Long-Range Optical Coherence Tomography of the Neonatal Upper Airway for Early Diagnosis of Intubation-related Subglottic Injury

Abstract

Rationale: Subglottic edema and acquired subglottic stenosis are potentially airway-compromising sequelae in neonates following endotracheal intubation. At present, no imaging modality is capable of in vivo diagnosis of subepithelial airway wall pathology as signs of intubation-related injury.

Objectives: To use Fourier domain long-range optical coherence tomography (LR-OCT) to acquire micrometer-resolution images of the airway wall of intubated neonates in a neonatal intensive care unit setting and to analyze images for histopathology and airway wall thickness.

Methods: LR-OCT of the neonatal laryngotracheal airway was performed a total of 94 times on 72 subjects (age, 1-175 d; total intubation, 1-104 d). LR-OCT images of the airway wall were analyzed in MATLAB. Medical records were reviewed retrospectively for extubation outcome.

Measurements and main results: Backward stepwise regression analysis demonstrated a statistically significant association between log(duration of intubation) and both laryngeal (P < 0.001; multiple r(2) = 0.44) and subglottic (P < 0.001; multiple r(2) = 0.55) airway wall thickness. Subjects with positive histopathology on LR-OCT images had a higher likelihood of extubation failure (odds ratio, 5.9; P = 0.007). Longer intubation time was found to be significantly associated with extubation failure.

Conclusions: LR-OCT allows for high-resolution evaluation and measurement of the airway wall in intubated neonates. Our data demonstrate a positive correlation between laryngeal and subglottic wall thickness and duration of intubation, suggestive of progressive soft tissue injury. LR-OCT may ultimately aid in the early diagnosis of postintubation subglottic injury and help reduce the incidences of failed extubation caused by subglottic edema or acquired subglottic stenosis in neonates. Clinical trial registered with www.clinicaltrials.gov (NCT 00544427).

Trial registration: ClinicalTrials.gov NCT00544427.

Keywords: diagnostic imaging; intubation injury; neonate; optical coherence tomography; subglottic stenosis.

Figures

Figure 1.

Comparative cross-sectional anatomy and airflow of mature pediatric and adult versus neonatal upper airways. One millimeter of circumferential subglottic edema in the adult and infant upper airways causes 44% and 75% reduction in cross-sectional area (CSA), respectively. Resistance to laminar airflow increases by a factor of 3 in adults and by a factor of 16 in infants.

Figure 2.

Schematics of long-range optical coherence tomography (OCT) system (A) and cross-section of the distal cap of a 0.7-mm outer diameter scanning probe (B). AOM = acoustooptic modulator; BD = balance detector; Circ = circulator; Coup = coupler; GRIN = gradient refractive index; M = mirror; PC = polarization controller; S/S = swept source.

Figure 3.

Bedside long-range (LR) optical coherence tomography (OCT) of the intubated neonatal airway. A 0.7-mm outer diameter OCT probe (75–80 cm length) is housed in a transparent sheath (1.17-mm outer diameter) and proximally connected to a combined motor unit. The probe is inserted through an external Y-connector and advanced inside the endotracheal tube. LR-OCT signal is reflected at 90° and penetrates the airway wall perpendicular to the tissue plane. Data are acquired in a retrograde, helical pattern as the probe undergoes high-speed 360° rotation and retraction through the upper airway. ETT = endotracheal tube; FEP = fluorinated ethylene propylene.

Figure 4.

Long-range optical coherence tomography image of the neonatal larynx, represented in a select region of Cartesian coordinates (A) and polar coordinates (B). Noise bands digitally removed for image clarity. Scale bar = 500 μm. ETT = endotracheal tube; S = sheath; SM = submucosa; VF = free edge of vocal fold.

Figure 5.

Long-range optical coherence tomography image of the neonatal subglottis, represented in a select region of Cartesian coordinates (A) and polar coordinates (B). Noise bands digitally removed for image clarity. Scale bar = 500 μm. BM = basement membrane; E = epithelium; ETT = endotracheal tube; S = sheath; SM = submucosa.

Figure 6.

Long-range optical coherence tomography image of the neonatal trachea, represented in a select region of Cartesian coordinates (A) and polar coordinates (B). Noise bands digitally removed for image clarity. Scale bar = 500 μm. BM = basement membrane; E = epithelium; ETT = endotracheal tube; S = sheath; SM = submucosa; T = tracheal cartilage.

Figure 7.

Long-range optical coherence tomography image of the neonatal subglottis following 9 days of intubation, represented in a select region of Cartesian coordinates (A) and polar coordinates (B). Noise bands digitally removed for image clarity. Scale bar = 500 μm. BM = basement membrane; ETT = endotracheal tube; FB = fluid bar; G = glandular structures; S = sheath; SM = submucosa.

Figure 8.

Long-range optical coherence tomography image of the neonatal subglottis following 104 days of continuous intubation, represented in a select region of Cartesian coordinates (A) and polar coordinates (B). Noise bands digitally removed for image clarity. Scale bar = 500 μm. ETT = endotracheal tube; F = fibrosis; S = sheath; SM = submucosa.

Figure 9.

Operative bronchoscopy and long-range optical coherence tomography images of a neonatal airway following 42 days of intubation, including two failed extubation attempts. Significant edema and granulation, circumferential laryngeal stenosis (A), and grade 2 subglottic stenosis (C) are noted on endoscopy. Long-range optical coherence tomography of the larynx (B) and subglottis (D) demonstrates a thick, hyperintense submucosa with focal patches of hypointensity. ETT = endotracheal tube; F = fibrosis; G = glandular structures; S = sheath.

Figure 10.

Associations between laryngeal (A), subglottic (B), and tracheal (C) airway wall thickness (y-axis) and total duration of intubation plotted on a logarithmic scale (x-axis). Data points represent mean measurements from 48 long-range optical coherence tomography cases. Linear regression lines (dashed line) are plotted at the mean patient weight.