The effect of live music therapy on white matter microstructure in very preterm infants - A randomized controlled trial.

OBJECTIVE: Music therapy (MT) is proposed to enrich the acoustic environment of very preterm infants (VPT) on the neonatal intensive care unit during a vulnerable period of brain development. The objective of this study was to investigate the effect of MT on the white matter (WM) microstructure. It is hypothesized that MT affects WM integrity in VPT. METHODS: Randomized controlled trial enrolling infants born <32 weeks' gestation. Infants were randomized to MT or standard care. Live MT was provided twice weekly from the second postnatal week onwards by a trained music therapist. At term equivalent age, participants underwent a cranial magnetic resonance imaging scan including sequences for diffusion tensor imaging analysis. Differences in WM microstructure were assessed using tract based spatial statistics with fractional anisotropy. RESULTS: Of 80 infants enrolled, 42 were eligible for diffusion tensor imaging analysis (MT: n = 22, standard care: n = 20). While primary tract based spatial statistics analysis revealed no significant differences between groups, post hoc analysis with uncorrected p-values and a significance threshold of p < 0.01 revealed significant fractional anisotropy differences in several WM tracts including the bilateral superior longitudinal fasciculus, the left forceps minor and left fasciculus uncinatus, the corpus callosum, the left external capsule, and the right corticospinal tract. CONCLUSION: Post hoc analysis results suggest an effect of MT on WM integrity in VPT. Larger studies including long-term outcome are necessary to confirm these effects of MT on WM microstructure and to assess its impact on clinical neurodevelopment. CLINICAL TRIAL REGISTRATION: Clinical trial number DRKS00025753.

Incidence of brain injuries in a large cohort of very preterm and extremely preterm infants at term-equivalent age: results of a single tertiary neonatal care center over 10 years.

OBJECTIVES: Cerebral magnetic resonance imaging (cMRI) at term-equivalent age (TEA) can detect brain injury (BI) associated with adverse neurological outcomes in preterm infants. This study aimed to assess BI incidences in a large, consecutive cohort of preterm infants born < 32 weeks of gestation, the comparison between very (VPT, ≥ 28 + 0 to < 32 + 0 weeks of gestation) and extremely preterm infants (EPT, < 28 + 0 weeks of gestation) and across weeks of gestation. METHODS: We retrospectively analyzed cMRIs at TEA of VPT and EPT infants born at a large tertiary center (2009-2018). We recorded and compared the incidences of BI, severe BI, intraventricular hemorrhage (IVH), periventricular hemorrhagic infarction (PVHI), cerebellar hemorrhage (CBH), cystic periventricular leukomalacia (cPVL), and punctate white matter lesions (PWML) between VPTs, EPTs, and across weeks of gestation. RESULTS: We included 507 preterm infants (VPT, 335/507 (66.1%); EPT, 172/507 (33.9%); mean gestational age (GA), 28 + 2 weeks (SD 2 + 2 weeks); male, 52.1%). BIs were found in 48.3% of the preterm infants (severe BI, 12.0%) and increased with decreasing GA. IVH, PVHI, CBH, cPVL, and PWML were seen in 16.8%, 0.8%, 10.5%, 3.4%, and 18.1%, respectively. EPT vs. VPT infants suffered more frequently from BI (59.3% vs. 42.7%, p < 0.001), severe BI (18.6% vs. 8.7%, p = 0.001), IVH (31.9% vs. 9.0%, p < 0.001), and CBH (18.0% vs. 6.6%, p < 0.001). CONCLUSION: Brain injuries are common cMRI findings among preterm infants with a higher incidence of EPT compared to VPT infants. These results may serve as reference values for clinical management and research. CLINICAL RELEVANCE STATEMENT: Our results with regard to gestational age might provide valuable clinical insights, serving as a key reference for parental advice, structured follow-up planning, and enhancing research and management within the Neonatal Intensive Care Unit. KEY POINTS: • Brain injury is a common cMRI finding in preterm infants seen in 48.3% individuals. • Extremely preterm compared to very preterm infants have higher brain injury incidences driven by brain injuries such as intraventricular and cerebellar hemorrhage. • Reference incidence values are crucial for parental advice and structured follow-up planning.

European Society of Pediatric Radiology survey of perioperative imaging in pediatric liver transplantation: (3) postoperative imaging.

BACKGROUND: Liver transplantation is the state-of-the-art curative treatment for end-stage liver disease. Imaging is a key element in the detection of postoperative complications. So far, limited data is available regarding the best radiologic approach to monitor children after liver transplantation. OBJECTIVE: To harmonize the imaging of pediatric liver transplantation, the European Society of Pediatric Radiology Abdominal Taskforce initiated a survey addressing the current status of imaging including the pre-, intra-, and postoperative phases. This paper reports the responses related to postoperative imaging. MATERIALS AND METHODS: An online survey, initiated in 2021, asked European centers performing pediatric liver transplantation 48 questions about their imaging approach. In total, 26 centers were contacted, and 22 institutions from 11 countries returned the survey. RESULTS: All sites commence ultrasound (US) monitoring within 24 h after liver transplantation. Monitoring frequency varies across sites, ranging from every 8 h to 72 h in early, and from daily to sporadic use in late postoperative phases. Predefined US protocols are used by 73% of sites. This commonly includes gray scale, color Doppler, and quantitative flow assessment. Alternative flow imaging techniques, contrast-enhanced US, and elastography are applied at 31.8%, 18.2%, and 63.6% of sites, respectively. Computed tomography is performed at 86.4% of sites when clarification is needed. Magnetic resonance imaging is used for selected cases at 36.4% of sites, mainly for assessment of biliary abnormalities or when blood tests are abnormal. CONCLUSION: Diagnostic imaging is extensively used for postoperative surveillance of children after liver transplantation. While US is generally prioritized, substantial differences were noted in US protocol, timing, and monitoring frequency. The study highlights potential areas for future optimization and standardization of imaging, essential for conducting multicenter studies.

European Society of Pediatric Radiology survey of perioperative imaging in pediatric liver transplantation: (2) intraoperative imaging.

BACKGROUND: Liver transplantation is the state-of-the-art curative treatment for end-stage liver disease. Imaging is a key element in the detection of intraoperative and postoperative complications. So far, only limited data regarding the best radiological approach to monitor children during liver transplantation is available. OBJECTIVE: To harmonize the imaging of pediatric liver transplantation, the European Society of Pediatric Radiology Abdominal Taskforce initiated a survey addressing the current status of imaging including the pre-, intra- and postoperative phase. This paper reports the responses related to intraoperative imaging. MATERIALS AND METHODS: An online survey, initiated in 2021, asked European centers performing pediatric liver transplantation 48 questions about their imaging approach. In total, 26 centers were contacted, and 22 institutions from 11 countries returned the survey. RESULTS: Intraoperative ultrasound (US) is used by all sites to assess the quality of the vascular anastomosis in order to ensure optimal perfusion of the liver transplant. Vessel depiction is commonly achieved using color Doppler (95.3%). Additional US-based techniques are employed by fewer centers (power angio mode, 28.6%; B-flow, 19%; contrast-enhanced US, 14.3%). Most centers prefer a collaborative approach, with surgeons responsible for probe handling, while radiologists operate the US machine (47.6%). Less commonly, the intraoperative US is performed by the surgeon alone (28.6%) or by the radiologist alone (23.8%). Timing of US, imaging frequency, and documentation practices vary among centers. CONCLUSION: Intraoperative US is consistently utilized across all sites during pediatric liver transplantation. However, considerable variations were observed in terms of the US setup, technique preferences, timing of controls, and documentation practices. These differences provide valuable insights for future optimization and harmonization studies.

European Society of Pediatric Radiology survey of perioperative imaging in pediatric liver transplantation: (1) pre-transplant evaluation.

BACKGROUND: Liver transplantation is the state-of-the-art curative treatment in end-stage liver disease. Imaging is a key element for successful organ-transplantation to assist surgical planning. So far, only limited data regarding the best radiological approach to prepare children for liver transplantation is available. OBJECTIVES: In an attempt to harmonize imaging surrounding pediatric liver transplantation, the European Society of Pediatric Radiology (ESPR) Abdominal Taskforce initiated a survey addressing the current status of imaging including the pre-, intra-, and postoperative phase. This paper reports the responses on preoperative imaging. MATERIAL AND METHODS: An online survey, initiated in 2021, asked European centers performing pediatric liver transplantation 48 questions about their imaging approach. In total, 26 centers were contacted and 22 institutions from 11 countries returned the survey. From 2018 to 2020, the participating centers collectively conducted 1,524 transplantations, with a median of 20 transplantations per center per annum (range, 8-60). RESULTS: Most sites (64%) consider ultrasound their preferred modality to define anatomy and to plan surgery in children before liver transplantation, and additional cross-sectional imaging is only used to answer specific questions (computed tomography [CT], 90.9%; magnetic resonance imaging [MRI], 54.5%). One-third of centers (31.8%) rely primarily on CT for pre-transplant evaluation. Imaging protocols differed substantially regarding applied CT scan ranges, number of contrast phases (range 1-4 phases), and applied MRI techniques. CONCLUSION: Diagnostic imaging is generally used in the work-up of children before liver transplantation. Substantial differences were noted regarding choice of modalities and protocols. We have identified starting points for future optimization and harmonization of the imaging approach to multicenter studies.

[18F]FDG PET/MRI in children suffering from lymphoma: does MRI contrast media make a difference?

OBJECTIVES: Evaluate the influence of an MRI contrast agent application on primary and follow-up staging in pediatric patients with newly diagnosed lymphoma using [18F]FDG PET/MRI to avoid adverse effects and save time and costs during examination. METHODS: A total of 105 [18F]FDG PET/MRI datasets were included for data evaluation. Two different reading protocols were analyzed by two experienced readers in consensus, including for PET/MRI-1 reading protocol unenhanced T2w and/or T1w imaging, diffusion-weighted imaging (DWI), and [18F]FDG PET imaging and for PET/MRI-2 reading protocol an additional T1w post contrast imaging. Patient-based and region-based evaluation according to the revised International Pediatric Non-Hodgkin's Lymphoma (NHL) Staging System (IPNHLSS) was performed, and a modified standard of reference was applied comprising histopathology and previous and follow-up cross-sectional imaging. Differences in staging accuracy were assessed using the Wilcoxon and McNemar tests. RESULTS: In patient-based analysis, PET/MRI-1 and PET/MRI-2 both determined a correct IPNHLSS tumor stage in 90/105 (86%) exams. Region-based analysis correctly identified 119/127 (94%) lymphoma-affected regions. Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for PET/MRI-1 and PET/MRI-2 were 94%, 97%, 90%, 99%, 97%, respectively. There were no significant differences between PET/MRI-1 and PET/MRI-2. CONCLUSIONS: The use of MRI contrast agents in [18F]FDG PET/MRI examinations has no beneficial effect in primary and follow-up staging of pediatric lymphoma patients. Therefore, switching to a contrast agent-free [18F]FDG PET/MRI protocol should be considered in all pediatric lymphoma patients. CLINICAL RELEVANCE STATEMENT: This study gives a scientific baseline switching to a contrast agent-free [18F]FDG PET/MRI staging in pediatric lymphoma patients. This could avoid side effects of contrast agents and saves time and costs by a faster staging protocol for pediatric patients. KEY POINTS: • No additional diagnostic benefit of MRI contrast agents at [18F]FDG PET/MRI examinations of pediatric lymphoma primary and follow-up staging • Highly accurate primary and follow-up staging of pediatric lymphoma patients at MRI contrast-free [18F]FDG PET/MRI.

Utility of Integrated PET/MRI for the Primary Diagnostic Work-Up of Patients with Ewing Sarcoma: Preliminary Results.

BACKGROUND: This study was conducted to evaluate the clinical applicability of integrated PET/MRI for staging and monitoring the effectiveness of neoadjuvant chemotherapy in Ewing sarcoma patients. METHODS: A total of 11 juvenile patients with confirmed Ewing sarcoma, scheduled for induction polychemotherapy, were prospectively enrolled for a PET/MR examination before, during and after the end of treatment. Two experienced physicians analysed the imaging datasets. They were asked to perform a whole-body staging in all three examinations and to define treatment response according to the RECIST1.1 and PERCIST criteria for each patient. RESULTS: In eight patients lymph node and/or distant metastases were detected at initial diagnosis. According to the reference standard, three patients achieved complete response, six patients partial response, and one patient showed stable disease while another patient showed progressive disease. RECIST1.1 categorized the response to treatment in 5/11 patients correctly and showed a tendency to underestimate the response to treatment in the remaining six patients. PERCIST defined response to treatment in 9/11 patients correctly and misclassified two patients with a PR as CR. CONCLUSION: PET/MRI may serve as a valuable imaging tool for primary staging and response assessment of juvenile patients with Ewing sarcoma to induction chemotherapy, accompanied by a reasonable radiation dose for the patient.

[Imaging of retinoblastoma : Current state-of-the-art and future prospects]. / Bildgebung des Retinoblastoms : Aktueller Stand der Technik und Ausblick in die Zukunft.

BACKGROUND: Retinoblastoma is the most common malignant eye tumor in children and is associated with tumor predisposition syndrome (RB1 mutation) in up to 40% of cases. Imaging is an important part of the diagnostic workup of children with retinoblastoma both during the initial diagnosis and follow-up. OBJECTIVES: The goal of this review is to present the current state-of-the-art regarding imaging of children with retinoblastoma, including technical background and diagnostic clues with a brief discussion of future prospects. In addition, we summarize the general clinical diagnostic workup and therapeutic options. MATERIALS AND METHODS: Review of the literature and our own experience in the imaging of retinoblastoma. CONCLUSION: High-resolution magnetic resonance imaging (MRI) is the imaging modality of choice in children with retinoblastoma for diagnosis (estimation of diagnosis/differential diagnosis, evaluation of local and intracranial tumor extension) and during follow-up. Despite the characteristic calcifications, computed tomography (CT) examinations are no longer indicated in these patients. Due to the high association with tumor predisposition syndrome, genetic counselling is recommended.

Diagnostic reference levels for chest computed tomography in children as a function of patient size.

BACKGROUND: Radiation exposures from computed tomography (CT) in children are inadequately studied. Diagnostic reference levels (DRLs) can help optimise radiation doses. OBJECTIVE: To determine local DRLs for paediatric chest CT performed mainly on modern dual-source, multi-slice CT scanners as a function of patient size. MATERIALS AND METHODS: Five hundred thirty-eight chest CT scans in 345 children under 15 years (y) of age (median age: 8 y, interquartile range [IQR]: 4-13 y) performed on four different CT scanners (38% on third-generation and 43% on second-generation dual-source CT) between November 2013 and December 2020 were retrospectively analysed. Examinations were grouped by water-equivalent diameter as a measure of patient size. DRLs for volume CT dose index (CTDIvol) and dose-length product (DLP) were determined for six different patient sizes and compared to national and European DRLs. RESULTS: The DRLs for CTDIvol and DLP are determined for each patient size group as a function of water-equivalent diameter as follows: (I) < 13 cm (n = 22; median: age 7 months): 0.4 mGy, 7 mGy·cm; (II) 13 cm to less than 17 cm (n = 151; median: age 3 y): 1.2 mGy, 25 mGy·cm; (III) 17 cm to less than 21 cm (n = 211; median: age 8 y): 1.7 mGy, 44 mGy·cm; (IV) 21 cm to less than 25 cm (n = 97; median: age 14 y): 3.0 mGy, 88 mGy·cm; (V) 25 cm to less than 29 cm (n = 42; median: age 14 y): 4.5 mGy, 135 mGy·cm; (VI) ≥ 29 cm (n = 15; median: age 14 y): 8.0 mGy, 241 mGy·cm. Compared with corresponding age and weight groups, our size-based DRLs for DLP are 54% to 71% lower than national and 23% to 85% lower than European DRLs. CONCLUSION: We developed DRLs for paediatric chest CT as a function of patient size with substantially lower values than national and European DRLs. Precise knowledge of size-based DRLs may assist other institutions in further dose optimisation in children.

A de novo CSDE1 variant causing neurodevelopmental delay, intellectual disability, neurologic and psychiatric symptoms in a child of consanguineous parents.

CSDE1 encodes the cytoplasmic cold shock domain-containing protein E1 (CSDE1), which is highly conserved across species and functions as an RNA-binding protein involved in translationally coupled mRNA turnover. CSDE1 displays a bidirectional role: promoting and repressing the translation of RNAs but also increasing and decreasing the abundance of RNAs. Preclinical studies highlighted an involvement of CSDE1 in different forms of cancer. Moreover, CSDE1 is highly expressed in human embryonic stem cells and plays a role in neuronal migration and differentiation. A genome-wide association study suggested CSDE1 as a potential autism-spectrum disorder risk gene. A multicenter next generation sequencing approach unraveled likely causative heterozygous variants in CSDE1 in 18 patients, identifying a new autism spectrum disorder-related syndrome consisting of autism, intellectual disability, and neurodevelopmental delay. Since then, no further patients with CSDE1 variants have been reported in the literature. Here, we report a 9.5-year-old girl from a consanguineous family of Turkish origin suffering from profound delayed speech and motor development, moderate intellectual disability, neurologic and psychiatric symptoms as well as hypoplasia of corpus callosum and mildly reduced brain volume on brain magnetic resonance imaging associated with a recurrent de novo mutation in CSDE1 (c.367C > T; p.R123*) expanding the phenotypical spectrum associated with pathogenic CSDE1 variants.

Clinical Course, Myopathology and Challenge of Therapeutic Intervention in Pediatric Patients with Autoimmune-Mediated Necrotizing Myopathy.

(1) Background: Immune-mediated necrotizing myopathy (IMNM) is a rare form of inflammatory muscle disease which is even more rare in pediatric patients. To increase the knowledge of juvenile IMNM, we here present the clinical findings on long-term follow-up, myopathological changes, and therapeutic strategies in two juvenile patients. (2) Methods: Investigations included phenotyping, determination of antibody status, microscopy on muscle biopsies, MRI, and response to therapeutic interventions. (3) Results: Anti-signal recognition particle (anti-SRP54) and anti- 3-hydroxy-3-methylglutarly coenzyme A reductase (anti-HMGCR) antibodies (Ab) were detected in the patients. Limb girdle presentation, very high CK-levels, and a lack of skin rash at disease-manifestation and an absence of prominent inflammatory signs accompanied by an abnormal distribution of α-dystroglycan in muscle biopsies initially hinted toward a genetically caused muscle dystrophy. Further immunostaining studies revealed an increase of proteins involved in chaperone-assisted autophagy (CASA), a finding already described in adult IMNM-patients. Asymmetrical muscular weakness was present in the anti-SRP54 positive Ab patient. After initial stabilization under therapy with intravenous immunoglobulins and methotrexate, both patients experienced a worsening of their symptoms and despite further therapy escalation, developed a permanent reduction of their muscle strength and muscular atrophy. (4) Conclusions: Diagnosis of juvenile IMNM might be complicated by asymmetric muscle weakness, lack of cutaneous features, absence of prominent inflammatory changes in the biopsy, and altered α-dystroglycan.

Expansion of the mutational spectrum of BMPER leading to diaphanospondylodysostosis and description of the associated disease process.

BACKGROUND: Diaphanospondylodysostosis (DSD) is a rare congenital, lethal skeletal disorder caused by recessively inherited mutations in the BMPER gene, which encodes the bone morphogenetic protein-binding endothelial cell precursor-derived regulator. The most prominent features of DSD are missing ossification of the axial skeleton, rib abnormalities and thoracic hypoplasia/insufficiency, as well as intralobar nephrogenic rests within the kidneys. METHODS: We report on the case of a 22-month-old patient with DSD where trio-exome sequencing was performed. RESULTS: Genetic testing revealed a homozygous nonsense variant c.1577G>A (p.Trp526*) in the BMPER gene, leading to a premature stop in protein translation. Both parents are asymptomatic carriers for the BMPER variant, which has not been described in the literature before. CONCLUSIONS: Our findings expand the genotypic and phenotypic spectrum of BMPER variants leading to DSD.

Further evidence for POMK as candidate gene for WWS with meningoencephalocele.

BACKGROUND: Walker-Warburg syndrome (WWS) is a rare form of alpha-dystroglycanopathy characterized by muscular dystrophy and severe malformations of the CNS and eyes. Bi-allelic pathogenic variants in POMK are the cause of a broad spectrum of alpha-dystroglycanopathies. POMK encodes protein-O-mannose kinase, which is required for proper glycosylation and function of the dystroglycan complex and is crucial for extracellular matrix composition. RESULTS: Here, we report on male monozygotic twins with severe CNS malformations (hydrocephalus, cortical malformation, hypoplastic cerebellum, and most prominently occipital meningocele), eye malformations and highly elevated creatine kinase, indicating the clinical diagnosis of a congenital muscular dystrophy (alpha-dystroglycanopathy). Both twins were found to harbor a homozygous nonsense mutation c.640C>T, p.214* in POMK, confirming the clinical diagnosis and supporting the concept that POMK mutations can be causative of WWS. CONCLUSION: Our combined data suggest a more important role for POMK in the pathogenesis of meningoencephalocele. Only eight different pathogenic POMK variants have been published so far, detected in eight families; only five showed the severe WWS phenotype, suggesting that POMK-associated WWS is an extremely rare disease. We expand the phenotypic and mutational spectrum of POMK-associated WWS and provide evidence of the broad phenotypic variability of POMK-associated disease.

Are Simple Magnetic Resonance Imaging Biomarkers Predictive of Neurodevelopmental Outcome at Two Years in Very Preterm Infants?

BACKGROUND: Preterm infants are at increased risk of neurodevelopmental impairment due to the vulnerability of the immature brain. Early risk stratification is necessary for predicting outcome in the period of highest neuroplasticity. Several biomarkers in magnetic resonance imaging (MRI) at term equivalent age (TEA) have therefore been suggested. OBJECTIVE: To assess the predictive value of simple brain metrics and the total abnormality score (TAS) - a modified score for brain injury and growth - in relation to neurodevelopmental outcome of very preterm infants in MRI at TEA. METHODS: Single-centre cohort study including preterm infants with gestational age (GA) ≤32 weeks and birth weight ≤1,500 g. Biparietal width (BPW), interhemispheric distance, transcerebellar diameter (TCD) and TAS were assessed. To detect subtle haemorrhages, additional susceptibility-weighted imaging (SWI) was used in addition to conventional MRI to evaluate its clinical relevance. Neurodevelopment was tested by the Mental and Psychomotor Developmental Index (MDI/PDI) of the Bayley Scales of Infant Development II at a corrected age of 24 months. RESULTS: One hundred twenty-nine children with median GA of 28.1 weeks and median birth weight of 980 g were included. BPW significantly correlated with PDI (p= 0.01, R2 = 0.06) and TCD with MDI (p < 0.01, R2 = 0.05) and PDI (p < 0.01, R2 = 0.06) but explained variances were low. TAS was not predictive of neurodevelopmental outcome. By using SWI, additional 4 cases of low grade haemorrhages were identified compared to conventional sequences. In one case this additional information was clinically relevant (MDI/PDI below average). CONCLUSION: Simple brain metrics and TAS did not reliably predict neurodevelopmental outcome in a cohort with low prevalence of high grade brain injury. The additional value of SWI is yet to be determined in larger cohorts. The combination of imaging and functional biomarkers may be advisable for the prediction of neurodevelopmental outcome.

Relationship between brain function (aEEG) and brain structure (MRI) and their predictive value for neurodevelopmental outcome of preterm infants.

To improve the prediction of neurodevelopmental outcome in very preterm infants, this study used the combination of amplitude-integrated electroencephalography (aEEG) within the first 72 h of life and cranial magnetic resonance imaging (MRI) at term equivalent age. A single-center cohort of 38 infants born before 32 weeks of gestation was subjected to both investigations. Structural measurements were performed on MRI. Multiple regression analysis was used to identify independent factors including functional and structural brain measurements associated with outcome at a corrected age of 24 months. aEEG parameters significantly correlated with MRI measurements. Reduced deep gray matter volume was associated with low Burdjalov Score on day 3 (p < 0.0001) and day 1-3 (p = 0.0012). The biparietal width and the transcerebellar diameter were related to Burdjalov Score on day 1 (p = 0.0111; p = 0.0002). The final multiple regression analysis revealed independent predictors of neurodevelopmental outcome: intraventricular hemorrhage (p = 0.0060) and interhemispheric distance (p = 0.0052) for mental developmental index; Burdjalov Score day 1 (p = 0.0201) and interhemispheric distance (p = 0.0142) for psychomotor developmental index. CONCLUSION: Functional aEEG parameters were associated with altered brain maturation on MRI. The combination of aEEG and MRI contributes to the prediction of outcome at 24 months. What is Known: • Prematurity remains a risk factor for impaired neurodevelopment. • aEEG is used to measure brain activity in preterm infants and cranial MRI is performed to identify structural gray and white matter abnormalities with impact on neurodevelopmental outcome. What is New: • aEEG parameters observed within the first 72 h of life were associated with altered deep gray matter volumes, biparietal width, and transcerebellar diameter at term equivalent age. • The combination of aEEG and MRI contributes to the prediction of neurodevelopmental outcome at 2 years of corrected age in very preterm infants.

Spectral Beam Shaping in Unenhanced Chest CT Examinations: A Phantom Study on Dose Reduction and Image Quality.

RATIONALE AND OBJECTIVES: This study aimed to determine the optimal tube potential for unenhanced chest computed tomographies (CTs) with age-related phantoms. MATERIALS AND METHODS: Three physical anthropomorphic phantoms (newborn, 5-year-old child, and adult) were scanned on a third-generation dual-source CT using CAREkV in semi-mode and CAREDose4D (ref. KV: 120; ref. mAs 50). Scans were performed with all available tube potentials (70-150 kV and Sn150 kV). The lowest volume computed tomography dose index (CTDIvol) was selected to perform additional Sn100-kV scans with matched and half (Sn100-half) CTDIvol value. Image quality was evaluated on the basis of contrast-to-noise ratio (CNR). RESULTS: For the newborn phantom, 70-110 kV was selected as the optimal range (0.36-0.37 mGy). Using Sn150 kV led to an increase in radiation dose (0.75 mGy) without improving CNR (96.9 vs 101.5). Sn100-half showed a decrease in CNR (73.1 vs 101.5). The lowest CTDIvol for the child phantom was achieved between 100 and 120 kV (0.78-0.80 mGy). Using Sn150 kV increased radiation dose (1.02 mGy) without improvement of CNR (92.4 vs 95.8). At Sn100-half CNR was decreased (61.4 vs 95.8). For adults, 140 and 150 kV revealed the lowest CTDIvol (2.68 and 2.67 mGy). The Sn150 kV scan delivered comparable CNR (54.4 vs 56.6), but a lower CTDIvol (2.08 mGy). At Sn100-half CNR was comparable to the 150 kV scan (58.1 vs 56.6). CONCLUSION: Unenhanced chest CT performed at 100 kV or 150 kV with tin filtration enables radiation dose reduction for the adult phantom, but not for the pediatric phantoms.

Cerebellar-dependent associative learning is impaired in very preterm born children and young adults.

Preterm birth incorporates an increased risk for cerebellar developmental disorders likely contributing to motor and cognitive abnormalities. Experimental evidence of cerebellar dysfunction in preterm subjects, however, is sparse. In this study, classical eyeblink conditioning was used as a marker of cerebellar dysfunction. Standard delay conditioning was investigated in 20 adults and 32 preschool children born very preterm. Focal lesions were excluded based on structural magnetic resonance imaging. For comparison, an equal number of matched term born healthy peers were tested. Subgroups of children (12 preterm, 12 controls) were retested. Preterm subjects acquired significantly less conditioned responses (CR) compared to controls with slower learning rates. A likely explanation for these findings is that preterm birth impedes function of the cerebellum even in the absence of focal cerebellar lesions. The present findings are consistent with the assumption that prematurity results in long-term detrimental effects on the integrity of the cerebellum. It cannot be excluded, however, that extra-cerebellar pathology contributed to the present findings.

Imaging children suffering from lymphoma: an evaluation of different 18F-FDG PET/MRI protocols compared to whole-body DW-MRI.

OBJECTIVES: The objectives of this study were to evaluate and compare the diagnostic potential of different PET/MRI reading protocols, entailing non-enhanced / contrast-enhanced and diffusion-weighted 18F-FDG PET/MR imaging and whole-body diffusion-weighted MRI for lesion detection and determination of the tumor stage in pediatric lymphoma patients. METHODS: A total of 28 18F-FDG PET/MRI datasets were included for analysis of four different reading protocols: (1) PET/MRI utilizing sole unenhanced T2w and T1w imaging, (2) PET/MRI utilizing additional contrast enhanced sequences, (3) PET/MR imaging utilizing unenhanced, contrast enhanced and DW imaging or (4) WB-DW-MRI. Statistical analyses were performed on a per-patient and a per-lesion basis. Follow-up and prior examinations as well as histopathology served as reference standards. RESULTS: PET/MRI correctly identified all 17 examinations with active lymphoma disease, while WB-DW-MRI correctly identified 15/17 examinations. Sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy were 96%, 96.5%, 97%, 95%, and 96% for PET/MRI1; 97%, 96.5%, 97%, 96.5%, and 97% for PET/MRI2; 97%, 96.5%, 97%, 96.5%, and 97% for PET/MRI3 and 77%, 96%, 96%, 78.5% and 86% for MRI-DWI. CONCLUSION: 18F-FDG PET/MRI is superior to WB-DW-MRI in staging pediatric lymphoma patients. Neither application of contrast media nor DWI leads to a noticeable improvement of the diagnostic accuracy of PET/MRI. Thus, unenhanced PET/MRI may play a crucial role for the diagnostic work-up of pediatric lymphoma patients in the future.

Loss of Functional Osteoprotegerin: More Than a Skeletal Problem.

Introduction: Juvenile Paget's disease (JPD), an ultra-rare, debilitating bone disease due to loss of functional osteoprotegerin (OPG), is caused by recessive mutations in TNFRFSF11B. A genotype-phenotype correlation spanning from mild to very severe forms is described. Aim: This study aimed to describe the complexity of the human phenotype of OPG deficiency in more detail and to investigate heterozygous mutation carriers for clinical signs of JPD. Patients: We investigated 3 children with JPD from families of Turkish, German, and Pakistani descent and 19 family members (14 heterozygous). Results: A new disease-causing 4 bp-duplication in exon 1 was detected in the German patient, and a microdeletion including TNFRFSF11B in the Pakistani patient. Skeletal abnormalities in all affected children included bowing deformities and fractures, contractures, short stature and skull involvement. Complex malformation of the inner ear and vestibular structures (2 patients) resulted in early deafness. Patients were found to be growth hormone deficient (2), displayed nephrocalcinosis (1), and gross motor (3) and mental (1) retardation. Heterozygous family members displayed low OPG levels (12), elevated bone turnover markers (7), and osteopenia (6). Short stature (1), visual impairment (2), and hearing impairment (1) were also present. Conclusion: Diminished OPG levels cause complex changes affecting multiple organ systems, including pituitary function, in children with JPD and may cause osteopenia in heterozygous family members. Diagnostic and therapeutic measures should aim to address the complex phenotype.