Quantification of Positron Emission Tomography Data Using Simultaneous Estimation of the Input Function: Validation with Venous Blood and Replication of Clinical Studies
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To determine if one venous blood sample can substitute full arterial sampling in quantitative modeling for multiple positron emission tomography (PET) radiotracers using simultaneous estimation of the input function (SIME).
Participants underwent PET imaging with [11C]ABP688, [11C]CUMI-101, and [11C]DASB. Full arterial sampling and additional venous blood draws were performed for quantification with the arterial input function (AIF) and SIME using one arterial or venous (vSIME) sample.
Venous and arterial metabolite-corrected plasma activities were within 6 % of each other at varying time points. vSIME- and AIF-derived outcome measures were in good agreement, with optimal sampling times of 12 min ([11C]ABP688), 90 min ([11C]CUMI-101), and 100 min ([11C]DASB). Simulation-based power analyses revealed that SIME required fewer subjects than the AIF method to achieve statistical power, with significant reductions for [11C]CUMI-101 and [11C]DASB with vSIME. Replication of previous findings and test-retest analyses bolstered the simulation analyses.
We demonstrate the feasibility of AIF recovery using SIME with one venous sample for [11C]ABP688, [11C]CUMI-101, and [11C]DASB. This method simplifies PET acquisition while allowing for fully quantitative modeling, although some variability and bias are present with respect to AIF-based quantification, which may depend on the accuracy of the single venous blood measurement.
Key wordsVenous blood Less invasive PET Simultaneous estimation Sample size considerations
We thank the Center for Understanding Biology using Imaging Technology image analysts at Stony Brook University for their work in image importing, processing, and quality control. We also thank Rajapillai Pillai, PhD, for his contributions to early versions of the paper. We acknowledge the consultation and support provided by the Biostatistical Consulting Core at the Stony Brook University School of Medicine.
This study was funded by the National Institute of Mental Health awards: K01MH091354 (PI: Christine DeLorenzo, PhD), R01MH104512 (PI: Christine DeLorenzo, PhD), and R01MH090276 (PI: Ramin V Parsey, MD, PhD).
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
All procedures performed were in accordance with the ethical standards of the institutional committee and with the 1964 Helsinki Declaration and its later amendments.
Informed consent was obtained from all individual participants included in the study.
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