Biomedical subjects

M Filippi

Publications and source records attributed to M Filippi.

At least 271 records · Page 15Linked to original sources

PubMed1998

The role of non-conventional magnetic resonance techniques in monitoring evolution of multiple sclerosis.

Conventional magnetic resonance imaging (MRI) techniques have proved to be extremely useful to monitor multiple sclerosis activity and evolution. The recent development and clinical application of non-conventional MR techniques has the potential to further increase the importance of MR in the evaluation of multiple sclerosis by reducing the time needed for acquisition of the data, by improving sensitivity, and by increasing the pathological specificity of the abnormalities detected. In the present review, the main results obtained using these newer techniques in the study of the natural history of the disease and the future possible applications in clinical trials are presented.

Brain↗

PubMed1998

The role of techniques characterised by faster acquisition times in the evaluation of multiple sclerosis.

Magnetic resonance imaging (MRI) methods with shorter acquisition times are considered. Fast spin echo sequences allow faster scanning with images comparable with conventional spin echo. Fast fluid attenuated inversion recovery (fast FLAIR) may provide a more complete picture of multiple sclerosis evolution, but more validation studies are still needed. Faster imaging methods, such as turbogradient spin echo and echo planar imaging, have marked advantages for uncooperative patients for diagnostic purposes and reduced motion related artifacts but may involve sacrifices of signal to noise, contrast, spatial resolution, and image quality. All methods are useful for clinical diagnosis, with fast spin echo generally accepted as equivalent to conventional spin echo. For quantitative evaluation in multiple sclerosis, further work is needed to define the utility of the faster and ultrafast methods.

Brain↗

PubMed1998

Magnetisation transfer imaging: theory and application to multiple sclerosis.

Magnetic resonance imaging techniques based on magnetisation transfer exploit the inherent heterogeneity of tissue with respect to relaxation times T1 and T2. Contrast reflecting the interactions between distinct relaxation "environments" may be exploited via novel quantitative analysis for potential gains in specificity of the MR examination in multiple sclerosis.

Brain↗

PubMed1998

Functional magnetic resonance imaging in multiple sclerosis.

Functional magnetic resonance imaging (fMRI) is a method that combines high anatomical spatial resolution with the ability to localise function. Visual and motor systems are among those that have received most attention. Yet the clinical application is still limited. Recently, some investigators applied fMRI to study patients with multiple sclerosis. Patients with partial motor weakness disclosed a larger area of cortical activation bilaterally by contrast with healthy volunteers when using the affected arm, whereas patients with optical neuritis disclosed a smaller area of activation, when stimulating the affected eye. These results show that different systems might react heterogeneously.

Brain↗

PubMed1998

Quantitative assessment of magnetic resonance imaging lesion load in multiple sclerosis.

Changes of lesion load on yearly conventional spin echo (CSE) T2-weighted scans of the brain from patients with multiple sclerosis, measured using computer assisted techniques, are used to monitor long term disease evolution, either natural or modified by treatment. Although lesion load measurements have several advantages over clinical measures of outcome (they provide a more objective and sensitive measure of disease evolution, which has a linear distribution and a more strict relation with the underlying pathology), the poor correlation between changes of lesion load and changes of disability is of concern when using such an approach for monitoring multiple sclerosis trials. In this review, the main sources of variation in T2 lesion load from brain MRI of patients with multiple sclerosis will be considered, along with possible strategies to, at least partially, overcome them. Also, some of the newer fully automated techniques to segment multiple sclerosis lesions, which have been validated against manual outlining, and a recently developed coregistration technique are presented. It is hoped that a more reliable and standardised approach to lesion load measurements in multiple sclerosis will lead to better correlation with clinical disease course, to a higher confidence in the results of trials, and to reduced numbers of scans needed to conduct the trials, thus improving cost efficiency and reducing discomfort of the patients.

Brain↗

PubMed1997

Tumor necrosis factor alpha and its receptors in relapsing-remitting multiple sclerosis.

In the attempt to further characterize the extent and timing of tumor necrosis factor (TNF)alpha-system activation during multiple sclerosis (MS), we performed a cross-sectional and a longitudinal study in a total of 73 relapsing-remitting MS patients. We assessed serum levels of soluble TNFalpha, soluble TNFalpha receptor 1 (R1) and soluble TNFalpha receptor 2 (R2) in 65 relapsing-remitting MS patients in different phases of disease. TNFalpha, R1 and R2 serum levels measured in MS patients did not differ from those measured in healthy individuals and did not correlate with (a) clinical relapses, (b) presence of gadolinium-enhancing brain-magnetic resonance imaging (MRI) lesions, and (c) bioactivity of TNFalpha. We also measured in 8 additional relapsing-remitting MS patients peripheral blood mononuclear cells (PBMC) mRNA levels of TNFalpha, R1 and R2 every 15 days for one year. In 4 of these patients we also measured levels of soluble TNFalpha, R1 and R2 every 15 days for 5 months across a clinical exacerbation. PBMC TNFalpha, R1 and R2 mRNA levels and serum levels of soluble R1 and R2, but not TNFalpha, fluctuated concordantly (P<0.05) and peaked a mean of 6 weeks before clinical and MRI evidence of disease activity. Moreover, we found a significant positive correlation between cumulative TNFalpha and R2 mRNA levels (measured during the follow-up period in the 8 MS patients studied serially) and the number of clinical attacks recorded in these patients during the study. Our data show that serum levels of soluble TNFalpha, R1, and R2 in MS patients do not differ from those of healthy individuals. However, although within normal values, the transcription and production rate of all these molecules fluctuate concordantly in the peripheral blood during the course of the disease (with the exception of soluble TNFalpha) and their maximal elevation significantly precedes the occurrence of clinical exacerbations. It is not clear whether soluble TNFalpha escapes recognition by commonly used assays or is simply not released in its soluble form in MS patients. In any case, measurement of TNFalpha mRNA levels and R1 and R2 mRNA and protein levels appears to be a better indicator of disease fluctuations during the course of MS than assessments of soluble TNFalpha protein.

Adult↗

PubMed1997

Magnetization transfer ratio changes in a symptomatic lesion of a patient at presentation with possible multiple sclerosis.

Short-term changes of magnetization transfer ratio (MTR) of a symptomatic lesion in a patient at presentation with clinically isolated syndrome suggestive of multiple sclerosis (MS) are presented. These changes strictly correlated with the evolution of the corresponding clinical symptomatology. This suggests that following changes of individual strategically located lesions might be useful to monitor evolution of demyelinating white matter diseases.

Adult↗

PubMed1997

A magnetization transfer study of white matter in siblings of multiple sclerosis patients.

In this study, we evaluated magnetization transfer ratio values in the brain white matter of siblings of multiple sclerosis (MS) patients and compared them to those obtained in sex- and age-matched normal controls. No statistically significant difference was found between the two groups for all the white matter areas studied (frontal and occipital lobes, centrum semiovale, periventricular white matter, internal capsule, genu and splenium of the corpus callosum).

Adult↗

PubMed1997

Strategies for optimizing MRI techniques aimed at monitoring disease activity in multiple sclerosis treatment trials.

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.

Clinical Trials as Topic↗

PubMed1997

Intra-observer reproducibility in measuring new putative MR markers of demyelination and axonal loss in multiple sclerosis: a comparison with conventional T2-weighted images.

New magnetic resonance (MR) measures considered to be putative workers of demyelination and axonal loss were found to be more closely related to clinical disability than T2-weighted MR imaging (MRI) findings in patients with multiple sclerosis (MS). In this study, we evaluated the reproducibility of such measurements in order to assess their reliability for longitudinal studies in MS. The intra-observer coefficients of variation for repeated measurements did not significantly differ among the MR techniques studied [2.6% for T2-weighted MR, 4.38% for unenhanced T1-weighted MRI, 3.65% for magnetisation transfer imaging (MTI) and 2.28% for spinal cord cross-sectional area at C5]. Our findings suggest that non-conventional MR techniques may be reliable outcome measures for clinical trials in MS.

Adult↗

PubMed1997

An oblique cylinder contrast-adjusted (OCCA) phantom to measure the accuracy of MRI brain lesion volume estimation schemes in multiple sclerosis.

A new OCCA phantom using Oblique Cylinders and Contrast Adjustment for measuring the accuracy of brain lesion volume estimation schemes is described. It uses obliquely oriented cylinders made from acrylic rod, mounted in a water bath, to give realistic partial volume errors. Image intensities are inverted, scaled, and shifted, and noise is added, to form images that have realistic values of lesion-white matter contrast (5-30%) and contrast-to-noise ratio (3-20%). Artificial gray matter, CSF (cerebrospinal fluid), and scalp lipid are added because these bright areas may determine how the gray level display window is set. The performance of manual and contouring methods for estimating lesion volume was measured for three observers and nine lesions with individual volumes from 0.3 to 6.2 ml. There was a large variation, depending on the choice of method, the observer, and the lesion contrast. Volumes were usually overestimated, with the error increasing at high contrasts. The average error in estimating total lesion volume was 17% (range -16% to +30%). The OCCA phantom may have a role in training observers to improve their accuracy (and hence inter- and intraobserver reproducibility).

Brain↗

PubMed1997

Comparison of MRI criteria at first presentation to predict conversion to clinically definite multiple sclerosis.

We compared MRI criteria used to predict conversion of suspected multiple sclerosis to clinically definite multiple sclerosis. Seventy-four patients with clinically isolated neurological symptoms suggestive of multiple sclerosis were studied with MRI. Logistic regression analysis was used to remove redundant information, and a diagnostic model was built after each MRI parameter was dichotomized according to maximum accuracy using receiver operating characteristic analysis. Clinically definite multiple sclerosis developed in 33 patients (prevalence 45%). The optimum cut-off point (number of lesions) was one for most MRI criteria (including gadolinium-enhancement and juxta-cortical lesions), but three for periventricular lesions, and nine for the total number of T2-lesions. Only gadolinium-enhancement and juxta-cortical lesions provided independent information. A final model which, in addition, included infratentorial and periventricular lesions, had an accuracy of 80%, and having more abnormal criteria, predicted conversion to clinically definite multiple sclerosis strongly. The model performed better than the criteria of Paty et al. (Neurology 1988; 38: 180-5) and of Fazekas et al. (Neurology 1988; 38: 1822-5). We concluded that a four-parameter dichotomized MRI model including gadolinium-enhancement, juxtacortical, infratentorial and periventricular lesions best predicts conversion to clinically definite multiple sclerosis.

False Negative Reactions↗

PubMed1997

Sensitivity of delayed gadolinium-enhanced MRI in multiple sclerosis.

INTRODUCTION: We performed this study to define the sensitivity of delayed gadolinium-enhanced magnetic resonance imaging (MRI) in detecting active lesions in the brains of patients with multiple sclerosis (MS). MATERIAL AND METHODS: T1-weighted images were obtained in 27 patients with relapsing-remitting or secondary progressive MS before, 5-7 min and 20-30 min after the injection of 0.1 mmol/kg gadolinium-DTPA. RESULTS: One-hundred-and-three enhancing lesions were found on the early and 110 on the delayed scans (increase=6.4%). Six patients had 8 additional lesions in the delayed scans, while 1 patient had 1 more lesion on the early scan. Two of the 12 (17%) patients with no enhancing lesions on the early scans had 2 enhancing lesions on the delayed scans. The average increase of enhancing lesion detection with delayed scanning was 14.5% for those patients who already had enhancing lesions on the early post-contrast scans. A significant increase of the enhancing lesion volume was found with delayed scanning (P=0.004). CONCLUSION: These data indicate that it is possible to increase MRI sensitivity in detecting MS active lesions by delaying the scanning after gadolinium injection.

Adult↗

PubMed1997

A longitudinal magnetic resonance imaging study of the cervical cord in multiple sclerosis.

This study was performed to evaluate the correlation between changes of cross-sectional cord area and disability in multiple sclerosis. Axial magnetic resonance images at the C-5 spinal level were obtained at entry and 12 months later for 29 patients with clinically definite multiple sclerosis. The degree of disability was inversely correlated at entry and follow-up with the cross-sectional area and the transverse diameter of the spinal cord. In addition, changes in disability correlated inversely with changes in cross-sectional area (r = -0.4, p = 0.04). These findings suggest that cross-sectional cord area at C-5 might be a useful marker of disease evolution.

Adult↗

PubMed1997

Sensitivity and reproducibility of fast-FLAIR, FSE, and TGSE sequences for the MRI assessment of brain lesion load in multiple sclerosis: a preliminary study.

Fast fluid-attenuated inversion recovery (fast-FLAIR), fast spin echo (FSE), and turbo-gradient spin echo (TGSE), new pulse sequences for magnetic resonance imaging (MRI), are able to display multiple sclerosis (MS) lesions more conspicuously (fast-FLAIR) and with shorter imaging times (FSE, TGSE) than is conventional spin-echo MRI. In this study, we scanned 7 MS patients, using fast-FLAIR (18 axial brain slices), FSE (27 slices), and TGSE (9 slices) sequences in the same session, to compare the brain MRI lesion loads detected by these different sequences and the intraobserver reproducibility of these measurements. On the subset of slices (n = 9) covered by all three measurements, the mean lesion load was 7.577 mm3 on fast-FLAIR, 5.248 mm3 on FSE, and 3.080 mm3 on TGSE (p = 0.006) sequences. The mean intraobserver coefficients of variation were 2.92% for fast-FLAIR, 2.86% for FSE, and 4.31% for TGSE (not significant). These findings demonstrate that both fast-FLAIR and FSE sequences may be potentially useful for serial MRI studies for monitoring clinical trials, while TGSE might be useful for speeding diagnostic MRI in MS patients. Longitudinal, clinically correlated studies using these new MRI sequences are needed to confirm these preliminary data.

Brain↗

PubMed1997

Interferon-gamma induced increases in intracellular calcium in T lymphocytes from patients with multiple sclerosis precede clinical exacerbations and detection of active lesions on MRI.

BACKGROUND: Interferon (IFN)-gamma exerts a multiplicity of actions potentially relevant for the pathogenesis of multiple sclerosis, including the expression of a transplasmalemma calcium (Ca2+) influx leading to an intracellular Ca2+ ([Ca2+]i) increase able to lower T lymphocyte threshold of excitability. It has been previously shown in a cross sectional cumulative study that this influx is associated with clinical and MRI evidence of disease activity. METHODS: To evaluate the temporal relation between disease activity and the IFN-gamma activated Ca2+ influx in individual patients, a fluorimetric analysis was performed on peripheral blood lymphocytes from eight patients with relapsing-remitting multiple sclerosis every 15 days for one year. RESULTS: Fluctuations of the influx were correlated with clinical events and monthly enhanced brain MRI. The influx was detected a mean of 10.4 (range 7-17) times per patient during our analysis. In 61% of the occasions, influx induced [Ca2+]i increases were recorded in each patient in more than two consecutive measurements, determining sustained [Ca2+]i increases lasting for a mean of 31.5 days. Peak [Ca2+]i increases preceded clinical attacks (P=0.04) or maximal detection of brain MRI enhancing lesions (P=0.05) by a mean of 30.8 and 34.2 days respectively. Spectral analysis of time series further indicated that the fluctuation frequency of [Ca2+]i increases due to the influx over time were superimposable on the appearance of new MRI lesions in all patients and confirmed that in two thirds of the patients these [Ca2+]i increases occurred significantly before (P<0.005) or concurred with new lesion appearance. Finally, the overall presence of the influx throughout the follow up period correlated (P=0.03) with the patients' exacerbation rates. CONCLUSIONS: Intracellular events leading to T lymphocyte activation in multiple sclerosis occur in the peripheral blood before CNS specific events become evident and are, in part, sustained by cytokine induced Ca2+ mediated phenomena.

Adult↗

PubMed1997

Inter-rater variability in reporting enhancing lesions present on standard and triple dose gadolinium scans of patients with multiple sclerosis.

In this study we evaluated and compared the inter-rater variabilities in detecting enhancing lesions in patients with MS after injection of a standard dose (s.d.) and a triple dose (TD) of gadolinium (Gd). Enhanced magnetic resonance imaging (MRI) were obtained in 15 patients, consisting of T1-weighted images 5 to 7 min after the injection of the s.d. (0.1 mmol/kg) of Gd and, after an interval of 6 to 24 h, 5 to 7 min after the injection of the TD (0.3 mmol/kg). An additional scan 1 h after the TD injection (delayed scanning-DS) was obtained in 11 patients. The scans were independently evaluated in a random order by four observers. Lesions were counted and scored according to size and location. The level of inter-observer observer concordance was very high for reporting the total numbers of enhancing lesions, their sizes and sites for the three experimental conditions. No significant differences were found in inter-observer variability in reporting the total number of enhancing lesions and their location in different brain sites in the three conditions. Our data indicate that the gain in sensitivity in detecting enhancing lesions in MS with the TD is not counteracted by a loss in reproducibility. This is important in planning clinical trials in which the number of enhancing lesions is used as a measure of outcome.

Brain↗

PubMed1997

The influence of slice orientation on brain MRI lesion load measurement in multiple sclerosis.

This study aimed at evaluating the influence of a different slice orientation on brain magnetic resonance imaging (MRI) lesion load in multiple sclerosis (MS). Fifteen MS patients were scanned obtaining both axial and sagittal conventional spin echo (24 slices; TR 2400, TE 30/80) brain MRI. The total lesion load (TLL) was assessed twice for each scan, using a semi-automated local thresholding technique and the same marked hardcopies. The mean TLL was 22734 mm3 for axial and 22003 mm3 for sagittal scans. The mean intra-observer coefficient of variation (COV) was 4.65% for the axial acquisitions and 4.52% for the sagittal acquisitions. This difference was not statistically significant (one-way ANOVA, P > 0.1). The lesion load was significantly higher from axial MRI as compared to the intra-observer variability (two-way ANOVA, P=0.01), but the fluctuations around this average difference between axial and sagittal scan TLL were significantly large (test for interaction, P < 0.001). Our data indicate that the use of sagittal conventional MRI scans does not seem to be worthwhile for the quantitative assessment of lesion load in MS patients.

Adult↗