Local motion correction for lung tumours in PET/CT first results

Transcription

1 Eur J Nucl Med Mol Imagng (2008) 35: DOI /s ORIGINAL ARTICLE Local moton correcton for lung tumours n PET/CT frst results Ralph A. Bundschuh & Axel Martínez-Möller & Markus Essler & Stephan G. Nekolla & Sbylle I. Zegler & Markus Schwager Receved: 5 March 2008 /Accepted: 9 June 2008 / Publshed onlne: 6 August 2008 # Sprnger-Verlag 2008 Abstract Purpose Respratory moton of lung lesons s a lmtng factor of quantfcaton of postron emsson tomography (PET) data. As some mportant applcatons of PET such as therapy montorng and radaton therapy treatment plannng requre precse quantfcaton, t s necessary to correct PET data for moton artefacts. Methods The method s based on lst-mode data. Frst, the moton of the leson was detected by a centre of mass approach. In the second step, data were sorted correspondng to the breathng state. A volume of nterest (VOI) around the leson was defned manually, and the moton of the leson n ths VOI was measured wth reference to the end-expraton mage. Then, all voxels n the VOI were shfted accordng to the measured leson moton. After optmsaton of parameters and verfcaton of the method usng a computer-controlled moton phantom, t was appled to nne patents wth soltary lesons of the lung. Results Ffty percent dfference n measured leson volume and 26% n mean actvty concentraton were found comparng PET data before and after applyng the correcton algorthm when smulatng a moton ampltude of 28 mm n phantom studes. For patents, maxmum changes of 27% n volume and 13% n mean standardsed uptake values (SUV) were found. Concluson As respratory moton s affectng quantfcaton of PET mages, correcton algorthms are essental for applcatons that requre precse quantfcaton. We descrbed R. A. Bundschuh (*) : A. Martínez-Möller : M. Essler : S. G. Nekolla : S. I. Zegler : M. Schwager Nuklearmedznsche Klnk und Polklnk, Klnkum rechts der Isar der Technschen Unverstät München, Ismannger Str. 22, Munch, Germany e-mal: ralph.bundschuh@tum.de a method whch mproves the quantfcaton of movng lesons by a local moton correcton usng lst-mode data wthout ncreasng acquston tme or reduced sgnal-tonose rato of the mages. Keywords Tumour targetng. Localsaton. Dual-modalty. PET/CT. Image processng. Lung cancer PET Introducton The value of combned postron emsson tomography and computed tomography (PET/CT) for dagnoss and stagng of malgnant dsease s well accepted. Wthn the last years, two addtonal applcatons are of growng mportance for PET/CT: rado therapy plannng (RTP) and therapy montorng. Both applcatons set new challenges for PET/CT very precse quantfcaton of tumour localsaton and tracer uptake. In RTP, the exact localsaton of the tumour must be known to delneate the target volume that wll be rradated, often called bologcal target volume when usng PET [1, 2]. Therefore, correct volume delneaton s substantal to acheve local tumour control. Addtonally, the volume of rradated healthy tssue can be reduced, and hence, the dose n malgnant tssue can be escalated. In therapy montorng, tumour volume s also of nterest, but more mportant s to measure the tracer uptake of the leson wth hgh accuracy. It may be the decsve factor n the choce of therapy scheme and may nfluence the future therapy decsons and fnally the outcome of the patent [3 5]. Regardless of dscussons about algorthms for tumour volume defnton n PET [6], t s clear that moton of tumours durng the PET acquston, whch takes several mnutes per bed poston, s one of the lmtng factors. PET

2 1982 Eur J Nucl Med Mol Imagng (2008) 35: presents data averaged over many breathng cycles, whch leads to smearng artefacts. Another problem n PET/CT measurements s the possble msalgnment between PET and CT data, snce CT data are acqured as a snapshot of one breathng state [7]. Especally the lung s of nterest, as non-small-cell lung cancer s a major target n the feld of usng PET n RTP [1, 8] Studes evaluatng tumour moton n the lung usng 4D MRI found crano-caudal moton ampltudes of (24±17 mm) n the lower regons of the lung, reportng a sgnfcantly hgher moblty n tumours of the lower regon of the lung than of the mddle and upper regons [9]. Such tumour moton can lead to errors n quantfcaton of actvty uptake and sze of the tumour [10]. Among the attempts to reduce the effects of respraton artefacts, respratory gatng (RG) s currently the mostly used method. In RG, the acqured events are sorted nto dfferent respratory gates dependng on the breathng state of the patent. Then, dfferent mages are reconstructed for each state whch are free of respraton artefacts [11]. Ths method shows mprovements n quantfcaton: Nehmeh et al. [10] reported about a reducton of tumour volume of up to 34% and an ncrease n the standardsed uptake values (SUV) of up to 159% comparng gated mages to non-gated mages. The dsadvantage of RG s the reducton of sgnal-tonose rato, as for each gate, only a fracton of the acqured counts s used for mage reconstructon. Ths can be mproved by ncreasng the scan tme [12, 13]. But on the other sde, due to dscomfort for patents and for economcal reasons, scan tme cannot be ncreased by a factor of four or more, whch would be the mnmum number of requred gates n whch a breathng cycle needs to be dvded [14]. Hence, for clncal routne, algorthms are needed, whch reduce moton artefacts wthout reducng the mage qualty. There are varous approaches fulfllng ths requrement, each wth ts own advantages and dsadvantages: The frst of these correcton methods has been reported for patent shfts n PET of the bran where a rgd transformaton s suffcent to correct for the moton [15]. Outsde the cranum, rgd transformaton was used successfully for correcton of sngle organ moton, e.g. for cardac studes [16]. For moton correcton of large felds of vew, coverng several organs, non-rgd methods seem to be superor and are therefore nvestgated by several groups. Schaefers et al. [17] recently reported about a correcton based on optcal flow methods, and Lamare et al. [18] mplemented an affne transformaton of lst-mode data for the correcton of respratory moton over the thorax. Whle all these methods correct the whole data set, we nvestgated an alternatve approach based on local moton correcton. Ths means that only the volume around the tumour s corrected, whle the rest of the data set remans unchanged. Such an approach s based on the assumpton that as long as a lmted volume around the tumour s consdered, a local rgd transformaton may be suffcent to compensate the effects of respratory moton. Ths method ams at usng all counts for the reconstructed mage, combned wth a short computatonal tme. Materals and methods PET/CT scanner PET data were acqured wth the PET/CT Bograph Sensaton 16 scanner (Semens Medcal Solutons, Erlangen, Germany). The PET component of ths tomograph conssts of 24 detector rngs of LSO detectors and s a 3D-only tomograph. The axal and transversal feld of vew s 16.2 and 58.5 cm, respectvely. The transverse resoluton of the scanner s 6.5 mm, whle the axal resoluton s 6.0 mm both at a radus of 1 cm. The CT component of the tomograph s a 16-slce spral CT wth a varable slce thckness of mm and a 50-cm transverse feld of vew that can be extended to 70 cm by means of a fttng algorthm. A detaled charactersaton of the scanner can be found elsewhere [19]. The scanner s equpped wth a research package for lstmode acquston (Semens Medcal Solutons). Data processng and correcton algorthm For both phantom and patent studes, lst-mode data were taken for 10 mn. In a frst step, a summed mage usng all data was reconstructed wth an attenuaton-weghted ordered-subset expectaton maxmsaton algorthm usng four teratons and eght subsets. Attenuaton correcton based on CT data was performed as well as scatter correcton. Ths data set s called uncorrected mage n the followng. A rectangular volume of nterest (VOI) was defned manually around the leson; ths could be done usng sagttal, coronal and transversal vews. Wthn ths VOI, the crano-caudal moton of the tumour over the whole lst-mode acquston was regstered by a centre of mass (COM) approach prevously descrbed by our group [20]. The resultng curve represented the tumour poston n unts of plane numbers (0 s the most cranal plane of the acqured bed poston) over tme. By dvdng the nterval between the two maxmum end postons of the tumour poston nto n frames (n rangng from 4 to 40 for the phantom studes and n=12 for the patent studes), n frames for n dfferent tumour postons were obtaned. In the next step, the acqured events were sorted nto bns correspondng to the tumour poston. Ths resembles respratory gatng, but n our case, the real tumour poston was used as trgger sgnal and not only a tme sgnal obtaned from, for example, the pont of maxmum nspraton of the patent.

3 Eur J Nucl Med Mol Imagng (2008) 35: The sorted events were rebnned nto snograms and reconstructed wth the same algorthm as the summed mage before. Then, n each of these reconstructed mages, the COM of the tumour was estmated wthn the VOI defned before. To avod nfluence of the background actvty on the value of the COM of the tumour, only voxels whch contan actvty concentratons hgher than 60% of the maxmum concentraton wthn the selected VOI were used for ths calculaton. Before the next step, a reference frame was chosen: Ths reference frame reflected the respratory state of the patent to whch the mages were corrected. We decded arbtrarly to use the end-expraton state. All other states can be chosen as well dependng on the clncal needs. The dfference of the COM between the reference frame and all other frames was calculated. Ths resulted n n 1 3D vectors for each frame except the reference frame. Then for each frame, the actvty dstrbuton nsde the VOI was shfted accordng to ths vector, representng the measured tumour moton. The actvty dstrbuton outsde the VOI was not changed. The shft of the actvty dstrbuton was done for each drecton separately and accordng to the followng formulas: km cor k km cor k km cor k ½x; y; zš ¼ 1 x k h X kmk x ΔCOM k X ;down ; y; z ð1þ h þ x k X km x ΔCOM k X ;up ; y; z ½x; y; zš ¼ 1 x k h Y kmk x; y ΔCOM k Y;down ; z ð2þ h þ x k Y km x; y ΔCOM k Y;up ; z ½x; y; zš ¼ 1 x k h Z kmk x; y; z ΔCOM k Z;down ð3þ h þ x k Z km x; y; z ΔCOM k Z;up where Im k represents the mage matrx of the k-th frame before the correcton, whle Im k [x, y, z] s the element of ths matrx at the postons x, y and z. Im cor k s the mage matrx after the correcton. ΔCOM k ;up and ΔCOMk ;down are the values for shftng the actvty dstrbuton n frame k n drecton, rounded up and rounded down, respectvely. The factor s gven by: x k d ¼ ΔCOMk d mod 1 ; ð4þ where ΔCOM k d represents the value for shftng the actvty dstrbuton n frame k nto drecton d. Wth ths formula, shfts of the actvty dstrbuton n fractons of planes are performed equvalent to a trlnear nterpolaton. Voxels at the border of the VOI are treated as llustrated n Fg. 1. Fg. 1 Example of voxel shft n VOI: the left sde represents the uncorrected and the rght sde the corrected frame; the VOI s gven by the thck rectangle. All voxels wthn the VOI are shfted upwards by one voxel. Voxels whch are shfted out of the VOI are not taken nto account for the corrected mage (e.g. number 7). Mssng voxels at the opposte border are flled by a copy of the closest voxel outsde of the VOI (number 2). No voxel outsde of the VOI s changed After performng ths step for all frames except the reference frame, the mages for all frames were summed to end up wth one data set, n the followng called corrected mage. When the maxmum dfference of the poston of the leson n one drecton was smaller than the dmenson of one voxel,.e. 2.7 mm n transversal drectons and 3.4 mm n axal drecton, ths was consdered as nose, and hence, no correcton n ths drecton was done. A flow dagram of the whole method s shown n Fg. 2. After applyng the correcton algorthm, the lesons n the uncorrected and the corrected mage were analysed for actvty concentraton and sze of the lesons. For the latter, a threshold of 45% of the maxmum actvty concentraton of the leson was used to delneate the volume. Accordng to [21], ths threshold was found to be approprate for the typcal leson volumes and sgnal-to-nose ratos found n our patents scans. Addtonally, the mean actvty concentraton wthn the delneated volume was measured. For the patent data, nstead of actvty concentraton, standardsed uptake values normalsed to body mass were used (SUV). Moton phantom To defne the optmal number of frames for the correcton algorthm and for valdaton of the method, a phantom was bult, smulatng respratory moton n crano-caudal drecton n the presence of background actvty. The phantom conssted of a Plexglas cylnder wth a dameter of 30 cm. Insde the cylnder, a moveable holder for fllable Plexglas spheres was attached. The moton of the holder was controlled by a lnear stepper motor, whch was attached to t at the top of the cylnder. The stepper motor was controlled by a computer to smulate the respratory moton. The moton ampltude can be vared between

4 1984 Eur J Nucl Med Mol Imagng (2008) 35: Results Moton phantom Fg. 2 Flow dagram of moton correcton algorthm The maxmum detected movement n crano-caudal drecton, measured leson volume and mean actvty concentraton wthn ths volume were used as qualty factor of the correcton algorthm to fnd the optmal number of frames used to dvde the respraton cycle (n). In all measurements, frame numbers hgher than 12 showed best values, meanng that the curves of leson volume as functon of n showed mnmum values and curves of detected movement and mean actvty concentraton showed maxmum values. The curves for the measurements wth 28 mm ampltude are shown n Fg. 3. Although the nose n the curves was dfferent, the tendency was the same for all the curves: Startng from the uncorrected data, the mprovement was most pronounced usng four and sx frames. For values over 16 frames, results 0 and 30 mm wth an accuracy of 0.1 mm. For ths study, the phantom was set up wth a Plexglas sphere wth a volume of 23 ml flled wth 18 F-FDG soluton. Actvty concentratons were chosen to represent a sgnal-tobackground rato of 1:8, wth absolute concentraton n the sphere between 20 and 28 kbq/ml. Four measurements were performed wth ampltudes of 15 and 28 mm and a breathng frequency of 13 and 20 cycles per mnute for each ampltude. For each of these settngs, CT for attenuaton correcton was acqured, followed by PET acquston n lst-mode format for 10 mn. As standard of reference, a data set wthout moton was acqured. All data were transferred to a workstaton for further processng. Patents Lst-mode data were acqured for nne patents wth soltary lung lesons. All patents underwent a routne clncal 18 F-FDG protocol for oncologcal stagng or restagng ncludng a dagnostc CT or a low-dose CT. Standard protocol durng CT requres the patents to hold ther breath wthout extreme nhalaton. For three patents (patents 1, 2 and 4), lst-mode data were acqured after the clncal protocol was fnshed ( mn after njecton of MBq dependng on the weght of the patent), and for sx patents, lst-mode data were acqured before the clncal protocol ( mn after njecton of MBq). The bed poston of the PET was centred on the expected leson, and lst-mode data were acqured for 10 mn. The lst-mode data were transferred to a workstaton for further processng. All patents gave wrtten nformed consent for the PET and CT studes. Fg. 3 Measured movement n crano-caudal drecton (a), leson volume (b) and mean actvty concentraton n ths volume (c) as functon of the number of the frames (n). Phantom wth 28-mm ampltude and 20/mn frequency (sold lne) and 13/mn frequency (dotted lne)

5 Eur J Nucl Med Mol Imagng (2008) 35: Table 1 Results measured for moton phantom (23-ml hot sphere) for dfferent ampltude and frequency settngs; comparson between corrected and uncorrected data Ampltude/frequency settngs Corrected/uncorrected data Measured leson volume (ampltude/frequency) Vol uncor (ccm) Vol cor (ccm) Rel. dff. (%) 28 mm, 20/mn mm, 13/mn mm, 20/mn mm, 13/mn Maxmum (ampltude/frequency) A max uncor (kbq/ml) A max cor (kbq/ml) Rel. dff. (%) 28 mm, 20/mn mm, 13/mn mm, 20/mn mm, 13/mn Mean actvty concentraton n the segmented volume of the leson A mean uncor (kbq/ml) A mean cor (kbq/ml) Rel. dff. (%) (ampltude/frequency) 28 mm, 20/mn mm, 13/mn mm, 20/mn mm, 13/mn were suboptmal and gradually got more fluctuatng. Thus, for further analyss, n=12 was chosen as mnmal number of frames to acheve best values for leson volume and actvty concentraton. For ths number of frames, data for the acqured phantom studes were used to verfy the local moton correcton algorthm. Values for measured volume, maxmum and mean actvty concentraton before and after correcton of the data are shown n Table 1. In case of maxmum moton of 28-mm ampltude, leson volume mproved up to 50% and reached the true volume of the sphere of 23 ml wthn 3.5%, whle measured max actvty concentraton ncreased up to 14% and mean actvty concentraton up to 26%. Patent studes Sx patents had soltary lesons n the lung surrounded only by lung tssue. In two patents, the leson was attached to the posteror thorax wall, and n one patent, the leson was at the border lver lung. Vsual analyss of co-regstered PET and CT data dd not show notceable msmatch n any of the nne patents. In Table 2, the maxmum moton ampltude for each drecton, the leson volume after the correcton and the change of leson volume, maxmum and mean SUV before and after the correcton of the data are shown for each data set. Changes n mean SUV and volume are vsualsed n Fg. 4. The tumour volume was between 2.0 and 17.4 ccm (mean 10.9) before and between 1.7 and 15.6 ccm (mean 9.6) after the correcton. The maxmum change n measured leson volume was for patent 1 wth 27%. The max SUV (mean SUV) was between 5.5 and 12.4 (3.3 and 8.0) before and between 5.5 and 14.3 (3.3 and 8.7) after the correcton. The maxmum change n maxmum SUV was 15% n patent 4 and n mean SUV for patent 1, 13%. Fgure 5 shows the leson n patent 1 n a sagttal vew before and after applyng the correcton algorthm. Table 2 Results for patent examnatons Patent Nr. Δ x (mm) Δ y (mm) Δ z (mm) Vol cor (ccm) Rel. dff. vol (%) Rel. dff. SUV max (%) Rel. dff. SUV mean (%) Δ x/y/z s the maxmum ampltude n coronal (x), sagttal (y) and longtudnal (z) drectons for whch moton was corrected

6 1986 Eur J Nucl Med Mol Imagng (2008) 35: Fg. 4 Change of measured leson volume and mean SUV Dscusson Due to the long acquston tme, moton s a well-known problem n PET. Especally perodc moton, as t s caused by respraton, can nfluence the quantfcaton of PET data n areas lke thorax or upper abdomen [10]. In ths study, we focused on lung lesons, but other organs are also affected by respratory moton [20], and local moton correcton may be appled. Whle non-rgd transformatons for moton correctons [17, 18] are currently under nvestgaton by others, we present a method that mght offer advantages over such transformatons. The proposed method s based on the assumpton, that an exact quantfcaton n only a lmted area around the leson tself s needed. Ths assumpton holds true for applcatons lke RTP or therapy montorng. Secondly, the leson s assumed to be a rgd structure; hence, a lnear transformaton n the three coordnate axes s suffcent to correct for the moton. Although ths assumpton mght not be fully true, t can be consdered as correct wthn the lmts of the spatal resoluton of PET. One bg advantage of the rgd correcton s that the volume of the leson for each frame s fully mantaned. For non-rgd algorthms, there may be a problem of how the volume of a leson wll be changed due to the correcton algorthm. Another pont s Fg. 5 CT fused wth uncorrected (a) and corrected (b) PET mage that the proposed method wll also and most lkely even better work wth new more specfc tracers: frstly, because measurng the COM of a lesons may be related to the sgnalto-background rato, whch s hgher for more specfc tracers. Secondly, our method does not depend on detecton of lung lver or lung medastnum borders, as some other methods. Thus, t wll stll work wth more specfc tracers, although they may not delneate these borders as well as FDG. We have shown that wth local moton correcton, the moton artefacts nduced by perodc moton lke respraton can be reduced. Measured leson volume was reduced by up to 50% and was accurate wthn 3% n phantom studes. The value of 50% was found for a smulated moton of 28 mm, the maxmum n our phantom. For smaller ampltudes, the effect of moton s less pronounced, and hence, the mprovement of the moton correcton s less. Ths s reflected by a maxmum change of 7% for 15-mm moton ampltude. Relatve changes n mean actvty concentraton are lower than changes n leson volume, but are stll up to 26% for an ampltude of 28 mm. In patent data, we found changes of up to 27% for leson volume, whch s lower than what we measured n the phantom studes. In addton, we found that n patent studes, the mprovement by moton correcton s less dependent on the ampltude of moton of the leson. Other mportant factors are leson sze and tracer uptake. For example, n patent no. 6, who showed only leson moton of 5 mm n crano-caudal drecton; a dfference of 22% n lesons volume was found. Ths, however, needs to be nvestgated n a larger patent populaton. In RTP, the precse tumour localsaton, represented by the bologcal target volume, s essental to delver hgh dose to the malgnant tssue and keepng the dose to surroundng tssue low. Therefore, dfferences found n leson volume assessment after moton correcton may nfluence treatment plannng. Another advantage for RTP s the possblty offered by our method to correct to the partcular respratory state whch radotherapsts use for ther treatment. For example, f respratory-gated radotherapy s done n end-expraton phase, the plannng CT s acqured n ths phase as well. In the PET data, the leson s corrected to

7 Eur J Nucl Med Mol Imagng (2008) 35: the end-expraton phase by our method. As CT and PET data are acqured n the same machne, they are co-regstered and the data can be transferred to the treatment plannng system. Fnally, two PET data sets can be created (one n maxmum nspraton and the other n maxmum expraton), whch show the area over whch the tumour s movng. Snce ths represents an average of many respraton cycles, t may be superor to moton of the tumour measured by 4DCT. The latter s acqured only over one or a few breathng cycles n order to safe radaton dose, so the probablty to have representatve breathng cycles s less. We used a method of ntrnsc moton assessment based on lst-mode data [20] to delneate the respraton curve. From ths curve, the dfferent frames used by the correcton algorthm are determned. Ths assures that real tumour moton s used for the correcton, ncludng even moton whch s non-perodc, e.g. moton caused by muscle relaxaton. In prncple, also externally gated studes can be used as nput for the correcton algorthm presented here. The result wll be affected by the fact that only an ndcator such as the expanson of the thorax s measured. Advantages of the data-drven method are dscussed n [20]. Snce after correcton all measured events are ncluded n the fnal mage, sgnal-to-nose rato s not reduced compared to an uncorrected mage. Therefore, scan tme does not need to be ncreased, as t would be the case when analysng frames of gated studes. Thus, ths local moton correcton method can easly be mplemented n the clncal workflow. Although there s no addtonal acquston tme necessary, the presented method needs some addtonal processng tme and a mnmum of manual nteracton. The latter s the defnton of the VOI n the non-corrected mage. Ths can be done by the technologst performng the acquston. Then, the reconstructon of the 12 frames takes about 10 mn on a standard PC and the correcton process tself about 1 mn addtonal effort n tme. When the data-drven moton detecton s used to create the respraton curve, about 17 h are necessary for a 10-mn PET acquston and about 5 h for a 3-mn acquston, whch corresponds to routne scans n our department. All these steps besdes the frst VOI defnton can be done automatcally, for example overnght. The processng tme for the data-drven moton detecton can be reduced by the use of faster computers or parallel processng on several processors. Besdes ths longer processng tme, there are lmtatons for local moton correctons n some settngs. It wll fal n stuatons where the detecton of lesons s of prmary nterest. But the major advantage can be found wth known lesons whch are recommended to undergo PET to obtan addtonal nformaton for RTP. In patents n whch leson uptake s used for therapy montorng, quantfcaton can be hghly mproved for movng lesons. The mpact of such a correcton on local tumour control or patent outcome needs to be nvestgated n further studes. Another ssue n the context of moton correcton s the problem of an naccurate attenuaton correcton due to msalgnment between PET and CT data. The problem s that f only one CT s used, whch corresponds to another breathng cycle, PET frames whch correspond to another breathng cycle are corrected wth the approprate attenuaton map. Although beyond the scope of ths study, especally because we are not able to acqure 4DCTs wth our current hardware, t would be of nterest to nvestgate the addtonal effect of usng optmsed attenuaton maps for reconstructon of the dfferent frames (e.g. by usng 4DCT). To elmnate addtonal radaton dose, an alternatve would be to modfy the attenuaton map by an algorthm that assgns for each voxel, consdered to be wthn the tumour n the PET, the attenuaton value of soft tssue n the correspondng attenuaton map. Such an emsson-drven correcton was used by Martínez-Möller and colleagues n [22] for cardac PET/CT studes. Concluson We presented a method of local moton correcton whch mproved the accuracy of the quantfcaton of leson volume and actvty uptake, whle the mage qualty was equvalent compared to non-corrected mages wthout ncreasng the acquston tme. Hence, ths method s an optmal preprocessng step for radaton therapy plannng especally when hgh precson s requred lke n stereotactc radaton therapy. Furthermore, for therapy montorng, the accuracy n uptake quantfcaton essental for therapy decsons s mproved. Acknowledgements We acknowledge the excellent techncal assstance of Brgtte Dzewas, Helga Fernolendt, Coletta Kruschke and Anna Wnter from the PET/CT staff. The authors are grateful to Maranne Angelberger for edtoral assstance. References 1. Bradley JD, Perez CA, Dehdasht F, Segel BA. Implementng bologc target volumes n radaton treatment plannng for nonsmall-cell lung cancer. J Nucl Med 2004;45:96S 101S. 2. Baardwjk Av, Baumert BG, Bosmans G, Kroonenburgh Mv, Stroobants S, Gregore V, et al. The current status of FDG-PET n tumour volume defnton n radotherapy treatment plannng. Cancer Treat Rev 2006;32: Hoekstra CJ, Hoekstra OS, Stroobants SG, Vansteenkste J, Nuyts J, Smt EF, et al. Methods to montor response to chemotherapy n non-small-cell lung cancer wth 18 F-FDG PET. J Nucl Med 2002;43: Schwarz JD, Bader M, Jencke L, Hemmnger G, Jäncke F, Avrl N. Early predcton of response to chemotherapy n metastatc

8 1988 Eur J Nucl Med Mol Imagng (2008) 35: breast cancer usng sequental 18 F-FDG PET. J Nucl Med 2005;46: Ott K, Weber WA, Lordck F, Becker K, Busch R, Herrmann K, et al. Metabolc magng predcts response, survval, and recurrence n adenocarcnomas of the esophagogastrc juncton. J Cln Oncol 2006;24: Nestle U, Kremp S, Schaefer-Schuler A, Sebastan-Welsch C, Hellwg D, Rübe C, et al. Comparson of dfferent methods for delneaton of 18 F-FDG PET-postve tssue for target volume defnton n radotherapy of patents wth non-small cell lung cancer. J Nucl Med 2005;46: Goerres GW, Kamel E, Sefert B, Burger C, Buck A, Hany TF, et al. Accuracy of mage coregstraton of pulmonary lesons n patents wth non-small cell lung cancer usng an ntegrated PET/ CT system. J Nucl Med 2002;43: Ashamalla H, Rafla S, Parkh K, Mokhtar B, Goswam G, Kambam S, et al. The contrbuton of ntegrated PET/CT to the evolvng defnton of treatment volumes n radaton treatment plannng n lung cancer. Int J Radat Oncol Bol Phys 2005;63: Plathow C, Ley S, Fnk C, Puderbach M, Hosch W, Schmähl A, et al. Analyss of ntrathoracc tumor moblty durng whole breathng cycle by dynamc MRI. Int J Radat Oncol Bol Phys 2004;59: Nehmeh SA, Erd YE, Lng CC, Rosenzweg KE, Schoder H, Larson SM, et al. Effects of respratory gatng on quantfyng PET mages of lung cancer. J Nucl Med 2002;43: Nehmeh SA, Erd YE, Lng CC, Rosenzweg KE, Squre OD, Braban LE, et al. Effect of respratory gatng on reducng lung moton artfacts n PET magng of lung cancer. Med Phys 2002;29: Vsvks D, Barret O, Fryer TD, Lamare F, Turzo A, Bazs Y, et al. Evaluaton of respratory moton effects n comparson wth other parameters affectng PET mage qualty. IEEE Nuclear Scence Symposum; Martnez-Moller A, Zkc D, Botnar RM, Bundschuh RA, Howe W, Zegler SI, et al. Dual cardac-respratory gated PET: mplementaton and results from a feasblty study. Eur J Nucl Med Mol Imagng 2007;34: Detore NC, Kesner AL, Solberg TD, Dahlbom M. Evaluaton of mage nose n respratory gated PET. IEEE Trans Nucl Sc 2007;54: Hutton BF, Kyme AZ, Lau YH, Skerrett DW, Fulton RR. Hybrd 3-D reconstructon/regstraton algorthm for correcton of head moton n emsson tomography. IEEE Trans Nucl Sc 2002;49: Lveratos L, Stegger L, Bloomfeld PM, Schafers K, Baley DL, Camc PG. Rgd-body transformaton of lst-mode projecton data for respratory moton correcton n cardac PET. Phys Med Bol 2005;50: Schäfers KP, Dawood M, Lang N, Büther F, Schäfers M, Schober O. Moton correcton n PET/CT. Nuklearmedzn 2005;5a:S46 S Lamare F, Cresson T, Savean J, Cheze Le Rest C, Reader AJ, Vsvks D. Respratory moton correcton for PET oncology applcatons usng affne transformaton of lst mode data. Phys Med Bol 2007;52: Martnez MJ, Bercer Y, Schwager M, Zegler SI. PET/CT bograph sensaton 16: performance mprovement usng faster electroncs. Nuklearmedzn 2006;3: Bundschuh RA, Martnez-Moeller A, Essler M, Martnez MJ, Nekolla SG, Zegler SI, et al. Postacquston detecton of tumor moton n the lung and upper abdomen usng lst-mode PET data: a feasblty study. J Nucl Med 2007;48: Erd YE, Mawlaw O, Larson SM, Imbraco M, Yeung H, Fnn R, et al. Segmentaton of lung leson volume by adaptve postron emsson tomography mage thresholdng. Cancer 1997;80: Martnez-Möller A, Souvatzoglou M, Navab N, Schwager M, Nekolla SG. Artfacts from msalgned CT n cardac perfuson PET/CT studes: frequency, effects, and potental solutons. J Nucl Med 2007;48: