What happens to brain outside the thermal ablation zones? An assessment of needle-based therapeutic ultrasound in survival swine.

BACKGROUND: In stereotactic radiosurgery, isodose lines must be considered to determine how surrounding tissue is affected. In thermal ablative therapy, such as laser interstitial thermal therapy (LITT), transcranial MR-guided focused ultrasound (tcMRgFUS), and needle-based therapeutic ultrasound (NBTU), how the surrounding area is affected has not been well studied. OBJECTIVE: We aimed to quantify the transition zone surrounding the ablation core created by magnetic resonance-guided robotically-assisted (MRgRA) delivery of NBTU using multi-slice volumetric 2-D magnetic resonance thermal imaging (MRTI) and subsequent characterization of the resultant tissue damage using histopathologic analysis. METHODS: Four swine underwent MRgRA NBTU using varying duration and wattage for treatment delivery. Serial MRI images were obtained, and the most representative were overlaid with isodose lines and compared to brain tissue acquired postmortem which underwent histopathologic analysis. These results were also compared to predicted volumes using a finite element analysis model. Contralateral brain tissue was used for control data. RESULTS: Intraoperative MRTI thermal isodose contours were characterized and comprehensively mapped to post-operative MRI images and qualitatively compared with histological tissue sections postmortem. NBTU 360° ablations induced smaller lesion volumes (33.19 mm3; 120 s, 3 W; 30.05 mm3, 180 s, 4 W) versus 180° ablations (77.20 mm3, 120 s, 3 W; 109.29 mm3; 180 s; 4 W). MRTI/MRI overlay demonstrated the lesion within the proximal isodose lines. The ablation-zone was characterized by dense macrophage infiltration and glial/neuronal loss as demonstrated by glial fibrillary acidic protein (GFAP) and neurofilament (NF) absence and avid CD163 staining. The transition-zone between lesion and normal brain demonstrated decreased macrophage infiltration and measured ∼345 microns (n - 3). We did not detect overt hemorrhages or signs of edema in the adjacent spared tissue. CONCLUSION: We successfully performed MRgRA NBTU ablation in swine and demonstrated minimal histologic changes extended past the ablation-zone. The lesion was characterized by macrophage infiltration and glial/neuronal loss which decreased through the transition-zone.

Predicting ablation zones with multislice volumetric 2-D magnetic resonance thermal imaging.

BACKGROUND: High-intensity focused ultrasound (HIFU) serves as a noninvasive stereotactic system for the ablation of brain metastases; however, treatments are limited to simple geometries and energy delivery is limited by the high acoustic attenuation of the calvarium. Minimally-invasive magnetic resonance-guided robotically-assisted (MRgRA) needle-based therapeutic ultrasound (NBTU) using multislice volumetric 2-D magnetic resonance thermal imaging (MRTI) overcomes these limitations and has potential to produce less collateral tissue damage than current methods. OBJECTIVE: To correlate multislice volumetric 2-D MRTI volumes with histologically confirmed regions of tissue damage in MRgRA NBTU. METHODS: Seven swine underwent a total of 8 frontal MRgRA NBTU lesions. MRTI ablation volumes were compared to histologic tissue damage on brain sections stained with 2,3,5-triphenyltetrazolium chloride (TTC). Bland-Altman analyses and correlation trends were used to compare MRTI and TTC ablation volumes. RESULTS: Data from the initial and third swine's ablations were excluded due to sub-optimal tissue staining. For the remaining ablations (n = 6), the limits of agreement between the MRTI and histologic volumes ranged from -0.149 cm3 to 0.252 cm3 with a mean difference of 0.052 ± 0.042 cm3 (11.1%). There was a high correlation between the MRTI and histology volumes (r2 = 0.831) with a strong linear relationship (r = 0.868). CONCLUSION: We used a volumetric MRTI technique to accurately track thermal changes during MRgRA NBTU in preparation for human trials. Improved volumetric coverage with MRTI enhanced our delivery of therapy and has far-reaching implications for focused ultrasound in the broader clinical setting.

NeuroPlan: A Surgical Planning Toolkit for an MRI-Compatible Stereotactic Neurosurgery Robot.

The adoption of robotic image-guided surgeries has enabled physicians to perform therapeutic and diagnostic procedures with less invasiveness and higher accuracy. One example is the MRI-guided stereotactic robotic-assisted surgery for conformal brain tumor ablation, where the robot is used to position and orient a thin probe to target a desired region within the brain. Requirements such as the remote center of motion and precise manipulation, impose the use of complex kinematic structures, which result in non-trivial workspaces in these robots. The lack of workspace visualization poses a challenge in selecting valid entry and target points during the surgical planning and navigation stage. In this paper, we present a surgical planning toolkit called the "NeuroPlan" for our MRI-compatible stereotactic neurosurgery robot developed as a module for 3D Slicer software. This toolkit streamlines the current surgical workflow by rendering and overlaying the robot's reachable workspace on the MRI image. It also assists with identifying the optimal entry point by segmenting the cranial burr hole volume and locating its center. We demonstrate the accuracy of the workspace rendering and burr hole parameter detection through both phantom and MR-images acquired from previously conducted animal studies.

Modeling of Interstitial Ultrasound Ablation for Continuous Applicator Rotation With MR Validation.

The primary objective of cancer intervention is the selective removal of malignant cells while conserving surrounding healthy tissues. However, the accessibility, size and shape of the cancer can make achieving appropriate margins a challenge. One minimally invasive treatment option for these clinical cases is interstitial needle based therapeutic ultrasound (NBTU). In this work, we develop a finite element model (FEM) capable of simulating continuous rotation of a directional NBTU applicator. The developed model was used to simulate the thermal deposition for different rotation trajectories. The actual thermal deposition patterns for the simulated trajectories were then evaluated using magnetic resonance thermal imaging (MRTI) in a porcine skin gelatin phantom. An MRI-compatible robot was used to control the rotation motion profile of the physical NBTU applicator to match the simulated trajectory. The model showed agreement when compared to experimental measurements with Pearson correlation coefficients greater than 0.839 when comparing temperature fields within an area of 12.6 mm radius from the ultrasound applicator. The average temperature error along a 6.3 mm radius profile from the applicator was 1.27 °C. The model was able to compute 1 s of thermal deposition by the applicator in 0.2 s on average with a 0.1 mm spatial resolution and 0.5 s time steps. The developed simulation demonstrates performance suitable for real-time control which may enable robotically-actuated closed-loop conformal tumor ablation.

Pediatric Airway Stent Designed to Facilitate Mucus Transport and Atraumatic Removal.

OBJECTIVE: The goal was to develop a pediatric airway stent for treating tracheobronchomalacia that could be used as an alternative to positive pressure ventilation. The design goals were for the stent to allow mucus flow and to resist migration inside the airways, while also enabling easy insertion and removal. METHODS: A helical stent design, together with insertion and removal tools, is presented. A mechanics model of stent compression is derived to assist in selecting stent design parameters (pitch and wire diameter) that provide the desired amount of tracheal support, while introducing the minimal amount of foreign material into the airway. Worst-case airway area reduction with stent support is investigated experimentally using a pressurized tracheal phantom matched to porcine tracheal tissue properties. The stent design is then evaluated in a porcine in vivo experiment. RESULTS: Phantom testing validated the mechanics model of stent compression. In vivo testing demonstrated that the stent was well tolerated by the animal. Since the helical design covers only a small portion of the epithelium, mucus transport through the stented region was minimally impeded. Furthermore, the screw-like stent resisted migration, while also providing for atraumatic removal through the use of an unscrewing motion during removal. CONCLUSION: The proposed stent design and tools represent a promising approach to prevent airway collapse in children with tracheobronchomalacia. SIGNIFICANCE: The proposed technology overcomes the limitations of existing airway stents and may provide an alternative to maintaining children on a ventilator.