The main objective of this study was to demonstrate that computational fluid dynamics (CFD) modeling can be used to study the contribution of covert and overt vascular architecture to the risk for cerebrovascular disease in sickle cell disease (SCD) and to determine the mechanisms of response to therapy such as chronic red blood cell (cRBC) transfusions. We analyzed baseline (screening), pre-randomization and study exit magnetic resonance angiogram (MRA) images from 10 (5 each from the transfusion and observation arms) pediatric sickle SCD participants in the silent cerebral infarct transfusion (SIT) trial using CFD modeling. We reconstructed the intracranial portion of the internal carotid artery and branches and extracted the geometry using 3D Slicer. We cut specific portions of the large intracranial artery to include segments of the internal carotid, middle, anterior, and posterior cerebral arteries such that the vessel segment analyzed extended from the intracranial beginning of the internal carotid artery up to immediately after (~0.25 inches) the middle cerebral artery branching point. Cut models were imported into Ansys 2021R2/2022R1 and laminar and time-dependent flow simulation was performed. Change in time averaged mean velocity, wall shear stress, and vessel tortuosity were compared between the observation and cRBC arms. We did not observe a correlation between time averaged mean velocity (TAMV) and mean transcranial Doppler (TCD) velocity at study entry. There was also no difference in change in time average mean velocity, wall shear stress (WSS), and vessel tortuosity between the observation and cRBC transfusion arms. WSS and TAMV were abnormal for 2 (developed TIA) out of the 3 participants (one participant had silent cerebral infarctions) that developed neurovascular outcomes. CFD approaches allow for the evaluation of vascular topology and hemodynamics in SCD using MRA images. In this proof of principle study, we show that CFD could be a useful tool and we intend to carry out future studies with a larger sample to enable more robust conclusions.
For centuries, animal experiments have contributed much to our understanding of mechanisms of human disease, but their value in predicting the effectiveness of drug treatments in the clinic has remained controversial. Animal models, including genetically modified ones and experimentally induced pathologies, often do not accurately reflect disease in humans, and therefore do not predict with sufficient certainty what will happen in humans. Organ-on-chip (OOC) technology and bioengineered tissues have emerged as promising alternatives to traditional animal testing for a wide range of applications in biological defence, drug discovery and development, and precision medicine, offering a potential alternative. Recent technological breakthroughs in stem cell and organoid biology, OOC technology, and 3D bioprinting have all contributed to a tremendous progress in our ability to design, assemble and manufacture living organ biomimetic systems that more accurately reflect the structural and functional characteristics of human tissue in vitro, and enable improved predictions of human responses to drugs and environmental stimuli. Here, we provide a historical perspective on the evolution of the field of bioengineering, focusing on the most salient milestones that enabled control of internal and external cell microenvironment. We introduce the concepts of OOCs and Microphysiological systems (MPSs), review various chip designs and microfabrication methods used to construct OOCs, focusing on blood-brain barrier as an example, and discuss existing challenges and limitations. Finally, we provide an overview on emerging strategies for 3D bioprinting of MPSs and comment on the potential role of these devices in precision medicine.
After the independent invention of radar in the early 1930s, the development of radar went rapidly during World War II (1939-1945) when both Axis and Allied forces relied on the system to get an edge over the other. Ever since the war, radar technology has substantially increased in its innovation and capability throughout the years. This paper examines the progress of radar technology following World War II (1939-1945) with an aim to provide a landscape of the prevalent radar system during the war which was mono-pulse tracking radar systems and moving-target indication (MTI) system. After a thorough background study of the past radar system, the paper highlights application of the newer developed Phased Array Radar System which was formulated out through the implementation of the improved capabilities of both prevalent systems. Moreover, the paper provides a brief overview of the modular system and formulates a time frame relating to the development of radar research. Thus, the paper, later on, foresees the prominent future where phased array systems could be expanded to civilian and non-civilian technological research by providing thorough research and comparative analysis. Phased array systems are found to a prominent possible cheaper alternative for the civilian and non-civilian system. It shows prominence to be an effective useful tool for radar systems.
The main objective of this study is to demonstrate proof of principle that computational fluid dynamics (CFD) modeling is a tool for studying the contribution of covert and overt vascular architecture to the risk of cerebrovascular disease in in sickle cell disease (SCD) as well as uncover one or more mechanism of response to therapy such as chronic red blood cell (cRBC) transfusion. We analyzed baseline (screening), pre-randomization and study exit magnetic resonance angiogram (MRA) images from 10 (5 each from the transfusion and observation arms) pediatric sickle SCD participants in the silent cerebral infarct transfusion (SIT) trial, using CFD modeling. We reconstructed the intracranial portion of the internal carotid artery and branches and extracted the geometry using 3D Slicer. We cut specific potions of the large intracranial artery to include segments of the internal carotid, middle, anterior, and posterior cerebral artery such that the vessel segment analyzed extended from the intracranial beginning of the internal carotid artery up to immediately after (~0.25 inches) the middle cerebral artery branching point. Cut models were imported into Ansys 2021R2/2022R1 and laminar and time-dependent flow simulation was performed. Change in time averaged mean velocity, wall shear stress, and vessel tortuosity were compared between the observation and cRBC arm. We did not observe a correlation between time averaged mean velocity (TAMV) and mean transcranial doppler (TCD) velocity at study entry. There was also no difference in change in time average mean velocity, wall shear stress (WSS), and vessel tortuosity between the observation and cRBC transfusion arms. WSS and TAMV were abnormal for 2 (developed TIA) out of the 3 participants (one participant had SCI) that developed neurovascular outcomes. CFD approaches allows for the evaluation of vascular topology and hemodynamics in SCD using MRA images. In this proof of principle study, we show that CFD could be a useful tool and we intend to carry out future studies with a larger sample to enable more robust conclusions.
The blood-brain barrier (BBB) restricts the penetration of therapeutic agents to the brain. Focused ultrasound (FUS) insonation of microbubbles has enhanced drug delivery via a temporary opening of the tight junctions of the BBB. Rodents are often used for testing novel therapeutic strategies. However, biological discrepancies existing between rodents and humans impedes the translation of some results. We investigated the effect of FUS transient disruption of a human microphysiological model of the BBB consisting of human brain endothelial cells cultured within a 3D-bio printed scaffold designed to reconstitute the architecture of a perfused blood vessel. Cavitation activity was detected in the model when perfused with Lumason microbubbles and exposed to 500 kHz ultrasound at 0.4 MPa for 10 ms pulse duration and 2 Hz pulse repetition frequency. An increase in extravasation of a dye beyond the endothelial layer was detected within 2–3 h of ultrasound insonation. Our results support that this system could be used for targeted BBB opening with a human cell culture model. Moreover, this system holds a promise to further the translational study on US-mediated drug delivery and the development of personalized therapies for patients with brain cancer and other neurovascular disorders.
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