Biomedical subjects

M Cercignani

Publications and source records attributed to M Cercignani.

At least 19 recordsLinked to original sources

PubMed2002

Intra-voxel and inter-voxel coherence in patients with multiple sclerosis assessed using diffusion tensor MRI.

Previous diffusion tensor magnetic resonance imaging (DT-MRI) studies reported mean diffusivity () and fractional anisotropy (FA) changes in lesions and normal-appearing white matter (NAWM) of patients with multiple sclerosis (MS), but neglected the additional information which can be obtained by the analysis of the inter-voxel coherence (C). The present study is based on a large sample of patients with MS and it is aimed at assessing the potential role of C in the quantification of MS-related tissue damage of T2-visible lesions and NAWM. We obtained dual-echo, T1-weighted and DT-MRI scans from 78 patients with relapsing-remitting (RR), secondary progressive (SP), or primary progressive (PP) MS and from 26 healthy volunteers. We calculated, FA and C of T2-hyperintense lesions, T1-isointense lesions, T1-hypointense lesions and several areas of the NAWM. and FA of the majority of NAWM regions studied from MS patients were different from the corresponding quantities of the white matter from controls. NAWM C from patients was lower than white matter C from controls only for the parietal pericallosal areas. SPMS patients had higher corpus callosum and lower corpus callosum FA and C than patients with either RRMS or PPMS. Average lesion was higher, and average FA and C lower than the corresponding quantities measured in the NAWM. Average T1-hypointense lesion was higher and average FA lower than the corresponding quantities of T1-isointense lesions, whereas average C of these two lesion populations were not different. SPMS had higher average lesion than both PPMS and RRMS patients. NAWM and C of the corpus callosum were moderately correlated with disability. This study confirms the role of DT-MRI metrics to identify MS lesions with different amounts of tissue damage and to detect diffuse changes in the NAWM. It also shows that measuring C enables us to obtain additional information about tissue damage, which is complementary to that given by the analysis of and FA.

Adult↗

PubMed2002

Time-dependent effect of statins on platelet function in hypercholesterolaemia.

BACKGROUND: Reduction of platelet activity induced by statins has been described as a positive effect exerted by such molecules on vascular thrombotic events. However, the relations among cholesterol (LDL-C) reduction, the timing of the antiplatelet effect, the involved mechanisms and the doses of each statin able to reduce platelet function are not actually well known. The aim of our study was to evaluate the impact of simvastatin (20 mg day-1), atorvastatin (10 mg day-1), fluvastatin (40 mg day-1) and pravastatin (40 mg day-1) on platelet function in hypercholesterolaemic subjects with relation to (LDL-C), oxidized-LDL (ox-LDL) and antiport mechanism modifications. MATERIALS AND METHODS: Sixteen subjects were assigned to each treatment (40 males, 24 females, mean age 48.7 +/- 13.4, LDL-C 5.13 +/- 0,23 mmol L-1) and evaluated for platelet surface P-selectin (P-sel), lipid profile, ox-LDL, platelet-associated ox-LDL (Pox-LDL), platelet cholesterol content, antiport mechanisms, and intracellular and systemic NO synthase every 7 days for one month. RESULTS: Our data show a strong relation between enhanced P-sel and Pox-LDL (r = 0.68, P < 0.01). Simvastatin, atorvastatin, fluvastatin and pravastatin reduce platelet activity after 1, 2, 3 and 4 weeks of treatment, respectively (P < 0.001, P < 0.001, P < 0.01, P < 0.05). Pox-LDL are modulated early by simvastatin, atorvastatin and fluvastatin Pox-LDL (r = 0.66, 0.65 and 0.52; P < 0.001, 0.001 and 0.01, respectively) whereas LDL-C and ox-LDL reductions associated to modifications of antiport activity act later. Moreover, they are the most relevant finding in pravastatin-related subjects. CONCLUSIONS: Our data suggest a different impact of several statins on platelet function, which is initially related to interference with Pox-LDL rather than LDL-C reduction.

Adult↗

PubMed2002

White matter damage in Alzheimer's disease assessed in vivo using diffusion tensor magnetic resonance imaging.

OBJECTIVE: To investigate the extent and the nature of white matter tissue damage of patients with Alzheimer's disease using diffusion tensor magnetic resonance imaging (DT-MRI). BACKGROUND: Although Alzheimer's disease pathology mainly affects cortical grey matter, previous pathological and MRI studies showed that also the brain white matter of patients is damaged. However, the nature of Alzheimer's disease associated white matter damage is still unclear. METHODS: Conventional and DT-MRI scans were obtained from 16 patients with Alzheimer's disease and 10 sex and age matched healthy volunteers. The mean diffusivity (D), fractional anisotropy (FA), and inter-voxel coherence (C) of several white matter regions were measured. RESULTS: D was higher and FA lower in the corpus callosum, as well as in the white matter of the frontal, temporal, and parietal lobes from patients with Alzheimer's disease than in the corresponding regions from healthy controls. D and FA of the white matter of the occipital lobe and internal capsule were not different between patients and controls. C values were also not different between patients and controls for any of the regions studied. Strong correlations were found between the mini mental state examination score and the average overall white matter D (r=0.92, p<0.001) and FA (r=0.78; p<0.001). CONCLUSIONS: White matter changes in patients with Alzheimer's disease are likely to be secondary to wallerian degeneration of fibre tracts due to neuronal loss in cortical associative areas.

Aged↗

PubMed2001

Quantification of tissue damage in AD using diffusion tensor and magnetization transfer MRI.

The authors measured mean diffusivity (D) and magnetization transfer ratio (MTR) of the brain from 18 patients with AD and 16 healthy control subjects. The peak heights of cortical gray matter (cGM) D (p < 0.001) and MTR (p < 0.001) histograms were lower and average cGM D (p < 0.01) higher in patients with AD than in control subjects. A composite MR score based on brain volume and cGM MTR peak height was correlated with patient cognitive impairment (r = 0.65, p = 0.003). This preliminary study presents a novel approach to quantify AD-related tissue damage in-vivo.

Aged↗

PubMed2001

The physical basis of diffusion-weighted MRI.

Diffusion-weighted (DW) magnetic resonance imaging (MRI) is the only technique that permits a non-invasive in vivo assessment of water molecular diffusion, which reflects tissue configuration at a microscopic level. Therefore, this technique appears to be particularly useful in monitoring brain abnormalities. However, the quantitative measurement of diffusion is not without problems, which may limit the widespread use of diffusion-weighted MRI. In this report, the phenomenon of diffusion is described, together with its effect on the nuclear magnetic resonance signal. The concepts of diffusion anisotropy and diffusion tensor are also introduced, and the technical and hardware requirements are discussed.

Algorithms↗

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

Segmenting brain white matter, gray matter and cerebro-spinal fluid using diffusion tensor-MRI derived indices.

Based on its ability to provide quantitative information about tissue microstructure, diffusion tensor magnetic resonance imaging (DT-MRI) might be a valuable approach to improve the reliability of segmentation of the various brain tissues. In this study, a fully automated and easy-to-implement technique based on 2D histogram analysis of DT-MRI derived images was used to segment white and gray matter of the brain from 10 healthy subjects (aged = 27-56 years). The results obtained with this novel segmentation strategy were compared to those achieved by two experienced observers using an operator-dependent segmentation on the dual-echo scans. Visual inspection of the segmented tissues from a third senior observer disclosed that the automated technique worked properly on all images from all subjects and was more accurate than the human raters in defining thalamus white and gray matter portions as well as in tissue classification at the external brain edge. In addition, this segmentation technique resulted in an average gray/white matter ratio similar to that reported by post-mortem assessment. The application of the operator-dependent segmentation strategy was extremely time-consuming and the two observers achieved poorly reproducible results. Segmenting brain white and gray matter using information from DT-MRI proved to be an accurate approach with the potential for improving the understanding of the pathophysiology of many neurologic conditions.

Anisotropy↗

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↗

PubMed2001

Mean diffusivity and fractional anisotropy histograms of patients with multiple sclerosis.

BACKGROUND AND PURPOSE: Compared with conventional T2-weighted MR imaging, diffusion tensor MR imaging provides quantitative indices with increased specificity to the most destructive aspects of multiple sclerosis. In this study, we obtained brain mean diffusivity (_D) and fractional anisotropy histograms of patients with multiple sclerosis to compare them with those of healthy volunteers and to investigate the correlation between diffusion tensor MR imaging histogram-derived measures and the level of disability and quantities derived from conventional MR imaging. METHODS: Dual-echo and diffusion tensor MR images were obtained from 78 patients with relapsing-remitting, secondary progressive, or primary progressive multiple sclerosis and from 20 healthy control volunteers. After obtaining mean diffusivity (_D) and fractional anisotropy images and image coregistration, _D and fractional anisotropy histograms were created. From each histogram, the following measures were derived: the average _D and fractional anisotropy, the histogram peak heights, and the histogram peak locations. RESULTS: All the _D and fractional anisotropy histogram-derived measures were different between patients and controls at a significance level of P <.001. No differences were found in any of the considered quantities among the three multiple sclerosis phenotypes. In patients with relapsing-remitting multiple sclerosis, disability was correlated with histogram average_D (r = 0.4, P =.01) and peak height (r = -0.4, P =.01). In patients with secondary progressive multiple sclerosis, disability was correlated with fractional anisotropy histogram peak position (r = -0.6, P =.01). Significant correlations were also found between T2 lesion load and various diffusion tensor MR quantities. CONCLUSION: This study shows that brain _D and fractional anisotropy histograms are different for patients with multiple sclerosis compared with control volunteers. This study also shows that quantities derived from diffusion tensor MR imaging are correlated with disability in patients with relapsing-remitting multiple sclerosis and secondary progressive multiple sclerosis, suggesting that they might serve as additional measures of outcome when monitoring multiple sclerosis evolution in these patients.

Adult↗

PubMed2001

Effect of diet and treatment with statins on platelet-dependent thrombin generation in hypercholesterolemic subjects.

BACKGROUND AND AIM: Platelets are strictly involved in arterial thrombosis and their hyperactivity has been shown in hypercholesterolemia. It has been reported that drugs affecting cholesterol metabolism (statins) decrease cardiovascular events by lowering lipid levels or by means of non-lipidic actions such as the direct inhibition of platelet function. The aim of this study was to detect the effect on platelet-dependent thrombin generation (PDTG) of a reduction in cholesterol obtained by means of a lipid-lowering diet or treatment with statins. METHODS AND RESULTS: We compared PDTG (T0) in 144 hypercholesterolemic subjects (94 males and 50 females of child-bearing age, mean age 48.2 +/- 13.8, plasma total cholesterol 6.93 +/- 0.64, high density lipoprotein cholesterol 1.25 +/- 0.14, triglycerides 1.15 +/- 0.19 mmol/L) and 70 normolipidemic controls (37 males and 33 females, mean age 43.1 +/- 12.6. After six weeks on an appropriate diet, the patients were randomised to receive different statin therapies if there was no reduction in their lipid profile and/or PDTG (T1). They were re-evaluated six weeks later, and the drug doses were maintained or increased on the basis of the variables (T2). A final evaluation was made after a further six weeks (T3). All of the data were evaluated using ANOVA and Spearman's correlation coefficent. The results showed increased PDTG in hypercholesterolemic subjects (418.2 +/- 29.2 mIU/mL, p < 0.001 vs controls). Diet alone did not reduce PDTG (380.2 +/- 28.5 mIU/mL, p = 0.226 vs controls). At T2, simvastatin and atorvastatin significantly decreased PDTG (P < 0.001 vs T0-1) and low-density lipoprotein cholesterol (LDL-C). No correlation was found between the two variables in the simvastatin group (r = 0.16). Cerivastatin reduced PDTG without significantly decreasing LDL-C (p < 0.001 and p = 0.476, r = 0.14). Pravastatin and fluvastatin significantly reduced thrombin generation only at T3 (40 mg/day); pravastatin was also associated with a decrease in LDL-C (p < 0.01, r = 0.66). CONCLUSIONS: Our results confirm an increased PDTG in patients with type IIa hyperlipoproteinemia, which is not reduced by diet. Statins at different doses significantly decrease PDTG but do not correlate with a reduction in LDL-C.

Adult↗

PubMed2001

Different mechanisms of fibrinolysis impairment among dyslipidemic subjects.

To determine whether there is a correlation between fibrinolytic activity and dyslipidemia, we performed a study of 72 subjects (20 patients with hypercholesterolemia, 20 with hypertriglyceridemia, 12 with isolated low high-density lipoprotein (HDL)-cholesterol (mean age 47.7 +/- 6.3, body mass index 24.7 +/- 0.4) and 20 healthy controls. Plasminogen activator inhibitor-1 (PAI-1), tissue-plasminogen activator activity and plasmin-antiplasmin complexes (PAP) were detected at baseline and after venous occlusion test. We also measured at baseline lipidic pattern, soluble E and P selectins (sE-sel, sP-sel), prothrombin factor 1+2 (F1+2), lipoprotein(a), factor VII, plasma insulin, fibrinogen, homocysteine, and thrombin activable fibrinolysis inhibitor (TAFI) activity. Fibrinolysis was significantly reduced in hypertriglyceridemic patients compared with hypercholesterolemic patients and control subjects (PAP, p < 0.01 and p < 0.001) and was associated with increased PAI-1 (at baseline and after venous occlusion test, p < 0.001). sP-sel, F1 +2 and TAFI were not significantly different compared with controls, while hypercholesterolemic subjects showed a significant increase in these parameters (p < 0.001), which were related to decreased PAP only at the upper low-density lipoprotein (LDL)-cholesterol levels (>160 mg/dl) (p < 0.001, r = -0.76). Moreover, there was no significant difference in PAI-1 activity (at baseline and after venous occlusion test) compared with controls. In conclusion, endothelial dysfunction was the main mechanism of decreased fibrinolysis in subjects with hypertriglyceridemia and low HDL-cholesterol, while enhanced thrombin generation and TAFI activity were the main determinants in hypercholesterolemia.

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↗