Initial clinical experience with high-pitch dual-source CT as a rapid technique for thoraco-abdominal evaluation in awake infants and young children.

AIM: To evaluate dual-source high-pitch computed tomography (HPCT) imaging of the chest and abdomen as a rapid scanning technique to obtain diagnostic-quality imaging evaluation of infants and young children without sedation. MATERIALS AND METHODS: Fifty-three paediatric patients (age 24.1±2 months) who underwent chest or abdomen HPCT (≥1.5) and standard pitch CT (SPCT, <1.5) on a dual-source 128-row multidetector CT system were included in the study. Image quality assessment was performed by two paediatric radiologists for diagnostic confidence, image artefacts, and image noise. Objective image noise was measured. RESULTS: Most of the CT examinations were performed in children who were >1 year old (n=15 and n=20) followed by ≤1 year old (n=8 and n=10) in SPCT and HPCT, respectively. The mean radiation dose (SSDE) from HPCT was 1.96±1 mGy compared to 2.2±1 mGy for SPCT (p=0.3). No major artefacts were reported and overall image quality of all HPCT examinations was acceptable diagnostically. In addition, objective image noise values were not significantly different between HPCT compared with SPCT (11±3 versus 11±5, p=0.7). CONCLUSION: Ultra-fast, HPCT can be performed without the need for sedation as a potential alternative to anaesthetised magnetic resonance imaging in infants and young children.

Pulmonary hemorrhage in neonatal respiratory distress syndrome: Radiographic evolution, course, complications and long-term clinical outcomes.

BACKGROUND: Pulmonary hemorrhage (PH) is occasionally seen in premature infants after surfactant treatment for respiratory distress syndrome (RDS). These infants receive frequent chest radiographs (CXR) during and after hospitalization enabling long-term radiographic-clinical correlation. OBJECTIVE: To chart the natural evolution of CXR findings of PH in RDS and correlate radiographic patterns to supplemental oxygen requirement. MATERIALS AND METHODS: Retrospective review of clinical notes for gestational age (GA), birth weight (BW), intraventricular hemorrhage (IVH) and oxygen requirement were performed. CXRs were reviewed at 4 time-points; during PH, 28 days postnatal age, 36 weeks and at farthest available clinical follow-up. RESULTS: 18 infants born (2003-2016), GA (24-30 weeks); BW (482-1590 grams) were included. Mean onset of PH was 1.94 (0-5) days. 9/18 (50%) had IVH. 3 died during PH; all had IVH. During PH, CXR showed whiteout 9/18 (50%); patchy opacities 5/18 (27%); diffuse haziness 1/18 (6%) and no change 3/18 (17%). At 28 days postnatal age, CXR showed fine-interstitial (FI) markings 14/15 (93%) and whiteout 1/15 (7%). At 36 weeks,12/14 (85%) had FI and 2/14 (15%) developed cystic-interstitial changes. At farthest follow-up, FI 3/13 (23%); coarse-interstitial 4/13 (30%); peri-bronchial cuffing 5/13 (38%); normal 1/13 (9%) and the majority had hyperinflation 9/13 (69%). At discharge, 9/14 (64%) required home-oxygen and 5/14 (36%) were on room-air. At farthest follow-up, 6/14 (42%) required home-oxygen and 8/14 (58%) were on room-air. CONCLUSION: Premature infants that survive PH may later develop chronic lung disease of prematurity with an evolving interstitial pattern on CXR that clears overtime as they outgrow the need for supplemental oxygen.

Inter-rater Variability in the Interpretation of Pre and Post Contrast MRI for Pre-Surgical Evaluation of Osteosarcoma in Long Bones in Pediatric Patients and Young Adults.

BACKGROUND AND OBJECTIVES: The value of gadolinium enhanced magnetic resonance imaging (MRI) sequences for extremity osteosarcoma resection planning is unverified. We evaluate the performance of intravenous gadolinium enhanced MRI for identification of neurovascular bundle involvement (NBI) and intraarticular extension (IAE) in patients with osteosarcoma. METHODS: Two pediatric radiologists independently analyzed MRI examinations of patients with pathology proven extremity osteosarcoma for NBI and IAE. Initial evaluation utilized only non-contrast MRI images (PRE) and, after 2 weeks, subsequent evaluation included both the pre and post contrast images (POST). Cohen's Kappa and McNemar's test were calculated to assess agreement between PRE and POST image interpretations of NBI and IAE. RESULTS: 56 patients with 90 preoperative MRI examinations were analyzed. PRE and POST interpretations were rarely discordant; 4/90 cases for NBI (Kappa 0.91) and 2/90 cases for IAE (Kappa 0.95). McNemar's test did not show a difference between PRE and POST imaging (NBI p=0.62; IAE p=0.48). CONCLUSION: No significant difference between PRE and POST image interpretation was found. A high level of agreement between PRE and POST image interpretation suggests that pre-contrast MRI may be sufficient for pre-surgical planning for pediatric patients with long bone osteosarcoma.

Type 2 iodothyronine deiodinase expression in the cochlea before the onset of hearing.

Thyroid hormone signaling during a postnatal period in the mouse is essential for cochlear development and the subsequent onset of hearing. To study the control of this temporal dependency, we investigated the role of iodothyronine deiodinases, which in target tissues convert the prohormone thyroxine into triiodothyronine (T3), the active ligand for the thyroid hormone receptor (TR). Type 2 5'-deiodinase (D2) activity rose dramatically in the mouse cochlea to peak around postnatal day 7 (P7), after which activity declined by P10. This activity peak a few days before the onset of hearing suggests a role for D2 in amplifying local T3 levels at a critical stage of cochlear development. A mouse cochlear D2 cDNA was isolated and demonstrated near identity to rat D2. In situ hybridization localized D2 mRNA in periosteal connective tissue in the modiolus, the cochlear outer capsule and the septal divisions between the turns of the cochlea. Surprisingly, D2 expression in these regions that give rise to the bony labyrinth was complementary to TR expression in the sensory epithelium. Thus, the connective tissue may control deiodination of thyroxine and release of T3 to confer a paracrine-like control of TR activation. These results suggest that temporal and spatial control of ligand availability conferred by D2 provides an unexpectedly important level of regulation of the TR pathways required for cochlear maturation.

Expression of Math1 and HES5 in the cochleae of wildtype and Jag2 mutant mice.

The sensory epithelium within the mammalian cochlea (the organ of Corti) is a strictly ordered cellular array consisting of sensory hair cells and nonsensory supporting cells. Previous research has demonstrated that Notch-mediated lateral inhibition plays a key role in the determination of cell types within this array. Specificallly, genetic deletion of the Notch ligand, Jagged2, results in a significant increase in the number of hair cells that develop within the sensory epithelium, presumably as a result of a decrease in Notch activation. In contrast, the downstream mediators and targets of the Notch pathway in the inner ear have not been determined but they may include genes encoding the proneural gene Math1 as well as the HES family of inhibitory bHLH proteins. To determine the potential roles of these genes in cochlear development, in situ hybridization for Math1 and HES5 was performed on the cochleae of wild-type vs. Jagged2 mutants (Jag2deltaDSL). Results in wild-type cochleae show that expression of Math1 transcripts in the duct begins on E13 and ultimately becomes restricted to hair cells in the sensory epithelium. In contrast, expression of HES5 begins on E15 and becomes restricted to supporting cells in the epithelium. Results in Jag2 mutant cochleae suggest that Math1 transcripts are ultimately maintained in a larger number of cells as compared with wild-type, while transcripts for HES5 are dramatically reduced throughout the epithelium. These results are consistent with the hypothesis that activation of Notch via Jagged2 acts to inhibit expression of Math1 in cochlear progenitor cells, possibly through the activity of HES5.

Expression of proneural and neurogenic genes in the embryonic mammalian vestibular system.

One of the most striking aspects of all auditory and vestibular sensory epithelia is the mosaic pattern of hair cells and supporting cells. The factors that are required for the development of this mosaic have not been determined, however the results of recent studies have demonstrated that components of the neurogenic (Notch) signaling pathway are expressed in the developing inner ears of a number of different vertebrate species. To examine whether this signaling pathway may play a similar role in the development of the hair cell mosaic in the mammalian vestibular system, the expression patterns of proneural (Math1) and neurogenic (Notch1, Jagged2, HES5) genes were examined in the developing mouse inner ear. Results indicate that Notch1 is initially expressed throughout the developing inner ear and becomes restricted to non-sensory cells within the developing sensory epithelia. In contrast, initial expression of Math1 and Jagged2 is localized to the developing sensory epithelia and ultimately becomes restricted to hair cells. Interestingly, transcripts for HES5, a target of Notch activation, are expressed in the developing cristae but not in the saccule or utricle. These results are consistent with the hypothesis that formation of the hair cell mosaic is regulated through the neurogenic pathway. However the differential expression of HES5 within the ear indicates that the downstream targets of Notch1 activation are not consistent across all of the sensory epithelia and suggests that the effects of activation of Notch1 in the saccule and utricle must be regulated through alternate target genes.