Abstract
Photothermal OCT (PTOCT) provides high sensitivity to molecular targets in tissue, and occupies a spatial imaging regime that is attractive for small animal imaging. However, current implementations of PTOCT require extensive temporal sampling, resulting in slow frame rates and a large data burden that limit its in vivo utility. To address these limitations, we have implemented optical lock-in techniques for photothermal optical lock-in OCT (poli-OCT), and demonstrated the in vivo imaging capabilities of this approach. The poli-OCT signal was assessed in tissue-mimicking phantoms containing indocyanine green (ICG), an FDA approved small molecule that has not been previously imaged in vivo with PTOCT. Then, the effects of in vivo blood flow and motion artifact were assessed and attenuated, and in vivo poli-OCT was demonstrated with both ICG and gold nanorods as contrast agents. Experiments revealed that poli-OCT signals agreed with optical lock-in theory and the bio-heat equation, and the system exhibited shot noise limited performance. In phantoms containing biologically relevant concentrations of ICG (1 µg/ml), the poli-OCT signal was significantly greater than control phantoms (p<0.05), demonstrating sensitivity to small molecules. Finally, in vivo poli-OCT of ICG identified the lymphatic vessels in a mouse ear, and also identified low concentrations (200 pM) of gold nanorods in subcutaneous injections at frame rates ten times faster than previously reported. This work illustrates that future in vivo molecular imaging studies could benefit from the improved acquisition and analysis times enabled by poli-OCT.
Highlights
In vivo molecular imaging in animal models serves a vital role in medical research, providing fundamental insights into mechanisms of disease formation and progression [1], as well as drug discovery [2]
Tissue-mimicking phantoms containing indocyanine green (ICG) (8 μg/ml) and TiO2 were imaged under variable system parameters to quantify poli-Optical coherence tomography (OCT) performance and to optimize the system for in vivo imaging
We have incorporated optical lock-in methods into traditional Photothermal OCT (PTOCT), and for the first time demonstrated in vivo poli-OCT
Summary
In vivo molecular imaging in animal models serves a vital role in medical research, providing fundamental insights into mechanisms of disease formation and progression [1], as well as drug discovery [2]. In the traditional PTOCT implementation for imaging trace concentrations of contrast agents, one A-scan position is temporally sampled hundreds to thousands of times, and heating dynamics are identified from the phase of the depth-resolved OCT signal using post-acquisition frequency analysis. This post-acquisition frequency analysis scheme requires time consuming data acquisition, excessive data collection, and lengthy offline signal analysis. Optical lock-in detection, a real-time alternative to post-acquisition frequency analysis, has been previously implemented for photothermal microscopy of cell monolayers [18] This approach was recently expanded to depth-resolved photothermal optical coherence microscopy [19] and two-dimensional wide field photothermal microscopy [20] of gold nanospheres in cell monolayers.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
