Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging

By B. Vakoc, Ryan M Lanning, J. Tyrrell, T. Padera, Lisa A Bartlett, Triantafyllos Stylianopoulos, Lance L. Munn, G. Tearney, Dai Fukumura, Rakesh K. Jain and 1 more. Nature Medicine, 2009

735 citations recorded by the source corpus.

Intravital multiphoton microscopy has provided powerful mechanistic insights into health and disease and has become a common instrument in the modern biological laboratory. The requisite high numerical aperture and exogenous contrast agents that enable multiphoton microscopy, however, limit the ability to investigate substantial tissue volumes or to probe dynamic changes repeatedly over prolonged periods. Here we introduce optical frequency domain imaging (OFDI) as an intravital microscopy that circumvents the technical limitations of multiphoton microscopy and, as a result, provides unprecedented access to previously unexplored, crucial aspects of tissue biology. Using unique OFDI-based approaches and entirely intrinsic mechanisms of contrast, we present rapid and repeated measurements of tumor angiogenesis, lymphangiogenesis, tissue viability and both vascular and cellular responses to therapy, thereby demonstrating the potential of OFDI to facilitate the exploration of physiological and pathological processes and the evaluation of treatment strategies.

Subfields: Biomedical Engineering, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/815e8f3f3943802670019c4ab271e81047babae3

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Citations in the corpus

Angiotensin inhibition enhances drug delivery and potentiates chemotherapy by decompressing tumour blood vessels (2013, positive): “Optical frequency-domain imaging was carried out after 7 days of treatments using a custom-built microscope 61 .”
Delivering nanomedicine to solid tumors (2010, background): “Instead, tumor vessels are heterogeneous in their spatial distribution, dilated and tortuous, leaving avascular spaces of various sizes”
Normalizing tumor microenvironment to treat cancer: bench to bedside to biomarkers. (2013, background): “Reproduced from.(1) (C) Unlike normal valves (left), the valves in the lymphatic vessels draining a tumor are malformed (right).”
ANTIANGIOGENESIS STRATEGIES REVISITED: FROM STARVING TUMORS TO ALLEVIATING HYPOXIA (2014, positive): “The inset shows heterogeneous perfusion in a tumor, leading to hypoxic and acidic regions (reproduced from Vakoc et al., 2009).”
The role of mechanical forces in tumor growth and therapy (2014, neutral): “Tumor vessels are usually immature and have an abnormal structure and function (1, 48, 63, 64).”
The lymphatic vasculature in disease (2011, background): “Other promising new approaches are also under development, for example optical frequency-domain imaging, which overcomes the limitations of fluorescent tracers such as their tissue penetration and extravasation and is also suited for high-resolution imaging of tumor microvasculatur”
Tumor Targeting via EPR: Strategies to Enhance Patient Responses (2018, background): “Newly formed blood vessels typically occur in higher densities in tumor tissue [32,33], they often lack a smooth muscle layer and pericytes [34], they have a larger lumen and wider Golombek et al.”
Through-skull fluorescence imaging of the brain in a new near-infrared window (2014, background): “44,45 To avoid the invasive treatment of the extracerebral tissue, optical coherence tomography (OCT) and photoacoustic microscopy have both shown the capability of visualizing cortical vasculature at the cost of spatial resolution (10–100 µm), unable to resolve sub-10 µm capillary vessels in vivo.”