Detection Of White Matter Injury Research Articles

Quantification of brain-wide vascular resistivity via ultrafast Doppler in human neonates helps early detection of white matter injury

Preterm birth is associated with cerebrovascular development disruption and can induce white matter injuries (WMI). Transfontanellar ultrasound Doppler is the most widely used clinical imaging technique to monitor neonatal cerebral vascularisation and haemodynamics based on vascular indexes such as the resistivity index (RI); however, it has poor predictive value for brain damage. Indeed, these RI measurements are currently limited to large vessels, leading to a very limited probing of the brain’s vascularisation, which may hinder prognosis. Here we show that ultrafast Doppler imaging (UfD) enables simultaneous quantification, in the whole field of view, of the local RI and vessel diameter, even in small vessels. Combining both pieces of information, we defined two new comprehensive resistivity parameters of the vascular trees. First, we showed that our technique is more sensitive in the early characterisation of the RI modifications between term and preterm neonates and for the first time we could show that the RI depends both on the vessel diameter and vascular territory. We then showed that our parameters can be used for early prediction of WMI. Our results demonstrate the potential of UfD to provide new biomarkers and pave the way for continuous monitoring of neonatal brain resistivity.

Replicability of proton MR spectroscopic imaging findings in mild traumatic brain injury: Implications for clinical applications

PurposeProton magnetic resonance spectroscopy (1H MRS) offers biomarkers of metabolic damage after mild traumatic brain injury (mTBI), but a lack of replicability studies hampers clinical translation. In a conceptual replication study design, the results reported in four previous publications were used as the hypotheses (H1-H7), specifically: abnormalities in patients are diffuse (H1), confined to white matter (WM) (H2), comprise low N-acetyl-aspartate (NAA) levels and normal choline (Cho), creatine (Cr) and myo-inositol (mI) (H3), and correlate with clinical outcome (H4); additionally, a lack of findings in regional subcortical WM (H5) and deep gray matter (GM) structures (H6), except for higher mI in patients’ putamen (H7). Methods26 mTBI patients (20 female, age 36.5 ± 12.5 [mean ± standard deviation] years), within two months from injury and 21 age-, sex-, and education-matched healthy controls were scanned at 3 Tesla with 3D echo-planar spectroscopic imaging. To test H1-H3, global analysis using linear regression was used to obtain metabolite levels of GM and WM in each brain lobe. For H4, patients were stratified into non-recovered and recovered subgroups using the Glasgow Outcome Scale Extended. To test H5-H7, regional analysis using spectral averaging estimated metabolite levels in four GM and six WM structures segmented from T1-weighted MRI. The Mann-Whitney U test and weighted least squares analysis of covariance were used to examine mean group differences in metabolite levels between all patients and all controls (H1-H3, H5-H7), and between recovered and non-recovered patients and their respectively matched controls (H4). Replicability was defined as the support or failure to support the null hypotheses in accordance with the content of H1-H7, and was further evaluated using percent differences, coefficients of variation, and effect size (Cohen’s d). ResultsPatients’ occipital lobe WM Cho and Cr levels were 6.0% and 4.6% higher than controls’, respectively (Cho, d = 0.37, p = 0.04; Cr, d = 0.63, p = 0.03). The same findings, i.e., higher patients’ occipital lobe WM Cho and Cr (both p = 0.01), but with larger percent differences (Cho, 8.6%; Cr, 6.3%) and effect sizes (Cho, d = 0.52; Cr, d = 0.88) were found in the comparison of non-recovered patients to their matched controls. For the lobar WM Cho and Cr comparisons without statistical significance (frontal, parietal, temporal), unidirectional effect sizes were observed (Cho, d = 0.07 – 0.37; Cr, d = 0.27 – 0.63). No differences were found in any metabolite in any lobe in the comparison between recovered patients and their matched controls. In the regional analyses, no differences in metabolite levels were found in any GM or WM region, but all WM regions (posterior, frontal, corona radiata, and the genu, body, and splenium of the corpus callosum) exhibited unidirectional effect sizes for Cho and Cr (Cho, d = 0.03 – 0.34; Cr, d = 0.16 – 0.51). ConclusionsWe replicated findings of diffuse WM injury, which correlated with clinical outcome (supporting H1-H2, H4). These findings, however, were among the glial markers Cho and Cr, not the neuronal marker NAA (not supporting H3). No differences were found in regional GM and WM metabolite levels (supporting H5-H6), nor in putaminal mI (not supporting H7). Unidirectional effect sizes of higher patients’ Cho and Cr within all WM analyses suggest widespread injury, and are in line with the conclusion from the previous publications, i.e., that detection of WM injury may be more dependent upon sensitivity of the 1H MRS technique than on the selection of specific regions. The findings lend further support to the corollary that clinic-ready 1H MRS biomarkers for mTBI may best be achieved by using high signal-to-noise-ratio single-voxels placed anywhere within WM. The biochemical signature of the injury, however, may differ and therefore absolute levels, rather than ratios may be preferred. Future replication efforts should further test the generalizability of these findings.

Demystifying White Matter Injury in the Unconscious Patients with Diffusion Tensor Imaging.

Background:Diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) provide a noninvasive window to study the neural connectivity and reconstruct the tracts. Detection of white matter injury (WMI) by DTT is a recent application being used in stroke, diffuse axonal injury, and neurodegenerative disorders. Fiber tracking in patients with brain hemorrhage can detect loss of fibers and anatomical disruption of the tracts, which can be useful in the prognostication of patient outcome.Materials and Methods:DTI and fiber tracking was done in four patients admitted at Fujita Health University Banbuntane Hospital, Japan, with decreased consciousness following brain hemorrhage (3 patients with aneurysmal subarachnoid hemorrhage and one patient with bifrontal hemorrhage), and WMI was analyzed. We also reviewed the literature on tractography in patients with brain hemorrhage and its correlation with consciousness.Results:We found significant frontal WMI in the form of thinning and anatomical disruption in all four cases. The frontal white matter tracts form an important component of the limbic system and ascending reticular activating system and frontal WMI correlated with the poor conscious level and cognitive dysfunction. Structural damage to the fiber tracts demonstrated as thinning, reduction in the volume or absence on tractography with corresponding reduction in the mean fractional anisotropy values in the frontal white matter of the affected side.Conclusion:DTI can be useful as a critical tool for revealing the anatomical basis for the cognitive dysfunction and unconsciousness and can be possibly used to prognosticate patient recovery. Early detection of WMI by DTI can also help in tailored rehabilitation. The authors believe that DTT could have a crucial role in the future for detecting structural changes which lead to cognitive dysfunction and further studies are needed to arrive at a specific protocol for detecting WMI.

Can diffusion tensor imaging predict cerebral palsy in term neonates with hypoxic ischemic encephalopathy?

BackgroundHypoxic ischemic encephalopathy (HIE) is a principal cause of pediatric mortality and morbidity, with possible neurologic sequel, such as cerebral palsy. Thus, it is of outmost importance to assess, shortly after birth, the prognosis of neonates with HIE. The purpose of this study was to assess the role of diffusion tensor imaging (DTI) in early prediction of cerebral palsy in term neonates with HIE. The study was carried out initially on 35 full-term neonates admitted to the neonatal intensive care unit (NICU) with manifestations of HIE. Imaging was done at the age of 10.32 ± 1.78 days including conventional MRI and DTI (for detection of white matter injury). Thirty-three infants out of the initially examined 35 were finally evaluated at the age of 1 year with the Bayley Scales of Infant and Toddler Development 3rd edition for development of cerebral palsy. Another MRI brain study was done at 1 year of age to evaluate the final brain imaging features and assess white matter integrity.ResultsSeventeen infants (17/33) were clinically normal while 16 (16/33) acquired cerebral palsy (CP) by the end of the first year. Initial conventional MRI showed false-negative results in 7 patients. Diffusion tensor imaging showed significantly different reduction in fractional anisotropy within the examined brain regions of interest (ROIs) between CP and normal outcome infants mostly at the posterior limb of the internal capsule, centrum semiovale, and corpus callosum with significant cutoff values of ≤ 0.435, ≤ 0.235, and ≤ 0.45, respectively.ConclusionsDiffusion tensor imaging is a valuable tool for early prediction of CP in HIE neonates.

Brain imaging in preterm infants

The aim is to review the evidence about the utility of term-equivalent age (TEA) magnetic resonance imaging (MRI) in predicting neurodevelopmental outcomes for preterm neonates. Preterm birth accounts for ~12% of all deliveries in the United States and is the leading cause of neurologic disabilities in children. From the neonatologist perspective, it is critically important to identify preterm infants at risk of subsequent neurodevelopmental disability who may benefit from early intervention services. However "the choose wisely campaign" also emphasizes the need to have ongoing cost/benefit discussions regarding care of preterm newborns to avoid waste that comes from subjecting infants to procedures that do not help. We performed a MEDLINE EMBASE database review from 2000 to 2018 to account for the technical evolution in the cranial ultrasound machines and introduction of MRI imaging in the NICU. Studies were graded based on the strength of their design using the GRADE guidelines and summarized with respect to brain MRI vs. cranial US (1) detection of white matter injury; (2) cerebellar hemorrhage; (3) long-term neurodevelopmental outcomes and impact on parental anxiety. We conclude with a hospital-specific guideline algorithm for performing TEA MRI based on risk evaluations ≤32 weeks.

Abstract 13741: Neurologic Injury and Cerebral Blood Flow In Single Ventricles Throughout Staged Surgical Reconstruction

Introduction: Single ventricle pts experience a high rate of brain injury and adverse neurodevelopmental outcome. Hypothesis: The incidence of brain abnormalities is different at various surgical stages and is linked with cerebral blood flow (CBF), oxygen delivery and carbon dioxide reactivity. Methods: Single ventricle pts were studied with MRI scans immediately prior to bidirectional Glenn (pre-BDG), prior to Fontan and then 3-9 months after Fontan reconstruction. Results: 168 consecutive subjects recruited into the project underwent 235 scans: 63 pre-BDG (4.8±1.7 months), 118 BDG (2.9±1.4 years) and 54 after Fontan (3.4±1.1 years). Non-acute ischemic white matter changes on T2 weighted imaging, focal tissue loss, punctate microbleeds and ventriculomegaly were all more commonly detected in BDG and Fontans compared to pre-BDG (see figure); punctate microbleeds were also more common in Fontan than pre-BDG (P<0.05). CBF was higher in BDG than Fontan and almost reached statistical significance versus pre-BDG (see graph). The odds of discovering brain injury adjusting for surgical stage as well as 2 or more co-existing lesions within a patient all decreased (63-97% and 44% respectively) with increasing amount of CBF (P<0.05). In general, there was no association of oxygen delivery or carbon dioxide reactivity with neurological injury. Conclusion: Significant brain abnormalities are commonly present in single ventricle pts and detection of these lesions increase as children progress through staged surgical reconstruction with multiple co-existing lesions more common earlier than later. Cumulative exposures to surgery may account for increased incidence, though changes in brain maturation may increase detection of white matter injury. In addition, an inverse association of various indices of CBF with these brain lesions is present (CBF highest in BDG stage), however, CO 2 reactivity, oxygen delivery were not associated with brain lesion development.

Detection of white matter injury in concussion using high-definition fiber tractography.

Over the last few decades, structural imaging techniques of the human brain have undergone significant strides. High resolution provided by recent developments in magnetic resonance imaging (MRI) allows improved detection of injured regions in patients with moderate-to-severe traumatic brain injury (TBI). In addition, diffusion imaging techniques such as diffusion tensor imaging (DTI) has gained much interest recently due to its possible utility in detecting structural integrity of white matter pathways in mild TBI (mTBI) cases. However, the results from recent DTI studies in mTBI patients remain equivocal. Also, there are important shortcomings for DTI such as limited resolution in areas of multiple crossings and false tract formation. The detection of white matter damage in concussion remains challenging, and development of imaging biomarkers for mTBI is still in great need. In this chapter, we discuss our experience with high-definition fiber tracking (HDFT), a diffusion spectrum imaging-based technique. We also discuss ongoing developments and specific advantages HDFT may offer concussion patients.

Ultrasound detection of white matter injury in very preterm neonates: practical implications

Diffuse white matter injury is not well detected by cranial ultrasonography (CUS). The aim of this study was twofold: (1) to assess in very preterm neonates the predictive values of individual CUS abnormalities for white matter injury on MRI and neurological outcome; (2) to develop a strategy optimizing CUS detection of white matter injury. Very preterm neonates (n=67; 44 males, 23 females) underwent serial CUS and single MRI. Predictive values of CUS findings for a white matter classification on MRI, individual MRI findings, and neurological outcome at 2 years corrected age were calculated. The effects of timing and frequency of CUS were evaluated. Periventricular echodensities (PVEs) predicted abnormal white matter on MRI, but absence of PVEs did not predict absence of white matter changes. Peri- and intraventricular haemorrhage (P/IVH) was highly predictive of abnormal white matter on MRI. Frequency and timing of CUS did not influence predictive values. P/IVH and abnormal ventricular size/shape were reasonably predictive of unfavourable outcome, whereas absence of CUS abnormalities predicted a favorable outcome. (1) If PVEs are present, there is a significant chance of abnormal white matter on MRI. (2) Increasing frequency of CUS does not increase its diagnostic performance for white matter injury. (3) P/IVH is highly predictive of abnormal white matter on MRI and reasonably predictive of unfavourable outcome. (4) Absence of PVEs and P/IVH on CUS does not guarantee normal white matter, but predicts a favourable outcome.

Is sequential cranial ultrasound reliable for detection of white matter injury in very preterm infants?

IntroductionCranial ultrasound (cUS) may not be reliable for detection of diffuse white matter (WM) injury. Our aim was to assess in very preterm infants the reliability of a classification system for WM injury on sequential cUS throughout the neonatal period, using magnetic resonance imaging (MRI) as reference standard.MethodsIn 110 very preterm infants (gestational age <32 weeks), serial cUS during admission (median 8, range 4–22) and again around term equivalent age (TEA) and a single MRI around TEA were performed. cUS during admission were assessed for presence of WM changes, and contemporaneous cUS and MRI around TEA additionally for abnormality of lateral ventricles. Sequential cUS (from birth up to TEA) and MRI were classified as normal/mildly abnormal, moderately abnormal, or severely abnormal, based on a combination of findings of the WM and lateral ventricles. Predictive values of the cUS classification were calculated.ResultsSequential cUS were classified as normal/mildly abnormal, moderately abnormal, and severely abnormal in, respectively, 22%, 65%, and 13% of infants and MRI in, respectively, 30%, 52%, and 18%. The positive predictive value of the cUS classification for the MRI classification was high for severely abnormal WM (0.79) but lower for normal/mildly abnormal (0.67) and moderately abnormal (0.64) WM.ConclusionSequential cUS during the neonatal period detects severely abnormal WM in very preterm infants but is less reliable for mildly and moderately abnormal WM. MRI around TEA seems needed to reliably detect WM injury in very preterm infants.

Transport, monitoring, and successful brain MR imaging in unsedated neonates

Neonatal cerebral MR imaging is a sensitive technique for evaluating brain injury in the term and preterm infant. In term encephalopathic infants, MR imaging reliably detects not only the pattern of brain injury but might also provide clues about the timing of injury. In premature infants, MR imaging has surpassed US in the detection of white matter injury, a common lesion in this population. Concerns remain about the safety and transport of sedated neonates for MR examination to radiology suites, which are usually located at a distance from neonatal intensive care units. We present our own institutional experience and guidelines used to optimize the performance of cerebral MR examinations in neonates without sedation or anesthesia.

Systemic endotoxin administration results in increased S100B protein blood levels and periventricular brain white matter injury in the preterm fetal sheep

Objective Intrauterine infection is suggested to cause perinatal brain white matter injury. The aim of the present study was to clarify, whether intravenous application of endotoxin results in neuropathological findings and increased blood levels of the S100B protein, which is a consolidated marker of brain injury. Methods Twenty-one fetal sheep were chronically catheterized at a mean gestational age of 107 ± 1 days (0.7 of gestation). Three days after surgery fetuses received either 100 ( n = 9), 500 ( n = 5) or 2500 ng ( n = 1) lipopolysaccharide (LPS; E. coli; O127:B8, Sigma–Aldrich) or 2 ml 0.9% saline ( n = 6) i.v. S100B protein blood levels were assessed before during and after LPS or placebo administration. Brain damage was evaluated by light microscopy. Selected areas of the periventricular white matter were also examined by electron microscopy. Results Histopathological screening revealed no evidence for cortical neuronal cell damage in both groups. However, LPS treatment resulted in inflammatory infiltrates in all animals and cystic lesions in the periventricular brain white matter in two fetuses. On electron micrographs, infiltrate forming cells appeared to be activated microglia. S100B protein blood levels were significantly higher in the LPS group at 1 h ( p < 0.01) after LPS injection, peaking at 3 h ( p < 0.001) and returning to baseline between 12 and 72 h. Conclusion Intravenous application of endotoxin caused focal periventricular brain white matter injury, inflammation and an increase in S100B protein release. It is suggested that longitudinal investigations of S100B protein blood levels offer a tool for the early detection of white matter injury.