Juliane Schneider

Evolution of T1 Relaxation, ADC, and Fractional Anisotropy during Early Brain Maturation: A Serial Imaging Study on Preterm Infants

BACKGROUND AND PURPOSE: The alteration of brain maturation in preterm infants contributes to neurodevelopmental disabilities during childhood. Serial imaging allows understanding of the mechanisms leading to dysmaturation in the preterm brain. The purpose of the present study was to provide reference quantitative MR imaging measures across time in preterm infants, by using ADC, fractional anisotropy, and T1 maps obtained by using the magnetization-prepared dual rapid acquisition of gradient echo technique. MATERIALS AND METHODS: We included preterm neonates born at <30 weeks of gestational age without major brain lesions on early cranial sonography and performed 3 MRIs (3T) from birth to term-equivalent age. Multiple measurements (ADC, fractional anisotropy, and T1 relaxation) were performed on each examination in 12 defined white and gray matter ROIs. RESULTS: We acquired 107 MRIs (35 early, 33 intermediary, and 39 at term-equivalent age) in 39 cerebral low-risk preterm infants. Measures of T1 relaxation time showed a gradual and significant decrease with time in a region- and hemispheric-specific manner. ADC values showed a similar decline with time, but with more variability than T1 relaxation. An increase of fractional anisotropy values was observed in WM regions and inversely a decrease in the cortex. CONCLUSIONS: The gradual change with time reflects the progressive maturation of the cerebral microstructure in white and gray matter. Our study provides reference trajectories from 25 to 40 weeks of gestation of T1 relaxation, ADC, and fractional anisotropy values in low-risk preterm infants. We speculate that deviation thereof might reflect disturbed cerebral maturation; the correlation of this disturbed maturation with neurodevelopmental outcome remains to be addressed.

Exploring the role of white matter connectivity in cortex maturation

The maturation of the cortical gray matter (GM) and white matter (WM) are described as sequential processes following multiple, but distinct rules. However, neither the mechanisms driving brain maturation processes, nor the relationship between GM and WM maturation are well understood. Here we use connectomics and two MRI measures reflecting maturation related changes in cerebral microstructure, namely the Apparent Diffusion Coefficient (ADC) and the T1 relaxation time (T1), to study brain development. We report that the advancement of GM and WM maturation are inter-related and depend on the underlying brain connectivity architecture. Particularly, GM regions and their incident WM connections show corresponding maturation levels, which is also observed for GM regions connected through a WM tract. Based on these observations, we propose a simple computational model supporting a key role for the connectome in propagating maturation signals sequentially from external stimuli, through primary sensory structures to higher order functional cortices.

Impact of Early Nutritional Intake on Preterm Brain: A Magnetic Resonance Imaging Study

Objectives To investigate the association between early nutritional intake and brain development assessed by magnetic resonance imaging (MRI). Study design A cohort of neonates born at ≤30 weeks gestational age underwent MRI at term equivalent age. Brain maturation and injury were assessed using the Kidokoro score. Two groups were defined by severity of the scores. The associations between macronutrients intake during the first 2 weeks of life, clinical factors, and imaging scores were analyzed using logistic regression. Results MRI scores from group 1 patients (n = 27) were normal to mildly abnormal (0‐5). Group 2 (n = 15) had more abnormal scores (6‐12). The median gestational ages (IQR) were 27.4 (1.9) weeks in group 1 and 27.0 (2.9) weeks in group 2, with birth weights of 900 (318) g (group 1) and 844 (293) g (group 2). In group 2, energy, lipid, and carbohydrate intake were significantly lower than in group 1. Group 2 also showed higher rates of sepsis and clinical risk scores than group 1. After adjustments in bivariate models, higher energy and lipid intake remained significantly associated with improved scores on MRI. This association was stronger for the gray matter component of the score. Conclusions Higher energy and lipid intake during the first 2 weeks after birth was associated with a lower incidence of brain lesions and dysmaturation at term equivalent age in preterm neonates.

No Impact of Body Mass Index on Outcome in Stroke Patients Treated with IV Thrombolysis BMI and IV Thrombolysis Outcome

Background and Purpose The impact of excess body weight on prognosis after stroke is controversial. Many studies report higher survival rates in obese patients (“obesity paradox”). Recently, obesity has been linked to worse outcomes after intravenous (IV) thrombolysis, but the number and sample size of these studies were small. Here, we aimed to assess the relationship between body weight and stroke outcome after IV thrombolysis in a large cohort study. Methods In a prospective observational multicenter study, we analyzed baseline and outcome data of 896 ischemic stroke patients who underwent IV thrombolysis. Patients were categorized according to body mass index (BMI) as underweight (<18.5 kg/m2), normal weight (18.5–24.9 kg/m2), overweight (25–29.9 kg/m2), obese (30–34.9 kg/m2) or severely obese (>35 kg/m2). Using uni- and multivariate modeling, we assessed the relationship of BMI with favorable outcome (defined as modified Rankin Scale 0 or 1) and mortality 3 months after stroke as well as the occurrence of symptomatic intracerebral hemorrhages (sICH). We also measured the incidence of patients that had an early neurological improvement of >40% on the National Institutes of Health Stroke Scale (NIHSS) after 24 hours. Results Among 896 patients, 321 were normal weight (35.8%), 22 underweight (2.5%), 378 overweight (42.2%), 123 obese (13.7%) and 52 severely obese (5.8%). Three-month mortality was comparable in obese vs. non-obese patients (8.1% vs. 8.3%) and did not differ significantly among different BMI groups. This was also true for favorable clinical outcome, risk of sICH and early neurological improvement on NIHSS at 24 hours. These results remained unchanged after adjusting for potential confounding factors in the multivariate analyses. Conclusion BMI was not related to clinical outcomes in stroke patients treated with IVT. Our data suggest that the current weight-adapted dosage scheme of IV alteplase is appropriate for different body weight groups, and challenge the existence of the obesity paradox after stroke.

Nutrient Intake in the First Two Weeks of Life and Brain Growth in Preterm Neonates

In this preterm cohort study, we investigate the relationship between early macronutrient intake and brain macro- and microstructural growth, the influence of neonatal morbidity, and subsequent neurodevelopment. BACKGROUND: Optimizing early nutritional intake in preterm neonates may promote brain health and neurodevelopment through enhanced brain maturation. Our objectives were (1) to determine the association of energy and macronutrient intake in the first 2 weeks of life with regional and total brain growth and white matter (WM) maturation, assessed by 3 serial MRI scans in preterm neonates; (2) to examine how critical illness modifies this association; and (3) to investigate the relationship with neurodevelopmental outcomes. METHODS: Forty-nine preterm neonates (21 boys, median [interquartile range] gestational age: 27.6 [2.3] weeks) were scanned serially at the following median postmenstrual weeks: 29.4, 31.7, and 41. The total brain, basal nuclei, and cerebellum were semiautomatically segmented. Fractional anisotropy was extracted from diffusion tensor imaging data. Nutritional intake from day of life 1 to 14 was monitored and clinical factors were collected. RESULTS: Greater energy and lipid intake predicted increased total brain and basal nuclei volumes over the course of neonatal care to term-equivalent age. Similarly, energy and lipid intake were significantly associated with fractional anisotropy values in selected WM tracts. The association of ventilation duration with smaller brain volumes was attenuated by higher energy intake. Brain growth predicted psychomotor outcome at 18 months’ corrected age. CONCLUSIONS: In preterm neonates, greater energy and enteral feeding during the first 2 weeks of life predicted more robust brain growth and accelerated WM maturation. The long-lasting effect of early nutrition on neurodevelopment may be mediated by enhanced brain growth. Optimizing nutrition in preterm neonates may represent a potential avenue to mitigate the adverse brain health consequences of critical illness.

Ultrasound and Clinical Predictors of Recurrent Ischemia in Symptomatic Internal Carotid Artery Occlusion

Background and Purpose— Occlusion of the internal carotid artery puts patients at risk of recurrent ischemic events because of hemodynamic compromise. Our goal was to characterize clinical and duplex parameters indicating patients at risk of recurrent ischemia. Methods— We retrospectively identified patients with symptomatic internal carotid artery occlusion. Clinical characteristics and ultrasound parameters, including collateral networks, were analyzed. Predictors for recurrent ipsilateral ischemia were investigated by Cox regression analysis. Results— Of 68 patients, at least 1 recurrent ischemic event within the same vascular territory was observed in 14 patients (20.6%) within 2 to 92 days (median, 29.5 days). The median follow-up period was 6 months. Diabetes mellitus and previous transient ischemic attack were associated with recurrence, as was activation of the maximum number of collateral pathways on transcranial ultrasound (28.6% versus 5.6%; P=0.03). Furthermore, flow in the posterior cerebral arteries was higher in patients with recurrence in ipsilateral and contralateral posterior cerebral artery P2 segments (76 IQR 37.5 versus 59, IQR 22.5 cm/s and 68, IQR 35.6 versus 52, IQR 21 cm/s; P<0.01 and 0.02). Conclusions— Flow increases in both posterior cerebral artery P2 segments suggest intensified compensatory efforts when other collaterals are insufficient. Together with the presence of diabetes mellitus and a history of transient ischemic attack, this duplex parameter indicates that patients with internal carotid artery are at particular risk of recurrent ischemia.

Midregional proatrial natriuretic peptide improves risk stratification after ischemic stroke: Association with mortality and cardioembolic etiology

Objective To validate midregional proatrial natriuretic peptide (MR-proANP) for outcome prediction and diagnosis of cardioembolic stroke etiology compared to established clinical variables. Methods In this prospective multicenter cohort study, we quantified MR-proANP levels in ischemic stroke patients within 24 hours of onset. Primary outcome measures were 90-day mortality, unfavorable functional outcome (modified Rankin Scale score >2), and cardioembolic stroke etiology diagnosed during hospitalization. Results Of 788 included patients, 783 completed their 90-day follow-up, and 118 patients (15%) died. After full adjustment, MR-proANP levels were associated with 90-day mortality (adjusted hazard ratio 6.12, 95% confidence interval [CI] 2.36–15.84, p = 0.01) and functional outcome (adjusted odds ratio [aOR] 2.46, 95% CI 1.05–5.74, p = 0.038). For mortality prediction, adding MR-proANP to the regression model increased its discriminatory accuracy, and the continuous net reclassification index (cNRI) was 49% (95% CI 26%–78%, p < 0.001). For functional outcome, there was no significant improvement in discrimination or reclassification. Cardioembolic stroke etiology and the diagnosis of atrial fibrillation at hospital discharge were associated with MR-proANP with an aOR of 2.10 (95% CI 1.11–3.97, p = 0.02) and 18.35 (95% CI 7.94–42.45, p < 0.001), respectively. The cNRI of MR-proANP for cardioembolic stroke etiology was not significant, as opposed to atrial fibrillation (78%, 95% CI 60%–89%, p < 0.001). MR-proANP levels ≥289 pmol/L had a specificity of 86% and sensitivity of 48% for the diagnosis of atrial fibrillation. Conclusion MR-proANP is a newly validated blood biomarker providing additional prognostic information for mortality after stroke. Higher MR-proANP levels were associated with cardioembolic stroke etiology and, even more strongly, atrial fibrillation.

PROCEDURAL PAIN AND ORAL GLUCOSE IN PRETERM NEONATES: BRAIN DEVELOPMENT AND SEX-SPECIFIC EFFECTS

Abstract Our objectives were to determine whether procedural pain and glucose exposure are associated with altered structural and functional brain development differently in preterm males and females, and neurodevelopment at 18-month corrected age. Fifty-one very preterm neonates (22 males; median [interquartile range] gestational age 27.6 [2.0] weeks) underwent 3 serial scans including T1-weighted and resting-state functional magnetic resonance imaging (MRI) at median postmenstrual weeks: 29.4, 31.9, and 41.1. Thalamus, basal ganglia, and total brain volumes were segmented. Functional resting-state MRI data were extracted from the independent-components maps. Pain was operationalized as the total number of neonatal intensive care unit–administered invasive procedures. Neurodevelopmental outcomes at 18-month corrected age were assessed with the Bayley Scales of Infant Development, second edition. Generalized estimating equations assessed the association of pain and glucose exposure with brain structural and functional development. More invasive procedures were independently associated with slower growth of thalamic (P < 0.001), basal ganglia (P = 0.028), and total brain volumes (P = 0.001), particularly in females. Similar relationships were observed between glucose exposure and brain volumes. Functional connectivity between thalamus and sensorimotor cortices was negatively associated with number of invasive procedures. Greater procedural pain and higher glucose exposure were related to poorer neurodevelopmental outcomes. These findings suggest that structural and functional brain development is vulnerable to procedural pain. Glucose used for analgesia does not appear to mitigate the adverse impact of pain on brain development. The vulnerability of brain development in females towards early pain is distinct from other neonatal morbidities. The link between pain and glucose with neurodevelopment suggests that these factors have long-lasting impact.

Impact of perinatal asphyxia on parental mental health and bonding with the infant: a questionnaire survey of Swiss parents

Objective To compare current mental health symptoms and infant bonding in parents whose infants survived perinatal asphyxia in the last 2 years with control parents and to investigate which sociodemographic, obstetric and neonatal variables correlated with parental mental health and infant bonding in the asphyxia group. Design Cross-sectional questionnaire survey of parents whose children were registered in the Swiss national Asphyxia and Cooling register and of control parents (Post-traumatic Diagnostic Scale, Hospital Anxiety and Depression Scale, Mother-to-Infant Bonding Scale). Results The response rate for the asphyxia group was 46.5%. Compared with controls, mothers and fathers in the asphyxia group had a higher frequency of post-traumatic stress disorder (PTSD) symptoms (p<0.001). More mothers (n=28, 56%) had a symptom diagnosis of either full or partial PTSD than controls (n=54, 39%) (p=0.032). Similarly, more fathers (n=31, 51%) had a symptom diagnosis of either partial or full PTSD than controls (n=19, 33%) (p=0.034). Mothers reported poorer bonding with the infant (p=0.043) than controls. Having a trauma in the past was linked to more psychological distress in mothers (r=0.31 (95% CI 0.04 to 0.54)) and fathers (r=0.35 (95% CI 0.05 to 0.59)). For mothers, previous pregnancy was linked to poorer bonding (r=0.41 (95% CI 0.13 to 0.63)). In fathers, therapeutic hypothermia of the infant was related to less frequent PTSD symptoms (r=−0.37 (95% CI −0.61 to −0.06)) and past psychological difficulties (r=0.37 (95% CI 0.07 to 0.60)) to more psychological distress. A lower Apgar score was linked to poorer bonding (r=−0.38 (95% CI −0.64 to −0.05)). Conclusions Parents of infants hospitalised for perinatal asphyxia are more at risk of developing PTSD than control parents.