Comparison of weighting algorithms to mitigate respiratory motion in free-breathing neonatal pulmonary radial UTE-MRI.

Background. Thoracoabdominal MRI is limited by respiratory motion, especially in populations who cannot perform breath-holds. One approach for reducing motion blurring in radially-acquired MRI is respiratory gating. Straightforward 'hard-gating' uses only data from a specified respiratory window and suffers from reduced SNR. Proposed 'soft-gating' reconstructions may improve scan efficiency but reduce motion correction by incorporating data with nonzero weight acquired outside the specified window. However, previous studies report conflicting benefits, and importantly the choice of soft-gated weighting algorithm and effect on image quality has not previously been explored. The purpose of this study is to map how variable soft-gated weighting functions and parameters affect signal and motion blurring in respiratory-gated reconstructions of radial lung MRI, using neonates as a model population.Methods. Ten neonatal inpatients with respiratory abnormalities were imaged using a 1.5 T neonatal-sized scanner and 3D radial ultrashort echo-time (UTE) sequence. Images were reconstructed using ungated, hard-gated, and several soft-gating weighting algorithms (exponential, sigmoid, inverse, and linear weighting decay outside the period of interest), with %Nprojrepresenting the relative amount of data included. The apparent SNR (aSNR) and motion blurring (measured by the maximum derivative of image intensity at the diaphragm, MDD) were compared between reconstructions.Results. Soft-gating functions produced higher aSNR and lower MDD than hard-gated images using equivalent %Nproj, as expected. aSNR was not identical between different gating schemes for given %Nproj. While aSNR was approximately linear with %Nprojfor each algorithm, MDD performance diverged between functions as %Nprojdecreased. Algorithm performance was relatively consistent between subjects, except in images with high noise.Conclusion. The algorithm selection for soft-gating has a notable effect on image quality of respiratory-gated MRI; the timing of included data across the respiratory phase, and not simply the amount of data, plays an important role in aSNR. The specific soft-gating function and parameters should be considered for a given imaging application's requirements of signal and sharpness.

Tracheomalacia Reduces Aerosolized Drug Delivery to the Lung.

Rationale: Neonates with respiratory issues are frequently treated with aerosolized medications to manage lung disease or facilitate airway clearance. Dynamic tracheal collapse (tracheomalacia [TM]) is a common comorbidity in these patients, but it is unknown whether the presence of TM alters the delivery of aerosolized drugs. Objectives: To quantify the effect of neonatal TM on the delivery of aerosolized drugs. Methods: Fourteen infant subjects with respiratory abnormalities were recruited; seven with TM and seven without TM. Respiratory-gated 3D ultrashort echo time magnetic resonance imaging (MRI) was acquired covering the central airway and lungs. For each subject, a computational fluid dynamics simulation modeled the airflow and particle transport in the central airway based on patient-specific airway anatomy, motion, and airflow rates derived from MRI. Results: Less aerosolized drug reached the distal airways in subjects with TM than in subjects without TM: of the total drug delivered, less particle mass passed through the main bronchi in subjects with TM compared with subjects without TM (33% vs. 47%, p = 0.013). In subjects with TM, more inhaled particles were deposited on the surface of the airway (48% vs. 25%, p = 0.003). This effect becomes greater with larger particle sizes and is significant for particles with a diameter >2 µm (2-5 µm, p ≤ 0.025 and 5-15 µm, p = 0.004). Conclusions: Neonatal patients with TM receive less aerosolized drug delivered to the lungs than subjects without TM. Currently, infants with lung disease and TM may not be receiving adequate and/or expected medication. Particles >2 µm in diameter are likely to deposit on the surface of the airway due to anatomical constrictions such as reduced tracheal and glottal cross-sectional area in neonates with TM. This problem could be alleviated by delivering smaller aerosolized particles.

Predicting tracheal work of breathing in neonates based on radiological and pulmonary measurements.

Tracheomalacia is an airway condition in which the trachea excessively collapses during breathing. Neonates diagnosed with tracheomalacia require more energy to breathe, and the effect of tracheomalacia can be quantified by assessing flow-resistive work of breathing (WOB) in the trachea using computational fluid dynamics (CFD) modeling of the airway. However, CFD simulations are computationally expensive; the ability to instead predict WOB based on more straightforward measures would provide a clinically useful estimate of tracheal disease severity. The objective of this study is to quantify the WOB in the trachea using CFD and identify simple airway and/or clinical parameters that directly relate to WOB. This study included 30 neonatal intensive care unit subjects (15 with tracheomalacia and 15 without tracheomalacia). All subjects were imaged using ultrashort echo time (UTE) MRI. CFD simulations were performed using patient-specific data obtained from MRI (airway anatomy, dynamic motion, and airflow rates) to calculate the WOB in the trachea. Several airway and clinical measurements were obtained and compared with the tracheal resistive WOB. The maximum percent change in the tracheal cross-sectional area (ρ = 0.560, P = 0.001), average glottis cross-sectional area (ρ = -0.488, P = 0.006), minute ventilation (ρ = 0.613, P < 0.001), and lung tidal volume (ρ = 0.599, P < 0.001) had significant correlations with WOB. A multivariable regression model with three independent variables (minute ventilation, average glottis cross-sectional area, and minimum of the eccentricity index of the trachea) can be used to estimate WOB more accurately (R2 = 0.726). This statistical model may allow clinicians to estimate tracheal resistive WOB based on airway images and clinical data.NEW & NOTEWORTHY The work of breathing due to resistance in the trachea is an important metric for quantifying the effect of tracheal abnormalities such as tracheomalacia, but currently requires complex dynamic imaging and computational fluid dynamics simulation to calculate it. This study produces a method to predict the tracheal work of breathing based on readily available imaging and clinical metrics.

Laryngotracheal separation through the cricoid ring for management of tracheobronchomegaly.

Tracheobronchomegaly is a rare condition characterized by diffuse dilation of the trachea and main bronchi. In ventilator-dependent neonates with tracheobronchomegaly, a tracheostomy may be hazardous due to the lack of an appropriate tracheostomy tube size that can fit the enlarged trachea. Here, we describe a modification of the laryngotracheal separation procedure to permit ventilation in a child with tracheobronchomegaly and severe bronchopulmonary dysplasia.

Bronchopulmonary dysplasia from chest radiographs to magnetic resonance imaging and computed tomography: adding value.

Bronchopulmonary dysplasia (BPD) is a common long-term complication of preterm birth. The chest radiograph appearance and survivability have evolved since the first description of BPD in 1967 because of improved ventilation and clinical strategies and the introduction of surfactant in the early 1990s. Contemporary imaging care is evolving with the recognition that comorbidities of tracheobronchomalacia and pulmonary hypertension have a great influence on outcomes and can be noninvasively evaluated with CT and MRI techniques, which provide a detailed evaluation of the lungs, trachea and to a lesser degree the heart. However, echocardiography remains the primary modality to evaluate and screen for pulmonary hypertension. This review is intended to highlight the important findings that chest radiograph, CT and MRI can contribute to precision diagnosis, phenotyping and prognosis resulting in optimal management and therapeutics.

Human upper-airway respiratory airflow: In vivo comparison of computational fluid dynamics simulations and hyperpolarized 129Xe phase contrast MRI velocimetry.

Computational fluid dynamics (CFD) simulations of respiratory airflow have the potential to change the clinical assessment of regional airway function in health and disease, in pulmonary medicine and otolaryngology. For example, in diseases where multiple sites of airway obstruction occur, such as obstructive sleep apnea (OSA), CFD simulations can identify which sites of obstruction contribute most to airway resistance and may therefore be candidate sites for airway surgery. The main barrier to clinical uptake of respiratory CFD to date has been the difficulty in validating CFD results against a clinical gold standard. Invasive instrumentation of the upper airway to measure respiratory airflow velocity or pressure can disrupt the airflow and alter the subject's natural breathing patterns. Therefore, in this study, we instead propose phase contrast (PC) velocimetry magnetic resonance imaging (MRI) of inhaled hyperpolarized 129Xe gas as a non-invasive reference to which airflow velocities calculated via CFD can be compared. To that end, we performed subject-specific CFD simulations in airway models derived from 1H MRI, and using respiratory flowrate measurements acquired synchronously with MRI. Airflow velocity vectors calculated by CFD simulations were then qualitatively and quantitatively compared to velocity maps derived from PC velocimetry MRI of inhaled hyperpolarized 129Xe gas. The results show both techniques produce similar spatial distributions of high velocity regions in the anterior-posterior and foot-head directions, indicating good qualitative agreement. Statistically significant correlations and low Bland-Altman bias between the local velocity values produced by the two techniques indicates quantitative agreement. This preliminary in vivo comparison of respiratory airway CFD and PC MRI of hyperpolarized 129Xe gas demonstrates the feasibility of PC MRI as a technique to validate respiratory CFD and forms the basis for further comprehensive validation studies. This study is therefore a first step in the pathway towards clinical adoption of respiratory CFD.

Neonates With Tracheomalacia Generate Auto-Positive End-Expiratory Pressure via Glottis Closure.

BACKGROUND: In pediatrics, tracheomalacia is an airway condition that causes tracheal lumen collapse during breathing and may lead to the patient requiring respiratory support. Adult patients can narrow their glottis to self-generate positive end-expiratory pressure (PEEP) to raise the pressure in the trachea and prevent collapse. However, auto-PEEP has not been studied in newborns with tracheomalacia. The objective of this study was to measure the glottis cross-sectional area throughout the breathing cycle and to quantify total pressure difference through the glottis in patients with and without tracheomalacia. RESEARCH QUESTION: Do neonates with tracheomalacia narrow their glottises? How does the glottis narrowing affect the total pressure along the airway? STUDY DESIGN AND METHODS: Ultrashort echo time MRI was performed in 21 neonatal ICU patients (11 with tracheomalacia, 10 without tracheomalacia). MRI scans were reconstructed at four different phases of breathing. All patients were breathing room air or using noninvasive respiratory support at the time of MRI. Computational fluid dynamics simulations were performed on patient-specific virtual airway models with airway anatomic features and motion derived via MRI to quantify the total pressure difference through the glottis and trachea. RESULTS: The mean glottis cross-sectional area at peak expiration in the patients with tracheomalacia was less than half that in patients without tracheomalacia (4.0 ± 1.1 mm2 vs 10.3 ± 4.4 mm2; P = .002). The mean total pressure difference through the glottis at peak expiration was more than 10 times higher in patients with tracheomalacia compared with patients without tracheomalacia (2.88 ± 2.29 cm H2O vs 0.26 ± 0.16 cm H2O; P = .005). INTERPRETATION: Neonates with tracheomalacia narrow their glottises, which raises pressure in the trachea during expiration, thereby acting as auto-PEEP.

Quantitative Evaluation of Subglottic Stenosis Using Ultrashort Echo Time MRI in a Rabbit Model.

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.

Subglottic Stenosis Position Affects Work of Breathing.

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.

The effect of airway motion and breathing phase during imaging on CFD simulations of respiratory airflow.

RATIONALE: Computational fluid dynamics (CFD) simulations of respiratory airflow can quantify clinically useful information that cannot be obtained directly, such as the work of breathing (WOB), resistance to airflow, and pressure loss. However, patient-specific CFD simulations are often based on medical imaging that does not capture airway motion and thus may not represent true physiology, directly affecting those measurements. OBJECTIVES: To quantify the variation of respiratory airflow metrics obtained from static models of airway anatomy at several respiratory phases, temporally averaged airway anatomies, and dynamic models that incorporate physiological motion. METHODS: Neonatal airway images were acquired during free-breathing using 3D high-resolution MRI and reconstructed at several respiratory phases in two healthy subjects and two with airway disease (tracheomalacia). For each subject, five static (end expiration, peak inspiration, end inspiration, peak expiration, averaged) and one dynamic CFD simulations were performed. WOB, airway resistance, and pressure loss across the trachea were obtained for each static simulation and compared with the dynamic simulation results. RESULTS: Large differences were found in the airflow variables between the static simulations at various respiratory phases and the dynamic simulation. Depending on the static airway model used, WOB, resistance, and pressure loss varied up to 237%, 200%, and 94% compared to the dynamic simulation respectively. CONCLUSIONS: Changes in tracheal size and shape throughout the breathing cycle directly affect respiratory airflow dynamics and breathing effort. Simulations incorporating realistic airway wall dynamics most closely represent airway physiology; if limited to static simulations, the airway geometry must be obtained during the respiratory phase of interest for a given pathology.

Increased Work of Breathing due to Tracheomalacia in Neonates.

Rationale: Dynamic collapse of the tracheal lumen (tracheomalacia) occurs frequently in premature neonates, particularly in those with common comorbidities such as bronchopulmonary dysplasia. The tracheal collapse increases the effort necessary to breathe (work of breathing [WOB]). However, quantifying the increased WOB related to tracheomalacia has previously not been possible. Therefore, it is also not currently possible to separate the impact of tracheomalacia on patient symptoms from parenchymal abnormalities.Objectives: To measure the increase in WOB due to airway motion in individual subjects with and without tracheomalacia and with different types of respiratory support.Methods: Fourteen neonatal intensive care unit subjects not using invasive mechanical ventilation were recruited. In eight, tracheomalacia was diagnosed via clinical bronchoscopy, and six did not have tracheomalacia. Self-gated three-dimensional ultrashort-echo-time magnetic resonance imaging (MRI) was performed on each subject with clinically indicated respiratory support to obtain cine images of tracheal anatomy and motion during the respiratory cycle. The component of WOB due to resistance within the trachea was then calculated via computational fluid dynamics (CFD) simulations of airflow on the basis of the subject's anatomy, motion, and respiratory airflow rates. A second CFD simulation was performed for each subject with the airway held static at its largest (i.e., most open) position to determine the increase in WOB due to airway motion and collapse.Results: The tracheal-resistive component of WOB was increased because of airway motion by an average of 337% ± 295% in subjects with tracheomalacia and 24% ± 14% in subjects without tracheomalacia (P < 0.02). In the tracheomalacia group, subjects who were treated with continuous positive airway pressure (CPAP) using a RAM cannula expended less energy for breathing compared with the subjects who were breathing room air or on a high-flow nasal cannula.Conclusions: Neonatal subjects with tracheomalacia have increased energy expenditure compared with neonates with normal airways, and CPAP may be able to attenuate the increase in respiratory work. Subjects with tracheomalacia expend more energy on the tracheal-resistive component of WOB alone than nontracheomalacia patients expend on the resistive WOB for the entire respiratory system, according to previously reported values. CFD may be able to provide an objective measure of treatment response for children with tracheomalacia.