Small animal radiotherapy research platforms

International Nuclear Information System (INIS)

Verhaegen, Frank; Granton, Patrick; Tryggestad, Erik

2011-01-01

Advances in conformal radiation therapy and advancements in pre-clinical radiotherapy research have recently stimulated the development of precise micro-irradiators for small animals such as mice and rats. These devices are often kilovolt x-ray radiation sources combined with high-resolution CT imaging equipment for image guidance, as the latter allows precise and accurate beam positioning. This is similar to modern human radiotherapy practice. These devices are considered a major step forward compared to the current standard of animal experimentation in cancer radiobiology research. The availability of this novel equipment enables a wide variety of pre-clinical experiments on the synergy of radiation with other therapies, complex radiation schemes, sub-target boost studies, hypofractionated radiotherapy, contrast-enhanced radiotherapy and studies of relative biological effectiveness, to name just a few examples. In this review we discuss the required irradiation and imaging capabilities of small animal radiation research platforms. We describe the need for improved small animal radiotherapy research and highlight pioneering efforts, some of which led recently to commercially available prototypes. From this, it will be clear that much further development is still needed, on both the irradiation side and imaging side. We discuss at length the need for improved treatment planning tools for small animal platforms, and the current lack of a standard therein. Finally, we mention some recent experimental work using the early animal radiation research platforms, and the potential they offer for advancing radiobiology research. (topical review)

Microscopy of bacterial translocation during small bowel obstruction and ischemia in vivo – a new animal model

Directory of Open Access Journals (Sweden)

Hafner Mathias

2002-08-01

Full Text Available Abstract Background Existing animal models provide only indirect information about the pathogenesis of infections caused by indigenous gastrointestinal microflora and the kinetics of bacterial translocation. The aim of this study was to develop a novel animal model to assess bacterial translocation and intestinal barrier function in vivo. Methods In anaesthetized male Wistar rats, 0.5 ml of a suspension of green fluorescent protein-transfected E. coli was administered by intraluminal injection in a model of small bowel obstruction. Animals were randomly subjected to non-ischemic or ischemic bowel obstruction. Ischemia was induced by selective clamping of the terminal mesenteric vessels feeding the obstructed bowel loop. Time intervals necessary for translocation of E. coli into the submucosal stroma and the muscularis propria was assessed using intravital microscopy. Results Bacterial translocation into the submucosa and muscularis propria took a mean of 36 ± 8 min and 80 ± 10 min, respectively, in small bowel obstruction. Intestinal ischemia significantly accelerated bacterial translocation into the submucosa (11 ± 5 min, p E. coli were visible in frozen sections of small bowel, mesentery, liver and spleen taken two hours after E. coli administration. Conclusions Intravital microscopy of fluorescent bacteria is a novel approach to study bacterial translocation in vivo. We have applied this technique to define minimal bacterial transit time as a functional parameter of intestinal barrier function.

Theoretical considerations on maximum running speeds for large and small animals.

Science.gov (United States)

Fuentes, Mauricio A

2016-02-07

Mechanical equations for fast running speeds are presented and analyzed. One of the equations and its associated model predict that animals tend to experience larger mechanical stresses in their limbs (muscles, tendons and bones) as a result of larger stride lengths, suggesting a structural restriction entailing the existence of an absolute maximum possible stride length. The consequence for big animals is that an increasingly larger body mass implies decreasing maximal speeds, given that the stride frequency generally decreases for increasingly larger animals. Another restriction, acting on small animals, is discussed only in preliminary terms, but it seems safe to assume from previous studies that for a given range of body masses of small animals, those which are bigger are faster. The difference between speed scaling trends for large and small animals implies the existence of a range of intermediate body masses corresponding to the fastest animals. Copyright © 2015 Elsevier Ltd. All rights reserved.

Precise image-guided irradiation of small animals: a flexible non-profit platform

International Nuclear Information System (INIS)

Tillner, Falk; Thute, Prasad; Löck, Steffen; Dietrich, Antje; Fursov, Andriy; Haase, Robert; Lukas, Mathias; Krause, Mechthild; Baumann, Michael; Bütof, Rebecca; Enghardt, Wolfgang; Rimarzig, Bernd; Sobiella, Manfred

2016-01-01

Preclinical in vivo studies using small animals are essential to develop new therapeutic options in radiation oncology. Of particular interest are orthotopic tumour models, which better reflect the clinical situation in terms of growth patterns and microenvironmental parameters of the tumour as well as the interplay of tumours with the surrounding normal tissues. Such orthotopic models increase the technical demands and the complexity of preclinical studies as local irradiation with therapeutically relevant doses requires image-guided target localisation and accurate beam application. Moreover, advanced imaging techniques are needed for monitoring treatment outcome. We present a novel small animal image-guided radiation therapy (SAIGRT) system, which allows for precise and accurate, conformal irradiation and x-ray imaging of small animals. High accuracy is achieved by its robust construction, the precise movement of its components and a fast high-resolution flat-panel detector. Field forming and x-ray imaging is accomplished close to the animal resulting in a small penumbra and a high image quality. Feasibility for irradiating orthotopic models has been proven using lung tumour and glioblastoma models in mice. The SAIGRT system provides a flexible, non-profit academic research platform which can be adapted to specific experimental needs and therefore enables systematic preclinical trials in multicentre research networks. (paper)

Non-Invasive in vivo Imaging in Small Animal Research

Directory of Open Access Journals (Sweden)

V. Koo

2006-01-01

Full Text Available Non-invasive real time in vivo molecular imaging in small animal models has become the essential bridge between in vitro data and their translation into clinical applications. The tremendous development and technological progress, such as tumour modelling, monitoring of tumour growth and detection of metastasis, has facilitated translational drug development. This has added to our knowledge on carcinogenesis. The modalities that are commonly used include Magnetic Resonance Imaging (MRI, Computed Tomography (CT, Positron Emission Tomography (PET, bioluminescence imaging, fluorescence imaging and multi-modality imaging systems. The ability to obtain multiple images longitudinally provides reliable information whilst reducing animal numbers. As yet there is no one modality that is ideal for all experimental studies. This review outlines the instrumentation available together with corresponding applications reported in the literature with particular emphasis on cancer research. Advantages and limitations to current imaging technology are discussed and the issues concerning small animal care during imaging are highlighted.

Small animal imaging. Basics and practical guide

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Kiessling, Fabian [Aachen Univ. (RWTH) (Germany). Chair of Experimental Molecular Imaging; Pichler, Bernd J. (eds.) [Tuebingen Univ. (Germany). Lab. for Preclinical Imaging and Imaging Technology of the Werner Siemens-Foundation

2011-07-01

Small animal imaging has been recognized as an important tool in preclinical research. Nevertheless, the results of non-invasive imaging are often disappointing owing to choice of a suboptimal imaging modality and/or shortcomings in study design, experimental setup, and data evaluation. This textbook is a practical guide to the use of non-invasive imaging in preclinical research. Each of the available imaging modalities is discussed in detail, with the assistance of numerous informative illustrations. In addition, many useful hints are provided on the installation of a small animal unit, study planning, animal handling, and the cost-effective performance of small animal imaging. Cross-calibration methods, data postprocessing, and special imaging applications are also considered in depth. This is the first book to cover all the practical basics in small animal imaging, and it will prove an invaluable aid for researchers, students, and technicians. (orig.)

Small animal imaging. Basics and practical guide

International Nuclear Information System (INIS)

Kiessling, Fabian; Pichler, Bernd J.

2011-01-01

Small animal imaging has been recognized as an important tool in preclinical research. Nevertheless, the results of non-invasive imaging are often disappointing owing to choice of a suboptimal imaging modality and/or shortcomings in study design, experimental setup, and data evaluation. This textbook is a practical guide to the use of non-invasive imaging in preclinical research. Each of the available imaging modalities is discussed in detail, with the assistance of numerous informative illustrations. In addition, many useful hints are provided on the installation of a small animal unit, study planning, animal handling, and the cost-effective performance of small animal imaging. Cross-calibration methods, data postprocessing, and special imaging applications are also considered in depth. This is the first book to cover all the practical basics in small animal imaging, and it will prove an invaluable aid for researchers, students, and technicians. (orig.)

Establishing a small animal model for evaluating protective immunity against mumps virus.

Directory of Open Access Journals (Sweden)

Adrian Pickar

Full Text Available Although mumps vaccines have been used for several decades, protective immune correlates have not been defined. Recently, mumps outbreaks have occurred in vaccinated populations. To better understand the causes of the outbreaks and to develop means to control outbreaks in mumps vaccine immunized populations, defining protective immune correlates will be critical. Unfortunately, no small animal model for assessing mumps immunity exists. In this study, we evaluated use of type I interferon (IFN alpha/beta receptor knockout mice (IFN-α/βR-/- for such a model. We found these mice to be susceptible to mumps virus administered intranasally and intracranially. Passive transfer of purified IgG from immunized mice protected naïve mice from mumps virus infection, confirming the role of antibody in protection and demonstrating the potential for this model to evaluate mumps immunity.

High-resolution SPECT for small-animal imaging

International Nuclear Information System (INIS)

Qi Yujin

2006-01-01

This article presents a brief overview of the development of high-resolution SPECT for small-animal imaging. A pinhole collimator has been used for high-resolution animal SPECT to provide better spatial resolution and detection efficiency in comparison with a parallel-hole collimator. The theory of imaging characteristics of the pinhole collimator is presented and the designs of the pinhole aperture are discussed. The detector technologies used for the development of small-animal SPECT and the recent advances are presented. The evolving trend of small-animal SPECT is toward a multi-pinhole and a multi-detector system to obtain a high resolution and also a high detection efficiency. (authors)

Cell and small animal models for phenotypic drug discovery

Directory of Open Access Journals (Sweden)

Szabo M

2017-06-01

Full Text Available Mihaly Szabo,1 Sara Svensson Akusjärvi,1 Ankur Saxena,1 Jianping Liu,2 Gayathri Chandrasekar,1 Satish S Kitambi1 1Department of Microbiology Tumor, and Cell Biology, 2Department of Biochemistry and Biophysics, Karolinska Institutet, Solna, Sweden Abstract: The phenotype-based drug discovery (PDD approach is re-emerging as an alternative platform for drug discovery. This review provides an overview of the various model systems and technical advances in imaging and image analyses that strengthen the PDD platform. In PDD screens, compounds of therapeutic value are identified based on the phenotypic perturbations produced irrespective of target(s or mechanism of action. In this article, examples of phenotypic changes that can be detected and quantified with relative ease in a cell-based setup are discussed. In addition, a higher order of PDD screening setup using small animal models is also explored. As PDD screens integrate physiology and multiple signaling mechanisms during the screening process, the identified hits have higher biomedical applicability. Taken together, this review highlights the advantages gained by adopting a PDD approach in drug discovery. Such a PDD platform can complement target-based systems that are currently in practice to accelerate drug discovery. Keywords: phenotype, screening, PDD, discovery, zebrafish, drug

Treatment planning for a small animal using Monte Carlo simulation

International Nuclear Information System (INIS)

Chow, James C. L.; Leung, Michael K. K.

2007-01-01

The development of a small animal model for radiotherapy research requires a complete setup of customized imaging equipment, irradiators, and planning software that matches the sizes of the subjects. The purpose of this study is to develop and demonstrate the use of a flexible in-house research environment for treatment planning on small animals. The software package, called DOSCTP, provides a user-friendly platform for DICOM computed tomography-based Monte Carlo dose calculation using the EGSnrcMP-based DOSXYZnrc code. Validation of the treatment planning was performed by comparing the dose distributions for simple photon beam geometries calculated through the Pinnacle3 treatment planning system and measurements. A treatment plan for a mouse based on a CT image set by a 360-deg photon arc is demonstrated. It is shown that it is possible to create 3D conformal treatment plans for small animals with consideration of inhomogeneities using small photon beam field sizes in the diameter range of 0.5-5 cm, with conformal dose covering the target volume while sparing the surrounding critical tissue. It is also found that Monte Carlo simulation is suitable to carry out treatment planning dose calculation for small animal anatomy with voxel size about one order of magnitude smaller than that of the human

Animal welfare and use of silkworm as a model animal.

Science.gov (United States)

Sekimizu, N; Paudel, A; Hamamoto, H

2012-08-01

Sacrificing model animals is required for developing effective drugs before being used in human beings. In Japan today, at least 4,210,000 mice and other mammals are sacrificed to a total of 6,140,000 per year for the purpose of medical studies. All the animals treated in Japan, including test animals, are managed under control of "Act on Welfare and Management of Animals". Under the principle of this Act, no person shall kill, injure, or inflict cruelty on animals without due cause. "Animal" addressed in the Act can be defined as a "vertebrate animal". If we can make use of invertebrate animals in testing instead of vertebrate ones, that would be a remarkable solution for the issue of animal welfare. Furthermore, there are numerous advantages of using invertebrate animal models: less space and small equipment are enough for taking care of a large number of animals and thus are cost-effective, they can be easily handled, and many biological processes and genes are conserved between mammals and invertebrates. Today, many invertebrates have been used as animal models, but silkworms have many beneficial traits compared to mammals as well as other insects. In a Genome Pharmaceutical Institute's study, we were able to achieve a lot making use of silkworms as model animals. We would like to suggest that pharmaceutical companies and institutes consider the use of the silkworm as a model animal which is efficacious both for financial value by cost cutting and ethical aspects in animals' welfare.

Technology challenges in small animal PET imaging

International Nuclear Information System (INIS)

Lecomte, Roger

2004-01-01

Positron Emission Tomography (PET) is a non-invasive nuclear imaging modality allowing biochemical processes to be investigated in vivo with sensitivity in the picomolar range. For this reason, PET has the potential to play a major role in the emerging field of molecular imaging by enabling the study of molecular pathways and genetic processes in living animals non-invasively. The challenge is to obtain a spatial resolution that is appropriate for rat and mouse imaging, the preferred animal models for research in biology, while achieving a sensitivity adequate for real-time measurement of rapid dynamic processes in vivo without violating tracer kinetic principles. An overview of the current state of development of dedicated small animal PET scanners is given, and selected applications are reported and discussed with respect to performance and significance to research in biology

Thermoacoustic Molecular Imaging of Small Animals

Directory of Open Access Journals (Sweden)

Robert A. Kruger

2003-04-01

Full Text Available We have designed, constructed, and tested a thermoacoustic computed tomography (TCT scanner for imaging optical absorption in small animals in three dimensions. The device utilizes pulsed laser irradiation (680–1064 nm and a unique, 128-element transducer array. We quantified the isotropic spatial resolution of this scanner to be 0.35 mm. We describe a dual-wavelength subtraction technique for isolating optical dyes with TCT. Phantom experiments demonstrate that we can detect 5 fmol of a near-infrared dye (indocyanine green, ICG in a 1-ML volume using dual-wavelength subtraction. Initial TCT imaging in phantoms and in two sacrificed mice suggests that three-dimensional, optical absorption patterns in small animals can be detected with an order of magnitude better spatial resolution and an order of magnitude better low-contrast detectability in small animals when compared to fluorescence imaging or diffusion optical tomography.

Pre-clinical research in small animals using radiotherapy technology. A bidirectional translational approach

International Nuclear Information System (INIS)

Tillner, Falk; Buetof, Rebecca; Krause, Mechthild; Enghardt, Wolfgang; Helmholtz-Zentrum Dresden-Rossendorf, Dresden; Technische Univ. Dresden; Helmholtz-Zentrum Dresden-Rossendorf, Dresden

2014-01-01

For translational cancer research, pre-clinical in-vivo studies using small animals have become indispensable in bridging the gap between in-vitro cell experiments and clinical implementation. When setting up such small animal experiments, various biological, technical and methodical aspects have to be considered. In this work we present a comprehensive topical review based on relevant publications on irradiation techniques used for pre-clinical cancer research in mice and rats. Clinical radiotherapy treatment devices for the application of external beam radiotherapy and brachytherapy as well as dedicated research irradiation devices are feasible for small animal irradiation depending on the animal model and the experimental goals. In this work, appropriate solutions for the technological transfer of human radiation oncology to small animal radiation research are summarised. Additionally, important information concerning the experimental design is provided such that reliable and clinically relevant results can be attained.

Pre-clinical research in small animals using radiotherapy technology. A bidirectional translational approach

Energy Technology Data Exchange (ETDEWEB)

Tillner, Falk; Buetof, Rebecca [Technische Univ. Dresden (Germany). OncoRay - National Center for Radiation Research in Oncology; Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Technische Univ. Dresden (Germany). Dept. of Radiation Oncology; Thute, Prasad [Technische Univ. Dresden (Germany). OncoRay - National Center for Radiation Research in Oncology; Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Krause, Mechthild [Technische Univ. Dresden (Germany). OncoRay - National Center for Radiation Research in Oncology; Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Technische Univ. Dresden (Germany). Dept. of Radiation Oncology; German Cancer Consortium (DKTK), Dresden (Germany); German Cancer Research Center (DKFZ), Heidelberg (Germany); Enghardt, Wolfgang [Technische Univ. Dresden (Germany). OncoRay - National Center for Radiation Research in Oncology; Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Technische Univ. Dresden (Germany). Dept. of Radiation Oncology; Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany). Inst. of Radiooncology

2014-07-01

For translational cancer research, pre-clinical in-vivo studies using small animals have become indispensable in bridging the gap between in-vitro cell experiments and clinical implementation. When setting up such small animal experiments, various biological, technical and methodical aspects have to be considered. In this work we present a comprehensive topical review based on relevant publications on irradiation techniques used for pre-clinical cancer research in mice and rats. Clinical radiotherapy treatment devices for the application of external beam radiotherapy and brachytherapy as well as dedicated research irradiation devices are feasible for small animal irradiation depending on the animal model and the experimental goals. In this work, appropriate solutions for the technological transfer of human radiation oncology to small animal radiation research are summarised. Additionally, important information concerning the experimental design is provided such that reliable and clinically relevant results can be attained.

Animals In Synchrotrons: Overcoming Challenges For High-Resolution, Live, Small-Animal Imaging

International Nuclear Information System (INIS)

Donnelley, Martin; Parsons, David; Morgan, Kaye; Siu, Karen

2010-01-01

Physiological studies in small animals can be complicated, but the complexity is increased dramatically when performing live-animal synchrotron X-ray imaging studies. Our group has extensive experience in high-resolution live-animal imaging at the Japanese SPring-8 synchrotron, primarily examining airways in two-dimensions. These experiments normally image an area of 1.8 mmx1.2 mm at a pixel resolution of 0.45 μm and are performed with live, intact, anaesthetized mice.There are unique challenges in this experimental setting. Importantly, experiments must be performed in an isolated imaging hutch not specifically designed for small-animal imaging. This requires equipment adapted to remotely monitor animals, maintain their anesthesia, and deliver test substances while collecting images. The horizontal synchrotron X-ray beam has a fixed location and orientation that limits experimental flexibility. The extremely high resolution makes locating anatomical regions-of-interest slow and can result in a high radiation dose, and at this level of magnification small animal movements produce motion-artifacts that can render acquired images unusable. Here we describe our experimental techniques and how we have overcome several challenges involved in performing live mouse synchrotron imaging.Experiments have tested different mouse strains, with hairless strains minimizing overlying skin and hair artifacts. Different anesthetics have also be trialed due to the limited choices available at SPring-8. Tracheal-intubation methods have been refined and controlled-ventilation is now possible using a specialized small-animal ventilator. With appropriate animal restraint and respiratory-gating, motion-artifacts have been minimized. The animal orientation (supine vs. head-high) also appears to affect animal physiology, and can alter image quality. Our techniques and image quality at SPring-8 have dramatically improved and in the near future we plan to translate this experience to the

Molecular Imaging with Small Animal PET/CT

DEFF Research Database (Denmark)

Binderup, T.; El-Ali, H.H.; Skovgaard, D.

2011-01-01

is also described. In addition, the non-invasive nature of molecular imaging and the targets of these promising new tracers are attractive for other research areas as well, although these fields are much less explored. We present an example of an interesting research field with the application of small......Small animal positron emission tomography (PET) and computer tomography (CT) is an emerging field in pre-clinical imaging. High quality, state-of-the-art instruments are required for full optimization of the translational value of the small animal studies with PET and CT. However...... in this field of small animal molecular imaging with special emphasis on the targets for tissue characterization in tumor biology such as hypoxia, proliferation and cancer specific over-expression of receptors. The added value of applying CT imaging for anatomical localization and tumor volume measurements...

Pre-clinical research in small animals using radiotherapy technology--a bidirectional translational approach.

Science.gov (United States)

Tillner, Falk; Thute, Prasad; Bütof, Rebecca; Krause, Mechthild; Enghardt, Wolfgang

2014-12-01

For translational cancer research, pre-clinical in-vivo studies using small animals have become indispensable in bridging the gap between in-vitro cell experiments and clinical implementation. When setting up such small animal experiments, various biological, technical and methodical aspects have to be considered. In this work we present a comprehensive topical review based on relevant publications on irradiation techniques used for pre-clinical cancer research in mice and rats. Clinical radiotherapy treatment devices for the application of external beam radiotherapy and brachytherapy as well as dedicated research irradiation devices are feasible for small animal irradiation depending on the animal model and the experimental goals. In this work, appropriate solutions for the technological transfer of human radiation oncology to small animal radiation research are summarised. Additionally, important information concerning the experimental design is provided such that reliable and clinically relevant results can be attained. Copyright © 2014. Published by Elsevier GmbH.

In vivo small animal imaging: Current status and future prospects

International Nuclear Information System (INIS)

Kagadis, George C.; Loudos, George; Katsanos, Konstantinos; Langer, Steve G.; Nikiforidis, George C.

2010-01-01

The use of small animal models in basic and preclinical sciences constitutes an integral part of testing new pharmaceutical agents prior to commercial translation to clinical practice. Whole-body small animal imaging is a particularly elegant and cost-effective experimental platform for the timely validation and commercialization of novel agents from the bench to the bedside. Biomedical imaging is now listed along with genomics, proteomics, and metabolomics as an integral part of biological and medical sciences. Miniaturized versions of clinical diagnostic modalities, including but not limited to microcomputed tomography, micromagnetic resonance tomography, microsingle-photon-emission tomography, micropositron-emission tomography, optical imaging, digital angiography, and ultrasound, have all greatly improved our investigative abilities to longitudinally study various experimental models of human disease in mice and rodents. After an exhaustive literature search, the authors present a concise and critical review of in vivo small animal imaging, focusing on currently available modalities as well as emerging imaging technologies on one side and molecularly targeted contrast agents on the other. Aforementioned scientific topics are analyzed in the context of cancer angiogenesis and innovative antiangiogenic strategies under-the-way to the clinic. Proposed hybrid approaches for diagnosis and targeted site-specific therapy are highlighted to offer an intriguing glimpse of the future.

WE-AB-207B-10: On Spinal Nerve Toxicity from Single-Session SAbR in Pigs and the Translation of Small Animal NTCP Models

Energy Technology Data Exchange (ETDEWEB)

Hrycushko, B; Medin, P [UT Southwestern Medical Center, Dallas, TX (United States)

2016-06-15

Purpose: The incidence of peripheral neuropathy has risen with increased utilization of SAbR. There is no consensus regarding the dose-tolerance of the peripheral nervous system. In 2015, we commenced an investigation to test the hypotheses that single-session irradiation to the pig spinal nerves exhibit a similar dose-tolerance as that of the spinal cord and that a dose-length effect exists. This work evaluates the direct application of small animal NTCP models to both large animal spinal cord and preliminary peripheral nerve data. Methods: To date, 16 of 25 Yucatan minipigs have received single-session SAbR to a 1.5cm length and 4 of 25 have received irradiation to a 0.5cm length of left-sided C6-C8 spinal nerves. Toxicity related gait change has been observed in 13 animals (9 from the long length group and 4 from the short). This preliminary data is overlaid on several dose-response models which have been fit to rodent spinal cord tolerance experiments. Model parameters define a toxicity profile between a completely serial or parallel behaving organ. Adequacy of model application, including how length effects are handled, to published minipig spinal cord dose-response data and to preliminary peripheral nerve response data was evaluated through residual analysis. Results: No rodent-derived dose-response models were directly applicable to all pig data for the different lengths irradiated. Several models fit the long-length irradiated spinal cord data well, with the more serial-like models fitting best. Preliminary data on the short-length irradiation suggests no length effect exists, disproving our hypothesis. Conclusion: Direct application of small-animal NTCP models to pig data suggests dose-length effect predictions from small animal data may not translate clinically. However, the small animal models used have not considered dose heterogeneity and it is expected that including the low-to-mid dose levels in the penumbral region will improve this match. This work

WE-AB-207B-10: On Spinal Nerve Toxicity from Single-Session SAbR in Pigs and the Translation of Small Animal NTCP Models

International Nuclear Information System (INIS)

Hrycushko, B; Medin, P

2016-01-01

Purpose: The incidence of peripheral neuropathy has risen with increased utilization of SAbR. There is no consensus regarding the dose-tolerance of the peripheral nervous system. In 2015, we commenced an investigation to test the hypotheses that single-session irradiation to the pig spinal nerves exhibit a similar dose-tolerance as that of the spinal cord and that a dose-length effect exists. This work evaluates the direct application of small animal NTCP models to both large animal spinal cord and preliminary peripheral nerve data. Methods: To date, 16 of 25 Yucatan minipigs have received single-session SAbR to a 1.5cm length and 4 of 25 have received irradiation to a 0.5cm length of left-sided C6-C8 spinal nerves. Toxicity related gait change has been observed in 13 animals (9 from the long length group and 4 from the short). This preliminary data is overlaid on several dose-response models which have been fit to rodent spinal cord tolerance experiments. Model parameters define a toxicity profile between a completely serial or parallel behaving organ. Adequacy of model application, including how length effects are handled, to published minipig spinal cord dose-response data and to preliminary peripheral nerve response data was evaluated through residual analysis. Results: No rodent-derived dose-response models were directly applicable to all pig data for the different lengths irradiated. Several models fit the long-length irradiated spinal cord data well, with the more serial-like models fitting best. Preliminary data on the short-length irradiation suggests no length effect exists, disproving our hypothesis. Conclusion: Direct application of small-animal NTCP models to pig data suggests dose-length effect predictions from small animal data may not translate clinically. However, the small animal models used have not considered dose heterogeneity and it is expected that including the low-to-mid dose levels in the penumbral region will improve this match. This work

Techniques necessary for multiple tracer quantitative small-animal imaging studies

International Nuclear Information System (INIS)

Sharp, Terry L.; Dence, Carmen S.; Engelbach, John A.; Herrero, Pilar; Gropler, Robert J.; Welch, Michael J.

2005-01-01

Introduction: An increasing number and variety of studies on rodent models are being conducted using small-animal positron emission tomography scanners. We aimed to determine if animal handling techniques could be developed to perform routine animal imaging in a timely and efficient manner and with minimal effect on animal physiology. These techniques need to be reproducible in the same animal while maintaining hemodynamic and physiological stability. Methods: The necessary techniques include (a) the use of inhalant anesthesia, (b) arterial and venous cannulation for multiple tracer administrations and blood sampling, (c) development of small-volume analytic columns and techniques and (d) measurement of the physiological environment during the imaging session. Results: We provide an example of a cardiac imaging study using four radiotracers ( 15 O-water, 1-[ 11 C]-acetate, 1-[ 11 C]-palmitate and 1-[ 11 C]-glucose) injected into normal rats. Plasma substrates, CO 2 production and total metabolites were measured. The animals remained anesthetized over the entire imaging session, and their physiological state was maintained. Conclusion: The intrastudy stability of the physiological measurements and substrate levels and interstudy reproducibility of the measurements are reported

Animal Models of Calcific Aortic Valve Disease

Directory of Open Access Journals (Sweden)

Krista L. Sider

2011-01-01

Full Text Available Calcific aortic valve disease (CAVD, once thought to be a degenerative disease, is now recognized to be an active pathobiological process, with chronic inflammation emerging as a predominant, and possibly driving, factor. However, many details of the pathobiological mechanisms of CAVD remain to be described, and new approaches to treat CAVD need to be identified. Animal models are emerging as vital tools to this end, facilitated by the advent of new models and improved understanding of the utility of existing models. In this paper, we summarize and critically appraise current small and large animal models of CAVD, discuss the utility of animal models for priority CAVD research areas, and provide recommendations for future animal model studies of CAVD.

Clinical aspects of toxoplasmosis in small animal

Directory of Open Access Journals (Sweden)

André Luiz Baptista Galvão

2014-02-01

Full Text Available Toxoplasmosis, a zoonosis of worldwide distribution, has importance in human and veterinary medicine. Animals can be direct or indirect source of infection to man, and this intermediate host, the disease may be responsible for encephalitis and deaths due to congenital form as coinfection in neonates and patients with acquired immunodeficiency syndrome. The man and animals can acquire the disease by eating undercooked meat or cures, infected with tissue cysts, as well as food and water contaminated with oocysts. Iatrogenic, such as, blood transfusion and organ transplantation are other less frequent routes of transmission. The causative agent of this disease is Toxoplasma gondii, a protozoan obligate intracellular coccidian. In small animals, the infection has been reported in several countries, promoting varied clinical manifestations and uncommon but severe and fatal, which is a challenge in the clinical diagnosis of small animals, especially when the nervous system involvement. Thus, constitute the purpose of this review address the participation of small animals in the spread of the disease, clinical aspects related to it, as well as discuss methods of diagnosis, therapeutic measures, prophylaxis and control of this disease.

Small animal PET: aspects of performance assessment

International Nuclear Information System (INIS)

Weber, Simone; Bauer, Andreas

2004-01-01

Dedicated small animal positron emission tomography (PET) systems are increasingly prevalent in industry (e.g. for preclinical drug development) and biological research. Such systems permit researchers to perform animal studies of a longitudinal design characterised by repeated measurements in single animals. With the advent of commercial systems, scanners have become readily available and increasingly popular. As a consequence, technical specifications are becoming more diverse, making scanner systems less broadly applicable. The investigator has, therefore, to make a decision regarding which type of scanner is most suitable for the intended experiments. This decision should be based on gantry characteristics and the physical performance. The first few steps have been taken towards standardisation of the assessment of performance characteristics of dedicated animal PET systems, though such assessment is not yet routinely implemented. In this review, we describe current methods of evaluation of physical performance parameters of small animal PET scanners. Effects of methodologically different approaches on the results are assessed. It is underscored that particular attention has to be paid to spatial resolution, sensitivity, scatter fraction and count rate performance. Differences in performance measurement methods are described with regard to commercially available systems, namely the Concorde MicroPET systems P4 and R4 and the quad-HIDAC. Lastly, consequences of differences in scanner performance parameters are rated with respect to applications of small animal PET. (orig.)

Dose evaluation of three-dimensional small animal phantom with film dosimetry

International Nuclear Information System (INIS)

Han, Su Chul; Park, Seung Woo

2017-01-01

The weight of small animal dosimetry has been continuously increased in pre-clinical studies using radiation in small animals. In this study, three-dimensional(3D) small animal phantom was fabricated using 3D printer which has been continuously used and studied in the various fields. The absorbed dose of 3D animal phantom was evaluated by film dosimetry. Previously, the response of film was obtained from the materials used for production of 3D small animal phantom and compared with the bolus used as the tissue equivalent material in the radiotherapy. When irradiated with gamma rays from 0.5 Gy to 6 Gy, it was confirmed that there was a small difference of less than 1% except 0.5 Gy dose. And when small animal phantom was irradiated with 5 Gy, the difference between the irradiated dose and calculated dose from film was within 2%. Based on this study, it would be possible to increase the reliability of dose in pre-clinical studies using irradiation in small animals by evaluating dose of 3D small animal phantom

Dose evaluation of three-dimensional small animal phantom with film dosimetry

Energy Technology Data Exchange (ETDEWEB)

Han, Su Chul [Div. of Medical Radiation Equipment, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Park, Seung Woo [Radilogcial and Medico-Oncological Sciences, University of Sciences and Technology, Daejeon (Korea, Republic of)

2017-03-15

The weight of small animal dosimetry has been continuously increased in pre-clinical studies using radiation in small animals. In this study, three-dimensional(3D) small animal phantom was fabricated using 3D printer which has been continuously used and studied in the various fields. The absorbed dose of 3D animal phantom was evaluated by film dosimetry. Previously, the response of film was obtained from the materials used for production of 3D small animal phantom and compared with the bolus used as the tissue equivalent material in the radiotherapy. When irradiated with gamma rays from 0.5 Gy to 6 Gy, it was confirmed that there was a small difference of less than 1% except 0.5 Gy dose. And when small animal phantom was irradiated with 5 Gy, the difference between the irradiated dose and calculated dose from film was within 2%. Based on this study, it would be possible to increase the reliability of dose in pre-clinical studies using irradiation in small animals by evaluating dose of 3D small animal phantom.

Integration of optical imaging with a small animal irradiator

International Nuclear Information System (INIS)

Weersink, Robert A.; Ansell, Steve; Wang, An; Wilson, Graham; Shah, Duoaud; Lindsay, Patricia E.; Jaffray, David A.

2014-01-01

Purpose: The authors describe the integration of optical imaging with a targeted small animal irradiator device, focusing on design, instrumentation, 2D to 3D image registration, 2D targeting, and the accuracy of recovering and mapping the optical signal to a 3D surface generated from the cone-beam computed tomography (CBCT) imaging. The integration of optical imaging will improve targeting of the radiation treatment and offer longitudinal tracking of tumor response of small animal models treated using the system. Methods: The existing image-guided small animal irradiator consists of a variable kilovolt (peak) x-ray tube mounted opposite an aSi flat panel detector, both mounted on a c-arm gantry. The tube is used for both CBCT imaging and targeted irradiation. The optical component employs a CCD camera perpendicular to the x-ray treatment/imaging axis with a computer controlled filter for spectral decomposition. Multiple optical images can be acquired at any angle as the gantry rotates. The optical to CBCT registration, which uses a standard pinhole camera model, was modeled and tested using phantoms with markers visible in both optical and CBCT images. Optically guided 2D targeting in the anterior/posterior direction was tested on an anthropomorphic mouse phantom with embedded light sources. The accuracy of the mapping of optical signal to the CBCT surface was tested using the same mouse phantom. A surface mesh of the phantom was generated based on the CBCT image and optical intensities projected onto the surface. The measured surface intensity was compared to calculated surface for a point source at the actual source position. The point-source position was also optimized to provide the closest match between measured and calculated intensities, and the distance between the optimized and actual source positions was then calculated. This process was repeated for multiple wavelengths and sources. Results: The optical to CBCT registration error was 0.8 mm. Two

Small-animal dark-field radiography for pulmonary emphysema evaluation

Science.gov (United States)

Yaroshenko, Andre; Meinel, Felix G.; Hellbach, Katharina; Bech, Martin; Velroyen, Astrid; Müller, Mark; Bamberg, Fabian; Nikolaou, Konstantin; Reiser, Maximilian F.; Yildirim, Ali Ã.-.; Eickelberg, Oliver; Pfeiffer, Franz

2014-03-01

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality worldwide and emphysema is one of its main components. The disorder is characterized by irreversible destruction of the alveolar walls and enlargement of distal airspaces. Despite the severe changes in the lung tissue morphology, conventional chest radiographs have only a limited sensitivity for the detection of mild to moderate emphysema. X-ray dark-field is an imaging modality that can significantly increase the visibility of lung tissue on radiographic images. The dark-field signal is generated by coherent, small-angle scattering of x-rays on the air-tissue interfaces in the lung. Therefore, morphological changes in the lung can be clearly visualized on dark-field images. This is demonstrated by a preclinical study with a small-animal emphysema model. To generate a murine model of pulmonary emphysema, a female C57BL/6N mouse was treated with a single orotracheal application of porcine pancreatic elastase (80 U/kg body weight) dissolved in phosphate-buffered saline (PBS). Control mouse received PBS. The mice were imaged using a small-animal dark-field scanner. While conventional x-ray transmission radiography images revealed only subtle indirect signs of the pulmonary disorder, the difference between healthy and emphysematous lungs could be clearly directly visualized on the dark-field images. The dose applied to the animals is compatible with longitudinal studies. The imaging results correlate well with histology. The results of this study reveal the high potential of dark-field radiography for clinical lung imaging.

FDG small animal PET permits early detection of malignant cells in a xenograft murine model

International Nuclear Information System (INIS)

Nanni, Cristina; Spinelli, Antonello; Trespidi, Silvia; Ambrosini, Valentina; Castellucci, Paolo; Farsad, Mohsen; Franchi, Roberto; Fanti, Stefano; Leo, Korinne di; Tonelli, Roberto; Pession, Andrea; Pettinato, Cinzia; Rubello, Domenico

2007-01-01

The administration of new anticancer drugs in animal models is the first step from in vitro to in vivo pre-clinical protocols. At this stage it is crucial to ensure that cells are in the logarithmic phase of growth and to avoid vascular impairment, which can cause inhomogeneous distribution of the drug within the tumour and thus lead to bias in the final analysis of efficacy. In subcutaneous xenograft murine models, positivity for cancer is visually recognisable 2-3 weeks after inoculation, when a certain amount of necrosis is usually already present. The aim of this study was to evaluate the accuracy of FDG small animal PET for the early detection of malignant masses in a xenograft murine model of human rhabdomyosarcoma. A second goal was to analyse the metabolic behaviour of this xenograft tumour over time. We studied 23 nude mice, in which 7 x 10 6 rhabdomyosarcoma cells (RH-30 cell line) were injected in the dorsal subcutaneous tissues. Each animal underwent four FDG PET scans (GE, eXplore Vista DR) under gas anaesthesia. The animals were studied 2, 5, 14 and 20 days after inoculation. We administered 20 MBq of FDG via the tail vein. Uptake time was 60 min, and acquisition time, 20 min. Images were reconstructed with OSEM 2D iterative reconstruction and the target to background ratio (TBR) was calculated for each tumour. Normal subcutaneous tissue had a TBR of 0.3. Necrosis was diagnosed when one or more cold areas were present within the mass. All the animals were sacrificed and histology was available to verify PET results. PET results were concordant with the findings of necropsy and histology in all cases. The incidence of the tumour was 69.6% (16/23 animals); seven animals did not develop a malignant mass. Ten of the 23 animals had a positive PET scan 2 days after inoculation. Nine of these ten animals developed a tumour; the remaining animal became negative, at the third scan. The positive predictive value of the early PET scan was 90% (9/10 animals

Intrathecal Catheterization and Drug Delivery in Guinea Pigs: A Small-animal Model for Morphine-evoked Granuloma Formation.

Science.gov (United States)

Eddinger, Kelly A; Rondon, Eric S; Shubayev, Veronica I; Grafe, Marjorie R; Scadeng, Miriam; Hildebrand, Keith R; Page, Linda M; Malkmus, Shelle A; Steinauer, Joanne J; Yaksh, Tony L

2016-08-01

Intrathecal infusion of opioids in dogs, sheep, and humans produces local space-occupying masses. To develop a small-animal model, the authors examined effects of intrathecal catheterization and morphine infusion in guinea pigs. Under isoflurane, polyethylene or polyurethane catheters were advanced from the cisterna magna to the lumbar enlargement. Drugs were delivered as a bolus through the externalized catheter or continuously by subcutaneous minipumps. Hind paw withdrawal to a thermal stimulus was assessed. Spinal histopathology was systematically assessed in a blinded fashion. To assist in determining catheter placement, ex vivo images were obtained using magnetic resonance imaging in several animals. Canine spinal tissue from previous intrathecal morphine studies was analyzed in parallel. (1) Polyethylene (n = 30) and polyurethane (n = 25) catheters were implanted in the lumbar intrathecal space. (2) Bolus intrathecal morphine produced a dose-dependent (20 to 40 μg/10 μl) increase in thermal escape latencies. (3) Absent infusion, a catheter-associated distortion of the spinal cord and a fibrotic investment were noted along the catheter tract (polyethylene > polyurethane). (4) Intrathecal morphine infusion (25 mg/ml/0.5 μl/h for 14 days) resulted in intrathecal masses (fibroblasts, interspersed collagen, lymphocytes, and macrophages) arising from meninges proximal to the catheter tip in both polyethylene- and polyurethane-catheterized animals. This closely resembles mass histopathology from intrathecal morphine canine studies. Continuous intrathecal infusion of morphine leads to pericatheter masses that morphologically resemble those observed in dogs and humans. This small-animal model may be useful for studying spinal drug toxicology in general and the biology of intrathecal granuloma formation in particular.

Small and large animal models in cardiac contraction research: advantages and disadvantages.

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Milani-Nejad, Nima; Janssen, Paul M L

2014-03-01

The mammalian heart is responsible for not only pumping blood throughout the body but also adjusting this pumping activity quickly depending upon sudden changes in the metabolic demands of the body. For the most part, the human heart is capable of performing its duties without complications; however, throughout many decades of use, at some point this system encounters problems. Research into the heart's activities during healthy states and during adverse impacts that occur in disease states is necessary in order to strategize novel treatment options to ultimately prolong and improve patients' lives. Animal models are an important aspect of cardiac research where a variety of cardiac processes and therapeutic targets can be studied. However, there are differences between the heart of a human being and an animal and depending on the specific animal, these differences can become more pronounced and in certain cases limiting. There is no ideal animal model available for cardiac research, the use of each animal model is accompanied with its own set of advantages and disadvantages. In this review, we will discuss these advantages and disadvantages of commonly used laboratory animals including mouse, rat, rabbit, canine, swine, and sheep. Since the goal of cardiac research is to enhance our understanding of human health and disease and help improve clinical outcomes, we will also discuss the role of human cardiac tissue in cardiac research. This review will focus on the cardiac ventricular contractile and relaxation kinetics of humans and animal models in order to illustrate these differences. © 2013.

Small Animal Models for Human Metapneumovirus: Cotton Rat is More Permissive than Hamster and Mouse

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Zhang, Yu; Niewiesk, Stefan; Li, Jianrong

2014-01-01

Human metapneumovirus (hMPV) is the second most prevalent causative agent of pediatric respiratory infections worldwide. Currently, there are no vaccines or antiviral drugs against this virus. One of the major hurdles in hMPV research is the difficulty to identify a robust small animal model to accurately evaluate the efficacy and safety of vaccines and therapeutics. In this study, we compared the replication and pathogenesis of hMPV in BALB/c mice, Syrian golden hamsters, and cotton rats. It was found that BALB/c mice are not permissive for hMPV infection despite the use of a high dose (6.5 log10 PFU) of virus for intranasal inoculation. In hamsters, hMPV replicated efficiently in nasal turbinates but demonstrated only limited replication in lungs. In cotton rats, hMPV replicated efficiently in both nasal turbinate and lung when intranasally administered with three different doses (4, 5, and 6 log10 PFU) of hMPV. Lungs of cotton rats infected by hMPV developed interstitial pneumonia with mononuclear cells infiltrates and increased lumen exudation. By immunohistochemistry, viral antigens were detected at the luminal surfaces of the bronchial epithelial cells in lungs. Vaccination of cotton rats with hMPV completely protected upper and lower respiratory tract from wildtype challenge. The immunization also elicited elevated serum neutralizing antibody. Collectively, these results demonstrated that cotton rat is a robust small animal model for hMPV infection. PMID:25438015

Advances in Small Animal Imaging Systems

International Nuclear Information System (INIS)

Loudos, George K.

2007-01-01

The rapid growth in genetics and molecular biology combined with the development of techniques for genetically engineering small animals has led to an increased interest in in vivo laboratory animal imaging during the past few years. For this purpose, new instrumentation, data acquisition strategies, and image processing and reconstruction techniques are being developed, researched and evaluated. The aim of this article is to give a short overview of the state of the art technologies for high resolution and high sensitivity molecular imaging techniques, primarily positron emission tomography (PET) and single photon emission computed tomography (SPECT). The basic needs of small animal imaging will be described. The evolution in instrumentation in the past two decades, as well as the commercially available systems will be overviewed. Finally, the new trends in detector technology and preliminary results from challenging applications will be presented. For more details a number of references are provided

Animal Models of Hemophilia

Science.gov (United States)

Sabatino, Denise E.; Nichols, Timothy C.; Merricks, Elizabeth; Bellinger, Dwight A.; Herzog, Roland W.; Monahan, Paul E.

2013-01-01

The X-linked bleeding disorder hemophilia is caused by mutations in coagulation factor VIII (hemophilia A) or factor IX (hemophilia B). Unless prophylactic treatment is provided, patients with severe disease (less than 1% clotting activity) typically experience frequent spontaneous bleeds. Current treatment is largely based on intravenous infusion of recombinant or plasma-derived coagulation factor concentrate. More effective factor products are being developed. Moreover, gene therapies for sustained correction of hemophilia are showing much promise in pre-clinical studies and in clinical trials. These advances in molecular medicine heavily depend on availability of well-characterized small and large animal models of hemophilia, primarily hemophilia mice and dogs. Experiments in these animals represent important early and intermediate steps of translational research aimed at development of better and safer treatments for hemophilia, such a protein and gene therapies or immune tolerance protocols. While murine models are excellent for studies of large groups of animals using genetically defined strains, canine models are important for testing scale-up and for longer-term follow-up as well as for studies that require larger blood volumes. PMID:22137432

Animal models for rotator cuff repair.

Science.gov (United States)

Lebaschi, Amir; Deng, Xiang-Hua; Zong, Jianchun; Cong, Guang-Ting; Carballo, Camila B; Album, Zoe M; Camp, Christopher; Rodeo, Scott A

2016-11-01

Rotator cuff (RC) injuries represent a significant source of pain, functional impairment, and morbidity. The large disease burden of RC pathologies necessitates rapid development of research methodologies to treat these conditions. Given their ability to model anatomic, biomechanical, cellular, and molecular aspects of the human RC, animal models have played an indispensable role in reducing injury burden and advancing this field of research for many years. The development of animal models in the musculoskeletal (MSK) research arena is uniquely different from that in other fields in that the similarity of macrostructures and functions is as critical to replicate as cellular and molecular functions. Traditionally, larger animals have been used because of their anatomic similarity to humans and the ease of carrying out realistic surgical procedures. However, refinement of current molecular methods, introduction of novel research tools, and advancements in microsurgical techniques have increased the applicability of small animal models in MSK research. In this paper, we review RC animal models and emphasize a murine model that may serve as a valuable instrument for future RC tendon repair investigations. © 2016 New York Academy of Sciences.

Animal models of cardiovascular diseases.

Science.gov (United States)

Zaragoza, Carlos; Gomez-Guerrero, Carmen; Martin-Ventura, Jose Luis; Blanco-Colio, Luis; Lavin, Begoña; Mallavia, Beñat; Tarin, Carlos; Mas, Sebastian; Ortiz, Alberto; Egido, Jesus

2011-01-01

Cardiovascular diseases are the first leading cause of death and morbidity in developed countries. The use of animal models have contributed to increase our knowledge, providing new approaches focused to improve the diagnostic and the treatment of these pathologies. Several models have been developed to address cardiovascular complications, including atherothrombotic and cardiac diseases, and the same pathology have been successfully recreated in different species, including small and big animal models of disease. However, genetic and environmental factors play a significant role in cardiovascular pathophysiology, making difficult to match a particular disease, with a single experimental model. Therefore, no exclusive method perfectly recreates the human complication, and depending on the model, additional considerations of cost, infrastructure, and the requirement for specialized personnel, should also have in mind. Considering all these facts, and depending on the budgets available, models should be selected that best reproduce the disease being investigated. Here we will describe models of atherothrombotic diseases, including expanding and occlusive animal models, as well as models of heart failure. Given the wide range of models available, today it is possible to devise the best strategy, which may help us to find more efficient and reliable solutions against human cardiovascular diseases.

Use of 5-mm Laparoscopic Stapler to Perform Open Small Bowel Anastomosis in a Neonatal Animal Model.

Science.gov (United States)

Glenn, Ian C; Bruns, Nicholas E; Ponsky, Todd A

2016-10-01

While adult bowel anastomoses are typically performed with staplers, neonatal small bowel anastomoses have traditionally been performed in a hand-sewn manner due to the large size of surgical staplers. The purpose of this study was to compare stapled anastomosis using a newly available, 5-mm laparoscopic stapler to a hand-sewn anastomosis in an open animal model. Twenty anastomoses were performed by two general surgery residents (10 stapled and 10 hand-sewn) in an adult New Zealand white rabbit. The small bowel was divided with a scalpel. Surgical technique was alternated between single-layer hand-sewn and stapled anastomoses. Each anastomosis was resected for ex vivo testing. Measurements collected were outer diameter of the bowel before division, time to perform the anastomosis, anastomosis inner diameter (ID), and leak test. IDs were measured by cutting the anastomosis in cross-section, taking a photograph, and measuring the diameter by computer software. In addition, the surgeons qualitatively evaluated the anastomoses for hemostasis and overall quality. Statistical significance was determined using the Student's t-test. There were statistically significant differences between stapled and hand-sewn anastomosis, respectively, for average operative time (4 minutes 2 seconds versus 16 minutes 6 seconds, P animal model, a 5-mm stapled anastomosis is an acceptable alternative to hand-sewn small bowel anastomosis. The stapler is faster and creates a larger diameter anastomosis, however, there was one leak when closing the enterotomy in the stapled group and overlapping staple lines should be avoided.

Efficient system modeling for a small animal PET scanner with tapered DOI detectors

International Nuclear Information System (INIS)

Zhang, Mengxi; Zhou, Jian; Yang, Yongfeng; Qi, Jinyi; Rodríguez-Villafuerte, Mercedes

2016-01-01

A prototype small animal positron emission tomography (PET) scanner for mouse brain imaging has been developed at UC Davis. The new scanner uses tapered detector arrays with depth of interaction (DOI) measurement. In this paper, we present an efficient system model for the tapered PET scanner using matrix factorization and a virtual scanner geometry. The factored system matrix mainly consists of two components: a sinogram blurring matrix and a geometrical matrix. The geometric matrix is based on a virtual scanner geometry. The sinogram blurring matrix is estimated by matrix factorization. We investigate the performance of different virtual scanner geometries. Both simulation study and real data experiments are performed in the fully 3D mode to study the image quality under different system models. The results indicate that the proposed matrix factorization can maintain image quality while substantially reduce the image reconstruction time and system matrix storage cost. The proposed method can be also applied to other PET scanners with DOI measurement. (paper)

Intrinsic respiratory gating in small-animal CT

International Nuclear Information System (INIS)

Bartling, Soenke H.; Dinkel, Julien; Kauczor, Hans-Ulrich; Stiller, Wolfram; Semmler, Wolfhard; Grasruck, Michael; Madisch, Ijad; Gupta, Rajiv; Kiessling, Fabian

2008-01-01

Gating in small-animal CT imaging can compensate artefacts caused by physiological motion during scanning. However, all published gating approaches for small animals rely on additional hardware to derive the gating signals. In contrast, in this study a novel method of intrinsic respiratory gating of rodents was developed and tested for mice (n=5), rats (n=5) and rabbits (n=2) in a flat-panel cone-beam CT system. In a consensus read image quality was compared with that of non-gated and retrospective extrinsically gated scans performed using a pneumatic cushion. In comparison to non-gated images, image quality improved significantly using intrinsic and extrinsic gating. Delineation of diaphragm and lung structure improved in all animals. Image quality of intrinsically gated CT was judged to be equivalent to extrinsically gated ones. Additionally 4D datasets were calculated using both gating methods. Values for expiratory, inspiratory and tidal lung volumes determined with the two gating methods were comparable and correlated well with values known from the literature. We could show that intrinsic respiratory gating in rodents makes additional gating hardware and preparatory efforts superfluous. This method improves image quality and allows derivation of functional data. Therefore it bears the potential to find wide applications in small-animal CT imaging. (orig.)

Prompt gamma-ray imaging for small animals

Science.gov (United States)

Xu, Libai

Small animal imaging is recognized as a powerful discovery tool for small animal modeling of human diseases, which is providing an important clue to complete understanding of disease mechanisms and is helping researchers develop and test new treatments. The current small animal imaging techniques include positron emission tomography (PET), single photon emission tomography (SPECT), computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound (US). A new imaging modality called prompt gamma-ray imaging (PGI) has been identified and investigated primarily by Monte Carlo simulation. Currently it is suggested for use on small animals. This new technique could greatly enhance and extend the present capabilities of PET and SPECT imaging from ingested radioisotopes to the imaging of selected non-radioactive elements, such as Gd, Cd, Hg, and B, and has the great potential to be used in Neutron Cancer Therapy to monitor neutron distribution and neutron-capture agent distribution. This approach consists of irradiating small animals in the thermal neutron beam of a nuclear reactor to produce prompt gamma rays from the elements in the sample by the radiative capture (n, gamma) reaction. These prompt gamma rays are emitted in energies that are characteristic of each element and they are also produced in characteristic coincident chains. After measuring these prompt gamma rays by surrounding spectrometry array, the distribution of each element of interest in the sample is reconstructed from the mapping of each detected signature gamma ray by either electronic collimations or mechanical collimations. In addition, the transmitted neutrons from the beam can be simultaneously used for very sensitive anatomical imaging, which provides the registration for the elemental distributions obtained from PGI. The primary approach is to use Monte Carlo simulation methods either with the specific purpose code CEARCPG, developed at NC State University or with the general purpose

Prevalence and pattern of small animal orthopaedic conditions at ...

African Journals Online (AJOL)

Small animal orthopaedic case records of a 20-year period were surveyed to obtain the prevalence and pattern of orthopaedic conditions presented to the Veterinary Teaching Hospital (VTH), University of Ibadan, Nigeria, with the objective of providing data for planning on small animal healthcare facilities, policy ...

Animal Models of Cardiovascular Diseases

Directory of Open Access Journals (Sweden)

Carlos Zaragoza

2011-01-01

Full Text Available Cardiovascular diseases are the first leading cause of death and morbidity in developed countries. The use of animal models have contributed to increase our knowledge, providing new approaches focused to improve the diagnostic and the treatment of these pathologies. Several models have been developed to address cardiovascular complications, including atherothrombotic and cardiac diseases, and the same pathology have been successfully recreated in different species, including small and big animal models of disease. However, genetic and environmental factors play a significant role in cardiovascular pathophysiology, making difficult to match a particular disease, with a single experimental model. Therefore, no exclusive method perfectly recreates the human complication, and depending on the model, additional considerations of cost, infrastructure, and the requirement for specialized personnel, should also have in mind. Considering all these facts, and depending on the budgets available, models should be selected that best reproduce the disease being investigated. Here we will describe models of atherothrombotic diseases, including expanding and occlusive animal models, as well as models of heart failure. Given the wide range of models available, today it is possible to devise the best strategy, which may help us to find more efficient and reliable solutions against human cardiovascular diseases.

Fundamental image quality limits for microcomputed tomography in small animals

International Nuclear Information System (INIS)

Ford, N.L.; Thornton, M.M.; Holdsworth, D.W.

2003-01-01

Small-animal imaging has become increasingly more important as transgenic and knockout mice are produced to model human diseases. One imaging technique that has emerged is microcomputed tomography (micro-CT). For live-animal imaging, the precision in the images will be determined by the x-ray dose given to the animal. As a result, we propose a simple method to predict the noise performance of an x-ray micro-CT system as a function of dose and image resolution. An ideal, quantum-noise limited micro-CT scanner, assumed to have perfect resolution and ideal efficiency, was modeled. Using a simplified model, the coefficient of variation (COV) of the linear attenuation coefficient was calculated for a range of entrance doses and isotropic voxel sizes. COV calculations were performed for the ideal case and with simulated imperfections in efficiency and resolution. Our model was validated in phantom studies and mouse images were acquired with a specimen scanner to illustrate the results. A simplified model of noise propagation in the case of isotropic resolution indicates that the COV in the linear attenuation coefficient is proportional to (dose) -1/2 and to the (isotropic voxel size) -2 in the reconstructed volume. Therefore an improvement in the precision can be achieved only by increasing the isotropic voxel size (thereby decreasing the resolution of the image) or by increasing the x-ray dose. For the ideal scanner, a COV of 1% in the linear attenuation coefficient for an image of a mouse exposed to 0.25 Gy is obtained with a minimum isotropic voxel size of 135 μm. However, the same COV is achieved at a dose of 5.0 Gy with a 65 μm isotropic voxel size. Conversely, for a 68 mm diameter rat, a COV of 1% obtained from an image at 5.0 Gy would require an isotropic voxel size of 100 μm. These results indicate that short-term, potentially lethal, effects of ionizing radiation will limit high-resolution live animal imaging. As improvements in detector technology allow the

Prototype design of singles processing unit for the small animal PET

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Deng, P.; Zhao, L.; Lu, J.; Li, B.; Dong, R.; Liu, S.; An, Q.

2018-05-01

Position Emission Tomography (PET) is an advanced clinical diagnostic imaging technique for nuclear medicine. Small animal PET is increasingly used for studying the animal model of disease, new drugs and new therapies. A prototype of Singles Processing Unit (SPU) for a small animal PET system was designed to obtain the time, energy, and position information. The energy and position is actually calculated through high precison charge measurement, which is based on amplification, shaping, A/D conversion and area calculation in digital signal processing domian. Analysis and simulations were also conducted to optimize the key parameters in system design. Initial tests indicate that the charge and time precision is better than 3‰ FWHM and 350 ps FWHM respectively, while the position resolution is better than 3.5‰ FWHM. Commination tests of the SPU prototype with the PET detector indicate that the system time precision is better than 2.5 ns, while the flood map and energy spectra concored well with the expected.

Contemporary Animal Models For Human Gene Therapy Applications.

Science.gov (United States)

Gopinath, Chitra; Nathar, Trupti Job; Ghosh, Arkasubhra; Hickstein, Dennis Durand; Nelson, Everette Jacob Remington

2015-01-01

Over the past three decades, gene therapy has been making considerable progress as an alternative strategy in the treatment of many diseases. Since 2009, several studies have been reported in humans on the successful treatment of various diseases. Animal models mimicking human disease conditions are very essential at the preclinical stage before embarking on a clinical trial. In gene therapy, for instance, they are useful in the assessment of variables related to the use of viral vectors such as safety, efficacy, dosage and localization of transgene expression. However, choosing a suitable disease-specific model is of paramount importance for successful clinical translation. This review focuses on the animal models that are most commonly used in gene therapy studies, such as murine, canine, non-human primates, rabbits, porcine, and a more recently developed humanized mice. Though small and large animals both have their own pros and cons as disease-specific models, the choice is made largely based on the type and length of study performed. While small animals with a shorter life span could be well-suited for degenerative/aging studies, large animals with longer life span could suit longitudinal studies and also help with dosage adjustments to maximize therapeutic benefit. Recently, humanized mice or mouse-human chimaeras have gained interest in the study of human tissues or cells, thereby providing a more reliable understanding of therapeutic interventions. Thus, animal models are of great importance with regard to testing new vector technologies in vivo for assessing safety and efficacy prior to a gene therapy clinical trial.

Coded Aperture Nuclear Scintigraphy: A Novel Small Animal Imaging Technique

Directory of Open Access Journals (Sweden)

Dawid Schellingerhout

2002-10-01

Full Text Available We introduce and demonstrate the utility of coded aperture (CA nuclear scintigraphy for imaging small animals. CA imaging uses multiple pinholes in a carefully designed mask pattern, mounted on a conventional gamma camera. System performance was assessed using point sources and phantoms, while several animal experiments were performed to test the usefulness of the imaging system in vivo, with commonly used radiopharmaceuticals. The sensitivity of the CA system for 99mTc was 4.2 × 103 cps/Bq (9400 cpm/μCi, compared to 4.4 × 104 cps/Bq (990 cpm/μCi for a conventional collimator system. The system resolution was 1.7 mm, as compared to 4–6 mm for the conventional imaging system (using a high-sensitivity low-energy collimator. Animal imaging demonstrated artifact-free imaging with superior resolution and image quality compared to conventional collimator images in several mouse and rat models. We conclude that: (a CA imaging is a useful nuclear imaging technique for small animal imaging. The advantage in signal-to-noise can be traded to achieve higher resolution, decreased dose or reduced imaging time. (b CA imaging works best for images where activity is concentrated in small volumes; a low count outline may be better demonstrated using conventional collimator imaging. Thus, CA imaging should be viewed as a technique to complement rather than replace traditional nuclear imaging methods. (c CA hardware and software can be readily adapted to existing gamma cameras, making their implementation a relatively inexpensive retrofit to most systems.

Endoscopic Cerenkov luminescence imaging: in vivo small animal tumor model validation

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Song, Tianming; Bao, Chengpeng; Hu, Zhenhua; Wang, Kun; Liu, Xia; Tian, Jie

2015-03-01

Background: Cerenkov luminescence imaging (CLI) provides a great potential for clinical translation of optical molecular imaging techniques through using clinical approved radiotracers. However, it is difficult to obtain the Cerenkov luminescence signal of deeper biological tissues due to the small magnitude of the signal. To efficiently acquire the weak Cerenkov luminescence, we developed an endoscopic Cerenkov luminescence imaging (ECLI) system to reduce the in vivo imaging depth with minimum invasion, and validated the system on small animal tumor models. Methods: For the ECLI system, the laparoscope was connected to a high sensitive charge-couple device (CCD) camera (DU888+, Andor, UK) by a custom made adapter. We conducted a series of in vitro and in vivo experiments by use of the system. In the in vitro experiment, the endoscopic luminescence images of the 18F-FDG with various activities in EP tubes were acquired using ECLI system, and the sensitivity was compared with conventional CLI system. In the in vivo tumor experiment, 18F-FDG with the activity of 200μCi were intravenously injected into 3 tumor mice. Then the ECLI system was used to acquire the optical images for both non-invasive and invasive conditions. Conclusion: Experimental data showed the ECLI system could detect the 18F-FDG with the activity as low as 1μCi. Furthermore, our preliminary results indicated the possibility of ECLI technique for detecting Cerenkov signals inside the tumor tissue with deeper depth and guiding the surgical operation of tumor excision. We believe that this technique can help to accelerate the clinical translation of CLI.

Advances in Animal Models of Hepatitis B Virus Infection

Directory of Open Access Journals (Sweden)

Zhang Hang

2015-12-01

Full Text Available Hepatitis B virus (HBV infection seriously affects human health. Stable and reliable animal models of HBV infection bear significance in studying pathogenesis of this health condition and development of intervention measures. HBV exhibits high specificity for hosts, and chimpanzee is long used as sole animal model of HBV infection. However, use of chimpanzees is strictly constrained because of ethical reasons. Many methods were used to establish small-animal models of HBV infection. Tupaia is the only nonprimate animal that can be infected by HBV. Use of HBV-related duck hepatitis virus and marmot hepatitis virus infection model contributed to evaluation of mechanism of HBV replication and HBV treatment methods. In recent years, development of human–mouse chimeric model provided possibility of using common experimental animals to carry out HBV research. These models feature their own advantages and disadvantages and can be complementary in some ways. This study provides an overview of current and commonly used animal models of HBV infection.

Synchrotron-based intravenous cerebral angiography in a small animal model

International Nuclear Information System (INIS)

Kelly, Michael E; Schueltke, Elisabeth; Fiedler, Stephan; Nemoz, Christian; Guzman, Raphael; Corde, Stephanie; Esteve, Francois; LeDuc, Geraldine; Juurlink, Bernhard H J; Meguro, Kotoo

2007-01-01

K-edge digital subtraction angiography (KEDSA), a recently developed synchrotron-based technique, utilizes monochromatic radiation and allows acquisition of high-quality angiography images after intravenous administration of contrast agent. We tested KEDSA for its suitability for intravenous cerebral angiography in an animal model. Adult male New Zealand rabbits were subjected to either angiography with conventional x-ray equipment or synchrotron-based intravenous KEDSA, using an iodine-based contrast agent. Angiography with conventional x-ray equipment after intra-arterial administration of contrast agent demonstrated the major intracranial vessels but no smaller branches. KEDSA was able to visualize the major intracranial vessels as well as smaller branches in both radiography mode (planar images) and tomography mode. Visualization was achieved with as little as 0.5 ml kg -1 of iodinated contrast material. We were able to obtain excellent visualization of the cerebral vasculature in an animal model using intravenous injection of contrast material, using synchrotron-based KEDSA

New experimental model for single liver lobe hyperthermia in small animals using non-directional microwaves.

Directory of Open Access Journals (Sweden)

Ionuț Tudorancea

Full Text Available Our aim was to develop a new experimental model for in vivo hyperthermia using non-directional microwaves, applicable to small experimental animals. We present an affordable approach for targeted microwave heat delivery to an isolated liver lobe in rat, which allows rapid, precise and stable tissue temperature control.A new experimental model is proposed. We used a commercial available magnetron generating 2450 MHz, with 4.4V and 14A in the filament and 4500V anodic voltage. Modifications were required in order to adjust tissue heating such as to prevent overheating and to allow for fine adjustments according to real-time target temperature. The heating is controlled using a virtual instrument application implemented in LabView® and responds to 0.1° C variations in the target. Ten healthy adult male Wistar rats, weighing 250-270 g were used in this study. The middle liver lobe was the target for controlled heating, while the rest of the living animal was protected.In vivo microwave delivery using our experimental setting is safe for the animals. Target tissue temperature rises from 30°C to 40°C with 3.375°C / second (R2 = 0.9551, while the increment is lower it the next two intervals (40-42°C and 42-44°C with 0.291°C/ s (R2 = 0.9337 and 0.136°C/ s (R2 = 0.7894 respectively, when testing in sequences. After reaching the desired temperature, controlled microwave delivery insures a very stable temperature during the experiments.We have developed an inexpensive and easy to manufacture system for targeted hyperthermia using non-directional microwave radiation. This system allows for fine and stable temperature adjustments within the target tissue and is ideal for experimental models testing below or above threshold hyperthermia.

Development of a Magnetoencephalograph System for Small Animals

International Nuclear Information System (INIS)

Kim, J. E.; Kim, I. S.; Kang, C. S.; Kwon, H.; Kim, J. M.; Lee, Y. H.; Kim, K.

2011-01-01

We developed a four-channel first order gradiometer system to measure magnetoencephalogram for mice. We used double relaxation oscillation SQUID (DROS). The diameter of the pickup coil is 4 mm and the distance between the coils is 5 mm. Coil distance was designed to have good spatial resolution for a small mouse brain. We evaluated the current dipole localization confidence region for a mouse brain, using the spherical conductor model. The white noise of the measurement system was about 30 fT/Hz 1/2 /cm when measured in a magnetically shielded room. We measured magnetic signal from a phantom having the same size of a mouse brain, which was filled with 0.9% saline solution. The results suggest that the developed system has a feasibility to study the functions of brain of small animals.

Semiautomated analysis of small-animal PET data.

Science.gov (United States)

Kesner, Adam L; Dahlbom, Magnus; Huang, Sung-Cheng; Hsueh, Wei-Ann; Pio, Betty S; Czernin, Johannes; Kreissl, Michael; Wu, Hsiao-Ming; Silverman, Daniel H S

2006-07-01

The objective of the work reported here was to develop and test automated methods to calculate biodistribution of PET tracers using small-animal PET images. After developing software that uses visually distinguishable organs and other landmarks on a scan to semiautomatically coregister a digital mouse phantom with a small-animal PET scan, we elastically transformed the phantom to conform to those landmarks in 9 simulated scans and in 18 actual PET scans acquired of 9 mice. Tracer concentrations were automatically calculated in 22 regions of interest (ROIs) reflecting the whole body and 21 individual organs. To assess the accuracy of this approach, we compared the software-measured activities in the ROIs of simulated PET scans with the known activities, and we compared the software-measured activities in the ROIs of real PET scans both with manually established ROI activities in original scan data and with actual radioactivity content in immediately harvested tissues of imaged animals. PET/atlas coregistrations were successfully generated with minimal end-user input, allowing rapid quantification of 22 separate tissue ROIs. The simulated scan analysis found the method to be robust with respect to the overall size and shape of individual animal scans, with average activity values for all organs tested falling within the range of 98% +/- 3% of the organ activity measured in the unstretched phantom scan. Standardized uptake values (SUVs) measured from actual PET scans using this semiautomated method correlated reasonably well with radioactivity content measured in harvested organs (median r = 0.94) and compared favorably with conventional SUV correlations with harvested organ data (median r = 0.825). A semiautomated analytic approach involving coregistration of scan-derived images with atlas-type images can be used in small-animal whole-body radiotracer studies to estimate radioactivity concentrations in organs. This approach is rapid and less labor intensive than are

State-of-the-art of small animal imaging with high-resolution SPECT

International Nuclear Information System (INIS)

Nikolaus, S.; Wirrwar, A.; Antke, C.; Kley, K.; Mueller, H.W.

2005-01-01

During the recent years, in vivo imaging of small animals using SPECT has become of growing relevance. Along with the development of dedicated high-resolution small animal SPECT cameras, an increasing number of conventional clinical scanners has been equipped with single or multipinhole collimators. This paper reviews the small animal tomographs, which are operating at present and compares their performance characteristics. Furthermore, we describe the in vivo imaging studies, which have been performed so far with the individual scanners and survey current approaches to optimize molecular imaging with small animal SPECT. (orig.)

Simulation of time curves in small animal PET using GATE

International Nuclear Information System (INIS)

Simon, Luc; Strul, Daniel; Santin, Giovanni; Krieguer, Magalie; Morel, Christian

2004-01-01

The ClearPET project of the Crystal Clear Collaboration (CCC) is building spin-off technology for high resolution small animal Positron Emission Tomography (PET). Monte Carlo simulation is essential for optimizing the specifications of these systems with regards to their most important characteristics, such as spatial resolution, sensitivity, or count rate performance. GATE, the Geant4 Application for Tomographic Emission simulates the passing of time during real acquisitions, allowing to handle dynamic systems such as decaying source distributions or moving detectors. GATE output is analyzed on an event-by-event basis. The time associated with each single event allows to sort coincidences and to model dead-time. This leads to the study of time curves for a prospective small animal PET scanner design. The count rates of true, and random coincidences are discussed together with the corresponding Noise Equivalent Count (NEC) rates as a function of some PET scanner specifications such as detector dead time, or coincidence time window

In Vivo Respiratory-Gated Micro-CT Imaging in Small-Animal Oncology Models

Directory of Open Access Journals (Sweden)

Dawn Cavanaugh

2004-01-01

Full Text Available Micro-computed tomography (micro-CT is becoming an accepted research tool for the noninvasive examination of laboratory animals such as mice and rats, but to date, in vivo scanning has largely been limited to the evaluation of skeletal tissues. We use a commercially available micro-CT device to perform respiratory gated in vivo acquisitions suitable for thoracic imaging. The instrument is described, along with the scan protocol and animal preparation techniques. Preliminary results confirm that lung tumors as small as 1 mm in diameter are visible in vivo with these methods. Radiation dose was evaluated using several approaches, and was found to be approximately 0.15 Gy for this respiratory-gated micro-CT imaging protocol. The combination of high-resolution CT imaging and respiratory-gated acquisitions appears well-suited to serial in vivo scanning.

Design of a multimodal fibers optic system for small animal optical imaging.

Science.gov (United States)

Spinelli, Antonello E; Pagliazzi, Marco; Boschi, Federico

2015-02-01

Small animals optical imaging systems are widely used in pre-clinical research to image in vivo the bio-distribution of light emitting probes using fluorescence or bioluminescence modalities. In this work we presented a set of simulated results of a novel small animal optical imaging module based on a fibers optics matrix, coupled with a position sensitive detector, devoted to acquire bioluminescence and Cerenkov images. Simulations were performed using GEANT 4 code with the GAMOS architecture using the tissue optics plugin. Results showed that it is possible to image a 30 × 30 mm region of interest using a fiber optics array containing 100 optical fibers without compromising the quality of the reconstruction. The number of fibers necessary to cover an adequate portion of a small animal is thus quite modest. This design allows integrating the module with magnetic resonance (MR) in order to acquire optical and MR images at the same time. A detailed model of the mouse anatomy, obtained by segmentation of 3D MRI images, will improve the quality of optical 3D reconstruction. Copyright © 2014 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Development of a Magnetoencephalograph System for Small Animals

Energy Technology Data Exchange (ETDEWEB)

Kim, J. E.; Kim, I. S.; Kang, C. S.; Kwon, H.; Kim, J. M.; Lee, Y. H.; Kim, K. [Brain and Cognition Measurement Laboratory, Korea Research Institute of Standards and Science(KRISS), Daejeon (Korea, Republic of)

2011-08-15

We developed a four-channel first order gradiometer system to measure magnetoencephalogram for mice. We used double relaxation oscillation SQUID (DROS). The diameter of the pickup coil is 4 mm and the distance between the coils is 5 mm. Coil distance was designed to have good spatial resolution for a small mouse brain. We evaluated the current dipole localization confidence region for a mouse brain, using the spherical conductor model. The white noise of the measurement system was about 30 fT/Hz{sup 1/2}/cm when measured in a magnetically shielded room. We measured magnetic signal from a phantom having the same size of a mouse brain, which was filled with 0.9% saline solution. The results suggest that the developed system has a feasibility to study the functions of brain of small animals.

Verification of photon attenuation characteristics for 3D printer based small animal lung model

International Nuclear Information System (INIS)

Lee, Se Ho; Lee, Seung Wook; Han, Su Chul; Park, Seung Woo

2016-01-01

Since it is difficult to measure absorbed dose to mice in vivo, replica mice are mostly used as alternative. In this study, realistic mouse phantom was fabricated by using 3D printer (object500 connex3, Stratasys, USA). Elemental inks as material of 3D printer were selected corresponding to mouse tissue. To represent lung, selected material was partially used with air layer. In order to verify material equivalent, super-flex bolus was simply compared to verify photon attenuation characteristics. In the case of lung, Hounsfield unit (HU) of the phantom were compared with a live mouse. In this study, we fabricated mouse phantom by using 3D printer, and practically verified photon attenuation characteristics. The fabricated phantom shows tissue equivalence as well as similar geometry with live mouse. As more and more growing of 3D printer technique, 3D printer based small preclinical animal phantom would increase reliability of verification of absorbed dose in small animal for preclinical study

Verification of photon attenuation characteristics for 3D printer based small animal lung model

Energy Technology Data Exchange (ETDEWEB)

Lee, Se Ho; Lee, Seung Wook [Pusan National University, Busan (Korea, Republic of); Han, Su Chul; Park, Seung Woo [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

2016-05-15

Since it is difficult to measure absorbed dose to mice in vivo, replica mice are mostly used as alternative. In this study, realistic mouse phantom was fabricated by using 3D printer (object500 connex3, Stratasys, USA). Elemental inks as material of 3D printer were selected corresponding to mouse tissue. To represent lung, selected material was partially used with air layer. In order to verify material equivalent, super-flex bolus was simply compared to verify photon attenuation characteristics. In the case of lung, Hounsfield unit (HU) of the phantom were compared with a live mouse. In this study, we fabricated mouse phantom by using 3D printer, and practically verified photon attenuation characteristics. The fabricated phantom shows tissue equivalence as well as similar geometry with live mouse. As more and more growing of 3D printer technique, 3D printer based small preclinical animal phantom would increase reliability of verification of absorbed dose in small animal for preclinical study.

Anesthesia condition for 18F-FDG imaging of lung metastasis tumors using small animal PET

International Nuclear Information System (INIS)

Woo, Sang-Keun; Lee, Tae Sup; Kim, Kyeong Min; Kim, June-Youp; Jung, Jae Ho; Kang, Joo Hyun; Cheon, Gi Jeong; Choi, Chang Woon; Lim, Sang Moo

2008-01-01

Small animal positron emission tomography (PET) with 18 F-FDG has been increasingly used for tumor imaging in the murine model. The aim of this study was to establish the anesthesia condition for imaging of lung metastasis tumor using small animal 18 F-FDG PET. Methods: To determine the impact of anesthesia on 18 F-FDG distribution in normal mice, five groups were studied under the following conditions: no anesthesia, ketamine and xylazine (Ke/Xy), 0.5% isoflurane (Iso 0.5), 1% isoflurane (Iso 1) and 2% isoflurane (Iso 2). The ex vivo counting, standard uptake value (SUV) image and glucose SUV of 18 F-FDG in various tissues were evaluated. The 18 F-FDG images in the lung metastasis tumor model were obtained under no anesthesia, Ke/Xy and Iso 0.5, and registered with CT image to clarify the tumor region. Results: Blood glucose concentration and muscle uptake of 18 F-FDG in the Ke/Xy group markedly increased more than in the other groups. The Iso 2 group increased 18 F-FDG uptake in heart compared with the other groups. The Iso 0.5 anesthesized group showed the lowest 18 F-FDG uptake in heart and chest wall. The small size of lung metastasis tumor (2 mm) was clearly visualized by 18 F-FDG image with the Iso 0.5 anesthesia. Conclusion: Small animal 18 F-FDG PET imaging with Iso 0.5 anesthesia was appropriate for the detection of lung metastasis tumor. To acquire 18 F-FDG PET images with small animal PET, the type and level of anesthetic should be carefully considered to be suitable for the visualization of target tissue in the experimental model

Latest animal models for anti-HIV drug discovery.

Science.gov (United States)

Sliva, Katja

2015-02-01

HIV research is limited by the fact that lentiviruses are highly species specific. The need for appropriate models to promote research has led to the development of many elaborate surrogate animal models. This review looks at the history of animal models for HIV research. Although natural animal lentivirus infections and chimeric viruses such as chimera between HIV and simian immunodeficiency virus and simian-tropic HIV are briefly discussed, the main focus is on small animal models, including the complex design of the 'humanized' mouse. The review also traces the historic evolution and milestones as well as depicting current models and future prospects for HIV research. HIV research is a complex and challenging task that is highly manpower-, money- and time-consuming. Besides factors such as hypervariability and latency, the lack of appropriate animal models that exhibit and recapitulate the entire infectious process of HIV, is one of the reasons behind the failure to eliminate the lentivirus from the human population. This obstacle has led to the exploitation and further development of many sophisticated surrogate animal models for HIV research. While there is no animal model that perfectly mirrors and mimics HIV infections in humans, there are a variety of host species and viruses that complement each other. Combining the insights from each model, and critically comparing the results obtained with data from human clinical trials should help expand our understanding of HIV pathogenesis and drive future drug development.

The Combination of In vivo 124I-PET and CT Small Animal Imaging for Evaluation of Thyroid Physiology and Dosimetry

Directory of Open Access Journals (Sweden)

Henrik H. El-Ali

2012-06-01

Full Text Available Objective: A thyroid rat model combining functional and anatomical information would be of great benefit for better modeling of thyroid physiology and for absorbed dose calculations. Our aim was to show that 124I-PET and CT small animal imaging are useful as a combined model for studying thyroid physiology and dose calculation. Methods: Seven rats were subjects for multiple thyroid 124I-imaging and CT-scans. S-values [mGy/MBqs] for different thyroid sizes were simulated. A phantom with spheres was designed for validation of performances of the small animal PET and CT imaging systems. Results: Small animal image-based measurements of the activity amount and the volumes of the spheres with a priori known volumes showed a good agreement with their corresponding actual volumes. The CT scans of the rats showed thyroid volumes from 34–70 mL. Conclusions: The wide span in volumes of thyroid glands indicates the importance of using an accurate volume-measuring technique such as the small animal CT. The small animal PET system was on the other hand able to accurately estimate the activity concentration in the thyroid volumes. We conclude that the combination of the PET and CT image information is essential for quantitative thyroid imaging and accurate thyroid absorbed dose calculation.

A computational pipeline for quantification of pulmonary infections in small animal models using serial PET-CT imaging.

Science.gov (United States)

Bagci, Ulas; Foster, Brent; Miller-Jaster, Kirsten; Luna, Brian; Dey, Bappaditya; Bishai, William R; Jonsson, Colleen B; Jain, Sanjay; Mollura, Daniel J

2013-07-23

Infectious diseases are the second leading cause of death worldwide. In order to better understand and treat them, an accurate evaluation using multi-modal imaging techniques for anatomical and functional characterizations is needed. For non-invasive imaging techniques such as computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET), there have been many engineering improvements that have significantly enhanced the resolution and contrast of the images, but there are still insufficient computational algorithms available for researchers to use when accurately quantifying imaging data from anatomical structures and functional biological processes. Since the development of such tools may potentially translate basic research into the clinic, this study focuses on the development of a quantitative and qualitative image analysis platform that provides a computational radiology perspective for pulmonary infections in small animal models. Specifically, we designed (a) a fast and robust automated and semi-automated image analysis platform and a quantification tool that can facilitate accurate diagnostic measurements of pulmonary lesions as well as volumetric measurements of anatomical structures, and incorporated (b) an image registration pipeline to our proposed framework for volumetric comparison of serial scans. This is an important investigational tool for small animal infectious disease models that can help advance researchers' understanding of infectious diseases. We tested the utility of our proposed methodology by using sequentially acquired CT and PET images of rabbit, ferret, and mouse models with respiratory infections of Mycobacterium tuberculosis (TB), H1N1 flu virus, and an aerosolized respiratory pathogen (necrotic TB) for a total of 92, 44, and 24 scans for the respective studies with half of the scans from CT and the other half from PET. Institutional Administrative Panel on Laboratory Animal Care approvals were

State of the art in both in vitro and in vivo aspects of small animal imaging

International Nuclear Information System (INIS)

Maziere, B.; Lebars, D.

2002-01-01

Full text: In vivo imaging for small animals is dramatically expanding due to the coincidence of mainly three technical factors: 1. the explosion in computer power 2. the enhancement in image processing 3. the accessibility and affordability of digital autoradiography systems and small-animal scanners. Among these imaging techniques let us mention the anatomical imaging techniques such as ultrasonography, X-rays and IRM and the functional imaging radioisotopic techniques SPECT and TEP. The main advantage of the first group of imaging techniques is essentially linked to the high resolution of the anatomical images (with the drawback of the necessity of putting the animal at rest using anaesthesia). The main advantages of SPECT and PET are their high sensitivity and the vast number of functions or metabolism they allow to image. The applications for isotopic functional imaging in small animals are increasing rapidly. Factors contributing to this dramatic expansion include the three previous technical factors plus, at least, three methodological factors: 1. the drug discovery process based on receptor / mechanism of action 2. the increasing number of rodent models of human diseases (SCID mice implanted with human tumors, gene knock-out mice, transgene mice) 3. the advances in isotope and validated tracer availability performances Small animal radioisotopic functional imaging for drug development. In vivo quantification of biological processes to measure the mechanism of action of a potential drug and its concentration at the site of action has become mandatory for developing a drug. Rational and efficient means of confirming mechanisms of action are required. For this purpose, PET and/or SPECT functional - biochemical - molecular imaging in small animals are tools of choice for economical reasons (in the domain of drug development, industry is suffering huge opportunity costs by failing to weed out non-performing new active substances until late phases II and III) and

Advances in endoscopic surgery for small animal reproduction.

Science.gov (United States)

Katic, N; Dupré, G

2016-09-01

Although endoscopic surgery entered its "golden era" in the mid-1980s, it is still advancing at a tremendous pace. Novel surgical techniques and devices are continuously developed and applied, and new indications (and/or contraindications) for the use of endoscopic surgery are routinely reported in the literature and subjected to systematic assessments. Although endoscopic surgery (laparoscopy in particular) has already become established as the gold standard in human medicine, it has yet to be proven as a viable alternative to open surgery in the field of veterinary medicine. The advantages of minimally invasive surgery include better intra-operative visualization, reduced postoperative pain, reduced scar formation and increased postoperative mobility. Therefore, it is reasonable to expect that the application of this will continue to expand. Small animal reproduction, a field within the broad discipline of veterinary medicine, has already recognized and begun to reap the benefits of endoscopic surgery. Herein, we retrospectively review the most recent successful novel applications of endoscopic surgery in the small animal reproduction system to provide small animal reproductive surgeons with important knowledge to help improve their own veterinarian medical practice. © 2016 Blackwell Verlag GmbH.

Automated analysis of small animal PET studies through deformable registration to an atlas

NARCIS (Netherlands)

Gutierrez, Daniel F.; Zaidi, Habib

This work aims to develop a methodology for automated atlas-guided analysis of small animal positron emission tomography (PET) data through deformable registration to an anatomical mouse model. A non-rigid registration technique is used to put into correspondence relevant anatomical regions of

Animal models for evaluation of oral delivery of biopharmaceuticals

DEFF Research Database (Denmark)

Harloff-Helleberg, Stine; Nielsen, Line Hagner; Nielsen, Hanne Mørck

2017-01-01

of systems for oral delivery of biopharmaceuticals may result in new treatment modalities to increase the patient compliance and reduce product cost. In the preclinical development phase, use of experimental animal models is essential for evaluation of new formulation designs. In general, the limited oral...... bioavailability of biopharmaceuticals, of just a few percent, is expected, and therefore, the animal models and the experimental settings must be chosen with utmost care. More knowledge and focus on this topic is highly needed, despite experience from the numerous studies evaluating animal models for oral drug...... delivery of small molecule drugs. This review highlights and discusses pros and cons of the most currently used animal models and settings. Additionally, it also looks into the influence of anesthetics and sampling methods for evaluation of drug delivery systems for oral delivery of biopharmaceuticals...

Antimicrobial stewardship in small animal veterinary practice

DEFF Research Database (Denmark)

Guardabassi, Luca; Prescott, John F

2015-01-01

Despite the increasing recognition of the critical role for antimicrobial stewardship in preventing the spread of multidrug-resistant bacteria, examples of effective antimicrobial stewardship programs are rare in small animal veterinary practice. This article highlights the basic requirements...

Modality comparison for small animal radiotherapy: A simulation study

Energy Technology Data Exchange (ETDEWEB)

Bazalova, Magdalena, E-mail: bazalova@stanford.edu; Nelson, Geoff; Noll, John M.; Graves, Edward E. [Department of Radiation Oncology, Molecular Imaging Program at Stanford, Stanford University, Stanford, California 94305 (United States)

2014-01-15

Purpose: Small animal radiation therapy has advanced significantly in recent years. Whereas in the past dose was delivered using a single beam and a lead shield for sparing of healthy tissue, conformal doses can be now delivered using more complex dedicated small animal radiotherapy systems with image guidance. The goal of this paper is to investigate dose distributions for three small animal radiation treatment modalities. Methods: This paper presents a comparison of dose distributions generated by the three approaches—a single-field irradiator with a 200 kV beam and no image guidance, a small animal image-guided conformal system based on a modified microCT scanner with a 120 kV beam developed at Stanford University, and a dedicated conformal system, SARRP, using a 220 kV beam developed at Johns Hopkins University. The authors present a comparison of treatment plans for the three modalities using two cases: a mouse with a subcutaneous tumor and a mouse with a spontaneous lung tumor. A 5 Gy target dose was calculated using the EGSnrc Monte Carlo codes. Results: All treatment modalities generated similar dose distributions for the subcutaneous tumor case, with the highest mean dose to the ipsilateral lung and bones in the single-field plan (0.4 and 0.4 Gy) compared to the microCT (0.1 and 0.2 Gy) and SARRP (0.1 and 0.3 Gy) plans. The lung case demonstrated that due to the nine-beam arrangements in the conformal plans, the mean doses to the ipsilateral lung, spinal cord, and bones were significantly lower in the microCT plan (2.0, 0.4, and 1.9 Gy) and the SARRP plan (1.5, 0.5, and 1.8 Gy) than in single-field irradiator plan (4.5, 3.8, and 3.3 Gy). Similarly, the mean doses to the contralateral lung and the heart were lowest in the microCT plan (1.5 and 2.0 Gy), followed by the SARRP plan (1.7 and 2.2 Gy), and they were highest in the single-field plan (2.5 and 2.4 Gy). For both cases, dose uniformity was greatest in the single-field irradiator plan followed by

On the surveillance for animal diseases in small herds

DEFF Research Database (Denmark)

Greiner, Matthias; Dekker, Aldo

2005-01-01

Small herds may present a problem in surveillance for infectious animal diseases because typical levels of a within-herd design prevalence are not directly applicable. We suggest a definition of small herds as those smaller than 2/(within-herd design prevalence) on the basis that such herds would...... be expected to have less than two (i.e. only one) infected animals. Consequently, the probability of detecting small herds cannot be improved by choosing a larger sample size within the herd. We derive necessary sample sizes of herds and the probability ("confidence") of detecting disease within a stratum...... conservative (lower) estimates of the confidence for a given sample size and should therefore be preferred....

Small animal MRI: clinical MRI as an interface to basic biomedical research

International Nuclear Information System (INIS)

Pinkernelle, J.G.; Stelter, L.; Hamm, B.; Teichgraeber, U.

2008-01-01

The demand for highly resolved small animal MRI for the purpose of biomedical research has increased constantly. Dedicated small animal MRI scanners working at ultra high field strengths from 4.7 to 7.0 T and even above are MRI at its best. However, using high resolution RF coils in clinical scanners up to 3.0 T, small animal MRI can achieve highly resolved images showing excellent tissue contrast. In fact, in abundant experimental studies, clinical MRI is used for small animal imaging. Mostly clinical RF coils in the single-loop design are applied. In addition, custom-built RF coils and even gradient inserts are used in a clinical scanner. For the reduction of moving artifacts, special MRI-compatible animal ECG und respiration devices are available. In conclusion, clinical devices offer broad availability, are less expense in combination with good imaging performance and provide a translational nature of imaging results. (orig.)

SU-E-T-124: Anthropomorphic Phantoms for Confirmation of Linear Accelerator Based Small Animal Irradiation

Energy Technology Data Exchange (ETDEWEB)

Perks, J; Benedict, S [UC Davis Cancer Center, Sacramento, CA (United States); Lucero, S [UC Davis, Davis, CA (United States)

2015-06-15

Purpose: To document the support of radiobiological small animal research by a modern radiation oncology facility. This study confirms that a standard, human use linear accelerator can cover the range of experiments called for by researchers performing animal irradiation. A number of representative, anthropomorphic murine phantoms were made. The phantoms confirmed the small field photon and electron beams dosimetry validated the use of the linear accelerator for rodents. Methods: Laser scanning a model, CAD design and 3D printing produced the phantoms. The phantoms were weighed and CT scanned to judge their compatibility to real animals. Phantoms were produced to specifically mimic lung, gut, brain, and othotopic lesion irradiations. Each phantom was irradiated with the same protocol as prescribed to the live animals. Delivered dose was measured with small field ion chambers, MOS/FETs or TLDs. Results: The density of the phantom material compared to density range across the real mice showed that the printed material would yield sufficiently accurate measurements when irradiated. The whole body, lung and gut irradiations were measured within 2% of prescribed doses with A1SL ion chamber. MOSFET measurements of electron irradiations for the orthotopic lesions allowed refinement of the measured small field output factor to better than 2% and validated the immunology experiment of irradiating one lesion and sparing another. Conclusion: Linacs are still useful tools in small animal bio-radiation research. This work demonstrated a strong role for the clinical accelerator in small animal research, facilitating standard whole body dosing as well as conformal treatments down to 1cm field. The accuracy of measured dose, was always within 5%. The electron irradiations of the phantom brain and flank tumors needed adjustment; the anthropomorphic phantoms allowed refinement of the initial output factor measurements for these fields which were made in a large block of solid water.

Real-time bladder volume monitoring by the application of a new implantable bladder volume sensor for a small animal model

Directory of Open Access Journals (Sweden)

Dong Sup Lee

2011-04-01

Full Text Available Although real-time monitoring of bladder volume together with intravesical pressure can provide more information for understanding the functional changes of the urinary bladder, it still entails difficulties in the accurate prediction of real-time bladder volume in urodynamic studies with small animal models. We studied a new implantable bladder volume monitoring device with eight rats. During cystometry, microelectrodes prepared by the microelectromechanical systems process were placed symmetrically on both lateral walls of the bladder, and the expanded bladder volume was calculated. Immunohistological study was done after 1 week and after 4 weeks to evaluate the biocompatibility of the microelectrode. From the point that infused saline volume into the bladder was higher than 0.6 mL, estimated bladder volume was statistically correlated with the volume of saline injected (p<0.01. Additionally, the microelectromechanical system microelectrodes used in this study showed reliable biocompatibility. Therefore, the device can be used to evaluate changes in bladder volume in studies with small animals, and it may help to provide more information about functional changes in the bladder in laboratory studies. Furthermore, owing to its biocompatibility, the device could be chronically implanted in conscious ambulating animals, thus allowing a novel longitudinal study to be performed for a specific purpose.

Anesthesia condition for {sup 18}F-FDG imaging of lung metastasis tumors using small animal PET

Energy Technology Data Exchange (ETDEWEB)

Woo, Sang-Keun; Lee, Tae Sup; Kim, Kyeong Min; Kim, June-Youp; Jung, Jae Ho; Kang, Joo Hyun [Division of Nuclear Medicine and RI Application, Korea Institute of Radiological and Medical Sciences (KIRAMS), Nowon-Gu, Seoul 139-706 (Korea, Republic of); Cheon, Gi Jeong [Division of Nuclear Medicine and RI Application, Korea Institute of Radiological and Medical Sciences (KIRAMS), Nowon-Gu, Seoul 139-706 (Korea, Republic of); Department of Nuclear Medicine, Korea Institute of Radiological and Medical Sciences (KIRAMS), Nowon-Gu, Seoul 139-706 (Korea, Republic of)], E-mail: larry@kcch.re.kr; Choi, Chang Woon; Lim, Sang Moo [Division of Nuclear Medicine and RI Application, Korea Institute of Radiological and Medical Sciences (KIRAMS), Nowon-Gu, Seoul 139-706 (Korea, Republic of); Department of Nuclear Medicine, Korea Institute of Radiological and Medical Sciences (KIRAMS), Nowon-Gu, Seoul 139-706 (Korea, Republic of)

2008-01-15

Small animal positron emission tomography (PET) with {sup 18}F-FDG has been increasingly used for tumor imaging in the murine model. The aim of this study was to establish the anesthesia condition for imaging of lung metastasis tumor using small animal {sup 18}F-FDG PET. Methods: To determine the impact of anesthesia on {sup 18}F-FDG distribution in normal mice, five groups were studied under the following conditions: no anesthesia, ketamine and xylazine (Ke/Xy), 0.5% isoflurane (Iso 0.5), 1% isoflurane (Iso 1) and 2% isoflurane (Iso 2). The ex vivo counting, standard uptake value (SUV) image and glucose SUV of {sup 18}F-FDG in various tissues were evaluated. The {sup 18}F-FDG images in the lung metastasis tumor model were obtained under no anesthesia, Ke/Xy and Iso 0.5, and registered with CT image to clarify the tumor region. Results: Blood glucose concentration and muscle uptake of {sup 18}F-FDG in the Ke/Xy group markedly increased more than in the other groups. The Iso 2 group increased {sup 18}F-FDG uptake in heart compared with the other groups. The Iso 0.5 anesthesized group showed the lowest {sup 18}F-FDG uptake in heart and chest wall. The small size of lung metastasis tumor (2 mm) was clearly visualized by {sup 18}F-FDG image with the Iso 0.5 anesthesia. Conclusion: Small animal {sup 18}F-FDG PET imaging with Iso 0.5 anesthesia was appropriate for the detection of lung metastasis tumor. To acquire {sup 18}F-FDG PET images with small animal PET, the type and level of anesthetic should be carefully considered to be suitable for the visualization of target tissue in the experimental model.

Physical and biological dosimetry at the RA-3 facility for small animal irradiation: preliminary BNCT studies in an experimental model of oral cancer

International Nuclear Information System (INIS)

Pozzi, Emiliano; Miller, Marcelo; Thorp, Silvia I.; Heber, Elisa M.; Trivillin, Veronica A.; Zarza, Leandro; Estryk, Guillermo; Schwint, Amanda E.; Nigg, David W.

2007-01-01

Boron Neutron Capture Therapy (BNCT) is a binary treatment modality based on the capture reaction that occurs between thermal neutrons and boron-10 atoms that accumulate selectively in tumor tissue, emitting high linear energy transfer (LET), short range (5-9 microns) particles (alpha y 7 Li). Thus, BNCT would potentially target tumor tissue selectively, sparing normal tissue. Herein we evaluated the feasibility of treating experimental oral mucosa tumors with BNCT at RA-3 (CAE) employing the hamster cheek pouch oral cancer model and characterized the irradiation field at the RA-3 facility. We evaluated the therapeutic effect on tumor of BNCT mediated by BPA in the hamster cheek pouch oral cancer model and the potential radio toxic effects in normal tissue. We evidenced a moderate biological response in tumor, with no radio toxic effects in normal tissue following irradiations with no shielding for the animal body. Given the sub-optimal therapeutic response, we designed and built a 6 Li 2 CO 3 shielding for the body of the animal to increase the irradiation dose to tumor, without exceeding normal tissue radio tolerance. The measured absolute magnitude of thermal neutron flux and the characterization of the beam with and without the shielding in place, suggest that the irradiation facility in the thermal column of RA-3 would afford an excellent platform to perform BNCT studies in vitro and in vivo in small experimental animals. The present findings must be confirmed and extended by performing in vivo BNCT radiobiological studies in small experimental animals, employing the shielding device for the animal body. (author) [es

Animal Models of Zika Virus

Science.gov (United States)

Bradley, Michael P; Nagamine, Claude M

2017-01-01

Zika virus has garnered great attention over the last several years, as outbreaks of the disease have emerged throughout the Western Hemisphere. Until quite recently Zika virus was considered a fairly benign virus, with limited clinical severity in both people and animals. The size and scope of the outbreak in the Western Hemisphere has allowed for the identification of severe clinical disease that is associated with Zika virus infection, most notably microcephaly among newborns, and an association with Guillian–Barré syndrome in adults. This recent association with severe clinical disease, of which further analysis strongly suggested causation by Zika virus, has resulted in a massive increase in the amount of both basic and applied research of this virus. Both small and large animal models are being used to uncover the pathogenesis of this emerging disease and to develop vaccine and therapeutic strategies. Here we review the animal-model–based Zika virus research that has been performed to date. PMID:28662753

An integrated multimodality image-guided robot system for small-animal imaging research

International Nuclear Information System (INIS)

Hsu, Wen-Lin; Hsin Wu, Tung; Hsu, Shih-Ming; Chen, Chia-Lin; Lee, Jason J.S.; Huang, Yung-Hui

2011-01-01

We design and construct an image-guided robot system for use in small-animal imaging research. This device allows the use of co-registered small-animal PET-MRI images to guide the movements of robotic controllers, which will accurately place a needle probe at any predetermined location inside, for example, a mouse tumor, for biological readouts without sacrificing the animal. This system is composed of three major components: an automated robot device, a CCD monitoring mechanism, and a multimodality registration implementation. Specifically, the CCD monitoring mechanism was used for correction and validation of the robot device. To demonstrate the value of the proposed system, we performed a tumor hypoxia study that involved FMISO small-animal PET imaging and the delivering of a pO 2 probe into the mouse tumor using the image-guided robot system. During our evaluation, the needle positioning error was found to be within 0.153±0.042 mm of desired placement; the phantom simulation errors were within 0.693±0.128 mm. In small-animal studies, the pO 2 probe measurements in the corresponding hypoxia areas showed good correlation with significant, low tissue oxygen tensions (less than 6 mmHg). We have confirmed the feasibility of the system and successfully applied it to small-animal investigations. The system could be easily adapted to extend to other biomedical investigations in the future.

Technical Note: How to use Winbugs to infer animal models

DEFF Research Database (Denmark)

Damgaard, Lars Holm

2007-01-01

This paper deals with Bayesian inferences of animal models using Gibbs sampling. First, we suggest a general and efficient method for updating additive genetic effects, in which the computational cost is independent of the pedigree depth and increases linearly only with the size of the pedigree....... Second, we show how this approach can be used to draw inferences from a wide range of animal models using the computer package Winbugs. Finally, we illustrate the approach in a simulation study, in which the data are generated and analyzed using Winbugs according to a linear model with i.i.d errors...... having Student's t distributions. In conclusion, Winbugs can be used to make inferences in small-sized, quantitative, genetic data sets applying a wide range of animal models that are not yet standard in the animal breeding literature...

Implementation of immobilization accessories for positioning of small animals for radiation therapy

International Nuclear Information System (INIS)

Vettorato, M.C.; Girotto, C.H.; Fogaça, J.L.; Vulcano, L.C.; Fernandes, M.A.R.

2017-01-01

Radiation therapy is a modality that is presenting great advances in veterinary medicine worldwide. In Brazil, this therapeutic option is underachieved. The success of this method depends on several factors, including the use of appropriate accessories for protection and immobilization of patients. For the immobilization of small animals during treatment, in addition to sedation and anesthesia, immobilizing accessories, similar to those used in human radiotherapy, are used. This study aimed to present proposals for immobilizing accessories adapted to the positioning of small animals in order to be used in radiotherapy planning. In order to achieve results, accessories were made and tested in a living animal simulating a radiotherapy planning, which proved to be favorable to use in positioning small animals undergoing radiotherapy and for implementation processes. (author)

Implementation of immobilization accessories for positioning of small animals for radiation therapy

Energy Technology Data Exchange (ETDEWEB)

Vettorato, M.C.; Girotto, C.H.; Fogaça, J.L.; Vulcano, L.C.; Fernandes, M.A.R., E-mail: m_vettorato@hotmail.com [Universidade Estadual Paulista Júlio de Mesquita Filho (UNESP), Botucatu, SP (Brazil)

2017-11-15

Radiation therapy is a modality that is presenting great advances in veterinary medicine worldwide. In Brazil, this therapeutic option is underachieved. The success of this method depends on several factors, including the use of appropriate accessories for protection and immobilization of patients. For the immobilization of small animals during treatment, in addition to sedation and anesthesia, immobilizing accessories, similar to those used in human radiotherapy, are used. This study aimed to present proposals for immobilizing accessories adapted to the positioning of small animals in order to be used in radiotherapy planning. In order to achieve results, accessories were made and tested in a living animal simulating a radiotherapy planning, which proved to be favorable to use in positioning small animals undergoing radiotherapy and for implementation processes. (author)

The biological application of small animal PET imaging

International Nuclear Information System (INIS)

Myers, Ralph

2001-01-01

The short history of small animal PET is reviewed in the context of its application in the laboratory. Early work has demonstrated a role for the technique in both drug development and in the in vivo monitoring of neuroreceptor function with time. As spatial resolution approaches 1 mm, challenges in quantification remain. However, the ability to carry out animal PET studies that are analogous to human PET will form an important bridge between laboratory and clinical sciences

Potential Applications of Flat-Panel Volumetric CT in Morphologic, Functional Small Animal Imaging

Directory of Open Access Journals (Sweden)

Susanne Greschus

2005-08-01

Full Text Available Noninvasive radiologic imaging has recently gained considerable interest in basic, preclinical research for monitoring disease progression, therapeutic efficacy. In this report, we introduce flat-panel volumetric computed tomography (fpVCT as a powerful new tool for noninvasive imaging of different organ systems in preclinical research. The three-dimensional visualization that is achieved by isotropic high-resolution datasets is illustrated for the skeleton, chest, abdominal organs, brain of mice. The high image quality of chest scans enables the visualization of small lung nodules in an orthotopic lung cancer model, the reliable imaging of therapy side effects such as lung fibrosis. Using contrast-enhanced scans, fpVCT displayed the vascular trees of the brain, liver, kidney down to the subsegmental level. Functional application of fpVCT in dynamic contrast-enhanced scans of the rat brain delivered physiologically reliable data of perfusion, tissue blood volume. Beyond scanning of small animal models as demonstrated here, fpVCT provides the ability to image animals up to the size of primates.

Animal models of gastrointestinal and liver diseases. Animal models of acute and chronic pancreatitis

Science.gov (United States)

Zhan, Xianbao; Wang, Fan; Bi, Yan

2016-01-01

Animal models of pancreatitis are useful for elucidating the pathogenesis of pancreatitis and developing and testing novel interventions. In this review, we aim to summarize the most commonly used animal models, overview their pathophysiology, and discuss their strengths and limitations. We will also briefly describe common animal study procedures and refer readers to more detailed protocols in the literature. Although animal models include pigs, dogs, opossums, and other animals, we will mainly focus on rodent models because of their popularity. Autoimmune pancreatitis and genetically engineered animal models will be reviewed elsewhere. PMID:27418683

Scalable electrophysiology in intact small animals with nanoscale suspended electrode arrays

Science.gov (United States)

Gonzales, Daniel L.; Badhiwala, Krishna N.; Vercosa, Daniel G.; Avants, Benjamin W.; Liu, Zheng; Zhong, Weiwei; Robinson, Jacob T.

2017-07-01

Electrical measurements from large populations of animals would help reveal fundamental properties of the nervous system and neurological diseases. Small invertebrates are ideal for these large-scale studies; however, patch-clamp electrophysiology in microscopic animals typically requires invasive dissections and is low-throughput. To overcome these limitations, we present nano-SPEARs: suspended electrodes integrated into a scalable microfluidic device. Using this technology, we have made the first extracellular recordings of body-wall muscle electrophysiology inside an intact roundworm, Caenorhabditis elegans. We can also use nano-SPEARs to record from multiple animals in parallel and even from other species, such as Hydra littoralis. Furthermore, we use nano-SPEARs to establish the first electrophysiological phenotypes for C. elegans models for amyotrophic lateral sclerosis and Parkinson's disease, and show a partial rescue of the Parkinson's phenotype through drug treatment. These results demonstrate that nano-SPEARs provide the core technology for microchips that enable scalable, in vivo studies of neurobiology and neurological diseases.

Management of occupational health risks in small-animal veterinary practices.

Science.gov (United States)

D'Souza, Eva; Barraclough, Richard; Fishwick, David; Curran, Andrew

2009-08-01

Small-animal work is a major element of veterinary practice in the UK and may be hazardous, with high levels of work-related injuries and ill-health reported in Australia and USA. There are no studies addressing the management of occupational health risks arising from small-animal work in the UK. To investigate the sources of health and safety information used and how health and safety and 12 specific occupational health risks are managed by practices. A cross-sectional postal survey of all small-animal veterinary practices in Hampshire. A response was mandatory as this was a Health & Safety Executive (HSE) inspection activity. A total of 118 (100%) practices responded of which 93 were eligible for inclusion. Of these, 99 and 86%, respectively, were aware of the Royal College of Veterinary Surgeons (RCVS) practice standards and had British Small Animal Veterinary Association (BSAVA) staff members, while only 51% had previous contact with HSE (publications, advice and visit). Ninety per cent had health and safety policies, but only 31% had trained responsible staff in health and safety. Specific health hazards such as occupational allergens and computer use were relatively overlooked both by practices and the RCVS/BSAVA guidance available in 2002. Failings in active health risk management systems could be due to a lack of training to ensure competence in those with responsibilities. Practices rely on guidance produced by their professional bodies. Current RCVS guidance, available since 2005, has remedied some previous omissions, but further improvements are recommended.

Animal models of gastrointestinal and liver diseases. Animal models of acute and chronic pancreatitis.

Science.gov (United States)

Zhan, Xianbao; Wang, Fan; Bi, Yan; Ji, Baoan

2016-09-01

Animal models of pancreatitis are useful for elucidating the pathogenesis of pancreatitis and developing and testing novel interventions. In this review, we aim to summarize the most commonly used animal models, overview their pathophysiology, and discuss their strengths and limitations. We will also briefly describe common animal study procedures and refer readers to more detailed protocols in the literature. Although animal models include pigs, dogs, opossums, and other animals, we will mainly focus on rodent models because of their popularity. Autoimmune pancreatitis and genetically engineered animal models will be reviewed elsewhere. Copyright © 2016 the American Physiological Society.

Factors influencing common diagnoses made during first-opinion small-animal consultations in the United Kingdom.

Science.gov (United States)

Robinson, N J; Dean, R S; Cobb, M; Brennan, M L

2016-09-01

It is currently unclear how frequently a diagnosis is made during small-animal consultations or how much of a role making a diagnosis plays in veterinary decision-making. Understanding more about the diagnostic process will help direct future research towards areas relevant to practicing veterinary surgeons. The aim of this study was to determine the frequency with which a diagnosis was made, classify the types of diagnosis made (and the factors influencing these) and determine which specific diagnoses were made for health problems discussed during small-animal consultations. Data were gathered during real-time direct observation of small-animal consultations in eight practices in the United Kingdom. Data collected included characteristics of the consultation (e.g. consultation type), patient (e.g. breed), and each problem discussed (e.g. new or pre-existing problem). Each problem discussed was classified into one of the following diagnosis types: definitive; working; presumed; open; previous. A three-level multivariable logistic-regression model was developed, with problem (Level 1) nested within patient (Level 2) nested within consulting veterinary surgeon (Level 3). Problems without a previous diagnosis, in cats and dogs only, were included in the model, which had a binary outcome variable of definitive diagnosis versus no definitive diagnosis. Data were recorded for 1901 animals presented, and data on diagnosis were gathered for 3192 health problems. Previous diagnoses were the most common diagnosis type (n=1116/3192; 35.0%), followed by open (n=868/3192; 27.2%) then definitive (n=660/3192; 20.7%). The variables remaining in the final model were patient age, problem history, consultation type, who raised the problem, and body system affected. New problems, problems in younger animals, and problems raised by the veterinary surgeon were more likely to result in a definitive diagnosis than pre-existing problems, problems in older animals, and problems raised by

Development of an Extracorporeal Perfusion Device for Small Animal Free Flaps.

Directory of Open Access Journals (Sweden)

Andreas M Fichter

Full Text Available Extracorporeal perfusion (ECP might prolong the vital storage capabilities of composite free flaps, potentially opening a wide range of clinical applications. Aim of the study was the development a validated low-cost extracorporeal perfusion model for further research in small animal free flaps.After establishing optimal perfusion settings, a specially designed extracorporeal perfusion system was evaluated during 8-hour perfusion of rat epigastric flaps followed by microvascular free flap transfer. Controls comprised sham-operation, ischemia and in vivo perfusion. Flaps and perfusate (diluted blood were closely monitored by blood gas analysis, combined laser Doppler flowmetry and remission spectroscopy and Indocyanine-Green angiography. Evaluations were complemented by assessment of necrotic area and light microscopy at day 7.ECP was established and maintained for 8 hours with constant potassium and pH levels. Subsequent flap transfer was successful. Notably, the rate of necrosis of extracorporeally perfused flaps (27% was even lower than after in vivo perfusion (49%, although not statistically significant (P = 0,083. After sham-operation, only 6% of the total flap area became necrotic, while 8-hour ischemia led to total flap loss (98%. Angiographic and histological findings confirmed these observations.Vital storage capabilities of microvascular flaps can be prolonged by temporary ECP. Our study provides important insights on the pathophysiological processes during extracorporeal tissue perfusion and provides a validated small animal perfusion model for further studies.

Hyperpolarized singlet NMR on a small animal imaging system

DEFF Research Database (Denmark)

Laustsen, Christoffer; Pileio, Giuseppe; Tayler, Michael C. D.

2012-01-01

Nuclear spin hyperpolarization makes a significant advance toward overcoming the sensitivity limitations of in vivo magnetic resonance imaging, particularly in the case of low-gamma nuclei. The sensitivity may be improved further by storing the hyperpolarization in slowly relaxing singlet...... populations of spin- 1/2 pairs. Here, we report hyperpolarized 13C spin order transferred into and retrieved from singlet spin order using a small animal magnetic resonance imaging scanner. For spins in sites with very similar chemical shifts, singlet spin order is sustained in high magnetic field without...... requiring strong radiofrequency irradiation. The demonstration of robust singlet-to-magnetization conversion, and vice versa, on a small animal scanner, is promising for future in vivo and clinical deployments....

Marketing small animal theriogenology services--one perspective.

Science.gov (United States)

Barber, J A

2007-08-01

Once a decision is made to add small animal theriogenology services to a practice, marketing strategies must be developed and implemented to attract clients to the new services. Marketing strategies for the niche market of theriogenology include start-up marketing methods, referral programs, internal marketing, and continued marketing. Marketing theriogenology services is a dynamic, ongoing process that never ends.

Development of computational small animal models and their applications in preclinical imaging and therapy research

NARCIS (Netherlands)

Xie, Tianwu; Zaidi, Habib

The development of multimodality preclinical imaging techniques and the rapid growth of realistic computer simulation tools have promoted the construction and application of computational laboratory animal models in preclinical research. Since the early 1990s, over 120 realistic computational animal

TH-EF-207A-05: Feasibility of Applying SMEIR Method On Small Animal 4D Cone Beam CT Imaging

International Nuclear Information System (INIS)

Zhong, Y; Zhang, Y; Shao, Y; Wang, J

2016-01-01

Purpose: Small animal cone beam CT imaging has been widely used in preclinical research. Due to the higher respiratory rate and heat beats of small animals, motion blurring is inevitable and needs to be corrected in the reconstruction. Simultaneous motion estimation and image reconstruction (SMEIR) method, which uses projection images of all phases, proved to be effective in motion model estimation and able to reconstruct motion-compensated images. We demonstrate the application of SMEIR for small animal 4D cone beam CT imaging by computer simulations on a digital rat model. Methods: The small animal CBCT imaging system was simulated with the source-to-detector distance of 300 mm and the source-to-object distance of 200 mm. A sequence of rat phantom were generated with 0.4 mm 3 voxel size. The respiratory cycle was taken as 1.0 second and the motions were simulated with a diaphragm motion of 2.4mm and an anterior-posterior expansion of 1.6 mm. The projection images were calculated using a ray-tracing method, and 4D-CBCT were reconstructed using SMEIR and FDK methods. The SMEIR method iterates over two alternating steps: 1) motion-compensated iterative image reconstruction by using projections from all respiration phases and 2) motion model estimation from projections directly through a 2D-3D deformable registration of the image obtained in the first step to projection images of other phases. Results: The images reconstructed using SMEIR method reproduced the features in the original phantom. Projections from the same phase were also reconstructed using FDK method. Compared with the FDK results, the images from SMEIR method substantially improve the image quality with minimum artifacts. Conclusion: We demonstrate that it is viable to apply SMEIR method to reconstruct small animal 4D-CBCT images.

Preclinical Testing of Antihuman CD28 Fab' Antibody in a Novel Nonhuman Primate Small Animal Rodent Model of Xenogenic Graft-Versus-Host Disease.

Science.gov (United States)

Hippen, Keli L; Watkins, Benjamin; Tkachev, Victor; Lemire, Amanda M; Lehnen, Charles; Riddle, Megan J; Singh, Karnail; Panoskaltsis-Mortari, Angela; Vanhove, Bernard; Tolar, Jakub; Kean, Leslie S; Blazar, Bruce R

2016-12-01

Graft-versus-host disease (GVHD) is a severe complication of hematopoietic stem cell transplantation. Current therapies to prevent alloreactive T cell activation largely cause generalized immunosuppression and may result in adverse drug, antileukemia and antipathogen responses. Recently, several immunomodulatory therapeutics have been developed that show efficacy in maintaining antileukemia responses while inhibiting GVHD in murine models. To analyze efficacy and better understand immunological tolerance, escape mechanisms, and side effects of clinical reagents, testing of species cross-reactive human agents in large animal GVHD models is critical. We have previously developed and refined a nonhuman primate (NHP) large animal GVHD model. However, this model is not readily amenable to semi-high throughput screening of candidate clinical reagents. Here, we report a novel, optimized NHP xenogeneic GVHD (xeno-GVHD) small animal model that recapitulates many aspects of NHP and human GVHD. This model was validated using a clinically available blocking, monovalent anti-CD28 antibody (FR104) whose effects in a human xeno-GVHD rodent model are known. Because human-reactive reagents may not be fully cross-reactive or effective in vivo on NHP immune cells, this NHP xeno-GVHD model provides immunological insights and direct testing on NHP-induced GVHD before committing to the intensive NHP studies that are being increasingly used for detailed evaluation of new immune therapeutic strategies before human trials.

Diffusion tensor and volumetric magnetic resonance measures as biomarkers of brain damage in a small animal model of HIV.

Directory of Open Access Journals (Sweden)

Margaret R Lentz

Full Text Available There are currently no widely accepted neuro-HIV small animal models. We wanted to validate the HIV-1 Transgenic rat (Tg as an appropriate neuro-HIV model and then establish in vivo imaging biomarkers of neuropathology, within this model, using MR structural and diffusion tensor imaging (DTI.Young and middle-aged Tg and control rats were imaged using MRI. A subset of middle-aged animals underwent longitudinal repeat imaging six months later. Total brain volume (TBV, ventricular volume (VV and parenchymal volume (PV = TBV-VV were measured. Fractional anisotropy (FA and mean diffusivity (MD values of the corpus callosum (CC were calculated from DTI data.TBV and PV were smaller in Tg compared to control rats in young and middle-aged cohorts (p0.05.We detected brain volume loss in the Tg rat, probably due to astrocytic dysfunction/loss, loss of structural/axonal matrix and striatal neuronal loss as suggested by immunofluorescence. Increased MD and decreased FA in the CC probably reflect microstructural differences between the Tg and Control rats which could include increased extracellular space between white matter tracts, demyelination and axonal degeneration, among other pathologies. We believe that the Tg rat is an adequate model of neuropathology in HIV and that volumetric MR and DTI measures can be potentially used as biomarkers of disease progression.

Anaphylaxis Imaging: Non-Invasive Measurement of Surface Body Temperature and Physical Activity in Small Animals.

Directory of Open Access Journals (Sweden)

Krisztina Manzano-Szalai

Full Text Available In highly sensitized patients, the encounter with a specific allergen from food, insect stings or medications may rapidly induce systemic anaphylaxis with potentially lethal symptoms. Countless animal models of anaphylaxis, most often in BALB/c mice, were established to understand the pathophysiology and to prove the safety of different treatments. The most common symptoms during anaphylactic shock are drop of body temperature and reduced physical activity. To refine, improve and objectify the currently applied manual monitoring methods, we developed an imaging method for the automated, non-invasive measurement of the whole-body surface temperature and, at the same time, of the horizontal and vertical movement activity of small animals. We tested the anaphylaxis imaging in three in vivo allergy mouse models for i milk allergy, ii peanut allergy and iii egg allergy. These proof-of-principle experiments suggest that the imaging technology represents a reliable non-invasive method for the objective monitoring of small animals during anaphylaxis over time. We propose that the method will be useful for monitoring diseases associated with both, changes in body temperature and in physical behaviour.

Cardiovascular Changes in Animal Models of Metabolic Syndrome

Directory of Open Access Journals (Sweden)

Alexandre M. Lehnen

2013-01-01

Full Text Available Metabolic syndrome has been defined as a group of risk factors that directly contribute to the development of cardiovascular disease and/or type 2 diabetes. Insulin resistance seems to have a fundamental role in the genesis of this syndrome. Over the past years to the present day, basic and translational research has used small animal models to explore the pathophysiology of metabolic syndrome and to develop novel therapies that might slow the progression of this prevalent condition. In this paper we discuss the animal models used for the study of metabolic syndrome, with particular focus on cardiovascular changes, since they are the main cause of death associated with the condition in humans.

Hyperspectral small animal fluorescence imaging: spectral selection imaging

Science.gov (United States)

Leavesley, Silas; Jiang, Yanan; Patsekin, Valery; Hall, Heidi; Vizard, Douglas; Robinson, J. Paul

2008-02-01

Molecular imaging is a rapidly growing area of research, fueled by needs in pharmaceutical drug-development for methods for high-throughput screening, pre-clinical and clinical screening for visualizing tumor growth and drug targeting, and a growing number of applications in the molecular biology fields. Small animal fluorescence imaging employs fluorescent probes to target molecular events in vivo, with a large number of molecular targeting probes readily available. The ease at which new targeting compounds can be developed, the short acquisition times, and the low cost (compared to microCT, MRI, or PET) makes fluorescence imaging attractive. However, small animal fluorescence imaging suffers from high optical scattering, absorption, and autofluorescence. Much of these problems can be overcome through multispectral imaging techniques, which collect images at different fluorescence emission wavelengths, followed by analysis, classification, and spectral deconvolution methods to isolate signals from fluorescence emission. We present an alternative to the current method, using hyperspectral excitation scanning (spectral selection imaging), a technique that allows excitation at any wavelength in the visible and near-infrared wavelength range. In many cases, excitation imaging may be more effective at identifying specific fluorescence signals because of the higher complexity of the fluorophore excitation spectrum. Because the excitation is filtered and not the emission, the resolution limit and image shift imposed by acousto-optic tunable filters have no effect on imager performance. We will discuss design of the imager, optimizing the imager for use in small animal fluorescence imaging, and application of spectral analysis and classification methods for identifying specific fluorescence signals.

Animal models of gastrointestinal and liver diseases. Animal models of acute and chronic pancreatitis

OpenAIRE

Zhan, Xianbao; Wang, Fan; Bi, Yan; Ji, Baoan

2016-01-01

Animal models of pancreatitis are useful for elucidating the pathogenesis of pancreatitis and developing and testing novel interventions. In this review, we aim to summarize the most commonly used animal models, overview their pathophysiology, and discuss their strengths and limitations. We will also briefly describe common animal study procedures and refer readers to more detailed protocols in the literature. Although animal models include pigs, dogs, opossums, and other animals, we will mai...

Animal models of dementia

DEFF Research Database (Denmark)

Olsson, I. Anna S.; Sandøe, Peter

2011-01-01

This chapter aims to encourage scientists and others interested in the use of animal models of disease – specifically, in the study of dementia – to engage in ethical reflection. It opens with a general discussion of the moral acceptability of animal use in research. Three ethical approaches...... are here distinguished. These serve as points of orientation in the following discussion of four more specific ethical questions: Does animal species matter? How effective is disease modelling in delivering the benefits claimed for it? What can be done to minimize potential harm to animals in research? Who...... bears responsibility for the use of animals in disease models?...

Longitudinal Raman Spectroscopic Observation of Skin Biochemical Changes due to Chemotherapeutic Treatment for Breast Cancer in Small Animal Model

Directory of Open Access Journals (Sweden)

Myeongsu Seong

2017-01-01

Full Text Available The cancer field effect (CFE has been highlighted as one of indirect indications for tissue variations that are insensitive to conventional diagnostic techniques. In this research, we had a hypothesis that chemotherapy for breast cancer would affect skin biochemical compositions that would be reflected by Raman spectral changes. We used a fiber-optic probe-based Raman spectroscopy to perform preliminary animal experiments to validate the hypothesis. Firstly, we verified the probing depth of the fiber-optic probe (~800 μm using a simple intravenous fat emulsion-filled phantom having a silicon wafer at the bottom inside a cuvette. Then, we obtained Raman spectra during breast cancer treatment by chemotherapy from a small animal model in longitudinal manner. Our results showed that the treatment causes variations of biochemical compositions in the skin. For further validation, the Raman spectra will have to be collected from more populations and spectra will need to be compared with immunohistochemistry of the breast tissue.

Modelling Farm Animal Welfare

Science.gov (United States)

Collins, Lisa M.; Part, Chérie E.

2013-01-01

Simple Summary In this review paper we discuss the different modeling techniques that have been used in animal welfare research to date. We look at what questions they have been used to answer, the advantages and pitfalls of the methods, and how future research can best use these approaches to answer some of the most important upcoming questions in farm animal welfare. Abstract The use of models in the life sciences has greatly expanded in scope and advanced in technique in recent decades. However, the range, type and complexity of models used in farm animal welfare is comparatively poor, despite the great scope for use of modeling in this field of research. In this paper, we review the different modeling approaches used in farm animal welfare science to date, discussing the types of questions they have been used to answer, the merits and problems associated with the method, and possible future applications of each technique. We find that the most frequently published types of model used in farm animal welfare are conceptual and assessment models; two types of model that are frequently (though not exclusively) based on expert opinion. Simulation, optimization, scenario, and systems modeling approaches are rarer in animal welfare, despite being commonly used in other related fields. Finally, common issues such as a lack of quantitative data to parameterize models, and model selection and validation are discussed throughout the review, with possible solutions and alternative approaches suggested. PMID:26487411

Dynamic studies of small animals with a four-color diffuse optical tomography imager

International Nuclear Information System (INIS)

Schmitz, Christoph H.; Graber, Harry L.; Pei Yaling; Farber, Mark; Stewart, Mark; Levina, Rita D.; Levin, Mikhail B.; Xu Yong; Barbour, Randall L.

2005-01-01

We present newly developed instrumentation for full-tomographic four-wavelength, continuous wave, diffuse optical tomography (DOT) imaging on small animals. A small-animal imaging stage was constructed, from materials compatible with in-magnet studies, which offers stereotaxic fixation of the animal and precise, stable probe positioning. Instrument performance, based on calibration and phantom studies, demonstrates excellent long-term signal stability. DOT measurements of the functional rat brain response to electric paw stimulation are presented, and these demonstrate high data quality and excellent sensitivity to hemodynamic changes. A general linear model analysis on individual trials is used to localize and quantify the occurrence of functional behavior associated with the different hemoglobin state responses. Statistical evaluation of outcomes of individual trials is employed to identify significant regional response variations for different stimulation sites. Image results reveal a diffuse cortical response and a strong reaction of the thalamus, both indicative of activation of pain pathways by the stimulation. In addition, a weaker lateralized functional component is observed in the brain response, suggesting presence of motor activation. An important outcome of the experiment is that it shows that reactions to individual provocations can be monitored, without having to resort to signal averaging. Thus the described technology may be useful for studies of long-term trends in hemodynamic response, as would occur, for example, in behavioral studies involving freely moving animals

Small Animal Massage Therapy: A Brief Review and Relevant Observations.

Science.gov (United States)

Formenton, Maira Rezende; Pereira, Marco Aurélio Amador; Fantoni, Denise Tabacchi

2017-12-01

Massage therapy is becoming increasingly popular in human and animal physiotherapy and rehabilitation. Wider application of the technique led to research efforts aimed at providing scientific support to anecdotal beneficial effects, particularly pain relief. Recent studies have shown that massage therapy alters dopamine and serotonin levels, decreases noradrenaline levels, and modulates the immune system. Psychological effects such as reduction of stress and anxiety, with improvement of depressive patients, have been reported in humans. This article set out to review the major aspects of massage therapy based on recent publications on the topic, and to extrapolate concepts and practical aspects described in human physiotherapy to the veterinary patient, particularly the applicability of different techniques in Small Animal Medicine. Indications of massage therapy in small animals include pain relief, orthopedic rehabilitation, Canine Sports Medicine, intensive care, and management of nonspecific edema. Techniques described in this article were originally intended for use in humans and scientific data supporting anecdotal, beneficial effects in domestic animals are still lacking; this fruitful area for research is therefore open to veterinary professionals. Copyright © 2017 Elsevier Inc. All rights reserved.

Model-Based Normalization of a Fractional-Crystal Collimator for Small-Animal PET Imaging.

Science.gov (United States)

Li, Yusheng; Matej, Samuel; Karp, Joel S; Metzler, Scott D

2017-05-01

Previously, we proposed to use a coincidence collimator to achieve fractional-crystal resolution in PET imaging. We have designed and fabricated a collimator prototype for a small-animal PET scanner, A-PET. To compensate for imperfections in the fabricated collimator prototype, collimator normalization, as well as scanner normalization, is required to reconstruct quantitative and artifact-free images. In this study, we develop a normalization method for the collimator prototype based on the A-PET normalization using a uniform cylinder phantom. We performed data acquisition without the collimator for scanner normalization first, and then with the collimator from eight different rotation views for collimator normalization. After a reconstruction without correction, we extracted the cylinder parameters from which we generated expected emission sinograms. Single scatter simulation was used to generate the scattered sinograms. We used the least-squares method to generate the normalization coefficient for each LOR based on measured, expected and scattered sinograms. The scanner and collimator normalization coefficients were factorized by performing two normalizations separately. The normalization methods were also verified using experimental data acquired from A-PET with and without the collimator. In summary, we developed a model-base collimator normalization that can significantly reduce variance and produce collimator normalization with adequate statistical quality within feasible scan time.

A Modified Carbon Monoxide Breath Test for Measuring Erythrocyte Lifespan in Small Animals

Directory of Open Access Journals (Sweden)

Yong-Jian Ma

2016-01-01

Full Text Available This study was to develop a CO breath test for RBC lifespan estimation of small animals. The ribavirin induced hemolysis rabbit models were placed individually in a closed rebreath cage and air samples were collected for measurement of CO concentration. RBC lifespan was calculated from accumulated CO, blood volume, and hemoglobin concentration data. RBC lifespan was determined in the same animals with the standard biotin-labeling method. RBC lifespan data obtained by the CO breath test method for control (CON, 49.0±5.9 d rabbits, rabbits given 10 mg/kg·d−1 of ribavirin (RIB10, 31.0±4.0 d, and rabbits given 20 mg/kg·d−1 of ribavirin (RIB20, 25.0±2.9 d were statistically similar (all p>0.05 to and linearly correlated (r=0.96, p<0.01 with the RBC lifespan data obtained for the same rabbits by the standard biotin-labeling method (CON, 51.0±2.7 d; RIB10, 33.0±1.3 d; and RIB20, 27.0±0.8 d. The CO breath test method takes less than 3 h to complete, whereas the standard method requires at least several weeks. In conclusion, the CO breath test method provides a simple and rapid means of estimating RBC lifespan and is feasible for use with small animal models.

Preliminary study for small animal preclinical hadrontherapy facility

Energy Technology Data Exchange (ETDEWEB)

Russo, G. [Institute of Molecular Bioimaging and Physiology, IBFM CNR-LATO, Cefalú (Italy); Pisciotta, P., E-mail: pietro.pisciotta@ibfm.cnr.it [Institute of Molecular Bioimaging and Physiology, IBFM CNR-LATO, Cefalú (Italy); National Institute for Nuclear Physics, Laboratori Nazionali del Sud, INFN-LNS, Catania (Italy); Cirrone, G.A.P.; Romano, F. [National Institute for Nuclear Physics, Laboratori Nazionali del Sud, INFN-LNS, Catania (Italy); Cammarata, F.; Marchese, V.; Forte, G.I.; Lamia, D.; Minafra, L.; Bravatá, V. [Institute of Molecular Bioimaging and Physiology, IBFM CNR-LATO, Cefalú (Italy); Acquaviva, R. [University of Catania, Catania (Italy); Gilardi, M.C. [Institute of Molecular Bioimaging and Physiology, IBFM CNR-LATO, Cefalú (Italy); Cuttone, G. [National Institute for Nuclear Physics, Laboratori Nazionali del Sud, INFN-LNS, Catania (Italy)

2017-02-21

Aim of this work is the study of the preliminary steps to perform a particle treatment of cancer cells inoculated in small animals and to realize a preclinical hadrontherapy facility. A well-defined dosimetric protocol was developed to explicate the steps needed in order to perform a precise proton irradiation in small animals and achieve a highly conformal dose into the target. A precise homemade positioning and holding system for small animals was designed and developed at INFN-LNS in Catania (Italy), where an accurate Monte Carlo simulation was developed, using Geant4 code to simulate the treatment in order to choose the best animal position and perform accurately all the necessary dosimetric evaluations. The Geant4 application can also be used to realize dosimetric studies and its peculiarity consists in the possibility to introduce the real target composition in the simulation using the DICOM micro-CT image. This application was fully validated comparing the results with the experimental measurements. The latter ones were performed at the CATANA (Centro di AdroTerapia e Applicazioni Nucleari Avanzate) facility at INFN-LNS by irradiating both PMMA and water solid phantom. Dosimetric measurements were performed using previously calibrated EBT3 Gafchromic films as a detector and the results were compared with the Geant4 simulation ones. In particular, two different types of dosimetric studies were performed: the first one involved irradiation of a phantom made up of water solid slabs where a layer of EBT3 was alternated with two different slabs in a sandwich configuration, in order to validate the dosimetric distribution. The second one involved irradiation of a PMMA phantom made up of a half hemisphere and some PMMA slabs in order to simulate a subcutaneous tumour configuration, normally used in preclinical studies. In order to evaluate the accordance between experimental and simulation results, two different statistical tests were made: Kolmogorov test and

Preliminary study for small animal preclinical hadrontherapy facility

Science.gov (United States)

Russo, G.; Pisciotta, P.; Cirrone, G. A. P.; Romano, F.; Cammarata, F.; Marchese, V.; Forte, G. I.; Lamia, D.; Minafra, L.; Bravatá, V.; Acquaviva, R.; Gilardi, M. C.; Cuttone, G.

2017-02-01

Aim of this work is the study of the preliminary steps to perform a particle treatment of cancer cells inoculated in small animals and to realize a preclinical hadrontherapy facility. A well-defined dosimetric protocol was developed to explicate the steps needed in order to perform a precise proton irradiation in small animals and achieve a highly conformal dose into the target. A precise homemade positioning and holding system for small animals was designed and developed at INFN-LNS in Catania (Italy), where an accurate Monte Carlo simulation was developed, using Geant4 code to simulate the treatment in order to choose the best animal position and perform accurately all the necessary dosimetric evaluations. The Geant4 application can also be used to realize dosimetric studies and its peculiarity consists in the possibility to introduce the real target composition in the simulation using the DICOM micro-CT image. This application was fully validated comparing the results with the experimental measurements. The latter ones were performed at the CATANA (Centro di AdroTerapia e Applicazioni Nucleari Avanzate) facility at INFN-LNS by irradiating both PMMA and water solid phantom. Dosimetric measurements were performed using previously calibrated EBT3 Gafchromic films as a detector and the results were compared with the Geant4 simulation ones. In particular, two different types of dosimetric studies were performed: the first one involved irradiation of a phantom made up of water solid slabs where a layer of EBT3 was alternated with two different slabs in a sandwich configuration, in order to validate the dosimetric distribution. The second one involved irradiation of a PMMA phantom made up of a half hemisphere and some PMMA slabs in order to simulate a subcutaneous tumour configuration, normally used in preclinical studies. In order to evaluate the accordance between experimental and simulation results, two different statistical tests were made: Kolmogorov test and

Preliminary study for small animal preclinical hadrontherapy facility

International Nuclear Information System (INIS)

Russo, G.; Pisciotta, P.; Cirrone, G.A.P.; Romano, F.; Cammarata, F.; Marchese, V.; Forte, G.I.; Lamia, D.; Minafra, L.; Bravatá, V.; Acquaviva, R.; Gilardi, M.C.; Cuttone, G.

2017-01-01

Aim of this work is the study of the preliminary steps to perform a particle treatment of cancer cells inoculated in small animals and to realize a preclinical hadrontherapy facility. A well-defined dosimetric protocol was developed to explicate the steps needed in order to perform a precise proton irradiation in small animals and achieve a highly conformal dose into the target. A precise homemade positioning and holding system for small animals was designed and developed at INFN-LNS in Catania (Italy), where an accurate Monte Carlo simulation was developed, using Geant4 code to simulate the treatment in order to choose the best animal position and perform accurately all the necessary dosimetric evaluations. The Geant4 application can also be used to realize dosimetric studies and its peculiarity consists in the possibility to introduce the real target composition in the simulation using the DICOM micro-CT image. This application was fully validated comparing the results with the experimental measurements. The latter ones were performed at the CATANA (Centro di AdroTerapia e Applicazioni Nucleari Avanzate) facility at INFN-LNS by irradiating both PMMA and water solid phantom. Dosimetric measurements were performed using previously calibrated EBT3 Gafchromic films as a detector and the results were compared with the Geant4 simulation ones. In particular, two different types of dosimetric studies were performed: the first one involved irradiation of a phantom made up of water solid slabs where a layer of EBT3 was alternated with two different slabs in a sandwich configuration, in order to validate the dosimetric distribution. The second one involved irradiation of a PMMA phantom made up of a half hemisphere and some PMMA slabs in order to simulate a subcutaneous tumour configuration, normally used in preclinical studies. In order to evaluate the accordance between experimental and simulation results, two different statistical tests were made: Kolmogorov test and

Advances in SPECT Instrumentation (Including Small Animal Scanners). Chapter 4

International Nuclear Information System (INIS)

Di Domenico, G.; Zavattini, G.

2009-01-01

Fundamental major efforts have been devoted to the development of positron emission tomography (PET) imaging modality over the last few decades. Recently, a novel surge of interest in single photon emission computed tomography (SPECT) technology has occurred, particularly after the introduction of the hybrid SPECT-CT imaging system. This has led to a flourishing of investigations in new types of detectors and collimators, and to more accurate refinement of reconstruction algorithms. Along with SPECT-CT, new, fast gamma cameras have been developed for dedicated cardiac imaging. The existing gap between PET and SPECT in sensitivity and spatial resolution is progressively decreasing, and this trend is particularly apparent in the field of small animal imaging where the most important advances have been reported in SPECT tomographs. An outline of the basic features of SPECT technology, and of recent developments in SPECT instrumentation for both clinical applications and basic biological research on animal models is described. (author)

Technical note - Considerations for MR imaging of small animals

International Nuclear Information System (INIS)

Baker, Martin A.

2011-01-01

Routine clinical veterinary use of MR scanning is becoming more common. This article addresses the major technical considerations for radiographers performing MR examinations on small animals and provides practical advice for scanning techniques.

Dry coupling for whole-body small-animal photoacoustic computed tomography

Science.gov (United States)

Yeh, Chenghung; Li, Lei; Zhu, Liren; Xia, Jun; Li, Chiye; Chen, Wanyi; Garcia-Uribe, Alejandro; Maslov, Konstantin I.; Wang, Lihong V.

2017-04-01

We have enhanced photoacoustic computed tomography with dry acoustic coupling that eliminates water immersion anxiety and wrinkling of the animal and facilitates incorporating complementary modalities and procedures. The dry acoustic coupler is made of a tubular elastic membrane enclosed by a closed transparent water tank. The tubular membrane ensures water-free contact with the animal, and the closed water tank allows pressurization for animal stabilization. The dry coupler was tested using a whole-body small-animal ring-shaped photoacoustic computed tomography system. Dry coupling was found to provide image quality comparable to that of conventional water coupling.

In vivo fluorescence enhanced optical tomography reconstruction of lung cancer of non immersed small animals

Science.gov (United States)

Hervé, L.; Koenig, A.; Da Silva, A.; Berger, M.; Boutet, J.; Dinten, J. M.; Peltié, P.; Rizo, P.

2007-02-01

Fluorescence enhanced diffuse optical tomography (fDOT) is envisioned to be useful to collect functional information from small animal models. For oncology applications, cancer-targeted fluorescent markers can be used as a surrogate of the cancer activity. We are developing a continuous wave fDOT bench intended to be integrated in systems dedicated to whole body small animal fluorescence analyses. The focus is currently put on the reconstruction of non immersed small animals imaged by a CCD camera. The reconstruction stage already corrects the tissue heterogeneity artifacts through the computation of an optical heterogeneity map. We will show how this formalism coupled with the determination of the animal boundaries performed by a laser scanner, can be used to manage non contact acquisitions. The time of reconstruction for a 10 × 9 laser source positions, 45 × 40 detector elements and 14 × 11 × 14 mesh voxels is typically 10 minutes on a 3GHz PCs corresponding to the acquisition time allowing the two tasks to be performed in parallel. The system is validated on an in vivo experiment performed on three healthy nude mice and a mouse bearing a lung tumor at 10, 12 and 14 days after implantation allowing the follow up of the disease. The 3D fluorescence reconstructions of this mouse are presented and the total fluorescence amounts are compared.

A small nonhuman primate model for filovirus-induced disease.

Science.gov (United States)

Carrion, Ricardo; Ro, Youngtae; Hoosien, Kareema; Ticer, Anysha; Brasky, Kathy; de la Garza, Melissa; Mansfield, Keith; Patterson, Jean L

2011-11-25

Ebolavirus and Marburgvirus are members of the filovirus family and induce a fatal hemorrhagic disease in humans and nonhuman primates with 90% case fatality. To develop a small nonhuman primate model for filovirus disease, common marmosets (Callithrix jacchus) were intramuscularly inoculated with wild type Marburgvirus Musoke or Ebolavirus Zaire. The infection resulted in a systemic fatal disease with clinical and morphological features closely resembling human infection. Animals experienced weight loss, fever, high virus titers in tissue, thrombocytopenia, neutrophilia, high liver transaminases and phosphatases and disseminated intravascular coagulation. Evidence of a severe disseminated viral infection characterized principally by multifocal to coalescing hepatic necrosis was seen in EBOV animals. MARV-infected animals displayed only moderate fibrin deposition in the spleen. Lymphoid necrosis and lymphocytic depletion observed in spleen. These findings provide support for the use of the common marmoset as a small nonhuman primate model for filovirus induced hemorrhagic fever. Copyright © 2011 Elsevier Inc. All rights reserved.

Modelling Farm Animal Welfare

Directory of Open Access Journals (Sweden)

Chérie E. Part

2013-05-01

Full Text Available The use of models in the life sciences has greatly expanded in scope and advanced in technique in recent decades. However, the range, type and complexity of models used in farm animal welfare is comparatively poor, despite the great scope for use of modeling in this field of research. In this paper, we review the different modeling approaches used in farm animal welfare science to date, discussing the types of questions they have been used to answer, the merits and problems associated with the method, and possible future applications of each technique. We find that the most frequently published types of model used in farm animal welfare are conceptual and assessment models; two types of model that are frequently (though not exclusively based on expert opinion. Simulation, optimization, scenario, and systems modeling approaches are rarer in animal welfare, despite being commonly used in other related fields. Finally, common issues such as a lack of quantitative data to parameterize models, and model selection and validation are discussed throughout the review, with possible solutions and alternative approaches suggested.

Modeling and characterization of a SPECT system with pinhole collimation for the imaging of small animals

International Nuclear Information System (INIS)

Auer, Benjamin

2017-01-01

My thesis work focuses on the development of several quantitative reconstruction methods dedicated to small animal Single Photon Emission Computed Tomography (SPECT). The latter is based on modeling the acquisition process of the 4-heads pinhole SPECT system available at Institut Pluridisciplinaire Hubert Curien (IPHC) and fully integrated to the AMISSA platform using Monte Carlo simulations. The system matrix approach, combined with the OS-EM iterative reconstruction algorithm, enabled to characterize the system performances and to compare it to the state of the art. Sensitivity of about 0,027% in the center of the field of view associated to a tomographic spatial resolution of 0, 875 ± 0, 025 mm were obtained. The major drawbacks of Monte Carlo methods led us to develop an efficient and simplified modeling of the physical effects occurring in the subject. My approach based on a system matrix decomposition, associated to a scatter pre-calculated database method, demonstrated an acceptable time for a daily imaging subject follow-up (∼ 1 h), leading to a personalized imaging reconstruction (article accepted). The inherent approximations of the scatter pre-calculated approach (first order scattering modeling and segmented emission) have a moderate impact on the recovery coefficients results, nevertheless a correction of about 10% was achieved. (author) [fr

Application of MOSFET detectors for dosimetry in small animal radiography using short exposure times.

Science.gov (United States)

De Lin, Ming; Toncheva, Greta; Nguyen, Giao; Kim, Sangroh; Anderson-Evans, Colin; Johnson, G Allan; Yoshizumi, Terry T

2008-08-01

Digital subtraction angiography (DSA) X-ray imaging for small animals can be used for functional phenotyping given its ability to capture rapid physiological changes at high spatial and temporal resolution. The higher temporal and spatial requirements for small-animal imaging drive the need for short, high-flux X-ray pulses. However, high doses of ionizing radiation can affect the physiology. The purpose of this study was to verify and apply metal oxide semiconductor field effect transistor (MOSFET) technology to dosimetry for small-animal diagnostic imaging. A tungsten anode X-ray source was used to expose a tissue-equivalent mouse phantom. Dose measurements were made on the phantom surface and interior. The MOSFETs were verified with thermoluminescence dosimeters (TLDs). Bland-Altman analysis showed that the MOSFET results agreed with the TLD results (bias, 0.0625). Using typical small animal DSA scan parameters, the dose ranged from 0.7 to 2.2 cGy. Application of the MOSFETs in the small animal environment provided two main benefits: (1) the availability of results in near real-time instead of the hours needed for TLD processes and (2) the ability to support multiple exposures with different X-ray techniques (various of kVp, mA and ms) using the same MOSFET. This MOSFET technology has proven to be a fast, reliable small animal dosimetry method for DSA imaging and is a good system for dose monitoring for serial and gene expression studies.

Developments in undergraduate teaching of small-animal soft-tissue surgical skills at the University of Sydney.

Science.gov (United States)

Gopinath, Deepa; McGreevy, Paul D; Zuber, Richard M; Klupiec, Corinna; Baguley, John; Barrs, Vanessa R

2012-01-01

This article discusses recent developments in soft-tissue surgery teaching at the University of Sydney, Faculty of Veterinary Science. An integrated teaching program was developed for Bachelor of Veterinary Science (BVSc) students with the aim of providing them with optimal learning opportunities to meet "Day One" small-animal soft-tissue surgical competencies. Didactic lectures and tutorials were introduced earlier into the curriculum to prepare students for live-animal surgery practical. In addition to existing clinics, additional spay/neuter clinics were established in collaboration with animal welfare organizations to increase student exposure to live-animal surgery. A silicon-based, life-like canine ovariohysterectomy model was developed with the assistance of a model-making and special effects company. The model features elastic ovarian pedicles and suspensory ligaments, which can be stretched and broken like those of an actual dog. To monitor the volume and type of student surgical experience, an E-portfolio resource was established. This resource allows for the tracking of numbers of live, student-performed desexing surgeries and incorporates competency-based assessments and reflective tasks to be completed by students. Student feedback on the integrated surgical soft-tissue teaching program was assessed. Respondents were assessed in the fourth year of the degree and will have further opportunities to develop Day One small-animal soft-tissue surgical competencies in the fifth year. Ninety-four percent of respondents agreed or strongly agreed that they were motivated to participate in all aspects of the program, while 78% agreed or strongly agreed that they received an adequate opportunity to develop their skills and confidence in ovariohysterectomy or castration procedures through the fourth-year curriculum.

Euthanasia of Small Animals with Nitrogen; Comparison with Intravenous Pentobarbital

OpenAIRE

Quine, John P.; Buckingham, William; Strunin, Leo

1988-01-01

Intravenous pentobarbital (with or without addition of saturated potassium chloride) was compared with nitrogen gas exposure for euthanasia of small animals (dogs, cats, and rabbits) in a humane society environment. Initially, electrocardiographic) and electroencephalographic monitoring were used to establish the time of death in presedated animals given either pentobarbital or exposed to nitrogen; later, nitrogen euthanasia alone was studied. Sedation with acepromazine delayed the effects of...

Quantification in dynamic and small-animal positron emission tomography

NARCIS (Netherlands)

Disselhorst, Johannes Antonius

2011-01-01

This thesis covers two aspects of positron emission tomography (PET) quantification. The first section addresses the characterization and optimization of a small-animal PET/CT scanner. The sensitivity and resolution as well as various parameters affecting image quality (reconstruction settings, type

Development of a SiPM-based PET imaging system for small animals

International Nuclear Information System (INIS)

Lu, Yanye; Yang, Kun; Zhou, Kedi; Zhang, Qiushi; Pang, Bo; Ren, Qiushi

2014-01-01

Advances in small animal positron emission tomography (PET) imaging have been accelerated by many new technologies such as the successful incorporation of silicon photomultiplier (SiPM). In this paper, we have developed a compact, lightweight PET imaging system that is based on SiPM detectors for small animals imaging, which could be integrated into a multi-modality imaging system. This PET imaging system consists of a stationary detector gantry, a motor-controlled animal bed module, electronics modules, and power supply modules. The PET detector, which was designed as a multi-slice circular ring geometry of 27 discrete block detectors, is composed of a cerium doped lutetium–yttrium oxyorthosilicate (LYSO) scintillation crystal and SiPM arrays. The system has a 60 mm transaxial field of view (FOV) and a 26 mm axial FOV. Performance tests (e.g. spatial resolution, energy resolution, and sensitivity) and phantom and animal imaging studies were performed to evaluate the imaging performance of the PET imaging system. The performance tests and animal imaging results demonstrate the feasibility of an animal PET system based on SiPM detectors and indicate that SiPM detectors can be promising photodetectors in animal PET instrumentation development

Development of a SiPM-based PET imaging system for small animals

Energy Technology Data Exchange (ETDEWEB)

Lu, Yanye [Department of Biomedicine and Engineering, College of Engineering, Peking University, Beijing 100871 (China); Yang, Kun, E-mail: yangkun9999@hotmail.com [Department of Control Technology and Instrumentation, College of Quality and Technical Supervision, Hebei University, Baoding, 071000 (China); Zhou, Kedi; Zhang, Qiushi; Pang, Bo [Department of Biomedicine and Engineering, College of Engineering, Peking University, Beijing 100871 (China); Ren, Qiushi, E-mail: renqsh@coe.pku.edu.cn [Department of Biomedicine and Engineering, College of Engineering, Peking University, Beijing 100871 (China)

2014-04-11

Advances in small animal positron emission tomography (PET) imaging have been accelerated by many new technologies such as the successful incorporation of silicon photomultiplier (SiPM). In this paper, we have developed a compact, lightweight PET imaging system that is based on SiPM detectors for small animals imaging, which could be integrated into a multi-modality imaging system. This PET imaging system consists of a stationary detector gantry, a motor-controlled animal bed module, electronics modules, and power supply modules. The PET detector, which was designed as a multi-slice circular ring geometry of 27 discrete block detectors, is composed of a cerium doped lutetium–yttrium oxyorthosilicate (LYSO) scintillation crystal and SiPM arrays. The system has a 60 mm transaxial field of view (FOV) and a 26 mm axial FOV. Performance tests (e.g. spatial resolution, energy resolution, and sensitivity) and phantom and animal imaging studies were performed to evaluate the imaging performance of the PET imaging system. The performance tests and animal imaging results demonstrate the feasibility of an animal PET system based on SiPM detectors and indicate that SiPM detectors can be promising photodetectors in animal PET instrumentation development.

Technical Note: System for evaluating local hypothermia as a radioprotector of the rectum in a small animal model.

Science.gov (United States)

Hrycushko, Brian A; Bing, Chenchen; Futch, Cecil; Wodzak, Michelle; Stojadinovic, Strahinja; Medin, Paul M; Chopra, Rajiv

2017-08-01

The protective effects of induced or even accidental hypothermia on the human body are widespread with several medical uses currently under active research. In vitro experiments using human cell lines have shown hypothermia provides a radioprotective effect that becomes more pronounced at large, single-fraction doses common to stereotactic body radiotherapy (SBRT) and stereotactic radiosurgery (SRS) treatments. This work describes the development of a system to evaluate local hypothermia for a radioprotective effect of the rat rectum during a large dose of radiation relevant to prostate SBRT. This includes the evaluation of a 3D-printed small animal rectal cooling device and the integration with a small animal irradiator. A 3-cm long, dual-lumen rectal temperature control apparatus (RTCA) was designed in SOLIDWORKS CAD for 3D printing. The RTCA was capable of recirculating flow in a device small enough for insertion into the rat rectum, with a metal support rod for strength as well as visibility during radiation treatment planning. The outer walls of the RTCA comprised of thin heat shrink plastic, achieving efficient heat transfer into adjacent tissues. Following leak-proof testing, fiber optic temperature probes were used to evaluate the temperature over time when placed adjacent to the cooling device within the rat rectum. MRI thermometry characterized the relative temperature distribution in concentric ROIs surrounding the probe. Integration with an image-guided small animal irradiator and associated treatment planning system included evaluation for imaging artifacts and effect of brass tubing on dose calculation. The rectal temperature adjacent to the cooling device decreased from body temperature to 15°C within 10-20 min from device insertion and was maintained at 15 ± 3°C during active cooling for the evaluated time of one hour. MR thermometry revealed a steep temperature gradient with increasing distance from the cooling device with the desired

Design of an advanced positron emission tomography detector system and algorithms for imaging small animal models of human disease

Science.gov (United States)

Foudray, Angela Marie Klohs

Detecting, quantifying and visualizing biochemical mechanism in a living system without perturbing function is the goal of the instrument and algorithms designed in this thesis. Biochemical mechanisms of cells have long been known to be dependent on the signals they receive from their environment. Studying biological processes of cells in-vitro can vastly distort their function, since you are removing them from their natural chemical signaling environment. Mice have become the biological system of choice for various areas of biomedical research due to their genetic and physiological similarities with humans, the relatively low cost of their care, and their quick breeding cycle. Drug development and efficacy assessment along with disease detection, management, and mechanism research all have benefited from the use of small animal models of human disease. A high resolution, high sensitivity, three-dimensional (3D) positioning positron emission tomography (PET) detector system was designed through device characterization and Monte Carlo simulation. Position-sensitive avalanche photodiodes (PSAPDs) were characterized in various packaging configurations; coupled to various configurations of lutetium oxyorthosilicate (LSO) scintillation crystals. Forty novelly packaged final design devices were constructed and characterized, each providing characteristics superior to commercially available scintillation detectors used in small animal imaging systems: ˜1mm crystal identification, 14-15% of 511 keV energy resolution, and averaging 1.9 to 5.6 ns coincidence time resolution. A closed-cornered box-shaped detector configuration was found to provide optimal photon sensitivity (˜10.5% in the central plane) using dual LSO-PSAPD scintillation detector modules and Monte Carlo simulation. Standard figures of merit were used to determine optimal system acquisition parameters. A realistic model for constituent devices was developed for understanding the signals reported by the

UTIs in small animal patients: part 1: etiology and pathogenesis.

Science.gov (United States)

Smee, Nicole; Loyd, Kimberly; Grauer, Greg

2013-01-01

Understanding how urinary tract infections (UTIs) can occur and how to classify them can help the practitioner to make a plan for treatment. This review summarizes the etiology, pathogenesis, and host defense mechanisms associated with bacterial UTIs in dogs and cats. UTIs in Small Animal Patients: Part 2: Diagnosis, Treatment, and Complications will appear in the March/April 2013 issue of the Journal of the American Animal Hospital Association.

Animal models of tinnitus.

Science.gov (United States)

Brozoski, Thomas J; Bauer, Carol A

2016-08-01

Presented is a thematic review of animal tinnitus models from a functional perspective. Chronic tinnitus is a persistent subjective sound sensation, emergent typically after hearing loss. Although the sensation is experientially simple, it appears to have central a nervous system substrate of unexpected complexity that includes areas outside of those classically defined as auditory. Over the past 27 years animal models have significantly contributed to understanding tinnitus' complex neurophysiology. In that time, a diversity of models have been developed, each with its own strengths and limitations. None has clearly become a standard. Animal models trace their origin to the 1988 experiments of Jastreboff and colleagues. All subsequent models derive some of their features from those experiments. Common features include behavior-dependent psychophysical determination, acoustic conditions that contrast objective sound and silence, and inclusion of at least one normal-hearing control group. In the present review, animal models have been categorized as either interrogative or reflexive. Interrogative models use emitted behavior under voluntary control to indicate hearing. An example would be pressing a lever to obtain food in the presence of a particular sound. In this type of model animals are interrogated about their auditory sensations, analogous to asking a patient, "What do you hear?" These models require at least some training and motivation management, and reflect the perception of tinnitus. Reflexive models, in contrast, employ acoustic modulation of an auditory reflex, such as the acoustic startle response. An unexpected loud sound will elicit a reflexive motor response from many species, including humans. Although involuntary, acoustic startle can be modified by a lower-level preceding event, including a silent sound gap. Sound-gap modulation of acoustic startle appears to discriminate tinnitus in animals as well as humans, and requires no training or

Monte Carlo simulation of small field electron beams for small animal irradiation

International Nuclear Information System (INIS)

Lee, Chung-Chi; Chen, Ai-Mei; Tung, Chuan-Jong; Chao, Tsi-Chian

2011-01-01

The volume effect of detectors in the dosimetry of small fields for photon beams has been well studied due to interests in radiosurgery and small beamlets used in IMRT treatments; but there is still an unexplored research field for small electron beams used in small animal irradiation. This study proposes to use the BEAM Monte Carlo (MC) simulation to assess characteristics of small electron beams (4, 6, 14, 30 mm in diameter) with the kinetic energies of 6 and 18 MeV. Three factors influencing beam characteristics were studied (1) AE and ECUT settings, (2) photon jaw settings and (3) simulation pixel sizes. Study results reveal that AE/ECUT settings at 0.7 MeV are adequate for linear accelerator treatment head simulation, while 0.521 MeV is more favorable to be used for the phantom study. It is also demonstrated that voxel size setting at 1/4 of the simulation field width in all directions is sufficient to achieve accurate results. As for the photon jaw setting, it has great impact on the absolute output of different field size setting (i.e. output factor) but with minimum effect on the relative lateral distribution.

Performance evaluation of a mouse-sized camera for dynamic studies in small animals

International Nuclear Information System (INIS)

Loudos, George; Majewski, Stan; Wojcik, Randy; Weisenberger, Andrew; Sakellios, Nicolas; Nikita, Konstantina; Uzunoglu, Nikolaos; Bouziotis, Penelope; Varvarigou, Alexandra

2007-01-01

A mouse sized camera has been built in terms of collaboration between the presenting institutions. The system is used for the performance of dynamic studies in small animals, in order to evaluate novel radiopharmaceuticals. The active area of the detector is approximately 48x96 mm allowing depiction of the entire mouse in a single view. The system is based on two flat-panel Hamamatsu H8500 position sensitive photomultiplier tubes (PSPMT), a pixellated NaI(Tl) scintillator and a copper-beryllium (CuBe) parallel-hole collimator. In this work, the evaluation results of the system are presented, using phantoms and small animals injected with conventional radiophrmaceuticals. Average resolution was ∼1.6 mm on the collimator surface and increased to ∼4.1 mm in 12 cm distance from the detector. The average energy resolution was measured and found to be ∼15.6% for Tc 99m . Results from imaging thin capillaries demonstrated system's high resolution and sensitivity in activity variations was shown. Initial dynamic studies have been carried out in small animals injected with Tc 99m -DTPA and Tc 99m -MDP. The results show system's ability to perform kinetic imaging in small animals

Programmable electronics for low-cost small animal PET/SPECT imaging

International Nuclear Information System (INIS)

Guerra, Pedro; Rubio, Jose L.; Kontaxakis, Georgios; Ortuno, Juan E.; Ledesma, Maria J.; Santos, Andres

2006-01-01

This work describes and characterizes the detector module of a novel positron/single photon emission (PET/SPECT) scanner for small animals. This detector consists of a YAP/LSO phoswich, a photomultiplier and acquisition front-end, and will be used as building block of a low-cost hybrid tomograph. The front-end processes data sampled at a fixed frequency, where a state-of-the-art programmable device estimates scintillation pulse parameters by means of digital algorithms. Finally, the estimated properties of the proposed detector module are used to model a rotating four-head scanner. The performance of the proposed PET/SPECT scanner is estimated and first results are promising in both modalities, deserving further research and optimization

Development of Optical Molecular Imaging System for the Acquisition of Bioluminescence Signals from Small Animals

International Nuclear Information System (INIS)

Lee, Byeong Il; Kim, Hyeon Sik; Jeong, Hye Jin; Lee, Hyung Jae; Moon, Seung Min; Kwon, Seung Young; Jeong, Shin Young; Bom, Hee Seung; Min, Jung Joon; Choi, Eun Seo

2009-01-01

Optical imaging is providing great advance and improvement in genetic and molecular imaging of animals and humans. Optical imaging system consists of optical imaging devices, which carry out major function for monitoring, tracing, and imaging in most of molecular in-vivo researches. In bio-luminescent imaging, small animals containing luciferase gene locally irradiate light, and emitted photons transmitted through skin of the small animals are imaged by using a high sensitive charged coupled device (CCD) camera. In this paper, we introduced optical imaging system for the image acquisition of bio-luminescent signals emitted from small animals. In the system, Nikon lens and four LED light sources were mounted at the inside of a dark box. A cooled CCD camera equipped with a control module was used. We tested the performance of the optical imaging system using effendorf tube and light emitting bacteria which injected intravenously into CT26 tumor bearing nude mouse. The performance of implemented optical imaging system for bio-luminescence imaging was demonstrated and the feasibility of the system in small animal imaging application was proved. We anticipate this system could be a useful tool for the molecular imaging of small animals adaptable for various experimental conditions in future

Evaluation of attenuation and scatter correction requirements in small animal PET and SPECT imaging

Science.gov (United States)

Konik, Arda Bekir

Positron emission tomography (PET) and single photon emission tomography (SPECT) are two nuclear emission-imaging modalities that rely on the detection of high-energy photons emitted from radiotracers administered to the subject. The majority of these photons are attenuated (absorbed or scattered) in the body, resulting in count losses or deviations from true detection, which in turn degrades the accuracy of images. In clinical emission tomography, sophisticated correction methods are often required employing additional x-ray CT or radionuclide transmission scans. Having proven their potential in both clinical and research areas, both PET and SPECT are being adapted for small animal imaging. However, despite the growing interest in small animal emission tomography, little scientific information exists about the accuracy of these correction methods on smaller size objects, and what level of correction is required. The purpose of this work is to determine the role of attenuation and scatter corrections as a function of object size through simulations. The simulations were performed using Interactive Data Language (IDL) and a Monte Carlo based package, Geant4 application for emission tomography (GATE). In IDL simulations, PET and SPECT data acquisition were modeled in the presence of attenuation. A mathematical emission and attenuation phantom approximating a thorax slice and slices from real PET/CT data were scaled to 5 different sizes (i.e., human, dog, rabbit, rat and mouse). The simulated emission data collected from these objects were reconstructed. The reconstructed images, with and without attenuation correction, were compared to the ideal (i.e., non-attenuated) reconstruction. Next, using GATE, scatter fraction values (the ratio of the scatter counts to the total counts) of PET and SPECT scanners were measured for various sizes of NEMA (cylindrical phantoms representing small animals and human), MOBY (realistic mouse/rat model) and XCAT (realistic human model

Open-Source Medical Devices (OSMD) Design of a Small Animal Radiotherapy System

Science.gov (United States)

Prajapati, S.; Mackie, T. R.; Jeraj, R.

2014-03-01

Open-Source Medical Devices (OSMD) was initiated with the goal of facilitating medical research by developing medical technologies including both hardware and software on an open-source platform. Our first project was to develop an integrated imaging and radiotherapy device for small animals that includes computed tomography (CT), positron emission tomography (PET) and radiation therapy (RT) modalities for which technical specifications were defined in the first OSMD conference held in Madison, Wisconsin, USA in December 2011. This paper specifically focuses on the development of a small animal RT (micro-RT) system by designing a binary micro multileaf collimator (bmMLC) and a small animal treatment planning system (SATPS) to enable intensity modulated RT (IMRT). Both hardware and software projects are currently under development and their current progresses are described. After the development, both bmMLC and TPS will be validated and commissioned for a micro-RT system. Both hardware design and software development will be open-sourced after completion.

Assessment of the sources of error affecting the quantitative accuracy of SPECT imaging in small animals

Energy Technology Data Exchange (ETDEWEB)

Joint Graduate Group in Bioengineering, University of California, San Francisco and University of California, Berkeley; Department of Radiology, University of California; Gullberg, Grant T; Hwang, Andrew B.; Franc, Benjamin L.; Gullberg, Grant T.; Hasegawa, Bruce H.

2008-02-15

Small animal SPECT imaging systems have multiple potential applications in biomedical research. Whereas SPECT data are commonly interpreted qualitatively in a clinical setting, the ability to accurately quantify measurements will increase the utility of the SPECT data for laboratory measurements involving small animals. In this work, we assess the effect of photon attenuation, scatter and partial volume errors on the quantitative accuracy of small animal SPECT measurements, first with Monte Carlo simulation and then confirmed with experimental measurements. The simulations modeled the imaging geometry of a commercially available small animal SPECT system. We simulated the imaging of a radioactive source within a cylinder of water, and reconstructed the projection data using iterative reconstruction algorithms. The size of the source and the size of the surrounding cylinder were varied to evaluate the effects of photon attenuation and scatter on quantitative accuracy. We found that photon attenuation can reduce the measured concentration of radioactivity in a volume of interest in the center of a rat-sized cylinder of water by up to 50percent when imaging with iodine-125, and up to 25percent when imaging with technetium-99m. When imaging with iodine-125, the scatter-to-primary ratio can reach up to approximately 30percent, and can cause overestimation of the radioactivity concentration when reconstructing data with attenuation correction. We varied the size of the source to evaluate partial volume errors, which we found to be a strong function of the size of the volume of interest and the spatial resolution. These errors can result in large (>50percent) changes in the measured amount of radioactivity. The simulation results were compared with and found to agree with experimental measurements. The inclusion of attenuation correction in the reconstruction algorithm improved quantitative accuracy. We also found that an improvement of the spatial resolution through the

SU-G-IeP4-11: Monitoring Tumor Growth in Subcutaneous Murine Tumor Model in Vivo: A Comparison Between MRI and Small Animal CT

Energy Technology Data Exchange (ETDEWEB)

Wang, B; He, W; Cvetkovic, D; Chen, L; Fan, J; Ma, C [Fox Chase Cancer Center, Philadelphia, PA (United States)

2016-06-15

Purpose: The purpose of the study is to compare the volume measurement of subcutaneous tumors in mice with different imaging platforms, namely a GE MRI and a Sofie-Biosciences small animal CT scanner. Methods: A549 human lung carcinoma cells and FaDu human head and neck squamous cell carcinoma cells were implanted subcutaneously into flanks of nude mice. Three FaDu tumors and three A549 tumors were included in this study. The MRI scans were done with a GE Signa 1.5 Tesla MR scanner using a fast T2-weighted sequence (70mm FOV and 1.2mm slice thickness), while the CT scans were done with the CT scanner on a Sofie-Biosciences G8 PET/CT platform dedicated for small animal studies (48mm FOV and 0.2mm slice thickness). Imaging contrast agent was not used in this study. Based on the DICOM images from MRI and CT scans, the tumors were contoured with Philips DICOM Viewer and the tumor volumes were obtained by summing up the contoured area and multiplied by the slice thickness. Results: The volume measurements based on the CT scans agree reasonably with that obtained with MR images for the subcutaneous tumors. The mean difference in the absolute tumor volumes between MRI- and CT-based measurements was found to be −6.2% ± 1.0%, with the difference defined as (VMR – VCT)*100%/VMR. Furthermore, we evaluated the normalized tumor volumes, which were defined for each tumor as V/V{sub 0} where V{sub 0} stands for the volume from the first MR or CT scan. The mean difference in the normalized tumor volumes was found to be 0.10% ± 0.96%. Conclusion: Despite the fact that the difference between normal and abnormal tissues is often less clear on small animal CT images than on MR images, one can still obtain reasonable tumor volume information with the small animal CT scans for subcutaneous murine xenograft models.

Animal models of sarcoidosis.

Science.gov (United States)

Hu, Yijie; Yibrehu, Betel; Zabini, Diana; Kuebler, Wolfgang M

2017-03-01

Sarcoidosis is a debilitating, inflammatory, multiorgan, granulomatous disease of unknown cause, commonly affecting the lung. In contrast to other chronic lung diseases such as interstitial pulmonary fibrosis or pulmonary arterial hypertension, there is so far no widely accepted or implemented animal model for this disease. This has hampered our insights into the etiology of sarcoidosis, the mechanisms of its pathogenesis, the identification of new biomarkers and diagnostic tools and, last not least, the development and implementation of novel treatment strategies. Over past years, however, a number of new animal models have been described that may provide useful tools to fill these critical knowledge gaps. In this review, we therefore outline the present status quo for animal models of sarcoidosis, comparing their pros and cons with respect to their ability to mimic the etiological, clinical and histological hallmarks of human disease and discuss their applicability for future research. Overall, the recent surge in animal models has markedly expanded our options for translational research; however, given the relative early stage of most animal models for sarcoidosis, appropriate replication of etiological and histological features of clinical disease, reproducibility and usefulness in terms of identification of new therapeutic targets and biomarkers, and testing of new treatments should be prioritized when considering the refinement of existing or the development of new models.

[Application of paramunity inducers in small animal practice].

Science.gov (United States)

Proksch, A L; Hartmann, K

2016-01-01

Paramunity inducers have been used to treat small animals for decades. Paramunity inducers are based on attenuated and inactivated poxviruses (avipox virus and parapox virus). Their applications include both therapeutic and prophylactic use in various diseases. Despite their wide and variable use, only a very small number of placebo-controlled studies has been published. Positive effects in preventing kitten mortality and in treating feline stomatitis have been reported, however, no statistically significant effect of their therapeutic use in canine parvovirus infection, feline leukemia infection virus infection or canine papillomavirus infection could be demonstrated. For these infectious diseases, paramunity inducers do not appear to be effective.

Recommendations on vaccination for Asian small animal practitioners: a report of the WSAVA Vaccination Guidelines Group.

Science.gov (United States)

Day, M J; Karkare, U; Schultz, R D; Squires, R; Tsujimoto, H

2015-02-01

In 2012 and 2013, the World Small Animal Veterinary Association (WSAVA) Vaccination Guidelines Group (VGG) undertook fact-finding visits to several Asian countries, with a view to developing advice for small companion animal practitioners in Asia related to the administration of vaccines to dogs and cats. The VGG met with numerous first opinion practitioners, small animal association leaders, academic veterinarians, government regulators and industry representatives and gathered further information from a survey of almost 700 veterinarians in India, China, Japan and Thailand. Although there were substantial differences in the nature and magnitude of the challenges faced by veterinarians in each country, and also differences in the resources available to meet those challenges, overall, the VGG identified insufficient undergraduate and postgraduate training in small companion animal microbiology, immunology and vaccinology. In most of the countries, there has been little academic research into small animal infectious diseases. This, coupled with insufficient laboratory diagnostic support, has limited the growth of knowledge concerning the prevalence and circulating strains of key infectious agents in most of the countries visited. Asian practitioners continue to recognise clinical infections that are now considered uncommon or rare in western countries. In particular, canine rabies virus infection poses a continuing threat to animal and human health in this region. Both nationally manufactured and international dog and cat vaccines are variably available in the Asian countries, but the product ranges are small and dominated by multi-component vaccines with a licensed duration of immunity (DOI) of only 1 year, or no description of DOI. Asian practitioners are largely unaware of current global trends in small animal vaccinology or of the WSAVA vaccination guidelines. Consequently, most practitioners continue to deliver annual revaccination with both core and non

Animal models and therapeutic molecular targets of cancer: utility and limitations

Directory of Open Access Journals (Sweden)

Cekanova M

2014-10-01

Full Text Available Maria Cekanova, Kusum Rathore Department of Small Animal Clinical Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN, USA Abstract: Cancer is the term used to describe over 100 diseases that share several common hallmarks. Despite prevention, early detection, and novel therapies, cancer is still the second leading cause of death in the USA. Successful bench-to-bedside translation of basic scientific findings about cancer into therapeutic interventions for patients depends on the selection of appropriate animal experimental models. Cancer research uses animal and human cancer cell lines in vitro to study biochemical pathways in these cancer cells. In this review, we summarize the important animal models of cancer with focus on their advantages and limitations. Mouse cancer models are well known, and are frequently used for cancer research. Rodent models have revolutionized our ability to study gene and protein functions in vivo and to better understand their molecular pathways and mechanisms. Xenograft and chemically or genetically induced mouse cancers are the most commonly used rodent cancer models. Companion animals with spontaneous neoplasms are still an underexploited tool for making rapid advances in human and veterinary cancer therapies by testing new drugs and delivery systems that have shown promise in vitro and in vivo in mouse models. Companion animals have a relatively high incidence of cancers, with biological behavior, response to therapy, and response to cytotoxic agents similar to those in humans. Shorter overall lifespan and more rapid disease progression are factors contributing to the advantages of a companion animal model. In addition, the current focus is on discovering molecular targets for new therapeutic drugs to improve survival and quality of life in cancer patients. Keywords: mouse cancer model, companion animal cancer model, dogs, cats, molecular targets

Carriage of methicillin-resistant Staphylococcus pseudintermedius in small animal veterinarians

DEFF Research Database (Denmark)

Paul, Narayan Chandra; Moodley, Arshnee; Ghibaudo, G.

2011-01-01

Methicillin-resistant Staphylococcus pseudintermedius (MRSP) is increasingly reported in small animals and cases of human infections have already been described despite its recent emergence in veterinary practice. We investigated the prevalence of MRSP and methicillin-resistant Staphylococcus...... aureus (MRSA) among small animal dermatologists attending a national veterinary conference in Italy. Nasal swabs were obtained from 128 veterinarians, seven of which harboured MRSP (n = 5; 3.9%) or MRSA (n = 2; 1.6%). A follow-up study of two carriers revealed that MRSP persisted for at least 1 month...... by spa typing. Methicillin-resistant isolates were further typed by antimicrobial susceptibility testing, SCCmec and multi-locus sequence typing. Two lineages previously associated with pets were identified among the five MRSP isolates; the European epidemic clone ST71-SCCmec II-III and ST106-SCCmec IV...

Multi-institutional MicroCT image comparison of image-guided small animal irradiators

Science.gov (United States)

Johnstone, Chris D.; Lindsay, Patricia; E Graves, Edward; Wong, Eugene; Perez, Jessica R.; Poirier, Yannick; Ben-Bouchta, Youssef; Kanesalingam, Thilakshan; Chen, Haijian; E Rubinstein, Ashley; Sheng, Ke; Bazalova-Carter, Magdalena

2017-07-01

To recommend imaging protocols and establish tolerance levels for microCT image quality assurance (QA) performed on conformal image-guided small animal irradiators. A fully automated QA software SAPA (small animal phantom analyzer) for image analysis of the commercial Shelley micro-CT MCTP 610 phantom was developed, in which quantitative analyses of CT number linearity, signal-to-noise ratio (SNR), uniformity and noise, geometric accuracy, spatial resolution by means of modulation transfer function (MTF), and CT contrast were performed. Phantom microCT scans from eleven institutions acquired with four image-guided small animal irradiator units (including the commercial PXi X-RAD SmART and Xstrahl SARRP systems) with varying parameters used for routine small animal imaging were analyzed. Multi-institutional data sets were compared using SAPA, based on which tolerance levels for each QA test were established and imaging protocols for QA were recommended. By analyzing microCT data from 11 institutions, we established image QA tolerance levels for all image quality tests. CT number linearity set to R 2  >  0.990 was acceptable in microCT data acquired at all but three institutions. Acceptable SNR  >  36 and noise levels  1.5 lp mm-1 for MTF  =  0.2) was obtained at all but four institutions due to their large image voxel size used (>0.275 mm). Ten of the eleven institutions passed the set QA tolerance for geometric accuracy (2000 HU for 30 mgI ml-1). We recommend performing imaging QA with 70 kVp, 1.5 mA, 120 s imaging time, 0.20 mm voxel size, and a frame rate of 5 fps for the PXi X-RAD SmART. For the Xstrahl SARRP, we recommend using 60 kVp, 1.0 mA, 240 s imaging time, 0.20 mm voxel size, and 6 fps. These imaging protocols should result in high quality images that pass the set tolerance levels on all systems. Average SAPA computation time for complete QA analysis for a 0.20 mm voxel, 400 slice Shelley phantom microCT data set

Small-Animal Imaging Using Diffuse Fluorescence Tomography.

Science.gov (United States)

Davis, Scott C; Tichauer, Kenneth M

2016-01-01

Diffuse fluorescence tomography (DFT) has been developed to image the spatial distribution of fluorescence-tagged tracers in living tissue. This capability facilitates the recovery of any number of functional parameters, including enzymatic activity, receptor density, blood flow, and gene expression. However, deploying DFT effectively is complex and often requires years of know-how, especially for newer mutlimodal systems that combine DFT with conventional imaging systems. In this chapter, we step through the process of using MRI-DFT imaging of a receptor-targeted tracer in small animals.

Animal Models in Burn Research

Science.gov (United States)

Abdullahi, A.; Amini-Nik, S.; Jeschke, M.G

2014-01-01

Burn injury is a severe form of trauma affecting more than two million people in North America each year. Burn trauma is not a single pathophysiological event but a devastating injury that causes structural and functional deficits in numerous organ systems. Due to its complexity and the involvement of multiple organs, in vitro experiments cannot capture this complexity nor address the pathophysiology. In the past two decades, a number of burn animal models have been developed to replicate the various aspects of burn injury; to elucidate the pathophysiology and explore potential treatment interventions. Understanding the advantages and limitations of these animal models is essential for the design and development of treatments that are clinically relevant to humans. This review paper aims to highlight the common animal models of burn injury in order to provide investigators with a better understanding of the benefits and limitations of these models for translational applications. While many animal models of burn exist, we limit our discussion to the skin healing of mouse, rat, and pig. Additionally, we briefly explain hypermetabolic characteristics of burn injury and the animal model utilized to study this phenomena. Finally, we discuss the economic costs associated with each of these models in order to guide decisions of choosing the appropriate animal model for burn research. PMID:24714880

Blended learning in the small animal clinic

DEFF Research Database (Denmark)

Langebæk, Rikke

2011-01-01

At the Department of Small Animal Clinical Sciences, Basic Surgical Skills are taught in groups of 30-35 students in the first year of the master program (4th year students). The eight day course is an example of ‘blended learning’ in which students use our e-learning-material (Step 1) to prepare...... for the practical part of the course (Step 2, 3 and 4). From their home computers, students log on to the e-learning platform of Copenhagen University: https://absalon.ku.dk and go to the Basic Surgical Skills course, which consist of a line of chapters concerning a variety of surgical subjects. Each subject...... the implementation of these new teaching methods (e-learning and Skills Lab), teachers have ascertained a more satisfactory level of preparation, students that seem more focused and live-animal surgery that is conducted at a more ‘professional’ level than before. Finally, our research in this field shows...

Steroid-associated osteonecrosis animal model in rats

Directory of Open Access Journals (Sweden)

Li-Zhen Zheng

2018-04-01

lower at 6 weeks after SAON induction. Histomorphometry revealed significantly lower osteoblast surface and higher marrow fat fraction and oedema area in SAON group. Hepatic oedema appeared 2 weeks after SAON induction, and lipid accumulation appeared in the liver of SAON rats 6 weeks after SAON induction. Conclusion: The present study successfully induced SAON in rats with pulsed injection of LPS and MPS, which was well simulating the clinical feature and pathology. Apart from available large animal models, such as bipedal emus or quadrupedal rabbits, our current SAON small model in rats could be a cost-effective preclinical experimental model to study body metabolism, molecular mechanism of SAON and potential drugs developed for prevention or treatment of SAON. The translational potential of this article: The present study successfully induced SAON in a small animal model in rats with pulsed injection of LPS and MPS. The evaluation protocols with typical histopathologic ON features and advanced evaluation approaches to identify the metabolic disorders of SAON could be used in future rat SAON studies. The SAON rat model is a suitable and cost-effective animal model to study molecular mechanism of SAON and potential drugs developed for prevention and treatment of SAON. Keywords: Animal model, Corticosteroid, Osteonecrosis

Precision of high-resolution dual energy x-ray absorptiometry of bone mineral status and body composition in small animal models

Directory of Open Access Journals (Sweden)

Lochmüller E. M.

2001-01-01

Full Text Available The purpose of this study was to analyze the in situ precision (reproducibility of bone mineral and body composition measurements in mice of different body weights and rats, using a high-resolution DXA (dual energy X-ray absorptiometry scanner. We examined 48 NMRI mice weighing approximately 10 to 60 g, and 10 rats weighing approximately 140 g. Four repeated measurements were obtained on different days. In mice, the standard deviations of repeated measurements ranged from 2.5 to 242 mg for bone mineral content (BMC, from 0.16 to 3.74 g for fat, and from 0.40 to 4.21 g for lean mass. The coefficient of variation in percent (CV% for BMC/BMD (bone mineral density was highest in the 10 g mice (12.8% / 4.9% and lowest in the 40 g mice (3.5% /1.7%. In rats, it was 2.5 /1.2% in the lower extremity, 7.1/3.0 % in the spine, 5.7/2.0 % in the femur, and 3.6%/2.1% in the tibia. The CV% for fat and lean mass in mice was higher than for BMC. The study demonstrates good precision of bone mineral and moderate precision of body composition measure-ments in small animals, using a high-resolution DXA system. The technique can be used for testing the efficacy of drugs in small animal models, for muta-genesis screens, and for the phenotypic characterization of transgenic mice.

Animal models for oral transmission of Listeria monocytogenes

Directory of Open Access Journals (Sweden)

Sarah E F D'Orazio

2014-02-01

Full Text Available Listeria monocytogenes has been recognized as a food borne pathogen in humans since the 1980s, but we still understand very little about oral transmission of L. monocytogenes or the host factors that determine susceptibility to gastrointestinal infection, due to the lack of an appropriate small animal model of oral listeriosis. Early feeding trials suggested that many animals were highly resistant to oral infection, and the more reproducible intravenous or intraperitoneal routes of inoculation soon came to be favored. There are a fair number of previously published studies using an oral infection route, but the work varies widely in terms of bacterial strain choice, the methods used for oral transmission, and various manipulations used to enhance infectivity. This mini review will summarize the published literature using oral routes of L. monocytogenes infection and will highlight recent technological advances that have made oral infection a more attractive model system.

Animal models of cerebral ischemia

Science.gov (United States)

Khodanovich, M. Yu.; Kisel, A. A.

2015-11-01

Cerebral ischemia remains one of the most frequent causes of death and disability worldwide. Animal models are necessary to understand complex molecular mechanisms of brain damage as well as for the development of new therapies for stroke. This review considers a certain range of animal models of cerebral ischemia, including several types of focal and global ischemia. Since animal models vary in specificity for the human disease which they reproduce, the complexity of surgery, infarct size, reliability of reproduction for statistical analysis, and adequate models need to be chosen according to the aim of a study. The reproduction of a particular animal model needs to be evaluated using appropriate tools, including the behavioral assessment of injury and non-invasive and post-mortem control of brain damage. These problems also have been summarized in the review.

Current concepts in oncologic surgery in small animals.

Science.gov (United States)

Matz, Brad M

2015-05-01

Surgical oncology is experiencing rapid transition in veterinary medicine. Mast cell tumors and soft tissue sarcomas are two of the most common neoplasms in small animal patients. Clinicians should be familiar with the need for staging and the procedures involved in treating patients with these tumors. Clinicians should be comfortable with available adjuvant therapies and when to use them in certain patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Scalable Electrophysiology in Intact Small Animals with Nanoscale Suspended Electrode Arrays

OpenAIRE

Gonzales, Daniel L.; Badhiwala, Krishna N.; Vercosa, Daniel G.; Avants, Ben W.; Liu, Zheng; Zhong, Weiwei; Robinson, Jacob T.

2017-01-01

Electrical measurements from large populations of animals would help reveal fundamental properties of the nervous system and neurological diseases. Small invertebrates are ideal for these large-scale studies; however, patch-clamp electrophysiology in microscopic animals typically requires low-throughput and invasive dissections. To overcome these limitations, we present nano-SPEARs: suspended electrodes integrated into a scalable microfluidic device. Using this technology, we have made the fi...

Partial body irradiation of small laboratory animals with an industrial X-ray tube

International Nuclear Information System (INIS)

Frenzel, Thorsten; Kruell, Andreas; Grohmann, Carsten; Schumacher, Udo

2014-01-01

Dedicated precise small laboratory animal irradiation sources are needed for basic cancer research and to meet this need expensive high precision radiation devices have been developed. To avoid such expenses a cost efficient way is presented to construct a device for partial body irradiation of small laboratory animals by adding specific components to an industrial X-ray tube. A custom made radiation field tube was added to an industrial 200 kV X-ray tube. A light field display as well as a monitor ionization chamber were implemented. The field size can rapidly be changed by individual inserts of MCP96 that are used for secondary collimation of the beam. Depth dose curves and cross sectional profiles were determined with the use of a custom made water phantom. More components like positioning lasers, a custom made treatment couch, and a commercial isoflurane anesthesia unit were added to complete the system. With the accessories described secondary small field sizes down to 10 by 10 mm 2 (secondary collimator size) could be achieved. The dosimetry of the beam was constructed like those for conventional stereotactical clinical linear accelerators. The water phantom created showed an accuracy of 1 mm and was well suited for all measurements. With the anesthesia unit attached to the custom made treatment couch the system is ideal for the radiation treatment of small laboratory animals like mice. It was feasible to shrink the field size of an industrial X-ray tube from whole animal irradiation to precise partial body irradiation of small laboratory animals. Even smaller secondary collimator sizes than 10 by 10 mm 2 are feasible with adequate secondary collimator inserts. Our custom made water phantom was well suited for the basic dosimetry of the X-ray tube.

Reducing the number of laboratory animals used in tissue engineering research by restricting the variety of animal models. Articular cartilage tissue engineering as a case study.

Science.gov (United States)

de Vries, Rob B M; Buma, Pieter; Leenaars, Marlies; Ritskes-Hoitinga, Merel; Gordijn, Bert

2012-12-01

The use of laboratory animals in tissue engineering research is an important underexposed ethical issue. Several ethical questions may be raised about this use of animals. This article focuses on the possibilities of reducing the number of animals used. Given that there is considerable debate about the adequacy of the current animal models in tissue engineering research, we investigate whether it is possible to reduce the number of laboratory animals by selecting and using only those models that have greatest predictive value for future clinical application of the tissue engineered product. The field of articular cartilage tissue engineering is used as a case study. Based on a study of the scientific literature and interviews with leading experts in the field, an overview is provided of the animal models used and the advantages and disadvantages of each model, particularly in terms of extrapolation to the human situation. Starting from this overview, it is shown that, by skipping the small models and using only one large preclinical model, it is indeed possible to restrict the number of animal models, thereby reducing the number of laboratory animals used. Moreover, it is argued that the selection of animal models should become more evidence based and that researchers should seize more opportunities to choose or create characteristics in the animal models that increase their predictive value.

The motivations and methodology for high-throughput PET imaging of small animals in cancer research

Energy Technology Data Exchange (ETDEWEB)

Aide, Nicolas [Francois Baclesse Cancer Centre, Nuclear Medicine Department, Caen Cedex (France); Caen University, BioTICLA team, EA 4656, IFR 146, Caen (France); Visser, Eric P. [Radboud University Nijmegen Medical Center, Nuclear Medicine Department, Nijmegen (Netherlands); Lheureux, Stephanie [Caen University, BioTICLA team, EA 4656, IFR 146, Caen (France); Francois Baclesse Cancer Centre, Clinical Research Unit, Caen (France); Heutte, Natacha [Francois Baclesse Cancer Centre, Clinical Research Unit, Caen (France); Szanda, Istvan [King' s College London, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); Hicks, Rodney J. [Peter MacCallum Cancer Centre, Centre for Molecular Imaging, East Melbourne (Australia)

2012-09-15

Over the last decade, small-animal PET imaging has become a vital platform technology in cancer research. With the development of molecularly targeted therapies and drug combinations requiring evaluation of different schedules, the number of animals to be imaged within a PET experiment has increased. This paper describes experimental design requirements to reach statistical significance, based on the expected change in tracer uptake in treated animals as compared to the control group, the number of groups that will be imaged, and the expected intra-animal variability for a given tracer. We also review how high-throughput studies can be performed in dedicated small-animal PET, high-resolution clinical PET systems and planar positron imaging systems by imaging more than one animal simultaneously. Customized beds designed to image more than one animal in large-bore small-animal PET scanners are described. Physics issues related to the presence of several rodents within the field of view (i.e. deterioration of spatial resolution and sensitivity as the radial and the axial offsets increase, respectively, as well as a larger effect of attenuation and the number of scatter events), which can be assessed by using the NEMA NU 4 image quality phantom, are detailed. (orig.)

High-resolution short-exposure small-animal laboratory x-ray phase-contrast tomography

Science.gov (United States)

Larsson, Daniel H.; Vågberg, William; Yaroshenko, Andre; Yildirim, Ali Önder; Hertz, Hans M.

2016-12-01

X-ray computed tomography of small animals and their organs is an essential tool in basic and preclinical biomedical research. In both phase-contrast and absorption tomography high spatial resolution and short exposure times are of key importance. However, the observable spatial resolutions and achievable exposure times are presently limited by system parameters rather than more fundamental constraints like, e.g., dose. Here we demonstrate laboratory tomography with few-ten μm spatial resolution and few-minute exposure time at an acceptable dose for small-animal imaging, both with absorption contrast and phase contrast. The method relies on a magnifying imaging scheme in combination with a high-power small-spot liquid-metal-jet electron-impact source. The tomographic imaging is demonstrated on intact mouse, phantoms and excised lungs, both healthy and with pulmonary emphysema.

Animal models of gene-environment interactions in schizophrenia.

Science.gov (United States)

Ayhan, Yavuz; Sawa, Akira; Ross, Christopher A; Pletnikov, Mikhail V

2009-12-07

The pathogenesis of schizophrenia and related mental illnesses likely involves multiple interactions between susceptibility genes of small effects and environmental factors. Gene-environment interactions occur across different stages of neurodevelopment to produce heterogeneous clinical and pathological manifestations of the disease. The main obstacle for mechanistic studies of gene-environment interplay has been the paucity of appropriate experimental systems for elucidating the molecular pathways that mediate gene-environment interactions relevant to schizophrenia. Recent advances in psychiatric genetics and a plethora of experimental data from animal studies allow us to suggest a new approach to gene-environment interactions in schizophrenia. We propose that animal models based on identified genetic mutations and measurable environment factors will help advance studies of the molecular mechanisms of gene-environment interplay.

Development of in-vivo micro CT system for small animals

Energy Technology Data Exchange (ETDEWEB)

Nam, Ki Yong; Lim, Jong Hyeok; Jeong, Young Jo; Park, Jeong Gwon [Institute for Radiological Imaging Science, Iksan (Korea, Republic of); Park, Jung Bung [DRGEM Corp., Seoul (Korea, Republic of); Yoon, Kwon Ha [Institute for Radiological Imaging Science and Medical School of Radiology, Iksan (Korea, Republic of)

2005-07-01

Computed tomography system with the spatial resolution of {approx}25 {mu}m has been developed for the application to small animals. This system is designed by gantry-rotation type for minimizing animal movement. To get image with micro-spatial resolution, system characteristic such as geometry between main components of source, specimen and detector, field of view, etc., is described in this paper. The requirements of x-ray spot size and CCD pixel size to approach the resolution are discussed. In-vivo imaging test for mouse is also presented as a result.

Development of in-vivo micro CT system for small animals

International Nuclear Information System (INIS)

Nam, Ki Yong; Lim, Jong Hyeok; Jeong, Young Jo; Park, Jeong Gwon; Park, Jung Bung; Yoon, Kwon Ha

2005-01-01

Computed tomography system with the spatial resolution of ∼25 μm has been developed for the application to small animals. This system is designed by gantry-rotation type for minimizing animal movement. To get image with micro-spatial resolution, system characteristic such as geometry between main components of source, specimen and detector, field of view, etc., is described in this paper. The requirements of x-ray spot size and CCD pixel size to approach the resolution are discussed. In-vivo imaging test for mouse is also presented as a result

Imaging of hypoxia in small animals with 18F fluoromisonidasole

Directory of Open Access Journals (Sweden)

Kilian Krzysztof

2016-06-01

Full Text Available A method of automated synthesis of [18F]fluoromisonidazole ([18F]FMISO for application in preclinical studies on small animals was presented. A remote-controlled synthesizer Synthra RNplus was used for nucleophilic substitution of NITTP (1′-(2′-nitro-1-imidazolyl-2-O-tetrahydropyranyl-3-O-toluenesulfonyl-propanediol with 18F anion. Labeling of 5 mg of precursor was performed in anhydrous acetonitrile at 100°C for 10 min, and the hydrolysis with HCl was performed at 100°C for 5 min. Final purification was done with high-performance liquid chromatography (HPLC and the radiochemical purity of radiotracer was higher than 99%. Proposed [18F]FMISO synthesis was used as a reliable tool in studies on hypoxia in Lewis lung carcinoma (LLC in mouse models.

Accessories for detention and protection used in small animals radiation therapy

International Nuclear Information System (INIS)

Vettorato, Michel Campos; Vulcano, Luiz Carlos; Fernandes, Marco Antonio Rodrigues

2016-01-01

Radiation therapy is a medical method well established in the treatment of cancer in veterinary medicine worldwide. The radiotherapy protocols applied in animals vary according to several factors. In most procedures require sedation or anesthesia of the animal and this fact imposes the use of immobilization accessories specially developed for the different species of animals and treated as their specified procedures. Therefore, this study aims to describe the types of accessories used for immobilization and for the protection of small animals undergoing radiotherapy. For its development a literature search was performed by search sites like Google Scholar, Scielo, Bireme, PubMed, and consultations in books campus library Botucatu UNESP. Despite the limitations of each accessory rated this review, it was possible to identify the use of each and how this can be advantageous for the treatment of animals undergoing radiation therapy. (author)

Computed tomography of the central nervous system in small animals

International Nuclear Information System (INIS)

Tipold, A.; Tipold, E.

1991-01-01

With computed tomography in 44 small animals some well defined anatomical structures and pathological processes of the central nervous system are described. Computed tomography is not only necessary for the diagnosis of tumors; malformations, inflammatory, degenerative and vascular diseases and traumas are also visible

Experience with a small animal hyperthermia ultrasound system (SAHUS): report on 83 tumours

International Nuclear Information System (INIS)

Novak, P; Moros, E G; Parry, J J; Rogers, B E; Myerson, R J; Zeug, A; Locke, J E; Rossin, R; Straube, W L; Singh, A K

2005-01-01

An external local ultrasound (US) system was developed to induce controlled hyperthermia of subcutaneously implanted tumours in small animals (e.g., mice and rats). It was designed to be compatible with a small animal positron emission tomography scanner (microPET) to facilitate studies of hyperthermia-induced tumour re-oxygenation using a PET radiopharmaceutical, but it is applicable for any small animal study requiring controlled heating. The system consists of an acrylic applicator bed with up to four independent 5 MHz planar disc US transducers of 1 cm in diameter, a four-channel radiofrequency (RF) generator, a multiple thermocouple thermometry unit, and a personal computer with custom monitoring and controlling software. Although the system presented here was developed to target tumours of up to 1 cm in diameter, the applicator design allows for different piezoelectric transducers to be exchanged and operated within the 3.5-6.5 MHz band to target different tumour sizes. Temperature feedback control software was developed on the basis of a proportional-integral-derivative (PID) approach when the measured temperatures were within a selectable temperature band about the target temperature. Outside this band, an on/off control action was applied. Perfused tissue-mimicking phantom experiments were performed to determine optimum controller gain constants, which were later employed successfully in animal experiments. The performance of the SAHUS (small animal hyperthermia ultrasound system) was tested using several tumour types grown in thighs of female nude (nu/nu) mice. To date, the system has successfully treated 83 tumours to target temperatures in the range of 41-43 deg. C for periods of 65 min on average

Overview of Animal Models of Obesity

Science.gov (United States)

Lutz, Thomas A.; Woods, Stephen C.

2012-01-01

This is a review of animal models of obesity currently used in research. We have focused upon more commonly utilized models since there are far too many newly created models to consider, especially those caused by selective molecular genetic approaches modifying one or more genes in specific populations of cells. Further, we will not discuss the generation and use of inducible transgenic animals (induced knock-out or knock-in) even though they often bear significant advantages compared to traditional transgenic animals; influences of the genetic modification during the development of the animals can be minimized. The number of these animal models is simply too large to be covered in this chapter. PMID:22948848

Preliminary Experience with Small Animal SPECT Imaging on Clinical Gamma Cameras

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P. Aguiar

2014-01-01

Full Text Available The traditional lack of techniques suitable for in vivo imaging has induced a great interest in molecular imaging for preclinical research. Nevertheless, its use spreads slowly due to the difficulties in justifying the high cost of the current dedicated preclinical scanners. An alternative for lowering the costs is to repurpose old clinical gamma cameras to be used for preclinical imaging. In this paper we assess the performance of a portable device, that is, working coupled to a single-head clinical gamma camera, and we present our preliminary experience in several small animal applications. Our findings, based on phantom experiments and animal studies, provided an image quality, in terms of contrast-noise trade-off, comparable to dedicated preclinical pinhole-based scanners. We feel that our portable device offers an opportunity for recycling the widespread availability of clinical gamma cameras in nuclear medicine departments to be used in small animal SPECT imaging and we hope that it can contribute to spreading the use of preclinical imaging within institutions on tight budgets.

Characterization of a high-purity germanium detector for small-animal SPECT.

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Johnson, Lindsay C; Campbell, Desmond L; Hull, Ethan L; Peterson, Todd E

2011-09-21

We present an initial evaluation of a mechanically cooled, high-purity germanium double-sided strip detector as a potential gamma camera for small-animal SPECT. It is 90 mm in diameter and 10 mm thick with two sets of 16 orthogonal strips that have a 4.5 mm width with a 5 mm pitch. We found an energy resolution of 0.96% at 140 keV, an intrinsic efficiency of 43.3% at 122 keV and a FWHM spatial resolution of approximately 1.5 mm. We demonstrated depth-of-interaction estimation capability through comparison of pinhole acquisitions with a point source on and off axes. Finally, a flood-corrected flood image exhibited a strip-level uniformity of less than 1%. This high-purity germanium offers many desirable properties for small-animal SPECT.

Improvement of semi-quantitative small-animal PET data with recovery coefficients: a phantom and rat study.

Science.gov (United States)

Aide, Nicolas; Louis, Marie-Hélène; Dutoit, Soizic; Labiche, Alexandre; Lemoisson, Edwige; Briand, Mélanie; Nataf, Valérie; Poulain, Laurent; Gauduchon, Pascal; Talbot, Jean-Noël; Montravers, Françoise

2007-10-01

To evaluate the accuracy of semi-quantitative small-animal PET data, uncorrected for attenuation, and then of the same semi-quantitative data corrected by means of recovery coefficients (RCs) based on phantom studies. A phantom containing six fillable spheres (diameter range: 4.4-14 mm) was filled with an 18F-FDG solution (spheres/background activity=10.1, 5.1 and 2.5). RCs, defined as measured activity/expected activity, were calculated. Nude rats harbouring tumours (n=50) were imaged after injection of 18F-FDG and sacrificed. The standardized uptake value (SUV) in tumours was determined with small-animal PET and compared to ex-vivo counting (ex-vivo SUV). Small-animal PET SUVs were corrected with RCs based on the greatest tumour diameter. Tumour proliferation was assessed with cyclin A immunostaining and correlated to the SUV. RCs ranged from 0.33 for the smallest sphere to 0.72 for the largest. A sigmoidal correlation was found between RCs and sphere diameters (r(2)=0.99). Small-animal PET SUVs were well correlated with ex-vivo SUVs (y=0.48x-0.2; r(2)=0.71) and the use of RCs based on the greatest tumour diameter significantly improved regression (y=0.84x-0.81; r(2)=0.77), except for tumours with important necrosis. Similar results were obtained without sacrificing animals, by using PET images to estimate tumour dimensions. RC-based corrections improved correlation between small-animal PET SUVs and tumour proliferation (uncorrected data: Rho=0.79; corrected data: Rho=0.83). Recovery correction significantly improves both accuracy of small-animal PET semi-quantitative data in rat studies and their correlation with tumour proliferation, except for largely necrotic tumours.

Studying the Immunomodulatory Effects of Small Molecule Ras-Inhibitors in Animal Models of Rheumatoid Arthritis

Science.gov (United States)

2016-10-01

dependent cancers. Thus, in collaboration with Concordia Pharmaceuticals Inc., FTS was developed into and oral drug, Salirasib®. The drug has been already...AIA) rat model − a classical animal model for RA − imply that FTS attenuates disease manifestation, as assessed by: clinical scores; MRI imaging...be used to assess joint inflammation/damage and the immune response, as follows: arthritis clinical scores; MRI scans, micro-CT; histopathology

Measurement of flow velocity fields in small vessel-mimic phantoms and vessels of small animals using micro ultrasonic particle image velocimetry (micro-EPIV).

Science.gov (United States)

Qian, Ming; Niu, Lili; Wang, Yanping; Jiang, Bo; Jin, Qiaofeng; Jiang, Chunxiang; Zheng, Hairong

2010-10-21

Determining a multidimensional velocity field within microscale opaque fluid flows is needed in areas such as microfluidic devices, biofluid mechanics and hemodynamics research in animal studies. The ultrasonic particle image velocimetry (EchoPIV) technique is appropriate for measuring opaque flows by taking advantage of PIV and B-mode ultrasound contrast imaging. However, the use of clinical ultrasound systems for imaging flows in small structures or animals has limitations associated with spatial resolution. This paper reports on the development of a high-resolution EchoPIV technique (termed as micro-EPIV) and its application in measuring flows in small vessel-mimic phantoms and vessels of small animals. Phantom experiments demonstrate the validity of the technique, providing velocity estimates within 4.1% of the analytically derived values with regard to the flows in a small straight vessel-mimic phantom, and velocity estimates within 5.9% of the computationally simulated values with regard to the flows in a small stenotic vessel-mimic phantom. Animal studies concerning arterial and venous flows of living rats and rabbits show that the micro-EPIV-measured peak velocities within several cardiac cycles are about 25% below the values measured by the ultrasonic spectral Doppler technique. The micro-EPIV technique is able to effectively measure the flow fields within microscale opaque fluid flows.

Measurement of flow velocity fields in small vessel-mimic phantoms and vessels of small animals using micro ultrasonic particle image velocimetry (micro-EPIV)

International Nuclear Information System (INIS)

Qian Ming; Niu Lili; Jiang Bo; Jin Qiaofeng; Jiang Chunxiang; Zheng Hairong; Wang Yanping

2010-01-01

Determining a multidimensional velocity field within microscale opaque fluid flows is needed in areas such as microfluidic devices, biofluid mechanics and hemodynamics research in animal studies. The ultrasonic particle image velocimetry (EchoPIV) technique is appropriate for measuring opaque flows by taking advantage of PIV and B-mode ultrasound contrast imaging. However, the use of clinical ultrasound systems for imaging flows in small structures or animals has limitations associated with spatial resolution. This paper reports on the development of a high-resolution EchoPIV technique (termed as micro-EPIV) and its application in measuring flows in small vessel-mimic phantoms and vessels of small animals. Phantom experiments demonstrate the validity of the technique, providing velocity estimates within 4.1% of the analytically derived values with regard to the flows in a small straight vessel-mimic phantom, and velocity estimates within 5.9% of the computationally simulated values with regard to the flows in a small stenotic vessel-mimic phantom. Animal studies concerning arterial and venous flows of living rats and rabbits show that the micro-EPIV-measured peak velocities within several cardiac cycles are about 25% below the values measured by the ultrasonic spectral Doppler technique. The micro-EPIV technique is able to effectively measure the flow fields within microscale opaque fluid flows.

Geo-PET: A novel generic organ-pet for small animal organs and tissues

Science.gov (United States)

Sensoy, Levent

Reconstructed tomographic image resolution of small animal PET imaging systems is improving with advances in radiation detector development. However the trend towards higher resolution systems has come with an increase in price and system complexity. Recent developments in the area of solid-state photomultiplication devices like silicon photomultiplier arrays (SPMA) are creating opportunities for new high performance tools for PET scanner design. Imaging of excised small animal organs and tissues has been used as part of post-mortem studies in order to gain detailed, high-resolution anatomical information on sacrificed animals. However, this kind of ex-vivo specimen imaging has largely been limited to ultra-high resolution muCT. The inherent limitations to PET resolution have, to date, excluded PET imaging from these ex-vivo imaging studies. In this work, we leverage the diminishing physical size of current generation SPMA designs to create a very small, simple, and high-resolution prototype detector system targeting ex-vivo tomographic imaging of small animal organs and tissues. We investigate sensitivity, spatial resolution, and the reconstructed image quality of a prototype small animal PET scanner designed specifically for imaging of excised murine tissue and organs. We aim to demonstrate that a cost-effective silicon photomultiplier (SiPM) array based design with thin crystals (2 mm) to minimize depth of interaction errors might be able to achieve sub-millimeter resolution. We hypothesize that the substantial decrease in sensitivity associated with the thin crystals can be compensated for with increased solid angle detection, longer acquisitions, higher activity and wider acceptance energy windows (due to minimal scatter from excised organs). The constructed system has a functional field of view (FoV) of 40 mm diameter, which is adequate for most small animal specimen studies. We perform both analytical (3D-FBP) and iterative (ML-EM) methods in order to

Animal Models for Periodontal Disease

Directory of Open Access Journals (Sweden)

Helieh S. Oz

2011-01-01

Full Text Available Animal models and cell cultures have contributed new knowledge in biological sciences, including periodontology. Although cultured cells can be used to study physiological processes that occur during the pathogenesis of periodontitis, the complex host response fundamentally responsible for this disease cannot be reproduced in vitro. Among the animal kingdom, rodents, rabbits, pigs, dogs, and nonhuman primates have been used to model human periodontitis, each with advantages and disadvantages. Periodontitis commonly has been induced by placing a bacterial plaque retentive ligature in the gingival sulcus around the molar teeth. In addition, alveolar bone loss has been induced by inoculation or injection of human oral bacteria (e.g., Porphyromonas gingivalis in different animal models. While animal models have provided a wide range of important data, it is sometimes difficult to determine whether the findings are applicable to humans. In addition, variability in host responses to bacterial infection among individuals contributes significantly to the expression of periodontal diseases. A practical and highly reproducible model that truly mimics the natural pathogenesis of human periodontal disease has yet to be developed.

Animal Models for Periodontal Disease

Science.gov (United States)

Oz, Helieh S.; Puleo, David A.

2011-01-01

Animal models and cell cultures have contributed new knowledge in biological sciences, including periodontology. Although cultured cells can be used to study physiological processes that occur during the pathogenesis of periodontitis, the complex host response fundamentally responsible for this disease cannot be reproduced in vitro. Among the animal kingdom, rodents, rabbits, pigs, dogs, and nonhuman primates have been used to model human periodontitis, each with advantages and disadvantages. Periodontitis commonly has been induced by placing a bacterial plaque retentive ligature in the gingival sulcus around the molar teeth. In addition, alveolar bone loss has been induced by inoculation or injection of human oral bacteria (e.g., Porphyromonas gingivalis) in different animal models. While animal models have provided a wide range of important data, it is sometimes difficult to determine whether the findings are applicable to humans. In addition, variability in host responses to bacterial infection among individuals contributes significantly to the expression of periodontal diseases. A practical and highly reproducible model that truly mimics the natural pathogenesis of human periodontal disease has yet to be developed. PMID:21331345

Evaluation of animal models of neurobehavioral disorders

Directory of Open Access Journals (Sweden)

Nordquist Rebecca E

2009-02-01

Full Text Available Abstract Animal models play a central role in all areas of biomedical research. The process of animal model building, development and evaluation has rarely been addressed systematically, despite the long history of using animal models in the investigation of neuropsychiatric disorders and behavioral dysfunctions. An iterative, multi-stage trajectory for developing animal models and assessing their quality is proposed. The process starts with defining the purpose(s of the model, preferentially based on hypotheses about brain-behavior relationships. Then, the model is developed and tested. The evaluation of the model takes scientific and ethical criteria into consideration. Model development requires a multidisciplinary approach. Preclinical and clinical experts should establish a set of scientific criteria, which a model must meet. The scientific evaluation consists of assessing the replicability/reliability, predictive, construct and external validity/generalizability, and relevance of the model. We emphasize the role of (systematic and extended replications in the course of the validation process. One may apply a multiple-tiered 'replication battery' to estimate the reliability/replicability, validity, and generalizability of result. Compromised welfare is inherent in many deficiency models in animals. Unfortunately, 'animal welfare' is a vaguely defined concept, making it difficult to establish exact evaluation criteria. Weighing the animal's welfare and considerations as to whether action is indicated to reduce the discomfort must accompany the scientific evaluation at any stage of the model building and evaluation process. Animal model building should be discontinued if the model does not meet the preset scientific criteria, or when animal welfare is severely compromised. The application of the evaluation procedure is exemplified using the rat with neonatal hippocampal lesion as a proposed model of schizophrenia. In a manner congruent to

Animal models.

Science.gov (United States)

Walker, Ellen A

2010-01-01

As clinical studies reveal that chemotherapeutic agents may impair several different cognitive domains in humans, the development of preclinical animal models is critical to assess the degree of chemotherapy-induced learning and memory deficits and to understand the underlying neural mechanisms. In this chapter, the effects of various cancer chemotherapeutic agents in rodents on sensory processing, conditioned taste aversion, conditioned emotional response, passive avoidance, spatial learning, cued memory, discrimination learning, delayed-matching-to-sample, novel-object recognition, electrophysiological recordings and autoshaping is reviewed. It appears at first glance that the effects of the cancer chemotherapy agents in these many different models are inconsistent. However, a literature is emerging that reveals subtle or unique changes in sensory processing, acquisition, consolidation and retrieval that are dose- and time-dependent. As more studies examine cancer chemotherapeutic agents alone and in combination during repeated treatment regimens, the animal models will become more predictive tools for the assessment of these impairments and the underlying neural mechanisms. The eventual goal is to collect enough data to enable physicians to make informed choices about therapeutic regimens for their patients and discover new avenues of alternative or complementary therapies that reduce or eliminate chemotherapy-induced cognitive deficits.

Control of positive end-expiratory pressure (PEEP for small animal ventilators

Directory of Open Access Journals (Sweden)

Leão Nunes Marcelo V

2010-07-01

Full Text Available Abstract Background The positive end-expiratory pressure (PEEP for the mechanical ventilation of small animals is frequently obtained with water seals or by using ventilators developed for human use. An alternative mechanism is the use of an on-off expiratory valve closing at the moment when the alveolar pressure is equal to the target PEEP. In this paper, a novel PEEP controller (PEEP-new and the PEEP system of a commercial small-animal ventilator, both based on switching an on-off valve, are evaluated. Methods The proposed PEEP controller is a discrete integrator monitoring the error between the target PEEP and the airways opening pressure prior to the onset of an inspiratory cycle. In vitro as well as in vivo experiments with rats were carried out and the PEEP accuracy, settling time and under/overshoot were considered as a measure of performance. Results The commercial PEEP controller did not pass the tests since it ignores the airways resistive pressure drop, resulting in a PEEP 5 cmH2O greater than the target in most conditions. The PEEP-new presented steady-state errors smaller than 0.5 cmH2O, with settling times below 10 s and under/overshoot smaller than 2 cmH2O. Conclusion The PEEP-new presented acceptable performance, considering accuracy and temporal response. This novel PEEP generator may prove useful in many applications for small animal ventilators.

Coil concepts for rapid and motion-compensated MR-Imaging of small animals

International Nuclear Information System (INIS)

Korn, Matthias

2009-01-01

In this work radiofrequency-coils for the imaging of small animals in clinical whole-body MRI-systems were developed. Therefore in a first step single-channel solenoids were designed and characterized. The solenoids had two and three windings respectively, which were implemented as double wires to increase the homogeneity of the receive profile. These coils allow the acquisition of whole-body images of mice with high signal-to-noise ratio and homogeneity over a distance of at least 6.3 cm. Since many imaging experiments require rapid image acquisition, in the next step a novel coil concept was developed, which, due to its geometry, enables parallel imaging in arbitrary directions. A prototype was assembled and tested on phantom and small-animal experiments. With an accelerating factor of R=2, the difference of the SNR in all directions from the theoretical maximum, was less than 1%. In order to compensate physiological motion by the self-gating technique, in this work a coil is presented for the first time, which selectively amplifies the self-gating signal, while - due to a optical detuning technique - preserving the homogeneous illumination of the image. In vivo experiments on a small animal show an amplification of the self-gating signal by at least 40%. (orig.)

Reaction-based small-molecule fluorescent probes for dynamic detection of ROS and transient redox changes in living cells and small animals.

Science.gov (United States)

Lü, Rui

2017-09-01

Dynamic detection of transient redox changes in living cells and animals has broad implications for human health and disease diagnosis, because intracellular redox homeostasis regulated by reactive oxygen species (ROS) plays important role in cell functions, normal physiological functions and some serious human diseases (e.g., cancer, Alzheimer's disease, diabetes, etc.) usually have close relationship with the intracellular redox status. Small-molecule ROS-responsive fluorescent probes can act as powerful tools for dynamic detection of ROS and redox changes in living cells and animals through fluorescence imaging techniques; and great advances have been achieved recently in the design and synthesis of small-molecule ROS-responsive fluorescent probes. This article highlights up-to-date achievements in designing and using the reaction-based small-molecule fluorescent probes (with high sensitivity and selectivity to ROS and redox cycles) in the dynamic detection of ROS and transient redox changes in living cells and animals through fluorescence imaging. Copyright © 2017. Published by Elsevier Ltd.

Enclosure for small animals during awake animal imaging

Science.gov (United States)

Goddard, Jr., James S

2013-11-26

An enclosure or burrow restrains an awake animal during an imaging procedure. A tubular body, made from a radiolucent material that does not attenuate x-rays or gamma rays, accepts an awake animal. A proximal end of the body includes an attachment surface that corresponds to an attachment surface of an optically transparent and optically uniform window. An anti-reflective coating may be applied to an inner surface, an outer surface, or both surfaces of the window. Since the window is a separate element of the enclosure and it is not integrally formed as part of the body, it can be made with optically uniform thickness properties for improved motion tracking of markers on the animal with a camera during the imaging procedure. The motion tracking information is then used to compensate for animal movement in the image.

Potency of Animal Models in KANSEI Engineering

Science.gov (United States)

Ozaki, Shigeru; Hisano, Setsuji; Iwamoto, Yoshiki

Various species of animals have been used as animal models for neuroscience and provided critical information about the brain functions. Although it seems difficult to elucidate a highly advanced function of the human brain, animal models have potency to clarify the fundamental mechanisms of emotion, decision-making and social behavior. In this review, we will pick up common animal models and point to both the merits and demerits caused by the characteristics. We will also mention that wide-ranging approaches from animal models are advantageous to understand KANSEI as well as mind in humans.

An animal model for tinnitus.

Science.gov (United States)

Jastreboff, P J; Brennan, J F; Sasaki, C T

1988-03-01

Subjective tinnitus remains obscure, widespread, and without apparent cure. In the absence of a suitable animal model, past investigations took place in humans, resulting in studies that were understandably restricted by the nature of human investigation. Within this context, the development of a valid animal model would be considered a major breakthrough in this field of investigation. Our results showed changes in the spontaneous activity of single neurons in the inferior colliculus, consistent with abnormally increased neuronal activity within the auditory pathways after manipulations known to produce tinnitus in man. A procedure based on a Pavlovian conditioned suppression paradigm was recently developed that allows us to measure tinnitus behaviorally in conscious animals. Accordingly, an animal model of tinnitus is proposed that permits tests of hypotheses relating to tinnitus generation, allowing the accommodation of interventional strategies for the treatment of this widespread auditory disorder.

SU-E-T-217: Intrinsic Respiratory Gating in Small Animal CT

Energy Technology Data Exchange (ETDEWEB)

Liu, Y; Smith, M; Mistry, N [University of Maryland School of Medicine, Baltimore, MD (United States)

2014-06-01

Purpose: Preclinical animal models of lung cancer can provide a controlled test-bed for testing dose escalation or function-based-treatment-planning studies. However, to extract lung function, i.e. ventilation, one needs to be able to image the lung at different phases of ventilation (in-hale / ex-hale). Most respiratory-gated imaging using micro-CT involves using an external ventilator and surgical intervention limiting the utility in longitudinal studies. A new intrinsic respiratory retrospective gating method was developed and tested in mice. Methods: A fixed region of interest (ROI) that covers the diaphragm was selected on all projection images to estimate the mean intensity (M). The mean intensity depends on the projection angle and diaphragm position. A 3-point moving average (A) of consecutive M values: Mpre, Mcurrent and Mpost, was calculated to be subtracted from Mcurrent. A fixed threshold was used to enable amplitude based sorting into 4 different phases of respiration. Images at full-inhale and end-exhale phases of respiration were reconstructed using the open source OSCaR. Lung volumes estimated at the 2 phases of respiration were validated against literature values. Results: Intrinsic retrospective gating was accomplished without the use of any external breathing waveform. While projection images were acquired at 360 different angles. Only 138 and 104 projections were used to reconstruct images at full-inhale and end-exhale. This often results in non-uniform under-sampled angular projections leading to some minor streaking artifacts. The calculated expiratory, inspiratory and tidal lung volumes correlated well with the values known from the literature. Conclusion: Our initial result demonstrates an intrinsic gating method that is suitable for flat panel cone beam small animal CT systems. Reduction in streaking artifacts can be accomplished by oversampling the data or using iterative reconstruction methods. This initial experience will enable

XX. Animal models of pneumocystosis

DEFF Research Database (Denmark)

Dei-Cas, E.; Brun-Pascaud, M.; Bille-Hansen, Vivi

1998-01-01

As in vitro culture systems allowing to isolate Pneumocystis samples from patients or other mammal hosts are still not available, animal models have critical importance in Pneumocystis research. The parasite was reported in numerous mammals but P. carinii pneumonia (PCP) experimental models were...... a source of parasites taxonomically related to P. carinii sp. f hominis. Moreover, primates might be used as experimental hosts to human Pneumocystis. A marked variability of parasite levels among corticosteroid-treated animals and the fact that the origin of the parasite strain remains unknown......, are important drawbacks of the corticosteroid-treated models. For these reasons, inoculated animal models of PCP were developed. The intratracheal inoculation of lung homogenates containing viable parasites in corticosteroid-treated non-latently infected rats resulted in extensive, reproducible Pneumocystis...

Importance of Attenuation Correction (AC) for Small Animal PET Imaging

DEFF Research Database (Denmark)

El Ali, Henrik H.; Bodholdt, Rasmus Poul; Jørgensen, Jesper Tranekjær

2012-01-01

was performed. Methods: Ten NMRI nude mice with subcutaneous implantation of human breast cancer cells (MCF-7) were scanned consecutively in small animal PET and CT scanners (MicroPETTM Focus 120 and ImTek’s MicroCATTM II). CT-based AC, PET-based AC and uniform AC methods were compared. Results: The activity...

Determination of tolerance dose uncertainties and optimal design of dose response experiments with small animal numbers

International Nuclear Information System (INIS)

Karger, C.P.; Hartmann, G.H.

2001-01-01

Background: Dose response experiments aim to determine the complication probability as a function of dose. Adjusting the parameters of the frequently used dose response model P(D)=1/[1+(D 50 /D) k ] to the experimental data, 2 intuitive quantities are obtained: The tolerance dose D 50 and the slope parameter k. For mathematical reasons, however, standard statistic software uses a different set of parameters. Therefore, the resulting fit parameters of the statistic software as well as their standard errors have to be transformed to obtain D 50 and k as well as their standard errors. Material and Methods: The influence of the number of dose levels on the uncertainty of the fit parameters is studied by a simulation for a fixed number of animals. For experiments with small animal numbers, statistical artifacts may prevent the determination of the standard errors of the fit parameters. Consequences on the design of dose response experiments are investigated. Results: Explicit formulas are presented, which allow to calculate the parameters D 50 and k as well as their standard errors from the output of standard statistic software. The simulation shows, that the standard errors of the resulting parameters are independent of the number of dose levels, as long as the total number of animals involved in the experiment, remains constant. Conclusion: Statistical artifacts in experiments containing small animal numbers may be prevented by an adequate design of the experiment. For this, it is suggested to select a higher number of dose levels, rather than using a higher number of animals per dose level. (orig.) [de

Monitoring of small laboratory animal experiments by a designated web-based database.

Science.gov (United States)

Frenzel, T; Grohmann, C; Schumacher, U; Krüll, A

2015-10-01

Multiple-parametric small animal experiments require, by their very nature, a sufficient number of animals which may need to be large to obtain statistically significant results.(1) For this reason database-related systems are required to collect the experimental data as well as to support the later (re-) analysis of the information gained during the experiments. In particular, the monitoring of animal welfare is simplified by the inclusion of warning signals (for instance, loss in body weight >20%). Digital patient charts have been developed for human patients but are usually not able to fulfill the specific needs of animal experimentation. To address this problem a unique web-based monitoring system using standard MySQL, PHP, and nginx has been created. PHP was used to create the HTML-based user interface and outputs in a variety of proprietary file formats, namely portable document format (PDF) or spreadsheet files. This article demonstrates its fundamental features and the easy and secure access it offers to the data from any place using a web browser. This information will help other researchers create their own individual databases in a similar way. The use of QR-codes plays an important role for stress-free use of the database. We demonstrate a way to easily identify all animals and samples and data collected during the experiments. Specific ways to record animal irradiations and chemotherapy applications are shown. This new analysis tool allows the effective and detailed analysis of huge amounts of data collected through small animal experiments. It supports proper statistical evaluation of the data and provides excellent retrievable data storage. © The Author(s) 2015.

Primary functions of the first Japanese large-scale facility for exposing small animals to radon

International Nuclear Information System (INIS)

Ishimori, Yuu; Tanaka, Hiroshi; Mitsunobu, Fumihiro; Yamaoka, Kiyonori; Kataoka, Takahiro; Sakoda, Akihiro

2010-01-01

The Japan Atomic Energy Agency (JAEA) and Okayama University have carried out the experimental animal study and its related studies since 2007 in order to examine the physiological effects of radon in detail. Thus, a radon test facility for small animals was developed in order to increase the statistical certainty of our animal tests. This paper illustrates the performances of that facility, the first large-scale facility of its types in Japan. The facility has a potential of approximately 150 mouse-scale tests at the same time. The apparatus for exposing small animals to radon has six animal chamber groups each of which consists of five independent cages. Different radon concentrations in each animal chamber group are available. The major functions of the facility controlling radon and avoiding thoron were shown theoretically and experimentally. The relative standard deviation of radon concentration at the highest concentration group was about 5%, although the lower concentration groups seemed to be affected by variations in background radon. (author)

The guinea pig as an animal model for developmental and reproductive toxicology studies.

Science.gov (United States)

Rocca, Meredith S; Wehner, Nancy G

2009-04-01

Regulatory guidelines for developmental and reproductive toxicology (DART) studies require selection of "relevant" animal models as determined by kinetic, pharmacological, and toxicological data. Traditionally, rats, mice, and rabbits are the preferred animal models for these studies. However, for test articles that are pharmacologically inactive in the traditional animal models, the guinea pig may be a viable option. This choice should not be made lightly, as guinea pigs have many disadvantages compared to the traditional species, including limited historical control data, variability in pregnancy rates, small and variable litter size, long gestation, relative maturity at birth, and difficulty in dosing and breeding. This report describes methods for using guinea pigs in DART studies and provides results of positive and negative controls. Standard study designs and animal husbandry methods were modified to allow mating on the postpartum estrus in fertility studies and were used for producing cohorts of pregnant females for developmental studies. A positive control study with the pregnancy-disrupting agent mifepristone resulted in the anticipated failure of embryo implantation and supported the use of the guinea pig model. Control data for reproductive endpoints collected from 5 studies are presented. In cases where the traditional animal models are not relevant, the guinea pig can be used successfully for DART studies. (c) 2009 Wiley-Liss, Inc.

Bone scintigraphy for the investigation of lameness in small animals

International Nuclear Information System (INIS)

Bolln, G.; Franke, C.

2010-01-01

Bone scintigraphy has been used as a helpful method in diagnosing lameness in small animals. It is a sensitive, non-invasive method to evaluate bone lesions and orthopaedic disorders. It provides a functional image of the skeleton and thereby aiding in the localisation and diagnosing of obscure lameness. Compared to human medicine one important difference is the inability of an animal to characterize its pain to the examiner. Another difference is the lacking cooperation of an animal during bone scintigraphy. Before this background are shown on the basis of 5 examples the advantages, the method and the different indication of bone scintigraphy. The technique of this method arrives from a human medicine protocol of a 2-phase-bone-scintigraphy and has to be done under light anaesthesia, to avoid artefacts of movement during acquisitions. The authors are convinced that bone scintigraphy is a very useful and diagnostic method for evaluation of obscure lameness because it can give a quick diagnosis and aimed therapy. Therefore secondary changes and additional costs can be avoided for the animal and its owner. (orig.)

A framework for inverse planning of beam-on times for 3D small animal radiotherapy using interactive multi-objective optimisation

International Nuclear Information System (INIS)

Balvert, Marleen; Den Hertog, Dick; Van Hoof, Stefan J; Granton, Patrick V; Trani, Daniela; Hoffmann, Aswin L; Verhaegen, Frank

2015-01-01

Advances in precision small animal radiotherapy hardware enable the delivery of increasingly complicated dose distributions on the millimeter scale. Manual creation and evaluation of treatment plans becomes difficult or even infeasible with an increasing number of degrees of freedom for dose delivery and available image data. The goal of this work is to develop an optimisation model that determines beam-on times for a given beam configuration, and to assess the feasibility and benefits of an automated treatment planning system for small animal radiotherapy.The developed model determines a Pareto optimal solution using operator-defined weights for a multiple-objective treatment planning problem. An interactive approach allows the planner to navigate towards, and to select the Pareto optimal treatment plan that yields the most preferred trade-off of the conflicting objectives. This model was evaluated using four small animal cases based on cone-beam computed tomography images. Resulting treatment plan quality was compared to the quality of manually optimised treatment plans using dose-volume histograms and metrics.Results show that the developed framework is well capable of optimising beam-on times for 3D dose distributions and offers several advantages over manual treatment plan optimisation. For all cases but the simple flank tumour case, a similar amount of time was needed for manual and automated beam-on time optimisation. In this time frame, manual optimisation generates a single treatment plan, while the inverse planning system yields a set of Pareto optimal solutions which provides quantitative insight on the sensitivity of conflicting objectives. Treatment planning automation decreases the dependence on operator experience and allows for the use of class solutions for similar treatment scenarios. This can shorten the time required for treatment planning and therefore increase animal throughput. In addition, this can improve treatment standardisation and

Evaluating performance of a pixel array semiconductor SPECT system for small animal imaging

International Nuclear Information System (INIS)

Kubo, Naoki; Zhao, Songji; Fujiki, Yutaka

2005-01-01

Small animal imaging has recently been focused on basic nuclear medicine. We have designed and built a small animal SPECT imaging system using a semiconductor camera and a newly designed collimator. We assess the performance of this system for small object imaging. We employed an MGC 1500 (Acrorad Co.) camera including a CdTe semiconductor. The pixel size was 1.4 mm/pixel. We designed and produced a parallel-hole collimator with 20-mm hole length. Our SPECT system consisted of a semiconductor camera with the subject holder set on an electric rotating stage controlled by a computer. We compared this system with a conventional small animal SPECT system comprising a SPECT-2000H scanner with four Anger type cameras and pinhole collimators. The count rate linearity for estimation of the scatter was evaluated for a pie-chart phantom containing different concentrations of 99m Tc. We measured the full width half maximum (FWHM) of the 99m Tc SPECT line source along with scatter. The system volume sensitivity was examined using a flood source phantom which was 35 mm long with a 32-mm inside diameter. Additionally, an in vivo myocardial perfusion SPECT study was performed with a rat. With regards to energy resolution, the semiconductor camera (5.6%) was superior to the conventional Anger type camera (9.8%). In the count rate linearity evaluation, the regression lines of the SPECT values were y=0.019x+0.031 (r 2 =0.999) for our system and y=0.018x+0.060 (r 2 =0.997) for the conventional system. Thus, the scatter count using the semiconductor camera was less than that using the conventional camera. FWHMs of our system and the conventional system were 2.9±0.1 and 2.0±0.1 mm, respectively. Moreover, the system volume sensitivity of our system [0.51 kcps/(MBq/ml)/cm] was superior to that of the conventional system [0.44 kcps/(MBq/ml)/cm]. Our system provided clear images of the rat myocardium, sufficient for practical use in small animal imaging. Our SPECT system, utilizing a

Cardiac regeneration using pluripotent stem cells—Progression to large animal models

Directory of Open Access Journals (Sweden)

James J.H. Chong

2014-11-01

Full Text Available Pluripotent stem cells (PSCs have indisputable cardiomyogenic potential and therefore have been intensively investigated as a potential cardiac regenerative therapy. Current directed differentiation protocols are able to produce high yields of cardiomyocytes from PSCs and studies in small animal models of cardiovascular disease have proven sustained engraftment and functional efficacy. Therefore, the time is ripe for cardiac regenerative therapies using PSC derivatives to be tested in large animal models that more closely resemble the hearts of humans. In this review, we discuss the results of our recent study using human embryonic stem cell derived cardiomyocytes (hESC-CM in a non-human primate model of ischemic cardiac injury. Large scale remuscularization, electromechanical coupling and short-term arrhythmias demonstrated by our hESC-CM grafts are discussed in the context of other studies using adult stem cells for cardiac regeneration.

Open-source, small-animal magnetic resonance-guided focused ultrasound system.

Science.gov (United States)

Poorman, Megan E; Chaplin, Vandiver L; Wilkens, Ken; Dockery, Mary D; Giorgio, Todd D; Grissom, William A; Caskey, Charles F

2016-01-01

MR-guided focused ultrasound or high-intensity focused ultrasound (MRgFUS/MRgHIFU) is a non-invasive therapeutic modality with many potential applications in areas such as cancer therapy, drug delivery, and blood-brain barrier opening. However, the large financial costs involved in developing preclinical MRgFUS systems represent a barrier to research groups interested in developing new techniques and applications. We aim to mitigate these challenges by detailing a validated, open-source preclinical MRgFUS system capable of delivering thermal and mechanical FUS in a quantifiable and repeatable manner under real-time MRI guidance. A hardware and software package was developed that includes closed-loop feedback controlled thermometry code and CAD drawings for a therapy table designed for a preclinical MRI scanner. For thermal treatments, the modular software uses a proportional integral derivative controller to maintain a precise focal temperature rise in the target given input from MR phase images obtained concurrently. The software computes the required voltage output and transmits it to a FUS transducer that is embedded in the delivery table within the magnet bore. The delivery table holds the FUS transducer, a small animal and its monitoring equipment, and a transmit/receive RF coil. The transducer is coupled to the animal via a water bath and is translatable in two dimensions from outside the magnet. The transducer is driven by a waveform generator and amplifier controlled by real-time software in Matlab. MR acoustic radiation force imaging is also implemented to confirm the position of the focus for mechanical and thermal treatments. The system was validated in tissue-mimicking phantoms and in vivo during murine tumor hyperthermia treatments. Sonications were successfully controlled over a range of temperatures and thermal doses for up to 20 min with minimal temperature overshoot. MR thermometry was validated with an optical temperature probe, and focus

Small-animal SPECT and SPECT/CT: application in cardiovascular research

Energy Technology Data Exchange (ETDEWEB)

Golestani, Reza; Dierckx, Rudi A.J.O. [University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen (Netherlands); Wu, Chao [University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen (Netherlands); University Medical Center Utrecht, Image Sciences Institute and Rudolf Magnus Institute of Neurosciences, Utrecht (Netherlands); Tio, Rene A. [University Medical Center Groningen, Thorax Center, Department of Cardiology, Groningen (Netherlands); University Medical Center Groningen, Cardiovascular Imaging Group, P.O. Box 30001, Groningen (Netherlands); Zeebregts, Clark J. [University Medical Center Groningen, Department of Surgery, Division of Vascular Surgery, Groningen (Netherlands); University Medical Center Groningen, Cardiovascular Imaging Group, P.O. Box 30001, Groningen (Netherlands); Petrov, Artiom D. [University of California, Irvine, Division of Cardiology, School of Medicine, Irvine, California (United States); Beekman, Freek J. [University Medical Center Utrecht, Image Sciences Institute and Rudolf Magnus Institute of Neurosciences, Utrecht (Netherlands); Delft University of Technology, Faculty of Applied Sciences, Section Radiation Detection and Medical Imaging, Delft (Netherlands); MILabs, Utrecht (Netherlands); Boersma, Hendrikus H. [University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen (Netherlands); University Medical Center Groningen, Department of Clinical and Hospital Pharmacy, Hanzeplein 1, P.O. Box 30001, Groningen (Netherlands); University Medical Center Groningen, Cardiovascular Imaging Group, P.O. Box 30001, Groningen (Netherlands); Slart, Riemer H.J.A. [University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen (Netherlands); University Medical Center Groningen, Cardiovascular Imaging Group, P.O. Box 30001, Groningen (Netherlands)

2010-09-15

Preclinical cardiovascular research using noninvasive radionuclide and hybrid imaging systems has been extensively developed in recent years. Single photon emission computed tomography (SPECT) is based on the molecular tracer principle and is an established tool in noninvasive imaging. SPECT uses gamma cameras and collimators to form projection data that are used to estimate (dynamic) 3-D tracer distributions in vivo. Recent developments in multipinhole collimation and advanced image reconstruction have led to sub-millimetre and sub-half-millimetre resolution SPECT in rats and mice, respectively. In this article we review applications of microSPECT in cardiovascular research in which information about the function and pathology of the myocardium, vessels and neurons is obtained. We give examples on how diagnostic tracers, new therapeutic interventions, pre- and postcardiovascular event prognosis, and functional and pathophysiological heart conditions can be explored by microSPECT, using small-animal models of cardiovascular disease. (orig.)

Small-animal SPECT and SPECT/CT: application in cardiovascular research

International Nuclear Information System (INIS)

Golestani, Reza; Dierckx, Rudi A.J.O.; Wu, Chao; Tio, Rene A.; Zeebregts, Clark J.; Petrov, Artiom D.; Beekman, Freek J.; Boersma, Hendrikus H.; Slart, Riemer H.J.A.

2010-01-01

Preclinical cardiovascular research using noninvasive radionuclide and hybrid imaging systems has been extensively developed in recent years. Single photon emission computed tomography (SPECT) is based on the molecular tracer principle and is an established tool in noninvasive imaging. SPECT uses gamma cameras and collimators to form projection data that are used to estimate (dynamic) 3-D tracer distributions in vivo. Recent developments in multipinhole collimation and advanced image reconstruction have led to sub-millimetre and sub-half-millimetre resolution SPECT in rats and mice, respectively. In this article we review applications of microSPECT in cardiovascular research in which information about the function and pathology of the myocardium, vessels and neurons is obtained. We give examples on how diagnostic tracers, new therapeutic interventions, pre- and postcardiovascular event prognosis, and functional and pathophysiological heart conditions can be explored by microSPECT, using small-animal models of cardiovascular disease. (orig.)

Performance characteristics of a small animal PET camera for molecular imaging

International Nuclear Information System (INIS)

Hastings, D.L.; Reader, A.J.; Julyan, P.J.; Zweit, J.; Jeavons, A.P.; Jones, T.

2007-01-01

The performance of a novel type of animal PET camera, the quad High-Density Avalanche Chamber (HIDAC) was assessed for a non-rotating 16-module system. Spatial resolution was 1.0 mm, and invariant within a standard deviation ≤5%. Absolute sensitivity was 0.95%, and the scatter-background corrected sensitivity was 0.75%. The count rate capability was linear at typical activities used in animal imaging, with a 20% loss at 11.5 MBq. The camera demonstrates small regions of radiotracer uptake with excellent detail in the mouse

The therapeutic lamp: treating small-animal phobias.

Science.gov (United States)

Wrzesien, Maja; Alcañiz, Mariano; Botella, Cristina; Burkhardt, Jean-Marie; Bretón-López, Juana; Ortega, Mario; Brotons, Daniel Beneito

2013-01-01

We all have an irrational fear or two. Some of us get scared by an unexpected visit from a spider in our house; others get nervous when they look down from a high building. Fear is an evolutionary and adaptive function that can promote self-preservation and help us deal with the feared object or situation. However, when this state becomes excessive, it might develop into psychological disorders such as phobias, producing high anxiety and affecting everyday life. The Therapeutic Lamp is an interactive projection-based augmented-reality system for treating small-animal phobias. It aims to increase patient-therapist communication, promote more natural interaction, and improve the patient's engagement in the therapy.

Tupaia belangeri as an experimental animal model for viral infection.

Science.gov (United States)

Tsukiyama-Kohara, Kyoko; Kohara, Michinori

2014-01-01

Tupaias, or tree shrews, are small mammals that are similar in appearance to squirrels. The morphological and behavioral characteristics of the group have been extensively characterized, and despite previously being classified as primates, recent studies have placed the group in its own family, the Tupaiidae. Genomic analysis has revealed that the genus Tupaia is closer to humans than it is to rodents. In addition, tupaias are susceptible to hepatitis B virus and hepatitis C virus. The only other experimental animal that has been demonstrated to be sensitive to both of these viruses is the chimpanzee, but restrictions on animal testing have meant that experiments using chimpanzees have become almost impossible. Consequently, the development of the tupaia for use as an animal infection model could become a powerful tool for hepatitis virus research and in preclinical studies on drug development.

Comprehensive small animal imaging strategies on a clinical 3 T dedicated head MR-scanner; adapted methods and sequence protocols in CNS pathologies.

Directory of Open Access Journals (Sweden)

Deepu R Pillai

Full Text Available BACKGROUND: Small animal models of human diseases are an indispensable aspect of pre-clinical research. Being dynamic, most pathologies demand extensive longitudinal monitoring to understand disease mechanisms, drug efficacy and side effects. These considerations often demand the concomitant development of monitoring systems with sufficient temporal and spatial resolution. METHODOLOGY AND RESULTS: This study attempts to configure and optimize a clinical 3 Tesla magnetic resonance scanner to facilitate imaging of small animal central nervous system pathologies. The hardware of the scanner was complemented by a custom-built, 4-channel phased array coil system. Extensive modification of standard sequence protocols was carried out based on tissue relaxometric calculations. Proton density differences between the gray and white matter of the rodent spinal cord along with transverse relaxation due to magnetic susceptibility differences at the cortex and striatum of both rats and mice demonstrated statistically significant differences. The employed parallel imaging reconstruction algorithms had distinct properties dependent on the sequence type and in the presence of the contrast agent. The attempt to morphologically phenotype a normal healthy rat brain in multiple planes delineated a number of anatomical regions, and all the clinically relevant sequels following acute cerebral ischemia could be adequately characterized. Changes in blood-brain-barrier permeability following ischemia-reperfusion were also apparent at a later time. Typical characteristics of intra-cerebral haemorrhage at acute and chronic stages were also visualized up to one month. Two models of rodent spinal cord injury were adequately characterized and closely mimicked the results of histological studies. In the employed rodent animal handling system a mouse model of glioblastoma was also studied with unequivocal results. CONCLUSIONS: The implemented customizations including extensive

Comprehensive Small Animal Imaging Strategies on a Clinical 3 T Dedicated Head MR-Scanner; Adapted Methods and Sequence Protocols in CNS Pathologies

Science.gov (United States)

Pillai, Deepu R.; Heidemann, Robin M.; Lanz, Titus; Dittmar, Michael S.; Sandner, Beatrice; Beier, Christoph P.; Weidner, Norbert; Greenlee, Mark W.; Schuierer, Gerhard; Bogdahn, Ulrich; Schlachetzki, Felix

2011-01-01

Background Small animal models of human diseases are an indispensable aspect of pre-clinical research. Being dynamic, most pathologies demand extensive longitudinal monitoring to understand disease mechanisms, drug efficacy and side effects. These considerations often demand the concomitant development of monitoring systems with sufficient temporal and spatial resolution. Methodology and Results This study attempts to configure and optimize a clinical 3 Tesla magnetic resonance scanner to facilitate imaging of small animal central nervous system pathologies. The hardware of the scanner was complemented by a custom-built, 4-channel phased array coil system. Extensive modification of standard sequence protocols was carried out based on tissue relaxometric calculations. Proton density differences between the gray and white matter of the rodent spinal cord along with transverse relaxation due to magnetic susceptibility differences at the cortex and striatum of both rats and mice demonstrated statistically significant differences. The employed parallel imaging reconstruction algorithms had distinct properties dependent on the sequence type and in the presence of the contrast agent. The attempt to morphologically phenotype a normal healthy rat brain in multiple planes delineated a number of anatomical regions, and all the clinically relevant sequels following acute cerebral ischemia could be adequately characterized. Changes in blood-brain-barrier permeability following ischemia-reperfusion were also apparent at a later time. Typical characteristics of intra-cerebral haemorrhage at acute and chronic stages were also visualized up to one month. Two models of rodent spinal cord injury were adequately characterized and closely mimicked the results of histological studies. In the employed rodent animal handling system a mouse model of glioblastoma was also studied with unequivocal results. Conclusions The implemented customizations including extensive sequence protocol

Laser-enhanced high-intensity focused ultrasound heating in an in vivo small animal model

Science.gov (United States)

Jo, Janggun; Yang, Xinmai

2016-11-01

The enhanced heating effect during the combination of high-intensity focused ultrasound (HIFU) and low-optical-fluence laser illumination was investigated by using an in vivo murine animal model. The thighs of murine animals were synergistically irradiated by HIFU and pulsed nano-second laser light. The temperature increases in the target region were measured by a thermocouple under different HIFU pressures, which were 6.2, 7.9, and 9.8 MPa, in combination with 20 mJ/cm2 laser exposures at 532 nm wavelength. In comparison with conventional laser therapies, the laser fluence used here is at least one order of magnitude lower. The results showed that laser illumination could enhance temperature during HIFU applications. Additionally, cavitation activity was enhanced when laser and HIFU irradiation were concurrently used. Further, a theoretical simulation showed that the inertial cavitation threshold was indeed decreased when laser and HIFU irradiation were utilized concurrently.

Cone Beam Micro-CT System for Small Animal Imaging and Performance Evaluation

Directory of Open Access Journals (Sweden)

Shouping Zhu

2009-01-01

in this paper. Experimental results show that the system is suitable for small animal imaging and is adequate to provide high-resolution anatomic information for bioluminescence tomography to build a dual modality system.

Animal models for testing anti-prion drugs.

Science.gov (United States)

Fernández-Borges, Natalia; Elezgarai, Saioa R; Eraña, Hasier; Castilla, Joaquín

2013-01-01

Prion diseases belong to a group of fatal infectious diseases with no effective therapies available. Throughout the last 35 years, less than 50 different drugs have been tested in different experimental animal models without hopeful results. An important limitation when searching for new drugs is the existence of appropriate models of the disease. The three different possible origins of prion diseases require the existence of different animal models for testing anti-prion compounds. Wild type, over-expressing transgenic mice and other more sophisticated animal models have been used to evaluate a diversity of compounds which some of them were previously tested in different in vitro experimental models. The complexity of prion diseases will require more pre-screening studies, reliable sporadic (or spontaneous) animal models and accurate chemical modifications of the selected compounds before having an effective therapy against human prion diseases. This review is intended to put on display the more relevant animal models that have been used in the search of new antiprion therapies and describe some possible procedures when handling chemical compounds presumed to have anti-prion activity prior to testing them in animal models.

Experimental task-based optimization of a four-camera variable-pinhole small-animal SPECT system

Science.gov (United States)

Hesterman, Jacob Y.; Kupinski, Matthew A.; Furenlid, Lars R.; Wilson, Donald W.

2005-04-01

We have previously utilized lumpy object models and simulated imaging systems in conjunction with the ideal observer to compute figures of merit for hardware optimization. In this paper, we describe the development of methods and phantoms necessary to validate or experimentally carry out these optimizations. Our study was conducted on a four-camera small-animal SPECT system that employs interchangeable pinhole plates to operate under a variety of pinhole configurations and magnifications (representing optimizable system parameters). We developed a small-animal phantom capable of producing random backgrounds for each image sequence. The task chosen for the study was the detection of a 2mm diameter sphere within the phantom-generated random background. A total of 138 projection images were used, half of which included the signal. As our observer, we employed the channelized Hotelling observer (CHO) with Laguerre-Gauss channels. The signal-to-noise (SNR) of this observer was used to compare different system configurations. Results indicate agreement between experimental and simulated data with higher detectability rates found for multiple-camera, multiple-pinhole, and high-magnification systems, although it was found that mixtures of magnifications often outperform systems employing a single magnification. This work will serve as a basis for future studies pertaining to system hardware optimization.

WE-H-206-02: Recent Advances in Multi-Modality Molecular Imaging of Small Animals

Energy Technology Data Exchange (ETDEWEB)

Tsui, B. [Johns Hopkins University (United States)

2016-06-15

to biomedical research during the past decade. The initial development was an extension of clinical PET/CT and SPECT/CT from human to small animals and combine the unique functional information obtained from PET and SPECT with anatomical information provided by the CT in registered multi-modality images. The requirements to image a mouse whose size is an order of magnitude smaller than that of a human have spurred advances in new radiation detector technologies, novel imaging system designs and special image reconstruction and processing techniques. Examples are new detector materials and designs with high intrinsic resolution, multi-pinhole (MPH) collimator design for much improved resolution and detection efficiency compared to the conventional collimator designs in SPECT, 3D high-resolution and artifact-free MPH and sparse-view image reconstruction techniques, and iterative image reconstruction methods with system response modeling for resolution recovery and image noise reduction for much improved image quality. The spatial resolution of PET and SPECT has improved from ∼6–12 mm to ∼1 mm a few years ago to sub-millimeter today. A recent commercial small animal SPECT system has achieved a resolution of ∼0.25 mm which surpasses that of a state-of-art PET system whose resolution is limited by the positron range. More recently, multimodality SA PET/MRI and SPECT/MRI systems have been developed in research laboratories. Also, multi-modality SA imaging systems that include other imaging modalities such as optical and ultrasound are being actively pursued. In this presentation, we will provide a review of the development, recent advances and future outlook of multi-modality molecular imaging of small animals. Learning Objectives: To learn about the two major multi-modality molecular imaging techniques of small animals. To learn about the spatial resolution achievable by the molecular imaging systems for small animal today. To learn about the new multi

WE-H-206-02: Recent Advances in Multi-Modality Molecular Imaging of Small Animals

International Nuclear Information System (INIS)

Tsui, B.

2016-01-01

to biomedical research during the past decade. The initial development was an extension of clinical PET/CT and SPECT/CT from human to small animals and combine the unique functional information obtained from PET and SPECT with anatomical information provided by the CT in registered multi-modality images. The requirements to image a mouse whose size is an order of magnitude smaller than that of a human have spurred advances in new radiation detector technologies, novel imaging system designs and special image reconstruction and processing techniques. Examples are new detector materials and designs with high intrinsic resolution, multi-pinhole (MPH) collimator design for much improved resolution and detection efficiency compared to the conventional collimator designs in SPECT, 3D high-resolution and artifact-free MPH and sparse-view image reconstruction techniques, and iterative image reconstruction methods with system response modeling for resolution recovery and image noise reduction for much improved image quality. The spatial resolution of PET and SPECT has improved from ∼6–12 mm to ∼1 mm a few years ago to sub-millimeter today. A recent commercial small animal SPECT system has achieved a resolution of ∼0.25 mm which surpasses that of a state-of-art PET system whose resolution is limited by the positron range. More recently, multimodality SA PET/MRI and SPECT/MRI systems have been developed in research laboratories. Also, multi-modality SA imaging systems that include other imaging modalities such as optical and ultrasound are being actively pursued. In this presentation, we will provide a review of the development, recent advances and future outlook of multi-modality molecular imaging of small animals. Learning Objectives: To learn about the two major multi-modality molecular imaging techniques of small animals. To learn about the spatial resolution achievable by the molecular imaging systems for small animal today. To learn about the new multi

Improved instrumentation for blood flow velocity measurements in the microcirculation of small animals

International Nuclear Information System (INIS)

Mesquita, Jayme Alves Jr. de; Bouskela, Eliete; Wajnberg, Eliane; Lopes de Melo, Pedro

2007-01-01

Microcirculation is the generic name of vessels with internal diameter less than 100 μm of the circulatory system, whose main functions are tissue nutrition and oxygen supply. In microcirculatory studies, it is important to know the amount of oxyhemoglobin present in the blood and how fast it is moving. The present work describes improvements introduced in a classical hardware-based instrument that has usually been used to monitor blood flow velocity in the microcirculation of small animals. It consists of a virtual instrument that can be easily incorporated into existing hardware-based systems, contributing to reduce operator related biases and allowing digital processing and storage. The design and calibration of the modified instrument are described as well as in vitro and in vivo results obtained with electrical models and small animals, respectively. Results obtained in in vivo studies showed that this new system is able to detect a small reduction in blood flow velocity comparing arteries and arterioles (p<0.002) and a further reduction in capillaries (p<0.0001). A significant increase in velocity comparing capillaries and venules (p<0.001) and venules and veins (p<0.001) was also observed. These results are in close agreement with biophysical principles. Moreover, the improvements introduced in the device allowed us to clearly observe changes in blood flow introduced by a pharmacological intervention, suggesting that the system has enough temporal resolution to track these microcirculatory events. These results were also in close conformity to physiology, confirming the high scientific potential of the modified system and indicating that this instrument can also be useful for pharmacological evaluations

Animal models of exercise and obesity.

Science.gov (United States)

Kasper, Christine E

2013-01-01

Animal models have been invaluable in the conduct of nursing research for the past 40 years. This review will focus on specific animal models that can be used in nursing research to study the physiologic phenomena of exercise and obesity when the use of human subjects is either scientifically premature or inappropriate because of the need for sampling tissue or the conduct of longitudinal studies of aging. There exists an extensive body of literature reporting the experimental use of various animal models, in both exercise science and the study of the mechanisms of obesity. Many of these studies are focused on the molecular and genetic mechanisms of organ system adaptation and plasticity in response to exercise, obesity, or both. However, this review will narrowly focus on the models useful to nursing research in the study of exercise in the clinical context of increasing performance and mobility, atrophy and bedrest, fatigue, and aging. Animal models of obesity focus on those that best approximate clinical pathology.

Fully automated intrinsic respiratory and cardiac gating for small animal CT

Energy Technology Data Exchange (ETDEWEB)

Kuntz, J; Baeuerle, T; Semmler, W; Bartling, S H [Department of Medical Physics in Radiology, German Cancer Research Center, Heidelberg (Germany); Dinkel, J [Department of Radiology, German Cancer Research Center, Heidelberg (Germany); Zwick, S [Department of Diagnostic Radiology, Medical Physics, Freiburg University (Germany); Grasruck, M [Siemens Healthcare, Forchheim (Germany); Kiessling, F [Chair of Experimental Molecular Imaging, RWTH-Aachen University, Medical Faculty, Aachen (Germany); Gupta, R [Department of Radiology, Massachusetts General Hospital, Boston, MA (United States)], E-mail: j.kuntz@dkfz.de

2010-04-07

A fully automated, intrinsic gating algorithm for small animal cone-beam CT is described and evaluated. A parameter representing the organ motion, derived from the raw projection images, is used for both cardiac and respiratory gating. The proposed algorithm makes it possible to reconstruct motion-corrected still images as well as to generate four-dimensional (4D) datasets representing the cardiac and pulmonary anatomy of free-breathing animals without the use of electrocardiogram (ECG) or respiratory sensors. Variation analysis of projections from several rotations is used to place a region of interest (ROI) on the diaphragm. The ROI is cranially extended to include the heart. The centre of mass (COM) variation within this ROI, the filtered frequency response and the local maxima are used to derive a binary motion-gating parameter for phase-sensitive gated reconstruction. This algorithm was implemented on a flat-panel-based cone-beam CT scanner and evaluated using a moving phantom and animal scans (seven rats and eight mice). Volumes were determined using a semiautomatic segmentation. In all cases robust gating signals could be obtained. The maximum volume error in phantom studies was less than 6%. By utilizing extrinsic gating via externally placed cardiac and respiratory sensors, the functional parameters (e.g. cardiac ejection fraction) and image quality were equivalent to this current gold standard. This algorithm obviates the necessity of both gating hardware and user interaction. The simplicity of the proposed algorithm enables adoption in a wide range of small animal cone-beam CT scanners.

An automated robot arm system for small animal tissue biopsy under dual-image modality

International Nuclear Information System (INIS)

Huang, Y.H.; Wu, T.H.; Lin, M.H.; Yang, C.C.; Guo, W.Y.; Wang, Z.J.; Chen, C.L.; Lee, J.S.

2006-01-01

The ability to non-invasively monitor cell biology in vivo is one of the most important goals of molecular imaging. Imaging procedures could be inter-subject performed repeatedly at different investigating stages; thereby need not sacrifice small animals during the entire study period. Thus, the ultimate goal of this study was to design a stereotactic image-guided system for small animals and integrated it with an automatic robot arm for in vivo tissue biopsy analysis. The system was composed of three main parts, including one small animal stereotactic frame, one imaging-fusion software and an automatic robot arm system. The system has been thoroughly evaluated with three components; the robot position accuracy was 0.05±0.02 mm, the image registration accuracy was 0.37±0.18 mm and the system integration was satisfactorily within 1.20±0.39 mm of error. From these results, the system demonstrated sufficient accuracy to guide the micro-injector from the planned delivery routes into practice. The entire system accuracy was limited by the image fusion and orientation procedures, due to its nature of the blurred PET imaging obtained from the small objects. The primary improvement is to acquire as higher resolution as possible the fused imaging for localizing the targets in the future

Testing flow diversion in animal models: a systematic review.

Science.gov (United States)

Fahed, Robert; Raymond, Jean; Ducroux, Célina; Gentric, Jean-Christophe; Salazkin, Igor; Ziegler, Daniela; Gevry, Guylaine; Darsaut, Tim E

2016-04-01

Flow diversion (FD) is increasingly used to treat intracranial aneurysms. We sought to systematically review published studies to assess the quality of reporting and summarize the results of FD in various animal models. Databases were searched to retrieve all animal studies on FD from 2000 to 2015. Extracted data included species and aneurysm models, aneurysm and neck dimensions, type of flow diverter, occlusion rates, and complications. Articles were evaluated using a checklist derived from the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines. Forty-two articles reporting the results of FD in nine different aneurysm models were included. The rabbit elastase-induced aneurysm model was the most commonly used, with 3-month occlusion rates of 73.5%, (95%CI [61.9-82.6%]). FD of surgical sidewall aneurysms, constructed in rabbits or canines, resulted in high occlusion rates (100% [65.5-100%]). FD resulted in modest occlusion rates (15.4% [8.9-25.1%]) when tested in six complex canine aneurysm models designed to reproduce more difficult clinical contexts (large necks, bifurcation, or fusiform aneurysms). Adverse events, including branch occlusion, were rarely reported. There were no hemorrhagic complications. Articles complied with 20.8 ± 3.9 of 41 ARRIVE items; only a small number used randomization (3/42 articles [7.1%]) or a control group (13/42 articles [30.9%]). Preclinical studies on FD have shown various results. Occlusion of elastase-induced aneurysms was common after FD. The model is not challenging but standardized in many laboratories. Failures of FD can be reproduced in less standardized but more challenging surgical canine constructions. The quality of reporting could be improved.

Performance of the first Japanese large-scale facility for radon inhalation experiments with small animals

International Nuclear Information System (INIS)

Ishimori, Y.; Mitsunobu, F.; Yamaoka, K.; Tanaka, H.; Kataoka, T.; Sakoda, A.

2011-01-01

A radon test facility for small animals was developed in order to increase the statistical validity of differences of the biological response in various radon environments. This paper illustrates the performances of that facility, the first large-scale facility of its kind in Japan. The facility has a capability to conduct approximately 150 mouse-scale tests at the same time. The apparatus for exposing small animals to radon has six animal chamber groups with five independent cages each. Different radon concentrations in each animal chamber group are available. Because the first target of this study is to examine the in vivo behaviour of radon and its effects, the major functions to control radon and to eliminate thoron were examined experimentally. Additionally, radon progeny concentrations and their particle size distributions in the cages were also examined experimentally to be considered in future projects. (authors)

Veterinarians' perceptions of behaviour support in small-animal practice.

Science.gov (United States)

Roshier, A L; McBride, E A

2013-03-09

Veterinarians are professionals considered to be at the forefront of animal welfare, including behaviour medicine. However, concerns raised, both within the profession and without, highlight that the support offered is not optimal, due to deficiencies in veterinary training, which focuses on physical aspects and overlooks psychological aspects. This preliminary study explored the experiences and perceptions of six veterinarians (three male, three female, age range: 23-55 years) in two UK small-animal practices. Seventeen annual booster consultations were videoed and conversations thematically analysed for welfare topics discussed. Both veterinarians and clients completed questionnaires to gather demographic information and perspectives. All veterinarians recognised behaviour as a component of their caseload, and acknowledged that clients expected them to provide behaviour support. Veterinarians varied in their experiences of and confidence in providing behaviour support. Five felt unable to meet client expectations; four did not feel their training had prepared them sufficiently. Only one provided dedicated behaviour consultations, the others referred cases. All provided suggestions for behaviour skills needed for new veterinary graduates. The study has afforded an insight into the experiences of a small opportunistic sample of veterinarians. The data indicated important limitations regarding time available in general consultations to discuss behaviour concerns, and practitioner knowledge and skill in detection, anamnesis, assessment and provision of appropriate behaviour information. Suggestions for veterinary training in behaviour are provided.

Animal models: an important tool in mycology.

Science.gov (United States)

Capilla, Javier; Clemons, Karl V; Stevens, David A

2007-12-01

Animal models of fungal infections are, and will remain, a key tool in the advancement of the medical mycology. Many different types of animal models of fungal infection have been developed, with murine models the most frequently used, for studies of pathogenesis, virulence, immunology, diagnosis, and therapy. The ability to control numerous variables in performing the model allows us to mimic human disease states and quantitatively monitor the course of the disease. However, no single model can answer all questions and different animal species or different routes of infection can show somewhat different results. Thus, the choice of which animal model to use must be made carefully, addressing issues of the type of human disease to mimic, the parameters to follow and collection of the appropriate data to answer those questions being asked. This review addresses a variety of uses for animal models in medical mycology. It focuses on the most clinically important diseases affecting humans and cites various examples of the different types of studies that have been performed. Overall, animal models of fungal infection will continue to be valuable tools in addressing questions concerning fungal infections and contribute to our deeper understanding of how these infections occur, progress and can be controlled and eliminated.

Contribution of customised dosimetry for small animal to the treatments of cancers by metabolic radiotherapy

International Nuclear Information System (INIS)

Boutaleb, Samir

2010-01-01

This research thesis first reports a bibliographical study which addressed the use of ionizing radiations in cancer therapy (evolution from ionizing radiation to metabolic radiotherapy, biological and physical parameters, and absorbed dose in metabolic radiotherapy) and the role imagery has in customised dosimetry (absorbed dose calculation methods, determination of cumulative activity, dosimetric models for S factor calculation). Then, the author presents a software which has been specifically developed for the creation of dosimetric models, and reports its validation. He reports the comparison between different dosimetric models in the case of mice. He highlights two applications of the developed tool: radio-immunotherapy and metabolic radiotherapy. He finally proposes a general discussion on the impact of small animal dosimetry on metabolic radiotherapy [fr

Animal models of attention-deficit hyperactivity disorder

Directory of Open Access Journals (Sweden)

Sagvolden Terje

2005-07-01

Full Text Available Abstract Although animals cannot be used to study complex human behaviour such as language, they do have similar basic functions. In fact, human disorders that have animal models are better understood than disorders that do not. ADHD is a heterogeneous disorder. The relatively simple nervous systems of rodent models have enabled identification of neurobiological changes that underlie certain aspects of ADHD behaviour. Several animal models of ADHD suggest that the dopaminergic system is functionally impaired. Some animal models have decreased extracellular dopamine concentrations and upregulated postsynaptic dopamine D1 receptors (DRD1 while others have increased extracellular dopamine concentrations. In the latter case, dopamine pathways are suggested to be hyperactive. However, stimulus-evoked release of dopamine is often decreased in these models, which is consistent with impaired dopamine transmission. It is possible that the behavioural characteristics of ADHD result from impaired dopamine modulation of neurotransmission in cortico-striato-thalamo-cortical circuits. There is considerable evidence to suggest that the noradrenergic system is poorly controlled by hypofunctional α2-autoreceptors in some models, giving rise to inappropriately increased release of norepinephrine. Aspects of ADHD behaviour may result from an imbalance between increased noradrenergic and decreased dopaminergic regulation of neural circuits that involve the prefrontal cortex. Animal models of ADHD also suggest that neural circuits may be altered in the brains of children with ADHD. It is therefore of particular importance to study animal models of the disorder and not normal animals. Evidence obtained from animal models suggests that psychostimulants may not be acting on the dopamine transporter to produce the expected increase in extracellular dopamine concentration in ADHD. There is evidence to suggest that psychostimulants may decrease motor activity by

Management and Level of Asian small-clawed otter (Aonyx cinereus Illinger, 1815 as Display Animal in Indonesia Conservation Institution

Directory of Open Access Journals (Sweden)

Ulfa Hansyari Ar-Rasyid

2017-09-01

Full Text Available Education and breeding become main reasons for asian small-clawed otter placement as display animal in zoo. Proper management is needed to maintain asian small-clawed otter welfare. This research objectives were to examine and assess asian small-clawed otter welfare in three Indonesia zoos. The study was conducted from December 2016 to February 2017 in Bandung Zoo, Ragunan Zoo and Ocean Dream Samudra Ancol. The methods of this research were literature review, interview and field observation. Data were analyzed using the suitability of management and animal welfare assessment. The result showed that there were three main management activities conducted at the three study locations, i.e., nutrition, housing, and health management. Bandung Zoo achieved the lowest score of asian small-clawed otter welfare (45,24% compared to Ragunan Zoo (62,24% and Ocean Dream Samudra (65,90%. Asian small-clawed otter welfare in three institutions were relatively low to fair category, this was due to the unfilled quality of food and water i.e.,  the type, amount, feeding frequency, diet and preparing of food; the unavailability of suitable and favorable environmental conditions; the care facilities provided could not ensure the health of animal; the appearance of abnormal behavior that affected the growth and breeding of animal; and animal had no freedom to behave as in their natural habitat. Keywords: animal display, animal welfare, Asian small-clawed otter, zoo 

The zoonotic potential of Clostridium difficile from small companion animals and their owners.

Science.gov (United States)

Rabold, Denise; Espelage, Werner; Abu Sin, Muna; Eckmanns, Tim; Schneeberg, Alexander; Neubauer, Heinrich; Möbius, Nadine; Hille, Katja; Wieler, Lothar H; Seyboldt, Christian; Lübke-Becker, Antina

2018-01-01

Clostridium difficile infections (CDI) in humans range from asymptomatic carriage to life-threatening intestinal disease. Findings on C. difficile in various animal species and an overlap in ribotypes (RTs) suggest potential zoonotic transmission. However, the impact of animals for human CDI remains unclear. In a large-scale survey we collected 1,447 fecal samples to determine the occurrence of C. difficile in small companion animals (dogs and cats) and their owners and to assess potential epidemiological links within the community. The Germany-wide survey was conducted from July 2012-August 2013. PCR ribotyping, Multilocus VNTR Analysis (MLVA) and PCR detection of toxin genes were used to characterize isolated C. difficile strains. A database was defined and logistic regression used to identify putative factors associated with fecal shedding of C. difficile. In total, 1,418 samples met the inclusion criteria. The isolation rates for small companion animals and their owners within the community were similarly low with 3.0% (25/840) and 2.9% (17/578), respectively. PCR ribotyping revealed eight and twelve different RTs in animals and humans, respectively, whereas three RTs were isolated in both, humans and animals. RT 014/0, a well-known human hospital-associated lineage, was predominantly detected in animal samples. Moreover, the potentially highly pathogenic RTs 027 and 078 were isolated from dogs. Even though, C. difficile did not occur simultaneously in animals and humans sharing the same household. The results of the epidemiological analysis of factors associated with fecal shedding of C. difficile support the hypothesis of a zoonotic potential. Molecular characterization and epidemiological analysis revealed that the zoonotic risk for C. difficile associated with dogs and cats within the community is low but cannot be excluded.

MOSFET assessment of radiation dose delivered to mice using the Small Animal Radiation Research Platform (SARRP).

Science.gov (United States)

Ngwa, Wilfred; Korideck, Houari; Chin, Lee M; Makrigiorgos, G Mike; Berbeco, Ross I

2011-12-01

The Small Animal Radiation Research Platform (SARRP) is a novel isocentric irradiation system that enables state-of-the-art image-guided radiotherapy research to be performed with animal models. This paper reports the results obtained from investigations assessing the radiation dose delivered by the SARRP to different anatomical target volumes in mice. Surgically implanted metal oxide semiconductor field effect transistors (MOSFET) dosimeters were employed for the dose assessment. The results reveal differences between the calculated and measured dose of -3.5 to 0.5%, -5.2 to -0.7%, -3.9 to 0.5%, -5.9 to 2.5%, -5.5 to 0.5%, and -4.3 to 0% for the left kidney, liver, pancreas, prostate, left lung, and brain, respectively. Overall, the findings show less than 6% difference between the delivered and calculated dose, without tissue heterogeneity corrections. These results provide a useful assessment of the need for tissue heterogeneity corrections in SARRP dose calculations for clinically relevant tumor model sites.

Current status and future perspectives of in vivo small animal imaging using radiolabeled nanoparticles

International Nuclear Information System (INIS)

Loudos, George; Kagadis, George C.; Psimadas, Dimitris

2011-01-01

Small animal molecular imaging is a rapidly expanding efficient tool to study biological processes non-invasively. The use of radiolabeled tracers provides non-destructive, imaging information, allowing time related phenomena to be repeatedly studied in a single animal. In the last decade there has been an enormous progress in related technologies and a number of dedicated imaging systems overcome the limitations that the size of small animal possesses. On the other hand, nanoparticles (NPs) gain increased interest, due to their unique properties, which make them perfect candidates for biological applications. Over the past 5 years the two fields seem to cross more and more often; radiolabeled NPs have been assessed in numerous pre-clinical studies that range from oncology, till HIV treatment. In this article the current status in the tools, applications and trends of radiolabeled NPs reviewed.

Discrete tomography in an in vivo small animal bone study.

Science.gov (United States)

Van de Casteele, Elke; Perilli, Egon; Van Aarle, Wim; Reynolds, Karen J; Sijbers, Jan

2018-01-01

This study aimed at assessing the feasibility of a discrete algebraic reconstruction technique (DART) to be used in in vivo small animal bone studies. The advantage of discrete tomography is the possibility to reduce the amount of X-ray projection images, which makes scans faster and implies also a significant reduction of radiation dose, without compromising the reconstruction results. Bone studies are ideal for being performed with discrete tomography, due to the relatively small number of attenuation coefficients contained in the image [namely three: background (air), soft tissue and bone]. In this paper, a validation is made by comparing trabecular bone morphometric parameters calculated from images obtained by using DART and the commonly used standard filtered back-projection (FBP). Female rats were divided into an ovariectomized (OVX) and a sham-operated group. In vivo micro-CT scanning of the tibia was done at baseline and at 2, 4, 8 and 12 weeks after surgery. The cross-section images were reconstructed using first the full set of projection images and afterwards reducing them in number to a quarter and one-sixth (248, 62, 42 projection images, respectively). For both reconstruction methods, similar changes in morphometric parameters were observed over time: bone loss for OVX and bone growth for sham-operated rats, although for DART the actual values were systematically higher (bone volume fraction) or lower (structure model index) compared to FBP, depending on the morphometric parameter. The DART algorithm was, however, more robust when using fewer projection images, where the standard FBP reconstruction was more prone to noise, showing a significantly bigger deviation from the morphometric parameters obtained using all projection images. This study supports the use of DART as a potential alternative method to FBP in X-ray micro-CT animal studies, in particular, when the number of projections has to be drastically minimized, which directly reduces

Nigerian Veterinary Journal The record of J 14small animal trauma ...

African Journals Online (AJOL)

base for the establishment of protocols for trauma patient care. Trauma cases ranked first and accounted fOT46.3% of all small animal surgical cases presented during the period. Species involvement markedly favoured the canine species. Incidence of trauma was significantly higher (1)<0.05) in males (60.5%) and younger.

New design of a quasi-monolithic detector module with DOI capability for small animal pet

International Nuclear Information System (INIS)

Chung, Yong Hyun; Lee, Seung-Jae; Baek, Cheol-Ha; Choi, Yong

2008-01-01

We report a new design of a detector module with depth of interaction (DOI) based on a quasi-monolithic LSO crystal, a multi-channel sensor, and maximum-likelihood position-estimation (MLPE) algorithm. Light transport and detection were modeled in a quasi-monolithic crystal using DETECT2000 code, with lookup tables (LUTs) built by simulation. Events were well separated by applying the MLPE method within 2.0 mm spatial resolution in both trans-axial and DOI directions. These results demonstrate that the proposed detector provides dependable positioning capability for small animal positron emission tomography (PET)

Attitudes of Austrian veterinarians towards euthanasia in small animal practice: impacts of age and gender on views on euthanasia

OpenAIRE

Hartnack, Sonja; Springer, Svenja; Pittavino, Marta; Grimm, Herwig

2016-01-01

Background Euthanasia of pets has been described by veterinarians as ?the best and the worst? of the profession. The most commonly mentioned ethical dilemmas veterinarians face in small animal practice are: limited treatment options due to financial constraints, euthanizing of healthy animals and owners wishing to continue treatment of terminally ill animals. The aim of the study was to gain insight into the attitudes of Austrian veterinarians towards euthanasia of small animals. This include...

Evaluation of a cone beam computed tomography geometry for image guided small animal irradiation

International Nuclear Information System (INIS)

Yang, Yidong; Armour, Michael; Wang, Ken Kang-Hsin; Gandhi, Nishant; Wong, John; Iordachita, Iulian; Siewerdsen, Jeffrey

2015-01-01

The conventional imaging geometry for small animal cone beam computed tomography (CBCT) is that a detector panel rotates around the head-to-tail axis of an imaged animal (‘tubular’ geometry). Another unusual but possible imaging geometry is that the detector panel rotates around the anterior-to-posterior axis of the animal (‘pancake’ geometry). The small animal radiation research platform developed at Johns Hopkins University employs the pancake geometry where a prone-positioned animal is rotated horizontally between an x-ray source and detector panel. This study is to assess the CBCT image quality in the pancake geometry and investigate potential methods for improvement. We compared CBCT images acquired in the pancake geometry with those acquired in the tubular geometry when the phantom/animal was placed upright simulating the conventional CBCT geometry. Results showed signal-to-noise and contrast-to-noise ratios in the pancake geometry were reduced in comparison to the tubular geometry at the same dose level. But the overall spatial resolution within the transverse plane of the imaged cylinder/animal was better in the pancake geometry. A modest exposure increase to two folds in the pancake geometry can improve image quality to a level close to the tubular geometry. Image quality can also be improved by inclining the animal, which reduces streak artifacts caused by bony structures. The major factor resulting in the inferior image quality in the pancake geometry is the elevated beam attenuation along the long axis of the phantom/animal and consequently increased scatter-to-primary ratio in that orientation. Not withstanding, the image quality in the pancake-geometry CBCT is adequate to support image guided animal positioning, while providing unique advantages of non-coplanar and multiple mice irradiation. This study also provides useful knowledge about the image quality in the two very different imaging geometries, i.e. pancake and tubular geometry

Evaluation of a cone beam computed tomography geometry for image guided small animal irradiation.

Science.gov (United States)

Yang, Yidong; Armour, Michael; Wang, Ken Kang-Hsin; Gandhi, Nishant; Iordachita, Iulian; Siewerdsen, Jeffrey; Wong, John

2015-07-07

The conventional imaging geometry for small animal cone beam computed tomography (CBCT) is that a detector panel rotates around the head-to-tail axis of an imaged animal ('tubular' geometry). Another unusual but possible imaging geometry is that the detector panel rotates around the anterior-to-posterior axis of the animal ('pancake' geometry). The small animal radiation research platform developed at Johns Hopkins University employs the pancake geometry where a prone-positioned animal is rotated horizontally between an x-ray source and detector panel. This study is to assess the CBCT image quality in the pancake geometry and investigate potential methods for improvement. We compared CBCT images acquired in the pancake geometry with those acquired in the tubular geometry when the phantom/animal was placed upright simulating the conventional CBCT geometry. Results showed signal-to-noise and contrast-to-noise ratios in the pancake geometry were reduced in comparison to the tubular geometry at the same dose level. But the overall spatial resolution within the transverse plane of the imaged cylinder/animal was better in the pancake geometry. A modest exposure increase to two folds in the pancake geometry can improve image quality to a level close to the tubular geometry. Image quality can also be improved by inclining the animal, which reduces streak artifacts caused by bony structures. The major factor resulting in the inferior image quality in the pancake geometry is the elevated beam attenuation along the long axis of the phantom/animal and consequently increased scatter-to-primary ratio in that orientation. Not withstanding, the image quality in the pancake-geometry CBCT is adequate to support image guided animal positioning, while providing unique advantages of non-coplanar and multiple mice irradiation. This study also provides useful knowledge about the image quality in the two very different imaging geometries, i.e. pancake and tubular geometry, respectively.

Modelling group dynamic animal movement

DEFF Research Database (Denmark)

Langrock, Roland; Hopcraft, J. Grant C.; Blackwell, Paul G.

2014-01-01

makes its movement decisions relative to the group centroid. The basic idea is framed within the flexible class of hidden Markov models, extending previous work on modelling animal movement by means of multi-state random walks. While in simulation experiments parameter estimators exhibit some bias......, to date, practical statistical methods which can include group dynamics in animal movement models have been lacking. We consider a flexible modelling framework that distinguishes a group-level model, describing the movement of the group's centre, and an individual-level model, such that each individual......Group dynamic movement is a fundamental aspect of many species' movements. The need to adequately model individuals' interactions with other group members has been recognised, particularly in order to differentiate the role of social forces in individual movement from environmental factors. However...

Imaging system models for small-bore DOI-PET scanners

International Nuclear Information System (INIS)

Takahashi, Hisashi; Kobayashi, Tetsuya; Yamaya, Taiga; Murayama, Hideo; Kitamura, Keishi; Hasegawa, Tomoyuki; Suga, Mikio

2006-01-01

Depth-of-interaction (DOI) information, which improves resolution uniformity in the field of view (FOV), is expected to lead to high-sensitivity PET scanners with small-bore detector rings. We are developing small-bore PET scanners with DOI detectors arranged in hexagonal or overlapped tetragonal patterns for small animal imaging or mammography. It is necessary to optimize the imaging system model because these scanners exhibit irregular detector sampling. In this work, we compared two imaging system models: (a) a parallel sub-LOR model in which the detector response functions (DRFs) are assumed to be uniform along the line of responses (LORs) and (b) a sub-crystal model in which each crystal is divided into a set of smaller volumes. These two models were applied to the overlapped tetragonal scanner (FOV 38.1 mm in diameter) and the hexagonal scanner (FOV 85.2 mm in diameter) simulated by GATE. We showed that the resolution non-uniformity of system model (b) was improved by 40% compared with that of system model (a) in the overlapped tetragonal scanner and that the resolution non-uniformity of system model (a) was improved by 18% compared with that of system model (b) in the hexagonal scanner. These results indicate that system model (b) should be applied to the overlapped tetragonal scanner and system model (a) should be applied to the hexagonal scanner. (author)

Ethical guidelines, animal profile, various animal models used in periodontal research with alternatives and future perspectives.

Science.gov (United States)

Pasupuleti, Mohan Kumar; Molahally, Subramanya Shetty; Salwaji, Supraja

2016-01-01

Laboratory animal models serve as a facilitator to investigate the etiopathogenesis of periodontal disease, are used to know the efficacy of reconstructive and regenerative procedures, and are also helpful in evaluation of newer therapeutic techniques including laser and implant therapies prior to application in the human beings. The aim of this review is to know the different animal models used in various specialties of dental research and to know the ethical guidelines prior to the usage of experimental models with main emphasis on how to refine, replace, and reduce the number of animal models usage in the laboratory. An online search for experimental animal models used in dental research was performed using MEDLINE/PubMed database. Publications from 2009 to May 2013 in the specialty of periodontics were included in writing this review. A total of 652 references were published in PubMed/MEDLINE databases based on the search terms used. Out of 245 studies, 241 were related to the periodontal research published in English from 2009 to 2013. Relevant papers were chosen according to the inclusion and exclusion criteria. After extensive electronic and hand search on animal models, it has been observed that various animal models were used in dental research. Search on animal models used for dental research purpose revealed that various animals such as rats, mice, guinea pigs, rabbit, beagle dogs, goats, and nonhuman primates were extensively used. However, with the new advancement of ex vivo animal models, it has become easy to investigate disease pathogenesis and to test the efficacy of newer therapeutic modalities with the reduced usage of animal models. This review summarized the large amount of literature on animal models used in periodontal research with main emphasis on ethical guidelines and on reducing the animal model usage in future perspective.

Ethical guidelines, animal profile, various animal models used in periodontal research with alternatives and future perspectives

Directory of Open Access Journals (Sweden)

Mohan Kumar Pasupuleti

2016-01-01

Full Text Available Laboratory animal models serve as a facilitator to investigate the etiopathogenesis of periodontal disease, are used to know the efficacy of reconstructive and regenerative procedures, and are also helpful in evaluation of newer therapeutic techniques including laser and implant therapies prior to application in the human beings. The aim of this review is to know the different animal models used in various specialties of dental research and to know the ethical guidelines prior to the usage of experimental models with main emphasis on how to refine, replace, and reduce the number of animal models usage in the laboratory. An online search for experimental animal models used in dental research was performed using MEDLINE/PubMed database. Publications from 2009 to May 2013 in the specialty of periodontics were included in writing this review. A total of 652 references were published in PubMed/MEDLINE databases based on the search terms used. Out of 245 studies, 241 were related to the periodontal research published in English from 2009 to 2013. Relevant papers were chosen according to the inclusion and exclusion criteria. After extensive electronic and hand search on animal models, it has been observed that various animal models were used in dental research. Search on animal models used for dental research purpose revealed that various animals such as rats, mice, guinea pigs, rabbit, beagle dogs, goats, and nonhuman primates were extensively used. However, with the new advancement of ex vivo animal models, it has become easy to investigate disease pathogenesis and to test the efficacy of newer therapeutic modalities with the reduced usage of animal models. This review summarized the large amount of literature on animal models used in periodontal research with main emphasis on ethical guidelines and on reducing the animal model usage in future perspective.

Validity of bioluminescence measurements for noninvasive in vivo imaging of tumor load in small animals

NARCIS (Netherlands)

Klerk, Clara P. W.; Overmeer, Renée M.; Niers, Tatjana M. H.; Versteeg, Henri H.; Richel, Dick J.; Buckle, Tessa; van Noorden, Cornelis J. F.; van Tellingen, Olaf

2007-01-01

A relatively new strategy to longitudinally monitor tumor load in intact animals and the effects of therapy is noninvasive bioluminescence imaging (BLI). The validity of BLI for quantitative assessment of tumor load in small animals is critically evaluated in the present review. Cancer cells are

The motivations and methodology for high-throughput PET imaging of small animals in cancer research.

NARCIS (Netherlands)

Aide, N.; Visser, E.P.; Lheureux, S.; Heutte, N.; Szanda, I.; Hicks, R.J.

2012-01-01

Over the last decade, small-animal PET imaging has become a vital platform technology in cancer research. With the development of molecularly targeted therapies and drug combinations requiring evaluation of different schedules, the number of animals to be imaged within a PET experiment has

Near Field UHF RFID Antenna System Enabling the Tracking of Small Laboratory Animals

Directory of Open Access Journals (Sweden)

Luca Catarinucci

2013-01-01

Full Text Available Radio frequency identification (RFID technology is more and more adopted in a wide range of applicative scenarios. In many cases, such as the tracking of small-size living animals for behaviour analysis purposes, the straightforward use of commercial solutions does not ensure adequate performance. Consequently, both RFID hardware and the control software should be tailored for the particular application. In this work, a novel RFID-based approach enabling an effective localization and tracking of small-sized laboratory animals is proposed. It is mainly based on a UHF Near Field RFID multiantenna system, to be placed under the animals’ cage, and able to rigorously identify the NF RFID tags implanted in laboratory animals (e.g., mice. Once the requirements of the reader antenna have been individuated, the antenna system has been designed and realized. Moreover, an algorithm based on the measured Received Signal Strength Indication (RSSI aiming at removing potential ambiguities in data captured by the multiantenna system has been developed and integrated. The animal tracking system has been largely tested on phantom mice in order to verify its ability to precisely localize each subject and to reconstruct its path. The achieved and discussed results demonstrate the effectiveness of the proposed tracking system.

Low relative error in consumer-grade GPS units make them ideal for measuring small-scale animal movement patterns

Directory of Open Access Journals (Sweden)

Greg A. Breed

2015-08-01

Full Text Available Consumer-grade GPS units are a staple of modern field ecology, but the relatively large error radii reported by manufacturers (up to 10 m ostensibly precludes their utility in measuring fine-scale movement of small animals such as insects. Here we demonstrate that for data collected at fine spatio-temporal scales, these devices can produce exceptionally accurate data on step-length and movement patterns of small animals. With an understanding of the properties of GPS error and how it arises, it is possible, using a simple field protocol, to use consumer grade GPS units to collect step-length data for the movement of small animals that introduces a median error as small as 11 cm. These small error rates were measured in controlled observations of real butterfly movement. Similar conclusions were reached using a ground-truth test track prepared with a field tape and compass and subsequently measured 20 times using the same methodology as the butterfly tracking. Median error in the ground-truth track was slightly higher than the field data, mostly between 20 and 30 cm, but even for the smallest ground-truth step (70 cm, this is still a signal-to-noise ratio of 3:1, and for steps of 3 m or more, the ratio is greater than 10:1. Such small errors relative to the movements being measured make these inexpensive units useful for measuring insect and other small animal movements on small to intermediate scales with budgets orders of magnitude lower than survey-grade units used in past studies. As an additional advantage, these units are simpler to operate, and insect or other small animal trackways can be collected more quickly than either survey-grade units or more traditional ruler/gird approaches.

Human Enteroids as a Model of Upper Small Intestinal Ion Transport Physiology and Pathophysiology

NARCIS (Netherlands)

J. Foulke-Abel (Jennifer); J. In (Julie); Yin, J. (Jianyi); N.C. Zachos (Nicholas C.); O. Kovbasnjuk (Olga); M.K. Estes (Mary K.); H.R. de Jonge (Hugo); M. Donowitz (Mark)

2016-01-01

textabstractBackground & Aims Human intestinal crypt-derived enteroids are a model of intestinal ion transport that require validation by comparison with cell culture and animal models. We used human small intestinal enteroids to study neutral Na+ absorption and stimulated fluid and anion secretion

Investigation of incidence and risk factors for surgical glove perforation in small animal surgery.

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Hayes, Galina M; Reynolds, Deborah; Moens, Noel M M; Singh, Ameet; Oblak, Michelle; Gibson, Thomas W G; Brisson, Brigitte A; Nazarali, Alim; Dewey, Cate

2014-05-01

To identify incidence and risk factors for surgical glove perforation in small animal surgery. Observational cohort study. Surgical gloves (n = 2132) worn in 363 surgical procedures. All gloves worn by operative personnel were assessed for perforation at end-procedure using a water leak test. Putative risk factors were recorded by a surgical team member. Associations between risk factors and perforation were assessed using multivariable multi-level random-effects logistic regression models to control for hierarchical data structure. At least 1 glove perforation occurred in 26.2% of procedures. Identified risk factors for glove perforation included increased surgical duration (surgery >1 hour OR = 1.79, 95% CI = 1.12-2.86), performing orthopedic procedures (OR = 1.88; 95% CI = 1.23-2.88), any procedure using powered instruments (OR = 1.93; 95% CI = 1.21-3.09) or surgical wire (OR = 3.02; 95% CI = 1.50-6.05), use of polyisoprene as a glove material (OR = 1.59, 95% CI = 1.05-2.39), and operative role as primary surgeon (OR = 2.01; 95% CI = 1.35-2.98). The ability of the wearer to detect perforations intraoperatively was poor, with a sensitivity of 30.8%. There is a high incidence of unrecognized glove perforations in small animal surgery. © Copyright 2014 by The American College of Veterinary Surgeons.

Studying the Immunomodulatory Effects of Small Molecule Ras Inhibitors in Animal Models of Rheumatoid Arthritis

Science.gov (United States)

2016-10-01

collaboration with Concordia Pharmaceuticals Inc., FTS was developed into and oral drug, Salirasib®. The drug has been already tested in the clinic for the...animal model for RA − imply that FTS attenuates disease manifestation, as assessed by: clinical scores; MRI imaging; histopathology; and serum levels...inflammation/damage and the immune response, as follows: arthritis clinical scores; MRI scans, micro-CT; histopathology examination by a blinded pathologist

Development of Input Function Measurement System for Small Animal PET Study

International Nuclear Information System (INIS)

Kim, Jong Guk; Kim, Byung Su; Kim, Jin Su

2010-01-01

For quantitative measurement of radioactivity concentration in tissue and a validated tracer kinetic model, the high sensitive detection system has been required for blood sampling. With the accurate measurement of time activity curves (TACs) of labeled compounds in blood (plasma) enable to provide quantitative information on biological parameters of interest in local tissue. Especially, the development of new tracers for PET imaging requires knowledge of the kinetics of the tracer in the body and in arterial blood and plasma. Conventional approaches of obtaining an input function are to sample arterial blood sequentially by manual as a function of time. Several continuous blood sampling systems have been developed and used in nuclear medicine research field to overcome the limited temporal resolution in sampling by the conventional method. In this work, we developed the high sensitive and unique geometric design of GSO detector for small animal blood activity measurement

Ethical dilemmas encountered by small animal veterinarians: characterisation, responses, consequences and beliefs regarding euthanasia.

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Kipperman, Barry; Morris, Patricia; Rollin, Bernard

2018-05-12

Small animal veterinarians' opinions were investigated regarding the frequency and nature of ethical dilemmas encountered, beliefs regarding euthanasia and balancing client and animal interests, prevalence and value of ethics training and proposals to mitigate the stressful effects of ethical dilemmas. The majority (52 per cent) of 484 respondents in the USA indicated via an online survey experiencing an ethical dilemma regarding the interests of clients and those of their patients at least weekly. Scenarios involving client financial concerns were commonly reported causes of ethical conflicts. While only 20 per cent of respondents indicated that other practitioners prioritise patient interests, 50 per cent of respondents characterised their own behaviour as prioritising patients. Most respondents (52 per cent) reported that ethical dilemmas are the leading cause, or are one of many equal causes, of work-related stress. Less experienced practitioners, general practitioners and associate veterinarians were more likely to encounter situations they defined as ethical dilemmas, and female respondents were more likely to find ethical dilemmas stressful. Most small animal veterinarians experience ethical dilemmas regularly, which contribute to moral stress. Results suggested that most small animal practitioners believe that greater awareness of moral stress and providing training in ethical theories and tools for coping with ethical dilemmas can ameliorate moral stress. © British Veterinary Association (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Social defeat models in animal science: What we have learned from rodent models.

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Toyoda, Atsushi

2017-07-01

Studies on stress and its impacts on animals are very important in many fields of science, including animal science, because various stresses influence animal production and animal welfare. In particular, the social stresses within animal groups have profound impact on animals, with the potential to induce abnormal behaviors and health problems. In humans, social stress induces several health problems, including psychiatric disorders. In animal stress models, social defeat models are well characterized and used in various research fields, particularly in studies concerning mental disorders. Recently, we have focused on behavior, nutrition and metabolism in rodent models of social defeat to elucidate how social stresses affect animals. In this review, recent significant progress in studies related to animal social defeat models are described. In the field of animal science, these stress models may contribute to advances in the development of functional foods and in the management of animal welfare. © 2017 The Authors. Animal Science Journal published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Animal Science.

Osteoarthritis: new insights in animal models.

Science.gov (United States)

Longo, Umile Giuseppe; Loppini, Mattia; Fumo, Caterina; Rizzello, Giacomo; Khan, Wasim Sardar; Maffulli, Nicola; Denaro, Vincenzo

2012-01-01

Osteoarthritis (OA) is the most frequent and symptomatic health problem in the middle-aged and elderly population, with over one-half of all people over the age of 65 showing radiographic changes in painful knees. The aim of the present study was to perform an overview on the available animal models used in the research field on the OA. Discrepancies between the animal models and the human disease are present. As regards human 'idiopathic' OA, with late onset and slow progression, it is perhaps wise not to be overly enthusiastic about animal models that show severe chondrodysplasia and very early OA. Advantage by using genetically engineered mouse models, in comparison with other surgically induced models, is that molecular etiology is known. Find potential molecular markers for the onset of the disease and pay attention to the role of gender and environmental factors should be very helpful in the study of mice that acquire premature OA. Surgically induced destabilization of joint is the most widely used induction method. These models allow the temporal control of disease induction and follow predictable progression of the disease. In animals, ACL transection and meniscectomy show a speed of onset and severity of disease higher than in humans after same injury.

Modelos animais de aneurisma de aorta Animal models of aortic aneurysm

Directory of Open Access Journals (Sweden)

Rodrigo Argenta

2009-06-01

of this device in the vessel wall. Significant disadvantages include difficulty in handling, high costs, difficult maintenance, and government regulations, hindering the availability of several animal species. Small animal models, such as rabbits and mice, despite being inexpensive and easily available, are not appropriate for studies of endovascular techniques because of their small-diameter vessels. To date, none of the models described could mimic all features of human aneurysms. In this review, we describe the available models and discuss their advantages and limitations.

Animal models of osteoporosis - necessity and limitations

Directory of Open Access Journals (Sweden)

Turner A. Simon

2001-06-01

Full Text Available There is a great need to further characterise the available animal models for postmenopausal osteoporosis, for the understanding of the pathogenesis of the disease, investigation of new therapies (e.g. selective estrogen receptor modulators (SERMs and evaluation of prosthetic devices in osteoporotic bone. Animal models that have been used in the past include non-human primates, dogs, cats, rodents, rabbits, guinea pigs and minipigs, all of which have advantages and disadvantages. Sheep are a promising model for various reasons: they are docile, easy to handle and house, relatively inexpensive, available in large numbers, spontaneously ovulate, and the sheep's bones are large enough to evaluate orthopaedic implants. Most animal models have used females and osteoporosis in the male has been largely ignored. Recently, interest in development of appropriate prosthetic devices which would stimulate osseointegration into osteoporotic, appendicular, axial and mandibular bone has intensified. Augmentation of osteopenic lumbar vertebrae with bioactive ceramics (vertebroplasty is another area that will require testing in the appropriate animal model. Using experimental animal models for the study of these different facets of osteoporosis minimizes some of the difficulties associated with studying the disease in humans, namely time and behavioral variability among test subjects. New experimental drug therapies and orthopaedic implants can potentially be tested on large numbers of animals subjected to a level of experimental control impossible in human clinical research.

A small animal peripheral challenge model of yellow fever using interferon-receptor deficient mice and the 17D-204 vaccine strain.

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Thibodeaux, Brett A; Garbino, Nina C; Liss, Nathan M; Piper, Joseph; Blair, Carol D; Roehrig, John T

2012-05-02

Yellow fever virus (YFV), a member of the genus Flavivirus, is a mosquito-borne pathogen that requires wild-type (wt), virulent strains to be handled at biosafety level (BSL) 3, with HEPA-filtration of room air exhaust (BSL3+). YFV is found in tropical regions of Africa and South America and causes severe hepatic disease and death in humans. Despite the availability of effective vaccines (17D-204 or 17DD), YFV is still responsible for an estimated 200,000 cases of illness and 30,000 deaths annually. Besides vaccination, there are no other prophylactic or therapeutic strategies approved for use in human YF. Current small animal models of YF require either intra-cranial inoculation of YF vaccine to establish infection, or use of wt strains (e.g., Asibi) in order to achieve pathology. We have developed and characterized a BSL2, adult mouse peripheral challenge model for YFV infection in mice lacking receptors for interferons α, β, and γ (strain AG129). Intraperitoneal challenge of AG129 mice with 17D-204 is a uniformly lethal in a dose-dependent manner, and 17D-204-infected AG129 mice exhibit high viral titers in both brain and liver suggesting this infection is both neurotropic and viscerotropic. Furthermore the use of a mouse model permitted the construction of a 59-biomarker multi-analyte profile (MAP) using samples of brain, liver, and serum taken at multiple time points over the course of infection. This MAP serves as a baseline for evaluating novel therapeutics and their effect on disease progression. Changes (4-fold or greater) in serum and tissue levels of pro- and anti-inflammatory mediators as well as other factors associated with tissue damage were noted in AG129 mice infected with 17D-204 as compared to mock-infected control animals. Published by Elsevier Ltd.

SU-E-T-457: Design and Characterization of An Economical 192Ir Hemi-Brain Small Animal Irradiator

International Nuclear Information System (INIS)

Grams, M; Wilson, Z; Sio, T; Beltran, C; Tryggestad, E; Gupta, S; Blackwell, C; McCollough, K; Sarkaria, J; Furutani, K

2014-01-01

Purpose: To describe the design and dosimetric characterization of a simple and economical small animal irradiator. Methods: A high dose rate 192Ir brachytherapy source from a commercially available afterloader was used with a 1.3 centimeter thick tungsten collimator to provide sharp beam penumbra suitable for hemi-brain irradiation of mice. The unit is equipped with continuous gas anesthesia to allow robust animal immobilization. Dosimetric characterization of the device was performed with Gafchromic film. The penumbra from the small animal irradiator was compared under similar collimating conditions to the penumbra from 6 MV photons, 6 MeV electrons, and 20 MeV electrons from a linear accelerator as well as 300 kVp photons from an orthovoltage unit and Monte Carlo simulated 90 MeV protons. Results: The tungsten collimator provides a sharp penumbra suitable for hemi-brain irradiation, and dose rates on the order of 200 cGy/minute were achieved. The sharpness of the penumbra attainable with this device compares favorably to those measured experimentally for 6 MV photons, and 6 and 20 MeV electron beams from a linear accelerator. Additionally, the penumbra was comparable to those measured for a 300 kVp orthovoltage beam and a Monte Carlo simulated 90 MeV proton beam. Conclusions: The small animal irradiator described here can be built for under $1,000 and used in conjunction with any commercial brachytherapy afterloader to provide a convenient and cost-effective option for small animal irradiation experiments. The unit offers high dose rate delivery and sharp penumbra, which is ideal for hemi-brain irradiation of mice. With slight modifications to the design, irradiation of sites other than the brain could be accomplished easily. Due to its simplicity and low cost, the apparatus described is an attractive alternative for small animal irradiation experiments requiring a sharp penumbra

Animal models for microbicide safety and efficacy testing.

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Veazey, Ronald S

2013-07-01

Early studies have cast doubt on the utility of animal models for predicting success or failure of HIV-prevention strategies, but results of multiple human phase 3 microbicide trials, and interrogations into the discrepancies between human and animal model trials, indicate that animal models were, and are, predictive of safety and efficacy of microbicide candidates. Recent studies have shown that topically applied vaginal gels, and oral prophylaxis using single or combination antiretrovirals are indeed effective in preventing sexual HIV transmission in humans, and all of these successes were predicted in animal models. Further, prior discrepancies between animal and human results are finally being deciphered as inadequacies in study design in the model, or quite often, noncompliance in human trials, the latter being increasingly recognized as a major problem in human microbicide trials. Successful microbicide studies in humans have validated results in animal models, and several ongoing studies are further investigating questions of tissue distribution, duration of efficacy, and continued safety with repeated application of these, and other promising microbicide candidates in both murine and nonhuman primate models. Now that we finally have positive correlations with prevention strategies and protection from HIV transmission, we can retrospectively validate animal models for their ability to predict these results, and more importantly, prospectively use these models to select and advance even safer, more effective, and importantly, more durable microbicide candidates into human trials.

An application of a new planar positron imaging system (PPIS) in a small animal. MPTP-induced parkinsonism in mouse

International Nuclear Information System (INIS)

Takamatsu, Hiroyuki; Noda, Akihiro; Kakiuchi, Takeharu

2004-01-01

Recent animal PET research has led to the development of PET scanners for small animals. A planar positron imaging system (PPIS) was newly developed to study physiological function in small animals and plants in recent years. To examine the usefulness of PPIS for functional study in small animals, we examined dopaminergic images of mouse striata in MPTP-induced parkinsonism. Male C57BL/6NCrj mice were treated with MPTP 7 days before the PPIS study. Scans were performed to measure dopamine D 1 receptor binding and dopamine transporter availability with [ 11 C]SCH23390 (about 2 MBq) and [ 11 C]β-CFT (about 2 MBq), respectively. After the PPIS study, dopamine content in the striatum was measured by high-performance liquid chromatography (HPLC). The MPTP treatment significantly reduced dopamine content in the striatum 7 days after treatment. In the MPTP-treated group, [ 11 C]β-CFT binding in the striatum was significantly decreased compared with the control group, while striatal [ 11 C]SCH23390 binding was not affected. Dopamine content in the striatum was significantly correlated with the striatal binding of [ 11 C]β-CFT. The present results suggest that PPIS is able to determine brain function in a small animal. Using PPIS, high throughput imaging of small animal brain functions could be achieved. (author)

Animal Models of Chemotherapy-induced Mucositis

DEFF Research Database (Denmark)

Sangild, Per T; Shen, René Liang; Pontoppidan, Peter Erik Lotko

2018-01-01

constitution). Here, we briefly describe CIM pathophysiology, particularly the basic knowledge that has been obtained from CIM animal models. These model studies have indicated potential new preventive and ameliorating interventions, including supplementation with natural bioactive diets (e.g. milk fractions...... easier make clinically-relevant treatment regimens possible. In synergy, animal models improve the basic pathophysiological understanding of CIM and provide new ideas for treatment that are required to make competent decisions in clinical practice....

Noninvasive Assessment of Tumor Cell Proliferation in Animal Models

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Matthias Edinger

1999-10-01

Full Text Available Revealing the mechanisms of neoplastic disease and enhancing our ability to intervene in these processes requires an increased understanding of cellular and molecular changes as they occur in intact living animal models. We have begun to address these needs by developing a method of labeling tumor cells through constitutive expression of an optical reporter gene, noninvasively monitoring cellular proliferation in vivo using a sensitive photon detection system. A stable line of HeLa cells that expressed a modified firefly luciferase gene was generated, proliferation of these cells in irradiated severe combined immunodeficiency (SCID mice was monitored. Tumor cells were introduced into animals via subcutaneous, intraperitoneal and intravenous inoculation and whole body images, that revealed tumor location and growth kinetics, were obtained. The number of photons that were emitted from the labeled tumor cells and transmitted through murine tissues was sufficient to detect 1×103 cells in the peritoneal cavity, 1×104 cells at subcutaneous sites and 1×106 circulating cells immediately following injection. The kinetics of cell proliferation, as measured by photon emission, was exponential in the peritoneal cavity and at subcutaneous sites. Intravenous inoculation resulted in detectable colonies of tumor cells in animals receiving more than 1×103 cells. Our demonstrated ability to detect small numbers of tumor cells in living animals noninvasively suggests that therapies designed to treat minimal disease states, as occur early in the disease course and after elimination of the tumor mass, may be monitored using this approach. Moreover, it may be possible to monitor micrometastases and evaluate the molecular steps in the metastatic process. Spatiotemporal analyses of neoplasia will improve the predictability of animal models of human disease as study groups can be followed over time, this method will accelerate development of novel therapeutic

Collimator optimization for small animal radiation therapy at a micro-CT

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Felix, Manuela C. [Heidelberg Univ., Mannheim (Germany). Medical Radiation Physics/Radiation Protection; Heidelberg Univ., Mannheim (Germany). Dept. of Radiation Oncology; Glatting, Gerhard [Heidelberg Univ., Mannheim (Germany). Medical Radiation Physics/Radiation Protection; Giordano, Frank A.; Wenz, Frederik; Fleckenstein, Jens [Heidelberg Univ., Mannheim (Germany). Dept. of Radiation Oncology; Brockmann, Marc A. [Heidelberg Univ., Mannheim (Germany). Dept. of Neuroradiology; University Medical Center Mainz (Germany). Dept. of Neuroradiology

2017-05-01

In radiation therapy of small animals treatment depths range from a few millimetres to several centimetres. In order to spare surrounding organs at risk steep dose gradients are necessary. To minimize the treatment time, and therefore the strain to the animals, a high dose rate is required. A description how these parameters can be optimized through an appropriate choice of collimators with different source surface distances (SSD) as well as different materials and geometries is presented. An industrial micro-CT unit (Y.Fox, YXLON GmbH, Hamburg, Germany) was converted into a precision irradiator for small animals. Different collimators of either stainless steel (Fe) with cylindrical bores (SSD = 42 mm) or tungsten (W) with conical bores (SSD = 14 mm) were evaluated. The dosimetry of very small radiation fields presents a challenge and was performed with GafChromic EBT3 films (Ashland, Vayne, KY, USA) in a water phantom. The films were calibrated with an ionization chamber in the uncollimated field. Treatments were performed via a rotation of the objects with a fixed radiation source. As expected, the shorter SSD of the W-collimators resulted in a (4.5 ± 1.6)-fold increase of the dose rates compared to the corresponding Fe-collimators. The ratios of the dose rates at 1 mm and 10 mm depth in the water phantom was (2.6 ± 0.2) for the Fe- and (4.5 ± 0.1) for the W-collimators. For rotational treatments in a cylindrical plastic phantom maximum dose rates of up to 1.2 Gy/min for Fe- and 5.1 Gy/min for W-collimators were measured. Choosing the smallest possible SSD leads to a high dose rate and a high surface dose, which is of advantage for the treatment of superficial target volumes. For larger SSD the dose rate is lower and the depth dose curve is shallower. This leads to a reduction of the surface dose and is best suited for treatments of deeper seated target volumes. Divergent collimator bores have, due to the reduced scatter within the collimators, a steeper

High-throughput screen for novel antimicrobials using a whole animal infection model.

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Moy, Terence I; Conery, Annie L; Larkins-Ford, Jonah; Wu, Gang; Mazitschek, Ralph; Casadei, Gabriele; Lewis, Kim; Carpenter, Anne E; Ausubel, Frederick M

2009-07-17

The nematode Caenorhabditis elegans is a unique whole animal model system for identifying small molecules with in vivo anti-infective properties. C. elegans can be infected with a broad range of human pathogens, including Enterococcus faecalis, an important human nosocomial pathogen. Here, we describe an automated, high-throughput screen of 37,200 compounds and natural product extracts for those that enhance survival of C. elegans infected with E. faecalis. Using a robot to dispense live, infected animals into 384-well plates and automated microscopy and image analysis, we identified 28 compounds and extracts not previously reported to have antimicrobial properties, including six structural classes that cure infected C. elegans animals but do not affect the growth of the pathogen in vitro, thus acting by a mechanism of action distinct from antibiotics currently in clinical use.

Computer aided vertebral visualization and analysis: a methodology using the sand rat, a small animal model of disc degeneration

Directory of Open Access Journals (Sweden)

Hanley Edward N

2003-03-01

Full Text Available Abstract Background The purpose of this study is to present an automated system that analyzes digitized x-ray images of small animal spines identifying the effects of disc degeneration. The age-related disc and spine degeneration that occurs in the sand rat (Psammomys obesus has previously been documented radiologically; selected representative radiographs with age-related changes were used here to develop computer-assisted vertebral visualization/analysis techniques. Techniques presented here have the potential to produce quantitative algorithms that create more accurate and informative measurements in a time efficient manner. Methods Signal and image processing techniques were applied to digitized spine x-ray images the spine was segmented, and orientation and curvature determined. The image was segmented based on orientation changes of the spine; edge detection was performed to define vertebral boundaries. Once vertebrae were identified, a number of measures were introduced and calculated to retrieve information on the vertebral separation/orientation and sclerosis. Results A method is described which produces computer-generated quantitative measurements of vertebrae and disc spaces. Six sand rat spine radiographs illustrate applications of this technique. Results showed that this method can successfully automate calculation and analysis of vertebral length, vertebral spacing, vertebral angle, and can score sclerosis. Techniques also provide quantitative means to explore the relation between age and vertebral shape. Conclusions This method provides a computationally efficient system to analyze spinal changes during aging. Techniques can be used to automate the quantitative processing of vertebral radiographic images and may be applicable to human and other animal radiologic models of the aging/degenerating spine.

Animal models for dengue vaccine development and testing.

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Na, Woonsung; Yeom, Minjoo; Choi, Il-Kyu; Yook, Heejun; Song, Daesub

2017-07-01

Dengue fever is a tropical endemic disease; however, because of climate change, it may become a problem in South Korea in the near future. Research on vaccines for dengue fever and outbreak preparedness are currently insufficient. In addition, because there are no appropriate animal models, controversial results from vaccine efficacy assessments and clinical trials have been reported. Therefore, to study the mechanism of dengue fever and test the immunogenicity of vaccines, an appropriate animal model is urgently needed. In addition to mouse models, more suitable models using animals that can be humanized will need to be constructed. In this report, we look at the current status of model animal construction and discuss which models require further development.

Biological X-ray irradiator characterization for use with small animals and cells.

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Bruno, A Colello; Mazaro, S J; Amaral, L L; Rego, E M; Oliveira, H F; Pavoni, J F

2017-03-02

This study presents the characterization of an X-ray irradiator through dosimetric tests, which confirms the actual dose rate that small animals and cells will be exposed to during radiobiological experiments. We evaluated the linearity, consistency, repeatability, and dose distribution in the positions in which the animals or cells are placed during irradiation. In addition, we evaluated the performance of the X-ray tube (voltage and tube operating current), the radiometric survey (leakage radiation) and safety devices. The irradiator default setting was established as 160 kV and 25 mA. Tests showed that the dose rate was linear overtime (R2=1) and remained stable for long (constant) and short (repeatability) intervals between readings. The mean dose rate inside the animal cages was 1.27±0.06 Gy/min with a uniform beam of 95.40% (above the minimum threshold guaranteed by the manufacturer). The mean dose rate inside the cell plates was 0.92±0.19 Gy/min. The dose rate dependence with tube voltage and current presented a quadratic and linear relationship, respectively. There was no observed mechanical failure during evaluation of the irradiator safety devices and the radiometric survey obtained a maximum ambient equivalent dose rate of 0.26 mSv/h, which exempts it from the radiological protection requirements of the International Atomic Energy Agency. The irradiator characterization enables us to perform radiobiological experiments, and assists or even replaces traditional therapy equipment (e.g., linear accelerators) for cells and small animal irradiation, especially in early research stages.

Biological X-ray irradiator characterization for use with small animals and cells

Directory of Open Access Journals (Sweden)

A. Colello Bruno

Full Text Available This study presents the characterization of an X-ray irradiator through dosimetric tests, which confirms the actual dose rate that small animals and cells will be exposed to during radiobiological experiments. We evaluated the linearity, consistency, repeatability, and dose distribution in the positions in which the animals or cells are placed during irradiation. In addition, we evaluated the performance of the X-ray tube (voltage and tube operating current, the radiometric survey (leakage radiation and safety devices. The irradiator default setting was established as 160 kV and 25 mA. Tests showed that the dose rate was linear overtime (R2=1 and remained stable for long (constant and short (repeatability intervals between readings. The mean dose rate inside the animal cages was 1.27±0.06 Gy/min with a uniform beam of 95.40% (above the minimum threshold guaranteed by the manufacturer. The mean dose rate inside the cell plates was 0.92±0.19 Gy/min. The dose rate dependence with tube voltage and current presented a quadratic and linear relationship, respectively. There was no observed mechanical failure during evaluation of the irradiator safety devices and the radiometric survey obtained a maximum ambient equivalent dose rate of 0.26 mSv/h, which exempts it from the radiological protection requirements of the International Atomic Energy Agency. The irradiator characterization enables us to perform radiobiological experiments, and assists or even replaces traditional therapy equipment (e.g., linear accelerators for cells and small animal irradiation, especially in early research stages.

Stem cell therapy for joint problems using the horse as a clinically relevant animal model

DEFF Research Database (Denmark)

Koch, Thomas Gadegaard; Betts, Dean H.

2007-01-01

of experimentally induced lesions. The horse lends itself as a good animal model of spontaneous joint disorders that are clinically relevant to similar human disorders. Equine stem cell and tissue engineering studies may be financially feasible to principal investigators and small biotechnology companies...

A 3D HIDAC-PET camera with sub-millimeter resolution for imaging small animals

International Nuclear Information System (INIS)

Jeavons, A.P.; Chandler, R.A.; Dettmar, C.A.R.

1999-01-01

A HIDAC-PET camera consisting essentially of 5 million 0.5 mm gas avalanching detectors has been constructed for small-animal imaging. The particular HIDAC advantage--a high 3D spatial resolution--has been improved to 0.95 mm fwhm and to 0.7 mm fwhm when reconstructing with 3D-OSEM methods incorporating resolution recovery. A depth-of-interaction resolution of 2.5 mm is implicit, due to the laminar construction. Scatter-corrected sensitivity, at 8.9 cps/kBq (i.e. 0.9%) from a central point source, or 7.2 cps/kBq (543 cps/kBq/cm 3 ) from a distributed (40 mm diameter, 60 mm long) source is now much higher than previous, and other, work. A field-of-view of 100 mm (adjustable to 200 mm) diameter by 210 mm axially permits whole-body imaging of small animals, containing typically 4MBqs of activity, at 40 kcps of which 16% are random coincidences, with a typical scatter fraction of 44%. Throughout the field-of-view there are no positional distortions and relative quantitation is uniform to ± 3.5%, but some variation of spatial resolution is found. The performance demonstrates that HIDAC technology is quite appropriate for small-animal PET cameras

Animal Model of Sensorineural Hearing Loss Associated with Lassa Virus Infection.

Science.gov (United States)

Yun, Nadezhda E; Ronca, Shannon; Tamura, Atsushi; Koma, Takaaki; Seregin, Alexey V; Dineley, Kelly T; Miller, Milagros; Cook, Rebecca; Shimizu, Naoki; Walker, Aida G; Smith, Jeanon N; Fair, Joseph N; Wauquier, Nadia; Bockarie, Bayon; Khan, Sheik Humarr; Makishima, Tomoko; Paessler, Slobodan

2015-12-30

Approximately one-third of Lassa virus (LASV)-infected patients develop sensorineural hearing loss (SNHL) in the late stages of acute disease or in early convalescence. With 500,000 annual cases of Lassa fever (LF), LASV is a major cause of hearing loss in regions of West Africa where LF is endemic. To date, no animal models exist that depict the human pathology of LF with associated hearing loss. Here, we aimed to develop an animal model to study LASV-induced hearing loss using human isolates from a 2012 Sierra Leone outbreak. We have recently established a murine model for LF that closely mimics many features of human disease. In this model, LASV isolated from a lethal human case was highly virulent, while the virus isolated from a nonlethal case elicited mostly mild disease with moderate mortality. More importantly, both viruses were able to induce SNHL in surviving animals. However, utilization of the nonlethal, human LASV isolate allowed us to consistently produce large numbers of survivors with hearing loss. Surviving mice developed permanent hearing loss associated with mild damage to the cochlear hair cells and, strikingly, significant degeneration of the spiral ganglion cells of the auditory nerve. Therefore, the pathological changes in the inner ear of the mice with SNHL supported the phenotypic loss of hearing and provided further insights into the mechanistic cause of LF-associated hearing loss. Sensorineural hearing loss is a major complication for LF survivors. The development of a small-animal model of LASV infection that replicates hearing loss and the clinical and pathological features of LF will significantly increase knowledge of pathogenesis and vaccine studies. In addition, such a model will permit detailed characterization of the hearing loss mechanism and allow for the development of appropriate diagnostic approaches and medical care for LF patients with hearing impairment. Copyright © 2016, American Society for Microbiology. All Rights

Animal models of pancreatic cancer for drug research.

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Kapischke, Matthias; Pries, Alexandra

2008-10-01

The operative and conservative results of therapy in pancreatic ductal adenocarcinoma remain appallingly poor. This underlines the demand for further research for effective anticancer drugs. The various animal models remain the essential method for the determination of efficacy of substances during preclinical phase. Unfortunately, most of these tested substances showed a good efficacy in pancreatic carcinoma in the animal model but were not confirmed during the clinical phase. The available literature in PubMed, Medline, Ovid and secondary literature was searched regarding the available animal models for drug testing against pancreatic cancer. The models were analyzed regarding their pros and cons in anticancer drug testing. The different modifications of the orthotopic model (especially in mice) seem at present to be the best model for anticancer testing in pancreatic carcinoma. The value of genetically engineered animal model (GEM) and syngeneic models is on debate. A good selection of the model concerning the questions supposed to be clarified may improve the comparability of the results of animal experiments compared to clinical trials.

Animal models of cardiac cachexia.

Science.gov (United States)

Molinari, Francesca; Malara, Natalia; Mollace, Vincenzo; Rosano, Giuseppe; Ferraro, Elisabetta

2016-09-15

Cachexia is the loss of body weight associated with several chronic diseases including chronic heart failure (CHF). The cachectic condition is mainly due to loss of skeletal muscle mass and adipose tissue depletion. The majority of experimental in vivo studies on cachexia rely on animal models of cancer cachexia while a reliable and appropriate model for cardiac cachexia has not yet been established. A critical issue in generating a cardiac cachexia model is that genetic modifications or pharmacological treatments impairing the heart functionality and used to obtain the heart failure model might likely impair the skeletal muscle, this also being a striated muscle and sharing with the myocardium several molecular and physiological mechanisms. On the other hand, often, the induction of heart damage in the several existing models of heart failure does not necessarily lead to skeletal muscle loss and cachexia. Here we describe the main features of cardiac cachexia and illustrate some animal models proposed for cardiac cachexia studies; they include the genetic calsequestrin and Dahl salt-sensitive models, the monocrotaline model and the surgical models obtained by left anterior descending (LAD) ligation, transverse aortic constriction (TAC) and ascending aortic banding. The availability of a specific animal model for cardiac cachexia is a crucial issue since, besides the common aspects of cachexia in the different syndromes, each disease has some peculiarities in its etiology and pathophysiology leading to cachexia. Such peculiarities need to be unraveled in order to find new targets for effective therapies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

9.4 T small animal MRI using clinical components for direct translational studies.

Science.gov (United States)

Felder, Jörg; Celik, A Avdo; Choi, Chang-Hoon; Schwan, Stefan; Shah, N Jon

2017-12-28

Magnetic resonance is a major preclinical and clinical imaging modality ideally suited for longitudinal studies, e.g. in pharmacological developments. The lack of a proven platform that maintains an identical imaging protocol between preclinical and clinical platforms is solved with the construction of an animal scanner based on clinical hard- and software. A small animal magnet and gradient system were connected to a clinical MR system. Several hardware components were either modified or built in-house to achieve compatibility. The clinical software was modified to account for the different field-of-view of a preclinical MR system. The established scanner was evaluated using clinical QA protocols, and platform compatibility for translational research was verified against clinical scanners of different field strength. The constructed animal scanner operates with the majority of clinical imaging sequences. Translational research is greatly facilitated as protocols can be shared between preclinical and clinical platforms. Hence, when maintaining sequences parameters, maximum similarity between pulses played out on a human or an animal system is maintained. Coupling of a small animal magnet with a clinical MR system is a flexible, easy to use way to establish and advance translational imaging capability. It provides cost and labor efficient translational capability as no tedious sequence reprogramming between moieties is required and cross-platform compatibility of sequences facilitates multi-center studies.

Animal models for auditory streaming

Science.gov (United States)

Itatani, Naoya

2017-01-01

Sounds in the natural environment need to be assigned to acoustic sources to evaluate complex auditory scenes. Separating sources will affect the analysis of auditory features of sounds. As the benefits of assigning sounds to specific sources accrue to all species communicating acoustically, the ability for auditory scene analysis is widespread among different animals. Animal studies allow for a deeper insight into the neuronal mechanisms underlying auditory scene analysis. Here, we will review the paradigms applied in the study of auditory scene analysis and streaming of sequential sounds in animal models. We will compare the psychophysical results from the animal studies to the evidence obtained in human psychophysics of auditory streaming, i.e. in a task commonly used for measuring the capability for auditory scene analysis. Furthermore, the neuronal correlates of auditory streaming will be reviewed in different animal models and the observations of the neurons’ response measures will be related to perception. The across-species comparison will reveal whether similar demands in the analysis of acoustic scenes have resulted in similar perceptual and neuronal processing mechanisms in the wide range of species being capable of auditory scene analysis. This article is part of the themed issue ‘Auditory and visual scene analysis’. PMID:28044022

The Small Heat Shock Protein α-Crystallin B Shows Neuroprotective Properties in a Glaucoma Animal Model

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Fabian Anders

2017-11-01

Full Text Available Glaucoma is a neurodegenerative disease that leads to irreversible retinal ganglion cell (RGC loss and is one of the main causes of blindness worldwide. The pathogenesis of glaucoma remains unclear, and novel approaches for neuroprotective treatments are urgently needed. Previous studies have revealed significant down-regulation of α-crystallin B as an initial reaction to elevated intraocular pressure (IOP, followed by a clear but delayed up-regulation, suggesting that this small heat-shock protein plays a pathophysiological role in the disease. This study analyzed the neuroprotective effect of α-crystallin B in an experimental animal model of glaucoma. Significant IOP elevation induced by episcleral vein cauterization resulted in a considerable impairment of the RGCs and the retinal nerve fiber layer. An intravitreal injection of α-crystallin B at the time of the IOP increase was able to rescue the RGCs, as measured in a functional photopic electroretinogram, retinal nerve fiber layer thickness, and RGC counts. Mass-spectrometry-based proteomics and antibody-microarray measurements indicated that a α-crystallin injection distinctly up-regulated all of the subclasses (α, β, and γ of the crystallin protein family. The creation of an interactive protein network revealed clear correlations between individual proteins, which showed a regulatory shift resulting from the crystallin injection. The neuroprotective properties of α-crystallin B further demonstrate the potential importance of crystallin proteins in developing therapeutic options for glaucoma.

The necessity of animal models in pain research.

Science.gov (United States)

Mogil, Jeffrey S; Davis, Karen D; Derbyshire, Stuart W

2010-10-01

There exists currently a fair degree of introspection in the pain research community about the value of animal research. This review represents a defense of animal research in pain. We discuss the inherent advantage of animal models over human research as well as the crucial complementary roles animal studies play vis-à-vis human imaging and genetic studies. Finally, we discuss recent developments in animal models of pain that should improve the relevance and translatability of findings using laboratory animals. We believe that pain research using animal models is a continuing necessity-to understand fundamental mechanisms, identify new analgesic targets, and inform, guide and follow up human studies-if novel analgesics are to be developed for the treatment of chronic pain. Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Animal models of papillomavirus pathogenesis.

Science.gov (United States)

Campo, M Saveria

2002-11-01

Tumorigenesis due to papillomavirus (PV) infection was first demonstrated in rabbits and cattle early last century. Despite the evidence obtained in animals, the role of viruses in human cancer was dismissed as irrelevant. It took a paradigm shift in the late 1970s for some viruses to be recognised as 'tumour viruses' in humans, and in 1995, more than 60 years after Rous's first demonstration of CRPV oncogenicity, WHO officially declared that 'HPV-16 and HPV-18 are carcinogenic to humans'. Experimental studies with animal PVs have been a determining factor in this decision. Animal PVs have been studied both as agents of disease in animals and as models of human PV infection. In addition to the study of PV infection in whole animals, in vitro studies with animal PV proteins have contributed greatly to the understanding of the mechanisms of cell transformation. Animal PVs cause distressing diseases in both farm and companion animals, such as teat papillomatosis in cattle, equine sarcoids and canine oral papillomatosis and there is an urgent need to understand the pathogenesis of these problematic infections. Persistent and florid teat papillomatosis in cows can lead to mastitis, prevent the suckling of calves and make milking impossible; heavily affected animals are culled and so occasionally are whole herds. Equine sarcoids are often recurrent and untreatable and lead to loss of valuable animals. Canine oral papillomatosis can be very extensive and persistent and lead to great distress. Thus the continuing research in the biology of animal PVs is amply justified. BPVs and CRPV have been for many years the model systems with which to study the biology of HPV. Induction of papillomas and their neoplastic progression has been experimentally demonstrated and reproduced in cattle and rabbits, and virus-cofactor interactions have been elucidated in these systems. With the advancements in molecular and cell culture techniques, the direct study of HPV has become less

First application of liquid-metal-jet sources for small-animal imaging: High-resolution CT and phase-contrast tumor demarcation

Energy Technology Data Exchange (ETDEWEB)

Larsson, Daniel H.; Lundstroem, Ulf; Burvall, Anna; Hertz, Hans M. [Department of Applied Physics, KTH Royal Institute of Technology/Albanova, 10691 Stockholm (Sweden); Westermark, Ulrica K.; Arsenian Henriksson, Marie [Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, 17177 Stockholm (Sweden)

2013-02-15

Purpose: Small-animal studies require images with high spatial resolution and high contrast due to the small scale of the structures. X-ray imaging systems for small animals are often limited by the microfocus source. Here, the authors investigate the applicability of liquid-metal-jet x-ray sources for such high-resolution small-animal imaging, both in tomography based on absorption and in soft-tissue tumor imaging based on in-line phase contrast. Methods: The experimental arrangement consists of a liquid-metal-jet x-ray source, the small-animal object on a rotating stage, and an imaging detector. The source-to-object and object-to-detector distances are adjusted for the preferred contrast mechanism. Two different liquid-metal-jet sources are used, one circulating a Ga/In/Sn alloy and the other an In/Ga alloy for higher penetration through thick tissue. Both sources are operated at 40-50 W electron-beam power with {approx}7 {mu}m x-ray spots, providing high spatial resolution in absorption imaging and high spatial coherence for the phase-contrast imaging. Results: High-resolution absorption imaging is demonstrated on mice with CT, showing 50 {mu}m bone details in the reconstructed slices. High-resolution phase-contrast soft-tissue imaging shows clear demarcation of mm-sized tumors at much lower dose than is required in absorption. Conclusions: This is the first application of liquid-metal-jet x-ray sources for whole-body small-animal x-ray imaging. In absorption, the method allows high-resolution tomographic skeletal imaging with potential for significantly shorter exposure times due to the power scalability of liquid-metal-jet sources. In phase contrast, the authors use a simple in-line arrangement to show distinct tumor demarcation of few-mm-sized tumors. This is, to their knowledge, the first small-animal tumor visualization with a laboratory phase-contrast system.

A small animal holding fixture system with positional reproducibility for longitudinal multimodal imaging

Energy Technology Data Exchange (ETDEWEB)

Kokuryo, Daisuke; Kimura, Yuichi; Obata, Takayuki; Yamaya, Taiga; Kawamura, Kazunori; Zhang, Ming-Rong; Kanno, Iwao; Aoki, Ichio, E-mail: ukimura@ieee.or [Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage, Chiba 263-8555 (Japan)

2010-07-21

This study presents a combined small animal holding fixture system, termed a 'bridge capsule', which provides for small animal re-fixation with positional reproducibility. This system comprises separate holding fixtures for the head and lower body and a connecting part to a gas anesthesia system. A mouse is fixed in place by the combination of a head fixture with a movable part made from polyacetal resin, a lower body fixture made from vinyl-silicone and a holder for the legs and tail. For re-fixation, a similar posture could be maintained by the same holding fixtures and a constant distance between the head and lower body fixtures is maintained. Artifacts caused by the bridge capsule system were not observed on magnetic resonance (MRI) and positron emission tomography (PET) images. The average position differences of the spinal column and the iliac body before and after re-fixation for the same modality were approximately 1.1 mm. The difference between the MRI and PET images was approximately 1.8 mm for the lower body fixture after image registration using fiducial markers. This system would be useful for longitudinal, repeated and multimodal imaging experiments requiring similar animal postures.

Animal models of preeclampsia; uses and limitations.

LENUS (Irish Health Repository)

McCarthy, F P

2012-01-31

Preeclampsia remains a leading cause of maternal and fetal morbidity and mortality and has an unknown etiology. The limited progress made regarding new treatments to reduce the incidence and severity of preeclampsia has been attributed to the difficulties faced in the development of suitable animal models for the mechanistic research of this disease. In addition, animal models need hypotheses on which to be based and the slow development of testable hypotheses has also contributed to this poor progress. The past decade has seen significant advances in our understanding of preeclampsia and the development of viable reproducible animal models has contributed significantly to these advances. Although many of these models have features of preeclampsia, they are still poor overall models of the human disease and limited due to lack of reproducibility and because they do not include the complete spectrum of pathophysiological changes associated with preeclampsia. This review aims to provide a succinct and comprehensive assessment of current animal models of preeclampsia, their uses and limitations with particular attention paid to the best validated and most comprehensive models, in addition to those models which have been utilized to investigate potential therapeutic interventions for the treatment or prevention of preeclampsia.

Anatomical and metabolic small-animal whole-body imaging using ring-shaped confocal photoacoustic computed tomography

Science.gov (United States)

Xia, Jun; Chatni, Muhammad; Maslov, Konstantin; Wang, Lihong V.

2013-03-01

Due to the wide use of animals for human disease studies, small animal whole-body imaging plays an increasingly important role in biomedical research. Currently, none of the existing imaging modalities can provide both anatomical and glucose metabolic information, leading to higher costs of building dual-modality systems. Even with image coregistration, the spatial resolution of the metabolic imaging modality is not improved. We present a ring-shaped confocal photoacoustic computed tomography (RC-PACT) system that can provide both assessments in a single modality. Utilizing the novel design of confocal full-ring light delivery and ultrasound transducer array detection, RC-PACT provides full-view cross-sectional imaging with high spatial resolution. Scanning along the orthogonal direction provides three-dimensional imaging. While the mouse anatomy was imaged with endogenous hemoglobin contrast, the glucose metabolism was imaged with a near-infrared dye-labeled 2-deoxyglucose. Through mouse tumor models, we demonstrate that RC-PACT may be a paradigm shifting imaging method for preclinical research.

Neurological examination in small animals

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Viktor Paluš

2014-03-01

Full Text Available This clinical review about the neurological examination in small animals describes the basics about the first steps of investigation when dealing with neurological patients. The knowledge of how to perform the neurological examination is important however more important is how to correctly interpret these performed tests. A step-by-step approach is mandatory and examiners should master the order and the style of performing these tests. Neurological conditions can be sometimes very distressing for owners and for pets that might not be the most cooperating. The role of a veterinary surgeon, as a professional, is therefore to collect the most relevant history, to examine a patient in a professional manner and to give to owners an educated opinion about the further treatment and prognosis. However neurological examinations might look challenging for many. But it is only the clinical application of neuroanatomy and neurophysiology to an every-day situation for practicing veterinarians and it does not require any specific in-to-depth knowledge. This clinical review is aimed not only to provide the information on how to perform the neurological examination but it is also aimed to appeal on veterinarians to challenge their daily routine and to start practicing on neurologically normal patients. This is the best and only way to differentiate between the normal and abnormal in a real situation.

An animal model that reflects human disease: the common marmoset (Callithrix jacchus).

Science.gov (United States)

Carrion, Ricardo; Patterson, Jean L

2012-06-01

The common marmoset is a new world primate belonging to the Callitrichidae family weighing between 350 and 400 g. The marmoset has been shown to be an outstanding model for studying aging, reproduction, neuroscience, toxicology, and infectious disease. With regard to their susceptibility to infectious agents, they are exquisite NHP models for viral, protozoan and bacterial agents, as well as prions. The marmoset provides the advantages of a small animal model in high containment coupled with the immunological repertoire of a nonhuman primate and susceptibility to wild type, non-adapted viruses. Copyright © 2012 Elsevier B.V. All rights reserved.

Animation of 3D Model of Human Head

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V. Michalcin

2007-04-01

Full Text Available The paper deals with the new algorithm of animation of 3D model of the human head in combination with its global motion. The designed algorithm is very fast and with low calculation requirements, because it does not need the synthesis of the input videosequence for estimation of the animation parameters as well as the parameters of global motion. The used 3D model Candide generates different expressions using its animation units which are controlled by the animation parameters. These ones are estimated on the basis of optical flow without the need of extracting of the feature points in the frames of the input videosequence because they are given by the selected vertices of the animation units of the calibrated 3D model Candide. The established multiple iterations inside the designed animation algorithm of 3D model of the human head between two successive frames significantly improved its accuracy above all for the large motion.

Animation Augmented Reality Book Model (AAR Book Model) to Enhance Teamwork

Science.gov (United States)

Chujitarom, Wannaporn; Piriyasurawong, Pallop

2017-01-01

This study aims to synthesize an Animation Augmented Reality Book Model (AAR Book Model) to enhance teamwork and to assess the AAR Book Model to enhance teamwork. Samples are five specialists that consist of one animation specialist, two communication and information technology specialists, and two teaching model design specialists, selected by…

Animal models of cerebral arterial gas embolism

NARCIS (Netherlands)

Weenink, Robert P.; Hollmann, Markus W.; van Hulst, Robert A.

2012-01-01

Cerebral arterial gas embolism is a dreaded complication of diving and invasive medical procedures. Many different animal models have been used in research on cerebral arterial gas embolism. This review provides an overview of the most important characteristics of these animal models. The properties

Zebrafish: A Versatile Animal Model for Fertility Research

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Jing Ying Hoo

2016-01-01

Full Text Available The utilization of zebrafish in biomedical research is very common in the research world nowadays. Today, it has emerged as a favored vertebrate organism for the research in science of reproduction. There is a significant growth in amount numbers of scientific literature pertaining to research discoveries in reproductive sciences in zebrafish. It has implied the importance of zebrafish in this particular field of research. In essence, the current available literature has covered from the very specific brain region or neurons of zebrafish, which are responsible for reproductive regulation, until the gonadal level of the animal. The discoveries and findings have proven that this small animal is sharing a very close/similar reproductive system with mammals. More interestingly, the behavioral characteristics and along with the establishment of animal courtship behavior categorization in zebrafish have laid an even stronger foundation and firmer reason on the suitability of zebrafish utilization in research of reproductive sciences. In view of the immense importance of this small animal for the development of reproductive sciences, this review aimed at compiling and describing the proximate close similarity of reproductive regulation on zebrafish and human along with factors contributing to the infertility, showing its versatility and its potential usage for fertility research.

Towards a reliable animal model of migraine

DEFF Research Database (Denmark)

Olesen, Jes; Jansen-Olesen, Inger

2012-01-01

The pharmaceutical industry shows a decreasing interest in the development of drugs for migraine. One of the reasons for this could be the lack of reliable animal models for studying the effect of acute and prophylactic migraine drugs. The infusion of glyceryl trinitrate (GTN) is the best validated...... and most studied human migraine model. Several attempts have been made to transfer this model to animals. The different variants of this model are discussed as well as other recent models....

X-ray micro-tomography system for small-animal imaging with zoom-in imaging capability

International Nuclear Information System (INIS)

Chun, In Kon; Cho, Myung Hye; Lee, Sang Chul; Cho, Min Hyoung; Lee, Soo Yeol

2004-01-01

Since a micro-tomography system capable of μm-resolution imaging cannot be used for whole-body imaging of a small laboratory animal without sacrificing its spatial resolution, it is desirable for a micro-tomography system to have local imaging capability. In this paper, we introduce an x-ray micro-tomography system capable of high-resolution imaging of a local region inside a small animal. By combining two kinds of projection data, one from a full field-of-view (FOV) scan of the whole body and the other from a limited FOV scan of the region of interest (ROI), we have obtained zoomed-in images of the ROI without any contrast anomalies commonly appearing in conventional local tomography. For experimental verification of the zoom-in imaging capability, we have integrated a micro-tomography system using a micro-focus x-ray source, a 1248 x 1248 flat-panel x-ray detector, and a precision scan mechanism. The mismatches between the two projection data caused by misalignments of the scan mechanism have been estimated with a calibration phantom, and the mismatch effects have been compensated in the image reconstruction procedure. Zoom-in imaging results of bony tissues with a spatial resolution of 10 lp mm -1 suggest that zoom-in micro-tomography can be greatly used for high-resolution imaging of a local region in small-animal studies

Large animal models for vaccine development and testing.

Science.gov (United States)

Gerdts, Volker; Wilson, Heather L; Meurens, Francois; van Drunen Littel-van den Hurk, Sylvia; Wilson, Don; Walker, Stewart; Wheler, Colette; Townsend, Hugh; Potter, Andrew A

2015-01-01

The development of human vaccines continues to rely on the use of animals for research. Regulatory authorities require novel vaccine candidates to undergo preclinical assessment in animal models before being permitted to enter the clinical phase in human subjects. Substantial progress has been made in recent years in reducing and replacing the number of animals used for preclinical vaccine research through the use of bioinformatics and computational biology to design new vaccine candidates. However, the ultimate goal of a new vaccine is to instruct the immune system to elicit an effective immune response against the pathogen of interest, and no alternatives to live animal use currently exist for evaluation of this response. Studies identifying the mechanisms of immune protection; determining the optimal route and formulation of vaccines; establishing the duration and onset of immunity, as well as the safety and efficacy of new vaccines, must be performed in a living system. Importantly, no single animal model provides all the information required for advancing a new vaccine through the preclinical stage, and research over the last two decades has highlighted that large animals more accurately predict vaccine outcome in humans than do other models. Here we review the advantages and disadvantages of large animal models for human vaccine development and demonstrate that much of the success in bringing a new vaccine to market depends on choosing the most appropriate animal model for preclinical testing. © The Author 2015. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Elements of episodic-like memory in animal models.

Science.gov (United States)

Crystal, Jonathon D

2009-03-01

Representations of unique events from one's past constitute the content of episodic memories. A number of studies with non-human animals have revealed that animals remember specific episodes from their past (referred to as episodic-like memory). The development of animal models of memory holds enormous potential for gaining insight into the biological bases of human memory. Specifically, given the extensive knowledge of the rodent brain, the development of rodent models of episodic memory would open new opportunities to explore the neuroanatomical, neurochemical, neurophysiological, and molecular mechanisms of memory. Development of such animal models holds enormous potential for studying functional changes in episodic memory in animal models of Alzheimer's disease, amnesia, and other human memory pathologies. This article reviews several approaches that have been used to assess episodic-like memory in animals. The approaches reviewed include the discrimination of what, where, and when in a radial arm maze, dissociation of recollection and familiarity, object recognition, binding, unexpected questions, and anticipation of a reproductive state. The diversity of approaches may promote the development of converging lines of evidence on the difficult problem of assessing episodic-like memory in animals.

Pain control in small animalsControle da dor em pequenos animais

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Julia Duarte Penter

2011-12-01

Full Text Available Pain is an unpleasant sensory or emotional experience that follows the application of a noxious stimulus. Can be experienced with or without the concomitant occurrence of physical stress signs, which occurs frequently in animals caused by trauma, systemic disease or surgical procedures. The control depends on length, where there are painful impulses and mental status of the animal. It is an important clinical condition, resulting in suffer that will affect quality life. This paper is a review of pathophysiology and pain control in small animals.A dor é uma experiência sensorial ou emocional desagradável que se segue à aplicação de um estímulo nocivo. Pode ser vivenciada com ou sem o acontecimento concomitante de sinais físicos de estresse, trauma, doença sistêmica ou procedimento cirúrgico. Seu controle depende de sua duração, de onde surgem os impulsos dolorosos e do estado de consciência do animal. É uma condição clinicamente importante, que resulta em sofrimento e afeta a qualidade de vida dos animais. O objetivo deste trabalho é a revisão da fisiopatologia e controle da dor em pequenos animais.

Tree shrew (Tupaia belangeri as a novel laboratory disease animal model

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Ji Xiao

2017-05-01

Full Text Available The tree shrew (Tupaia belangeri is a promising laboratory animal that possesses a closer genetic relationship to primates than to rodents. In addition, advantages such as small size, easy breeding, and rapid reproduction make the tree shrew an ideal subject for the study of human disease. Numerous tree shrew disease models have been generated in biological and medical studies in recent years. Here we summarize current tree shrew disease models, including models of infectious diseases, cancers, depressive disorders, drug addiction, myopia, metabolic diseases, and immune-related diseases. With the success of tree shrew transgenic technology, this species will be increasingly used in biological and medical studies in the future.

Chimeric animal models in human stem cell biology.

Science.gov (United States)

Glover, Joel C; Boulland, Jean-Luc; Halasi, Gabor; Kasumacic, Nedim

2009-01-01

The clinical use of stem cells for regenerative medicine is critically dependent on preclinical studies in animal models. In this review we examine some of the key issues and challenges in the use of animal models to study human stem cell biology-experimental standardization, body size, immunological barriers, cell survival factors, fusion of host and donor cells, and in vivo imaging and tracking. We focus particular attention on the various imaging modalities that can be used to track cells in living animals, comparing their strengths and weaknesses and describing technical developments that are likely to lead to new opportunities for the dynamic assessment of stem cell behavior in vivo. We then provide an overview of some of the most commonly used animal models, their advantages and disadvantages, and examples of their use for xenotypic transplantation of human stem cells, with separate reviews of models involving rodents, ungulates, nonhuman primates, and the chicken embryo. As the use of human somatic, embryonic, and induced pluripotent stem cells increases, so too will the range of applications for these animal models. It is likely that increasingly sophisticated uses of human/animal chimeric models will be developed through advances in genetic manipulation, cell delivery, and in vivo imaging.

Syrian Hamster as an Animal Model for the Study of Human Influenza Virus Infection.

Science.gov (United States)

Iwatsuki-Horimoto, Kiyoko; Nakajima, Noriko; Ichiko, Yurie; Sakai-Tagawa, Yuko; Noda, Takeshi; Hasegawa, Hideki; Kawaoka, Yoshihiro

2018-02-15

Ferrets and mice are frequently used as animal models for influenza research. However, ferrets are demanding in terms of housing space and handling, whereas mice are not naturally susceptible to infection with human influenza A or B viruses. Therefore, prior adaptation of human viruses is required for their use in mice. In addition, there are no mouse-adapted variants of the recent H3N2 viruses, because these viruses do not replicate well in mice. In this study, we investigated the susceptibility of Syrian hamsters to influenza viruses with a view to using the hamster model as an alternative to the mouse model. We found that hamsters are sensitive to influenza viruses, including the recent H3N2 viruses, without adaptation. Although the hamsters did not show weight loss or clinical signs of H3N2 virus infection, we observed pathogenic effects in the respiratory tracts of the infected animals. All of the H3N2 viruses tested replicated in the respiratory organs of the hamsters, and some of them were detected in the nasal washes of infected animals. Moreover, a 2009 pandemic (pdm09) virus and a seasonal H1N1 virus, as well as one of the two H3N2 viruses, but not a type B virus, were transmissible by the airborne route in these hamsters. Hamsters thus have the potential to be a small-animal model for the study of influenza virus infection, including studies of the pathogenicity of H3N2 viruses and other strains, as well as for use in H1N1 virus transmission studies. IMPORTANCE We found that Syrian hamsters are susceptible to human influenza viruses, including the recent H3N2 viruses, without adaptation. We also found that a pdm09 virus and a seasonal H1N1 virus, as well as one of the H3N2 viruses, but not a type B virus tested, are transmitted by the airborne route in these hamsters. Syrian hamsters thus have the potential to be used as a small-animal model for the study of human influenza viruses. Copyright © 2018 American Society for Microbiology.

Small animal positron emission tomography imaging and in vivo studies of atherosclerosis

DEFF Research Database (Denmark)

Hag, Anne Mette Fisker; Ripa, Rasmus Sejersten; Pedersen, Sune Folke

2013-01-01

Atherosclerosis is a growing health challenge globally, and despite our knowledge of the disease has increased over the last couple of decades, many unanswered questions remain. As molecular imaging can be used to visualize, characterize and measure biological processes at the molecular and cellu...... knowledge obtained from in vivo positron emission tomography studies of atherosclerosis performed in small animals....

Animal models of erectile dysfunction

Directory of Open Access Journals (Sweden)

Snehlata V Gajbhiye

2015-01-01

Full Text Available Animal models have contributed to a great extent to understanding and advancement in the field of sexual medicine. Many current medical and surgical therapies in sexual medicine have been tried based on these animal models. Extensive literature search revealed that the compiled information is limited. In this review, we describe various experimental models of erectile dysfunction (ED encompassing their procedures, variables of assessment, advantages and disadvantages. The search strategy consisted of review of PubMed based articles. We included original research work and certain review articles available in PubMed database. The search terms used were "ED and experimental models," "ED and nervous stimulation," "ED and cavernous nerve stimulation," "ED and central stimulation," "ED and diabetes mellitus," "ED and ageing," "ED and hypercholesteremia," "ED and Peyronie′s disease," "radiation induced ED," "telemetric recording," "ED and mating test" and "ED and non-contact erection test."

78 FR 59624 - Guidance for Industry #223: Small Entity Compliance Guide-Declaring Color Additives in Animal...

Science.gov (United States)

2013-09-27

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 501 [Docket No. FDA-2013-D-1088] Guidance for Industry 223: Small Entity Compliance Guide--Declaring Color Additives... industry 223 entitled ``Small Entity Compliance Guide--Declaring Color Additives in Animal Foods.'' This...

Cone Beam X-Ray Luminescence Tomography Imaging Based on KA-FEM Method for Small Animals.

Science.gov (United States)

Chen, Dongmei; Meng, Fanzhen; Zhao, Fengjun; Xu, Cao

2016-01-01

Cone beam X-ray luminescence tomography can realize fast X-ray luminescence tomography imaging with relatively low scanning time compared with narrow beam X-ray luminescence tomography. However, cone beam X-ray luminescence tomography suffers from an ill-posed reconstruction problem. First, the feasibility of experiments with different penetration and multispectra in small animal has been tested using nanophosphor material. Then, the hybrid reconstruction algorithm with KA-FEM method has been applied in cone beam X-ray luminescence tomography for small animals to overcome the ill-posed reconstruction problem, whose advantage and property have been demonstrated in fluorescence tomography imaging. The in vivo mouse experiment proved the feasibility of the proposed method.

Animal models for Gaucher disease research

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Tamar Farfel-Becker

2011-11-01

Full Text Available Gaucher disease (GD, the most common lysosomal storage disorder (LSD, is caused by the defective activity of the lysosomal hydrolase glucocerebrosidase, which is encoded by the GBA gene. Generation of animal models that faithfully recapitulate the three clinical subtypes of GD has proved to be more of a challenge than first anticipated. The first mouse to be produced died within hours after birth owing to skin permeability problems, and mice with point mutations in Gba did not display symptoms correlating with human disease and also died soon after birth. Recently, conditional knockout mice that mimic some features of the human disease have become available. Here, we review the contribution of all currently available animal models to examining pathological pathways underlying GD and to testing the efficacy of new treatment modalities, and propose a number of criteria for the generation of more appropriate animal models of GD.

Animal models for Gaucher disease research.

Science.gov (United States)

Farfel-Becker, Tamar; Vitner, Einat B; Futerman, Anthony H

2011-11-01

Gaucher disease (GD), the most common lysosomal storage disorder (LSD), is caused by the defective activity of the lysosomal hydrolase glucocerebrosidase, which is encoded by the GBA gene. Generation of animal models that faithfully recapitulate the three clinical subtypes of GD has proved to be more of a challenge than first anticipated. The first mouse to be produced died within hours after birth owing to skin permeability problems, and mice with point mutations in Gba did not display symptoms correlating with human disease and also died soon after birth. Recently, conditional knockout mice that mimic some features of the human disease have become available. Here, we review the contribution of all currently available animal models to examining pathological pathways underlying GD and to testing the efficacy of new treatment modalities, and propose a number of criteria for the generation of more appropriate animal models of GD.

Coupler for surgery on small animals

Science.gov (United States)

Johnson, J. E., Jr.; Swartz, P. F.

1979-01-01

Minicoupler simplifies exchange of fluids with organs of laboratory animals enabling one person to perform surgery on experimental animals such as rats and mice. Innovation eliminates obstructing hands and instruments from areas of surgery.

Absolute quantitative total-body small-animal SPECT with focusing pinholes

International Nuclear Information System (INIS)

Wu, Chao; Have, Frans van der; Vastenhouw, Brendan; Beekman, Freek J.; Dierckx, Rudi A.J.O.; Paans, Anne M.J.

2010-01-01

In pinhole SPECT, attenuation of the photon flux on trajectories between source and pinholes affects quantitative accuracy of reconstructed images. Previously we introduced iterative methods that compensate for image degrading effects of detector and pinhole blurring, pinhole sensitivity and scatter for multi-pinhole SPECT. The aim of this paper is (1) to investigate the accuracy of the Chang algorithm in rodents and (2) to present a practical Chang-based method using body outline contours obtained with optical cameras. Here we develop and experimentally validate a practical method for attenuation correction based on a Chang first-order method. This approach has the advantage that it is employed after, and therefore independently from, iterative reconstruction. Therefore, no new system matrix has to be calculated for each specific animal. Experiments with phantoms and animals were performed with a high-resolution focusing multi-pinhole SPECT system (U-SPECT-II, MILabs, The Netherlands). This SPECT system provides three additional optical camera images of the animal for each SPECT scan from which the animal contour can be estimated. Phantom experiments demonstrated that an average quantification error of -18.7% was reduced to -1.7% when both window-based scatter correction and Chang correction based on the body outline from optical images were applied. Without scatter and attenuation correction, quantification errors in a sacrificed rat containing sources with known activity ranged from -23.6 to -9.3%. These errors were reduced to values between -6.3 and +4.3% (with an average magnitude of 2.1%) after applying scatter and Chang attenuation correction. We conclude that the modified Chang correction based on body contour combined with window-based scatter correction is a practical method for obtaining small-animal SPECT images with high quantitative accuracy. (orig.)

Percutaneous radiofrequency ablation of lung tumors in a large animal model.

Science.gov (United States)

Ahrar, Kamran; Price, Roger E; Wallace, Michael J; Madoff, David C; Gupta, Sanjay; Morello, Frank A; Wright, Kenneth C

2003-08-01

Percutaneous radiofrequency ablation (RFA) is accepted therapy for liver tumors in the appropriate clinical setting, but its use in lung neoplasms remains investigational. We undertook this study to evaluate the feasibility and immediate effectiveness of RFA for treatment of both solitary pulmonary nodules and clusters of lung tumors in a large animal model. Percutaneous RFA of 14 lung tumors in five dogs was performed under CT guidance. Animals were euthanatized 8-48 hours after the procedure. The lungs and adjacent structures were harvested for gross and histopathologic evaluation. Five solitary pulmonary nodules (range, 17-26 mm) and three clusters of three nodules each (range, 7-17 mm per nodule) were treated with RFA. All ablations were technically successful. Perilesional ground-glass opacity and small asymptomatic pneumothoraces (n = 4) were visualized during the RFA sessions. One dog developed a large pneumothorax treated with tube thoracostomy but was euthanatized 8 hours post-RFA for persistent pneumothorax and continued breathing difficulty. Follow-up CT 48 hours post-RFA revealed opacification of the whole lung segment. Gross and histopathologic evaluation showed complete thermal coagulation necrosis of all treated lesions without evidence of any viable tumor. The region of thermal coagulation necrosis typically extended to the lung surface. Small regions of pulmonary hemorrhage and congestion often surrounded the areas of coagulation necrosis. RFA can be used to treat both solitary pulmonary nodules and clusters of tumor nodules in the canine lung tumor model. This model may be useful for development of specific RFA protocols for human lung tumors.

Final model of multicriterionevaluation of animal welfare

DEFF Research Database (Denmark)

Bonde, Marianne; Botreau, R; Bracke, MBM

One major objective of Welfare Quality® is to propose harmonized methods for the overall assessment of animal welfare on farm and at slaughter that are science based and meet societal concerns. Welfare is a multidimensional concept and its assessment requires measures of different aspects. Welfar......, acceptable welfare and not classified. This evaluation model is tuned according to the views of experts from animal and social sciences, and stakeholders....... Quality® proposes a formal evaluation model whereby the data on animals or their environment are transformed into value scores that reflect compliance with 12 subcriteria and 4 criteria of good welfare. Each animal unit is then allocated to one of four categories: excellent welfare, enhanced welfare...

Retinal Cell Degeneration in Animal Models

Directory of Open Access Journals (Sweden)

Masayuki Niwa

2016-01-01

Full Text Available The aim of this review is to provide an overview of various retinal cell degeneration models in animal induced by chemicals (N-methyl-d-aspartate- and CoCl2-induced, autoimmune (experimental autoimmune encephalomyelitis, mechanical stress (optic nerve crush-induced, light-induced and ischemia (transient retinal ischemia-induced. The target regions, pathology and proposed mechanism of each model are described in a comparative fashion. Animal models of retinal cell degeneration provide insight into the underlying mechanisms of the disease, and will facilitate the development of novel effective therapeutic drugs to treat retinal cell damage.

Animal Models of Hemophilia and Related Bleeding Disorders

Science.gov (United States)

Lozier, Jay N.; Nichols, Timothy C.

2013-01-01

Animal models of hemophilia and related diseases are important for development of novel treatments and to understand the pathophysiology of bleeding disorders in humans. Testing in animals with the equivalent human disorder provides informed estimates of doses and measures of efficacy, which aids in design of human trials. Many models of hemophilia A, hemophilia B, and von Willebrand disease have been developed from animals with spontaneous mutations (hemophilia A dogs, rats, sheep; hemophilia B dogs; and von Willebrand disease pigs and dogs), or by targeted gene disruption in mice to create hemophilia A, B, or VWD models. Animal models have been used to generate new insights into the pathophysiology of each bleeding disorder and also to perform pre-clinical assessments of standard protein replacement therapies as well as novel gene transfer technology. Both the differences between species and differences in underlying causative mutations must be considered in choosing the best animal for a specific scientific study PMID:23956467

Henipavirus Infections: Lessons from Animal Models

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Kévin P. Dhondt

2013-04-01

Full Text Available The Henipavirus genus contains two highly lethal viruses, the Hendra and Nipah viruses and one, recently discovered, apparently nonpathogenic member; Cedar virus. These three, negative-sense single-stranded RNA viruses, are hosted by fruit bats and use EphrinB2 receptors for entry into cells. The Hendra and Nipah viruses are zoonotic pathogens that emerged in the middle of 90s and have caused severe, and often fatal, neurologic and/or respiratory diseases in both humans and different animals; including spillover into equine and porcine species. Development of relevant models is critical for a better understanding of viral pathogenesis, generating new diagnostic tools, and assessing anti-viral therapeutics and vaccines. This review summarizes available data on several animal models where natural and/or experimental infection has been demonstrated; including pteroid bats, horses, pigs, cats, hamsters, guinea pigs, ferrets, and nonhuman primates. It recapitulates the principal features of viral pathogenesis in these animals and current knowledge on anti-viral immune responses. Lastly it describes the recently characterized murine animal model, which provides the possibility to use numerous and powerful tools available for mice to further decipher henipaviruses immunopathogenesis, prophylaxis, and treatment. The utility of different models to analyze important aspects of henipaviruses-induced disease in humans, potential routes of transmission, and therapeutic approaches are equally discussed.

Animal models of asthma: utility and limitations

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Aun MV

2017-11-01

Full Text Available Marcelo Vivolo Aun,1,2 Rafael Bonamichi-Santos,1,2 Fernanda Magalhães Arantes-Costa,2 Jorge Kalil,1 Pedro Giavina-Bianchi1 1Clinical Immunology and Allergy Division, Department of Internal Medicine, University of São Paulo School of Medicine, São Paulo, Brazil, 2Laboratory of Experimental Therapeutics (LIM20, Department of Internal Medicine, University of Sao Paulo, Sao Paulo, Brazil Abstract: Clinical studies in asthma are not able to clear up all aspects of disease pathophysiology. Animal models have been developed to better understand these mechanisms and to evaluate both safety and efficacy of therapies before starting clinical trials. Several species of animals have been used in experimental models of asthma, such as Drosophila, rats, guinea pigs, cats, dogs, pigs, primates and equines. However, the most common species studied in the last two decades is mice, particularly BALB/c. Animal models of asthma try to mimic the pathophysiology of human disease. They classically include two phases: sensitization and challenge. Sensitization is traditionally performed by intraperitoneal and subcutaneous routes, but intranasal instillation of allergens has been increasingly used because human asthma is induced by inhalation of allergens. Challenges with allergens are performed through aerosol, intranasal or intratracheal instillation. However, few studies have compared different routes of sensitization and challenge. The causative allergen is another important issue in developing a good animal model. Despite being more traditional and leading to intense inflammation, ovalbumin has been replaced by aeroallergens, such as house dust mites, to use the allergens that cause human disease. Finally, researchers should define outcomes to be evaluated, such as serum-specific antibodies, airway hyperresponsiveness, inflammation and remodeling. The present review analyzes the animal models of asthma, assessing differences between species, allergens and routes

Animal models for the study of hepatitis C virus infection and related liver disease

DEFF Research Database (Denmark)

Bukh, Jens

2012-01-01

Hepatitis C virus (HCV) causes liver-related death in more than 300,000 people annually. Treatments for patients with chronic HCV are suboptimal, despite the introduction of directly acting antiviral agents. There is no vaccine that prevents HCV infection. Relevant animal models are important...... for HCV research and development of drugs and vaccines. Chimpanzees are the best model for studies of HCV infection and related innate and adaptive host immune responses. They can be used in immunogenicity and efficacy studies of HCV vaccines. The only small animal models of robust HCV infection are T......- and B- cell deficient mice with human chimeric livers. Although these mice cannot be used in studies of adaptive immunity, they have provided new insights into HCV neutralization, interactions between virus and receptors, innate host responses, and therapeutic approaches. Recent progress in developing...

Laser surgery for selected small animal soft-tissue conditions

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Bartels, Kenneth E.

1991-05-01

With the acquisition of a Nd:YAG and a CO2 laser in the College of Veterinary Medicine at Oklahoma State University in 1989, over 100 small animal clinical cases have been managed with these modern modalities for surgical excision and tissue vaporization. Most procedures have been for oncologic problems, but inflammatory, infectious, or congenital conditions including vaporization of acral lick 'granulomas,' excision/vaporization of foreign body induced, infected draining tracts, and resection of elongated soft palates have been successfully accomplished. Laser excision or vaporization of both benign and malignant neoplasms have effectively been performed and include feline nasal squamous cell carcinoma, mast cell tumors, and rectal/anal neoplasms. Results to date have been excellent with animals exhibiting little postoperative pain, swelling, and inflammation. Investigations involving application of laser energy for tissue welding of esophageal lacerations and hepatitic interstitial hyperthermia for metastatic colorectal cancer have also shown potential. A review of cases with an emphasis on survival time and postoperative morbidity suggests that carefully planned laser surgical procedures in clinical veterinary practice done with standardized protocols and techniques offer an acceptable means of treating conditions that were previously considered extremely difficult or virtually impossible to perform.

Sub-millimetre DOI detector based on monolithic LYSO and digital SiPM for a dedicated small-animal PET system

International Nuclear Information System (INIS)

Marcinkowski, Radosław; Mollet, Pieter; Van Holen, Roel; Vandenberghe, Stefaan

2016-01-01

The mouse model is widely used in a vast range of biomedical and preclinical studies. Thanks to the ability to detect and quantify biological processes at the molecular level in vivo, PET has become a well-established tool in these investigations. However, the need to visualize and quantify radiopharmaceuticals in anatomic structures of millimetre or less requires good spatial resolution and sensitivity from small-animal PET imaging systems. In previous work we have presented a proof-of-concept of a dedicated high-resolution small-animal PET scanner based on thin monolithic scintillator crystals and Digital Photon Counter photosensor. The combination of thin monolithic crystals and MLE positioning algorithm resulted in an excellent spatial resolution of 0.7 mm uniform in the entire field of view (FOV). However, the limitation of the scanner was its low sensitivity due to small thickness of the lutetium-yttrium oxyorthosilicate (LYSO) crystals (2 mm). Here we present an improved detector design for a small-animal PET system that simultaneously achieves higher sensitivity and sustains a sub-millimetre spatial resolution. The proposed detector consists of a 5 mm thick monolithic LYSO crystal optically coupled to a Digital Photon Counter. Mean nearest neighbour (MNN) positioning combined with depth of interaction (DOI) decoding was employed to achieve sub-millimetre spatial resolution. To evaluate detector performance the intrinsic spatial resolution, energy resolution and coincidence resolving time (CRT) were measured. The average intrinsic spatial resolution of the detector was 0.60 mm full-width-at-half-maximum (FWHM). A DOI resolution of 1.66 mm was achieved. The energy resolution was 23% FWHM at 511 keV and CRT of 529 ps were measured. The improved detector design overcomes the sensitivity limitation of the previous design by increasing the nominal sensitivity of the detector block and retains an excellent intrinsic spatial resolution. (paper)

Evaluation of absorbed doses in voxel-based and simplified models for small animals

International Nuclear Information System (INIS)

Mohammadi, A.; Kinase, S.; Saito, K.

2008-01-01

Internal dosimetry in non-human biota is desirable from the viewpoint of radiation protection of the environment. The International Commission on Radiological Protection (ICRP) proposed Reference Animals and Plants using simplified models, such as ellipsoids and spheres and calculated absorbed fractions (AFs) for whole bodies. In this study, photon and electron AFs in whole bodies of voxel-based rat and frog models have been calculated and compared with AFs in the reference models. It was found that the voxel-based and the reference frog (or rat) models can be consistent for the whole-body AFs within a discrepancy of 25 %, as the source was uniformly distributed in the whole body. The specific absorbed fractions (SAFs) and S values were also evaluated in whole bodies and all organs of the voxel-based frog and rat models as the source was distributed in the whole body or skeleton. The results demonstrated that the whole-body SAFs reflect SAFs of all individual organs as the source was uniformly distributed per mass within the whole body by about 30 % uncertainties with exceptions for body contour (up to -40 %) for both electrons and photons due to enhanced radiation leakages, and for the skeleton for photons only (up to +185 %) due to differences in the mass attenuation coefficients. For nuclides such as 90 Y and 90 Sr, which were concentrated in the skeleton, there were large differences between S values in the whole body and those in individual organs, however the whole-body S values for the reference models with the whole body as the source were remarkably similar to those for the voxel-based models with the skeleton as the source, within about 4 and 0.3 %, respectively. It can be stated that whole-body SAFs or S values in simplified models without internal organs are not sufficient for accurate internal dosimetry because they do not reflect SAFs or S values of all individual organs as the source was not distributed uniformly in whole body. Thus, voxel

Modeling individual animal histories with multistate capture–recapture models

Science.gov (United States)

Lebreton, Jean-Dominique; Nichols, James D.; Barker, Richard J.; Pradel, Roger; Spendelow, Jeffrey A.

2009-01-01

Many fields of science begin with a phase of exploration and description, followed by investigations of the processes that account for observed patterns. The science of ecology is no exception, and recent decades have seen a focus on understanding key processes underlying the dynamics of ecological systems. In population ecology, emphasis has shifted from the state variable of population size to the demographic processes responsible for changes in this state variable: birth, death, immigration, and emigration. In evolutionary ecology, some of these same demographic processes, rates of birth and death, are also the determinants of fitness. In animal population ecology, the estimation of state variables and their associated vital rates is especially problematic because of the difficulties in sampling such populations and detecting individual animals. Indeed, early capture–recapture models were developed for the purpose of estimating population size, given the reality that all animals are not caught or detected at any sampling occasion. More recently, capture–recapture models for open populations were developed to draw inferences about survival in the face of these same sampling problems. The focus of this paper is on multi‐state mark–recapture models (MSMR), which first appeared in the 1970s but have undergone substantial development in the last 15 years. These models were developed to deal explicitly with biological variation, in that animals in different “states” (classes defined by location, physiology, behavior, reproductive status, etc.) may have different probabilities of survival and detection. Animal transitions between states are also stochastic and themselves of interest. These general models have proven to be extremely useful and provide a way of thinking about a remarkably wide range of important ecological processes. These methods are now at a stage of refinement and sophistication where they can readily be used by biologists to tackle a wide

Animal model of thermal injuries

Directory of Open Access Journals (Sweden)

F. Bečić

2003-11-01

Full Text Available Experimental studies of burns require the use of different animal models with the aim to imitate and reproduce pathophysiological conditions. The aim of this work was to establish experimental model of thermal injury.New Zealand rabbits, weighted from 1.8 kg to 2.3 kg, were utilised during our study. Another, also utilized, animal types were laboratory Rattus rats, species Wistar, albino type, females with body weight of about 232 g. All animals were from our own litter (Institute of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine in Sarajevo. During the experiment, animal were properly situated in adequate cages and rooms, at the controlled temperature (22 ± 2°C, and in the air with normal humidity level. All animals took food and water ad libitum.Rabbits received anesthesia - intravenous pentobarbital sodium in a dose of 60 mg/kg, and then, hair from the upper side of the each rabbit ear was removed and burns were caused by a metal seal in the same manner as in rats. Rats were primarily anesthesied by intraperitoneal pentobarbital sodium in a dose of 35 mg/kg, and then, their hair was removed from the scapula zone (5 cm x 5 cm. Burns were caused by contact with a round metal seal, heated at 80°C in a water bath, during the period of 14 seconds together with contact thermometer control. Round metal seal (radius: 2.5 cm; weight: 100 g; surface: 5 cm2 was just placed on the rat skin without any additional pressure. In order to maintain the microcirculation in the burn wound and to reduce the conversion of partial-thickness skin burns to the burns of the full-thickness skin, all burn wounds were immediately sunk in the 4°C water. Subsequent to that procedure, all animals were individually situated in the proper cages, and left to rest for 4 hours with a constant cautious monitoring of the wound development and animal general state.

Animal models of drug addiction.

Science.gov (United States)

García Pardo, María Pilar; Roger Sánchez, Concepción; De la Rubia Ortí, José Enrique; Aguilar Calpe, María Asunción

2017-09-29

The development of animal models of drug reward and addiction is an essential factor for progress in understanding the biological basis of this disorder and for the identification of new therapeutic targets. Depending on the component of reward to be studied, one type of animal model or another may be used. There are models of reinforcement based on the primary hedonic effect produced by the consumption of the addictive substance, such as the self-administration (SA) and intracranial self-stimulation (ICSS) paradigms, and there are models based on the component of reward related to associative learning and cognitive ability to make predictions about obtaining reward in the future, such as the conditioned place preference (CPP) paradigm. In recent years these models have incorporated methodological modifications to study extinction, reinstatement and reconsolidation processes, or to model specific aspects of addictive behavior such as motivation to consume drugs, compulsive consumption or drug seeking under punishment situations. There are also models that link different reinforcement components or model voluntary motivation to consume (two-bottle choice, or drinking in the dark tests). In short, innovations in these models allow progress in scientific knowledge regarding the different aspects that lead individuals to consume a drug and develop compulsive consumption, providing a target for future treatments of addiction.

Homogenization of a Directed Dispersal Model for Animal Movement in a Heterogeneous Environment.

Science.gov (United States)

Yurk, Brian P

2016-10-01

The dispersal patterns of animals moving through heterogeneous environments have important ecological and epidemiological consequences. In this work, we apply the method of homogenization to analyze an advection-diffusion (AD) model of directed movement in a one-dimensional environment in which the scale of the heterogeneity is small relative to the spatial scale of interest. We show that the large (slow) scale behavior is described by a constant-coefficient diffusion equation under certain assumptions about the fast-scale advection velocity, and we determine a formula for the slow-scale diffusion coefficient in terms of the fast-scale parameters. We extend the homogenization result to predict invasion speeds for an advection-diffusion-reaction (ADR) model with directed dispersal. For periodic environments, the homogenization approximation of the solution of the AD model compares favorably with numerical simulations. Invasion speed approximations for the ADR model also compare favorably with numerical simulations when the spatial period is sufficiently small.

Osteoarthritis: New Insights in Animal Models

OpenAIRE

Longo, Umile Giuseppe; Loppini, Mattia; Fumo, Caterina; Rizzello, Giacomo; Khan, Wasim Sardar; Maffulli, Nicola; Denaro, Vincenzo

2012-01-01

Osteoarthritis (OA) is the most frequent and symptomatic health problem in the middle-aged and elderly population, with over one-half of all people over the age of 65 showing radiographic changes in painful knees. The aim of the present study was to perform an overview on the available animal models used in the research field on the OA. Discrepancies between the animal models and the human disease are present. As regards human ‘idiopathic’ OA, with late onset and slow progression, it is perha...

Method to reduce non-specific tissue heating of small animals in solenoid coils.

Science.gov (United States)

Kumar, Ananda; Attaluri, Anilchandra; Mallipudi, Rajiv; Cornejo, Christine; Bordelon, David; Armour, Michael; Morua, Katherine; Deweese, Theodore L; Ivkov, Robert

2013-01-01

Solenoid coils that generate time-varying or alternating magnetic fields (AMFs) are used in biomedical devices for research, imaging and therapy. Interactions of AMF and tissue produce eddy currents that deposit power within tissue, thus limiting effectiveness and safety. We aim to develop methods that minimise excess heating of mice exposed to AMFs for cancer therapy experiments. Numerical and experimental data were obtained to characterise thermal management properties of water using a continuous, custom water jacket in a four-turn simple solenoid. Theoretical data were obtained with method-of-moments (MoM) numerical field calculations and finite element method (FEM) thermal simulations. Experimental data were obtained from gel phantoms and mice exposed to AMFs having amplitude >50 kA/m and frequency of 160 kHz. Water has a high specific heat and thermal conductivity, is diamagnetic, polar, and nearly transparent to magnetic fields. We report at least a two-fold reduction of temperature increase from gel phantom and animal models when a continuous layer of circulating water was placed between the sample and solenoid, compared with no water. Thermal simulations indicate the superior efficiency in thermal management by the developed continuous single chamber cooling system over a double chamber non-continuous system. Further reductions of heating were obtained by regulating water temperature and flow for active cooling. These results demonstrate the potential value of a contiguous layer of circulating water to permit sustained exposure to high intensity alternating magnetic fields at this frequency for research using small animal models exposed to AMFs.

A 3D high-resolution gamma camera for radiopharmaceutical studies with small animals

CERN Document Server

Loudos, G K; Giokaris, N D; Styliaris, E; Archimandritis, S C; Varvarigou, A D; Papanicolas, C N; Majewski, S; Weisenberger, D; Pani, R; Scopinaro, F; Uzunoglu, N K; Maintas, D; Stefanis, K

2003-01-01

The results of studies conducted with a small field of view tomographic gamma camera based on a Position Sensitive Photomultiplier Tube are reported. The system has been used for the evaluation of radiopharmaceuticals in small animals. Phantom studies have shown a spatial resolution of 2 mm in planar and 2-3 mm in tomographic imaging. Imaging studies in mice have been carried out both in 2D and 3D. Conventional radiopharmaceuticals have been used and the results have been compared with images from a clinically used system.

Evaluation of 3D reconstruction algorithms for a small animal PET camera

International Nuclear Information System (INIS)

Johnson, C.A.; Gandler, W.R.; Seidel, J.

1996-01-01

The use of paired, opposing position-sensitive phototube scintillation cameras (SCs) operating in coincidence for small animal imaging with positron emitters is currently under study. Because of the low sensitivity of the system even in 3D mode and the need to produce images with high resolution, it was postulated that a 3D expectation maximization (EM) reconstruction algorithm might be well suited for this application. We investigated four reconstruction algorithms for the 3D SC PET camera: 2D filtered back-projection (FBP), 2D ordered subset EM (OSEM), 3D reprojection (3DRP), and 3D OSEM. Noise was assessed for all slices by the coefficient of variation in a simulated uniform cylinder. Resolution was assessed from a simulation of 15 point sources in the warm background of the uniform cylinder. At comparable noise levels, the resolution achieved with OSEM (0.9-mm to 1.2-mm) is significantly better than that obtained with FBP or 3DRP (1.5-mm to 2.0-mm.) Images of a rat skull labeled with 18 F-fluoride suggest that 3D OSEM can improve image quality of a small animal PET camera

Pencilbeam irradiation technique for whole brain radiotherapy: technical and biological challenges in a small animal model.

Science.gov (United States)

Schültke, Elisabeth; Trippel, Michael; Bräuer-Krisch, Elke; Renier, Michel; Bartzsch, Stefan; Requardt, Herwig; Döbrössy, Máté D; Nikkhah, Guido

2013-01-01

We have conducted the first in-vivo experiments in pencilbeam irradiation, a new synchrotron radiation technique based on the principle of microbeam irradiation, a concept of spatially fractionated high-dose irradiation. In an animal model of adult C57 BL/6J mice we have determined technical and physiological limitations with the present technical setup of the technique. Fifty-eight animals were distributed in eleven experimental groups, ten groups receiving whole brain radiotherapy with arrays of 50 µm wide beams. We have tested peak doses ranging between 172 Gy and 2,298 Gy at 3 mm depth. Animals in five groups received whole brain radiotherapy with a center-to-center (ctc) distance of 200 µm and a peak-to-valley ratio (PVDR) of ∼ 100, in the other five groups the ctc was 400 µm (PVDR ∼ 400). Motor and memory abilities were assessed during a six months observation period following irradiation. The lower dose limit, determined by the technical equipment, was at 172 Gy. The LD50 was about 1,164 Gy for a ctc of 200 µm and higher than 2,298 Gy for a ctc of 400 µm. Age-dependent loss in motor and memory performance was seen in all groups. Better overall performance (close to that of healthy controls) was seen in the groups irradiated with a ctc of 400 µm.

Basic mechanisms of MCD in animal models.

Science.gov (United States)

Battaglia, Giorgio; Becker, Albert J; LoTurco, Joseph; Represa, Alfonso; Baraban, Scott C; Roper, Steven N; Vezzani, Annamaria

2009-09-01

Epilepsy-associated glioneuronal malformations (malformations of cortical development [MCD]) include focal cortical dysplasias (FCD) and highly differentiated glioneuronal tumors, most frequently gangliogliomas. The neuropathological findings are variable but suggest aberrant proliferation, migration, and differentiation of neural precursor cells as essential pathogenetic elements. Recent advances in animal models for MCDs allow new insights in the molecular pathogenesis of these epilepsy-associated lesions. Novel approaches, presented here, comprise RNA interference strategies to generate and study experimental models of subcortical band heterotopia and study functional aspects of aberrantly shaped and positioned neurons. Exciting analyses address impaired NMDA receptor expression in FCD animal models compared to human FCDs and excitatory imbalances in MCD animal models such as lissencephaly gene ablated mice as well as in utero irradiated rats. An improved understanding of relevant pathomechanisms will advance the development of targeted treatment strategies for epilepsy-associated malformations.

Imaging of Small Animal Peripheral Artery Disease Models: Recent Advancements and Translational Potential

Directory of Open Access Journals (Sweden)

Jenny B. Lin

2015-05-01

Full Text Available Peripheral artery disease (PAD is a broad disorder encompassing multiple forms of arterial disease outside of the heart. As such, PAD development is a multifactorial process with a variety of manifestations. For example, aneurysms are pathological expansions of an artery that can lead to rupture, while ischemic atherosclerosis reduces blood flow, increasing the risk of claudication, poor wound healing, limb amputation, and stroke. Current PAD treatment is often ineffective or associated with serious risks, largely because these disorders are commonly undiagnosed or misdiagnosed. Active areas of research are focused on detecting and characterizing deleterious arterial changes at early stages using non-invasive imaging strategies, such as ultrasound, as well as emerging technologies like photoacoustic imaging. Earlier disease detection and characterization could improve interventional strategies, leading to better prognosis in PAD patients. While rodents are being used to investigate PAD pathophysiology, imaging of these animal models has been underutilized. This review focuses on structural and molecular information and disease progression revealed by recent imaging efforts of aortic, cerebral, and peripheral vascular disease models in mice, rats, and rabbits. Effective translation to humans involves better understanding of underlying PAD pathophysiology to develop novel therapeutics and apply non-invasive imaging techniques in the clinic.

Filtering and deconvolution for bioluminescence imaging of small animals

International Nuclear Information System (INIS)

Akkoul, S.

2010-01-01

This thesis is devoted to analysis of bioluminescence images applied to the small animal. This kind of imaging modality is used in cancerology studies. Nevertheless, some problems are related to the diffusion and the absorption of the tissues of the light of internal bioluminescent sources. In addition, system noise and the cosmic rays noise are present. This influences the quality of the images and makes it difficult to analyze. The purpose of this thesis is to overcome these disturbing effects. We first have proposed an image formation model for the bioluminescence images. The processing chain is constituted by a filtering stage followed by a deconvolution stage. We have proposed a new median filter to suppress the random value impulsive noise which corrupts the acquired images; this filter represents the first block of the proposed chain. For the deconvolution stage, we have performed a comparative study of various deconvolution algorithms. It allowed us to choose a blind deconvolution algorithm initialized with the estimated point spread function of the acquisition system. At first, we have validated our global approach by comparing our obtained results with the ground truth. Through various clinical tests, we have shown that the processing chain allows a significant improvement of the spatial resolution and a better distinction of very close tumor sources, what represents considerable contribution for the users of bioluminescence images. (author)

Osteoporotic Animal Models of Bone Healing: Advantages and Pitfalls.

Science.gov (United States)

Calciolari, Elena; Donos, Nikolaos; Mardas, Nikos

2017-10-01

The aim of this review was to summarize the advantages and pitfalls of the available osteoporotic animal models of bone healing. A thorough literature search was performed in MEDLINE via OVID and EMBASE to identify animal studies investigating the effect of experimental osteoporosis on bone healing and bone regeneration. The osteotomy model in the proximal tibia is the most popular osseous defect model to study the bone healing process in osteoporotic-like conditions, although other well-characterized models, such as the post-extraction model, might be taken into consideration by future studies. The regenerative potential of osteoporotic bone and its response to biomaterials/regenerative techniques has not been clarified yet, and the critical size defect model might be an appropriate tool to serve this purpose. Since an ideal animal model for simulating osteoporosis does not exist, the type of bone remodeling, the animal lifespan, the age of peak bone mass, and the economic and ethical implications should be considered in our selection process. Furthermore, the influence of animal species, sex, age, and strain on the outcome measurement should be taken into account. In order to make future studies meaningful, standardized international guidelines for osteoporotic animal models of bone healing need to be set up.

[Strategic considerations on the design and choice of animal models for non-clinical investigations of cell-based medicinal products].

Science.gov (United States)

Lehmann, Jörg; Schulz, Ronny M; Sanzenbacher, Ralf

2015-11-01

For the development of medicinal products animal models are still indispensable to demonstrate efficacy and safety prior to first use in humans. Advanced therapy medicinal products (ATMP), which include cell-based medicinal products (CBMP), differ in their pharmacology and toxicology compared to conventional pharmaceuticals, and thus, require an adapted regime for non-clinical development. Developers are, therefore, challenged to develop particular individual concepts and to reconcile these with regulatory agencies. Guidelines issued by the European Medicines Agency (EMA), the U.S. Food and Drug Administration (FDA) and other sources can provide direction.The published approaches for non-clinical testing of efficacy document that homologous animal models where the therapeutic effect is investigated in a disease-relevant animal model utilizing cells derived from the same species are commonly used. The challenge is that the selected model should reflect the human disease in all critical features and that the cells should be comparable to the investigated human medicinal product in terms of quality and biological activity. This is not achievable in all cases. In these cases, alternative methods may provide supplemental information. To demonstrate the scientific proof-of-concept (PoC), small animal models such as mice or rats are preferred. During the subsequent product development phase, large animal models (i.e. sheep, minipigs, dogs) must be considered, as they may better reflect the anatomical or physiological situation in humans. In addition to efficacy, those models may also be suitable to prove some safety aspects of ATMP (e.g. regarding dose finding, local tolerance, or undesired interactions and effects of the administered cells in the target tissue). In contrast, for evaluation of the two prominent endpoints for characterizing the safety of ATMP (i.e. biodistribution, tumorigenicity) heterologous small animal models, especially immunodeficient mouse strains

A comprehensive system for dosimetric commissioning and Monte Carlo validation for the small animal radiation research platform.

Science.gov (United States)

Tryggestad, E; Armour, M; Iordachita, I; Verhaegen, F; Wong, J W

2009-09-07

Our group has constructed the small animal radiation research platform (SARRP) for delivering focal, kilo-voltage radiation to targets in small animals under robotic control using cone-beam CT guidance. The present work was undertaken to support the SARRP's treatment planning capabilities. We have devised a comprehensive system for characterizing the radiation dosimetry in water for the SARRP and have developed a Monte Carlo dose engine with the intent of reproducing these measured results. We find that the SARRP provides sufficient therapeutic dose rates ranging from 102 to 228 cGy min(-1) at 1 cm depth for the available set of high-precision beams ranging from 0.5 to 5 mm in size. In terms of depth-dose, the mean of the absolute percentage differences between the Monte Carlo calculations and measurement is 3.4% over the full range of sampled depths spanning 0.5-7.2 cm for the 3 and 5 mm beams. The measured and computed profiles for these beams agree well overall; of note, good agreement is observed in the profile tails. Especially for the smallest 0.5 and 1 mm beams, including a more realistic description of the effective x-ray source into the Monte Carlo model may be important.

A comprehensive system for dosimetric commissioning and Monte Carlo validation for the small animal radiation research platform

Energy Technology Data Exchange (ETDEWEB)

Tryggestad, E; Armour, M; Wong, J W [Deptartment of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, Baltimore, MD (United States); Iordachita, I [Laboratory for Computational Sensing and Robotics, Johns Hopkins University, Baltimore, MD (United States); Verhaegen, F [Department of Radiation Oncology (MAASTRO Physics), GROW School, Maastricht University Medical Center, Maastricht (Netherlands)

2009-09-07

Our group has constructed the small animal radiation research platform (SARRP) for delivering focal, kilo-voltage radiation to targets in small animals under robotic control using cone-beam CT guidance. The present work was undertaken to support the SARRP's treatment planning capabilities. We have devised a comprehensive system for characterizing the radiation dosimetry in water for the SARRP and have developed a Monte Carlo dose engine with the intent of reproducing these measured results. We find that the SARRP provides sufficient therapeutic dose rates ranging from 102 to 228 cGy min{sup -1} at 1 cm depth for the available set of high-precision beams ranging from 0.5 to 5 mm in size. In terms of depth-dose, the mean of the absolute percentage differences between the Monte Carlo calculations and measurement is 3.4% over the full range of sampled depths spanning 0.5-7.2 cm for the 3 and 5 mm beams. The measured and computed profiles for these beams agree well overall; of note, good agreement is observed in the profile tails. Especially for the smallest 0.5 and 1 mm beams, including a more realistic description of the effective x-ray source into the Monte Carlo model may be important.

What Is the Predictive Value of Animal Models for Vaccine Efficacy in Humans? Consideration of Strategies to Improve the Value of Animal Models.

Science.gov (United States)

Herati, Ramin Sedaghat; Wherry, E John

2018-04-02

Animal models are an essential feature of the vaccine design toolkit. Although animal models have been invaluable in delineating the mechanisms of immune function, their precision in predicting how well specific vaccines work in humans is often suboptimal. There are, of course, many obvious species differences that may limit animal models from predicting all details of how a vaccine works in humans. However, careful consideration of which animal models may have limitations should also allow more accurate interpretations of animal model data and more accurate predictions of what is to be expected in clinical trials. In this article, we examine some of the considerations that might be relevant to cross-species extrapolation of vaccine-related immune responses for the prediction of how vaccines will perform in humans. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

Experimental protocols for behavioral imaging: seeing animal models of drug abuse in a new light.

Science.gov (United States)

Aarons, Alexandra R; Talan, Amanda; Schiffer, Wynne K

2012-01-01

Behavioral neuroimaging is a rapidly evolving discipline that represents a marriage between the fields of behavioral neuroscience and preclinical molecular imaging. This union highlights the changing role of imaging in translational research. Techniques developed for humans are now widely applied in the study of animal models of brain disorders such as drug addiction. Small animal or preclinical imaging allows us to interrogate core features of addiction from both behavioral and biological endpoints. Snapshots of brain activity allow us to better understand changes in brain function and behavior associated with initial drug exposure, the emergence of drug escalation, and repeated bouts of drug withdrawal and relapse. Here we review the development and validation of new behavioral imaging paradigms and several clinically relevant radiotracers used to capture dynamic molecular events in behaving animals. We will discuss ways in which behavioral imaging protocols can be optimized to increase throughput and quantitative methods. Finally, we discuss our experience with the practical aspects of behavioral neuroimaging, so investigators can utilize effective animal models to better understand the addicted brain and behavior.

Reviewing model application to support animal health decision making.

Science.gov (United States)

Singer, Alexander; Salman, Mo; Thulke, Hans-Hermann

2011-04-01

Animal health is of societal importance as it affects human welfare, and anthropogenic interests shape decision making to assure animal health. Scientific advice to support decision making is manifold. Modelling, as one piece of the scientific toolbox, is appreciated for its ability to describe and structure data, to give insight in complex processes and to predict future outcome. In this paper we study the application of scientific modelling to support practical animal health decisions. We reviewed the 35 animal health related scientific opinions adopted by the Animal Health and Animal Welfare Panel of the European Food Safety Authority (EFSA). Thirteen of these documents were based on the application of models. The review took two viewpoints, the decision maker's need and the modeller's approach. In the reviewed material three types of modelling questions were addressed by four specific model types. The correspondence between tasks and models underpinned the importance of the modelling question in triggering the modelling approach. End point quantifications were the dominating request from decision makers, implying that prediction of risk is a major need. However, due to knowledge gaps corresponding modelling studies often shed away from providing exact numbers. Instead, comparative scenario analyses were performed, furthering the understanding of the decision problem and effects of alternative management options. In conclusion, the most adequate scientific support for decision making - including available modelling capacity - might be expected if the required advice is clearly stated. Copyright © 2011 Elsevier B.V. All rights reserved.

Classic and New Animal Models of Parkinson's Disease

Directory of Open Access Journals (Sweden)

Javier Blesa

2012-01-01

Full Text Available Neurological disorders can be modeled in animals so as to recreate specific pathogenic events and behavioral outcomes. Parkinson’s Disease (PD is the second most common neurodegenerative disease of an aging population, and although there have been several significant findings about the PD disease process, much of this process still remains a mystery. Breakthroughs in the last two decades using animal models have offered insights into the understanding of the PD disease process, its etiology, pathology, and molecular mechanisms. Furthermore, while cellular models have helped to identify specific events, animal models, both toxic and genetic, have replicated almost all of the hallmarks of PD and are useful for testing new neuroprotective or neurorestorative strategies. Moreover, significant advances in the modeling of additional PD features have come to light in both classic and newer models. In this review, we try to provide an updated summary of the main characteristics of these models as well as the strengths and weaknesses of what we believe to be the most popular PD animal models. These models include those produced by 6-hydroxydopamine (6-OHDA, 1-methyl-1,2,3,6-tetrahydropiridine (MPTP, rotenone, and paraquat, as well as several genetic models like those related to alpha-synuclein, PINK1, Parkin and LRRK2 alterations.

Optimization and performance evaluation of the microPET II scanner for in vivo small-animal imaging

International Nuclear Information System (INIS)

Yang Yongfeng; Tai Yuanchuan; Siegel, Stefan; Newport, Danny F; Bai, Bing; Li, Quanzheng; Leahy, Richard M; Cherry, Simon R

2004-01-01

MicroPET II is a newly developed PET (positron emission tomography) scanner designed for high-resolution imaging of small animals. It consists of 17 640 LSO crystals each measuring 0.975 x 0.975 x 12.5 mm 3 , which are arranged in 42 contiguous rings, with 420 crystals per ring. The scanner has an axial field of view (FOV) of 4.9 cm and a transaxial FOV of 8.5 cm. The purpose of this study was to carefully evaluate the performance of the system and to optimize settings for in vivo mouse and rat imaging studies. The volumetric image resolution was found to depend strongly on the reconstruction algorithm employed and averaged 1.1 mm (1.4 μl) across the central 3 cm of the transaxial FOV when using a statistical reconstruction algorithm with accurate system modelling. The sensitivity, scatter fraction and noise-equivalent count (NEC) rate for mouse- and rat-sized phantoms were measured for different energy and timing windows. Mouse imaging was optimized with a wide open energy window (150-750 keV) and a 10 ns timing window, leading to a sensitivity of 3.3% at the centre of the FOV and a peak NEC rate of 235 000 cps for a total activity of 80 MBq (2.2 mCi) in the phantom. Rat imaging, due to the higher scatter fraction, and the activity that lies outside of the field of view, achieved a maximum NEC rate of 24 600 cps for a total activity of 80 MBq (2.2 mCi) in the phantom, with an energy window of 250-750 keV and a 6 ns timing window. The sensitivity at the centre of the FOV for these settings is 2.1%. This work demonstrates that different scanner settings are necessary to optimize the NEC count rate for different-sized animals and different injected doses. Finally, phantom and in vivo animal studies are presented to demonstrate the capabilities of microPET II for small-animal imaging studies

Elementary of animal model for percutaneous and ocular penetration

Directory of Open Access Journals (Sweden)

Kalpesh Chhotalal Ashara

2016-12-01

Full Text Available Models of animal are the most appropriate method for assessments of human in-vivo percutaneous and ocular penetrations. Monkey and rodents are used for the same. There are several nuts and bolts of each one, so it is necessary to study each one separately. Monkey, porcine and guinea pig penetration are correlated with that of human skin. The skin of rodents, lupus, pigs, etc. has more penetration properties than human skin. Rabbit, goat and sheep eye are mostly used for ocular penetration. The researcher also used hen’s egg chorioallantoic membrane test for ocular irritation study. The other animals’ cornea, cul-de-sac, eyeballs and prepared corneal epithelial models are very less in practice. Web-based alternative non-animal models are also available instead of animal models too. This article describes characteristics of monkeys, pigs, rats, rabbits, guinea pigs and hairless rodents, HuSki model, Cellophane® membrane, egg membrane, gelatin membrane, animal models for ophthalmic delivery, hen’s egg chorioallantoic membrane test, prepared corneal epithelial models and web-based alternative non-animal database.

Computer-animated model of accommodation and presbyopia.

Science.gov (United States)

Goldberg, Daniel B

2015-02-01

To understand, demonstrate, and further research the mechanisms of accommodation and presbyopia. Private practice, Little Silver, New Jersey, USA. Experimental study. The CAMA 2.0 computer-animated model of accommodation and presbyopia was produced in collaboration with an experienced medical animator using Autodesk Maya animation software and Adobe After Effects. The computer-animated model demonstrates the configuration and synchronous movements of all accommodative elements. A new classification of the zonular apparatus based on structure and function is proposed. There are 3 divisions of zonular fibers; that is, anterior, crossing, and posterior. The crossing zonular fibers form a scaffolding to support the lens; the anterior and posterior zonular fibers work reciprocally to achieve focused vision. The model demonstrates the important support function of Weiger ligament. Dynamic movement of the ora serrata demonstrates that the forces of ciliary muscle contraction store energy for disaccommodation in the elastic choroid. The flow of aqueous and vitreous provides strong evidence for our understanding of the hydrodynamic interactions during the accommodative cycle. The interaction may result from the elastic stretch in the choroid transmitted to the vitreous rather than from vitreous pressue. The model supports the concept that presbyopia results from loss of elasticity and increasing ocular rigidity in both the lenticular and extralenticular structures. The computer-animated model demonstrates the structures of accommodation moving in synchrony and might enhance understanding of the mechanisms of accommodation and presbyopia. Dr. Goldberg is a consultant to Acevision, Inc., and Bausch & Lomb. Copyright © 2015 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Animal models in plastic and reconstructive surgery simulation-a review.

Science.gov (United States)

Loh, Charles Yuen Yung; Wang, Aline Yen Ling; Tiong, Vincent Tze Yang; Athanassopoulos, Thanassi; Loh, Meiling; Lim, Philip; Kao, Huang-Kai

2018-01-01

The use of live and cadaveric animal models in surgical training is well established as a means of teaching and improving surgical skill in a controlled setting. We aim to review, evaluate, and summarize the models published in the literature that are applicable to Plastic Surgery training. A PubMed search for keywords relating to animal models in Plastic Surgery and the associated procedures was conducted. Animal models that had cross over between specialties such as microsurgery with Neurosurgery and pinnaplasty with ear, nose, and throat surgery were included as they were deemed to be relevant to our training curriculum. A level of evidence and recommendation assessment was then given to each surgical model. Our review found animal models applicable to plastic surgery training in four major categories namely-microsurgery training, flap raising, facial surgery, and hand surgery. Twenty-four separate articles described various methods of practicing microsurgical techniques on different types of animals. Fourteen different articles each described various methods of conducting flap-based procedures which consisted of either local or perforator flap dissection. Eight articles described different models for practicing hand surgery techniques. Finally, eight articles described animal models that were used for head and neck procedures. A comprehensive summary of animal models related to plastic surgery training has been compiled. Cadaveric animal models provide a readily available introduction to many procedures and ought to be used instead of live models when feasible. Copyright © 2017 Elsevier Inc. All rights reserved.

Stress and adaptation : Toward ecologically relevant animal models

NARCIS (Netherlands)

Koolhaas, Jaap M.; Boer, Sietse F. de; Buwalda, Bauke

Animal models have contributed considerably to the current understanding of mechanisms underlying the role of stress in health and disease. Despite the progress made already, much more can be made by more carefully exploiting animals' and humans' shared biology, using ecologically relevant models.

A new generation of PET scanners for small animal studies

International Nuclear Information System (INIS)

Hegyesi, G.; Imrek, J.; Kalinka, G.; Molnar, J.; Novak, D.; Valastyan, I.; Balkay, L.; Emri, M.; Kis, S.; Tron, L.

2008-01-01

Complete text of publication follows. Research on small animal PET scanners has been a hot topic in recent years. These devices are used in the preclinical phases of drug tests and during the development of new radiopharmaceuticals. They also provide a cost efficient way to test new materials, new design concepts and new technologies that later can be used to build more efficient human medical imaging devices. The development of a PET scanner requires expertise on different fields, therefore a consortium was formed that brought together Hungarian academic and industrial partners: the Nuclear Research Institute (which has experience in the development of nuclear detectors and data acquisition systems), the PET Center of the University of Debrecen (which has clinical experience in the application of nuclear imaging devices and background in image processing software), Mediso Ltd. (which has been developing, manufacturing, selling and servicing medical imaging devices since 1990) and other academic partners. This consortium has been working together since 2003: the knowledge base acquired during the development of our small animal PET scanners (miniPET-I and miniPET-II) is now being utilized to build a commercial multimodal human PET scanner. The operation of a PET scanner is based on the simultaneous detection ('coincidence') of two gamma photons originating from a positron annihilation. In traditional PET scanners coincidence is detected by a central unit during the measurement. In our system there is no such central module: all detected single gamma events are recorded (list mode data acquisition), and the list of events are processed using a computer cluster (built from PCs). The usage of independent detector modules and commercial components reduce both development and maintenance costs. Also, this mode of data acquisition is more suitable for development purposes, since once the data is collected and stored it can be used many times to test different signal

3D absorbed dose calculation with GATE Monte Carlo simulation for the image-guided radiation therapy dedicated to the small animal

International Nuclear Information System (INIS)

Noblet, Caroline

2014-01-01

Innovating irradiators dedicated to small animal allow to mimic clinical treatments in image-guided radiation therapy. Clinical practice is scaled down to the small animal by reducing beam dimensions (from cm to mm) and energy (from MeV to keV). Millimeter medium energy beams ( [fr

RFID Technology for Continuous Monitoring of Physiological Signals in Small Animals.

Science.gov (United States)

Volk, Tobias; Gorbey, Stefan; Bhattacharyya, Mayukh; Gruenwald, Waldemar; Lemmer, Björn; Reindl, Leonhard M; Stieglitz, Thomas; Jansen, Dirk

2015-02-01

Telemetry systems enable researchers to continuously monitor physiological signals in unrestrained, freely moving small rodents. Drawbacks of common systems are limited operation time, the need to house the animals separately, and the necessity of a stable communication link. Furthermore, the costs of the typically proprietary telemetry systems reduce the acceptance. The aim of this paper is to introduce a low-cost telemetry system based on common radio frequency identification technology optimized for battery-independent operational time, good reusability, and flexibility. The presented implant is equipped with sensors to measure electrocardiogram, arterial blood pressure, and body temperature. The biological signals are transmitted as digital data streams. The device is able of monitoring several freely moving animals housed in groups with a single reader station. The modular concept of the system significantly reduces the costs to monitor multiple physiological functions and refining procedures in preclinical research.

Principles of animal extrapolation

Energy Technology Data Exchange (ETDEWEB)

Calabrese, E.J.

1991-01-01

Animal Extrapolation presents a comprehensive examination of the scientific issues involved in extrapolating results of animal experiments to human response. This text attempts to present a comprehensive synthesis and analysis of the host of biomedical and toxicological studies of interspecies extrapolation. Calabrese's work presents not only the conceptual basis of interspecies extrapolation, but also illustrates how these principles may be better used in selection of animal experimentation models and in the interpretation of animal experimental results. The book's theme centers around four types of extrapolation: (1) from average animal model to the average human; (2) from small animals to large ones; (3) from high-risk animal to the high risk human; and (4) from high doses of exposure to lower, more realistic, doses. Calabrese attacks the issues of interspecies extrapolation by dealing individually with the factors which contribute to interspecies variability: differences in absorption, intestinal flora, tissue distribution, metabolism, repair mechanisms, and excretion. From this foundation, Calabrese then discusses the heterogeneticity of these same factors in the human population in an attempt to evaluate the representativeness of various animal models in light of interindividual variations. In addition to discussing the question of suitable animal models for specific high-risk groups and specific toxicological endpoints, the author also examines extrapolation questions related to the use of short-term tests to predict long-term human carcinogenicity and birth defects. The book is comprehensive in scope and specific in detail; for those environmental health professions seeking to understand the toxicological models which underlay health risk assessments, Animal Extrapolation is a valuable information source.

Advancing Toxicology Research Using In Vivo High Throughput Toxicology with Small Fish Models

Science.gov (United States)

Planchart, Antonio; Mattingly, Carolyn J.; Allen, David; Ceger, Patricia; Casey, Warren; Hinton, David; Kanungo, Jyotshna; Kullman, Seth W.; Tal, Tamara; Bondesson, Maria; Burgess, Shawn M.; Sullivan, Con; Kim, Carol; Behl, Mamta; Padilla, Stephanie; Reif, David M.; Tanguay, Robert L.; Hamm, Jon

2017-01-01

Summary Small freshwater fish models, especially zebrafish, offer advantages over traditional rodent models, including low maintenance and husbandry costs, high fecundity, genetic diversity, physiology similar to that of traditional biomedical models, and reduced animal welfare concerns. The Collaborative Workshop on Aquatic Models and 21st Century Toxicology was held at North Carolina State University on May 5-6, 2014, in Raleigh, North Carolina, USA. Participants discussed the ways in which small fish are being used as models to screen toxicants and understand mechanisms of toxicity. Workshop participants agreed that the lack of standardized protocols is an impediment to broader acceptance of these models, whereas development of standardized protocols, validation, and subsequent regulatory acceptance would facilitate greater usage. Given the advantages and increasing application of small fish models, there was widespread interest in follow-up workshops to review and discuss developments in their use. In this article, we summarize the recommendations formulated by workshop participants to enhance the utility of small fish species in toxicology studies, as well as many of the advances in the field of toxicology that resulted from using small fish species, including advances in developmental toxicology, cardiovascular toxicology, neurotoxicology, and immunotoxicology. We also review many emerging issues that will benefit from using small fish species, especially zebrafish, and new technologies that will enable using these organisms to yield results unprecedented in their information content to better understand how toxicants affect development and health. PMID:27328013

Development and applications of TOHR, an original emission tomography system, adapted to small animals

International Nuclear Information System (INIS)

Ploux, Lydie

1997-01-01

For many neuro-biological studies, it is necessary to link microscopic aspects of the brain's organization with integrated brain functions. Details of the former are obtained by in vitro and in situ molecular biology techniques, whereas the latter are acquired through behavioural studies. In vivo radio-imaging methods, like emission tomography are the ideal tools to investigate the links between these two levels of brain organization. The work which is presented here focuses on a new approach of emission tomography adapted to small animal studies: TOHR (French, acronym for TOmographe Haute Resolution). The principle is based on the use of a large solid angle, high resolution and high efficiency focusing collimator. High resolution and high signal to noise ratio are improved by using nuclides having a two-photon decay with small angular correlation ( 125 I, 123 I, 111 In,...). The image is built step-by-step, by moving the animal relative to the collimator focal point. First, numerical simulation showed the possibility of reaching sub-millimetric resolutions; these results led to the collimator geometry (at present 10 over the 20 faces of an icosahedron, 15 faces in the future). Then, a prototype of TOHR has been built and characterized. Its performance is very close to the numerical prediction: spatial resolution of 1.4 mm and detection efficiency 0.64%. Finally, experiments on a rat thyroid allowed the preparation and realization of the first experiments on a rat striatum. The good quality of these images shows that it is now possible to evaluate TOHR capabilities on a dopaminergic neuron degeneration model in rats in the field of neuro-degenerative disease studies. (author)

Imaging circulating tumor cells in freely moving awake small animals using a miniaturized intravital microscope.

Directory of Open Access Journals (Sweden)

Laura Sarah Sasportas

Full Text Available Metastasis, the cause for 90% of cancer mortality, is a complex and poorly understood process involving the invasion of circulating tumor cells (CTCs into blood vessels. These cells have potential prognostic value as biomarkers for early metastatic risk. But their rarity and the lack of specificity and sensitivity in measuring them render their interrogation by current techniques very challenging. How and when these cells are circulating in the blood, on their way to potentially give rise to metastasis, is a question that remains largely unanswered. In order to provide an insight into this "black box" using non-invasive imaging, we developed a novel miniature intravital microscopy (mIVM strategy capable of real-time long-term monitoring of CTCs in awake small animals. We established an experimental 4T1-GL mouse model of metastatic breast cancer, in which tumor cells express both fluorescent and bioluminescent reporter genes to enable both single cell and whole body tumor imaging. Using mIVM, we monitored blood vessels of different diameters in awake mice in an experimental model of metastasis. Using an in-house software algorithm we developed, we demonstrated in vivo CTC enumeration and computation of CTC trajectory and speed. These data represent the first reported use we know of for a miniature mountable intravital microscopy setup for in vivo imaging of CTCs in awake animals.

Imaging circulating tumor cells in freely moving awake small animals using a miniaturized intravital microscope.

Science.gov (United States)

Sasportas, Laura Sarah; Gambhir, Sanjiv Sam

2014-01-01

Metastasis, the cause for 90% of cancer mortality, is a complex and poorly understood process involving the invasion of circulating tumor cells (CTCs) into blood vessels. These cells have potential prognostic value as biomarkers for early metastatic risk. But their rarity and the lack of specificity and sensitivity in measuring them render their interrogation by current techniques very challenging. How and when these cells are circulating in the blood, on their way to potentially give rise to metastasis, is a question that remains largely unanswered. In order to provide an insight into this "black box" using non-invasive imaging, we developed a novel miniature intravital microscopy (mIVM) strategy capable of real-time long-term monitoring of CTCs in awake small animals. We established an experimental 4T1-GL mouse model of metastatic breast cancer, in which tumor cells express both fluorescent and bioluminescent reporter genes to enable both single cell and whole body tumor imaging. Using mIVM, we monitored blood vessels of different diameters in awake mice in an experimental model of metastasis. Using an in-house software algorithm we developed, we demonstrated in vivo CTC enumeration and computation of CTC trajectory and speed. These data represent the first reported use we know of for a miniature mountable intravital microscopy setup for in vivo imaging of CTCs in awake animals.

Small-Diameter Awls Improve Articular Cartilage Repair After Microfracture Treatment in a Translational Animal Model.

Science.gov (United States)

Orth, Patrick; Duffner, Julia; Zurakowski, David; Cucchiarini, Magali; Madry, Henning

2016-01-01

Microfracture is the most commonly applied arthroscopic marrow stimulation procedure. Articular cartilage repair is improved when the subchondral bone is perforated by small-diameter microfracture awls compared with larger awls. Controlled laboratory study. Standardized rectangular (4 × 8 mm) full-thickness chondral defects (N = 24) were created in the medial femoral condyle of 16 adult sheep and debrided down to the subchondral bone plate. Three treatment groups (n = 8 defects each) were tested: 6 microfracture perforations using small-diameter awls (1.0 mm; group 1), large-diameter awls (1.2 mm; group 2), or without perforations (debridement control; group 3). Osteochondral repair was assessed at 6 months in vivo using established macroscopic, histological, immunohistochemical, biochemical, and micro-computed tomography analyses. Compared with control defects, histological cartilage repair was always improved after both microfracture techniques (P Subchondral bone cysts and intralesional osteophytes were frequently observed after either microfracture treatment. Macroscopic grading, DNA, proteoglycan, and type I and type II collagen contents as well as degenerative changes within the adjacent cartilage remained unaffected by the awl diameter. Small-diameter microfracture awls improve articular cartilage repair in the translational sheep model more effectively than do larger awls. These data support the use of small microfracture instruments for the surgical treatment of cartilage defects and warrant prolonged clinical investigations. © 2015 The Author(s).

Design of small-animal thermal neutron irradiation facility at the Brookhaven Medical Research Reactor

International Nuclear Information System (INIS)

Liu, H.B.

1996-01-01

The broad beam facility (BBF) at the Brookhaven Medical Research Reactor (BMRR) can provide a thermal neutron beam with flux intensity and quality comparable to the beam currently used for research on neutron capture therapy using cell-culture and small-animal irradiations. Monte Carlo computations were made, first, to compare with the dosimetric measurements at the existing BBF and, second, to calculate the neutron and gamma fluxes and doses expected at the proposed BBF. Multiple cell cultures or small animals could be irradiated simultaneously at the so-modified BBF under conditions similar to or better than those individual animals irradiated at the existing thermal neutron irradiation Facility (TNIF) of the BMRR. The flux intensity of the collimated thermal neutron beam at the proposed BBF would be 1.7 x 10 10 n/cm 2 ·s at 3-MW reactor power, the same as at the TNIF. However, the proposed collimated beam would have much lower gamma (0.89 x 10 -11 cGy·cm 2 /n th ) and fast neutron (0.58 x 10 -11 cGy·cm 2 /n th ) contaminations, 64 and 19% of those at the TNIF, respectively. The feasibility of remodeling the facility is discussed

Animal Models Used to Explore Abdominal Aortic Aneurysms

DEFF Research Database (Denmark)

Lysgaard Poulsen, J; Stubbe, J; Lindholt, J S

2016-01-01

OBJECTIVE: Experimental animal models have been used to investigate the formation, development, and progression of abdominal aortic aneurysms (AAAs) for decades. New models are constantly being developed to imitate the mechanisms of human AAAs and to identify treatments that are less risky than...... those used today. However, to the authors' knowledge, there is no model identical to the human AAA. The objective of this systematic review was to assess the different types of animal models used to investigate the development, progression, and treatment of AAA and to highlight their advantages...... and limitations. METHODS: A search protocol was used to perform a systematic literature search of PubMed and Embase. A total of 2,830 records were identified. After selection of the relevant articles, 564 papers on animal AAA models were included. RESULTS: The most common models in rodents, including elastase...

Combinations of chromosome transfer and genome editing for the development of cell/animal models of human disease and humanized animal models.

Science.gov (United States)

Uno, Narumi; Abe, Satoshi; Oshimura, Mitsuo; Kazuki, Yasuhiro

2018-02-01

Chromosome transfer technology, including chromosome modification, enables the introduction of Mb-sized or multiple genes to desired cells or animals. This technology has allowed innovative developments to be made for models of human disease and humanized animals, including Down syndrome model mice and humanized transchromosomic (Tc) immunoglobulin mice. Genome editing techniques are developing rapidly, and permit modifications such as gene knockout and knockin to be performed in various cell lines and animals. This review summarizes chromosome transfer-related technologies and the combined technologies of chromosome transfer and genome editing mainly for the production of cell/animal models of human disease and humanized animal models. Specifically, these include: (1) chromosome modification with genome editing in Chinese hamster ovary cells and mouse A9 cells for efficient transfer to desired cell types; (2) single-nucleotide polymorphism modification in humanized Tc mice with genome editing; and (3) generation of a disease model of Down syndrome-associated hematopoiesis abnormalities by the transfer of human chromosome 21 to normal human embryonic stem cells and the induction of mutation(s) in the endogenous gene(s) with genome editing. These combinations of chromosome transfer and genome editing open up new avenues for drug development and therapy as well as for basic research.

Laboratory animal models for esophageal cancer

Directory of Open Access Journals (Sweden)

Dhanya Venugopalan Nair

2016-11-01

Full Text Available The incidence of esophageal cancer is rapidly increasing especially in developing countries. The major risk factors include unhealthy lifestyle practices such as alcohol consumption, smoking, and chewing tobacco to name a few. Diagnosis at an advanced stage and poor prognosis make esophageal cancer one of the most lethal diseases. These factors have urged further research in understanding the pathophysiology of the disease. Animal models not only aid in understanding the molecular pathogenesis of esophageal cancer but also help in developing therapeutic interventions for the disease. This review throws light on the various recent laboratory animal models for esophageal cancer.

Animal Models of Allergic Diseases

Directory of Open Access Journals (Sweden)

Domenico Santoro

2014-12-01

Full Text Available Allergic diseases have great impact on the quality of life of both people and domestic animals. They are increasing in prevalence in both animals and humans, possibly due to the changed lifestyle conditions and the decreased exposure to beneficial microorganisms. Dogs, in particular, suffer from environmental skin allergies and develop a clinical presentation which is very similar to the one of children with eczema. Thus, dogs are a very useful species to improve our understanding on the mechanisms involved in people’s allergies and a natural model to study eczema. Animal models are frequently used to elucidate mechanisms of disease and to control for confounding factors which are present in studies with patients with spontaneously occurring disease and to test new therapies that can be beneficial in both species. It has been found that drugs useful in one species can also have benefits in other species highlighting the importance of a comprehensive understanding of diseases across species and the value of comparative studies. The purpose of the current article is to review allergic diseases across species and to focus on how these diseases compare to the counterpart in people.

High Throughput Screen for Novel Antimicrobials using a Whole Animal Infection Model

Science.gov (United States)

Moy, Terence I.; Conery, Annie L.; Larkins-Ford, Jonah; Wu, Gang; Mazitschek, Ralph; Casadei, Gabriele; Lewis, Kim; Carpenter, Anne E.; Ausubel, Frederick M.

2009-01-01

The nematode Caenorhabditis elegans is a unique whole animal model system for identifying small molecules with in vivo anti-infective properties. C. elegans can be infected with a broad range of human pathogens, including Enterococcus faecalis, an important human nosocomial pathogen with a mortality rate of up to 37% that is increasingly acquiring resistance to antibiotics. Here, we describe an automated, high throughput screen of 37,200 compounds and natural product extracts for those that enhance survival of C. elegans infected with E. faecalis. The screen uses a robot to accurately dispense live, infected animals into 384-well plates, and automated microscopy and image analysis to generate quantitative, high content data. We identified 28 compounds and extracts that were not previously reported to have antimicrobial properties, including 6 structural classes that cure infected C. elegans animals but do not affect the growth of the pathogen in vitro, thus acting by a mechanism of action distinct from antibiotics currently in clinical use. Our versatile and robust screening system can be easily adapted for other whole animal assays to probe a broad range of biological processes. PMID:19572548

Animal Models of Diabetic Retinopathy: Summary and Comparison

Science.gov (United States)

Lo, Amy C. Y.

2013-01-01

Diabetic retinopathy (DR) is a microvascular complication associated with chronic exposure to hyperglycemia and is a major cause of blindness worldwide. Although clinical assessment and retinal autopsy of diabetic patients provide information on the features and progression of DR, its underlying pathophysiological mechanism cannot be deduced. In order to have a better understanding of the development of DR at the molecular and cellular levels, a variety of animal models have been developed. They include pharmacological induction of hyperglycemia and spontaneous diabetic rodents as well as models of angiogenesis without diabetes (to compensate for the absence of proliferative DR symptoms). In this review, we summarize the existing protocols to induce diabetes using STZ. We also describe and compare the pathological presentations, in both morphological and functional aspects, of the currently available DR animal models. The advantages and disadvantages of using different animals, ranging from zebrafish, rodents to other higher-order mammals, are also discussed. Until now, there is no single model that displays all the clinical features of DR as seen in human. Yet, with the understanding of the pathological findings in these animal models, researchers can select the most suitable models for mechanistic studies or drug screening. PMID:24286086

Small-animal whole-body imaging using a photoacoustic full ring array system

Science.gov (United States)

Xia, Jun; Guo, Zijian; Aguirre, Andres; Zhu, Quing; Wang, Lihong V.

2011-03-01

In this report, we present a novel 3D photoacoustic computed tomography (PACT) system for small-animal whole-body imaging. The PACT system, based on a 512-element full-ring transducer array, received photoacoustic signals primarily from a 2-mm-thick slice. The light was generated by a pulse laser, and can either illuminate from the top or be reshaped to illuminate the sample from the side, using a conical lens and an optical condenser. The PACT system was capable of acquiring an in-plane image in 1.6 s; by scanning the sample in the elevational direction, a 3D tomographic image could be constructed. We tested the system by imaging a cylindrical phantom made of human hairs immersed in a scattering medium. The reconstructed image achieved an in-plane resolution of 0.1 mm and an elevational resolution of 1 mm. After deconvolution in the elevational direction, the 3D image was found to match well with the phantom. The system was also used to image a baby mouse in situ; the spinal cord and ribs can be seen easily in the reconstructed image. Our results demonstrate that the PACT system has the potential to be used for fast small-animal whole-body tomographic imaging.

Bioadhesive agents in addition to oral contrast media - evaluation in an animal model

International Nuclear Information System (INIS)

Conrad, R.; Schneider, G.; Textor, J.; Schild, H.H.; Fimmers, R.

1998-01-01

Purpose: To evaluate the additional effect of bioadhesives in combination with iotrolan and barium as oral contrast media in an animal model. Method: The bioadhesives Noveon, CMC, Tylose and Carbopol 934 were added to iotrolan and barium. The solutions were administered to rabbits by a feeding tube. The animals were investigated by computed tomography (CT) and radiography after 0,5, 4, 12, 24 and in part after 48 hours. Mucosal coating and contrast filling of the bowel were evaluated. Results: Addition of bioadhesives to oral contrast media effected long-term contrast in the small intestine and colon, but no improvement in continuous filling and coating of the gastrointestinal tract was detected. Mucosal coating was seen only in short regions of the caecum and small intestine. In CT the best results for coating were observed with tylose and CMC, in radiography additionally with carbopol and noveon. All contrast medium solutions were well tolerated. Conclusion: The evaluated contrast medium solutions with bioadhesives have shown long-term contrast but no improvement in coating in comparison to conventional oral contrast media. (orig.) [de

Establishment study of the in vivo imaging analysis with small animal imaging modalities for bio-durg development

International Nuclear Information System (INIS)

Jang, Beomsu; Park, Sanghyeon; Choi, Dae Seong; Park, Jeonghoon; Jung, Uhee; Lee, Yun Jong

2012-01-01

In this study, we established the image modalities (micro-PET, SPECT/CT) using the experimental animal (mouse) for the development of imaging assessment method for the bio-durg and extramural collaboration proposal. We examined the micro-SPECT/CT, PET imaging study using the Siemens Inveon micro-multimodality system (SPECT/CT) and imaging study using the Siemens Inveon micro-multimodality system (SPECT/CT) and micro-PET with 99m Tc tricarbonyl bifunctional chelators and 18 F-clotrimazole derivative. SPECT imaging studies were performed with 99m Tc tricarbonyl BFCs. PET imaging study was performed with 18 F-clotrimazole derivatives. We performed the PET image study of 18 F-clotrimazole derivatives using U87MG tumor bearing mice. Also we tested the intramural and extramural collaboration using small animal imaging modalities and prepared the draft of extramural R and D operation manual for small animal imaging modalities and the experimental animal imaging facility. These research results can be utilized as a basic image study protocols and data for the image assessment of drugs including biological drug

Quantitation of dopamine transporter blockade by methylphenidate: first in vivo investigation using [123I]FP-CIT and a dedicated small animal SPECT

International Nuclear Information System (INIS)

Nikolaus, Susanne; Wirrwar, Andreas; Antke, Christina; Arkian, Shahram; Mueller, Hans-Wilhelm; Larisch, Rolf; Schramm, Nils

2005-01-01

The aim of this study was to investigate the feasibility of assessing dopamine transporter binding after treatment with methylphenidate in the rat using a recently developed high-resolution small animal single-photon emission computed tomograph (TierSPECT) and [ 123 I]FP-CIT. [ 123 I]FP-CIT was administered intravenously 1 h after intraperitoneal injection of methylphenidate (10 mg/kg) or vehicle. Animals underwent scanning 2 h after radioligand administration. The striatum was identified by superimposition of [ 123 I]FP-CIT scans with bone metabolism and perfusion scans obtained with 99m Tc-DPD and 99m Tc-tetrofosmin, respectively. As these tracers do not pass the blood-brain barrier, their distribution permits the identification of extracerebral anatomical landmarks such as the orbitae and the harderian glands. The cerebellum was identified by superimposing [ 123 I]FP-CIT scans with images of brain perfusion obtained with 99m Tc-HMPAO. Methylphenidate-treated animals and vehicle-treated animals yielded striatal equilibrium ratios (V '' 3 ) of 0.24±0.26 (mean ± SD) and 1.09±0.42, respectively (ttest, two-tailed, p '' 3 values amounted to 0.05±0.28 (methylphenidate) and 0.3±0.39 (saline, p=0.176). This first in vivo study of rat dopamine transporter binding after pre-treatment with methylphenidate showed a mean reduction of 78% in striatal [ 123 I]FP-CIT accumulation. The results can be interpreted in terms of a pharmacological blockade in the rat striatum and show that in vivo quantitation of dopamine transporter binding is feasible with [ 123 I]FP-CIT and the TierSPECT. This may be of future relevance for in vivo investigations on rat models of attention deficit/hyperactivity disorder. Furthermore, our findings suggest that investigations in other animal models, e.g. of Parkinson's and Huntington's disease, may be feasible using SPECT radioligands and small animal imaging systems. (orig.)

Large Animal Stroke Models vs. Rodent Stroke Models, Pros and Cons, and Combination?

Science.gov (United States)

Cai, Bin; Wang, Ning

2016-01-01

Stroke is a leading cause of serious long-term disability worldwide and the second leading cause of death in many countries. Long-time attempts to salvage dying neurons via various neuroprotective agents have failed in stroke translational research, owing in part to the huge gap between animal stroke models and stroke patients, which also suggests that rodent models have limited predictive value and that alternate large animal models are likely to become important in future translational research. The genetic background, physiological characteristics, behavioral characteristics, and brain structure of large animals, especially nonhuman primates, are analogous to humans, and resemble humans in stroke. Moreover, relatively new regional imaging techniques, measurements of regional cerebral blood flow, and sophisticated physiological monitoring can be more easily performed on the same animal at multiple time points. As a result, we can use large animal stroke models to decrease the gap and promote translation of basic science stroke research. At the same time, we should not neglect the disadvantages of the large animal stroke model such as the significant expense and ethical considerations, which can be overcome by rodent models. Rodents should be selected as stroke models for initial testing and primates or cats are desirable as a second species, which was recommended by the Stroke Therapy Academic Industry Roundtable (STAIR) group in 2009.

The complete guide to blender graphics computer modeling and animation

CERN Document Server

Blain, John M

2014-01-01

Smoothly Leads Users into the Subject of Computer Graphics through the Blender GUIBlender, the free and open source 3D computer modeling and animation program, allows users to create and animate models and figures in scenes, compile feature movies, and interact with the models and create video games. Reflecting the latest version of Blender, The Complete Guide to Blender Graphics: Computer Modeling & Animation, 2nd Edition helps beginners learn the basics of computer animation using this versatile graphics program. This edition incorporates many new features of Blender, including developments

GATE simulation of a new design of pinhole SPECT system for small animal brain imaging

International Nuclear Information System (INIS)

Ozsahin, D. Uzun; Bläckberg, L.; Fakhri, G. El; Sabet, H.

2017-01-01

Small animal SPECT imaging has gained an increased interest over the past decade since it is an excellent tool for developing new drugs and tracers. Therefore, there is a huge effort on the development of cost-effective SPECT detectors with high capabilities. The aim of this study is to simulate the performance characteristics of new designs for a cost effective, stationary SPECT system dedicated to small animal imaging with a focus on mice brain. The conceptual design of this SPECT system platform, Stationary Small Animal SSA-SPECT, is to use many pixelated CsI:TI detector modules with 0.4 mm × 0.4 mm pixels in order to achieve excellent intrinsic detector resolution where each module is backed by a single pinhole collimator with 0.3 mm hole diameter. In this work, we present the simulation results of four variations of the SSA-SPECT platform where the number of detector modules and FOV size is varied while keeping the detector size and collimator hole size constant. Using the NEMA NU-4 protocol, we performed spatial resolution, sensitivity, image quality simulations followed by a Derenzo-like phantom evaluation. The results suggest that all four SSA-SPECT systems can provide better than 0.063% system sensitivity and < 1.5 mm FWHM spatial resolution without resolution recovery or other correction techniques. Specifically, SSA-SPECT-1 showed a system sensitivity of 0.09% in combination with 1.1 mm FWHM spatial resolution.

Animal models of GM2 gangliosidosis: utility and limitations

Science.gov (United States)

Lawson, Cheryl A; Martin, Douglas R

2016-01-01

GM2 gangliosidosis, a subset of lysosomal storage disorders, is caused by a deficiency of the glycohydrolase, β-N-acetylhexosaminidase, and includes the closely related Tay–Sachs and Sandhoff diseases. The enzyme deficiency prevents the normal, stepwise degradation of ganglioside, which accumulates unchecked within the cellular lysosome, particularly in neurons. As a result, individuals with GM2 gangliosidosis experience progressive neurological diseases including motor deficits, progressive weakness and hypotonia, decreased responsiveness, vision deterioration, and seizures. Mice and cats are well-established animal models for Sandhoff disease, whereas Jacob sheep are the only known laboratory animal model of Tay–Sachs disease to exhibit clinical symptoms. Since the human diseases are relatively rare, animal models are indispensable tools for further study of pathogenesis and for development of potential treatments. Though no effective treatments for gangliosidoses currently exist, animal models have been used to test promising experimental therapies. Herein, the utility and limitations of gangliosidosis animal models and how they have contributed to the development of potential new treatments are described. PMID:27499644

Role of surgery in multimodal cancer therapy for small animals.

Science.gov (United States)

Boston, Sarah; Henderson, Ralph A

2014-09-01

Surgery is a critical component in the treatment of most solid tumors in small animals. Surgery is increasingly combined with adjuvant therapies such as chemotherapy and radiation so surgeons who are treating cancer must have a good understanding of surgical oncology principles, cancer biology, and the roles and potential interactions of surgery, radiation, and chemotherapy. The sequencing plan for these modalities should be determined before treatment is initiated. The surgical oncologist must have a working knowledge of chemotherapy agents and radiation and the effect of these treatments on the ability of tissues to heal and the outcome for the patient. Copyright © 2014 Elsevier Inc. All rights reserved.

From animal models to human disease: a genetic approach for personalized medicine in ALS.

Science.gov (United States)

Picher-Martel, Vincent; Valdmanis, Paul N; Gould, Peter V; Julien, Jean-Pierre; Dupré, Nicolas

2016-07-11

Amyotrophic Lateral Sclerosis (ALS) is the most frequent motor neuron disease in adults. Classical ALS is characterized by the death of upper and lower motor neurons leading to progressive paralysis. Approximately 10 % of ALS patients have familial form of the disease. Numerous different gene mutations have been found in familial cases of ALS, such as mutations in superoxide dismutase 1 (SOD1), TAR DNA-binding protein 43 (TDP-43), fused in sarcoma (FUS), C9ORF72, ubiquilin-2 (UBQLN2), optineurin (OPTN) and others. Multiple animal models were generated to mimic the disease and to test future treatments. However, no animal model fully replicates the spectrum of phenotypes in the human disease and it is difficult to assess how a therapeutic effect in disease models can predict efficacy in humans. Importantly, the genetic and phenotypic heterogeneity of ALS leads to a variety of responses to similar treatment regimens. From this has emerged the concept of personalized medicine (PM), which is a medical scheme that combines study of genetic, environmental and clinical diagnostic testing, including biomarkers, to individualized patient care. In this perspective, we used subgroups of specific ALS-linked gene mutations to go through existing animal models and to provide a comprehensive profile of the differences and similarities between animal models of disease and human disease. Finally, we reviewed application of biomarkers and gene therapies relevant in personalized medicine approach. For instance, this includes viral delivering of antisense oligonucleotide and small interfering RNA in SOD1, TDP-43 and C9orf72 mice models. Promising gene therapies raised possibilities for treating differently the major mutations in familial ALS cases.

New approach to intracardiac hemodynamic measurements in small animals

DEFF Research Database (Denmark)

Eskesen, Kristian; Olsen, Niels T; Dimaano, Veronica L

2012-01-01

Invasive measurements of intracardiac hemodynamics in animal models have allowed important advances in the understanding of cardiac disease. Currently they are performed either through a carotid arteriotomy or via a thoracotomy and apical insertion. Both of these techniques have disadvantages...... and are not conducive to repeated measurements. Therefore, the purpose of this study was to develop a new technique for measuring intracardiac hemodynamics....

Animal models of chronic obstructive pulmonary disease.

Science.gov (United States)

Pérez-Rial, Sandra; Girón-Martínez, Álvaro; Peces-Barba, Germán

2015-03-01

Animal models of disease have always been welcomed by the scientific community because they provide an approach to the investigation of certain aspects of the disease in question. Animal models of COPD cannot reproduce the heterogeneity of the disease and usually only manage to represent the disease in its milder stages. Moreover, airflow obstruction, the variable that determines patient diagnosis, not always taken into account in the models. For this reason, models have focused on the development of emphysema, easily detectable by lung morphometry, and have disregarded other components of the disease, such as airway injury or associated vascular changes. Continuous, long-term exposure to cigarette smoke is considered the main risk factor for this disease, justifying the fact that the cigarette smoke exposure model is the most widely used. Some variations on this basic model, related to exposure time, the association of other inducers or inhibitors, exacerbations or the use of transgenic animals to facilitate the identification of pathogenic pathways have been developed. Some variations or heterogeneity of this disease, then, can be reproduced and models can be designed for resolving researchers' questions on disease identification or treatment responses. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

Denoising of high resolution small animal 3D PET data using the non-subsampled Haar wavelet transform

International Nuclear Information System (INIS)

Ochoa Domínguez, Humberto de Jesús; Máynez, Leticia O.; Vergara Villegas, Osslan O.; Mederos, Boris; Mejía, José M.; Cruz Sánchez, Vianey G.

2015-01-01

PET allows functional imaging of the living tissue. However, one of the most serious technical problems affecting the reconstructed data is the noise, particularly in images of small animals. In this paper, a method for high-resolution small animal 3D PET data is proposed with the aim to reduce the noise and preserve details. The method is based on the estimation of the non-subsampled Haar wavelet coefficients by using a linear estimator. The procedure is applied to the volumetric images, reconstructed without correction factors (plane reconstruction). Results show that the method preserves the structures and drastically reduces the noise that contaminates the image

Denoising of high resolution small animal 3D PET data using the non-subsampled Haar wavelet transform

Energy Technology Data Exchange (ETDEWEB)

Ochoa Domínguez, Humberto de Jesús, E-mail: hochoa@uacj.mx [Departamento de Ingeniería Eléctrica y computación, Universidad Autónoma de Ciudad Juárez, Ciudad Juárez, Chih. (Mexico); Máynez, Leticia O. [Departamento de Ingeniería Eléctrica y computación, Universidad Autónoma de Ciudad Juárez, Ciudad Juárez, Chih. (Mexico); Vergara Villegas, Osslan O. [Departamento de Ingeniería Industrial, Universidad Autónoma de Ciudad Juárez, Ciudad Juárez, Chih. (Mexico); Mederos, Boris; Mejía, José M.; Cruz Sánchez, Vianey G. [Departamento de Ingeniería Eléctrica y computación, Universidad Autónoma de Ciudad Juárez, Ciudad Juárez, Chih. (Mexico)

2015-06-01

PET allows functional imaging of the living tissue. However, one of the most serious technical problems affecting the reconstructed data is the noise, particularly in images of small animals. In this paper, a method for high-resolution small animal 3D PET data is proposed with the aim to reduce the noise and preserve details. The method is based on the estimation of the non-subsampled Haar wavelet coefficients by using a linear estimator. The procedure is applied to the volumetric images, reconstructed without correction factors (plane reconstruction). Results show that the method preserves the structures and drastically reduces the noise that contaminates the image.

Design, construction and testing of a DC bioeffects test enclosure for small animals. Final report

Energy Technology Data Exchange (ETDEWEB)

Frazier, M J; Preache, M M

1980-11-01

This final report describes both the engineering development of a DC bioeffects test enclosure for small laboratory animals, and the biological protocol for the use of such enclosures in the testing of animals to determine possible biological effects of the environment associated with HVDC transmission lines. The test enclosure which has been designed is a modular unit, which will house up to eight rat-sized animals in individual compartments. Multiple test enclosures can be used to test larger numbers of animals. A prototype test enclosure has been fabricated and tested to characterize its electrical performance characteristics. The test enclosure provides a simulation of the dominant environment associated with HVDC transmission lines; namely, a static electric field and an ion current density. A biological experimental design has been developed for assessing the effects of the dominant components of the HVDC transmission line environment.

Two new animal models for actinide toxicity studies

International Nuclear Information System (INIS)

Taylor, G.N.; Gardner, P.A.; Jones, C.W.; Lloyd, R.D.; Mays, C.W.

1979-01-01

Two small rodent species, the grasshopper mouse (Onychomys leucogaster) and the deer mouse (Peromyscus maniculatus) have tenacious retention in the liver and skeleton of plutonium and americium. The retention following intraperitoneal injection of Pu and Am in citrate solution ranged from 20 to 47% (liver) and 19 to 42% (skeleton), relatively independent of post-injection times, varying from 30 to 125 days. Based on observations extended to 125 days post-injection, the biological half-times appeared to be long. Both of these rodents are relatively long-lived (median lifespans of approximately 1400 days), breed well in captivity, and adapt suitably to laboratory conditions. It is suggested that these two species of mice, in which plutonium is partitioned between the skeleton and liver in a manner similar to that of man, may be useful animal models for actinide toxicity studies

Accuracy and Radiation Dose of CT-Based Attenuation Correction for Small Animal PET: A Monte Carlo Simulation Study

International Nuclear Information System (INIS)

Yang, Ching-Ching; Chan, Kai-Chieh

2013-06-01

-Small animal PET allows qualitative assessment and quantitative measurement of biochemical processes in vivo, but the accuracy and reproducibility of imaging results can be affected by several parameters. The first aim of this study was to investigate the performance of different CT-based attenuation correction strategies and assess the resulting impact on PET images. The absorbed dose in different tissues caused by scanning procedures was also discussed to minimize biologic damage generated by radiation exposure due to PET/CT scanning. A small animal PET/CT system was modeled based on Monte Carlo simulation to generate imaging results and dose distribution. Three energy mapping methods, including the bilinear scaling method, the dual-energy method and the hybrid method which combines the kVp conversion and the dual-energy method, were investigated comparatively through assessing the accuracy of estimating linear attenuation coefficient at 511 keV and the bias introduced into PET quantification results due to CT-based attenuation correction. Our results showed that the hybrid method outperformed the bilinear scaling method, while the dual-energy method achieved the highest accuracy among the three energy mapping methods. Overall, the accuracy of PET quantification results have similar trend as that for the estimation of linear attenuation coefficients, whereas the differences between the three methods are more obvious in the estimation of linear attenuation coefficients than in the PET quantification results. With regards to radiation exposure from CT, the absorbed dose ranged between 7.29-45.58 mGy for 50-kVp scan and between 6.61-39.28 mGy for 80-kVp scan. For 18 F radioactivity concentration of 1.86x10 5 Bq/ml, the PET absorbed dose was around 24 cGy for tumor with a target-to-background ratio of 8. The radiation levels for CT scans are not lethal to the animal, but concurrent use of PET in longitudinal study can increase the risk of biological effects. The

Th17 in Animal Models of Rheumatoid Arthritis

Directory of Open Access Journals (Sweden)

Motomu Hashimoto

2017-07-01

Full Text Available IL-17-secreting helper CD4 T cells (Th17 cells constitute a newly identified subset of helper CD4 T cells that play a key role in the development of rheumatoid arthritis (RA in its animal models. Recently, several models of spontaneous RA, which elucidate the mechanism of RA onset, have been discovered. These animal models shed new light on the role of Th17 in the development of autoimmune arthritis. Th17 cells coordinate inflammation and promote joint destruction, acting on various cells, including neutrophils, macrophages, synovial fibroblasts, and osteoclasts. Regulatory T cells cannot control Th17 cells under conditions of inflammation. In this review, the pathogenic role of Th17 cells in arthritis development, which was revealed by the recent animal models of RA, is discussed.

Experimental animal models for COPD: a methodological review

Directory of Open Access Journals (Sweden)

Vahideh Ghorani

2017-05-01

The present review provides various methods used for induction of animal models of COPD, different animals used (mainly mice, guinea pigs and rats and measured parameters. The information provided in this review is valuable for choosing appropriate animal, method of induction and selecting parameters to be measured in studies concerning COPD.

Animal Cancer Models of Skeletal Metastasis

Directory of Open Access Journals (Sweden)

Catherine Hibberd

2013-01-01

Full Text Available The bony skeleton is one of the most common sites of metastatic spread of cancer and is a significant source of morbidity in cancer patients, causing pain and pathologic fracture, impaired ambulatory ability, and poorer quality of life. Animal cancer models of skeletal metastases are essential for better understanding of the molecular pathways behind metastatic spread and local growth and invasion of bone, to enable analysis of host-tumor cell interactions, identify barriers to the metastatic process, and to provide platforms to develop and test novel therapies prior to clinical application in human patients. Thus, the ideal model should be clinically relevant, reproducible and representative of the human condition. This review summarizes the current in vivo animal models used in the study of cancer metastases of the skeleton.

Lanchester's attrition models and fights among social animals

OpenAIRE

Eldridge S. Adams; Michael Mesterton-Gibbons

2003-01-01

Lanchester's models of attrition during warfare have served as the basis for several predictions about conflicts between groups of animals. These models and their extensions describe rates of mortality during battles as functions of the number and fighting abilities of individuals in each group, allowing analysis of the determinants of group strength and of the cumulative numbers of casualties. We propose modifications to Lanchester's models to improve their applicability to social animals. I...

Research progress on animal models of Alzheimer's disease

Directory of Open Access Journals (Sweden)

Wen DONG

2015-08-01

Full Text Available Alzheimer's disease (AD is a degenerative disease of the central nervous system, and its pathogenesis is complex. Animal models play an important role in study on pathogenesis and treatment of AD. This paper summarized methods of building models, observation on animal models and evaluation index in recent years, so as to provide related evidence for basic and clinical research in future. DOI: 10.3969/j.issn.1672-6731.2015.08.003

Animal models of obesity and diabetes mellitus

DEFF Research Database (Denmark)

Kleinert, Maximilian; Clemmensen, Christoffer; Hofmann, Susanna M

2018-01-01

More than one-third of the worldwide population is overweight or obese and therefore at risk of developing type 2 diabetes mellitus. In order to mitigate this pandemic, safer and more potent therapeutics are urgently required. This necessitates the continued use of animal models to discover......, validate and optimize novel therapeutics for their safe use in humans. In order to improve the transition from bench to bedside, researchers must not only carefully select the appropriate model but also draw the right conclusions. In this Review, we consolidate the key information on the currently...... available animal models of obesity and diabetes and highlight the advantages, limitations and important caveats of each of these models....

Feasibility of a CdTe-based SPECT for high-resolution low-dose small animal imaging: a Monte Carlo simulation study

International Nuclear Information System (INIS)

Park, S-J; Yu, A R; Lee, Y-J; Kim, Y-S; Kim, H-J

2014-01-01

Dedicated single-photon-emission computed tomography (SPECT) systems based on pixelated semiconductors such as cadmium telluride (CdTe) are in development to study small animal models of human disease. In an effort to develop a high-resolution, low-dose system for small animal imaging, we compared a CdTe-based SPECT system and a conventional NaI(Tl)-based SPECT system in terms of spatial resolution, sensitivity, contrast, and contrast-to-noise ratio (CNR). In addition, we investigated the radiation absorbed dose and calculated a figure of merit (FOM) for both SPECT systems. Using the conventional NaI(Tl)-based SPECT system, we achieved a spatial resolution of 1.66 mm at a 30 mm source-to-collimator distance, and a resolution of 2.4-mm hot-rods. Using the newly-developed CdTe-based SPECT system, we achieved a spatial resolution of 1.32 mm FWHM at a 30 mm source-to-collimator distance, and a resolution of 1.7-mm hot-rods. The sensitivities at a 30 mm source-to-collimator distance were 115.73 counts/sec/MBq and 83.38 counts/sec/MBq for the CdTe-based SPECT and conventional NaI(Tl)-based SPECT systems, respectively. To compare quantitative measurements in the mouse brain, we calculated the CNR for images from both systems. The CNR from the CdTe-based SPECT system was 4.41, while that from the conventional NaI(Tl)-based SPECT system was 3.11 when the injected striatal dose was 160 Bq/voxel. The CNR increased as a function of injected dose in both systems. The FOM of the CdTe-based SPECT system was superior to that of the conventional NaI(Tl)-based SPECT system, and the highest FOM was achieved with the CdTe-based SPECT at a dose of 40 Bq/voxel injected into the striatum. Thus, a CdTe-based SPECT system showed significant improvement in performance compared with a conventional system in terms of spatial resolution, sensitivity, and CNR, while reducing the radiation dose to the small animal subject. Herein, we discuss the feasibility of a CdTe-based SPECT system for high