Measuring the degree of spatial correlation between histological features in thin sections of brain tissue

Histological features visible in thin sections of brain tissue, such as neuronal perikarya, blood vessels, or pathological lesions may exhibit a degree of spatial association or correlation. In neurodegenerative disorders such as AD, Pick's disease, and CJD, information on whether different types of pathological lesion are spatially correlated may be useful in elucidating disease pathogenesis. In the present article the statistical methods available for studying spatial association in histological sections are reviewed. These include tests of interspecific association between two or more histological features using χ2 contingency tables, measurement of 'complete' and 'absolute' association, and more complex methods that use grids of contiguous samples. In addition, the use of correlation matrices and stepwise multiple regression methods are described. The advantages and limitations of each method are reviewed and possible future developments discussed.

Measuring the degree of spatial correlation between pathological lesions in Alzheimer's disease

The pathological lesions characteristic of Alzheimer's disease (AD), viz., senile plaques (SP) and neurofibrillary tangles (NFT) may not be randomly distributed with reference to each other but exhibit a degree of sptial association or correlation, information on the degree of association between SP and NFT or between the lesions and normal histological features, such as neuronal perikarya and blood vessels, may be valuable in elucidating the pathogenesis of AD. This article reviews the statistical methods available for studying the degree of spatial association in histological sections of AD tissue. These include tests of interspecific association between two or more histological features using chi-square contingency tables, measurement of 'complete' and 'absolute' association, and more complex methods that use grids of contiguous samples. In addition, analyses of association using correlation matrices and stepwise multiple regression methods are described. The advantages and limitations of each method are reviewed and possible future developments discussed.

Spatial arrangement patterns of senile plaques in post-mortem senile dementia of the Alzheimer type brains

We have studied the spatial distribution of plaques in coronal and tangential sections of the parahippocampal gyrus (PHG), the hippocampus, the frontal lobe and the temporal lobe of five SDAT patients. Sections were stained with cresyl violet and examined at two magnifications (x100 and x400). in all cases (and at both magnifications) statistical analysis using the Poisson distribution showed that the plaques were arranged in clumps (x100: V/M = 1.48 - 4.49; x400 V/M = 1.17 - 1.95). this indicates that both large scale and small scale clumping occurs. Application of the statistical techniques of pattern analysis to coronal sections of frontal and temporal cortex and PHG showed. furthermore, that both large (3200-6400 micron) and small scale (100 - 400 micron) clumps were arranged with a high degree of regularity in the tissue. This suggests that the clumps of plaques reflect underlying neural structure.

Size frequency distribution of senile plaques in post-mortem brains of five patients with senile dementia of the Alzheimer type (SDAT)

Numerous senile plaques are one of the most characteristic histological findings in SDAT brains. Large classical plaques may develop from smaller uncored forms. There is no strong evidence that, once formed, plaques disappear from the tissue. We have examined cresyl-violet stained sections of the parahippocampal gyrus (PHG), hippocampus, frontal lobe and temporal lobe of five SDAT patients. The frequency of various sizes of plaques were determined in each of these brain regions. Statistical analysis showed that the ratio of large plaques to small plaques was greater in the hippocampal formation (especially the PHG) than in the neocortex. One explanation of these results is that plaques grow more rapidly in the hippocampal formation than elsewhere. Alternatively, if the rate of plaque growth is much the same in different brain regions, the data suggest that plaques develop first in the hippocampal formation (especially the PHG) and only later spread to the neocortex. This interpretation is also consistent with the theory that the neuropathology of SDAT spreads from the olfactory cortex via the hippocampal formation to the neocortex. Further development of this technique may help identify the site of the primary lesion in SDAT.

Are there two distinct populations of cored senile plaques in senile dementia of the Alzheimer type?

The relationship between plaque diameter (PD) and core diameter (CD) was studied in four brains from each of four SDAT brains. The regions studied were parahippocampal gyrus (PHG), hippocampus, frontal and inferior temporal lobes. The largest diameters of 100 cored classical plaques and their cores were measured. CD was positively correlated with PD (Pearson's 'r' 0.4 - 0.95) in all region studied. Significant linear regressions of CD on PD with positive slopes (0.10 - 0.65) were found. Two distinct types of regression were found. Type A had a steep slope and a negative intercept on the ordinate whereas Type B had a shallow slope and a positive intercept. Both types can be found within the same brain but Type A or B predominate in a particular tissue. The data suggest that core development may occur either early or late in the development of the plaque. The two types of plaque may thus have different aetiologies. Such an interpretation is consistent with current ideas of plaque formation.

Studies on the growth rates of lichens

Progress in the field of lichen growth rate studies is briefly reviewed. The application of a new method of measuring growth rate to thalli of different size has led to the conclusion that there are changes in the radial growth rate during the life of a lichen thallus. For most of the life of a lichen thallus the radial growth rate is constant and the thallus radius increases linearly. Preceding the linear phase the radial growth rate increases with time and the thallus radius increases logarithmically. There is no evidence for a postlinear phase in the radial growth of a lichen thallus. Studies on the growth rate of lichens are applied both to the problems of determining the age of a lichen thallus on an undated susbtratum and to an ecological investigation in the field.

Document retrieval based on a cognitive model of dialogue

Owing to the rise in the volume of literature, problems arise in the retrieval of required information. Various retrieval strategies have been proposed, but most of that are not flexible enough for their users. Specifically, most of these systems assume that users know exactly what they are looking for before approaching the system, and that users are able to precisely express their information needs according to l aid- down specifications. There has, however, been described a retrieval program THOMAS which aims at satisfying incompletely- defined user needs through a man- machine dialogue which does not require any rigid queries. Unlike most systems, Thomas attempts to satisfy the user's needs from a model which it builds of the user's area of interest. This model is a subset of the program's "world model" - a database in the form of a network where the nodes represent concepts since various concepts have various degrees of similarities and associations, this thesis contends that instead of models which assume equal levels of similarities between concepts, the links between the concepts should have values assigned to them to indicate the degree of similarity between the concepts. Furthermore, the world model of the system should be structured such that concepts which are related to one another be clustered together, so that a user- interaction would involve only the relevant clusters rather than the entire database such clusters being determined by the system, not the user. This thesis also attempts to link the design work with the current notion in psychology centred on the use of the computer to simulate human cognitive processes. In this case, an attempt has been made to model a dialogue between two people - the information seeker and the information expert. The system, called Thomas-II, has been implemented and found to require less effort from the user than Thomas.

A semantic modelling approach to knowledge based statistical software

The topic of this thesis is the development of knowledge based statistical software. The shortcomings of conventional statistical packages are discussed to illustrate the need to develop software which is able to exhibit a greater degree of statistical expertise, thereby reducing the misuse of statistical methods by those not well versed in the art of statistical analysis. Some of the issues involved in the development of knowledge based software are presented and a review is given of some of the systems that have been developed so far. The majority of these have moved away from conventional architectures by adopting what can be termed an expert systems approach. The thesis then proposes an approach which is based upon the concept of semantic modelling. By representing some of the semantic meaning of data, it is conceived that a system could examine a request to apply a statistical technique and check if the use of the chosen technique was semantically sound, i.e. will the results obtained be meaningful. Current systems, in contrast, can only perform what can be considered as syntactic checks. The prototype system that has been implemented to explore the feasibility of such an approach is presented, the system has been designed as an enhanced variant of a conventional style statistical package. This involved developing a semantic data model to represent some of the statistically relevant knowledge about data and identifying sets of requirements that should be met for the application of the statistical techniques to be valid. Those areas of statistics covered in the prototype are measures of association and tests of location.