"Good Stereology Through Good Engineering"

New STEREOLOGER users

"From my experience, the STEREOLOGER is more user-friendly than StereoInvestigator. I wish my lab would switch to the Stereologer software."
Graduate student, Rochester, New York

“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 StereoInvestigator. Also, real scientists answer my questions about histology and stereology. ”
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 prefer the STEREOLOGER."
Professor, 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."
Post-doctoral Scientist, National Institute on Aging, NIH, Baltimore, MD.

Recent peer-reviewed publications using the STEREOLOGER

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 203:293-301, 2007.

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.

• Can I count fluorescence-immunostained biological features (e.g., cells, fibers) using the STEREOLOGER? Yes. 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.
• Can I use video or digital cameras for stereology? Yes. The STEREOLOGER supports a wide variety of cameras, from straight video to the most advanced Firewire-compatible cameras.
• Does the STEREOLOGER analyze stored images from other sources, i.e., confocal and electron microscopy? Yes. The STEREOLOGER carries out design-based stereology using live video images orstacks 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 necessary 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.
• Does the SRC sell "add-ons" for semi-quantitative analysis of images? No. Other vendors work hard to "upsell" their computerized stereology systems with modules for tracing, mapping, image processing, etc. that are provided at no-cost to all biomedical scientists by the NIH (see Image J below). These vendors may also require that you purchase over priced hardwware to support thse add-ons, all of which include mandatory maintenence contracts. While once popular, these add-ons provide limited benefit today and cost a great deal in terms of time, labor, and support. Despite their hard sell from the vendor, the fact is that the majority of those who purchase these add-ons rarely, if ever, use them. Rather than promote such "add-ons" out of profit motives, we prefer that you use these funds to support your research in more productive ways.
• 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.
• 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.