Design considerations for ultrasound-coupled depth sensing systems for fluorescence imaging of pancreatic cancer with indocyanine green and protoporphyrin-IX

Two key limitations of clinical fluorescence-guided surgery systems is that 1) they can only image a few millimeters into tissue [1] and 2) imaging internal structures usually requires surgical incision. These limitations have restricted the use of fluorescence-based systems in oncology. Herein, we demonstrate 2 systems, one single-channel and one multi-channel, with 3D-printed attachments to house ultrasound transducers, laser fibers, and detector fibers. The transducer allows for specific location of internal structures, and the optical fiber system allows for real-time measurement of the vascular fluorescent contrast agent indocyanine green (ICG), potentially up to 20mm into tissue [2-3]. The two modalities combined may allow for simultaneous non-invasive tissue fluorescence and ultrasound elastography measurements, which has special relevance to pancreatic cancer. A prototype single-channel system was constructed using a combination of 3d-printed parts and specialized optical components. This system was tested in tissue-mimicking phantoms to determine the depth of sensing and optimal source-detector distance, followed by validation using murine models injected with pancreatic adenocarcinoma tumors, which were imaged at several timepoints throughout the tumor growth. These tests demonstrated that the system can track longitudinal changes in ICG kinetics as the tumor becomes larger. After testing, the components were packaged into a compact box to allow for easy and convenient use. The multi-channel system allows for the generation of a fluorescence images from combining the multiple sources via several laser and detector fibers positioned along the length of the ultrasound transducer on the tissue contact. Future directions for this project include: (i) finalizing and optimizing the LabVIEW for the multi-source-detector sequencing for tomography acquisition, (ii) designing attachments for the fibers to match with multiple ultrasound transducer types, (iii) testing the ability of the multichannel system to image during ultrasound, as well as (iv) potentially assessing the feasibility of imaging other fluorophores simultaneously, particularly protoporphyrin-IX (PPIX).