Optimizing sampling efficiency of stereological studies in biology: or ‘Do more less well!‘

Gundersen, Hans Jørgen G.; Østerby, Ruth

doi:10.1111/j.1365-2818.1981.tb01199.x

Cited by 503 publications

(261 citation statements)

References 8 publications

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“…Stereology Using computer-assisted stereology, volumes for MRI slices and tissue sections were estimated using the Cavalieri principle with point counting (Gundersen and Østerby 1981;Gunderson Fig. 1 a-j Representative T2-weighted MRI of serial sections through the entire mouse hippocampus (outlined), with an interslice distance of 1 mm.…”

Section: Methodsmentioning

confidence: 99%

“…In order to capture the majority of variability withinand between-mice for each group, data were collected at a high level of stringency, i.e., the coefficient of error (CE) was less than one-half of the biological variability (Gundersen and Østerby 1981;Long et al 1998;Gundersen et al 1999). The results were calculated as mean +/− (SEM) for each group and for each modality (MRI or histology); inter-rater variation between the volumetric measurements was less than 2%.…”

Section: Methodsmentioning

confidence: 99%

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Neuropathological quantification of dtg APP/PS1: neuroimaging, stereology, and biochemistry

Manaye

Wang

O’Neil

et al. 2007

AGE

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Murine models that mimic the neuropathology of Alzheimer's disease (AD) have the potential to provide insight into the pathogenesis of the disease and lead to new strategies for the therapeutic management of afflicted patients. We used magnetic resonance imaging (MRI), design-based stereology, and high performance liquid chromatography (HPLC) to assess the age-related neuropathology in double transgenic mice that overexpress two AD-related proteins-amyloid precursor protein (APP) and presenilin 1 (PS1)-and age-and gender-matched wild-type (WT) controls. In mice ranging in age from 4-28 months, total volumes of the hippocampal formation (V HF ) and whole brain (V brain ) were quantified by the Cavalieri-point counting method on a systematic-random sample of coronal T2-weighted MRI images; the same stereological methods were used to quantify V HF and V brain after perfusion and histological processing. To assess changes in ADtype beta-amyloid (Aβ) plaques, sections from the hippocampal formation and amylgdaloid complex of mice aged 5, 12, and 15 months were stained by Congo Red histochemistry. In aged mice with large numbers of amyloid plaques, systematic-random samples of sections were stained by GFAP immunocytochemistry to assess gender and genotype effects on total numbers of astrocytes. In addition, levels of norepinephrine (NE), dopamine (DA), serotonin (5-HT) and 5-HT metabolites were assayed by HPLC in fresh-frozen samples from neocortex, striatum, hippocampus, and brainstem. We confirmed age-related increases in amyloid plaques, beginning with a few plaques at 5 months of age and increasing densities by AGE (2007) 12 and 15 months. At 15 months of age, there were robust genotype effects, but no gender effects, on GFAP-immunopositive astrocytes in the amygdaloid complex and hippocampus. There were no effects on monoamine levels in all brain regions examined, and no volume changes in hippocampal formation or whole brain as quantified on either neuroimages or tissue sections. Strong correlations were present between volume estimates from MRI images and histological sections, with about 85% reduction in mean V HF or mean V brain between MRI and processed histological sections. In summary, these findings show that the double transgenic expression of AD-type mutations is associated with age-related increases in amyloid plaques and astrocytosis; however, this model does not recapitulate the cortical atrophy or neurochemical changes that are characteristic of AD.29:87-96 DOI 10.1007/s11357-007-9035-

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Neuropathological quantification of dtg APP/PS1: neuroimaging, stereology, and biochemistry

Manaye

Wang

O’Neil

et al. 2007

AGE

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“…For many features of interest in biological tissues, the observed biological variation among individuals is large, and it is useful to know whether it is worth increasing the precision of the stereological sampling or including more animals in the study (Gundersen and Osterby, 1981). One may divide the observed variance (OCV) into its two components, the true biological variation (CV) and the average sampling variation of the stereological measurement (CE) in the following equation for the number of features, N:…”

Section: Variance and Efficiency Considerationsmentioning

confidence: 99%

Total number and mean size of alveoli in mammalian lung estimated using fractionator sampling and unbiased estimates of the Euler characteristic of alveolar openings

et al. 2004

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Estimation of alveolar number in the lung has traditionally been done by assuming a geometric shape and counting alveolar profiles in single, independent sections. In this study, we used the unbiased disector principle to estimate the Euler characteristic (and thereby the number) of alveolar openings in rat lungs and rhesus monkey lung lobes and to obtain robust estimates of average alveolar volume. The estimator of total alveolar number was based on systematic, uniformly random sampling using the fractionator sampling design. The number of alveoli in the rat lung ranged from 17.3 ⅐ 10 6 to 24.6 ⅐ 10 6 , with a mean of 20.1 ⅐ 10 6 . The average number of alveoli in the two left lung lobes in the monkey ranged from 48.8 ⅐ 10 6 to 67.1 ⅐ 10 6 with a mean of 57.7 ⅐ 10 6 . The coefficient of error due to stereological sampling was of the order of 0.06 in both rats and monkeys and the biological variation (coefficient of variance between individuals) was 0.15 in rat and 0.13 in monkey (left lobe, only). Between subdivisions (left/right in rat and cranial/caudal in monkey) there was an increase in variation, most markedly in the rat. With age (2Ϫ13 years) the alveolar volume increased 3-fold (as did parenchymal volume) in monkeys, but the alveolar number was unchanged. This study illustrates that use of the Euler characteristic and fractionator sampling is a robust and efficient, unbiased principle for the estimation of total alveolar number in the lung or in well-defined parts of it. Anat Rec Part A 274A: 216 -226, 2004.

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“…Reliability of quantitative results from morphometrical methods (Gundersen and Osterby, 1981;Gundersen and Jensen, 1987) depends on uniform sampling at all levels from a random systematic approach, however, in clinicopathological practice, such a procedure is not always possible to achieve. In this study, all sampling steps were performed in a uniform way, with the exception of the first step when a strict systematic sampling was used.…”

Section: Morphometrical Analysismentioning

confidence: 99%

Systematic heterogeneity and prognostic significance of cell proliferation in colorectal cancer

Palmqvist

Öberg²,

Bergström³

et al. 1998

Br J Cancer

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Summary The prognosis of colorectal cancer has not significantly changed during the last 30 years. While evaluation of tumour cell proliferation may provide prognostic information, results obtained so far have been contradictory. Heterogeneity in tumour cell proliferation may explain these contradictions. With in vivo injection of iododeoxyuridine (IdUrd), estimation of labelling index (LI), S-phase transit time (Ts) and potential doubling time (Tpot) may be performed from a single sample. A total of 109 colorectal cancers were studied after in vivo injection of IdUrd before surgical removal. From each cancer, four to eight samples were processed for both flow cytometrical (FCM) and immunohistochemical (IHC) visualization of IdUrd incorporation. Ll/IHC was morphometrically quantified at both the luminal border and the invasive margin of these tumours. LI was significantly higher at the luminal border compared with the invasive margin, although they were correlated with each other. Using combined IHC and FCM methods, rapidly growing colorectal cancers (high Li and/or low Tpot) showed an increased survival (significant for LI at the invasive margin and for 7pt at both the invasive margin and the luminal border) in the entire unselected material and for radically removed Dukes' B tumours. FCM data alone did not discriminate for survival, with the exception of T5 in diploid and radically removed Dukes' B tumours.

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Optimizing sampling efficiency of stereological studies in biology: or ‘Do more less well!‘

Cited by 503 publications

References 8 publications

Neuropathological quantification of dtg APP/PS1: neuroimaging, stereology, and biochemistry

Neuropathological quantification of dtg APP/PS1: neuroimaging, stereology, and biochemistry

Total number and mean size of alveoli in mammalian lung estimated using fractionator sampling and unbiased estimates of the Euler characteristic of alveolar openings

Systematic heterogeneity and prognostic significance of cell proliferation in colorectal cancer

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