ItemHand-Injectable Acrylic Bone Cement Applicator for Skull Base Bone ReplacementGonos, James; Levatich, Mark; Smith, Ryan; Zappacosta, Corinne (2009-05-08T15:20:08Z)One of the only existing procedures to remove brain tumors at the skull base is endoscopic endonasal neurosurgery. The most difficult part of this surgery is closing the hole created in the skull, which currently is solved by stuffing fat and biocompatible foam in the hole and sealing it with glue. A better way of sealing this hole would be to use poly methyl methacrylate (PMMA) so that the hole is replaced with a material which more closely resembles bone. In order to better understand the delivery and application of PMMA bone cement into a patient?s skull through the nasal passages by a surgeon, we modeled three-dimensional viscous fluid flow within a surgical device prototype. The model is comprised of a 5-mm diameter tube with a 1-mm diameter wire running through its center. This wire is secured in place with vertical and horizontal supports. We analyzed the effects of the supports and wire on velocity and pressure drop of PMMA material moving through the tube to see if there was any resistance created in the tube that would be unmanageable by an unaided surgeon. To model the fluid flow, we created a three dimensional geometric schematic of the device in COMSOL. We acquired material properties from related literature and ran multiple simulations with several mesh sizes with COMSOL using the 3-D incompressible Navier-Stokes steady state application mode. The overall goal of this project was to determine if a surgeon could push PMMA through the tube without assistance from machines. Using this model we could then determine the manual pressure needed to administer the PMMA into a patient?s skull at an appropriate velocity. Our results indicated that the amount of applied pressure required would be 1.7 lbf, which is much less than the minimal value (~17 lbf) found in the literature regarding thumb strength. From simulations we obtained multiple velocity profiles and plots of pressure drop. Pressure decreases at a constant rate until the tube bends, the wire is introduced, or fluid passes by an obstruction at each point drop in pressure increases. The total amount of pressure drop in the tube was found to be 380 kPa. As we increased inlet velocity, the required applied pressure increased significantly, but not to a magnitude that would be unbearable to a human thumb. The model also gives valuable insight on the effects of obstructions on continuous, viscous fluid flow in a narrow tube. ItemModeling a Freeze-Thaw Cycle to Treat Lung CancerDugard, Lauren; Hayes, Scott; Holter, Tara; Leviter, Julie (2009-05-08T15:14:50Z)This study examines the effects of pre-freezing on the RF ablation of lung cancer, a widespread disease in the United States. While current treatments utilize cryosurgery or RF ablation to destroy lung tumors, neither method ensures the tumor destruction. Sun et al. (2008) describes an alternative treatment combining both cryosurgery and RF heating techniques, consisting of 10 minutes of pre-freezing with a -150 degrees C probe followed by 30 minutes of RF heating (1). Pre-freezing acts to lower the inactivation energy of the tissue, resulting in an increased radius of tumor death for the same duration of resistive heating. The study aims to examine the effects of pre-freezing on RF ablation surgery of a lung tumor, verify the findings of Sun et al. using COMSOL, and examine the sensitivity of the freeze-thaw procedure to tumor and tissue material properties. COMSOL Multiphysics was used to model the freeze-thaw procedure for a lung tumor with a 16.7 mm radius, in comparison with simple RF heating. Pre-freezing was simulated as heat transfer by conduction with a constant -150 degrees C temperature probe with a 2.5 mm probe radius, and accounted for latent heat in tabulated data for apparent specific heat of the tissue. RF heating was simulated by implementing the voltage equation to account for resistive heat generation in the tissue. Cell radius of tumor death was calculated using an equation for cell death due to heating formulated by Sun et al. (2008). The COMSOL model was verified by comparing the cell death radius to values reported by Sun (2008). The applied voltage was first set to 17.6 V to destroy a tumor radius of 8.7 mm with simple RF heating as observed by Sun et al. (2008). The freeze-thaw procedure was implemented for a range of inactivation energy values from 136 to150 kcal/mol. The energy of inactivation energy required for a tumor death radius of 12.7 mm was143200 cal/mol, a 0.0485% difference from the literature reported of 143,898 cal/mol. For the tumor we modeled in COMSOL, the voltage was adjusted to 20 V to destroy the entire area of tumor and minimize damage to normal tissue. A sensitivity analysis was conducted for thermal conductivity, density, and specific heats of the tissue and tumor, and inactivation energy. The model demonstrated that ten minutes of pre-freezing can increase the effectiveness of RF ablation. This resulted in a larger area of tumor destruction and allows for a lower voltage or reduced duration of probe contact. Furthermore, the material properties of the tumor and surrounding tissue had a minimal effect on the radius of tumor death, suggesting variation between patients and tumor composition would have little effect on the effectiveness of the freeze-thaw treatment. Before the procedure could be used for animal trials or human use, the required voltage for the freeze-thaw treatment of various tumor sizes and geometries must be calculated, and the model should be run using all biologically probable parameters. Nonetheless, the freeze-thaw procedure combines cryosurgical and RF ablation surgical techniques that have already been proven safe and effective for human use. Therefore, the freeze-thaw procedure may improve the outcome of lung cancer cases with minimal cost to develop and comparable patient risk to current treatment procedures. ItemPaclitaxel Drug Elution from a Biodegradable StentLam, Gary; Lee, Jason; Nguyen, Nam; Wu, Kevin (2009-05-08T14:59:49Z)Recently, drug-eluting stents have become a common treatment for coronary heart disease. These stents are usually loaded with a drug that prevents restenosis. Unfortunately, there are risks associated with the placement of these metallic structures in the body. Stent thrombosis is one such problem, and can lead to restenosis despite the presence of drug. Advances in biomaterials have led to the development of biodegradable stents, which can reduce the risks associated with stents. However, since it is a relatively new technology, it is not known to what degree the biodegradability affects the drug releasing properties of the stent. We hope to characterize these effects and to determine if the biodegradability reduces the efficacy of the stent when compared to normal non-degradable stents. To accomplish this, we modeled a stent that diminished in size over time using COMSOL Multiphysics, and monitored the drug concentration in the nearby tissue. We established that our model was a viable predictor of actual stent behavior by comparing our simulated results with previous studies. We were then able to determine the optimal initial loading stent concentration of our modeled drug, paclitaxel, to ensure therapeutic levels in the tissue. Lastly, we found that drug concentrations in the tissue were not substantially different between the degradable and non-degradable models. This affirms the effectiveness of using biodegradable stents, showing them as a viable alternative to traditional metal stents. ItemModeling Heat Transfer in the Eye during Cataract SurgeryAkkar, Sona; Bharadwaj, Koonal; Paya, Naweed; Shai, Adam (2009-05-08T14:55:00Z)Cataract surgery is one of the most commonly performed surgical procedures in the world, and it involves using a technique called phacoemulsification. With this technique, the cloudy, crystalline lens in the eye is mechanically disrupted using a probe that vibrates at an ultrasonic frequency. However, this vibrating tip mechanism leads to frictional heat generation, which can potentially cause extensive thermal damage to fragile tissue structures surrounding the lens. In order to minimize damage due to this frictional heat, a coolant is typically used while the phaco probe is in operation. In this report, our goal is to model heat transfer in the eye using COMSOL Multiphysics software in three different scenarios: (1) under normal physiological conditions, (2) considering only the frictional heat generation from the phaco probe, (3) and considering both heat generation as well as heat removal by the coolant. Using a 2-D axisymmetric geometry to model the eye structure, we determined that using the heat source by itself results in temperatures far above the threshold of 328 K for thermal wound injury. However, with the addition of the coolant for heat removal, temperatures in the iris were lowered to less than 320 K, thereby reducing any thermal burn risk to the patient. Further analysis demonstrated that decreasing the coolant temperature or decreasing the probe?s operational power can significantly improve the safety of the procedure. ItemThe Way to Spray: Modeling Nasal Spray DepositionMahtani, Amrita; Mendoza, Guilly; Yang, Weilin; Zhou, Robin (2009-05-08T14:50:25Z)Intranasal drug delivery is an alternative method in addition to traditional oral and intravenous doses. Nasal drug delivery has proven to be a very effective technique for nicotine cessation (Hjalmarson et al., 1994), the influenza vaccine (Jackson et al. 1999), and drugs that need to be take continuously, such as insulin (Dondeti et al., 1995). Studies have found that for effective fast-acting body response, the drug needs to be deposited in the highly vascularized mucosal tissue lining the bony turbinates in the nasal cavity. Commercial nasal sprays are continuously optimizing parameters to develop the most effective deposition patterns. In this project, drug deposition is modeled using a simplified 2D depiction of the nasal passageway with uniformly-shaped, spherical spray particles. This problem is implemented in COMSOL by using 2D Navier Stokes fluid flow equations to model the airflow through the nose, and the Particle Tracing module to model the spray trajectory and deposition. The model output was validated by determining the percentages of particles in each region of the nasal passage - anterior, turbinate, posterior, and outlet - and comparing with published experimental data by Cheng et al (2001). A sensitivity analysis was done on the following parameters: particle density, particle size, nozzle spray angle, and nozzle penetration depth. It was found that this model was sensitive to only penetration depth. As penetration depth through the nostril increased, there was a decrease in the particle deposition in the anterior region of the nasal cavity and an increase in the percentage of particles that exited through the outlet. Deposition in the middle and posterior regions was not affected by variation in penetration depth. Our sensitivity analysis demonstrated that variations in spray angle, particle size, and density of the nasal spray fluid do not significantly affect deposition pattern. Therefore, when designing nasal sprays, as long as these parameters remain within the specified ranges, consistent deposition patterns will be achieved. This result also allows for further research on creating sprays that are more concentrated and have encapsulated drugs. ItemUse of Microneedle Arrays for the Treatment of Second Degree BurnsCutter, Caitlin; Ince, Aylin; Matlock, Lauren; Rutkowski, Tomasz (2009-05-08T14:39:50Z)Although a hypodermic needle inserted through the stratum corneum, the uppermost layer of skin, and into the tissue can deliver drugs effectively, it can lead to infection and be very painful. Transdermal drug delivery mediated by various microneedle technologies is a less painful method of drug delivery that also limits infection. Also, as with hypodermic needles, the microneedles successfully bypass the thick stratum corneum which is a limiting factor in transdermal drug delivery. One application of this technology is the delivery of pain medication to the skin of burn victims. A drug patch containing ibuprofen can be placed over an array of microneedles inserted into the patient?s damaged skin. In this study, the drug concentration in the burn victim?s dermis over time was modeled using COMSOL software. The effects of initial drug concentration in the patch and spacing between needles of the microarray were examined to develop an optimized model of drug delivery through second degree burns. Initially, a two dimensional model of a single microneedle inserted into the dermis was used to test assumptions made about drug diffusion through burnt skin. A three dimensional model was then constructed to examine the effects of microneedle spacing on the drug concentration profile. To determine the optimal setup, the average drug concentration in the burnt skin was measured while varying initial ibuprofen concentration in the patch and microneedle spacing. The results showed that the patch should contain a 0.4 mol/m3 concentration for a two hour application with 100 micrometer spacing. The optimal microneedle spacing was found to be a nearly linear function of the patch drug concentration the manufacturer aims to use. ItemLaser Hair Removal: Comparative Study of Light Wavelength and its Effect on Laser Hair RemovalCheung, Ling; Mitrea, Diana; Suhrland, Cassandra; Zeng, Henry (2009-05-08T14:35:19Z)For some people, hirsuteness (having excess body hair) can be an embarrassing problem. Many attempts have been made to find a solution to these problems, including electrolysis, tweezing, shaving, and waxing. However, most of these solutions are painful, are not useful in treating large areas of skin, or are not permanent. Laser hair removal stands out amongst these other methods as a permanent method of reducing hirsuteness that can cover large areas of the body, such as the chest or the legs. While laser hair removal is a widely used technology, few studies have explored the physical aspects of why it works so well. More specifically, there is a significant lack of computer models that show how temperature profiles look inside the hair and surrounding skin. Using the physical properties and dimensions of hair, we constructed a model of the hair that approximates how actual hair resides in the skin. Using COMSOL Multiphysics, we tested this model with five different lasers of varying wavelengths in order to determine the relationship between laser wavelength and temperature in the hair. Using a laser pulse duration of 0.01 seconds (10 milliseconds), we found a positive correlation between wavelength and temperature, with all wavelengths except the lowest (595 nm) achieving a temperature above the threshold temperature required for hair destruction. In addition, while all lasers caused a temperature rise in the surrounding skin, the extent of thermal damage was minimal. However, since we could not find physical properties of the hair follicle itself, we were forced to approximate those properties using the hair shaft properties, ultimately leading us to treat the follicle and shaft as one entity. This is a slight limitation with our design. Regardless, we have provided a greater understanding of the physiological temperatures involved in hair removal, and have reinforced the fact that laser hair removal can be a safe method and effective method for treating hirsuteness by showing that hair follicles can be heated to a temperature that kill them by using lasers, and that this heating does not severely or irreparably damage surrounding skin. ItemThe Heat Transfer Modeling for Minimization of Thermal Necrosis in Hip Resurfacing ArthroplastyBaskind, Daniel; Kim, Hyunjin; Min, Flora; Park, Hyeongsu (2009-05-08T14:20:56Z)In the past, the only option for replacing broken or otherwise malfunctioning hip bones was total hip replacement (THR), which involved the removal of the body's natural hip joint and replacing it with an entirely synthetic joint. However, the complications involved with such extensive surgery have led to the push for less invasive therapies. One such idea that has gained popularity for younger patients is hip resurfacing arthroplasty (HRA), which focuses on repairing the joint rather than entirely replacing it. However, there are some issues with HRA, namely thermal bone necrosis due to the heat of polymerization during cement hardening. This paper examines this necrosis as well as the thermal trends of hip resurfacing surgery through the use of COMSOL, a computer aided engineering tool. In COMSOL, a 2D-axisymetric geometry was developed to model the leg bone, cement, ball, cap, and the hipbone. Boundary condition and initial condition was set to portray a realistic surgical environment. With the objective of minimizing bone necrosis, the model's parameters were adjusted to simulate a variety of material properties (different prosthetic material, and different bone conditions), as well as plausible surgical conditions (pre-cooled cement, and convective cooling). Sensitivity analysis was also conducted to gain a better understanding of the thermal tendencies of HRA. Based on the data from these simulations we were able to provide some insight into what approaches may be best for minimizing the extent of the thermal necrosis. The following paragraphs describe the most significant among these conclusions. First of all, we found that precooling the implant from room temperature to 5 degrees C resulted in a drop in the maximum temperature by 7 degrees C. It appears that precooling the cement in addition to the implant had no additional significant temperature reduction. Also, our sensitivity analysis revealed that our system was most sensitive to changes in precooling temperature. All of these factors seem to suggest that precooling may be an effective means for reducing thermal bone necrosis. Secondly, simulations of cancellous bone showed a maximum temperature lower than that of normal bone. As cancellous bone is typical of elderly patients, these results suggest that there is a lower risk of complications due to thermal necrosis during HRA for elderly patients than for younger individuals. Third, when varying our parameters, we often incurred computational failure due to the presence of "hot spots," small regions of the cement that reached extremely high values. Our sensitivity analysis revealed that our system at its default parameter values was extremely close to values that resulted in these hot spots. While it's questionable if these hot spot events are consistent with realistic physics, the topic deserves further investigation considered the potentially damaging results. While our model does not conclusively provide guidelines for reducing thermal necrosis, it does provide some ideas for successful prevention. Computational analysis as a first step helps us understand the thermal effects of HRA and sets the stage for subsequent experimentation. ItemBiodegradable Implant with TGF-beta Delivery for Enhanced Healing of Bone Tissue: A Computational ModelEckes, Kevin; Post, David; Sutermaster, Bryan; Villarreal, Sarah (2009-05-08T14:12:27Z)In most common fractures, bone is able to heal itself over a six week time period. Catastrophic fractures, however, may require that shards of bone be removed surgically, leaving critical size defects in fracture areas that are unable to heal in a reasonable amount of time. For this reason, bone is frequently targeted by tissue engineering and drug delivery strategies aiming to encourage bone regeneration. Often, such strategies involve scaffolds or implants in combination with cells and/or growth factors. One major design requirement in growth factor delivery from such an implant is that it must exhibit controlled growth factor release, defined by relatively constant flux over time. Additionally, the growth factor must remain in the tissue at an effective concentration over the time required for healing. We report on a computational model and analysis of the release of Transforming Growth Factor beta (TGF-beta) from a spherical, collagen-based implant with biodegradable polymer-coated layers containing varying concentrations of TGF-beta. This model, created using COMSOL Multiphysics software, allows for rational design of a biodegradable, drug-eluting implant for tissue regeneration. Using such a model, it is easily possible to simulate a variety of conditions (such as different numbers of layers or different initial concentrations of drug within each layer) in order to achieve relatively constant flux and sustain a physiologically effective concentration of the growth factor over time. The following simulations were run: non-layered construct with uniform growth factor concentration throughout; five-layered sphere with radially increasing concentrations; five-layered sphere with radially decreasing concentrations; ten-layered sphere with radially increasing concentrations; ten-layered sphere with uniform concentration; ten-layered sphere with radially decreasing concentrations. We observed that spheres with more layers exhibited a quasi-linear drug release profile, and that radially increasing initial growth factor concentration in the layers, such that the highest concentration is at the center, results in relatively constant flux. We also show that over time, an implant with radially increasing initial TGF-beta concentration exhibits sustained release within the range of the effective concentration of TGF-beta in hyaline cartilage. Our model is important because it can be used to design drug delivery devices rationally before costly and time-consuming wet-lab experiments are done. Furthermore, our model can be extended to a variety of other drug delivery situations which require construct degradation coupled with controlled release. ItemVaporization of Prostatic Tissue to Treat Benign Prostatic HyperplasiaCurrie, Dan; Griffo, Elaina; Kim, Jin; Wheeling, Sarah (2009-05-08T14:08:21Z)The prostate is a key component of the male reproductive system. Often, due to age, the prostate becomes enlarged resulting in a condition known as Benign Prostatic Hyperplasia (BPH). While pharmacological options are generally the first choice, surgery is sometimes necessary to treat this condition. Laser procedures are ideal because of the decreased risks to the patient, but complications arise when the layer of coagulated tissue created by the laser becomes too thick. An ideal laser wattage and application time must be determined in order to minimize the coagulation layer while achieving an effective level of vaporization. The goal of this simulation was to create a model from which an ideal set of laser parameters for the laser treatment of BPH can be determined. This was achieved using finite-element analysis of the laser heating of a 2-dimensional axisymmetric prostate model using COMSOL Multiphysics software. Using this simulation, the vaporization and coagulation thicknesses in prostatic tissue treated for 5 seconds with a 40W, 80W, or 120W laser, or treated for 1 second with a 60W, 80W or 120W laser were determined. The results indicated that increasing laser wattage and/or application time increases the thickness of vaporized tissue and decreases the thickness of coagulation. Furthermore, the results suggested that the thickness of the coagulation zone converges to a minimum value as wattage and/or application time is increased. This simulation was preliminary; however, this model can ideally be used to determine an ideal laser wattage-application time combination that produces the desired level of vaporization while minimizing tissue coagulation. ItemControlled-Release of Tegretol-XR for Treatment of Epileptic SeizuresCheung, Tracy; Floyd, Laura Autumn; Kim, Sunmin; Velott, Anthony (2009-05-08T13:58:20Z)Fifty million people around the world are currently affected by epilepsy. Fortunately, the disease responds to treatment 70% of the time, but many of the medications prescribed require multiple dosages per day. To ensure patient compliance, prevent adverse consequences due to missed dosing, and to enhance medicative convenience for the patient, Tegretol has engineered as extended-release pill, Tegretol-XR, which delivers carbamazepine at a nearly constant rate for a twelve hour time period. The design of these tablets involves a drug infused matrix surrounded by an insoluble shell, with a small orifice to allow drug release. When water diffuses through the orifice, the interior pill matrix saturates, and carbamazepine begins to elute out of the orifice until depletion, a process that is designed to take twelve hours. Using COMSOL, a Tegretol-XR tablet was modeled as a 2D rectangular, axisymmetrical slab. Researched diffusivity constants were found to precisely model the water and drug flow into and out of the pills. The diffusion of the drug is coupled with the concentration of water, and as the water infuses into the pill, the diffusivity of the drug is altered, ultimately leading to a sustained release of carbamazepine over the allotted twelve hours. Results from our model indicate that drug release closely follows ideal release kinetics and keeps an ample amount of drug in the bloodstream at all times. It was found that altering the orifice size by 5% resulted in changes of up to 16% in final average drug concentration, implicating that this is the most sensitive variable analyzed. Variables like water diffusivity were much less influential to the final solution. Our model of Tegretol-XR gives epileptic patients the option of taking only two pills a day, and thus, significantly lowers the risk of a missed dose. ItemConvection Enhanced Drug Delivery for the Treatment of Brain GliomasBrennan, James; Colangelo, Nicholas; Pendery, Leslie; Skeans, Weston (2009-05-08T13:49:21Z)Malignant brain gliomas are almost always fatal, with a five year survival rate of only 3%. This is due in part to the difficulty of treating tumors chemically or surgically. They are often deep within the brain, where drugs cannot easily diffusive due to the blood-brain barrier and where surgery could be deadly. Emerging techniques for improved treatment include direct infusion of treatment drugs, like Paclitaxel, into the tumor in a procedure known as convection-enhanced drug delivery. These procedures require days of carefully monitored infusion to ensure tumor destruction while preserving surrounding tissue. To better understand the drug distribution and dosing options for different tumor sizes without dangerous medical tests, we have modeled the drug distribution within the tumor and surrounding tissue computationally. The model shows drug distributions consistent with current clinical results after a five day procedure. This model could now be used to better define dosing levels and procedure parameters to maximize tumor removal while preserving healthy tissue in individually unique cases.