Optimized classification of 18F-Florbetaben PET scans as positive and negative using an SUVR quantitative approach and comparison to visual assessment

Introduction: Standardized uptake value ratios (SUVRs) calculated from cerebral cortical areas can be used to categorize 18F-Florbetaben (FBB) PET scans by applying appropriate cutoffs. The objective of this work was first to generate FBB SUVR cutoffs using visual assessment (VA) as standard of truth (SoT) for a number of reference regions (RR) (cerebellar gray matter (GCER), whole cerebellum (WCER), pons (PONS), and subcortical white matter (SWM)). Secondly, to validate the FBB PET scan categorization performed by SUVR cutoffs against the categorization made by post-mortem histopathological confirmation of the Aβ presence. Finally, to evaluate the added value of SUVR cutoff categorization to VA. Methods: SUVR cutoffs were generated for each RR using FBB scans from 143 subjects who were visually assessed by 3 readers. SUVR cutoffs were validated in 78 end-of life subjects using VA from 8 independent blinded readers (3 expert readers and 5 non-expert readers) and histopathological confirmation of the presence of neuritic beta-amyloid plaques as SoT. Finally, the number of correctly or incorrectly classified scans according to pathology results using VA and SUVR cutoffs was compared. Results: Composite SUVR cutoffs generated were 1.43 (GCER), 0.96 (WCER), 0.78 (PONS) and 0.71 (SWM). Accuracy values were high and consistent across RR (range 83–94% for histopathology, and 85–94% for VA). SUVR cutoff performed similarly as VA but did not improve VA classification of FBB scans read either by expert readers or the majority read but provided higher accuracy than some non-expert readers. Conclusion: The accurate scan classification obtained in this study supports the use of VA as SoT to generate site-specific SUVR cutoffs. For an elderly end of life population, VA and SUVR cutoff categorization perform similarly in classifying FBB scans as Aβ-positive or Aβ-negative. These results emphasize the additional contribution that SUVR cutoff classification may have compared with VA performed by non-expert readers. Keywords: Florbetaben, PET, SUVR, Quantification, Visual assessmen

Age dependence of brain b-amyloid deposition in Down syndrome: An [18F]florbetaben PET study

Objective: To investigate brain β-amyloid binding in subjects with Down syndrome (DS) using [18F] florbetaben PET imaging. Methods: Thirty-nine subjects with DS (46.3 ± 4.7 years) were assessed with [18F]florbetaben PET imaging. Three blinded independent readers assessed the scans to provide a visual analysis. The primary quantitative imaging outcome was a standardized uptake value ratio (SUVR) obtained for 6 brain regions. Cognitive status was evaluated using the Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID). Results: [18F]Florbetaben uptake was correlated with age (p , 0.0001, R2 5 0.39); 90%of scans in subjects with DS aged 50 years or older (SUVR 5 1.62 ± 0.26), 53% in those aged 45 to 49 years (SUVR 5 1.43 ± 0.16), and 7%in those aged 40 to 45 years (SUVR 5 1.27 ± 0.11) were visually assessed as positive. Visual and quantitative assessments were highly related (x2 5 11.3823, p 5 0.0007; Cohen k 5 0.58). Only 2 of 34 participants were considered to have dementia by the DSQIID. Conclusions: Brain β-amyloid binding, as measured by [18F]florbetaben, increases with age in DS. Subjects with DS who have no evidence of dementia demonstrate brain β-amyloid binding in vivo, suggesting that [18F]florbetaben PET imaging may detect β-amyloid in this at-risk population

Randomized placebo-controlled phase II trial of autologous mesenchymal stem cells in multiple sclerosis.

Uncontrolled studies of mesenchymal stem cells (MSCs) in multiple sclerosis suggested some beneficial effect. In this randomized, double-blind, placebo-controlled, crossover phase II study we investigated their safety and efficacy in relapsing-remitting multiple sclerosis patients. Efficacy was evaluated in terms of cumulative number of gadolinium-enhancing lesions (GEL) on magnetic resonance imaging (MRI) at 6 months and at the end of the study.Patients unresponsive to conventional therapy, defined by at least 1 relapse and/or GEL on MRI scan in past 12 months, disease duration 2 to 10 years and Expanded Disability Status Scale (EDSS) 3.0-6.5 were randomized to receive IV 1-2×10(6) bone-marrow-derived-MSCs/Kg or placebo. After 6 months, the treatment was reversed and patients were followed-up for another 6 months. Secondary endpoints were clinical outcomes (relapses and disability by EDSS and MS Functional Composite), and several brain MRI and optical coherence tomography measures. Immunological tests were explored to assess the immunomodulatory effects.At baseline 9 patients were randomized to receive MSCs (n = 5) or placebo (n = 4). One patient on placebo withdrew after having 3 relapses in the first 5 months. We did not identify any serious adverse events. At 6 months, patients treated with MSCs had a trend to lower mean cumulative number of GEL (3.1, 95% CI = 1.1-8.8 vs 12.3, 95% CI = 4.4-34.5, p = 0.064), and at the end of study to reduced mean GEL (-2.8±5.9 vs 3±5.4, p = 0.075). No significant treatment differences were detected in the secondary endpoints. We observed a non-significant decrease of the frequency of Th1 (CD4+ IFN-γ+) cells in blood of MSCs treated patients.Bone-marrow-MSCs are safe and may reduce inflammatory MRI parameters supporting their immunomodulatory properties. ClinicalTrials.gov NCT01228266

Impact of florbetaben PET imaging on diagnosis and management of patients with suspected Alzheimer's Disease eligible for CSF analysis in France

Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI), Denver, CO, JUN 10-14, 2017International audienc

Impact of florbetaben PET imaging on diagnosis and management of patients with suspected Alzheimer's Disease eligible for CSF analysis in France

Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI), Denver, CO, JUN 10-14, 2017International audienc

Impact of florbetaben PET imaging on diagnosis and management of patients with suspected Alzheimer's Disease eligible for CSF analysis in France

Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI), Denver, CO, JUN 10-14, 2017International audienc

Randomized placebo-controlled phase II trial of autologous mesenchymal stem cells in multiple sclerosis

Bone-marrow-MSCs are safe and may reduce inflammatory MRI parameters supporting their immunomodulatory properties. ClinicalTrials.gov NCT01228266

Effects of MSCs in T and B cell population frequency in blood.

<p>Results are shown as percentages respect to the referring cell population (Th1, Th17, CD19 and Treg) and not referred to the total lymphocyte counts. Treatment with mesenchymal stem cells showed a non-significant decrease of the Th1/Th17 populations, increase in regulatory B cells (B reg) population and no changes regarding natural (Nat T reg) and induced (Ind T reg) regulatory T cells populations. Percentage of each population is shown in the graphics regarding the type of therapy, placebo (P) or mesenchymal stem cells (MSCs) and period of treatment, 1 (first period, from month 0 to month 6) or 2 (second period, from month 6 to 12 months).</p