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N C Silver

Publications and source records attributed to N C Silver.

At least 19 recordsLinked to original sources
PubMed2005

Object strength--an accurate measure for small objects that is insensitive to partial volume effects.

There are currently four problems in characterising small nonuniform lesions or other objects in Magnetic Resonance images where partial volume effects are significant. Object size is over- or under-estimated; boundaries are often not reproducible; mean object value cannot be measured; and fuzzy borders cannot be accommodated. A new measure, Object Strength, is proposed. This is the sum of all abnormal intensities, above a uniform background value. For a uniform object, this is simply the product of the increase in intensity and the size of the object. Biologically, this could be at least as relevant as existing measures of size or mean intensity. We hypothesise that Object Strength will perform better than traditional area measurements in characterising small objects. In a pilot study, the reproducibility of object strength measurements was investigated using MR images of small multiple sclerosis (MS) lesions. In addition, accuracy was investigated using artificial lesions of known volume (0.3-6.2 ml) and realistic appearance. Reproducibility approached that of area measurements (in 33/90 lesion reports the difference between repeats was less than for area measurements). Total lesion volume was accurate to 0.2%. In conclusion, Object Strength has potential for improved characterisation of small lesions and objects in imaging and possibly spectroscopy.

Algorithms↗
PubMed2005

Guillain Barré syndrome precipitated by the use of antilymphocyte globulin in the treatment of severe aplastic anaemia.

This report describes the case of a 54 year old woman with very severe aplastic anaemia who was treated with antilymphocyte globulin (ALG) and developed Guillain Barré syndrome (GBS). No antecedent infective aetiology was identified. Although there are numerous reports of autoimmune disease after treatment with ALG in aplastic anaemia, and GBS after immunosuppressive treatment, there are none reporting GBS after the use of ALG for severe aplastic anaemia. The occurrence of autoimmune disease after immunosuppressive treatment, in particular ALG, is discussed, together with the possible mechanisms that result from T cell depression.

Anemia, Aplastic↗
PubMed2003

The normal appearing grey matter in primary progressive multiple sclerosis: a magnetisation transfer imaging study.

BACKGROUND: In 10-15 % of patients with multiple sclerosis (MS), the clinical course is characterized by slow progression in disability without relapses (primary progressive (PP) MS). The mechanism of disability in this form of MS is poorly understood. Using magnetization transfer ratio (MTR) imaging, we investigated normal appearing white matter (NAWM) and normal appearing grey matter (NAGM) in PPMS and explored the relationship of MTR measures with disability. METHODS: Thirty patients with PPMS and 30 age matched controls had spin echo based MTR imaging to study lesions and normal appearing tissues. The brain was segmented into NAWM and NAGM using SPM99 with lesions segmented using a semiautomated local thresholding technique. A 75% probability threshold for classification of NAWM and NAGM was used to diminish partial volume effects. From normalized histograms of MTR intensity values, six MTR parameters were measured. Mean lesion MTR and T2 lesion volume were also measured. Disability was assessed using Kurtzke's expanded disability status scale (EDSS). RESULTS: Compared with controls, patients exhibited a significant reduction in mean NAWM (p = 0.001) and NAGM (p = 0.004) MTR. Spearman's rank correlation of EDSS with the six MTR parameters in NAWM and NAGM, mean lesion MTR, and T2 lesion volume, was only significant with mean NAGM MTR (r = -0.41, p = 0.02), the 25th percentile of NAGM MTR intensity (r = -0.37, p = 0.05), and T2 lesion volume (r = 0.39, p = 0.04). Multiple regression analysis of the relationship between EDSS and 4 MR parameters representing each tissue type (mean NAWM MTR, mean NAGM MTR, mean lesion MTR, T2 lesion volume) showed that the association of EDSS with mean NAGM MTR remained significant. CONCLUSIONS: There appear to be significant abnormalities in the NAGM in PP MS. Further investigation of the pathological basis and functional significance of grey matter abnormality in PPMS is warranted.

Adult↗
PubMed2001

Infratentorial hypointense lesion volume on T1-weighted magnetic resonance imaging correlates with disability in patients with chronic cerebellar ataxia due to multiple sclerosis.

In multiple sclerosis (MS), hypointense lesions on T1-weighted magnetic resonance imaging are thought to represent areas of tissue disruption and axonal loss. In previous studies of MS patients, infratentorial T1 hypointense lesions were found to be rare. In MS patients selected to have chronic cerebellar ataxia, we have determined the extent of infratentorial T1 hypointense lesions and their relationship with disability. We recruited nine patients with chronic cerebellar ataxia due to MS. An expanded disability status scale (EDSS) assessment was performed on each. The patients' brains were then imaged with axial-oblique dual-echo fast spin-echo and contrast-enhanced T1-weighted conventional spin-echo sequences. The number and total volume of infratentorial high-signal lesions on T2-weighted images and infratentorial hypointense lesions on T1-weighted images were calculated by a blinded observer using a computer-assisted contouring technique. A total of 96 infratentorial high-signal lesions were present, of which 62 (64.6%) appeared isointense and 34 (35.4%) hypointense with respect to the surrounding brain substance on the T1-weighted images. There was a median of 3 (range 0-10) and median volume of 0.43 ml (range 0-0.85 ml) infratentorial T1 hypointense lesions per patient. The EDSS score correlated with both the number (r=0.68, p=0.043) and the volume per patient (r=0.89, p=0.001) of infratentorial T1 hypointense but not T2 high-signal lesions. Infratentorial T1 hypointense lesions are often seen in patients with MS and chronic cerebellar ataxia. They may play a significant role in the disability suffered by these patients.

Adolescent↗
PubMed2001

Magnetisation transfer ratio histogram analysis of primary progressive and other multiple sclerosis subgroups.

INTRODUCTION: Global magnetisation transfer ration (MTR) histogram analysis in the brain offers a method for evaluating pathological change both as a result of lesions and microscopic changes in normal appearing tissues. METHODS: 39 controls and 83 MS patients (46 primary progressive, 11 benign, 10 relapsing-remitting, 16 secondary progressive) were studied to explore the relationship of six conventional MTR histogram parameters with MS clinical subgroups and disability. Principal component (PC) analysis, which makes use of all the histogram data, was also used to examine the relationship between the MTR histogram and disability. RESULTS: When primary progressive patients were compared to controls, there were abnormalities of average MTR, and MTR at the 25th, 50th and 75th percentile. Disabled relapsing onset patients exhibited abnormalities in the same four parameters. Benign and nondisabled relapsing onset patients exhibited no significant abnormalities. Modest correlations were observed between disability and individual MTR parameters in relapse onset but not primary progressive patients--PC analysis revealed stronger and significant associations with disability in both subgroups. (r=0.40 for primary progressive and r=0.51 for relapsing onset). CONCLUSION: A number of MTR parameters are abnormal in primary progressive MS. MTR abnormalities are seen in disabled patients, whether of relapsing or primary progressive onset. The improved correlation with disability obtained by PC analysis suggests a useful role of this method for following clinically relevant pathological changes depicted in the MTR histogram.

Adult↗
PubMed2001

Analysis of MTR histograms in multiple sclerosis using principal components and multiple discriminant analysis.

Magnetization transfer ratio (MTR) histograms have the potential to characterize subtle diffuse changes in multiple sclerosis (MS) and other white matter disease. A new method is described which gives improved correlation with the Expanded Disability Status Scale (EDSS). Classification of individual subjects into normal and MS subgroups is shown. Principal component analysis (PCA) and multiple discriminant analysis (MDA) are shown to give results superior to methods of MTR histogram analysis using traditional features such as peak height and peak location. Scatterplots confirm the improved separation between groups achieved using the MDA score. The histogram analysis provides a comparison of two classification approaches, based on PCA and MDA, to recognize differences between normal controls and the four different subgroups of MS disease (and all MS patients). Multiple linear regression of these PCs vs. EDSS established an MR-based measure of disease. Using a central 60-mm slab of brain tissue, the success rate of binary classification between control and MS subgroups using MDA was 75-95%, depending on which two groups were being compared. Multiple regression analysis of EDSS with the first three PCs as independent variables was significant (r = 0.83 for secondary progressive MS, and r = 0.80 for all MS patients).

Brain↗
PubMed2001

Detection of optic nerve atrophy following a single episode of unilateral optic neuritis by MRI using a fat-saturated short-echo fast FLAIR sequence.

We describe an MRI technique for quantifying optic nerve atrophy resulting from a single episode of unilateral optic neuritis. We imaged 17 patients, with a median time since onset of optic neuritis of 21 months (range 3-81 months), using a coronal-oblique fat-saturated short-echo fast fluid-attenuated inversion-recovery (sTE fFLAIR) sequence. The mean cross-sectional area of the intraorbital portion of the optic nerves was calculated by a blinded observer from five consecutive 3 mm slices from the orbital apex forwards using a semiautomated contouring technique and compared with data from 16 controls. The mean optic nerve area was 11.2 mm2 in the affected eye of the patients, 12.9 mm2 in the contralateral eye (P = 0.006 compared to the affected eye) and 12.8 mm2 in controls (P = 0.03 compared to the affected eyes). There was a significant negative correlation between disease duration and the size of the affected optic nerve (r = -0.59, P = 0.012). The measurement coefficient of variation was 4.8%. The sTE fFLAIR sequence enables measurement of optic nerve area with sufficient reproducibility to show optic nerve atrophy following a single episode of unilateral optic neuritis. The correlation of increasing optic nerve atrophy with disease duration would be consistent with ongoing axonal loss in a persistently demyelinated lesion, or Wallerian degeneration following axonal damage during the acute inflammatory phase.

Adult↗
PubMed2001

A modified protocol to improve the detection of enhancing brain and spinal cord lesions in multiple sclerosis.

By detecting focal blood-brain barrier (BBB) breakdown, gadolinium (Gd-DTPA) contrast-enhanced T1-weighted magnetic resonance imaging (MRI) allows assessment of inflammatory activity in multiple sclerosis (MS) and provides a sensitive means of monitoring immunomodulatory therapies in exploratory trials. Serial monthly studies were performed in eight relapsing-remitting and eight secondary progressive patients to assess new and more sensitive techniques for enhanced MRI. Brain and spine imaging was carried out at 1.5-T on two occasions 24-72 h apart using a conventional imaging protocol with T1-weighted MRI at single-dose (0.1 mmol/kg) Gd-DTPA and a potentially more sensitive "modified" protocol with T1-weighted MRI at triple-dose (0.3 mmol/kg) Gd-DTPA (with addition of delay and magnetisation transfer presaturation for brain imaging). For each MRI protocol the total numbers of enhancing lesions (97 paired studies) and new enhancing lesions (81 paired studies) were assessed. The total number of enhancing lesions seen was 347/75 on conventional brain/cord MRI respectively, and 754/123 on modified brain/cord MRI. The respective numbers of new enhancing lesions were 168/40 on conventional and 276/71 on modified scans. Smaller increases were seen in the proportion of active scans using the modified protocol. Sample size calculations showed no reduction in sample sizes required for a parallel group study but a reduced sample size for crossover studies using the modified protocol; the addition of cord to brain imaging did not improve power for either trial design. A combined modified brain and cord imaging protocol markedly improves the detection of areas of focal BBB leakage in MS and may be useful in selected natural history studies. The modified brain protocol reduces sample size requirements for crossover studies but not necessarily for parallel design trials.

Adult↗
PubMed2001

Quantitative contrast-enhanced magnetic resonance imaging to evaluate blood-brain barrier integrity in multiple sclerosis: a preliminary study.

Gadolinium enhanced magnetic resonance imaging detects focal blood-brain barrier breakdown in new inflammatory multiple sclerosis lesions, but such lesions do not correlate with disease progression. To explore whether the latter might relate to subtle but widespread blood-brain barrier (BBB) breakdown with low grade inflammation mediating tissue damage, quantitative techniques were used to detect subtle gadolinium enhancement within otherwise normal-appearing white matter and within lesions not showing visible enhancement. T1-weighted imaging was performed prior to and at 5, 20 and 40 min following injection of 0.3 mmol/kg gadopentate dimeglumine in 33 patients with multiple sclerosis and five healthy control subjects. In healthy controls, a significant increase in white matter signal 5 min following contrast injection was observed (1.8%, P < 0.0005); the signal returned to baseline values by 20 min. In multiple sclerosis patients, a non-significant trend was noted for signal to remain elevated in normal-appearing white matter at the 20 and 40 min post-contrast time points; this was most apparent in primary progressive multiple sclerosis. Significant increases in signal intensity were noted at all time points post contrast in apparent non-enhancing lesions. The transient post contrast signal increase in controls is likely due to intravascular gadopentate dimeglumine. The persistent increases in signal intensity in non-enhancing lesions suggest more widespread abnormalities in BBB than is visually apparent, but substantiation of BBB leakage in normal appearing white matter will require further study using more sensitive methods.

Adult↗
PubMed2000

Immunological time-course of gadolinium-enhancing MRI lesions in patients with multiple sclerosis.

In multiple sclerosis (MS) gadolinium (Gd)-enhanced MRI activity correlates weakly with immunological markers of disease activity. We, therefore, tested the hypothesis that the poor correlation could be partly explained by the temporal profile of Gd enhancement. We measured urinary neopterin:creatinine ratios (neopt.:creat.(urine)) in 5 patients with active MS undergoing weekly Gd-enhanced MRI studies of the brain. The neopt.:creat.(urine) associated with new Gd-enhancing lesions (<8 days) was significantly higher than the ratio not associated with new Gd-enhancing lesions [mean(geometric) neopt.: creat.(urine) = 413 micromol/mol (range = 207-521) vs. 250 micromol/mol (range = 132-492), p = 0.03]. Pro-inflammatory immunological markers, which are probably produced early on in the life cycle of an active MS lesion, should preferably be correlated with newly enhancing lesions (<8 days). Failure to do this may explain the poor and unpredictable correlations between immunological markers and Gd-enhanced MRI activity, which cannot be accurately aged in cross-sectional and serial monthly MRI studies.

Adrenal Cortex Hormones↗
PubMed1999

Does the extent of axonal loss and demyelination from chronic lesions in multiple sclerosis correlate with the clinical subgroup?

OBJECTIVE: To determine non-invasively the relation between the degree of axonal loss and the extent of demyelination in chronic lesions visible on MRI in patients with different subgroups of clinically definite multiple sclerosis using (1)H magnetic resonance spectroscopy ((1)H MRS) and magnetisation transfer imaging (MT). Conventional MRI is unable to differentiate between the various pathological processes occurring in the multiple sclerosis lesion. There are, however, newer MR techniques which show promise in this respect. METHODS: (1)H MRS and MT were performed in 18 patients with clinically definite multiple sclerosis who had a wide range of disability and disease duration. RESULTS: A significant correlation was found between a reduction in the concentration of N-acetyl aspartate (NAA; an in vivo marker of axonal loss or dysfunction) and a reduction in MT ratio (a probable marker of demyelination) in patients who had entered the secondary progressive stage of the disease. Patients with minimal disability after a disease duration of greater than 10 years-so called benign multiple sclerosis-showed a relative preservation of NAA and MT. CONCLUSIONS: Because a reduction in MT seems to be a relative marker for demyelination and a reduction of NAA from chronic lesions is indicative of axonal loss, this study supports the hypothesis that demyelination and axonal loss occur in the same chronic multiple sclerosis lesions. In addition, the degree of axonal loss and demyelination correlates with clinical heterogeneity.

Aspartic Acid↗
PubMed1999

Magnetisation transfer of normal appearing white matter in primary progressive multiple sclerosis.

Patients with primary progressive multiple sclerosis may develop severe disability despite a paucity of lesions on conventional magnetic resonance imaging, raising the possibility that intrinsic changes in normal appearing white matter (NAWM) contribute to disability. This study has measured magnetisation transfer ratio (MTR), an index of tissue damage, of NAWM in 52 patients with primary progressive multiple sclerosis and 26 healthy controls. Absolute values of MTR were obtained from the genu of the corpus callosum and pons, and mean values were calculated from bilateral regions in the centrum semiovale, frontal white matter, parieto-occipital white matter and posterior limb of the internal capsule. The median MTR was lower in all regions in patients compared to controls. Median values (per cent units) were significantly lower in corpus callosum (39.73 vs 40.63; P=0.01), frontal white matter (39.11 vs 39.59; P=0.01) and centrum semiovale (37.21 vs37.82; P<0.05). This study has demonstrated small but widespread decreases in MTR in NAWM in primary progressive multiple sclerosis supporting the hypothesis that there are intrinsic changes in NAWM which may contribute to disability in this patient group.

Adult↗
PubMed1999

Increased urinary nitric oxide metabolites in patients with multiple sclerosis correlates with early and relapsing disease.

Nitric oxide (NO) has been implicated in the immunopathogenesis of MS as a potential mediator of neuronal loss. To investigate the role of.NO in the development of progressive disease we measured the NO metabolites (nitrate and nitrite) and neopterin, in the urine of 129 patients with demyelinating disease (DD): 23 with clinically isolated syndromes compatible with demyelination and in 46 relapsing remitting (RR) and 60 patients with progressive MS. Eighty-nine of these 129 patients underwent Gd-enhanced MRI. In addition 58 normal control subjects (NC), 19 AIDS and 35 rheumatoid arthritis (RA) patients were studied. Patients with DD, AIDS and RA had significantly elevated urinary nitrate plus nitrite (nit : creat. urine) and neopterin (neopt : creat.urine) to creatinine ratios compared to NC subjects. (Median[25th - 75th%] nit : creat.urine: NC=1183[962 - 1365] vs DD=1245[875 - 2403], AIDS=1686[1231 - 2531], and RA=1950[1214 - 2726] mumol/mol, P<0.001 and median[25th - 75th%] neopt : creat.urine: NC=99[76 - 151] vs DD=163[119 - 266], AIDS=972[653 - 1456], and RA=389[257 - 623] mu mol/mol, P<0.001). Patients with early DD and RR MS had significantly elevated nit : creat.urine compared to patients with progressive MS (nit : creat. urine: 1612[1020 - 2733] vs 1159[790 - 1641] mu mol/mol, P=0.006). The nit : creat.urine and neopt : creat.urine did not correlate with clinical relapse or MRI activity. Excretion of.NO metabolites is increased in patients with early or relapsing-remitting disease.NO appears to be a double-edged sword, mediating tissue damage and modulating complex immunological functions which may be protective in MS.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Standardization of magnetization transfer imaging for multicenter studies.

Magnetization transfer (MT) techniques may be applied to magnetic resonance imaging (MRI) to evaluate the inherent relaxation properties of heterogeneous tissues. In addition to providing a unique contrast mechanism for the purpose of qualitative imaging, the MT effect may be quantified by various means to provide useful data that relate either to the pathological or associated clinical features of multiple sclerosis (MS) and other neurological disorders. The variable and relatively unpredictable course of neurological disorders such as MS often necessitates the study of large patient cohorts in multiple MRI centers to define either the natural history of the disease or its modification by potential therapies. For multicenter studies, precision (reproducibility, or lack of random error) and accuracy (closeness to the truth, or lack of systematic error) are important requirements for the acquisition of standardized and comparable data. For serial studies, quality assurance is important to determine pathological change from fluctuation in scanner performance. This review addresses how MT imaging techniques may be utilized to provide standardized and clinically relevant measures.

Brain↗
PubMed1998

Serial magnetization transfer imaging to characterize the early evolution of new MS lesions.

OBJECTIVE: To explore the temporal relation of demyelination and blood-brain barrier breakdown during new lesion formation. BACKGROUND: Conventional MRI appears sensitive for detecting changes due to MS, but may be limited by poor pathologic specificity. By indirectly assessing protons bound to rigid macromolecules, magnetization transfer (MT) imaging may provide information relating to tissue structure and, by inference, myelin integrity. METHODS: Gadolinium contrast-enhanced MRI and MT imaging were performed at weekly intervals for 3 months in three patients with MS. For each enhancing lesion, the largest corresponding area of proton density hyperintensity seen during the study was outlined and magnetization transfer ratio (MTR) calculated at each time point from coregistered calculated MTR images. Lesions greater than 20 mm2, not affected by partial volume effects, and first enhancing after the baseline study were analyzed. Two-dimensional registration software allowed accurate evaluation of MTR in regions both before and after the initial appearance of MS lesions. RESULTS: Mean lesion MTR decreased significantly during the first week of enhancement (29.6 percent units [pu] immediately pre-enhancement versus 28.2 pu at first documented stage of enhancement). No significant MTR reduction was noted before this. CONCLUSION: The lack of observable change in MTR before the first detectable gadolinium enhancement within MS lesions suggests that blood-brain barrier disruption is closely related to, but not preceded by, demyelination.

Adult↗
PubMed1997

Fast FLAIR of the brain: the range of appearances in normal subjects and its application to quantification of white-matter disease.

Axial fast FLAIR images of the brains of 40 normal volunteers in four age groups between 16 and 55 years were examined and the number and size of areas of increased white-matter signal recorded. Increased signal in the corticospinal tract region was seen at the level of the internal capsule in all subjects, extending up towards the centrum semiovale and down towards the pons for 0.5-5.5 cm (median 2.5 cm). In all cases the IIIrd and IVth ventricles were outlined by a thin line of high signal. Focal areas of high signal (caps) were seen around the frontal and occipital horns in 90% and 77% respectively; 54% of caps were asymmetrical. None of the above features varied with the age or sex of the subject, but the numbers of discrete white matter 'lesions' increased with age. The findings are used to suggest guidelines for the identification of areas of 'normal' high signal to be excluded in quantification of lesions on fast FLAIR images.

Adolescent↗
PubMed1997

Magnetisation transfer ratio measurement in the cervical spinal cord: a preliminary study in multiple sclerosis.

MRI readily detects the lesions of multiple sclerosis (MS) in the brain and spinal cord. Conventional MRI sequences do not, however, permit distinction between the various pathological characteristics (oedema, demyelination, axonal loss and gliosis) of lesions in MS. Magnetisation transfer (MT) imaging may be more specific in distinguishing the pathologies responsible for disability in MS, namely demyelination and axonal loss, and therefore may have a potential role in monitoring treatment. We have applied MT imaging to the cervical spinal cord to see if it is feasible to measure MT ratios (MTR) in this region where pathological changes may result in considerable disability. We studied 12 patients with MS and 12 age- and sex-matched normal controls using a sagittal T2-weighted fast spin-echo sequence with and without an MT pulse. The median value for cervical cord mean MTR measurement in normal controls was 19.30% units (interquartile range 19.05-19.55), whereas values were significantly lower in MS patients (median = 17.95% units, interquartile range 17.25-19.00, P = 0.0004). There was a low intrarater variability for repeated mean MTR measurements. We conclude that it is possible to measure MTR in the cervical spinal cord, that a significant reduction occurs in patients with MS, and that there may be a role for this measure in future MS treatment trials.

Adult↗