Preparing children with a mock scanner training protocol results in high quality structural and functional MRI scans

We evaluated the use of a mock scanner training protocol as an alternative for sedation and for preparing young children for (functional) magnetic resonance imaging (MRI). Children with severe mental retardation or developmental disorders were excluded. A group of 90 children (median age 6.5 years, range 3.65–14.5 years) participated in this study. Children were referred to the actual MRI investigation only when they passed the training. We assessed the pass rate of the mock scanner training sessions. In addition, the quality of both structural and functional MRI (fMRI) scans was rated on a semi-quantitative scale. The overall pass rate of the mock scanner training sessions was 85/90. Structural scans of diagnostic quality were obtained in 81/90 children, and fMRI scans with sufficient quality for further analysis were obtained in 30/43 of the children. Even in children under 7 years of age, who are generally sedated, the success rate of structural scans with diagnostic quality was 53/60. FMRI scans with sufficient quality were obtained in 23/36 of the children in this younger age group. The association between age and proportion of children with fMRI scans of sufficient quality was not statistically significant. We conclude that a mock MRI scanner training protocol can be useful to prepare children for a diagnostic MRI scan. It may reduce the need for sedation in young children undergoing MRI. Our protocol is also effective in preparing young children to participate in fMRI investigations

Model selection criteria for dynamic brain PET studies

BACKGROUND: Several criteria exist to identify the optimal model for quantification of tracer kinetics. The purpose of this study was to evaluate the correspondence in kinetic model preference identification for brain PET studies among five model selection criteria: Akaike Information Criterion (AIC), AIC unbiased (AICC), model selection criterion (MSC), Schwartz Criterion (SC), and F-test. MATERIALS AND METHODS: Six tracers were evaluated: [11C]FMZ, [11C]GMOM, [11C]PK11195, [11C]Raclopride, [18F]FDG, and [11C]PHT, including data from five subjects per tracer. Time activity curves (TACs) were analysed using six plasma input models: reversible single-tissue model (1T2k), irreversible two-tissue model (2T3k), and reversible two-tissue model (2T4k), all with and without blood volume fraction parameter (V B). For each tracer and criterion, the percentage of TACs preferring a certain model was calculated. RESULTS: For all radiotracers, strong agreement was seen across the model selection criteria. The F-test was considered as the reference, as it is a frequently used hypothesis test. The F-test confirmed the AIC preferred model in 87% of all cases. The strongest (but minimal) disagreement across regional TACs was found when comparing AIC with AICC. Despite these regional discrepancies, same preferred kinetic model was obtained using all criteria, with an exception of one FMZ subject. CONCLUSION: In conclusion, all five model selection criteria resulted in similar conclusions with only minor differences that did not affect overall model selection

The effect of amyloid pathology and glucose metabolism on cortical volume loss over time in Alzheimer’s disease

Purpose: The present multimodal neuroimaging study examined whether amyloid pathology and glucose metabolism are related to cortical volume loss over time in Alzheimer’s disease (AD) patients and healthy elderly controls. Methods: Structural MRI scans of eleven AD patients and ten controls were available at baseline and follow-up (mean interval 2.5 years). Change in brain structure over time was defined as percent change of cortical volume within seven a-priori defined regions that typically show the strongest structural loss in AD. In addition, two PET scans were performed at baseline: [[superscript 11]C]PIB to assess amyloid-β plaque load and [[superscript 18]F]FDG to assess glucose metabolism. [[superscript 11]C]PIB binding and [[superscript 18]F]FDG uptake were measured in the precuneus, a region in which both amyloid deposition and glucose hypometabolism occur early in the course of AD. Results: While amyloid-β plaque load at baseline was not related to cortical volume loss over time in either group, glucose metabolism within the group of AD patients was significantly related to volume loss over time (rho=0.56, p<0.05). Conclusion:The present study shows that in a group of AD patients amyloid-β plaque load as measured by [[superscript 11]C]PIB behaves as a trait marker (i.e., all AD patients showed elevated levels of amyloid, not related to subsequent disease course), whilst hypometabolism as measured by [[superscript 18]F]FDG changed over time indicating that it could serve as a state marker that is predictive of neurodegeneration.Hersenstichting Nederland (KS2011(1)-24)Athinoula A. Martinos Center for Biomedical ImagingInternationale Stichting Alzheimer Onderzoek (Project Number 11539

Prevalence of amyloid PET positivity in dementia syndromes: a meta-analysis

IMPORTANCE: Amyloid-β positron emission tomography (PET) imaging allows in vivo detection of fibrillar plaques, a core neuropathological feature of Alzheimer disease (AD). Its diagnostic utility is still unclear because amyloid plaques also occur in patients with non-AD dementia. OBJECTIVE: To use individual participant data meta-analysis to estimate the prevalence of amyloid positivity on PET in a wide variety of dementia syndromes. DATA SOURCES: The MEDLINE and Web of Science databases were searched from January 2004 to April 2015 for amyloid PET studies. STUDY SELECTION: Case reports and studies on neurological or psychiatric diseases other than dementia were excluded. Corresponding authors of eligible cohorts were invited to provide individual participant data. DATA EXTRACTION AND SYNTHESIS: Data were provided for 1359 participants with clinically diagnosed AD and 538 participants with non-AD dementia. The reference groups were 1849 healthy control participants (based on amyloid PET) and an independent sample of 1369 AD participants (based on autopsy). MAIN OUTCOMES AND MEASURES: Estimated prevalence of positive amyloid PET scans according to diagnosis, age, and apolipoprotein E (APOE) ε4 status, using the generalized estimating equations method. RESULTS: The likelihood of amyloid positivity was associated with age and APOE ε4 status. In AD dementia, the prevalence of amyloid positivity decreased from age 50 to 90 years in APOE ε4 noncarriers (86% [95% CI, 73%-94%] at 50 years to 68% [95% CI, 57%-77%] at 90 years; n = 377) and to a lesser degree in APOE ε4 carriers (97% [95% CI, 92%-99%] at 50 years to 90% [95% CI, 83%-94%] at 90 years; n = 593; P < .01). Similar associations of age and APOE ε4 with amyloid positivity were observed in participants with AD dementia at autopsy. In most non-AD dementias, amyloid positivity increased with both age (from 60 to 80 years) and APOE ε4 carriership (dementia with Lewy bodies: carriers [n = 16], 63% [95% CI, 48%-80%] at 60 years to 83% [95% CI, 67%-92%] at 80 years; noncarriers [n = 18], 29% [95% CI, 15%-50%] at 60 years to 54% [95% CI, 30%-77%] at 80 years; frontotemporal dementia: carriers [n = 48], 19% [95% CI, 12%-28%] at 60 years to 43% [95% CI, 35%-50%] at 80 years; noncarriers [n = 160], 5% [95% CI, 3%-8%] at 60 years to 14% [95% CI, 11%-18%] at 80 years; vascular dementia: carriers [n = 30], 25% [95% CI, 9%-52%] at 60 years to 64% [95% CI, 49%-77%] at 80 years; noncarriers [n = 77], 7% [95% CI, 3%-18%] at 60 years to 29% [95% CI, 17%-43%] at 80 years. CONCLUSIONS AND RELEVANCE: Among participants with dementia, the prevalence of amyloid positivity was associated with clinical diagnosis, age, and APOE genotype. These findings indicate the potential clinical utility of amyloid imaging for differential diagnosis in early-onset dementia and to support the clinical diagnosis of participants with AD dementia and noncarrier APOE ε4 status who are older than 70 years

Clinical evaluation of [123I]FP-CIT SPECT scans on the novel brain-dedicated InSPira HD SPECT system: a head-to-head comparison

The InSPira HD system, a novel brain-dedicated SPECT scanner, allows for imaging with a high spatial resolution. Here, we tested whether this scanner can be used to image the dopamine transporter adequately. Therefore, striatal phantom and patient data acquired on the InSPira were compared head-to-head with the well-validated brain-dedicated NeuroFocus system. A striatal phantom filled with [123I] and 14 subjects (after [123I]FP-CIT injection) were scanned on both systems. [123I]FP-CIT SPECT scans were visually assessed. Striatal binding ratios were calculated automatically using the software package BRASS. Striatal phantom and patient data showed strong correlations with respect to striatal ratios (R = 0.99 and R = 0.92; p < 0.05 and p < 0.01, respectively). Slightly higher ratios were found for the NeuroFocus patient data, probably due to differences in system performance. Visual assessment of [123I]FP-CIT scans showed agreement between systems in 13 of the 14 cases. We conclude that [123I]FP-CIT SPECT imaging can be performed adequately on the new InSPira system

Timing of caloric intake during weight loss differentially affects striatal dopamine transporter and thalamic serotonin transporter binding

Recent studies have shown that meal timing throughout the day contributes to maintaining or regaining weight after hypocaloric diets. Although brain serotonin and dopamine are well known to be involved in regulating feeding, it is unknown whether meal timing during energy restriction affects these neurotransmitter systems. We studied the effect of a 4 wk hypocaloric diet with either 50% of daily calories consumed at breakfast (BF group) or at dinner (D group) on hypothalamic and thalamic serotonin transporter (SERT) binding and on striatal dopamine transporter (DAT) binding. The BF and D groups lost a similar amount of weight. Striatal DAT and thalamic SERT binding increased in the BF group, while decreasing in the D group after the diet (Delta DAT 0.37 +/- 0.63 vs. -0.53 +/- 0.77, respectively; P = 0.005; Delta SERT 0.12 +/- 0.25 vs. -0.13 +/- 0.26 respectively, P = 0.032). Additional voxel-based analysis showed an increase in DAT binding in the ventral striatum in the BF group and a decrease in the dorsal striatum in the D group. During weight loss, striatal DAT and thalamic SERT binding increased weight independently when 50% of daily calories were consumed at breakfast, whereas it decreased when caloric intake was highest at dinner. These findings may contribute to the earlier reported favorable effect of meal timing on weight maintenance after hypocaloric diets.-Versteeg, R. I., Schrantee, A., Adriaanse, S. M., Unmehopa, U. A., Booij, J., Reneman, L., Fliers, E., la Fleur, S. E., Serlie, M. J. Timing of caloric intake during weight loss differentially affects striatal dopamine transporter and thalamic serotonin transporter bindin

Widespread disruption of functional brain organization in early-onset Alzheimer's disease.

Early-onset Alzheimer's disease (AD) patients present a different clinical profile than late-onset AD patients. This can be partially explained by cortical atrophy, although brain organization might provide more insight. The aim of this study was to examine functional connectivity in early-onset and late-onset AD patients. Resting-state fMRI scans of 20 early-onset (<65 years old), 28 late-onset (≥65 years old) AD patients and 15 "young" (<65 years old) and 31 "old" (≥65 years old) age-matched controls were available. Resting-state network-masks were used to create subject-specific maps. Group differences were examined using a non-parametric permutation test, accounting for gray-matter. Performance on five cognitive domains were used in a correlation analysis with functional connectivity in AD patients. Functional connectivity was not different in any of the RSNs when comparing the two control groups (young vs. old controls), which implies that there is no general effect of aging on functional connectivity. Functional connectivity in early-onset AD was lower in all networks compared to age-matched controls, where late-onset AD showed lower functional connectivity in the default-mode network. Functional connectivity was lower in early-onset compared to late-onset AD in auditory-, sensory-motor, dorsal-visual systems and the default mode network. Across patients, an association of functional connectivity of the default mode network was found with visuoconstruction. Functional connectivity of the right dorsal visual system was associated with attention across patients. In late-onset AD patients alone, higher functional connectivity of the sensory-motor system was associated with poorer memory performance. Functional brain organization was more widely disrupted in early-onset AD when compared to late-onset AD. This could possibly explain different clinical profiles, although more research into the relationship of functional connectivity and cognitive performance is needed

Comparison of simplified parametric methods for visual interpretation of 11C-Pittsburgh compound-B PET images

UNLABELLED: This study compared several parametric imaging methods to determine the optimal approach for visual assessment of parametric Pittsburgh compound-B ((11)C-PIB) PET images to detect cortical amyloid deposition in different memory clinic patient groups. METHODS: Dynamic (11)C-PIB scanning of 120 memory clinic patients was performed. Parametric nondisplaceable binding potential (BPND) images were compared with standardized uptake value (SUV) and SUV ratio images. Images were visually assessed by 3 independent readers, and both interreader and intermethod agreement was determined. RESULTS: Both 90-min (Fleiss κ = 0.88) and 60-min (Fleiss κ = 0.89) BPND images showed excellent interreader agreement, whereas agreement was good to moderate for SUV ratio images (Fleiss κ = 0.68) and SUV images (Fleiss κ = 0.59). Intermethod agreement varied substantially between readers, although BPND images consistently showed the best performance. CONCLUSION: The use of BPND images provided the highest interreader and intermethod agreement and is therefore the method of choice for optimal visual interpretation of (11)C-PIB PET scans

Quantification of [ 18 F]florbetapir: A test–retest tracer kinetic modelling study

Accumulation of amyloid beta can be visualized using [18F]florbetapir positron emission tomography. The aim of this study was to identify the optimal model for quantifying [18F]florbetapir uptake and to assess test–retest reliability of corresponding outcome measures. Eight Alzheimer’s disease patients (age: 67 ± 6 years, Mini-Mental State Examination (MMSE): 23 ± 3) and eight controls (age: 63 ± 4 years, MMSE: 30 ± 0) were included. Ninety-minute dynamic positron emission tomography scans, together with arterial blood sampling, were acquired immediately following a bolus injection of 294 ± 32 MBq [18F]florbetapir. Several plasma input models and the simplified reference tissue model (SRTM) were evaluated. The Akaike information criterion was used to identify the preferred kinetic model. Compared to controls, Alzheimer’s disease patients had lower MMSE scores and evidence for cortical Aβ pathology. A reversible two-tissue compartment model with fitted blood volume fraction (2T4k_VB) was the preferred mode..