Application And Research Of Image Registration Based On Four-dimensional Cone Beam CT And Three-dimensional Cone Beam CT In Stereotactic Ablation Radiotherapy Of Lung Cancer

Background and ObjectivesRadiotherapy is an important method for the treatment of lung cancer.In the late 21st century,with the combination of computer automatic control technology and radiotherapy technology,three-dimensionalconformal radiotherapy(3DCRT),intensity modulated radiotherapy(IMRT)volumetric modulated arc therapy(VMAT),stereotactic radiosurgery(SRS),stereoscopic ablation radiotherapy(SABR)and other new radiotherapy techniques are widely used in clinical treatment.Stereotactic ablation radiotherapy,also known as stereotactic body radiation therapy(SBRT)has achieved good results in early inoperable or unwilling non-small cell lung cancer(NSCLC)and lung oligometastatic lung cancer.SABR has the characteristics of single high-dose radiotherapy,less radiotherapy times,high conformability of the target area,rapid drop of external radiation dose of the target area,and the lowest radiation dose of surrounding normal tissues and organs,so it is more and more used in radiotherapy of small lesions with limited location(lung cancer,liver cancer,pancreatic cancer,etc).Image-guided radiotherapy(IGRT)combines the linear accelerator with the imaging system to correct the errors caused by tumor and organ movement during and within the fractionation of radiotherapy.The application of SABR and image-guided radiotherapy can improve the high precision,high dose,high curative effect and minimal injury in radiotherapy.However,the location of chest tumor may change due to involuntary movements such as respiratory movement and cardiac movement,resulting in geometric and dosimetry uncertainty of dose transfer in the target area.In the current clinical treatment of SABR,patients receive image-guided radiotherapy before each treatment,and most tumor centers use three-dimensional cone beam CT(3D-CBCT)to calibrate the location of the target,which can only provide static images and can not well reflect the changes of respiratory movement of tumors and visceral organs.In order to solve the influence of respiratory movement on tumor trajectory and dose delivery during radiotherapy.Time factor was included on the basis of respiratory gating technique and 3D-CBCT.4D-CBCT is a three-dimensional dynamic sequence image formed by reconstructing the projected image data.Depending on the patient’s respiratory signal,which can monitor the tumor trajectory in 10 respiratory phases in real time.4D-CBCT can understand the law of tumor movement,ensure that the treatment of the tumor during respiratory movement is more accurate and reduce radiation dose of endangering organs.With the development of 4D-CBCT for more than ten years,a large number of clinical studies are devoted to the progress of new 4D-CBCT technology.4D-CBCT is gradually studied and popularized in radiotherapy image registration,tumor trajectory,target delineation and so on.But the application of 4D-CBCT technology in clinical radiotherapy still faces many problems.In our study,we compare and analyze the 3D-CBCT and 4D-CBCT image registration and the positioning errors of CBCT images in X axis.Y axis and Z axis directions before each radiotherapy.The purpose of this study is to provide a basis for application of 4D-CBCT in SABR image guided radiotherapy and the verification of adaptive radiotherapy for lung cancer.Materials and MethodsFrom April 2019 to January 2020,23 patients(25 tumors)with early inoperable or unwilling non-small cell lung cancer(N=7,stage Ⅰ or Ⅱ)or pulmonary oligometastatic carcinoma(N=16,primary focus controlled,≤3 pulmonary metastases)were treated with SABR in the Department of radiotherapy,Henan Cancer Hospital.23 patients underwent 4D CT simulation localization on the CT simulator(Phillip Brilliance TM Big Bore CT)in our department.The patients were first scanned by 3D CT in the state of free breathing,scanning of the chest to the bottom of the lung.Then the patient is still breathe freely,according to the RPM system to record the respiratory cycle.Waiting for the patient’s respiratory waveform to be stable,then 4D CT scanning range is similar to above.The images obtained by 4D CT were reconstructed and transferred to the Eclipse treatment system.PTV was delineated in 4D CT on the basis of ITV:the head and foot,ventral dorsum,and left and right directions was evenly expanded 5mm.The tumor target was delineated according to the RTOG1106 standard.After the radiotherapy plan was done,CBCT images were scanned in the XVI Symmetry respiratory management system of Infinity linear accelerator.3D-CBCT images were scanned before each SABR treatment,and Clipbox registration was made in the XVI system.Then 4D-CBCT images were scanned and 4D gray scale translation registration of the Mask was carried out.3D-CBCT images and 4D-CBCT images were registered with 4D CT images respectively,and then manual registration was performed after automatic registration.The displacement data of 3D-CBCT and 4D-CBCT registration images in LR,SI,AP direction were recorded before each radiotherapy.A total of 160 sets of 3D-CBCT and 4D-CBCT image registration direction displacement data at left and right(left-right,LR/X),head and foot(superior-inferior,SI/Y),anterior and posterior(anterior-posterior,AP/Z)were obtained.Results1.The registration errors of 3D-CBCT and 4D-CBCT in X axis,Y axis and Z axis are-0.03±0.68cm and-0.10±0.62cm,-0.05±0.23cm and-0.12±0.39 cm,-0.06±0.41cm and 0.09±0.31cm respectively.There was significant difference in registration error between 3D-CBCT and 4D-CBCT registration images in Z axis direction(P<0.05),but no significant difference in the X axis and Y axis direction(P>0.05).The difference of setting error of 4D-CBCT is smaller than that of 3D-CBCT.2.Statistical results of 3D-CBCT and 4D-CBCT registration errors of tumors in upper lobe group(n=13)and middle and lower lobe group(n=12):there was significant difference in Z axis orientation error between upper lobe group and middle and lower lobe group in 3D-CBCT image registration(P=0.005<0.05),but there was no significant difference in X axis and Y axis orientation error between upper lobe group and middle and lower lobe group.There was significant difference in the positioning error between the upper lobe group and the middle and lower lobe group in Y axis and Z axis direction(P=0.048,0.215,all P<0.05),but there was no significant difference in X axis positioning error between the upper lobe group and the middle and lower lobe group under the guidance of 4D-CBCT images.However,4D-CBCT can significantly reduce the absolute value of positioning error in all directions in the upper lobe group and the middle and lower lobe group,and the positioning error in the upper lobe group is smaller than that in the lower lobe group.4D-CBCT technique can be used in radiotherapy for tumors in the middle and lower lobe group.3.Comparison of positioning error data between left lung(n=9)and right lung(n=16)in two kinds of image-guided radiotherapy:there was significant difference in 3D-CBCT positioning error in Y axis direction(P=0.004<0.05),but there was no significant difference in X axis and Z axis direction(P=0.429,0.064,all P>0.05)In 4D-CBCT reconstruction image registration,there was no significant difference in positioning error among X axis,Y axis and Z axis(P=0.649,0.414,0.054,all P>0.05).There was no difference in radiotherapy for different lung tumors by 4D-CBCT technique.4.The positioning error data of patients with radiotherapy dose 50Gy/5 times(n=11)and radiotherapy dose times 60Gy/8 times(n=9)in two kinds of registration images:the difference of positioning error in Y axis and Z axis direction of 3D-CBCT image registration was statistically significant(P=0.027,0,all P<0.05),but there was no significant difference in X axis direction(P=0.545>0.05).In the result of 4D-CBCT image registration,there was statistical significance in the direction of Z axis(P=0<0.05).There was no significant difference in the positioning error of X axis and Y axis(P=0.496,0.177,all P>0.05)。4D-CBCT technique can reduce the difference caused by different times of radiotherapy.5.The absolute values of registration errors of 3D-CBCT and 4D-CBCT registration images in X axis,Y axis and Z axis are 0.49 ±0.47cm and 0.15 ±0.16 cm(P<0.001),0.46 ±0.41cm and 0.29±0.27 cm(P<0.001),0.33 ±0.23cm and 0.24±0.21 cm(P<0.001).There are significant differences in absolute values of positioning errors between 4D-CBCT and 3D-CBCT image registration in X axis,Y axis and Z axis.4D-CBCT has more advantages than 3D-CBCT image registration.The absolute value of 3D-CBCT positioning error in X axis is the largest,followed by that in Y axis direction,and the absolute value in Z axis direction is the smallest.The absolute value of the positioning error of 4D-CBCT is the largest in the Y axis direction,followed by the absolute value of the Z axis direction,and the maximum absolute value of the X axis direction.6.The setting boundaries of manual registration in different registration modes of 3D-CBCT and 4D-CBCT are calculated by using the formula 2.5 Σ+0.7σ.3D-CBCT image matching time:the positioning boundary of lung cancer on X axis,Y axis and Z axis in upper lobe group was 5.0mm,3.0mm and 2.1mm,respectively,and that in middle and lower lobe group was 7.4mm,7.1mm and 2mm in X axis,Y axis and Z axis respectively,and that in left lobe group was 8.0mm in X axis,3.1mm in Y axis and 3mm in Z axis,and that in left lobe group was 3.1mm in X axis,3.1mm in Y axis and 3.1mm in Z axis,and that in left lobe group was 3.1mm in X axis,3.1mm in Y axis and 3mm in Z axis.In the right lobe group,the boundary of X axis,Y axis and Z axis was 8mm,6.4mm and 0.5mm,respectively.4D-CBCT image matching time:the positioning boundary of lung cancer on the X axis,Y axis and Z axis:in upper lobe group was 1.5mm,0.3mm and 3.3mm,respectively,in the middle and lower lobe group was 2.0mm,4.5mm and 4.3mm respectively.In left lobe group were 1.7mm 3.7mm and 3.1mm.In the right lobe group were 2.2mm,3.1mm and 0.6mm,respectively.There was no significant difference between the upper lobe and the middle lobe of the lung,the left lung and the right lung in the X axis,Y axis and Z axis boundaries in 3D-CBCT and 4D-CBCT image registration.4D-CBCT technology ensures that the tumor trajectory during radiotherapy is within the range of PTV,which meets the radiotherapy requirements of SABR.ConclusionsWe compared 160 groups of 4D-CBCT and 3D-CBCT registration images in X axis,Y axis and Z axis of the positioning errors and absolute values.1.4D-CBCT may have an advantage over 3D-CBCT in the treatment of SABR in patients with lung cancer.Because it reduces the positioning error of patients during radiotherapy,and reduces the positioning error within and between fractions of radiotherapy.Complying with the requirements of radiotherapy of SABR.2.It is suggested that 4D-CBCT technique should be selected for pre-radiotherapy verification during SABR in patients with middle and lower lobe tumors of the lung.4D-CBCT image verification can be properly selected when the tumor is located in the left or right lung or the number of radiotherapy is 5 or 8 times,and for the older age patients and irregular respiratory movement.When tumor target area near the transverse septum,mediastinum,chest wall a-nd so on,it is preferable to use 4D-CBCT technology for image registration to reduce respiratory movement artifacts.3.4D-CBCT images reduce the external expansion boundary of the target volume in all directions of the tumor.It can ensure that the range of movement of the tumor on ITV in all directions is within the range of PTV during radiotherapy.Meeting the requirements of SABR radiotherapy,to decrease the dose drop outside the target area and to decrease the side effects of radiotherapy.