Relative Equilibrium Plot Improves Graphical Analysis and Allows Bias Correction of Standardized Uptake Value Ratio in Quantitative ¹¹C-PiB PET Studies

Abstract

Both the standardized uptake value ratio (SUVR) and the Logan plot result in biased distribution volume ratios (DVR) in ligand-receptor dynamic PET studies. The objective of this study is to use a recently developed relative equilibrium-based graphical plot (RE plot) method to improve and simplify the two commonly used methods for quantification of [11C]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 [11C]PiB dynamic PET scans (66 from controls and 12 from mildly cognitively impaired participants (MCI) from the Baltimore Longitudinal Study of Aging (BLSA)) were acquired over 90 minutes. Regions of interest (ROIs) were defined on coregistered MRIs. Both the ROI and pixelwise time activity curves (TACs) were used to evaluate the estimates of DVR. DVRs obtained using the Logan plot applied to ROI TACs were used as a reference for comparison of DVR estimates. Results Results from the theoretical 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 TACs. In contrast, ROI estimates from DVR images in frontal, temporal, parietal, 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 pixel-wise quantification of [11C]PiB dynamic PET compared to the conventional Logan plot. The bcSUVR results in lower bias and higher consistency of DVR estimates compared to SUVR. The RE plot and the bcSUVR are practical quantitative approaches that improve the analysis of [11C]PiB studies.

Voxelwise Relationships Between Distribution Volume Ratio and Cerebral Blood Flow: Implications for Analysis of β-Amyloid Images

“…DVRs estimated by the Logan plot with reference tissue input are comparable to those estimated by SRTM at low noise levels of ROI kinetics but are underestimated in the presence of increased noise (23, 24). We also recognize that SUVR is commonly used for semi-quantitative measurement of PiB binding, due to simplified data acquisition and quantification, and note that highly linear correlations between DVR and SUVR were reported in previous studies with low noise levels of ROI kinetics (34-35). However, SUVR measurements are dependent on the time-window of acquisition (24, 34) and bias relative to DVR estimation is correlated with magnitude (35).…”

“…We also recognize that SUVR is commonly used for semi-quantitative measurement of PiB binding, due to simplified data acquisition and quantification, and note that highly linear correlations between DVR and SUVR were reported in previous studies with low noise levels of ROI kinetics (34-35). However, SUVR measurements are dependent on the time-window of acquisition (24, 34) and bias relative to DVR estimation is correlated with magnitude (35). Therefore, correlations of SUVR with CBF or R 1 will vary with time-window of acquisition and magnitude of amyloid-deposition.…”

Longitudinal Amyloid Imaging Using 11C-PiB: Methodologic Considerations

“…In the present study, there was a difference of 17%-19% between SUVr and reference Logan values. In a recent study in MCI patients (27), SUVrs were up to 31% higher than reference Logan DVRs. These discrepancies between methods have important implications for determination of quantitative thresholds for PiB positivity, because these thresholds depend critically on the method that is used to analyze the data.…”

The influence of biological and technical factors on quantitative analysis of amyloid PET: Points to consider and recommendations for controlling variability in longitudinal data

“…These include a bolus plus infusion approach that provides true equilibrium between plasma and tissue in late time frames [57] but presents implementation challenges and a regional equilibrium correction that reduces the bias in late time frame estimations [59]. Regardless of the acquisition and analysis approach used, however, amyloid burden measurement can only be valid if the raw PET signal is without artifact.…”