Ventilation inhomogeneity in patients with cystic fibrosis measured by
electrical impedance tomography
Zhanqi Zhao
1
, Rainald Fischer
2
, Ullrich Müller-Lisse
3
, Knut Moeller
1
1
Department of Biomedical Engineering, Furtwangen University, Villingen-Schwenningen, Germany; zhanqi.zhao@hs-
furtwangen.de
2
Department of Pneumology, University of Munich, Munich, Germany
3
Department of Radiology, University of Munich, Munich, Germany
Abstract
Objective: The distribution of ventilation within the lung is inhomogeneous. We hypothesized that the degree of inho-
mogeneity in patients with cystic fibrosis (CF) differs from that in healthy subjects.
Method: Three adult patients with cystic fibrosis (CF) and two healthy subjects were recruited for this preliminary study.
Subjects were asked to breathe in as deep and exhale as hard as possible three times. Electrical impedance tomography
(EIT) measurements were performed during spirometry tests. The global inhomogeneity index(GI) was applied to assess
the degree of ventilation homogeneity at 25%, 50%, 75% and 100% of maximum inspiratory volume.
Results: Airway obstruction was detected in CF patients but not in healthy volunteers during spirometry tests. GI de-
creased as inspiratory volume increased in CF patients (0.59±0.20 at 25% and 0.39±0.09 at 100%, p<0.01, mean±SD)
while GI remained unchanged in healthy subjects (0.40±0.05 at 25% and 0.37±0.03 at 100%, p=0.31).
Conclusion: Degree of ventilation homogeneity appears to vary during forced respiration in CF patients, but not in
healthy volunteers. EIT is a practical method to measure the inhomogeneity of ventilation distribution.
1 Introduction
Cystic fibrosis (CF) is an inherited, chronic disease of the
body’s mucus and sweat glands that mainly affects the
lungs and the digestive system. The alteration of lung
structure and small airways leads to flow reduction during
in- and expiration [1-2]. There is still no cure for CF, and it
tends to increase in severity over time [3]. Despite im-
proved treatment, mean survival time of CF patients is
only 37 years [4].
Distribution of tidal volume in lungs is often inhomogene-
ous. The degree of inhomogeneity reveals information
about the patients’ respective lung conditions. The routine
diagnosis tools for CF patients such as spirometry and
body plethysmography are unable to assess ventilation dis-
tribution. Other methods such as multibreath washout
technique and computed tomography (CT) are inconven-
ient or even potentially harmful to the patient and therefore
not suitable for outpatients.
Electrical Impedance Tomography (EIT) is a noninvasive,
radiation-free imaging technique, which can monitor both
regional lung ventilation and tidal volume distribution, by
measuring the electrical potentials at the chest wall surface.
The rationale is that changes in regional air content and
regional blood flow modify the electrical impedance of
lung tissue [5-6]. We have recently developed an EIT-
based global inhomogeneity (GI) index to assess ventila-
tion inhomogeneity [7]. We hypothesized that due to dis-
ease-related airway obstruction, ventilation inhomogeneity
in CF patients varies during forced respiration and it can
be detected with EIT.
2 Patients and Methods
Three patients with cystic fibrosis (CF) (1 male and 2 fe-
male; body height, 180, 165 and 156 cm; body weight, 64,
58 and 55 kg; age at examination, 32, 35 and 30 years, re-
spectively) and two healthy volunteers (2 male; body
height, 178 and 168 cm; body weight, 62 and 60 kg; age at
examination, 50 and 28 years, respectively) were investi-
gated. Written informed consent was obtained from all pa-
tients prior to the study. The study was approved by the
local ethics committee.
All subjects were asked to breathe in as deep and exhale as
hard as possible three times at the spirometer, according to
standard ATS spirometry guidelines [8]. An EIT electrode
belt, which carries 16 electrodes with a width of 40 mm,
was placed around the chest in the fifth intercostal space
while one reference electrode was placed on the patients’
abdomen (EIT Evaluation KIT 2, Dräger Medical, Lübeck,
Germany). EIT images were continuously recorded at 20
Hz and stored during spirometry tests.
GI index has been described in previous studies [7, 9]. In
this preliminary study, the GI index was slightly modified
to evaluate the inhomogeneity degree at 25%, 50%, 75%
and 100% of maximum inspiratory volume. For every
forced respiration, four difference images, which represent
the respective differences of impedance between 25%,
50%, 75%, 100% of maximum inspiratory volume and in-
spiration begin (0%), were generated. Lung regions in EIT
images were defined using the LAE method [10]. The me-
dian value of the pixels in the lung area is calculated for
each difference image. The GI index is defined as the sum
Biomed Tech 2012; 57 (Suppl. 1) © 2012 by Walter de Gruyter · Berlin · Boston. DOI 10.1515/bmt-2012-4250
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of the absolute differences between the median value and
every pixel value, which is normalized with the sum of the
impedance values within the lung area:
()
∑
∑
∈
∈
−
=
lungyx
xy
lungyx
lungxy
DI
DIMedianDI
GI
,
,
(1)
where DI is the value of the differential impedance in the
difference images; DI
xy
denotes the pixel in the identified
lung area; DI
lung
are all pixels in the lung area under obser-
vation.
Data analysis was performed using MATLAB (The
MathWorks Inc., Natick, MA, USA). Lilliefors test was
used to confirm the distribution of the data. In case of
normal distribution, results were expressed as mean ± SD.
Unpaired t-test was used to evaluate the difference of GI
index between level 25% and 100%, 50% and 100%, 75%
and 100%. P < 0.05 was considered statistically significant.
The significant levels were corrected for multiple compari-
sons using Holm’s sequential Bonferroni method.
3 Results
Figure 1 shows the ventilation distribution during one
forced inspiration-expiration cycle and one normal sponta-
neous breath in a CF patient. According to the GI index,
air distribution was more homogeneous during forced
breathing than during spontaneous breathing.
When the forced breathing cycle was analyzed at 4 differ-
ent levels, the GI index decreased as inspiratory volume
increased in CF patients, while it remained unchanged in
healthy subjects (Table 1).
Fig. 1 Typical global impedance curve (A) and tidal im-
ages of EIT during forced breathing (B) and normal, spon-
taneous breathing (C) in one CF patient. AU: arbitrary unit.
Table 1 GI index of CF patients and healthy volunteers at
different levels of maximum inspiratory volume.
Subjects Category CF Healthy
25% 0.59±0.20 * 0.40±0.05
50% 0.49±0.15 0.36±0.03
75% 0.43±0.12 0.35±0.02
100% 0.39±0.09 * 0.37±0.03
* p-value P < 0.01
Figure 2 shows the difference images of one CF patient at
different preselected levels of the forced breathing cycle.
In this particular patient, the right lung (on the left side of
EIT images) was inhomogeneously ventilated at 25% and
50% of the maximum inspiratory volume. Ventilation dis-
tribution became more homogeneous at higher inspiratory
volume levels.
Biomed Tech 2012; 57 (Suppl. 1) © 2012 by Walter de Gruyter · Berlin · Boston. DOI 10.1515/bmt-2012-4250
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Fig. 2 Difference images of one CF patient at 25% (A),
50% (B), 75% (C) and 100% (D) of maximum inspiratory
volume.
4 Discussion
In this preliminary study of 5 spontaneously breathing
subjects, EIT, as applied during lung function tests dem-
onstrated that ventilation homogeneity differed between
CF patients and healthy subjects during forced respiration.
Since its early application in the 1980s [11], EIT analysis
of the inhomogeneity of air distribution within the lungs
has attracted the attention of researches all over the world
[7]. However, methods were missing which could both
simplify the complex information provided by EIT, and
consider the contribution of every pixel in EIT images [7].
Hence, we defined the GI index to quantify tidal volume
distribution within the lung. The reliability and potential
use of the GI index for mechanically ventilated patients
has previously been investigated [7, 9]. The GI index has
also been applied for spontaneously breathing subjects in
different body positions [12].
Differences in ventilation homogeneity between healthy
volunteers and patients with critical lung disease have
previously been reported [7]. In theory, the degree of ven-
tilation inhomogeneity should be relatively low for CF
patients when compared to patients with critical lung dis-
ease such as acute respiratory distress syndrome. There-
fore, it should be more difficult to distinguish patients
with CF from healthy volunteers by means of EIT. How-
ever, due to chronic airway obstruction in CF patients, it
may take longer for air to distribute within their lungs.
During cycles of forced inspiration and expiration, there
should be more time for air distribution. Thus we assessed
the ventilation distribution with EIT during lung function
tests, with recording of three subsequent cycles of forced
breathing. As we hypothesized, the EIT-based GI index
demonstrated ventilation inhomogeneity at the onset of
forced breathing in CF patients, while ventilation became
more homogeneous during later phases of inspiration. No
significant changes of ventilation over the breathing cycle
were found in healthy volunteers.
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A limitation of the present study is that only three patients
with CF and two healthy subjects were included. To cor-
roborate these early results, more subjects will be exam-
ined by means of EIT.
5 Conclusion
The degree of ventilation homogeneity varies during
forced respiration in CF patients. The EIT-based GI index
appears to be a practical method to measure the inho-
mogeneity of ventilation distribution.
6 Acknowledgment
This work was partially supported by Bundesministerium
für Bildung und Forschung (Grant 1781X08 MOTiF-A),
and Dräger Medical, Lübeck.
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