BEE 4530 - 2014 Student Papers

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https://hdl.handle.net/1813/36372

This is a collection of student research papers for Professor Ashim Datta's Biomed BEE 4530/Computer-aided Engineering course for 2014.

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Modeling Dye Assisted Photocoagulation of Age-Related Macular Degeneration
Cadesky, Lee; Suh, Jun Hyuk; Tian, Hongyi (2014-05-28)
Age-related macular degeneration (AMD) is major cause of blindness in Americans aged 50 years and up. In 2010, there were more than 2 million cases of AMD in the United States and the National Eye Institute projects that there will be nearly 5.5 million cases per year by 2050. The more detrimental form of AMD, the “wet” form, is caused by the development of new blood vessels within the macular region of the eye, a condition known as choroidal neovascularization (CNV). Several treatment modalities are available for AMD, however the most common is laser photocoagulation in which the abnormal blood vessels are coagulated using a high intensity laser as a heating source. While this treatment modality is effective, high temperatures within the deep eye tissue can cause unwanted collateral damage. Optimizing this thermal treatment thus amounts to minimizing the duration of treatment such that the abnormal blood vessels are destroyed but damage to other tissues is minimized. One possible extension was also explored in this study which is the injection of highly absorbent dye into the abnormal feeder vessel to improve the laser absorbance. The model used in this study employs a 3D Cartesian geometry over which Pennes bioheat equation is solved for the temperature profile over a time scale of 1 second. The thermal damage is then analyzed by observing the temperature history in abnormal and healthy tissue with the goal of achieving a cumulative effective number of minutes at 43oC greater than 80 minutes within the target tissue, the feeder vessel, while minimizing the thermal damage elsewhere. Results from the model suggest that after 1 second of laser application, temperatures in the feeder vessel rapidly rise to a maximum of 67oC and temperatures in the retinal pigment epithelium (RPE) rise to 86oC. In the hottest section of the feeder vessel, that section which is directly exposed to the center of the laser spot, the desired thermal damage is achieved within 0.55 s. The model was assessed for sensitivity to thermal properties as well as the absorbance coefficient, μa, in the feeder vessel and RPE sections. Results from this analysis suggested a change in temperature of less than 0.5% when these parameters were varied within the reasonable limits found in the literature. This suggests good applicability of the results to individual patients. The use of dye to target and improve heat transfer is a novel improvement to the existing photocoagulation process. To assess the efficacy of such a modification, the absorbance coefficient was increased from 4610 m-1 to 9000 m-1 to simulate the effect of the dye. The results show very little variation in feeder vessel temperatures suggesting that dye assisted photocoagulation is not a large improvement from the current process. The effect of blood flow velocity was also assessed in this study. As expected, it was found that increasing blood flow velocity shifted the maximum temperature in the feeder vessel along the direction of flow and resulted in slightly lower maximum feeder vessel temperatures as the blood cools the feeder vessel by convection. The results of this study suggest that shorter treatment times may be useful in reducing collateral tissue damage, however a treatment time of 1 second is justified as a margin of safety to ensure complete destruction of the desired tissue.
Modeling Heat Exchange in Spatial Steering of Deep Brain Stimulation
Mitchell, Matthew; Barghouthi, Khalid; Rebec, Mihailo (2014-05-28)
Deep brain stimulation (DBS) is a treatment that involves insertion of a probe and stimulation of brain tissue with an electric potential (or injection of current). Electrical stimulation has been demonstrated to be an effective treatment in a variety of neurological conditions, serving to relieve motor-symptoms and tremors in advanced stage Parkinson’s disease and Essential tremor. Current DBS therapy involves electrically stimulating a specific region of the brain symmetrically about the probe lead via pulses of electrical potential. Currently-used leads apply potential symmetrically about the cylindrical probe’s central axis. This, however, is problematic, since stimulation needs to be highly specific, yet there is little that can be done to alter the applied electric field after the probes have been implanted. Asymmetric stimulation, on the other hand, allows increased control over direction within these complex regions of the brain, affording more targeted stimulation following the implantation procedure. A problem with any form of electrical stimulation, however, is heating. Even a 1 °C change in temperature can cause adverse effects due to strong membrane potential and pump kinetics dependence on temperature. Heat is generated due to both Joule heat from the applied potential and through increased metabolism rates caused by physiological shifts in neurons influenced by the stimulation. Our project focused on creating a computer model of electrothermal deep brain stimulation utilizing a novel probe design based upon the one proposed in Martens, et al in order to ensure safety and efficacy of this probe. We created a 3D model in COMSOL representing a probe capable of asymmetric heating. A symmetric configuration of our model showed a similar temperature distribution to both computational models and experimental measurements made by Elwassif et al., as well as a similar electric potential profile to models by Martens, et al, demonstrating validity of our computational model. Stimulation due to asymmetric stimulation showed almost no significant temperature increase in the unstimulated direction when the probe was asymmetrically activated, and ultimately ensured safe deep brain stimulation and effective temperature and voltage control. The sensitivity analysis showed that voltage was the most important factor for temperature distribution. Because of this, we believe that optimization should be based on an individuals’ symptoms and geometry at which the probe is implanted. Models like ours lead to better understanding of heat distribution under asymmetric stimulation and more affective deep brain steering stimulation, ultimately leading to higher success rates for suffering neurological conditions and decreasing likelihood of brain damage.
Modeling the In Vivo Corrosion of Magnesium Alloys: A Biodegradable Alternative to Traditional Orthopedic Implants
Botto, Anna; Jain, Nina; Khan, Haadea; Man, Liza (2014-05-28)
Magnesium offers a promising alternative to traditional orthopedic implant materials, as it is both biodegradable and osteoconductive. Like traditional implants, magnesium has the mechanical properties necessary to support the surrounding tissue as it heals. Magnesium corrodes when placed into the body, and its osteoconductive properties allow it to be replaced by native bone, eliminating the need for further surgery. The main concern is that pure magnesium implants have been found to degrade too rapidly when studied in vitro. This may lead to catastrophic loss of mechanical integrity as well as potentially lethal production of magnesium ions, hydroxide ions, magnesium hydroxide, and hydrogen gas—all byproducts of the corrosion process. No animal studies using pure magnesium implants have been conducted. However, the magnesium alloy, LAE442, which as been studied in animal models, has been shown to have a slower corrosion rate when compared to pure magnesium in vitro models. Our goal for this study was twofold; we aimed to 1) determine the time required for complete corrosion of both materials after implantation and 2) monitor the concentrations of magnesium ions, hydroxide ions, and magnesium hydroxide as they were affected by the corrosion of both the pure magnesium and LAE442 implants. We developed a two-dimensional axisymmetric model of a rod implanted into the medullary cavity of a human femur using COMSOL Multiphysics 4.3b. Our computational domain consisted of the bone tissue that surrounded the implant. As the implant degraded over time, the boundary between the bone and the implant moved inward toward the axis of symmetry. There was also a corresponding flux of magnesium ions across this boundary, allowing us to model the diffusion and reaction of magnesium ions, hydroxide ions, and magnesium hydroxide in the bone. The main difference between the model of the pure magnesium and that of the LAE442 implant was that the velocity of the moving boundary and the flux of magnesium ions across the implant-bone interface were smaller in the latter model. Since the corrosion rate of the pure magnesium implant was faster than that of the LAE442 alloy, the pure magnesium implant completely degraded in 182 days, compared to 1570 days for the alloy. Due to this faster corrosion rate, there was a greater build-up of magnesium ions and magnesium hydroxide in the pure magnesium model than from the LAE442 alloy after 28 days. For both of these species, the highest concentrations occurred at the point where the line of planar symmetry intersected with the implant-bone interface. The hydroxide ion concentration, however, was lower in the pure magnesium model since the greater build up of magnesium ions lead to a faster consumption of hydroxide ions. The highest hydroxide ion concentration in both models was found at the outer edge of the femur, furthest from the implant. While our model indicated that the decrease in hydroxide concentration was small enough to prevent formation of a toxic acidic environment, our results also indicated that both implants resulted in intolerable concentrations of hydrogen gas. Therefore, neither the pure magnesium nor the LAE442 alloy implants are safe for use in human patients. Further work to develop a slower corroding magnesium alloy is necessary.
Application of Computational Tear Flow Models to Smart Contact Lens Design
Ashley, Ryan; Fida, Marsela; Li, Jeffrey; Ly, Jeffrey (2014-05-28)
Millions of diabetics could benefit from a noninvasive and cheaper method for monitoring their blood glucose. A solution recently popularized by Google makes use of smart contact lenses featuring embedded glucose sensors which can detect and wirelessly transmit their measurements. This technology takes advantage of the glucose present in the aqueous humor of the human eye, which is proportional to the glucose present in the blood. The technology to produce such contact lenses is well established, but few numerical models are available to characterize the system. In particular the tear fluid dynamics responsible for distributing the glucose on the eye surface is not well understood. A model describing this behavior would facilitate the development, optimization, and prototyping of a smart contact lens that diabetic patients can depend on. The goal of this project was to take advantage of 3D computational modeling to optimize glucose sensor placement on a contact lens. Several partial models were implemented to capture aspects of tear flow. An initial computational model was implemented based on a physical prototype [1]. It featured two inlets and one outlet, but did not provide a fully representative model with respect to physiological fluid flow on the eye. However, the experimental values from that project were sufficient to validate the physical accuracy of the computational model. Once this was established, a second model was implemented to take into account tear flow from the lacrimal gland across the eye to the lacrimal ducts. The locations of the inflow and outflow were selected to match physiological eye models [8]. A third model configuration simulates gravitational tear flow from the top eyelid to the bottom [7]. This was implemented as a constant inflow from the upper edge of the lens, and an outflow from the bottom edge. These three different models each captured a single aspect of physiological tear flow, so each predicted different profiles of fluid flow and glucose homogenization times. A combined model was created to weigh all these aspects of tear flow. This combined model was used to optimize locations for a glucose sensor based on glucose equilibration times at different locations within the model. The models were demonstrated to be physically consistent and to be insensitive to the variable physiological parameters of tear flow velocity and glucose diffusivity, as well as to the computational parameter of mesh resolution. Subsequent experiments in the combined model yielded an optimized location for the glucose sensor that fit all the design criteria: avoiding occlusion of vision, providing adequate space for the sensor, and demonstrating fast equilibration time. A new sensor placement was proposed for subsequent design iterations of the lens. This location is closer to the upper eyelid than in the initial physical model. This optimized position decreased concentration equilibration time by 30%. These results demonstrate the utility of computational models in the design of smart contact lenses. In particular the implementation of these models can allow very rapid prototyping of design concepts. These models demonstrate the viability of smart contact lenses and their potential as glucose monitoring solutions for diabetic patients, and to become a suitable alternative to lancet-based glucometers.
Antibiotic Releasing Biodegradable Sutures for the Prevention of Surgical Site Infections
Bowen, Caitlin; Kersbergen, Calvin; Rappazzo, C. Garrett; Weed, Beth (2014-05-28)
Although a necessary component of surgery, sutures have been shown to exhibit an affinity for microbial adherence and colonization. The sutures offer a conduit for bacteria directly into the wound and infection can be difficult to treat post-colonization, even with antibiotics that are traditionally very effective. Infections associated with sutures are often difficult to resolve and require extended hospitalization, therapy, or additional surgical procedures. Drug eluting sutures offer a potential solution to this issue. In order to maximize antibiotic delivery, modeling changes in suture size, placement, and concentration could provide valuable information for surgeons and manufacturers to better develop and implant sutures, reducing the number of surgical site infections (SSIs) and thus morbidity and mortality. Using COMSOL software, we first generated both a 2D and a 3D model of MONOCRYL plus antibiotic sutures in the skin. Next, we modeled antibiotic-release and biodegradation by tracing the distance the drug penetrates into the surrounding tissue while the suture and the antibiotic are simultaneously being degraded by the body’s enzymatic processes. Finally, we adjusted the distance between adjacent sutures and suture size to ensure that the minimum inhibitory concentration (MIC) of triclosan for various bacteria strains was met at the wound site, without increasing the difficulty for surgeons to implant the suture. In our model, we showed the dispersion of antibiotics into the surrounding tissue over time, demonstrating up to what time point the sutures are able to maintain at least the minimum effective concentration level of antibiotic. We show that antibiotic levels sufficient enough to inhibit bacterial growth can be reached in complex environments, such as the skin. Based on our 3D model, the maximum spacing between adjacent 4-0 sutures to maintain a MIC for S. aureus for 72 hours after suture implantation is 2 mm. Suture spacing for other strains of bacteria can be determined through our predictive equations. The duration of antibacterial properties increases as the spacing between sutures is decreased, but increasing the initial concentration of triclosan in the suture does not significantly increase the duration of antibacterial properties of the suture. The suture decreases in volume by 45% seven days after implantation in the skin, indicating proper surface erosion and a significant loss in tensile strength after that time. The integrity of the suture is necessary to keep the wound closed over the entire healing period, preventing bacteria from entering through the open site and entering the tissue and subsequently traveling through the bloodstream. In this model, we reinforce in vivo and in vitro studies that suggest the effectiveness of antibiotic releasing sutures by modeling antibiotic concentrations in the skin following suture placement. This model will help surgeons determine the spacing for a variety of commercially available sutures, based on the bacterial inhibition properties required, in an effort to reduce the number of surgical site infections that occur. By ensuring effective distribution of antibiotic, following our developed standards in the surgical suite will reduce the number of surgical site infections, significantly reducing costs, morbidity, and mortality from post-operative infections.
Modeling Ultrafast Laser Ablation on the Glenoid Bone for the Fitting of a Prosthetic Screw
Laibangyang, Anya; Liang, Allison; Wang, Jingyu; Wu, Xiaowei (2014-05-28)
In order to fit prosthetic screws, mechanical drilling of the bone has been the norm since the development of modern surgery. However, bone reabsorption, hyperthermia and thermo necrosis could occur depending on the exposure time to the drill and elevated temperature in the surrounding bone due to friction and drill pressure. Non-contact ablation using a CO2 laser can potentially increase the accuracy of the bone drilling and reduce the amount of friction applied to the bone, thus reducing the thermal effects on the surrounding tissue. A model of laser ablation of the human glenoid bone was done on COMSOL with a governing equation of transient state heat transfer from laser to bone. This heat transfer was then correlated to bone loss. According to previous studies, bone disintegration occurs at approximately 613 Kelvin. The bone’s geometry was simplified to a 2-D axisymmetric cylinder. The two domains of the 5mm deep screw region were also 2D-axisymmetric cylinders with varying radius and depth. The phase field model was used to take into account the ablation process of bone. Because the bone essentially disintegrates into “gas-like” particles after reaching this temperature, the phase field model was used to determine the downward velocity of the “air-bone” interface. An adaptive mesh was also developed to move in conjunction with the moving interface. The laser pattern consisted of consecutive concentric cylindrical shells, with the first pulse at the center of the targeted ablated site and the following pulses were cylindrical shells of increasing area. However, because the radial scanning speed was extremely small compared to the pulse duration, concentric cylindrical shells were assumed to occur simultaneously, creating a constant area of laser ablation for each of the two screw domains. Because the CO2 laser did not have a significant penetration depth as the heat generated by the laser was absorbed mainly at the bone surface, input laser heating was modeled as constant flux. Finally, the modeling results for laser ablation were compared to factors in mechanical bone drilling. By varying the input flux of the laser within a range of 300 W/cm2 to 1200 W/cm2 and measuring the total ablation time and the total damage in the surrounding tissue, an optimal flux range between 1050 W/cm2 and 1100 W/cm2 was found to minimize the end time (approximately 0.55 seconds) and thermal damage to the surrounding bone (3.5 mm3). Compared to mechanical drilling, laser ablation with the optimized flux value was much faster than mechanical drilling which can drill at approximately 0.33 mm per second. Generally, less surgery time decreases a patient’s risk when under anesthesia. An increased amount of thermal damage may also lead to refractures, loosening of the prosthetic and permanent loss of tissue function. As laser ablation minimized both these parameters, this model demonstrates that laser ablation of bone is a viable method to consider in future surgical orthopedic work.
A Computational Model of Oral Transmucosal Carvedilol Delivery
Jarmas, Alison; Ly, Olivia; Tang, Lauren; Zhao, Heming (2014-05-26)
In the past few decades, there has been a rapid growth in alternative drug delivery routes. The oral cavity has gained attention as an attractive drug delivery site because it enhances drug bioavailability, allows for rapid transport to the systemic circulation, and provides a convenient delivery route. The buccal mucosa is one of the most common routes for oral drug delivery because it is relatively permeable and robust in comparison to other mucosal tissues. The buccal mucosa offers a large surface for absorption, allows for prolonged localized therapy, and avoids first-pass metabolism effects and degradation in the gastrointestinal environment. One potential form of buccal drug therapy currently being investigated is the application of bioadhesive polymer patches to the buccal region of the mouth. Direct contact between a patch and the buccal mucosa allows a drug concentration gradient to favor diffusion into the tissue. Researchers have recently begun to use this innovative method of drug delivery with carvedilol, a non-selective β-adrenergic antagonist used to treat heart failure and high blood pressure. Recent studies have investigated the formulation of bioadhesive patches of carvedilol. The goals of the project are to model drug delivery from a biodegradable carvedilol patch prepared with the PLGA polymer and optimize carvedilol concentration in the blood. The COMSOL Multiphysics 4.3 simulation software was used to model drug diffusion through the buccal mucosa and solve the governing equations used in our simulation. Drug diffusion was modeled using the species mass transport equation through a two-dimensional cross section including the carvedilol patch and surrounding tissue. Saliva flow over the patch and in the mucus region was modeled with one-dimensional Navier-Stokes fluid flow equations. Concentration and flux profiles over the course of the three hour treatment confirm that carvedilol is able to diffuse from the patch and be delivered to the tissue and bloodstream. Approximately 100% of the patch is delivered within three hours. We evaluated patch efficiency using the concentration in the blood as a fraction of the initial patch concentration. The peak carvedilol concentration is reached at 1.8 hours. Drug degradation in the submucosa results in an observable reduction in carvedilol concentration in the bloodstream. Our results were validated based on cumulative drug release and peak concentration data from in vitro and in vivo studies. Since the availability of property data is limited, we performed sensitivity analysis over a range of diffusivity values and saliva flow velocities. Multiple drugs are currently being evaluated for oral mucosal therapy, but the high costs associated with developing these drug delivery systems have limited commercial availability. Computational fluid dynamics (CFD) modeling is necessary to determine the ideal parameters and properties to maximize drug efficacy and the percentage of drug that leaves the patch in an economical and safe method. Our observations will allow carvedilol treatment to be optimized by investigating initial drug concentration in the patch and treatment time. This computer model could potentially aid the design of clinical trials testing different patch configurations and treatment times.
Optimizing Ultrasonic Intensity for High Intensity Focused Ultrasound Therapy
Carter, Matt; Sullivan, Art; Byers, Kenny; Jessel, Michael (2014-05-28)
Every year as many as one million individuals worldwide are diagnosed with hepatocellular carcinoma (HCC), the most common form of liver cancer. Caused by cirrhosis, HCC is typically treated with surgery or chemotherapy. High intensity focused ultrasound (HIFU) therapy, an emerging treatment option, is a noninvasive alternative to these methods. HIFU targets a cancerous tumor and induces necrosis while reducing damage to surrounding tissue. Acoustic pressure waves propagate from a curved transducer head into the tissue medium. The curved nature of the transducer surface focuses the pressure waves into a selected region and the energy of the beam is converted into heat. HIFU allows for precise targeting of tumor regions and reduced necrosis of healthy tissue. It is easier to control the depth and position of interstitial ultrasound than it is for other interstitial heating methods, such as percutaneous ethanol injection and radiofrequency. This project models the treatment of liver cancer using HIFU therapy. We model the thermal necrosis of a liver tumor caused by an ultrasonic ransducer, and we optimize the process to maximize tumor ablation and minimize tissue damage. The process is modeled in COMSOL Multiphysics using 2-D axisymmetric oordinates which simplifies the tumor geometry as symmetric and includes the HIFU probe and surrounding tissue. Transducer size and parameters are that of the JC-model HIFU transducer from Haifutech, Inc. Relevant tumor and tissue parameters are taken from the literature. Pressure waves are modeled using the Helmholtz equation and heat transfer utilizes the Bioheat Equation. Tumor and tissue ablation are evaluated with a thermal dose equation. Our results show pressure wave propagation focused at the center of the liver tumor. Maximum heating occurs at the tumor center where pressures were the highest and lower temperatures are seen in healthy tissue regions, indicating a proper coupling of the ultrasound and heat transfer physics. A transducer frequency of 1 MHz with a power of 200W and a sonication time of 3.2 seconds maximizes tumor ablation while minimizing healthy tissue damage in a 0.8 cm diameter tumor. This model demonstrates the effective heating of HCC tumors by HIFU, and can be used as a reference for optimizing a heating dose for tumors of known sizes.
Hyperthermia Ablation of Breast Tumors Using Ultrasound
Jin, Shiyi; Wang, Xing; Yuan, Mona; Zheng, Anqi (2014-05-28)
Breast cancer is the most prevalent type of cancer, excluding lung cancer, for women in the United States. Left untreated, a malignant primary tumor in the breast can metastasize via the underarm lymph nodes, increasing risk of death. Invasive surgery techniques such as mastectomy and lumpectomy are used to treat breast cancer. Although breast-conserving therapies are successful in tumor removal, these surgeries still involve radical resection of the tumor, postoperative radiotherapy, and undesirable cosmetic effects. More recently, less invasive techniques such as cryotherapy and hyperthermia have gained wide appeal. One hyperthermia technique, radiofrequency ablation (RFA), delivers high-frequency alternating currents to heat tissue. This technique minimizes pain, avoids infections and scar formations, and reduces recovery time. However, RFA still requires a needle-like probe to be inserted directly into the breast to deliver heat. In contrast to open surgery and RFA techniques, ultrasound hyperthermia is the only non-invasive technique that does not require any incisions or percutaneous insertions. Ultrasound hyperthermia uses focused ultrasound waves to destroy targeted tissue. During this procedure, an ultrasound transducer delivers mechanical energy to tissues, resulting in temperature increase and thus cell death. Magnetic resonance imaging can be used to guide this non-invasive treatment, eliminating the need to insert a probe. Possible side effects of the procedure include local pain, skin burns, and sometimes injury to surrounding tissue. Our goal is to use COMSOL to model an ultrasound hyperthermia treatment of a breast tumor using a 2D axisymmetric geometry. By modeling the acoustic pressure field in the breast and surrounding water, we will determine the optimum combination of applied frequency and time to reach 42-45 °C for tumor destruction while minimizing damage to surrounding tissues. A frequency of 1 MHz will be used as a starting point, for which tissue properties are best defined.
Effects of Cell Phone Radiation on the Head
Cai, Angela; Cho, Youjin; Nguyen, Mytien; Polamraju, Praveen (2014-05-28)
The brain is sensitive to small changes in temperature. Temperature increases may affect enzyme function, leading to possible negative biological effects. Living tissues are dielectric materials, which are subjected to dielectric heating by radiation. A common source of radiation is the cell phone. People often hold cell phones next to their ears, which may exacerbate the effects of radiation, and therein, temperature change. The rate at which tissue absorbs heat from radiation is called the specific absorption rate (SAR). Through observations of SAR values, the thermal effect of the electromagnetic wave heating of superficial tissue within the brain can be quantified. The goal of this project is to model heating of tissue layers in the brain due to cell phone radiation exposure in order to evaluate implications of cell phone usage on brain function. Cranial temperature profiles were studied with varying cell phone distances from the ear, usage durations, and radiation intensities. Cell phone radiation in a model head was simulated in COMSOL Multiphysics 4.3b using governing equations for electromagnetic waves and temperature. Maxwell’s equation for electromagnetic waves was used to determine the electric field and the SAR that would determine heat generation terms. The three-dimensional heat equation was then used to determine the increase in temperature within the brain after a specific period of time. Three dimensions were necessary since there is no symmetry within the head in the presence of a cell phone. To accurately simulate thermoregulatory processes in the head, metabolic heat generation from these tissues and convective blood flow were included in the heat equation. Values for thermal conductivity, skull dimensions, metabolic heat generation, emissivity, radiofrequency, and power dissipation rate were found in relevant literature. In addition, we compared increases in temperature in the brain model with values found in literature to give us an approximation. The results indicate that after two hours of cell phone usage, the maximum increase in brain temperature was slightly greater than 0.2°C in an adult. These results show that there is a minimal effect on cranial temperature by cell phone radiation, even after a significant amount of cell phone usage. The head’s thermoregulatory processes of insulating layers and convective blood flow seem to successfully maintain brain temperature within 0.2°C. Thus, brain function is not severely impacted by the thermal effect of cell phone radiation. However, this model may help develop more accurate guidelines for appropriate cell phone usage.

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