Dr. Joanna Jankowsky at Caltech has developed a Tet-off APP model, in which the expression of APP can be controlled with antibiotic treatment. These mice show several significant advantages for use as a model for Alzheimers.

These mice show several significant advantages for use as a model for Alzheimers. Dr. Russ Jacobs at Caltech has collected in vivo and ex vivo high resolution volumes of 16 mice. Recently, higher resolution actively stained specimens were collected at CIVM to examine correlated changes in brain morphology accompanying the production of plaques.

Overview

Alzheimers Disease (AD) is the most common cause of senile dementia in elderly patients. It is characterized by the accumulation of a small peptide known as amyloid beta. While the presence of cognitive decline in 2 or more functional domains suggests the presence of AD, definitive diagnosis can only be made at autopsy. Current treatments for AD based on increasing cholinergic tone provide only temporary slowing of disease progression – staving off cognitive decline by 1 year at most before the disease worsens. Research is underway to enable early diagnosis of AD and to develop new therapies aimed at inhibiting amyloid beta production.

Magnetic resonance (MR) imaging may be especially useful for the diagnosis and treatment of AD. Several studies have been done both in-vivo and ex-vivo using mouse models to characterize the tissue changes in AD progression. Techniques have ranged from direct visualization of plaques to indirect measurement of co-morbid parameters that change with increasing pathology.

Here we aim to develop simple in-vivo/ex-vivo MR protocols that provide high resolution of the neuro-anatomy and amyloid pathology in a mouse model for AD. In-vivo images were analyzed using texture analysis to determine the validity of this technique for use in AD imaging. Ex-vivo images were analyzed by large volume techniques to visualize plaque load across the whole brain. While ex-vivo techniques will benefit the understanding of basic disease mechanisms in animal models of AD, the development of accurate in-vivo image analysis techniques will be critical to the use of MRI in human diagnosis.

Figure 1. All 15 mice survived the in-vivo imaging before being euthanized. Representative images of a control mouse and +/+ mouse at 12 months old are shown.

Usage

SHIVA or MBAT are recommended for visualizing the datasets.

Download

The individual data files in analyze format (hdr and img files required for each data set) are contained in the following archives:

exvivo
• Control (123 MB – 4 data sets) – Download
• ++ (61 MB – 2 data sets) – Download

invivo
• Control (104 MB – 10 data sets) – Download
• ++ (53 MB – 5 data sets) – Download

Multiple datasets for an Experimental Autoimmune Encephalitis (EAE) mouse model of Multiple Sclerosis.

Overview

This document describes multiple datasets for an Experimental Autoimmune Encephalitis (EAE) mouse model of Multiple Sclerosis. These datasets were collected by collaborators at Caltech BIC, Duke CIVM, and UCLA LONI to examine a mouse model of multiple sclerosis.

Figure 1. Minimum deformation atlas of 76 isotropic diffusion weighted images (iDWI) in MBAT.

Mouse BIRN and our collaborators have used the EAE model of MS to visualize disease induced structural changes in the brain. Continuing MR and histology experiments have focused on identifying the pathological underpinnings of grey matter atrophy. MR studies with the Caltech and Duke sites, have demonstrated that this model shows increased grey matter atrophy in the cerebellum and a profound affect of disease upon the Purkinje neurons of the cerebellum. Three different types of data are available via this project:

• Magnetic Resonance Microscopy (MRM) data collected by Dr. Russ Jacob’s group at Beckman Institute, California Institute of Technology
• Magnetic Resonance Histology (MRH) data collected by Dr. G. Allan Johnson’s group at CIVM, Duke University Medical Center
• Glial fibrillary acidic protein (GFAP) Immunohistology collected by Dr. Allan MacKenzie-Graham and others in his group at LONI, University of California, Los Angeles

Usage

This dataset can be viewed using the Mouse BIRN Atlasing Tool (MBAT). See the respective manual for the program.

Contributors

Allan MacKenzie-Graham1, Matthew R. Tinsley 2, Kaanan P. Shah1, Cynthia Aguilar1, Lauren V. Strickland1, Jyl Boline1, Melanie Martin3, Laurie Morales4 , David W. Shattuck1, Russell E. Jacobs5, Rhonda R. Voskuhl4, and Arthur W. Toga1

1. Laboratory of Neuro Imaging, Department of Neurology, University of California, Los Angeles.
2. Department of Psychology, University of California, Los Angeles.
3. Department of Physics, University of Winnipeg.
4. Multiple Sclerosis Program, Department of Neurology, University of California, Los Angeles.
5. Beckman Institute, California Institute of Technology.

References

MacKenzie-Graham, A., Tinsley, M.R., Shah, K.P., Aguilar, C., Strickland, L.V., Boline, J., Martin, M., Morales, L., Shattuck, D.W., Jacobs, R.E., Voskuhl, R.R., and Toga, A.W. (2006) Cerebellar Cortical Atrophy in Experimental Autoimmune Encephalomyelitis. Neuroimage, 32(3):1016-23.

Acknowledgement

This work was made possible by Grant Number U24 RR021760 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NCRR or NIH.

Downloads

Data are compressed and combined into a single tar for download. Unzip these before viewing. Mac users can automatically unzip these files, or a program may be used such as winzip (http://www.winzip.com/index.htm) for Windows or gzip (http://www.gzip.org/) for Unix. To view volumes in MBAT, select “Open Data” and select the file in the Open dialogue. To view .atlas or .keg files in MBAT select the “Open Atlas” option and select the file in the Open dialogue.

For more information about MBAT visit http://mbat.loni.ucla.edu/

Magnetic Resonance Microscopy (MRM) data collected by Dr. Russ Jacob’s group at Beckman Institute, California Institute of Technology. Participants include Caltech and LONI.

Raw data (2 GB) – Download

Inhomogeneity corrected images (300 MB) – Download

Minimum deformation atlases and labels (98 MB) – Download

Duke Center for In-Vivo Microscopy (CIVM) contains high resolution MR brain images of normal and human-disease-model mice, including multiple MRI modalities and structural segmentation.

All datasets for each study are available for review and download from CIVMSpace, the Duke Center for In-Vivo Microscopy’s Web portal.

System Requirements

CIVMSpace is designed to work on the Microsoft Windows and Mac OS X platforms. Supported browsers on Windows are Internet Explorer versions 6.0 and above, and Mozilla Firefox versions 1.0 and above. On the Mac, Safari versions 1.3 and above and Mozilla Firefox versions 1.0 and above are supported.

VoxStation requires a working Java installation. It has been tested with Java 1.4, 1.5 and 1.6 on Windows, and Java 1.4 and 1.5 on Mac OS X.

Common Specimen

A collection of 8 brains imaged with two protocols: a T1 and a T2 weighted protocol with 43×43x90 microns resolution.

The project efforts are focused on the development and application of correlated imaging approaches (confocal and electron microscopy, microscopic MRI) to Parkinson’s Disease (PD) – applied first to recently generated transgenic animal models of PD (alpha-synuclein). These MRI scans will allow the examination and comparison volumes of brain structures quantitatively, as well as qualitative changes in tissue content, in both the a-SYN transgenic and age-matched control animals.

DAT-KO

A collection of Male DAT-KO (n = 4) and WT mice (n = 4) between 4 and 8 months of age were used in this study. Images were acquired with 3 dimensional rf refocused spin warp encoding on 3 D (256 × 256 × 512) image arrays covering an 11 × 11 × 22 mm field of view yielding isotropic voxels of 43 × 43 × 43 μm (8 × 10−5 mm3) T1 weighted images were acquired with TR = 100 ms, TE = 5 ms, NEX = 4. Perfusion with contrast agent reduces the mean T1 to <200 ms allowing acquisition of a T2 weighted image with a much shorter TR (200 ms) and TE (15 ms) than might be used with unstained (formalin fixed) tissues. NEX was reduced to 2.

Reference

Neuroimage. 2005 May 15;26(1):83-90. Magnetic resonance imaging at microscopic resolution reveals subtle morphological changes in a mouse model of dopaminergic hyperfunction. Cyr M, Caron MG, Johnson GA, Laakso A. Department of Cell Biology, Center for Models of Human Disease, Duke University Medical Center, Durham, NC 27710, USA.

Unstained mouse brains

A collection of 6 brains imaged with a multispectral protocol (5 constrast). The three-dimensional (3D) MR datasets acquired at 90-microm isotropic resolution. 21 labeles structures and the whole brain were identified in those brains.

Reference

Neuroimage. 2005 Aug 15;27(2):425-35. Automated segmentation of neuroanatomical structures in multispectral MR microscopy of the mouse brain. Ali AA, Dale AM, Badea A, Johnson GA. Center for In Vivo Microscopy, Box 3302, Duke University Medical Center, Durham, NC 27710, USA. anjum.ali at duke dot edu

Stained Mouse Brain

A collection of 6 stained brains imaged witin the skull using two protocols: a T1 weighted protocol and a T2 image (MEFIC enhanced 3D CPMG). Automated segmentations of the brains in 33 structures are provided, as well as as an atlas brain.

References

Sharief et al. in press. Badea A, Ali-Sharief AA, Johnson GA. Morphometric analysis of the C57BL/6J mouse brain. Neuroimage. 2007 Sep 1;37(3):683-93. Epub 2007 Jun 7.

Johnson GA, Ali-Sharief A, Badea A, Brandenburg J, Cofer G, Fubara B, Gewalt S, Hedlund LW, Upchurch L. High-throughput morphologic phenotyping of the mouse brain with magnetic resonance histology.
Neuroimage. 2007 Aug 1;37(1):82-9. Epub 2007 May 18.

Reeler mouse model

A collection of 12 high resolution three-dimensional (3D) MR data acquired at 21.5-micron isotropic resolution.

Reference

Neuroimage. 2007 Feb 15;34(4):1363-74. Epub 2006 Dec 20. Neuroanatomical phenotypes in the reeler mouse. Badea A, Nicholls PJ, Johnson GA, Wetsel WC. Center for In Vivo Microscopy, Box 3302, Duke University Medical Center, Durham, NC 27710, USA.

Genetic reference population

A collection of 24 brains : C57BL/6, DBA2 and 10 BXD strains selected for large hippocampal volume variations. The images are high resolution three-dimensional (3D) MR data acquired at 21.5-micron isotropic resolution (T1) and matched 43-micron resolution MEFIC processed scans (T2). The results of automated segmentation into 33 structures are also provided.

The panel of isogenic BXD strains of mice provides a superb resource to study the genetic basis of differences in brain structure and function. In previous work several research groups have discovered significant heritable differences in the size of the hippocampus, striatum, cerebellum, thalamus, olfactory bulb, neocortex, and amygdala. In many cases this variation has been linked to gene loci. However, it has not yet been practical to systematically quantify genetic covariance across multiple brain regions using a single “coherent” set of animals. In this study we addressed this problem by exploiting high-resolution MR microscopy and automated segmentation. We segmented 33 brain regions in a subset of BXD strains with maximal differences in hippocampal weight. We describe between strain differences in the volumes of these 33 brain structures. These differences in volume range for example from 20.42 mm³ to 30.42 mm³, with a coefficient of variation of 12.99% for hippocampus, from 14.51 mm³ to 24.66 mm³, with a coefficient of variation of 12.58% for striatum, and from 43.95 mm³ to 62.69 mm³, with a coefficient of variation of 8.68% for cerebellum. Data on the volume variability across these BXD strains are accessible online at www.genenetwork.org.

alpha-synuclein Parkinson disease model

A collection of 10 high resolution three-dimensional (3D) MR data acquired at 21.5-micron isotropic resolution (T1) and 10 matched 43-micron resolution MEFIC processed scans (T2).

Correlated Imaging Approaches and Multi-scale Databases for Research in Parkinson’s Disease. The goal of this project is to examine the brains of a transgenic mouse model of Parkinsonism using rodent MRI imaging. Specimens will include age matched non-transgenic controls. All efforts will be made to have a sufficient number of animals per group (with equal numbers of male and female animals). This study is designed to clarify the results of an earlier pilot study (UCSD-CIVM) in which a low number of subjects precluded our ability to ascertain the presence of gross volumetric and regional signal intensity differences in alpha-synuclein transgenic animals in comparison with non-transgenic control animals. The changes in structural volumes should coincide with areas known to be predisposed to either neuronal cell death or reactive gliosis. Regional changes in signal intensity may be associated with protein aggregations, neuronal cell death, or reactive gliosis. The MRI scans can then be reconciled with large scale images of protein distributions in similar animals. We hypothesize that there are such differences in the transgenic animals and that this new MRI study (with higher group N’s and higher scanning resolutions) will provide us with the necessary information to determine which scenario is most likely.

This atlas is a reconstructed Nissl volume collected from a C57BL/6J neonatal mouse.

To access this data: http://www.loni.ucla.edu/Atlases/Atlas_Detail.jsp?atlas_id=14

This atlas is reconstructed from T2-weighted magnetic resonance images acquired from 8 normal C57BL/6J neonatal mice.

To access this data: http://www.loni.ucla.edu/Atlases/Atlas_Detail.jsp?atlas_id=9

High-resolution (80um isotropic) contrast-enhanced diffusion tensor data was acquired from six background control (C3HeB) and six dysmyelinating shiverer (C3Fe.SWV shi/shi) mouse brains. The data consists of nominally unweighted and diffusion weighted images with optimized icosahedral sampling.

Description

Animal Protocol — The brains of congenic male homozygous shiverer mutants (C3Fe.SWV Mbpshi/Mbpshi, Jackson Laboratories, mean age at fixation = 6.0 +- 0.2 weeks, n = 6) and control males with the same background as the shiverers (C3HeB/FeJ, Jackson Laboratories, mean age at fixation 6.9 +- 0.2 weeks, n = 6) were studied using diffusion tensor imaging. Mice were anesthetized deeply using 2.5% Avertin (0.017ml/g body weight). The mouse was then fixed by transcardiac perfusion using 30ml of room temperature heparinized phosphate buffered saline followed by 30ml of room temperature 4% paraformaldehyde (PFA). All experiments were performed in accordance with protocols approved by the Institutional Animal Care and Use Committee of the California Institute of Technology. After death, the head was removed and rocked in 4% PFA overnight at 4C. The skin, lower jaw, ears and cartilaginous nose tip were removed and the head rocked in 50ml 0.01% sodium azide in PBS for 7.0 +- 0.1 days (mean +- sd) at 4C. The head was then transferred to a 5mM solution of gadoteridol (Prohance, Bracco Diagnostics Inc, Princeton NJ) and 0.01% sodium azide in PBS and rocked for 13.5 +- 1.9 days at 4C prior to MR imaging. All brains were equilibrated at room temperature for 8.5 +- 3.0 hours immediately prior to imaging at 20C. In four control and four shiverer brains, DTI acquisitions were repeated to address B1 homogeneity concerns and the second dataset used in the results analysis. The additional time spent by these brains in 5mM gadoteridol is included in the quoted time intervals above. The repeated brains also spent an additional 6.8 +- 0.1 hours equilibrating to room temperature prior to imaging.

Magnetic Resonance Imaging — All images were acquired using a vertical bore 11.7 Tesla Bruker Avance DRX500 system (Bruker Biospin, Germany) equipped with a Micro2.5 imaging gradient set capable of a peak gradient strength of 1T/m and a maximum slew rate of 12.5kT/m/s. The intact head was secured in a Teflon holder and submerged in a perfluoropolyether (Fomblin, Solvay Solexis, Inc, Thorofare, NJ) within a 50ml vial and imaged using a 35mm birdcage transmit/receive volume resonator. The ambient bore temperature was maintained at 20C by thermostatically controlled airflow. Optimized second order shimming was achieved across the whole sample using the Bruker implementation of Fastmap 1. Diffusion weighted images were acquired using a conventional pulsed-gradient spin echo (PGSE) sequence (TR/TE = 150ms/11.6ms, 256 x 150 x 130 matrix, 19.2mm x 15mm x 12mm FOV, 80_m isotropic voxel size, 1 average, _ = 3ms, _ = 5ms, Gd = 750mT/m, nominal b-factor = 1450 s/mm2). An optimized six point icosahedral encoding scheme 2 was used for diffusion weighted acquisitions with a single un-weighted reference image for a total imaging time of 6 hours.

Figure: Students t-statistic map for the group mean comparison between the diffusion tensor trace in wild-type and shiverer mutant mice overlaid on the edge-detected mean iDWI image for the wild-type group.

Accession Number

TBD

Citations to Include

Tyszka, J.M., Readhead, C., Bearer, E.L., Pautler, R.G. & Jacobs, R.E. Statistical diffusion tensor histology reveals regional dysmyelination effects in the shiverer mouse mutant. Neuroimage (2005).

Contributors

J. Michael Tyszka¹, Carol Readhead¹, Elaine L. Bearer^1,2, Robia G. Pautler^1,3 and Russell E. Jacobs¹

1. Biological Imaging Center, Division of Biology, California Institute of Technology, Pasadena, CA
2. Department of Pathology and Medicine, Brown University, Providence, RI
3. Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX

Technical Contact

J. Michael Tyszka, Ph.D.
Director, MR Physics
Caltech Brain Imaging Center
Email: jmt *AT* caltech.edu

Acknowledgements

The authors wish to thank Tim Hiltner for mouse perfusions and brain preparation, Natasha Kovacevic, Josette Chen and Mark Henkelmann for invaluable discussions regarding image coregistration and tissue fixation. This work was funded in part by the Human Brain Project (EB00232) with contributions from the National Institute of Biomedical Imaging and Bioengineering and the National Institute of Mental Health, the NCRR (RR13625), and MH61223.

Download

Data are compressed and combined into a single tar for download. Unzip these before viewing. Mac users can automatically unzip these files, or a program may be used such as winzip (http://www.winzip.com/index.htm) for Windows or gzip (http://www.gzip.org/) for Unix. To view volumes in MBAT, select “Open Data” and select the file in the Open dialogue. To view .atlas or .keg files in MBAT select the “Open Atlas” option and select the file in the Open dialogue.

For more information about MBAT visit http://cms.loni.ucla.edu/MBAT.

Archives
• Full Archive (600 MB) – Download
• Shiverer Mutants (300 MB) – Download
• Control Males (300 MB) – Download

Embryonic and adult mouse brain images were acquired using three dimensional diffusion tensor magnetic resonance microimaging technique.

Description

An atlas of developing mouse brains from embryonic and adult mouse brain images. The images were acquired using three dimensional diffusion tensor magnetic resonance microimaging technique. The atlas consists of a viewing software and diffusion tensor MR images from E14, E15, E16, E17, E18 and adult mouse brains.

MR Data Acquisition: Mouse brain specimens were fixed using 4% paraformaldehyde in phosphate-buffered saline (PBS) and stayed in fixation solution for over one month. Before imaging, we placed specimens in PBS for 24 hours, then transferred them into home-built MR-compatible tubes. The tubes were then filled with fombin (Fomblin Profludropolyether, Ausimont, Thorofare, New Jersey, USA) to prevent dehydration. Imaging was performed using a Bruker Biospin 500MHz (11.7 Tesla) spectrometer. Diffusion-weighted images were acquired with the field of view of approximately 12 mm x 9 mm x 9 mm. For diffusion-weighted images, the imaging matrix had a dimension of 128 x 100 x 100, which was zero-filled to 256 x 200 x 200 after the spectral data was apodized by a 10% trapezoidal function. The nominal resolution for embryonic images was approximately 40 ~ 45 micrometer per pixel isotropic. Eight to fourteen diffusion-weighted images were acquired with different diffusion gradient directions and magnitudes. For diffusion-weighted images, 3D fast spin echo imaging sequence was used with a repetition time (TR) of 0.9s, an echo time (TE) of 35 ms, and echo train length of 4, with four signal averages were used, for a total imaging time of 24 hours.

Data Processing: The diffusion tensor was calculated using a multivariant linear fitting method, and three pairs of eigen-values and eigen-vectors were calculated for each pixel. The eigen-vector associated with the largest eigen-value was referred to as the primary eigenvector. For the quantification of anisotropy, fractional anisotropy (FA) was used. Average diffusion weighted images (DW) were the sum of six diffusion weighted images with different diffusion gradient directions. Using primary eigen-vector and FA, color maps (V1FA) were calculated. In the color map images, the R(ed), G(reen), and B(lue) value of each pixel was defined by the orientation of its primary eigen-vector, and the intensity was proportional to the FA. Red was assigned to the fiber orientation along the anterior-posterior axis, green to the right-left axis, and blue to the dorsal-ventral axis.

Usage

AtlasView, a data viewer (see figure above), is included with the image data. It is for Windows 2000/XP only. The program can be started by double-clicking on it. AtlasView automatically loads image data and displays three orthogonal view of the image data. User can change the viewpoint by changing the slice number in area 1 in the figure below, and can change to image by selecting from a drop-down list in area 2.

Accession Number

TBD

Contributors/Authors

Susumu Mori, Ph.D.
Jiangyang Zhang, Ph.D.
Linda J. Richards, Ph.D.
Paul Yarowksy, Ph.D.
Hangyi Jiang, Ph.D.
Peter C.M. van Zijl, Ph.D.

Citations

• Three-Dimensional Diffusion Tensor Magnetic Resonance Microimaging of Adult Mouse Brain and Hippocampus J. Zhang, P.C.M. van Zijl, S. Mori, NeuroImage, Vol 15, Issue 4, Page 892-901, April 2002
• Three-dimensional anatomical characterization of the developing mouse brain by diffusion tensor microimaging J. Zhang, L. Richards, P. Yarowsky, H. Huang, P.C.M. van Zijl, S. Mori, Vol. 20, Issue 3, Page 1639-1648, November 2003

Technical Contacts

Susumu Mori (susumu *AT* mri.jhu.edu)
Jiangyang Zhang (jzhang3 *AT* jhmi.edu)

Acknowledgements

This research was supported by NIH grants RO1 AG20012-01, RO3 HD41407-01A1 and P41 RR15241-01.

Download

This page allows you to download the Mouse DTI Atlas. Due to the size of some of the files, the atlas has been split into individual downloads that are easier to retrieve.

Embryonic Development

• MORI_embryonic_development [tgz] [zip] 352MB

Postnatal Development

• msadult_2005 [tgz] [zip] 352MB
• msp0_04_2002 [tgz] [zip] 49MB
• msp10_071802 [tgz] [zip] 77MB

An atlas based on a magnetic resonance microscopy (MRM) image diffusion-weighted in the Z-direction acquired from a normal, 100-day old male C57BL/6J mouse. The atlas is comprised of a diffusion-weighted image volume, a label volume, a mask volume, and a label index.

Note: A download for this dataset will be available soon.

Description

MRM. Mice were anesthetized initially with ketamine/xylzaine and then maintained on isofluorane for the duration of the imaging experiment. Magnetic resonance imaging was done at 37 C using an 89 mm vertical bore 11.7 T Bruker Avance imaging spectrometer with a micro-imaging gradient insert and 30 mm birdcage RF coil (Bruker Instruments). Typical imaging parameters were as follows: T2-weighted RARE 3D imaging protocol (8 echoes), matrix dimensions = 256 x 256 x 256; FOV = 3 cm x 1.5 cm x 1.5; repetition time (TR) = 1500 ms; effective time (TE) = 10 ms; number of averages = 4. The images were padded with zeros to double the number of time domain points in each dimension, the Fourier transformed to yield a matrix of 512 x 256 x 256. This procedure is commonly called zero-filling and is a well known interpolation method (Farrar and Becker, 1971; Fukushima and Roeder, 1981). Typical spatial resolution was approximately 60 um3 per voxel.

Nomenclature and Delineations. Neural structures (including cell groups, fiber tracts and gross anatomical features such as the ventricles) were determined under the microscope from the histologically stained sections. 3D label volumes were painted onto coregistered MRM, Nissl-, myelin-, and acetylcholine esterase-stained volumes using BrainSuite (Shattuck and Leahy, 2002). The delineations depict asymmetries present in the sections, making them more immediately useful than if they were stylized. Delineation of brain nuclei requires an expert neuroanatomist to draw on high-level knowledge, accumulated over a lifetime of careful study of disparate materials (Swanson, 1998). Consequently, manual input was necessary for even approximate parcellation of brain in its fine details. In the development of a comprehensive, standardized, and mutually exclusive nomenclature (Bowden and Martin, 1995; Bard et al., 1998) and anatomic delineation, our primary reference was the mouse brain atlas of Paxinos and Franklin (Paxinos and Franklin, 2001).

Usage

This atlas volume can be viewed using the Mouse BIRN Atlasing Tool (MBAT) or SHIVA. See the respective manuals for these programs.

Accession Number

TBD

Download

http://www.loni.ucla.edu/Atlases/Atlas_Detail.jsp?atlas_id=19

Contributors/Authors

Allan MacKenzie-Graham¹, Erh-Fang Lee¹, Ivo D. Dinov¹, Mihail Bota², David W. Shattuck¹, Seth Ruffins³, Heng Yuan¹, Fotios Konstantinidis¹, Alain Pitiot^1,4, Yi Ding¹, Guogang Hu¹, Russell E. Jacobs³, and Arthur W. Toga¹

1. Laboratory of Neuro Imaging, Department of Neurology, University of California, Los Angeles, 710 Westwood Plaza, Room 4-238, Los Angeles, California 90095-1769, USA
2. NIBS – Neuroscience Program, University of Southern California, Los Angeles, California 90089-2520, USA
3. Beckman Institute, California Institute of Technology, 1200 E. California Blvd., Pasadena, California 91125-7400, USA
4. EPIDAURE Laboratory, Institut National de Recherche en Informatique et en Automatique, Sophia Antipolis 06902, France

Technical Contacts

Allan MacKenzie-Graham (amg *AT* ucla.edu)

Acknowledgements

This work was generously supported by research grants from the National Institute of Mental Health (5 RO1 MH61223) and the National Institutes of Health/National Center for Research Resources (P41 RR13642).

These data provide a high resolution, large scale mosaic image of a cerebellar distribution of cell bodies and alpha-synuclein from a non-transgenic animal (M. Martone; UCSD).

Description

A high resolution multiphoton microscopy mosaic image of a cerebellar distribution of cell bodies (Hoescht 33342; blue) and alpha-synuclein (green) from a non-transgenic animal.

This large scale image was acquired using a customized RTS2000 multi-photon microscope (Fan et al., 1999) equipped with a custom automated high precision motorized stage (Applied Precision LLC, Issaquah, WA, USA), which allows for the automatic acquisition of ultra-large field image mosaics in 2 and 3 dimensions (Price et al., In Press; Chow et al., Submitted). A Nikon Plan Apo TIRF (60X 1.45) oil immersion objective was used. These mosaic images are acquired by rastering the specimen along the X, Y, and Z axes, introducing a prescribed amount of overlap between acquired images (in this case 10%) to aid alignment. Unprocessed data acquired on the RTS2000 microscope is subsequently stored as a single stack of images. The image stack is analyzed using the JAVA-based ImageJ, a freely available software package, using plugins developed at NCMIR for processing, aligning, and assembling these massive datasets. Briefly, each file is separated into three separate .tiff stacks, one for each channel. Each tile is normalized to eliminate shading gradients, followed by the automatic alignment of individual tiles to form a full size mosaic image of the data for each channel. A globally optimized, accuracy. The assembled mosaics are then combined into one full-scale color image. For 3D imaging, the process is repeated for each wide field image plane in Z. The resulting image mosaics provide detailed views of cellular and subcellular structure and macromolecular distributions in a larger tissue context. These maps are being used to characterize Parkinson’s Disease. These data will provide the bridge between whole brain imaging techniques such as MRI (Duke University, CIVM) and electron microscopic (UCSD-NCMIR) analysis.

Accession Number

TBD

Download

The individual data files for the cerebellum mosaic are listed below:

Images
• Thumbnail (20 KB) – Download
• Scaled JPG (192 KB) – Download
• Original JPG (46.6 MB) – Download
• Original TIFF (697 MB) – Download

Access via CCDB

This data can also be accessed via registration through the Cell Centered Database (ccdb.ucsd.edu). Upon login, the user may query the database using the Project ID number 1187. The dataset ID is 102003b. Raw (*.img) and processed data (*.tiff) are freely available, as well as accompanying specimen preparation details (*.pdf).

Citations to Include

D.L. Price, S.K. Chow, H. Hakozaki, V. Phung, B. Smarr, S. Peltier, M.E. Martone, and M.H. Ellisman Application of a Multi-Photon High-Resolution Large-Scale Montage Imaging Technique to Characterize Transgenic Mouse Models of Human Neurodisorders, 2003 Microscopy & Microanalysis conference proceedings, Savannah, GA.

Price DL, Chow SK, MacLean NAB, Hakozaki H, Peltier S, Martone ME, Ellisman MH (2006) High-Resolution Large-Scale Mosaic Imaging using Multiphoton Microscopy to Characterize Transgenic Mouse Models of Human Neurological Disorders. Neuroinformatics 4(1):65-80

Contributors

National Center for Microscopy and Imaging Research at UC San Diego
Diana Price, Ph.D
Mark H. Ellisman, Ph.D.
Maryann Martone, Ph.D.

Technical Contact

Diana L. Price, Ph.D. (diana *AT* ncmir.ucsd.edu)

Acknowledgements

This work was supported by The Branfman Family and MJ Fox Foundations, NCRR RR04050, NIDCD DC03192 (CCDB), RR043050 (Mouse BIRN), and NIH LM 07292.

Six treat and 6 normal mice from this experiment are shared on the BIRN Microarray Database and may be queried and visualized in the Mouse BIRN Atlasing Toolkit (MBAT).