PURPOSE: Advanced Image processing and options in Bronchoscopic Image-guided Interventions (BIGI) may improve diagnostic yield of peripheral lung lesions, and lead to future developments of novel in-situ therapeutics for thoracic malignancies. Currently there’ s no adequate large animal model with reliable lung lesions usable as model for creating bronchoscopic navigation or training for sampling peripheral “tumors”. We present work of Transbronchoscopic delivery of Radioopaque Hydrogels as potential targets.
METHODS: Animal IRB protocol: porcine subjects are intubated, anesthesized and monitored per protocol. Bronchoscopy with 5.0mm bronchoscope performed in Fluoro-CT(Philips FD-20) suite. To create stable non-migrating psuedo-tumor targets, Alginate biomaterial (PRONOVA UP MVM,FMC Biopolymers,Haugesund, Norway) is polymerized with 100mM CaCl. To provide radioopacity for image-guided biopsies, a variety of compounds (Iohexol, barium, tantulum)and concentartions were tested to optimize radiodensities seen radiologically. To confirm subsequent biopsies of targets, .01%w/v methylene blue was added as colorimetric marker. To deliver targets peripherally, a coaxial catheter system of 4-French inner-catheter for alginate-markers(Infinity(tm),Cordis Corporation, Miami,Florida) and 5-French outer catheter for CaCl (Envoy,Cordis, Miami,Florida) is extended peripherally under fluoroscopic guidance. 1.5ml-2.5ml mixture is injected to simulate 1-2 cm lesion. Animals are imaged in a Toshiba 320-slice-MDCT for assessment of target deposition and target density characteristics.
RESULTS: Optimum “lesions” were created using 2%w/v-Alginate mixed with 1/2-strength Iohexol(diluted 1:1 NS) and 2%w/v-Alginate in NS with 0.25mg/ml Tantulum powder. Higher concentrations of tantulum results in metallic artifacts. Iohexol-alginate mixture has an initial softer outline that better simulate “typical” parenchymal nodules, but Iohexol leaches out over 4-6 hours and the formed hydrogel will progressively lose fluoroscopic radioopacity. Methylene blue plus tantulum provide good colorimetric confirmation of follow-up transbronchoscopic forcep-biopsies. Complications include inadvertent catheter induced lung trauma including pneumothoraces.
CONCLUSION: Transbronchoscopic delivery of Radioopaque Hydrogels using a catheter system effectively create simulated lung tumors that are usable for development of bronchoscopy enhancement software, and as targets for pre-clinical animal lab practice.
CLINICAL IMPLICATIONS: Beyond usable as pseudo-targets for bronchoscopic image-guidance training, in future, alginate-based hydrogels may incorporate novel agents for tumor-targeted high-dose local-therapies.
DISCLOSURE: Rex Yung, Grant monies (from industry related sources) Philips Imaging USA - funding study of Image Guided Bronchoscopic Intervention through an institutional grant awarded to Johns Hopkins University, Department of Biomedical Engineering. Focus of the study is to design improved functionality for fluoroscopy guided bronchoscopy; the development of the current contrast enhanced markers as pseudo-tumors in the lung is related to the need for animal models with target lesions.; Product/procedure/technique that is considered research and is NOT yet approved for any purpose. I shall present technique of using contrast hydrogels to simulate lung tumors in order to create targets in peripheral lung parenchyma with which to develope refined image guided bronchoscopic interventions