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Biomedical subjects

M Filippi

Publications and source records attributed to M Filippi.

At least 289 records · Page 16Linked to original sources

The effect of imprecise repositioning on lesion volume measurements in patients with multiple sclerosis.

In this study, we evaluated the effect of imprecision in patient repositioning encountered in real life on multiple sclerosis (MS) lesion volumes measured from MRIs. We also evaluated two putative methods for reducing the variability in these lesion volume measurements: first, a reduction of slice thickness (from the conventional 5 mm to 3 mm) and second, the application of a new repositioning technique based on the use of head immobilization shells. We evaluated the errors in lesion volume by scanning 10 patients a total of four times using the two slice thicknesses and two repositioning methods (conventional and using a head immobilization shell). The mean absolute percentage difference between two corresponding scans was 6.8% (range, 1.24 to 11%) using conventional slice thickness and repositioning, 4.1% (range, 0.7 to 5.56%) using conventional slice thickness and head immobilization shells, 2.6% (range, 0.8 to 6.66%) using the conventional repositioning technique and 3-mm slice thickness, and 1.4% (range, 0.2 to 6.14%) using slice thickness of 3 mm and head immobilization shells. These mean absolute differences were significantly different (p = 0.0008). Our results indicate that the effect of repositioning errors of the order of those that can be encountered in the daily life situation of clinical trials affects significantly lesion load measurements in MS and that the combined use of thinner slices and more accurate repositioning techniques can markedly improve the reproducibility of such measurements.

Adult↗

Interscanner variation in brain MRI lesion load measurements in MS: implications for clinical trials.

We evaluated the effect of interscanner variation on brain MRI-measured lesion volumes and measurement reproducibility in MS. Twenty clinically definite MS patients were each scanned on two or three scanners (a total of 14 scanners were used). In addition, a formalin-fixed MS brain was studied on eight scanners from different manufacturers and with different field strengths. For the formalin-fixed MS brain, on each machine we obtained two scans with slice thicknesses of 5 and 3 mm. Only 5-mm-thick slices were obtained from patients. The lesion volume present on each scan was evaluated three times by a single observer in random order, using a local thresholding technique. In two groups of eight patients scanned on machines with different field strengths, the mean lesion volumes present on scans obtained at 1.5 T were significantly higher than those measured on scans obtained with machines operating at 0.5 and 1.0 T (p < 0.01). When a single observer repeatedly evaluated the same scan, a median introbserver agreement of 98.7% (95% CI, 97.9 to 99.1) was achieved. However, when the observer evaluated the scans from different MRI scanners, the agreement (an interscanner agreement) fell to 91.1% (CI, 90.2 to 94.1). When only scanners operating at 1.5 T were considered, the median interscanner agreement was 96.7% (CI, 95 to 97.5). Also, for the formalin-fixed MS brain, the intraobserver agreements obtained with both slice thicknesses were significantly higher than the corresponding interscanner agreements. The interscanner agreement, but not the intraobserver agreement, obtained with a slice thickness of 3 mm was higher than that obtained with a slice thickness of 5 mm. Our results indicate that lesion volume measurements in MS are influenced significantly by the use of different MR scanners and that a patient included in a serial study should be always scanned with the same MR machine using 3-mm thick slices.

Adult↗

Cerebral involvement in celiac disease: a serial MRI study in a patient with brainstem and cerebellar symptoms.

A patient with celiac disease and relapsing-progressive symptoms suggesting brainstem and cerebellar involvement underwent serial MRIs. The first examination revealed multiple enhancing and nonenhancing lesions. Thereafter, a large enhancing cerebellar lesion appeared, followed by severe cerebellar atrophy. The presence of structural neuronal damage was confirmed by proton MR spectroscopy and magnetization transfer imaging. MRI results and CSF findings suggested that neurologic complications were more likely due to an inflammatory process.

Adult↗

Improving interobserver variation in reporting gadolinium-enhanced MRI lesions in multiple sclerosis.

Gadolinium-enhanced MRI is a sensitive and objective means to monitor disease activity in multiple sclerosis (MS). We evaluated the interobserver agreement and the value of observer training in reporting enhancing lesions from serial MRI. Scans of 16 MS patients were evaluated by five inexperienced and five experienced observers before and after consensus formation and training. The number of lesions at baseline, and the number of new and persistent lesions at follow-up were scored. For each condition, weighted kappa values (kappa) and the mean average difference to the median (MADM) scores were calculated. Without training, the experienced readers showed good agreement on number of lesions at baseline and new lesions at follow-up, and moderate agreement for persistent lesions. The inexperienced readers showed poor agreement for baseline and persistent lesions, and moderate agreement for new lesions. After training, both groups reported lower absolute numbers of lesions, especially the inexperienced readers. The experienced readers showed good agreement for all lesion types, the inexperienced readers showed agreement for baseline and new lesions, and agreement was moderate for persistent lesions. In both groups MADM scores were < 0.72 for baseline and new lesions, but > 1.2 for persistent lesions. Interobserver agreement is improved by training, especially in inexperienced readers. Interobserver agreement in reporting gadolinium-enhanced lesions is high, which validates the use of serial, enhanced MRI as an outcome parameter in treatment trials in MS.

Analysis of Variance↗

Comparison of MR pulse sequences in the detection of multiple sclerosis lesions.

PURPOSE: To compare the sensitivity of conventional spin-echo, fast spin-echo, fast fluid-attenuated inversion recovery (FLAIR), and turbo gradient spin-echo MR sequences in the detection of multiple sclerosis lesions. METHODS: Conventional spin-echo, fast spin-echo, fast FLAIR, and turbo gradient spin-echo sequences were performed on a 1.0-T MR imager in seven patients with clinically definite multiple sclerosis. The images in each sequence were evaluated by two raters and consensus was reached by agreement. RESULTS: In comparing conventional spin-echo with fast spin-echo sequences, five lesions were seen only by conventional spin-echo and 63 were seen only by fast spin-echo; in comparing conventional spin-echo with fast FLAIR sequences, 18 lesions were seen only by conventional spin-echo and 109 only by fast FLAIR; in comparing conventional spin-echo with turbo gradient spin-echo sequences, 51 lesions were seen only by conventional spin-echo and seven only by turbo gradient spin-echo; in comparing fast spin-echo with fast FLAIR sequences, 45 lesions were seen only by fast spin-echo and 52 only by fast FLAIR. CONCLUSION: Fast spin-echo and fast FLAIR sequences improve the sensitivity of MR imaging in the detection of multiple sclerosis lesions with reduced acquisition time as compared with conventional spin-echo sequences. These sequences should therefore be considered for serial studies in patients with multiple sclerosis. The sensitivity of turbo gradient spin-echo was inferior to the other sequences, but its reduced acquisition time could make this technique the ideal choice for patients who cannot tolerate longer examination times.

Diagnosis, Differential↗

Serial contrast-enhanced MR in patients with multiple sclerosis and varying levels of disability.

PURPOSE: To compare the rates of enhancement and changes in lesion burden in patients with multiple sclerosis (MS) and varying levels of disability. METHODS: Monthly enhanced MR images of the brain were obtained for 6 months from seven patients with mildly disabling relapsing-remitting MS and from seven patients with secondary progressive MS and severe disability. At entry and 1 year later, two unenhanced T2-weighted images of the brain were also obtained. RESULTS: Despite the fact that both groups had clinically active disease and had similar increases in unenhanced MR lesion load, the total number of enhancing lesions was 239 in patients with relapsing-remitting MS (42 on the baseline images, 151 new and 46 persistent during follow-up) (average number of lesions per patient per year was 68) and 21 in those with secondary progressive MS (five on the baseline images, 13 new, and three persistent during follow-up) (average number of lesions per patients per year was seven). CONCLUSION: Our data indicate that the rate of enhancement significantly decreases in the more advanced phases of MS. This is important when planning clinical trials, and suggests that mechanisms underlying lesion formation might be dissimilar in different MS patient groups.

Activities of Daily Living↗

A high-resolution three-dimensional T1-weighted gradient echo sequence improves the detection of disease activity in multiple sclerosis.

In this study, we performed a post-contrast magnetization-prepared rapid acquisition gradient echo (MP RAGE) sequence with subsequent reconstruction of axial slices with 5-, 3-, and 1-mm thickness in 26 patients with multiple sclerosis (MS) to investigate the disease activity going on below the resolution of conventional scans. One hundred three enhancing lesions were detected using MP RAGE reconstructed with 1-mm-thick slices, 93 using MP RAGE reconstructed with 3-mm-thick slices and 82 using MP RAGE reconstructed with 5-mm-thick slices. The detection rate using 1-mm MP RAGE was 25.6% higher compared with 5-mm MP RAGE and 12% higher compared with 3-mm MP RAGE. Using 1-mm MP RAGE, we detected five enhancing lesions in 2 of the 12 patients (16.6%) who showed no enhancing lesions on the 5-mm MP RAGE and one enhancing lesion in 1 of the 10 patients (10%) who showed no enhancing lesions on the 3-mm MP RAGE. The increased sensitivity of 1-mm MP RAGE over the other two reconstruction slice thicknesses was due to improved detection of small lesions, located mainly in cortical/subcortical areas. These data indicate that the size of enhancing lesions in MS is highly variable, and that a significant proportion of disease activity goes undetected when performing conventional scans.

Adult↗

Functional basis of memory impairment in multiple sclerosis: a[18F]FDG PET study.

Structural neuroimaging has been used to correlate lesional patterns with the cognitive profile of patients with multiple sclerosis (MS), especially for "frontal" dysfunction. However, a clear-cut anatomical explanation has yet to be found for the long-term memory deficit which is a hallmark of MS cognitive impairment. We have used PET to measure regional cerebral glucose metabolism (rCMRglc) in a group of 15 MS patients with involvement of verbal and/or spatial long-term memory. These patients were compared with 10 normal controls and 13 MS patients unimpaired on all neuropsychological tests. Relative to the controls, MS patients with memory deficits showed a significant bilateral reduction of rCMRglc in the hippocampus, cingulate gyrus, thalamus, associative occipital cortex, and cerebellum. Direct comparisons between patients with memory deficits and the group of unimpaired MS patients showed a metabolic reduction in the left thalamus and in both hippocampi. Seven of the memory-impaired patients also had neuropsychological signs of frontal dysfunction. These patients were compared with patients who had isolated memory deficit. Here we observed a further metabolic reduction in a number of brain regions including bilateral prefrontal cortex, inferior parietal cortex, and basal ganglia. Our findings indicate that hypometabolism of thalamic and deep cortical gray structures of the temporal lobe is associated with episodic memory dysfunction in MS. On the other hand, pathological performance on tests designed to assess frontal functions was associated with widespread reduction of glucose metabolism.

Adult↗

Magnetisation transfer ratios of contrast-enhancing and nonenhancing lesions in multiple sclerosis.

Magnetisation transfer (MT) is a recently introduced technique for assessing the water content of tissues in vivo and its relationship to macromolecules or membranes. It has been suggested that MT could provide indirect evidence of the characteristics of multiple sclerosis (MS) lesions (oedema, demyelination, or gliosis). Our aims were to characterise brain MS lesions and to compare the magnetisation transfer ratio (MTR) values of lesions with different patterns of contrast enhancement. In patients with MS we measured the MTR of 65 gadolinium-enhancing and 292 nonenhancing lesions. Using the equation published by Dousset et al. we studied 29 patients with clinically definite MS and 10 healthy controls. Lesions had significantly lower MT than the normal-appearing white matter of the patients or the normal white matter of healthy controls. There was no difference in the MTR of enhancing and nonenhancing lesions. Enhancement was homogeneous in 45 and ring-like in 20 lesions; MTR values were lower in the latter. These findings are presumably related to the differences in pathological features of enhancing (different amounts of proteins and inflammatory cells, oedema and demyelination) and nonenhancing (gliosis, demyelination and axonal loss) lesions.

Adult↗

A spinal cord MRI study of benign and secondary progressive multiple sclerosis.

This study was performed to achieve a better definition of the nature of the disability in multiple sclerosis (MS). Axial spinal cord magnetic resonance imaging (MRI) at C5 was obtained in 15 patients with benign MS, 17 patients with secondary progressive MS and 10 healthy controls. Patients with secondary progressive MS had smaller spinal cord cross-sectional area (P = 0.01) and transverse diameter (P = 0.006) than patients with benign MS. The degree of disability was inversely correlated with both the cross-sectional area (r = -0.6, P = 0.0018) and transverse diameter (r = -0.5, P = 0.0032) of the cord. Spinal cord atrophy was found in 7 (41%) patients with secondary progressive MS and in 2 (13%) with benign MS. These findings suggest that destructive pathology within MS lesions might play a relevant role in the development of disability in MS.

Adult↗

Magnetic resonance in monitoring the natural history of multiple sclerosis and the effects of treatment.

In this review the main contributions of magnetic resonance (MR) techniques in the monitoring of multiple sclerosis (MS) course, both natural or modified by treatments, are presented. MR measures well correlate with short-term disease evolution and therefore their use is appropriate as primary end-points in preliminary clinical trials evaluating the effects of new treatments. In contrast, the correlation between MR measures and long-term clinical evolution in clinically definite MS is less clear, thus indicating that such measures can be used at present only as a secondary end-point in large scale definitive trials. The results coming from the clinical application of newer MR techniques with higher pathological specificity are also presented and their possible future roles in monitoring treatment aimed at preventing development of disability in MS are discussed.

Brain↗

Brain and spinal cord MR in benign multiple sclerosis: a follow-up study.

We performed a clinical and magnetic resonance (MR) longitudinal study in 19 patients with benign multiple sclerosis (MS) to achieve a better definition of the nature of disability in MS. Patients with higher lesion volumes on conventional T2-weighted images at entry were those with more frequent relapses (p = 0.0004) and more new MR lesions (p = 0.003) during the follow up. However, 1/3 of these new lesions were located periventricularly and about 2/3 were small or intermediate in size. Two of the 11 patients (18%) with higher lesion volumes at entry developed progressive neurological deficits: in these two patients the new lesions seen on conventional T2 images had lower magnetization transfer ratios (p = 0.005) than those present in patients who remained clinically stable and a marked increase in hypointense lesion volumes on T1-weighted images was also found. Spinal cord cross-sectional area at C5 and MTR values for the seemingly normal white matter were similar to those found in normal controls. This study suggests that patients with benign MS have two different patterns of disease evolution, one characterized by very low clinical and MR activities, the other in which the lack of disabling symptomatology might be related to factors like site, size and nature of lesions. It also indicates that in patients with benign MS and high MR lesion loads the risk of developing a secondary progressive form of the disease is still present even after many years after onset.

Adult↗

Quantitative assessment of MRI lesion load in multiple sclerosis. A comparison of conventional spin-echo with fast fluid-attenuated inversion recovery.

In this study, we compared a fast fluid-attenuated inversion recovery (fast-FLAIR) sequence to conventional spin-echo (CSE) in the evaluation of brain MRI lesion loads of seven patients with clinically definite multiple sclerosis. Interleaved CSE (3000/20, 5 mm contiguous axial slices) and fast-FLAIR (9000/150/2200, 5 mm contiguous axial slices) sequences were performed on a 1.0 T machine. Lesions were counted consensually by two observers and then segmented independently by two other observers using a local thresholding technique, with subsequent manual editing in the case of poorly defined lesions. Four hundred and two lesions were detected in at least one of the two sequences: 128 were seen only on fast-FLAIR, 17 only on CSE. Forty-one lesions were larger on fast-FLAIR, while no lesion was considered larger on CSE. The numbers of periventricular (P = 0.05), cortical/subcortical (P = 0.02) and discrete (P = 0.05) lesions detected using fast-FLAIR were higher than those detected using CSE. The median lesion load was 7185 mm3 on CSE and 8418 mm3 on the fast-FLAIR, the average being 18% (range = 11.6-29%) higher on the fast-FLAIR images. Lesion contrast ratio was higher for lesions on the fast-FLAIR than on the CSE sequence (P < 0.0001). The percentages of poorly defined lesions which needed manual editing after the local thresholding technique was applied and the total time needed for the measurements were lower (P < 0.001) when fast-FLAIR images were used compared with CSE. This resulted in a reduced inter-rater coefficient of variation in measuring lesion volumes. Our data indicate that fast-FLAIR sequences are more sensitive than CSE in detecting multiple sclerosis lesion burden and that fast-FLAIR is a promising technique for natural history studies and clinical trials in multiple sclerosis.

Adult↗

Magnetic resonance imaging in the differential diagnosis and monitoring of the treatment of multiple sclerosis.

Treatments with potentially beneficial effects on the course of multiple sclerosis are now emerging and magnetic resonance imaging techniques are needed which have a high specificity for diagnosing multiple sclerosis, and which can characterize the heterogeneous nature of multiple sclerosis lesions and define disease evolution over time. Differential diagnosis may be improved by the use of gadolinium-enhanced magnetic resonance imaging, high-resolution spinal cord and optic nerve magnetic resonance imaging and non-conventional magnetic resonance imaging techniques. In the monitoring of treatment, a number of different approaches have been used to increase magnetic resonance imaging accuracy in describing and predicting disease activity and evolution. These include optimization of the acquisition and post-processing of data obtained with conventional magnetic resonance imaging techniques (T2-weighted and postcontrast T1-weighted sequences) and the use of newer nonconventional magnetic resonance imaging techniques.

Diagnosis, Differential↗

Semi-automated thresholding technique for measuring lesion volumes in multiple sclerosis: effects of the change of the threshold on the computed lesion loads.

Quantitative evaluation of lesion load in multiple sclerosis (MS) from magnetic resonance imaging (MRI) scans is becoming important in understanding and monitoring the progression of the disease. Methods of MS lesion segmentation based on intensity thresholding offer one of the most robust and easily-implemented means of computing the total lesion volume. This study evaluated the effects of slight changes in the choice of intensity threshold on computed lesion volumes in 20 patients with MS using such a technique. After judging the optimum choice of threshold value, the threshold value was increased and decreased by 3% in 1% steps around this value; we observed a mean change of 15% in computed lesion volumes for 1% changes of threshold value. Larger changes in lesion volume were found when the threshold was changed by larger amounts. On the other hand, the amount of time required for manual review decreased, and the confidence with which manual review could be performed increased when using lower thresholds. This study shows that the choice of threshold is a crucial factor in measuring lesion volumes in MS when using intensity-based techniques. It also suggests that in multicenter and/or longitudinal studies, criteria for choosing the threshold should be developed whereby the threshold level should be set such that all MR visible lesions are above it, in order to minimise the human interaction and, consequently, the reproducibility of the results.

Brain↗

Correlation between brain MRI lesion volume and disability in patients with multiple sclerosis.

In this study we evaluated the relationships between clinical variables and lesion volumes measured from magnetic resonance imaging (MRI) scans in a large cohort of multiple sclerosis (MS) patients. One hundred and thirty patients with MS entered the study: 36 patients had relapsing-remitting (RR), 39 benign (B), 42 secondary progressive (SP) and 13 primary progressive (PP) courses. There was a significant correlation (r = 0.3; p = 0.0006) between the total lesion load and the EDSS score when the whole cohort of patients was considered. This correlation increased (r = 0.5) when only patients with RRMS and SPMS were considered. Our data indicate that a correlation between disability and MRI lesion volume in MS exists, but its strength is moderate.

Adult↗

Triple dose of gadolinium-DTPA and delayed MRI in patients with benign multiple sclerosis.

OBJECTIVES: To evaluate whether a triple dose of gadolinium-DTPA (Gd-DTPA) or delayed MRI increase the number, size, and conspicuousness of enhancing lesions in patients with benign multiple sclerosis. METHODS: T1 weighted brain MRI was carried out on 20 patients with benign multiple sclerosis (expanded disability status scale < 3 with a disease duration > 10 years) in two sessions. In the first session, one scan was obtained before and two scans five to seven minutes and 20-30 minutes after the injection of 0.1 mmol/kg Gd-DTPA (standard dose). In the second session, six to 24 hours later, the same procedure was repeated with 0.3 mmol/kg Gd-DTPA (triple dose). RESULTS: Nine enhancing lesions were found in seven patients (35%) using the standard dose of Gd-DTPA. The numbers of enhancing lesions increased to 13 (P = 0.03) and the number of patients with such lesions to eight (40%) on the delayed standard dose scans. On the early triple dose scans, we found 19 enhancing lesions in 10 patients (50%). The number of enhancing lesions was significantly higher (P = 0.01) than that obtained with the early standard dose. The number of enhancing lesions was 18 and the number of "active" patients 11 (55%) on the delayed triple dose scans. The enhancing areas increased progressively from the early standard dose scans to the delayed triple dose scans. The contrast ratios of the lesions detected in early standard dose scans was lower than those of lesions present in the early (P = 0.01) and delayed (P = 0.04) triple dose scans. CONCLUSIONS: More enhancing lesions were detected in patients with benign multiple sclerosis with both delay of MRI and the use of triple dose of Gd-DTPA suggesting that the amount of inflammation in the lesions of such patients is mild and heterogeneous.

Gadolinium DTPA↗