Local Pulmonary Ventilation Using
Nonradioactive
Xenon-enhanced
Ultrafast
Computed Tomography*
David
M.
F. Murphy,
Salvatore
Using
MB.;
M. Ztibbatino,
ultrafast
John
T Nicewicz,
M.D.;
computed
and
M.D.;
Roger
tomography,
A. Moore,
we have
M.D.
developed
a technique
for measuring
local ventilation
in a volume
of
1 cm3 in the normal
supine
lung. The technique
employs
the
inert
gas
xenon
in its nonradioactive
use of its radiopaque
results
properties.
in changes
measured
in
tomography.
Using
ponential
M
form
this
‘#{176}Xe.These
upright
of the
local
methods
assess
over
The
but
ofmeasuring
as 1 cm3.
The
scanning
of the
inert
dissolves
and
law,’
identity
and
ventilation
the
middle
one-half
using
inert
suffering
its passage
through
more
proteins.2
soluble
For
the
in the
ventilation
lower
nique
described
being
plotted
at a
was
periods
without
significant
development
of ultrafast
the
range
to be
detected
of 100 nis,
performed
has
within
standardiza-
ventilation
a minor
dorsal
and
ventral
position.
1989;
96:799-804)
organism
due
for
the
the
original
are
2).
from
against
units
open
a bag
incorporated
into
and
circuit
tidal
the
time.
in
was
a mixture
in the
box system
circuit
volume,
A linear
of xenon
studies
and
the
oxygen
with
spirometer
attached
measurement
for
is
subject
of 70 percent
to permit
allowing
relationship
ventilation
employed
rate
measurements
concentration
the
tech-
ofcount
density
and
used
containing
A bag
instead
in CT
plotted
circuit
An
xenon.
changes
pulmonary
#{176}Xe
washin
However,
Hounsfield
breathing
of local
radioactive
et al.
time,
CT
measurement
and
of minute
standardization
of these
variables.
Mathematical
the organism.
in water,
it is
in blood
units)
ventilation
in chem-
on
against
(Fig
shown
30 percent
purposes
the
in the supine
by Kl3ipping
1). The
inspired
to
based
on
treatment
the
analysis
ventilation
is
a continuous
solubility
ofzero,
and
Making
these
ofthe
washin
developed
by
process,
a constant
assumptions
curve
Kety,
and
inspired
and
for the
which
the
inert
inert
gas was
assumes
gas
that
has
the
concentration.
treating
ventilation
as a continuous
of this
on
differences
(Fig
described
used
between
radio-
based
density
exists
which
the reason
for using
xenon
is that it is radiowhich
allows
quantitation
of gas concentration
xenon
has anesthetic
below
40 percent
can
between
while
is based
(Hounsfield
CT
study,
paque,
Although
trations
technique
of the
the
permitting
METHODS
as small
no change
thus
(Chest
is one
in a manner
ventilation
of the lung
The
ultrafast
gas
in
regions
to develop
in volumes
tissues
times
with
and
was
procedure,
local level.
The
of minute
venti-
it is
ventilation
study
the
cur-
ventilation
quantitative
recovery
from
xenon
is relatively
insoluble
interaction
gas,
gradient
radioisotope
inhalation
An
thereby
inert
using
measure
during
and
a monoex-
performed
xenon.
during
allowing
Although
two
lungs
in blood
by Henry’s
ical
was
assuming
lung
ventilation
study
gas,
not
of this
and
computed
during
lation
a
tion.
of xenon
detected
of the
upper,
do
be
calculate
ventilation
at
also permits
measurements
Using this technique,
we calculated
local
in six normal
subjects
and have demonstrated
makes
ultrafast
regional
the
purpose
a method
paque
regional
techniques
lung,
level.
and
curve
employ
position
zones
property
of
can
using
washin
and
inhalation
which
units
the
for
easurements
rently
The
in density
Hounsfield
form
possible
to
methodology
during
XENON
CT.
CONCENTRATION
vs. DELTA
CT (ENHANCEMENT
I
:3
properties,4’5
concenbe inhaled
for extended
adverse
effects.6
The recent
CT, with scanning
times
in
enabled
whole
seconds.
This
lung
z
LU
LU
C.)
z
scanning
capability
I-
I
also
z
Ui
permits
lation
dynamic
measurements
of pulmonary
ventiU
to be performed.7
4
Ui
0
*F5)fl3
the
Pulmonary
Presented
51st Annual
Manuscript
13.
Reprint
0801.5
Deborah
Heart
and
Lung
Center,
Department
of
Diseases,
Browns
Mills,
NJ.
in part at the American
College
of Chest
Physicians
Scientific
Assembl;
New Orleans,
September
1985.
received
October
17, 1988; revision
accepted
March
0
Dr.
Murphy,
Deborah
Hospital.
Browns
Mills,
NJ
20
30
40
XENON CONCENTRATION
FIGURE
requests:
10
tion and
(or delta
1. Linear
relationship
between
change
in xenon
concentraenhancement
as measured
by change
in Hounsfield
units
CT for the ultrafast
CT scanner
use) in these
experiments.
CHEST
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I 96
I 4 I OCTOBER,
1989
799
BREATHING
SYSTEM
oxv
OXYGEN
SOURCE
:1
#{149}
:
OXYGEN
ANALYZER
..
,
WASH IN TRACING
iI
#{149}
[I
BAG
2. Arrangement
FIGURE
process,
the
equilibrium
exponential
gas
lungs
infinity
and
of the
respiratory
simplified
using
continuous
process,
the
semilog
gas
In
two
flows
regions
and
(‘
slower
rise
eventually
during
which
small.
normal
tion
reached,
the
The
curve
reached
the
distribution
to the
well
and
‘ ,
within
80
of gas
fashion
3). As the
a shorter
a minimum
total
than
ventilated
shorter
alveoli.
washin
period,
0.95
which
time
the
number
washout
there
allowing
scans.
are
calculation
An
time
open
a vater
its high
1(X) ns
speed
with
from
in 50 ns
0.75
333
CT
ins.
scanner
and
can
produce
stationary
resolutu)n.
electron
scanner
Calibration
images
This
bean
scanner
that
replaces
MODEL
E
.2
For
70
60
.0
Ct=
50
LU
to
flow
K= alveolar ventilation
alveolar
volume
20
10
and
0
0
proportions
1
xenon
3
4
5
6
7
CONSTANTS
3. Assun3ed
monoexponential
firn
of the
xenonloxvgen
mixture
wash-in
curve
plotted
as I)er#{128}eIItof equilibrium
on the
axis against
nun3her
of tin1e constants
on the x axis.
FICUKE
ventilation
maintains
2
TIME
disadvantages
of local
_kt)
0
washin
to breathe
C(1-e
40
builds
minute
the
The Equilibrium
of an inert gas in the
lungs may be described
by the
exponential
function:
80
finally
lungs
to small
system
The
heart
a scanning
ultrafast
of 100
90
concentra-
proportional
some
phanton.
l)eatmg
an
time
in
ventilation.
100
will
to ventilatory
for one
subjects
a
time
is
is limited,
curve
with
using
fat
in
ss’all fat results
in chest
pulnonarv
a scan
of a greater
soluble
will
is 2.99.
final
of normal
continues
it permits
of
not
for washin
Although
curve,
vet
alveoli
have
rates
(/vt)
is then
in the
achieves
regions
This
eq1ilil)rium
and
with
vith
ofthe
in
performed
cost
is more
the
is a finite
ventilated
of the
volunies
body
was
KETY’S
will
gas.
when
‘hen
)
the
of xenon
of local
Scaiiner)
at the
hut
xenon
of
ventilator’
of concentrations
of ventilated
sensitive
poorly
95 percent
out
images
of
regions
there
inert
scanning
carried
as a
accuntilatioii
in measurements
C-1()0
real-tine
al)ove,
ventilator
both
regional
reaches
‘“
s
aiid
of the
between
concentration
(Fig
between
be
with
ventilation
thus
was
the
and
error
CT
of xenon
concentration
As n1entioned
volume.’
different
least
ofactivit;
(1 - e
with
in vater,
The
Since
closely
thai
(Inatron
of distribution
tidal
of Xenon.
is time.
experiments.
inspired
loss
alveolar
gas
in these
a slight
of k can
inspired
However,
distribution
0.035
be
is less
ofpoorly
from
=
in an exponential
beyond
for
term
‘/v
the
‘t
employed
constant
constant
is treated
correspond
level
difference
distribution
rate.
up
The
lung,
will
in the
unity.
volume
v but
with
same
diflerences
if the
to
concentration.
the
to he
one-halfthe
volume
region
xenon
reflected
l)e shorter
are
the
2)
reach
be
will
plus
miii
dilutes
the
the
in the
relating
units
ventilation
and
shown
present
calculations
continuously
by
rate
BOX SYSTEM
systems
concentration
k is the
the
When
be
of e(lual
in
with
form,
capacity
described
of gas
is assumed
volume,
can
residual
be
breathing
C, is the
a parameter
-
(‘/v)
lung
can
to volume.
paper.
the
circuit
amount
monoexponential
lung
inspired
functional
gas
constant)
ratio
open
#{176})
where
is the
‘olufl’ie,
midinspiratory
the
e
-
is related
exchange
is of the
inert
(I
C.
time
to alveolar
equation
C.
t and
reciprocal
ventilation
The
C,
at tinie
at time
(the
of an
function
inspired
ofthe
IN THE
SPIROMETER
a
800
Downloaded From: http://publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21602/ on 06/18/2017
Local
Pulmonary
Ventilation
(Murphy
y
e( a!)
Table
2-Pulmonary
Function
Subjects)
Tests
(Normal
Mah
Subjects
1
Parameters
5.53
FVC,
L
FVC,
%pred
L
FEy,
%pred
FEF25-75,
The
were
CT one
image
obtained
xenon
breathing.
from
the
baseline
CT
and
mechanical
electron
motion
beam
ically
focused
electron
over
beam
beam
that
detector
In order
gas
interest
of 121
volume
of
obtained
for
seven
the
the
and
from
was
was
normal
of the
change
xenon,
to be measured.
detected
ment
model
calculation
and
the
as a function
nential
for
ofthe
v is
for
set
at
seconds
330
millirads.
region
the
of interest
of gas
concentration
washin
curve
ofconstant,
1 cm3,
then
and
k, was
rate
was
per
Table
=
Ifk
unit
scans,
anxiety
a
.
than
to
any
side
ventilation
is
Measurements
for
scanning
whom
at a single
of
and
in Table
(±3.8).
to the
change
side
effects
in CT
The
inhaling
from
pressure
is a slight
region.
noted.
One
described
the
mixture
there
dorsal
is 1.25:1.00.
had
of
ventilation
average
seen,
ratio
No blood
results
xenon-oxygen
be
is
results
questionnaire
subjects
calculated
3. The
can
test
of the
normal
The
of the
As
subjects
function
the
the
subject
some
mean
xenonreported
form
of
or electrocardiographic
were
recorded.
In
emphysema,
marked
the subject
reduction
to the bulla
was observed,
rates being
recorded.
enhance-
six normal
disease.
gas mixture
were
and
all subjects
changes
bullous
the
2. Results
of the six
in ventilation
sensation.
effects
inhalation
the
C,
prior
pressure
emphysema
rather
for
inhalation
to ventral
oxygen
coefficients
using
made.
31.08
dorsal
lung
to the
the
xenon
form
shown
after
increase
at
at a single
two
to the
knowing
of the
flow
the
ie, mm
hullous
tests
blood
local
a
respiratory
reported
mI/mI/mm,
pulmonary
number
No significant
out
in attenuation
and
scati
4) permitting
due
change
sites
percent
to standardize
administered
Using
(Fig
are
number
Finall,#{231}oxygen
carried
inspiration
per scan
in CT
rates
an
ventral
data
1 and
respiratory
change
analyzer.
coefficients,
From
was
chosen
another
subject
after
undertook
and
study,
performed
who,
on
particular
with
a subject
in Table
significant
oxygen
of 30
taken.
were
be generated
and
an1
was
IW an oxygen
was
rate
60
at end-tidal
of radiation
the
dorsal
a mixture
measurements
in attenuation
over
Both
inhaled
scan
of interest
subjects
EGG
venti-
approved
function
the
each
study,
numbers
are shown
in Table
revealed
that
none
a film
percent
The
pulmonary
this
men
to a protocol
questionnaire
the study,
the
Anthropometric
of
coefficients,
regions
of respiration
could
baseline
six healthy
the
of interest.
RESULTS
of the
a region
giving
100
performed
was
regions
according
Council
For
in
between
in Humans.
During
scanning
were
made
ventral
of
a data
inhalation
attenuation
for
vessels.
monitored
subject
image
a
Studies
and
5.83
7.95
The
by
over
study
studied
After
made
lung
dorsal
Research
also
6.23
level.
rings
two
of 8 mm,
breathing
derived
oxygen
subjects,
of the
subtraction
the
the
made
Initially,
then
phase
to
thickness
been
blood
70 percent
and
due
calculated
sul)ject
level.
Scans were taken
volume.
The
total dose
center
had
to avoid
level
In the
of
in this
on
6.81
comparisons
the
x-ray
is digitized
were
1 cm3.
The
concentration
one
detectors
a slice
subject
and
observer
same
This
rings.
also
whole
magnet-
a fan-shaped
into
in density
with
number
selected.
xenon
patient
measurements
mm2
minutes,
l)y the
were
target
produces
the
changes
approximately
CT
and
88
in absolute
shown
xenon,
after
average
from
scanners.
tungsten
targets
the
x-ray
chamber
92
experienced.
reported
. 2
to detect
radiopaque
of four
these
Output
system
a vacuum
a 210#{176}
arc
through
arrays.
conventional
through
striking
passes
aquisition
of the
is directed
93
3.40
were
monitored.
were
the
96
the study.
effects
a
80
used
and
performing
4. Subtraction
minute
after
75
Medical
symptoms’3
FIGURE
97
consent,
modified
5.25
109
from
by a Committee
5.02
92
approximate
subjects
3.59
91
109
measurements
informed
5.94
102
106
3.25
and
79
4.62
6
5.47
3.85
92
3.72
5
97
L’s
calculated
4
4.84
106
4.12
FEV/FVC%
3
4.63
105
FE\’,
lation
2
with
severe
of ventilation
with
very
low
CT
has
opened
ventilation
monoexpo-
C1
(I
is given
volume
e
-
DISCUSSION
by /v
can
The
be
1 -Anthropometric
Data
advent
(Normal
of
ultrafast
a new
Subjects)
Male
Subjects
Parameters
Age
Height,
in (cm)
Weight,
lb (kg)
1
31
70.5
175
2
3
37
(176)
(79.4)
66.0
165
4
34
(165)
(74.9)
71.0
200
5
32
(177)
(90.7)
68.0
185
6
22
(170)
72.0
(83.9)
240
CHEST
Downloaded From: http://publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21602/ on 06/18/2017
26
(180)
(112.8)
I 96 I 4 I OCTOBER,
75.0
200
1989
(187)
(90.7)
801
Table
3_Results*
the
Subjects
1
RNDLDe1taCT
42.5
Vfl3l/fl1inlflll
CT
CT
after
changes
inhalation
calibrated
Right
LNDL,
28.1
25.6
25.1
0.5
0.7
0.6
0.6
31.1
34.2
29.5
0.8
0.8
0.9
0.7
41.9
16.9
24.9
25.6
8.2
0.6
0.6
0.2
0.7
30.4
34.6
12.9
44.8
2.8
0.9
0.8
0.9
0.3
left
CT
in
number
recorded
xenon/oxygen
ventilation
rates
nondependent
are
lung;
nondependent
in
mixture
lung;
shown
for comparison.
right
LDL,
left
and
dependent
lung.
dimension
in pulmonary
function
evaluation,
ting both dynamic
airway’4
and cardiac
studies.7
titation
of ventilation
and
perfusio&5
can
carried
out,
perniitting
derivation
of local
sion,
can
with
permits
also
be
made.
measurements
permitQuan-
lower
detailed
more
analysis
function
than was previously
a “bag
in the box”
system
standardization
for minute
1)articula1
numbers
tO
stud)
allow
tissue
of
17
into
the
ventilation
for comparison
is
in
but
reported
with
other
in absolute
reported
have
results
betveen
the
in XeIX)I1
concentration
interest,
there
minute,
with
for
in
The
an
change
deviation
region
and
a given
are
change
region
in density
breathing
xenon
of
for
CT
large
is
due
used
to the
to
CT
and
reproducibility
measurements
are
of
dependent
the 120 KvP technique.2’
In our study,
enhancement
in the range
of 30 Hounsfield
units was
recorded
in areas oflung
parenchyma
without
overlapping blood
vessels
or bone,
and machine
drift did not
occur,
over
although
enhancement
this
is less
similar
can
than
studies
be
an
important
10 Hounsfield
were
performed
factor
units.21’22
previousl),
if
spirometer,
pulmonary
the
new
to the
and
used
been
ultra-
problem
of
differs
ventilation
from
using
to
xe-
standardize
to employ
monitorL
and
volume
durof minute
a simple
with
or
without
films,
it
monorn26
xenon
used
is an
as
regional
attenuator
a contrast
and
efi#{232}ctive
ofthe
digital
washout
washin
our
using
curve
Several
airways
hut
has
has
in
been
are more
sensitive
than washin
for analysis
ultrafast
the
that
the
permits
subject
involving
subject
is
scanner
with
two
subject.
This
nuclear
to
27
a reduction
is required
CT, the
the
the conventional
of regional
imaging
radiologv#{176}
studies
to
to
for
differences
delivered
is delivered
of x-ray
agent
CT.2#{176}
ill
ventilation
Using
ratio.
Both xenon’s
enhancement
and noise are functions
of the CT beam
energy.
It has
been
shown
that lower
energy
techniques
have
no
advantage
has
their
Using
volume
with
scanning
respiration
volume
volume.
oftraditional
approach
this
is
hold
tidal
of local
down-
lung
attached
technique
dosage
h ancement-to-noise
will
to reduce
attenuation
tidal
with
during
xenon-en-
en-
the
attenuation
subjects
techniques
in the amount
of time
breathe
xenon.
With any technique
on the
the
standardize
of respiration
Although
the
with
affect
times
tend
for mean
combination
Another
gauge
conventionaP8
as xenon.
accuracy
can
end-inspiratory
tidal
allowing
measurement
of contrast
describe
presence
to
measurements
phase
use
minutes
movement
method,’1
is a new
CT.
of
to
this
lung scancan now
measured
by CT is
and thus,
varies
inspiratory
possible
volumes
and
most
difficulty
times,
standardized
ofan
scanning
Since
These
± 3.8.
sufficiently
end
This
been
one
have
scan
Whole
subjects
artefact
particular,
measurement
of
significance.
enhancement
such
For
average
a standard
in CT number
I, anced
When
also
feedback
relationship
units
1).
after
a given
linear
Flounsfielci
units
term
The
a
Fig
was
statistical
increase
confirmed
change
Hounsfield
changes
agents
in the box”
it was
strain
Our
reach
a “bag
the
who
by having
at the
11011
breath
two
inspiration,24
breath
previous
data.
31 .08
during
inconstant
this
conven-
when
density,a3
Also,
In
accomplished
fast
permits
ventilation,
volume.
function
lung
Incorporating
circuit,
attenuation
physical
to
ventilation.
perfu-
local
for
their
short
in approximately
maintain
a constant
ing scanning,
while
technique,
local
times
scanner.
lung
was
be
ventilation-
This
of
disease
grade
images,
but rapid scan
problem.
Since
the range
perfusion
1 We
have described
the application
of ultrafast
CT to the measurement
of local ventilation
in the supine
position
and have shown
that whole
lung
measurements
combined
performed
lung
scan
scanning.
This reprewhen
evaluating
pa-
With
.
a few
long
to hold
has been
overconie.
normal
and abnormal
measurements.
now
actual
disadvantage
with
respiratory
their
breath
with
lung;
dependent
Scan
subjects
as 6 s during
Radiographic
proportional
The
delays.
required
a significant
ultrafast
units
minute.
RDL,
be
had been
that only
due to the relatively
interscan
have
disadvantage
ning in both
1.5
Hounsfield
for one
CT
sents
27.9
0.4
and
tional
tients
holding
1.4
34.5
times
for as long
42.8
53.8
of the
local
RNDL,
23.1
31.9
VnWminlnil
*t,Ieasured
6
0.5
1.3
Delta
5
3.1
Vmljminjml
LDL
4
54.7
Vml/min/ml
Delta
3
20.8
1.4
RDLDe1taCT
LNDL
2
major
limitation
could
be studied
slices
total
to
radiation
a consideration.
scans,
46
conipares
medicine
mrads
to
1 rad
measurement
ventilation.
authors
have
studied
the
anesthetic
effects
ofxenon,3’”6
and side effects
including
hallucinations,
euphoria,
somnolence,
and dysesthesias
have
been
reported
for inhaled
concentrations
greater
than
30
percent.6
reported
inhalation
In our studs;
no significant
side effects
were
by any of the subjects
after
one minute
of
of 30 percent
802
Downloaded From: http://publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21602/ on 06/18/2017
xenon.
Local
As the
Pulmonary
washin
Ventilation
curve
(Murphy
et a!)
reaches
98 percent
niost
normal
xenon
of equilibrium
subjects,
it
for longer
periods.
an open
system,
Using
errors
inherent
based
on
Kety’s
The
study,
after
revealed
local
ii,i3
obtaining
at end-inspiration
after
inhaling
tanee
with
equation.
some authors
use,22 while
density
change
in
and
same
of subtraction
over
a
obtained.
on three
xenon
authors
a (voxel)
lung
mixture
the
to
calculations.
This also permits
measurements
of minute
ventilation
at the time
of the study.
The
applications
of this
improved
technique
are several.
If one considers
the
washin
curve
obtained
from measurements
over the
reflects
the
at end-tidal
whole
system.
If
expiration,
then
the time constant
is related
to the functional
residual
capacity
divided
by the alveolar
ventilation.
Since the
technique
permits
calculation
of minute
ventilation
from the spirometry
tracing,
correction
for dead space
ventilation
permits
calculation
of alveolar
ventilation,
and, thus, functional
residual
capacity.
In the normal
subject,
equilibrium
is reached
a relatively
subject,
the
When
short
inert
equilibrium
period.
gas may
is reached,
flow
rate
is equal
to
compliance3’
for a given subject
with varying
time
measurements
calculation
ventilation
of
for
time the study
per scan was
the
during
made.)
the
product
of a given
there
will
constants,
static
where
t/T)
of
lung
the
unit,
be a whole
range
some faster
than
and
of units
others.
A normal
and
distribution
will be found in normal
subjects
an abnormal
distribution
in diseased
subjects.
For
any
given
subject,
a range
study,
between
of the
in
lungs
of time
state,
supine
we have
in ventilation
constants
better
position
demonstrated
the
the
a minor
dorsal
supine
can
ventilation
reflect
and
to
units
gradient
ventral
position.
be
regions
Using
similar
techniques,
Gur and co-workers22
identified
a slight
gradient
in animals.
Using ‘#{176}Xe
in the supine
position
for measuring
regional
distribution
of ventilation
in
human
subjects,
Bryan
and coworkers32
showed
that
the ventilation
index
gradient
present
in the upright
position
was abolished
in the
supine
position
l)ut
out
that
failure
to identify
a ventilation
dient
in the supine
position
could
overlap
between
the front and back
they
gra-
have been
counter-fields
due
to
that
employed.
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_
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=
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two
30 percent
is then
it
V
resistance
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aninial
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to inspire
of the monoexponential
high cost ofxenon,
system
to minimize
In our
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calculation
been
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is the tendency
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to
It has been
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error
in ‘#{176}Xe
studies.”
minute
have
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