

Download Full-text

White matter microstructure predicts longitudinal social cognitive outcomes after paediatric traumatic brain injury: a diffusion tensor imaging study

Psychological Medicine ◽

10.1017/s0033291717002057 ◽

2017 ◽

Vol 48 (4) ◽

pp. 679-691 ◽

Cited By ~ 21

Author(s):

N. P. Ryan ◽

S. Genc ◽

M. H. Beauchamp ◽

K. O. Yeates ◽

S. Hearps ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Diffusion Tensor Imaging ◽

White Matter ◽

Social Cognitive ◽

Diffusion Tensor ◽

Cognitive Outcomes ◽

Pragmatic Language ◽

Post Injury ◽

White Matter Microstructure

BackgroundDeficits in social cognition may be among the most profound and disabling sequelae of paediatric traumatic brain injury (TBI); however, the neuroanatomical correlates of longitudinal outcomes in this domain remain unexplored. This study aimed to characterize social cognitive outcomes longitudinally after paediatric TBI, and to evaluate the use of sub-acute diffusion tensor imaging (DTI) to predict these outcomes.MethodsThe sample included 52 children with mild complex-severe TBI who were assessed on cognitive theory of mind (ToM), pragmatic language and affective ToM at 6- and 24-months post-injury. For comparison, 43 typically developing controls (TDCs) of similar age and sex were recruited. DTI data were acquired sub-acutely (mean = 5.5 weeks post-injury) in a subset of 65 children (TBI = 35; TDC = 30) to evaluate longitudinal prospective relationships between white matter microstructure assessed using Tract-Based Spatial Statistics and social cognitive outcomes.ResultsWhole brain voxel-wise analysis revealed significantly higher mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) in the sub-acute TBI group compared with TDC, with differences observed predominantly in the splenium of the corpus callosum (sCC), sagittal stratum (SS), dorsal cingulum (DC), uncinate fasciculus (UF) and middle and superior cerebellar peduncles (MCP & SCP, respectively). Relative to TDCs, children with TBI showed poorer cognitive ToM, affective ToM and pragmatic language at 6-months post-insult, and those deficits were related to abnormal diffusivity of the sCC, SS, DC, UF, MCP and SCP. Moreover, children with TBI showed poorer affective ToM and pragmatic language at 24-months post-injury, and those outcomes were predicted by sub-acute alterations in diffusivity of the DC and MCP.ConclusionsAbnormal microstructure within frontal-temporal, limbic and cerebro-cerebellar white matter may be a risk factor for long-term social difficulties observed in children with TBI. DTI may have potential to unlock early prognostic markers of long-term social outcomes.

Download Full-text

Diffusion Tensor Imaging Changes Do Not Affect Long-Term Neurodevelopment Following Early Erythropoietin Among Extremely Preterm Infants in the Preterm Erythropoietin Neuroprotection Trial

Brain Sciences ◽

10.3390/brainsci11101360 ◽

2021 ◽

Vol 11 (10) ◽

pp. 1360

Author(s):

Janessa B. Law ◽

Bryan A. Comstock ◽

Todd L. Richards ◽

Christopher M. Traudt ◽

Thomas R. Wood ◽

...

Keyword(s):

Diffusion Tensor Imaging ◽

White Matter ◽

Linear Models ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Neurodevelopmental Outcomes ◽

Extremely Preterm ◽

Extremely Preterm Infants ◽

Postmenstrual Age

We aimed to evaluate diffusion tensor imaging (DTI) in infants born extremely preterm, to determine the effect of erythropoietin (Epo) on DTI, and to correlate DTI with neurodevelopmental outcomes at 2 years of age for infants in the Preterm Erythropoietin Neuroprotection (PENUT) Trial. Infants who underwent MRI with DTI at 36 weeks postmenstrual age were included. Neurodevelopmental outcomes were evaluated by Bayley Scales of Infant and Toddler Development (BSID-III). Generalized linear models were used to assess the association between DTI parameters and treatment group, and then with neurodevelopmental outcomes. A total of 101 placebo- and 93 Epo-treated infants underwent MRI. DTI white matter mean diffusivity (MD) was lower in placebo- compared to Epo-treated infants in the cingulate and occipital regions, and occipital white matter fractional isotropy (FA) was lower in infants born at 24–25 weeks vs. 26–27 weeks. These values were not associated with lower BSID-III scores. Certain decreases in clustering coefficients tended to have lower BSID-III scores. Consistent with the PENUT Trial findings, there was no effect on long-term neurodevelopment in Epo-treated infants even in the presence of microstructural changes identified by DTI.

Download Full-text

The role of preoperative diffusion tensor imaging in predicting and improving functional outcome in pediatric patients undergoing epilepsy surgery: a systematic review

BJR|Open ◽

10.1259/bjro.20200002 ◽

2021 ◽

Vol 3 (1) ◽

pp. 20200002

Author(s):

Jose Leon-Rojas ◽

Isabel Cornell ◽

Antonio Rojas-Garcia ◽

Felice D’Arco ◽

Jasmina Panovska-Griffiths ◽

...

Keyword(s):

Systematic Review ◽

Diffusion Tensor Imaging ◽

Functional Outcome ◽

Epilepsy Surgery ◽

Outcome Prediction ◽

Pediatric Patients ◽

Diffusion Tensor ◽

Pediatric Epilepsy ◽

Motor Outcome

Objective: Diffusion tensor imaging (DTI) is a useful neuroimaging technique for surgical planning in adult patients. However, no systematic review has been conducted to determine its utility for pre-operative analysis and planning of Pediatric Epilepsy surgery. We sought to determine the benefit of pre-operative DTI in predicting and improving neurological functional outcome after epilepsy surgery in children with intractable epilepsy. Methods: A systematic review of articles in English using PubMed, EMBASE and Scopus databases, from inception to January 10, 2020 was conducted. All studies that used DTI as either predictor or direct influencer of functional neurological outcome (motor, sensory, language and/or visual) in pediatric epilepsy surgical candidates were included. Data extraction was performed by two blinded reviewers. Risk of bias of each study was determined using the QUADAS 2 Scoring System. Results: 13 studies were included (6 case reports/series, 5 retrospective cohorts, and 2 prospective cohorts) with a total of 229 patients. Seven studies reported motor outcome; three reported motor outcome prediction with a sensitivity and specificity ranging from 80 to 85.7 and 69.6 to 100%, respectively; four studies reported visual outcome. In general, the use of DTI was associated with a high degree of favorable neurological outcomes after epilepsy surgery. Conclusion: Multiple studies show that DTI helps to create a tailored plan that results in improved functional outcome. However, more studies are required in order to fully assess its utility in pediatric patients. This is a desirable field of study because DTI offers a non-invasive technique more suitable for children. Advances in knowledge: This systematic review analyses, exclusively, studies of pediatric patients with drug-resistant epilepsy and provides an update of the evidence regarding the role of DTI, as part of the pre-operative armamentarium, in improving post-surgical neurological sequels and its potential for outcome prediction.

Download Full-text