Biomedical subjects

M Bozzali

Publications and source records attributed to M Bozzali.

At least 19 recordsLinked to original sources

PubMed2006

Left prefrontal cortex control of novel occurrences during recollection: a psychopharmacological study using scopolamine and event-related fMRI.

Recollection and familiarity represent two processes involved in episodic memory retrieval. We investigated how scopolamine (an antagonist of acetylcholine muscarinic receptors) influenced brain activity during memory retrieval, using a paradigm that separated recollection and familiarity. Eighteen healthy volunteers were recruited in a randomized, placebo-controlled, double-blind design using event-related fMRI. Participants were required to perform a verbal recognition memory task within the scanner, either under placebo or scopolamine conditions. Depending on the subcondition, participants were required to make a simple recognition decision (old/new items) or base their decision on more specific information related to prior experience (target/non-target/new items). We show a drug modulation in left prefrontal and perirhinal cortex during recollection. Such an effect was specifically driven by novelty and showed an inverse correlation with accuracy performance. Additionally, we show a direct correlation between drug-related signal change in left prefrontal and perirhinal cortices. We discuss the findings in terms of acetylcholine mediation of the familiarity/novelty signal through perirhinal cortex and the control of the relative signal strength through prefrontal cortex.

Adult↗

PubMed2006

The contribution of voxel-based morphometry in staging patients with mild cognitive impairment.

OBJECTIVE: To assess whether different patterns of regional gray matter loss in patients with mild cognitive impairment (MCI) are associated with different risks of conversion to Alzheimer disease (AD), using MRI and voxel-based morphometry (VBM). METHODS: The authors recruited 22 patients with MCI, 22 patients with probable AD, and 20 healthy subjects (HS). T1 volumes from each subject were postprocessed according to an optimized VBM protocol. All patients were clinically followed up (mean [SD] time = 28.7 [5.7] months), and patients with MCI were reclassified into two groups (converters and nonconverters to AD). RESULTS: When comparing patients with AD to HS, widespread areas of reduced gray matter density were found predominantly in temporal, frontal, and parietal lobes and in the insula. Comparing MCI converters and nonconverters with HS, the converters showed more widespread areas of reduced gray matter density than nonconverters, with a pattern of abnormalities similar to that seen in patients with AD. Conversely, when comparing the same groups with patients with AD, MCI nonconverters showed a pattern of gray matter density similar to that of HS. Areas of decreased gray matter density were also found in MCI converters compared with nonconverters. CONCLUSIONS: Different patterns of gray matter density distribution in patients with mild cognitive impairment may be associated to different rates of conversion to Alzheimer disease.

Aged↗

PubMed2005

A whole brain MR spectroscopy study from patients with Alzheimer's disease and mild cognitive impairment.

Brain damage in Alzheimer's disease (AD) and mild cognitive impairment (MCI) is widespread with involvement of large portions of the neocortex and the subcortical white matter. A quantitative measure of neuronal damage of the entire brain might be valuable in the context of large-scale, longitudinal studies of these patients. This study investigated the extent of neuroaxonal injury of patients with AD and MCI using a novel unlocalized proton magnetic resonance spectroscopy ((1)H-MRS) technique, which allows quantification of the concentration of N-acetylaspartate from the whole of the brain tissue (WBNAA). Conventional brain MRI and WBNAA were obtained from 28 AD patients, 27 MCI patients and 25 age-matched controls. Normalized brain volume (NBV) was also measured using an automated segmentation technique. WBNAA and NBV showed a significant heterogeneity between groups (P < 0.001). WBNAA concentration was different between controls and MCI patients (P = 0.003), but not between MCI and AD patients (P = 0.33). NBV differed both between controls and MCI patients (P = 0.02) and between MCI and AD patients (P = 0.03). A multivariate regression model retained WBNAA as the best MRI predictor of the Mini Mental State Examination score (P = 0.001). Significant neuronal damage, which is related to the extent of cognitive decline, can be quantified in the whole brain tissue of patients with AD, using a novel (1)H-MRS approach. The demonstration in patients with MCI of MR structural and metabolic findings, intermediate between those of healthy volunteers and those of AD patients, indicates that neuronal damage is already evident and widespread in individuals with MCI before they are clinically demented.

Aged↗

PubMed2005

Brain tissue damage in dementia with Lewy bodies: an in vivo diffusion tensor MRI study.

The aim of the present study was to apply diffusion tensor MRI (DT-MRI), a quantitative MRI measure which reflects tissue organization, to dementia with Lewy bodies (DLB). DT-MRI scans were obtained from 15 patients with probable DLB and 10 sex- and age-matched healthy controls. Abnormalities were found in the corpus callosum, pericallosal areas and the frontal, parietal, occipital and, less prominently, temporal white matter of patients compared with controls. Abnormalities were also found in the caudate nucleus and the putamen. The average grey matter volume was lower in patients than in controls. These findings of concomitant grey matter atrophy and white matter abnormalities (as detected by DT-MRI) in regions with a high prevalence of long connecting fibre tracts might suggest the presence of neurodegeneration involving associative cortices. The modest involvement of the temporal lobe fits with the relative preservation of global neuropsychological measures and memory tasks in the early stage of DLB. The selective involvement of parietal, frontal and occipital lobes might explain some of the clinical and neuropsychological features of DLB, providing a possible distinctive marker for this disease. The abnormalities found in the subcortical grey matter may indicate that DLB and Parkinson's disease share a similar nigrostriatal involvement caused by common pathophysiological mechanisms.

Aged↗

PubMed2004

An MT MRI study of the cervical cord in clinically isolated syndromes suggestive of MS.

Cervical cord magnetization transfer ratio (MTR) histograms were obtained from 45 patients at presentation with clinically isolated syndromes (CIS) suggestive of multiple sclerosis (MS). The mean values of MTR histogram-derived metrics were not different between CIS patients and healthy control subjects or between patients with and without evidence of disease dissemination in time. Only three patients showed significantly lower cord MTR values than control subjects. These findings suggest the absence of intrinsic structural damage of the cervical cord soon after the onset of CIS suggestive of MS, even in those patients with an early evolution to MS.

Adolescent↗

PubMed2003

Evidence for widespread axonal damage at the earliest clinical stage of multiple sclerosis.

Although axonal pathology is recognized as one of the major pathological features of multiple sclerosis, it is less clear how early in its course it occurs and how it correlates with MRI-visible lesion loads. To assess this early axonal pathology, we quantified the concentration of whole-brain N-acetylaspartate (WBNAA) in a group of patients at the earliest clinical stage of the disease and compared the results with those from healthy controls. Conventional brain MRI and WBNAA using unlocalized proton magnetic resonance spectroscopy were obtained from 31 patients at presentation with clinically isolated syndromes suggestive of multiple sclerosis and paraclinical evidence of dissemination in space, and from 16 matched controls. An additional conventional MRI scan was obtained in all patients 4-6 months later to detect dissemination of lesions in time. The mean WBNAA concentration was significantly lower in patients compared with the controls (P < 0.0001). It was not significantly different between patients with and without enhancing lesions at the baseline MRI or between patients with and without lesion dissemination in time. No correlation was found between WBNAA concentrations and lesion volumes. Widespread axonal pathology, largely independent of MRI-visible inflammation and too extensive to be completely reversible, occurs in patients even at the earliest clinical stage of multiple sclerosis. This finding lessens the validity of the current concept that the axonal pathology of multiple sclerosis is the end-stage result of repeated inflammatory events, and argues strongly in favour of early neuroprotective intervention.

Adult↗

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

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

Magnetization transfer and diffusion tensor MR imaging of basal ganglia from patients with multiple sclerosis.

Although post-mortem studies have shown that lesions of multiple sclerosis (MS) can be detected in the basal ganglia, conventional T2-weighted magnetic resonance (MR) imaging is poorly sensitive for detecting such abnormalities. This study was performed to investigate whether magnetization transfer (MT) and diffusion tensor MR imaging are able to detect in vivo basal ganglia changes in patients with MS. After image coregistration, MT ratio (MTR) and mean diffusivity (&Dmacr;) maps were obtained and MTR and &Dmacr; values of the putamen, head of the caudatus and thalamus measured from 31 patients with clinically definite MS and 14 age- and sex-matched healthy volunteers using region of interest analysis. Although we found slightly decreased MTR and increased &Dmacr; in the basal ganglia from patients compared to controls, suggesting increased extra-cellular water and reduced amount of 'barriers' restricting water molecular motion in the basal ganglia of patients with MS, none of the differences was statistically significant. These data suggest that the more sophisticated MR probes of tissue disruption and cellular integrity are no more sensitive than current conventional imaging for detecting basal ganglia abnormalities in patients with MS.

Adult↗

PubMed2001

An MR study of tissue damage in the cervical cord of patients with migraine.

Hyperintense abnormalities on T2-weighted magnetic resonance (MR) scans of the brain from patients with migraine are a relatively frequent finding and may represent a diagnostic challenge. We studied the cervical cord of patients with migraine using T2-weighted and magnetization transfer (MT) scans to assess whether the study of macro- and microscopic tissue damage in the cervical cord of these patients may have some diagnostic utility. T2-weighted and MT scans of the cervical cord and dual-echo scans of the brain were acquired from 16 patients with migraine and 17 sex- and age-matched healthy volunteers. Cervical cord MT ratio (MTR) histograms were obtained from all subjects and the relative peak height, the peak position, and the average MTR measured. Five migraine patients (31%) had hyperintense lesions in the brain. Neither healthy controls nor patients with migraine had any abnormalities on cervical cord MR scans. There was no difference for any of the cord MTR histogram-derived metrics between patients with migraine and healthy controls. No MTR histogram-derived measures from migraine patients were 2 standard deviations below the mean values from controls. Patients with migraine do not have MR or MT abnormalities in the cervical cord. MR scanning of the cervical cord in patients with migraine and hyperintense brain lesions of unknown etiology may be a useful investigation to facilitate the diagnostic workout.

Adolescent↗

PubMed2001

In vivo assessment of the brain and cervical cord pathology of patients with primary progressive multiple sclerosis.

In patients with primary progressive (PP) multiple sclerosis, brain MRI lesion activity and burden are low, despite the presence of severe neurological impairment. On the contrary, the degree of cord atrophy and diffuse tissue damage in the brain and cervical cord have been found to be associated with clinical disability. Against this background, this study aimed at providing an in vivo indirect assessment of brain and cervical cord pathology in a large cohort of PP multiple sclerosis patients, using conventional MRI and magnetization transfer imaging (MTI). Ninety-one PP multiple sclerosis patients, 36 secondary progressive (SP) multiple sclerosis patients and 30 healthy controls underwent brain and cervical cord MRI scans, using dual echo (brain) or fast short-tau inversion recovery (cervical cord) MTI and T(1)-weighted sequences. For the brain, T(2) hyperintense and T(1) hypointense lesion volumes were calculated and the volume of the whole of the brain tissue measured. For the cervical cord, the number and burden of lesions and the cross-sectional area were assessed. MTI scans were post-processed and analysed to obtain magnetization transfer ratio (MTR) histograms from the whole of the brain and cervical cord tissue and from the normal-appearing brain tissue in isolation. In PP multiple sclerosis patients, brain, normal-appearing brain tissue and cervical cord MTR histogram-derived metrics revealed the presence of diffuse tissue damage whose characteristics did not significantly differ from those of SP multiple sclerosis patients, even though SP multiple sclerosis patients had higher MRI-visible lesion burdens. None of the correlations between MRI or MTI measures obtained from the brain and the cord were significant. PP multiple sclerosis patients' disability was significantly, albeit weakly associated with a composite MR model including measures of loss and intrinsic damage of cervical cord tissue. Our data indicate the presence of a diffuse tissue damage undetectable by conventional MRI in PP multiple sclerosis patients, whose extent seems to match that of SP multiple sclerosis patients with similar levels of disability. They also suggest that the severity of multiple sclerosis pathology in the cervical cord is one of the factors contributing to neurological impairment in PP multiple sclerosis.

Adult↗

PubMed2001

Brain activation in normal subjects and in patients affected by mitochondrial disease without clinical central nervous system involvement: a phosphorus magnetic resonance spectroscopy study.

It remains unclear whether brain energetics is disturbed in patients with mitochondrial disease without clinical central nervous system involvement (MDW). The authors used the high temporal and spatial resolution phosphorus magnetic resonance spectroscopy (31P MRS) technique that they developed to study high energy phosphates (HEPs) and intracellular pH (pH) in the visual cortex of 9 normal subjects and 5 MDW patients with single mtDNA deletion at rest, during, and after visual activation. In normal subjects, HEPs remained unchanged during activation but rose significantly (by 17%) during recovery, and pH increased during visual activation with a slow return to rest values. In MDW patients, HEPs were within the normal range at rest and did not change during activation, but fell significantly (by 22%) in the recovery period; pH did not reveal a homogeneous pattern. In the brain of patients with MDW, energy balance remains normal until oxidative metabolism is intensively stressed, as during a postactivation phase. The heterogeneity of the physicochemical environment (that is, pH) suggests various degrees of subclinical brain involvement. The combined use of MRS and brain activation is fundamental for the study of brain energetics and may prove an important diagnostic tool in patients with MDW.

Adenosine Triphosphate↗

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

Cloning and molecular characterization of three ubiquitin fusion degradation 1 (Ufd1) ortholog genes from Xenopus laevis, Gallus gallus and Drosophila melanogaster.

The yeast ubiquitin fusion degradation 1 (Ufd1) protein is involved in a degradation pathway for ubiquitin fused products. The human ortholog gene (UFD1-like, UFD1L) is deleted in patients affected by the DiGeorge/velocardiofacial syndromes. We report the cloning of UFD1L orthologs from Drosophila melanogaster (dufd1l), Xenopus laevis and Gallus gallus. The 1,125-bp Drosophila cDNA encodes a protein of 316 amino acids, showing 60% identity with the human and murine proteins. The identity to the G. gallus, X. laevis, C. elegans and S. cerevisiae proteins is 95%, 83%, 32%, and 36%, respectively. Northern expression data in Drosophila indicate that dufd1l is expressed through embryonic, larval and pupal development, as well as in the adult fly.

Adaptor Proteins, Vesicular Transport↗

PubMed2001

A cluster of three single nucleotide polymorphisms in the 3'-untranslated region of human glycoprotein PC-1 gene stabilizes PC-1 mRNA and is associated with increased PC-1 protein content and insulin resistance-related abnormalities.

Glycoprotein PC-1 inhibits insulin signaling and, when overexpressed, plays a role in human insulin resistance. Mechanisms of PC-1 overexpression are unknown. We have identified a haplotype in the 3'-untranslated region of the PC-1 gene that may modulate PC-1 expression and confer an increased risk for insulin resistance. Individuals from Sicily, Italy, carrying the "P" haplotype (i.e., a cluster of three single nucleotide polymorphisms: G2897A, G2906C, and C2948T) were at higher risk (P < 0.01) for insulin resistance and had higher (P < 0.05) levels of plasma glucose and insulin during an oral glucose tolerance test and higher levels of cholesterol, HDL cholesterol, and systolic blood pressure. They also had higher (P < 0.05-0.01) PC-1 protein content in both skeletal muscle and cultured skin fibroblasts. In CHO cells transfected with either P or wild-type cDNA, specific PC-1 mRNA half-life was increased for those transfected with P (t/2 = 3.73 +/- 1.0 vs. 1.57 +/- 0.2 h; P < 0.01). In a population of different ethnicity (Gargano, East Coast Italy), patients with type 2 diabetes (the most likely clinical outcome of insulin resistance) had a higher P haplotype frequency than healthy control subjects (7.8 vs. 1.5%, P < 0.01), thus replicating the association between the P allele and the insulin resistance-related abnormalities observed among Sicilians. In conclusion, we have identified a possible molecular mechanism for PC-1 overexpression that confers an increased risk for insulin resistance-related abnormalities.

3' Untranslated Regions↗

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

A magnetization transfer histogram study of normal-appearing brain tissue in MS.

OBJECTIVE: To evaluate 1) the ability of magnetization transfer ratio (MTR) histogram analysis to detect the extent of changes occurring outside MS lesions seen on conventional scans, 2) whether such changes vary in the different MS clinical phenotypes, 3) whether the changes are associated with the extent and severity of the macroscopic lesion load, and 4) the contribution to brain atrophy. METHODS: Dual-echo, T1-weighted, and MT scans of the brain were obtained from 77 patients with varying MS courses and 20 age- and sex-matched control subjects. To create MT histograms of the normal-appearing cerebral tissue, MS lesions were segmented from dual-echo scans, superimposed automatically, and nulled out from the coregistered and scalp-stripped MTR maps. Average MTR, peak height, and peak position were considered. T2 and T1 lesion loads, average lesion MTR, and brain volume were also measured. RESULTS: Average histogram MTR (p<0.0001) and peak position (p<0.0001) from patients with relapsing-remitting MS (RMMS) were lower than those from control subjects. Patients with primary progressive MS (PPMS) had lower average histogram MTR (p = 0.002) and histogram peak height (p = 0.01) than control subjects. Patients with secondary progressive MS (SPMS) had a lower peak height (p = 0.05) than those with RRMS. Average lesion MTR (p<0.0001) correlated highly with the histogram MTR. Average histogram MTR (p<0.0001) and T2 lesion load (p = 0.001) correlated highly with brain volume. CONCLUSIONS: The amount of microscopic changes account for an important fraction of the lesion load in MS. They may contribute to the development of brain atrophy and tend to be more evident in patients with secondary progressive MS.

Adult↗