Paediatric lung disease
MRI of the upper airways in children and young
adults: the MUSIC study
Bernadette Elders,1,2 Pierluigi Ciet ,1,2 Harm Tiddens,1 Wytse van den Bosch,1,2
Piotr Wielopolski,2 Bas Pullens3
►► Additional material is
published online only. To view,
please visit the journal online
(http://d x.doi.o rg/10.1136/
thoraxjnl-2020-214921).
1
Department of Pediatric
Pulmonology, Erasmus MC
Sophia, Rotterdam, The
Netherlands
2
Department of Radiology and
Nuclear Medicine, Erasmus MC,
Rotterdam, The Netherlands
3
Department of Pediatric
Othorhinolaryngology, Erasmus
MC Sophia, Rotterdam, The
Netherlands
Correspondence to
Dr Harm Tiddens, Pediatric
pulmonology, Erasmus MC
Sophia, 3000 CB Rotterdam,
Zuid-Holland, The Netherlands;
h.tiddens@erasmusmc.nl
Received 6 April 2020
Revised 24 August 2020
Accepted 11 September 2020
ABSTRACT
Rationale Paediatric laryngotracheal stenosis (LTS) is
often successfully corrected with open airway surgery.
However, respiratory and vocal sequelae frequently
remain. Clinical care and surgical interventions could be
improved with better understanding of these sequelae.
Objective The objective of this cross-sectional study
was to develop an upper airway MRI protocol to obtain
information on anatomical and functional sequelae post-
LTS repair.
Methods Forty-eight patients (age 14.4 (range
7.5–30.7) years) and 11 healthy volunteers (15.9
(8.2–28.8) years) were included. Spirometry and static
and dynamic upper airway MRI (3.0 T, 30 min protocol)
were conducted. Analysis included assessment of
postoperative anatomy and airway lumen measurements
during static and dynamic (inspiration and phonation)
acquisitions.
Main results Good image quality without artefacts
was achieved for static and dynamic images in the
majority of MRIs. MRI showed vocal cord thickening
in 80.9% of patients and compared with volunteers, a
significant decrease in vocal cord lumen area (22.0 (IQR
17.7–30.3) mm2 vs 35.1 (21.2–54.7) mm2, p=0.03) but
not cricoid lumen area (62.3±27.0 mm2 vs 66.2±34.8
mm2, p=0.70). Furthermore, 53.2% of patients had an
A-frame deformation at site of previous tracheal cannula,
showing lumen collapse during inspiration. Dynamic
imaging showed incomplete vocal cord abduction during
inspiration in 42.6% and incomplete adduction during
phonation in 61.7% of patients.
Conclusions Static and dynamic MRI is an excellent
modality to non-invasively image anatomy, tissue
characteristics and vocal cord dynamics of the upper
airways. MRI-derived knowledge on postsurgical LTS
sequelae might be used to improve surgery.
INTRODUCTION
© Author(s) (or their
employer(s)) 2020. Re-use
permitted under CC BY.
Published by BMJ.
To cite: Elders B, Ciet P,
Tiddens H, et al. Thorax Epub
ahead of print: [please
include Day Month Year].
doi:10.1136/
thoraxjnl-2020-214921
Paediatric laryngotracheal stenosis (LTS), mostly
caused by prolonged intubation, can have lifelong consequences.1 Open airway surgery achieves
decannulation in up to 95% of severe cases, but
respiratory and vocal sequelae may occur.1–4 Up to
70% of children have impaired in and expiratory
pulmonary function and the majority reports poor
voice quality.5–7
The gold standard to assess the upper airways is
direct laryngotracheoscopy under general anaesthesia.2 8 However, this method has important
limitations, such as need for sedation, the semiquantitative character of information obtained
Key message
What is the key question?
►► Can MRI be used to image the upper airways in
patients after laryngotracheal stenosis repair?
What is the bottom line?
►► Static and dynamic MRI is an excellent modality
to non-invasively image anatomy, tissue
characteristics and vocal cord dynamics of the
upper airways.
Why read on?
►► This study reports novel findings on the
anatomy, tissue characteristics and dynamics
of the upper airways after laryngotracheal
stenosis repair on MRI.
with possible substantial interobserver variability,
suboptimal tissue characterisation and dynamic
evaluation, which can be limited by the depth of
anaesthesia or the presence of the endoscope in the
airway.9 To broaden our knowledge on postoperative sequelae, we need a safe and comprehensive
imaging method to visualise the upper airways in
static and dynamic conditions. CT has been used
to image paediatric laryngeal stenosis,10 11 but has
the important downside of ionising radiation,
especially in the region of the radiation-sensitive
thyroid.12 Thanks to improvements in MRI technology, high-
resolution images are achievable in
paediatric patients and can be used to evaluate the
upper airways.13 Notably, the absence of ionising
radiation, the improved tissue characterisation
and the possibility of dynamic imaging make MRI
suitable to image the upper airways after surgery.
However, several challenges remain, such as image
degradation from motion artefacts and long scan
times. Consequently, to date MRI has only been
used to detect and grade LTS in adult patients.14 15
The aim of this cross-
sectional study was to
develop a static and dynamic upper airways MRI
protocol to obtain information on anatomical and
functional sequelae after open airway surgery for
paediatric LTS.
METHODS
We invited all patients with a history of open
airway surgery for LTS to participate in the MRI
of the upper airways in children and young adults
(MUSIC) study. Inclusion and exclusion criteria are
Elders B, et al. Thorax 2020;0:1–9. doi:10.1136/thoraxjnl-2020-214921
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ORIGINAL RESEARCH
Paediatric lung disease
Diffusion-weighted imaging (DWI) analysis methods
T2-w imaging
Hyper
intensity
Thickening
DWI
ADC
Tissue characterisation
+
+
Hyper
Hyper
Oedema and fibrosis
+
–
Hyper
Hyper
Oedema
–
+
Hyper
Hyper
Fibrosis
+
+
No signal
No Signal
Mild oedema and fibrosis
+
–
No signal
No signal
Mild oedema
–
+
No signal
No signal
Mild fibrosis
+/–
+/–
Hyper
Hypo
Unknown
+/–
+/–
Hypo
Hyper
Unknown
–
–
Hyper
Hyper
Artefact
–
–
No signal
No signal
Normal tissue
+/–, either present of absent; +, present; –, absent; ADC, apparent diffusion coefficient.
Figure 1 Coil setup, healthy volunteer demonstrating positioning of
the 6CH carotid coil placed at the anterior side of the neck and secured
with tape, the head is immobilised by the coil placement.
shown in online supplemental file 1. Patients were compared
with healthy volunteers, consisting of patients’ siblings or
friends, without airway, vocal or pulmonary comorbidities.
A comparison between patients who did and did not participate in the MUSIC study is shown in online supplemental file
2. Participating patients appeared to be significantly younger
than those who did not participate (14.4 (IQR 11.7–19.4) vs
19.1 (14.3–24.0) years, p=0.01). Written informed consent was
obtained from all study participants.
Clinical status
The following data were collected from patients’ electronic
medical file: acquired or congenital stenosis, Cotton-Myer grade
of stenosis,16 location of stenosis (posterior glottis, subglottis,
both), presence of a tracheal cannula before repair (Yes/No), type
of surgery (single-stage (ss), double-stage laryngotracheal reconstruction (ds-
LTR), cricotracheal reconstruction (CTR)),2 age
at reconstruction and presence of comorbidities. Flow volume
spirometry was obtained according to European Respiratory
Society/American Thoracic Society guidelines by a certified
researcher (BE).17 Data are reported as percentage predicted or
z-scores according to Gli index.18 19
MRI
Figure 2 Example of MRI analysis on a healthy volunteer (A) axial
T2-weighted image showing the measurement of the lumen area (1),
Left right (2) and transversal diameter (3) at the level of the Cricoid, (B)
sagittal T2-weighted image showing the location of the cricoid (1), the
proximal trachea (2) and the most caudal slice (3).
2
A paediatric upper airway MRI protocol was developed on a
3.0 T scanner (Discovery MR750, GE Healthcare, Milwaukee,
Wisconsin, USA) using a six channel dedicated carotid coil
(Machnet B.V., Rhoden, The Netherlands and Flick Engineering
B.V., Winterswijk, The Netherlands) (figure 1).20 Total protocol
duration was 30 min. The protocol consisted of static-
free
breathing sequences to assess anatomy and tissue characterisation and dynamic sequences to assess upper airway movement.
Dynamic sequences consisted of two-dimensional (2D) and 3D
sequences, during which the following trained manoeuvres were
performed: a manoeuvre of inspiration and ‘AAA’ phonation of
7 s each performed separately during two static 2D sequences
and a manoeuvre of 2 s inspiration, followed by 6 s ‘AAA’ phonation during the dynamic 3D sequence. These sequences were
repeated until one of the manoeuvres was done correctly. Scan
parameters are included in online supplemental file 3A. The
principal investigator (PI) (BE) trained participants the manoeuvres and was present during all MRI sessions. Image quality and
presence and type of artefacts were recorded. Image analysis
was done using Advantage Windows Server platform (V.2.0, GE
Healthcare, Milwaukee, Wisconsin, USA), as shown in figure 2,
details are provided in online supplemental file 3B.
We assessed anatomy on the T2 (T2-w) and Proton Density-
weighted (PD-
w) static scans and recorded the presence of
arytenoid prolapse or vocal cord thickening, altered vocal cord
positioning, presence and displacement of autologous cartilage grafts (anterior, posterior, none) and airway deformations.
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Table 1
Paediatric lung disease
Patient and healthy volunteers characteristics
Patients (n=48)
Volunteers (n=11)
P value
Age at MRI (years)
14.4 (range 7.5–30.7)
15.9 (range 8.2–28.8)
0.92
Gender (n/% female)
25/52.1
4/36.4
0.37
Weight (kg)
45.2 (IQR 34.5–62.3)
60.8 (IQR 31.6–74.0)
0.34
Height (metre)
1.6 (IQR 1.4–1.7)
1.7 (IQR 1.4–1.8)
0.34
Type of stenosis (n/%)
Congenital
3/6.3
Acquired
45/93.8
Cotton Myer grade of stenosis (n/%)
Grade I
4/8.3
Grade II
15/31.3
Grade III
27/56.3
Grade IV
2/4.2
Location of stenosis (n/%)
Posterior glottis
11/22.9
Subglottis
17/35.4
Posterior glottis and subglottis
20/41.7
Tracheal cannula before repair (n/%)
38/79.2
Type of reconstruction (n/%)
ss-LTR
42/87.5
ds-LTR
2/4.2
CTR
4/8.3
Age at reconstruction (years)
2.2 (IQR 1.1–4.5)
Years since reconstruction
11.5±4.6
Comorbidities (n/%)
Asthma 2/4.2
BPD 9/18.8
Cardiac 3/6.3
DiGeorge syndrome 1/2.1
Oesophageal atresia 3/6.3
Kartagener syndrome 1/2.1
OSAS 1/2.1
PMR 6/12.5
Tracheomalacia 2/4.2
Descriptive statistics. Data are presented as mean±SD, median (range or IQR) or absolute number (n) and percentage.
BPD, bronchopulmonary dysplasia; CTR, cricotracheal resection; ds-LTR, double stage laryngotracheal reconstruction; OSAS, obstructive sleep apnoea syndrome; PMR, psychomotor retardation;
ss-LTR, single-stage laryngotracheal reconstruction.
Airway lumen area, anterior–posterior and transversal diameters
were measured on axial T2-w sequences at the level of the vocal
cords, cricoid, tracheal deformation (if present) and proximal
trachea and corrected for height in metres. Measurement of the
proximal trachea was done at the axial slice midway between
the cricoid and the most caudal slice. If this was the site of the
tracheal deformation, a superior axial slice was used.
We assessed tissue characteristics on T2-
w and diffusion-
weighted imaging (DWI) to identify structural tissue alterations such as fibrosis, (chronic) oedema or a combination, at
the following locations: arytenoids, vocal cords or cricoid.21 22
Tissue was characterised as described in table 1.
Movement of the upper airways was assessed on 2D and 3D
dynamic imaging. Correct performance of the manoeuvres was
evaluated in video format, defined as any vocal cord abduction
during inspiration and any vocal cord adduction during phonation on 2D images, and any vocal cord movement on 3D images.
Movement was evaluated on completeness and symmetry.
Airway lumen areas were measured on axial 2D sequences at
Elders B, et al. Thorax 2020;0:1–9. doi:10.1136/thoraxjnl-2020-214921
the vocal cords, cricoid, tracheal deformation (if present) and
proximal trachea during inspiration and phonation. Quantitative measurements were only made if 2D manoeuvres were
performed correctly.
Patients with a history of CTR, which is characterised by a
partially absent cricoid cartilage, were excluded from measurements at the cricoid level. Analysis was done by the PI (BE)
with 2 years experience in upper airways MRI. Intraobserver
and interobserver reproducibility was tested by reanalysing
12 randomly selected MRIs by the PI and a second researcher
appropriately trained in upper airways MRI (WvdB).
Statistics
The Shapiro-Wilk test was conducted to test data distribution.
Normally distributed data are presented as mean±SD and non-
normally distributed data are presented as median (range or IQR).
Data were compared using the parametric t-test for normally
distributed data, the Mann-
Whitney U test for not normally
3
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Table 2
Paediatric lung disease
RESULTS
Patient and healthy volunteer characteristics are presented in
table 2. Forty-eight patients and eleven healthy volunteers were
included, with a mean age of 14.4 (range 7.5–30.7) and 15.9
(range 8.2–28.8) years. Three patients (6.3%) had a congenital
LTS, and 45 patients (93.8%) had an acquired LTS. Patients most
often underwent ss-LTR (87.5%). The most common comorbidity was bronchopulmonary dysplasia (BPD) (18.8%).
Table 3 shows spirometry data for patients and healthy
volunteers. Patients’ expiratory and inspiratory (expressed as a
decrease in forced inspiratory volume in 1 s (FIV1) divided by
maximal vital capacity (VCmax) and an increase in Expiratory
Disproportion Index (EDI)) spirometry outcomes were lower
than those of healthy volunteers. Spirometry outcomes did not
differ significantly between LTS patients with and without BPD
(forced expiratory volume in 1 s (FEV1) z-score=−1.9 ± 1.7
vs -0.2±1.00, p=0.88, FEV1/functional vital capacity (FVC)
z-score=−2.3 (IQR -2.9 to −0.7) vs −1.2 (−2.0 to −0.3),
p=0.34, FIV1/VCmax=65.6 (IQR 49.8–80.0) vs 63.2 (54.2–
80.1),p=0.84, EDI=67.6% ± 15.0% vs 64.6±15.4%, p=0.94).
MRI
MRI was successfully performed in 47 patients and 10 healthy
volunteers (97%) (table 4). Two participants did not complete
the MRI protocol due to claustrophobia. Image quality of the
majority of the images was good, without artefacts in 66.7%.
Excellent image resolution was achieved with best spatial resolution of 0.5×0.5 (in plane) x 2 mm (slice thickness) and best
temporal resolution of 330 ms (3D dynamic scans).
Figure 3 shows an example of a patient’s static MRI. The
outcomes of the static and dynamic MR analyses are shown in
table 4. Thirty-eight patients (80.9%) and one healthy volunteer
(10%) showed vocal cord thickening on MRI. This volunteer
had a history of Tetralogy of Fallot, and had repeatedly been
intubated during surgery, without any current complaints of
respiratory distress. In patients with a history of LTR (n=43)
autologous cartilage grafts could be identified on MRI in all but
one patient, in whom the anterior graft could not be seen due to
an artefact caused by a recently repaired tracheal fistula. Thirteen patients (30.2%) showed displacement of cartilage graft(s)
into the airway lumen, namely displacement of the anterior
cartilage graft in 3/39 (7.7%) and displacement of the posterior
cartilage graft in 12/41 (29.3%) patients. Online supplemental
file 4 shows an example of displacement of a posterior cartilage
graft.
Patients’ vocal cord lumen area was significantly smaller than
that of healthy volunteers during free breathing. At the cricoid
level, the location of LTR, the lumen area was comparable
between patients and healthy volunteers. Additionally, in 25
patients (53.2%) an A-frame deformation at the level of previous
tracheal cannula was found with an average lumen area reduction of 37.5% (range −9.3% to −74.5%) compared with the
proximal trachea. Three patients showed other trachea deformations: one idiopathic saber-sheath deformation (an intrathoracic
4
Table 3
Flow volume spirometry data
Patients (n=48)
Volunteers (n=11)
P value
FVC
% predicted
86.5 (80.5–100.0)
z-s core
−1.0±1.3
97.0 (91.0–110.0)
0.1±1.1
0.02*
0.02*
FEV1
% predicted
80.5 (73.0–91.0)
97.0 (91.0–107.0)
0.001*
z-score
−1.6 (−2.3 to −0.8)
−0.3 (−0.8 to 0.6)
0.001*
FEV1/FVC
% predicted
91.0 (79.3–96.0)
z-s core
−1.4±1.6
100 (94.0–106.0)
−0.3±1.6
0.02*
0.04*
PEF
% predicted
58.5 (41.3–71.8)
z-s core
−3.1 (−4.4 to −2.2)
111.0 (78.0–123.0)
<0.001*
0.6 (−1.6 to 1.6)
<0.001*
109.0 (76.0–127.0)
<0.001*
FEF25
% predicted
61.5 (43.5–61.5)
z-s core
−2.8±1.4
−0.3±2.2
<0.001*
% predicted
62.1±21.8
93.1±44.8
<0.001*
z-score
−2.4±1.5
−0.8±2.3
FEF50
0.007*
FEF75
% predicted
81.5±36.2
z-score
−0.8±1.4
104.4±44.8
0.08
−0.1±1.4
0.11
MEF
% predicted
64.0±23.0
92.8±31.7
0.001*
z-score
−1.8±1.3
−0.4±1.5
0.003*
100.7±12.7
0.02*
VCmax
% predicted
89.1±15.2
z-score
−1.1 (−1.53–0.0)
−0.3 (−0.8–0.9)
0.02*
75.5±15.0
85.7±15.4
0.05*
FVC in
% predicted
FIV1 (L)
1.7 (1.3–2.5)
2.7 (1.6–5.6)
0.47
FIV1/FVC in (%)
78.5 (65.0–92.1)
99.8 (88.2–100.0)
0.01*
FIV1/VCmax (%)
66.3±16.5
80.9±9.5
0.007*
FEV1/FIV1 (%)
EDI (%)
119.0±25.8
62.6 (52.5–79.4)
105.3±17.6
45.3 (43.9–50.1)
0.1
0.001*
Spirometry data. Data are presented as mean±SD or median (IQR).
*P<0.05.
EDI, Expiratory Disproportion Index; FEF25-75, forced expiratory flow at 25%–75% of
expiration; FEV1, forced expiratory volume in 1 s; FIV1, forced inspiratory volume in 1 s;
FIV in, forced inspiratory volume; FVC, forced vital capacity; FVC in, forced vital capacity
inspiratory; MEF, mean expiratory flow; PEF, peak expiratory flow; VC max, maximum vital
capacity.
tracheal deformation in which the transversal diameter of the
trachea is smaller than the anterior–posterior diameter),23 one
saber-
sheath deformation with an oesophageal pouch after
oesophageal atresia repair, and one known malacia. In 78.3%
of patients the narrowest point of the airway was located at the
vocal cords, in 19.6% at the tracheal deformation, and in 2.2%
at the trachea. In all healthy volunteers the narrowest point was
located at the vocal cords.
A significant correlation between vocal cord lumen area and
both in- and expiratory spirometry was found (table 5, online
supplemental file 5).
As an incidental finding MRI showed hypointense regions on
PD-w images in 40 patients (85.1%), and none of the healthy
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distributed data and the χ2 test for categorical data. Similarly,
Pearson’s and Spearman’s r correlations were calculated for
normally and not normally distributed data respectively. Binary
logistic regression was used for categorical data. Intraobserver
and interobserver agreement was calculated with the intraclass
correlation coefficient. Correction for multiple testing was not
performed and a 5% significance level was assumed. Data analysis was done using SPSS Statistics (V.25, IBM).
Paediatric lung disease
MRI results
Patients and volunteers=59
Successful MRI (n/%)
57/97
Quality static images (n/%)
Bad 0/0.0
Fair 2/3.5
Moderate 8/14.0
Good 35/61.4
Excellent 12/21.1
Quality dynamic images (n/%)
Bad 2/3.5
Fair 5/8.8
Moderate 6/10.5
Good 40/70.2
Excellent 4/7.0
Artefacts (n/%)
None 38/66.7
Coil 12/21.1
General motion 6/10.5
Respiratory motion 1/1.8
Static
Patients=47†
Volunteers=10
Vocal cord thickening (n/%)
38/80.9
1/10
P value
Abnormal vocal cord positioning (n/%)
10/21.3
1/10
Area (mm2)
22.0 (17.7–30.3)
35.1 (21.2–54.7)
0.03*
AP diameter (mm)
8.4±2.0
9.0±2.3
0.37
Transversal diameter (mm)
2.8±1.0
3.8±1.2
0.01*
Area (mm2)
62.3±27.0
66.2±34.8
0.70
AP diameter (mm)
8.4±2.0
9.8±2.1
0.05
Transversal diameter (mm)
6.3±1.4
5.7±0.8
0.16
Presence of tracheal deformation (n/%)
25/53.2
0/0
Area (mm2)
28.6 (20.8–41.9)
–
AP diameter (mm)
6.6±1.7
–
Transversal diameter (mm)
4.4±1.1
–
Area (mm2)
61.0 (39.9–83.3)
86.1 (41.5–130.1)
0.19
AP diameter (mm)
7.3±1.5
8.1±2.1
0.16
Transversal diameter (mm)
7.3±1.6
8.2±1.3
0.10
Area decrease at deformation (area deformation/area
trachea,%)
37.5±23.5
–
–
Complete abduction during inspiration (n/%)
27/57.4
10/100
0.01*
Complete adduction during phonation (n/%)
18/38.3
10/100
<0.01*
2D
Patients=35†
Volunteers=9
Vocal cords
43.7±22.7
72.9±42.3
0.01*
Cricoid
67.5±26.9
84.3±42.4
0.15
Tracheal deformation
38.4±13.7
–
–
Trachea
79.5±28.5
104.2±50.5
0.07
Vocal cords
10.9±9.3
7.2±4.7
0.26
Cricoid
65.6±30.4
90.5±44.4
0.06
Tracheal deformation
46.9±16.7
–
–
Vocal cords
Cricoid†
Tracheal deformation
Proximal trachea
Dynamic
Inspiration areas (mm2)
Phonation areas (mm2)
Continued
Elders B, et al. Thorax 2020;0:1–9. doi:10.1136/thoraxjnl-2020-214921
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Table 4
General quality
Paediatric lung disease
Continued
General quality
Trachea
Patients and volunteers=59
77.0±27.7
105.2±49.9
0.03*
Vocal cords
−72.1±23.7
−88.9±7.3
0.04*
Cricoid
−7.5 (−22.7–6.0)
−5.5 (−0.4–19.0)
0.02*
Tracheal deformation
27.0±41.8
–
–
Trachea
−3.4 (−10.4–8.0)
2.2 (−4.6–10.5)
0.21
Difference in areas (%)
Data are presented as mean±SD, median (IQR) or absolute numbers (n) and percentages. All areas and diameters are corrected for height in metres.
*P<0.05, data are corrected for height in metres.
†Cricoid measurements conducted in n=43 for static and n=33 for dynamic images, due to exclusion of patients with history of CTR.
AP, anterior–posterior; CTR, cricotracheal reconstruction; 2D, two dimensional.
volunteers. Ultrasonography in four patients did not clarify the
origin of this artefact (online supplemental file 6), being either
postsurgical artefacts from the use of metal surgical instruments,
such as those detected in gradient-echo imaging of the postsurgical knee,24 25 or subcutaneous emphysema, despite on physical
examination no crackling could be felt on the neck.
An online supplemental video shows an example of the dynamic
MRI of a patient. Complete abduction during inspiration and
Figure 3 Example of static MRI image of a patient with a history of
LTS after prolonged intubation due to prematurity having undergone
both an SS-LTR and ds-LTR, showing deviation and thickening of the
vocal cords (A), asterisk indicating the posterior cartilage graft placed
during LTR (B) and the A-frame deformation of the trachea (C). ds-
LTR, double stage laryngotracheal reconstruction; LTS, laryngotracheal
stenosis; SS, single stage.
6
complete adduction during phonation was seen in 57.4% and
38.3% of patients, respectively, compared with 100% for both
in healthy volunteers. In 11 patients (23.4%) asymmetrical vocal
cord movement was observed. Quantitative analyses on the 2D
dynamic images could be performed in 37 patients (78.7%) and
9 healthy volunteers (90%), due to correct execution of the
manoeuvres. In two patients, 2D dynamic scans were of insufficient quality to perform the area measurements. Patients showed
a significantly smaller vocal cord lumen area during inspiration
compared with healthy volunteers. Binary logistic regression did
not show a correlation between posterior glottic involvement of
the stenosis and the area between the vocal cords during inspiration (OR 0.98, 95% CI 0.94 to 2.01, p=0.18) nor phonation
(OR 1.03, 95% CI 0.95 to 1.13, p=0.46) on MRI. A greater area
between the vocal cords during inspiration was correlated to an
increase in FIV1/VCmax (r=0.38, 95% CI 0.09 to 0.69, p=0.01)
but not to the EDI (r=−0.23, 95% CI −0.54–0.07, p=0.13).
In patients with an A-frame trachea deformation, an average
decrease in airway lumen area of 27% during inspiration was
observed. We did not find a correlation between the presence of
a tracheal deformation and a decrease in inspiratory spirometry
(FIV1/VCmax OR 0.98, 95% CI 0.94 to 1.02, p=0.35 and EDI
1.01, 95% CI 0.96 to 1.05, p=0.77)
On T2-
w sequences 37 (78.7%) patients showed signs of
fibrosis or chronic oedema, located at the arytenoids in 59.6%,
vocal cords in 57.4% and cricoid in 8.5%. Forty- six patients
(95.8%) and 10 healthy volunteers (90.9%) had DW images
available for analyses. On DWI 26.1% of patients showed
signs of oedema, 6.5% of patients showed signs of fibrosis, and
17.4% of patients showed signs of a combination of oedema and
fibrosis. One patient had a pattern on hyperintense signal on
DWI with hypointense signal on apparent diffusion coefficient
(ADC) and one patient had a pattern of hypointense signal on
DWI with hyperintense signal on ADC, both of unknown origin.
Eighteen patients (39.1%) had signs of tissue alteration on T2-w
imaging without signal abnormalities on DWI, corresponding
to mild fibrosis and/or oedema. Tissue alteration according to
the combination of T2-w and DW imaging did not correlate to
previous glottic involvement (1.7, 95% CI 0.5 to 5.9, p=0.40)
nor to impaired vocal movement on MRI (0.86, 95% CI 0.3 to
2.7, p=0.79). Tissue alteration according to T2-w images alone,
therefore, also including mild fibrosis and oedema, was significantly correlated to previous glottic involvement of the stenosis
(OR 9.5, 95% CI 1.7 to 53.4, p=0.01) as well as impaired vocal
cord movement on MRI (3.5, 95% CI 1.0 to 11.6, p=0.04).
Intravariability and intervariability analysis showed good
to excellent consistency for all static (online supplemental file
7) and dynamic MRI measurements, except for the subjective
scoring of complete abduction and adduction.
Elders B, et al. Thorax 2020;0:1–9. doi:10.1136/thoraxjnl-2020-214921
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Table 4
Paediatric lung disease
Correlations between areas at different levels of the upper airways on MRI and spirometry
FEV1 (%pred)
FEV1/FVC (%pred)
FIV1/VCmax (%)
EDI (%)
Vocal cord area
rs=0.30
(0.04 to 0.52)
p=0.02
rs=0.33
(0.06 to 0.54)
p=0.01
r=0.34
(0.08 to 0.58)
p=0.01
rs=−0.31
(−0.53 to 0.05)
p=0.02
Cricoid area
r=0.03
(−0.24 to 0.29)
p=0.85
r=−0.02
(−0.29 to 0.25)
p=0.88
r=0.03
(−0.24 to 0.29)
p=0.84
r=−0.08
(−0.19 to 0.35)
p=0.54
Tracheal deformation area
rs=0.25
(−0.16 to 0.59)
p=0.22
rs=0.19
(−0.23 to 0.54)
p=0.37
r=0.22
(−0.20 to 0.63)
p=0.30
rs=−0.01
(−0.19 to 0.35)
p=0.97
Trachea area
rs=0.18
(−0.09 to 0.42)
p=0.19
rs=0.14
(−0.13 to 0.39)
p=0.30
r=0.28
(0.01 to 0.53)
p=0.04
rs=−0.06
(−0.32 to 0.20)
p=0.65
Correlations between areas at different levels of the upper airways on MRI and spirometry. Data are presented as Pearson (r) or Spearman (rs) correlation coefficient (95% CI) and p value. P values
<0.05 are in bold.
EDI, Expiratory Disproportion Index; FEV1, forced expiratory volume in 1 s; FIV1, Forced inspiratory volume in 1 s; FVC, forced vital capacity; VCmax, maximal vital capacity.
DISCUSSION
We used static and dynamic MRI to evaluate the upper airways
after open airway surgery for paediatric LTS. MRI enabled visualisation of anatomical structures, tissue characterisation and
quantification of vocal cord and airway dynamics and thereby
provided a new imaging modality to assess postsurgical sequelae
of LTS.
Static MRI permitted quantification of the postsurgical upper
airway anatomy in an objective manner. Patients’ vocal cord
lumen area, but not cricoid lumen area, was smaller than that
of healthy volunteers. These static measurements proved to be
highly reproducible as shown by the excellent intraobserver and
interobserver agreement. Furthermore, we could visualise the
correct or incorrect position of autologous cartilage grafts in the
cricoid.
Dynamic MRI of the vocal cords showed a high prevalence
of impaired vocal cord movement. These sequences showed to
be important to assess respiratory and vocal sequelae of LTS
surgery and could be used as monitoring tool for different treatment options.5 However, subjective scoring of impaired vocal
cord abduction and adduction resulted in poor interobserver
agreement, presumably because abduction and adduction are
highly influenced by both thickening and abnormal positioning
of the vocal cords. Therefore, we did not use subjective scoring
of abduction and adduction for further analyses. To evaluate
vocal cord movement, we recommend to use area measurements
during inspiration and phonation. We furthermore recommend
the use of both 2D and 3D sequences, with 2D best suitable for
quantitative measurements and 3D best suitable for the overall
evaluation of upper airway dynamics.
Interestingly, dynamic MRI showed a high incidence of
tracheal deformations with lumen collapse during inspiration.
Previous studies have reported a lower incidence of A-frame
deformations of 10% after tracheal cannula removal.26 Likely
the higher incidence in our study related to the ability to detect
all A-frame deformations, irrespective of clinical symptoms. We
did not observe a correlation between the presence of a tracheal
deformation and impaired inspiratory spirometry outcomes.
This could either be caused by a small sample size, or more likely
by the malacic character of the tracheal deformation, where
elastic recoil due to an increased negative pressure at the level of
the stenosis (Bernoulli-Venturi effect) varies airway resistance at
the level of the stenosis.27 28
Tissue characterisation was evaluated on T2-
w and DW
imaging, showing good correlation between tissue alteration
according to T2-
w imaging and patient characteristics and
outcome. Tissue alteration of airway mucosa (such as the presence of fibrosis) is currently subjectively diagnosed by laryngotracheoscopy, known to be sensitive to observer bias and
Elders B, et al. Thorax 2020;0:1–9. doi:10.1136/thoraxjnl-2020-214921
poor interobserver correlations.29 30 T2-w MRI can be used as
a replacement as it allows to visualise oedema and fibrosis. In
addition, previous studies have shown the potential additional
benefit of DWI to detect tissue with decreased free movement of
hydrogen molecules due to cellular swelling or increased tissue
density, as has been observed in postradiation fibrosis.13 31 32
This is the first study using DWI to compare normal airway
tissue to postsurgical tissue alterations. Although we did not
have histology samples available for comparison, T2-w imaging
seems to be able to characterise tissue of the upper airways.
No added benefit of DWI compared with T2-w imaging was
found, either because DWI does not detect mild tissue alterations or because DWI is highly sensitive to technical variations such as poor signal-to-noise ratios from poor coil fitting,
inadequate fat suppression or motion artefacts in younger children. Contrast enhancement might be an alternative method to
further improve tissue characterisation, but this would require
intravenous access and could raise concerns related to the use of
MRI contrast agents as tissue deposition in the brain has been
reported.33 In selected patients, a combination of MRI with
positron emission tomography might be used to detect active
inflammation.34
Our overall findings suggest that MRI, when performed
successfully, can supply highly relevant information for follow-up
evaluation of LTS patients and provide similar information as
laryngotracheoscopy. MRI can overcome important downsides
of laryngotracheoscopy such as the need for anaesthesia, inter-
observer variability issues and it allows objective tissue characterisation. A challenge of our MRI protocol is the need for
patient cooperation, which precludes its use in children below
the age of 6 years and in older non-cooperative children. Good
correlations between spirometry outcomes and lumen areas
suggest that MRI measurements could aid in understanding the
anatomical substrate causing airflow obstruction, as indicated by
a previous study.14 A more affordable and widely available alternative method could be flexible nasal endoscopy, however, this
method is unsuitable to evaluate anatomy below the vocal cords,
is non- quantitative and can be challenging in case of arytenoid
prolapse. Therefore, we consider flexible nasal endoscopy not a
realistic alternative to laryngotracheoscopy nor to MRI.2
Our findings also show the diversity and complexity of the
postsurgical airway with patients presenting with a heterogeneity in the level(s) and severity of airway obstructions. The
effect of obstructions at consecutive airway levels on airway
dynamics and airway resistance is not entirely clear. We are
currently working on computational fluid dynamic modelling
studies to visualise airway mechanics in an attempt to determine
the contributions of separate obstructions on airflow patterns
and airway resistance.
7
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Table 5
Paediatric lung disease
Acknowledgements We would like to acknowledged Eleni Rosalina
Andrinopoulou for the statistical support on the article.
Contributors BE contributed to the design of the work, data collection and
analysis, drafted the manuscript and gave final approval to the manuscript. PC
contributed to the design of the work, data analysis, critically revised the manuscript
and gave final approval to the manuscript. HT contributed to the design of the
work, critically revised the manuscript and gave final approval to the manuscript,
WvdB contributed to data analysis, critically revised the manuscript and gave final
approval to the manuscript, PW contributed to the design of the study and data
collection, critically revised the manuscript and gave approval to the final version of
the manuscript. BP contributed to the design of the work and data analysis, critically
revised the manuscript and gave final approval to the manuscript.
Funding This study was funded by Vrienden van het Sophia (B17-02-Step 2017).
Competing interests None declared.
Patient consent for publication Obtained.
Ethics approval This study was approved by the local medical ethics review board
(MEC-2018–013).
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available on reasonable request. Data
consist of deidentified patient data such as clinical data and MRIs saved in the
electronic patient file and research analyses. All data are available from the
corresponding author, after permission.
Open access This is an open access article distributed in accordance with the
Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits
others to copy, redistribute, remix, transform and build upon this work for any
8
purpose, provided the original work is properly cited, a link to the licence is given,
and indication of whether changes were made. See: https://creativecommons.org/
licenses/by/4.0/.
ORCID iD
Pierluigi Ciet http://orcid.org/0000-0003-4017-8957
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