Assessment of upper airway patency in spontaneously breathing non-intubated neonates and infants undergoing conventional MRI of head and neck.

PURPOSE: Neonates and infants frequently undergo MRI examinations of the brain or head and neck in spontaneous respiration. This study aims to evaluate the patency of the upper airway and associated risk factors in spontaneously breathing neonates and infants undergoing MRI of head and neck. METHODS: Airway patency was assessed on sagittal and axial MRI images of the head and neck region for neonates and infants retrospectively. Anteroposterior diameters were measured at the soft palate and tongue levels as well as a lateral diameter at the tongue level for the patent airway. Chart review for risk factors was carried out. RESULTS: A total of 831 children between 0 and 12 months of age had an MRI. Eighty-two children with spontaneous ventilation were included. The airway was occluded in 29/82 (35%) of children. Twenty-four out of 29 (83%) children with airway occlusion had a depressed level of consciousness, 7/24 (29%) of whom were sedated with a single dose of benzodiazepine and 17/24 (71%) were on anti-epileptic therapy for an underlying seizure disorder and/or hypoxic ischemic encephalopathy. Forty-three out of 82 (65%) of children had an open airway. The airway diameters (mean ± SD) were 5.9 ± 2 mm (anteroposterior (AP) at soft palate), 7.4 ± 2.9 mm (lateral at soft palate), and 6.3 mm ± 1.6 (AP at dorsum of tongue). CONCLUSION: A significant proportion of spontaneously breathing neonates and infants with hypoxic ischemic encephalopathy or sedation show evidence of airway obstruction during MRI. Careful pre-MRI screening for decision of spontaneous breathing versus artificial airway support during MRI and robust airway monitoring during MRI are required for these vulnerable children.

Intracellular Expression of PAI-1 Specific Aptamers Alters Breast Cancer Cell Migration, Invasion and Angiogenesis.

Plasminogen activator inhibitor-1 (PAI-1) is elevated in various cancers, where it has been shown to effect cell migration and invasion and angiogenesis. While, PAI-1 is a secreted protein, its intercellular levels are increased in cancer cells. Consequently, intracellular PAI-1 could contribute to cancer progression. While various small molecule inhibitors of PAI-1 are currently being investigated, none specifically target intracellular PAI-1. A class of inhibitors, termed aptamers, has been used effectively in several clinical applications. We previously generated RNA aptamers that target PAI-1 and demonstrated their ability to inhibit extracellular PAI-1. In the current study we explored the effect of these aptamers on intracellular PAI-1. We transiently transfected the PAI-1 specific aptamers into both MDA-MB-231 human breast cancer cells, and human umbilical vein endothelial cells (HUVECs) and studied their effects on cell migration, invasion and angiogenesis. Aptamer expressing MDA-MB-231 cells exhibited a decrease in cell migration and invasion. Additionally, intracellular PAI-1 and urokinase plasminogen activator (uPA) protein levels decreased, while the PAI-1/uPA complex increased. Moreover, a significant decrease in endothelial tube formation in HUVECs transfected with the aptamers was observed. In contrast, conditioned media from aptamer transfected MDA-MB-231 cells displayed a slight pro-angiogenic effect. Collectively, our study shows that expressing functional aptamers inside breast and endothelial cells is feasible and may exhibit therapeutic potential.

Defining Optimal Head-Tilt Position of Resuscitation in Neonates and Young Infants Using Magnetic Resonance Imaging Data.

Head-tilt maneuver assists with achieving airway patency during resuscitation. However, the relationship between angle of head-tilt and airway patency has not been defined. Our objective was to define an optimal head-tilt position for airway patency in neonates (age: 0-28 days) and young infants (age: 29 days-4 months). We performed a retrospective study of head and neck magnetic resonance imaging (MRI) of neonates and infants to define the angle of head-tilt for airway patency. We excluded those with an artificial airway or an airway malformation. We defined head-tilt angle a priori as the angle between occipito-ophisthion line and ophisthion-C7 spinous process line on the sagittal MR images. We evaluated medical records for Hypoxic Ischemic Encephalopathy (HIE) and exposure to sedation during MRI. We analyzed MRI of head and neck regions of 63 children (53 neonates and 10 young infants). Of these 63 children, 17 had evidence of airway obstruction and 46 had a patent airway on MRI. Also, 16/63 had underlying HIE and 47/63 newborn infants had exposure to sedative medications during MRI. In spontaneously breathing and neurologically depressed newborn infants, the head-tilt angle (median ± SD) associated with patent airway (125.3° ± 11.9°) was significantly different from that of blocked airway (108.2° ± 17.1°) (Mann Whitney U-test, p = 0.0045). The logistic regression analysis showed that the proportion of patent airways progressively increased with an increasing head-tilt angle, with > 95% probability of a patent airway at head-tilt angle 144-150°.