Ferris C.F.,Northeastern University |
Marella M.,Scripps Research Institute |
Smerkers B.,New York University |
Barchet T.M.,Northeastern University |
And 3 more authors.
Brain and Behavior | Year: 2013
This study was undertaken to develop a phenotypic model recapitulating the neuropathology of Parkinson's disease (PD). Such a model would show loss of dopamine in the basal ganglia, appearance of Lewy bodies, and the early stages of motor dysfunction. The model was developed by subcutaneously injecting biodegradable microspheres of rotenone, a complex I inhibitor in 8-9 month old, ovariectomized Long-Evans rats. Animals were observed for changes in body weight and motor activity. At the end of 11-12 weeks animals were euthanized and the brains examined for histopathological changes. Rotenone treated animals gain weight and appear normal and healthy as compared to controls but showed modest hypokinesia around 5-6 weeks posttreatment. Animals showed loss of dopaminergic (DA) neurons and the appearance of putative Lewy bodies in the substantia nigra. Neuroinflammation and oxidative stress were evidenced by the appearance of activated microglia, iron precipitates, and 8-oxo-2′-deoxyguanosine a major product of DNA oxidation. The dorsal striatum, the projection site of midbrain DA neurons, showed a significant reduction in tyrosine hydroxylase immunostaining, together with an increase in reactive astrocytes, an early sign of DA nerve terminal damage. Levels of vesicular monoamine transporter 2 (VMAT2) were significantly reduced in the dorsal striatum; however, there was an unexpected increase in dopamine transporter (DAT) levels. Old, ovariectomized females treated with rotenone microspheres present with normal weight gain and good health but a modest hypokinesia. Accompanying this behavioral phenotype are a constellation of neuropathologies characteristic of PD that include loss of DA neurons, microglia activation, oxidative damage to nuclear DNA, iron deposition, and appearance of putative Lewy bodies. This phenotypic model recapitulating the neuropathology of Parkinson's disease could provide insight into early mechanisms of pathogenesis and could aid in the identification of biomarkers to identify patients in early stage, PD. © 2013 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.
Hoppin J.,InviCRO LLC |
Orcutt K.D.,Beth Israel Deaconess Medical Center |
Hesterman J.Y.,InviCRO LLC |
Silva M.D.,Millennium Pharmaceuticals Inc. |
And 3 more authors.
Journal of Pharmacology and Experimental Therapeutics | Year: 2011
Recent advances in small-animal molecular imaging instrumentation combined with well characterized antibody-labeling chemistry have enabled detailed in vivo measurements of antibody distribution in mouse models. This article reviews the strengths and limitations of in vivo antibody imaging methods with a focus on positron emission tomography and singlephoton emission computed tomography and a brief discussion of the role of optical imaging in this application. A description of the basic principles behind the imaging techniques is provided along with a discussion of radiolabeling methods relevant to antibodies. Practical considerations of study design and execution are presented through a discussion of sensitivity and resolution tradeoffs for these techniques as defined by modality, signaling probe (isotope or fluorophore) selection, labeling method, and radiation dosimetry. Images and analysis results from a case study are presented with a discussion of output data content and relevant informatics gained with this approach to studying antibody pharmacokinetics. Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics.
inviCRO LLC and Curadel LLC | Date: 2016-08-31
In one embodiment, a fluorescence histo-tomography (FHT) system is disclosed. The FHT system includes a housing, a fluorescence camera located within the housing, a white light camera located within the housing, and a fluorescence light source located within the housing. The FHT system further includes a support mount configured to support the housing within a chamber of a slicing apparatus such that the cameras and fluorescence light source are aimed towards a block face of a tissue specimen retained within the chamber.
Millennium Pharmaceuticals Inc., Invicro Llc, University of Iowa and Stc.Unm | Date: 2014-12-03
This disclosure provides radiolabeled compounds that bind to guanylyl cyclase C (GCC) and which can bind cancer cells that express GCC. Exemplary compounds comprise a chelating moiety capable of binding a radioactive atom, a peptide capable of binding GCC, and a linker moiety connecting the two. This disclosure also provides methods of detecting and treating cancer using the compounds described herein.
University of Arizona and inviCRO LLC | Date: 2015-02-03
The present invention provides methods and systems for 3D imaging of in vivo and ex vivo tissues. The disclosed systems and methods employ an autoradiographic approach where particles emitted by a radioactive composition within the tissue are detected. Once detected, a 3D representation of the source of particles within the tissue is reconstructed for viewing and analysis.
Invicro Llc | Date: 2011-12-08
A method is provided for estimating a parameter of physiological significance. One or more images are provided of a tissue in a subject to whom a dose of a contrast agent (CA) has been administered, using a computer equipped with image processing software, the concentration or relative concentration of the agent in a region or regions of interest in the tissue is determined, thus generating concentration data. The time-based behavior of concentrations of CA within the tissue is determined using a pharmacokinetic model that is based on a set of pharmacokinetic model parameters. Using computer code, the pharmacokinetic model is fit to the concentration data, varying one or more parameters, such that a best fit estimate of a parameter of physiological significance is provided.
inviCRO LLC | Date: 2013-01-08
inviCRO LLC | Date: 2010-03-09
Invicro Llc | Date: 2013-06-07
A method of estimating a parameter of physiological significance in the central nervous system (CNS) is provided. The method comprises (a) providing one or more images of the brain or cerebral spinal fluid (CSF) in a subject to whom a dose of a contrast agent (CA) has been administered; (b) determining, using a computer equipped with image processing software, the concentration or relative concentration of the agent in a region or regions of interest in the brain or CSF, thereby generating concentration data; (c) describing the time-based behavior of concentrations of CA within the brain or CSF using a pharmacokinetic model that is based on a set of pharmacokinetic model parameters; and (d) fitting, using computer code, the pharmacokinetic model to the concentration data, varying one or more parameters, wherein the best fit estimates a parameter of physiological significance in the CNS.
inviCRO LLC | Date: 2016-05-19
Disclosed is a computer-implemented method of creating an image of a specimen including receiving a first image of a first section of a specimen created using a first wavelength of invisible light a second image of a second section of the specimen adjacent to the first section and the second image created using the first wavelength of invisible light, co-registering the first image and the second image and creating, by the processor, a single-plane image of the first section using a next-image process.