Education-Adjusted Normality Thresholds for FDG-PET in the Diagnosis of Alzheimer Disease.

BACKGROUND: A corollary of the reserve hypothesis is that what is regarded as pathological cortical metabolism in patients might vary according to education. OBJECTIVE: The aim of this study is to assess the incremental diagnostic value of education-adjusted over unadjusted thresholds on the diagnostic accuracy of FDG-PET as a biomarker for Alzheimer disease (AD). METHODS: We compared cortical metabolism in 90 healthy controls and 181 AD patients from the Alzheimer Disease Neuroimaging Initiative (ADNI) database. The AUC of the ROC curve did not differ significantly between the whole group and the higher-education patients or the lower-education subjects. RESULTS: The threshold of wMetaROI values providing 80% sensitivity was lower in higher-education patients and higher in the lower-education patients, compared to the standard threshold derived over the whole AD collective, without, however, significant changes in sensitivity and specificity. CONCLUSION: These data show that education, as a proxy of reserve, is not a major confounder in the diagnostic accuracy of FDG-PET in AD and the adoption of education-adjusted thresholds is not required in daily practice.

[MRI of medial-temporal atrophy as a biomarker for Alzheimer's disease]. / L'atrophie du lobe temporal mésial détectée par IRM en tant que biomarqueur de la maladie d'Alzheimer.

Significant progresses have been made in the understanding of the pathological mechanisms of Alzheimer's disease (AD) and in developing tools enabling to detect its stages and its progression in vivo. At present, we know that the changes in AD pathophysiology occur many years before its clinical manifestations. Atrophy of the medial temporal lobe - containing anatomical structures essential for declarative memory, mostly impaired in AD - is one of the biomarkers detectable by magnetic resonance which can help us to predict the progression to dementia in patients with mild cognitive impairment. The atrophy assessment of the posterior cingulate cortex and the precuneus, other key hubs of the declarative memory network, can also be a useful complement.

Ces dernières années, des découvertes significatives ont été faites au niveau de la compréhension des mécanismes physiopathologiques de la maladie d'Alzheimer (MA), ainsi que dans le développement des techniques capables de visualiser in vivo les différents stades et la progression de la maladie. On sait actuellement que la MA entraîne des modifications au niveau neurobiologique bien des années avant que les premiers symptômes n'apparaissent. L'atrophie du lobe temporal mésial ­ contenant les structures anatomiques engagées dans la mémoire déclarative ­ est l'un des biomarqueurs pouvant nous aider à prédire que les patients avec un déficit cognitif léger sont plus à risque de progresser vers la démence. L'évaluation de l'atrophie du cortex cingulaire postérieur et du précunéus, autres centres clés du réseau de la mémoire déclarative, peut aussi constituer un complément utile.

[Brain imaging of Alzheimer' disease: state of the art and perspectives for clinicians]. / Imagerie cérébrale de la maladie d'Alzheimer: état de l'art et perspectives pour le clinician.

To improve the clinical detection of Alzheimer's disease (AD) new diagnostic criteria have been proposed, based on biomarkers of synaptic dysfunction, AD-related neurodegeneration, and Aß cerebral amyloidosis. Magnetic resonance imaging (MRI) and position emission tomography (PET) neuroimaging can be configured as powerful means for the detection of medial-temporal atrophy, reduced uptake of 18F-FDG PET or and increased retention of Aß amyloid protein by amyloïd-PET. In this review, we will discuss these promising techniques that allow assessing in vivo AD pathology and help clinicians to better diagnose and follow-up patients, particularly in clinical trials using disease-modifying treatments.

A Comparison of Two Statistical Mapping Tools for Automated Brain FDG-PET Analysis in Predicting Conversion to Alzheimer's Disease in Subjects with Mild Cognitive Impairment.

OBJECTIVE: Automated voxel-based analysis methods are used to detect cortical hypometabolism typical of Alzheimer's Disease (AD) on FDG-PET brain scans. We compared the accuracy of two clinically validated tools for their ability to identify those MCI subjects progressing to AD at followup, to evaluate the impact of the analysis method on FDG-PET diagnostic performance. METHODS: SPMGrid and BRASS (Hermes Medical Solutions, Stockholm, Sweden) were tested on 131 MCI and elderly healthy controls from the EADC PET dataset. The concordance between the tools was tested by correlating the quantitative parameters (z- and t-values), calculated by the two software tools, and by measuring the topographical overlap of the abnormal regions (Dice score). Three independent expert readers blindly assigned a diagnosis based on the two map sets. We used conversion to AD dementia as the gold standard. RESULTS: The t-map and z-map calculated with SPMGrid and BRASS, respectively, showed a good correlation (R > .50) for the majority of individual cases (128/131) and for the majority of selected regions of interest (ROIs) (98/116). The overlap of the hypometabolic patterns from the two tools was, however, poor (Dice score .36). The diagnostic performance was comparable, with BRASS showing significantly higher sensitivity (.82 versus .59) and SPMGrid showing higher specificity (.87 versus .52). CONCLUSION: Despite similar diagnostic performance in predicting conversion to AD in MCI subjects, the two tools showed significant differences, and the maps provided by the tools showed limited overlap. These results underline the urgency for standardization across FDG-PET analysis methods for their use in clinical practice.

Hybrid PET-MRI in Alzheimer's Disease Research.

Multiple factors, namely amyloid, tau, inflammation, metabolic, and perfusion changes, contribute to the cascade of neurodegeneration and functional decline occurring in Alzheimer's disease (AD). These molecular and cellular processes and related functional and morphological changes can be visualized in vivo by two imaging modalities, namely positron emission tomography (PET) and magnetic resonance imaging (MRI). These imaging biomarkers are now part of the diagnostic algorithm and of particular interest for patient stratification and targeted drug development.In this field the availability of hybrid PET/MR systems not only offers a comprehensive evaluation in a single imaging session, but also opens new possibilities for the integration of the two imaging information. Here, we cover the clinical protocols and practical details of FDG, amyloid, and tau PET/MR imaging as applied in our institutions.

[¹¹C]acetate and PET/CT assessment of muscle activation in rat studies.

PURPOSE: The purpose of the present study is to apply kinetic analysis to investigate exercise-related changes in the metabolism of the skeletal muscle of the rat hindlimb by [[Formula: see text]]acetate positron emission tomography and computed tomography (PET/CT). METHODS: Contractions were induced in Wistar rats' left hindlimb by electrostimulation of the Vastus Lateralis muscle motor point. After 15 min of muscle contractions, [[Formula: see text]]acetate was injected and PET/CT of both hindlimbs was acquired. The resting hindlimb was used as a control reference. The kinetic parameters [Formula: see text] and [Formula: see text] were calculated for the target muscles (exercised and control) and correlated with the corresponding standardized uptake values (SUVs). The ratio between each kinetic parameter values and the SUV extracted for the exercised muscle and the muscle at rest was computed ([Formula: see text] and [Formula: see text], respectively). RESULTS: Kinetic analysis quantitatively confirmed that net tracer uptake ([Formula: see text]) and washout ([Formula: see text]) were significantly higher in exercised muscles ([Formula: see text] for exercised muscles vs. [Formula: see text] for resting muscles, [Formula: see text]; [Formula: see text] for exercised muscle vs. [Formula: see text] for resting muscle, [Formula: see text]). On the other hand, SUV was not significantly different between active and inactive muscles ([Formula: see text] for exercised muscles vs. [Formula: see text] for resting muscles). Linear regression analysis revealed a good correlation ([Formula: see text]) between net tracer uptake ratio ([Formula: see text]) and the SUV ratio [Formula: see text]). A lower correlation was found between the net tracer washout ratio ([Formula: see text]) and the SUV ratio ([Formula: see text]). CONCLUSION: The present study showed that kinetic modelling can detect changes between active and inactive skeletal muscles with a higher sensitivity with respect to the SUV, when performed with [[Formula: see text]]acetate PET/CT.