Comparison of different registration landmarks for MRI‐CT fusion in radiotherapy for lung cancer with post‐obstructive lobar collapse

Abstract The registration of the two sets of images based on the spine and pulmonary artery landmarks and the geometric center difference of the mean displacement in the X, Y, and Z directions (X, Y, and Z represent the directions of the body from left to right, superior to inferior, and anterior to posterior) between their MRI‐CT fusions were compared, respectively. Fifty‐five lung cancer patients with post‐obstructive lobar collapse were enrolled in this study. Before radiation, two sets of simulating images according to the spine and the pulmonary artery registrations were obtained for each patient using MRI‐CT fusion. The differences of mean displacement in the X, Y, and Z directions based on spine and pulmonary artery landmarks were of −0.29, 0.25, and 0.18 cm, respectively. The mean displacements of the pulmonary artery based images in the three directions were smaller than that in the spine registration images (P < 0.05). By the method of pulmonary artery landmark, MRI‐CT has better registration accuracy and can better help confirm the target volume.


| INTRODUCTION
Lung cancer is one of the most common causes of death among all cancers. Over the past 20 years, intensity-modulated radiotherapy (IMRT) has rapidly developed as the main treatment method of lung cancer in radiation oncology. Accurate target volume delineation plays an important role in lung cancer radiotherapy. At present, the irradiation field setup and dose calculation are based on CT images, and the gross tumor volume (GTV) is contoured mostly from morphological features. 1 However, in clinical practice, CT images are deficient in identifying the tumor volume, the extent of invasion, and metastatic lymph nodes, and there is some blindness in GTV delineation, especially for central lung cancer with post-obstructive lobar collapse. Because of the decrease or disappearance of the alveolar gas content, which consolidates the CT image of the lung tissue and tumor fusion into a similar density of solid clumps, it is difficult to be distinguished from the tumor. PET-CT improves the accuracy and specificity of diagnosis and the identification between atelectasis and tumor for the differential diagnosis of lymph node metastasis. In radiation oncology, PET-CT is very helpful in target volume delineation, subsequently reducing the normal organ radiation dose while increasing the target dose and local control rate. However, because of its high cost, PET-CT is not widely used in radiotherapy in our hospital. In recent years, magnetic resonance imaging (MRI) has been are some issues that need to be resolved. First, a stable and accurate automatic image registration and fusion method is the main issue.
Second, the interpretation of the images is the ultimate goal of medical image fusion. Therefore, how to understand and use the image information should be explored. Third, there are many problems in image fusion; for example, there are uncertainties in the MRI-CT fusion when patients suffer from advanced lung cancer accompanying post-obstructive lobar collapse. We have accumulated some experience in the field of radiotherapy for dynamic contrastenhanced MRI-CT fusion of esophageal cancer. 3 Automatic registration is generally based on the spine. Because the esophagus and spine are closely adjoined, MRI-CT registration is relatively easy. In lung cancer, it is difficult to reflect the real location of the tumor if MRI and CT imaging is registered based on the spine due to respiratory movements and heartbeat, and this may result in some errors.
Image registration based on markers identified by the carina of the trachea has been reported in lung cancer. 4 However, the carina is short and small and is difficult to use for MRI-CT registration of lung cancer.
Lung cancer, which causes post-obstructive lobar collapse, is often located in the hilum. The pulmonary artery volume and its span near the bilateral hilum pulmonis are large. This paper evaluates the pulmonary artery as a MRI-CT landmark to identify lung tumors.  Table 1. All the patients' pathological results were confirmed by our hospital. They had complete imaging data, and imaging diagnosis was lung cancer with atelectasis, and the stages were III-IV. The patients' status scores were KPS ≥ 70.

2.A | Patients
A written informed consent was obtained from all patients and the protocol was approved by the ethics committee of The People's Hospital of Zhengzhou University.

2.C.1 | CT positioning
Patients were scanned on a CT simulator under calm breathing. Most patients were simulated with intravenous contrast (1.0 ml/kg, 320 mg/100 ml iodine). All patients were in the supine position and immobilized in a thermoplastic body mold. The CT scan images were transferred to a treatment planning system.

2.C.2 | Image fusion
Pretreatment MRI images were acquired from all patients to delineate the GTV. The MRI images were fused to the CT planning images.

2.C.3 | Imaging evaluation
The different geometric centers between spine and pulmonary artery registrations were compared by the mean displacement (MD) of the atelectasis area in the X, Y, and Z directions (X, Y, and Z represent the directions of left to right, superior to inferior, and anterior to posterior, respectively. Figures 1 and 2). In order to ensure the accuracy and repeatability of the coordinate delineation, all the delineations were completed by a deputy chief physician. The other two deputy chief physicians reviewed and discussed them and reached an agreement. The pulmonary arteries delineate the lower edge of the aortic arch to the lower edge of the right pulmonary artery and the right pulmonary vein.

| STATISTICAL ANALYSES
A database was created and statistics were calculated using SPSS 13.0 (SPSS, Inc., Chicago, IL, USA). The data between the two groups were analyzed using the rank sum test. The errors were calculated using the landmark registration method. According to the standard α = 0.05, P < 0.05 was statistically significant.

| RESULTS
The differences of MD in the X, Y, and Z directions between the two MRI-CT fusions (according to spine and pulmonary artery registrations, respectively) were −0.29, 0.25, and 0.18 cm, respectively.
The MD of the pulmonary artery image was less than that of the spine image (P < 0.05, Tables 2 and 3). According to the Response Evaluation Criteria in Solid Tumour (RECIST version 1.1), the shortterm clinical efficacy 4 months after radiotherapy is shown in Table 4. According to the RTOG/EORTC classification criteria for early and late radiation reactions, none of the studied patients had gastrointestinal adverse effects, radiation pneumonitis, and bone marrow arrest greater than grade 2.

| DISCUSSIONS
Medical image fusion is widely used in medical science. 5 Image registration is the basis of fusion, and its accuracy directly affects the accurate location and size of the target volume. 4,8 In this study, we considered the effect of respiratory movement and heartbeat on the location of lung tumors. We noted that it was Lung cancer, which causes atelectasis, is mainly central lung cancer, which is anatomically closer to the pulmonary artery. Based on our previous image registration experience in radiotherapy for esophageal cancer, 3 the esophageal stent is better than the spine as a registration landmark, which reduces the effects of breathing and heartbeat factors on chest tumor imaging.
In this study, we also conducted an observation on the efficacy of 52 patients who underwent multi-cycle chemotherapy (>4 cycles) and three patients who completed radiotherapy within two cycles. It was difficult to define sequential or concurrent radiotherapy and chemotherapy. In most cases, radiotherapy was used after chemotherapy failure. This study investigated the effectiveness of local radiotherapy with an objective response rate (CR + PR) of 41.8%. The objective response rate of randomized radiotherapy reported in the literature is 43%. [9][10][11][12][13] During the follow-up, these patients had no more than grade two radiation pneumonia, gastrointestinal reactions, and bone marrow suppression. This study showed that the target volume determined by pulmonary artery registry based MRI-CT can improve the reliable short-term efficacy.

| LIMITATION OF TH IS STUD Y
MRI is not a preferred modality for delineation of target volume in lung cancers since the distortion associated with MRI is quite high.
Hence, an alternate MRI protocol shall be considered for the further study. As well, MRI should be used in combination with CT. It has also been reported that diffusion-weighted MRI has the same effect as PET-CT. 14  sketches. In the future, the fusion of functional and anatomical images should be considered.

| CONCLUSIONS
The MD of the geometric center in X, Y, and Z directions in the pulmonary artery based image was less than that in the spine fusion.
Pulmonary artery MRI-CT fusion can help confirm target volumes.

This study was supported by Scientific and Technological Strategic
Project of Henan Province (152102310143).

ETHICS APPROVAL
A written informed consent was obtained from all patients and the study protocol was approved by the ethics committee of The People's Hospital of Zhengzhou University(Henan Provincial People's Hospital) Hospital.

CONF LICT OF I NTEREST
The authors declare that they have no competing interests.