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Purpose: The underlying functional and microstructural lung disease in neonates who are born preterm (bronchopulmonary dysplasia, BPD) remains poorly characterized. Moreover, there is a lack of suitable techniques to reliably assess lung function in this population. Here, we report our preliminary experience with hyperpolarized 129Xe MRI in neonates with BPD. Methods: Neonatal intensive care patients with established BPD were recruited (N = 9) and imaged at a corrected gestational age of median:40.7 (range:37.1, 44.4) wk using a 1.5T neonatal scanner. 2D 129Xe ventilation and diffusion‐weighted images and dissolved phase spectroscopy were acquired, alongside 1H 3D radial UTE. 129Xe images were acquired during a series of short apneic breath‐holds (˜3 s). 1H UTE images were acquired during tidal breathing. Ventilation defects were manually identified and qualitatively compared to lung structures on UTE. ADCs were calculated on a voxel‐wise basis. The signal ratio of the 129Xe red blood cell (RBC) and tissue membrane (M) resonances from spectroscopy was determined. Results: Spiral‐based 129Xe ventilation imaging showed good image quality and sufficient sensitivity to detect mild ventilation abnormalities in patients with BPD. 129Xe ADC values were elevated above that expected given healthy data in older children and adults (median:0.046 [range:0.041, 0.064] cm2s−1); the highest value obtained from an extremely pre‐term patient. 129Xe spectroscopy revealed a low RBC/M ratio (0.14 [0.06, 0.21]). Conclusion: We have demonstrated initial feasibility of 129Xe lung MRI in neonates. With further data, the technique may help guide management of infant lung diseases in the neonatal period and beyond. [ABSTRACT FROM AUTHOR]

The article discusses the potential of functional lung magnetic resonance imaging (MRI) as a clinical tool for evaluating pulmonary function. Traditional methods such as pulmonary function testing (PFT) and chest computed tomography (CT) have limitations, such as being effort-dependent or exposing patients to ionizing radiation. The article explores emerging methodologies that use 1H free-breathing MRI to map ventilatory lung function without the need for an inhaled gas. The authors present a study that combines ventilation-weighted mapping and ventilation flow capacity-weighted mapping to assess lung function in healthy subjects and those with chronic obstructive pulmonary disease (COPD). The results show promise for improved disease phenotyping and suggest that multifaceted MRI evaluation of lung function may enhance the characterization and treatment of pulmonary conditions. [Extracted from the article]

Chronic pain is an incapacitating condition that affects a large population worldwide. Until now, there is no drug treatment to relieve it. The impairment of GABAergic inhibition mediated by GABAA receptors (GABAAR) is considered a relevant factor in mediating chronic pain. Even though both synaptic and extrasynaptic GABAA inhibition are present in neurons that process nociceptive information, the latter is not considered relevant as a target for the development of pain treatments. In particular, the extrasynaptic α5GABAARs are expressed in laminae I‐II of the spinal cord neurons, sensory neurons, and motoneurons. In this review, we discuss evidence showing that blockade of the extrasynaptic α5GABAARs reduces mechanical allodynia in various models of chronic pain and restores the associated loss of rate‐dependent depression of the Hoffmann reflex. Furthermore, in healthy animals, extrasynaptic α5GABAAR blockade induces both allodynia and hyperalgesia. These results indicate that this receptor may have an antinociceptive and pronociceptive role in healthy and chronic pain‐affected animals, respectively. We propose a hypothesis to explain the relevant role of the extrasynaptic α5GABAARs in the processing of nociceptive information. The data discussed here strongly suggest that this receptor could be a valid pharmacological target to treat chronic pain states. [ABSTRACT FROM AUTHOR]

Objective/Hypothesis: To assess the ability of ultra‐short echo time (UTE)‐MRI to detect subglottic stenosis (SGS) and evaluate response to balloon dilation. To correlate measurements from UTE‐MRI with endotracheal‐tube (ETT)‐sizing and to investigate whether SGS causes change in airway dynamics. Study Design: Animal research study. Methods: Eight adult New‐Zealand white rabbits were used as they approximate neonatal airway‐size. The airways were measured using ETT‐sizing and 3D UTE‐MRI at baseline, 2 weeks post‐cauterization induced SGS injury, and post‐balloon dilation treatment. UTE‐MR images were acquired to determine airway anatomy and motion. Airways were segmented from MR images. Cross‐sectional area (CSA), major and minor diameters (Dmajor and Dminor), and eccentricity were measured. Results: Post‐injury CSA at SGS was significantly reduced (mean 38%) compared to baseline (P =.003) using UTE‐MRI. ETT‐sizing correlated significantly with MRI‐measured CSA at the SGS location (r = 0.6; P <.01), particularly at the post‐injury timepoint (r = 0.93; P <.01). Outer diameter from ETT‐sizing (OD) correlated significantly with Dmajor (r = 0.63; P <.01) from UTE‐MRI at the SGS location, especially for the post‐injury timepoint (r = 0.91; P <.01). Mean CSA of upper trachea did not change significantly between end‐expiration and end‐inspiration at any timepoint (all P >.05). Eccentricity of the upper trachea increased significantly post‐balloon dilation (P <.05). Conclusions: UTE‐MRI successfully detected SGS and treatment response in the rabbit model, with good correlation to ETT‐sizing. Balloon dilation increased CSA at SGS, but not to baseline values. SGS did not alter dynamic motion for the trachea in this rabbit model; however, tracheas were significantly eccentric post‐balloon dilation. UTE‐MRI can detect SGS without sedation or ionizing radiation and may be a non‐invasive alternative to ETT‐sizing. Level of Evidence: NA Laryngoscope, 131:E1971–E1979, 2021 [ABSTRACT FROM AUTHOR]

Objectives: Subglottic stenosis (SGS) is the most common type of laryngeal stenosis in neonates. SGS severity is currently graded based on percent area of obstruction (%AO) via the Myer‐Cotton grading scale. However, patients with similar %AO can have widely different clinical courses. Computational fluid dynamics (CFD) based on patient‐specific imaging can quantify the relationship between airway geometry and flow dynamics. We investigated the effect of %AO and axial position of SGS on work of breathing (WOB) in neonates using magnetic resonance imaging. Methods: High‐resolution ultrashort echo‐time MRI of the chest and airway was obtained in three neonatal patients with no suspected airway abnormalities; images were segmented to construct three‐dimensional (3D) models of the neonatal airways. These models were then modified with virtual SGSs of varying %AO and axial positioning. CFD simulations of peak inspiratory flow were used to calculate patient‐specific WOB in nonstenotic and artificially stenosed airway models. Results: CFD simulations demonstrated a relationship between stenosis geometry and WOB increase. WOB rapidly increased with %AO greater than about 70%. Changes in axial position could also increase WOB by approximately the same amount as a 10% increase in %AO. Increased WOB was particularly pronounced when the SGS lumen was misaligned with the glottic jet. Conclusion: The results indicate a strong, predictable relationship between WOB and axial position of the stenotic lumen relative to the glottis, which has not been previously reported. These findings may lead to precision diagnosis and treatment prediction tools in individual patients. Level of Evidence: 4 Laryngoscope, 131:E1220–E1226, 2021 [ABSTRACT FROM AUTHOR]

No direct observational evidence of sprite‐produced active radicals has been presented owing to the difficulty of observing a small event area in the nighttime mesosphere, whereas sprite chemical models have indicated that sprite discharge locally affects the atmospheric composition. We present the first observational evidence of a HO 2 production above sprite‐producing thunderstorms from the coincidence of temporal‐spatial observations of HO 2 spectra, sprite events, and thunderstorms by two space instruments, a submillimeter‐wave limb spectrometer and ultraviolet/visible Imager and a ground‐based very low frequency radiation lightning detection network. A total of three areas was identified with enhanced HO 2 levels of approximately 10 25 molecules. A chemical sprite model indicates an increase in HO 2 in the considered altitude region; however, the predicted production due to a single sprite event is smaller than the observed enhancement. Our observational results suggest that sprites potentially contribute 1% of nighttime background HO 2 generation at altitudes of 75–80 km globally. Plain Language Summary: HO 2 radical, a key atmospheric oxidant in the mechanisms that influence the atmospheric composition of our planet, has been predicted to be generated by lightning‐induced upper atmospheric discharge, called sprites, from water vapor. However, there has been no observational evidence of sprite‐producing active radicals due to the difficulty in specific observations that identify these radical productions by sprite, caused by factors such as a very small molecular abundance and narrow event area in the upper atmosphere. For the first time, we present observational evidence of a rise in HO 2 amount above sprite‐producing thunderstorms by using a unique method that combined observations between HO 2 detection by a super‐high‐sensitive space spectrometer, sprite emission detection using a satellite imager and ground‐based lightning detection using expand radio frequency receivers. The amount of HO 2 generated in the sprite event area can be approximated to be 40–190 times greater than the background values. Sprite chemical model simulations reproduced HO 2 enhancement by sprite events. These pieces of evidence suggest that sprites potentially contribute about 1% increase of background level of global HO 2 generation during nighttime at altitudes of 75–80 km, which can contribute to a change in the Earth's atmospheric composition. Key Points: Clear HO 2 enhancements above sprite‐producing thunderstorms were identified by coincidence of space and ground‐based observationsEnhanced HO 2 amounts in a sprite event area were estimated to be 10 25 moleculesSprites potentially contribute about 1% of nighttime background HO 2 generations at 75–80 km globally [ABSTRACT FROM AUTHOR]

Background: Neonatal dynamic tracheal collapse (tracheomalacia, TM) is a common and serious comorbidity in infants, particularly those with chronic lung disease of prematurity (bronchopulmonary dysplasia, BPD) or congenital airway or lung-related conditions such as congenital diaphragmatic hernia (CDH), but the underlying pathology, impact on clinical outcomes, and response to therapy are not well understood. There is a pressing clinical need for an accurate, objective, and safe assessment of neonatal TM.Purpose: To use retrospectively respiratory-gated ultrashort echo-time (UTE) MRI to noninvasively analyze moving tracheal anatomy for regional, quantitative evaluation of dynamic airway collapse in quiet-breathing, nonsedated neonates.Study Type: Prospective.Population/subjects: Twenty-seven neonatal subjects with varying respiratory morbidities (control, BPD, CDH, abnormal polysomnogram).Field Strength/sequence: High-resolution 3D radial UTE MRI (0.7 mm isotropic) on 1.5T scanner sited in the neonatal intensive care unit.Assessment: Images were retrospectively respiratory-gated using the motion-modulated time-course of the k-space center. Tracheal surfaces were generated from segmentations of end-expiration/inspiration images and analyzed geometrically along the tracheal length to calculate percent-change in luminal cross-sectional area (A % ) and ratio of minor-to-major diameters at end-expiration (r D,exp ). Geometric results were compared to clinically available bronchoscopic findings (n = 14).Statistical Tests: Two-sample t-test.Results: Maximum A % significantly identified subjects with/without a bronchoscopic TM diagnosis (with: 46.9 ± 10.0%; without: 27.0 ± 5.8%; P < 0.001), as did minimum r D,exp (with: 0.346 ± 0.146; without: 0.671 ± 0.218; P = 0.008). Subjects with severe BPD exhibited a far larger range of minimum r D,exp than subjects with mild/moderate BPD or controls (0.631 ± 0.222, 0.782 ± 0.075, and 0.776 ± 0.030, respectively), while minimum r D,exp was reduced in CDH subjects (0.331 ± 0.171) compared with controls (P < 0.001).Data Conclusion: Respiratory-gated UTE MRI can quantitatively and safely evaluate neonatal dynamic tracheal collapse, as validated with the clinical standard of bronchoscopy, without requiring invasive procedures, anesthesia, or ionizing radiation.Level Of Evidence: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;49:659-667. [ABSTRACT FROM AUTHOR]

Purpose: To demonstrate that ultrashort echo time (UTE) magnetic resonance imaging (MRI) can achieve computed tomography (CT)-like quantification of lung parenchyma in free-breathing, non-sedated neonates. Because infant CTs are used sparingly, parenchymal disease evaluation via UTE MRI has potential for translational impact.Materials and Methods: Two neonatal control cohorts without suspected pulmonary morbidities underwent either a research UTE MRI (n = 5; 1.5T) or a clinically-ordered CT (n = 9). Whole-lung means and anterior-posterior gradients of UTE-measured image intensity (arbitrary units, au, normalized to muscle) and CT-measured density (g/cm3 ) were compared (Mann-Whitney U-test). Separately, a diseased neonatal cohort (n = 5) with various pulmonary morbidities underwent both UTE MRI and CT. UTE intensity and CT density were compared with Spearman correlations within ∼33 anatomically matched regions of interest (ROIs) in each diseased subject, spanning low- to high-density tissues. Radiological classifications were evaluated in all ROIs, with mean UTE intensities and CT densities compared in each classification.Results: In control subjects, whole-lung UTE intensities (0.51 ± 0.04 au) were similar to CT densities (0.44 ± 0.09 g/cm3 ) (P = 0.062), as were UTE (0.021 ± 0.020 au/cm) and CT (0.034 ± 0.024 [g/cm3 ]/cm) anterior-posterior gradients (P = 0.351). In diseased subjects' ROIs, significant correlations were observed between UTE and CT (P ≤0.007 in each case). Relative differences between UTE and CT were small in all classifications (4-25%).Conclusion: These results demonstrate a strong association between UTE image intensity and CT density, both between whole-lung tissue in control patients and regional radiological pathologies in diseased patients. This indicates the potential for UTE MRI to longitudinally evaluate neonatal pulmonary disease and to provide visualization of pathologies similar to CT, without sedation/anesthesia or ionizing radiation.Level Of Evidence: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:992-1000. [ABSTRACT FROM AUTHOR]

Purpose To implement pulmonary three-dimensional (3D) radial ultrashort echo-time (UTE) MRI in non-sedated, free-breathing neonates and adults with retrospective motion tracking of respiratory and intermittent bulk motion, to obtain diagnostic-quality, respiratory-gated images. Methods Pulmonary 3D radial UTE MRI was performed at 1.5 tesla (T) during free breathing in neonates and adult volunteers for validation. Motion-tracking waveforms were obtained from the time course of each free induction decay's initial point (i.e., k-space center), allowing for respiratory-gated image reconstructions that excluded data acquired during bulk motion. Tidal volumes were calculated from end-expiration and end-inspiration images. Respiratory rates were calculated from the Fourier transform of the motion-tracking waveform during quiet breathing, with comparison to physiologic prediction in neonates and validation with spirometry in adults. Results High-quality respiratory-gated anatomic images were obtained at inspiration and expiration, with less respiratory blurring at the expense of signal-to-noise for narrower gating windows. Inspiration-expiration volume differences agreed with physiologic predictions (neonates; Bland-Altman bias = 6.2 mL) and spirometric values (adults; bias = 0.11 L). MRI-measured respiratory rates compared well with the observed rates (biases = −0.5 and 0.2 breaths/min for neonates and adults, respectively). Conclusions Three-dimensional radial pulmonary UTE MRI allows for retrospective respiratory self-gating and removal of intermittent bulk motion in free-breathing, non-sedated neonates and adults. Magn Reson Med 77:1284-1295, 2017. © 2016 International Society for Magnetic Resonance in Medicine [ABSTRACT FROM AUTHOR]

Purpose: To determine the feasibility of pulmonary magnetic resonance imaging (MRI) of neonatal lung structures enabled by combining two novel technologies: first, a 3D radial ultrashort echo time (UTE) pulse sequence capable of high spatial resolution full-chest imaging in nonsedated quiet-breathing neonates; and second, a unique, small-footprint 1.5T MRI scanner design adapted for neonatal imaging and installed within the neonatal intensive care unit (NICU).Materials and Methods: Ten patients underwent MRI within the NICU, in accordance with an approved Institutional Review Board protocol. Five had clinical diagnoses of bronchopulmonary dysplasia (BPD), and five had putatively normal lung function. Pulmonary imaging was performed at 1.5T using 3D radial UTE and standard 3D fast gradient recalled echo (FGRE). Diagnostic quality, presence of motion artifacts, and apparent severity of lung pathology were evaluated by two radiologists. Quantitative metrics were additionally used to evaluate lung parenchymal signal.Results: UTE images showed significantly higher signal in lung parenchyma (P < 0.0001) and fewer apparent motion artifacts compared to FGRE (P = 0.046). Pulmonary pathology was more severe in patients diagnosed with BPD relative to controls (P = 0.001). Infants diagnosed with BPD also had significantly higher signal in lung parenchyma, measured using UTE, relative to controls (P = 0.002).Conclusion: These results demonstrate the technical feasibility of pulmonary MRI in free-breathing, nonsedated infants in the NICU at high, isotropic resolutions approaching that achievable with computed tomography (CT). There is potential for pulmonary MRI to play a role in improving how clinicians understand and manage care of neonatal and pediatric pulmonary diseases. J. Magn. Reson. Imaging 2016.Level Of Evidence: 2 J. Magn. Reson. Imaging 2017;45:463-471. [ABSTRACT FROM AUTHOR]