Objective:To explore the feasibility of low-dose 4DCT scanning in simulation and target delineation for solitary pulmonary tumors (SPTs).Methods:23 patients with SPTs received 4DCT scanning simulation with the conventional scanning (CON), low voltage (LV), low current (LA) and low voltage combined with low current (LVA) in sequence. Based on the 4DCT images derived from the four sets of scanning parameters, the internal gross tumor volume (IGTV CON, IGTV V, IGTV A, IGTV VA) of SPTs were delineated and matched. Taking IGTV CON as reference, the tumor displacement and the centroid position of IGTV V, IGTV A and IGTV VA were compared with IGTV CON. The radiation doses under different scanning parameters were compared. Results:The volumes of IGTV CON, IGTV V and IGTV A were (12.26±12.30) cm 3, (12.21±12.16) cm 3 and (11.87±11.70) cm 3, respectively ( P=0.337). IGTV VA was (11.34±11.07) cm 3, significantly smaller than IGTV CON ( P=0.005). There was no significant difference in the centroid positions of IGTV CON, IGTV V, IGTV A and IGTV VA in three directions ( P=0.491, 0.360, 0.136). The Dice′s similarity coefficient (DSC VA) was significantly lower than DSC V and DSC A ( P=0.004, 0.030). The tumor displacement measured by the four sets of 4DCT images was similar in the LR direction ( P=0.470), and also in the AP direction ( P=0.108). For the displacement in the SI direction, LVA scanning was smaller than CON ( P=0.015). The radiation doses under four different scanning conditions were (397.0±140.3) mGy·cm, (175.0±61.8) mGy·cm, (264.8±95.3) mGy·cm and (116.8±41.2) mGy·cm, respectively ( P<0.001). Conclusions:LV or LA scanning exert no significant effect on the volume, centroid position of IGTV and the tumor displacement in 4DCT simulation for SPTs. The radiation dose that patients receive under LV and LV scanning is lower than that of CON. Consequently, LV or LA scanning is feasible in 4DCT simulation and target delineation for SPTs.

Objective:To measure the displacement of the solitary pulmonary lesion (SPL) located in different pulmonary segments based on 4D-CT technology (4DCT) and to establish and verify a relevant mathematical model of tumor displacement.Methods:The modeling samples of 290 SPLs were subject to both 4DCT and active breath control (ABC) spiral CT scans. The tumor displacement in different pulmonary segments was measured based on 4DCT images. The tumor volume was obtained by contouring the gross tumor volume (GTV) on ABC spiral CT images. The diaphragm movement was measured by X-ray simulator. The vital capacity and tidal volume were gained by pneumatometer. The baseline data, such as gender, age, height, weight, respiratory rate, and tumor lobe and segment where tumors were located, were collected. Multivariate linear regression was used to analyze the correlation between the 3D-tumor displacement and gender, age, height, weight, respiratory rate, tumor location, volume and diaphragm movement. The displacement model was established based on the modeling sample of 290 cases. Then, it was verified by comparing the tumor displacement derived from the model with that of 4DCT technology based on the randomly selected 17 SPLs.Results:The displacement model for tumors located in the upper lobe was established as Xup=-0.267+0.002TV+0.446DM, Yup=-1.704+0.004TV+0.725DM+2.250SII+1.349SIII and Zup=0.043+0.626DM+0.599SII+0.519SIII. The displacement model of the middle lobe tumors was Xmid=0.539+0.758DM, Ymid=-2.316+2.707DM+0.009TV and Zmid=0.717+1.112DM. The displacement model for tumors located in the lower lobe was Xlow=-0.425+0.004TV+0.857DM, Ylow=4.691+4.817DM+0.005TV-0.307RR+3.148SIX+2.655SX and Zlow=0.177+0.003TV+0.908DM.(DM: diaphragm movement, TV: tidal volume, RR: respiratory rate, SII: posterior segment, SIII: anterior segment, SIX: lateral basal segment, SX: posterior basal segment). There was no significant difference between two results derived from the displacement model and 4DCT technology.( P>0.05). Conclusions:The diaphragm movement and tidal volume are the main influencing factors of 3D lung tumor displacement. The tumor displacement in the superior-inferior direction is correlated with different pulmonary segments of the upper and lower lobes. The displacement of tumors located in different segments of middle lobes is similar. The displacement model can predict the displacement of SPLs located in different lobes, providing reference for individualized delineation of PTV.

Objective To explore the effect of pitch in three-dimensional computed tomography (3DCT)on the gross tumor volume(GTV)and spatial position of solitary pulmonary lesion(SPL), and to evaluate the feasibility of high-pitch 3DCT simulation for SPL. Methods Twenty-two patients with peripheral lung cancer or metastatic SPL were divided into groups A and B according to the tumor location. All patients underwent spiral CT scans at different pitches(pitchCON=0.938, pitchS=0.438, and pitchB=1.188)during free breathing. All GTVSwere delineated by the same radiation oncologist using the same contouring protocol. GTVCONgenerated at pitchCON, GTVSgenerated at pitches, and GTVBgenerated at pitchB were compared in terms of volume and geometric position, and GTVSand GTVBwere registered to GTVCONgained at the conventional pitch. The Friedman M and Wilcoxon rank-rum test were used for comparison. Results The volumes of GTVCON, GTVS, and GTVBwere 11.58± 16.42 cm3, 11.63± 17.73 cm3, and 12.09± 17.46 cm3, respectively(P=0.11). There were no significant differences in the centroid position in x,y,and z directions between GTVCON,GTVS,and GTVB(Px=0.33,Py=0.81, Pz=0.39). The same result was found in group B (Px=0.92,Py=0.05, Pz=0.37). The matching index(MI)between GTVSand GTVCONwas related to the tumor location,so was the MI between GTVBand GTVCON. Conclusions The pitch in 3DCT simulation has no significant effect on the GTV and spatial position of SPL. Increasing CT pitch appropriately can improve the scanning speed and shorten the duration of 3DCT simulation,so high-pitch 3DCT simulation is feasible for SPL.

Objective To investigate the feasibility of defining the radiotherapy target of primary liver cancer using four-dimensional computed tomography (4DCT) and T2-weighted magnetic resonance (MR-T2) deformable image registration.Methods Ten patients with hepatocellular carcinoma (HCC) who first received radiotherapy were included in this study.The 4DCT in free breathing and MR-T2 in deep breathing were acquired sequentially.4DCT were sorted into ten series of CT images according to the respiratory phase.MIM software was used for deformable image registration.The accuracy of deformable image registration was assessed by the maximal displacements in three-dimensional directions of the portal vein and the celiac trunk and the degree of liver overlapping (P-LIVER).Gross tumor volume (GTV) was delineated on different series of CT images and the internal GTV (IGTV) was merged by ten GTVs on 4DCT images in each phase.The MR-T2 image was deformably registered to 4DCT images in each phase to acquire ten GTVDR.The IGTVDRwas obtained by merging the ten GTVDR.The differences between different target volumes were compared by paired t-test.Results The maximal displacements in three-dimensional directions of the portal vein were 0.3±0.8 mm along the x-axis, 0.8±1.8 mm along the y-axis, and 0.5±1.5 mm along the z-axis.The maximal displacements in three-dimensional directions of the celiac trunk were 0.1±1.0 mm along the x-axis, 0.7±1.2 mm along the y-axis, and 0.6±2.0 mm along the z-axis.Overlapping degree was 115.4±13.8%.The volumes of GTVs obtained from 4DCT images in each phase after DR increased by an average of 8.18%(P<0.05), and were consistent with those delineated on MR-T2 images.The IGTV after DR increased by an average of 9.67%(P<0.05).Conclusions MRI image can show more information and have a higher contrast than CT image.MRI images should be combined with 4DCT images for delineating the GTV.It can better determine the scope and trajectory of the target and improve the delineation accuracy of HCC target.

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 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 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 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 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 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.