Medical Biophysics Commons^™

Mesoscale Structure-Function Relationships In Mitochondrial Transcriptional Condensates, Marina Feric, Azadeh Sarfallah, Furqan Dar, Dmitry Temiakov, Rohit V. Pappu, Tom Misteli

Department of Biochemistry and Molecular Biology Faculty Papers

In live cells, phase separation is thought to organize macromolecules into membraneless structures known as biomolecular condensates. Here, we reconstituted transcription in condensates from purified mitochondrial components using optimized in vitro reaction conditions to probe the structure-function relationships of biomolecular condensates. We find that the core components of the mt-transcription machinery form multiphasic, viscoelastic condensates in vitro. Strikingly, the rates of condensate-mediated transcription are substantially lower than in solution. The condensate-mediated decrease in transcriptional rates is associated with the formation of vesicle-like structures that are driven by the production and accumulation of RNA during transcription. The generation of RNA alters ...

Technical Adaptations For Cardiac Sodium Mri, Taylor L. Marcus

Electronic Thesis and Dissertation Repository

Cardiac sodium (Na⁺) MRI has the potential to unveil relationships between chronic kidney disease (CKD) and cardiovascular disease (CVD). Unfortunately, this modality requires many technical adaptations before it’s possible to extract and compare image data between individuals. This study investigated whether cardiac electrocardiogram (ECG) gating could improve image quality, and whether a uniform phantom could increase signal uniformity if a surface coil is used to acquire the image. Healthy participants were imaged with a custom-built surface coil and 3.0-T MR system. Cardiac gated images presented with a decreased signal-to-noise ratio (SNR), but intensity correction significantly increased image signal ...

Multi-Scale Computational Modeling Of Coronary Blood Flow: Application To Fractional Flow Reserve., Jermiah Joseph

Electronic Thesis and Dissertation Repository

Introduction. Fractional flow reserve (FFR) is presently an invasive coronary clinical index. Non-invasive CT imaging combined with computational coronary flow modelling may reduce the patient’s burden of undergoing invasive testing.

Research statement. The ability to obtain information of the hemodynamic significance of detected lesions would streamline decision making in escalation to invasive angiography.

Methods. A reduced order (lumped parameter) model of the coronary vasculature was further developed. The model was used in the assessment of the roles of structure and function on the FFR. Sophisticated methods were used to elicit numerical

solutions. Further, CT imaging (n = 10) provided multiple ...

Anatomical And Functional Lung Imaging With Volumetric Computed Tomography In Non-Small Cell Lung Cancer, Heather Young

Electronic Thesis and Dissertation Repository

Non-small cell lung cancer (NSCLC) is one of the most diagnosed cancers in Canada, and the leading cause of cancer deaths. A significant challenge in treating NSCLC is balancing aggressive treatment with the potentially severe side effects. In radiation therapy, the management of respiratory motion and the risks of radiation-induced lung injury (RILI) pose significant challenges. 4-dimensional computed tomography (4D-CT) is an important part of motion management, but images often suffer from motion-induced artifacts. Volumetric CT scanners with wide axial field-of-view (aFOV) may reduce these artifacts and present an opportunity to advance CT-based functional lung imaging.

Chapter 2 presents a ...

Atrial Fibrillation And Cognitive Decline: A Computational Hemodynamics Investigation, Timothy J. Hunter

Electronic Thesis and Dissertation Repository

Background: Atrial fibrillation (AF) is a prevalent cardiac disease which has been associated with increased risk of dementia and cognitive decline. We hypothesize that atrial fibrillation leads to regional transient hypoperfusion events in the brain, and that geometric variations in the arterial structure called the Circle of Willis (CoW) play a role in these events.

Methods: A computational model was developed to simulate cerebral blood flow in six common variations of the CoW. Risk was assessed based on frequency of beat-wise regional hypoperfusion events during AF, and sensitivity analysis was performed with respect to this model output.

Results: A key ...

Rheological Characterization Of Blood-Mimicking Fluids For Use In Particle Image Velocimetry, Anorin S. Ali

Undergraduate Student Research Internships Conference

Blood-mimicking fluids (BMFs) are often used to investigate blood flow using physical replicas of vessels with cardiovascular disease. Particle image velocimetry (PIV) is used with silicone poly-dimethyl siloxane (PDMS) vascular models to visualize this flow. The challenge is creating a blood-mimicking fluid that matches the viscosity profile, viscoelasticity, and density of whole blood while also matching the refractive index (RI) of PDMS. Water-glycerol solutions are commonly used with sodium iodide (NaI) added to increase the RI without changing viscosity. However, NaI is expensive, stains easily, and turns fluids from optically clear to yellow in less than a day. Furthermore, without ...

Ex-Smokers With And Without Copd: Investigating Ct Pulmonary Vascular, Airway, Pulmonary Artery And Aorta Measurements, Vedanth Desaigoudar, Paulina V. Wyszkiewicz, Alexander M. Matheson, Maksym Sharma, Marrissa J. Mcintosh, Harkiran K. Kooner, David G. Mccormack, Grace Parraga

Undergraduate Student Research Internships Conference

RATIONALE: Pulmonary hypertension is characterized by increased pressure in the pulmonary artery, and is a key contributor to worsening symptoms in individuals with chronic obstructive pulmonary disease (COPD). The pulmonary artery to aorta diameter ratio (PA:Ao), measured using computed tomography (CT), is a biomarker of pulmonary hypertension; however, longitudinal changes in this measurement and its relationship to pulmonary vascular and airway structural changes is not well understood. Our objective was to investigate longitudinal changes in PA:Ao and its relationship with CT pulmonary vascular and airway abnormalities, airflow limitation and exercise-capacity.

Microvascular Regulation Between Two Hemodynamic Steady States In The Forearm And Forehead Using Wavelet Phase Coherence, Yuki Bao

Undergraduate Student Research Internships Conference

Microvascular mechanisms that regulate the microcirculation can be observed within blood flow as coupled oscillations operating over a wide range of different frequencies and time scales. Abnormally discordant interactions between regulation mechanisms can cause derangement of microvascular flow patterns, which has been suggested to be indicative of increased cardiovascular disease risk. Based on the premise that interactions between microvascular mechanisms are key to understanding flow regulation and disease progression, wavelet-based phase coherence was used to characterize the relationship between cardiac, respiratory, myogenic, neurogenic, and metabolic regulation across different microvascular beds and physiological conditions.

Steady state cutaneous microvascular blood flow data ...

In-Vitro Validation Of Intratumoral Modulation Therapy For Glioblastoma, Abdulla Elsaleh

Undergraduate Student Research Internships Conference

Intratumoral modulation therapy (IMT) is a novel electrotherapy used to treat brain cancer tumours using electric fields applied directly to the tumours through implanted electrodes. Previous research has validated IMT's effectiveness and provided computer-simulated optimizations for IMT electric fields. This work validates these computer optimizations in-vitro, using a PCB construct to deliver electric fields, and bioluminescence imaging to assess cell viability.

We found electric field strength to correlate with cell viability, and found that rotating (phase-shifted) electric fields did not produce significant improvements in IMT efficacy. Future work will investigate different IMT frequencies and other parameters, while providing biological ...

Development Of Advanced Mr-Guided Adaptive Radiation Therapy Methods For Head & Neck Cancers On The 1.5t Mr-Linac, Brigid Mcdonald

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

The 1.5T hybrid MRI/linear accelerator (MR-linac) has recently been introduced into clinical practice and used for the treatment of head and neck cancers (HNC). This device enables on-line adaptive radiation therapy (ART) based on anatomical changes throughout treatment and variations in patient position. This novel technology also has the potential for advanced ART strategies such as dose-optimized ART, in which the treatment plan is optimized based on the accumulated dose over previous fractions, or biological image-guided ART, in which the plan is adapted based on individual tumor response as measured through quantitative imaging techniques such as diffusion-weighted imaging ...

Software And Hardware-Based Tools For Improving Ultrasound Guided Prostate Brachytherapy, Nathan Orlando

Electronic Thesis and Dissertation Repository

Minimally invasive procedures for prostate cancer diagnosis and treatment, including biopsy and brachytherapy, rely on medical imaging such as two-dimensional (2D) and three-dimensional (3D) transrectal ultrasound (TRUS) and magnetic resonance imaging (MRI) for critical tasks such as target definition and diagnosis, treatment guidance, and treatment planning. Use of these imaging modalities introduces challenges including time-consuming manual prostate segmentation, poor needle tip visualization, and variable MR-US cognitive fusion. The objective of this thesis was to develop, validate, and implement software- and hardware-based tools specifically designed for minimally invasive prostate cancer procedures to overcome these challenges.

First, a deep learning-based automatic 3D ...

Quantitative Mri And 3d-Printing For Monitoring Periprosthetic Joint Infection, Greg Hong

Electronic Thesis and Dissertation Repository

Joint replacements are becoming increasingly commonplace with over 130,000 joint arthroplasties being performed annually in Canada. Although joint replacement surgery is highly successful, implants do occasionally fail and need to be replaced via costly and difficult revision surgery. Periprosthetic joint infection (PJI) has recently become the leading reason for revision of both hip and knee replacements, which is unfortunate because PJI is difficult to diagnose and treat effectively; diagnosis is made particularly difficult by the lack of established non-invasive (imaging) means of evaluating PJI. This thesis aims to demonstrate that magnetic resonance imaging (MRI) has potential for diagnosing and ...

Magnetic Resonance Systems Development For Point-Of-Care Mri Platforms, Eric J. Lessard

Electronic Thesis and Dissertation Repository

Magnetic resonance imaging utilizes electromagnets to produce anatomical images in both clinical and research settings. In the race towards increasing performance head-optimized scanners have begun playing a significant role in providing high quality imaging of the head. However, they are implemented using smaller geometries and as such fail to allow entrance of the patient past their shoulders. This is overcome by designing asymmetric gradient coils which have their imaging region located towards one end of the gradient coil, as opposed to the geometric center, allowing brain imaging. There exists interest in compact configurations which allow imaging further into the cervical ...

Three-Dimensional Ultrasound Imaging For Characterization Of Synovitis In First Carpometacarpal Osteoarthritis, Carla Du Toit

Electronic Thesis and Dissertation Repository

First carpometacarpal osteoarthritis is one of the most common forms of OA and is a significant source of pain and disability for patients. Discrepancies between traditional imaging modalities and patient reported outcomes have led galvanized researchers to developing objective point of care based imaging tools for assessing OA progression and treatment response. This thesis aims to describe the development and validation of a semi-submerged mechanical three-dimensional ultrasound device against magnetic resonance imaging. The validation of the 3D US device was conducted on a series of imaging phantoms, as well as ten CMC1 OA patients. Two-raters manually segmented areas of synovial ...

Cost-Effective Non-Destructive Testing Of Biomedical Components Fabricated Using Additive Manufacturing, Santiago Fabian Cobos

Electronic Thesis and Dissertation Repository

Biocompatible titanium-alloys can be used to fabricate patient-specific medical components using additive manufacturing (AM). These novel components have the potential to improve clinical outcomes in various medical scenarios. However, AM introduces stability and repeatability concerns, which are potential roadblocks for its widespread use in the medical sector. Micro-CT imaging for non-destructive testing (NDT) is an effective solution for post-manufacturing quality control of these components. Unfortunately, current micro-CT NDT scanners require expensive infrastructure and hardware, which translates into prohibitively expensive routine NDT. Furthermore, the limited dynamic-range of these scanners can cause severe image artifacts that may compromise the diagnostic value of ...

Seizure Prediction In Epilepsy Patients, Gary Dean Cravens

NSU REACH and IPE Day

Purpose/Objective: Characterize rigorously the preictal period in epilepsy patients to improve the development of seizure prediction techniques. Background/Rationale: 30% of epilepsy patients are not well-controlled on medications and would benefit immensely from reliable seizure prediction. Methods/Methodology: Computational model consisting of in-silico Hodgkin-Huxley neurons arranged in a small-world topology using the Watts-Strogatz algorithm is used to generate synthetic electrocorticographic (ECoG) signals. ECoG data from 18 epilepsy patients is used to validate the model. Unsupervised machine learning is used with both patient and synthetic data to identify potential electrophysiologic biomarkers of the preictal period. Results/Findings: The model has ...

A Retrospective Dosimetry Comparison To Define Uncertainties Found In A Novel Intensity Modulated Electron Therapy (Imet) Treatment Technique For Use In Radiation Therapy, Marco A. Masciantonio

Honors Undergraduate Theses

This study will investigate the difference in radiation at different volumes between traditional electron beam therapy and a novel IMET. The difference in dose will be recorded between the novel IMET and the IMET with a slight shift in the target area. The percent difference between this new model treatment and the model treatment with a shift will be calculated. The main goal of this project is to determine if the target area is still sufficiently treated with this slight shift of the patient in different directions. The percent difference is crucial for the success of this project. It will ...

Deep Convolutional Neural Networks For Accurate Diagnosis Of Covid-19 Patients Using Chest X-Ray Image Databases From Italy, Canada, And The Usa, Amgad A. Salama, Samy H. Darwish, Samir M. Abdel-Mageed, Radwa A. Meshref, Ehab I. Mohamed

The University of Louisville Journal of Respiratory Infections

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), famously known as COVID-19, has quickly become a global pandemic. Chest X-ray (CXR) imaging has proven reliable, fast, and cost-effective for identifying COVID-19 infections, which proceeds to display atypical unilateral patchy infiltration in the lungs like typical pneumonia. We employed the deep convolutional neural network (DCNN) ResNet-34 to detect and classify CXR images from patients with COVID-19 and Viral Pneumonia and Normal Controls.

Methods: We created a single database containing 781 source CXR images from four different international sub-databases: the Società Italiana di Radiologia Medica e Interventistica (SIRM), the GitHub Database, the ...

Repetitive Mild Traumatic Brain Injury In Mice Triggers A Slowly Developing Cascade Of Long-Term And Persistent Behavioral Deficits And Pathological Changes, Xiaoyun Xu, Matthew Cowan, Flavio Beraldo, Amy Schranz, Patrick Mccunn, Nicole Geremia, Zalman Brown, Maitray Patel, Karen L. Nygard, Reza Khazaee, Lihong Lu, Xingyu Liu, Michael J. Strong, Gregory A. Dekaban, Ravi Menon, Robert Bartha, Mark Daley, Haojie Mao, Vania Prado, Marco A.M. Prado, Lisa Saksida, Tim Bussey, Arthur Brown

Medical Biophysics Publications

We have previously reported long-term changes in the brains of non-concussed varsity rugby players using magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI) and functional magnetic imaging (fMRI). Others have reported cognitive deficits in contact sport athletes that have not met the diagnostic criteria for concussion. These results suggest that repetitive mild traumatic brain injuries (rmTBIs) that are not severe enough to meet the diagnostic threshold for concussion, produce long-term consequences. We sought to characterize the neuroimaging, cognitive, pathological and metabolomic changes in a mouse model of rmTBI. Using a closed-skull model of mTBI that when scaled to human leads ...

Investigating Bone Cement Susceptibility Related Artifacts And Adhesion, Eric Kuindersma

Electronic Thesis and Dissertation Repository

Blood Oxygen Level Dependent (BOLD) functional Magnetic Resonance Imaging (fMRI) utilizes pulse sequences sensitive to changes in concentration of deoxyhemoglobin to indirectly measure neural activity. Sequences used for BOLD are sensitive to magnetic susceptibility differences that may cause signal voids. Our lab has designed an awake marmoset head coil that eliminates confounds associated with imaging an animal under anesthesia. This design requires a head chamber attached to an animal’s skull with a cement that may cause a susceptibility artifact. Motivation behind this project was to find an MRI compatible cement that remains secure to the skull with minimal artifacts ...