Synthetic MR Imaging-Based WM Signal Suppression Identifies Neonatal Brainstem Pathways in Vivo.

BACKGROUND AND PURPOSE: Multidynamic multiecho sequence-based imaging enables investigators to reconstruct multiple MR imaging contrasts on the basis of a single scan. This study investigated the feasibility of synthetic MRI-based WM signal suppression (syWMSS), a synthetic inversion recovery approach in which a short TI suppresses myelin-related signals, for the identification of early myelinating brainstem pathways. MATERIALS AND METHODS: Thirty-one cases of neonatal MR imaging, which included multidynamic multiecho data and conventionally acquired T1- and T2-weighted sequences, were analyzed. The multidynamic multiecho postprocessing software SyMRI was used to generate syWMSS data (TR/TE/TI = 3000/5/410 ms). Two raters discriminated early myelinating brainstem pathways (decussation of the superior cerebellar peduncle, medial lemniscus, central tegmental tract, and medial longitudinal fascicle [the latter 3 assessed at the level of the pons]) on syWMSS data and reference standard contrasts. RESULTS: On the basis of syWMSS data, the decussation of the superior cerebellar peduncle (31/31); left/right medial lemniscus (31/31; 30/31); left/right central tegmental tract (19/31; 20/31); and left/right medial longitudinal fascicle (30/31) were reliably identified by both raters. On the basis of T1-weighted contrasts, the decussation of the superior cerebellar peduncle (14/31); left/right medial lemniscus (22/31; 16/31); left/right central tegmental tract (1/31); and left/right medial longitudinal fascicle (9/31; 8/31) were reliably identified by both raters. On the basis of T2-weighted contrasts, the decussation of the superior cerebellar peduncle (28/31); left/right medial lemniscus (16/31; 12/31); left/right central tegmental tract (23/31; 18/31); and left/right medial longitudinal fascicle (15/31; 14/31) were reliably identified by both raters. CONCLUSIONS: syWMSS data provide a feasible imaging technique with which to study early myelinating brainstem pathways. MR imaging approaches that use myelin signal suppression contribute to a more sensitive assessment of myelination patterns at early stages of cerebral development.

Different from the Beginning: WM Maturity of Female and Male Extremely Preterm Neonates-A Quantitative MRI Study.

BACKGROUND AND PURPOSE: Former preterm born males are at higher risk for neurodevelopmental disabilities compared with female infants born at the same gestational age. This retrospective study investigated sex-related differences in the maturity of early myelinating brain regions in infants born <28 weeks' gestational age using diffusion tensor- and relaxometry-based MR imaging. MATERIALS AND METHODS: Quantitative MR imaging sequence acquisitions were analyzed in a sample of 35 extremely preterm neonates imaged at term-equivalent ages. Quantitative MR imaging metrics (fractional anisotropy; ADC [10-3mm2/s]; and T1-/T2-relaxation times [ms]) of the medulla oblongata, pontine tegmentum, midbrain, and the right/left posterior limbs of the internal capsule were determined on diffusion tensor- and multidynamic, multiecho sequence-based imaging data. ANCOVA and a paired t test were used to compare female and male infants and to detect hemispheric developmental asymmetries. RESULTS: Seventeen female (mean gestational age at birth: 26 + 0 [SD, 1 + 4] weeks+days) and 18 male (mean gestational age at birth: 26 + 1 [SD, 1 + 3] weeks+days) infants were enrolled in this study. Significant differences were observed in the T2-relaxation time (P = .014) of the pontine tegmentum, T1-relaxation time (P = .011)/T2-relaxation time (P = .024) of the midbrain, and T1-relaxation time (P = .032) of the left posterior limb of the internal capsule. In both sexes, fractional anisotropy (P [♀] < .001/P [♂] < .001) and ADC (P [♀] = .017/P [♂] = .028) differed significantly between the right and left posterior limbs of the internal capsule. CONCLUSIONS: The combined use of various quantitative MR imaging metrics detects sex-related and interhemispheric differences of WM maturity. The brainstem and the left posterior limb of the internal capsule of male preterm neonates are more immature compared with those of female infants at term-equivalent ages. Sex differences in WM maturation need further attention for the personalization of neonatal brain imaging.

Impact of Prematurity on the Tissue Properties of the Neonatal Brain Stem: A Quantitative MR Approach.

BACKGROUND AND PURPOSE: Preterm birth interferes with regular brain development. The aim of this study was to investigate the impact of prematurity on the physical tissue properties of the neonatal brain stem using a quantitative MR imaging approach. MATERIALS AND METHODS: A total of 55 neonates (extremely preterm [n = 30]: <28 + 0 weeks gestational age; preterm [n = 10]: 28 + 0-36 + 6 weeks gestational age; term [n = 15]: ≥37 + 0 weeks gestational age) were included in this retrospective study. In most cases, imaging was performed at approximately term-equivalent age using a standard MR protocol. MR data postprocessing software SyMRI was used to perform multidynamic multiecho sequence (acquisition time: 5 minutes, 24 seconds)-based MR postprocessing to determine T1 relaxation time, T2 relaxation time, and proton density. Mixed-model ANCOVA (covariate: gestational age at MR imaging) and the post hoc Bonferroni test were used to compare the groups. RESULTS: There were significant differences between premature and term infants for T1 relaxation time (midbrain: P < .001; pons: P < .001; basis pontis: P = .005; tegmentum pontis: P < .001; medulla oblongata: P < .001), T2 relaxation time (midbrain: P < .001; tegmentum pontis: P < .001), and proton density (tegmentum pontis: P = .004). The post hoc Bonferroni test revealed that T1 relaxation time/T2 relaxation time in the midbrain differed significantly between extremely preterm and preterm (T1 relaxation time: P < .001/T2 relaxation time: P = .02), extremely preterm and term (T1 relaxation time/T2 relaxation time: P < .001), and preterm and term infants (T1 relaxation time: P < .001/T2 relaxation time: P = .006). CONCLUSIONS: Quantitative MR parameters allow preterm and term neonates to be differentiated. T1 and T2 relaxation time metrics of the midbrain allow differentiation between the different stages of prematurity. SyMRI allows for a quantitative assessment of incomplete brain maturation by providing tissue-specific properties while not exceeding a clinically acceptable imaging time.

Functional maturation in preterm infants measured by serial recording of cortical activity.

Minimally invasive, automated cot-side tools for monitoring early neurological development can be used to guide individual treatment and benchmark novel interventional studies. We develop an automated estimate of the EEG maturational age (EMA) for application to serial recordings in preterm infants. The EMA estimate was based on a combination of 23 computational features estimated from both the full EEG recording and a period of low EEG activity (46 features in total). The combination function (support vector regression) was trained using 101 serial EEG recordings from 39 preterm infants with a gestational age less than 28 weeks and normal neurodevelopmental outcome at 12 months of age. EEG recordings were performed from 24 to 38 weeks post-menstrual age (PMA). The correlation between the EMA and the clinically determined PMA at the time of EEG recording was 0.936 (95%CI: 0.932-0.976; n = 39). All infants had an increase in EMA between the first and last EEG recording and 57/62 (92%) of repeated measures within an infant had an increasing EMA with PMA of EEG recording. The EMA is a surrogate measure of age that can accurately determine brain maturation in preterm infants.

Biometry of the corpus callosum assessed by 3D ultrasound and its correlation to neurodevelopmental outcome in very low birth weight infants.

OBJECTIVE: Several studies have shown a relation between the size of corpus callosum (CC) and outcome in preterm infants. Three-dimensional ultrasound (3D-US) offers new perspectives in cerebral imaging. To establish reference values for biometry of the CC in very low birth weight infants and to correlate these measurements to neurodevelopmental outcome at 5 years of age. STUDY DESIGN: Forty-three preterm infants with a gestational age <32 weeks were included. Transfontanellar 3D-US measurements were obtained at nine different timepoints. RESULTS: 3D-US-based reference values for size, length, circumference and surface area of the CC could be established. Measurements at term-equivalent age showed a correlation to neurodevelopment outcome. CONCLUSION: Reliable biometric data of the CC can be established in preterm infants by 3D-US and correlate with neurodevelopmental outcome.

Differences in attentional functioning between preterm and full-term children underline the importance of new neuropsychological detection techniques.

AIM: The aim of this study was to investigate specific attentional components in preterm born children who had not yet started school. METHODS: Between January and December 2011, we assessed 52 preterm and 52 full-term children aged between five years five months and six years two months, of comparable age and gender, at the Medical University of Vienna. Different attentional components were evaluated through selected subtests of the Test of Attentional Performance and the German version of the Wechsler Intelligence Scale for Children. Each child's behaviour was also evaluated using parental ratings and descriptive item-based evaluation during neuropsychological assessment. RESULTS: Children born preterm showed poor attentional performance in sustained attention, focused attention and distractibility, as well as reductions in processing speed in divided attention and flexibility tasks. Children born preterm also showed decreased volitional attention compared with automatic attention. No problems were detected in alertness or inhibition. In addition, a higher rate of aborted tests, decreased motivation and poorer parental ratings were detected among the preterm population compared with full-term born children. CONCLUSION: Our results highlighted differences in attentional functioning between preterm and full-term children, indicating the importance of new neuropsychological techniques for the detection of specific attentional disorders.

The impact of altitude on birth weight depends on further mother- and infant-related factors: a population-based study in an altitude range up to 1600 m in Austria between 1984 and 2013.

OBJECTIVE: A negative impact of altitude on birth weight has been demonstrated for medium to high-altitude countries. STUDY DESIGN: The present study aims to show a similar effect for a lower altitude range up to 1600 m in the country of Austria and to adjust for several further risk factors related to mother and infant. In addition, we analyzed whether the effect of altitude influenced birth weight independently or interacted with other factors. For the purpose of this study, almost 1.9 million individual birth certificates of Austrian newborns born between 1984 and 2013 were analyzed. In a multivariate linear regression model, birth weight was associated with altitude of living address and following variables: sex, birth length, gestational age, level of education, maternal age, year of birth, parity, time to previous birth and marital status. RESULT: Birth weight decreased by 150 g/1000 m altitude, demonstrating a clear effect of altitude on birth weight also in a low to medium altitude level. Additionally, we could show that this effect also depends on other factors, namely gestational age, education of the mother, sex, birth length, year of birth and time to previous delivery. All variables interacted significantly (p<0.0001) with altitude. CONCLUSION: We observed a negative effect of altitude in an altitude range up to 1600 m. Furthermore, this effect also depends on other risk factors. Therefore, unadjusted estimates as described in many studies may be biased. This population-based study describes the effect of low-to-medium altitude on birth weight in central Europe over a period of 30 years.

Management of hypothermia for perinatal asphyxia in Austria - a survey of current practice standards.

BACKGROUND: Therapeutic hypothermia (HT) has been shown to reduce the risk of death or disability and increase the rate of survival free of -disability at 18-24 months of age in hypoxic-ischemic encephalopathy (HIE). OBJECTIVES: The aim of this study was to take a national survey which (a) evaluated the practice of therapeutic HT for perinatal asphyxia in Austria, (b) evaluated the current clinical management of neonatal HIE and (c) evaluated the need for a national perinatal asphyxia and HT registry. METHODS: In January 2013, a questionnaire was sent out to the clinical heads of all neonatal level-II and level-III units in Austria. RESULTS: We received replies from all 30 level II and level III units in Austria (response rate 100%). 19 units (63%) answered that they applied HT, 11 units (37%) said they transferred patients for cooling to other units, 3 of those 11 units (27%) said they applied cooling during transport. 25 units (83%) felt the necessity to establish a national registry. CONCLUSION: The results of this survey show that there is already a high implementation of therapeutic HT in Austria, but there remains a need for information, awareness and training. Problem areas tend to be in the transport of asphyxiated neonates, brain monitoring during cooling and follow-up of affected patients. We believe, that the establishment of national guidelines and a national register could increase awareness for the importance of therapeutic HT in neonatal HIE, thus improve the Austrian management of those infants.

Neonatal abstinence syndrome in European and North American neonates: differences in clinical characteristics derived from a prospective randomized trial.

BACKGROUND: Due to the steady increase of substance-dependent pregnant women the neonatal abstinence syndrome has become an increasingly important issue in neonatology. The present study investigates site-specific differences of detailed symptoms and treatment of neonatal abstinence syndrome within the context of an international multicenter clinical trial. METHODS: Site specific neonatal data analyses from a prospective randomized, double-blind, double-dummy clinical trial (MOTHER study) was performed. A standardized NAS rating and treatment protocol was applied, while non-pharmacological care of NAS symptoms differed across the sites. RESULTS: Urban US neonates exhibited most neurological symptoms (p<0.001) while in Europe autonomous, respiratory and gastrointestinal symptoms were found significantly more often compared to urban and/or rural US (p<0.05). Methadone produced significantly greater scores than buprenorphine in neurological, behavioural and respiratory symptoms regardless of the sites (ps<0.05). NAS treatment rates in all site clusters were similar for methadone-exposed neonates, while in Europe significantly more buprenorphine-exposed neonates were treated (p=0.001) than in US site clusters. Urban US neonates had significantly higher NAS scores (p<0.01) compared to rural US and European neonates, and needed significantly higher morphine doses (p<0.05) with longer treatment duration. Birth weight, length and head circumference did not differ significantly among the site clusters, but APGAR scores were significantly higher in European (p<0.01) neonates. CONCLUSION: In addition to intrauterine medication exposure other aspects such as different addiction severity of the mothers, different treatment modalities including rooming-in as well as the frequency of NAS ratings may be influencing the course of NAS.

Intravenous sildenafil i.v. as rescue treatment for refractory pulmonary hypertension in extremely preterm infants.

BACKGROUND: Intravenous sildenafil treatment has recently shown promising results and good tolerability in the treatment of refractory pulmonary hypertension (PH) in term and near-term neonates, while comparable data in preterm infants are still lacking. However, for critically ill preterm infants suffering from PH refractory to conventional treatment, sildenafil may represent a last treatment resort. PATIENTS AND METHODS: We reviewed the records of 6 critically ill extremely preterm infants who had suffered from PH refractory to conventional treatment and had obtained intravenous sildenafil after careful consideration as ultima ratio treatment. AIM: To describe the responses to sildenafil in terms of hemodynamic and respiratory changes during treatment and outcome. RESULTS: 4/6 patients showed resolution of severe PH with full reversal of ductal shunt direction into pure left-to-right shunt within 82 ± 35 h after sildenafil start. Remarkably, 2/6 patients developed pulmonary hemorrhage at a time point when significant improvement of PH had already taken place, both of them survived. Overall 4/6 patients died, two deaths were related to treatment-refractory PH. CONCLUSION: Intravenous sildenafil treatment seems effective in improving severe PH and hemodynamic instability in extremely preterm infants with refractory PH. Pulmonary hemorrhage may represent a distinct adverse effect of sildenafil treatment in these patients, presumably due to sudden reversal of ductal shunt. Accordingly, sildenafil should be restricted to most severe and refractory cases in this population.

Regional cortical development in very low birth weight infants with normal neurodevelopmental outcome assessed by 3D-ultrasound.

OBJECTIVE: Three-dimensional ultrasound (3D-US) offers new perspectives in cerebral imaging. STUDY DESIGN: This prospective study aimed to determine whether 3D-US is appropriate to assess cortical development of the premature brain, and compare it to previously established reference values assessed by magnetic resonance imaging (MRI). Preterm infants with a gestational age (GA) of <32 weeks were examined by serial 3D-US scans. RESULT: Data of 30 patients with normal neurological development at the age of 5 years were included in the analysis. Cortical development was graded according to a five-point scoring system, and data were stratified into 6 age groups. Cortical developmental scores were established for various brain regions. In the frontal and frontoparietal regions, 3D-US reference values differed from published MRI reference values, but were consistent with the published data in all other regions. CONCLUSION: 3D-US reference values facilitate routine diagnostics and enable the evaluation of cortical development in preterm infants.

Impact of low-grade intraventricular hemorrhage on long-term neurodevelopmental outcome in preterm infants.

PURPOSE: Despite a decreasing incidence, intraventricular hemorrhage (IVH) remains a point of major concern in neonatology due to its association to adverse neurodevelopmental outcome (NDO). Aim of this study was to compare outcome of preterm infants with different grades of IVH born below 32 weeks of gestational age (GA) with outcome of controls without IVH and to especially evaluate the influence of low grade IVH on NDO. METHODS: Four hundred seventy-one preterm infants with a GA below 32 weeks were admitted to our neonatal intensive care unit between 1994 and 2005 and included into analysis. RESULTS: IVH patients showed significantly lower mean psychomotor and mental developmental indices and a significantly higher percentage of cerebral palsy and visual impairment. Results of IVH patients born below 28 weeks of GA were significantly worse than results of IVH patients born at or above 28 weeks of GA. In all parameters, an increase of abnormal results with increasing grade of IVH could be observed; even patients with low-grade IVH (grades I and II) showed higher percentages of impairment compared to controls without any IVH. CONCLUSION: Even low-grade IVH has an significant impact on neurodevelopmental outcome of preterm patients and gestational age influences the impact of intraventricular hemorrhage on neurodevelopmental outcome.