Transbronchial Contact Laser Ablation For Lung:a Preclinical Animal Study

Background:The advent of imaging technology and the widespread adoption of early lung cancer screening have led to a marked increase in the detection rate of ground-glass nodules(GGNs).Pulmonary Interventional Therapy(PIT)represents a non-surgical approach to diagnosis and treatment,whereby treatment instruments are introduced into the lungs via bronchoscopy.Cold and thermal ablation are commonly employed techniques for lung tissue ablation.In thermal ablation,changes in tissue temperature and heating rate determine the type of tissue changes,and thermal ablation is further classified according to tissue changes at different temperatures:coagulation damage that forms white tissue is called low power coagulation(LPC);The gasification or carbonization damage in which tissues directly form cavities is called high power ablation(HPA).The main methods available for transairway treatment of GGN are cryoablation,such as microwave and radiofrequency;However,there are still some problems in the long-term efficacy and complications of these treatments,including obvious heat sink effect,difficult to ensure the scope of ablation,and relatively long ablation time.Although the main method of thermal ablation of lung tissue through the airway is cryogenic ablation,thermal ablation in the atmospheric tract is mainly high-temperature ablation,and the different effects of high temperature and low temperature on lung tissue ablation have not been studied.The new contact laser changes the real-time output of thermal energy through the regulation of power through wavelength conversion technology,forming different types of tissue changes,which can not only produce the effect of low-temperature ablation,but also produce the effect of high-temperature ablation,and achieve the use of a single type of laser to complete various tissue treatment effects.In this study,the short-term and long-term effects of high and low temperature were compared after lung tissue ablation by using a novel semiconductor contact laser.The suitable conditions and key parameters of laser ablation of lung tissue were discussed,which provided a basic basis for clinical use.Part 1:In vitro experiments on the effect of contact laser ablation in lung tissueObjective:Explore the dose-response relationship between the key parameters of contact laser and lung tissue ablation.Methods:Equipment selection semiconductor laser treatment machine LaserPro980 and contact laser treatment head;Set the power is 5W,10W,15W,20W,the total energy is 100J,300J,600J,according to the total energy=power*time,adjust the ablation time,the parameters are(5W*20S)(5W*60S)(5W*120S)(10W*10S)(10W*30S)(10W*60S)(15W*6.7S)(15W*20S)(15W*40S)(20W*5S)(20W*15S)(20W*30S);Ablation test using 5 fresh ex vivo pig lungs with intact tracheal structure(ex vivo time not exceeding 5 h);Cut a shallow opening on the surface of the lung tissue,and extend the contact laser fiber with the knife head into the opening for intrapulmonary tissue ablation;After the ablation is completed,cut the lung tissue at the injury site along the midline of ablation,and measure the ablation diameter using a vernier caliper;Pathological section,HE staining,microscopic observation of tissue change partition.Results:Safety:All the ablation data used as planned has no damage to the optical fiber and the cutting head;Tissue changes:5W is low-power ablation,and the tissues from the cavity to the outside are:gasification area,coagulation necrosis area and normal lung tissue area;Above 10W is high-power ablation,and the tissue changes are:asification cavity area,carbonization area,coagulation necrosis area and normal lung tissue area;The ablation damage obtained by dissection is ellipsoidal and the anatomical plane is oval;The damage length diameter is significantly greater than the short diameter;Ablation damage diameter:the maximum ablation diameter is about 10 mm;The minimum effective ablation diameter is about 3 mm.Conclusion:Contact laser ablation in lung tissue has a certain safety.Adjusting the power of the contact laser can directly change the tissue effect produced by ablation:low-power produces tissue change of low-temperature ablation,that is,coagulation necrosis;High power produces tissue changes that are high temperature ablation,i.e.gasification and carbonization.The shape of the damage formed by contact laser ablation is ellipsoidal.The greater the total energy,the larger the ablation range;When the total ablation energy is the same,the thermal damage range increases with increasing power,reaches a threshold at 15W,and then decreases;With the same power,the range of thermal damage increases with time.Part 2:In vivo experiments on the effect of contact laser through airway lung tissue ablationObjective:Lung tissue ablation was performed by bronchoscopy to observe the ablation effect of laser ablation in a living environment.Methods:The equipment is used the same as the first part,and the setting parameters are(5W*60S)(10W,*30S)(20W*15S)(20W*30S);The experimental animals are 1 adult female fragrant pig about 1 year old,weighing about 45kg;Contact laser reaches lung tissue through bronchoscopy,uses CT positioning,adjusts power and time to complete ablation;Immediately evaluate the efficacy of on-site CT to observe whether there are complications;Replace the ablation site and complete the ablation according to the same method;Immediately dissect the whole lung tissue,observe the ablation,and measure the extent of injury.Send pathological sections for examination to observe the stratification of tissue damage.Results:Safety:the laser fiber and the cutter head after ablation are not damaged;During the operation,the pig had stable vital signs,that is,normal circulation such as respiration and blood flow;After the operation,Xiangxiang pig did not have complications such as pneumothorax and bleeding.CT measurement immediate damage range:(5W*60S)is 8.6mm;(10W*30S)is 11.6mm;(20W*15S)is 25.4mm;(20W*30S)is 32.1mm.Comparison of tissue damage:After low-power and high-power ablation,the tissue structure is clearly partitioned,which is consistent with ex vivo experiments.Measuring the ablation diameter,the in vivo ablation damage was significantly greater than the damage range of ex vivo experiment(P<0.05).Conclusion:Contact laser has a certain safety in the range of energy and power used in the experiment,lung tissue ablation.When the lung tissue in the body is ablated,when the total energy is the same,the damage range increases with the increase of power;When the power is constant,the damage range increases with time.Consistent with ex vivo experiments.In vivo lung tissue changes using low-power and high-power ablation,and the zoning is consistent with that of ex vivo pig lung.The scope of ablation damage in vivo is greater than that of ex vivo pig lung.Part 3:Immediate and long-term effects of different powers of laser on lung tissue ablationObjective:The immediate and long-term effects of ablation parameters of different powers after ablation of animal lung tissues were studied.Methods:The equipment use is the same as the above experiment;The short-term effect observation parameters were(5W*20S)(5W*60S)(5W*120S)(10W*10S)(10W*30S)(10W*60S)(15W*6.7S)(15W*20S)(15W*40S)(20W*5S)(20W*15S)(20W*30S);The observation parameters of long-term effects were(5W*20S)(5W*60S)(5W*120S)(10W*30S)(15W*20S)(20W*5S)(20W*15S)(20W*30S);The experimental animals used are 8 healthy adult beagles,males are about 1 year old,weighing about 11～13kg;Preoperative examination of CBC,CRP,CMP,CT images of beagles,and then anesthesia and tracheal intubation;The laser fiber with the knife head is inserted through the tracheoscopy to reach the lateral segment of the lower left lobe,and then the C-arm is used to locate the ablation;Immediately after ablation,CT examination was performed to evaluate the ablation effect;Postoperative D1,D7,D14,D28,D56 review the CBC,CRP,CT of the Beagle;After ablation in the right lung of the beagle on day 56,euthanasia was performed and lung tissue was taken to observe the extent of immediate ablation damage and the damage after 56 days.Results:A total of 8 beagles were established by ablation models,of which 7 completed the 2month feeding cycle as planned,and the other 1 died accidentally after postoperative anesthesia;Safety:After the planned ablation,the laser fiber and cutter head are not damaged;Complications:1 beagle developed 50ml of self-limited hemoptysis on the 5th postoperative day,and 2 developed pneumothorax during ablation,which gradually remission after interventions such as thoracentesis and bioglue closure.Ablation:CT measured the immediate damage range of the low power group and the range after 56 days of injury,and scar repair appeared 56 days after ablation,and there was no significant difference in scar size(P>0.05).Inflammatory conditions:On the 1st day after ablation,the CBC white blood cell count and CRP results of the beagle were significantly elevated in the low-power group and high-power group,and basically returned to normal on day 7.Conclusion:Under the planned ablation parameters,lung ablation in beagles has certain risks,and close observation is required to prevent complications.During ablation in the body,the greater the total energy,the greater the scope of damage;When the total energy is the same,the greater the power,the greater the damage range.The thermal after-effect of the low power group is more obvious than that of the high power group,and both groups can eventually form scar repair,and there is no obvious difference in scar size.The inflammation of the lower power group is mild in the higher power group.