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Biomedical subjects

N Roberts

Publications and source records attributed to N Roberts.

At least 91 records · Page 5Linked to original sources

Automatic analysis of cerebral atrophy.

3D MR data obtained for 10 healthy control subjects have been used to build a brain atlas. The atlas is built in four stages. First, a set of features that are unambiguously definable and anatomically relevant need to be computed for each item in the database. The chosen features are crest lines along which the maximal principal curvature of the surface of the brain is maximal in its associated principal direction. Second, a nonrigid registration algorithm is used to determine the common crest lines among the subjects in the database. These crest lines form the structure of the atlas. Third, a set of crest lines is taken as a reference set and a modal analysis is performed to determine the fundamental deformations that are necessary to bring the individual data in line with the reference set. The deformations are averaged and the set of mean crest lines becomes the atlas. Finally, the standard deviation of the deformations between the atlas and the items in the database defines the normal variation in the relative positions of the crest lines in a healthy population. In a fully automatic procedure, the crest lines on the surface of the brain adjacent to the cerebral ventricles in a patient with primary progressive aphasia were compared to the atlas; confirmation that the brain of this patient demonstrates atrophy was provided by stereological analysis that showed that the volume of the left cerebral hemisphere is 48.8 ml (CE 2.8%) less than the volume of the right cerebral hemisphere in the region of the temporal and frontal lobes. When the amplitude of the deformations necessary to register the crest lines obtained for the patient with the atlas were greater than three standard deviations beyond the variability inherent in the atlas, the deformation was considered significant. Four of the main deformation modes of the longest crest line of the surface of the brain adjacent to the cerebral ventricles were significantly different in the patient with primary progressive aphasia compared to the atlas. The ventricles are preferentially enlarged in the left cerebral hemisphere. Furthermore, they are closer together posteriorly and further apart anteriorly than in the atlas. These observations may be indicative of the atrophy of the temporal and frontal lobes of the left cerebral hemisphere noted in the patient. Ultimately, the approach may provide a useful screening technique for identifying brain diseases involving cerebral atrophy. Serial studies of individual patients may provide insights into the processes controlling or affected by particular disease.

Aged↗

Hominid thumb strength predicted by high resolution magnetic resonance imaging and force measurements in living subjects.

This study investigates whether in-vivo measurements of the morphology of the pollical distal phalanx (PDP) can be used to predict the maximum force that can be exerted by the thumb in flexion at the interphalangeal joint. A predictive equation was obtained via which measurements of fossil PDP's can be used to predict flexion force in hominids. A home-built insertable coil assembly, which increased the available magnetic field gradient strength from 10 to 40 (mT) m-1, was used to acquire high resolution T1-weighted 3D SPGR Magnetic Resonance (MR) images of the left and right thumbs of nine volunteers. The subjects' age, sex, weight, height and self-assessed hand-dominance were recorded. The MR images were transferred to a computer for reformatting of sections in the transverse and volar plane (VP). Measurements were made of the maximum length (ML), breadth (MB), tuft breadth (MT) and joint depth (JD) of the PDP. For each subject the maximum flexion force that could be exerted by each thumb was measured. The mean maximum flexion force generated was 8.21 kg (range 5.68-13.13 kg). Considerable inter-individual variability was observed in the magnitude of the force difference between the left and right thumbs and this is greatest in individuals with the strongest thumbs. The best model produced by multiple linear regression analysis of all the available data has a value of r = 0.77 and needs only the two covariates of sex and weight, i.e. FORCE = 2.217 + 0.6651 x WEIGHT + 2.488 x SEX. However, in order to be useful for predicting the maximum flexion force of the thumb in hominids the model should only contain those parameters which can be measured for fossil PDP's. Accordingly, the best predictive model has a value of r = 0.73 and needs only the two covariates of ML and JD, i.e. FORCE = -10.28 + 0.2053 x ML + 1.571 x JD. The maximum force predicted for any of the hominid fossil PDP's was not significantly different from those recorded for the volunteers in the present study, although they were on average somewhat lower than those obtained for modern humans. This may be a reflection of the hominid's overall smaller body weights.

Animals↗

Analysis of cardiac function by MRI and stereology.

Design-based stereology and phase contrast magnetic resonance imaging (MRI) were combined to monitor changes in the volume of the four chambers of the human heart during the cardiac cycle. The data set consisted of 18 adjacent slices (or 'scanning levels') of 0.5 cm thickness, perpendicular to the long axis of the body, and encompassing the whole heart of a healthy volunteer. At each scanning level, a cardiac gated MR image was obtained at each of 16 equally spaced time frames within the cardiac cycle. Given stationarity with respect to time, absence of image artefacts and appropriate definition of chamber boundaries, for each time frame unbiased estimates of total blood volume in the relevant heart chambers were efficiently obtained using the Cavalieri method and point counting. Combined with a proper MRI acquisition, modern stereological methods constitute an efficient and reliable tool to quantify cardiac function noninvasively.

Blood Volume↗

Measurement of the quadriceps femoris muscle using magnetic resonance and ultrasound imaging.

OBJECTIVES: To define a method for measurement of the cross sectional area and volume of the quadriceps femoris muscle using magnetic resonance imaging (MRI) in conjunction with stereology, and to compare the results of measurements obtained by the MRI method with those obtained by the conventional method of static B-mode ultrasound in order to evaluate whether MRI is a reliable alternative to ultrasound. METHODS: A preliminary MRI study was undertaken on a single female volunteer in order to optimise the scanning technique and sampling design for estimating the muscle volume using the Cavalieri method. Ten healthy volunteers participated in the method comparison study. Each volunteer underwent static B-mode ultrasonography, immediately followed by MRI. The cross sectional area of the quadriceps femoris was estimated at the junction of the proximal one third and distal two thirds of the thigh, and seven systematic sections of the thigh were obtained in order to estimate muscle volume by both modalities. RESULTS: Seven sections through the muscle are required to achieve a coefficient of error of 4-5%. There was no significant difference in the cross sectional area estimates or volume estimates when ultrasound and MRI were compared. CONCLUSION: Muscle cross sectional area and volume can be measured without bias by MRI in conjunction with stereological methods and the method is a reliable alternative to static B-mode ultrasound for this purpose.

Adult↗

A community based stroke register in a high risk area for stroke in north west England.

STUDY OBJECTIVE: To develop a community based stroke register to assess the magnitude of the problem of stroke in an entire health district in a high risk area for stroke. DESIGN: Community based stroke register from general practice data. SETTING: East Lancashire Health Authority with a 1995 population of 534,287. PATIENTS: The stroke register was developed and maintained for one calendar year in East Lancashire between 1 July 1994 and 30 June 1995. Efforts were made to include all patients who had a stroke during this period from participating general practices, using several sources of referral. MAIN RESULTS: Of the district's 118 general practices, 93 (79%) participated fully, covering a population of 405,272. A total of 932 strokes, including 642 first ever cases, were cross checked and confirmed, with only 50% from any single source, mainly the practices. The total stroke incidence rate was 1.60 per 1000 per year, adjusted for the England and Wales 1991 census population. The rate increased considerably with age from 0.88/1000 for ages 50-54 to 20.56/1000 for ages 85-89 years. From 50-74 years, the age specific incidence was higher in men, but overall it was higher in women (1.87; 95% confidence interval 1.67, 2.04 per 1000) than in men (1.31; 1.15, 1.47 per 1000), and slightly lower than in Oxford a decade earlier. The rate also varied in different localities, with higher rates in the central towns of Hyndburn (2.05/ 1000), Blackburn (1.63/1000), and Burnley (1.80/1000) and lowest values in rural areas (1.18/1000 in Pendle). Case fatality from stroke at 28 days was 34% and the hospital admission rate was high at 70%. CONCLUSIONS: The multiple source registration method is required for a stroke register. Stroke incidence in this area was still high and there was considerable variation across the district. Case fatality rates were similar to those in previous studies.

Adult↗

The three-dimensional structure of the connective tissue in the lamina cribrosa of the human optic nerve head.

Comprehensive understanding of the three-dimensional structure of the extracellular matrix (ECM) of the lamina cribrosa is central to understanding its role in health and disease, particularly how changes in configuration might precipitate nerve fibre death in glaucoma. Research until recently has relied almost entirely on light and scanning electron microscopy (SEM) to investigate the ECM of the lamina cribrosa. In this paper, we review the contribution of these methods to current understanding of the three-dimensional structure of the lamina ECM, highlight their potential weaknesses and emphasise that there is still much to be revealed about the structure of the lamina ECM. We then describe our development of confocal microscopy and computer reconstruction as a new and alternative method of investigating the three-dimensional structure of the lamina ECM. We show how optical sectioning allows the confocal microscope to acquire three-dimensional images of the lamina ECM without the degree of tissue disruption associated with preparation for SEM and demonstrate the versatility of analysis of these images by computer reconstructive software. A case is made for confocal microscopy and computer reconstruction contributing to our understanding of this important but complex and delicate structure.

Connective Tissue↗

Psychiatric admissions of Asian Canadians to an adolescent inpatient unit.

OBJECTIVE: To compare the psychiatric diagnoses for Asian Canadians admitted to an adolescent inpatient unit with those of their white Canadian peers. METHOD: A literature review was first completed and then followed by a hospital file review of the Asian Canadians admitted over a 5-year period to the adolescent inpatient psychiatric unit. The data extracted (relating to psychiatric diagnosis, age, length of stay, referral source, family type, and gender) were then compared with a random sample of white Canadians admitted to the same unit during the same 5-year time frame. RESULTS: There were far fewer Asian Canadians admitted than would be expected based on Calgary's demographics. There was equal gender representation among those who were admitted, and they tended to be older and to have a greater preponderance of severe psychiatric symptomatology than their white Canadian peers. CONCLUSIONS: This paper adds to previous research in emphasizing that ethnocultural factors play a significant role in the utilization of psychiatric services by immigrant populations.

Adolescent↗

Segmentation and numerical analysis of microcalcifications on mammograms using mathematical morphology.

The top-hat and watershed algorithms of mathematical morphology have been applied to detect automatically and segment microcalcifications on mammograms digitized to a pixel resolution of 40 microns using a CCD camera. The database comprised 38 cases from the breast assessment clinic in Liverpool. For all cases, both craniocaudal (CC) and lateral oblique (LO) views were available. 19 cases were proven to be benign and 19 malignant based on cytology and histology. Malignant clusters contained more microcalcifications (14 malignant, 10 benign), occupied a larger area (37 mm2, 9 mm2) and had longer cluster perimeters than benign clusters (33.2 mm, 15.5 mm). Malignant microcalcifications exhibited a wider variety of shapes and were more heterogeneous in terms of image signal intensity than benign microcalcifications. Further mathematical morphology algorithms were applied to describe microcalcification shape in terms of the presence or absence of infoldings, elongation, narrow irregularities and wide irregularities. The three largest microcalcifications were selected for each case and, using a "leave-one-out" approach, each microcalcification was classified in respect of its five nearest neighbours as either malignant or benign. The area under the curve of a receiver operating characteristic (ROC) analysis of the proportion of the three microcalcifications which agreed with the true diagnosis increased from 0.73 (CC) and 0.63 (LO) to 0.79 when both views were considered. Next, each cluster in turn was ranked according to its agreement with the database as a whole over 21 features. An ROC analysis was performed to investigate the effect on sensitivity and specificity of the proportion of the nine nearest neighbours that agreed with the true classification. The largest area under the ROC curve was 0.84 produced by the four features of proportion of irregular microcalcifications, proportion of round microcalcifications, number of microcalcifications in the cluster and the interquartile range of microcalcification area. The shape of microcalcifications is confirmed as being of overriding importance in classifying cases as either malignant or benign. This observation motivates a further study enhanced by using magnified views digitized to a higher resolution by a laser scanner. This will enable the reliable assessment of the shape of a greater number of microcalcifications in each cluster, which is likely to increase further the discriminating power of the image analysis routines and lead to the development of an expert system for automatic mammographic screening.

Aged↗

Objective quantification of muscle and fat in human dystrophic muscle by magnetic resonance image analysis.

Information about changes in muscle composition has to date been primarily restricted to histological examination of biopsy samples or qualitative assessment of images obtained using a variety of techniques (e.g., ultrasound, CT, and MRI). We describe the development of a quantitative method for the analysis of muscle composition using MR T2 relaxation time mapping and image analysis. This approach provides an objective means of studying muscle and, when used in conjunction with force production measurements, may provide an accurate measure of response to muscle therapy.

Adipose Tissue↗

Fetal and fetal organ volume estimations with magnetic resonance imaging.

OBJECTIVE: Our purpose was to estimate, with the Cavalieri method of stereology and a point-counting technique, the volume of the fetus, fetal brain, fetal liver, and fetal lungs. STUDY DESIGN: Four pregnancies were studied on three to five occasions at gestations from 27 weeks until term. RESULTS: In the four fetuses studied the total fetal volume increased at a rate of between 19.0 and 30.8 ml/day. The fetal liver constituted 2.5% to 4.9% of the total fetal volume; the fetal lung, 2.5% to 4.4%; and the fetal brain, 11.5% to 16.9%. The fetal liver increased in size by 0.4 to 1.3 ml/day; the lungs, by 1.2 to 1.4 ml/day; and the fetal brain, by 2.7 to 3.8 ml/day. The fetal brain/liver ratio, which may be an indicator of an asymmetric growth pattern, was between 2.4 and 5.6 with a tendency to a decreased ratio with increasing gestation. CONCLUSION: This is the first serial study of total fetal volume and fetal organ volume with magnetic resonance imaging and stereology. Measurement of the total fetal volume and differential growth of fetal organs may be a more sensitive method of assessing fetal intrauterine growth than two-dimensional measurements obtained with ultrasonography.

Adult↗

An in vitro assay for hepatitis C virus NS3 serine proteinase.

Hepatitis C virus (HCV) encodes a polyprotein of which the majority of nonstructural proteins are matured by the viral serine proteinase located in the N terminus of NS3. Intracellular studies using recombinant vaccinia virus have shown that both NS3 and its cofactor NS4A are required to enhance processing at the NS3-dependent cleavage sites. We developed an in vitro (cell-free) assay in which the HCV serine proteinase was shown to be enzymatically active, by mixing lysates of cells expressing either the serine proteinase or a nonstructural protein substrate. NS3 cleaved in a highly reproducible manner at the NS5A/5B site in the presence of NS4A, whereas NS3 alone was enzymatically inactive. NS4A could be provided either linked to NS3 or as part of the substrate. In contrast, irrespective of the presence or absence of NS4A, no NS3-mediated processing was observed at the NS3/4A, NS4A/4B, and NS4B/5A sites in this assay. In vitro cleavage at the NS5A/5B site occurred rapidly, within 1 min at temperatures ranging from 0 to 20 degrees, but was incomplete and required detergent-solubilized lysates. General serine proteinase inhibitors did not decrease processing activity. The in vitro model described in this study is a new tool: (1) to study the structure and the function of HCV serine proteinase and NS5A/5B cleavage site, and (2) to test NS3 serine proteinase inhibitors.

Binding Sites↗

Muscle imaging in health and disease.

Muscle imaging has been used largely as an adjunct in the assessment of patients with muscle disease and has been reported in descriptive terms only. Developments in computer-based image analysis techniques applied to muscle have enabled the quantification of muscle images using ultrasonography, computed tomography and magnetic resonance techniques. In conjunction with physiological measurements of muscle force, accurate determinations of muscle section area have allowed the determination of force per unit of cross-sectional area. This important measurement is essential if therapeutic approaches in muscle disease are to be adequately assessed. In this review the uses and merits of different imaging techniques are described with reference to new developments in quantitative analysis of muscle images and the possible utilisation of these techniques in neuromuscular disease is discussed.

Humans↗