Search PubMed⌕ Search

Biomedical subjects

M Filippi

Publications and source records attributed to M Filippi.

At least 253 records · Page 14Linked to original sources
PubMed1998

A multi-centre longitudinal study comparing the sensitivity of monthly MRI after standard and triple dose gadolinium-DTPA for monitoring disease activity in multiple sclerosis. Implications for phase II clinical trials.

In this study we assessed the safety, efficacy and cost-effectiveness of the use of triple dose gadolinium-DTPA (Gd) in serial monthly brain MRI of patients with multiple sclerosis, such as could be selected for clinical trials. The number of enhancing lesions, the number of new enhancing lesions and the number of active scans were used to evaluate the sensitivity of the contrast-enhanced MRI to disease activity. The dose of Gd, and the effect of introducing a delay between the contrast injection and the scan were both appraised. Every 4 weeks for 3 months, and in two separate sessions, scans were obtained from 40 patients with relapsing-remitting or secondary progressive multiple sclerosis, 5 min (early) and 20 min (delayed) after a standard dose (0.1 mmol/kg) or triple dose (0.3 mmol/kg) Gd injection. There were 435 enhancing lesions (242 of which were new) on the early standard dose scans, 479 (263 new) on the delayed standard dose, 772 (365 new) on the early triple dose and 827 (404 new) on the delayed triple dose. There were 109 scans revealing active disease on the early standard dose scans, 112 on the delayed standard dose, 119 on the early triple dose and 120 on the delayed triple dose. Statistical simulations indicated that the sample sizes needed for both cross-over and parallel-group trials with similar powers are lower if serial monthly triple dose MRI is used. No side-effects were reported and no significant changes in blood test parameters were found throughout the study. This study shows that the serial use of triple dose Gd is safe, and that it increases the sensitivity of serial monthly enhanced MRI in detecting multiple sclerosis activity significantly. Its use should enable preliminary trials of experimental therapies for multiple sclerosis to be conducted in small patient populations, over a short period of time.

Adult↗
PubMed1998

MRI evolution of new MS lesions enhancing after different doses of gadolinium.

OBJECTIVE: To investigate the evolution of multiple sclerosis (MS) lesions enhancing after single dose (SD) or triple dose (TD) of gadolinium-DTPA (Gd). MATERIAL AND METHODS: For 3 months, 30 relapsing-remitting MS patients underwent 2 monthly MRI sessions, consisting of Gd-enhanced T1-weighted scans, after SD (i.e., 0.1 mmol/kg) in one session and TD (i.e., 0.3 mmol/kg) in the other. New enhancing lesions on month 1 and month 2 follow-up scans were studied and for them any persistence of enhancement was evaluated on the scans obtained the next month. RESULTS: In all, 151 lesions enhancing after both SD and TD and 91 lesions enhancing only after TD entered the analysis. After 1 month, for the 151 lesions enhancing after both SD and TD, 73 (48%) were not enhancing, 50 (33%) were still enhancing after both SD and TD and 28 (19%) were enhancing only after TD. For the 91 lesions enhancing only after TD, 61 (67%; P<0.005) were not enhancing, 16 (18%; P<0.01) were still enhancing only after TD and 14 (15%; P=NS) showed enhancement after both SD and TD. CONCLUSION: Enhancing lesions in patients with MS are heterogeneous. Those enhancing only after TD of Gd are characterized by a milder and shorter opening of the blood-brain barrier.

Blood-Brain Barrier↗
PubMed1998

A preliminary study comparing the sensitivity of serial monthly enhanced MRI after standard and triple dose gadolinium-DTPA for monitoring disease activity in primary progressive multiple sclerosis.

We performed this study to evaluate and compare the numbers of total and new enhancing lesions detected on serial monthly brain magnetic resonance imaging (MRI) after the injection of a standard dose (SD) and a triple dose (TD) of gadolinium-DTPA (Gd) in patients with primary progressive multiple sclerosis (PPMS). Every 4 weeks for 3 months and in two separate sessions, MRI scans were obtained from 5 patients with PPMS, 5 (early) and 20 minutes (delayed) after SD (0.1 mmol/kg) or TD (0.3 mmol/kg) Gd injection. In 2 patients, T1-weighted scans with a magnetization transfer pulse (MT) after SD and TD injection were also obtained. There were 13 enhancing lesions (5 of which were new) on the early SD scans, 15 (5 new) on the delayed SD scans, 17 (6 new) on the early TD scans and 18 (7 new) on the delayed TD scans. TD MRI scans detected more enhancing lesions than SD scans in 3 patients (two of them were those with the lowest disability). The application of the MT pulse did not change the numbers of enhancing lesions seen after the injection of SD and TD of Gd in the remaining two patients. No side effects were reported and no significant changes in blood test parameters were found throughout the study. Our results suggest that serial monthly TD MRI, delayed scanning, MT T1-weighted scans or their combination, although safe, have a limited role for monitoring disease evolution in patients with PPMS.

Adult↗
PubMed1998

A comparison between the sensitivities of 3-mm and 5-mm thick serial brain MRI for detecting lesion volume changes in patients with multiple sclerosis.

In this longitudinal study the authors evaluated the sensitivity of 3-mm and 5-mm magnetic resonance imaging (MRI) of the brain in the detection of lesion load changes over time in multiple sclerosis (MS). The authors also correlated the changes detected with these two techniques with the changes in disability. Eighteen patients with MS underwent two MRI examinations of the brain--one at entrance into the study and one follow-up examination. At both sessions, images with 24 contiguous slices 5 mm thick and another with 40 contiguous axial slices 3 mm thick were consecutively acquired. On the same occasions, the patients' Expanded Disability Status Scale (EDSS) scores were rated. MR images with slices 3 mm thick showed higher lesion loads than those with slices 5 mm thick at both entrance and follow-up examinations (median, 13.4 vs 12.8 ml and 17.5 vs 17.0 ml, respectively; p < 0.0001). The correlation between MRI and EDSS changes was significant for both MRI acquisition schemes (3 mm, r = 0.64; 5 mm, r = 0.59). The data suggest that acquisition of thinner slices does not significantly increase the sensitivity of MRI of the brain in the detection of lesion load changes in MS.

Adult↗
PubMed1998

Detecting new lesion formation in multiple sclerosis: the relative contributions of monthly dual-echo and T1-weighted scans after triple-dose gadolinium.

In this study, we evaluated the frequency of formation of new lesions on brain magnetic resonance imaging (MRI) from patients with relapsing-remitting multiple sclerosis (MS) and defined the relative contributions of unenhanced and enhanced MRI. Every 4 weeks for 3 months, dual-echo and postcontrast T1-weighted (5 min after the injection of 0.3 mmol/kg gadolinium-DTPA) scans were obtained from 28 patients with relapsing-remitting MS. New lesions were defined as those present on dual-echo and/or postcontrast T1-weighted scans but with no corresponding MRI abnormalities on any of the preceding scans. A total of 111 newly formed lesions were detected during the follow-up on dual-echo and postcontrast T1-weighted scans (i.e., an average of 1.3 lesions per patient per month). Ninety-eight (88%) of such lesions were seen on both dual-echo and postcontrast T1-weighted scans, whilst 13 (12%) were seen only with one of the two techniques: 9 only on dual-echo and 4 only on postcontrast scans. Five of the 98 new lesions seen by both techniques were seen by postcontrast scans 1 month before their appearance on dual-echo scans. Our study suggests that both dual-echo and postcontrast T1-weighted scans are useful to detect newly formed lesions in patients with MS. This is of importance when using MRI to monitor the efficacy of treatments which may halt MS lesion formation.

Adult↗
PubMed1998

The effect of cross-talk on MRI lesion numbers and volumes in multiple sclerosis using conventional and turbo spin-echo.

We measured and compared lesion numbers and volumes present on brain magnetic resonance imaging (MRI) scans of patients with multiple sclerosis (MS) acquired with contiguous (scheme A) and interleaved (scheme B) slice acquisition, to evaluate whether there was a gain in sensitivity using the second pattern of acquisition and whether this counterbalanced the doubled acquisition time. Conventional spin-echo (CSE) sequences were performed for eight patients and turbo spin-echo (TSE) sequences for ten. Acquisition scheme B detected 3.8% more lesions than acquisition scheme A (the increase was 3.1% for CSE and 4.5% for TSE). These differences were not statistically significant. No significant difference in lesion numbers was found when different lesion locations were also considered. Lesions volumes were significantly higher when scheme B was used (P = 0.024). This was due to higher lesion volumes on TSE images (P = 0.006), especially on even-numbered slices (P = 0.008). Inter-slice cross-talk has a negligible effect on lesion numbers and volume estimates in MS for CSE sequence, whilst it cannot be neglected when TSE sequences are used to measure MS lesion volume.

Adult↗
PubMed1998

Effect of training and different measurement strategies on the reproducibility of brain MRI lesion load measurements in multiple sclerosis.

In this study, we evaluated the intra- and interobserver variabilities in measuring lesion load of brain MRI abnormalities present on proton-density scans from patients with MS, using using both manual outlining or a semiautomated local thresholding technique (LTT). We also evaluated how these variabilities were affected by the use of standard rules for lesion load measurements, training, and different measurement strategies. The intraobserver variabilities obtained after establishing rules for lesion load measurements and training were not significantly different from those obtained before any consensus among the observers, both for manual outlining and for the LTT. On the contrary, the interobserver variabilities obtained with manual outlining or the LTT were significantly reduced when rules for lesion load measurements were used. For manual outlining, the intraobserver variability did not significantly change when the measurements were performed after an experienced radiologist identified lesions or when using adjacent slices and the corresponding T2-weighted images as reference for lesion identification. On the contrary, for the LTT, the intraobserver variability was significantly reduced by the use of the radiologic marking. The interobserver variabilities for both manual outlining and the LTT were reduced compared with the free condition when these measurement strategies were used. Our findings demonstrate that both lesion identification and outlining are important sources of variation for MRI lesion load measurements in MS and that there are simple strategies to reduce such variation that might be useful when planning clinical trials.

Brain↗
PubMed1998

Characteristics of chronic MS lesions in the cerebrum, brainstem, spinal cord, and optic nerve on T1-weighted MRI.

We analyzed the prevalence of severely hypointense lesions on T1-weighted MRI in the brainstem, spinal cord, and optic nerve from 65 patients with MS. About half of 1,274 supratentorial lesions were classified as severely hypointense. Severe hypointensity was not seen in the optic nerve and spinal cord, and in only one of 168 chronic brainstem lesions. Tissue destruction in the brainstem, spinal cord, and optic nerve of MS patients does not usually result in severely hypointense lesions.

Adolescent↗
PubMed1998

Magnetization transfer ratios in multiple sclerosis lesions enhancing after different doses of gadolinium.

We performed serial monthly magnetization transfer (MT) imaging to evaluate whether MS lesions that enhance only after the injection of a triple dose (TD) of gadolinium-DTPA (Gd) have different pathologic characteristics and evolution than those that enhance after the injection of a standard dose (SD). Every 4 weeks for 3 months and in two separate sessions, we obtained T1-weighted scans from 10 patients with relapsing-remitting MS, 5 minutes after SD (0.1 mmol/kg) or TD (0.3 mmol/kg) Gd injection. During each of the first monthly sessions, we obtained MT images and dual-echo scans before Gd injection. We measured the MT ratio (MTR) of newly enhancing lesions on co-registered quantitative MTR images. During the 3-month follow-up, 81 newly enhancing lesions were seen on SD scans. An additional 46 lesions enhanced only on TD scans. The mean (+/- standard deviation) MTR values were 31.4% +/- 8.4% for lesions enhancing after SD and 38.2% +/- 6.0% for lesions enhancing only after TD injection (p < 0.0001). The mean MTR values of lesions seen with both SD (p < 0.00001) and TD (p = 0.002) increased significantly during the follow-up. At each time point during the follow-up, the MTR values of TD lesions were significantly higher than the SD lesions. These results indicate that the enhancing lesion population in MS is heterogeneous and that the tissue damage occurring within lesions enhancing only after TD injection is less severe than in lesions enhancing after the injection of an SD.

Adult↗
PubMed1998

Relation between MR abnormalities and patterns of cognitive impairment in multiple sclerosis.

OBJECTIVE: This study correlated the extent of abnormalities detected by different magnetic resonance imaging (MRI) techniques [proton density (PD)-weighted, T1-weighted, and magnetization transfer imaging (MTI)] with the overall cognitive, frontal lobe, and memory impairments in patients with MS. PATIENTS: There were 30 clinically definite MS patients, with different disease courses. EXCLUSION CRITERIA: psychoactive/steroid treatments, mood disorders, acute relapse phase. MAIN OUTCOME MEASURES: Neuropsychological test results. Total (TLL) and frontal (FLL) lesion loads assessed from PD-weighted, T1-weighted (22 patients), and MTI (22 patients) MRI scans. Average lesion MT ratios (MTR) and analysis of the MTR histograms from brain tissue axial slabs on MTI scans. RESULTS: Patients with frontal lobe deficits (n=15) or memory impairment (n-17) had a higher TLL on PD scans (p=0.04 and p=0.01, respectively). Patients with frontal lobe deficits had higher FLL on PD scans (p=0.01) and TLL on MTI (p=0.03) scans. No significant relationships between the extent of T1-weighted lesion loads and the presence of any neuropsychological impairment. Mean MTR of both MS lesions and whole brain tissue was lower in patients with frontal lobe impairment (p=0.04). MRI lesion loads correlated significantly with some neuropsychological test scores. CONCLUSIONS: Lesion loads on PD-weighted MRI and MTI-derived measures are associated with cognitive decline in MS patients. Overall macroscopic and microscopic brain damage is more important than the corresponding regional brain disease in determining deficits of selective cognitive domains.

Adult↗
PubMed1998

Benign versus secondary-progressive multiple sclerosis: the potential role of proton MR spectroscopy in defining the nature of disability.

PURPOSE: We determined the clinical utility of proton MR spectroscopy in defining the extent of disability in benign versus secondary-progressive multiple sclerosis (MS). METHODS: Thirty patients with clinically definite MS, including 16 patients with benign MS and 14 with secondary-progressive MS, and a group of 13 healthy volunteers were studied with combined stimulated-echo acquisition mode proton MR spectroscopy and MR imaging (all patients received contrast material). RESULTS: Acute enhancing lesions of benign and secondary-progressive MS were characterized by a reduction in N-acetylaspartate (NAA)/choline and NAA/creatine and an increase in inositol compounds/creatine as compared with normal white matter. Such variations were also detected in chronic unenhancing lesions in patients with secondary-progressive MS, although they were not found in chronic unenhancing lesions in patients with benign MS. Chronic lesions of the two forms of the disease have significative differences in NAA and inositol signals. CONCLUSION: Proton MR spectroscopy is able to show metabolic changes occurring in the white matter of patients with MS. Such changes differ according to the phase (acute versus chronic) and the clinical form (benign versus secondary-progressive) of the disease.

Adult↗
PubMed1998

Increased spatial resolution using a three-dimensional T1-weighted gradient-echo MR sequence results in greater hypointense lesion volumes in multiple sclerosis.

PURPOSE: Our goal was to evaluate whether improved spatial resolution of MR images results in the detection of higher volumes of hypointense lesions in patients with multiple sclerosis (MS). METHODS: A magnetization-prepared rapid acquisition gradient-echo (MP-RAGE) sequence with subsequent reconstruction of axial sections with 5-, 3-, and 1-mm thickness and a dual-echo sequence were obtained in 16 patients with relapsing-remitting or secondary-progressive MS. The volumes of MR imaging abnormalities present on each of these studies were measured using a semiautomated segmentation technique based on local thresholding. The hypointense lesion volumes seen on the three reconstructed MP-RAGE sets of images were compared using the Friedman test and correlated with the hyperintense lesion volume on proton density-weighted images and with scores on the Expanded Disability Status Scale using Spearman's rank correlation coefficient. RESULTS: The median volume of hypointense lesions increased from 1.2 mL (range, 0 to 14.9 mL) on the 5-mm-thick MP-RAGE images to 1.7 mL (range, 0 to 15.8 mL) on the 3-mm-thick images, and to 1.9 mL (range, 0 to 16.2 mL) on the 1-mm-thick images. The hypointense lesion volumes measured on the three MP-RAGE images correlated significantly with the degree of disability, whereas this correlation was not significant with the T2-weighted lesion load. CONCLUSION: Our findings indicate that a significant increase in the volume of potentially disabling MS lesions is observed when obtaining MR images with thin sections.

Adult↗
PubMed1998

Intraobserver and interobserver variability in schemes for estimating volume of brain lesions on MR images in multiple sclerosis.

PURPOSE: Our goal was to evaluate the intraobserver and interobserver reproducibility of measurements of brain lesion load in multiple sclerosis (MS) by using two proposed acquisition schemes. METHODS: Three-millimeter-thick conventional spin-echo (CSE) and fast fluid-attenuated inversion-recovery (FLAIR) sequences were obtained and the lesions segmented using a semiautomated technique based on local thresholding to calculate intraobserver and interobserver reproducibility. These were compared with images obtained from two separate MR units in which 5-mm CSE sequences were obtained and segmented by using the local thresholding technique and also by manual outlining. RESULTS: The intraobserver coefficient of variation was 4.0% (95% confidence interval [CI], 3.0% to 4.5%) for the 5-mm CSE sequence measured with manual outlining, 3.1% (95% CI, 2.5% to 3.2%) and 5.1% (95% CI, 4.1% to 5.6%) for the two sets of 5-mm CSE sequences measured using the local thresholding technique, 5.7% (95% CI, 3.9% to 6.6%) for the 3-mm CSE sequence, and 2.6% (95% CI, 2.1% to 2.7%) for the fast FLAIR sequence. The interobserver coefficient of variation was 7.1% (95% CI, 4.9% to 8.7%) and 8.3% (95% CI, 6.4% to 9.6%) for the two sets of 5-mm CSE sequences, 7.3% (95% CI, 4.7% to 9.1%) for the 3-mm CSE sequence, and 2.9% (95% CI, 2.3% to 3.3%) for the fast FLAIR sequence. The intraobserver and interobserver reproducibility of measurements obtained with the fast FLAIR technique was significantly better than those obtained with the other techniques. CONCLUSIONS: Our data indicate that the intraobserver and interobserver variability in quantifying MS lesions can be reduced significantly with the use of fast FLAIR sequences, while no significant improvement is gained by reducing the section thickness from 5 mm to 3 mm.

Adult↗
PubMed1998

Intraobserver and interobserver variability in measuring changes in lesion volume on serial brain MR images in multiple sclerosis.

PURPOSE: We evaluated the intraobserver and interobserver variability in measuring long-term changes in the volume of brain lesions on 5- and 3-mm-thick MR sections in patients with multiple sclerosis. METHODS: Eighteen 18 patients were scanned on two separate occasions with a mean interval of 16.4 months between the two examinations. In each session, a scan with 24 contiguous 5-mm-thick axial sections and another with 40 contiguous 3-mm-thick axial sections was acquired consecutively without moving the patient. We assessed MR lesion load by using a semiautomated local thresholding technique. RESULTS: Lesion volume was significantly higher on images with 3-mm-thick sections than on those with 5-mm-thick sections both at baseline and at follow up. Significant increases in total lesion volume were observed during the follow-up period on images obtained with both 5- and 3-mm-thick sections. The intra- and interobserver variability in measurements of changes in lesion volume was significantly higher on images with 5-mm-thick sections than on those with 3-mm-thick sections. CONCLUSION: Our data indicate that the acquisition of thinner sections increases the reliability of the assessment of changes in brain lesion load on MR images in patients with multiple sclerosis.

Adult↗
PubMed1998

Recurrent acute transverse myelopathy associated with anticardiolipin antibodies.

In three patients with recurrent episodes of acute transverse myelopathy, spinal MR imaging during each episode showed areas of hyperintensity on proton density- and T2-weighted images with inconsistent contrast enhancement. Cranial MR imaging, laboratory screenings, and CSF analysis showed only increased titers of anticardiolipin antibodies. Although a causative role in neurologic conditions has not been established conclusively, an association between these antibodies and acute transverse myelopathy and its recurrences cannot be ignored.

Acute Disease↗
PubMed1998

Unenhanced and enhanced magnetic resonance imaging in the diagnosis of multiple sclerosis.

Initial enthusiasm about the role of magnetic resonance imaging (MRI) in the diagnosis of multiple sclerosis decreased substantially with the notion that (a) lesions of various pathological origins may resemble demyelinating plaques and (b) a dissemination of lesions throughout the brain is not unique for multiple sclerosis but may even be a "normal" finding. Current experience still does not allow the identification of the aetiology of a single hyperintensity but has identified multiple features of multiple sclerosis related signal abnormalities which, in combination, provide rather high diagnostic accuracy. Useful characteristics include the distribution of lesions such as a strictly periventricular, infratentorial or juxtacortical location, and involvement of the corpus callosum. The presence of contrast enhancement in some but not all lesions-that is, evidence of both old and new lesions-provides additional diagnostic support. Improved instrumentation for imaging of the spine further extends the diagnostic options. Intramedullary signal abnormalities are detected with increased sensitivity and may disclose the presence of multiple lesions even in patients with an equivocal or a negative MRI of the brain. The high sensitivity to plaques and the opportunity to simultaneously rule out other gross morphological damage justifies the use of MRI as the primary diagnostic modality in the evaluation of multiple sclerosis.

Brain↗
PubMed1998

Clinical, neurophysiological, and magnetic resonance imaging correlations in multiple sclerosis.

Magnetic resonance imaging (MRI) has a pivotal role in diagnosis of multiple sclerosis and is being increasingly used as a paraclinical measure to assess treatment efficacy in clinical trials. However, the correlations between clinical and MRI findings in patients with multiple sclerosis are weak and, therefore, newer MR techniques are being developed to increase both MRI sensitivity for detecting disease activity and its pathological specificity for better assessing disease evolution. Evoked potentials (EPs) can be used to confirm the diagnosis of multiple sclerosis and their abnormalities are correlated with symptoms and signs referable to involvement of the corresponding nervous pathways. However, their use is limited when assessing disease progression and monitoring clinical trials in multiple sclerosis. Both magnetic resonance imaging (MRI) and evoked potentials (EPs) provide information which cannot be obtained by clinical evaluation, especially for assessing disease activity. Nevertheless, both these paraclinical techniques cannot substitute for clinical measures of disability when assessing disease progression and monitoring phase III clinical trials in multiple sclerosis.

Blood-Brain Barrier↗