Biological Tissue Analysis Software for Biomedical Research

Thomas Jefferson University, Philadelphia, PA
Georgetown Medical Center, Washington, DC
Emory University School of Medicine, Atlanta GA
Washington State University, Pullman, WA
Brown University School of Medicine, Providence, RI
Ohio University, Athens, OH

To prepare for your stimulus award, request a quote for your computerized stereology package. With the STEREOLOGER you are not only adding a computerized stereology system, you are putting stereology expertise to your research program.

Show Them The Data

Someone once said, "Images are worth a thousand words, but data is worth a thousand images." Though images convey remarkable anatomic features as shown above, images no longer provide convincing evidence to reviewers of journal manuscripts and funding agencies. In addition to images, the majority of reviewers now expect unbiased (accurate) data on cell loss, fiber degeneration, tissue atrophy, and other indices of morphological changes in tissue. The STEREOLOGER is the industry-leading, user-friendly, and most affordable option for computerized stereology available.

To see a video training exercise using the Stereologer system click here.

The STEREOLOGER is an integrated hardware-software-video microscopy system developed by Peter R. Mouton, Ph.D. of the Stereology Resource Center, the Johns Hopkins University School of Medicine, Baltimore, MD, and Systems Planning and Analysis, Inc. of Alexandria, VA. This multidisciplinary team of stereologists, biomedical scientists, and computer scientists designed and built this system with four peer-reviewed grants from the NIH's Small Business Innovative Research (SBIR) program. Today, biological scientists who use the STEREOLOGER in academic institutions, government agencies, and private industry enjoy the most trouble-free, user-friendly system available for the computerized applications of unbiased stereology, together with professional support from biostereologists.

Left: Unbiased stereology data for number of cells (microglia) in a defined brain region across different ages (Long et al., Neurobiology of Aging, 19:497-503, 1998).

Among the major attributes of the STEREOLOGER system are:

Best-selling computerized stereology system since 2003.
Most user-friendly stereology software.
Compatible with either Macintosh OSX and Window XP operating systems, microscopes, external motorized stages, and a variety of video and digital cameras.
Priced literally tens of thousands of dollars less than more aggressively marketed, more difficult systems.
Unbiased probes for all first- and second-order parameters, e.g., total cell number, total surface area, spatial distribution.
Highly efficient data collection using methods approved by the international stereology community.
On-site installation, professional training, and remote support available by stereology support staff.
Developed with funding from peer-reviewed Small Business Innovative Research grants from the NIH.

To see a video training exercise using the Stereologer system click here.

The STEREOLOGER packages, including current version of the software preloaded on a new Mac or PC computer, cost in the $30K - $35K for the Basic system, and $35K- $40K range for the Advanced system. Simply add to your microscope (sold separately) and you're ready to go*,**. Fast and simple.

*Price differences relate to different hardware options, e.g., cameras with differing resolutions and other features.
** Advanced system adds to the Basic system with an advanced XYZ motorized stage and encoder, high resolution color camera, on-site installation, stereology training, and annual maintenance agreement.

To receive a no-obligation quote that fits the needs of your research program, contact STEREOLOGER Specialist, Scott McElhiney, at:

Phone: 352-871-7045
Email: scott@disector.com.

Or click here to request an on-line quote.

Before you give in to the pushy and hyperagressive people from that "Marketing Before Function" bioscience company, give us a call. We provide the cutting-edge computerized stereology and professional expertise, without the over-priced hardware, outdated add-ons, and high annual maintenence fees.

Upgrade to the STEREOLOGER system

When you are ready to add stereology expertise to your research program, give us a call or request a quote on-line. Let us know what you have available or prefer in terms of PC or Mac computer, motorized XYZ stage, video or digital camera, etc. We will make maximum use of your equipment to provide state-of-the-art stereology at a significant savings off full system prices.

To receive a quote for a new STEREOLOGER system, or to convert your current system to the STEREOLOGER, contact Scott McElhiney at:

Phone: 352-871-7045
Email: scott@disector.com.

Click here to request an on-line quote.

Related Stereology Resources

Based on the simple goal of the SRC -- to increase the proficiency of design-based stereology in your research laboratory -- we support a number of other resources to assist in your stereology projects.

Comprehensive text by The Johns Hopkins University Press.
Well-organized stereology courses taught by professional scientists experienced in the biological applications of unbiased stereology.
"The Stereology Lowdown," the first and only blog that specializes in stereology-related issues of general interest to biomedical scientists.

Image Analysis and Stereology

The STEREOLOGER system meets this demand with all the critical features important to design-based stereology, including the optical fractionator, Cavalieri principle, physical disector, rotator, isotropic sphere probe (space balls), virtual cycloid, and many others too numerous to list, and all approved by experts in the international community of professional stereologists. You can capture and display images, export results to Excel, and even train new users using the Stereologer Tutorial.

For projects that require image analysis, and before you purchase expensive software and hardware, consider the powerful and highly respected Image J program, the cutting-edge image analysis system developed by the NIH for both Macintosh and PC platforms. Image J is provided free-of-charge to biomedical scientists, along with no-cost technical support and user assistance. The combination of STEREOLOGER and Image J provides a comprehensive and cost-effective stereology and image analysis at a small fraction of the cost for other commercially available stereology systems with image analysis add-ons, plug-in and packages. The bottom line -- why reduce your hard-earned research budget if you don't have to?

FAQs

Can I count fluorescence-immunostained biological features (e.g., cells, fibers) using the STEREOLOGER? Absolutely. The only requirement for counting cells, including single and multiple populations of cells immunostained with fluorescence-labeled antibodies, is that you can see the cells of interest. However, this raises an important limitation for all stereological applications using fluorescent staining -- fluorescent signals fade with time. For this reason, stereology results on fluorescence-immunostained sections carried out at time 0 will differ from similar counts carried out at time 0 + t, despite no underlying changes in the biological feature of interest. In contrast, biological features visualized with the diaminobenzidene (DAB) reaction remain immunopositive over years, if not decades. For this reason DAB-based visualization should be considered is the best option when possible, with fluorescent labeling of an adjacent set of sections for presentation of images in publications. For further discussion see the Stereology Lowdown.
What if I want a video camera for stereology and a digital camera on my microscope for publication photography? Both digital and video cameras use the same type of C-mount attachment to microscopes. With a trinocular nosepiece, essentially a tube above the oculars with dual camera-mounts, you can use a video or digital camera for stereology data collection and to capture high-resolution images for publication purposes.
Does the STEREOLOGER analyze stored images, as well as real-time video using design-based stereology? The STEREOLOGER carries out design-based stereology using both live video images, and stacks of digital images collected from other sources and saved in any of the major formats (TIFF, JPEG, etc.). Though slower than real-time analysis of video images, analysis of saved images is required for sections cut at an instrument setting of a few microns or less, e.g., electron and confocal image stacks, or as mentioned above to avoid the effects of fluorescent fading.
How much money should I spend on "add-ons" for semi-quantitative analysis of images? Some vendors try hard to "upsell" their computerized stereology systems with software for image analysis and image processing, including modules for tracing, mapping, and montaging. Some vendors also require that you purchase computers, video cards, cameras, and even microscopes, and they pay for installation, integration, and support for this hardware. While these add-ons have their uses, they also cost a great deal in terms of time, labor, and support. The fact is that the majority of those who purchase these add-ons rarely, if ever, use them.
How much time is required for stereological analysis of tissue? Analysis of a particular anatomically defined region of interest (reference space) requires one-hour or less of work. However, we recommend no more than 2-3 hours per work per day to avoid the introduction of bias from recognition errors. As a result, for a typical study data collection using the STEREOLOGER system requires a couple weeks of work on stained tissue sections, including the initial pilot study and optimization of sampling for maximal efficiency.
Does the STEREOLOGER allow for counting more than one feature on a single pass through the tissue sections for a single case? Yes, the STEREOLOGER allows you to count multiple objects on a single pass through the tissue. However, in the majority of cases this may not be overly useful. Optimal disector spacing is determined for a particular feature in order to achieve an optimal sampling efficiency, i.e., CE ~ 0.10. The driving force behind this optimal disector spacing is the spatial distribution of the cells in their reference space. If the same reference space contains two different features of interest, then the optimal spacing of disectors is usually very different due to differences in total numbers of each cell type. For example, the DG of the mouse brain contains ~ 24,000 microglial cells compared to ~ 70,000 for astrocytes in the same space (Long et al., 1998). For this reason, the optimal spacing of disectors for microglia counting will be about three times greater than that for astrocytes. In these cases, counting both cell types with two passes through the tissue usually takes less time than counting both with a single pass through the tissue. If all of these factors line up, then the STEREOLOGER allows counting up to three features during a single pass through a particular reference space. Some stereology software allows one to count 20 or more features at once, which sounds good for marketeering purposes, but for the reasons given above is not too useful for the day-to-day practice of stereology.
Why does the STEREOLOGER system cost tens of thousands of dollars less than some computerized stereology systems? Beware of significantly higher price quotes, in some cases two or three times higher than those quoted above for the STEREOLOGER system. These quotes contain numerous "add-on" hardware and software that has little if any to do with stereology or other state-of-the-art methods. This "feature creep" costs your research program hundreds, and in some cases tens of thousands of dollars for hardware, software, and maintenance costs that would be better spent in other areas of your research program. Also, like in the used car business, the large profit margins in these overpriced systems leads to aggressive sales and marketing tactics.
What is Image J? Formerly known as NIH Image, Image J is a comprehensive and powerful program for image processing/analysis with either PC or Mac platforms. This well-designed and professionally documented software is developed and supported by the NIH, and provided at no cost to the international scientific community. We highly recommend Image J for studies that require cutting-edge image analysis and image processing solutions. See links below for more information about Image J:

http://en.wikipedia.org/wiki/ImageJ
http://www.biocompare.com/prorev.asp?id=1090
http://www.indianjcancer.com/article.asp?issn=0019-509X;year=2004;volume=41;issue=1;spage=47;epage=47;aulast=Girish
http://rsb.info.nih.gov/nih-image/manual/faq.html

Does customer support differ for different computerized stereology systems? Vendors that use aggressive "marketeering before function" tactics put their effort into marketing, not technical support. Our customer-based philosophy ensures that your concerns and questions come before sales, marketing, and other considerations.
Can I convert my present stereology system to the STEREOLOGER? When you are ready to upgrade your current stereology system to the STEREOLOGER, call or email for a discounted quote that takes your current hardware into account.

To compare features of hardware and software, technical support, and other aspects of computerized stereology systems, call or email Scott McElhiney, Applications Specialist:

Phone: 352-871-7045
Email: scott@disector.com.

Click here to request an on-line quote for a STEREOLOGER system.

User Testimonials

“The STEREOLOGER system is enjoyable to use and, most importantly, I trust the data. The interface is far better organized and much easier to use than the other software. Also, real scientists are available to answer questions my histology and stereology questions. ”
Dr. D.L.L., Research Associate, The Johns Hopkins University School of Medicine, Baltimore, MD.

"I've tried them all, including the StereoInvestigator and CAST systems. I prefer the STEREOLOGER."
Dr. D.G.O., neuroscientist, user of the PC-version in University of Toledo, Spain.

"The students and technicians in my laboratory have different computerized stereology systems for data collection, and they all choose the STEREOLOGER."
Prof. R.B., behavioralist, user of the Mac-version University of California, Davis.

"...above all, we like the ease-of-use. Congrats on the user-interface and technical support in the STEREOLOGER system, which is far more straightforward and easier-to-use than the StereoInvestigator system (so 1995!)."
Dr. G.T., postdoctoral scientist, user of the PC-version at the National Institute On Aging, NIH, Baltimore, MD.

Recent peer-reviewed publications using the STEREOLOGER

The STEREOLOGER system is currently in use at hundreds of research institutions worldwide. Here is a partial list of studies that used the system, and were published in the past decade by our research group and our colleagues.

Burke, M, Zangenehpour, S, Mouton, PR, Ptito, M. (2009) Knowing What Counts: Unbiased Stereology In The Non-Human Primate Brain. Journal of Visual Experiments. http://www.jove.com/index/Details.stp?ID=1262.

Mouton, P.R., Gordon, M. Stereological and Image Analysis Techniques For Quantitative Assessment Of Neurotoxicology. In Neurotoxicology, 3rd Edition, Target Organ Toxicology Series. Eds. G. Jean Harry, Hugh A. Tilson. in press.

Berman, R.F., Pessah, I.N., Mouton, P.R., Mav, D. Harry J. Modeling neonatal thimerosal exposure in mice. Toxicol. Sci. Mar 25, 2008.

Berman, R.F., Pessah, I.N., Mouton, P.R. Mav, D., Harry, G.J. Low Level Neonatal Thimerosal Exposure: Further Evaluation of Altered Neurotoxic Potential in SJL Mice. Toxicol. Sci. Oct. 31, 2007.

Manaye, K.F., Wang, P., O’Neil, J., Huafu, S., Tizabi, Y., Thompson, N., Ottinger, M.A., Ingram, D.K., Mouton, P.R. Neuropathological Quantification Of Dtg APP/PS1: Neuroimaging, Stereology, And Biochemistry. AGE: 29:87-96, 2007.

Perry, T.A., Holloway, H.W., Weerasuriya, A., Mouton, P.R., Duffy, K., Mattison J.A. Evidence of GLP-1-mediated neuroprotection in an animal model of pyridoxine-induced peripheral sensory neuropathy. Exp Neurol 203:293-301, 2007.

Duffy, K.B, Spangler E.L., Devan B.D., Guo Z., Bowker J.L., Janas, A.M., Hagepanos, A., Minor, R.K., DeCabo R., Mouton, P.R., Shukitt-Hale, B., Joseph, J.A., Ingram, D.K. A blueberry-enriched diet provides cellular protection against oxidative stress and reduces a kainate-induced learning impairment in rats. Neurobiol Aging 2007, May 27.

O’Neil, J.N., Mouton, P.R., Tizabi Y., Ottinger, M.A., Lei, D-L., Ingram, D.K., Manaye, K.F. Catecholaminergic Neuron Number In Locus Coeruleus Of Aged Female Dtg APP/PS1 Mice. J. Chem. Neuroanat. Nov;34(3-4):102-7, 2007 .

Anderson, DW, Bradbury, KA,and Schneider, JA. Neuroprotection in Parkinson models varies with toxin administration protocol. Eur Journal Neurosci 24:3174, 2006.

Perry T, Holloway HW, Weerasuriya A, Mouton PR, Duffy K, Mattison JA, Greig NH. Evidence of GLP-1-mediated neuroprotection in an animal model of pyridoxine-induced peripheral sensory neuropathy. Exp Neurol. Nov 21, 2006.

Armstrong, R.C., Le, T.Q., Flint, N.C., Vana,A.C., Zhou., Y-X. Endogenous Cell Repair of Chronic Demyelination. J Neuropathol Exp Neurol. March; 65(3): 245–256, 2006.

RJ Roper, LL Baxter, NG Saran, DK Klinedinst, PA Beachy, RH Reeves. Defective cerebellar response to mitogenic Hedgehog signaling in Down syndrome mice. Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1452-6.

E. J. H. Schenck, C. L. Brooks Effects of an S84E Mutation of Bovine Growth Hormone in Transgenic Mice. Experimental Biology and Medicine, 231:296-302, 2006.

E. Aberg; T. M. Pham, M. Zwart, V. Baumans, S.C.A. Brene. Intermittent individual housing increases survival of newly proliferated cells. Neuroreport. 16(13):1419-1422, 2005.

Pimonporn Chaovipoch, Karen A. Bozak Jelks, Lynnette M. Gerhold, Eric J. West, Sukumal Chongthammakun, Candace L. Floyd. 17β-Estradiol Is Protective in Spinal Cord Injury in Post- and Pre-Menopausal Rats. J. Neurotrauma 2006, 23: 830-852.

Jianting Miao, Michael P. Vitek, Feng Xu, Mary Lou Previti, Judianne Davis, and William E. Van Nostrand Reducing Cerebral Microvascular Amyloid- Protein Deposition Diminishes Regional Neuroinflammation in Vasculotropic Mutant Amyloid Precursor Protein Transgenic Mice. J. Neurosci., 2005, 25:6271–6277.

Daniel Goti, Scott M. Katzen, Jesse Mez, Noam Kurtis, Jennifer Kiluk, Lea Ben-Haïem, Nancy A. Jenkins, Neal G. Copeland, Akira Kakizuka, Alan H. Sharp, Christopher A. Ross, Peter R. Mouton, and Veronica Colomer A Mutant Ataxin-3 Putative-Cleavage Fragment in Brains of Machado-Joseph Disease Patients and Transgenic Mice Is Cytotoxic above a Critical Concentration. J. Neurosci. 2004, 24:10266–10279.

Sarah A. Baker, K. Adam Baker, Theo Hagg. Dopaminergic nigrostriatal projections regulate neural precursor proliferation in the adult mouse subventricular zone. European J Neurosci 2004, 20: 575–579.

Kirkpatrick, Brian; Messias, Nidia C.; Conley, Robert R.; Roberts, Rosalinda C. Interstitial Cells of the White Matter in the Dorsolateral Prefrontal Cortex in Deficit and Nondeficit Schizophrenia. J Nervous & Mental Disease 2003, 191:563-567.

R.M. Sharpe, H.M. Fraser, M.F.H. Brougham, C. McKinnell, K.D. Morris, C.J.H. Kelnar, W.H.B. Wallace, M. Walker Role of the neonatal period of pituitary–testicular activity in germ cell proliferation and differentiation in the primate testis. Human Reproduction 2003, 18: 2110-2117.

JA Olschowka, WJ Bowers, SD Hurley, MA Mastrangelo, HJ Federoff. Helper-free HSV-1 amplicons elicit a markedly less robust innate immune response in the CNS. Mol Ther. 2003 Feb;7(2):218-27.

Regina C. Armstrong, Tuan Q. Le, Emma E. Frost, Rosemary C. Borke, and Adam C. Vana. Absence of Fibroblast Growth Factor 2 Promotes Oligodendroglial Repopulation of Demyelinated White Matter. J. Neurosci., 2002, 22:8574–8585.

Sonia Boncristiano, Michael E. Calhoun, Peter H. Kelly, Michelle Pfeifer, Luca Bondolfi, Martina Stalder, Amie L. Phinney, Dorothee Abramowski, Christine Sturchler-Pierrat, Albert Enz, Bernd Sommer, Matthias Staufenbiel, and Mathias Jucker Cholinergic Changes in the APP23 Transgenic Mouse Model of Cerebral Amyloidosis. J. Neurosci., 2002, 22:3234–3243.

Luca Bondolfi, Michael Calhoun, Florian Ermini, H. Georg Kuhn, Karl-Heinz Wiederhold, Lary Walker, Matthias Staufenbiel, and Mathias Jucker Amyloid-Associated Neuron Loss and Gliogenesis in the Neocortex of Amyloid Precursor Protein Transgenic Mice J. Neurosci., 2002, 22:515–522.

Paul T. Jantzen, Karen E. Connor, Giovanni DiCarlo, Gary L. Wenk, John L. Wallace, Amyn M. Rojiani, Domenico Coppola, Dave Morgan, and Marcia N. Gordon Microglial Activation and -Amyloid Deposit Reduction Caused by a Nitric Oxide-Releasing Nonsteroidal Anti-Inflammatory Drug in Amyloid Precursor Protein Plus Presenilin-1 Transgenic Mice. J. Neurosci., 2002, 22:2246–2254.

C.J.H. Kelnar, C. McKinnell, M. Walker, K.D. Morris, W.H.B. Wallace, P.T.K. Saunders, H.M. Fraser, R.M. Sharpe Testicular changes during infantile ‘quiescence’ in the marmoset and their gonadotrophin dependence: a model for investigating susceptibility of the prepubertal human testis to cancer therapy? Human Reproduction, 2002, 17:1367-1378.

Inna I. Kruman, T. S. Kumaravel, Althaf Lohani, Ward A. Pedersen, Roy G. Cutler, Yuri Kruman, Norman Haughey, Jaewon Lee, Michele Evans, and Mark P. Mattson Folic Acid Deficiency and Homocysteine Impair DNA Repair in Hippocampal Neurons and Sensitize Them to Amyloid Toxicity in Experimental Models of Alzheimer's DiseaseJ. Neurosci., 2002, 22:1752–1762.

Mouton PR, Gokhale AM, Ward NL, West MJ. Stereological Length Estimation Using Spherical Probes. J. Microscopy, 206: 54-64, 2002

Mouton, P.R., J.M. Long, E.A. Stocks, S. Rim, V. Howard, M. Jucker, M.E. Calhoun, D.K. Ingram. Age and Gender-based Differences in Astrocytes And Microglia in Hippocampal Subregions of C57BL/6J Mice. Brain Research 956:30-35, 2002.

Zanjani HS, , Vogel MW, Delhaye-Bouchaud N, Martinou JC, Mariani J. Increased cerebellar Purkinje cell numbers in mice overexpressing a human bcl-2 transgene. J Comp Neurol. 1996 Oct 21;374(3):332-41.

Govek EK, Wang J, Swann JM. Sex differences in the magnocellular subdivision of the medial preoptic nucleus in Syrian hamsters. Neuroscience. 2003;116(2):593-8.

Liu Z, Gastard M, Verina T, Bora S, Mouton PR, Koliatsos VE. Estrogens modulate experimentally induced apoptosis of granule cells in the adult hippocampus. J Comp Neurol 441:1-8, 2001.

Jucker M, Bondolfi L, Calhoun ME, Long JM, Ingram DK. Structural brain aging in inbred mice: potential for genetic linkage, Exp Gerontol 35:1383-1388, 2000.

Holtzman DM, Bales KR, Tenkova T, Fagan AM, Parsadanian M, Sartorius LJ, Mackey B, Olney J, McKeel D, Wozniak D, Paul SM. Apolipoprotein E isoform-dependent amyloid deposition and neuritic degeneration in a mouse model of Alzheimer's disease. Proc Natl Acad Sci U S A 14;97(6):2892-2897, 2000.

Farber NB, Rubin EH, Newcomer JW, Kinscherf DA, Miller JP, Morris JC, Olney JW, McKeel DW Jr. Increased neocortical neurofibrillary tangle density in subjects with Alzheimer disease and psychosis. Arch Gen Psychiatry 57:1165-1173, 2000.

Lee J, Duan W, Long JM, Ingram DK, Mattson MP. Dietary restriction increases the number of newly generated neural cells, and induces BDNF expression, in the dentate gyrus of rats. J Mol Neurosci 15(2): 99-108, 2000.

Calhoun ME, Mouton PR. New Developments In Neurostereology:Length Measurement And 3D Imagery. J Chem Neuroanat 1:61-9,2000.

Calhoun ME, Kurth D, Phinney AL, Long JM, Hengemihle J, Mouton PR, Ingram DK, Jucker M. Hippocampal neuron and synaptophysin-positive bouton number in aging C57BL/6 mice. Neurobiol Aging 1998 Nov; 19(6):599-606

Phinney AL, Calhoun ME, Wolfer DP, Lipp HP, Zheng H, Jucker M. No hippocampal neuron or synaptic bouton loss in learning-impaired aged beta-amyloid precursor protein-null mice. Neuroscience 90(4): 1207-1216, 1999.

Long JM, Mouton PR, Jucker M, Ingram DK: What Counts In Brain Aging? Design-Based Stereological Analysis Of Cell Number. J. Gerontology 54A: B407-B417, 1999.

Calhoun M.E., Wiederhold K.H., Abramowski D., Phinney A.L., Probst A., Sturcher-Pierrat C., Staufenbiel M., Sommer B., Jucker M. Neuron loss in APP transgenic mice. Nature, 395, 755-756, 1998.

Long, J.M., Kalehua A.N., Muth N.J., Hengemihle J.M., Jucker M., Calhoun M.E., Ingram D.K., and Mouton P.R. Stereological estimation of total microglia number in mouse hippocampus. J. Neuroscience Methods 1: 84:101-108, 1998.

Mouton PR, Martin LJ, Calhoun ME, Dal Forno G, Troncoso JC, Price DL. Cognitive Decline Strongly Correlates With Cortical Atrophy In Alzheimer’s Dementia. Neurobiol. Aging, 19: 371-377, 1998.


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