Photoacoustic (PA) imaging for biomedical applications has been under development for many years. Based on the many advances over the past decade, a new photoacoustic imaging system has been integrated into a micro-ultrasound platform for co-registered PA-ultrasound (US) imaging. The design and implementation of the new scanner is described and its performance quantified. Beamforming techniques and signal processing are described, in conjunction with in vivo PA images of normal subcutaneous mouse tissue and selected tumor models. In particular, the use of the system to estimate the spatial distribution of oxygen saturation (sO2) in blood and co-registered with B-mode images of the surrounding anatomy are investigated. The system was validated in vivo against a complementary technique for measuring partial pressure of oxygen in blood (pO2). The pO2 estimates were converted to sO2 values based on a standard dissociation curve found in the literature. Preliminary studies of oxygenation effects were performed in a mouse model of breast cancer (MDA-MB-231) in which control mice were compared with mice treated with a targeted antiangiogenic agent over a 3 d period. Treated mice exhibited a >90% decrease in blood volume, an 85% reduction in blood wash-in rate, and a 60% decrease in relative tissue oxygenation.

We tested the hypothesis that vascular endothelial growth factor (VEGF) increases microvascular permeability by increasing calcium influx into endothelial cells forming the vessel walls. We measured microvessel hydraulic conductivity (Lp) in isolated perfused MS-222-anesthetized frog mesenteric microvessels during perfusion with VEGF under conditions that attenuate calcium influx. VEGF increased Lp during a second successive perfusion in the same microvessel by 7.8-fold, which was not significantly different from that brought about by an initial application of VEGF (5.0-fold). However, under depolarizing conditions, the increase in Lp was reduced from 11.1- to 5.6-fold when depolarized to -10 mV (58 mM K+) and to 2.8-fold when depolarized to 0 mV (100 mM K+). Attenuating calcium influx by the addition of nickel ions resulted in a similar attenuation of the increase in Lp (from 13- to 2.5-fold). VEGF also increased the intracellular calcium concentration in endothelial cells of perfused microvessels as determined by measurement with fura 2. We therefore conclude that VEGF increases Lp by increasing calcium influx.

Pocock, T. M., R. R. Foster, and D. O. Bates. Evidence of a role for TRPC channels in VEGF-mediated increased vascular permeability in vivo.

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