Imaging of targeted lipid microbubbles to detect cancer cells using third harmonic generation microscopy

Abstract

Abstract:The use of receptor-targeted lipid microbubbles imaged by ultrasound is an innovative method of detecting and localizing disease. However, since ultrasound requires a medium between the transducer and the object being imaged, it is impractical to apply to an exposed surface in a surgical setting where sterile fields need be maintained and ultrasound gel may cause the bubbles to collapse. Multiphoton microscopy (MPM) is an emerging tool for accurate, label-free imaging of tissues and cells with high resolution and contrast. We have recently determined a novel application of MPM to be used for detecting targeted microbubble adherence to the upregulated plectin-receptor on pancreatic tumor cells. Specifically, the third-harmonic generation response can be used to detect bound microbubbles to various cell types presenting MPM as an alternative and useful imaging method. This is an interesting technique that can potentially be translated as a diagnostic tool for the early detection of cancer and inflammatory disorders.

All-reflective multiphoton microscope

“…Additionally, biomedical imaging without slicing and staining the tissue is one the promising applications of multiphoton imaging. Using the ARMPM enables deployment of various source wavelengths to investigate different structures in biological tissues or incorporating different fluorescent dyes to detect specific targets [34]. Figure 7(a) shows the image of an unstained ovary tissue captured using ARMPM.…”

Molecular mobility and activity in an intravital imaging setting – implications for cancer progression and targeting

“…Imaging cell invasion (Olivier et al, 2010;Rehberg et al, 2010;Tsai et al, 2012;Weigelin et al, 2012) Combination with theranostics (Harpel et al, 2016) Optical biopsies (Chen et al, 2010;Kuzmin et al, 2016;Liao et al, 2013;Tsai et al, 2014) Optical coherence tomography (OCT)…”

Compact fiber-based multi-photon endoscope working at 1700 nm

“…Multi-photon microscopy (MPM) has been recognized as a promising technique for label-free imaging of biological samples [1,2]. Various nonlinear imaging modalities such as third harmonic generation (THG), second harmonic generation (SHG), two and three photon excited auto-fluorescence (2PEF/3PEF) can provide valuable information about intrinsic properties of the biological samples which can be employed in diagnosis applications [3][4][5][6]. However, the key challenge to take advantage of these imaging modalities in gastrointestinal and colonic visualization is to miniaturize the MPM into a compact and lightweight distal probe while keeping the general performance.…”

“…To the best of our knowledge, this is the first flexible endoscope which has been successfully employed for THG imaging. Recently, THG microscopy has been used by multiple groups for label-free pathology, optical biopsy and detecting cancerous cells [3][4][5][6]. Therefore, development of a flexible endoscope with THG imaging capability will pave the way for future research in this field.…”