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Early detection of neonatal hypoxic-ischemic white matter injury: an MR diffusion tensor imaging study.

ABSTRACT: The purpose of this study was to compare diffusion tensor metrics in normal age-matched neonates with survivors of hypoxic-ischemic encephalopathy (HIE) and extracorporeal membrane oxygenation (ECMO). Thirty-five normal, 27 HIE, and 13 ECMO infants underwent MRI at 3 T. Neurodevelopmental assessments were performed. Fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) of the inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, anterior commissure, genu corpus callosum and splenium of the corpus callosum, anterior and posterior limb of the internal capsule, superior longitudinal fasciculus, and the centrum semiovale were analyzed with tract-based spatial statistics modified for use in neonates. Linear regression analysis was performed, and 95% confidence intervals were created for age effects on the tensor metrics with the control patients. Two-sample t-test was done to determine whether there was a difference in the tensor metrics between the normal and patient cohort. There was a statistically significant age effect on the FA and RD in the selected regions of the brain (F<0.05) and a group difference in the FA and RD between the normal and the HIE group (P<0.05). The group difference in the FA and RD between the normal and ECMO groups was seen in the anterior commissure, genu corpus callosum, right inferior longitudinal fasciculus, fronto-occipital fasciculus, centrum semiovale, and superior longitudinal fasciculus (P<0.05). Patients who were outside the 95% confidence intervals of the FA, AD, and RD overlapped with those with abnormalities clinically and on the conventional MRI. In conclusion, diffusion tensor imaging can play a significant role in detecting infants with early indications of hypoxic-ischemic brain injury.

SUBMITTER: Seo Y

PROVIDER: S-EPMC5548514 | biostudies-other | 2017 Sep

REPOSITORIES: biostudies-other

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Project description:BackgroundReducing neuroinflammatory damage is an effective strategy for treating white-matter damage (WMD) in premature infants. Caffeine can ameliorate hypoxia-ischemia-induced brain WMD; however, its neuroprotective effect and mechanism against hypoxic-ischemic WMD remain unclear.MethodsWe used 3-day-old Sprague-Dawley rats to establish a model of cerebral hypoxia-ischemia-induced brain WMD after unilateral common carotid artery ligation and hypoxia exposure (8% O2 + 92% N2) for 2.5 h. Mechanism experiments were conducted to detect M1/M2 polarization and activation of microglia and NLRP3 inflammasome.ResultsCaffeine inhibited NLRP3 inflammasome activation, reduced microglial Iba-1 activation, inhibited microglia M1 polarization, and promoted microglia M2 polarization by downregulating CD86 and iNOS protein expression, inhibiting the transcription of the proinflammatory TNF-α and IL-1β, upregulating CD206 and Arg-1 expression, and promoting the transcription of the anti-inflammatory factors IL-10 and TGF-β. Importantly, we found that these caffeine-mediated effects could be reversed after inhibiting A2aR activity.ConclusionsCaffeine improved long-term cognitive function in neonatal rats with hypoxic-ischemic WMD via A2aR-mediated inhibition of NLRP3 inflammasome activation, reduction of microglial activation, regulation of the phenotypic polarization of microglia and the release of inflammatory factors, and improvement of myelination development.ImpactThe direct protective effect of caffeine on hypoxic-ischemic white-matter damage (WMD) and its mechanism remains unclear. This study elucidated this mechanism using neonatal rats as an animal model of hypoxia-ischemia-induced cerebral WMD. The findings demonstrated caffeine as a promising therapeutic tool against immature WMD to protect neonatal cognitive function. We found that caffeine pretreatment reduced WMD in immature brains via regulation of microglial activation and polarization by adenosine A2a receptor, thereby, providing a scientific basis for future clinical application of caffeine.

Project description:BackgroundThe progression of FLAIR white matter hyperintensities (WMHs) on MRI heralds vascular-mediated cognitive decline. Even before FLAIR WMH progression, adjacent normal appearing white matter (NAWM) already demonstrates microstructural deterioration on diffusion tensor imaging (DTI). We hypothesized that elevated DTI free water (FW) would precede FLAIR WMH progression, implicating interstitial fluid accumulation as a key pathological step in the progression of cerebral small vessel disease.MethodsParticipants at least 3 months after an ischemic stroke or TIA with WMH on MRI underwent serial brain MRIs every 3 months over the subsequent year. For each participant, the WMHs were automatically segmented, serial MRIs were aligned, and a region of WMH penumbra tissue at risk was defined by dilating lesions at any time point and subtracting baseline lesions. Penumbra voxels were classified as either stable or progressing to WMH if they were segmented as new lesions and demonstrated increasing FLAIR intensity over time. Aligned DTI images included FW and FW-corrected fractional anisotropy (FATissue) and mean diffusivity (MDTissue). Logistic regression and area under the receiver-operator characteristic curve (AUC) were used to test whether baseline DTI predicted voxel-wise classification of stable penumbra or progression to WMH while covarying for clinical risk factors.ResultsIn the included participants (n = 26, mean age 71 ± 9 years, 31% female), we detected a median annual voxel-wise WMH growth of 2.9 ± 2.6 ml. Each baseline DTI metric was associated with lesion progression in the penumbra, but FW had the greatest AUC of 0.732 (0.730 - 0.733) for predicting voxel-wise WMH progression pooled across participants.DiscussionBaseline increased interstitial fluid, estimated as FW on DTI, predicted the progression of NAWM to WMH over the following year. These results implicate the presence of FW in the pathogenesis of cerebral small vessel disease progression.

Project description:Hypoxic-ischemic encephalopathy (HIE) is the most common cause of neonatal acquired brain injury. Although conventional MRI may predict neurodevelopmental outcomes, accurate prognostication remains difficult. As diffusion tensor imaging (DTI) may provide an additional diagnostic and prognostic value over conventional MRI, we aimed to develop a composite DTI (cDTI) score to relate to short-term neurological function. Sixty prospective neonates treated with therapeutic hypothermia (TH) for HIE were evaluated with DTI, with a voxel size of 1 × 1 × 2 mm. Fractional anisotropy (FA) and mean diffusivity (MD) from 100 neuroanatomical regions (FA/MD *100 = 200 DTI parameters in total) were quantified using an atlas-based image parcellation technique. A least absolute shrinkage and selection operator (LASSO) regression was applied to the DTI parameters to generate the cDTI score. Time to full oral nutrition [short-term oral feeding (STO) score] was used as a measure of short-term neurological function and was correlated with extracted DTI features. Seventeen DTI parameters were selected with LASSO and built into the final unbiased regression model. The selected factors included FA or MD values of the limbic structures, the corticospinal tract, and the frontotemporal cortices. While the cDTI score strongly correlated with the STO score (rho = 0.83, p = 2.8 × 10-16), it only weakly correlated with the Sarnat score (rho = 0.27, p = 0.035) and moderately with the NICHD-NRN neuroimaging score (rho = 0.43, p = 6.6 × 10-04). In contrast to the cDTI score, the NICHD-NRN score only moderately correlated with the STO score (rho = 0.37, p = 0.0037). Using a mixed-model analysis, interleukin-10 at admission to the NICU (p = 1.5 × 10-13) and tau protein at the end of TH/rewarming (p = 0.036) and after rewarming (p = 0.0015) were significantly associated with higher cDTI scores, suggesting that high cDTI scores were related to the intensity of the early inflammatory response and the severity of neuronal impairment after TH. In conclusion, a data-driven unbiased approach was applied to identify anatomical structures associated with some aspects of neurological function of HIE neonates after cooling and to build a cDTI score, which was correlated with the severity of short-term neurological functions.

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Early detection of neonatal hypoxic-ischemic white matter injury: an MR diffusion tensor imaging study.

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