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tumorvolumeinnonsmallcelllungcancer
Michael A Masoomi1*, Anne H McLean2, Yassine Bouchareb3, Will Ryder4,
AndyRobinson5
1DepartmentofNuclearMedicine,FarwaniyaHospital,Kuwait
2NuclearMedicinePhysics,QueenAlexandraHospital,Portsmouth,UK
3ClinicalPhysics,BartsHealthNHSTrust,UK
4FacultyofHealthScience,UniversityofSydney,Sydney,Australia
5TheHarleyStreetClinic,London,UK
ARTICLEINFO
Articletype:
Originalarticle
Articlehistory:
Received:12Jun2013
Revised:18Jul2013
Accepted:23Jul2013
Keywords:
Correction
PETCT
Lungcancer
NCAT
ABSTRACT
Objective(s): To investigate the impact of respiratory motion on localization, and
quantificationoflunglesionsfortheGrossTumorVolumeutilizingafullyautomated
Auto3Dreg program and dynamic NURBSbased cardiactorso digitized phantom
(NCAT).
Methods:Respiratorymotionmayresultinmorethan30%underestimationofthe
SUVvaluesoflung,liverandkidneytumorlesions.Themotioncorrectiontechnique
adoptedinthisstudywasanimagebasedmotioncorrectionapproachusing,avoxel
intensitybased and a multiresolution multioptimization (MRMO) algorithm. The
NCATphantomwasusedtogenerateCTattenuationmapsandactivitydistribution
volumes for the lung regions. All the generated frames were coregistered to a
reference frame using a time efficient scheme. Quantitative assessment including
RegionofInterest(ROI),imagefidelityandimagecorrelation techniques,aswellas
semiquantitative line profile analysis and qualitatively overlaying nonmotion and
motioncorrectedimageframeswereperformed.
Results:ThelargestmotionwasobservedintheZdirection.Thegreatesttranslation
was for the frame 3, end inspiration, and the smallest for the frame 5 which was
closet frame to the reference frame at 67% expiration. Visual assessment of the
lesion sizes, 2060mm at 3 different locations, apex, mid and base of lung showed
noticeable improvement for all the foci and their locations. The maximum
improvements for the image fidelity were from 0.395 to 0.930 within the lesion
volume of interest. The greatest improvement in activity concentration
underestimation was 7.7% below the true activity for the 20 mm lesion in
comparison to 34.4% below, prior to correction. The discrepancies in activity
underestimation were reduced with increasing the lesion sizes. Overlaying activity
distribution on the attenuation map showed improved localization of the PET
metabolicinformationtotheanatomicalCTimages.
Conclusion:The respiratory motion correction for the lung lesions has led to an
improvement in the lesion size, localization and activity quantification with a
potentialapplicationinreducingthesizeofthePETGTVforradiotherapytreatment
planningapplicationsandhenceimprovingtheaccuracyoftheregimeintreatment
oflungcancer.
Pleasecitethispaperas:
MasoomiMA,McLeanAH,BoucharebY,RyderW,RobinsonA.ImpactofPETCTmotioncorrection
inminimisingthegrosstumourvolumeinnonsmallcelllungcancer.AsiaOceaniaJNuclMedBiol.
2013;1(2):3546.
Introduction
* Corresponding author:Dr Michael A Masoomi, Department of Nuclear Medicine, Farwaniya Hospital, MOH,
PO Box 18373, Kuwait 81004, Email: masoomim@sky.com
2013 mums.ac.ir All rights reserved.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License
(http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
Masoomi MA et al
36
Methods
The NURBS that is a bidirectional parametric
representation of an object was utilized to
generate CT attenuation maps and activity
distribution volumes as a series of transaxial
slices for the lung region. The NURBS surfaces
define the respiratory structures in the spline
based NCAT, which can be altered via
affine/other
transformations
through
manipulation of control points, to simulate
respiration. The activity distribution in the
organswasbasedonliteraturereview,evaluating
uptake in the various healthy organs (24, 25).
Spherical lesions with the various sizes, 2060
mm, were generated using a separate program
within the NCAT phantom and incorporated
intothe NCAT phantom in the base of the right
and the left lungs. The positions of the lesion
werechosentoreflectthoseareasmostlikelyto
be affected by motion. Higher relative activity
concentrationwasassignedtothelesionsthanto
the surrounding lung tissue and organs. The
relativeconcentrationwasexpressedratherthan
lesiontoorganactivityratiotocreateimagesthat
will be quantitatively more descriptive and
Masoomi MA et al
Table1.RelativeactivityconcentrationsassignedtoNCATphantomforlungregion(24,25).
Relativeactivity
Organ
concentration
Organ
Bodybackground
Myocardium
Heartbloodpool
Lung
Lunglesions
1.00
4.44
1.42
0.60
Liver
Gallbladder
Stomach
Spleen
5.60
Spine
qualitativelycomparabletoclinicalimages(Table
1). To simulate the effect of the point spread
function (PSF) of a real PET scanner on the
activity images, each image volume was
convolved with a Gaussian Kernel as this has
been shown to be a good approximation to the
truePSFofaPETscanner.
Respiratorycycleandframegeneration
Five frames were generated throughout the
respiratory cycle using the NCAT phantom with
normal breathing parameters (Table 2).
Therespiratory motion was incorporated by
applying affine transformations to the different
respiratory structures. The period of the
respiratorycyclefornormaltidalbreathingwas5
secondswithinspirationlastingapproximately2
seconds and expiration lasting the remaining 3
seconds. The normal parameters were based on
respiratory mechanics and a respiratorygated
CTdatasetofanormalpatient(23).Theextent
of inspiration or expiration for each frame is
given by the NCAT phantom. The phantom
generates matching 3D distribution of
attenuationcoefficientsforagivenphotonenergy
(i.e. 511keV) and a 3D distribution of emission
radionuclide images corresponding to each of
thesefiveframes.
Respiratorymotioncorrection
The motion correction technique used in this
study (Figure 1) is an imagebased motion
correction approach; it uses of a voxelintensity
based and a multiresolution multioptimization
T21
0%
endexpiration
50%
midinspiration
Relativeactivity
Concentration
1.86
1.86
1.99
1.26
2.00
(MRMO)algorithm,firstdescribedbyBouchareb
et al (37). The technique takes advantage from
the convergence behavior of nonderivative
optimization methods when aligningimage sets
realized in extreme differences in term of
breathing protocols during data acquisition. The
key ideas of nonrigid voxel intensity based
registrationtechniqueconsistofmultiresolution
and hierarchical transformation model that uses
similarity measures to obtain an optimum
solution.
Table 2. Respiration parameters used for NCAT phantom
generation.
Parameter
Value
Lengthofrespiratorycycle
5seconds
Timeperframe
1second
Frame1startpoint
Fullexhalation
Maxdiaphragmmotion
2cm
Maxanteriorposteriorexpansion
1.2cm
TheprogramreadsinaCTtransmissionvolume
(reference), followed by a second CT trans
mission volume (floating) and an emission
volumethatwasacquiredatthesamerespiratory
point as the floating volume. The floating
transmission and emission volumes are
registered to the reference volume and the
motionparameters are estimated. The hierar
chical model first performs rigid body transfor
mations on a low resolution image; named
floatingimage(imagetoberegistered)toalignit
toareferenceimagebeforeperformingnonrigid
T31
100%
inspiration
T41
33%
expiration
T51
67%
expiration
Respiratorycycle
Figure1.Sketchofthemotioncorrectionmethodologytoestimatetheinterframe3Dmotionparameters(T21,T31,T41andT51);
T21 is the transformation which aligns frame 2 (50% inspiration) to the endexpiration frame (reference frame); T31 is the
transformationdescribingthe3Dmotionbetweenframe3(fullinspiration)andthereferenceframe,etc.Tospeedupthemotion
correctionprocess,transformationT21isusedtoinitialisetheestimationofT31andthesamefortheremainingframes.
37
Masoomi MA et al
F loating
im age
If
R e fe renc e
im age
Ir
Im a ge r es am pl ed
to is otropic vox els
Tinitial
If
Ir
If
R es olutio n le vel i
T ra ns fo rm
T ra ns fo rm
Ir
S u m o f sq u a red
d iffe re n ces
crite rio n
P o w e ll
o p tim is a tio n
If
Tnew
If
Tnew
Ir
Ir
S u m o f sq u a red
d iffe re n ces
crite rio n
S im ple x
o p tim is a tio n
Figure2.DiagramofMultiresolutionMultioptimisationalgorithmusingahierarchicaltransformationmodelandSSDsimilarity.I f
andIrrepresentfloatingandreferenceimages,TinitialandTnewrepresenttransformationparameters.
38
(a)
(b)
(c)
Figure3.Activitydistributionimagesoverwholerespiratory
cycle showing blurring due to respiration for lesions
positionedat(a)apexoflung;(b)midlung;(c)baseoflung.
[R(i, j, k ) T (i, j, k )]
Correlation =
Results
RegistrationParameters
For each registration, the software generates
the applied transformation parameters to match
the target frame to the reference frame.Table 3
showsanexampleoftheparametersfora20mm
lesion.Ingeneralthelargestestimatedmotionis
the translation in the zdirection (inferior
superior), followed by the translation in the y
direction (anteriorposterior). The translation is
greatest for the frame 3 which is at end
inspirationandsmallestfortheframe5,whichis
closesttothereferenceframeat67%expiration.
Equation1
[R(i, j, k )]2
i
j
k
i j k [R (i , j , k ) T (i , j , k )]
Equation2
2
[R (i , j , k )]
Fidelity factor = 1
Masoomi MA et al
VisualAssessment
Initially, the phantoms were generated with
lesionsinvariouspositionstovisuallyassessthe
extentofblurringincomparisontoamotionfree
image. Lesions in the range of 2060 mm
diametersweregeneratedindifferentlocationin
the lung to compare effect of the motion
correction (Figure3). The blurring due to
i
j
k
where R(i,j,k)=activityconcentrationinvoxel
(i, j, k) of the reference frame and T(i, j, k) =
activity concentration in voxel (i, j, k) of the
Table3.Theregistrationparametersforframes25fora20mmdiameterlesioninthecentralbaseoftherightlung.
Targetframe(registeredtoreferenceframe1)
Parameter
Direction
Frame2
Frame3
Frame4
Frame5
Translation
Rotation
Scaling
Shearing
0.607
0.554
0.547
0.354
3.402
7.660
6.278
1.347
1.690
8.465
22.887
17.560
0.023
0.046
1.455
0.119
0.017
0.007
0.859
0.064
0.083
0.051
0.027
0.035
0.999
0.998
0.999
1.000
0.969
0.932
0.943
0.991
1.049
1.186
1.142
0.992
0.183
0.101
0.114
0.055
0.071
0.201
0.982
0.123
0.302
0.021
1.210
0.344
39
Masoomi MA et al
(a)
(b)
MeasurementofLesionDimensions
The lesion dimensions in the anterior
posterior,inferiorsuperiorandlateraldirections
were measured, based on FWHM and FWTM,
before and after registration of frames using the
averageactivitydistributionimages.Inallcases,
the lesion dimensions were reduced following
the motion correction (Figure 8). The greatest
improvement was achieved in the inferior
superiordirection(4.513.8mm)andtendstobe
smallest in the lateral direction where there is
the least motion to respiration. The
improvements of 0.9 8.1 mm for the anterior
posterior and 0.4 2.2 mm for the lateral
directionswerealsoachieved.
(c)
Figure4.Activitydistributionimagesshowingpositionof20
mmlesions:(a)centralbaseofrightlung;(b)posteriorbase
ofrightlung;(c)posteriorbaseofleftlung.
FidelityandCorrelationFactors
The extent of the improvement was assessed
on a framebyframe basis in comparison to the
reference frame using the image FF and CF.
Figure 9 shows the results for the 20 60 mm
diameter lesions, indicating improvement in the
fidelityandcorrelationfactorsforallthelesions.
TheFFandCFwerelowestfortheframe3,which
is at full inspiration and therefore furthest from
LineProfileAnalysis
The improvement of activity within the lesion
was assessed using line profiles. Figure 7 shows
thesuperiorinferiorprofilesforthe2060mm
lesions in the central base of the right lung.
Ideally, the profile for the motion corrected
image should match the profile for the motion
freeimagegeneratedwithoutrespiratorymotion.
(a)
(b)
Figure 5.The average activity distribution in all five frames
fora20mmlesion(a)beforeregistrationofframes;(b)after
registrationofframes.
40
(a)
(b)
Figure6.Theaverageactivitydistributioninallfiveframes
fora60mmlesion(a)beforeregistrationofframes;(b)after
registrationofframes.
(a)20mmlesion
6
lesion
Motionfreeimage
Uncorrectedimage
Voxel value
Correctedimage
liver
lung
0
0
20
40
60
80
Voxel value
(b)30mmlesion
lesion
6
5
4
3
2
1
0
Motionfreeimage
Uncorrectedimage
Correctedimage
liver
lung
20
40
60
80
100
Voxel value
7
6
5
4
3
2
1
0
Motionfreeimage
140
180
200
220
240
220
240
220
240
lesion
Correctedimage
liver
lung
20
40
60
80
100
120
140
160
180
200
Millimetres
(d)50mmlesion
Voxel value
lesion
Motionfreeimage
Uncorrectedimage
Correctedimage
liver
lung
0
0
20
40
60
80
Voxel value
100
120
140
160
180
200
Millimetres
(d)50mmlesion
7
6
5
4
3
2
1
0
lesion
Motionfreeimage
Uncorrectedimage
Correctedimage
lung
20
40
60
80
100
120
140
Millimetres
160
Uncorrected
image
(e)60mmlesion
120
Millimetres
(c)40mmlesion
Masoomi MA et al
160
180
200
220
240
Figure7.Lineprofilesinthesuperiorinferiordirectionfordifferentlesiondiametersinthecentralbaseoftherightlung.
41
Masoomi MA et al
Trueactivityconcentration:5.6unitsper
voxel
Meanvoxel valueinVOI
20mm base
of left lung
posterior
20mm base
of right lung
posterior
20mm
30mm
40mm
50mm
60mm
Figure 8.The reduction in lesion dimensions following registration of frames 25 to the reference frame. The difference was
measuredbetweentheaverageuncorrectedandcorrectedactivitydistributionimages.
frame1.Forallthelesionofsizes10,20,30,40,
50and60mmwhichwereincorporatedintothe
NCAT phantom in the base of the right lung, the
improvementismoresignificantforthelocalized
rectangular volume surrounding the lesion. The
maximumimprovementinfidelityfrom0.395to
0.930 was calculated for a lesion within the
volumeofinterest.Futureworktoinvestigatethe
localized motion correction is appearing to be
informative.
AssessmentofLesionActivityConcentration
ForallmethodsofdefiningROIoverthelesion
sizes, an improvement in activity quantification
following motion correction was observed
(Fig10).Thegreatest underestimation of activity
concentration was noted down for the 20 mm
lesions although, the greatest improvements
were observed following registrations of the
frames.Ingeneral,asthelesionsizeisincreasing,
theactivityunderestimationisdecreasedwhichis
in agreement with the study performed by the
Boucheretal(3).
Overlay of Activity Distribution on Attenuation
Map
Followingthemotioncorrectionoftheframes,
the lesion in the activity distribution image
coincided better with the lesion in the
attenuation image (Fig11), indicating that the
image
registration
technique,
enables
improvementinthelocalisationofPETmetabolic
informationrelativetoananatomicalCTimage.
Discussion
Respiratory motion affects all tumor sites in
the thorax and abdomen (even the pelvis) (46),
motion varies from day to day, and tumor and
normal tissues can shrink, grow, and shift in
42
Masoo
omi MA et al
(a)20mmdiam
meterlesionoverrwholeimageVo
olume(b)20
0mmdiameterleesionoverlesion
nvolumeofinterrest
(c)30mmdiam
meterlesionoverrwholeimagevo
olume(d)30
0mmdiameterleesionoverlesion
nvolumeofinterrest
(e)40mmdiaameterlesionov
verwholeimagevolume(f)40mmdiameterlesionoverlesionvolumeofinterrest
verwholeimageevolume(h)50mmdiameterleesionoverlesion
nvolumeofinterrest
(g)50mmdiaameterlesionov
(i)60mmdiaameterlesionov
verwholeimageevolume(j)60
0mmdiameterleesionoverlesion
nvolumeofinterrest
Figure9.Im
mprovementin imagefidelityaandcorrelationffactorsbeforean
ndafterregistraationofeachfraametotherefereenceframe.
Thecompaarisonismadebetweeneachfraames,15,andth
hereferencefram
me1.
43
Masoomi MA et al
16
14
12
10
20mm diameter
20mm diameter
20mm diameter
30mm diameter
40mm diameter
50mm diameter
60mm diameter
8
6
4
2
0
Anterior-posterior
Lateral
Inferior-superior
(a)
(b)
Figure11.Overlayofactivitydistributiononreferenceframe
attenuation map for: (a) the uncorrected average activity
distribution; (b) the motion corrected average activity
distribution.
44
Therespiratorymotioncorrectionforthelung
lesions has led to an improvement in the lesion
size, localization and activity quantification with
apotentialapplicationinreducingthesizeofthe
PET GTV for radiotherapy treatment planning
applicationsandhenceimprovingtheaccuracyof
theregimeintreatmentofthelungcancer.
Acknowledgement
AuthorswouldliketothankDrPaulSegarsfor
provisionoftechnicalexpertiseandadviceusing
theNCATphantom.
11.
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