labeled blood-pool techniques to evaluate changes in penile
blood volume as measured by nonimaging scintillation
probes (11â€”14). Shirai et al. (15) and Wagner et al. (16)
also used probe systems to measure intracavernosal xenon
washout in the flaccid and stimulated penis, thereby esti
mating cavernosal blood flowat rest and poststimulation. A
limitation of the simple probe systems was that they could
not be directed to exclusivelysample activityfrom the penis
and not the adjacent structures. Shielding of neighboring
and underlying regions was often attempted, but in itself
was technically difficult.
Subsequent blood-pool (17â€”24) and xenon washout (25â€”
29) investigatorsuniversally replaced
probes with the gamma camera to measure penile radioac
tivity. Spatial data inherent in gamma camera images have
only been of value in defining penile regions of interest
(ROIs) and have not yielded diagnostic information in their
own right (30). In fact, quantitative gamma camera studies
have shown that the main corporal body and base of the
penis after pharmacologic stimulation demonstrate indis
(18,19) while the glans penis, an extension of the corpus
spongiosum, exhibits minimal blood-pool activity when ei
ther flaccid or erect (19). A major drawback of gamma
camera methods is the substantial reduction in counts ef
fected by the associated collimation, which markedly atten
uates photon flux, thereby necessitating larger does of ra
dionuclides and longer framing rates to achieve statistical
validity. Fifteen second (19,22) or greater (17,18,20,23,24)
framing rates have typically been used in gamma camera
studies of the penile blood pool.
We set out to design a penile nonimaging scintillation
(PNIS) probe that would provide a cost-effective alterna
tive to the gamma camera for hemodynamic
of the penis in the investigation of erectile dysfunction (30).
This portabledevice would be easily transportable
Sexual Dysfunction Clinic within the Department of Urol
ogy for integrationinto preexisting diagnostic protocols. In
contrast to the early probe systems, the PNIS probe sur
rounds the organ, largely excluding counts from external
structures. In comparison with gamma camera methods, it
does not require collimation; therefore, count rate sensitiv
ityissuperior and permits the use of fractional quantities of
radionuclides while maintaining elevated count rates and
We have developed a penile nonirnaging scintillation (PNIS)
probe consisting of a plastic well-type scintillation crystal inter
faced to a portablecomputer and acquisitionboard.Thisreport
describes the design of the PNIS probe, performance charac
tenstics, mode of usage and illustrativeresults which demon
strate its capabilities.Methods: Withthe PNIS probe, penile
blood-pool studies were performed in nine patients utilizing3.7
(RBC5). Venous blood standards were assayed to enable con
version of the count rate to volummetric measurements. Washin
analyzedto estimate penileblood volumeand cavemosal flow
rate in the flaccid state. The rate of change of penile blood
volume after intracavemosal vasodilators was used to generate
measures of stimulated flow. Results: Amajor advantage ofthis
deviceoverthe gamma-camera isa 3300-foldincreaseincount
rate sensitivity, which allows for markedly improved temporal
resolutionwhile significantlyreducing the radiopharrnaceutical
dosage. Additionally,the PNISprobe is portable, economical
and is not dependent on operator-defined regions of interest.
Count rate sensitivityis relativelyconstant within the bore,with
the exception of the proximalregionadjacent to the opening,
where geometric efficiency is reduced. Conclusion: The PNIS
probe is an effective device for measuring penile activityin
radionuclide studies, allowingfor acquisition of time-activity
curves of the penis during flaccid washin of peripherally labeled
red blood cells and after pharmacologic stimulation to induce
@rc-labeledred blood cells
@rc-RBCs was mathematically
Key Words: erectile dysfunction; scintillationprobe; techne
tium-99m-red-blood cells; penile hemodynamics
J NucI Med 1995; 362345â€”2351
logic methods to induce erection (1,2), in conjunction with
innovative therapeutic options for treating erectile dysfunc
tion (3â€”5)has led to renewed
methodsof quantitatingerectile function
methods of measuring penile blood flow (7â€”10) were initi
ated in the early 1970swhen Shirai and coworkers utilized
and heightenedinterest in
ReceivedDec.8, 1994;revisionacceptedApr.3, 1995.
For correspondenceorrepnnts contact Uonel S.Zuckier, MD, Department
Nuclear Medeine, 1300 Mortis Park Ave., Bronx, NY10461.
PenileScintillationProbe â€¢ Zuckieret al.
A Nonimaging Scintillation Probe to Measure
Lionel S. Zuckier, Gopal R. Korupolu, Mark Gladshteyn, Ronald Sattenberg, Richard Goldstein,
Richard Ricciardi, Paul Goodwin, Arnold Melman and M. Donald Blaufox
Departments ofNuclear Medicine and Urology,Albert Einstein College ofMedicine, Bronx, New York
protective steel casingwhich encircles the periphery of the assem
bly and is folded down to overlap the front rim of the detector.
Another 2.5mm of lead shields the lateral wallsand anterior lipof
Signal and high-voltage cables connect the PNIS probe to the
spectroscopy high-voltage and data acquisition board housed in a
portable computer (T3200, Toshiba America Information Sys
tems, Inc., Irvine, CA). Through software-selectable switches, the
PM tube is operated at 1200volts DC with gain optimizedfor
detection of the 99mTc signalpulses. Vendor-supplied softwarewas
customized to allow acquisition of time-activity curves with user
definable framing rates of 1 sec or greater. During dynamic stud
ies, the data matrix generated by the crystal was written to the
hard-disk from where it was subsequently imported for analysis
and display into a standard spreadsheet program (Quattro Pro,
Borland International, Inc., Scotts Valley, CA). Prior to use in
patients, the basic performance characteristics of the PNIS probe
were determined, including count rate linearity, sensitivity, geo
metric efficiency and adequacy of external shielding.
The research protocol for clinical studies was approved by both
the Montefiore Medical Center Institutional Review Board and
tamed from all participants.
Acquisitions were performed at 1- to 2-sec/frame temporal
resolution. The patients were comfortably seated in a private room
with their legs slightly abducted. A disposable plastic liner was
inserted into the bore of the crystal into which the penis was
placed. The distal portion of the PNIS probe was supported
slightlyelevatedstoolwhilethe patient firmlyheld the proximal
end of the crystal against his body. Approximately 10 ml blood
were asepticallydrawn prior to the study and labeled with 3.7MBq
(0.1 mCi) 99mTcby an in vitro technique.Labeled blood was
thereafter reinjected into an antecubital vein followed by a flaccid
washin acquisition lasting approximately 20 mm. The probe was
then removed and 30 mg papaverine, in a 1-mt volume, were
injected into one of the corpora cavernosa to induce erection. The
crystal was quickly repositioned and another 20â€”30 mm of data
collection was performed to characterize the erectile response. At
the conclusion of the study, approximately 5 ml of peripheral
venous blood were withdrawn from the opposite arm into an
evacuated preweighed phlebotomy tube. The blood was counted
within the bore of the probe and subsequently reweighed on an
analyticbalance to determine the sample volume. With this aliquot
as a reference standard, penile count-rate data were converted to
absolute blood volumes after subtraction of background and cor
rection for isotopic decay.
We applieda newmathematicalapproachfor analysisof the
washin curves of the flaccidpenis based on assumptionsthat
washm of activity into the blood pool of the flaccid penis is
considerably slower than the rapid dilution of labeled RBCs within
the body and that the concentration of activity within peripheral
werefitto the differentialequationappropriatefor thismodelof
washin,B(t) = V x (1 â€” et@<'@â€•)
derivation), using an algorithm for least squares minimization in
which B(t) represents the amount of labeled blood within the
corpora cavernosa. The initial half-minute of data were excluded
from curve fitting to avoid potential errors due to variation in
background during the initial distribution of activity throughout
+ Bk (see Appendixfor
FiGURE 1. Schematicviewofthe PNISprobeand electronics.
penile count rate TACs to volummetric curves (14,19).
Althoughthe goal of this report is to describe the PNIS
probe and its use, we also briefly discuss a quantitative
method of analyzing flaccid penile blood flow.
reliable data. A venous blood sample can be
countedwithinthe wellof the crystalto convert
MATERIALS AND METhODS
The PNIS probe systemconsists of a custom-designed well-type
scintillation crystal and photomultiplier
commercially available portable computer-based spectroscopy
board and high-voltage source (Tennelec/Nucleus PCA-P, Oxford
Instruments Inc., Oak Ridge, TN) (Figs. 1,2).The crystal is com
posed of a BC-400 plastic scintillator (31,32 ) (Bicron Corp., New
bury, OH), which is relatively inexpensive,
fabricate. External dimensions of the hollowed-out cylinder are 8.3
cm (3.25â€•) in diameter and 21cm (8.25â€•) in length, with the central
bore measuring5.1cm (2â€•) in diameterand 18cm (7â€•) in depth
and designedaccordingto limitedpublisheddata regardingerect
penile size (33,34). The crystal and PM tube are enclosed in a
(PM) tube attached to a
rugged and easy to
FiGURE2. Photographofthecomp@te PNISprobesystem.The
outer dimensions of the crystal measure 8.3 cm indiameter by 21
cm inlength.The software setup menu isvisibleon the computer's
TheJournalof NuclearMedicineâ€¢ Vol.36 â€¢ No.12â€¢ December 1995
using the PNIS probe and a 100-fold diluted source. Sen
sitivityof the gamma camera was 25 cpsfMBq,while that of
the probe was 8.4 x i0@cpsfMBq or approximately 3300-
fold greater than that of the gamma camera.
Count rate response was also determined
position both within and external to the crystal. An 18-KBq
(0.48 MCi) source was mechanically translated along three
axial rays (center, midradius and periphery) within the
cavity of the PNIS probe at a rate of approximately 1.7
cm/mm using a mechanical
apparatus to generate linear motion. Simultaneously, mul
tiple sequential15-sec acquisitions
regional count rate sensitivity (Fig. 5). Sensitivity was
slightly higher at the periphery of the cavity compared to
the center and midradius and diminished towards the front
opening as geometric efficiency decreased.
as a function of
were obtainedto map
III@@@@@ I I IIIIII I I IIIIIII I IIII I I
â€˜I MCA CHANNEL
FIGURE3. Spectraforbackground and15-KBq
As with other plastic scintillators,BC-400 has poor energy resolu
tion, resulting in a broad photopeak. The energy window used for
O9mTc is indicated.
activity.Both deadtime corrected and uncorrected count rates are
illustrated.M kieal curve, extrapolated from the lower count rate
points, is plotted for reference purposes.
Background-corrected count rate as a funCtionof
the body. Fitting of the flaccid washin curves to the above equation
generated values for total cavernosal blood volume (V), flaccid
blood flow(F) and extraneous background activity(Bk), the latter
expressed as an equivalent volume of labeled blood.
was identified based on a derivative of the smoothed blood-volume
curve. Average flow over the subsequent
mined by dividing the change in volume during this interval over
the elapsed time. This measurement is similar to the method of
Schwartz et al. who initiallytheorized (19) and subsequently dem
onstrated (35) that venous outflow during the period of early and
rapid fillingisnegligible and therefore correction of inflowrates to
account for egress of blood from the penis during this early period
is not needed.
1-mm period was deter
At a PM tube voltage of 1200volts and optimal amplifier
gain, @Tc and background spectra were obtained (Fig. 3).
An energy window within the
for use in all subsequent measurements.
@Tc photopeak was selected
Count Rate Unearity and Sensitivity
The range of count rate linearity was determined by
decaying a 9.2-MBq (250 MCi)source of 99mTcwithin the
crystal bore over 3 days, during which time, multiple Se
quential acquisitions were performed both with and without
intrinsic deadtime correction (Fig. 4). Using correction, the
count rate responseremained
activity of approximately 0.74 MBq (20 MCi),which corre
sponds to a count rate of approximately 70,000cps. Subse
quent studies were performed using deadtime correction
within the linear count range.
Count rate sensitivity of the probe was compared to that
of the gamma camera. Technetium-99m (1.5 MBq, 41 MCi)
was placed in a fluid-filled 50-ml conical test-tube and
images of this source were acquired on a portable gamma
camera with a low-energy, all-purpose collimator interfaced
to a nuclear medicine computer. Counts in the computer
derived ROl were compared to the count rate obtained
essentiallylinear up to an
FIGURE5. Countrateresponsetoan 18-KBq source,as afunc
tion of posft@nwithinthe crystal's cavity, along three-deelgnated
ax@rays BothSI(nghtaus)and per m@rocuhe(leftaxis)scales are
Penile Scintillation Probe â€¢ Zuckier at al.
cm anterkx to cr@I
cm anteriorto crystal0.48%0.23%0.06%
Relative Count Rate Sensitivities
volume increased to approximately 24 ml over the course of
an additional 25 mm. The slow increase in blood volume is
consistent with described patterns of arterial insufficiency
(20). Flow peaked immediately
ministration. Average flowduring the first minute following
papaverine administration was calculated by measuring the
change in volume over this interval, yielding a rate of 3.5
ml/min. In comparison to values generated
gamma camera(19,35),these findings are suggestive
arterial disease and demonstrate impaired filling of the
corpora cavernosa after pharmacologic stimulation, with
only a slight increase in the flowrate compared to baseline.
following papaverine ad
As greater understanding of the pathophysiology of erec
tile dysfunction evolves (36â€”38)and innovative treatments
are developed (4,5), increasing interest has been focused
on improving diagnostic methods of quantitating erectile
function(39â€”41 ). A recent National
consensus panel concluded that â€œthe development
ods to quantify the degree of erectile dysfunction objec
tivelywould be extremely useful in the assessment both of
the problem and of treatment outcomesâ€• (6). The present
study demonstrates the feasibility and advantages of using a
nonimaging probe to measure penile hemodynamics. Some
of the advantages include low equipment cost, portability,
increased count rate sensitivity, improved temporal resolu
tion and the lack of operator-defined ROIs.
The PNIS probe was successfully used in nine patients
who were administered 3.7 MBq (100 pCi) 99mTc@RBCs,
which is less than 1% of the clinical dose used in conven
tional blood-pool studies. In addition, the improved tem
poral resolution of the PNIS probe relative to the gamma
camera may permit observation of previously unresolvable
phenomena. In an initial trial which preceded the current
series of patients, two subjects were studied with a proto
type configurationof the probe consisting of the present
crystal interfacedto a dedicated
one subject, cyclicoscillations of approximately 1 mm fre
quency superimposed upon a gradually rising baseline were
observed following i.c. injection of 1mg papaverine
This finding clearly emphasizes
resolve periodic events occurring at frequencies that would
not be easilyidentifiable with gamma camera methods. The
present phenomenonmay represent a continuum with
coarser fluctuationsin penile TACs, occurring from 10 to
20 mm, that have been observed in gamma camera studies
and are postulated to represent a normal rhythmic flow
pattern consistent with episodic penile vascular and trabec
ular smooth muscle relaxation (23,24).
the PNIS probe's ability to
For construction of the PNIS probe, we used a plastic
scintillation crystal rather than one made of sodium iodide,
which is a higher resolution scintillation material commonly
used in nuclear medicine. This decision was based on du
Count rate sensitivity outside of the crystal was com
pared to sensitivity within the bore by positioning
source of 0.33 MBq (8.8 @.tCi) @mTc at multiple
locations (Table 1). With the exception of positions directly
opposite the bore (central axis), sensitivity was less than
0.25% of the midbore.
Feasibility of the PNIS probe was demonstrated in a pilot
group of nine patients,and the procedure
ated without any adverse occurrences. One patient (a 38-
yr-old man unable to maintain an erection) with both
washin and postpapaverine TACS demonstrates the utility
of the PNIS probe and highlights its features. After admin
istration of papaverine i.c., previously performed Doppler
flowin the left cavernosal artery and borderline flowon the
right side; the resultant erection was graded as 3 on a scale
of 1 to 5 (1 flaccid; 5 normal erection). Thickening of the
arterial walls was noted bilaterally, suggestive of arterio
genic erectile dysfunction.
Initial inspection of the flaccid TAC demonstrates
washin over the course of approximately 20mm to avolume
of approximately 15 ml (Fig. 6). Based on the fit of the
experimental data to the theoretical model, the flaccid
penile blood volume was estimated to be 12.9ml,the flaccid
blood flow was 2.9 ml/min and a constant background
component was determined to be 2.8 ml.
After injectionof 1 mg papaverine
was well toler
Flaccid washin andpostpapavenne datafroma 38-
The Journalof NuclearMedicineâ€¢ Vol.36 â€¢ No.12â€¢ December 1995
The problem of incomplete measurement of corpora
cavernosal counts isdue to two factors: a drop in count rate
sensitivity within the crystal cavity as one approaches the
opening of the bore (Fig. 5) and extension of the cavernosal
bodies outside the probe cavityto their point of attachment
on the pubic arches (33). Sensitivityof the crystal to a
source located Z5 cm opposite its opening is26% (Table 1),
which corresponds to the approximate location of activity
within the crura of the corpora cavernosa. The net effect of
undersampling the more proximal portions of the corpora
cavernosa during washin measurements, such as those we
performed,would be to underestimate
volume and blood flow. Measurement of the change in
blood volume after papaverine is affected less by under
sampling of the proximal penis because, during attainment
of erection, much of the increase in blood volume of the
penis occurs through longitudinal
portion of the bore where a more linear count-rate sensi
tivity prevails. More judicious positioning of the venous
standard to mimic the average position of the penis might
be helpful in improving the quantitative accuracy of the
flaccid studies. Alternatively, correction factors could be
developed for each patient based on the known response of
the instrument and the length of the penis before and after
Although the problemof underestimation
counts is intrinsic to the design of the PNIS probe and
cannot be completely circumvented, gamma camera meth
ods of measuring cavernosal activityalso do not completely
sample the most proximal cavernosal activity because of
attenuation (19) and obscuration by the bladder and soft
tissue structures. The effect of auto-attenuation
in a camera system than with the probe because of 180Â°
versus 360Â° sampling. There is also the potential of overes
timating penile counts when using a gamma camera due to
inclusion of count-contributing
testes and especially the bladder (19), stemming from over
lap of neighboring structures and ambiguity in defining
penile and background ROIs.
Siraj has raised the issue of hemodilution of the penile
blood pool after intracorporal injection of a vasodilator
(47). In our study, we injected
contrast to the 7 ml of medication
investigation. Assuming the worst-case scenario in our pa
tients, that the complete volume of vasodilator remains
within the corpora cavernosa, thereby displacing radiola
beled blood, the postpapaverine blood volume would only
be underestimated by 1 ml.
The calculated values for flaccid blood flow and blood
volume in the patient we described are in general agree
ment with normal values in the literature, as determined by
other radionuclide techniques. The patient's flaccid penile
blood volume and resting blood flowwere estimated at 12.9
ml and 2.9 ml/min, respectively. Based on analysis of Shi
rai's blood volume data (14), Wagner calculated an average
flaccid blood volume of approximately 8 ml in normal
subjects (34). In their gamma camera study, Schwartz et al.
flaccid penile blood
growth within the distal
soft tissues, including the
only 1 ml papaverine
and flush used in his
FiGURE7. Five-point smoothedcountratecurvefroma patient
studied using a prototype configuration of the PNIS probe corn
posed ofsummed2-sec data points.
rability, cost and ease of fabrication of the plastic scintilla
tor, even though poor energy resolution of this material
would preclude performance of simultaneous dual-isotope
studies (35,42â€”44). It would be possible to independently
perform 133Xe(26â€”29) or@â€˜@â€˜Tc-RBC
with this instrument. A NaI crystal for dual-isotope studies
with similar geometry could be built but at increased cost
and the risk of potential mechanical and thermal damage.
For counting electronics, we paired the plastic scintillation
crystal with an acquisition board housed in a portable com
puter, which represents a low cost and highly versatile
acquisition platform for nuclear medicine applications (46).
We chose to perform the studies in a sitting position rather
than supine, as this is in accord with the observation that a
semi-erect posture is superior for producing reliable phar
macologically induced erection (43).
washout (45) studies
Two potentially significant limitations of the probe relate
to inclusion of extraneous extrapenile counts and incom
plete measurement of corporal cavernosal counts. The
former concern is reasonable because of the large blood
pool within the patient's body which is external to the
probe. To minimize this problem, the outer surfaces of the
crystal were shielded with 2.5 mm of lead. An estimate of
the level of extracavernosal background, as derived from
fitting the washin curves to their theoretical model, was
relatively minimal. Furthermore, with the theoretical ex
ception of excretion into the urinary tract, the distribution
of activity external to the probe remains relatively constant
during the course of the study, once the initial bolus of
activity has passed through the body, and would therefore
not spuriously lead to perceived changes in penile blood
volume counts. To limit the effect of urinary activity, a
combination of shielding, optimal invitro RBC labeling and
caudal tilting of the crystal effectively minimized contribu
tion from the urinary bladder which, based on our experi
ence in positioning the device, did not noticeably affect the
measured penile activity.
PenileScintillationProbe â€¢ Zuckierat al.
(19) described initial flaccid volumes averaging30 ml, with
a range of 11â€”76 ml. Our value of 12.9ml,which isbased on
positioning of the standard and may slightly underestimate
the actual value, is in good agreement with these figures.
The rate of flaccid flow in the corpora cavernosa of the
flaccid penis has also been previously determined by xenon
washout studies, in which flow is expressed
tissue volume. Assuming a flaccid penile volume of 53 cc
(34) and a partition coefficient
estimates of flaccid flow are in the 1.3 to 4.8 ml/min range
(16,28,34,48,49), although some estimates have been under
1 ml/min (15,27). The flaccid blood flow of 2.9 ml/min, as
estimated in our patient, is in good agreement with normal
values as determined by the majority of investigators.
per 100 cc of
of 0.7, the most common
The PNIS probe has potential for both clinidal and re
search applications, but the validation needed for these
uses varies. The feasibility of the probe as a diagnostic tool
rests on its ability to discriminate between differing etiolo
gies of erectile dysfunction, including arterial, venous, neu
rologic and stress-related causes (7,8). A systematic under
or overestimation of volume would not be prohibitive as
long as it does not interfere with differentiation of various
disease categories. Additional
tient groups are therefore planned
dynamic curves generated bythis instrument and to validate
various indices of function, as described in previous gamma
camera studies (7,8).
In human and animal investigations, the high temporal
resolution and absolutequantitative
probe also may prove useful in contributing to a quantita
tive understanding of the physiology of erection and the
pathophysiology of dysfunction. High frequency phenom
ena, not readily resolved by gamma camera methods, can
be observed with the superior framing rate of this device.
From a count rate linearity and radiation safety standpoint,
there is still considerable room to increase the dose of
labeled RBCSto further improve the statistical reliability of
the data. Quantitative analysis of the wash-in data, as dem
onstrated in this study, can be a powerful technique of
extracting physiologic information from the TACs. Flaccid
blood flow patterns have attracted attention (9,23), al
though they have not been investigated by mathematical
fitting. One must caution that the use of the PNIS probe as
a quantitative tool to measure absolute blood volume and
flow rate is a rigorous demand that will require further
validation in view of the count rate sensitivity consider
ations previously discussed.
studies in well-defined
to evaluate the hemo
natureof the PNIS
Analysis of flaccid
After acquisition of the TACS, an aliquot of venous blood is
obtained from the arm and counted within the probe to establish
a relationship between count rate and labeled blood volume. This
factor is then used to convert the penile TAC to a labeled blood
volume curve [B(t)] that reflects the volume oflabeled blood being
counted within the bore of the probe. At the steady-state of flaccid
equilibrium, the rate of blood flow into and out of the corpora
cavernosa isequal and constant (F), and the total blood volume of
the corpora cavernosaalso is constant (V). At any time, the
fraction of the cavemosal blood pool which is labeled B(t)/V and
divided by its total volume. The change in volume of intracavern
osal labeled blood at any time (dB(t)/dt) is equal to labeled blood
entering the corpora (F) less the labeled blood leaving, the latter
term being equal to flow out of the corpus cavernosa (F) multi
plied by the fraction of labeled blood in this space (B(t)/V).
Expressing this in mathematical terms,
dB(t)/dt = F â€” F x B(t)/V.
This can be rearranged in the form of
and integratedto yield
dB(t)/(1â€” B(t)fV)= F x dt
B(t)=Vx(1 +K' xetX@@).
At t = 0, we knowthat the volumeof labeledbloodwithinthe
penis is zero, therefore K' = â€” 1. Rewriting the equation yields
B(t) = V x (1 â€” e_tX@@@').
The experimental washin curve consists of the above compo
nent in addition to a constant term representing noncavernosal
background activity (Bk), expressed as an equivalent volume of
labeled blood. The patient data can be fit to these terms to yield
estimates of flaccid blood flow (F), equilibrium cavernosal blood
volume(V) and Bk.
Nuclear Medicine Education and Research Foundation. We thank
Mallinckrodt Medical, Inc. for supplying the UltraTagÂ® RBC kits.
Physician Scientist Award CA 01503.
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