Abstract
Blood-perfused tissue models are joining the emerging field of tumor engineering because they provide new avenues for modulation of the tumor microenvironment and preclinical evaluation of the therapeutic potential of new treatments. The characterization of fluid flow parameters in such in-vitro perfused tissue models is a critical step towards better understanding and manipulating the tumor microenvironment. However, traditional optical flow measurement methods are inapplicable because of the opacity of blood and the thickness of the tissue sample. In order to overcome the limitations of optical method we demonstrate the feasibility of using phase-contrast x-ray imaging to perform microscale particle image velocimetry (PIV) measurements of flow in blood perfused hydrated tissue-representative microvessels. However, phase contrast x-ray images significantly depart from the traditional PIV image paradigm, as they have high intensity background, very low signal-to-noise ratio, and volume integration effects. Hence, in order to achieve accurate measurements special attention must be paid to the image processing and PIV cross-correlation methodologies. Therefore we develop and demonstrate a methodology that incorporates image preprocessing as well as advanced PIV cross-correlation methods to result in measured velocities within experimental uncertainty.
Highlights
Three-dimensional (3D) engineered microfluidic tissue models have recently emerged as valuable tools for the study of the progression of disease such as cancers, the development of therapeutics under controlled conditions, and regenerative medicine [1,2,3,4,5,6,7,8,9]
Because fluid shear stress is known to play a pivotal role in several disease development processes such as tumor cell expansion, angiogenesis and metastasis [6,17] as well as hemolysis and thrombosis formation [18], microfluidic vascular models are superior to static cultures
Particle image velocimetry (PIV) is a well-established noninvasive optical flow measurement technique that has been successfully used within various biological systems [20,21,22]
Summary
Three-dimensional (3D) engineered microfluidic tissue models have recently emerged as valuable tools for the study of the progression of disease such as cancers, the development of therapeutics under controlled conditions, and regenerative medicine [1,2,3,4,5,6,7,8,9]. Because fluid shear stress is known to play a pivotal role in several disease development processes such as tumor cell expansion, angiogenesis and metastasis [6,17] as well as hemolysis and thrombosis formation [18], microfluidic vascular models are superior to static cultures. Our group has recently developed a novel in-vitro 3D perfused collagen-based tissue model for the study of cancer development and metastasis and successfully measured flow in this platform using microscopic PIV (mPIV); our initial studies have provided new insights into tumor-endothelial crosstalk under dynamic conditions [23]
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