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  • 1
    ISSN: 1432-1459
    Keywords: Key words Multiple sclerosis ; Magnetic resonance imaging ; Trial design
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Serial magnetic resonance imaging (MRI) detects substantial subclinical disease activity in multiple sclerosis (MS) and is presently included in most treatment trials as an objective outcome measure. Our current knowledge of the role of MRI in MS treatment trials is derived from very limited patient studies, and the aim of this paper is to identify strategies to optimize the use of MRI in monitoring disease activity in treatment trials. The number of active lesions revealed by MRI can be used as the primary outcome measure in exploratory treatment trials. With monthly scanning, the majority of active lesions will be seen by virtue of a limited number of new areas of gadolinium enhancement. The contrast between enhancing lesions and background could be increased by: (1) using higher doses of gadolinium, (2) suppressing the background signal with magnetization transfer, (3) delayed scanning, or (4) a combination of these. Following a systematic comparison of those approaches, the effect on the sensitivity in detecting active lesions should be analysed with reference to the power of treatment trials. We present preliminary results showing marked agreement between observers in reporting enhancing lesions; however, with new acquisition strategies, the observer variation should be re-established in a multicentre fashion. In definitive trials, the increase in total lesion load serves as a secondary outcome measure. Since the majority of lesions making up the total lesion load are inactive during the study, spatial resolution should be maximized in order to preclude any artificial changes in lesion load to be superimposed (noise) upon the relatively small actual change (information). Reduction in measurement error can be attempted by improved acquisition techniques with increased lesion to background contrast. More importantly, improvement in quantitation techniques is warranted. With a 6% coefficient of variation in measuring a baseline lesion load, we calculate the standard error of the mean yearly increase in T2 lesion load (typically 10% in untreated patients) in a treatment arm of 124 patients to be 7.5%. A comparison of several quantitation techniques should be performed in a multicentre longitudinal fashion in order to include variation caused by both scanner and segmentation technique, in addition to biological activity.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1459
    Keywords: Key words Multiple sclerosis ; Magnetic resonance imaging ; Disease activity ; Fast spin echo ; Fast fluid-attenuated inversion ; recovery ; Reproducibility
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous studies have addressed the question of the precision in assessing multiple sclerosis (MS) activity by counting enhancing lesions on gadolinium enhanced brain magnetic resonance imaging (MRI). However, counting the active lesions on serial unenhanced MRI obtained by various pulse sequences has not been yet considered. We compared the interobserver levels of agreement in reporting active MS lesions on serial enhanced and unenhanced MRI to assess whether the use of various unenhanced techniques may change the degree of interobserver measurement reproducibility. Dual-echo conventional spin echo (CSE), dual-echo fast spin echo (FSE), fast fluid-attenuated inversion recovery (FLAIR) and Gd-enhanced T1-weighted brain MRI were obtained from five MS patients at baseline and monthly for 2 months. Six experienced observers independently identified and counted active MS lesions on the two follow-up MRI scans. Active lesions were considered to be all the enhancing lesions and any new or enlarging lesion on enhanced and unenhanced scans. Interobserver levels of agreement were calculated by weighted κ values. Very good agreement was reached only for counting total and new Gd-enhancing lesions. Good agreement was achieved for counting new lesions on the three unenhanced techniques, whereas the agreement for counting enlarging lesions was poor with all the MRI techniques. The level of agreement was significantly heterogeneous for various MRI techniques but not for various lesion sites. These results confirm that counting enhancing lesions is the most reliable method for assessing MS activity, but the use of any of the available unenhanced MRI techniques did not result in different levels of interobserver agreement when reporting new and enlarging MS lesions on serial scans.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1920
    Keywords: Huntington's disease ; Computed tomography ; Magnetic resonance imaging ; Single photon emission computed tomography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A Turkish family with Huntington's disease documented on CT, MRI and SPECT is reported. Whereas in clinically definite cases CT and MRI are of limited value and SPECT does not add anything of value, in one asymptomatic subject SPECT showed moderate caudate nucleus hypoperfusion, underlining the hypothesis that SPECT may have a role in predicting Huntington's disease.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1920
    Keywords: Multiple sclerosis ; Magnetic resonance imaging ; Corticosteroid ; Gadolinium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Treatment with methylprednisolone reduces the duration and severity of clinical relapses in multiple sclerosis (MS), while reducing the number of gadolinium-enhancing lesions on T1-weighted MRI. We performed serial MRI imaging after methylprednisolone treatment to see whether suppression of enhancement persists and whether related abnormalities on T2-weighted images disappear at follow-up. Thirteen patients with definite MS received a total of 31 courses of methylprednisolone over an average period of 50 weeks. Gadolinium-enhanced MRI was obtained before and after treatment, then at monthly intervals, using a standardised repositioning and imaging protocol. Two experienced readers in conference defined the number of active (gadolinium-enhancing and new or enlarging nonenhancing) lesions. We detected 609 active lesions on 195 examinations. Directly after treatment the reduction in the number of enhancing lesions was 78%, indicating restoration of the BBB and suppression of inflammation. It was uncommon for a lesion which stopped enhancing to show enhancement on a subsequent examination. No beneficial effect was observed on the rate of disappearance of related abnormalities on T2-weighted images, indicating persistent change such as oedema, cellular infiltration or demyelination. Moreover, in 89% of cases, an increase in the number of active lesions was observed before new clinical activity, if any, was observed (on average 52% earlier). MRI enabled us to demonstrate that the duration of the effect of methylprednisolone treatment is temporary (on average 9.7 weeks).
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1920
    Keywords: Key words Multiple sclerosis ; Magnetic resonance imaging ; Interobserver variation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract MRI is the paraclinical test most widely used to support the diagnosis of multiple sclerosis (MS). We evaluated interobserver agreement in applying diagnostic criteria to MRI obtained at first presentation. Five experienced observers scored 25 sets of images consisting of unenhanced T2- and gadolinium-enhanced T1-weighted images (approximately half the sets were normal). We scored frontal, parietal, temporal, occipital, infratentorial and basal ganglia lesions and the total number of lesions on T2-weighted images; periventricular, callosal, juxtacortical and ovoid lesions and those 〉 5 mm in maximum diameter; contrast-enhancing and hypointense lesions. Based on a combination of imaging findings patients were classified as compatible or not compatible with MS according to composite criteria. Observer concordance was characterised by weighted kappa values (ϰ) and mean average difference to the median (MADM) scores. Using the raw scores, there was poor agreement for the total number of lesions on T2-weighted images, and for occipital, oval, juxtacortical and hypointense lesions. Moderate agreement was found for frontal, callosal, basal ganglia and large lesions on T2 weighting. Good agreement was attained for parietal, temporal, infratentorial and periventricular lesions. After dichotomisation according to accepted cut-off values, most criteria performed better, especially the number of lesions on T2-weighted images (P 〈 0.05). Good agreement was found for the criteria of Paty and Fazekas and moderate agreement for those of Barkhof. While experienced observers may not agree on the total number of lesions, they show quite good agreement for commonly used cut-off points and elements in the composite criteria. This validates the use of MRI in the diagnosis of MS, and the use of dichotomised and composite criteria.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1920
    Keywords: Multiple sclerosis ; Magnetic resonance imaging ; Brain ; Gadolinium ; Database
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The unique sensitivity of magnetic resonance imaging (MRI) in detecting disease activity in multiple sclerosis (MS) and the objective nature of the information obtained suggest that MRI will be a useful and reliable way of monitoring treatment trials. There is a need to develop an appropriate database which would provide a standardised means of assessment, not only of MRI, but also of essential clinical information. As part of the program of Concerted Action in Multiple Sclerosis, funded by the Commission of the European Community (CEC), we have developed a database for recording serial brain MRI results. The database consists of core, entry and follow-up sections. Both entry and follow-up parts are subdivided into clinical, MR system and MRI data. We expect that the use of this database will maximise efficiency of MRI monitoring in MS treatment trials, particularly in multicentre studies.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-1920
    Keywords: Key words Multiple sclerosis ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We evaluated the effect of consensus formation and training on the agreement between observers in scoring the number of new and enlarging multiple sclerosis (MS) lesions on serial T2-weighted MRI studies. The baseline and month 9 MRI studies of 16 patients with a range of MRI activity were used (dual-echo conventional spin-echo sequence, TR 2000, TE 34 and 90 ms, 5 mm contiguous slices, in-plane resolution 1 mm). First, the serial studies were visually analysed for the presence of new and enlarging lesions, on two occasions, by five experienced observers, without adopting any consensus strategy and in isolation. Next, the observers met to identify the common sources of inconsistencies in reporting between observers and formulate consensus rules. Finally, a further independent reading session was performed on the same MRI dataset, this time applying the consensus rules. Agreement between observers was assessed using kappa scores. Without the consensus rules, interobserver kappa scores for the first and second reading sessions for new lesions were only 0.51 and 0.39 respectively; agreement for enlarging lesions was even worse. The mean intraobserver kappa score for new lesions was higher at 0.72, reflecting the fact that the observers were consistently applying their individual assessment strategies. Application of the consensus rules did not lead to a significant improvement in inter observer kappas; the kappa scores adopting the guidelines were 0.46 and 0.21 for new and enlarging lesions respectively. Consensus guidelines thus did not improve the reproducibility of visual analysis of serial T2-weighted MRI, and the level of agreement between observers remained only moderate. Suboptimal repositioning is likely to be a major source of residual variability and this suggests a future role for image registration strategies; until then, a single observer, or pair of observers working in consensus, should be used in MS studies.
    Type of Medium: Electronic Resource
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