Matching Items (4)
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- All Subjects: Drug Delivery
- Creators: Caplan, Michael
Description
A cerebral aneurysm is an abnormal ballooning of the blood vessel wall in the brain that occurs in approximately 6% of the general population. When a cerebral aneurysm ruptures, the subsequent damage is lethal damage in nearly 50% of cases. Over the past decade, endovascular treatment has emerged as an effective treatment option for cerebral aneurysms that is far less invasive than conventional surgical options. Nonetheless, the rate of successful treatment is as low as 50% for certain types of aneurysms. Treatment success has been correlated with favorable post-treatment hemodynamics. However, current understanding of the effects of endovascular treatment parameters on post-treatment hemodynamics is limited. This limitation is due in part to current challenges in in vivo flow measurement techniques. Improved understanding of post-treatment hemodynamics can lead to more effective treatments. However, the effects of treatment on hemodynamics may be patient-specific and thus, accurate tools that can predict hemodynamics on a case by case basis are also required for improving outcomes.Accordingly, the main objectives of this work were 1) to develop computational tools for predicting post-treatment hemodynamics and 2) to build a foundation of understanding on the effects of controllable treatment parameters on cerebral aneurysm hemodynamics. Experimental flow measurement techniques, using particle image velocimetry, were first developed for acquiring flow data in cerebral aneurysm models treated with an endovascular device. The experimental data were then used to guide the development of novel computational tools, which consider the physical properties, design specifications, and deployment mechanics of endovascular devices to simulate post-treatment hemodynamics. The effects of different endovascular treatment parameters on cerebral aneurysm hemodynamics were then characterized under controlled conditions. Lastly, application of the computational tools for interventional planning was demonstrated through the evaluation of two patient cases.
ContributorsBabiker, M. Haithem (Author) / Frakes, David H (Thesis advisor) / Adrian, Ronald (Committee member) / Caplan, Michael (Committee member) / Chong, Brian (Committee member) / Vernon, Brent (Committee member) / Arizona State University (Publisher)
Created2013
Description
Imaging analysis of local drug delivery is important because in both studies involving chemotherapy targeted toward glioblastoma and antimicrobial addressing infection, the drug concentration and distribution are unknown. There are a variety of studies focused on the local delivery of drug to a targeted location, but we are presenting a way of quantifying the concentration of the drug and the distribution of the drug during a period of time. This study aims to do that by utilizing Materialise Mimics to analyze the MRI images of local drug delivery in glioblastoma in canines and antimicrobial gel in rabbit femurs. The focus of the technique is to register the anatomy in T1-weighted spin echo images to the drug delivery in T2 flow attenuated inversion recovery (FLAIR) images in order to see where the drug went and did not go relative to the anatomical part. Both studies focus on addressing effective volumes of drug to a designated anatomical area, in which the delivery can be difficult as it involves bypassing the blood brain barrier in the first study and achieving effective volumes while preventing toxicity to the kidneys in the second study. The goal of this project lies in determining the drug volumes and location for the specified duration and anatomical part.
ContributorsJehng, Hope (Author) / Caplan, Michael (Thesis director) / Sirianni, Rachael (Committee member) / Chemical Engineering Program (Contributor) / School of International Letters and Cultures (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
The concentration necessary to kill bacterial biofilms with antimicrobials is the minimum biofilm eradication concentration (MBEC). This is usually determined using an in vitro approach and will vary within different strains of bacteria. Biomedical implants produce biofilm-related infections presenting a unique challenge due to the combination of subpopulations of the bacterial community and the polysaccharide matrix presented by biofilms. The purpose of this investigation is to determine how exposure times in the order of weeks to months affect the MBEC. Using an in vitro approach, Staphylococcus aureus (UAMS-1) and methicillin-resistant Staphylococcus aureus (MRSA) biofilms were produced with a 24 hour growth time and exposed to two antimicrobials, tobramycin and vancomycin, and one combination treatment that consisted of 1:1 tobramycin: vancomycin by weight. Crystal violet screening was used in order to ensure the integrity of the biofilm matrix throughout the full time of exposure. It was determined that UAMS-1 MBECs were lowered after 56 days of exposure than after 5 days for all three treatment groups. MRSA MBECs after 5 days of exposure decreased only with in vancomycin treatment group.
ContributorsSteinhauff, Douglas Busch (Author) / Caplan, Michael (Thesis director) / Overstreet, Derek (Committee member) / Castaneda, Paulo (Committee member) / Materials Science and Engineering Program (Contributor) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Annually, approximately 1.7 million people suffer a traumatic brain injury (TBI) in the United States. After initial insult, a TBI persists as a series of molecular and cellular events that lead to cognitive and motor deficits which have no treatment. In addition, the injured brain activates the regenerative niches of the adult brain presumably to reduce damage. The subventricular zone (SVZ) niche contains neural progenitor cells (NPCs) that generate astrocytes, oligodendrocyte, and neuroblasts. Following TBI, the injury microenvironment secretes signaling molecules like stromal cell derived factor-1a (SDF-1a). SDF-1a gradients from the injury contribute to the redirection of neuroblasts from the SVZ towards the lesion which may differentiate into neurons and integrate into existing circuitry. This repair mechanism is transient and does not lead to complete recovery of damaged tissue. Further, the mechanism by which SDF-1a gradients reach SVZ cells is not fully understood. To prolong NPC recruitment to the injured brain, exogenous SDF-1a delivery strategies have been employed. Increases in cell recruitment following stroke, spinal cord injury, and TBI have been demonstrated following SDF-1a delivery. Exogenous delivery of SDF-1a is limited by its 28-minute half-life and clearance from the injury microenvironment. Biomaterials-based delivery improves stability of molecules like SDF-1a and offer control of its release.
This dissertation investigates SDF-1a delivery strategies for neural regeneration in three ways: 1) elucidating the mechanisms of spatiotemporal SDF-1a signaling across the brain, 2) developing a tunable biomaterials system for SDF-1a delivery to the brain, 3) investigating SDF-1a delivery on SVZ-derived cell migration following TBI. Using in vitro, in vivo, and in silico analyses, autocrine/paracrine signaling was necessary to produce SDF-1a gradients in the brain. Native cell types engaged in autocrine/paracrine signaling. A microfluidics device generated injectable hyaluronic-based microgels that released SDF-1a peptide via enzymatic cleavage. Microgels (±SDF-1a peptide) were injected 7 days post-TBI in a mouse model and evaluated for NPC migration 7 days later using immunohistochemistry. Initial staining suggested complex presence of astrocytes, NPCs, and neuroblasts throughout the frontoparietal cortex.
Advancement of chemokine delivery was demonstrated by uncovering endogenous chemokine propagation in the brain, generating new approaches to maximize chemokine-based neural regeneration.
ContributorsHickey, Kassondra (Author) / Stabenfeldt, Sarah E (Thesis advisor) / Holloway, Julianne (Committee member) / Caplan, Michael (Committee member) / Brafman, David (Committee member) / Newbern, Jason (Committee member) / Arizona State University (Publisher)
Created2021