Medical Biophysics Commons^™

Diversity And Plasticity In Signaling Pathways That Regulate Smooth Muscle Responsiveness: Paradigms And Paradoxes For The Myosin Phosphatase, The Master Regulator Of Smooth Muscle Contraction., Masumi Eto, Toshio Kitazawa

Department of Molecular Physiology and Biophysics Faculty Papers

A hallmark of smooth muscle cells is their ability to adapt their functions to meet temporal and chronic fluctuations in their demands. These functions include force development and growth. Understanding the mechanisms underlying the functional plasticity of smooth muscles, the major constituent of organ walls, is fundamental to elucidating pathophysiological rationales of failures of organ functions. Also, the knowledge is expected to facilitate devising innovative strategies that more precisely monitor and normalize organ functions by targeting individual smooth muscles. Evidence has established a current paradigm that the myosin light chain phosphatase (MLCP) is a master regulator of smooth muscle responsiveness …

Role Of Translation Initiation In Regulation Of Epithelial Junctions And Cell Motility, Fahda Fawaz Alsharief

Theses and Dissertations

The integrity and barrier properties of intestinal epithelium are determined by specialized adhesive structures known as intercellular junctions; composed of adherens junctions (AJs), tight junctions (TJs) and focal adhesions that mediate cell-cell and cell matrix interactions, respectively. These two types of epithelial cell adhesions regulate each other during disruption and restitution of the epithelial barrier. Inflammatory cytokines such as interferon gamma (IFNγ) and tumor necrosis factor alpha (TNFα) are elevated during intestinal inflammation. The most notable effects of IFNγ and TNFα on intestinal epithelial homeostasis involve disruption of apical junctions and attenuation of cell migration. Although molecular mechanisms underlying these …

Biochemical And Biophysical Methods For Analysis Of Poly(Adp-Ribose) Polymerase 1 And Its Interactions With Chromatin., Maggie H. Chassé, Uma M. Muthurajan, Nicholas J. Clark, Michael A. Kramer, Srinivas Chakravarthy, Thomas Irving, Karolin Luger

Manuscripts, Articles, Book Chapters and Other Papers

Poly (ADP-Ribose) Polymerase I (PARP-1) is a first responder to DNA damage and participates in the regulation of gene expression. The interaction of PARP-1 with chromatin and DNA is complex and involves at least two different modes of interaction. In its enzymatically inactive state, PARP-1 binds native chromatin with similar affinity as it binds free DNA ends. Automodification of PARP-1 affects interaction with chromatin and DNA to different extents. Here we describe a series of biochemical and biophysical techniques to quantify and dissect the different binding modes of PARP-1 with its various substrates. The techniques listed here allow for high …

Mobilising Expertise And Resources To Close The Radiotherapy Gap In Cancer Care., D Rodin, J Longo, T Sherertz, M M Shah, O Balagun, N Wendling, Jacob Van Dyk, C N Coleman, M J Xu, S Grover

Oncology Publications

Closing the gap in cancer care within low- and middle-income countries and in indigenous and geographically isolated populations in high-income countries requires investment and innovation. This is particularly true for radiotherapy, for which the global disparity is one of the largest in healthcare today. New models and paradigms and non-traditional collaborations have been proposed to improve global equity in cancer control. We describe recent initiatives from within the radiation oncology community to increase access to treatment, build the low- and middle-income countries' radiation oncology workforce, mobilise more professionals from within high-income countries and raise awareness of the global need for …

Analysis Of Global Radiotherapy Needs And Costs By Geographic Region And Income Level., E Zubizarreta, Jacob Van Dyk, Y Lievens

Oncology Publications

Recent years have seen various reviews on the lack of access to radiotherapy often based on geographic regions of the world such as Africa, Asia Pacific, Europe, Latin America and North America. Countries are often defined by their national income per capita levels based on World Bank definitions of high income, upper middle income, lower middle income and low income. Within the world regions, there are significant variations in gross national income (GNI) per capita among the different countries, and even within similar income levels, large variations exist. This report presents the actual status of radiotherapy and analyses the current …

The Role Of The Mir-200 Family On The Tumor Suppressor Rassf2 And The Effect On Mapk Pathway Activity In Colorectal Cancer., Jane V. Carter

Electronic Theses and Dissertations

This dissertation investigated the role of the miR-200 family in normal colon epithelial (CCD 841) and Dukes’ C (HT-29) colorectal cancer (CRC) cell lines. Our aim was to characterize expression of the miR-200 family (miR-200a, miR-200b, miR-200c, miR-141, and miR-429) in colorectal cell lines, study their effect on the tumor suppressor Ras Associated Domain-Containing Protein (RASSF) 2 and on subsequent activity within the mitogen-activated protein kinase (MAPK) signaling pathway. We wanted to determine whether regulation of miR-200 family members could change cell behavior towards more “cancer-like” in a normal colon epithelium (CCD 841) cell line, or less “cancer-like” in a …

Accuracy Requirements And Uncertainties In Radiotherapy: A Report Of The International Atomic Energy Agency., Debbie Van Der Merwe, Jacob Van Dyk, Brendan Healy, Eduardo Zubizarreta, Joanna Izewska, Ben Mijnheer, Ahmed Meghzifene

Oncology Publications

BACKGROUND: Radiotherapy technology continues to advance and the expectation of improved outcomes requires greater accuracy in various radiotherapy steps. Different factors affect the overall accuracy of dose delivery. Institutional comprehensive quality assurance (QA) programs should ensure that uncertainties are maintained at acceptable levels. The International Atomic Energy Agency has recently developed a report summarizing the accuracy achievable and the suggested action levels, for each step in the radiotherapy process. Overview of the report: The report seeks to promote awareness and encourage quantification of uncertainties in order to promote safer and more effective patient treatments. The radiotherapy process and the radiobiological …

Radiation Oncology Quality And Safety Considerations In Low Resource Settings: A Medical Physics Perspective, Jacob Van Dyk, Ahmed Meghzifene

Oncology Publications

The last few years have seen a significant growth of interest in the global radiation therapy crisis. Various organizations have quantified the need and are providing aid in support of addressing the shortfalls existing in many low-to-middle income countries (LMICs). With the tremendous demand for new facilities, equipment and personnel, it is very important to recognize the quality and safety challenges and to address them directly. An examination of publications on quality and safety in radiation therapy indicates a consistency in a number of the recommendations; however, these authoritative reports were generally based on input from high-resourced contexts. Here we …

Effect Of Left Atrial Wall Thickness On Radiofrequency Ablation Success., Jiro Inoue, Allan C Skanes, Lorne J Gula, Maria Drangova

Medical Biophysics Publications

INTRODUCTION: Radiofrequency (RF) ablation in thicker regions of the left atrium (LA) may require increased ablation energy in order to achieve effective transmural lesions. Consequently, many cases of recurrent atrial fibrillation (AF) postablation may be due to thicker-than-normal atrial tissue. The aim of this study was to test the hypotheses that patients with recurrent AF have thicker tissue overall and that electrical reconnection is more likely in regions of thicker tissue.

METHODS AND RESULTS: Retrospective analysis was performed on 86 CT images acquired preoperatively from a cohort of 119 patients who had undergone RF ablation for AF. Of these, 33 …

Design And Evaluation Of A Catheter Contact-Force Controller For Cardiac Ablation Therapy., Daniel Gelman, Allan C Skanes, Mohammad A Tavallaei, Maria Drangova

Medical Biophysics Publications

GOAL: Maintaining a constant contact force (CF) of an ablation catheter during cardiac catheter ablation therapy is clinically challenging due to inherent myocardial motion, often resulting in poor ablation of arrhythmogenic substrates. To enable a prescribed contact force to be applied during ablation, a catheter contact force controller (CCFC) was developed.

METHODS: The system includes a hand-held device attached to a commercial catheter and steerable sheath. A compact linear motor assembly attaches to an ablation catheter and autonomously controls its relative position within the shaft of the steerable sheath. A closed-loop control system is implemented within embedded electronics to enable …

Global Access To Radiation Therapy For Cervical Cancer: The Cost Of Inaction, Jacob Van Dyk, D Rodin, Timothy Paul Hanna, E Burger, Eduardo Zubizarreta, Mei Ling Yap, Michael Barton, Rifat Atun, Felicia Marie Knaul, Y Lievens, Mary K. Gospodarowicz, D A. Jaffray, M Milosevic

Oncology Publications

No abstract provided.

Carotid Artery Atherosclerosis In Patients With Active Rheumatoid Arthritis: Predictors Of Plaque Occurrence And Progression Over 24 Weeks, Janet E Pope, Tatiana Nevskaya, Lillian Barra, Grace Parraga

Medical Biophysics Publications

INTRODUCTION: This study evaluated the prevalence and progression of subclinical carotid artery atherosclerosis in active rheumatoid arthritis (RA).

METHODS: Carotid arteries of RA patients were scanned using 3D ultrasound at baseline and 24 weeks for total plaque area, vessel wall volume, and intima-media thickness (IMT), as well as arterial stiffness measured using pulse wave velocity. Variables related to inflammation, lipids and cardiovascular (CV) risk were assessed for associations with plaque progression. Of 195 screened patients, 31 met inclusion criteria (66 Swollen joint count (SJC) plus 68 Tender joint count (TJC)≥8 OR SJC plus TJC≥4 with elevated acute phase reactants) and …

Method And Phantom To Study Combined Effects Of In-Plane (X,Y) And Z-Axis Resolution For 3d Ct Imaging., David Goodenough, Josh Levy, Smari Kristinsson, Jesper Fredriksson, Hildur Olafsdottir, Austin Healy

Radiology Faculty Publications

Increasingly, the advent of multislice CT scanners, volume CT scanners, and total body spiral acquisition modes has led to the use of Multi Planar Reconstruction and 3D datasets. In considering 3D resolution properties of a CT system it is important to note that both the in-plane (x,y) and z-axis (slice thickness) influence the visual-ization and detection of objects within the scanned volume. This study investigates ways to consider both the in-plane resolution and the z-axis resolution in a single phantom wherein analytic or visualized analysis can yield information on these combined effects. A new phantom called the "Wave Phantom" is …

Design, Development And Evaluation Of A Compact Telerobotic Catheter Navigation System., Mohammad Ali Tavallaei, Daniel Gelman, Michael Konstantine Lavdas, Allan C Skanes, Douglas L Jones, Jeffrey S Bax, Maria Drangova

Medical Biophysics Publications

BACKGROUND: Remote catheter navigation systems protect interventionalists from scattered ionizing radiation. However, these systems typically require specialized catheters and extensive operator training.

METHODS: A new compact and sterilizable telerobotic system is described, which allows remote navigation of conventional tip-steerable catheters, with three degrees of freedom, using an interface that takes advantage of the interventionalist's existing dexterity skills. The performance of the system is evaluated ex vivo and in vivo for remote catheter navigation and ablation delivery.

RESULTS: The system has absolute errors of 0.1 ± 0.1 mm and 7 ± 6° over 100 mm of axial motion and 360° of …

Development And Implementation Of An Anthropomorphic Head & Neck Phantom For The Assessment Of Proton Therapy Treatment Procedures, Daniela Branco

Dissertations and Theses (Open Access)

Proton therapy has been used to treat cancer for more than 50 years, and over the past decade, its use has grown rapidly. One of the main goals of modern radiation therapy is to deliver a high dose to the planning target volume (PTV) with minimal exposure and damage to the surrounding healthy tissue. Protons offer a unique advantage over photon radiotherapy in that they deposit dose over a finite range, in contrast to the more gradual energy deposition of photon and electron beams. At present, 23 proton centers are in operation in the United States and another 13 centers …

Encapsulated Contrast Agent Markers For Mri-Based Post-Implant Dosimetry, Tze Yee Lim

Dissertations and Theses (Open Access)

Low-dose-rate prostate brachytherapy involves the implantation of tiny radioactive seeds into the prostate to treat prostate cancer. The current standard post-implant imaging modality is computed tomography (CT). On CT images, the radioactive seeds can be distinctively localized but delineation of the prostate and surrounding soft tissue is poor. Magnetic resonance imaging (MRI) provides better prostate and soft tissue delineation, but seed localization is difficult. To aid with seed localization, MRI markers with encapsulated contrast agent that provide positive-contrast on MRI images (Sirius MRI markers; C4 Imaging, Houston, TX) have been proposed to be placed adjacent to the negative-contrast seeds. This …

Low Energy Defibrillation By Synchronization; 90 % Less Energy Compared To One Shock., Flavio H. Fenton, Yanyan Ji, Ilija Uzelac, Niels Otani, Elizabeth M. Cherry

Biology and Medicine Through Mathematics Conference

No abstract provided.

Strategies Of Balancing: Regulation Of Posture As A Complex Phenomenon, Allison Leich Hilbun

Electronic Theses and Dissertations

The complexity of the interface between the muscular system and the nervous system is still elusive. We investigated how the neuromuscular system functions and how it is influenced by various perturbations. Postural stability was selected as the model system, because this system provides complex output, which could indicate underlying mechanisms and feedback loops of the neuromuscular system. We hypothesized that aging, physical pain, and mental and physical perturbations affect balancing strategy, and based on these observations, we constructed a model that simulates many aspects of the neuromuscular system. Our results show that aging changes the control strategy of balancing from …

The Influence Of Mir-99a On Mtor Signaling Regulation In Colorectal Cancer Cell Lines., Jonathan Rice

Electronic Theses and Dissertations

Colorectal cancer (CRC) is the third most common cancer worldwide and the fourth most common cause of death. These are staggering statistics for a disease that can essentially be cured if caught early and the pathology is favorable to therapeutic intervention. There is currently a drastic decrease in five year survival as the cancer stage increases from locally confined disease to metastatic disease. These statistics suggest that although some strides have been made with colon cancer screening and early intervention, there is still much room for improvement in both screening and treatment of CRC. One of the pathways that have …

Synthesis And Characterization Of Nanoparticle-Coupled Proteins In Human Serum Albumin, Kyle M. Mahoney

Honors College Theses

Recently, cancer has become an ever-growing issue and has led to many researchers attempt to unravel the mystery of the disease. This research has led to a promising field of treatment: nanotechnology-coupled pharmaceuticals. Nanoparticles act as a whole unit when in conjugation with other molecules and add to the carrier molecule, most often proteins, benefits the nanoparticles themselves possess. One such carrier protein that can be conjugated with nanoparticles is Human Serum Albumin (HSA). Albumin is of interest in cancer research for two reasons: it is native to the human vasculature so it does not elicit immunological reactions, and it …

Hyperpolarized 3he Magnetic Resonance Imaging Ventilation Defects In Asthma: Relationship To Airway Mechanics, Del Leary, Sarah Svenningsen, Fumin Guo, Swati Bhatawadekar, Grace Parraga, Geoffrey N Maksym

Medical Biophysics Publications

In patients with asthma, magnetic resonance imaging (MRI) provides direct measurements of regional ventilation heterogeneity, the etiology of which is not well-understood, nor is the relationship of ventilation abnormalities with lung mechanics. In addition, respiratory resistance and reactance are often abnormal in asthmatics and the frequency dependence of respiratory resistance is thought to reflect ventilation heterogeneity. We acquiredMRIventilation defect maps, forced expiratory volume in one-second (FEV1), and airways resistance (Raw) measurements, and used a computational airway model to explore the relationship of ventilation defect percent (VDP) with simulated measurements of respiratory system resistance (Rrs) and reactance (Xrs).MRIventilation defect maps were …

Pulmonary Ct And Mri Phenotypes That Help Explain Chronic Pulmonary Obstruction Disease Pathophysiology And Outcomes, Eric A Hoffman, David A Lynch, R Graham Barr, Edwin J R Van Beek, Grace Parraga

Medical Biophysics Publications

Pulmonary x-ray computed tomographic (CT) and magnetic resonance imaging (MRI) research and development has been motivated, in part, by the quest to subphenotype common chronic lung diseases such as chronic obstructive pulmonary disease (COPD). For thoracic CT and MRI, the main COPD research tools, disease biomarkers are being validated that go beyond anatomy and structure to include pulmonary functional measurements such as regional ventilation, perfusion, and inflammation. In addition, there has also been a drive to improve spatial and contrast resolution while at the same time reducing or eliminating radiation exposure. Therefore, this review focuses on our evolving understanding of …

Imaging How And Where We Breathe Oxygen: Another Big Short?, Dante P I Capaldi, Fumin Guo, Grace Parraga

Medical Biophysics Publications

The Big Short tells the story of a small group of skeptics who profited from the financial crisis in 2007 by betting against collateralized (mortgage) debt obligations (CDO). Importantly, the novel paints a clear picture of the eccentric nature of contrarians who think divergently and against the grain or bet against an accepted truth or “sure” thing. In a similar manner, Ishii and co-workers’ recent work describes their team’s development of a pulmonary imaging technology that provides divergent and disruptive in vivo lung measurements of oxygen partial pressure in the context of the prevailing and longstanding consensus around FEV1 as …

Structure-Activity Relationships Governing The Interaction Of Nanoparticles With Mammalian Cells- Predictive Models For Toxicology And Medical Appliances, Marcus A. Maher

Doctoral

Nanoscience is seen as one of the key enabling technologies of the 20th century and as its range of applications increases it is important to look at how nanomaterials interact with biological environments. Some of these interactions have given rise to toxic effects and thus, the creation of the field of nanotoxicology, it has also been noted that current methods of evaluating toxicity may not be sufficient to keep up with the rapidly emerging range of nanomaterials becoming available. It is clear that alternatives are necessary. In this thesis, a phenomenological rate equation model is constructed to simulate nanoparticle uptake …

This Is What Copd Looks Like, Khadija Sheikh, Harvey O Coxson, Grace Parraga

Medical Biophysics Publications

Despite decades of research, and the growing healthcare and societal burden of chronic obstructive pulmonary disease (COPD), therapeutic COPD breakthroughs have not occurred. Sub-optimal COPD patient phenotyping, an incomplete understanding of COPD pathogenesis and a scarcity of sensitive tools that provide patient-relevant intermediate endpoints likely all play a role in the lack of new, efficacious COPD interventions. In other words, COPD patients are still diagnosed based on the presence of persistent airflow limitation measured using spirometry. Spirometry measurements reflect the global sum of all the different possible COPD pathologies and perhaps because of this, we lose sight of the different …

Pulmonary Imaging Biomarkers Of Gas Trapping And Emphysema In Copd: (3)He Mr Imaging And Ct Parametric Response Maps, Dante P I Capaldi, Nanxi Zha, Fumin Guo, Damien Pike, David G Mccormack, Miranda Kirby, Grace Parraga

Medical Biophysics Publications

PURPOSE: To directly compare magnetic resonance (MR) imaging and computed tomography (CT) parametric response map (PRM) measurements of gas trapping and emphysema in ex-smokers both with and without chronic obstructive pulmonary disease (COPD).

MATERIALS AND METHODS: Participants provided written informed consent to a protocol that was approved by a local research ethics board and Health Canada and was compliant with the HIPAA (Institutional Review Board Reg. #00000940). The prospectively planned study was performed from March 2014 to December 2014 and included 58 ex-smokers (mean age, 73 years ± 9) with (n = 32; mean age, 74 years ± 7) and …

Design And Evaluation Of An Mri-Compatible Linear Motion Stage., Mohammad Ali Tavallaei, Patricia M Johnson, Junmin Liu, Maria Drangova

Medical Biophysics Publications

PURPOSE: To develop and evaluate a tool for accurate, reproducible, and programmable motion control of imaging phantoms for use in motion sensitive magnetic resonance imaging (MRI) appli cations.

METHODS: In this paper, the authors introduce a compact linear motion stage that is made of nonmagnetic material and is actuated with an ultrasonic motor. The stage can be positioned at arbitrary positions and orientations inside the scanner bore to move, push, or pull arbitrary phantoms. Using optical trackers, measuring microscopes, and navigators, the accuracy of the stage in motion control was evaluated. Also, the effect of the stage on image signal-to-noise …

A Dielectric Rod Antenna For Picosecond Pulse Stimulation Of Neurological Tissue, Ross A. Petrella, Karl H. Schoenbach, Shu Xiao

Bioelectrics Publications

A dielectrically loaded wideband rod antenna has been studied as a pulse delivery system to subcutaneous tissues. Simulation results applying 100-ps electrical pulse show that it allows us to generate a critical electric field for biological effects, such as brain stimulation, in the range of several centimeters. In order to reach the critical electric field for biological effects, which is similar to 20 kV/cm, at a depth of 2 cm, the input voltage needs to be 175 kV. The electric field spot size in the brain at this position is similar to 1 cm(2). Experimental studies in free space with …

Biophysical Sources Of 1/F Noises In Neurological Tissue, Alan Paris

Electronic Theses and Dissertations

High levels of random noise are a defining characteristic of neurological signals at all levels, from individual neurons up to electroencephalograms (EEG). These random signals degrade the performance of many methods of neuroengineering and medical neuroscience. Understanding this noise also is essential for applications such as real-time brain-computer interfaces (BCIs), which must make accurate control decisions from very short data epochs. The major type of neurological noise is of the so-called 1/f-type, whose origins and statistical nature has remained unexplained for decades. This research provides the first simple explanation of 1/f-type neurological noise based on biophysical fundamentals. In addition, noise …

Investigation Of Quatitative Image Features From Pretreatment Ct And Fdg-Pet Scans In Stage Iii Nsclc Patients Undergoing Defintive Radiation Therapy, David Fried

Dissertations and Theses (Open Access)

The purpose of this work was to determine if quantitative image features (QIFs) extracted from computed tomography (CT) and flourodeoxyglucose (FDG) positron emission tomography (PET) could provide prognostic information to improve outcome models. Our goal for this work was to determine if it may one day be feasible to incorporate QIFs into personalized cancer care. QIFs were used to quantitatively characterize patient disease as seen on imaging. A leave-one-out cross-validation procedure was used to assess the prognostic ability of QIFs extracted from CT and PET in addition to conventional prognostic factors (CPFs). QIFs were found to improve model fit for …