The Applications of Microcavity Lasers in Multimodality Imaging

Abstract

Multimodality imaging technologies have attracted wide attention in both biological researches and clinical practice. However, the low image signal-to-noise ratio (SNR) and the limited capability to label multiple targets are the major challenges to use multimodality imaging in many in vivo biomedical applications. Due to the homogeneity of current optical imaging contrast agents (such as gold and polymer nanoparticles, and fluorophores), only the overall distribution of the targets can be observed. Precise tracking of the trajectory of each individual target is not possible. Microcavity lasers are emerging technologies that have broad applications in biomedical fields. Owing to the high emission intensity, rich spectral information, and narrow linewidth, microcavity lasers may provide a route to achieve deep tissue imaging with a high SNR and track implanted cells with unique identifiers. In this dissertation, I introduce the development of three applications of microcavity lasers in multimodality imaging: ultrasound modulated droplet lasers, in vivo single immune cell tracking, and longitudinal in vivo stem cell tracking for cell therapy. In contrast to fluorescence-based imaging and labeling, our microcavity laser emission-based technologies have demonstrated distinct advantages with significantly improved SNR, sensitivity, multimodality contrast, and unique spectral information for labeling different cells. For ultrasound modulated droplet lasers, this technology leverages both deep penetration depth and high resolution of ultrasound imaging, and the high SNR, imaging contrast and sensitivity of laser emission. I first demonstrated the ultrasound modulated microdroplet lasers in which the laser emission intensity from the whispering gallery mode (WGM) of a micro oil droplet laser can be enhanced up to 20-fold when the ultrasound pressure reaches a certain threshold. This enhancement in laser emission intensity is reversible when the ultrasound is turned off. Furthermore, the ultrasound modulation of the laser output in the frequency domain was achieved by controlling the ultrasound modulation frequency. Finally, I investigated a potential in vivo application of the ultrasound modulated droplet lasing using phantoms vessels containing human whole blood. For in vivo immune and stem cell tracking, I demonstrated a multimodality imaging technology combining optical coherence tomography (OCT), fluorescence microscopy (FM), and lasing emission labeling to longitudinally track the 3D migration trajectories of individual cells transplanted into the subretinal space in vivo. The CdS nanowire lasers, with the distinct lasing spectra generated from the subtle differences in the Fabry-Perot microcavity, were utilized as unique identifiers to label the cells. With strong optical scattering and fluorescence emission, CdS nanowires also served as OCT and FM contrast agents to indicate the spatial locations of the cells. FM could provide the overall 2D cell distribution pattern, whereas the nanowires internalized by cells provide unique lasing emission spectra for differentiating individual cells. Meanwhile, OCT imaging could provide both 3D retinal structure and spatial locations of the cells. By integrating the capabilities of FM, OCT, and lasing emission labeling, longitudinal 3D tracking of individual cells in the subretinal space in vivo was achieved. Our study opens a door to utilize microcavity lasers and multimodality imaging platforms to improve imaging quality and solve real-world clinical problems. In the future, our technologies can also be adopted to support both biological researches and clinical applications such as deep tissue cell tracking, and understanding of the pharmacodynamics (PD) and pharmacokinetics (PK) of cell-based therapies for a comprehensive evaluation of both safety and efficacy.