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 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.

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 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.

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 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.

Objective To compare and analyze the dosimetric characteristics of the intensity-modulated arc therapy (RapidArc) combined with active breathing coordinator (ABC) in the thoracic esophageal carcinoma radiation therapy. Methods Ten thoracic esophageal carcinoma patients undergoing radiotherapy were selected for this study.The CT simulations were performed under three breath patterns respectively:moderate deep inspiration breath-hold (mDIBH) with ABC aid; Set the trigger threshold to 80％ of the peak of the respiration curve; and free breathing (FB).Based on the corresponding CT image sets,three treatment plans were generated for each patient respectively:Arc-ABC( three small arcs),ArcFB (consisted of two coplanar full arcs) and IMRT-FB plan.The following dosimetric parameters were compared among different plans:D2％,D98％,V95,homogeneity index ( HI),conformal index ( CI ) the percentage of volume receiving dose of over x Gy (Vx),monitor unit (MU),control points and treatment time.Results The planning target volume ( PTV ) of FB was 376 cm3 which decreased to 260 cm3 after using ABC.For mDIBH and FB patients,the total lung volumes were 5964.6 cm3(35％ more than FB) and 3838.8 cm3 respectively; the heart volumes were 524.4 cm3 and 642.7 cm3 respectively. No significant difference was observed among Arc-ABC,IMRT-FB and Arc-FB in terms of D2,D98,V95,CI and HI.For Arc-ABC plans,there were significant decreases of radiation dose in total-lung's V10,V20,V30,V40 and mean lung dose ( F =4.38,5.34,4.07,3.89,4.28,P ＜0.05).Various dose decreases of heart V20,V3,V40,Dmean and spinal cord Dmax were observed,yet no statistically significant difference existed.The MUs and total control points of Arc-ABC plans were significantly lower than other plans ( F =26.86,12.56,P ＜ 0.05 ).Conclusions When thoracic esophageal carcinoma patients were treated with radiotherapy,the combined utilization of RapidArc and ABC can potentially decrease the volume of irradiated lung yet escalate the dose in target.