Biomedical subjects

M Filippi

Publications and source records attributed to M Filippi.

At least 217 records · Page 12Linked to original sources

PubMed1999

Method for intracellular magnetic labeling of human mononuclear cells using approved iron contrast agents.

A method for intracellular iron labeling of human mononuclear cells (lymphocytes and monocytes) for magnetic resonance imaging (MRI) using simple incubation of cells with approved MRI iron contrast agents is presented. Labeled cells can be detected by MRI in vitro, and this suggests the possibility that the technique could become a marker for in vivo lymphocyte and monocyte trafficking studies in acute inflammatory lesions such as those in Multiple Sclerosis.

Cell Survival↗

PubMed1999

A method to monitor motor cortical excitability in human stroke through motor evoked potentials.

We describe a procedure aimed to analyse Motor Evoked Potentials (MEPs) interhemispheric differences in motor excitability in a monohemispheric subacute stroke population. This protocol has specifically been oriented to scan for any differences in MEPs amplitude at rest and during contractions from a hand muscle, Abductor Digiti Minimi (ADM), after focal Transcranial Magnetic Stimulation (TMS) in both Affected (AH) and Unaffected (UH) Hemispheres. Stroke patients can be included in the protocol if they have suffered acute stroke during the two to four month period to the admission in our rehabilitation hospital. The purpose of this protocol is to establish whether any clear pattern of interhemispheric responsiveness exists and/or to define any possible correlation between MEPs and clinical data. Disability and neurological scores are evaluated to allow a numerical comparison with electrophysiological data. Two recording sessions are planned: the first when the selected patient is admitted (T1) and the second after 8 weeks (T2). Such a period has been arbitrarily chosen because it represents a reliable time after the first recording in order to observe clinical amelioration if present. Criteria for reproducibility of experimental conditions are illustrated.

Cerebrovascular Disorders↗

PubMed1999

[MRI follow-up in multiple sclerosis. A guideline for quality assurance].

Magnetic resonance imaging (MRI) is highly sensitive to pathological tissue changes in multiple sclerosis (MS) patients. It demonstrates the frequently subclinical disease activity and follow-up examinations regularly show the accumulation of new lesions and the development of atrophy. The increasing importance of follow-up examinations in MS patients makes it necessary to provide comparable MRI data even over long observation periods. This review article focusses on critical variables in this regard and technical issues; practical guidelines for MRI protocols in MS patients are presented. The influence of field strength, MR systems from different manufacturers, and new software releases is described. Guidelines concerning the graphic planning of the examination, sequence protocols, documentation and reporting of cranial MR studies in MS patients are presented.

Atrophy↗

PubMed1999

Spatial mapping of T2 and gadolinium-enhancing T1 lesion volumes in multiple sclerosis: evidence for distinct mechanisms of lesion genesis?

It is generally believed that most T2-weighted (T2) lesions in the central white matter of patients with multiple sclerosis begin with a variable period of T1-weighted (T1) gadolinium (Gd) enhancement and that T1 Gd-enhancing and T2 lesions represent stages of a single pathological process. Lesion probability maps can be used to test this hypothesis by providing a quantitative description of the spatial distribution of these two types of lesions across a patient population. The simplest prediction of this hypothesis would be that the spatial distributions of T1 Gd-enhancing and T2 lesions are identical. We generated T1 Gd-enhancing and T2 lesion probability maps from 19 patients with relapsing-remitting multiple sclerosis. There was a significantly higher probability (P = 0.001) for T2 lesions to be found in the central relative to the peripheral white matter (risk ratio 4.5), although the relative distribution of T1 Gd-enhancing lesions was not significantly different (P = 0.7) between central and peripheral white matter regions (risk ratio 0.6). Longitudinal data on the same population were used to demonstrate a similar distribution asymmetry between new T1 Gd-enhancing and new T2 lesions that developed over the course of 1 year. Alternative hypotheses to explain this observation were tested. We found no spatial difference in the likelihood of development of persistent T2 lesions following T1 Gd enhancement. The relative distribution of T1 Gd-enhancing lesions was shown to be independent of the dose of Gd contrast agent and the frequency of scanning. Our findings suggest that a proportion of the periventricular T2 lesion volume may arise from mechanisms other than those associated with early breakdown of the blood-brain barrier leading to T1 Gd enhancement.

Adult↗

PubMed1999

Cognitive function in primary progressive and transitional progressive multiple sclerosis: a controlled study with MRI correlates.

The relative rarity of primary progressive (PP) and transitional progressive (TP) multiple sclerosis has meant that little documentation of cognitive function in such patients is currently available. The aim of this study was to investigate the cognitive skills of patients with PP and TP multiple sclerosis relative to matched healthy controls, and to examine the relationship of this impairment to MRI parameters. Sixty-three patients (43 PP, 20 TP) were individually matched with healthy controls, who undertook the same cognitive tasks as the patient group. The neuropsychological assessment comprised Rao's brief repeatable battery, a reasoning test, and a measure of depression. Patients also underwent T1- and T2-weighted brain MRI. These patients were taken from a larger cohort (158 PP, 33 TP) in whom it had been demonstrated that the re were no significant differences between the mean scores of the PP and TP groups on any of the cognitive variables. The 63 patients were therefore taken as one group for comparison with the healthy controls. These patients performed significantly worse than the controls in tests of verbal memory, attention, verbal fluency and spatial reasoning. An impairment index was constructed and applied to the patient data. This correlated modestly with T2-lesion load (r = 0.45, P = 0.01), T1-hypointensity load (r = 0.45, P = 0.01) and cerebral volume (r = -0.35, P = 0.01). Thus, PP and TP multiple sclerosis patients demonstrate significant cognitive dysfunction when compared with matched healthy controls. The relationship between this impairment and MRI parameters is moderate, suggesting that cognitive dysfunction in PP and TP multiple sclerosis has a complex and multifactorial aetiology, which is not adequately explained by pathology as demonstrated on conventional MRI.

Adult↗

PubMed1999

Magnetic resonance techniques to monitor disease evolution and treatment trial outcomes in multiple sclerosis.

Although the correlations between magnetic resonance findings and long-term disease evolution range from poor to moderate, conventional precontrast and postcontrast magnetic resonance imaging provides sensitive and reliable measures to monitor multiple sclerosis activity over time. New pulse sequences with shorter acquisition times can be cost effective and reduce patients' discomfort. The application of other techniques that give more accurate estimates of disease burden and have higher pathological specificity might improve our understanding of multiple sclerosis evolution and provide new outcomes for monitoring clinical trials. Work is still needed to obtain optimal imaging of the spinal cord for multiple sclerosis diagnosis and monitoring.

Clinical Trials as Topic↗

PubMed1999

Statistical power of MRI monitored trials in multiple sclerosis: new data and comparison with previous results.

OBJECTIVES: To evaluate the durations of the follow up and the reference population sizes needed to achieve optimal and stable statistical powers for two period cross over and parallel group design clinical trials in multiple sclerosis, when using the numbers of new enhancing lesions and the numbers of active scans as end point variables. METHODS: The statistical power was calculated by means of computer simulations performed using MRI data obtained from 65 untreated relapsing-remitting or secondary progressive patients who were scanned monthly for 9 months. The statistical power was calculated for follow up durations of 2, 3, 6, and 9 months and for sample sizes of 40-100 patients for parallel group and of 20-80 patients for two period cross over design studies. The stability of the estimated powers was evaluated by applying the same procedure on random subsets of the original data. RESULTS: When using the number of new enhancing lesions as the end point, the statistical power increased for all the simulated treatment effects with the duration of the follow up until 3 months for the parallel group design and until 6 months for the two period cross over design. Using the number of active scans as the end point, the statistical power steadily increased until 6 months for the parallel group design and until 9 months for the two period cross over design. The power estimates in the present sample and the comparisons of these results with those obtained by previous studies with smaller patient cohorts suggest that statistical power is significantly overestimated when the size of the reference data set decreases for parallel group design studies or the duration of the follow up decreases for two period cross over studies. CONCLUSIONS: These results should be used to determine the duration of the follow up and the sample size needed when planning MRI monitored clinical trials in multiple sclerosis.

Adolescent↗

PubMed1999

Interferon beta treatment for multiple sclerosis has a graduated effect on MRI enhancing lesions according to their size and pathology.

OBJECTIVE: The ability of recombinant human interferon beta-1a (rh-IFN beta-1a) to suppress multiple sclerosis activity, evaluated from MRI, was assessed across a range of lesions enhancing at different gadolinium-DTPA (Gd) doses and with different sizes. METHODS: Every 4 weeks, standard dose (Sd; 0.1 mmol/kg Gd) and triple dose (Td; 0.3 mmol/kgGd) MRI were obtained from 18 patients with relapsing-remitting multiple sclerosis for 3 months before and 4 months after starting treatment with 44 microgram rh-IFN beta-1a subcutaneously, once a week. RESULTS: The total numbers of enhancing lesions were 145 and 126 on Sd scans and 278 and 192 on the Td scans obtained before and after treatment. The introduction of treatment decreased, on average, the rate of appearance of new enhancing lesions seen on Sd and Td scans by 37% (p<0.001). Treatment effects on new enhancing lesions seen on Td scans was, on average, 28% higher than on those seen on Sd scans. The distribution of lesion sizes on Td scans changed significantly during the treatment period (p=0.05), due to a marked decrease in the number of small lesions. CONCLUSIONS: The effect of 44 microgram rh-IFN beta-1a in reducing multiple sclerosis disease activity, as monitored by Gd enhanced MRI, is not homogeneous, but graduated according to the pathological characteristics and size of the lesions.

Adult↗

PubMed1999

Peripheral levels of caspase-1 mRNA correlate with disease activity in patients with multiple sclerosis; a preliminary study.

The cysteine protease caspase-1 plays a crucial part in the inflammatory process due to its ability to proteolitically activate proinflammatory cytokine precursors, such as interleukin (IL)-1beta and IL-18. Multiple sclerosis is a chronic inflammatory demyelinating disease of the CNS in which the pathogenic process is mainly orchestrated by proinflammatory cytokines. The role of caspase-1 in multiple sclerosis was evaluated by measuring its mRNA levels in peripheral blood mononuclear cells (PBMCs) from seven patients with relapsing-remitting multiple sclerosis every 15 days over a 1 year period. The recorded levels were compared with clinical and MRI evidence of disease activity. Brain MRI was performed monthly in each patient. Caspase-1 mRNA levels were significantly increased in PBMCs from patients with multiple sclerosis compared with healthy controls (p<0.001). In patients with multiple sclerosis, a twofold to threefold increase of caspase-1 mRNA mean level was found in the week preceding an acute attack (p<0. 05). The magnitude of caspase-1 mRNA increase correlated with the number of new (p=0.01) but not persisting gadolinium enhancing brain MRI lesions. In conclusion, caspase-1 might be involved in the immune mediated process underlying CNS inflammation and might represent a suitable peripheral immunological marker of disease activity in multiple sclerosis.

Adult↗

PubMed1999

Correlation between MRI and short-term clinical activity in multiple sclerosis: comparison between standard- and triple-dose Gd-enhanced MRI.

We assessed the relative sensitivities of standard (SD)- and triple-dose (TD) gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) for detecting enhancing lesions in different phases of multiple sclerosis (MS) disease activity. Ten MS patients were studied with monthly brain MRI scans for a 3-month follow-up (i.e., 4 scans were obtained for each patient with both SD and TD). A total of 11 relapses were recorded and treated with short-term high-dose steroid therapy. Enhancing lesion numbers and volumes were significantly higher for TD vs. SD scans (p < 0.0001). For both Gd doses, the numbers and volumes of lesions were higher during clinical relapses; the differences were statistically significant when comparing the results for scans obtained during and after a relapse. The gain in sensitivity of TD vs. SD scans for enhancing lesion detection was lower during relapses, whilst it was maximum after relapses, although these differences did not reach statistical significance. Our data confirm the potential role of TD MRI for monitoring MS activity, since, with its higher sensitivity, it may detect more subtle blood-brain barrier (BBB) damage. They also suggest that the degree of BBB damage in individual lesions changes during different phases of disease activity.

Adult↗

PubMed1999

Reproducibility of brain MRI lesion volume measurements in multiple sclerosis using a local thresholding technique: effects of formal operator training.

The assessment of lesion load (LL) on brain magnetic resonance imaging (MRI) scans from patients with multiple sclerosis (MS) is widely used to monitor disease evolution, natural or modified by treatments. In this study, we evaluated the effect of formal operator training on the intra- and inter-observer reproducibility of LL measurements obtained by several operators in a setting similar to that of clinical trials. Proton-density (PD)-weighted, unenhanced and enhanced T1-weighted brain MRI scans were obtained from 10 MS patients. Five naive technicians assessed LL on these images, using a semiautomated local thresholding technique for lesion segmentation and marked hardcopies as a reference. Measurements were performed twice before and twice after a 20-hour operator training. Mean intra-observer measurement coefficient of variations (COV) before and after the training were 3.1 and 1.6% for PD-weighted LL, 4.3 and 1.8% for unenhanced T1-weighted LL (p < 0. 001), 4.9 and 2.0% for enhanced T1-weighted LL (p = 0.002). Mean inter-observer COV were significantly reduced after training (from 10.0 to 5.6% for PD-weighted, from 11.0 to 7.3% for unenhanced T1-weighted and from 16.0 to 6.8% for enhanced T1-weighted LL). Our data indicate that LL assessment on serial MRI scans from MS patients performed by technicians, using a local thresholding technique for lesion segmentation, is characterized by low measurement variability which may be significantly improved by a short and cost-effective training.

Brain↗

PubMed1999

Normal-appearing white matter changes in multiple sclerosis: the contribution of magnetic resonance techniques.

Several magnetic resonance (MR) techniques have proved to be sensitive enough to detect the subtle pathological changes that post-mortem studies showed to occur in the normal-appearing white matter (NAWM) from patients with multiple sclerosis (MS). Although these abnormalities can be detected in other neurological conditions, they seem to be more frequent and diffuse in MS. However, the contribution of NAWM changes to the diagnosis is still unclear. Their nature is also unknown and perhaps differs in different phases and clinical manifestations of the disease. Nevertheless, the extent and severity of NAWM damage seems to be relevant in causing disability and influencing the clinical evolution in MS patients. This review will summarize the present knowledge about MR-detected NAWM changes in MS and their relevance to the diagnosis and the understanding of disease evolution.

Axons↗

PubMed1999

Comparison of MS clinical phenotypes using conventional and magnetization transfer MRI.

OBJECTIVE: To identify differences in pathology between the principal clinical phenotypes of MS using conventional and magnetization transfer (MT) MRI. METHODS: T1-weighted and T2-weighted images as well as MT scans were obtained from 20 controls, 21 patients presenting with clinically isolated syndromes suggestive of MS, and 93 MS patients with relapsing-remitting, secondary progressive, benign, or primary progressive course. Metrics considered: hypointense T1 and T2 lesion volumes, average lesion MT ratio, average brain MT ratio, peak height and position from MT histograms. RESULTS: MS patients had lower MT metrics than controls. Patients with clinically isolated syndromes had MT measures similar to controls, whereas primary progressive MS patients had lower histogram peak height with normal peak position. Relapsing-remitting MS patients had lower MT measures, higher T2 lesion load and ratio of hypointense T1 to T2 lesion volumes than patients with clinically isolated syndromes, and lower MT ratio and peak height than benign MS patients. Benign MS patients were similar to controls and patients with clinically isolated syndromes. Secondary progressive MS patients had the lowest MT measures and highest lesion loads. CONCLUSIONS: Pathology in patients with clinically isolated syndromes is confined to modest tissue damage in the lesions seen on T2-weighted scans. Severe damage is important for the later development of disability. However, microscopic damage in normal-appearing white matter may be a major contributor to disability in primary progressive MS.

Adult↗

PubMed1999

Relevance of hypointense lesions on fast fluid-attenuated inversion recovery MR images as a marker of disease severity in cases of multiple sclerosis.

BACKGROUND AND PURPOSE: Hypointense lesions can be visible on fast fluid-attenuated inversion recovery (FLAIR) MR images of the brain of patients with multiple sclerosis (MS), and they may be produced by severely damaged white matter. To test the role of these lesions as an MR marker of MS severity, we assessed their relationship with clinical findings and other MR measures. METHODS: Using a 1.5-T scanner, dual-echo rapid acquisition with relaxation enhancement, fast FLAIR, and T1-weighted MR images (24 axial, 5-mm-thick contiguous interleaved sections) were obtained from 50 patients (32 with relapsing-remitting and 18 with secondary progressive MS). RESULTS: Hypointense lesions were visible on the fast FLAIR images of 19 patients (mean number of lesions, 7.8; range 1-22); their median load was 1.4 mL (range, 0.05-12.6 mL). The median lesion load was significantly higher in patients with secondary progressive MS than in those with relapsing-remitting MS on the T1-weighted images. Both the number and the load of hypointense lesions shown by fast FLAIR imaging were significantly higher in patients with secondary progressive MS. Significant correlations were found between Expanded Disability Status Scale scores and MR lesion load. A multivariate analysis showed that only the presence of hypointense lesions on fast FLAIR images significantly separated cases of relapsing-remitting MS from cases of secondary progressive MS (relative risk, 7.1; 95% confidence interval, 2.0-25.9). CONCLUSION: The presence of hypointense lesions on fast FLAIR images was a strong predictor of disease severity in cases of MS, although the low sensitivity of this approach might limit its use for the assessment of MS evolution.

Adult↗

PubMed1999

Long-term changes of magnetization transfer-derived measures from patients with relapsing-remitting and secondary progressive multiple sclerosis.

BACKGROUND AND PURPOSE: For cases of multiple sclerosis (MS), magnetization transfer (MT) imaging may provide more pathologically specific and accurate estimates of the disease process than does conventional imaging. In this study, we evaluated changes of the MT ratio (MTR) of newly enhancing lesions, the MTR of normal-appearing white matter (NAWM), the average lesion MTR, and the MT histogram-derived metrics during a 3-year follow-up period for patients with relapsing-remitting or secondary progressive MS. METHODS: Dual-echo, conventional spin-echo, and MT images were obtained from seven patients with relapsing-remitting MS, seven patients with secondary progressive MS, and five age- and sex-matched control subjects at the time of study entry and 1, 13, and 37 months later. RESULTS: Newly enhancing lesions in the patients with secondary progressive MS presented a more severe and significant MTR reduction during the follow-up period as compared with those in the relapsing-remitting group. In cases of secondary progressive MS, we also observed a significant reduction of the MTR values of the NAWM and a trend toward reduction of average lesion MTR values. The patients with MS had mean percentage changes of MT histogram-derived measures that were approximately two to 10 times higher than those of the control subjects. CONCLUSION: This preliminary 3-year follow-up study shows that newly enhancing lesions and NAWM in patients with secondary progressive MS have significantly lower MTR values than do those in patients with relapsing-remitting MS. It also shows that the tissue damage that remains after enhancement ceases is more severe in secondary progressive disease.

Adult↗

PubMed1999

A longitudinal MR study of the presymptomatic phase in a patient with clinically definite multiple sclerosis.

We describe the dynamics and the nature of the presymptomatic phase of multiple sclerosis (MS) in a patient for whom MR abnormalities suggestive of MS were found before the development of clinical symptoms. The patient was monitored with serial monthly MR imaging of the brain and spinal cord for 5 months. Disease activity during the presymptomatic phase showed imaging characteristics comparable to that of early relapsing-remitting MS in terms of enhancing lesions, duration of enhancement, and new lesions depicted by T2-weighted imaging. Measurements derived from magnetization transfer imaging suggested that the amount and degree of tissue destruction within and outside the lesions revealed by T2-weighted imaging were mild. This, together with the fact that only one of the 43 new lesions that developed during the presymptomatic phase was located in a neurologically eloquent area, may be the reason why, for a relatively long period, the patient had no clinical manifestations of MS despite the marked MR findings of disease activity.

Adult↗

PubMed1999

Magnetization transfer imaging to monitor the evolution of individual multiple sclerosis lesions.

In multiple sclerosis (MS), conventional magnetic resonance imaging (MRI) is very sensitive in detecting new lesion formation and changes of lesion sizes over time. However, it lacks specificity to the heterogeneous pathological substrates of the MS lesions. This might explain the lack of correlation between MRI findings and the development of disability in MS. Magnetization transfer (MT) imaging is promising for a more accurate monitoring of the evolution of MS. MT changes indicate a reduced capacity of the macromolecules in brain tissue to exchange magnetization with the surrounding water molecules, thus reflecting matrix disorganization. The analysis of MT changes can be performed on a regional basis, thus obtaining information about individual lesions or discrete areas of the normal-appearing white matter, or on a more global basis, using MT histograms, thus estimating the amount and severity of microscopic and macroscopic disease burden in MS. The present review will summarize the major contributions given by MT for the understanding of how individual MS lesions evolve. Monitoring individual lesion evolution may be relevant not only for the understanding of the disease pathophysiology, but also as a new approach for assessing treatment efficacy in MS.

Brain↗

PubMed1999

Correlations between magnetization transfer metrics and other magnetic resonance abnormalities in multiple sclerosis.

Magnetization transfer imaging (MTI) is a magnetic resonance imaging (MRI) technique that is now used in multiple sclerosis (MS) studies, and is thought to have a higher pathological specificity than conventional T2-weighted imaging. This review outlines the correlations between magnetization transfer (MT) metrics and other MRI abnormalities in the study of individual MS lesions and in the assessment of MS disease burden. MTI studies of individual MS lesions confirm the pathological heterogeneity of T2-weighted MRI abnormalities and the potential role of unenhanced T1-weighted hypointensities as specific markers of localized severe white matter disruption. Correlative cross-sectional and longitudinal studies using MTI and gadolinium (Gd)-enhanced MRI reveal that MTI findings may vary in lesions with different patterns of enhancement, and that MTI abnormalities are closely related to the onset and recovery of blood-brain barrier disruption in new MS plaques. MTI lesion load (LL) is highly correlated with T2-weighted MRI LL, but it has a limited reliability as a measure of MS disease burden. On the contrary, measures obtained from MTI scans using whole-brain histogram analysis are highly correlated with the extent of MS abnormalities on conventional MRI scans, and predict patients' clinical disability well, since they are sensitive to the amounts of both macro- and microscopic MS disease burden in the whole brain and in specific regions. The correlations between MTI metrics and conventional MRI findings suggest that: (a) MTI is sensitive to different stages of lesion pathology and pathological evolution in MS patients; and (b) MT histogram analysis can provide a more global assessment of MS disease burden, since it encompasses both macro- and microscopic MS pathology.

Brain↗