Combined fluorescence and photoacoustic imaging of tozuleristide in muscle tissue in vitro -- toward optically-guided solid tumor surgery: feasibility studies

Near-infrared fluorescence (NIRF) can deliver high-contrast, video-rate, non-contact imaging of tumor-targeted contrast agents with the potential to guide surgeries excising solid tumors. However, it has been met with skepticism for wide-margin excision due to sensitivity and resolution limitations at depths larger than ~5 mm in tissue. To address this limitation, fast-sweep photoacoustic-ultrasound (PAUS) imaging is proposed to complement NIRF. In an exploratory in vitro feasibility study using dark-red bovine muscle tissue, we observed that PAUS scanning can identify tozuleristide, a clinical stage investigational imaging agent, at a concentration of 20 uM from the background at depths of up to ~34 mm, highly extending the capabilities of NIRF alone. The capability of spectroscopic PAUS imaging was tested by direct injection of 20 uM tozuleristide into bovine muscle tissue at a depth of ~ 8 mm. It is shown that laser-fluence compensation and strong clutter suppression enabled by the unique capabilities of the fast-sweep approach greatly improve spectroscopic accuracy and the PA detection limit, and strongly reduce image artifacts. Thus, the combined NIRF-PAUS approach can be promising for comprehensive pre- (with PA) and intra- (with NIRF) operative solid tumor detection and wide-margin excision in optically guided solid tumor surgery.

Large FOV short-wave infrared meta-lens for scanning fiber endoscopy

The scanning fiber endoscope (SFE), an ultra-small optical imaging device with a large field-of-view (FOV) for having a clear forward view into the interior of blood vessels, has great potential in the cardio-vascular disease diagnosis and surgery assistance, which is one of the key applications for short-wave infrared (SWIR) biomedical imaging. The state-of-the-art SFE system uses a miniaturized refractive spherical lens doublet for beam projection. A meta-lens is a promising alternative which can be made much thinner and has fewer off-axis aberrations than its refractive counterpart. We report an SFE system with meta-lens working at 1310nm to achieve a resolution ($\sim 140\mu m$ at the center of field and the imaging distance of $15mm$), FOV ($\sim 70 \circ$), and depth-of-focus (DOF $\sim 15mm$), which are comparable to a state-of-the-art refractive lens SFE. The use of the meta-lens reduces the length of the optical track from $1.2mm$ to $0.86mm$. The resolution of our meta-lens based SFE drops by less than a factor of $2$ at the edge of the FOV, while the refractive lens counterpart has a $\sim 3$ times resolution degradation. These results show the promise of integrating a meta-lens into an endoscope for device minimization and optical performance improvement.