What is Design-based Stereology

The term “design-based” is used to describe newer methods in stereology whose probes and the sampling schemes are ‘designed’, that is, defined a priori, so that the methods are independent of the size, shape, spatial orientation, and spatial distribution of the cells to be investigated. Older stereological methods were “model-based”, this means that they used models based on the geometric properties of the objects being studied. The design-based methods eliminate the need for using information about the geometry of the objects to be investigated, resulting in more robust data because potential sources of systematic errors in the calculations are eliminated.

Design-based stereology considers solutions in which models are avoided. In design-based stereology the objects are assumed to be fixed and the probes that investigate the objects are random. There are 4 basic assumptions that are avoided by design-based approaches:

  1. No assumptions about shape
  2. No assumptions about size
  3. No assumptions about orientation
  4. No assumptions about distributions

Design-based stereology can be divided into two main components: 1) analyses of the global and 2) local characteristics of tissues. Global charcteristics include volume, number, connectivity, and length of linear biological structures. These characteristics can be expressed as absolute values (e.g., the number of granule cells in the rat cerebellum, etc.) or as relative values (e.g., the volume fraction of the rat cerebellum occupied by the granule cell layer, the density of granule cells within the granule cell layer of the rat cerebellum, etc.). Local characteristics include the volume of a specific object (e.g. the volume of a pyramidal cell in the cortex). Both global and local characteristics can be analyzed by a variety of design-based probes. For example, the volume of the dentate gyrus is a global characteristic that can be analyzed with Cavalieri’s principle and point counting techniques; the mean nuclear volume of the cells is a local characteristic which can be analyzed with the Nucleator, the Planar Rotator, and the Point Sampled Intercepts method.

Why not use model based stereology?

Model based stereological methods use approximation methods to describe objects which are being studied. These approximations work only as well as the models truly represent the actual objects. The problems with models can be avoided by simply avoiding the use of models.

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