Biomedical subjects

M Cercignani

Publications and source records attributed to M Cercignani.

14 recordsLinked to original sources

PubMed2001

Diffusion tensor magnetic resonance imaging in multiple sclerosis.

OBJECTIVES: To quantify, using diffusion tensor imaging (DTI), the tissue damage in lesions and normal-appearing white matter (NAWM) from a large cohort of patients with MS and to investigate the magnitude of the correlation between DTI-derived metrics and clinical disability. METHODS: Dual-echo and DTI scans were obtained from 78 patients with relapsing-remitting, secondary progressive, or primary progressive MS and from 20 normal control participants. Post-contrast T1-weighted images were also obtained from the patients. After creating mean diffusivity (D) and fractional anisotropy (FA) images and image coregistration, D and FA values were measured for 4846 lesions (3207 nonenhancing T1-isointense, 1511 nonenhancing T1-hypointense, and 128 enhancing), 497 NAWM areas from patients, and 160 white matter areas from the controls. RESULTS: The average lesion D was higher and the average lesion FA was lower than the corresponding quantities of the NAWM (p < 0.001). The values of enhancing and nonenhancing lesions were not different, whereas enhancing lesions had lower FA (p < 0.001). T1-hypointense lesions had higher D and lower FA than T1-isointense lesions (p < 0.001). NAWM of patients had higher and lower FA than white matter of controls (p = 0.01). Significant correlations were found between T1 and T2 lesion volume and and FA of lesions and NAWM. In the overall patient sample, a moderate correlation was also found between lesion D and the Expanded Disability Status Scale score (r = 0.28, p = 0.01). However, the r value of this correlation was 0.48 in patients with secondary progressive MS, whose disability was also correlated with average lesion FA (r = -0.50). CONCLUSIONS: The results of this study show that DTI is able to identify MS lesions with severe tissue damage and to detect changes in the NAWM. They also indicate that DTI-derived measures are correlated with clinical disability, especially in patients with secondary progressive MS, thus suggesting a role for DTI in monitoring advanced phases of the disease.

Adult↗

PubMed2001

Magnetisation transfer ratio and mean diffusivity of normal appearing white and grey matter from patients with multiple sclerosis.

OBJECTIVE: To assess the feasibility of a new technique based on diffusion anisotropy to segment white and grey matter of the brain. To use this technique to measure the mean diffusivity () and magnetisation transfer ratio (MTR) of normal appearing white matter (NAWM) and grey matter (NAGM) from patients with multiple sclerosis. METHODS: Dual echo turbo spin echo, MT, and diffusion weighted scans of the brain were obtained from 30 patients with multiple sclerosis and 18 sex and age matched healthy controls. After image coregistration and removal of T2 visible lesions, white and grey matter were segmented from 10 supratentorial slices using diffusion anisotropy thresholds. Histograms of the average MTR and were created for normal white and grey matter of controls and NAWM and NAGM of patients with multiple sclerosis. RESULTS: All the MTR histogram derived metrics of the NAWM from patients with multiple sclerosis were significantly lower than those of white matter from controls. The peak height of the histogram of NAWM from patients with multiple sclerosis was also significantly different from that of normal white matter. The average MTR, the peak location of the MTR histogram, and peak height of the histogram of the NAGM of patients with multiple sclerosis were significantly lower than the corresponding quantities of grey matter from controls. CONCLUSIONS: A technique was developed for segmenting white and grey matter with the potential for improving the understanding of the pathophysiology of many neurological conditions. Its application to the study of multiple sclerosis confirms the presence of a diffuse tissue damage in the NAWM of these patients and suggests that subtle changes also occur in the NAGM.

Adult↗

PubMed2000

Weekly diffusion-weighted imaging of normal-appearing white matter in MS.

To elucidate the dynamics and the nature of normal-appearing white matter (NAWM) changes preceding new lesion formation in MS, the authors obtained weekly diffusion-weighted images for 12 weeks from 6 patients. NAWM areas subsequently involved by enhancement had a significant increase in mean diffusivity values starting 6 weeks before the appearance of enhancement (p values ranging between < 0.0001 and 0.04). This suggests that focal edema and demyelination play a part in the NAWM changes preceding new lesion formation in MS.

Adult↗

PubMed2000

Magnetization transfer and diffusion-weighted imaging in nocturnal frontal lobe epilepsy.

The authors assessed the presence of brain abnormalities in 21 patients with nocturnal frontal lobe epilepsy (NFLE), using magnetization transfer ratio (MTR) and mean diffusivity (;D) histograms. Compared with healthy volunteers and patients with idiopathic generalized epilepsy, patients with NFLE had lower MTR (p = 0.002 and 0.01) and;D (p = 0.03 and 0.04) histogram peak heights. Subtle and widespread abnormalities related to intra- and extracellular distribution and motion of water are detectable in the brains of patients with NFLE.

Adolescent↗

PubMed2000

Pathologic damage in MS assessed by diffusion-weighted and magnetization transfer MRI.

OBJECTIVE: To compare diffusion characteristics of MS lesions, normal-appearing white matter (NAWM) from patients, and normal white matter from control subjects, and to investigate the correlations between the magnetization transfer ratio (MTR) and a directionally averaged tissue water diffusion coefficient (D) in patients. BACKGROUND: MS and other pathologic processes that modify tissue integrity can result in abnormal diffusion of water molecules detectable by diffusion-weighted imaging (DWI). METHODS: Conventional dual-echo and DWI scans were obtained from 35 patients with relapsing-remitting MS and 24 healthy control subjects. MT scans were also obtained from the patients. After coregistration of all scans, MTR and D values from MS lesions and NAWM in different regions were marked using the dual-echo scans as a reference. D values from the same brain regions in control subjects were acquired. Histograms of MTR and D were also produced. RESULTS: Patients with MS had significantly higher D values in all the areas studied. Moreover, histogram metrics (peak height, peak site, and average D) from patients were substantially different from those of control subjects. In patients, average lesion D and MTR were markedly different from those in the NAWM. There was an inverse correlation between average lesion MTR and D inside lesions, whereas no correlation was found for average MTR and D taken from the histograms. CONCLUSIONS: DWI detects severe tissue disruption inside lesions and subtle widespread abnormalities in NAWM in patients with relapsing-remitting MS. MT and DWI may provide information about different aspects of brain pathology in MS.

Adult↗

PubMed2000

A quantitative study of water diffusion in multiple sclerosis lesions and normal-appearing white matter using echo-planar imaging.

OBJECTIVES: We used an optimized echo-planar pulse sequence for isotropically weighted diffusion imaging (1) to measure mean diffusivity (D) in lesions and normal-appearing white matter (NAWM) in the entire brain from patients with mildly disabling relapsing-remitting multiple sclerosis (MS), (2) to compare the D of NAWM from patients with that of white matter from normal controls, (3) to evaluate whether lesions classified on the basis of their appearance on enhanced T1-weighted scans have different D, and (4) to investigate the relationship between diffusion changes in lesions and NAWM. METHODS: Dual-echo and diffusion-weighted scans were obtained from 35 patients with relapsing-remitting MS and 24 sex- and age-matched normal controls. Postcontrast T1-weighted images were also obtained from the patients. After creating D maps and image coregistration, D values were measured for MS lesions larger than 5 mm and for 22 NAWM areas from each subject. RESULTS: All NAWM areas studied had significantly higher D in patients than in controls. A total of 173 lesions were identified on the dual-echo scans from patients. The average D for these lesions was significantly higher than that of NAWM. Twenty-two lesions were enhancing and 60 were classified as T1-hypointense. No significant difference in D values was found between enhancing and nonenhancing lesions, while the average D of T1-hypointense lesions was significantly higher than the average D of T1-isointense lesions. There was no significant correlation between the average D in lesions and NAWM. CONCLUSIONS: This study shows that diffusion-weighted imaging is able to identify MS lesions with severe tissue disruption. It also shows that widespread increased diffusion can be measured in the NAWM from patients with MS, and suggests that such changes are, at least partially, independent of larger abnormalities.

Adult↗

PubMed2000

Role of platelets in tissue factor expression by monocytes in normal and hypercholesterolemic subjects. In vitro effect of cerivastatin.

Thrombosis is a complication of atherosclerosis and monocytes play a determinant role either in the progression of atherosclerotic plaque or in blood coagulation by way of tissue factor expression. Platelets play a direct role in thrombosis and a hyperfunctional state has been described in hypercholesterolemic subjects. Moreover, platelets seem to be able to enhance monocyte activity. Cholesterol-lowering molecules (statins) are reported to reduce cardiovascular risk, either by decreasing the circulating level of cholesterol or by non-lipidic actions such as the reduction of monocyte and platelet activity. The aim of our study was to investigate the influence of platelets on the expression of tissue factor by monocytes and the effect induced by cerivastatin. We measured tissue factor levels by ELISA and the procoagulant activity of stimulated monocytes by a clotting assay on cellular preparations and whole blood in 40 hypercholesterolemic subjects (22 male, 18 female, mean age 52.7 +/- 12 years, total cholesterol 251.6 +/- 19.9 mg/dl) before and after cerivastatin addition. Tissue factor expression was enhanced in hypercholesterolemic subjects compared with normal subjects (31.6 +/- 7.6 vs. 23 +/- 5.8 pg/cells, P < 0.01). The presence of platelets increased the amount of tissue factor (55.3 +/- 7.3 pg/cells, P < 0.001) and cerivastatin reduced the expression of tissue factor in isolated monocytes, in the mixed cellular system, and in whole blood (19.6 +/- 4.1 pg/cells, P < 0.001). In conclusion, tissue factor expression by monocytes is enhanced in hypercholesterolemic subjects compared with normal controls. Platelets enhance monocyte production of tissue factor, and cerivastatin is able to counteract this prothrombotic mechanism.

Adult↗

PubMed2000

Activity revealed in MRI of multiple sclerosis without contrast agent. A preliminary report.

Disease activity in multiple sclerosis is usually accompanied by blood-brain barrier disruption, which can be assessed with contrast-enhanced magnetic resonance imaging (MRI). This paper describes a technique that gives information about disease activity using magnetization transfer MRI. Image combination methods using follow-up scans, like the one presented here, have the potential to show MS lesions that correlate with enhancement.

Blood-Brain Barrier↗

PubMed2000

Reproducibility of magnetization transfer ratio histogram-derived measures of the brain in healthy volunteers.

Using two MR scanners, we evaluated the intraobserver, interobserver, image-reimage, and interimager variabilities in the assessment of magnetization transfer ratio (MTR) histograms obtained monthly on four occasions from five healthy volunteers. With multiple observers, the mean coefficients of variations ranged from 2.2% to 8.2% for "pure" image-reimage variability, from 1.2% to 4.9% for interobserver variability, and from 2.1% to 4.9% for image-reimage variability. The mean intraobserver coefficients of variations were always lower than 1%. The mean coefficients of variations ranged from 10.2% to 14.6% for pure interimager variability and from 8.6% to 14.3% for interimager variability with multiple observers. Interimager variability accounted for 96.0% of the overall variability of average MTR, for 96.7% of peak location, and for 41.1% of the peak height. The use of different MR scanners is the main source of variability when obtaining MTR histograms.

Adult↗

PubMed1999

An optimized pulse sequence for isotropically weighted diffusion imaging.

Single-shot echo-planar imaging is becoming the most widely used technique for magnetic resonance diffusion imaging, since it enables measurement of diffusion coefficients in human brain without motion artifacts. However, its reliability is limited by geometrical distortions due to eddy currents. In this report, an isotropically weighted echo-planar pulse sequence, optimized to give the maximum signal-to-noise ratio in the computed trace image and designed to produce inherently low distortions, is presented. It is also shown how the residual translational distortion can be easily characterized and removed by postprocessing. A full characterization of the distortion artifact involves a few measurements on a phantom, in order to estimate the distortion as a function of slice orientation, which can then be used to correct any slice orientation. Results of applying the image translation correction to data collected from a patient are presented.

Artifacts↗

PubMed1999

Diffusion-weighted imaging in multiple sclerosis.

Diffusion-weighted imaging (DWI) provides a unique form of magnetic resonance (MR) contrast that enables the diffusional motion of water molecules to be quantitatively measured. As a consequence, DWI provides information about the orientation, size and geometry of brain structures. Cellular structures in the central nervous system restrict water molecular motion, and the apparent diffusion coefficient (ADC) is reduced compared to diffusion in bulk water. Pathological processes that modify tissue integrity, thus removing some of the "restricting" barriers, can result in increased ADC. Preliminary studies in multiple sclerosis (MS) using DWI showed that the ADC is higher in macroscopic lesions than in the normal appearing white matter (NAWM). The ADC is also dependent on the direction in which diffusion is measured, thus making comparison of ADC values meaningless without taking into account the measurement direction. One measurement of diffusion that is independent of the orientation of structures is provided by measuring the ADC in three orthogonal directions, and then averaging the results to form the mean diffusivity, D. We obtained DW scans from 35 patients with relapsing-remitting MS and 24 healthy volunteers. D was measured inside T2-visible lesions and regions located in different areas of the NAWM. D histograms from a large portion of the brain were created. MS lesions had a significantly higher D than NAWM. T1-hypointense lesions had the highest diffusion values, consistent with more severe tissue disruption. D was higher in the NAWM from patients than in the white matter from healthy controls. We also found significant differences between D histogram-derived measures from patients and controls, confirming the presence of diffuse damage in the brain of patients with MS.

Body Water↗

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↗

PubMedDate not supplied

A comparison of MR imaging with fast-FLAIR, HASTE-FLAIR, and EPI-FLAIR sequences in the assessment of patients with multiple sclerosis.

BACKGROUND AND PURPOSE: Fast fluid-attenuated inversion-recovery (FLAIR) sequences are sensitive for detecting lesions in patients with multiple sclerosis (MS). More rapid fast-FLAIR imaging of the brain can be achieved by the concomitant use of half-Fourier acquisition single-shot turbo spin-echo (HASTE-FLAIR) and echo-planar imaging (EPI-FLAIR). The present study was performed in a large cohort of subjects to assess and compare the number and volume of brain lesions detected by the fast-FLAIR, HASTE-FLAIR, and EPI-FLAIR sequences in patients with MS. METHODS: Fast-FLAIR, HASTE-FLAIR, and EPI-FLAIR sequences were obtained from 46 consecutive MS patients. Lesions seen on each type of sequence were counted and classified by consensus by two observers. Lesion volumes were measured using a semiautomated segmentation technique based on local thresholding. RESULTS: The quality of the fast-FLAIR images was significantly better than that of HASTE-FLAIR and EPI-FLAIR images. Fast-FLAIR revealed significantly more lesions and higher lesion volumes than did HASTE-FLAIR and EPI-FLAIR. A similar number of large lesions was detected by the three sequences, but HASTE-FLAIR and EPI-FLAIR showed significantly fewer small and intermediate lesions than did fast-FLAIR. The number of lesions seen on HASTE-FLAIR and EPI-FLAIR images was similar. CONCLUSION: HASTE-FLAIR and EPI-FLAIR sequences revealed as many large MS lesions as fast-FLAIR. Because their acquisition times are only a fraction of that needed for fast-FLAIR sequences, they may be useful for making a rapid diagnosis of MS in uncooperative patients. Their reduced ability to detect smaller lesions indicates that they should not be used as a routine approach to imaging patients with MS.

Adult↗

PubMedDate not supplied

Hypercoagulable state in hypercholesterolemic subjects assessed by platelet-dependent thrombin generation: in vitro effect of cerivastatin.

BACKGROUND: Hypercholesterolemia is an important risk factor to develop acute thrombotic complications of atherosclerosis like to myocardial infarction and ischemic stroke. Platelets and coagulation factors are strictly involved in the genesis of such thrombotic events and their hyperactivity in hypercholesterolemic patients has been previously reported. Moreover some cholesterol-lowering molecules (statins) seem to be able of reducing platelet activity. METHODS: We performed platelet-dependent thrombin generation (colorimetric method) to assess the coagulative potential of 40 caucasian hypercholesterolemic subjects with respect to normal controls and to the grade of hypercholesterolemia. Moreover we observed the effect of platelets from hypercholesterolemics on thrombin generation in plasma from normal subjects. The effect of Cerivastatin on thrombin generation was evaluated too. RESULTS: Our data show an increased thrombin generation both in mild and high hypercholesterolemic subjects with respect to controls (424.6+/-30.5 vs. 197.1+/-27.4 mIU/ml). No significant difference in the amount of thrombin generation was found between mild and high hypercholesterolemics (399.6+/-20.7 vs. 440.2+/-21.4 mIU/ml). Platelets directly influence thrombin generation and they present an intrinsic hyperactivity that can be modulated by Cerivastatin (223.6+/-24.8 vs. 424.6+/-30.5 mIU/ml). CONCLUSIONS: Mild hypercholesterolemia is associated with an increased thrombinic potential that may be considered an added risk factor to develop thrombotic events. Platelets directly influences this hypercoagulative state and Cerivastatin is able to reduce thrombin generation by way of a direct interaction with platelets.

Blood Coagulation Disorders↗