Abstract
There has been significant recent interest in the development of technologies for enumeration of rare circulating cells directly in the bloodstream in many areas of research, for example, in small animal models of circulating tumor cell dissemination during cancer metastasis. We describe a fiber-based optical probe that allows fluorescence detection of labeled circulating cells in vivo in a diffuse reflectance configuration. We validated this probe in a tissue-mimicking flow phantom model in vitro and in nude mice injected with fluorescently labeled multiple myeloma cells in vivo. Compared to our previous work, this design yields an improvement in detection signal-to-noise ratio of 10 dB, virtually eliminates problematic motion artifacts due to mouse breathing, and potentially allows operation in larger animals and limbs.
Highlights
There has been significant recent interest in the development of technologies for detection and enumeration of circulating cells in the bloodstream in many of areas of preclinical small animal research
Rare circulating cells are important in the study of, for example, circulating tumor cell (CTC) dissemination in cancer metastasis, where clinically and preclinically significant concentrations are in the range of only 1 to 100 cells∕mL.[10]
The “spikes” observed were similar to those in our previous work,[7,8] and we interpret these to be the fluorescence signal generated as microspheres pass through the instrument field of view (FOV)
Summary
There has been significant recent interest in the development of technologies for detection and enumeration of circulating cells in the bloodstream in many of areas of preclinical small animal research. Our group has worked on the problem of rare circulating cell detection, which we define as fewer than 1000 cells∕mL of peripheral blood.[7,8,9] Rare circulating cells are important in the study of, for example, circulating tumor cell (CTC) dissemination in cancer metastasis, where clinically and preclinically significant concentrations are in the range of only 1 to 100 cells∕mL.[10] CTC enumeration is widely needed in studying disease development or testing of new therapies. At such low concentrations, microscopy-based IVFC may require impractically long acquisition times to detect individual cells due to low blood flow rates in arterioles (1 to 5 μL∕ min)
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