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.

Objective To compare the position,volume and matching index (MI) of patientspecific internal gross tumor volume (IGTV)delineated by 4 different approaches based on three- dimensional and four - dimensional CT ( 3 DCT and 4 DCT ) image for primary esophageal cancers.Methods Thirteen patients with primary esophageal cancer underwent 3DCT and 4DCT simulation scans during free breathing,and the patient were divided into group A (tumor located in the proximal thoracic esophagus) and B (tumor located in the mid-and distal thoracic esophagus).IGTV were delineated using four approaches: The gross tumor volume (GTV) contours from 10 respiratory phases were combined into IGTV10 ;IGTV2 was acquired by combining the GTV from 0％ and 50％ phases; IGTVMIP was the GTV contour delineated from the maximum intensity projection (MIP) ;IGTV3D was acquired from the enlargement of 3 DCT-based GTV by each spatial direction on the motion amplitude measured in the 4DCT.ResultsTarget movement in lateral (LR),anterio-posterior (AP),superio-inferior (SI) directions showed no statistically significant difference (0.11 cm,0.09 cm,0.18 cm,respectively; χ2 =1.06,P=0.589),and there was no statistically significant difference in centroid positions between IGTV10 and IGTV2 or IGTV3D in group A (t =-2.24,-0.00,P =0.089,- 1.000 ),MI between IGTV10 and IGTV2,IGTV10 and IGTV3D were 0.88,0.54,respectively. For group B, target movement amplitude in SI direction was bigger than in LR, AP ( 0.47 cm,0. 15cm,0. 12 cm,X2= 12.00,P = 0.002).Therewasno significantdifference betweenIGTV10 andIGTV3D inLR, AP, SI ( t =- 0.80.- 0.82,- 1.16,P = 0.450.0.438.0.285 ), MI was 0.59 ; but the target center coordinates was demonstrated significant difference in SI between IGTV10 and ICTV2 for group B ( t = 2.97.P = 0.021 ), Mlwas 0.86.Thevolume of IGTVMIPwassmaller thanIGTV10 ( t =- 2.84,P = 0.025 ), but the position of IGTv10 and ICTVMIp were with no statistically significant difference in the LR,AP,SI ( t =- 0.25,0. 84. - 1.22,P = 0. 809,0.429.0.263 ) ,MIbetweenIGTV10andIGTVMIp was 0.78.Conclusions Patient-specific IGTV can be acquired from 4DCT with correct target coverage while avoiding a geographic miss for the thoracic esophageal cancer,but IGTV2 and IGTVMIP can not contain all the information about primary tumor position,shape.and size at different phases of the respiratory cycle.

Objective To research the feasibility of using three-dimensional CT (3DCT) associated with active breathing control (ABC) in determination of the individual internal tumor volume (ITV) for hepatocellular carcinoma (HCC) comparing the four-dimensional CT (4DCT).Methods After 4DCT scans of 15 HCC patients who had accepted TACE,completed the 3DCT scans associated with ABC in three ways of breathing:free breathing ( FB),end inspiration hold ( EIH),end expiration hold (EEH).4DCT images were sorted into 10 phases and the maximum intensity projection (MIP) images were constructed.The GTVs were manually contoured on 4DCT and 3DCT images (labeled as GTV0,GTV10.….GTV90,GTVMIP,,GTVFB,GTVEIH and GTVEEH).GTV0…GTV90,GTV0 and GTV50,GTV0,GTV20 and GTV50,GTVEIH and GTVEEH were respectively merged into IGTV1,IGTV2,IGTV3,IGTV4.The volume and geometry displacement of GTVs and IGTVs were compared.Results All patients were compatible with the ABC technique and completed the CT scans in two ways.The motion of diaphragm measured between 4DCT and 3DCT images was not significantly different ( 1.39 cm and 1.39 cm,t =-0.02,P =0.983 ),it was similar to the volume difference among GTV0,GTV20,GTV50,GTVEIH,GTVEEH and GTVFB (56.4,54.6,55.5,55.6,55.2,59.7 cm3,F =0.01,P =1.000 ).The comparison result of volume difference among IGTV1,IGTV2,IGTV3,IGTV4 and GTVMIP (77.9,71.4,73.4,72.3 and 66.3 cm3,F =0.02,P =1.000)were similar to the differences of geometry displacement in x,y and z axial among them (F =0.48,0.04,0.02,P =0.750,0.997,0.999,respectively).Conclusion The application of 3DCT associated with ABC in determination of the individual IGTV for HCC is feasible and safe comparing to 4DCT.

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.

Objecttve To compare the positional and volumetric differences of planning target volumes(PTVs)based on axial three-dimensional CT(3D-CT)and four-dimensional CT(4D-CT)for the primary tumor of non-small cell lung cancer(NSCLC).Methods Sixteen NSCLC patients with lesions located in the upper lobe and 12 patients with lesions in middle and lower lobes,totally 28 patients, initially underwent three-dimensional CT scans followed by 4D-CT scans of the thorax under normal free breathing.PTVvector was defined on gross tumor volume (GTV) contoured on 3D-CT and its motion vector. The clinical target volumes(CTVs)were created by adding 7 mm to GTVs,then, internal target volume (ITVs)were produced by enlarging CTVs isotropically based on the individually measured amount of motion in the 4D-CT,lastly,PTVs were created by adding 3 mm setup margin to ITVs. PTV4D was defined on the fusion of CTVs on all phases of the 4D data.The CTV wag generated by adding7 mm to the GTV on each phase.then,PIVs were produced by fusing CTVs on 10 phases and adding 3 mm setup margin.The position of the target center,the volume of target and the degree of inclusion(DI)were compared reciprocally between the PTVvector and the PTV 4D The difference of the position,volume and degree of inclusion of the targets between PTVvecter and PTV4D were compared,and the relevance between the relative characters of the targets and the three-dimensional vector was analyzed based on the groups of the patients. Results The median of the 3 D motion vector for the lesions in the upper lobe was 2.8 mm, significantly lower than that for the lesions in the middle and lower lobe ( 7.0 mm, z = - 3. 485, P < 0. 05 ). In the upper lobe group there was only significant spatial difference between the PTVvector and PTV4D targets in the center coordinate at the x axe (z = -2. 010, P < 0. 05 ), while in the middle and lower lobes there was only significant spatial difference between the PTVvector and PTV4D targets in the center coordinates at the z axe (z = -2. 136,P <0.05). The median of ratio of PTV4D and PTVvector, of the upper lobe group was 0. 75, significantly higher than that of the middle and lower lobes group (0. 52, z = - 2. 949, P < 0. 05 ).A significant correlation was found for the motion vector and the ratio of PTV and PTV4D in both groups ( r = - 0. 638, - 0. 850, P < 0. 05 ). For all patients, the median of D[ of PTV4D in PTVvector was 66. 39% ,while the median of DI of PTVvector, in PTV4D was 99. 55% , both showed a positive significant correlation with the motion vector (r = -0. 814,0. 613 ,P < 0. 05). Conclusions PTV4D defined based on 4D-CT simulation images is obviously less than PTV defined based on 3D-CT simulation images. The ratio and DI of both targets are related with the three-dimensional motion vector of the tumor.

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 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.