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Biomedical subjects

Massimo Filippi

Publications and source records attributed to Massimo Filippi.

104 records · Page 6Linked to original sources
PubMed2002

Adaptive functional changes in the cerebral cortex of patients with nondisabling multiple sclerosis correlate with the extent of brain structural damage.

In multiple sclerosis, the mechanisms underlying the accumulation of disability are poorly understood. Recently, it has been suggested that adaptive cortical changes may limit the clinical impact of multiple sclerosis injury. In this study, functional magnetic resonance imaging and a general search method were used to assess patterns of brain activation associated with a simple motor task in 14 right-handed, nondisabled relapsing-remitting multiple sclerosis patients that were compared to those from 15 right-handed, sex- and age-matched healthy volunteers. Also investigated were the extent to which the functional magnetic resonance imaging changes correlated with T2 lesion volume and severity of multiple sclerosis pathology in lesions and normal-appearing brain tissue, measured using magnetisation transfer and diffusion tensor magnetic resonance imaging. Compared to controls, multiple sclerosis patients showed increased activation in the contralateral primary sensorimotor cortex, bilaterally in the supplementary motor area, bilaterally in the cingulate motor area, in the contralateral ascending bank of the sylvian fissure, and in the contralateral intraparietal sulcus. T2 lesion volume was correlated with relative activation in the ipsilateral supplementary motor area, and in the ipsilateral and contralateral cingulate motor area. Average lesion magnetisaiton transfer ratio and average lesion water diffusivity were correlated with relative activation in the contralateral sensorimotor cortex. Average lesion magnetisation transfer ratio was also correlated with relative activation in the ipsilateral cingulate motor area. Average water diffusivity and peak height of the normal-appearing brain tissue diffusivity histogram were both correlated with relative activation in the contralateral intraparietal sulcus. This study shows that cortical activation occurs over a rather distributed sensorimotor network in nondisabled relapsing-remitting multiple sclerosis patients. It also suggests that increased recruitment of this cortical network contributes to the limitation of the functional impact of white matter multiple sclerosis injury.

Adaptation, Physiological↗
PubMed2002

Image registration and subtraction to detect active T(2) lesions in MS: an interobserver study.

Serial MRI studies are used to analyse change in multiple sclerosis (MS) lesion volume in clinical trials. As such an evaluation is very time consuming and subject to quantification errors, one might assess only the change in number or size of lesions using subtracted images. The advantage of subtracted images is that both new and/or enlarging and resolving and/or shrinking lesions can be evaluated, resulting in a more precise volume change than a net volume change. We studied the interobserver agreement in the detection of active MS lesions using paired dual-echo T(2)-weighted spin-echo studies (3-mm slices) of 30 MS patients with a range of MS disease activity on MRI from treatment trials. Using an automatic matching algorithm based on mutual information, the follow-up scan was registered to baseline, after which subtracted images were obtained. After a training session with formulation of guidelines, six observers identified new, enlarging, resolving and shrinking lesions on subtracted images. Weighted kappa (kappa) values were calculated to assess interobserver agreement. Good agreement was found for new lesions (kappa 0.69 +/- 0.08), while moderate agreement was found for enlarging lesions (kappa 0.52 +/- 0.06). When new and enlarging lesions were combined, good agreement was found for "positive" activity (kappa 0.71 +/-0.06). The interobserver agreement was poor for resolving lesions (kappa 0.31 +/- 0.07), and moderate for shrinking lesions (kappa 0.53 +/- 0.08). In conclusion, the use of subtracted images in the visual detection of new T(2) lesions resulted in a good level of interobserver agreement for "positive" disease activity. Subtraction of registered images is a reliable, time efficient method to assess disease progression in MS.

Adult↗
PubMed2002

MR correlates of cerebral atrophy in patients with multiple sclerosis.

OBJECTIVE: To investigate the in-vivo correlates of brain atrophy in patients with multiple sclerosis (MS) by assessing the relationship between normalized measures of brain volume (NBV) and other magnetic resonance (MR) measures of tissue damage. BACKGROUND: Brain atrophy diffusely occurs and progressively increases in patients with MS. Nevertheless, the mechanisms leading to brain atrophy in this disease are not fully understood. METHODS: MR examinations were performed in 20 patients with relapsing-remitting MS. Conventional MRI was used to assess NBV and total brain T2-hyperintense and T1-hypointense lesion volumes. Proton MR spectroscopic imaging and diffusion tensor MR imaging were also performed for large portions of brain containing mainly normal-appearing tissue to provide indices of tissue damage, including N-acetylaspartate to creatine ratio (NAA/Cr) and mean diffusivity (D). RESULTS: Values of NBV correlated significantly with those of average brain (r = -0.58, p = 0.007) and NAA/Cr (r = 0.67, p < 0.001). The relationship of these markers of tissue damage to NBV was also found when NAA/Cr and were computed together in a composite MR score (r = 0.70, p < 0.001). In contrast, NBV values did not correlate with measurements of average lesion, T(2) and T(1) weighted total brain MRI lesion volumes. CONCLUSIONS: This study suggests that brain atrophy in MS is not simply due to axonal loss, but rather reflects a more generalized process that involves various brain tissue components. Damage to the normal-appearing tissue rather than the extent and intrinsic pathology of macroscopic lesions seems to be important in the destructive process leading to MS-related irreversible cerebral atrophy.

Adult↗
PubMed2002

A preliminary study of magnetization transfer and diffusion tensor MRI of multiple sclerosis patients with fatigue.

To investigate whether multiple sclerosis (MS) tissue damage is associated with the presence and severity of fatigue, we obtained magnetization transfer (MT) and diffusion tensor (DT) magnetic resonance imaging from 28 patients with MS (14 with and 14 without fatigue). MT ratio and mean diffusivity did not differ between fatigued and non-fatigued MS patients. No correlation was found between Fatigue Severity Scale scores and any of the MT and DT MRI-derived quantities. This preliminary study suggests that the severity of overall MS pathology in the brain seems not to be a critical factor contributing to the development of fatigue in MS.

Adult↗
PubMed2002

Clinical trials and clinical practice in multiple sclerosis: conventional and emerging magnetic resonance imaging technologies.

Conventional magnetic resonance imaging (cMRI) is widely used for diagnosing multiple sclerosis (MS) and as a paraclinical tool to monitor disease activity and evolution in natural history studies and clinical trials. However, the correlation between cMRI and clinical findings is far from strict, and such a discrepancy is even more evident when moving from the setting of large-scale studies to the management of individual patients. Among the reasons for this "clinical-MRI paradox" is the limited specificity of cMRI to the heterogeneous pathologic substrates of MS and its inability to quantify the extent of damage in the normal-appearing tissues. Modern quantitative MR techniques have the potential to overcome some of the limitations of cMRI. Although the application of modern MR techniques is changing dramatically our understanding of how MS causes irreversible disability, their use for clinical trial monitoring and clinical practice is still very limited. Whereas there is increasing perception that modern quantitative MR techniques should be more extensively employed in clinical trials to advance the understanding of MS and derive innovative information, their use in clinical practice should still be regarded as premature.

Central Nervous System↗
PubMed2002

Inflammation in multiple sclerosis: the good, the bad, and the complex.

Inflammation has always been thought of as detrimental in the pathophysiology of multiple sclerosis (MS). However, emerging genetic data, magnetic-resonance-imaging studies, and immunopathological evidence challenge this simplistic view. The evidence leads to the conclusion that inflammation is tightly regulated, and that its net effect may be beneficial in MS, thus explaining some of the results from recent trials of anti-inflammatory agents. We argue that the use of anti-inflammatory drugs to treat MS may not be appropriate in all cases. Precise identification of the inflammatory pathways to be targeted in the different phases of the disease and the timing of such interventions are therefore crucial.

Brain↗
PubMed2002

Magnetic resonance imaging of multiple sclerosis.

Although conventional magnetic resonance imaging (cMRI) is widely used for diagnosing multiple sclerosis (MS) and monitoring disease activity and evolution, the correlation between cMRI and clinical findings is far from strict. Among the reasons for this "clinical-MRI paradox," a major role has been attributed to the limited specificity of cMRI to the heterogeneous pathological substrates of MS and to its inability to quantify the extent of damage in the normal-appearing tissue. Modern quantitative MRI techniques have the potential to overcome some of the limitations of cMRI. Metrics derived from magnetization transfer and diffusion-weighted MRI enable one to quantify the extent of structural changes occurring within and outside macroscopic MS lesions with increased pathological specificity over cMRI. Magnetic resonance spectroscopy can add information on the biochemical nature of such changes, with the potential to improve significantly our ability to monitor inflammatory demyelination and axonal injury. Finally, functional MRI might provide new insights into the role of cortical adaptive changes in limiting the clinical consequences of white-matter structural damage. This review outlines the major contributions given by MRI-based techniques to the diagnostic work-up of MS patients, to the understanding of the pathobiology of the disease, and to the assessment of the effects of new experimental treatments.

Contrast Media↗
PubMed2002

Magnetization transfer and diffusion tensor MR imaging of acute disseminated encephalomyelitis.

BACKGROUND AND PURPOSE: Patients with acute disseminated encephalomyelitis (ADEM) and multiple sclerosis (MS) have a similar pattern of abnormalities on conventional MR images. We used magnetization transfer and diffusion tensor MR imaging to quantify normal-appearing brain tissue and cervical cord disease in patients with ADEM and to compare findings with those in healthy volunteers and patients with MS. METHODS: Brain dual-echo, T1-weighted magnetization transfer, and diffusion tensor images were obtained in eight patients with ADEM, in 10 patients with MS, and in 10 healthy volunteers. Fast short-tau inversion recovery, T1-weighted, and magnetization transfer cervical cord images were also obtained. We identified lesions on the images and quantified their volumes. We performed histogram analysis of the magnetization transfer ratio (MTR) and average mean histogram analysis of the diffusivity (D) in normal-appearing brain tissue and MTR in the cervical cord. RESULTS: Histogram analysis of normal-appearing brain tissue in patients with MS showed significantly lower MTRs and peak positions and significantly higher D averages compared with those in patients with ADEM. Patients with MS had significantly lower MTRs and D peak heights and significantly higher average D compared with those in healthy volunteers. Between patients with ADEM and control subjects, normal-appearing brain tissue MTR and D histogram metrics did not differ significantly. Cervical cord MTRs did not differ between control subjects and patients with ADEM, whereas the average MTR and histogram peak position was significantly lower in patients with MS than in the other groups. CONCLUSION: Outside the acute phase of disease and as opposed to what happens in MS, the normal-appearing brain tissue and cervical cord in patients with ADEM are spared in the pathologic process.

Adult↗
PubMedDate not supplied

Interferon beta-1a for brain tissue loss in patients at presentation with syndromes suggestive of multiple sclerosis: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: In patients who present with clinically isolated syndromes suggestive of multiple sclerosis, interferon beta-1a is effective in delaying evolution to clinically definite disease and in reducing MRI-measured disease activity. We aimed to assess whether this drug can also reduce the rate of brain volume decrease in such patients enrolled in the ETOMS (early treatment of multiple sclerosis) trial. METHODS: MRI data for brain volume measurements at baseline, month 12, and month 24 were available from 131, 111, and 112 patients assigned treatment (22 microg interferon beta-1a), and 132, 98, and 99 patients assigned placebo respectively. Normalised brain parenchymal volume (NBV) at baseline and percentage brain volume changes (PBVC) were measured with a fully-automated segmentation technique. The primary endpoint was conversion to clinically definite multiple sclerosis due to clinical relapse. Analysis was by intention to treat. FINDINGS: 41 (31%) of 131 patients on interferon beta-1a and 62 (47%) of 132 on placebo converted to clinically definite multiple sclerosis (odds ratio 0.52 [95% CI 0.31-0.86], p=0.0115). Mean PBVC for patients on placebo was -0.83% during the first year, -0.67% during the second year, and -1.68% during the entire study period. Respective values for treated patients were -0.62%, -0.61%, and -1.18%. The changes in brain volume were significant in both groups at all timepoints. A significant treatment effect was detected for month 24 versus baseline values (p=0.0031). The number of new T2 lesions formed during the first year correlated weakly with PBVC during the second year. INTERPRETATION: Early treatment with interferon beta-1a is effective in reducing conversion to clinically definite multiple sclerosis and in slowing progressive loss of brain tissue in patients with clinically isolated syndromes. The modest correlation between new lesion formation and brain volume decrease suggests that inflammatory and neurodegenerative processes are, at least partly, dissociated from the earliest clinical stage of multiple sclerosis onwards.

Adolescent↗
PubMedDate not supplied

MR-based technology for in vivo detection, characterization, and quantification of pathology of relapsing-remitting multiple sclerosis.

In relapsing-remitting (RR) multiple sclerosis (MS), conventional magnetic resonance (MR) imaging (MRI) has proved to be a valuable tool to assess the lesion burden and activity over time. However, conventional MRI cannot characterize and quantify the tissue damage within and outside such lesions and only can provide some gross measures reflecting the presence of irreversible tissue damage, such as the load of T1 "black holes" and the severity of brain or cord atrophy. Other MR-based techniques, including cell-specific imaging, magnetization transfer (MT) MRI (MT-MRI), diffusion-weighted (DW) MRI (DW-MRI), proton magnetic resonance spectroscopy (1H-MRS), and functional MRI (fMRI), have the potential to overcome this limitation and, consequently, to provide additional information about the nature and the extent of MS tissue damage, which would inevitably remain undetected when only a conventional MRI is obtained. Cell-specific imaging should result in a better definition of the cellular mechanisms associated with MS inflammation. Metrics derived from MT- and DW-MRI can quantify the structural changes occurring within and outside lesions visible on conventional MRI scans. 1H-MRS could add information on the biochemical nature of such changes. fMRI is a promising technique to assess the mechanisms of cortical reorganization, which may limit the consequences of an MS-related injury. The application of these MR techniques to the study of RRMS is likely to provide useful insights into the pathophysiology of this disease and to improve our ability to assess the efficacy of experimental treatments.

Biopsy, Needle↗
PubMedDate not supplied

Quantification of brain gray matter damage in different MS phenotypes by use of diffusion tensor MR imaging.

BACKGROUND AND PURPOSE: Increasing evidence exists that cerebral gray matter (GM) from patients with multiple sclerosis (MS) is not spared. This study was performed to quantify in vivo the extent of cerebral GM pathologic abnormality in patients with relapsing-remitting (RR), secondary progressive (SP), and primary progressive MS, by using diffusion tensor (DT) MR imaging. METHODS: Dual-echo and DT MR imaging of the brain were performed in 102 patients with MS and 30 healthy volunteers. After GM segmentation using a technique based on diffusion anisotropy thresholding, average diffusivity (D) histograms of the cerebral GM were produced for all participants. RESULTS: All D histogram-derived metrics of the GM were significantly different between control volunteers and the whole MS population. No significant difference was found for any of the D histogram-derived metrics between control volunteers and patients with RRMS, whereas significant differences were found for D and D histogram peak location between control volunteers and patients with PPMS. All the D histogram-derived metrics differed significantly between patients with RRMS and patients with SPMS. Patients with SPMS also had significantly lower D than did patients with PPMS. All D histogram-derived metrics of the GM were strongly correlated with the T2 lesion volume. CONCLUSIONS: This study confirms the presence of brain GM changes in patients with MS. It also shows that the extent of such changes is greater during the progressive forms of the disease.

Adult↗
PubMedDate not supplied

Sensitivity-encoded diffusion tensor MR imaging of the cervical cord.

The aim of this study was to apply sensitivity-encoding (SENSE) echo-planar imaging (EPI) to diffusion tensor MR imaging of the cervical cord, an anatomic region where MR imaging is particularly challenging. This technique was implemented with a SENSE reduction factor of 2 and used for imaging a water phantom and five healthy volunteers. Off-resonance artifacts were notably reduced compared with those of full-FOV EPI sequences. This approach to diffusion tensor MR imaging of the cervical cord is promising for future, more extensive clinical applications.

Adult↗