Showing papers by "Daniela Perani published in 2014"

A Standardized [18F]-FDG-PET Template for Spatial Normalization in Statistical Parametric Mapping of Dementia

Abstract: [18F]-fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) is a widely used diagnostic tool that can detect and quantify pathophysiology, as assessed through changes in cerebral glucose metabolism. [18F]-FDG PET scans can be analyzed using voxel-based statistical methods such as Statistical Parametric Mapping (SPM) that provide statistical maps of brain abnormalities in single patients. In order to perform SPM, a "spatial normalization" of an individual's PET scan is required to match a reference PET template. The PET template currently used for SPM normalization is based on [15O]-H2O images and does not resemble either the specific metabolic features of [18F]-FDG brain scans or the specific morphological characteristics of individual brains affected by neurodegeneration. Thus, our aim was to create a new [18F]-FDG PET aging and dementia-specific template for spatial normalization, based on images derived from both age-matched controls and patients. We hypothesized that this template would increase spatial normalization accuracy and thereby preserve crucial information for research and diagnostic purposes. We investigated the statistical sensitivity and registration accuracy of normalization procedures based on the standard and new template-at the single-subject and group level-independently for subjects with Mild Cognitive Impairment (MCI), probable Alzheimer's Disease (AD), Frontotemporal lobar degeneration (FTLD) and dementia with Lewy bodies (DLB). We found a significant statistical effect of the population-specific FDG template-based normalisation in key anatomical regions for each dementia subtype, suggesting that spatial normalization with the new template provides more accurate estimates of metabolic abnormalities for single-subject and group analysis, and therefore, a more effective diagnostic measure.

Weighing brain activity with the balance: Angelo Mosso's original manuscripts come to light.

Abstract: Neuroimaging techniques, such as positron emission tomography and functional magnetic resonance imaging are essential tools for the analysis of organized neural systems in working and resting states, both in physiological and pathological conditions. They provide evidence of coupled metabolic and cerebral local blood flow changes that strictly depend upon cellular activity. In 1890, Charles Smart Roy and Charles Scott Sherrington suggested a link between brain circulation and metabolism. In the same year William James, in his introduction of the concept of brain blood flow variations during mental activities, briefly reported the studies of the Italian physiologist Angelo Mosso, a multifaceted researcher interested in the human circulatory system. James focused on Mosso’s recordings of brain pulsations in patients with skull breaches, and in the process only briefly referred to another invention of Mosso’s, the ‘human circulation balance’, which could non-invasively measure the redistribution of blood during emotional and intellectual activity. However, the details and precise workings of this instrument and the experiments Mosso performed with it have remained largely unknown. Having found Mosso’s original manuscripts in the archives, we remind the scientific community of his experiments with the ‘human circulation balance’ and of his establishment of the conceptual basis of non-invasive functional neuroimaging techniques. Mosso unearthed and investigated several critical variables that are still relevant in modern neuroimaging such as the ‘signal-to-noise ratio’, the appropriate choice of the experimental paradigm and the need for the simultaneous recording of differing physiological parameters.

FDG-PET and amyloid-PET imaging: the diverging paths.

Abstract: Purpose of review The availability of PET neuroimaging tools for the in-vivo assessment of metabolic dysfunction and amyloid burden in Alzheimer's disease has opened important methodological and practical issues in the diagnostic design and the conduct of new clinical trials. This review, addressing the different molecular information that the amyloid-PET and fluorodeoxyglucose-PET (FDG-PET) tools can provide, highlights their diverging paths in Alzheimer's disease and possible new perspectives in research and clinical applications. Recent findings Senile plaques and neurofibrillary tangles are prominent neuropathological hallmarks in Alzheimer's disease and are considered to be targets for therapeutic intervention and biomarkers for diagnostic in-vivo imaging agents. Alzheimer's disease is a slowly progressing disorder, in which pathophysiological abnormalities, detectable in vivo by PET biomarkers, precede clinical symptoms by many years to decades. The unitary view of Alzheimer's disease as a sequential pathological pathway, with beta-amyloid (Aβ) as the only initial and causal event (the 'amyloid cascade hypothesis'), is likely to be progressively replaced by a more complex picture, also on the basis of recent PET imaging findings showing that neuronal injury biomarkers and tau pathology can be independent of β-amyloid deposition. Summary The different molecular paths that PET in-vivo biomarkers can reveal in the timeframe of Alzheimer's disease progression reflect the events leading to deposition of Aβ and phosphorylated tau, neuronal injury and neurodegeneration, which can run in parallel instead of in a sequential manner. The amyloid and neuronal injury paths may diverge along the Alzheimer's disease cascade and bear separate relationships with Alzheimer's disease symptoms and clinical phenotypes. All these evidences are crucial for the diagnosis and the development of new drugs aimed at slowing or preventing dementia.

Brain Changes within the Visuo-Spatial Attentional Network in Posterior Cortical Atrophy

Abstract: Posterior cortical atrophy (PCA) is characterized by basic visual and high order visual-spatial dysfunctions. In this study, we investigated long-distance deafferentation processes within the frontal-parietal-occipital network in ten PCA patients using a MRI-PET combined approach. Objective voxel-based [18F]FDG-PET imaging measured metabolic changes in single patients. Comprehensive investigation of diffusion tensor imaging (DTI) metrics and grey-matter density with voxel-based morphometry were obtained in a subgroup of 6 patients. Fractional anisotropy in the superior longitudinal fasciculus correlated with the PET metabolic changes within the inferior parietal and frontal eye field regions. [18F]FDG-PET analysis showed in each PCA case the typical bilateral hypometabolic pattern, involving posterior temporal, parietal, and occipital cortex, with additional hypometabolic foci in the frontal eye fields. Voxel-based morphometry showed right-sided atrophy in the parieto-occipital cortex, as well as a limited temporal involvement. DTI revealed extensive degeneration of the major anterior-posterior connecting fiber bundles and of commissural frontal lobe tracts. Microstructural measures in the superior longitudinal fasciculus were correlated with the PET metabolic changes within the inferior parietal and frontal eye field regions. Our results confirmed the predominant occipital-temporal and occipital-parietal degeneration in PCA patients. [18F]FDG-PET and DTI-MRI combined approaches revealed neurodegeneration effects well beyond the classical posterior cortical involvement, most likely as a consequence of deafferentation processes within the occipital-parietal-frontal network that could be at the basis of visuo-perceptual, visuo-spatial integration and attention deficits in PCA.

Erratum to “A Survey of FDG- and Amyloid-PET Imaging in Dementia and GRADE Analysis”

Abstract: The authors' names were incorrectly listed as Perani Daniela, Schillaci Orazio, Padovani Alessandro, Nobili Flavio Mariano, Iaccarino Leonardo, Della Rosa Pasquale Anthony, Frisoni Giovanni, and Caltagirone Carlo; this error is corrected here. The addresses have been corrected.

PET Neuroimaging: Insights on Dystonia and Tourette Syndrome and Potential Applications

Abstract: Primary Dystonia (pD) is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both. Gilles de la Tourette Syndrome (GTS) is a childhood-onset neuropsychiatric developmental disorder characterised by motor and phonic tics, which could progress to behavioural changes. GTS and obsessive-compulsive disorders (OCD) are often seen in comorbidity, also suggesting a possible overlap in the pathophysiological bases of these two conditions. PET techniques are of considerable value in detecting functional and molecular abnormalities in vivo, according to the adopted radioligands. For example, PET is the unique technique that allows in vivo investigation of neurotransmitter systems, providing evidence of changes in GTS or pD. For example, presynaptic and postsynaptic dopaminergic studies with PET have shown alterations compatible with dysfunction or loss of D2-bearing neurons, increased synaptic dopamine levels, or both. Measures of cerebral glucose metabolism with 18F-fluorodeoxyglucose (18F-FDG PET) are very sensitive in showing brain functional alterations as well. 18F-FDG PET data have shown metabolic changes within the cortico-striato-pallido-thalamo-cortical and cerebello-thalamo-cortical networks, revealing possible involvement of brain circuits not limited to basal ganglia in pD and GTS. The aim of this work is to overview PET consistent neuroimaging literature on pD and GTS that has provided functional and molecular knowledge of the underlying neural dysfunction. Furthermore we suggest potential applications of these techniques in monitoring treatments.

PET radiotracers for molecular imaging in dementia.

Abstract: Molecular imaging with various biomarkers plays a significant role in the diagnostic assessment of patients with dementing disorders, by detecting functional and pathophysiologic changes in the brain. PET imaging, in particular, allows the measurements of different molecular targets, such as functional markers of neurodegeneration (glucose metabolism), markers for pathological aggregates (such as amyloid, tau and synuclein aggregates) and neuroinflammation, and also markers of several neurotransmission systems. In the current view, neurodegenerative diseases are associated with the development of pathologic changes that play a different role in disease onset and evolution, often starting long before the onset of clinically detectable impairment. Molecular imaging represents thus a unique tool to collect relevant information contributing to accurate diagnosis, treatment and response monitoring. In this article, we review the current literature focusing on the PET radiotracers used for molecular imaging in dementia.

The need for “objective measurements” in FDG and amyloid PET neuroimaging

Abstract: The process leading to the identification and validation of biomarkers for the diagnosis of early Alzheimer’s disease (early AD) has been a major focus of research interest in the past 10 years, and has been accompanied by a debate on the feasibility of implementing the research criteria in clinical practice. In the context of imaging performed using the two currently identified classes of AD biomarkers, i.e. markers of pathology and neurodegeneration, amyloid PET and 18F-FDG PET imaging are decisive tools whose crucial value is acknowledged in the recent guidelines for the early diagnosis of AD and other dementia conditions. The available recommendations draw on an extensive body of PET imaging literature, based mainly on visual methods. For the research criteria to be adopted in clinical settings, several uncertainties and gaps in knowledge must be overcome, in particular the low sensitivity and specificity provided by visual qualitative PET scan evaluation at the single-subject level. Indeed, the sensitivity and specificity of the 18F-FDG PET methods depend largely on the use of “objective methods” that result in improved accuracy for diagnosis and prognosis. Here, we review the most widely used parametric and semi-quantitative approaches to 18F-FDG PET and amyloid PET imaging, highlighting their importance in early and differential diagnosis in both research and clinical settings.

[18F]FDG PET Evidence Of Atypical Medial Temporal Lobe Dysfunction In Prodromal Alzheimer’s Disease (P6.325)

Abstract: Objective: We evaluated [ 18 F]FDG PET brain metabolic changes and hippocampus volume in a sample of mild cognitive impairment (MCI) subjects. Background: [ 18 F]FDG-PET imaging is a fundamental prognostic marker in MCI, supporting the presence of Alzheimer’s Disease (AD) pathology by the evidence of the typical temporo-parietal pattern. Beside the typical pathological pattern, however, a limbic-predominant AD subtype has been defined on the basis of the prevalent distribution of neurofibrillary tangles in the hippocampus compared with the cortex. Methods: Within a large series of MCI, we selected 13 subjects with a clinical-neuropsychological phenotype suggestive of selective episodic memory impairment. Single-subject voxel-based maps of [ 18 F]FDG distribution generated through statistical parametric mapping (SPM) assessed brain metabolic changes in a comparison to a database of 112 matched normal subjects. MRI volumetry measured medial temporal lobe atrophy. Clinical-neuropsychological features and CSF profile were also obtained. Results: The majority of cases showed an unusually selective unilateral or bilateral medial temporal hypometabolism; none showed the bilateral temporo-parietal metabolic pattern typical of AD. Additionally, in some cases, there was lateral temporal hypometabolism. VBM analysis showed significant atrophy in the hippocampal structures, even if less extended. Noteworthy, low Aβ42 values support the diagnosis of prodromal AD. Notwithstanding a long disease duration (mean duration from onset = 58.4±16.6 months; range 3-7 years), no subject progressed to dementia (mean follow-up 20.7±8.2 months). Conclusion: In this MCI group with predominant episodic memory deficits and very slow rate of progression, [ 18 F]FDG-PET and VBM-MRI findings suggest a specific and more limited anatomo-functional pattern, in comparison to the typical prodromal AD, compatible with the pathological limbic-predominant subtype. Single-subject [ 18 F]FDG-PET imaging can be useful in revealing MCI subtypes with more favourable prognosis and in MCI selection for clinical trials. Sources of support: Fondazione Eli-Lilly (grant 2011 "Imaging of neuroinflammation and neurodegeneration in prodromal and presymptomatic Alzheimer9s disease phases") and INMIND Project (FP7-HEALTH-2011-two stage "Imaging of neuroinflammation in neurodegenerative diseases" (grant agreement no. 278850). Disclosure: Dr. Cerami has nothing to disclose. Dr. Della Rosa has nothing to disclose. Dr. Dodich has nothing to disclose. Dr. Magnani has nothing to disclose. Dr. Marcone has nothing to disclose. Dr. Falini has nothing to disclose. Dr. Cappa has received personal compensation in an editorial capacity for Behavioral Neurology. Dr. Perani has nothing to disclose.