Biomedical Engineering and Bioengineering Commons^™

Tumor Cell Death After Electrotransfer Of Plasmid Dna Is Associated With Cytosolic Dna Sensor Upregulation, Katarina Znidar, Masa Bosnjak, Nina Semenova, Olga N. Pakhomova, Loree Heller, Maja Cemazar

Bioelectrics Publications

Cytosolic DNA sensors are a subgroup of pattern recognition receptors (PRRs) and are activated by the abnormal presence of the DNA in the cytosol. Their activation leads to the upregulation of pro-inflammatory cytokines and chemokines and can also induce cell death. The presence of cytosolic DNA sensors and inflammatory cytokines in TS/A murine mammary adenocarcinoma and WEHI 164 fibrosarcoma cells was demonstrated using real time reverse transcription polymerase chain reaction (RT-PCR), western blotting and enzyme-linked immunosorbent assay (ELISA). After electrotransfer of plasmid DNA (pDNA) using two pulse protocols, the upregulation of DNA-depended activator of interferon regulatory factor or Z-DNA binding …

Nano-Pulse Stimulation For The Treatment Of Pancreatic Cancer And The Changes In Immune Profile, Sigi Guo, Niculina I. Burcus, James Hornef, Yu Jing, Chunqi Jiang, Richard Heller, Stephen J. Beebe

Bioelectrics Publications

A Pancreatic cancer is a notorious malignant neoplasm with an extremely poor prognosis. Current standard of care is rarely effective against late-stage pancreatic cancer. In this study, we assessed nanopulse stimulation (NPS) as a local treatment for pancreatic cancer in a syngeneic mouse Pan02 pancreatic cancer model and characterized corresponding changes in the immune profile. A single NPS treatment either achieved complete tumor regression or prolonged overall survival in animals with partial tumor regression. While this is very encouraging, we also explored if this local ablation effect could also result in immune stimulation, as was observed when NPS led to …

Electrosensitization Increases Antitumor Effectiveness Of Nanosecond Pulsed Electric Fields In Vivo, Claudia Muratori, Andrei G. Pakhomov, Loree Heller, Maura Casciola, Elena Gianulis, Sergey Grigoryev, Shu Xiao, Olga N. Pakhomova

Bioelectrics Publications

Nanosecond pulsed electric fields are emerging as a new modality for tissue and tumor ablation. We previously reported that cells exposed to pulsed electric fields develop hypersensitivity to subsequent pulsed electric field applications. This phenomenon, named electrosensitization, is evoked by splitting the pulsed electric field treatment in fractions (split-dose treatments) and causes in vitro a 2- to 3-fold increase in cytotoxicity. The aim of this study was to show the benefit of split-dose treatments for in vivo tumor ablation by nanosecond pulsed electric field. KLN 205 squamous carcinoma cells were embedded in an agarose gel or grown subcutaneously as tumors …

Effect Of Twisted Fiber Anisotropy In Cardiac Tissue On Ablation With Pulsed Electric Fields, Fei Xie, Christian W. Zemlin

Bioelectrics Publications

Background: Ablation of cardiac tissue with pulsed electric fields is a promising alternative to current thermal ablation methods, and it critically depends on the electric field distribution in the heart.

Methods: We developed a model that incorporates the twisted anisotropy of cardiac tissue and computed the electric field distribution in the tissue. We also performed experiments in rabbit ventricles to validate our model. We find that the model agrees well with the experimentally determined ablation volume if we assume that all tissue that is exposed to a field greater than 3 kV/cm is ablated. In our numerical analysis, we considered …

Categorizing Fetal Heart Rate Variability With And Without Visual Aids, Amanda J. Ashdown, Mark W. Scerbo, Lee A. Belfore Ii, Stephen S. Davis, Alfred Z. Abuhamad

Psychology Faculty Publications

Objective This study examined the ability of clinicians to correctly categorize images of fetal heart rate (FHR) variability with and without the use of exemplars.

Study Design A sample of 33 labor and delivery clinicians inspected static FHR images and categorized them into one of four categories defined by the National Institute of Child Health and Human Development (NICHD) based on the amount of variability within absent, minimal, moderate, or marked ranges. Participants took part in three conditions: two in which they used exemplars representing FHR variability near the center or near the boundaries of each range, and a third …

Radio-Frequency Plasma Polymerized Biodegradable Carrier For In Vivo Release Of Cis-Platinum, Sudhir Bhatt, Fatemeh Valamanesh, Jerome Pulpytel, Rea Lo Dico, Aliby Baiyukha, Iman Al-Dybiat, Marc Pocard, Farzaneh Arefi-Khonsari, Massoud Mirshahi

Bioelectrics Publications

A low pressure plasma process based on plasma deposition has been used to develop a drug delivery strategy. In this study, a drug delivery system based on different layers of plasma co-polymerized Poly ε-caprolactone-Polyethylene glycol (PCL-PEG) co-polymers was deposited on biocompatible substrates. Cis-platinum (118 μgm/cm²) was used as an anti-cancer drug and incorporated for local delivery of the chemotherapeutic agent. The co-polymer layers and their interaction with cancer cells were analyzed by scanning electron microscopy. Our study showed that the plasma-PCL-PEG coated cellophane membranes, in which the drug, was included did not modify the flexibility and appearance of …

Bioactive Lipid Coating Of Bone Allografts Direct Engraftment And Fate Determination Of Bone Marrow-Derived Cells In Rat Gfp Chimeras, Anusuya Das, Claire E. Segar, Yihsuan Chu, Tiffany W. Wang, Yon Lin, Chunxi Yang, Roy C. Ogle

School of Medical Diagnostics & Translational Sciences Faculty Publications

Bone grafting procedures are performed to treat wounds incurred during wartime trauma, accidents, and tumor resections. Endogenous mechanisms of repair are often insufficient to ensure integration between host and donor bone and subsequent restoration of function. We investigated the role that bone marrow-derived cells play in bone regeneration and sought to increase their contributions by functionalizing bone allografts with bioactive lipid coatings. Polymer-coated allografts were used to locally deliver the immunomodulatory small molecule FTY720 in tibial defects created in rat bone marrow chimeras containing genetically-labeled bone marrow for monitoring cell origin and fate. Donor bone marrow contributed significantly to both …

Application And Histology-Driven Refinement Of Active Contour Models To Functional Region And Nerve Delineation: Towards A Digital Brainstem Atlas, Nimal Patel, Sharmin Sultana, Tanweer Rashid, Dean Krusienski, Michel A. Audette

Electrical & Computer Engineering Faculty Publications

This paper presents a methodology for the digital formatting of a printed atlas of the brainstem and the delineation of cranial nerves from this digital atlas. It also describes on-going work on the 3D resampling and refinement of the 2D functional regions and nerve contours. In MRI-based anatomical modeling for neurosurgery planning and simulation, the complexity of the functional anatomy entails a digital atlas approach, rather than less descriptive voxel or surface-based approaches. However, there is an insufficiency of descriptive digital atlases, in particular of the brainstem. Our approach proceeds from a series of numbered, contour-based sketches coinciding with slices …

A Comparative Study Of Two Prediction Models For Brain Tumor Progression, Deqi Zhou, Loc Tran, Jihong Wang, Jiang Li, Karen O. Egiazarian (Ed.), Sos S. Agaian (Ed.), Atanas P. Gotchev (Ed.)

Electrical & Computer Engineering Faculty Publications

MR diffusion tensor imaging (DTI) technique together with traditional T1 or T2 weighted MRI scans supplies rich information sources for brain cancer diagnoses. These images form large-scale, high-dimensional data sets. Due to the fact that significant correlations exist among these images, we assume low-dimensional geometry data structures (manifolds) are embedded in the high-dimensional space. Those manifolds might be hidden from radiologists because it is challenging for human experts to interpret high-dimensional data. Identification of the manifold is a critical step for successfully analyzing multimodal MR images.

We have developed various manifold learning algorithms (Tran et al. 2011; Tran et al. …

Ablation Of Myocardial Tissue With Nanosecond Pulsed Electric Fields, Fei Xie, Frency Varghese, Andrei G. Pakhomov, Iurii Semenov, Shu Xiao, Jonathan Philpott, Christian Zemlin

Bioelectrics Publications

Background

Ablation of cardiac tissue is an essential tool for the treatment of arrhythmias, particularly of atrial fibrillation, atrial flutter, and ventricular tachycardia. Current ablation technologies suffer from substantial recurrence rates, thermal side effects, and long procedure times. We demonstrate that ablation with nanosecond pulsed electric fields (nsPEFs) can potentially overcome these limitations.

Methods

We used optical mapping to monitor electrical activity in Langendorff-perfused New Zealand rabbit hearts (n = 12). We repeatedly inserted two shock electrodes, spaced 2–4 mm apart, into the ventricles (through the entire wall) and applied nanosecond pulsed electric fields (nsPEF) (5–20 kV/cm, 350 ns duration, …

A Nonrigid Registration Method For Correcting Brain Deformation Induced By Tumor Resection, Yixun Liu, Chengjun Yao, Fotis Drakopoulos, Jinsong Wu, Liangfu Zhou, Nikos Chrisochoides

Computer Science Faculty Publications

Purpose: This paper presents a nonrigid registration method to align preoperative MRI with intraoperative MRI to compensate for brain deformation during tumor resection. This method extends traditional point-based nonrigid registration in two aspects: (1) allow the input data to be incomplete and (2) simulate the underlying deformation with a heterogeneous biomechanical model.

Methods: The method formulates the registration as a three-variable (point correspondence, deformation field, and resection region) functional minimization problem, in which point correspondence is represented by a fuzzy assign matrix; Deformation field is represented by a piecewise linear function regularized by the strain energy of a heterogeneous biomechanical …

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 …

Evaluation Of A Novel Non-Penetrating Electrode For Use In Dna Vaccination, Amy Donate, Domenico Coppola, Yolmari Cruz, Richard Heller

Bioelectrics Publications

Current progress in the development of vaccines has decreased the incidence of fatal and non-fatal infections and increased longevity. However, new technologies need to be developed to combat an emerging generation of infectious diseases. DNA vaccination has been demonstrated to have great potential for use with a wide variety of diseases. Alone, this technology does not generate a significant immune response for vaccination, but combined with delivery by electroporation (EP), can enhance plasmid expression and immunity. Most EP systems, while effective, can be invasive and painful making them less desirable for use in vaccination. Our lab recently developed a non-invasive …

Prediction Of Brain Tumor Progression Using Multiple Histogram Matched Mri Scans, Debrup Banerjee, Loc Tran, Jiang Li, Yuzhong Shen, Frederic Mckenzie, Jihong Wang, Ronald M. Summers (Ed.), Bram Van Ginneken (Ed.)

Electrical & Computer Engineering Faculty Publications

In a recent study [1], we investigated the feasibility of predicting brain tumor progression based on multiple MRI series and we tested our methods on seven patients' MRI images scanned at three consecutive visits A, B and C. Experimental results showed that it is feasible to predict tumor progression from visit A to visit C using a model trained by the information from visit A to visit B. However, the trained model failed when we tried to predict tumor progression from visit B to visit C, though it is clinically more important. Upon a closer look at the MRI scans …

Prostate Cancer Region Prediction Using Maldi Mass Spectra, Ayyappa Vadlamudi, Shao-Hui Chuang, Xiaoyan Sun, Lisa Cazares, Julius Nyalwidhe, Dean Troyer, O. John Semmes, Jiang Li, Frederic D. Mckenzie

Electrical & Computer Engineering Faculty Publications

For the early detection of prostate cancer, the analysis of the Prostate-specific antigen (PSA) in serum is currently the most popular approach. However, previous studies show that 15% of men have prostate cancer even their PSA concentrations are low. MALDI Mass Spectrometry (MS) proves to be a better technology to discover molecular tools for early cancer detection. The molecular tools or peptides are termed as biomarkers. Using MALDI MS data from prostate tissue samples, prostate cancer biomarkers can be identified by searching for molecular or molecular combination that can differentiate cancer tissue regions from normal ones. Cancer tissue regions are …

Automatic Diagnosis For Prostate Cancer Using Run-Length Matrix Method, Xiaoyan Sun, Shao-Hui Chuang, Jiang Li, Frederic Mckenzie, Nico Karssemeijer (Ed.), Maryellen L. Giger (Ed.)

Electrical & Computer Engineering Faculty Publications

Prostate cancer is the most common type of cancer and the second leading cause of cancer death among men in US¹. Quantitative assessment of prostate histology provides potential automatic classification of prostate lesions and prediction of response to therapy. Traditionally, prostate cancer diagnosis is made by the analysis of prostate-specific antigen (PSA) levels and histopathological images of biopsy samples under microscopes. In this application, we utilize a texture analysis method based on the run-length matrix for identifying tissue abnormalities in prostate histology. A tissue sample was collected from a radical prostatectomy, H&E fixed, and assessed by a pathologist …

Optimizing Computer-Aided Colonic Polyp Detection For Ct Colonography By Evolving The Pareto Front, Jiang Li, Adam Huang, Jack Tao, Jiamin Liu, Robert L. Van Uitert, Nicholas Petrick, Ronald Summers

Electrical & Computer Engineering Faculty Publications

A multiobjective genetic algorithm is designed to optimize a computer-aided detection (CAD) system for identifying colonic polyps. Colonic polyps appear as elliptical protrusions on the inner surface of the colon. Curvature-based features for colonic polyp detection have proved to be successful in several CT colonography (CTC) CAD systems. Our CTC CAD program uses a sequential classifier to form initial polyp detections on the colon surface. The classifier utilizes a set of thresholds on curvature-based features to cluster suspicious colon surface regions into polyp candidates. The thresholds were previously chosen experimentally by using feature histograms. The chosen thresholds were effective for …

A New Pulsed Electric Field Therapy For Melanoma Disrupts The Tumor's Blood Supply And Causes Complete Remission Without Recurrence, Richard Nuccitelli, Xinhua Chen, Andrei G. Pakhomov, Wallace H. Baldwin, Saleh Sheikh, Jennifer L. Pomicter, Wei Ren, Chris Osgood, R. James Swanson, Juergen F. Kolb, Stephen J. Beebe, Karl H. Schoenbach

Bioelectrics Publications

We have discovered a new, ultrafast therapy for treating skin cancer that is extremely effective with a total electric field exposure time of only 180 mu sec. The application of 300 high-voltage (40 kV/cm), ultrashort (300 nsec) electrical pulses to murine melanomas in vivo triggers both necrosis and apoptosis, resulting in complete tumor remission within an average of 47 days in the 17 animals treated. None of these melanomas recurred during a 4-month period after the initial melanoma had disappeared. These pulses generate small, long-lasting, rectifying nanopores in the plasma membrane of exposed cells, resulting in increased membrane permeability to …

Implementation Of Gy-Eq For Deterministic Effects Limitation In Shield Design, John W. Wilson, Myung-Hee Y. Kim, Giovanni De Angelis, Francis A. Cucinotta, Nobuaki Yoshizawa, Francis F. Badavi

Mathematics & Statistics Faculty Publications

The NCRP has recently defined RBE values and a new quantity (Gy-Eq) for use in estimation of deterministic effects in space shielding and operations. The NCRP's RBE for neutrons is left ambiguous and not fully defined. In the present report we will suggest a complete definition of neutron RBE consistent with the NCRP recommendations and evaluate attenuation properties of deterministic effects (Gy-Eq) in comparison with other dosimetric quantities.