Amygdala volumes and associations with socio-emotional competencies in preterm youth: cross-sectional and longitudinal data.

BACKGROUND: Socio-emotional difficulties often result from very preterm (VPT) birth. The amygdala's developmental trajectory, including its nuclei, has been recognized as a significant factor in observed difficulties. This study aims to assess the relationship between amygdala volume and socio-emotional competencies in VPT children and adolescents. METHODS: Socio-emotional competencies were assessed, and amygdala volumes, including subnuclei, were extracted automatically from structural scans in a cross-sectional cohort of VPT (n = 75) and full-term (FT, n = 41) aged 6-14 years. Group differences in amygdala volumes were assessed using ANCOVA, and associations with socio-emotional competencies were studied using partial least squares correlation (PLSC). In a VPT subgroup, additional longitudinal data with amygdala volumes at term-equivalent age (TEA) were manually extracted, growth rates calculated, and associations with school-age socio-emotional competencies investigated using PLSC. RESULTS: Using cross-sectional data at school-age, amygdala volumes displayed comparable developmental patterns between the VPT and the FT groups. Greater volumes were associated with more emotional regulation difficulties in VPT and lower affect recognition competencies in FT. In the longitudinal VPT subgroup, no significant associations were found between amygdala volume trajectory and socio-emotional competencies. CONCLUSION: Although our findings suggest typical amygdala development after VPT birth, further research is necessary to elucidate the developmental trajectory of amygdala and the role of resilience factors. IMPACT: In our cohort, amygdala volumes, including subnuclei, displayed comparable developmental trajectories between the very preterm and the full-term groups. Higher amygdala volumes at school-age were associated with higher emotional regulation difficulties in the very-preterm born group, and with lower affect recognition abilities in full-term born children and adolescents. In a subgroup of very-preterm children and adolescents followed from birth to school-age, no significant associations were found between amygdala volumes at term-equivalent age and socio-emotional competencies at school-age.

Behavioral outcome of very preterm children at 5 years of age: Prognostic utility of brain tissue volumes at term-equivalent-age, perinatal, and environmental factors.

OBJECTIVE: Prematurity is associated with a high risk of long-term behavioral problems. This study aimed to assess the prognostic utility of volumetric brain data at term-equivalent-age (TEA), clinical perinatal factors, and parental social economic risk in the prediction of the behavioral outcome at 5 years in a cohort of very preterm infants (VPT, <32 gestational weeks). METHODS: T2-weighted magnetic resonance brain images of 80 VPT children were acquired at TEA and automatically segmented into cortical gray matter, deep subcortical gray matter, white matter (WM), cerebellum (CB), and cerebrospinal fluid. The gray matter structure of the amygdala was manually segmented. Children were examined at 5 years of age with a behavioral assessment, using the strengths and difficulties questionnaire (SDQ). The utility of brain volumes at TEA, perinatal factors, and social economic risk for the prediction of behavioral outcome was investigated using support vector machine classifiers and permutation feature importance. RESULTS: The predictive modeling of the volumetric data showed that WM, amygdala, and CB volumes were the best predictors of the SDQ emotional symptoms score. Among the perinatal factors, sex, sepsis, and bronchopulmonary dysplasia were the best predictors of the hyperactivity/inattention score. When combining the social economic risk with volumetric and perinatal factors, we were able to accurately predict the emotional symptoms score. Finally, social economic risk was positively correlated with the scores of conduct problems and peer problems. CONCLUSIONS: This study provides information on the relation between brain structure at TEA and clinical perinatal factors with behavioral outcome at age 5 years in VPT children. Nevertheless, the overall predictive power of our models is relatively modest, and further research is needed to identify factors associated with subsequent behavioral problems in this population.

A Novel Concept of a Phased-Array HIFU Transducer Optimized for MR-Guided Hepatic Ablation: Embodiment and First In-Vivo Studies.

Purpose: High-intensity focused ultrasound (HIFU) is challenging in the liver due to the respiratory motion and risks of near-/far-field burns, particularly on the ribs. We implemented a novel design of a HIFU phased-array transducer, dedicated to transcostal hepatic thermo-ablation. Due to its large acoustic window and strong focusing, the transducer should perform safely for this application. Material and Methods: The new HIFU transducer is composed of 256 elements distributed on 5 concentric segments of a specific radius (either 100, 111, or 125 mm). It has been optimally shaped to fit the abdominal wall. The shape and size of the acoustic elements were optimized for the largest emitting surface and the lowest symmetry. Calibration tests have been conducted on tissue-mimicking gels under 3-T magnetic resonance (MR) guidance. In-vivo MR-guided HIFU treatment was conducted in two pigs, aiming to create thermal ablation deep in the liver without significant side effects. Imaging follow-up was performed at D0 and D7. Sacrifice and post-mortem macroscopic examination occurred at D7, with the ablated tissue being fixed for pathology. Results: The device showed -3-dB focusing capacities in a volume of 27 × 46 × 50 mm3 as compared with the numerical simulation volume of 18 × 48 × 60 mm3. The shape of the focal area was in millimeter-range agreement with the numerical simulations. No interference was detected between the HIFU sonication and the MR acquisition. In vivo, the temperature elevation in perivascular liver parenchyma reached 28°C above physiological temperature, within one breath-hold. The lesion was visible on Gd contrast-enhanced MRI sequences and post-mortem examination. The non-perfused volume was found in pig #1 and pig #2 of 8/11, 6/8, and 7/7 mm along the LR, AP, and HF directions, respectively. No rib burns or other near-field side effects were visually observed on post-mortem gross examination. High-resolution contrast-enhanced 3D MRI indicated a minor lesion on the sternum. Conclusion: The performance of this new HIFU transducer has been demonstrated in vitro and in vivo. The transducer meets the requirement to perform thermal lesions in deep tissues, without the need for rib-sparing means.

PFOB sonosensitive microdroplets: determining their interaction radii with focused ultrasound using MR thermometry and a Gaussian convolution kernel computation.

Purpose: Micron-sized perfluorocarbon droplet adjuvants to focused ultrasound therapies allow lower applied power, circumvent unwanted prefocal heating, and enhance thermal dose in highly perfused tissues. The heat enhancement has been shown to saturate at increasing concentrations. Experiments were performed to empirically model the saturating heating effects during focused ultrasound.Materials and methods: The measurements were made at varying concentrations using magnetic resonance thermometry and focused ultrasound by circulating droplets of mean diameter 1.9 to 2.3 µm through a perfused phantom. A simulation was performed to estimate the interaction radius size, empirically.Results: The interaction radius, representing the radius of a sphere encompassing 90% of the probability for the transformation of acoustic energy into heat deposition around a single droplet, was determined experimentally from ultrasonic absorption coefficient measurements The simulations suggest the interaction radius was approximately 12.5-fold larger than the geometrical radius of droplets, corresponding to an interaction volume on the order of 2000 larger than the geometrical volume.Conclusions: The results provide information regarding the dose-response relationship from the droplets, a measure with 15% precision of their interaction radii with focused ultrasound, and subsequent insights into the underlying physical heating mechanism.

Preterm birth leads to impaired rich-club organization and fronto-paralimbic/limbic structural connectivity in newborns.

Prematurity disrupts brain development during a critical period of brain growth and organization and is known to be associated with an increased risk of neurodevelopmental impairments. Investigating whole-brain structural connectivity alterations accompanying preterm birth may provide a better comprehension of the neurobiological mechanisms related to the later neurocognitive deficits observed in this population. Using a connectome approach, we aimed to study the impact of prematurity on neonatal whole-brain structural network organization at term-equivalent age. In this cohort study, twenty-four very preterm infants at term-equivalent age (VPT-TEA) and fourteen full-term (FT) newborns underwent a brain MRI exam at term age, comprising T2-weighted imaging and diffusion MRI, used to reconstruct brain connectomes by applying probabilistic constrained spherical deconvolution whole-brain tractography. The topological properties of brain networks were quantified through a graph-theoretical approach. Furthermore, edge-wise connectivity strength was compared between groups. Overall, VPT-TEA infants' brain networks evidenced increased segregation and decreased integration capacity, revealed by an increased clustering coefficient, increased modularity, increased characteristic path length, decreased global efficiency and diminished rich-club coefficient. Furthermore, in comparison to FT, VPT-TEA infants had decreased connectivity strength in various cortico-cortical, cortico-subcortical and intra-subcortical networks, the majority of them being intra-hemispheric fronto-paralimbic and fronto-limbic. Inter-hemispheric connectivity was also decreased in VPT-TEA infants, namely through connections linking to the left precuneus or left dorsal cingulate gyrus - two regions that were found to be hubs in FT but not in VPT-TEA infants. Moreover, posterior regions from Default-Mode-Network (DMN), namely precuneus and posterior cingulate gyrus, had decreased structural connectivity in VPT-TEA group. Our finding that VPT-TEA infants' brain networks displayed increased modularity, weakened rich-club connectivity and diminished global efficiency compared to FT infants suggests a delayed transition from a local architecture, focused on short-range connections, to a more distributed architecture with efficient long-range connections in those infants. The disruption of connectivity in fronto-paralimbic/limbic and posterior DMN regions might underlie the behavioral and social cognition difficulties previously reported in the preterm population.

Enhancement of HIFU thermal therapy in perfused tissue models using micron-sized FTAC-stabilized PFOB-core endovascular sonosensitizers.

BACKGROUND: High intensity focused ultrasound (HIFU) is clinically accepted for the treatment of solid tumors but remains challenging in highly perfused tissue due to the heat sink effect. Endovascular liquid-core sonosensitizers have been previously suggested to enhance the thermal energy deposition at the focal area and to lower the near-/far-field heating. We are investigating the therapeutic potential of PFOB-FTAC micro-droplets in a perfused tissue-mimicking model and postmortem excised organs. METHOD: A custom-made in vitro perfused tissue-mimicking model, freshly excised pig kidneys (n = 3) and liver (n = 1) were perfused and subjected to focused ultrasound generated by an MR-compatible HIFU transducer. PFOB-FTAC sonosensitizers were injected in the perfusion fluid up to 0.235% v/v ratio. Targeting and on-line PRFS thermometry were performed on a 3 T MR scanner. Assessment of the fluid perfusion was performed with pulsed color Doppler in vitro and with dynamic contrast-enhanced (DCE)-MRI in excised organs. RESULTS: Our in vitro model of perfused tissue demonstrated re-usability. Sonosensitizer concentration and perfusion rate were tunable in situ. Differential heating under equivalent HIFU sonications demonstrated a dramatic improvement in the thermal deposition due to the sonosensitizers activity. Typically, the energy deposition was multiplied by a factor between 2.5 and 3 in perfused organs after the administration of micro-droplets, while DCE-MRI indicated an effective perfusion. CONCLUSION: The current PFOB-FTAC micro-droplet sonosensitizers provided a large and sustained enhancement of the HIFU thermal deposition at the focal area, suggesting solutions for less technological constraints, lower risk for the near-/far- field heating. We also report a suitable experimental model for other MRgHIFU studies.

Ultrasound-driven cardiac MRI.

PURPOSE: One of the challenges of cardiac MR imaging is the compensation of respiratory motion, which causes the heart and the surrounding tissues to move. Commonly-used methods to overcome this effect, breath-holding and MR navigation, present shortcomings in terms of available acquisition time or need to periodically interrupt the acquisition, respectively. In this work, an implementation of respiratory motion compensation that obtains information from abdominal ultrasound and continuously adapts the imaged slice position in real time is presented. METHODS: A custom workflow was developed, comprising an MR-compatible ultrasound acquisition system, a feature-motion-tracking system with polynomial predictive capability, and a custom MR sequence that continuously adapts the position of the acquired slice according to the tracked position. The system was evaluated on a moving phantom by comparing sharpness and image blurring between static and moving conditions, and in vivo by tracking the motion of the blood vessels of the liver to estimate the cardiac motion. Cine images of the heart were acquired during free breathing. RESULTS: In vitro, the predictive motion correction yielded significantly better results than non-predictive or non-corrected acquisitions (p â‰ª 0.01). In vivo, the predictive correction resulted in an image quality very similar to the breath-hold acquisition, whereas the uncorrected images show noticeable blurring artifacts. CONCLUSION: In this work, the possibility of using ultrasound navigation with tracking for the real-time adaptation of MR imaging slices was demonstrated. The implemented technique enabled efficient imaging of the heart with resolutions that would not be feasible in a single breath-hold.

Music enhances structural maturation of emotional processing neural pathways in very preterm infants.

Prematurity disrupts brain maturation by exposing the developing brain to different noxious stimuli present in the neonatal intensive care unit (NICU) and depriving it from meaningful sensory inputs during a critical period of brain development, leading to later neurodevelopmental impairments. Musicotherapy in the NICU environment has been proposed to promote sensory stimulation, relevant for activity-dependent brain plasticity, but its impact on brain structural maturation is unknown. Neuroimaging studies have demonstrated that music listening triggers neural substrates implied in socio-emotional processing and, thus, it might influence networks formed early in development and known to be affected by prematurity. Using multi-modal MRI, we aimed to evaluate the impact of a specially composed music intervention during NICU stay on preterm infant's brain structure maturation. 30 preterm newborns (out of which 15 were exposed to music during NICU stay and 15 without music intervention) and 15 full-term newborns underwent an MRI examination at term-equivalent age, comprising diffusion tensor imaging (DTI), used to evaluate white matter maturation using both region-of-interest and seed-based tractography approaches, as well as a T2-weighted image, used to perform amygdala volumetric analysis. Overall, WM microstructural maturity measured through DTI metrics was reduced in preterm infants receiving the standard-of-care in comparison to full-term newborns, whereas preterm infants exposed to the music intervention demonstrated significantly improved white matter maturation in acoustic radiations, external capsule/claustrum/extreme capsule and uncinate fasciculus, as well as larger amygdala volumes, in comparison to preterm infants with standard-of-care. These results suggest a structural maturational effect of the proposed music intervention on premature infants' auditory and emotional processing neural pathways during a key period of brain development.

Mild hyperthermia by MR-guided focused ultrasound in an ex vivo model of osteolytic bone tumour: optimization of the spatio-temporal control of the delivered temperature.

BACKGROUND: Magnetic resonance guided focused ultrasound was suggested for the induction of deep localized hyperthermia adjuvant to radiation- or chemotherapy. In this study we are aiming to validate an experimental model for the induction of uniform temperature elevation in osteolytic bone tumours, using the natural acoustic window provided by the cortical breakthrough. MATERIALS AND METHODS: Experiments were conducted on ex vivo lamb shank by mimicking osteolytic bone tumours. The cortical breakthrough was exploited to induce hyperthermia inside the medullar cavity by delivering acoustic energy from a phased array HIFU transducer. MR thermometry data was acquired intra-operatory using the proton resonance frequency shift (PRFS) method. Active temperature control was achieved via a closed-loop predictive controller set at 6 °C above the baseline. Several beam geometries with respect to the cortical breakthrough were investigated. Numerical simulations were used to further explain the observed phenomena. Thermal safety of bone heating was assessed by cross-correlating MR thermometry data with the measurements from a fluoroptic temperature sensor inserted in the cortical bone. RESULTS: Numerical simulations and MR thermometry confirmed the feasibility of spatio-temporal uniform hyperthermia (± 0.5 °C) inside the medullar cavity using a fixed focal point sonication. This result was obtained by the combination of several factors: an optimal positioning of the focal spot in the plane of the cortical breakthrough, the direct absorption of the HIFU beam at the focal spot, the "acoustic oven effect" yielded by the beam interaction with the bone, and a predictive temperature controller. The fluoroptical sensor data revealed no heating risks for the bone and adjacent tissues and were in good agreement with the PRFS thermometry from measurable voxels adjacent to the periosteum. CONCLUSION: To our knowledge, this is the first study demonstrating the feasibility of MR-guided focused ultrasound hyperthermia inside the medullar cavity of bones affected by osteolytic tumours. Our results are considered a promising step for combining adjuvant mild hyperthermia to external beam radiation therapy for sustained pain relief in patients with symptomatic bone metastases.

Self-Scanned HIFU Ablation of Moving Tissue Using Real-Time Hybrid US-MR Imaging.

OBJECTIVE: High intensity focused ultrasound (HIFU) treatment in the abdominal cavity is challenging due to the respiratory motion. In the self-scanning HIFU ablation method, the focal spot is kept static and the heating pattern is obtained through natural tissue motion. This paper describes a novel approach for modulating the HIFU power during self-scanning in order to compensate for the effect of tissue motion on thermal buildup. METHODS: The therapy, using hybrid ultrasound (US)/magnetic resonance (MR) imaging, consists of detecting and tracking speckle on US images in order to predict the next tissue position, and modulating the HIFU power according to the tissue speed in order to obtain a rectilinear pattern of uniform temperature elevation. Experiments were conducted on ex vivo tissue subjected to a breathing-like motion generated by an MR-compatible robot and sonicated by a phased array HIFU transducer. RESULTS: US and MR data were free from interferences. For both periodic and non-periodic motion, MR temperature maps showed a substantial improvement in the uniformity of the temperature elevation by using acoustic power modulation. CONCLUSION: The presented method does not require a learning stage and enables a duty cycle close to 100%, higher average acoustic intensity and avoidance of side lobe effects versus performing HIFU beam steering to compensate tissue motion. SIGNIFICANCE: To our knowledge, the proposed method provides the first experimental validation of the self-scanning HIFU ablation paradigm via a real-time hybrid MRI/US imaging, opening the path toward self-scanning in vivo therapies.

Molecular oxygen loading in candidate theranostic droplets stabilized with biocompatible fluorinated surfactants: Particle size effect and application to in situ19F MRI mapping of oxygen partial pressure.

OBJECTIVE: Perfluorocarbon nano- and micron-sized emulsions are a new field of investigation in cancer treatment due to their ability to be used as imaging contrast agents, or as delivery vectors for pharmaceuticals. They also demonstrated capability to enhance the efficiency of high intensity focused ultrasound thermo-therapy. In the context of new biomedical applications we investigated perfluorooctyl bromide (PFOB) theranostic droplets using 19F NMR. Each droplet contains biocompatible fluorinated surfactants composed of a polar Tris(hydroxymethyl)aminomethane head unit and hydrophobic perfluorinated tail (abbreviated as F-TAC). The influence of the droplet size on the oxygen loading capacity was determined from longitudinal relaxation (T1) data of 19F NMR signal. MATERIAL AND METHODS: Liquid PFOB and five samples of PFOB droplets of average diameter 0.177, 0.259, 1.43, 3.12 and 4.53 µm were tested with different oxygen levels. A dedicated gas exchange system was validated to maintain steady state oxygen concentrations, including a spatial gradient of oxygen concentration. A prototyped transmit-receive switchable 19F/1H quadrature coil was integrated on a 3 T clinical scanner. The coil is compatible with focused ultrasound sonication for future application. A spectroscopy FID inversion-recovery (IR) sequence was used to measure the T1 value per sample and per value of equilibrium oxygen pressure. Pixel wise, spatial T1 mapping was performed with magnetization prepared 2D gradient echo sequences in tissue mimicking gels doped with theranostic droplets. RESULTS: Experimental data indicated that the longitudinal relaxation rate of 19F signal of the investigated theranostic droplets depended approximately linearly on the oxygen level and its slope decreased with the particle size according to a second order polynomial over the investigated range. This semi-empirical model was derived from general thermodynamics and weak electrostatic forces theory and fitted the experimental data within 0.75% precision. The capacity of oxygen transportation for the described theranostic droplets tended to that of pure PFOB, while micron-sized droplets lost up to 50% of this capacity. In a specific setup producing a steady state gradient of oxygen concentration, we demonstrated spatial mapping of oxygen pressure gradient of 6 kPa/mm with 1 mm in-plane resolution. CONCLUSION: The size-tunable PFOB theranostic droplets stabilized with F-TAC surfactants could be characterized by 19F MRI in a clinical setup readily compatible with interventional in vivo studies under MR guidance. Current precision and spatial resolution of T1 mapping are promising. A potential challenge for further in vivo studies is the reduction of the imaging time.

Altered Amygdala Development and Fear Processing in Prematurely Born Infants.

CONTEXT: Prematurely born children have a high risk of developmental and behavioral disabilities. Cerebral abnormalities at term age have been clearly linked with later behavior alterations, but existing studies did not focus on the amygdala. Moreover, studies of early amygdala development after premature birth in humans are scarce. OBJECTIVE: To compare amygdala volumes in very preterm infants at term equivalent age (TEA) and term born infants, and to relate premature infants' amygdala volumes with their performance on the Laboratory Temperament Assessment Battery (Lab-TAB) fear episode at 12 months. PARTICIPANTS: Eighty one infants born between 2008 and 2014 at the University Hospitals of Geneva and Lausanne, taking part in longitudinal and functional imaging studies, who had undergone a magnetic resonance imaging (MRI) scan at TEA enabling manual amygdala delineation. OUTCOMES: Amygdala volumes assessed by manual segmentation of MRI scans; volumes of cortical and subcortical gray matter, white matter and cerebrospinal fluid (CSF) automatically segmented in 66 infants; scores for the Lab-TAB fear episode for 42 premature infants at 12 months. RESULTS: Amygdala volumes were smaller in preterm infants at TEA than term infants (mean difference 138.03 mm(3), p < 0.001), and overall right amygdala volumes were larger than left amygdala volumes (mean difference 36.88 mm(3), p < 0.001). White matter volumes were significantly smaller (p < 0.001) and CSF volumes significantly larger (p < 0.001) in preterm than in term born infants, while cortical and subcortical gray matter volumes were not significantly different between groups. Amygdala volumes showed significant correlation with the intensity of the escape response to a fearsome toy (rs = 0.38, p = 0.013), and were larger in infants showing an escape response compared to the infants showing no escape response (mean difference 120.97 mm(3), p = 0.005). Amygdala volumes were not significantly correlated with the intensity of facial fear, distress vocalizations, bodily fear and positive motor activity in the fear episode. CONCLUSION: Our results indicate that premature birth is associated with a reduction in amygdala volumes and white matter volumes at TEA, suggesting that altered amygdala development might be linked to alterations in white matter connectivity reported in premature infants. Moreover, our data suggests that such alterations might affect infants' fear-processing capabilities.

Evaluation of automatic neonatal brain segmentation algorithms: the NeoBrainS12 challenge.

A number of algorithms for brain segmentation in preterm born infants have been published, but a reliable comparison of their performance is lacking. The NeoBrainS12 study (http://neobrains12.isi.uu.nl), providing three different image sets of preterm born infants, was set up to provide such a comparison. These sets are (i) axial scans acquired at 40 weeks corrected age, (ii) coronal scans acquired at 30 weeks corrected age and (iii) coronal scans acquired at 40 weeks corrected age. Each of these three sets consists of three T1- and T2-weighted MR images of the brain acquired with a 3T MRI scanner. The task was to segment cortical grey matter, non-myelinated and myelinated white matter, brainstem, basal ganglia and thalami, cerebellum, and cerebrospinal fluid in the ventricles and in the extracerebral space separately. Any team could upload the results and all segmentations were evaluated in the same way. This paper presents the results of eight participating teams. The results demonstrate that the participating methods were able to segment all tissue classes well, except myelinated white matter.

Association between early administration of high-dose erythropoietin in preterm infants and brain MRI abnormality at term-equivalent age.

IMPORTANCE: Premature infants are at risk of developing encephalopathy of prematurity, which is associated with long-term neurodevelopmental delay. Erythropoietin was shown to be neuroprotective in experimental and retrospective clinical studies. OBJECTIVE: To determine if there is an association between early high-dose recombinant human erythropoietin treatment in preterm infants and biomarkers of encephalopathy of prematurity on magnetic resonance imaging (MRI) at term-equivalent age. DESIGN, SETTING, AND PARTICIPANTS: A total of 495 infants were included in a randomized, double-blind, placebo-controlled study conducted in Switzerland between 2005 and 2012. In a nonrandomized subset of 165 infants (n=77 erythropoietin; n=88 placebo), brain abnormalities were evaluated on MRI acquired at term-equivalent age. INTERVENTIONS: Participants were randomly assigned to receive recombinant human erythropoietin (3000 IU/kg; n=256) or placebo (n=239) intravenously before 3 hours, at 12 to 18 hours, and at 36 to 42 hours after birth. MAIN OUTCOMES AND MEASURES: The primary outcome of the trial, neurodevelopment at 24 months, has not yet been assessed. The secondary outcome, white matter disease of the preterm infant, was semiquantitatively assessed from MRI at term-equivalent age based on an established scoring method. The resulting white matter injury and gray matter injury scores were categorized as normal or abnormal according to thresholds established in the literature by correlation with neurodevelopmental outcome. RESULTS: At term-equivalent age, compared with untreated controls, fewer infants treated with recombinant human erythropoietin had abnormal scores for white matter injury (22% [17/77] vs 36% [32/88]; adjusted risk ratio [RR], 0.58; 95% CI, 0.35-0.96), white matter signal intensity (3% [2/77] vs 11% [10/88]; adjusted RR, 0.20; 95% CI, 0.05-0.90), periventricular white matter loss (18% [14/77] vs 33% [29/88]; adjusted RR, 0.53; 95% CI, 0.30-0.92), and gray matter injury (7% [5/77] vs 19% [17/88]; adjusted RR, 0.34; 95% CI, 0.13-0.89). CONCLUSIONS AND RELEVANCE: In an analysis of secondary outcomes of a randomized clinical trial of preterm infants, high-dose erythropoietin treatment within 42 hours after birth was associated with a reduced risk of brain injury on MRI. These findings require assessment in a randomized trial designed primarily to assess this outcome as well as investigation of the association with neurodevelopmental outcomes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00413946.

Morphology-driven automatic segmentation of MR images of the neonatal brain.

The segmentation of MR images of the neonatal brain is an essential step in the study and evaluation of infant brain development. State-of-the-art methods for adult brain MRI segmentation are not applicable to the neonatal brain, due to large differences in structure and tissue properties between newborn and adult brains. Existing newborn brain MRI segmentation methods either rely on manual interaction or require the use of atlases or templates, which unavoidably introduces a bias of the results towards the population that was used to derive the atlases. We propose a different approach for the segmentation of neonatal brain MRI, based on the infusion of high-level brain morphology knowledge, regarding relative tissue location, connectivity and structure. Our method does not require manual interaction, or the use of an atlas, and the generality of its priors makes it applicable to different neonatal populations, while avoiding atlas-related bias. The proposed algorithm segments the brain both globally (intracranial cavity, cerebellum, brainstem and the two hemispheres) and at tissue level (cortical and subcortical gray matter, myelinated and unmyelinated white matter, and cerebrospinal fluid). We validate our algorithm through visual inspection by medical experts, as well as by quantitative comparisons that demonstrate good agreement with expert manual segmentations. The algorithm's robustness is verified by testing on variable quality images acquired on different machines, and on subjects with variable anatomy (enlarged ventricles, preterm- vs. term-born).