Dataset Information

Quantification of blood flow-dependent component in estimates of beta-amyloid load obtained using quasi-steady-state standardized uptake value ratio.

ABSTRACT: Longitudinal positron emission tomography (PET) imaging of beta-amyloid is used in basic research and in drug efficacy trials in Alzheimer's disease (AD). However, the extent of amyloid accumulation after clinical onset is not fully known. Importantly, regional PET data are typically quantified using the standardized uptake value ratio (SUVR), which according to simulations is sensitive to changes in regional cerebral blood flow (rCBF). We aimed to better understand the potentials of longitudinal amyloid imaging by disentangling the influence of blood flow on SUVR using experimental data. [18F]AV-45 PET data from 101 subjects, ranging from cognitively normal to AD patients, in the Alzheimer's Disease Neuroimaging Initiative were extracted. The relationship between global cortical distribution volume ratio, indicator of rCBF (R1), and SUVR was examined using multilinear regression. There was a significant effect of rCBF on SUVR. The effect increased by disease severity. Results suggest that changes in rCBF can produce apparent changes in SUVR in AD. Therefore, future longitudinal studies should measure amyloid changes in a way not sensitive to this effect, ideally using quantitative PET imaging. Furthermore, the results suggest no true accumulation beyond clinical onset and highlight the risks of longitudinal amyloid imaging in drug trials in AD.

SUBMITTER: Cselenyi Z

PROVIDER: S-EPMC4640337 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Quantification of blood flow-dependent component in estimates of beta-amyloid load obtained using quasi-steady-state standardized uptake value ratio.

Cselényi Zsolt Z Farde Lars L

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20150415 9

Longitudinal positron emission tomography (PET) imaging of beta-amyloid is used in basic research and in drug efficacy trials in Alzheimer's disease (AD). However, the extent of amyloid accumulation after clinical onset is not fully known. Importantly, regional PET data are typically quantified using the standardized uptake value ratio (SUVR), which according to simulations is sensitive to changes in regional cerebral blood flow (rCBF). We aimed to better understand the potentials of longitudina ...[more]

PMID: 25873425

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Project description:PET-based treatment response assessment typically measures the change in maximum standardized uptake value (SUV(max)), which is adversely affected by noise. Peak SUV (SUV(peak)) has been recommended as a more robust alternative, but its associated region of interest (ROI(peak)) is not uniquely defined. We investigated the impact of different ROI(peak) definitions on quantification of SUV(peak) and tumor response.Seventeen patients with solid malignancies were treated with a multitargeted receptor tyrosine kinase inhibitor resulting in a variety of responses. Using the cellular proliferation marker 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT), whole-body PET/CT scans were acquired at baseline and during treatment. (18)F-FLT-avid lesions (?2/patient) were segmented on PET images, and tumor response was assessed via the relative change in SUV(peak). For each tumor, 24 different SUV(peaks) were determined by changing ROI(peak) shape (circles vs. spheres), size (7.5-20 mm), and location (centered on SUV(max) vs. placed in highest-uptake region), encompassing different definitions from the literature. Within each tumor, variations in the 24 SUV(peaks) and tumor responses were measured using coefficient of variation (CV), standardized deviation (SD), and range. For each ROI(peak) definition, a population average SUV(peak) and tumor response were determined over all tumors.A substantial variation in both SUV(peak) and tumor response resulted from changing the ROI(peak) definition. The variable ROI(peak) definition led to an intratumor SUV(peak) variation ranging from 49% above to 46% below the mean (CV, 17%) and an intratumor SUV(peak) response variation ranging from 49% above to 35% below the mean (SD, 9%). The variable ROI(peak) definition led to a population average SUV(peak) variation ranging from 24% above to 28% below the mean (CV, 14%) and a population average SUV(peak) response variation ranging from only 3% above to 3% below the mean (SD, 2%). The size of ROI(peak) caused more variation in intratumor response than did the location or shape of ROI(peak). Population average tumor response was independent of size, shape, and location of ROI(peak).Quantification of individual tumor response using SUV(peak) is highly sensitive to the ROI(peak) definition, which can significantly affect the use of SUV(peak) for assessment of treatment response. Clinical trials are necessary to compare the efficacy of SUV(peak) and SUV(max) for quantification of response to therapy.

Project description:BackgroundTo plan for the financial sustainability of immunization programs and make informed decisions to improve immunization coverage and equity, decision-makers need to know how much these programs cost beyond the cost of the vaccine. Non-vaccine delivery cost estimates can significantly influence the cost-effectiveness estimates used to allocate resources at the country level. However, many low- and middle-income countries (LMICs) do not have immunization delivery unit cost estimates available, or have estimates that are uncertain, unreliable, or old. We undertook a Bayesian evidence synthesis to generate country-level estimates of immunization delivery unit costs for LMICs.MethodsFrom a database of empirical immunization costing studies, we extracted estimates of the delivery cost per dose for routine childhood immunization services, excluding vaccine costs. A Bayesian meta-regression model was used to regress delivery cost per dose estimates, stratified by cost category, against a set of predictor variables including country-level [gross domestic product per capita, reported diphtheria-tetanus-pertussis third dose coverage (DTP3), population, and number of doses in the routine vaccination schedule] and study-level (study year, single antigen or programmatic cost per dose, and financial or economic cost) predictors. The fitted prediction model was used to generate standardized estimates of the routine immunization delivery cost per dose for each LMIC for 2009-2018. Alternative regression models were specified in sensitivity analyses.ResultsWe estimated the prediction model using the results from 29 individual studies, covering 24 countries. The predicted economic cost per dose for routine delivery of childhood vaccines (2018 US dollars), not including the price of the vaccine, was $1.87 (95% uncertainty interval $0.64-4.38) across all LMICs. By individual cost category, the programmatic economic cost per dose for routine delivery of childhood vaccines was $0.74 ($0.26-1.70) for labor, $0.26 ($0.08-0.67) for supply chain, $0.22 ($0.06-0.57) for capital, and $0.65 ($0.20-1.66) for other service delivery costs.ConclusionsAccurate immunization delivery costs are necessary for assessing the cost-effectiveness and strategic planning needs of immunization programs. The cost estimates from this analysis provide a broad indication of immunization delivery costs that may be useful when accurate local data are unavailable.

Project description:UNLABELLED:Both the standardized uptake value ratio (SUVR) and the Logan plot result in biased distribution volume ratios (DVRs) in ligand-receptor dynamic PET studies. The objective of this study was to use a recently developed relative equilibrium-based graphical (RE) plot method to improve and simplify the 2 commonly used methods for quantification of (11)C-Pittsburgh compound B ((11)C-PiB) PET. METHODS:The overestimation of DVR in SUVR was analyzed theoretically using the Logan and the RE plots. A bias-corrected SUVR (bcSUVR) was derived from the RE plot. Seventy-eight (11)C-PiB dynamic PET scans (66 from controls and 12 from participants with mild cognitive impaired [MCI] from the Baltimore Longitudinal Study of Aging) were acquired over 90 min. Regions of interest (ROIs) were defined on coregistered MR images. Both the ROI and the pixelwise time-activity curves were used to evaluate the estimates of DVR. DVRs obtained using the Logan plot applied to ROI time-activity curves were used as a reference for comparison of DVR estimates. RESULTS:Results from the theoretic analysis were confirmed by human studies. ROI estimates from the RE plot and the bcSUVR were nearly identical to those from the Logan plot with ROI time-activity curves. In contrast, ROI estimates from DVR images in frontal, temporal, parietal, and cingulate regions and the striatum were underestimated by the Logan plot (controls, 4%-12%; MCI, 9%-16%) and overestimated by the SUVR (controls, 8%-16%; MCI, 16%-24%). This bias was higher in the MCI group than in controls (P < 0.01) but was not present when data were analyzed using either the RE plot or the bcSUVR. CONCLUSION:The RE plot improves pixelwise quantification of (11)C-PiB dynamic PET, compared with the conventional Logan plot. The bcSUVR results in lower bias and higher consistency of DVR estimates than of SUVR. The RE plot and the bcSUVR are practical quantitative approaches that improve the analysis of (11)C-PiB studies.

Dataset Information

Quantification of blood flow-dependent component in estimates of beta-amyloid load obtained using quasi-steady-state standardized uptake value ratio.

Publications

Quantification of blood flow-dependent component in estimates of beta-amyloid load obtained using quasi-steady-state standardized uptake value ratio.

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