The Most Comprehensive Source of Stereology Information on the Web

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Stereology Information for the Biological Sciences

This site introduces both basic and advanced concepts of Stereology. The emphasis is on the use of stereology in biological research, though anyone interested in learning concepts of stereology will find something of interest. The application of stereological methods to biological studies permits researchers to effectively and efficiently gather unbiased, accurate data. This site is dedicated to helping researchers understand the principles of design-based stereology and its advantages over less sophisticated approaches in quantitative histology.

What is Stereology?

Design-based stereology is a set of methods to ensure rigorous quantitative analysis of the size, shape, and number of objects. When properly used, stereology plays an important role in validating and rejecting experimental hypotheses in biological research. It produces results that are unbiased, efficient, and more reliable than other ad hoc quantitative analyses. Unbiased stereology provides an important contribution to the advancement in biological research by improving the consistency and dependability of quantitative analytical results produced in the laboratory and reported in scientific publications.

An Introduction to Stereology Probes

The most modern unbiased stereology probes are used to quantify aspects of biological tissue in a reproducible and efficient manner. These stereological probes are appropriate for many fields of basic and applied biological and medical research. These probes should always be used in conjunction with systematic random sampling.



Estimate the size of cell populations with the optical fractionator in thick tissue sections. In this probe, sub-volumes are sampled and then are extrapolated to arrive at an estimate of the entire cell population. A virtual space called an optical disector is used in thick sections that can be oriented anyway you like. Disector counting rules are followed to avoid overestimating, and an oil objective lens is employed for imaging, since fine z-resolution is needed to find the leading edge of the cell and to have enough focal planes to determine if it is in the disector. Note: avoid counting pieces of cells when you really want to count whole cells.    OPTICAL FRACTIONATOR


NUCLEATOR to estimate VOLUME of cells

Estimate individual cell volumnucleator-2es with the nucleator. A point in the cell is identified, then one to four rays are marked and their mean length is used in the formula for the volume of a sphere, generating an estimate of the cell volume. The volume estimate is number-weighted; the sampling is done with a disector in thick sections so that it is not more likely to sample larger cells than smaller cells. It is important to use a method to select cells without bias by picking them in a manner that does not favor any position of the cell in space; you won’t overestimate by sampling too many larger cross-sections or underestimate by sampling too many smaller cross-sections.    NUCLEATOR




This probe is versatile in that it can be used on thin optical or physical sections that are oriented according to the preference of the researcher. A fraction of the tissue is marked with points over the region(s) of interest, and an extrapolation is carried out to arrive at the estimate. Unbiased estimates of regional volume are easy to obtain efficiently using Cavalieri point-counting.     CAVALIERI/POINT-COUNTING


SPACEBALLS to estimate LENGTH of fibers and vessels


Estimate length of biological filaments such as axons or blood vessels without facing the herculean task of tracing them all. Instead the intersections of the filaments with a virtual sphere are marked and converted to a length estimate. Thick sections may be oriented as the researcher prefers. This probe is implemented along with the fractionator method; a volume-fraction is sampled and extrapolated using the reciprocal of the volume fraction to arrive at the estimate of length.    SPACEBALLS


ISOTROPIC FAKIR to estimate SURFACE of membranes


To estimate surface area, a triplet of line segments that has the property of being isotropic in space is used to probe in thick sections. Intersections of the triplet with the surface are counted and a formula is used to arrive at an estimate of the surface area; the more intersections recorded the greater the surface. Like the other regional probes on this page, thick, preferentially oriented sections are used and the fractionator method works to make an extrapolation based on the fraction of volume that was sampled.     ISOTROPIC FAKIR

more probes including solutions for thin tissue sections


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Recent Noteworthy Stereology Publications

Published papers using unbiased stereology; last updated on 08/26/2016.

starindicates that the researchers did a good job reporting stereological parameters

starIdentification of Multiple QTLs Linked to Neuropathology in the Engrailed-1 Heterozygous Mouse Model of Parkinson’s Disease

Type-1 interferons contribute to the neuroinflammatory response and disease progression of the MPTP mouse model of Parkinson’s disease

Lithium suppression of tau induces brain iron accumulation and neurodegeneration

High-fat diet-induced brain region-specific phenotypic spectrum of CNS resident microglia

Repeated treatment with oxytocin promotes hippocampal cell proliferation, dendritic maturation and affects socio-emotional behavior

Effects of a higher dose of near-infrared light on clinical signs and neuroprotection in a monkey model of Parkinson’s disease

The number of striatal cholinergic interneurons expressing calretinin is increased in parkinsonian monkeys

Near-infrared light treatment reduces astrogliosis in MPTP-treated monkeys

Sensitivity of the prefrontal GABAergic system to chronic stress in male and female mice: Relevance for sex differences in stress-related disorders

The effect of AMPA receptor blockade on spatial information acquisition, consolidation and expression in juvenile rats

Neonatal Bacillus Calmette-Guérin vaccination alleviates lipopolysaccharide-induced neurobehavioral impairments and neuroinflammation in adult mice

Mesocortical Dopamine Phenotypes in Mice Lacking the Sonic Hedgehog Receptor Cdon

Infiltrating T lymphocytes reduce myeloid phagocytosis activity in synucleinopathy model

18F-AV-1451 tau PET imaging correlates strongly with tau neuropathology in MAPT mutation carriers

Selective plasticity of hippocampal GABAergic interneuron populations following kindling of different brain regions

Caspase-1 Deficiency Alleviates Dopaminergic Neuronal Death via Inhibiting Caspase-7/AIF Pathway in MPTP/p Mouse Model of Parkinson’s Disease

Cholinergic innervation of the basal ganglia in human and other anthropoid primates

Age-Dependent Neurogenesis and Neuron Numbers within the Olfactory Bulb and Hippocampus of Homing Pigeons

starManganese-Enhanced Magnetic Resonance Imaging for Detection of Vasoactive Intestinal Peptide Receptor 2 Agonist Therapy in a Model of Parkinson’s Disease

Dopaminergic neuron-specific deletion of p53 gene is neuroprotective in an experimental Parkinson’s disease model

Differential Apoptosis Radiosensitivity of Neural Progenitors in Adult Mouse Hippocampus

Transplantation of human oligodendrocyte progenitor cells in an animal model of diffuse traumatic axonal injury: survival and differentiation

Kallikrein-8 inhibition attenuates Alzheimer’s pathology in mice

EphB3 signaling propagates synaptic dysfunction in the traumatic injured brain

Continue reading “Recent Noteworthy Stereology publications”

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What’s New in

Added on 09.25.2015
Added on: 11.05.2015
Reviewed paper: Schmitz, C. and P.R. Hof (2005) Design-Based Stereology in Neuroscience. Neuroscience 130, 813-831. Added on: 03.10.2016
In 2014 researchers used Stereo Investigator in 698 peer-reviewed papers – citing it nearly 3x more than all other stereology systems combined.

Learn how to prepare your tissue accurately and efficiently.
Learn more about estimating your probe
Added on 04.10.2015

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developers of Stereo Investigator, the world’s most cited stereology system