<p>The work in this thesis deals with pre-clinical development of rapid in vivo ³¹P mag- netic resonance spectroscopy (MRS) techniques. Current MRI literature of ³¹P spec- troscopy presents evidence of increased concentrations of phosphomonoesters (PME), and phosphodiester (PDE) as well as inorganic phosphate concentrations in tumor tissue. Human breast cancer studies have demonstrated correlation between disease progression and both PME and PDE peaks. Furthermore, ³¹P MRS can be used to detect, grade tumours and monitor response to chemo and radiation therapy.<br />Tumor measurements are typically static (i.e. single measurement per scan). In other experiments, on muscle for example, dynamic measures are required the purpose of which is to assess temporal function and recovery. In all ³¹P acquisitions there are problems surrounding RF coil design, pulse sequence speed, localization and system calibration. The work presented here focused on improving all these aspects and provide easy and reliable work flow to use ³¹P MRS in a clinical setting.<br />One of the aspects of this thesis lies in designing and construction of an RF coil that is well suited for integration with a clinical MRI breast imaging and biopsy system. The designed coil was tuned for simultaneous operation at ³¹P (51.73 MHz) and ¹H (127.88MHz) Larmor frequencies. This design has advantages in the fact that complex pulse sequences with heteronuclear decoupling could be performed easily. The additional features of the coil design is that it is possible to swap it into the breast imaging system without moving the patient. Along with the designed coil, custom software was written to assist with transmit gain calibration of ³¹P RF pulses, to ensure maximum MR signal. The automated prescan ensures easy work flow and minimizes the operator variability and patient time inside the MR scanner.<br />Another aspect of this thesis deals with rapid pulse sequence development, to further speed up the ³¹P MRS data acquisition. Echo planar spectroscopic imaging (EPSI) with a fly–back gradient trajectory is currently one of the most reliable and robust techniques for speeding up chemical shift imaging (CSI) acquisitions. A ³¹P EPSI sequence was written to acquire spectroscopic imaging data at 1, 2 and 2.6 cm spatial resolution and spectral bandwidth of 3125 Hz. The sequence showed an ability to speed up data acquisition up to 16 times, where SNR permits.<br />Phantom studies were used to verify the double tuned coil and EPSI sequence en- suring proper and safe operation. In vivo measurements of an exercising muscle demonstrated the ability of ³¹P EPSI to play an important role in rapidly acquiring spatially localized ³¹P spectroscopic data.<br />With these preclinical developments in place a clinical trial is possible using ³¹P MRS rapidly and efficiently. Furthermore the increased usability of ³¹P MRS provided by the tools developed in this thesis can prove to be beneficial by integrating ³¹P MRS into existing clinical protocols.</p> / Doctor of Science (PhD)

<p>Sight-threatening diseases, such as age-related macular degeneration (AMD), affect the tissues of the posterior segment of the eye. Though modern classes of biomolecular based drugs are therapeutically useful, drug targeting for prolonged bioavailability to pathological sites within the eye is challenging. Current delivery approaches are invasive and lack control over drug release rates and tissue-specific localization. In this thesis, a device using microneedles embedded in a flexible platform was developed that could potentially overcome these challenges.</p> <p>New methods for microneedle fabrication were developed by co-opting simple chemical etch methods commonly used for optical probe fabrication as an alternative to current complex and expensive photolithographic technologies to produce out-of-plane, high aspect ratio microneedles which are often constrained materially to silicon and metal. Microneedles with repeatable tip and taper sizes were obtained using hydrofluoric acid, an organic phase and fused-silica capillary tubing. Microneedles with 10 um tips were made using single and batch mode methods and were then integrated into poly (dimethylsiloxane) (PDMS) for alignment using low cost micromolding approaches offering the same degree of accuracy provided by conventional photolithography<strong>. </strong></p> <p>Single microneedle-based devices successfully delivered rhodamine intrasclerally, intravitreally, suprachoroidally and to the retina. This is the first demonstration of active delivery to specific spatial regions within the posterior eye at controllable rates using a non-implantable, biocompatible device – with minimal fabrication facilities, equipment and cost. The fabricated device demonstrated a new hybrid approach of coupling a rigid microneedle with a soft and pliable substrate that could conform to biological tissues.</p> / Doctor of Philosophy (PhD)

<p>Minimally invasive operations have gained popularity over open surgical procedures in the recent years. These procedures, require the surgeon to perform highly specialized tasks including manipulation of tools through small incisions on the surface of the skin while looking at the images that are displayed on a screen. Therefore, effective training is required for the surgeons prior to performing such procedures on patients.</p> <p>In this thesis I explored a novel idea for creating a training system for arthroscopic surgery. Previously obtained CT images of a patient model and the surgical tools are manipulated to create a library of fluoroscopy images. The surgical tools are tracked (a mechanical tracker and an electromagnetic tracker used in each iterations) in order to generate a spacial relationship between the patient model and the surgical tools. The position and orientation information from the tracking system is translated into the image coordinate frame. These homologous points in the two images (of surgical tools and the patient model), are used to co-register and overlay the two images and create a virtual fluoroscopy image.</p> <p>The output image and the system performance was found to be very good and quite similar to that of a fluoroscopy system. The registration accuracy was evaluated using Root Mean Square Target Registration Error (RMS TRE). The RMS TRE for the system setup with the mechanical tracker was evaluated at 2:0 mm, 2:1 mm, and 2:5 mm, for 4, 5, and 6 control points, respectively. In the system setup with the electromagnetic tracking system the RMS TRE was evaluated at 7:6 mm, 12:4 mm, and 11:3 mm, for 5, 7, and 9 control points, respectively. The acceptable range of error for arthroscopy procedures has been proposed to be 1-2 mm.</p> <p>It was concluded that by using a tracking system, which is not prone to interference and allows for a wide range of motion this system can be completed to the point of manufacturing and use in training new surgeons.</p> / Master of Applied Science (MASc)

The Tissue Engineering Lab at California Polytechnic State University San Luis Obispo focuses on creating tissue-engineered Blood Vessel Mimics (BVMs) designed for the preclinical testing of neurovascular devices. These BVMs are composed of silicone models, representing anatomically accurate neurovasculatures, that are sodded with vascular cell types and then cultivated in bioreactors (which maintain physiologic conditions). These silicone models are currently sourced externally from industry partners, so the primary goal of this thesis was to develop the means and methods for the Tissue Engineering Lab to manufacture silicone models in-house. The first aim of this thesis was to develop and explore injection molding as a possible technique for manufacturing silicone models; this included prototyping various designs of molds, developing a viable workflow for injection molding, then assessing the resulting silicone models through measurement characterization, cytotoxicity screening, and BVM set-ups. The first aim found that injection molding was a viable manufacturing technique for making silicone models. The second aim of this thesis explored an alternative manufacturing method, dip-casting, to produce silicone models. The development of dip-casting was similar to injection molding, where several prototyping stages resulted in a viable workflow for making silicone models; the resulting silicone models were then assessed via measurement characterization and a BVM set-up. The second aim found that, in addition to injection molding, dip-casting was a viable technique for making silicone models, although the overall morphology of the resulting models was less desirable than those made by injection molding. The third and final aim of this thesis compared both manufacturing techniques (i.e., injection molding and dip-casting); this aim established that injection molding was preferable for making simple (less intricate) silicone models, whereas dip-casting was preferable for producing complex (more intricate) silicone models. Although the dip-casting technique requires more development to capture complex shapes and produce models with desirable morphologies, the injection molding protocol was formalized into a prescribed workflow for the Tissue Engineering Lab to reference. Overall, this thesis developed and explored two different manufacturing techniques for making silicone models and found that both were capable of making silicone models that could be used to create tissue-engineered BVMs, with injection molded models being ready to implement as the dip-casting process continues to be refined.

Physical activity plays a crucial role in maintaining overall health and reducing the risk of various chronic diseases. Step counting has emerged as a popular method for assessing physical activity levels, given its simplicity and ease of use. However, accurately measuring step counts in free-living environments presents significant challenges, with most activity trackers exhibiting a percent error above 20%. This study aims to address these challenges by creating a machine learning algorithm that leverages activity labels to improve step count accuracy in real-world conditions. Two approaches to balancing data were used: one employed a simpler oversampling technique, while the other adopted a more nuanced approach involving the removal of outliers. Models 1 and 2 were trained on each of these uniquely balanced datasets. Model 1 performed much better than Model 2 on testing datasets, but both achieved better than 20% error on new datasets, indicating their potential for more accurate step counting in real-world conditions. Despite challenges such as data imbalance, the study demonstrated the viability of using activity labels to enhance step counting accuracy. Future research should focus on addressing data imbalances and exploring more advanced machine learning techniques for more reliable activity monitoring.

In the human control of motor vehicles, there are situations regularly encountered wherein the vehicle operator becomes drowsy and fatigued due to the influence of long work days, long driving hours, or low amounts of sleep. Although various methods are currently proposed to detect drowsiness in the operator, they are either obtrusive, expensive, or otherwise impractical. The method of drowsy driving detection through the collection of Steering Wheel Movement (SWM) signals has become an important measure as it lends itself to accurate, effective, and cost-effective drowsiness detection. In this dissertation, novel technologies for drowsiness detection using Inertial Measurement Units (IMUs) are investigated and described. IMUs are an umbrella group of kinetic sensors (including accelerometers and gyroscopes) which transduce physical motions into data. Driving performances were recorded using IMUs as the primary sensors, and the resulting data were used by artificial intelligence algorithms, specifically Support Vector Machines (SVMs) to determine whether or not the individual was still fit to operate a motor vehicle. Results demonstrated high accuracy of the method in classifying drowsiness. It was also shown that the use of a smartphone-based approach to IMU monitoring of drowsiness will result in the initiation of feedback mechanisms upon a positive detection of drowsiness. These feedback mechanisms are intended to notify the driver of their drowsy state, and to dissuade further driving which could lead to crashes and/or fatalities. The novel methods not only demonstrated the ability to qualitatively determine a drivers drowsy state, but they were also low-cost, easy to implement, and unobtrusive to drivers. The efficacy, ease of use, and ease of access to these methods could potentially eliminate many barriers to the implementation of the technologies. Ultimately, it is hoped that these findings will help enhance traveler safety and prevent deaths and injuries to users.

Advanced biomaterials and sophisticated processing technologies aim to fabricate tissue-engineering scaffolds that can predictably interact within a biological environment at a cellular level. Sterilization of such scaffolds is at the core of patient safety and is an important regulatory issue that needs to be addressed prior to clinical translation. In addition, it is crucial that meticulously engineered micro- and nano- structures are preserved after sterilization. Conventional sterilization methods involving heat, steam and radiation are not compatible with engineered polymeric systems because of scaffold degradation and loss of architecture. Using electrospun scaffolds made from polycaprolactone (PCL), a low melting polymer, and employing spores of Bacillus atrophaeus as biological indicators, we compared ethylene oxide, autoclaving and 80% ethanol to a known chemical sterilant, peracetic acid (PAA), for their ability to sterilize as well as their effects on scaffold properties. PAA diluted in 20% ethanol to 1000 ppm or above, sterilized electrospun scaffolds in 15 min at room temperature while maintaining nano-architecture and mechanical properties. Scaffolds treated with PAA at 5000 ppm were rendered hydrophilic, with contact angles reduced to zero degrees. Therefore, PAA can provide economical, rapid and effective sterilization of heat-sensitive polymeric electrospun scaffolds used in tissue-engineering.

Heart failure is expected to ail over 8 million people in America by 2030 leaving many in need of cardiac replacement. To accommodate this large volume of people, ventricular assist devices (VADs) are necessary to provide mechanical circulatory support. Current VADs exhibit issues such as thrombosis and hemolysis caused by large local pressure drops and turbulent flow within the pump. Multiple disk centrifugal pumps (MDCPs) use shearing and centrifugal forces to produce laminar flow patterns and eliminate large pressure drops within the pump which greatly reduce risks that are in current VADs. The MDCP has a shaft drive system (SDS) that causes leakage between the motor and housing that when implanted can cause blood loss, infection, thrombosis and hemolysis. To eliminate these adverse effects, a magnetic external motor-driven system (MEMDS) was implemented. An efficiency study was performed to examine the efficacy of the MEMDS by comparing the hydraulic work of the MDCP to the power required to run the pump. This was done by measuring inlet and outlet pressures, outlet flow rate and input current at various input voltages and resistances. The results showed the MDCP could produce physiologic flow characteristics with a flow rate of 4.90 L/min and outlet pressure of 61.33 mmHg at an impeller speed of 989.79 rpm. Other VADs generate flow rates around 5 L/min at rotational speeds of 2400 rpm for centrifugal pumps and 12000 rpm for axial pumps. When compared to the SDS, the MEMDS exhibited similar efficiencies of 3.89% and 3.50% respectively. This study shows promise in the advancement of MDCP.

Hip resurfacing arthroplasty has changed the treatment of end stage arthritis without severe deformity for young, active adults. Presently, there are varying clinical approaches to implant design selection and cementation techniques. The purpose of this project is to determine what amount of reamer-femoral component offset allows for the best cement penetration into the femoral head. Rapid prototyped femoral component models were produced with reamer femoral component offsets of 0.0 mm, 0.5 mm, and 1.0 mm. After implantation onto models of reamed femoral heads made from high-density open-cell reticulated carbon foam, cement penetration was assessed from cross-sections of the foam-implant unit. Increased offset was found to decrease the extent of cement over penetration from the dome and chamfer. Increased offset also yielded optimal cement penetration as measured from the walls. Finally, increased offset was found to increase the height of cement mantle formation while maintaining complete seating of all implants.

Off-label use of traditional Oropharyngeal Airway (OPA) as a bite-block, and the subsequential procedure of force exertion of the device by physician has caused many cases of patient’s teeth damage and monetary loss, as the patient’s incisors were damaged while clenching on the OPA during an adverse scenario called “Emergency Clenching”. To remedy this harmful situation, Bardo OPA was developed by Dr. Theodore Burdumy. The Bardo airway has unique design to transfer the clenching force from incisor to the molar. However, the Bardo OPA is one-sized, and cannot fit most of the patients like the commonly-used OPAs, such as the Berman and Gudel OPA, which have a spectrum of sizes to ensure fit. In this project, a Computer Assisted Design (CAD) simulation platform was developed to simulate the scenario where OPA is placed in a patient’s oral cavity. CAD – related technique and tools, such as 3D scanner (ScanStudio HD), RapidWorks, SolidWorks and Mimics were utilized to create the models used to construct the platform. The purpose of this platform is to generate data to support the development of additional sizes and other modification to improve the current design of the Bardo OPA. MRI sets of nine (9) patients were obtained and converted into STL mesh models. Berman and Guedel OPA were used as the standard for comparison against the Bardo OPA. It was found that the Bardo OPA was able to fit into all sample patients’ models, while these models were fitted with Berman and Guedel OPA of 70-90mm (Small to medium adult) sizes. It can only be concluded that the Bardo is compatible with these OPA sizes and there was not enough evidence to show the need for additional sizes. Nevertheless, some functional features of the Bardo OPA were found potentially harmful to the patients or ineffective. Three approaches were suggested to improve the design of the Bardo to achieve better safety and efficacy.