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1.
J Synchrotron Radiat ; 19(Pt 6): 1050-5, 2012 Nov.
Article in English | MEDLINE | ID: mdl-23093769

ABSTRACT

X-ray velocimetry offers a non-invasive method by which blood flow, blood velocity and wall shear stress can be measured in arteries prone to atherosclerosis. Analytical tools for measuring haemodynamics in artificial arteries have previously been developed and here the first quantification of haemodynamics using X-ray velocimetry in a living mammalian artery under physiologically relevant conditions is demonstrated. Whole blood seeded with a clinically used ultrasound contrast agent was pumped with a steady flow through live carotid arterial tissue from a rat, which was kept alive in a physiological salt solution. Pharmacological agents were then used to produce vascular relaxation. Velocity measurements were acquired with a spatial resolution of 14 µm × 14 µm and at a rate of 5000 acquisitions per second. Subtle velocity changes that occur are readily measurable, demonstrating the ability of X-ray velocimetry to sensitively and accurately measure haemodynamics ex vivo. Future applications and possible limitations of the technique are discussed, which allows for detailed living tissue investigations to be carried out for various disease models, including atherosclerosis and diabetic vasculopathy.


Subject(s)
Carotid Arteries/physiology , Humans , In Vitro Techniques , X-Rays
2.
Gene Ther ; 19(1): 8-14, 2012 Jan.
Article in English | MEDLINE | ID: mdl-21654825

ABSTRACT

Although airway gene transfer research in mouse models relies on bolus fluid dosing into the nose or trachea, the dynamics and immediate fate of delivered gene transfer agents are poorly understood. In particular, this is because there are no in vivo methods able to accurately visualize the movement of fluid in small airways of intact animals. Using synchrotron phase-contrast X-ray imaging, we show that the fate of surrogate fluid doses delivered into live mouse airways can now be accurately and non-invasively monitored with high spatial and temporal resolution. This new imaging approach can help explain the non-homogenous distributions of gene expression observed in nasal airway gene transfer studies, suggests that substantial dose losses may occur at deliver into mouse trachea via immediate retrograde fluid motion and shows the influence of the speed of bolus delivery on the relative targeting of conducting and deeper lung airways. These findings provide insight into some of the factors that can influence gene expression in vivo, and this method provides a new approach to documenting and analyzing dose delivery in small-animal models.


Subject(s)
Gene Transfer Techniques , Respiratory System/diagnostic imaging , Synchrotrons , Tomography, X-Ray Computed/methods , Animals , Female , Genetic Therapy , Image Processing, Computer-Assisted/methods , Iopamidol/administration & dosage , Iopamidol/analogs & derivatives , Lung/anatomy & histology , Lung/diagnostic imaging , Mice , Mice, Inbred C57BL , Respiratory Mechanics , Respiratory System/anatomy & histology
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