Jennifer Kehlet Barton

The role of the endothelium in regulating transmural fluid filtration into the artery wall under pulsatile pressure and the effects of changes in pulsatile frequency on filtration have received little attention. Previous experiments (Alberding JP, Baldwin AL, Barton JK, and Wiley E. Am J Physiol Heart Circ Physiol 286: H1827-H1835, 2004) demonstrated significantly increased filtration after initial onset of pulsatile pressure compared with that predicted by using parameters measured under steady pressure. To determine the role of the endothelium in this phenomenon, the following experiments were performed on five New Zealand White rabbits (anesthetized with 30 mg/kg pentobarbital sodium). One of each pair of carotid arteries was deendothelialized, and filtration measurements under steady and pulsatile pressure were compared with those made in intact vessels (Alberding JP, Baldwin AL, Barton JK, and Wiley E. Am J Physiol Heart Circ Physiol 286: H1827-H1835, 2004). To determine the effect of increasing pulsatile frequency on arterial filtration, transmural filtration was measured by using pulsatile pressure frequencies of 1 Hz, followed by 2 Hz, in another set of intact arteries (6 arteries and 3 animals). For deendothelialized vessels, the initial increase in filtration after onset of pulsatility was similar to that observed in intact vessels, but the subsequent reduction in filtration was less abrupt. When pulsatile frequency was increased from 1 to 2 Hz in intact arteries, an initial increase in filtration was observed, similar to that obtained after onset of pulsatile pressure subsequent to a steady pressure. The observed responses of arteries to pulsatile pressure, with and without endothelium, or undergoing a frequency change, suggest a dynamic role for the endothelium in regulating transvascular transport in vivo.

We successfully labeled colorectal cancer in vivo using quantum dots targeted to vascular endothelial growth factor receptor 2 (VEGFR2). Quantum dots with emission centered at 655 nm were bioconjugated to anti-VEGFR2 antibodies through streptavidin/biotin linking. The resulting QD655-VEGFR2 contrast agent was applied in vivo to the colon of azoxymethane (AOM) treated mice via lavage and allowed to incubate. The colons were then excised, cut longitudinally, opened to expose the lumen, and imaged en face using a fluorescence stereoscope. The QD655-VEGFR2 contrast agent produced a significant increase in contrast between diseased and undiseased tissues, allowing for fluorescence-based visualization of the diseased areas of the colon. Specificity was assessed by observing insignificant contrast increase when labeling colons of AOM-treated mice with quantum dots bioconjugated to isotype control antibodies, and by labeling the colons of saline-treated control mice. This contrast agent has a great potential for in vivo imaging of the colon through endoscopy.

Depth dependent broadening of the axial point spread function due to dispersion in the imaged media, and algorithms for postprocess correction, have been previously described for both time domain and frequency domain optical coherence tomography. We show that homogeneous media dispersion artifacts disappear when frequency domain samples are acquired with uniform spacing in circular wavenumber, as opposed to uniform sampling in optical frequency. We further explicate the source of this point spread broadening and simulate its magnitude in aqueous media. We experimentally demonstrate media dispersion compensation in high dispersion glass by choosing sample frequencies at equal intervals of media index of refraction divided by vacuum wavelength, and we recover unbroadened reflections without an additional postprocessing step.

A three-dimensional imaging system incorporating multiplexed holographic gratings to visualize fluorescence tissue structures is presented. Holographic gratings formed in volume recording materials such as a phenanthrenquinone poly(methyl methacrylate) photopolymer have narrowband angular and spectral transmittance filtering properties that enable obtaining spatial-spectral information within an object. We demonstrate this imaging system's ability to obtain multiple depth-resolved fluorescence images simultaneously.