BEE 4530 - 2023 Student Papers
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Item Unleashing the Potential of Photodynamic Therapy (PDT) for Targeted Tumor Treatment Using Magnetic Heat Therapy (MHT) and Hyperbaric Oxygen Treatment (HBOT)Schnell, Evan; Zhang, Kang (2023-05-17)Meningiomas are the most common primary brain tumors in adults. They originate from the dura tissue, which is the closest layer of tissue to the skull, and often develop in the parasagittal region of the brain. Non-specific tumor treatments, including state of the art microsurgical techniques, cannot remove tumor tissue that has infiltrated major blood vessels in the parasagittal region. Tumor specific treatments are needed to eliminate cancerous tissue without damaging essential underlying tissues. Photodynamic Therapy (PDT) is a tumor specific treatment where oxygen molecules (3O2) react with a photosensitizer drug (S0) in the presence of high energy light to produce oxygen free radicals (1O2) that trigger apoptotic pathways. PDT is limited by the effective penetration depth of 3O2 in tissue. The penetration depth of 3O2 in tissue can be increased by maximizing the amount of oxygen carried in the blood and by accelerating the rate at which blood flows within the tissue. In Hyperbaric Oxygen Therapy (HBOT) patients are placed in a high pressure and oxygen environment which leads to massive increases in blood oxygen concentration. In Magnetic Heat Therapy (MHT), magnetic nanoparticles generate heat which is dispersed by increased blood flow within the tissue. The Finite Element Method (FEM) is used to simulate the treatment of a parasagittal meningioma and breakaway layer of cancerous cells within healthy tissue. The effects of PDT/MHT and PDT on patients in a hyperbaric chamber were simulated. Negligible differences were found between treatments as HBOT is sufficient to saturate the tissue with oxygen. Our model corroborates existing literature suggesting that PDT can be used to specifically treat a tumor. A lethal dosage of oxygen free radicals accumulated in both the primary and breakaway cancerous layers following 100 seconds of PDT. The surrounding healthy tissue was left unharmed throughout the procedure. The results suggest that the [S0] remains approximately constant throughout PDT. Future models may treat the [S0] as a constant to greatly reducing the amount of coupling between equations. This allows future models to account for factors including reduced blood flow within tissue that is damaged by PDT. Although there is considerable research on PDT/MHT and PDT/HBOT, no existing literature investigates the potential of PDT/MHT/HBOT for treating brain tumors. The novelty of our project and the ethics involved with studying cancer treatment in human patients reduces the availability of data that can be used for validation of models. Thus, experiments should be conducted to improve the quality of our validation and support or refute the trends identified in our results.Item Thermal Biology: Thermoregulation of the Galapagos Marine IguanaBarrera, Nicole; Ramasray, Neil (2023-05-17)Within the reptilian world, many of these cold-blooded creatures lack a physiological bodily feature known as thermoregulation. This is what allows living creatures to regulate their body temperatures on a homeostatic level. Because creatures like marine iguanas, or more scientifically known as Amblyrhynchus cristatus, lack thermoregulation, they are forced to maintain an internal temperature through other means. In the Galapagos Islands, these means are by basking in the sunlight to heat up whenever they are cold, or by bathing in the ocean water whenever they are too hot. Based on the behaviors that these creatures exhibit, a question that comes across is how often and for how long these creatures exhibit these behaviors.To get a clearer idea of how marine iguanas survive, we decided to understand their behavior mechanistically. We studied the behavior of marine iguanas in the Galapagos and how they react with the environment to regulate their body temperatures since they lack internal thermoregulation. The goal of our project is to model how marine iguanas use their environment to regulate their temperature and determine how long it takes to reach a new thermal steady-state at its ideal body temperature of 36°C after exiting the water. n order to achieve this goal, we decided to model a marine iguana after it has exited the ocean water and is then basking in the sun on a hot molten rock surface in order to heat up. Using results from already existing research combined with background information, we were able to support our analysis by validating the results of our model. Additionally, thorough pre-processing of the proper boundary conditions, governing equations, and estimations for our key variables were used in the model so that in processing, COMSOL was able to solve the heat transfer equations with the provided information. The main governing equation that was used was the heat equation, which is more explicitly defined later in the report. The boundary conditions used were that involving radiation, convection, and evaporation of water on the iguana’s surface as well as conduction of the molten rock through the iguana body. Through post-processing of the 3D heat exchange, the model will be able to provide us with insight as to how the temperature quickly rises in the core of the iguana, of which we defined as its large intestine. Through this analysis, we will be able to gain a better understanding of how external heat sources benefit creatures that lack internal thermoregulation in the natural world. The process being modeled involves an iguana heating itself from an initial temperature out of the water of about 26°C to its ideal body temperature at 36°C through means of external heat sources. Such sources come from heat conduction from the warm igneous rock beneath it, convection from the surrounding environment, and solar flux from the iguana’s sunbathing. The solar flux will take into account the changing sun angle and temperature with time as the process will last a few hours. The result will be an increase in temperature until a new steady-state is reached at the ideal body temperature of 35-37°C at the iguana’s core.Item Hot Cabbage: Thermoregulation in Eastern Skunk CabbageAltera, Ashley; Dressel, Anastacia; van Osselaer, Johannes; Souchet, Nathan (2023-05-17)Maintaining a safe temperature is essential for nearly all forms of life. Animals have developed complex systems to maintain an ideal temperature such as shivering and sweating, but such thermoregulatory systems are not unique animals. The eastern skunk cabbage (Symplocarpus foetidus) utilizes controlled metabolic heating to maintain a specific elevated temperature in its flower. Other plant species have evolved the ability to generate heat, but the skunk cabbage is unique in its ability to maintain its temperature within approximately 1℃ from its ideal 23.6℃, even in variable and freezing conditions. We have mechanistically modeled skunk cabbage thermogenesis by developing a finite element model of heat transfer and fluid flow in the blooming skunk cabbage. The model includes a variable heat generation function which mimics the natural heating behavior under changing outside conditions, allowing for close analysis of the thermoregulatory behavior and the energetic costs of heating. In simulated outside temperatures from 10℃ to -10℃, the generation ranged from 0.07W to 0.17W to maintain ideal temperatures in the center of the flower. This model displays the impact that changes in temperature can have on the skunk cabbage due to the dramatically increased energetic cost of heating at colder temperatures. The complex behavior of the skunk cabbage has evolved to maintain temperatures within an acceptable range at a minimized energetic cost. Understanding this thermoregulatory system provides insights that may be used in future development of surfaces used to prevent ice accumulation and other systems that require low cost thermal regulation.Item Reducing Chemotherapy Induced Alopecia: Scalp Cooling for Reduced Docetaxel TransportPincus, Marlee; Rosin, Mackenzie; Seifert, Julianna (2023-05-17)Since chemotherapy drugs target rapidly dividing cells, hair follicles are often damaged and many cancer patients develop chemotherapy-induced alopecia (CIA). One strategy used to combat hair loss is scalp cooling, where chemotherapy recipients wear a cold cap before, during, and after infusion. Scalp cooling causes vasoconstriction and decreases drug uptake by follicular cells, thus reducing the cells’ overall exposure to the cytotoxic drugs. Our one-dimensional model seeks to understand how the heat transfer of scalp cooling affects the mass transfer of drug diffusion to the hair follicle. We will first model the pre-cooling time, where the cap is placed on the head for thirty minutes before infusion. This will show the temperature drop over time in each layer of the scalp. Then, we will model the transport of the drug during and after the infusion is completed. Drug concentration at the follicle will first increase and then decrease after infusion ends since the drug is metabolized throughout the body and the overall systemic concentration drops. After the model is set up, we will vary the temperature of the cold cap to determine how this affects steady-state temperature and drug concentration at the follicle level. We predicted that by decreasing the upper boundary condition representing the temperature of he cold cap, the scalp would reach lower temperatures and there would be lower drug concentrations at the hair follicle due to a greater degree of vasoconstriction. Our results showed that while the scalp reached lower temperatures, the concentration at the follicle did not change significantly. Decreasing the cold cap temperature only slowed drug transport. This indicates that the physical scenario may not be fully understood and may explain why cold caps have variable efficacy.Item Can You Take the Heat? Model of Temperature and Neuronal Membrane Potential Changes in the Brain Tissue due to Deep Brain StimulationDawson, Cole; Díaz, Ana Paula López Guerrero; Jain, Devanshi; Subhani, Tooba (2023-05-17)In the world, millions of people live with neurological conditions such as epilepsy, Parkinson's or major depression disorder (MDD). As a viable treatment for their symptoms, Deep Brain Stimulation (DBS) was created. This medical procedure involves a surgery where a magnetic probe (neurostimulator) is implanted into a specific region of the brain. There, the electrodes in the probe produce electromagnetic pulses to regulate neuronal activity. Albeit this is a verified and reliable procedure, many unknowns arise from DBS; such as the extent of neuronal activity alterations due to the increase of brain temperature due to electromagnetic stimulation. Hence, the objective of this project is to simulate in COMSOL how DBS can influence the brain tissue in terms of temperature variation and neuronal activation. A 2D model of the thalamic and hypothalamic regions of the brain in contact with the DBS probe was created. The model solved the bioheat equation, the Laplace equation for the voltage of the electrodes, the Nernst equation and Hodgkin-Huxley equation for the membrane potential. To attain an accurate model, the process of validation, verification, mesh convergence and sensitivity analysis were also conducted and included in the paper. The results of the model provided insights on how heat transfer takes place from the probe to the thalamus and the hypothalamus as a result of electrical heating. Essentially, the change in temperature in the tissues considering a point 0.01 mm away from the electrode was of 0.0055 ºC in the thalamic region (starting from the initial temperature of 38.5 ºC in the brain, to 38.5055 ºC), whereas in the hypothalamic region it was 0.0048 ºC (where the peak temperature was 38.5048 ºC), after 1 second of heating. The same analysis was performed for a point 0.73 mm away from the electrode and the temperature change was 0.0023 ºC and 0.0020 ºC for the thalamic and hypothalamic regions respectively. When extended to a minute, the thalamus increased in temperature by around 0.042 ºC. The increase in temperature did not exceed 1 ºC, and thus, it can be inferred that the temperature change was optimal. This was validated by a study made by Elwassif et al., where they modeled a brain temperature increase of nearly 0.8 °C after 15 minutes during DBS. Approximating this rate for 1 minute gives a temperature increase of 0.053 ºC, exceeding the 0.042 ºC observed at the point 0.73 mm away from the electrodes. Additionally, considering that same point, the membrane potential sharply increases from -70 mV, which is the resting membrane potential, all the way to +25 mV. The closer point’s membrane potential experienced an increase to +60 mV, which is the maximum action potential. The membrane potential at both points then continues to periodically oscillate between -35 mV and either +25 or +60 mV, respectively. This oscillation is closely mimicking the changes in membrane potential during normal neuronal activity. The temperature and membrane potential trend with varying distance (along a line), in the tissue domain was also observed, exhibiting expected trends of reduction in values with increasing distance from the electrodes with the highest temperature for the thalamic region being 38.5055 ºC and that for the hypothalamic region being 38.5048 ºC after 1 second of stimulation. The membrane potential along an arc in the tissue domain shows a gradual decrease with a maximum value of 60 mV near the electrode and -35 mV at a distance of 10 mm from the electrode. As both temperature and membrane potential values are directly influenced by the voltage from the electrodes, the trend of the 1.8 V pulse sent by the electrode over distance was also assessed. The voltages at 0.01 mm, 0.73 mm, and 6.73 mm from the electrode were found to be 1.8 V, 1.15 V and 0.15 V respectively. Conclusively, the simulation supports the notion that the voltage from the DBS procedure does have an effect on increasing the temperature and the membrane potential of the brain. These results are significant because DBS can induce a high amount of heat accumulation over time in patients who have undergone the procedure, which can also cause serious side effects which may impact brain function. The results of this study welcome further investigation and this can be done by examining modifications in probe features and placement of electrodes to maximize efficiency and reduce overall increase in brain temperature. A study can also be performed to understand the kind of changes induced in the tissue microenvironment due to increase in temperature. Understanding the dynamics of heat transfer can help estimate which regions of the brain can be highly impacted and how this can be mitigated.Item Got a Bone To Pick? An Investigation Into the Efficacy of Tibial Intraosseous InfusionsHtun, San Lin; Hughes, Sean; Sammartino, Frank; Sheerin, Max (2023-05-20)Intraosseous (IO) infusions are an emergency procedure for injection directly into the bone marrow when other routes of fluid resuscitation are impossible and the patient’s life or limb is at risk. Across the U.S., medical providers and state protocols recommend IO injections when intravenous (IV) access is unavailable. Despite its widespread use in some of the most acutely life-threatening conditions in the emergency room (ER), there is a lack of scientific studies supporting many IO protocols—like injection pressure—for which medical providers are legally obligated to abide by. In this paper, we mechanistically modeled a 15-gauge EZ-IO injection of saline into the proximal tibia of an average human adult to arrive at an evidence-based clinical recommendation for injection pressure. Our model solved the mass transfer equation for the transport of water and the Darcy equation together with the continuity equation for fluid flow in porous media. We modeled the proximal tibia as a 3D cylinder with a linearly varying diameter consisting of bone marrow concentric with a surrounding cortical bone layer. We assumed the tibia was thermally insulated from the rest of the circulatory system for the short time frame of the injection and the saline was pre-heated to body temperature prior to injection. We varied the input pressure for the infusion and reported its effect on both the infusion flow rate and the total volume of water delivered to the patient. Our simulations support the idea that IO injections offer a comparable alternative to IV injections in terms of both flow rate and total water uptake (i.e. patient rehydration). The simulation tracked the concentration of water associated with different injection pressures and found that increased pressure had diminishing returns on the infusion flow rate. From this novel finding, we recommend that IO device manufacturers prioritize using larger bore needle tips with lower inlet pressure to maximize flow rate while minimizing patient pain. Additionally, since our model found that the optimal pressure for a 15-gauge EZ-IO infusion was equivalent to current protocol recommendations (300 mmHg), future tests should model if IO infusion with other fluids and needle gauges produces different results. Moreover, the effectiveness of IO infusion in patients with “abnormal” bone conditions could also be modeled by changing the material properties of the tibia in the simulation, which could ultimately lead to different pressure recommendations depending on the patient’s anatomy and medical condition(s).