Dynamic PET/CT measurements of induced positron activity in a prostate cancer patient after 50-MV photon radiation therapy.

1.7 MB·English

by  Janek Straat, Sara

JanekStrååtetal.EJNMMIResearch2013,3:6
http://www.ejnmmires.com/content/3/1/6
ORIGINAL RESEARCH Open Access
Dynamic PET/CT measurements of induced
positron activity in a prostate cancer patient after
50-MV photon radiation therapy
Sara Janek Strååt1*, Hans Jacobsson2, Marilyn E Noz3, Björn Andreassen1, Ingemar Näslund4 and Cathrine Jonsson5
Abstract
Background: The purpose of this work was to reveal theresearch interest value ofpositron emission tomography
(PET) imaging invisualizing the induced tissue activity post high-energy photonradiation treatment. More
specifically, thefocus was onthe possibility of retrieving data such as tissue composition and physical half-lives
from dynamic PET acquisitions, as positron-emitting radionuclides such as 15O, 11C,and 13N are produced in vivo
during radiation treatment withhigh-energy photons (>15 MeV). The type, amount, and distribution of induced
positron-emitting radionuclides depend on the irradiated tissue cross section, the photon spectrum, and the
possible perfusion-driven washout.
Methods: A 62-year-oldman diagnosed withprostate cancer was referred for palliative radiation treatment of the
pelvis minor. A total dose of 8Gy was given using high-energy photon beams (50 MV) witha racetrack
microtron, and 7min after theend of irradiation, the patient was positioned ina PET/computed tomography (CT)
camera, and a list-mode acquisition was performed for 30 min. Twovolumes of interests (VOIs) were positioned on
thedynamicPET/CTimages, one inthe urinary bladder and the otherin the subcutaneous fat.Analysis ofthe
measured relative count rate was performed inorder to computethe tissue compositionsand physical half-lives in
thetwo regions.
Results: Dynamic analysis from the two VOIs showed that thedecay constants of activated oxygen and carbon
could be deduced. Calculation oftissue composition from analyzing the VOIcontainingsubcutaneous fat only
moderately agreed withthat ofthetabulated International Commission onRadiation Units &Measurements (ICRU)
data oftheadipose tissue. However, thesame analysis for thebladder showed a good agreement with that of the
tabulated ICRU data.
Conclusions: PET can be used invisualizing the induced activitypost high-energy photon radiation treatment.
Despite the very low count rate inthis specific application, wherein7 min after treatment was about 5% of that of
a standard 18F-FDG PET scan, thedistribution ofactivated tissue elements (15O and 11C) could be calculated from
thedynamicPET data.One possible future application of this method could possibly be to measure and determine
thetumor tissue composition in order to identify any hypoxic or necrotic region, which is information that can be
used in theongoing therapy planning process.
Trial registration: The official name of thetrial committee of this study is ‘Regionala etikprövningsnämndeni
Stockholm’ (FE289, Stockholm, SE-17177, Sweden).The unique identifying numberis 2011/1789-31/2.
Keywords: High-energy photons,PET, Induced tissue activity,Photonuclear reactions, Radiation therapy, Treatment
beam verification.
*Correspondence:[email protected]
1DepartmentofMedicalRadiationPhysics,KarolinskaInstitutetand
StockholmUniversity,StockholmPOBox260SE-17176,Sweden
Fulllistofauthorinformationisavailableattheendofthearticle
©2013JanekStrååtetal.;licenseeSpringer.ThisisanOpenAccessarticledistributedunderthetermsoftheCreative
CommonsAttributionLicense(http://creativecommons.org/licenses/by/2.0),whichpermitsunrestricteduse,distribution,and
reproductioninanymedium,providedtheoriginalworkisproperlycited.
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Background Radiationtreatmentandbeamsetup
Georg de Hevesy became the father of nuclear medicine The patient was scheduled for palliative radiation treat-
when he formulated the famous ‘Tracer Principle’ in ment consisting of five fractions delivered in a span of 1
1913 (G Jr. de Hevesy, personal communication) [1]. week. Thefirst four fractions weredelivered to thepatient
This means that by the administration of minute using 18-MV photons. The last fraction was delivered
amounts of a chemical compound labeled with a proper using50-MVscannedphotonbeams(RacetrackMicrotron
radionuclide, it is possible to study functional mechan- MM50Scanditronix,IBA,Uppsala, Sweden),givingatotal
isms in living plants, animals, or humans without dose of 8 Gy. For the purpose of this and another patient
interfering with their functional properties. Diagnostic study,theracetrackmicrotronhadtoberestoredtoitsori-
nuclear medicine is usually based on the administration ginal clinical state; thus, only one of the five fractions was
of a radiopharmaceutical which undergoes a biological delivered using 50-MV photons. In Figure 1, the 50-MV
or physiological process in the body that can be photon treatment plan is shown (together with the PET/
depictedandanalyzed. computed tomography (CT) image) for selected transaxial
During external beam radiation therapy with high- andcoronalplanes.Thetargetincludedtheprimarytumor
energy photons (>15 MeV), short-lived positron-emitting and the metastases of the right pelvic bones. The target
radionuclides are generated in the normaltissues through dose delivery was divided equally between four beams in
theprocessesofphotonuclearreactions.For12C,14N,and the following order: (1) posterior-anterior, (2) right, (3)
16O in the living tissue, the photoneutron reaction, anterior-posterior, and (4) left. The total irradiation time,
denotedas(γ,n),hasathresholdenergyofabout15to18 includingrotationofthegantry,was6minand52s.
MeV [2-4]. The process leads to the positron-emitting
radionuclides 11C, 13N, and 15O withphysical half-lives of PET/CTacquisitionandpatientpositioning
20, 10, and 2 min, respectively. The amount of positron ThePET/CTscanwasperformedwithaSiemensBiograph
emitters produced per unit volume will depend on the TrueV PET/CTscanner (Siemens Medical USA, Knoxville,
shape of the photoneutron cross section for the specific TN, USA) located at the Nuclear Medicine Department.
element and on the tissue density as well as the energy The time span between the end of the irradiation and the
spectrumoftheincidentphotonbeam. startofthePET/CTscanwasapproximately7min.Patient
Theaimofthisreportistohighlightawayofproducing transportwasarrangedwithawheelchair.TheCTscanwas
radionuclidesinapatient,thusprovidinginformationthat a ‘low-dose attenuation correction CT’ (ACCT) for
may be complementary to that from traditional nuclear necessary corrections and an anatomical reference. The
medicine. Therefore, we describe a positron emission PET acquisition was performed in list mode, allowing for
tomography (PET) study in a male patient after high- theoptionalselectionofframelengths.Inordertoeliminate
energy photon treatment of the pelvis minor because of decay correction issues when reconstructing time frames,
the local spread of prostate cancer. The examination was theisotopeinformationfortheacquisitionprotocolwasset
done as an extension of earlier work described in [5] to68Ge(half-life,T =271days).Reconstructionwasper-
1/2
which was an attempt to verify the dose location of the formedwithfilteredbackprojection(FBP)andattenuation-
radiationbeams.AnalysisoftheseriesofconsecutivePET weighted three-dimensional ordered subset expectation
acquisitions initiated at the end of the treatment showed minimization (3D-OSEM) (two iterations and eight sub-
a cascade of decaying radionuclides with different decay sets), creating images with somewhat different characteris-
patterns depending on the composition of the various tics but derived from the same raw data. A 5-mm post-
tissues irradiated. The amount of information was more reconstructionGaussianfilterwasappliedinallreconstruc-
than one could achieve on the basis of a regular nuclear tions. All data were corrected for random coincidences,
medicine examination. As for today, a total number of dead time, scatter, and attenuation. Reconstructed dynamic
four racetrack microtrons using 50-MV photons are in serieswerecreatedusingaprotocolconsistingof15frames
clinical use in China, and more units are being installed of2mineach.Inaddition,asummationimagewascreated
(EJöreskog,personalcommunication).Consequently,this using the complete acquired dataset, i.e., 30 min in dur-
or a similar technique based on nuclear activation may ation.ThePETstudywas,thus,performedonclinicalindi-
havefutureapplications. cation.Afteraretrospectiveapplication,theregionalethical
committee,‘Regionala etikprövningsnämnden i Stockholm’
Methods (Stockholm,Sweden),declarednoobjectiontothestudy.
Patient
A 61-year-old man was diagnosed with prostate cancer ImagefusionofPET/CTanddoseplanningCT
with extensive local growth. Bone scintigraphy also Thevolumeco-registrationsoftware,Mirada(XD3,Mirada
showed an uptake in the right os ischii and os pubis due Medical, Oxford UK) [6], was used to align the ACCT to
tometastases. the planning CT. Mirada uses a voxel intensity-based
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Figure1Transaxialoverlaid50-MVradiationtreatmentplanonPET/CT(0to30min)image.Thisisforthree-dimensionalorderedsubset
expectationminimization(3D-OSEM,upper)andfilteredbackprojection(FBP,lower)reconstruction.Thetreatment,hereshownforplanesection
throughthenormalizationpoint(Norm),isafour-fieldboxtechniquewiththetargetdosedeliveryof8Gyintotaldividedequallybetweenthe
fourbeamportals.Theisodosecurvesdisplayedcovertheranges35%(yellow),65%(green),85%(orange),and95%(blue)ofthetotaldose.The
tworedcurvesdepicttheinteractivelydefinedclinicaltargetvolume(innerline)andplanningtargetvolume(outerline).Thegrosstumor
volumeisnotdepictedbutincludestheprostatetogetherwiththemetastasisoftherightosischiiandthemedialportionoftherightospubis.
registration algorithm that can be both rigid and deform- of the measured relative count rate in the two regions was
able. In this study, the deformable registration was used. performedwithMATLAB[9].Duetothefactthatthether-
The fusion was performed by an experienced radiologist apy machine and the PET/CT unit were not co-located,
interactivelymovingandrotatingtheACCTvolumeuntila any washout of positron emitters in the patient was not
satisfactory fit to the planning CT was found. All four measurable from the PET data. In order to obtain such
image sets (PET, ACCT, planning CT, and treatment plan data, preferably in-beam PET measurements need to be
data)weresimultaneouslydisplayed,allowingproperalign- performed as indicated by animal and patient studies dur-
mentoftheACCTandtheplanningCT. ing 11C and 12C beam irradiation [10-12]. Thus, decay of
biological components was not considered in the analysis.
Imageanalysis Assuming 12C, 16O, and 14N to be the most dominant in
The PET/CT images were interpreted by an experienced the tissue, the time-dependent measured total count rate
radiologist.Twovolumesofinterest(VOIs)werepositioned (per second; proportional to the activity), S(t), can be
onthedynamicPET/CTimages.VOI1waspositionedata writtenasthesumofthreeexponentialterms:
regionhighlightedinthePETimages,correspondingtothe
t
subcutaneous fat lateral to the left hip joint. VOI 2 was SðtÞ¼S expð(cid:2)lnð2Þ(cid:3) ÞþS expð(cid:2)lnð2Þ
1 T 2
drawn with a certain margin within the urinary bladder as 1; 1
t 2 t
depictedintheCTsections.ImageviewingandVOIevalu- (cid:3) ÞþS expð(cid:2)lnð2Þ(cid:3) ÞþK; ð1Þ
T 3 T
ationwasperformedusingAMIDEsoftware[7,8].Analysis 1; 2 1; 3
2 2
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where S , S , and S represent the count rates from DynamicVOIanalysis
1 2 3
radionuclideswithphysicalhalf-livesT ,T ,andT , 1. VOI 1. The VOI drawn over the subcutaneous fat on
½,1 ½,2 ½,3
respectively, at the end of the irradiation (corrected for the PET image is presented in Figure 2 for transaxial
radioactive decay is 7 min, i.e., the transport time and coronal planes. The relative number of counts as a
between when the irradiation finished to the start of the function of time for VOI 1 is shown in Figure 3, with
PETscan).Kisaconstant.ThequantitiesS ,S ,S ,T , the lines representing the best fit to Equations 2 and 3
1 2 3 ½,1
T ,andT arecomputedbyperformingaleastsquare insolidredanddashedblue,respectively.ForEquation2,
½,2 ½,3
fit, which minimizes the sum of the squares of the differ- it was found that S = 0.32 ± 0.11, S = 0.65 ± 0.21, S =
1 2 3
ences of measured data from Equation 1. A solution was 0.03 ± 0.24, and K = 0 representing the relative count
obtainedforthefollowingtwocases:(i)S ,S ,andS were rate, with calculated 95% confidence interval, from 11C,
1 2 3
set as unknowns whileT ,T , and T were held fixed 15O, and 13N at the end of irradiation. For Equation 3
½,1 ½,2 ½,3
and set according to the half-lives of 11C, 15O, and 13N, instead, it was found that S = 0.33 ± 0.01, Τ = 19.4 ±
1 1
respectively, and (ii) S , S , S ,T ,T , and T were 1.1 min, S = 0.67 ± 0.11, Τ = 1.99 ± 0.74 min, S = 0,
1 2 3 ½,1 ½,2 ½,3 2 2 3
all set as unknowns. Thus, the following constraints and K = 0. The values of S , S , and S are compared
1 2 3
were set for the two cases (i and ii for Equations 2 and 3, with the 1H-adjusteda ICRU elemental compositions for
respectively): the adipose tissue of adult 2a in [13] which have the
following values:67.7%C,31.5O,and0.8% N.
S1; S2;andS3≥0; ð2Þ 2. VOI 2. The urinary bladder as defined by the CT
images is shown in Figure 4; it also shows the sum of the
T1;1 ¼T1;11C ¼ 20:39min; completedynamicPETstudy(0to30min).Anearlyimage
2 2
T1;2 ¼T1;15O ¼ 2:04min; (0 to 2 min) and three added late images (25 to 30 min)
2 2
T12;3 ¼T12;13N ¼ 9:97min; frraoteminthtehdeyunraimnaircyPbElTadsdteurdyisahreigahlsaotptrheesebnetgeidn.nTinhgeocfouthnet
acquisition but declines to almost zero after 25 min. The
and
relativenumberofcountsasafunctionoftimeforVOI2is
S ; S ;andS ≥0; ð3Þ shown in Figure 3, with lines representing the best fit to
1 2 3
Equation 2 in solid red and Equation 3 in dashed blue. It
T1;1;T1;2;andT1;3≥0: wasfoundthattherelativecountrates,withcalculated95%
2 2 2
In equation 3, T , T , and T were used to extract
½,1 ½,2 ½,3
theestimatedphysicalhalf-lives(T ,T ,andT )
½,11C ½,15O ½,13N
of11C,15O,and13N,respectively.Thecomputedquantities
S , S , and S are compared to 1H-adjusteda International
1 2 3
Commission on Radiation Units & Measurements (ICRU)
elemental composition for the urinary bladder (filled) and
adiposetissue[13].
Results and discussion
Results
InvivovisualizationofthetreatmentbeamsbyPET
It could be estimated that the activity concentration in a
radiotherapy-treated patient, 7 min after a 5- to 8-Gy
treatment, is close to 5% of that of a patient injected
with 18F-FDG for a standard PETscan. Even if FBP has
its strength in being a linear process, there are obvious
drawbacks looking at the visual appearance of the
images. The resulting images using FBP were noisy and
contained pronounced streak artifacts. Therefore, to
facilitate outlining of the VOI, images from iterative 3D-
OSEM reconstruction were used. In Figure 1, the PET/CT
(0 to 30 min) image is shown side by side for both recon- Figure2Transaxial(upper)andcoronal(lower)PET/CT
structionmethods.Clearlyvisibleinbothreconstructionsis (0to30min)sections.ThefigureillustrateshowVOI1(arrow)
wasdrawnonthedynamicPETimageintheregionofthebeam
a high-induced activity seen in the subcutaneous fat where
entranceinthesubcutaneousfat.
thefourbeamsenteredthepatient.
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Figure3RelativenumberofcountsforbothVOIsasfunctionoftimedisplayedinlinear-logarithmicdiagram.Measureddataareshown
ascirclesandsquarestogetherwiththebestfittoEquations2and3representedasasolidredlineandadashedblueline,respectively.
confidence interval, from 11C, 15O, and 13N at the end of Discussion
irradiation were S = 0.08 ± 0.00, S = 0.92 ± 0.03, S = 0, This work focused on the potential use of PET for
1 2 3
and K = 0 for Equation 2. Applying the constraints in measuring the in vivo-induced tissue activity due to
Equation3,thecomputationgavethatS =0.08±0.00, radiation treatment with high-energy photons, which
1
Τ = 20.9 ± 1.6 min, S = 0.92 ± 0.04, Τ = 2.01 ± 0.18 is 50 MV in this case. Since 1972, attempts were
1 2 2
min, S = 0, and K = 0. The values of S , S , and S are already made at our institution using a gamma camera
3 1 2 3
compared with the 1H-adjusteda ICRU elemental com- to depict the distribution of the positron-emitting
positions for the urinary bladder (filled) of the adult in radionuclides produced in patients being irradiated with
[13] which have the following values: 4% 12C, 94% 16O, 42-MV photons from a betatron. The acquired images
1.7%and14N. could clearly verify that the radionuclide distribution
Figure4TransaxialsectionsoftheACCT(left)andPET/CT(right)(0to30min).TheimageshowstheVOIdrawnintheurinarybladder
(upperrow).LowerrowshowsthetransaxialsectionofthePETimageacquiredfrom0to2min(left)andfrom25to30min(right)alongwith
theVOIimposedintheurinarybladder.Duringthistimeperiod,thebladderactivityrepresenting15Ohasalmostcompletelydeclinedwhilethe
surroundingsofttissueactivity,mainlyrepresenting11C,isstillclearlyvisible.
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coincided with the irradiated regions. However, as the Upon arrival at the Nuclear Medicine department, the
sensitivity of the camera was very low and the output setup and positioning of the patient on the PET/CT
only analogous, no further such attempts were made couch were done as fast as possible in order to avoid
(L Johansson, personal communication). Other early further loss of induced activity. The main focus was to
studies have shown the potential use of tissue activation ensure that the radiation treatment volume was covered
for the analysis of tumor blood flow in animal studies by the axial field of view of the PETcamera. Subsequent
[14-16].Morerecently,bythestudyofbiologicalwashout reconstructions showed that the patient had become
processes of ion-beam-induced positron emitters, half-lives slightly mis-positioned in all three planes. In addition,
of various washout components could be measured in the regular curved PET/CTcouch did not match the flat
animals [10,11] and in patients [12,17]. Furthermore, couch used during the radiation treatment and the CT
dose and treatment beam verification during as well as planning, resulting in a deformed activity distribution
immediately after treatment with ion-beams [18,19] and toward the outer edges of the patient as seen on the
protons[17,20,21]inpatientsandforhigh-energyphotons treatment plan overlaid on the PET/CT image. However,
intheanimaltissue[5]havebeenreported. the deformable registration compensated for the different
In this study, measurements of biological washout couches in the main part of the abdomen where the
processesinthepatientwere not relevantdue tothefact beamsintersect.
that the therapy machine and the PET/CT were not co- Reconstruction with FBP [24-26], which is based on
located, and most of the radioactivity had been eliminated the inverse of the radon transform [27], is fast, robust,
before the PET examination. Studying half-lives of various linear, and known to yield quantitative results. However,
washout components, particularly in blood-rich organs in the low count data such as in this study, the results
such as the lungs and the liver, generally needs activity showed a poor visual image quality, disturbing streak
measurementsto beperformedduringoratleastindirect artifacts, and high noise. In order to better visualize the
connectiontotheirradiation[22].Theurineofthebladder, activatedtissueand,thereby,thepositioningoftheVOIs,
on the other hand, represents an enclosed compartment the iterative reconstruction method, 3D-OSEM [28], was
withanegligibleexchangewithothertissues.FromtheCT preferred.Theimagesreconstructedby3D-OSEMlackthe
scan,itwasestimatedthattheurinevolumeofthebladder streak artifacts and contain no data outside the object.
atthebeginningofPETacquisitionwasapproximately200 However, further studies are required to assess the quanti-
cm3. Assuming a urine excretion of about 0.5 ml/min, the tative accuracy of the two methods. It might be that the
dilution of activity in this case is almost negligible. Also in VOIs preferably are outlined using the 3D-OSEM algo-
fat, the dynamic portion constitutes only of a very small rithm, while the data from the VOIs preferably should be
fraction, and most of the induced PET activity originates extractedfromtheFBPreconstructeddata.
fromradionuclidesthatarestationarywithinthetissue.
VOI analysis of the subcutaneous fat gave a compos- Conclusions
ition that did not completely agree with ICRU-tabulated The purpose of this work was to reveal the research
values for the adipose tissue [13], although the fitted interest value of PET imaging in visualizing the induced
half-lives were found to agree well for both 11C and 15O. tissue activity post high-energy photon radiation
The reason for the restricted agreement in composition treatment. Despite the very low count rate, the work
may be the variations in the actual composition of the demonstrates that the distribution of activated tissue
subcutaneous fat of the current patient. According to elements (mainly 15O and 11C) could, for stationary
[13], the adipose tissue is the most variable tissue in the tissues, be calculated from the dynamic PET data. The
body regarding elemental composition. Water content measurement of the mobile as well as stationary tissue
may vary from 10.9% to 21.0%, and lipid content can might be possible if the PET/CT unit is located close
range from 62% to 91% [23]. From the analysis of totheradiationtreatmentfacilityasthismethodwould
urinary bladder contents (i.e., urine), a high level of be more sensitive. This has been demonstrated in the
oxygen content was found, which is expected as it case of ions [12,17]. As the radionuclides produced in
mainly is composed of water. The calculated half-lives thepatientduringphotonirradiationalloriginatefrom
and composition were found to correlate well with the body tissue (and not from the beam itself), the
tabulated ICRU values [13]. In bone tissues, a high measured PETactivity will, with some corrections, be
content of 40Ca and 31P will produce positron-emitting strictly proportional to the body tissue composition.
radionuclides when they are irradiated with high-energy The idea of being able to measure the true body tissue
photons. However, as the half-life of 39Ca is only 0.86 s, composition and map anatomical structures is interesting
this activity will probably never be measurable, and 30P [29] and could have future applications. One possible
that has a half-life of 2.5 min will most likely not be aspect of this method would be to measure and deter-
distinguishable from 15O. mine the tumor tissue composition in order to identify
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Authordetails
1DepartmentofMedicalRadiationPhysics,KarolinskaInstitutetand developmentandclinicaluseofabeamON-LINEPETsystemmounted
StockholmUniversity,StockholmPOBox260SE-17176,Sweden.2Department onarotatinggantryportinprotontherapy.IntJRadiatOncolBiolPhys
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