Combined Needle-based Confocal Laser Endomicroscopy Cone-Beam Computed Tomography Navigation Bronchoscopy: a Proof of Principle Study

Lung cancer remains a significant problem in current society with one of the higher cancer related mortality rates. The increased use of chest computed tomography (CT) and the po-tential future lung cancer screening result in an increased detection of early-stage peripheral lung cancer. Bronchoscopies are often indicated to collect tissue for diagnosis and to aid treatment decision making.

Diagnostic bronchoscopy for peripheral lung nodules remains challenging despite many tech-nological innovations. The procedure comprises three essential pillars needed for a diagnos-tic success: navigation to the lesion, tool-in-lesion confirmation and adequate tissue retrieval.

Cone beam computed tomography navigation bronchoscopy (CBCT-NB) is a fairly new tech-nique that provides coarse navigation to the pulmonary lesion with real-time guidance using augmented fluoroscopy (AF). An initial CBCT scan allows for segmentation of the target le-sion and selecting the optimal pathway. Repeated CBCT scanning allows for confirmation that the target has been reached (navigation success) or if repositioning is needed.

Although the technique is very promising, an often discussed disadvantage of CBCT is the inherent use of ionizing radiation, limited availability and challenges with small nodules lo-cated in the basal and posterior fields due to respiratory motion. Most procedures ask for multiple CBCT spins both for trajectory planning, tool adjustments and tool-in-lesion confir-mation. This, combined with extensive use of fluoroscopy is associated with radiation expo-sure for both patients and the investigation team. Additionally, CBCT-NB with AF provides information from a global perspective rather than a local perspective. In experienced centers, coarse navigation guidance seems of lesser concern and fine positioning and optimal tissue sampling are the biggest problems to be overcome. The persistently low diagnostic yield of navigation bronchoscopies can for the majority be attributed mispositioning of the tools in "the last centimeter". Therefore there is a need for complementary techniques providing real-time information for fine-tuning the needle position such as needle-based confocal laser en-domicroscopy (nCLE) also called the "smart needle".

Confocal laser endomicroscopy (CLE) is a high-resolution microscopic technique that visual-izes individual cells in real-time at the tip of the biopsy needle, allowing for real-time micro-scopic feedback for fine tuning needle positioning and tool-in-lesion confirmation. Currently, it is unknown which (combination of) techniques are the most optimal (i.e., leading to a high di-agnostic yield and cost-effective). Therefore, research is needed to investigate the potential of new (combinations of) techniques. To date, there are no reports on the combination of CBCT-NB with nCLE.