Diagnosis Of Peripheral Pulmonary Lesions Using Virtual Bronchoscopic Navigation Combined With Endobronchial Ultrasonography

BackgroundWith the continuous development of economy and society, people’s health awareness was gradually improved. Together with the rapid advancement of medical imaging equipment and technology, the detection rate of pulmonary lesions (some did not lead to obvious symptoms) was significantly increased. And the detection rate of solitary pulmonary nodules (SPNs) was about 8%-51% in clinical practice. However, malignant tumor (especially early lung cancers) accounted for about 10%-68% in SPNs. According to the report, the overall 5-year survival rate of lung cancer patients was only about 15.6%, while 5-year survival rate could be as high as 80% in patients with lung cancer under early postoperative period. Therefore, early diagnosis and early treatment of pulmonary lesions were a hot issue that clinicians often faced.Most of the solitary pulmonary lesions appeared in the peripheral position of the lung. As an important mean to obtain diagnosis of peripheral pulmonary lesions (PPLs), conventional transbronchial lung biopsy (TBLB) was economical, practical, and with fewer complications, but its diagnosis rate was low In order to improve the diagnostic yield of TBLB, radial probe of endobronchial ultrasound (RP-EBUS) was used to locate the PPLs to help conduct TBLB. According to the clinical practice, compared to the traditional TBLB with non-assisted positioning, EBUS-TBLB could greatly improve the positive rate of diagnosing PPLs. However, as the flexible bronchoscope was being inserted from the central airway to the peripheral bronchi, more and more bronchial openings were appearing. In addition, the bronchoscopists1 level about positioning lesions through CT axial slices was not equivalent. It was not easy to select the correct path which could directly guide the probe into the peripheral lesion site to scanning. Bronchoscopists usually needed to use the probe to explore more peripheral bronchi to located the lesion in actual operation. Therefore, on the one hand, the inspection time and patients’discomfort increased, the ultrasonic probe’s life was also shortened because of multiple examination; on the other hand, about 8%-20.8% of the PPLs could not be found due to foiling to get into the right bronchus. Since the small ultrasound probe itself could not navigate a bronchoscope to insert, theoretically, combining with navigation tools could not only help guide EBUS into the target bronchus to detect lesions, but also shorten the inspection time and decrease the patients’discomfort. There were two kinds of navigation tools used in clinical practice currently, one was electromagnetic navigation bronchoscopy (ENB), and the other one was virtual bronchoscopic navigation (VBN). ENB could preciously navigate an operating catheter even into a peripheral lung bronchus with diameter about 2mm to help conduct lung biopsies in real-time guidance. The lesions’detection rate and diagnostic rate could be improved by using EBUS combined with ENB. However, the complexity of the operation, high cost of inspection and price of the equipment limited its clinical application However, compared to ENB, VBN system was simple and inexpensive, bronchoscopists with basic skills could easily operate the system. Many foreign reports had confirmed that VBN could shorten the EBUS scanning time the X-ray exposure time, even improve the diagnostic yield of small peripheral lung nodules combined with endobronchial ultrasonography with a guide sheath. However, VBN combined with EBUS to diagnose peripheral lung lesions was rarely reported in the domestic. We wanted to explore the prospect of VBN application in the country.ObjectiveThis study aimed to explore the guiding ability of a new system of VBN-Directpath and assess the diagnostic value in PPLs by using VBN combined with RP-EBUS.Part 1 Explore the ability of reconstructing and guiding of DirectPath based on different slice thickness computed tomography images1.1 Subjects and Methods1.1.1 Subjects:Inclusion criteria:Eligible patients were adults(≧18year), whose chest computed tomography (CT) revealed SPNs which were defined as lesions (diameter≤30mm) encircled by the normal lung parenchyma. Exclusion criteria contained the evidence of serious structural lung diseases (such as severe emphysema, severe bronchiectasis, et al) showed by chest CT. SPNs located in right B1 or right B6 or right B10 of the lung were excluded. Patients who had a history of lung surgery or did not acquire suitable chest CT images were also excluded.The ethics committee of medical research had approved the study protocol. And all the subjects including the outpatient and the inpatient signed the informed consent. Part one of the study was conducted in Guangdong General Hospital between lth November 2013 and 1th April 2014.1.1.2 Methods:Sixty patients with SPNs discovered by chest CT scan were selected. Computed tomography of the chest was performed by 8-row or 64-row multidetector. CT images of thirty patients in 8-row multidetector group were recorded to 1.25 mm slices. And thirty patients in 64-row multidetector group were recorded to 1.25 mm and 0.625mm slices respectively. All CT data sets were transferred from CDs into the software-DirectPath which could automatically reconstruct the three-dimensional bronchial tree and simulate the virtual endoscopic images of the target bronchus. Data of bronchus generation and minimum diameter of right B1a、right B6a、right B10a of each patients in different slice thickness were collected.1.1.3 Statistical analysis:Measurement data was assessed for normality in distribution and description as means+standard deviation (x±s) was used, for data of skewed distribution, description as median (range) was used. We used the independent-samples t-test or non-parametric test to analyze the difference between two groups or two levels. All p values were two-sided and Ap value< 0.05 indicated statistical significance. All data was analyzed using IBM SPSS,version 13.0.1.2 ResultsThree-dimensional bronchial trees and virtual bronchoscopic images were successfully reconstructed in all subjects. And the median time for reconstructing a three-dimensional bronchial tree was no more than five minutes. In slice thickness of 1.25mm,64-row multidetector group were reconstructed better in three-dimensional bronchial tree than 8-row multidetector group (P=0.004), especially in further bronchus generation of right Bla and right B6a. In 64-row multidetector group, 0.625mm slices were reconstructed with further bronchus generation and smaller diameter bronchi in right B1a、right B6a、right B10a than those in 1.25mm slices. But there was no statistic differences in the three-dimensional bronchial tree reconstruction between these two slice thicknesses (P=0.083). There was also no statistic differences in bronchus generation and minimum diameter among right Bla, right B6a and right B 10a in 60 patients of 1.25mm slices. The proportion of more than sixth generation(including sixth) bronchi reconstructed by the software among the three bronchi above was 66.7%,60.0% and 65.0% respectively, but 90.0%,90.0% and 88.3% in 0.625mm slices in 64-row multidetector CT group.1.3 Conclusions1. Directpath could directly reconstruct a three-dimensional bronchial tree by using chest CT data and its rebuilding process was simple and fast.2. DirectPath could acquire a better reconstructed results based on 0.625mm thickness slice images of 64-row multidetector CT. It had the ability to guide a conventional bronchoscope or an ultrathin bronchoscope to the peripheral target bronchus.3. Whether virtual endoscopic images and actual endoscopic images were consistent or VBN could help improve the diagnostic yield of TBLB in PPLs, warranted further study.Part 2 Diagnosis of peripheral pulmonary lesions using virtual bronchoscopic navigation combined with endobronchial ultrasonography2.1 Subjects and Methods2.1.1 SubjectsInclusion criteria:Eligible patients were adults(≥18year), whose chest computed tomography revealed peripheral pulmonary lesions(PPLs) which were not diagnosed pathologically. PPLs were defined as that surrounded by normal lung parenchyma and located below the segmental bronchus. The study protocol was approved by the ethics committee and all patients signed the informed consent before their examination.Exclusion criteria contained the evidence of endobronchial diseases (including bronchial mucosal changes) discovered directly by the conventional video-bronchoscopy. Any conditions as we are known that were not indicated for bronchoscopy or endobronchial ultrasonography or lung biopsy. Ground-glass opacities showed by chest CT were also excluded.The prospective non-randomized clinical trial was conducted in the department of Respiratory Medicine, Lung or Thoracic Surgery in Guangdong General Hospital between 1th November 2013 and 31th January 2015.2.1.2 MethodsSubjects were enrolled into VBN assisted group and non-VBN assisted group. All subjects accepted the flexible video-bronchoscopy and radial endobronchial ultrasonography. In the two groups, bronchoscopy preparation, bronchoscopic taking photos of the endobronchial images before EBUS scanning, electrocardiographic monitoring and blood pressure, blood oxygen monitoring during the bronchoscopy, all the procedures above, were same with conventional bronchoscopy process.Bronchoscopic insertion was guided with VBN support in VBN assisted group. While the bronchoscope was introduced with the reference only to chest computed tomography axial images in non-VBN assisted group. For the two groups, when the inserting was arrived at the target bronchus, lesions were scanned by inserting a 20 MHz radial EBUS probe through an endoscopic channel. The probe was withdrawn as soon as the lesion was well visualized. Then, pathological samples were collected using forceps and brush introduced through the endoscopic channel. The target bronchus was washed with saline determined by the bronchoscopists as a supplement when necessary. If the bronchoscopists were not satisfied with the ultrasound image of one lesion, they were allowed to select another path to insert the probe to giving a scan again and chose the site showing the better ultrasound image as the sampling site. All sampling was conducted without using x-ray. If the lesion was not visualized by EBUS finally, we recommended patients consider undergoing other diagnostic methods, such as CT-guided percutaneous lung biopsy, surgical intervention or clinical follow-up.Whether virtual images were consistent with the actual images in VBN group should be analyzed. The positioning time by EBUS for a lesion and the total operating time, bronchial generation inserted by bronchoscopes in the two groups were recorded. Sampling by biopsy and significant complications during the operation would be also recorded. Final diagnoses were established according to comprehensive analysis of pathological evidence, microbiologic results and clinical follow-up.2.1.3 Statistical analysis Continuous variables were assessed for normality in distribution and description as medians was used, we used χ2-test and Mann-Whitney U test to analyze the diagnostic yield and to compare means between two groups. All p values were two-sided, A p value< 0.05 indicated statistical significance. All data was analyzed using IBM SPSS,version 13.0.2.2 ResultsThe preliminary screening result contained 227 patients in the study, and 52 of them were excluded since endobronchial diseases (including bronchial mucosal changes)were discovered directly by the conventional video-bronchoscopy. The remaining 175 cases accepted conventional video-bronchoscopy and endobronchial ultrasonography. One case was not acquired the final diagnosis in VBN group and non-VBN group, respectively, undergoing follow-up. A total of 173 cases with definite diagnoses were included in the final analysis, Including 64 cases in VBN group,109 cases in non-VBN group. Pathological diagnoses were established by EBUS-TBLB in 106 cases, and the remaining 67 cases were diagnosed by other ways, containing 31 cases by CT-guided percutaneous lung biopsy,22 cases by surgical diagnosis,14 cases by clinical follow-up. The final diagnosis established was 102 cases of cancers and 71 of benign lesions. The overall visualization yield was 85.5%(148/173) by EBUS. And the EBUS visualization yield in VBN group was not significantly different with that in non-VBN group (90.6%(58/64) vs 82.6%(90/109), P=0.146). The overall diagnostic yield was 61.3%(106/173) by EBUS-TBLB. Malignant lesions had a higher diagnostic yield(67.6%(69/102))than benign lesions (52.1%(37/71), P=0.039); Lesions in diameter>30mm had a higher diagnostic yield than lesions in diameter<30mm (70.9%(56/79) vs 53.2%(50/94), P=0.017); The EBUS probe within the lesion had a higher diagnostic yield than it adjacent to the lesion (82.0%(91/111) vs 40.5%(15/37), P<0.001). The diagnostic yield of EBUS-TBLB in VBN group was not significantly higher than that in non-VBN group(64.1%(41/64) vs 59.6%(65/109), P=0.564). The EBUS examination time for positioning lesions in VBN group was less than that in non-VBN group(3.5(2.9-6.1)min vs 4.1(3.0-6.5)min, P<0.001). But the total operating time was not significantly different between the two groups(24.0(19.5-36.5)min vs 24.7(16.0-55.2)min, P=0.330).The consistency between virtual endoscopic images and the actual images was 87.5%(56/64) in VBN group, and conventional bronchoscope could be guided into the fourth to sixth bronchial generation generally by VBN. There were two complications in the non-VBN group(one case with mild pneumothorax(<20%) not requiring drainage, one case with lung hemorrhage), and one case with lung hemorrhage in VBN group. All pulmonary hemorrhage was cured after conducting endoscopic hemo stasis. No severe adverse complications were observed in the two groups.2.3 Conclusions1. Virtual bronchoscopic images and actual images were highly consistenct, and VBN could guide the conventional bronchoscope exactly into the fourth to sixth bronchial generation.2. VBN could help reduce the EBUS examination time of positioning lesions.3. Malignancy lesions, lesions in diameter>30mm and probe located within the lesion were the factors that promote a significantly higher diagnostic yield of EBUS-TBLB, respectively. Clinicians should review these factors to select patients to conduct EBUS-TBLB to diagnose PPLs.4. VBN did not improve the diagnostic yield of EBUS-TBLB in the conventional bronchoscopy.5. VBN was a safe navigation tool without increasing the incidence of complications during the EBUS-TBLB.Summary on the full text1. Directpath could directly reconstruct a three-dimensional bronchial tree by using chest CT data and its rebuilding process was simple and fast. 2. DirectPath could acquire a better reconstructed results based on 0.625mm thickness slice images of 64-row multidetector CT. It had the ability to guide a conventional bronchoscope or an ultrathin bronchoscope to the peripheral target bronchus.3. Virtual bronchoscopic images and actual images were highly consistent, and VBN could guide the conventional bronchoscope exactly into the fourth to sixth bronchial generation.4. VBN could help reduce the EBUS examination time of positioning lesions.5. Malignancy lesions, lesions in diameter>30mm and probe located within the lesion were the factors that promote a significantly higher diagnostic yield of EBUS-TBLB, respectively. Clinicians should review these factors to select patients to conduct EBUS-TBLB to diagnose PPLs.6. VBN did not improve the diagnostic yield of EBUS-TBLB in the conventional bronchoscopy.7. VBN was a safe navigation tool without increasing the incidence of complications during the EBUS-TBLB.