Change in Volumes and Location of Preterm White Matter Injury over a Period of 15 Years.

OBJECTIVE: To evaluate whether white matter injury (WMI) volumes and spatial distribution, which are important predictors of neurodevelopmental outcomes in preterm infants, have changed over a period of 15 years. STUDY DESIGN: Five hundred and twenty-eight infants born <32 weeks' gestational age from 2 sequential prospective cohorts (cohort 1: 2006 through 2012; cohort 2: 2014 through 2019) underwent early-life (median 32.7 weeks postmenstrual age) and/or term-equivalent-age MRI (median 40.7 weeks postmenstrual age). WMI were manually segmented for quantification of volumes. There were 152 infants with WMI with 74 infants in cohort 1 and 78 in cohort 2. Multivariable linear regression models examined change in WMI volume across cohorts while adjusting for clinical confounders. Lesion maps assessed change in WMI location across cohorts. RESULTS: There was a decrease in WMI volume in cohort 2 compared with cohort 1 (ß = -0.6, 95% CI [-0.8, -0.3], P < .001) with a shift from more central to posterior location of WMI. There was a decrease in clinical illness severity of infants across cohorts. CONCLUSIONS: We found a decrease in WMI volume and shift to more posterior location in very preterm infants over a period of 15 years. This may potentially reflect more advanced maturation of white matter at the time of injury which may be related to changes in clinical practice over time.

Pediatric orbital lesions: ocular pathologies.

Orbital pathologies can be broadly classified as ocular, extra-ocular soft-tissue (non-neoplastic and neoplastic), osseous, and traumatic. In part 1 of this orbital series, the authors will discuss the differential diagnosis and key imaging features of pediatric ocular pathologies. These include congenital and developmental lesions (microphthalmos, anophthalmos, persistent fetal vasculature, coloboma, morning glory disc anomaly, retinopathy of prematurity, Coats disease), optic disc drusen, infective and inflammatory lesions (uveitis, toxocariasis, toxoplasmosis), and ocular neoplasms (retinoblastoma, retinal hamartoma, choroidal melanoma, choroidal nevus). This pictorial review provides a practical approach to the imaging work-up of these anomalies with a focus on ocular US as the first imaging modality and additional use of CT and/or MRI for the evaluation of intracranial abnormalities. The characteristic imaging features of the non-neoplastic mimics of retinoblastoma, such as persistent fetal vasculature and Coats disease, are also highlighted.

Imaging approach to pediatric calvarial bulges.

Palpable calvarial lesions in children may require multi-modality imaging for adequate characterization due to non-specific clinical features. Causative lesions range from benign incidental lesions to highly aggressive pathologies. While tissue sampling may be required for some lesions, others have a typical imaging appearance, and an informed imaging approach facilitates diagnosis. This review illustrates imaging findings of common and clinically important focal pediatric calvarial bulges to aid the radiologist in narrowing the differential diagnosis and directing appropriate referral. We focus on birth-related lesions, congenital abnormalities, and modeling disturbances (i.e., those that produce a change in calvarial contour early in development), normal variants, and neoplastic lesions with their mimics.

Pediatric orbital lesions: neoplastic extraocular soft-tissue lesions.

Pediatric neoplastic extraocular soft-tissue lesions in the orbit are uncommon. Early multimodality imaging work-up and recognition of the key imaging features of these lesions allow narrowing of the differential diagnoses in order to direct timely management. In this paper, the authors present a multimodality approach to the imaging work-up of these lesions and highlight the use of ocular ultrasound as a first imaging modality where appropriate. We will discuss vascular neoplasms (congenital hemangioma, infantile hemangioma), optic nerve lesions (meningioma, optic nerve glioma), and other neoplastic lesions (plexiform neurofibroma, teratoma, chloroma, rhabdomyosarcoma, infantile fibrosarcoma, schwannoma).

Pediatric orbital lesions: bony and traumatic lesions.

Orbital pathologies can be broadly classified as ocular lesions, extraocular soft-tissue pathologies (non-neoplastic and neoplastic), and bony and traumatic lesions. In this paper, we discuss the key imaging features and differential diagnoses of bony and traumatic lesions of the pediatric orbit and globe, emphasizing the role of CT and MRI as the primary imaging modalities. In addition, we highlight the adjunctive role of ocular sonography in the diagnosis of intraocular foreign bodies and discuss the primary role of sonography in the diagnosis of traumatic retinal detachment.

Pediatric orbital lesions: non-neoplastic extraocular soft-tissue lesions.

Orbital pathologies can be broadly classified as ocular, extraocular soft-tissue (non-neoplastic and neoplastic), osseous, and traumatic. In this paper, we discuss the key imaging features and differential diagnoses of congenital and developmental lesions (dermoid cyst, dermolipoma), infective and inflammatory pathologies (pre-septal cellulitis, orbital cellulitis, optic neuritis, chalazion, thyroid ophthalmopathy, orbital pseudotumor), and non-neoplastic vascular anomalies (venous malformation, lymphatic malformation, carotid-cavernous fistula), emphasizing the key role of CT and MRI in the imaging work-up. In addition, we highlight the adjunctive role of ocular ultrasound in the diagnosis of dermoid cyst and chalazion, and discuss the primary role of ultrasound in the diagnosis of vascular malformations.

Imaging findings and MRI patterns in a cohort of 18q chromosomal abnormalities.

BACKGROUND AND PURPOSE: The abnormalities of long arm of chromosome 18 (18q) constitute a complex spectrum. We aimed to systematically analyze their MRI features. We hypothesized that there would be variable but recognizable white matter and structural patterns in this cohort. MATERIALS AND METHODS: In this retrospective cohort study, we included pediatric patients with a proven abnormality of 18q between 2000-2022. An age and sex matched control cohort was also constructed. RESULTS: Thirty-six cases, median MRI age 19.6 months (4.3 - 59.3), satisfied our inclusion criteria. Majority were females (25, 69%, F:M ratio 2.2:1). Fifty MR imaging studies were analyzed and 35 (70%) had delayed myelination. Two independent readers scored brain myelination with excellent interrater reliability. Three recognizable evolving MRI patterns with distinct age distributions and improving myelination scores were identified - PMD-like (9.9 months, 37), intermediate (22 months, 48) and washed-out pattern (113.6 months, 53). Etiologically, MRIs were analyzed across three subgroups - 18q- (34, 69%), trisomy 18 (10, 21%) and ring chromosome 18 (5, 10%). Ring chromosome 18 had the highest myelination lag (27, P value = 0.005) and multifocal white matter changes (P value = 0.001). Trisomy 18 had smaller pons and cerebellar dimensions (APD pons P value = 0.002, CC vermis P value <0.001 and TCD P value = 0.04). CONCLUSIONS: In this cohort of 18q chromosomal abnormalities, MRI revealed recognizable patterns correlating with improving brain myelination. Imaging findings appear to be on a continuum with more severe white matter abnormalities in ring chromosome 18 and greater prevalence of structural abnormalities of pons and cerebellum in trisomy 18. ABBREVIATIONS: 18q-: 18q deletion; CC: corpus callosum; CC-APD: CC anteroposterior diameter; FOD: fronto-occipital diameter; TCD: transverse cerebellar diameter; APD: anteroposterior diameter; CCD: craniocaudal diameter; MBP: myelin basic protein; PMD: Pelizaeus-Merzbacher Disease; GWMD: gray-white matter differentiation.

Nasal monobloc osteotomy for correction of late nasal and orbital asymmetry of unicoronal synostosis: A morphometric and outcomes study.

BACKGROUND: Craniofacial asymmetry associated with unicoronal synostosis (UCS) may persist into the teenage years despite surgery in infancy. This study evaluated outcomes following a nasal monobloc procedure by mobilizing a united nasomaxillary and bilateral medial orbital segment of bone (nasal monobloc) to perform corrective translational and rotational movement for secondary correction of residual nasal-orbital asymmetry associated with UCS. METHODS: A retrospective review of all UCS patients treated with nasal monobloc at our institution was performed. Demographic information was recorded, and pre- and postoperative 2D imaging was used for morphometric outcome analysis. Outcomes and complications were tabulated. RESULTS: The study included 14 patients (5 males, 9 females; mean age 14.6 years; range 9.6 to 22.5 years; mean follow-up 70.6 months range 12 to 132 months). Ancillary procedures (scar revision, forehead/orbital contouring, MEDPOR® augmentation) were performed in all patients at the time of the nasal monobloc. One patient underwent a repeat procedure 6 years later following technique modification. Additionally, another patient experienced late overgrowth of the frontal sinus with forehead asymmetry. The morphometric analysis demonstrated significant (p < 0.05) pre-op to post-op improvements in naso-orbital asymmetry, as demonstrated by horizontal orbital aperture ratio (0.88 vs 0.99), midline to exocanthion ratio (0.91 vs 0.98), orbital index ratio (1.15 vs 1.01), and midline discrepancy (7.1 degrees vs 2.7 degrees). CONCLUSION: Nasal monobloc osteotomy provides a reasonable surgical treatment to improve both the nasal and orbital asymmetries associated with unicoronal synostosis, including frontal nasal deviation, basal nasal deviation, and orbital aperture asymmetry. It is important to note that confounding anatomic variables such as globe dystopia, strabismus, and scleral show may affect the perception of orbital symmetry.

Size and Location of Preterm Brain Injury and Associations With Neurodevelopmental Outcomes.

BACKGROUND AND OBJECTIVES: We examined associations of white matter injury (WMI) and periventricular hemorrhagic infarction (PVHI) volume and location with 18-month neurodevelopment in very preterm infants. METHODS: A total of 254 infants born <32 weeks' gestational age were prospectively recruited across 3 tertiary neonatal intensive care units (NICUs). Infants underwent early-life (median 33.1 weeks) and/or term-equivalent-age (median 41.9 weeks) MRI. WMI and PVHI were manually segmented for quantification in 92 infants. Highest maternal education level was included as a marker of socioeconomic status and was defined as group 1 = primary/secondary school; group 2 = undergraduate degree; and group 3 = postgraduate degree. Eighteen-month neurodevelopmental assessments were completed with Bayley Scales of Infant and Toddler Development, Third Edition. Adverse outcomes were defined as a score of less than 85 points. Multivariable linear regression models were used to examine associations of brain injury (WMI and PVHI) volume with neurodevelopmental outcomes. Voxel-wise lesion symptom maps were developed to assess relationships between brain injury location and neurodevelopmental outcomes. RESULTS: Greater brain injury volume was associated with lower 18-month Motor scores (ß = -5.7, 95% CI -9.2 to -2.2, p = 0.002) while higher maternal education level was significantly associated with higher Cognitive scores (group 3 compared 1: ß = 14.5, 95% CI -2.1 to 26.9, p = 0.03). In voxel-wise lesion symptom maps, brain injury involving the central and parietal white matter was associated with an increased risk of poorer motor outcomes. DISCUSSION: We found that brain injury volume and location were significant predictors of motor, but not cognitive outcomes, suggesting that different pathways may mediate outcomes across domains of neurodevelopment in preterm infants. Specifically, assessing lesion size and location may allow for more accurate identification of infants with brain injury at highest risk of poorer motor outcomes. These data also highlight the importance of socioeconomic status in cognitive outcomes, even in preterm infants with brain injury.

Pain Exposure and Brain Connectivity in Preterm Infants.

Importance: Early-life exposure to painful procedures has been associated with altered brain maturation and neurodevelopmental outcomes in preterm infants, although sex-specific differences are largely unknown. Objective: To examine sex-specific associations among early-life pain exposure, alterations in neonatal structural connectivity, and 18-month neurodevelopment in preterm infants. Design, Setting, and Participants: This prospective cohort study recruited 193 very preterm infants from April 1, 2015, to April 1, 2019, across 2 tertiary neonatal intensive care units in Toronto, Canada. Structural connectivity data were available for 150 infants; neurodevelopmental outcomes were available for 123 infants. Data were analyzed from January 1, 2022, to December 31, 2023. Exposure: Pain was quantified in the initial weeks after birth as the total number of invasive procedures. Main Outcome and Measure: Infants underwent early-life and/or term-equivalent-age magnetic resonance imaging with diffusion tensor imaging to quantify structural connectivity using graph theory measures and regional connection strength. Eighteen-month neurodevelopmental outcomes were assessed with the Bayley Scales of Infant and Toddler Development, Third Edition. Stratifying by sex, generalized estimating equations were used to assess whether pain exposure modified the maturation of structural connectivity using an interaction term (early-life pain exposure × postmenstrual age [PMA] at scan). Generalized estimating equations were used to assess associations between structural connectivity and neurodevelopmental outcomes, adjusting for extreme prematurity and maternal education. Results: A total of 150 infants (80 [53%] male; median [IQR] gestational age at birth, 27.1 [25.4-29.0] weeks) with structural connectivity data were analyzed. Sex-specific associations were found between early-life pain and neonatal brain connectivity in female infants only, with greater early-life pain exposure associated with slower maturation in global efficiency (pain × PMA at scan interaction P = .002) and local efficiency (pain × PMA at scan interaction P = .005). In the full cohort, greater pain exposure was associated with lower global efficiency (coefficient, -0.46; 95% CI, -0.78, to -0.15; P = .004) and local efficiency (coefficient, -0.57; 95% CI, -1.04 to -0.10; P = .02) and regional connection strength. Local efficiency (coefficient, 0.003; 95% CI, 0.001-0.004; P = .005) and regional connection strength in the striatum were associated with cognitive outcomes. Conclusions and Relevance: In this cohort study of very preterm infants, greater exposure to early-life pain was associated with altered maturation of neonatal structural connectivity, particularly in female infants. Alterations in structural connectivity were associated with neurodevelopmental outcomes, with potential regional specificities.

Early nutritional influences on brain regions related to processing speed in children born preterm: A secondary analysis of a randomized trial.

BACKGROUND: Processing speed is a foundational skill supporting intelligence and executive function, areas often delayed in preterm-born children. The impact of early-life nutrition on gray matter facilitating processing speed for this vulnerable population is unknown. METHODS: Magnetic resonance imaging and the Wechsler Preschool and Primary Scale of Intelligence-IV Processing Speed Index were acquired in forty 5-year-old children born preterm with very low birth weight. Macronutrient (grams per kilogram per day) and mother's milk (percentage of feeds) intakes were prospectively collected in the first postnatal month and associations between early-life nutrition and the primary outcome of brain regions supporting processing speed were investigated. RESULTS: Children had a mean (SD) gestational age of 27.8 (1.8) weeks and 45% were male. Macronutrient intakes were unrelated, but mother's milk was positively related, to greater volumes in brain regions, including total cortical gray matter, cingulate gyri, and occipital gyri. CONCLUSION: First postnatal month macronutrient intakes showed no association, but mother's milk was positively associated, with volumetric measures of total and regional cortical gray matter related to processing speed in preterm-born children. This exploratory analysis suggests early-life mother's milk supports processing speed by impacting structural underpinnings. Further research is needed on this potential strategy to improve preterm outcomes.

Socioeconomic status moderates associations between hippocampal development and cognition in preterms.

OBJECTIVE: The hippocampus plays a critical role in cognitive networks. The anterior hippocampus is vulnerable to early-life stress and socioeconomic status (SES) with alterations persisting beyond childhood. How SES modifies the relationship between early hippocampal development and cognition remains poorly understood. This study examined associations between SES, structural and functional development of neonatal hippocampus, and 18-month cognition in very preterm neonates. METHODS: In total, 179 preterm neonates were followed prospectively. Structural and resting-state functional MRI were obtained early-in-life and at term-equivalent age (median 32.9 and 41.1 weeks post-menstrual age) to calculate anterior and posterior hippocampal volumes and hippocampal functional connectivity strength. Eighteen-month cognition was assessed via Bayley-III. Longitudinal statistical analysis using generalized estimating equations, accounting for birth gestational age, post-menstrual age at scan, sex, and motion, was performed. RESULTS: SES, measured as maternal education level, modified associations between anterior but not posterior hippocampal volumes and 18-month cognition (interaction term p = 0.005), and between hippocampal connectivity and cognition (interaction term p = 0.05). Greater anterior hippocampal volumes and hippocampal connectivity were associated with higher cognitive scores only in the lowest SES group. Maternal education alone did not predict neonatal hippocampal volume from early-in-life and term. INTERPRETATION: SES modified the relationship between neonatal hippocampal development and 18-month cognition in very preterm neonates. The lack of direct association between maternal education and neonatal hippocampal volumes indicates that socio-environmental factors beyond the neonatal period contribute to modifying the relationship between hippocampal development and cognition. These findings point toward opportunities to more equitably promote optimal neurodevelopmental outcomes in very preterm infants.