Browsing by Subject "perfusion"

Now showing 1 - 3 of 3
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    Development of Pre-Vascularized Tissues Containing Aligned and Perfusable Microvessels
    (2016-05) Riemenschneider, Sonja
    The single greatest restraint in tissue engineering is the inability to create and perfuse functional microvasculature in dense engineered tissues of physiological stiffness. Without active delivery of nutrients and oxygen, tissue size is diffusion-limited to thicknesses of around 400 µm, or much less for highly metabolic tissues. Thus, the creation of pre-vascularized tissues that have a high density of organized microvessels that could be perfused is a major goal of tissue engineering. The present work makes significant advances toward this goal. Tissue patches containing a high density of human microvessels that were either randomly oriented or aligned were placed acutely on rat hearts post-infarction and in both cases, inosculation occurred and perfusion of the transplanted human microvessels was maintained, proving the in vivo vascularization potential of these engineered tissues. In vitro, a high-throughput assay was developed to investigate optimal conditions for angiogenic sprouting, vasculogenic microvascular network formation, and inosculation of the sprouts and microvessels in 3D fibrin gels. Samples loaded with vascular endothelial growth factor and fibroblast growth factor exhibited enhanced angiogenic sprouting, and a hybrid medium culture regimen resulted in enhanced sprouting, well-developed microvascular networks, and inosculation of the microvessels and sprouts. These results showed potential for the in vitro perfusion of larger-scale microvascular tissues. An engineering strategy was developed to perfuse endothelialized microchannels that could form sprouts into fibrin gels containing a microvascular network. An in vitro perfusion bioreactor was designed and tested that enabled these microvascular tissues to be cultured, compacted, and aligned to form a dense network of microvessels that also contained perfusable microchannels with sprouts. Different microchannel seeding regimens and perfusion regimens were applied and it was determined which conditions ultimately led to microchannel endothelialization, sprouting, perfusion, and maintenance during gel compaction. While inosculation and perfusion of the microvessels has yet to be achieved, this work presents the building blocks for a potential strategy that could ultimately enable the perfusion of a dense, aligned microvascular network through anastomoses of sprouts and microvessels. Achievement of this goal would unlock a number of tissue engineering opportunities in the development of large engineered tissues for regenerative therapies.
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    An Evaluation of Perfusion in Human Body Thermal Modeling through the Integration of a Porous Media Model for Tissue
    (2023-02) Smith, Christopher
    Historically there has been one primary method for modeling the thermal condition of the human body. This method, referencing the bioheat equation, has been and is used widely across the medical device and human comfort industries. The present work leverages an alternate method to biological tissue modeling by using a porous media approach. In doing so, it provides a more physiologically and anatomically representative alternative to human body thermal modeling to contrast the computationally efficient, but low fidelity bioheat method. The present work shows the feasibility of using this porous media approach for high fidelity tissue modeling, allowing both researchers and designers to have an alternative modeling method to leverage – ensuring that they can choose a method best fit for their need.
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    Saturation-Recovery T1 (SR-T1) Method: A Dynamic Neuroimaging Tool for Assessment of Perfusion Change
    (2013-10) Wang, Xiao
    A working brain requires continuous oxygen and nutrition supply through the circulation of Cerebral Blood Flow (CBF). CBF and its change closely reflect the energy demand of neuron activity and are highly related to variety of cerebral diseases as well. It is of great importance to noninvasively and reliably mapping CBF and its change under physiological and pathological conditions. The goal of this research is to develop a sensitive, reliable and noninvasive MRI neuroimaging technique based on Saturation-recovery longitudinal relaxation time (SR-T1) method to imaging CBF change and Blood Oxygen-Level Dependent (BOLD) signal simultaneously. First, the theoretical and mathematical model of SR-T1 method is derived and MRI sequence design is described. This technique is tested on physiological and pathological rat models at 9.4T and is validated by indirect Laser Doppler Flowmetry (LDF) and direct Continuous Arterial Spin Labeling (CASL) CBF approaches. Some technical confounding factors are also investigated and discussed (Chapter 2 to 4). Second, the SR-T1 method of imaging CBF change is applied at two different magnetic fields (9.4T and 16.4T) to examine the notion that T1 is field dependent whereas CBF change in response to physiological or pathological perturbation is field independent (Chapter 5). Third, the SR-T1 method is performed to quantitatively investigate the perfusion contribution to the total functional MRI (fMRI) signal using a rat model with mild hypercapnia at 9.4T and human subjects with visual stimulation at 4T. It reveals that an improved fMRI contrast-to-noise ratio and spatial specificity for mapping brain activity and physiology changes could benefit from appropriately choosing the MRI parameters in enhancing perfusion contribution to the total fMRI signal (Chapter 6). Fourth, the SR-T1 method is carried out on Middle Cerebral Artery Occlusion (MCAO) rat model at 1 day and 7 days of post-ischemia and then is compared to the CBF change measured by the CASL technique in varied lesion regions of rat brain. The comparison reveals a good correlation of CBF change measured with these two perfusion techniques. A variety of MR imaging modalities, such as Apparent Diffusion Coefficient (ADC) images and Cerebral Vascular Reactivity (CVR) images as well as histology are also performed on the MCAO rat brain to longitudinally study the reperfusion injury (Chapter 7). Finally, the major conclusions are summarized and the future prospects are discussed and proposed in Chapter 8. In conclusion, the SR-T1 method developed and applied in this thesis should provide an alternative, noninvasive and reliable neuroimaging tool to study CBF change and BOLD under both physiological and pathological conditions.