Mechanical compression drives cancer cells toward invasive phenotype.

Uncontrolled growth in a confined space generates mechanical compressive stress within tumors, but little is known about how such stress affects tumor cell behavior. Here we show that compressive stress stimulates migration of mammary carcinoma cells. The enhanced migration is accomplished by a subset of "leader cells" that extend filopodia at the leading edge of the cell sheet.

Simultaneous measurement of RBC velocity, flux, hematocrit and shear rate in vascular networks.

Not all tumor vessels are equal. Tumor-associated vasculature includes immature vessels, regressing vessels, transport vessels undergoing arteriogenesis and peritumor vessels influenced by tumor growth factors. Current techniques for analyzing tumor blood flow do not discriminate between vessel subtypes and only measure average changes from a population of dissimilar vessels.

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

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.

PDGF-C induces maturation of blood vessels in a model of glioblastoma and attenuates the response to anti-VEGF treatment.

Background: Recent clinical trials of VEGF inhibitors have shown promise in the treatment of recurrent glioblastomas (GBM). However, the survival benefit is usually short-lived as tumors escape anti-VEGF therapies. Here we tested the hypothesis that Platelet Derived Growth Factor-C (PDGF-C), an isoform of the PDGF family, affects GBM progression independent of VEGF pathway and hinders anti-VEGF therapy.

Perivascular nitric oxide gradients normalize tumor vasculature.

Normalization of tumor vasculature is an emerging strategy to improve cytotoxic therapies. Here we show that eliminating nitric oxide (NO) production from tumor cells via neuronal NO synthase silencing or inhibition establishes perivascular gradients of NO in human glioma xenografts in mice and normalizes the tumor vasculature, resulting in improved tumor oxygenation and response to radiation treatment. Creation of perivascular NO gradients may be an effective strategy for normalizing abnormal vasculature.

Differential in vivo potential of endothelial progenitor cells from human umbilical cord blood and adult peripheral blood to form functional long-lasting vessels.

Tissue engineering requires formation of a de novo stable vascular network. Because of their ability to proliferate, differentiate into endothelial cells, and form new vessels, blood-derived endothelial progenitor cells (EPCs) are attractive source of cells for use in engineering blood vessels. However, the durability and function of EPC-derived vessels implanted in vivo are unclear.

Robust 3-D modeling of vasculature imagery using superellipsoids.

This paper presents methods to model complex vasculature in three-dimensional (3-D) images using cylindroidal superellipsoids, along with robust estimation and detection algorithms for automated image analysis. This model offers an explicit, low-order parameterization, enabling joint estimation of boundary, centerlines, and local pose. It provides a geometric framework for directed vessel traversal, and extraction of topological information like branch point locations and connectivity.

A 2-D/3-D model-based method to quantify the complexity of microvasculature imaged by in vivo multiphoton microscopy.

This paper presents model-based information-theoretic methods to quantify the complexity of tumor microvasculature, taking into account shape, textural, and structural irregularities. The proposed techniques are completely automated, and are applicable to optical slices (3-D) or projection images (2-D). Improvements upon the prior literature include: (i) measuring local (vessel segment) as well as global (entire image) vascular complexity without requiring explicit segmentation or tracing; (ii) focusing on the vessel boundaries in the complexity estimate; and (iii) added robustness to image artifacts common to tumor microvasculature images.

Efficient migration of complex off-line computer vision software to real-time system implementation on generic computer hardware.

This paper addresses the problem of migrating large and complex computer vision code bases that have been developed off-line, into efficient real-time implementations avoiding the need for rewriting the software, and the associated costs. Creative linking strategies based on Linux loadable kernel modules are presented to create a simultaneous realization of real-time and off-line frame rate computer vision systems from a single code base. In this approach, systemic predictability is achieved by inserting time-critical components of a user-level executable directly into the kernel as a virtual device driver.