Mathematical Modeling of 18^{18}F-Fluoromisonidazole (18^{18}F-FMISO) Radiopharmaceutical Transport in Vascularized Solid Tumors

$^{18}$F-Fluoromisonidazole ($^{18}$F-FMISO) is a highly promising positron emission tomography radiopharmaceutical for identifying hypoxic regions in solid tumors. This research employs spatiotemporal multi-scale mathematical modeling to explore how different levels of angiogenesis influence the transport of radiopharmaceuticals within tumors. In this study, two tumor geometries with heterogeneous and uniform distributions of capillary networks were employed to incorporate varying degrees of microvascular density. The synthetic image of the heterogeneous and vascularized tumor was generated by simulating the angiogenesis process. The proposed multi-scale spatiotemporal model accounts for intricate physiological and biochemical factors within the tumor microenvironment, such as the transvascular transport of the radiopharmaceutical agent, its movement into the interstitial space by diffusion and convection mechanisms, and ultimately its uptake by tumor cells. Results showed that both quantitative and semi-quantitative metrics of $^{18}$F-FMISO uptake differ spatially and temporally at different stages during tumor growth. The presence of a high microvascular density in uniformly vascularized tumor increases cellular uptake, as it allows for more efficient release and rapid distribution of radiopharmaceutical molecules. This results in enhanced uptake compared to the heterogeneous vascularized tumor. In both heterogeneous and uniform distribution of microvessels in tumors, the diffusion transport mechanism has a more pronounced than convection. The findings of this study shed light on the transport phenomena behind $^{18}$F-FMISO radiopharmaceutical distribution and its delivery in the tumor microenvironment, aiding oncologists in their routine decision-making processes

Radiopharmaceutical transport in solid tumors via a 3-dimensional image-based spatiotemporal model

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Towards principled design of cancer nanomedicine to accelerate clinical translation

Nanotechnology in medical applications, especially in oncology as drug delivery systems, has recently shown promising results. However, although these advances have been promising in the pre-clinical stages, the clinical translation of this technology is challenging. To create drug delivery systems with increased treatment efficacy for clinical translation, the physicochemical characteristics of nanoparticles such as size, shape, elasticity (flexibility/rigidity), surface chemistry, and surface charge can be specified to optimize efficiency for a given application. Consequently, interdisciplinary researchers have focused on producing biocompatible materials, production technologies, or new formulations for efficient loading, and high stability. The effects of design parameters can be studied in vitro, in vivo, or using computational models, with the goal of understanding how they affect nanoparticle biophysics and their interactions with cells. The present review summarizes the advances and technologies in the production and design of cancer nanomedicines to achieve clinical translation and commercialization. We also highlight existing challenges and opportunities in the field

A comprehensive study of geothermal heating and cooling systems

The final publication is available at Elsevier via https://doi.org/10.1016/j.scs.2018.09.036� 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/Geothermal heat is an energy source that is local, reliable, resilient, environmentally-friendly, and sustainable. This natural energy is produced from the heat within the earth, and has different applications, such as heating and cooling of buildings, generating electricity, providing warm/cold water for agricultural products in greenhouses, and balneological use. Geothermal energy is not dependent on weather or climate and can supply heat and electricity almost continuously throughout the year. It may even be possible to use geothermal projects as �thermal batteries�, wherein waste or collected heat is stored for future use, even seasonal use, making geothermal energy �renewable� at a time scale of years. Extensive research has been carried out on different technologies and applications of geothermal energy, but comprehensive assessment of geothermal heating and cooling systems is relevant because of changing understanding, scale of application, and technology evolution. This study presents a general overview of geothermal heating and cooling systems. We provide an introduction to energy and the environment as well as the relationship between them; a brief history of geothermal energy; a discussion of district energy systems; a review of geothermal heating and cooling systems; a survey of geothermal energy distribution systems; an overview of ground source heat pumps; and, a discussion of ground heat exchangers. Recognition and accommodation of several factors addressed and discussed in our review will enhance the design and implementation of any geothermal heating or cooling system

Numerical Assessment of an Air Cleaner Device under Different Working Conditions in an Indoor Environment

Transmission and spread of exhaled contaminants in the air may cause many airborne infectious diseases. In addition to appropriate ventilation, air cleaner devices are used as one of the most common ways to improve the indoor air quality. Therefore, it is necessary to understand the performance of an air cleaner under different operating conditions. This study mainly concerns investigating the effect of presence or absence of furniture and its displacement on the removal rate of the particles leaving a person’s mouth while coughing in an isolated room. Moreover, the effect of air exit angle of the device on removal rate of contaminated particles and the pattern of their dispersion within a room was studied. To this aim, computational fluid dynamics were employed to examine the mentioned effects by using the Eulerian− Lagrangian method. As the results indicated, when the furniture was placed farther away from the device, more particles were removed by the device. Additionally, the air ejection angle of the air cleaner device significantly affects the removal of particles. Results of the present study could improve use of air cleaner devices for maximum reduction of particles in the indoor environment

Effect of Upstream Side Flow of Wind Turbine on Aerodynamic Noise: Simulation Using Open-Loop Vibration in the Rod in Rod-Airfoil Configuration

Adaptive and flexible control techniques have recently been examined as methods of controlling flow and reducing the potential noise in vertical axis wind turbines. Two-Dimensional (2D) fluid flow simulation around rod-airfoil is addressed in this study as a simple component of the wind turbine by using Unsteady Reynolds Averaged Navier–Stokes (URANS) equations for prediction of noise using Ffowcs Williams-Hawkings (FW-H) analogy. To control the flow and reduce noise, the active controlling vibration rod method is utilized with a maximum displacement ranging from 0.01 C to 1 C (C: airfoil chord). Acoustic assessment indicates that the leading edge of the blade produces noise, that by applying vibration in cylinder, blade noise in 0.1 C and 1 C decreases by 22 dB and 35 dB, respectively. Applying vibration is aerodynamically helpful since it reduces the fluctuations in the airfoil lift force by approximately 48% and those in the rod by about 46%. Strouhal assessment (frequency) shows that application of control is accompanied by 20% increase. Applying vibration in the rod reduces the flow fluctuations around the blade, thus reduces the wind turbine blade noise. This idea, as a simple example, can be used to study the incoming flow to turbines and their blades that are affected by the upstream flow

Synthetic 18F-FDG PET Image Generation Using a Combination of Biomathematical Modeling and Machine Learning

No previous works have attempted to combine generative adversarial network (GAN) architectures and the biomathematical modeling of positron emission tomography (PET) radiotracer uptake in tumors to generate extra training samples. Here, we developed a novel computational model to produce synthetic 18F-fluorodeoxyglucose (18F-FDG) PET images of solid tumors in different stages of progression and angiogenesis. First, a comprehensive biomathematical model is employed for creating tumor-induced angiogenesis, intravascular and extravascular fluid flow, as well as modeling of the transport phenomena and reaction processes of 18F-FDG in a tumor microenvironment. Then, a deep convolutional GAN (DCGAN) model is employed for producing synthetic PET images using 170 input images of 18F-FDG uptake in each of 10 different tumor microvascular networks. The interstitial fluid parameters and spatiotemporal distribution of 18F-FDG uptake in tumor and healthy tissues have been compared against previously published numerical and experimental studies, indicating the accuracy of the model. The structural similarity index measure (SSIM) and peak signal-to-noise ratio (PSNR) of the generated PET sample and the experimental one are 0.72 and 28.53, respectively. Our results demonstrate that a combination of biomathematical modeling and GAN-based augmentation models provides a robust framework for the non-invasive and accurate generation of synthetic PET images of solid tumors in different stages

A spatiotemporal computational model of focused ultrasound heat-induced nano-sized drug delivery system in solid tumors

AbstractFocused Ultrasound (FUS)-triggered nano-sized drug delivery, as a smart stimuli-responsive system for treating solid tumors, is computationally investigated to enhance localized delivery of drug and treatment efficacy. Integration of thermosensitive liposome (TSL), as a doxorubicin (DOX)-loaded nanocarrier, and FUS, provides a promising drug delivery system. A fully coupled partial differential system of equations, including the Helmholtz equation for FUS propagation, bio-heat transfer, interstitial fluid flow, drug transport in tissue and cellular spaces, and a pharmacodynamic model is first presented for this treatment approach. Equations are then solved by finite element methods to calculate intracellular drug concentration and treatment efficacy. The main objective of this study is to present a multi-physics and multi-scale model to simulate drug release, transport, and delivery to solid tumors, followed by an analysis of how FUS exposure time and drug release rate affect these processes. Our findings not only show the capability of model to replicate this therapeutic approach, but also confirm the benefits of this treatment with an improvement of drug aggregation in tumor and reduction of drug delivery in healthy tissue. For instance, the survival fraction of tumor cells after this treatment dropped to 62.4%, because of a large amount of delivered drugs to cancer cells. Next, a combination of three release rates (ultrafast, fast, and slow) and FUS exposure times (10, 30, and 60 min) was examined. Area under curve (AUC) results show that the combination of 30 min FUS exposure and rapid drug release leads to a practical and effective therapeutic response

Fluid Flow and Heat Transfer Analysis of a Nanofluid Containing Motile Gyrotactic Micro-Organisms Passing a Nonlinear Stretching Vertical Sheet in the Presence of a Non-Uniform Magnetic Field; Numerical Approach.

The behavior of a water-based nanofluid containing motile gyrotactic micro-organisms passing an isothermal nonlinear stretching sheet in the presence of a non-uniform magnetic field is studied numerically. The governing partial differential equations including continuity, momentums, energy, concentration of the nanoparticles, and density of motile micro-organisms are converted into a system of the ordinary differential equations via a set of similarity transformations. New set of equations are discretized using the finite difference method and have been linearized by employing the Newton's linearization technique. The tri-diagonal system of algebraic equations from discretization is solved using the well-known Thomas algorithm. The numerical results for profiles of velocity, temperature, nanoparticles concentration and density of motile micro-organisms as well as the local skin friction coefficient Cfx, the local Nusselt number Nux, the local Sherwood number Shx and the local density number of the motile microorganism Nnx are expressed graphically and described in detail. This investigation shows the density number of the motile micro-organisms enhances with rise of M, Gr/Re2, Pe and Ω but it decreases with augment of Rb and n. Also, Sherwood number augments with an increase of M and Gr/Re2, while decreases with n, Rb, Nb and Nr. To show the validity of the current results, a comparison between the present results and the existing literature has been carried out

Computational modeling of PET tracer distribution in solid tumors integrating microvasculature

Background We present computational modeling of positron emission tomography radiotracer uptake with consideration of blood flow and interstitial fluid flow, performing spatiotemporally-coupled modeling of uptake and integrating the microvasculature. In our mathematical modeling, the uptake of fluorodeoxyglucose F-18 (FDG) was simulated based on the Convection–Diffusion–Reaction equation given its high accuracy and reliability in modeling of transport phenomena. In the proposed model, blood flow and interstitial flow are solved simultaneously to calculate interstitial pressure and velocity distribution inside cancer and normal tissues. As a result, the spatiotemporal distribution of the FDG tracer is calculated based on velocity and pressure distributions in both kinds of tissues. Results Interstitial pressure has maximum value in the tumor region compared to surrounding tissue. In addition, interstitial fluid velocity is extremely low in the entire computational domain indicating that convection can be neglected without effecting results noticeably. Furthermore, our results illustrate that the total concentration of FDG in the tumor region is an order of magnitude larger than in surrounding normal tissue, due to lack of functional lymphatic drainage system and also highly-permeable microvessels in tumors. The magnitude of the free tracer and metabolized (phosphorylated) radiotracer concentrations followed very different trends over the entire time period, regardless of tissue type (tumor vs. normal). Conclusion Our spatiotemporally-coupled modeling provides helpful tools towards improved understanding and quantification of in vivo preclinical and clinical studies.Applied Science, Faculty ofMedicine, Faculty ofNon UBCBiomedical Engineering, School ofPhysics and Astronomy, Department ofRadiology, Department ofReviewedFacultyResearche