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N Roberts

Publications and source records attributed to N Roberts.

At least 55 records · Page 3Linked to original sources
PubMed2000

Automatic measurement of changes in brain volume on consecutive 3D MR images by segmentation propagation.

This article presents a technique to automatically measure changes in the volume of a structure of interest in successive 3D magnetic resonance (MR) images and its application in the study of the brain and lateral cerebral ventricles. The only manual step is a segmentation of the structure of interest in the first image. The analysis comprises, first, precise rigid co-registration of the time series of images; second, computation of residual deformations between pairs of images; third, automatic quantification of the volume change, obtained by propagation of the segmentation of the structure of interest through the series of MR images. This approach has been applied to monitor changes in the volume of the brain and lateral cerebral ventricles in a healthy subject and a patient with primary progressive aphasia (PPA). Results are consistent with those obtained by application of the boundary shift integral (BSI) and by stereology in the same subjects.

Aged↗
PubMed2000

Statistical analysis of normal and abnormal dissymmetry in volumetric medical images.

We present a general method to study the dissymmetry of anatomical structures such as those found in the human brain. Our method relies on the estimate of 3D dissymmetry fields, the use of 3D vector field operators, and T2 statistics to compute significance maps. We also present a fully automated implementation of this method which relies mainly on the intensive use of a 3D non-rigid inter-patient matching tool. Such a tool is applied successively between the images and their symmetric versions with respect to an arbitrary plane, both to realign the images with respect to the mid-plane of the subject and to compute a dense 3D dissymmetry map. Inter-patient matching is also used to fuse the data of a population of subjects. We then describe three main application fields: the study of the normal dissymmetry within a given population, the comparison of the dissymmetry between two populations, and the detection of the significant abnormal dissymmetries of a patient with respect to a reference population. Finally, we present preliminary results illustrating these three applications for the case of the human brain.

Aphasia↗
PubMed2000

Short-term ventricular volume changes on serial MRI in multiple sclerosis.

Axonal loss is likely to be an important component of atrophy and the pathological substrate for the fixed disability of MS. To estimate the rate of central white matter reduction we investigated ventricular volume change and disease activity on monthly MRI in 19 patients over 6 months. At baseline, ventricular volumes were largest in primary progressive MS and smallest in relapsing-remitting MS. Over the study period ventricular volumes increased overall by 0.2% (F= 2.75, P = 0.02), but the percentage changes in relapsing-remitting MS were much larger (median increase 14.9%). Lesion volumes were also highest at baseline in relapsing-remitting MS, but serial changes in ventricular volumes were not correlated with serial changes in lesions. This study shows that ventricular enlargement in MS may occur over short epochs, particularly in relapsing-remitting cases. However, the loss of central white matter volume observed in any brief period may be related to inflammatory activity that occurred in a preceding or earlier epoch, a delayed post-inflammatory degenerative process, or most likely, a combination of both.

Adult↗
PubMed2000

A comparison in normal individuals and sickle cell patients of reduced glutathione precursors and their transport between plasma and red cells.

INTRODUCTION: Reduced glutathione is an important antioxidant in red cells whose depletion may contribute to the pathophysiology of sickle cell disease. The current study was designed to examine the availability of reduced glutathione precursors (glutamate, cysteine, glycine and possibly glutamine) together with the activity of the main transport pathways for their uptake (system ASC for cysteine and glycine; system gly for glycine). MATERIALS AND METHODS: Blood samples were obtained from normal (HbAA, HbA cells) and sickle cell disease patients (HbSS, HbS cells); amino acids were measured by HPLC; and transporter activity was measured by radioactive tracer fluxes (using serine and glycine for activity of system ASC; and glycine for that of system gly). RESULTS: Plasma concentrations of cysteine and glycine were increased and concentrations of all amino acids were elevated in HbS cells. The activity of system ASC was increased in HbS cells (both transport capacity and affinity were elevated for serine transport; transport capacity only for glycine). Activity of system gly was also increased (twofold increase in V(max) for glycine flux), though not significantly. Oxygenation also increased the activity of both transporters in normal and HbS cells. CO prevented deoxy-inhibition of glycine transport. Staurosporine (5 microM) inhibited O(2)-stimulated glycine transport through system ASC. It also inhibited the absolute magnitude of transport through system gly, but the O(2)-dependent flux was unaffected. CONCLUSION: Low reduced glutathione levels in HbS cells were not due to decreased substrate availability and O(2) stimulated transport of reduced glutathione precursors in both normal and HbS cells, through a mechanism that is likely to involve Hb and possibly protein phosphorylation.

Adult↗
PubMed2000

Single nucleotide polymorphisms in an intron of the ovine calpastatin gene.

Calpastatin is the specific inhibitor of the ubiquitous calcium-dependent proteases mu-calpain and m-calpain. Enzyme assay data from sheep and cattle inversely correlates post-mortem muscle calpastatin levels with ultimate meat tenderness. Genetic markers of meat quality may therefore be found linked to the calpastatin gene (CAST). A three-allele system detected by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) has been observed in the ovine CAST. The three allele amplimers have been fully nucleotide sequenced and their differences in terms of single nucleotide polymorphism (SNPs) in the intron region of the amplimer are reported and compared to a consensus sequence of the orthologous region of the cattle CAST. A PCR-RFLP for more rapid CAST genotyping of all three ovine alleles was also developed.

Alleles↗
PubMed2000

The benefit of stereology for quantitative radiology.

A knowledge of stereology (i.e. proper sampling), the opportunities provided by computers for image analysis (i.e. image segmentation, image registration, data base exploration, 3D reconstruction), and the strengths (i.e. non-invasive) and limitations (i.e. finite resolution, image artefacts) of medical imaging equipment must all be combined for reliable quantitative magnetic resonance imaging (MRI), the goal of which is to obtain a deeper understanding of the structure, function, life cycle and evolution of the human body, especially the brain, and a more objective diagnosis of disease and assessment of its response to treatment. In this article we illustrate the first of these requirements. We describe the application of proper sampling strategies and efficient computer-based counting procedures for obtaining unbiased estimates of volume by the Cavalieri method and of surface area from vertical sections. In particular, we estimate the volume of a brain tumour from Cavalieri sections, the volume of grey matter in the cerebral hemispheres from Cavalieri slices and the surface area of the cerebral cortex from vertical sections. The estimates obtained are mathematically unbiased. In each case, we assess the precision of the estimates empirically. Application of formulae available for predicting the precision of volume estimates obtained using the Cavalieri sections and slices methods is also described.

Algorithms↗
PubMed2000

Proton magnetic resonance spectroscopy and morphometry of the hippocampus in chronic fatigue syndrome.

Seven patients with chronic fatigue syndrome (CFS) were matched with ten healthy control subjects of similar age. Hippocampal volume, obtained from magnetic resonance images using an unbiased method, showed no difference between the two groups, whereas proton magnetic resonance spectroscopy showed a significantly reduced concentration of N-acetylaspartate in the right hippocampus of CFS patients (p = 0.005).

Adult↗
PubMed2000

Comparison of five cyclosporin immunoassays with HPLC.

High performance liquid chromatography (HPLC) is the reference method for cyclosporin (CyA) measurements but therapeutic monitoring of the drug is frequently made using the more practical immunoassays. Cross-reactivity with CyA metabolites may compromise the specificity of immunoassays, particularly in liver graft recipients where metabolites may accumulate. The aim of this study was to compare with HPLC the performance of two recently introduced CyA immunoassays (the AxSYM fluorescent polarisation immunoassay (FPIA) and non-extraction CEDIA assay). The comparison was extended to the well-established TDx monoclonal FPIA (TDx mono) and the enzyme multiplied (EMIT)-specific assays and to the polyclonal FPIA (TDx poly), in which metabolite cross-reactivity is extensive. Assays were performed on 106 blood samples (taken 6 days to 118 months post-liver transplant) and results were compared by non-parametric regression analysis and difference plots. AxSYM and CEDIA showed both constant and proportional bias against HPLC (unlike EMIT) but the mean difference from HPLC was least for AxSYM (2.7 microg/l vs. 11.7, 9.4 and 54 microg/l for CEDIA, EMIT and TDx mono, respectively. (TDx poly - HPLC) values were proportional to all immunoassay results, with slopes of 0.33, 0.38 and 0.45 for EMIT, AxSYM and CEDIA, respectively. Our data suggest close agreement between AxSYM, CEDIA and EMIT results.

Chromatography, High Pressure Liquid↗
PubMed2000

Ground penetrating radar surveys to locate 1918 Spanish flu victims in permafrost.

The "Spanish Flu" killed over 40 million people worldwide in 1918. Archival records helped us identify seven men who died of influenza in 1918 and were interred in Longyearbyen, Svalbard, Norway, 1,300 km from the North Pole. Ground Penetrating Radar (GPR) was used successfully, in a high-resolution field survey mode, to locate a large excavation with seven coffins, near the existing seven grave markers. The GPR indicated that the ground was disturbed to 2 m depth and was frozen below 1 m. Subsequent excavation showed that: a) the GPR located the position of the graves accurately, b) the coffins were buried less than 1 m deep, and c) that the frozen ground was 1.2 m deep where the coffins were located. The GPR assisted in planning the exhumation, safely and economically, under the high degree of containment required. Virologic and bacteriologic investigations on recovered tissues may give us an opportunity to isolate and identify the micro-organisms involved in the 1918 influenza and expand our knowledge on the pathogenesis of influenza.

Burial↗
PubMed2000

Oral oseltamivir in human experimental influenza B infection.

Oseltamivir is the prodrug of Ro64-0802 (GS4071), a potent and selective inhibitor of influenza A and B virus neuraminidases. Three randomized, double-blind, placebo-controlled, parallel-group studies evaluated oral oseltamivir for early treatment (75 or 150 mg twice daily for 5 days) or prevention (75 mg once or twice daily for 7 days) of experimental influenza B virus infection in healthy susceptible adults. Treatment study A (n=60) demonstrated similar trends to treatment study B (n=117), in which 75 mg doses of oseltamivir introduced 24 h after inoculation reduced median area under curve (AUC) virus titre (oseltamivir, 22.7; placebo, 131.1 log10 TCID50 x h/ml; P=0.002) and duration of viral shedding (oseltamivir, 23.9 h; placebo, 95.8 h; P=0.0005). In prevention study C (n=58), oseltamivir did not reduce infection rates (85 versus 84%) but significantly reduced median AUC virus titre (10.0 versus 66.9 log10 TCID50 x h/ml; P=0.03) and duration of viral shedding (36 versus 84 h; P=0.03) compared with placebo. Oseltamivir was well tolerated. No emergence of drug-resistant variants was detected by testing last-day isolates (n=112) in neuraminidase inhibition assays. These results indicate that oseltamivir has significant antiviral activity in experimental human influenza B virus infection when used for prophylaxis or early treatment.

Acetamides↗
PubMed1999

Localisation of connective tissue and inhibition of autofluorescence in the human optic nerve and nerve head using a modified picrosirius red technique and confocal microscopy.

The use of picrosirius red to localise connective tissue in thin tissue sections viewed by bright-field microscopy is well documented. Its use on thin tissue sections imaged by fluorescence confocal microscopy has also been reported. Here we describe modifications to published procedures that allow picrosirius red staining of thick 60-microm sections and their subsequent analysis by confocal microscopy. The use of phosphomolybdic acid pre-treatment was found to be essential for confocal analysis; in addition to preventing non-specific staining, it also quenched tissue autofluorescence. By incubating sections free-floating, pre-treating them with phosphomolybdic acid for 30 min and imaging them using an argon ion laser we were able to use confocal microscopy to image the entire depth of 60-microm human optic nerve and nerve head sections stained with picrosirius red. The application of this modified picrosirius red and confocal microscopy technique should be useful for analysing the three-dimensional structure of the optic nerve and other tissues with a similarly complex arrangement of connective tissue.

Adult↗
PubMed1999

Magnetic resonance imaging-based compartmentation and its application to measuring metabolite concentrations in the frontal lobe.

Partial volume mixing of water compartments within a spectroscopy voxel (e.g. cerebrospinal fluid within a "brain" voxel) may, if not corrected for, lead to underestimation of brain metabolite concentrations. To correct for this source of bias, a new imaging-based method of compartmentation analysis is presented. Brain water, cerebrospinal fluid and solid matter content were obtained from proton density- and T2-weighted images of the brain and an external standard in 10 healthy young males (21 to 30 years), and results compared with a previously-described technique based on spectroscopy. Mean (SD) fractional water content (betaMR) of the 2 x 2 x 2 cm3 voxel in the frontal lobes was 0.79 (0.03) by imaging, slightly but significantly (p = 0.03) smaller than the value of 0.83 (0.03) obtained by spectroscopy. From water-suppressed spectra recorded at five echo times, using betaMR determined by imaging, the T2-corrected concentrations of compounds containing N-acetylaspartate, creatine, choline and myo-inositol were 10.6 (1.0), 8.0 (0.9), 1.6 (0.3) and 3.7 (0.7) mmol.l(-1) of brain, respectively. Imaging-based compartmentation is a rapid and straightforward technique, and can be performed on standard MR systems.

Adult↗
PubMed1999

A comparison of egocentric and allocentric spatial memory in medial temporal lobe and Korsakoff amnesics.

Two patients with medial temporal lobe damage, seven Korsakoff amnesics and fourteen healthy control subjects were tested on three conditions of a spatial memory test ('short delay', 'allocentric' and 'egocentric'). The task required subjects to recall the position of a single spot of light presented on a board after various delays. The 'short delay' condition tested memory over very short, unfilled intervals. The other two conditions used longer, filled delays. The allocentric condition required subjects to move to a different place around the board before recalling the position of the light. In the egocentric condition stimuli were presented in darkness, which eliminated allocentric cues. The Korsakoff amnesics were impaired at all delays of the short delay tasks, suggesting poor encoding. On the allocentric and egocentric tasks the Korsakoff amnesics showed a comparable impairment in the two conditions, which worsened with delay. This accelerated forgetting suggested that the Korsakoff amnesics also had impaired memory for allocentric and egocentric information. The patients with medial temporal lobe damage were unimpaired in the 'short delay' condition suggesting intact encoding and short-term memory of spatial information. However, they were impaired in the allocentric condition and showed accelerated loss of allocentric spatial information. In the egocentric condition, while the performance of one patient was impaired, the performance of the other was as good as controls. This result suggests that, in contrast to allocentric spatial memory, which is sensitive to medial temporal lobe damage, an intact medial temporal lobe need not be necessary for successful performance on an egocentric spatial memory task.

Aged↗
PubMed1999

Automatic detection of hippocampal atrophy on magnetic resonance images.

An automatic method for identifying hippocampal atrophy on magnetic resonance (MR) images obtained from patients with clinical evidence of temporal lobe epilepsy (TLE) is described. The method is based on the analysis of image intensity differences between patients and controls within a volume of interest (VOI) centred on the hippocampus. The core of the method is a fully automatic signal intensity-based inter-subject image registration technique. In particular, a global affine registration to a reference image is performed, followed by a local affine registration within the VOI. A mask produced by manual segmentation of the mean hippocampus for 30 control subjects enabled investigations to be restricted to a specified region of the VOI approximately corresponding to the hippocampus. Normal variations of hippocampal signal intensity were computed from images obtained for the 30 control subjects. The manual method of hippocampal volumetry, currently an important component of the pre-surgical evaluation of patients with clinical evidence of medically intractable TLE, is used to determine the lower 1st percentile limits of normal hippocampal volume. Hippocampi with volumes below this limit are defined as atrophic. We investigated whether the automatic method can correctly distinguish between 15 patients with significant hippocampal atrophy according to absolute volumes and a further 14 controls. ROC curves enabled evaluation of sensitivity and specificity in respect of an intensity threshold. 100% specificity is required when determining suitability of patients for neurosurgery, resulting in levels of 50% and 70% sensitivity in detecting atrophy in the right and left hippocampus, respectively. We propose that the method can be developed as an automatic screening procedure.

Adolescent↗
PubMed1999

Infratentorial atrophy on magnetic resonance imaging and disability in multiple sclerosis.

Loss of tissue volume in the central nervous system may provide an index of fixed neurological dysfunction in multiple sclerosis. Recent magnetic resonance studies have shown a modest relationship between clinical disability rating scores and transverse sectional area of the cervical spinal cord. To explore further the relationship between atrophy and disability in multiple sclerosis, we estimated the volumes of infratentorial structures from MRIs in a cross-sectional study of 41 patients, 21 with relapsing-remitting multiple sclerosis and 20 with secondary progressive multiple sclerosis. We used the Cavalieri method of modern design stereology with point counting to estimate the volume of brainstem, cerebellum and upper cervical spinal cord from three-dimensional MRIs acquired with an MPRAGE (Magnetization-prepared Rapid Acquisition Gradient Echo) sequence. The volume of the upper (C1-C3) cervical spinal cord was significantly correlated with a composite spinal cord score derived from the appropriate Functional Scale scores of the Expanded Disability Status Scale (r = -0.50, P < 0.01). The cerebellar (r = 0.49, P < 0.01) and brainstem (r = 0.34, P < 0.05) volumes correlated with the Scripp's Neurological Disability Rating Scale scores. The upper cervical cord volumes (r = -0.39, P < 0.01), but not the brainstem or cerebellar volumes, were significantly associated with disease duration. MRI-estimated structural volumes may provide a simple index of axonal and/or myelin loss, the presumed pathological substrates of irreversible impairment and disability in multiple sclerosis.

Activities of Daily Living↗