Microwave ablation of lung tumors: A probabilistic approach for simulation-based treatment planning.

PURPOSE: Microwave ablation (MWA) is a clinically established modality for treatment of lung tumors. A challenge with existing application of MWA, however, is local tumor progression, potentially due to failure to establish an adequate treatment margin. This study presents a robust simulation-based treatment planning methodology to assist operators in comparatively assessing thermal profiles and likelihood of achieving a specified minimum margin as a function of candidate applied energy parameters. METHODS: We employed a biophysical simulation-based probabilistic treatment planning methodology to evaluate the likelihood of achieving a specified minimum margin for candidate treatment parameters (i.e., applied power and ablation duration for a given applicator position within a tumor). A set of simulations with varying tissue properties was evaluated for each considered combination of power and ablation duration, and for four different scenarios of contrast in tissue biophysical properties between tumor and normal lung. A treatment planning graph was then assembled, where distributions of achieved minimum ablation zone margins and collateral damage volumes can be assessed for candidate applied power and treatment duration combinations. For each chosen power and time combination, the operator can also visualize the histogram of ablation zone boundaries overlaid on the tumor and target volumes. We assembled treatment planning graphs for generic 1, 2, and 2.5 cm diameter spherically shaped tumors and also illustrated the impact of tissue heterogeneity on delivered treatment plans and resulting ablation histograms. Finally, we illustrated the treatment planning methodology on two example patient-specific cases of tumors with irregular shapes. RESULTS: The assembled treatment planning graphs indicate that 30 W, 6 min ablations achieve a 5-mm minimum margin across all simulated cases for 1-cm diameter spherical tumors, and 70 W, 10 min ablations achieve a 3-mm minimum margin across 90% of simulations for a 2.5-cm diameter spherical tumor. Different scenarios of tissue heterogeneity between tumor and lung tissue revealed 2 min overall difference in ablation duration, in order to reliably achieve a 4-mm minimum margin or larger each time for 2-cm diameter spherical tumor. CONCLUSIONS: An approach for simulation-based treatment planning for microwave ablation of lung tumors is illustrated to account for the impact of specific geometry of the treatment site, tissue property uncertainty, and heterogeneity between the tumor and normal lung.

Bronchoscopically delivered microwave ablation in an in vivo porcine lung model.

BACKGROUND: Percutaneous microwave ablation is clinically used for inoperable lung tumour treatment. Delivery of microwave ablation applicators to tumour sites within lung parenchyma under virtual bronchoscopy guidance may enable ablation with reduced risk of pneumothorax, providing a minimally invasive treatment of early-stage tumours, which are increasingly detected with computed tomography (CT) screening. The objective of this study was to integrate a custom microwave ablation platform, incorporating a flexible applicator, with a clinically established virtual bronchoscopy guidance system, and to assess technical feasibility for safely creating localised thermal ablations in porcine lungs in vivo. METHODS: Pre-ablation CTs of normal pigs were acquired to create a virtual model of the lungs, including airways and significant blood vessels. Virtual bronchoscopy-guided microwave ablation procedures were performed with 24-32 W power (at the applicator distal tip) delivered for 5-10 mins. A total of eight ablations were performed in three pigs. Post-treatment CT images were acquired to assess the extent of damage and ablation zones were further evaluated with viability stains and histopathologic analysis. RESULTS: The flexible microwave applicators were delivered to ablation sites within lung parenchyma 5-24 mm from the airway wall via a tunnel created under virtual bronchoscopy guidance. No pneumothorax or significant airway bleeding was observed. The ablation short axis observed on gross pathology ranged 16.5-23.5 mm and 14-26 mm on CT imaging. CONCLUSION: We have demonstrated the technical feasibility for safely delivering microwave ablation in the lung parenchyma under virtual bronchoscopic guidance in an in vivo porcine lung model.

Accounting for respiratory motion in small serial structures during radiotherapy planning: proof of concept in virtual bronchoscopy-guided lung functional avoidance radiotherapy.

Respiratory motion management techniques in radiotherapy (RT) planning are primarily focused on maintaining tumor target coverage. An inadequately addressed need is accounting for motion in dosimetric estimations in smaller serial structures. Accurate dose estimations in such structures are more sensitive to motion because respiration can cause them to move completely in or out of a high dose-gradient field. In this work, we study three motion management strategies (m1-m3) to find an accurate method to estimate the dosimetry in airways. To validate these methods, we generated a 'ground truth' digital breathing model based on a 4DCT scan from a lung stereotactic ablative radiotherapy (SAbR) patient. We simulated 225 breathing cycles with ±10% perturbations in amplitude, respiratory period, and time per respiratory phase. A high-resolution breath-hold CT (BHCT) was also acquired and used with a research virtual bronchoscopy software to autosegment 239 airways. Contours for planning target volume (PTV) and organs at risk (OARs) were defined on the maximum intensity projection of the 4DCT (CTMIP) and transferred to the average of the 10 4DCT phases (CTAVG). To design the motion management methods, the RT plan was recreated using different images and structure definitions. Methods m1 and m2 recreated the plan using the CTAVG image. In method m1, airways were deformed to the CTAVG. In m2, airways were deformed to each of the 4DCT phases, and union structures were transferred onto the CTAVG. In m3, the RT plan was recreated on each of the 10 phases, and the dose distribution from each phase was deformed to the BHCT and summed. Dose errors (mean [min, max]) in airways were: m1: 21% (0.001%, 93%); m2: 45% (0.1%, 179%); and m3: 4% (0.006%, 14%). Our work suggests that accurate dose estimation in moving small serial structures requires customized motion management techniques (like m3 in this work) rather than current clinical and investigational approaches.

A new bronchoscopic catheter for the transbronchial ablation of pulmonary nodules.

OBJECTIVES: With the objective of simultaneous bronchoscopic biopsy and ablation of malignant solitary pulmonary nodules, we have developed a flexible monopolar radiofrequency (RF) catheter that can be deployed through the working channel of most bronchoscopes. MATERIALS AND METHODS: Fresh tumor specimens were heated in a water bath to 37 °C, and the RF catheter was inserted into the tumors within the specimen. Temperature sensors were positioned 3 mm, 5 mm and 7 mm from the electrode to measure the temperature of the surrounding tissue every 1 s. The ablation was conducted by applying RF energy for 8 min. The ablated specimens were evaluated by cutting the tissue samples along the top of the device and measuring the ablation zones. RESULTS: Five ablations were performed in 3 specimens. All of the ablation zones had a major axis length (along the electrode axis) between 18.9 mm and 22.8 mm and a minor axis length (perpendicular to the major axis) between 13.3 mm and 18.0 mm. The temperature data showed that all of the temperature sensors detected 60 °C or higher. These results demonstrate that the RF catheter was capable of generating ablation zones that were locally contained in ex vivo human cancerous lung specimens and that incorporated the tumor tissues. CONCLUSION: We present the results of a benchtop study demonstrating the local control of ablation achieved using the RF device. This study suggests that the ex vivo ablation of lung malignancy with a new bronchoscopic RF catheter is feasible and that in vivo tumor ablation with this method in humans merits further study.

Virtual Bronchoscopy-Guided Treatment Planning to Map and Mitigate Radiation-Induced Airway Injury in Lung SAbR.

PURPOSE: Radiation injury to the bronchial tree is an important yet poorly understood potential side effect in lung stereotactic ablative radiation therapy (SAbR). We investigate the integration of virtual bronchoscopy in radiation therapy planning to quantify dosage to individual airways. We develop a risk model of airway collapse and develop treatment plans that reduce the risk of radiation-induced airway injury. METHODS AND MATERIALS: Pre- and post-SAbR diagnostic-quality computerized tomography (CT) scans were retrospectively collected from 26 lung cancer patients. From each scan, the bronchial tree was segmented using a virtual bronchoscopy system and registered deformably to the planning CT. Univariate and stepwise multivariate Cox regressions were performed, examining factors such as age, comorbidities, smoking pack years, airway diameter, and maximum point dosage (Dmax). Logistic regression was utilized to formulate a risk function of segmental collapse based on Dmax and diameter. The risk function was incorporated into the objective function along with clinical dosage volume constraints for planning target volume (PTV) and organs at risk (OARs). RESULTS: Univariate analysis showed that segmental diameter (P = .014) and Dmax (P = .007) were significantly correlated with airway segment collapse. Multivariate stepwise Cox regression showed that diameter (P = .015), Dmax (P < .0001), and pack/years of smoking (P = .02) were significant independent factors associated with collapse. Risk management-based plans enabled significant dosage reduction to individual airway segments while fulfilling clinical dosimetric objectives. CONCLUSION: To our knowledge, this is the first systematic investigation of functional avoidance in lung SAbR based on mapping and minimizing doses to individual bronchial segments. Our early results show that it is possible to substantially lower airway dosage. Such dosage reduction may potentially reduce the risk of radiation-induced airway injury, while satisfying clinically prescribed dosimetric objectives.

High yield of bronchoscopic transparenchymal nodule access real-time image-guided sampling in a novel model of small pulmonary nodules in canines.

BACKGROUND: Bronchoscopic transparenchymal nodule access (BTPNA) is a novel approach to accessing pulmonary nodules. This real-time, image-guided approach was evaluated for safety, accuracy, and yield in the healthy canine model. METHODS: A novel, inorganic model of subcentimeter pulmonary nodules was developed, consisting of 0.25-cc aliquots of calcium hydroxylapatite (Radiesse) implanted via transbronchial access in airways seven generations beyond the main bronchi to represent targets for evaluation of accuracy and yield. Thoracic CT scans were acquired for each subject, and from these CT scans LungPoint Virtual Bronchoscopic Navigation software provided guidance to the region of interest. Novel transparenchymal nodule access software algorithms automatically generated point-of-entry recommendations, registered CT images, and real-time fluoroscopic images and overlaid guidance onto live bronchoscopic and fluoroscopic video to achieve a vessel-free, straight-line path from a central airway through parenchymal tissue for access to peripheral lesions. RESULTS: In a nine-canine cohort, the BTPNA procedure was performed to sample 31 implanted Radiesse targets, implanted to simulate pulmonary nodules, via biopsy forceps through a specially designed sheath. The mean length of the 31 tunnels was 35 mm (20.5-50.3-mm range). Mean tunnel creation time was 16:52 min, and diagnostic yield was 90.3% (28 of 31). No significant adverse events were noted in the status of any of the canine subjects post BTPNA, with no pneumothoraces and minimal bleeding (all bleeding events < 2 mL in volume). CONCLUSIONS: These canine studies demonstrate that BTPNA has the potential to achieve the high yield of transthoracic needle aspiration with the low complication profile associated with traditional bronchoscopy. These results merit further study in humans.

Feasibility and safety of bronchoscopic transparenchymal nodule access in canines: a new real-time image-guided approach to lung lesions.

BACKGROUND: The current approaches for tissue diagnosis of a solitary pulmonary nodule are transthoracic needle aspiration, guided bronchoscopy, or surgical resection. The choice of procedure is driven by patient and radiographic factors, risks, and benefits. We describe a new approach to the diagnosis of a solitary pulmonary nodule, namely bronchoscopic transparenchymal nodule access (BTPNA). METHODS: In anesthetized dogs, fiducial markers were placed and thoracic CT images acquired. From the CT scan, the BTPNA software provided automatic point-of-entry prescribing of a bronchoscopic path (tunnel) through parenchymal tissue directly to the lesion. The preplanned procedure was uploaded to a virtual bronchoscopic navigation system. Bronchoscopic access was performed through the tunnels created. Proximity of the distal end of the tunnel sheath to the target was measured, and safety was recorded. RESULTS: In four canines, 13 tunnels were created. The average length of the tunnels was 32.3 mm (range, 24.7-46.7 mm). The average proximity measure was 5.7 mm (range, 0.1-12.9 mm). The distance from the pleura to the nearest point within the target was 7.4 mm (range, 0.1-15 mm). Estimated blood loss was <2 mL per case. There were no pneumothoraces. CONCLUSIONS: We describe a new approach to accessing lesions in the lung parenchyma. BTPNA allows bronchoscopic creation of a direct path with a sheath placed in proximity to the target, creating the potential to deliver biopsy tools within a lesion to acquire tissue. The technology appears safe. Further experiments are needed to assess the diagnostic yield of this procedure in animals and, if promising, to assess this technology in humans.