In vivo flow cytometry: A new method for monitoring circulating cancer cells

Georgakoudi, Irene; Solban, Nicolas; Novak, John; Hasan, Tayyaba; Lin, Charles P.

doi:10.1364/bio.2004.thc6

Cited by 56 publications

(89 citation statements)

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“…Microcirculation has been successfully studied using optical microscopy in various animal models (e.g., rabbit or mouse ear, hamster or mouse dorsal skin-flap window or skin-fold chamber, or open cremaster muscle) [52][53][54][55]59,63,[70][71][72][73] . The use of these models for high-resolution imaging of individual flowing or static cells may be somewhat limited because of significant light scattering from surrounding tissue (e.g., skin or muscles) and/or the relatively deep location of vessels below the skin.…”

Section: Animal Modelsmentioning

confidence: 99%

“…The primary application of this system was for in vivo FC. Indeed, although in vitro FC is a powerful, established diagnostic method [102] , only an in vivo study can assess physiologic and pathologic processes involving cell metabolism and cell-cell interactions (e.g., adhesion, aggregation, rolling effects, migration through vessel walls) in the real, complex environment of living organisms [53][54][55]84,99,103] . Further, invasive isolation of cells from their native environment and their processing may not only introduce artifacts, but also make it impossible to examine the same cell population over long time periods.…”

Section: Integrated Imaging Systemmentioning

confidence: 99%

“…Fluorescence imaging of lymphatics by injecting fluorescein isothiocyanate (FITC)-dextran into the interstitial space led to elevated interstitial pressure and altered lymph viscosity [52] . These findings may raise some concern about the kinetics of labeled cells in flow, particularly about the main cause and the real rate of cell elimination from circulation, the actual properties of apoptotic or cancer cells, or the strong influence of the tags due to phagocytosis, or the interaction of tags with other cells [53][54][55] . All these concerns gain importance in in vivo studies in humans, and add to interest in developing label-free imaging.…”

Section: Introductionmentioning

confidence: 99%

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Advances in small animal mesentery models for in vivo flow cytometry, dynamic microscopy, and drug screening

Galanzha¹

2007

WJG

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Using animal mesentery with intravital optical microscopy is a well-established experimental model for studying blood and lymph microcirculation in vivo . Recent advances in cell biology and optical techniques provide the basis for extending this model for new applications, which should generate significantly improved experimental data. This review summarizes the achievements in this specific area, including in vivo label-free blood and lymph photothermal flow cytometry, super-sensitive fluorescence image cytometry, light scattering and speckle flow cytometry, microvessel dynamic microscopy, infrared (IR) angiography, and high-speed imaging of individual cells in fast flow. The capabilities of these techniques, using the rat mesentery model, were demonstrated in various studies; e.g., real-time quantitative detection of circulating and migrating individual blood and cancer cells, studies on vascular dynamics with a focus on lymphatics under normal conditions and under different interventions (e.g. lasers, drugs, nicotine), assessment of lymphatic disturbances from experimental lymphedema, monitoring cell traffic between blood and lymph systems, and high-speed imaging of cell transient deformability in flow. In particular, the obtained results demonstrated that individual cell transportation in living organisms depends on cell type (e.g., normal blood or leukemic cells), the cell's functional state (e.g., live, apoptotic, or necrotic), and the functional status of the organism. Possible future applications, including in vivo early diagnosis and prevention of disease, monitoring immune response and apoptosis, chemo-and radio-sensitivity tests, and drug screening, are also discussed. TOPIC HIGHLIGHT

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Section: Animal Modelsmentioning

confidence: 99%

Section: Integrated Imaging Systemmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Advances in small animal mesentery models for in vivo flow cytometry, dynamic microscopy, and drug screening

Galanzha¹

2007

WJG

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“…However, most of these existing technologies require blood to be drawn to isolate and capture CTCs ex vivo, reducing the effective CTC detection sensitivity. Optical imaging technologies, such as confocal microscopy, in vivo flow cytometry, and optical coherence tomography, have been applied to detect CTCs in vivo [8][9][10][11] . However, suffering from strong optical scattering in biological tissue, these techniques have shallow penetration, limiting them to imaging only small blood vessels, which results in low throughput for CTC detection.…”

Section: Introductionmentioning

confidence: 99%

Linear-array-based photoacoustic tomography for label-free high-throughput detection and quantification of circulating melanoma tumor cell clusters

et al. 2017

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Circulating tumor cell (CTC) clusters arise from multicellular grouping in the primary tumor and elevate the metastatic potential by 23 to 50 fold compared to single CTCs. High throughout detection and quantification of CTC clusters is critical for understanding the tumor metastasis process and improving cancer therapy. In this work, we report a lineararray-based photoacoustic tomography (LA-PAT) system capable of label-free high-throughput CTC cluster detection and quantification in vivo. LA-PAT detects CTC clusters and quantifies the number of cells in them based on the contrast-to-noise ratios (CNRs) of photoacoustic signals. The feasibility of LA-PAT was first demonstrated by imaging CTC clusters ex vivo. LA-PAT detected CTC clusters in the blood-filled microtubes and computed the number of cells in the clusters. The size distribution of the CTC clusters measured by LA-PAT agreed well with that obtained by optical microscopy. We demonstrated the ability of LA-PAT to detect and quantify CTC clusters in vivo by imaging injected CTC clusters in rat tail veins. LA-PAT detected CTC clusters immediately after injection as well as when they were circulating in the rat bloodstreams. Similarly, the numbers of cells in the clusters were computed based on the CNRs of the photoacoustic signals. The data showed that larger CTC clusters disappear faster than the smaller ones. The results prove the potential of LA-PAT as a promising tool for both preclinical tumor metastasis studies and clinical cancer therapy evaluation.

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“…A video rate laser scanning confocal microscope (LSCM) was optimized for live small animal imaging that is capable of imaging moving objects and searching for rare cells, as well as rapidly acquiring 3D data sets for assessing large tissue volumes (6). Complementing in vivo imaging, an in vivo flow cytometer (IVFC) was developed for real-time detection and enumeration of circulating fluorescent cells in mouse circulation (7,8), in which an excitation laser beam is focused to a slit across a blood vessel. Each time a fluorescently labeled cell crosses the laser slit, an emission is detected and counted.…”

Section: Introductionmentioning

confidence: 99%

An optical platform for cell tracking in adult zebrafish

Zhang

Alt

et al. 2011

Cytometry Pt A

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Adult zebrafish are being increasingly used as a model in cancer and stem cell research. Here we describe an integrated optical system that combines a laser scanning confocal microscope (LSCM) and an in vivo flow cytometer (IVFC) for simultaneous visualization and cell quantification. The system is set up specifically for non-invasive tracking of both stationary and circulating cells in adult zebrafish (casper) that have been engineered to be optically transparent. Confocal imaging in this instrument serves the dual purpose of visualizing fish tissue microstructure and an imaging-based guide to locate a suitable vessel for quantitative analysis of circulating cells by IVFC. We demonstrate initial testing of this novel instrument by imaging the transparent adult zebrafish casper vasculature and tracking circulating cells in CD41-GFP/Gata1-DsRed transgenic fish whose thrombocytes/erythrocytes express the green and red fluorescent proteins. In vivo measurements allow cells to be tracked under physiological conditions in the same fish over time, without drawing blood samples or sacrificing animals. We also discuss the potential applications of this instrument in biomedical research. ' 2011 International Society for Advancement of Cytometry

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In vivo flow cytometry: A new method for monitoring circulating cancer cells

Cited by 56 publications

References 0 publications

Advances in small animal mesentery models for in vivo flow cytometry, dynamic microscopy, and drug screening

Advances in small animal mesentery models for in vivo flow cytometry, dynamic microscopy, and drug screening

Linear-array-based photoacoustic tomography for label-free high-throughput detection and quantification of circulating melanoma tumor cell clusters

An optical platform for cell tracking in adult zebrafish

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