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Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis.

Introducing Experimental Agents into the Mouse

JoVE 5161

Many investigations performed in mice (Mus musculus) require the administration of an experimental agent to the animal. For example, it may be of interest to test the efficacy of a specific therapy, to induce a pathologic condition, or to administer anesthesia or palliative care. In order to ensure safe and efficient delivery, it is important to consider a variety of factors prior to the administration of the treatment. This video, which reviews agent administration in the mouse, begins by highlighting properties to consider, such as viscosity, dose, and palatability, when planning the administration of an experimental agent. The subsequent discussion focuses on injection methods, including delineation of the structural components of the syringe and needle, how to interpret needle gauge, and safe mouse restraint methods for common injection sites. Detailed instructions are provided for performing subcutaneous (SC/SubQ), intraperitoneal (IP), and tail vein (IV) injections in mice. Furthermore, applications of these techniques as well as alternative administration routes are discussed.


 Biology II

An Introduction to the Laboratory Mouse: Mus musculus

JoVE 5129

Mice (Mus musculus) are an important research tool for modeling human disease progression and development in the lab. Despite differences in their size and appearance, mice share a distinct genetic similarity to humans, and their ability to reproduce and mature quickly make them efficient and economical candidate mammals for scientific study.

This video provides a brief overview of mice, both as organisms and in terms of their many advantages as experimental models. The discussion features an introduction to common laboratory mouse strains, including the nude mouse, whose genetic makeup renders them both hairless and immunodeficient. A brief history of mouse research is also offered, ranging from their first use in genetics experiments to Nobel prize-winning discoveries in immunology and neurobiology. Finally, representative examples of the diverse types of research that can be performed in mice are presented, such as classic behavioral tests like the Morris water maze and in-depth investigations of mammalian embryonic development.


 Biology II

Near-infrared Fluorescence Imaging of Abdominal Aortic Aneurysms

JoVE 10394

Source: Arvin H. Soepriatna1, Kelsey A. Bullens2, and Craig J. Goergen1

1 Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana

2 Department of Biochemistry, Purdue University, West Lafayette, Indiana Near-infrared fluorescence (NIRF) imaging is an exciting optical technique that utilizes fluorescent probes to visualize complex biomolecular assemblies in tissues. NIRF imaging has many advantages over conventional imaging methods for noninvasive imaging of diseases. Unlike single photon emission computed tomography (SPECT) and positron emission tomography (PET), NIRF imaging is rapid, high-throughput, and does not involve ionizing radiation. Furthermore, recent developments in engineering target-specific and activatable fluorescent probes provide NIRF with high specificity and sensitivity, making it an attractive modality in studying cancer and cardiovascular disease. The presented procedure is designed to demonstrate the principles behind NIRF imaging and how to conduct in vivo and ex vivo experiments in small animals to study a variety of diseases. The specific example shown here employs an activatab


 Biomedical Engineering

Combined SPECT and CT Imaging to Visualize Cardiac Functionality

JoVE 10396

Source: Alycia G. Berman, James A. Schaber, and Craig J. Goergen, Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana

Here we will demonstrate the fundamentals of single-photon emission computed tomography/computed tomography (SPECT/CT) imaging using mice. The technique involves injecting a radionuclide into a mouse, imaging the animal after it is distributed throughout the body, and then reconstructing the produced images to create a volumetric dataset. This can provide information about anatomy, physiology, and metabolism to improve disease diagnosis and monitor its progression. In terms of collected data, SPECT/CT provides similar information as positron emission tomography (PET)/CT. However, the underlying principles of these two techniques are fundamentally different since PET requires the detection of two gamma photons, which are emitted in opposite directions. In contrast, SPECT imaging directly measures radiation via a gamma camera. As a result, SPECT imaging has lower spatial resolution than PET. However, it is also less expensive because the SPECT radioactive isotopes are more readily available. SPECT/CT imaging provides both noninvasive metabolic and anatomical information that can be useful for a wide variety of applications.


 Biomedical Engineering

Computational Fluid Dynamics Simulations of Blood Flow in a Cerebral Aneurysm

JoVE 10479

The objective of this video is to describe recent advancements of computational fluid dynamic (CFD) simulations based on patient- or animal-specific vasculature. Here, subject-based vessel segmentations were created, and, using a combination of open-source and commercial tools, a high-resolution numerical solution was determined within a flow model. Numerous studies have demonstrated that the hemodynamic conditions within the vasculature affect the development and progression of atherosclerosis, aneurysms, and other peripheral artery diseases; concomitantly, direct measurements of intraluminal pressure, wall shear stress (WSS), and particle residence time (PRT) are difficult to acquire in vivo. CFD allow such variables to be assessed non-invasively. In addition, CFD is used to simulate surgical techniques, which provides physicians better foresight regarding post-operative flow conditions. Two methods in magnetic resonance imaging (MRI), magnetic resonance angiography (MRA) with either time of flight (TOF-MRA) or contrast-enhanced MRA (CE-MRA) and phase-contrast (PC-MRI), allow us to obtain vessel geometries and time-resolved 3D velocity fields, respectively. TOF-MRA is based on the suppression of the signal from static tissue by repeated RF pulses that are applied to the imaged volume. A signal is obtained from un


 Biomedical Engineering

Photoacoustic Tomography to Image Blood and Lipids in the Infrarenal Aorta

JoVE 10395

Source: Gurneet S. Sangha and Craig J. Goergen, Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana

Photoacoustic tomography (PAT) is an emerging biomedical imaging modality that utilizes light generated acoustic waves to obtain compositional information from tissue. PAT can be used to image blood and lipid components, which is useful for a wide variety of applications, including cardiovascular and tumor imaging. Currently used imaging techniques have inherent limitations that restrict their use with researchers and physicians. For example, long acquisition times, high costs, use of harmful contrast, and minimal to high invasiveness are all factors that limit the use of various modalities in the laboratory and clinic. Currently, the only comparable imaging techniques to PAT are emerging optical techniques. But these also have disadvantages, such as limited depth of penetration and the need for exogenous contrast agents. PAT provides meaningful information in a rapid, noninvasive, label-free manner. When coupled with ultrasound, PAT can be used to obtain structural, hemodynamic, and compositional information from tissue, thereby complementing currently used imaging techniques. The advantages of PAT illustrate its capabilities to make an impact in both the preclinical and clinical


 Biomedical Engineering

Quantitative Strain Mapping of an Abdominal Aortic Aneurysm

JoVE 10480

Authors: Hannah L. Cebull1, Arvin H. Soepriatna1, John J. Boyle2 and Craig J. Goergen1 1Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana 2Mechanical Engineering & Materials Science, Washington University in St. Louis, St Louis, Missouri

The mechanical behavior of soft tissues, such as blood vessels, skin, tendons, and other organs, are strongly influenced by their composition of elastin and collagen, which provide elasticity and strength. The fiber orientation of these proteins depends on the type of soft tissue and can range from a single preferred direction to intricate meshed networks, which can become altered in diseased tissue. Therefore, soft tissues often behave anisotropically on the cellular and organ level, creating a need for three-dimensional characterization. Developing a method for reliably estimating strain fields within complex biological tissues or structures is important to mechanically characterize and understande disease. Strain represents how soft tissue relatively deforms over time, and it can be described mathematically through various estimations. Acquiring image data over time allows deformation and strain to be estimated. However, all medica


 Biomedical Engineering

Shunt Surgery, Right Heart Catheterization, and Vascular Morphometry in a Rat Model for Flow-induced Pulmonary Arterial Hypertension

1Center for Congenital Heart Diseases, Department of Pediatric Cardiology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, 2Research and Development Facility, University Medical Center Groningen, University of Groningen

JoVE 55065


 Medicine

Cardiac Magnetic Resonance Imaging

JoVE 10393

Source: Frederick W. Damen and Craig J. Goergen, Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana

In this video, high field, small-bore magnetic resonance imaging (MRI) with physiological monitoring is demonstrated to acquire gated cine loops of the murine cardiovascular system. This procedure provides a basis for assessing left-ventricular function, visualizing vascular networks, and quantifying motion of organs due to respiration. Comparable small animal cardiovascular imaging modalities include high-frequency ultrasound and micro-computed tomography (CT); however, each modality is associated with trade-offs that should be considered. While ultrasound does provide high spatial and temporal resolution, imaging artifacts are common. For example, dense tissue (i.e., the sternum and ribs) can limit imaging penetration depth, and hyperechoic signal at the interface between gas and liquid (i.e., pleura surrounding the lungs) can blur contrast in nearby tissue. Micro-CT in contrast does not suffer from as many in-plane artifacts, but does have lower temporal resolution and limited soft-tissue contrast. Furthermore, micro-CT uses X-ray radiation and often requires the use of contrast agents to visualize vasculature, both of which are known to cause side effects at high doses incl


 Biomedical Engineering

In vivo Imaging of Transgenic Leishmania Parasites in a Live Host

1Interdisciplinary Immunology Program, University of Iowa, and the VA Medical Center, 2Department of Biochemistry, University of Iowa, and the VA Medical Center, 3Department of Internal Medicine, University of Iowa, 4Department of Molecular Microbiology, Washington University School of Medicine, 5Division of Dermatology, Harbor-UCLA Medical Center, Hanley-Hardison Research Center, 6Interdisciplinary Immunology Program, Iowa City VA Medical Center, 7Departments of Internal Medicine, Microbiology and Epidemiology, University of Iowa

JoVE 1980


 Immunology and Infection

Analysis of 18FDG PET/CT Imaging as a Tool for Studying Mycobacterium tuberculosis Infection and Treatment in Non-human Primates

1Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, 2Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center

JoVE 56375


 Immunology and Infection

Novel Atomic Force Microscopy Based Biopanning for Isolation of Morphology Specific Reagents against TDP-43 Variants in Amyotrophic Lateral Sclerosis

1School for Engineering of Matter, Transport and Energy, Arizona State University, 2Department of Neurology, Georgetown University Medical Center, 3Department of Pathology, Georgetown University Medical Center

JoVE 52584


 Bioengineering

Characterization of Tumor Cells Using a Medical Wire for Capturing Circulating Tumor Cells: A 3D Approach Based on Immunofluorescence and DNA FISH

1Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 2Associazione Annastaccatolisa Onlus, 3Nuclear Medicine Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS

JoVE 56936


 Cancer Research

Determining Immune System Suppression versus CNS Protection for Pharmacological Interventions in Autoimmune Demyelination

1Physical Medicine and Rehabilitation, University of Alabama at Birmingham, 2Department of Pathology, University of Alabama at Birmingham, 3Department of Neurobiology, University of Alabama at Birmingham, 4Center for Glial Biology and Medicine, University of Alabama at Birmingham

JoVE 54348


 Immunology and Infection

Laser Capture Microdissection of Highly Pure Trabecular Meshwork from Mouse Eyes for Gene Expression Analysis

1Immunity, Inflammation, and Disease Laboratory, Division of Intramural Research, National Institute of Environmental Health Sciences, NIH, 2Cellular and Molecular Pathology Branch, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, NIH, 3Integrated Laboratory Systems Inc., 4Experimental Pathology Laboratories Inc.

JoVE 57576


 Biology

Transposon Mediated Integration of Plasmid DNA into the Subventricular Zone of Neonatal Mice to Generate Novel Models of Glioblastoma

1Department of Neurosurgery, University of Michigan School of Medicine, 2Department of Pediatrics, Division of Hematology-Oncology, University of Michigan School of Medicine, 3Department of Cell and Developmental Biology, University of Michigan

JoVE 52443


 Medicine

Analyzing Beneficial Effects of Nutritional Supplements on Intestinal Epithelial Barrier Functions During Experimental Colitis

1Department of Molecular Biomedicine, Center for Research and Advanced Studies of the National Polytechnic Institute, 2Department of Physiology, Biophysics and Neurosciences, Center for Research and Advanced Studies of the National Polytechnic Institute, 3Department of Infectomics and Molecular Pathogenesis, Center for Research and Advanced Studies of the National Polytechnic Institute

JoVE 55095


 Medicine

In Vivo Model for Testing Effect of Hypoxia on Tumor Metastasis

1Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, 2Department of Nursing, Georgetown University, School of Nursing and Health Studies, 3Department of Human Science, Georgetown University, School of Nursing and Health Studies, 4School of Medicine, Georgetown University Medical Center, 5Department of Pathology and Neuropathology, Medical University of Gdańsk, 6Department of Oncology, Georgetown University Medical Center, 7Department of Pathology, Georgetown University Medical Center

JoVE 54532


 Cancer Research

Evaluation of Biomarkers in Glioma by Immunohistochemistry on Paraffin-Embedded 3D Glioma Neurosphere Cultures

1Department of Neurosurgery, University of Michigan Medical School, 2Department of Cell & Developmental Biology, University of Michigan, 3INIBIOLP, Histology B-Pathology B, School of Medicine, UNLP

Video Coming Soon

JoVE 58931


 JoVE In-Press

Detection of a Circulating MicroRNA Custom Panel in Patients with Metastatic Colorectal Cancer

1Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 2Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 3Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS

Video Coming Soon

JoVE 58615


 JoVE In-Press

Measurements of Motor Function and Other Clinical Outcome Parameters in Ambulant Children with Duchenne Muscular Dystrophy

1Division of Pediatric Neurology, University Children's Hospital Basel (UKBB), University of Basel, 2Department of Neurology, University of Basel Hospital, 3Division of Neurology, Medical University Clinic, Kantonsspital Baselland, 4Division of Pediatric Neurology, CHUV, 5Division of Neuropaediatrics, Inselspital, University Children's Hospital Bern, 6Department of Radiology, Division of Radiological Physics, University of Basel Hospital, 7Hospices Civils de Lyon, Hôpital Femme-Mère-Enfant, L'Escale, Service de Médecine Physique et de Réadaptation Pédiatrique

Video Coming Soon

JoVE 58784


 JoVE In-Press

Multimodal Bioluminescent and Positronic-emission Tomography/Computational Tomography Imaging of Multiple Myeloma Bone Marrow Xenografts in NOG Mice

1Greater Los Angeles Veteran Administration Healthcare System, 2San Diego Veterans Administration Healthcare System, 3University of California, Los Angeles, 4Perkin Elmer

Video Coming Soon

JoVE 58056


 JoVE In-Press

Cell-based Assay to Study Antibody-mediated Tau Clearance by Microglia

1Neuroscience Discovery, Janssen Pharmaceutical Company of Johnson & Johnson, Belgium, 2Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, The Netherlands, 3Janssen Prevention Center, Janssen Pharmaceutical Company of Johnson & Johnson, The Netherlands, 4Neuroscience Discovery, Janssen Pharmaceutical Company of Johnson & Johnson, Pennsylvania

Video Coming Soon

JoVE 58576


 JoVE In-Press

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