Biomedical subjects
Publications and source records attributed to M J Cookson.
A method is described for the cutting of fragile material with a laser scalpel which minimizes damage to friable materials, making the interior of structures accessible for optical sectioning microscopy or for high resolution X-ray microtomography followed by 3D reconstruction.
The objective of this study was to analyse the location in the bone marrow of deposits of low-grade non-Hodgkin's lymphoma. This was achieved using computer-generated three-dimensional reconstruction techniques applied to serial tissue sections of five bone marrow trephines involved by lymphoma. For comparative purposes, previously published three-dimensional models of benign lymphoid aggregates in the bone marrow were need. The images generated by this new study showed that deposits of low-grade non-Hodgkin's lymphoma involving the bone marrow always assumed a paratrabecular pattern of infiltration at some point. This is in direct contrast to the pattern of bone marrow infiltration shown by benign lymphoid aggregates. It is concluded that location within the marrow space is a crucial factor in distinguishing between benign and low-grade malignant lymphoid infiltrates in the bone marrow.
Distinguishing between deposits of low-grade non-Hodgkin's lymphoma and benign lymphoid aggregates in bone marrow trephine sections is a recognized problem in haematopathology. To test the hypothesis that benign lymphoid aggregates do not make contact with a trabecular surface, three-dimensional models were constructed of five serially sectioned bone marrow trephines, containing a total of 19 lymphoid aggregates known to be benign. The computer-generated images showed that benign lymphoid aggregates were located in the central marrow space and did not become paratrabecular. This suggests that a paratrabecular location may help in some cases to distinguish deposits of low-grade non-Hodgkin's lymphoma from benign lymphoid aggregates.
3DR techniques are under continuous development, as is the technology which supports them. Systems developed for engineering and other applications are coming within the price range of many users. Recently publications have started to appear using standard high-quality graphics workstations. As these are coming down in price, more applications will be possible. The advent of new computer technology, notably possible. The advent of new computer technology, notably highly parallel systems and chips such as the Intel i860, offer the prospect of very fast reconstructions and the software to make 3DR a routine technique. Most significant however is the continuing increase in type and numbers of scanning systems, both macroscopic and microscopic. Prior to these systems becoming available, the critical limiting factor inhibiting the wide application of 3DR was generating adequately registered, undistorted, complete sets of serial section data for the reconstruction process. The fact that scanning optical microscopes can produce such datasets easily means that the everyday use of 3DR for studies of pathology is now feasible.
High resolution NMR images of sixgill shark (Hexanchus griseus) tissue from both horizontal and sagittal orientations are presented. Structures normally radiographically undetectable are visualised here with NMR. Proton density, spin-lattice and spin-spin relaxation time maps as well as various relaxation weighted images show selective enhancement of different tissue types. Quantitative analysis of major anatomical features in the shark head is provided.
Firstly, to assess the reproducibility of a computerised image analysis method of measuring alveolar size in terms of the alveolar wall surface area per unit volume (AWUV) in normal non-smoking adult human lungs fixed in inflation, one lung was fixed by simple manual prebronchial perfusion with formaldehyde (wet-fix), another by prolonged perfusion with formaldehyde followed by air until semi-dried (semi-dry). Blocks from both lungs were taken to assess the relative value of plastic and paraffin wax embedding. There was no statistical difference in AWUV between plastic and paraffin sections from each lung, but the wet-fix method gave statistically significantly (P < 0.05) higher AWUV readings than the semi-dry method. Secondly, when a whole semi-dry lung slice was divided into 66 blocks, the AWUV distribution was not random but largest in the centre and smallest in the periphery anteriorly and superiorly. This is obviously important in sampling of lung tissue for morphometry and other purposes.
Three-dimensional reconstruction experiments performed on serial sections of human embryos showed that the anatomy of the caudal and rostral ends of the notochord was complex. Forking of the ends, with separate fragments of chordal tissue, was demonstrated and these provide a way by which notochordal cell rests could be left behind in the basicranial and sacral regions when the notochord involutes elsewhere. Assuming the histogenesis of chordomas from notochordal cell rests, this would furnish an explanation for the observed skeletal distribution of chordomas.
(i) Image registration. The use of serial images for computerised three-dimensional reconstruction necessitates the inclusion of three separate sources of information at the stage of data input. These are (i) artificial registration points or fiducials, (ii) a calibration scale and (iii) an outline of each slab of the section to be included in the reconstruction. Most traditional methods rely on the production of drawings of the contours of the structure under investigation which also include both registration points and a calibration scale. We report on a method which considerably reduces the time involved at this labour intensive stage of reconstruction and in addition allows subsequent reconstructions of different structures to be performed without new drawings. Use is made of computerised alignment of tissue sections and the production of composite photomicrographs of both the tissue under investigation and an accurately registered stage micrometer scale. (ii) Improving image interpretation. Images derived from computerised three-dimensional reconstruction can be affected by the number of coordinates used to form the contour of each slice of a structure and by the number of slices that are used to construct the final model. Too little or too much data can considerably reduce the ability of the observer to interpret accurately the image generated by the computer. We report on a feature-based method which enables the experimenter to assess objectively the amount of data required in the two-dimensional plane, i.e. the number of data points per slice, and the three-dimensional plane, i.e. number of slices per structure, so that optimal reconstructions are generated.
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A frame-based computer-aided learning system for use on microcomputers has been developed for teaching clinical chemistry. The system presents a case-study model that can be used by students to assess their ability to make a diagnosis, to select patterns of investigations and to institute treatment.
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The most widely accepted model of human lung alveolar duct systems is that they are constructed from central helical fibres between the turns of which lie alveolar opening. Experimental difficulties of handling and sectioning lung tissue have made it difficult to confirm this. Confocal laser scanning microscopy (CLSM) was therefore used to generate optical serial sections of the lung that were reconstructed in three dimensions and displayed using volume rendering techniques. From images of the reconstructions, a new structure is proposed in which alveolar ducts consist of collections of connected oval, twisted loop structures with eccentric openings.
Expert systems, also known as intelligent knowledge based systems (IKBS), are computer programs which act as decision-support systems. They are currently being applied to a number of medical domains, most notably diagnosis and treatment planning. Their function is to assist the medical practitioner by giving ready access to the levels of skill shown by experts in a particular field. Much research effort has been expended but few systems have reached routine medical use. This paper presents a tutorial introduction to expert systems in medicine, explaining the basis of the technology, its current limitations and its prospective uses.
A microcomputer-based system is described that generates three-dimensional shaded images from serial section data. It is implemented on the IBM PC-AT microcomputer, using a graphics display card (Real World Graphics PC 4000) to provide sufficient colours for the production of realistically shaded and highlighted images. Image generation time is typically less than 10 min. The capabilities of the system are illustrated by reconstructions of the Kurloff cell from the guinea-pig (based on serial electron micrographs), human teeth (based on light microscope data), the human leg (from gross anatomical sections) and the human brainstem (from stereotaxic atlas data). The system is applicable to a wide variety of serial section data from histological, anatomical and medical imaging systems and ultrastructural studies.