Intraoperative lung edema monitoring by microwave reflectometry.

Abstract

Microwave reflectometry might be a suitable tool for the thoracic surgeon to monitor edema formation of the lung during lung surgery. A new setup of microwave reflectometry for lung water measurements was developed and tested for clinical application. Three lung models were used for the microwave reflectometry tests: 1) the model of an ex vivo isolated perfused rat lung to investigate lung edema formation during ischemia-reperfusion (n=6), 2) the in situ lung of a human patient to demonstrate the feasibility of lung water monitoring during a surgical operation, 3) the model of an ex vivo isolated perfused human lung to investigate edema formation during postischemic reperfusion and to investigate the changes in water content in the region of a tumor. During human lung operation, significant changes in water content occurred in different lung areas. During isolated perfusion, a significant increase in lung water was measured in models 1) and 3) (P=0.03). Water content of tumor tissue was higher than in the surrounding healthy lung tissue. Microwave reflectometry offers a non-invasive approach to monitor lung edema formation in experimental models and during thoracic surgery.

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doi:10.1510/icvts.2010.243691
Interactive CardioVascular and Thoracic Surgery 12 (2011) 540–544
? 2011 Published by European Association for Cardio-Thoracic Surgery
Institutional report - Thoracic non-oncologic
Intraoperative lung edema monitoring by microwave reflectometry?
Kai Nowak *, Wolfgang Gross , Kathrin Nicksch , Christine Hanusch , Marko Helbig , Peter Hohenberger ,
Martha M. Gebhard , Michael Schaefer
a,
bacda
bb
Division of Thoracic Surgery, Department of Surgery, Mannheim University Medical Center, University of Heidelberg, Theodor-Kutzer-Ufer 1-3,
68135 Mannheim, Germany
Experimental Surgery, Faculty of Medicine Heidelberg, Germany
Department of Anesthesia and Critical Care Medicine, Medical Faculty Mannheim, University of Heidelberg, Germany
Department of Electrical Engineering and Information Technology, Illmenau University of Technology, Illmenau, Germany
a
b
c
d
Received 9 June 2010; received in revised form 23 November 2010; accepted 29 November 2010
Abstract
Microwave reflectometry might be a suitable tool for the thoracic surgeon to monitor edema formation of the lung during lung surgery.
A new setup of microwave reflectometry for lung water measurements was developed and tested for clinical application. Three lung models
were used for the microwave reflectometry tests: 1) the model of an ex vivo isolated perfused rat lung to investigate lung edema formation
during ischemia-reperfusion (ns6), 2) the in situ lung of a human patient to demonstrate the feasibility of lung water monitoring during a
surgical operation, 3) the model of an ex vivo isolated perfused human lung to investigate edema formation during postischemic reperfusion
and to investigate the changes in water content in the region of a tumor. During human lung operation, significant changes in water
content occurred in different lung areas. During isolated perfusion, a significant increase in lung water was measured in models 1) and 3)
(Ps0.03). Water content of tumor tissue was higher than in the surrounding healthy lung tissue. Microwave reflectometry offers a non-
invasive approach to monitor lung edema formation in experimental models and during thoracic surgery.
? 2011 Published by European Association for Cardio-Thoracic Surgery. All rights reserved.
Keywords: Microwave reflectometry; Lung ischemia; Lung edema; Thoracic surgery
1. Background
Changes during ischemia and reperfusion of the lung
trigger inflammatory responses leading to pulmonary ede-
ma and gain of lung wet to dry weight with a source of
considerable mortality w1–4x. If pathophysiological changes
in fluid homeostasis within the lung could be observed
during operation, precautions could be made for the
patients. Continuous intraoperative monitoring of lung ede-
ma formation might therefore be of special interest in
thoracic surgery.
Recently, the method of determination of lung dry on wet
weight ratio measured by microwave reflectometry has
shown to be equal to drying and weighing by our group w5,
6x. As up to now the instrumental setup employed was not
suitable for a clinical, and especially not for the intraoper-
ative scenario, we developed an improved setup in coop-
eration with the Technical University of Ilmenau (Germany).
An ultra-wide-band (UWB) 9 GHz Evaluation-Kit (Meodat
GmbH, Ilmenau, Germany) was combined with an open-
ended coaxial line probe to measure the dielectric permit-
tivity of lung tissue and lung water was calculated by a
formerly validated dielectric mixture formula w5x. The
?Presented at the 18th European Conference on General Thoracic Surgery,
Valladolid, Spain, May 30–June 2, 2010.
*Corresponding author. Tel.: q49 621 3832447; fax: q49 621 3831479.
E-mail address: kai.nowak@umm.de (K. Nowak).
required load of the specimen with microwave radiation
was extremely reduced and water content measurement
required an acquisition time of -1 ms (up to now 25 s).
These improvements reduce the microwave exposure of
the patient and the fast acquisition time makes intraoper-
ative handling easier. We tested this new experimental
setup by measuring the water content of an ex vivo per-
fused lung tissue after ischemia and demonstrated the
feasibility of the method during an intraoperative human
lung operation.
2. Methods
2.1. Animal model
Experiments have been approved by the institutional
Ethics Committee and animals received human care in
compliance with the European Convention on Animal Care.
Wistar rats were used in all experiments (ns6).
Lungs were retrieved, preserved, stored (4 8C; eight hours
to be ventilated perfused at 37 8C over three hours as
described w7x. Before lung retrieval and during lung reper-
fusion lung water was monitored continuously by microwave
reflectometry under use of an open-ended coaxial line
(inner diameter: 1 mm, outer: 4 mm).
2.2. Intraoperative lung water monitoring
Microwave reflection measurements on the lung were
performed during lower lobe resection of a patient with

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Fig. 1. Setup and probes. (a) The computer controlled UWB 9 GHz M-
Sequence Evaluation Unit. (b) Open-ended coaxial line probe used for meas-
urement on human lung. (c) Demonstration of the probe function. The
reflection coefficient depend on the electrical properties if the in front of
the open-ended coaxial line. UWB, ultra-wide-band.
Fig. 2. Intraoperative probe application. (a) Probe position duringintraopera-
tive measurement of human lung water. (b) Microwave probe positioned on
an isolated perfused human lung.
non-small cell lung cancer (NSCLC) Union for International
Cancer Control (UICC IB). Lung water was determined in
normal lung tissue, tumor tissue and peritumorous tissue
during different stages of the operation. Measurements
were performed by positioning the microwave reflection
probe on the lung surface (Fig. 1c). The probe (Fig. 1c)
was connected to the microwave measurement system via
a coaxial line under sterile conditions (Fig. 2a).
2.3. Isolated human lung resection model
The human lung lobe was isolated perfused and ventilated
w8x to monitor changes in lung water. The same probe as
used for the measurements during the human operation
was used for these ex vivo measurements. The probe (inner
diameter: 6 mm; outer: 21 mm; Fig. 1c) was positioned at
the lung surface (Fig. 2b).
2.4. Determination of lung water content by
microwave reflectometry
The dielectric properties of lung tissue were measured
with the above-described probes. The measurement system
was a newly developed computer controlled UWB 9 GHz
M-Sequence Evaluation Unit (Meodat GmbH, Ilmenau, Ger-
many, Fig. 1a) based on the analysis of microwave noise
codes. The induced noise signals were much smaller in
amplitude than the required signals of conventional net-
work analyzers with impulse radar or microwave techniques
w5, 9x. The complex reflection coefficient of the open-
ended coaxial line probe (Fig. 1b) was obtained from the
measured noise codes by Fourier transformation. After
system calibration with three standards the dielectric per-
mittivity of lung tissue was calculated between 500 MHz
and 3.3 GHz w10, 11x. The contribution of water to the
dielectric polarization determined by the fitting procedure
was used to calculate the water content by a dielectric
mixture formula for lung tissue. System validation was
performed in a rat model by comparing the results in water
content gained by microwave reflection measurements with
the results from drying and weighing. We found a good
correlation of both methods with a correlation factor
Rs0.899 w5, 6x. All values of the water content in this
paper are given in percent wet weight.
2.5. Statistical analysis
In rat lungs statistical differences between data sets were
calculated by non-parametric exact test for paired data
(SPSS scientific software, version 13.0, SPSS Inc., Chicago,
IL, USA). Results are quoted as mean"standard deviation
(SD). The null hypothesis was rejected when PF0.05.
To demonstrate the feasibility of the application of the
newly developed UWB 9 GHz M-Sequence evaluation device
for intraoperative lung water monitoring we started only
one pilot experiment. Therefore, no statistical treatment
of the data was possible.
During the human surgical operation, different regions of
the lung lobes were detected and the variations in water
content in each lobe were quoted in SD.
3. Results
The influence of lung ventilation can be seen by compar-
ing Fig. 3a and b. Without ventilation, measured water
content was smaller than with ventilation. The reason for
these ventilation-induced changes is the collapse of the
alveoles. Without ventilation and collapsed alveoles more
lung tissue is inside the restricted area of the measuring
field of the microwave probe and therefore lung water
content seems to increase in this case. This ventilation
dependence is small when compact tissue without air
content is inside the measuring field of the probe which
can be seen by comparing the measurements with and
without ventilation in the region of the tumor (Fig. 3a and
b).
Independent from the ventilation effects we found chang-
es in lung water content during human lung operation and
these changes differed between the lung lobes (Fig. 3a and
b). The changes were higher than the error bars in this
figure. The error bars were obtained by repeating the water
content measurements at different positions on the same
lobe. A moderate increase in water content was measured
during operation in the upper lobe but it was high in the
lower lobe. The damage in the lower lobe was higher
because of the higher stress by the surgical prep-
aration. No changes were measured in the region of the
lung tumor during surgery (Fig. 3b).
As mentioned before, lung water measurements by micro-
wave reflectometry clearly depend on the ventilation state

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Fig. 3. Microwave reflectometry measurements of lung water content during
operation showed (error bars are the standard deviation obtained by mea-
surements performed on different regions in each lobe). Results are
expressed in mean"SD (a) Measurements have been performed without ven-
tilation at the start of operation and after 60 and 75 min. (b) Measurements
have been performed with ventilation at the start of operation and after
75 min. SD, standard deviation.
Fig. 5. Changes in lung water content during isolated perfusion of human
lung resection. The recordings were started 60 min after vessel clamping
(start of ischemia). After 200 min of ischemia, 140 min of lung perfusion,
the curve of lung edema generation flattened and no further increase had
been recorded.
Fig. 4. Rat lung water content during isolated reperfusion (ns6, mean"SD,
*P-0.05), water content at 20 min was tested vs. water content at 120 min.
The data at 20 min were chosen for the test, because temperature equili-
bration during reperfusion after cold ischemia was finished. SD, standard
deviation.
Fig. 6. Water content measurements on lung tissue and lung tissue with
tumor in vitro (right after lung resection) without ventilation. Water content
in the tumor tissue was higher compared to the regions of healthy lung tissue.
Results are expressed in mean"SD. SD, standard deviation.
of the lung tissue. Therefore, to monitor time-dependent
edema development the ventilation state of the lung tissue
must be constant. We monitored the water content in lung
tissue of rats and in the resection of the human lung during
reperfusion after ischemia. The water content of ventilated
rat lung tissue increased significantly between 20 and
120 min from 80.6% to 83.7% during postischemic reperfu-
sion (Ps0.03, Fig. 4). In isolated perfused and ventilated
human lung resection water content increased from 73% at
70 min perfusion up to 83% at 220 min perfusion (Fig. 5).
As a result we found, water content showed a large increase
in isolated perfused rat lungs as well as human lung tissue
and it depended on the duration of perfusion with the
saline solution.
Without ventilation we investigated the healthy lung area
in comparison to the lung area containing the tumor (Fig.
6). Healthy tissue in vitro showed a water content of 77.5%
and water content increased continuously when the probe
was moved towards the position of the tumor. Above the
tumor position water content was approximately 85%.
4. Discussion
Microwave reflectometry has been proved to be a suitable
method for monitoring non-invasively the water content of

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rat lung tissue in vivo and in vitrow5x. Lung damage caused
by ischemia was accompanied by functional losses and an
increase in water content w6x. The measurements were
performed with a network analyzer HP8753C (Hewlett Pack-
ard, Palo Alto, CA, USA) in reflection measurement tech-
nique, and the required dielectric spectrum was obtained
by sweeping stepwise the mono-frequent microwave gen-
erator from 5 MHz to 3 GHz. The data acquisition of this
precise measurement technique took 25 s for each mea-
surement and required a constant contact between the
open-ended coaxial line probe and the lung tissue during
this period. These boundary conditions were not feasible
for a clinical application of this method. A faster measure-
ment system was required to test this system during surgical
intervention.
The basic working principle of the UWB 9 GHz M-Sequence
evaluation unit was completely different to that of the
network analyzerw9x. The UWB system injected a sequence
of pulses into the tissue and tapped the measurement
signals in the time domain. Shorter data acquisition times
and a smaller voltage stress for the lung tissue with similar
spectral power within 1 ms were possible, which made it
much easier to keep the probe in constant contact to the
lung tissue surface during the data acquisition period.
Under constant ventilation conditions the sensitivity of
the new UWB measurement system was high enough to
detect edema formation in human and rat lung tissue.
Our results of changes in lung tissue water content during
operation in adjacent lung lobes are novel. These changes
in lung edema formation might influence the postoperative
care of the patient as regards the likelihood of undetected
retention and pneumonia. These findings could be evalu-
ated in a prospective trial. It would be of pathophysiological
and clinical interest, as regards how far a significant gain
in lung water during thoracic surgery is followed by com-
plicated recovery postoperatively in terms of for example,
fluid imbalance. If that was the case the system could help
to detect patients at risk. Early precautions could be made
in terms of pharmacological and other interventions.
Our model of in vivo lung tissue water measurement by
microwave reflectometry might be used in several clinical
situations like lung transplantation and isolated lung per-
fusion w12, 13x. In these scenarios ischemia reperfusion of
the lung occurs, which can easily be monitored for lung
edema formation by this method during operation. Inter-
ventions could be performed directly and while being
monitored to limit reperfusion injury.
To overcome the methodological problems in measure-
ment of lung edema by microwave reflectometry, we have
of late developed a mathematical model adjusted to the
anatomical and physiological structure of the lung w5, 6x.
Various studies describe the determination of lung edema
by transthoracic bioimpedance measurements in pulmonary
critical care, but the method has been found to be critical
in lung tissue w14, 15x. Measurements depend on the varia-
tions of air volume within the tissue, on a number of factors
including body weight and position, lung volume and pleural
effusions. Compared to the transthoracic bioimpedance
method our microwave reflectometry system requires the
contact between probe and tissue and an application to
patients is only possible during surgical operations with an
open thorax. But microwave reflectometry gathers infor-
mation directly from the tissue and the reflection coeffi-
cient depends on the dielectric properties of the lung. Data
analysis with our model enables the online monitoring of
lung edema and quantification of the dry matter content
is possible. Successful online documentation of lung water
has been performed on an isolated perfused and ventilated
human lung resection by this enhanced model of microwave
reflectometry. Repetitive measurements during human lung
resection have shown strong fluctuations in tissue water
during lung surgery.
In the non-ventilated human lung tissue, the water con-
tent increases rapidly moving the microwave probe from a
healthy lung area towards the tumor region. This is consis-
tent with findings of Goldsmith et al. who found also a
higher water content in cancer tissue compared to normal
lung tissue by nuclear magnetic resonance (NMR) measure-
ments w16x. These findings suggest that microwave reflec-
tometry method could be used to detect tumors in lung
tissue. This may be right in the case of a non-damaged
tissue with a tumor, but this ambiguous diagnosis must be
handled with caution because lung water content can also
be increased by tissue damage. This can be seen from our
results comparing the water content of the tumor tissue
with the operational-affected damage of the lower lobe in
Fig. 3a and b.
5. Conclusions
Intraoperative monitoring of lung water is of scientific
interest and could ultimately become an additional tool for
the surgeon in thoracic operations with increased risk of
lung injury like lung transplantation.
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eComment: The sound of silence: the harmonic analysis in thoracic
surgery
Authors: Luca Bertolaccini, Thoracic Surgery Unit, S. Croce e Carle
Hospital, Cuneo, Italy; Giovanna Rizzardi, Alberto Terzi
doi:10.1510/icvts.2010.243691A
We have read with interest the paper by Nowak et al. about microwave
reflectometry as a tool to observe edema formation of the lung during
thoracic surgery w1x. The authors describe that the dielectric properties of
the lung tissue were measured based on the analysis of microwave noise
codes and reflection coefficient of the open-ended coaxial line probe
obtained from the noise codes by Fourier transform.
In mathematics, the Fourier transform is the operation that decomposes
a signal into its constituent frequencies. For example, the Fourier transform
of a musical chord is a mathematical representation of the amplitudes of
the individual notes that make it up. The original signal depends on time
(time-domain representation of signal), whereas the Fourier transform
depends on frequency (frequency-domain representation of signal) w2x.
As reported by Nowak et al. w1x in the discussion section, shorter data
acquisition times and smaller voltage stress for lung tissue with similar
spectral power would make it much easier to keep the probe in constant
contact to the lung tissue during the data acquisition period. However, to
reduce the time of data acquisition bias, we suggest using, instead of the
traditional harmonic analysis, the De Groot Fourier transform, a simple
method which introduces variable time and frequency resolution in spectro-
gram analysis. The short-time Fourier transform uses the harmonics, but it
has a fixed time and frequency resolution depending on the chosen window
size. When the window size is decreased, time resolution increases, but
frequency resolution decreases.
In conclusion, the De Groot Fourier transform brings variable time and
frequency resolutions to the Fourier analysis and it could be useful for
specific applications, such as the interesting microwave analysis of intra-
operative lung edema.
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Gebhard MM, Schaefer M. Intraoperative lung edema monitoring by
microwave reflectometry. Interact CardioVasc Thorac Surg 2011;
12:540–544.
w2x Bracewell R. The Fourier transform and its applications. New York:
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