Objective To investigate the impact of movement frequency on gross tumor volume (GTV) of moving tumors and coordinate position of the central point based on three-and four-dimensional CT scans.Methods The respiratory motion platform from Modus and 8 phantoms with different shapes and volumes were used to simulate the movement of lung tumors.Three-and four-dimensional CT scans were performed at movement frequencies of 10,15,and 20 times/min.GTV (GTV10,GTV15,and GTV20) and IGTV (IGTV10,IGTV15,and IGTV20) were delineated,and the coordinate position of the central point was obtained.The Friedman test was performed for GTV10,GTV15,GTV20,IGTV10,IGTV15,IGTV20,and the coordinate position of the central point.Results GTV10,GTV15,and GTV20 at the three movement frequencies were 12.41±14.26 cm3,10.38±11.18 cm3,and 12.50±15.23 cm3,respectively (P=0.687),and the positional values were-8.2±96.2 mm,-8.6±96.1 mm,and-8.6±95.7 mm in x-axis (P=0.968),108.2±25.0 mm,110.4±22.5 mm,and 109.0±24.2 mm in y-axis (P=0.028),and 65.2±13.7 mm,65.4± 13.4 mm,and 65.4± 13.2 mm in z-axis (P =0.902).IGTV10,IGTV15,and IGTV20 at the three movement frequencies were 17.78± 19.42 cm3,17.43± 19.56 cm3,and 17.44± 18.80 cm3,respectively (P=0.417),and the positional values were-7.7±95.9 mm,-7.9±95.6 mm,and-7.9±95.1 mm in x-axis (P=0.325),109.4±24.5 mm,109.6±24.1 mm,and 109.2±24.3 mm in y-axis (P=0.525),and 65.5±13.3 mm,65.6±13.4 mm,and 65.5±13.3 mm in z-axis (P=0.093).Conclusions During simulated positioning of thoracic tumors,respiratory movement frequency has no significant impact on target volume established by four-dimensional CT scan.There are no significant differences in three-dimensional target volume established at different respiratory frequencies,but respiratory frequency has a significant impact on the position of the central point of the target volume in y-axis.

Objective To explore the influence of different reconstruction modes with time?weighted respiratory phases on the internal tumor volume ( ITV) of solitary pulmonary lesion ( SPL) , and to evaluate the feasibilities of 8 and 4 equal time?weighted respiratory phases in 4DCT simulation. Methods 24 patients with SPL underwent 4D scanning. Images were reconstructed with 10, 8 and 4 equal time?weighted phases of the respiratory cycles, respectively. Gross tumor volumes ( GTVs ) were delineated on the three sets of reconstructed images and fused into ITVs, which were ITV10 , ITV8 and ITV4 respectively. The differences of volumes, centroid of the ITVs and motions of GTV centroids in three?dimensional directions were compared. Statistical analysis was performed using the Friedman M test. Results The volumes of ITV10 , ITV8 and ITV4 were (9.09±12?29) cm3,(9.10±12?47) cm3 and (8.98±12?61) cm3(P=0?001), respectively. There were no differences between the volumes of ITV10 and ITV8 after the Bonferroni correction ( P=0?721) , while the opposite between those of ITV10 and ITV4 ( P=0?002 ) . The differences of centroid positions of ITV10, ITV8 and ITV4 in x?, y?and z?axes were all less than 1 mm ((12.22±7?71),(12.23± 7?71),(12.22±7?71),Px =0?668);(43.30±29?38),(43.30±29?40),(43.31±29?39),Py =0?643;(5.66±3?67),(5.66±3?67),(5.66±3?67),Pz=0?878), similar to the motions of GTV centroids in three reconstructed modes ((0.69±0?56),(0.69±0?68),(0.79±0?51) mm,Px=0?356;(3.13±3?78),(3.13± 4?05),(3.19±4?06) mm,Py =0?978;(1.18±1?31),(1.03±1?32),(1.16±1?34) mm,Pz=0?302). Conclusions There were no differences in volumes, centroid positions and motions between ITV10 and ITV8 . The quantity of reconstruction images and GTV delineations according to 8 time?weighted phases were both less than conventional 10 phases. 8 time?weighted respiratory phases mode was feasible in 4DCT simulation for SPL.

ObjectiveTo measure the displacement of solitary pulmonary lesion (SPL) using fourdimensional CT (4DCT), and to compare the planning target volume using 4D maximum intensity projection (MIPMIP) ( PTV4DMIP ) with the empirical PTV3D.Methods Data were acquired from 24 consecutive patients with SPL. For each patient, respiration-synchronized 4DCT images and standard axial CT scans were obtained during free breathing.In lung window setting,the 4D technique was used to measure the displacement of SPL in three dimensions. We compared an PTV created using the MIP (PTV4DMIP) to the PTV created from the gross tumor volume (GTV) enlarged isotropically for each spatial direction by 1.0 cm and 1. 5 cm in the PTV3D1.0cm and PTV3D1.5cm. Results The SPL located in the lower lobe showed significant difference with the upper and middle lobe in y axis (0. 44 cm,0. 92 cm, t =2. 87, P =0. 000),but there was no difference in both x and z axis (0. 27 cm,0. 39 cm,t =1.44 ,P =0. 116 and 0. 29 cm,0. 40 cm,t =1.51, P =0. 227). SPL showed significantly greater displacement in y axis than in both x and z axis [0.60 cm and0. 31 cm (t =4.23,P=0.000) ,0.60 cm and 0.32 cm (t =4.65,P=0. 000)], but there was no significant difference between x and z axis (0. 31 cm,0. 32 cm,t =0. 33 ,P =0. 741 ). There was no statistically difference between the peripheral lung cancer and the pulmonary metastasis tumor in three directions ( x axis : 0. 37 cm,0. 32 cm, t =0. 52, P =0. 223 ; y axis : 0. 54 cm, 0. 95 cm, t =- 1.38, P =0.061;z axis:0.42 cm,0.37 cm, t=0.29, P=0.859).Both PTV3D1.0cm and PTV3D1.5cm showed significantly greater volume than PTV4DMIP(46. 73 cm3 ,86. 52 cm3 and 30. 02 cm3 ,t =- 11.35, - 12. 09,P =0. 000,0. 000). ConclusionsThe displacement of SPL in y axis is much greater than x and z axis. The empirical PTV3D is much bigger than PTV4DMIP, which suggests that 4DMIP provide adequate coverage of the moving target and minimize dose to normal tissues.

Objective To compare positional and volumetric differences of internal gross tumor volume (IGTV) delineated separately by three approaches based on four-dimensional CT (4DCT) for the primary tumor of non-small cell lung cancer (NLCLC). Methods Twenty-one patients with NLCLC underwent big bore 4DCT simulation scan of the thorax. IGTVs of the primary tumor of NSCLC were tumor on the MIP images were delineated to produce IGTVMIP. The position of the target center, the volume of target, the degree of inclusion (DI) and the matching index (MI) were compared reciprocally between IGTV10, IGTVEI+EE and IGTVMIP. Results Average differences between the position of the center of IGTVs on direction of x,y and z axes were less than 1 mm, with no statistically significant difference. The volume of IGTV10 was larger than that of IGTVEI+EE, the difference was statistically significant (t=2.37,P=0.028);the volume of IGTV10 was larger than that of IGTVMIP, but the difference was not statistically significant(t=1.95 ,P=0.065). The ratio of IGTVEI+EE with IGTV10, IGTVMIP with IGTV10 were 0.85±0.08 and 0.92±0.11, respectively. DI of IGTVEI+EE in IGTV10, IGTVMIP in IGTV10 were 84.78% ± 8. 95% and 88.47% ±9.04%. MI between IGTV10 and IGTVEI+EE, IGTV10 and IGTVMIP were 0.85 ±0.09, 0.86±0. 09, respectively. Conclusions The center displacement of the IGTVs delineated separately by the three different techniques based on 4DCT images are not obvious; IGTVEI+EE and IGTVMIP can not replace IGTV10 , however , IGTVMIP is more close to IGTV10 comparing to IGTVEI+EE . The ratio of GTVEI+EE with IGTV10 is correlated to the tumor motion vector. As the vector increases, the ratio of GTVEI+EE with IGTV10decreases, especially for small tumors.

Objective To investigate the motion characteristics of primary thoracic esophageal carcinoma with four-dimensional computed tomography(4DCT).Methods Sixteen patients with primary thoracic esophageal carcinoma received respiratory gated 4DCT imaging,mapping the GTV1-GTV10 on every patient's each subsequent CT image of 10 images in the full-respiratory phase,and measuring the displacement of each centre of GTV.These displacements and directions were analyzed on different segments of esophagus.Results The mean total lung volume and GTV volume was 2993.5 cm3,35.00 cm3 and 3362.12 cm3,34.84 cm'respectively on end-expiration and end-inspiration phases(t=12.36,P=0.000and t=-0.61,P=0.546).The total mean peak to peak displacement of GTV were 0.65 mm,0.55 mm,and 2.03 nnn in x,y-and z-axis direction,respectively(F=41.14,P=0.000).The motion in x-axis,y-axis and z-axis were 0.50 mm,0.48mm,1.23 mm in the upper segment(F=5.45,P=0.017),0.68 mm,0.62 mm,1.97 mm in the middle segment(F=27.74,P=0.000),0.72 mm,0.38 mm,3.05 mm in the lower segment,respectively(F=15.61,P=0.000).Conclusions The displacement of tumor in z axis is more notable than x-,y-axis in thoracic esophageal carcinoma.The displacement of tumor x-,y-and z-axis is different in different segment of thoracic esophageal carcinoma.

Objective To investigate the correlations of the whole breast displacement in different respiratory cycle during free breathing (FB) following breast-conserving surgery to the displacement of selected skin marker,nipple,and selected surgical clip based on four-dimensional computed tomography (4D-CT).Methods Thirteen breast cancer patients who had undergone breast-conserving surgery received whole breast intensity-modulated radiotherapy (IMRT).Respiration-synchronized 4D-CT image data were gathered during FB and were exported to the Varian Eclipse treatment planning system,and the whole breast target,nipple,superior clip,and metal marker on the skin at the anterior body midline were delineated on the CT images of ten phases of the respiratory cycle by the same radiotherapist based on the same delineating criteria.The displacement distances of the delineated target in the mediolateral (x),anteroposterior (y),and superoinferior (z) axles were achieved,and the correlations of the whole breast target displacement to the displacement of the clip,nipple,and skin marker were analyzed.The ipsilateral lung was delineated on the CT images of every phase of the respiratory cycle,and the changes in ipsilateral lung volume were analyzed during the respiratory cycle relative to the displacement of the breast.Results The maximal displacement distances of the whole breast target in the x,y,and z axles during FB were 0.71,0.76 and 1.29 mm,respectively ( F =5.755,P ＜ 0.05 ).There was no relationship between the three-dimensional (3D) displacement of the whole breast and the volume of the whole breast (r =-0.264,P ＜ 0.05 ),and there was no relationship between the displacemeat of the whole breast and the volume change of the ipsilateral lung ( r =0.346,P ＜ 0.05).There was no significant difference among the mean target displacement distances in 3 axles,and among 2 selected successive end-inspiration (EI) phases and 3 selected successive end-expiration (EE) phases.There was no significant difference between the volumes of the whole breast targets at the selected El and EE phases.There was no relationship between the displacement of the whole breast target and the displacement of the nipple,skin marker or superior clip in the cavity along the x- and z-axles.Along the y-axle,8/13,7/11 and 9/13 of the patients showed displacement of the whole breast target relative to the displacement of the nipple,skin marker and superior clip respectively.However,according to a population-based analysis,the displacement of the whole breast target was only significantly associated with the displacement of the superior clip ( r =0.657,P ＜ 0.05 ).Conclusions The clip registration is more credible and sensitive than a skin marker or the nipple for measuring and correcting the displacement of the whole breast target during radiotherapy.

Objective To compare volumetric size, conformity index (CI), degree of inclusion (DI) of internal gross target volumes (IGTV) delineated on 4D-CT-MIP and PET-CT images for primary thoracic esophageal cancer. Methods Fifteen patients with thoracic esophageal cancer sequentially underwent enhanced 3D-CT, 4D-CT and PET-CT simulation scans. IGTVMIP was obtained by contouring on 4D-CT maximum intensity projection ( MIP). The PET contours were determined with nine different threshold methods (SUV≥2?0, 2?5, 3?0, 3?5), the percentages of the SUVmax(≥20%, 25%, 30%, 35%, 40%) and manual contours. The differences in size, conformity index (CI), degree of inclusion ( DI) of different volumes were compared. Results The volume ratios ( VRs) of IGTVPET2. 5 to IGTVMIP , IGTVPET20% to IGTVMIP, IGTVPETMAN to IGTVMIP were 0?86, 0?88, 1?06, respectively, which approached closest to 1. The CIs of IGTVPET2?0,IGTVPET2.5,IGTVPET20%,IGTVPETMAN and IGTVMIP which were 0?55, 0?56, 0?56, 0?54,0?55, respectively, were significantly larger than other CIs of IGTVPET and IGTVMIP (Z= -3?408-2?215,P <0?05). There were no statistical significance in the DIs of IGTVMIP and IGTVPET2.5,IGTVMIP and IGTVPET20%, IGTVMIP and IGTVPETMAN(0?77,0?82,0?71,0?67, 0?68,0?82,P>0?05). Conclusions The targets delineated based on SUV threshold setting of≥2?5, 20% of the SUVmax and manual contours on PET images correspond better with the target delineated on maximum intensity projection of 4D-CT images than other SUV thresholding methods.

Objective To investigate the variations of the spatial position and overlap ratio of the internal target volume (ITV) and planning target volume (PTV) of primary thoracic esophagus carcinoma using repeated four-dimensional computed tomography (4D-CT) scanning during conventional fractionated radiotherapy.Methods Thirty patients with thoracic esophageal carcinoma were included whose 4D-CT scans were conducted before radiotherapy and between every ten fractions.The gross tumor volumes (GTVs) were delineated by the same radiation oncologist on each 4D-CT image phase,and the ITV and PTV were constructed afterwards.Results No significant difference of the isocenters was observed for the ITV and PTV during the treatment course,yet both the volumes of the ITV and PTV decreased.The median DI (the degree of inclusion) of the target acquired subsequently in the original target were 0.85,0.77 (Z=-3.10,P ＜0.05) for ITV and 0.86、0.82(Z =-2.49,P ＜0.05)for PTV respectively during entire treatment.The variation of volume ratio correlated strongly with the variation of DI (the DI of the target acquired subsequent in the original target) (rITV =0.71,rPTV =0.77,P ＜0.05).The variation of volume ratio and the variation of the matching index (MI) were positively correlated (rITV =0.47,rPTV =0.59,P ＜ 0.05).The 3D vectors of ITV and PTV motions were negatively correlated with the corresponding MI (rITV =--0.52,rPTV =-0.36,P ＜ 0.05).If the initial PTV was used for treatment planning,8.80％ and 6.37％ of the target volume would be missed at the tenth and twentieth fraction (Z =-0.55,P ＞ 0.05),respectively.In the meanwhile,11.45％ and 18.49％ of the normal tissues would be wrongly irradiated at the corresponding time points (Z =-2.49,P ＜ 0.05).Conclusions The variations of the spatial position of all targets were all less than 0.6 cm.The DI and the MI of the target decrease by various degrees during the treatment course,which lead to target mispositioning and normal tissue irradiation at different levels.

Objective To study the feasibility of defining the internal gross tumor volume (IGTV) of hepatocellular carcinoma applying the enhanced four-dimensional computed tomography (4DCT) images with deformable registration technology.Methods Ten HCC patients who accepted radiation therapy were selected in this study.The 4DCT in free breathing,non-enhanced 3DCT and arterial phase enhanced 3DCT in end inspiration breath holding associated with active breathing coordinator were acquired sequentially.4DCT were sorted into ten series CT images according to breath phase,and named CT00,CT10..…CT90.Gross tumor volume (GTV) were contoured on different CT series and the IGTV1 was merged by ten phases GTVs of 4DCT.The GTV of enhanced 3DCT was registered to different CT series of 4DCT and the IGTVDR was obtained by merging the GTVs after deformable registration.The target volumes differences were compared by paired t-test.Results The edge of tumor was difficult to define on 4DCT and non-enhanced 3DCT images.The enhanced 3DCT image showed clearer tumor edge,and the GTV increased by mean 37.99％ compared to GTV on 4DCT different series images and non-enhanced 3DCT image (P =0.002).The GTV after deformable registration on 4DCT different phase images increased by mean 36.34％ (P =0.011),which were similar to GTV on enhanced 3DCT image (P =0.632).The IGTVDR increased by 19.91％ (P =0.017),compared to IGTV1.Conclusions The contrast-enhanced 4DCT image which was obtained by combining enhanced 3DCT and 4DCT images with deformable registration technology could raise the position precision of the HCC IGTV effectively.

Objective To investigate the variations of the spatial position and overlap ratio for gross tumor volume (respiratory phase 50％) (GTV50) and internal gross tumor volume (IGTV) of primary thoracic esophageal cancer during conventional fractionated radiotherapy based on repeated four-dimensional computed tomography (4DCT) scans.Methods Thirty-three patients with thoracic esophageal cancer underwent contrast-enhanced 4DCT scans before radiotherapy and at the 10th and 20th fractions of radiotherapy.Scans were registered to the baseline 4DCT scan using bony landmarks.The GTV50 was delineated by the same radiotherapist on each 4DCT imaging data set,and the IGTV was constructed accordingly.The target volume,degree of inclusion (DI),and matching index (MI) were compared in different phases.Results The volumes of GTV50 and IGTV decreased along with treatment course.No significant changes in the centroid position were observed for the GTV50 and IGTV.The median DIs of the target volumes at the 10th and 20th fractions in the original target volume were 0.75 and 0.63(P =0.000) for GTV50 and were 0.79 and 0.66(P=0.000) for IGTV,while the median MIs were 0.61 and 0.56(P=0.002) for GTV50 and were 0.68 and 0.58 (P =0.005) for IGTV.A positive correlation between the variation of volume ratio and the variation of DI was found for GTV50 and IGTV (r =0.632,r =0.783),and the variation of volume ratio was also positively correlated with the variation of MI (r =0.387,r =0.483) ;the 3D vector was negatively correlated with the MI (r =-0.455,r =-0.438).Conclusions During conventional fractionated radiotherapy,the variation of spatial position is less than 0.8 cm for GTV50 and IGTV of primary thoracic esophageal cancer,and the decline of the target leads to varying degrees of decreases in DI and the MI.