Medical Biophysics Commons^™

Noninvasive Quantification Of Alveolar Morphometry In Elderly Never- And Ex-Smokers, Gregory A Paulin, Alexei Ouriadov, Eric Lessard, Khadija Sheikh, David G Mccormack, Grace Parraga

Medical Biophysics Publications

Diffusion-weighted magnetic resonance imaging (MRI) provides a way to generate in vivo lung images with contrast sensitive to the molecular displacement of inhaled gas at subcellular length scales. Here, we aimed to evaluate hyperpolarized (3)He MRI estimates of the alveolar dimensions in 38 healthy elderly never-smokers (73 ± 6 years, 15 males) and 21 elderly ex-smokers (70 ± 10 years, 14 males) with (n = 8, 77 ± 6 years) and without emphysema (n = 13, 65 ± 10 years). The ex-smoker and never-smoker subgroups were significantly different for FEV1/FVC (P = 0.0001) and DLCO (P = 0.009); while ex-smokers …

Improving Attenuation Correction In Hybrid Positron Emission To Mography, Hua Asher Ai

Dissertations and Theses (Open Access)

Hybrid positron emission tomography imaging techniques such as PET/CT and PET/MR have undergone significant developments over the last two decades and have played increasingly more important roles both in research and in the clinic. A unique advantage PET has over other clinical imaging modalities is its capability of accurate quantification. However, as the most critical component of PET quantification, attenuation correction in hybrid PET systems is challenged in several different aspects, including the spatial- temporal mismatch between the PET emission images and the associated attenuation images provided by the complementary modality, and the difficulty in bone identification in the MR-based …

Prophylactic Cranial Irradiation Reduces The Incidence Of Brain Metastasis In A Mouse Model Of Metastatic Breast Cancer, Daniel L. Smith

Dissertations and Theses (Open Access)

Prophylactic cranial irradiation (PCI) is a preventative whole-brain irradiation technique used to reduce the incidence of brain metastasis and improve overall survival in select patients with small cell lung cancer and acute lymphoblastic leukemia. A population of breast cancer patients – stage IV, HER2+ or triple-negative – has emerged as having a high risk of developing brain metastases. Because only 10-20% of breast cancer patients diagnosed with brain metastases survive longer than one year, in this high-risk population the benefit of PCI – potential for reduced incidence of brain metastasis and improved overall survival – may outweigh the risks – …

Copd: Do Imaging Measurements Of Emphysema And Airway Disease Explain Symptoms And Exercise Capacity?, Miranda Kirby, Damien Pike, Don D Sin, Harvey O Coxson, David G Mccormack, Grace Parraga

Medical Biophysics Publications

PURPOSE: To determine the role of imaging measurements of emphysema and airway disease in determining chronic obstructive pulmonary disease (COPD) symptoms and exercise limitation in patients with COPD, particularly in patients with mild-to-moderate disease.

MATERIALS AND METHODS: Participants (n = 116) with Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade U (unclassified) or grade I-IV COPD provided informed consent to an ethics board-approved HIPAA-compliant protocol and underwent spirometry and plethysmography, completed the St George's Respiratory Questionnaire (SGRQ), completed a 6-minute walk test for the 6-minute walk distance (6MWD), and underwent hyperpolarized helium 3 ((3)He) magnetic resonance (MR) imaging and …

Serum Vitamin D Status Is Associated With The Presence But Not The Severity Of Primary Open Angle Glaucoma., Aurélien Goncalves, Dan Milea, Philippe Gohier, Ghislaine Jallet, Stéphanie Leruez, Mani Baskaran, Tin Aung, Cédric Annweiler

Medical Biophysics Publications

OBJECTIVES: Vitamin D is involved in visual health and function. Our objective was to determine whether age-related vitamin D insufficiency was associated with the presence and the severity of primary open angle glaucoma (POAG) in a case-control study of older adults.

STUDY DESIGN: Case-control study.

MAIN OUTCOME MEASURES: One hundred fifty cases diagnosed with moderate-to-severe POAG (mean, 75.1±8.5 years; 42.0% female) and 164 healthy controls (mean, 73.0±7.9 years; 59.8% female) were included. POAG diagnosis was based on classical diagnostic criteria of optic nerve cupping and/or RNFL thinning, measured with optical coherence tomography. Severe POAG was defined as Humphrey visual field …

Ventilation Heterogeneity In Ex-Smokers Without Airflow Limitation., Damien Pike, Miranda Kirby, Fumin Guo, David G Mccormack, Grace Parraga

Medical Biophysics Publications

RATIONALE AND OBJECTIVES: Hyperpolarized (3)He magnetic resonance imaging (MRI) ventilation abnormalities are visible in ex-smokers without airflow limitation, but the clinical relevance of this is not well-understood. Our objective was to phenotype healthy ex-smokers with normal and abnormally elevated ventilation defect percent (VDP).

MATERIALS AND METHODS: Sixty ex-smokers without airflow limitation provided written informed consent to (3)He MRI, computed tomography (CT), and pulmonary function tests in a single visit. (3)He MRI VDP and apparent diffusion coefficients (ADCs) were measured for whole-lung and each lung lobe as were CT measurements of emphysema (relative area [RA] with attenuation ≤-950 HU, RA950) and …

Structural Studies Of The Ig58 Domain Of The Giant Muscle Protein Obscurin, Matthew C. Oehler

Senior Honors Projects, 2010-2019

Obscurin (720-900 kD) is a giant sarcomeric signaling protein that is the only known link

between the cytoskeleton and the surrounding membrane structure. Mutations to obscurin

and to obscurin binding partners have been linked to human muscle diseases such as

hypertrophic cardiomyopathies and muscular dystrophy. These diseases likely occur due

to the abrogation of specific molecular interactions necessary for suitable function. To

more fully understand how specific mutations lead to disease, here we solve the highresolution

structure of obscurin Ig58. The literature shows that an Arg8Gln mutation to

the Ig58 domain of obscurin is associated with hypertrophic cardiomyopathy (HCM).

Chemical …

Characterization Of Low Density Intracranial Lesions Using Dual-Energy Computed To Mography, Jessica L. Nute

Dissertations and Theses (Open Access)

Calcific and hemorrhagic foci of susceptibility are frequently encountered on routine brain MR studies. Both etiologies cause variations in local magnetic field strength, leading to dark regions on the MR images that cannot be classified. Single-energy CT (SECT) can be used to identify lesions with attenuation over 100 HU as calcific, however lesions with lower attenuation cannot be reliably identified. While calcific lesions are unlikely to cause harm, hemorrhagic lesions carry a risk of subsequent intracranial bleeding; as such, identification of hemorrhage is vital in preventing the inappropriate use of anticoagulant medications in patients with hemorrhagic lesions.

Given there currently …

Sec17 Can Trigger Fusion Of Trans-Snare Paired Membranes Without Sec18, Michael Zick, Amy Orr, Matthew L. Schwartz, Alexey J. Merz, William Wickner

Dartmouth Scholarship

Sec17 [soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein; α-SNAP] and Sec18 (NSF) perform ATP-dependent disassembly of cis-SNARE complexes, liberating SNAREs for subsequent assembly of trans-complexes for fusion. A mutant of Sec17, with limited ability to stimulate Sec18, still strongly enhanced fusion when ample Sec18 was supplied, suggesting that Sec17 has additional functions. We used fusion reactions where the four SNAREs were initially separate, thus requiring no disassembly by Sec18. With proteoliposomes bearing asymmetrically disposed SNAREs, tethering and trans-SNARE pairing allowed slow fusion. Addition of Sec17 did not affect the levels of trans-SNARE complex but triggered sudden fusion of trans-SNARE paired proteoliposomes. …

Survival Prediction In High-Grade Gliomas Using Ct Perfusion Imaging., Timothy Pok Chi Yeung, Yong Wang, Wenqing He, Benedetta Urbini, Roberta Gafà, Linda Ulazzi, Slav Yartsev, Glenn Bauman, Ting-Yim Lee, Enrico Fainardi

Medical Biophysics Publications

Patients with high-grade gliomas usually have heterogeneous response to surgery and chemoirradiation. The objectives of this study were (1) to evaluate serial changes in tumor volume and perfusion imaging parameters and (2) to determine the value of these data in predicting overall survival (OS). Twenty-nine patients with World Health Organization grades III and IV gliomas underwent magnetic resonance (MR) and computed tomography (CT) perfusion examinations before surgery, and 1, 3, 6, 9, and 12 months after radiotherapy. Serial measurements of tumor volumes and perfusion parameters were evaluated by receiver operating characteristic analysis, Cox proportional hazards regression, and Kaplan-Meier survival analysis …

In-Vivo Longitudinal Mri Study: An Assessment Of Melanoma Brain Metastases In A Clinically Relevant Mouse Model., Mariama N Henry, Yuhua Chen, Catherine D Mcfadden, Felicia C Simedrea, Paula J Foster

Medical Biophysics Publications

Brain metastases are an important clinical problem. Few animal models exist for melanoma brain metastases; many of which are not clinically relevant. Longitudinal MRI was implemented to examine the development of tumors in a clinically relevant mouse model of melanoma brain metastases. Fifty thousand human metastatic melanoma (A2058) cells were injected intracardially into nude mice. Three Tesla MRI was performed using a custom-built gradient insert coil and a mouse solenoid head coil. Imaging was performed on consecutive days at four time points. Tumor burden and volumes of metastases were measured from balanced steady-state free precession image data. Metastases with a …

Impact Of Incremental Perfusion Loss On Oxygen Transport In A Capillary Network Mathematical Model., Graham M Fraser, Michael D Sharpe, Daniel Goldman, Christopher G Ellis

Medical Biophysics Publications

OBJECTIVES: To quantify how incremental capillary perfusion loss, such as that seen in experimental models of sepsis, affects tissue oxygenation using a computation model of oxygen transport.

METHODS: A computational model was applied to capillary networks with dimensions 84x168x342 (NI) and 70x157x268 (NII) μm, reconstructed in vivo from rat skeletal muscle. Functional capillary density (FCD) loss was applied incrementally up to ~40% and combined with high tissue oxygen consumption to simulate severe sepsis.

RESULTS: A loss of ~40% FCD loss decreased median tissue PO2 to 22.9 and 20.1 mmHg in NI and NII compared to 28.1 and 27.5 mmHg under …

The Dissociative Subtype Of Posttraumatic Stress Disorder: Unique Resting-State Functional Connectivity Of Basolateral And Centromedial Amygdala Complexes., Andrew A Nicholson, Maria Densmore, Paul A Frewen, Jean Théberge, Richard W J Neufeld, Margaret C Mckinnon, Ruth A Lanius

Medical Biophysics Publications

Previous studies point towards differential connectivity patterns among basolateral (BLA) and centromedial (CMA) amygdala regions in patients with posttraumatic stress disorder (PTSD) as compared to controls. Here, we describe the first study to compare directly connectivity patterns of the BLA and CMA complexes between PTSD patients with and without the dissociative subtype (PTSD+DS and PTSD-DS, respectively). Amygdala connectivity to regulatory prefrontal regions and parietal regions involved in consciousness and proprioception were expected to differ between these two groups based on differential limbic regulation and behavioural symptoms. PTSD patients (n=49), with (n=13) and without (n=36) the dissociative subtype, and age-matched healthy …

A Biomechanical Approach For In Vivo Lung Tumor Motion Prediction During External Beam Radiation Therapy, Abbas Samani, Elham Karami, Ting-Yim Lee, Stewart Gaede

Medical Biophysics Publications

No abstract provided.

Collectivization Of Vascular Smooth Muscle Cells Via Tgf-Β-Cadherin-11-Dependent Adhesive Switching., Brittany Balint, Hao Yin, Subrata Chakrabarti, Michael W A Chu, Stephen M Sims, J Geoffrey Pickering

Medical Biophysics Publications

OBJECTIVE: Smooth muscle cells (SMCs) in healthy arteries are arranged as a collective. However, in diseased arteries, SMCs commonly exist as individual cells, unconnected to each other. The purpose of this study was to elucidate the events that enable individualized SMCs to enter into a stable and interacting cell collective.

APPROACH AND RESULTS: Human SMCs stimulated to undergo programmed collectivization were tracked by time-lapse microscopy. We uncovered a switch in the behavior of contacting SMCs from semiautonomous motility to cell-cell adherence. Central to the cell-adherent phenotype was the formation of uniquely elongated adherens junctions, ≤60 μm in length, which appeared …

Evidence Of Ventricular Contamination Of The Optical Signal In Preterm Neonates With Post Hemorrhagic Ventricle Dilation, J Kishimoto, M Diop, S De Ribaupierre, Dsc Lee, K St. Lawrence

Medical Biophysics Publications

No abstract provided.

Resting State And Diffusion Neuroimaging Predictors Of Clinical Improvements Following Constraint-Induced Movement Therapy In Children With Hemiplegic Cerebral Palsy., Kathryn Y Manning, Darcy Fehlings, Ronit Mesterman, Jan Willem Gorter, Lauren Switzer, Craig Campbell, Ravi S Menon

Medical Biophysics Publications

The aim was to identify neuroimaging predictors of clinical improvements following constraint-induced movement therapy. Resting state functional magnetic resonance and diffusion tensor imaging data was acquired in 7 children with hemiplegic cerebral palsy. Clinical and magnetic resonance imaging (MRI) data were acquired at baseline and 1 month later following a 3-week constraint therapy regimen. A more negative baseline laterality index characterizing an atypical unilateral sensorimotor resting state network significantly correlated with an improvement in the Canadian Occupational Performance Measure score (r = -0.81, P = .03). A more unilateral network with decreased activity in the affected hemisphere was associated with …

Investigation Of The Best Model To Characterize Diffuse Correlation Spectroscopy Measurements Acquired Directly On The Brain, K Verdecchia, M Diop, K St. Lawrence

Medical Biophysics Publications

No abstract provided.

Follow-Up Of Patients After Stereotactic Radiation For Lung Cancer: A Primer For The Nonradiation Oncologist., Kitty Huang, David A Palma

Medical Biophysics Publications

BACKGROUND: The use of stereotactic ablative radiotherapy (SABR) as primary treatment for early stage non-small-cell lung cancer, or for ablation of metastases, has increased rapidly in the past decade. With local recurrence rates reported at approximately 10%, and a patient population that is becoming increasingly fit and amenable to salvage treatment, appropriate multidisciplinary follow-up care is critical. Appropriate follow-up will allow for detection and management of radiation-related toxicity, early detection of recurrent disease and differentiation of recurrence from radiation-induced lung injury.

METHODS: This narrative review summarizes issues surrounding follow-up of patients treated with SABR in the context of a multidisciplinary …

Effect Of Taper Design On Trunnionosis In Metal On Polyethylene Total Hip Arthroplasty., Sok Chuen Tan, Matthew G Teeter, Christopher Del Balso, James L Howard, Brent A Lanting

Medical Biophysics Publications

This study examines how taper design affects corrosion and fretting at the head trunnion surface. All hip prostheses retrieved between 1999 and 2013 with 28mm/+0 heads were selected, resulting in 44 cobalt-chrome-on-polyethylene implants, representing six taper designs. Mean implantation time: 8.9±3.7years. The femoral head tapers were scored for fretting and corrosion using the Goldberg scale as both a combined score and by three zones (apex, central and base). There was no difference in age (P=0.34), BMI (P=0.29), or implantation time (P=0.19) between taper groups. The 11/13 taper had the highest combined corrosion and fretting score, but no difference (P=0.22) between …

Effect Of Ascorbate On Plasminogen Activator Inhibitor-1 Expression And Release From Platelets And Endothelial Cells In An In-Vitro Model Of Sepsis., Scott B Swarbreck, Dan Secor, Christopher G Ellis, Michael D Sharpe, John X Wilson, Karel Tyml

Medical Biophysics Publications

The microcirculation during sepsis fails due to capillary plugging involving microthrombosis. We demonstrated that intravenous injection of ascorbate reduces this plugging, but the mechanism of this beneficial effect remains unclear. We hypothesize that ascorbate inhibits the release of the antifibrinolytic plasminogen activator inhibitor-1 (PAI-1) from endothelial cells and platelets during sepsis. Microvascular endothelial cells and platelets were isolated from mice. Cells were cultured and stimulated with lipopolysaccharide (LPS), tumor necrosis factor alpha (TNFα), or thrombin (agents of sepsis), with/without ascorbate for 1-24 h. PAI-1 mRNA was determined by quantitative PCR. PAI-1 protein release into the culture medium was measured by …

Dynamic Perfusion Ct In Brain Tumors., Timothy Pok Chi Yeung, Glenn Bauman, Slav Yartsev, Enrico Fainardi, David Macdonald, Ting-Yim Lee

Medical Biophysics Publications

Dynamic perfusion CT (PCT) is an imaging technique for assessing the vascular supply and hemodynamics of brain tumors by measuring blood flow, blood volume, and permeability-surface area product. These PCT parameters provide information complementary to histopathologic assessments and have been used for grading brain tumors, distinguishing high-grade gliomas from other brain lesions, differentiating true progression from post-treatment effects, and predicting prognosis after treatments. In this review, the basic principles of PCT are described, and applications of PCT of brain tumors are discussed. The advantages and current challenges, along with possible solutions, of PCT are presented.

Right Ventricular Segmentation In Cardiac Mri With Moving Mesh Correspondences., Kumaradevan Punithakumar, Michelle Noga, Ismail Ben Ayed, Pierre Boulanger

Medical Biophysics Publications

This study investigates automatic propagation of the right ventricle (RV) endocardial and epicardial boundaries in 4D (3D+time) magnetic resonance imaging (MRI) sequences. Based on a moving mesh (or grid generation) framework, the proposed algorithm detects the endocardium and epicardium within each cardiac phase via point-to-point correspondences. The proposed method has the following advantages over prior RV segmentation works: (1) it removes the need for a time-consuming, manually built training set; (2) it does not make prior assumptions as to the intensity distributions or shape; (3) it provides a sequence of corresponding points over time, a comprehensive input that can be …

Feasibility Of A Unified Approach To Intensity-Modulated Radiation Therapy And Volume-Modulated Arc Therapy Optimization And Delivery, Jerry J. Battista, Michael Macfarlane, Eugene Wong, Jeff Z. Chen, Douglas A. Hoover

Medical Biophysics Publications

Purpose:

To study the feasibility of unified intensity-modulated arc therapy (UIMAT) which combines intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT)optimization and delivery to produce superior radiation treatment plans, both in terms of dosedistribution and efficiency of beam delivery when compared with either VMAT or IMRT alone.

Methods:

An inverse planning algorithm for UIMAT was prototyped within the pinnacle treatment planningsystem (Philips Healthcare). The IMRT and VMAT deliveries are unified within the same arc, with IMRT being delivered at specific gantry angles within the arc. Optimized gantry angles for the IMRT and VMAT phases are assigned automatically by the inverse …

Rapid Desiccation Hardening Changes The Cuticular Hydrocarbon Profile Of Drosophila Melanogaster., Joseph R Stinziano, Richard J Sové, Howard D Rundle, Brent J Sinclair

Medical Biophysics Publications

The success of insects in terrestrial environments is due in large part to their ability to resist desiccation stress. Since the majority of water is lost across the cuticle, a relatively water-impermeable cuticle is a major component of insect desiccation resistance. Cuticular permeability is affected by the properties and mixing effects of component hydrocarbons, and changes in cuticular hydrocarbons can affect desiccation tolerance. A pre-exposure to a mild desiccation stress increases duration of desiccation survival in adult female Drosophila melanogaster, via a decrease in cuticular permeability. To test whether this acute response to desiccation stress is due to a change …

Pulmonary Abnormalities And Carotid Atherosclerosis In Ex-Smokers Without Airflow Limitation., Damien Pike, Miranda Kirby, Tamas J Lindenmaier, Khadija Sheikh, Casey E Neron, Daniel G Hackam, J David Spence, Aaron Fenster, Nigel A M Paterson, Don D Sin, Harvey O Coxson, David G Mccormack, Grace Parraga

Medical Biophysics Publications

Abstract It is well-established that COPD patients have a burden of vascular disease that cannot be fully-explained by smoking history but the mechanistic links between atherosclerosis and pulmonary disease in COPD patients are not well-understood. Moreover, in ex-smokers without symptoms or other evidence of COPD, subclinical pulmonary and vascular disease, although potentially present, has not been described or evaluated. Hence our aim was to use sensitive three-dimensional (3D) pulmonary and carotid imaging to quantify pulmonary airway/parenchyma abnormalities and atherosclerosis in ex-smokers without airflow limitation or symptoms consistent with COPD. We evaluated 61 subjects without airflow limitation including 34 never- (72 …

Pulmonary Imaging Abnormalities In An Adult Case Of Congenital Lobar Emphysema., Damien Pike, Sindu Mohan, Weijing Ma, James F Lewis, Grace Parraga

Medical Biophysics Publications

Congenital lobar emphysema is mainly diagnosed in infants, although rare cases are reported in adults. A 20-yr-old female with acute dyspnea, chest pain and left upper lobe (LUL) chest x-ray hyperlucency underwent 3He magnetic resonance imaging (MRI) for ventilation and apparent diffusion coefficient (ADC) measurements, as well as CT for emphysema and airway wall measurements. Forced expiratory volume in 1s, residual volume, and airways-resistance were abnormal, but there was normal carbon-monoxide-diffusing-capacity. The LUL relative area of the density histogram

Skeletal Muscle Fibrosis In The Mdx/Utrn+/- Mouse Validates Its Suitability As A Murine Model Of Duchenne Muscular Dystrophy, Lisa M. Hoffman, William T. Hrinivich, Kelly M. Gutpell

Medical Biophysics Publications

Various therapeutic approaches have been studied for the treatment of Duchenne muscular dystrophy (DMD), but none of these approaches have led to significant long-term effects in patients. One reason for this observed inefficacy may be the use of inappropriate animal models for the testing of therapeutic agents. The mdx mouse is the most widely used murine model of DMD, yet it does not model the fibrotic progression observed in patients. Other murine models of DMD are available that lack one or both alleles of utrophin, a functional analog of dystrophin. The aim of this study was to compare fibrosis and …

Feasibility Of Simultaneous Whole-Brain Imaging On An Integrated Pet-Mri System Using An Enhanced 2-Point Dixon Attenuation Correction Method., Udunna C Anazodo, Jonathan D Thiessen, Tracy Ssali, Jonathan Mandel, Matthias Günther, John Butler, William Pavlosky, Frank S Prato, R Terry Thompson, Keith S St Lawrence

Medical Biophysics Publications

PURPOSE: To evaluate a potential approach for improved attenuation correction (AC) of PET in simultaneous PET and MRI brain imaging, a straightforward approach that adds bone information missing on Dixon AC was explored.

METHODS: Bone information derived from individual T1-weighted MRI data using segmentation tools in SPM8, were added to the standard Dixon AC map. Percent relative difference between PET reconstructed with Dixon+bone and with Dixon AC maps were compared across brain regions of 13 oncology patients. The clinical potential of the improved Dixon AC was investigated by comparing relative perfusion (rCBF) measured with arterial spin labeling to relative glucose …

Detective Quantum Efficiency Of Photon-Counting X-Ray Detectors., Jesse Tanguay, Seungman Yun, Ho Kyung Kim, Ian A Cunningham

Medical Biophysics Publications

PURPOSE: Single-photon-counting (SPC) x-ray imaging has the potential to improve image quality and enable novel energy-dependent imaging methods. Similar to conventional detectors, optimizing image SPC quality will require systems that produce the highest possible detective quantum efficiency (DQE). This paper builds on the cascaded-systems analysis (CSA) framework to develop a comprehensive description of the DQE of SPC detectors that implement adaptive binning.

METHODS: The DQE of SPC systems can be described using the CSA approach by propagating the probability density function (PDF) of the number of image-forming quanta through simple quantum processes. New relationships are developed to describe PDF transfer …