Medicine and Health Sciences Commons^™

Contrast Enhanced-Magnetic Resonance Imaging As A Surrogate To Map Verteporfin Delivery In Photodynamic Therapy, Kimberley S. Samkoe, Amber Bryant, Jason R. Gunn, Stephen P. Pereira, Tayyaba Hasan, Brian W. Pogue

Dartmouth Scholarship

The use of in vivo contrast-enhanced magnetic resonance (MR) imaging as a surrogate for photosensitizer (verteporfin) dosimetry in photodynamic therapy of pancreas cancer is demonstrated by correlating MR contrast uptake to ex vivo fluorescence images on excised tissue. An orthotopic pancreatic xenograft mouse model was used for the study. A strong correlation ([i]r=0.57 ) was found for bulk intensity measurements of T1-weighted gadolinium enhancement and verteporfin fluorescence in the tumor region of interest. The use of contrast-enhanced MR imaging shows promise as a method for treatment planning and photosensitizer dosimetry in human photodynamic therapy (PDT) of pancreas …

Interactions Of Peptide Triazole Thiols With Env Gp120 Induce Irreversible Breakdown And Inactivation Of Hiv-1 Virions, Arangassery Bastian, Mark Contarino, Lauren D. Bailey, Rachna Aneja, Diogo Rodrigo Magalhaes Moreira, Kevin Freedman, Karyn Mcfadden, Caitlin Duffy, Ali Emileh

Dartmouth Scholarship

Background: We examined the underlying mechanism of action of the peptide triazole thiol, KR13 that has been shown previously to specifically bind gp120, block cell receptor site interactions and potently inhibit HIV-1 infectivity.

Results: KR13, the sulfhydryl blocked KR13b and its parent non-sulfhydryl peptide triazole, HNG156, induced gp120 shedding but only KR13 induced p24 capsid protein release. The resulting virion post virolysis had an altered morphology, contained no gp120, but retained gp41 that bound to neutralizing gp41 antibodies. Remarkably, HIV-1 p24 release by KR13 was inhibited by enfuvirtide, which blocks formation of the gp41 6-helix bundle during membrane fusion, while …

Situational Awareness/Triage Tool For Use In A Chemical, Biological, Radiological Nuclear Explosive (Cbrne) Environment, John N. Scarlett, Heather L. Gallup, David A. Smith

AFIT Patents

A method of managing patient care and emergency response following a Chemical, Biological, Radiological, or Nuclear Explosive (CBRNE) attack and maintaining compliance with the Health Insurance Portability and Accountability Act (HIPAA). The method including identifying each patient with a unique patient identifier, the identifier based upon the geospatial location of the patient, the geospatial location including at least the latitude and longitude of the patient when first treated, the unique patient identifier being part of patient data. Providing a collection point of patient data to form a patient data database where in the patient location data may be used to …

Electrotransfer Of Single-Stranded Or Double-Stranded Dna Induces Complete Regression Of Palpable B16.F10 Mouse Melanomas, Loree Heller, Vesba Todorovic, Maja Cemazar

Bioelectrics Publications

Enhanced tumor delivery of plasmid DNA with electric pulses in vivo has been confirmed in many preclinical models. Intratumor electrotransfer of plasmids encoding therapeutic molecules has reached Phase II clinical trials. In multiple preclinical studies, a reduction in tumor growth, increased survival or complete tumor regression have been observed in control groups in which vector or backbone plasmid DNA electrotransfer was performed. This study explores factors that could produce this antitumor effect. The specific electrotransfer pulse protocol employed significantly potentiated the regression. Tumor regression was observed after delivery of single-stranded or double-stranded DNA with or without CpG motifs in both …

Layered Long Term Co-Culture Of Hepatocytes And Endothelial Cells On A Transwell Membrane: Toward Engineering The Liver Sinusoid, Young Bok (Abraham) Kang, Siddhartha Rawat, Joseph Cirillo, Michael Bouchard, Hongseok (Moses) Noh

Faculty Publications - Biomedical, Mechanical, and Civil Engineering

This paper presents a novel liver model that mimics the liver sinusoid where most liver activities occur. A key aspect of our current liver model is a layered co-culture of primary rat hepatocytes (PRHs) and primary rat liver sinusoidal endothelial cells (LSECs) or bovine aortic endothelial cells (BAECs) on a transwell membrane. When a layered co-culture was attempted with a thin matrigel layer placed between hepatocytes and endothelial cells to mimic the Space of Disse, the cells did not form completely separated monolayers. However, when hepatocytes and endothelial cells were cultured on the opposite sides of a transwell membrane, PRHs …

Improving Patient Length-Of-Stay In Emergency Department Through Dynamic Queue Management, Kar Way Tan, Hoong Chuin Lau, Francis Chun Yue Lee

Research Collection School Of Computing and Information Systems

Addressing issue of crowding in an Emergency Department (ED) typically takes the form of process engineering or single-faceted queue management strategies such as demand restriction, queue prioritization or staffing the ED. This work provides an integrated framework to manage queue dynamically from both demand and supply perspectives. More precisely, we introduce intelligent dynamic patient prioritization strategies to manage the demand concurrently with dynamic resource adjustment policies to manage supply. Our framework allows decision-makers to select both the demand-side and supply-side strategies to suit the needs of their ED. We verify through a simulation that such a framework improves the patients' …

Dopaminergic Modulation Of Memory And Affective Processing In Parkinson Depression, Lee X. Blonder, John T. Slevin, Richard J. Kryscio, Catherine A. Martin, Anders H. Andersen, Charles D Smith, Frederick A. Schmitt

Magnetic Resonance Imaging and Spectroscopy Center Faculty Publications

Depression is common in Parkinson's disease and is associated with cognitive impairment. Dopaminergic medications are effective in treating the motor symptoms of Parkinson's disease; however, little is known regarding the effects of dopaminergic pharmacotherapy on cognitive function in depressed Parkinson patients. This study examines the neuropsychological effects of dopaminergic pharmacotherapy in Parkinsonian depression. We compared cognitive function in depressed and non-depressed Parkinson patients at two time-points: following overnight withdrawal and after the usual morning regimen of dopaminergic medications. A total of 28 non-demented, right-handed patients with mild to moderate idiopathic Parkinson's disease participated. Ten of these patients were depressed according …

Binding, Transcytosis And Biodistribution Of Anti-Pecam-1 Iron Oxide Nanoparticles For Brain-Targeted Delivery, Mo Dan, David B. Cochran, Robert A. Yokel, Thomas D. Dziubla

Pharmaceutical Sciences Faculty Publications

OBJECTIVE: Characterize the flux of platelet-endothelial cell adhesion molecule (PECAM-1) antibody-coated superparamagnetic iron oxide nanoparticles (IONPs) across the blood-brain barrier (BBB) and its biodistribution in vitro and in vivo.

METHODS: Anti-PECAM-1 IONPs and IgG IONPs were prepared and characterized in house. The binding affinity of these nanoparticles was investigated using human cortical microvascular endothelial cells (hCMEC/D3). Flux assays were performed using a hCMEC/D3 BBB model. To test their immunospecificity index and biodistribution, nanoparticles were given to Sprague Dawley rats by intra-carotid infusion. The capillary depletion method was used to elucidate their distribution between the BBB and brain parenchyma.

RESULTS: Anti-PECAM-1 …

Real-Time In Vivo Cherenkoscopy Imaging During External Beam Radiation Therapy, Rongxiao Zhang, David J. Gladstone, Lesley A. Jarvis, Rendall R. Strawbridge, P Jack Hoopes, Oscar D. Friedman, Adam K. Glaser, Brian W. Pogue

Dartmouth Scholarship

Cherenkov radiation is induced when charged particles travel through dielectric media (such as biological tissue) faster than the speed of light through that medium. Detection of this radiation or excited luminescence during megavoltage external beam radiotherapy (EBRT) can allow emergence of a new approach to superficial dose estimation, functional imaging, and quality assurance for radiation therapy dosimetry. In this letter, the first in vivo Cherenkov images of a real-time Cherenkoscopy during EBRT are presented. The imaging system consisted of a time-gated intensified charge coupled device (ICCD) coupled with a commercial lens. The ICCD was synchronized to the linear accelerator to …

A Novel Signal Processing Method For Intraoperative Neurophysiological Monitoring In Spinal Surgeries, Krishnatej Vedala

FIU Electronic Theses and Dissertations

Intraoperative neurophysiologic monitoring is an integral part of spinal surgeries and involves the recording of somatosensory evoked potentials (SSEP). However, clinical application of IONM still requires anywhere between 200 to 2000 trials to obtain an SSEP signal, which is excessive and introduces a significant delay during surgery to detect a possible neurological damage. The aim of this study is to develop a means to obtain the SSEP using a much less, twelve number of recordings. The preliminary step involved was to distinguish the SSEP with the ongoing brain activity. We first establish that the brain activity is indeed quasi-stationary whereas …

The Spatial Distribution Of Cancer Incidence In Fars Province: A Gis-Based Analysis Of Cancer Registry Data, Ali Goli, Mahbobeh Oroei, Mehdi Jalalpour, Hossein Faramarzi, Mehrdad Askarian

Civil and Environmental Engineering Faculty Publications

Background: Cancer is a major health problem in the developing countries. Variations of its incidence rate among geographical areas are due to various contributing factors. This study was performed to assess the spatial patterns of cancer incidence in the Fars Province, based on cancer registry data and to determine geographical clusters.

Methods: In this cross sectional study, the new cases of cancer were recorded from 2001 to 2009. Crude incidence rate was estimated based on age groups and sex in the counties of the Fars Province. Age standardized incidence rates (ASR) per 100,000 was calculated in each year. …

Impact Of Treatment Response Metrics On Photodynamic Therapy Planning And Outcomes In A Three-Dimensional Model Of Ovarian Cancer, Sriram Anbil, Imran Rizvi, Jonathan P. Celli, Nermina Alagic, Brian W. Pogue, Tayyaba Hasan

Dartmouth Scholarship

Common methods to characterize treatment efficacy based on morphological imaging may misrepresent outcomes and exclude effective therapies. Using a three-dimensional model of ovarian cancer, two functional treatment response metrics are used to evaluate photodynamic therapy (PDT) efficacy: total volume, calculated from viable and nonviable cells, and live volume, calculated from viable cells. The utility of these volume-based metrics is corroborated using independent reporters of photodynamic activity: viability, a common fluorescence-based ratiometric analysis, and photosensitizer photobleaching, which is characterized by a loss of fluorescence due in part to the production of reactive species during PDT. Live volume correlated with both photobleaching …

Averting Hiv Infections In New York City: A Modeling Approach Estimating The Future Impact Of Additional Behavioral And Biomedical Hiv Prevention Strategies, Jason Kessler, Julie E. Myers, Kimberly A. Nucifora, Nana Mensah, Alexis Kowalski, Monica Sweeney, Christopher Toohey, Amin Khademi, Colin Shepard, Blayne Cutler, R. Scott Braithwaite

Publications

Background: New York City (NYC) remains an epicenter of the HIV epidemic in the United States. Given the variety of evidence-based HIV prevention strategies available and the significant resources required to implement each of them, comparative studies are needed to identify how to maximize the number of HIV cases prevented most economically.

Methods: A new model of HIV disease transmission was developed integrating information from a previously validated micro-simulation HIV disease progression model. Specification and parameterization of the model and its inputs, including the intervention portfolio, intervention effects and costs were conducted through a collaborative process between the academic modeling …

Semi-Automated Curation Of Metabolic Models Via Flux Balance Analysis: A Case Study With Mycoplasma Gallisepticum, Eddy J. Bautista, Joseph Zinski, Steven M. Szczepanek, Erik L. Johnson, Edan R. Tulman, Steven J. Geary, Ranjan Srivastava

Open Access Author Fund Awardees' Articles

Primarily used for metabolic engineering and synthetic biology, genome-scale metabolic modeling shows tremendous potential as a tool for fundamental research and curation of metabolism. Through a novel integration of flux balance analysis and genetic algorithms, a strategy to curate metabolic networks and facilitate identification of metabolic pathways that may not be directly inferable solely from genome annotation was developed. Specifically, metabolites involved in unknown reactions can be determined, and potentially erroneous pathways can be identified. The procedure developed allows for new fundamental insight into metabolism, as well as acting as a semi-automated curation methodology for genome-scale metabolic modeling. To validate …

Enzymatic Hydrolysis Of Biomass At High-Solids Loadings – A Review, Alicia A. Modenbach, Sue E. Nokes

Biosystems and Agricultural Engineering Faculty Publications

Enzymatic hydrolysis is the unit operation in the lignocellulose conversion process that utilizes enzymes to depolymerize lignocellulosic biomass. The saccharide components released are the feedstock for fermentation. When performed at high-solids loadings (≥ 15% solids, w/w), enzymatic hydrolysis potentially offers many advantages over conversions performed at low- or moderate-solids loadings, including increased sugar and ethanol concentrations and decreased capital and operating costs.

The goal of this review is to provide a consolidated source of information on studies using high-solids loadings in enzymatic hydrolysis. Included in this review is a brief discussion of the limitations, such as a lack of available …

Changes In Hemodynamic Responses In Chronic Stroke Survivors Do Not Affect Fmri Signal Detection In A Block Experimental Design, Nutta-On Promjunyakul, Brian D. Schmit, Sheila Schindler-Ivens

Physical Therapy Faculty Research and Publications

The use of canonical functions to model BOLD-fMRI data in people post-stroke may lead to inaccurate descriptions of task-related brain activity. The purpose of this study was to determine whether the spatiotemporal profile of hemodynamic responses (HDRs) obtained from stroke survivors during an event-related experiment could be used to develop individualized HDR functions that would enhance BOLD-fMRI signal detection in block experiments. Our long term goal was to use this information to develop individualized HDR functions for stroke survivors that could be used to analyze brain activity associated with locomotor-like movements. We also aimed to examine the reproducibility of HDRs …

Spectral Discrimination Of Breast Pathologies In Situ Using Spatial Frequency Domain Imaging, Ashley M. Laughney, Venkataramanan Krishnaswamy, Elizabeth J. Rizzo, Mary C. Schwab, Richard J. Barth, David J. Cuccia, Bruce J. Tromberg, Keith D. Paulsen, Brian W. Pogue, Wendy A. Wells

Dartmouth Scholarship

Introduction: Nationally, 25% to 50% of patients undergoing lumpectomy for local management of breast cancer require a secondary excision because of the persistence of residual tumor. Intraoperative assessment of specimen margins by frozen-section analysis is not widely adopted in breast-conserving surgery. Here, a new approach to wide-field optical imaging of breast pathology in situ was tested to determine whether the system could accurately discriminate cancer from benign tissues before routine pathological processing.

Effects Of Two Inhaled Corticosteroid/Long-Acting Beta-Agonist Combinations On Small-Airway Dysfunction In Mild Asthmatics Measured By Impulse Oscillometry, Bill Diong, Kshitiz Singh, Rogelio Menendez

Faculty and Research Publications

Background: We previously showed that the long-acting beta agonist (LABA) salmeterol as inhalation powder or metered-dose inhaler improves lung-function parameters assessed by impulse oscillometry (IOS) in 2- to 5-year-old children with reversible-airway disease within 15 minutes. Objective: We studied 12- to 45-year-olds with mild persistent asthma in order to compare the onset and extent of peripheral airway effects following the first dose and after 4 weeks dosing with two inhaled corticosteroid (ICS)/LABA combinations: fluticasone propionate/salmeterol 115/21 and budesonide/formoterol 160/4.5. Methods: Thirty subjects with mild persistent asthma using only an as-needed short-acting beta-agonist (albuterol) who had at least a 40% change …

Measurement And Description Of Dynamics Required For In Vivo Surgical Robotics Via Kinematic Methods, Jacob G. Greenburg

Department of Mechanical and Materials Engineering: Dissertations, Theses, and Student Research

With the goal of improved recovery times and reduced trauma to the patient there has been a substantial shift in the medical community’s demand for minimally invasive surgical (MIS) techniques. With the standardization of MIS becoming more commonplace in the medical field there are still many improvements that are desired. Traditional, manual methods of these surgeries require multiple incisions on the abdomen for the tools and instruments to be inserted. The more recent demand has been to localize the incisions into what is being referred to as a Laparoendoscopic Single-Site (LESS) surgery. Furthermore, the manual instruments that are commonly used …

2013 Tsu Undergraduate Research Program, David Owerbach

Office of Research Institutional Research and Scholarship

No abstract provided.

Juxtaposing Nasa’S Aeronet Aod With Carb Pm Data Over The San Joaquin Valley To Facilitate Multi-Angle Imaging Spectroradiometer (Misr) Pm Pollution Research, John Kanemoto

STAR Program Research Presentations

Airborne particulate matter (PM) has been shown to increase the risk for asthma, chronic bronchitis, cardiopulmonary complications, and respiratory cell membrane damage/infection/leakage. PM levels are currently analyzed from two perspectives: stationary land-based monitoring (LBM) sites and total Aerosol Optical Depth (AOD) atmospheric column measurements. Both perspectives often leave miles of space between measuring locations and will have a continually increasing cost from introducing/maintaining sites. The Multi-angle Imaging SpectroRadiometer (MISR) satellite team hopes to begin investigating/archiving PM levels comprehensively via inputting MISR AOD measurements into a function/model which predicts the amount of ground level PM.

In the future, multivariable spatial correlations …

Interleukin Expression After Injury And The Effects Of Interleukin-1 Receptor Antagonist, Connie S. Chamberlain, Ellen M. Leiferman, Kayt E. Frisch, Stacey L. Brickson, William L. Murphy, Geoffrey S. Baer

Faculty Publications - Biomedical, Mechanical, and Civil Engineering

Ligament and tendon repair involves a complex series of coordinated events orchestrated by various cell types, cytokines and other factors. The repair process extends months to years and results in scar tissue mechanically inferior to native tissue. This is in clear contrast to tissue "regeneration" which would recapitulate the native tissue. Numerous approaches to stimulate a regenerative scenario have been attempted, including tissue-engineering, non-steroidal anti-inflammatories, ultrasonic, or electrical stimulation, but none have resulted in complete regeneration. In pursuit of a more regenerative outcome, it is important to understand the fundamentals of the normal healing process. Previous work from our lab …

Efferent Copy And Corollary Discharge Motor Control Behavior Associated With A Hopping Activity, Wangdo Kim, António P. Veloso, Filipa João, Sean S. Kohles

Mechanical and Materials Engineering Faculty Publications and Presentations

Hoppers respond not only to stimuli from the ground surfaces but also to cues generated by their own behaviors. This leads to desensitization because although the afferent and reafferent signals have distinct causes, they are carried by the same sensory channels. From a behavioral viewpoint, it may be necessary to distinguish between signals from the two causes especially when monitoring changes in the external environment separate from those due to self-movement. We were able to separate afferent sensory stimuli from self-generated, reafferent signals using an action oriented perception system and dynamic programming approach. This effort addressed the question of how …

Pilot Study Assessment Of Dynamic Vascular Changes In Breast Cancer With Near-Infrared Tomography From Prospectively Targeted Manipulations Of Inspired End-Tidal Partial Pressure Of Oxygen And Carbon Dioxide, Shudong Jiang, Brian W. Pogue, Kelly E. Michaelsen, Michael Jermyn, Michael A. Mastanduno, Tracy E. Frazee, Peter A. Kaufman, Keith D. Paulsen

Dartmouth Scholarship

The dynamic vascular changes in the breast resulting from manipulation of both inspired end-tidal partial pressure of oxygen and carbon dioxide were imaged using a 30 s per frame frequency-domain near-infrared spectral (NIRS) tomography system. By analyzing the images from five subjects with asymptomatic mammography under different inspired gas stimulation sequences, the mixture that maximized tissue vascular and oxygenation changes was established. These results indicate maximum changes in deoxy-hemoglobin, oxygen saturation, and total hemoglobin of 21, 9, and 3%, respectively. Using this inspired gas manipulation sequence, an individual case study of a subject with locally advanced breast cancer undergoing neoadjuvant …

Metal-Based Nanoparticle Interactions With The Nervous System: The Challenge Of Brain Entry And The Risk Of Retention In The Organism, Robert A. Yokel, Eric A. Grulke, Robert C. Macphail

Pharmaceutical Sciences Faculty Publications

This review of metal-based nanoparticles focuses on factors influencing their distribution into the nervous system, evidence they enter brain parenchyma, and nervous system responses. Gold is emphasized as a model metal-based nanoparticle and for risk assessment in the companion review. The anatomy and physiology of the nervous system, basics of colloid chemistry, and environmental factors that influence what cells see are reviewed to provide background on the biological, physical–chemical, and internal milieu factors that influence nervous system nanoparticle uptake. The results of literature searches reveal little nanoparticle research included the nervous system, which about equally involved in vitro and in …

Influence Of Media Composition On The Growth Rate Of Chlorella Vulgaris And Scenedesmus Acutus Utilized For Co2 Mitigation, Czarena L. Crofcheck, Xinyi E, Aubrey Shea, Michael D. Montross, Mark Crocker, Rodney Andrews

Biosystems and Agricultural Engineering Faculty Publications

Atmospheric carbon dioxide levels have increased since the industrial revolution due to increasing combustion of fossil fuels. One possible CO₂ mitigation strategy is the use of microalgae for mitigation of CO₂. This paper focuses on the influence of media composition on the growth rate of two microalgae strains, Chlorella vulgaris and Scenedesmus actus. A KNO₃ based medium was found to work better for Chlorella, while a urea based equivalent worked better for Scenedesmus. The urea based media investigated here resulted in growth similar to that found with previously reported KNO₃ based media. …

An Assessment Of Novel Biodegradable Magnesium Alloys For Endovascular Biomaterial Applications, Dharam Persaud-Sharma

FIU Electronic Theses and Dissertations

Magnesium alloys have been widely explored as potential biomaterials, but several limitations to using these materials have prevented their widespread use, such as uncontrollable degradation kinetics which alter their mechanical properties. In an attempt to further the applicability of magnesium and its alloys for biomedical purposes, two novel magnesium alloys Mg-Zn-Cu and Mg-Zn-Se were developed with the expectation of improving upon the unfavorable qualities shown by similar magnesium based materials that have previously been explored. The overall performance of these novel magnesium alloys has been assessesed in three distinct phases of research: 1) analysing the mechanical properties of the as-cast …

Experimental Assessment Of The Impact Of Asymptomatic Gas Emboli On The Vessel Wall, Linxia Gu, Eric L. Cutler

Department of Mechanical and Materials Engineering: Faculty Publications

Quantitative evaluation of shear stress in the vessel wall due to the presence of asymptomatic gas emboli is lacking. The goal of this work was to assess the impact of chronic asymptomatic gas emboli on the risk of atherosclerosis through a custom-built cardiovascular flow simulator. Gas bubbles were created by forced air from a syringe pump. The influences of embolism injection rate, pulse rate, and time-averaged flow rate on the wall mean shear stress were investigated at resting and elevated heart rate conditions. The recorded pressure and volumetric flow rate from 24 experimental settings with four repetitions each were used …

Dynamic Dual-Tracer Mri-Guided Fluorescence Tomography To Quantify Receptor Density In Vivo, Scott C. Davis, Kimberley S. Samkoe, Kenneth M. Tichauer, Kristian J. Sexton, Jason R. Gunn, Sophie J. Deharvengt, Tayyaba Hasan, Brian W. Pogue

Dartmouth Scholarship

The up-regulation of cell surface receptors has become a central focus in personalized cancer treatment; however, because of the complex nature of contrast agent pharmacokinetics in tumor tissue, methods to quantify receptor binding in vivo remain elusive. Here, we present a dual-tracer optical technique for noninvasive estimation of specific receptor binding in cancer. A multispectral MRI-coupled fluorescence molecular tomography system was used to image the uptake kinetics of two fluorescent tracers injected simultaneously, one tracer targeted to the receptor of interest and the other tracer a nontargeted reference. These dynamic tracer data were then fit to a dual-tracer compartmental model …

Individual Articulator's Contribution To Phoneme Production, Jun Wang, Jordan R. Green, Ashok Samal

CSE Conference and Workshop Papers

Speech sounds are the result of coordinated movements of individual articulators. Understanding each articulator’s role in speech is fundamental not only for understanding how speech is produced, but also for optimizing speech assessments and treatments. In this paper, we studied the individual contributions of six articulators, tongue tip, tongue blade, tongue body front, tongue body back, upper lip, and lower lip to phoneme classification. A total of 3,838 vowel and consonant production samples were collected from eleven native English speakers. The results of speech movement classification using a support vector machine indicated that the tongue encoded significantly more information than …