Longitudinal Amyloid Imaging Using ¹¹C-PiB: Methodologic Considerations

Abstract

Several methods are in use for analyzing 11 C-Pittsburgh compound-B ( 11 C-PiB) data. The objective of this study was to identify the method of choice for measuring longitudinal changes in specific 11 C-PiB binding. Methods: Dynamic 90-min 11 C-PiB baseline and follow-up scans (interval, 30 6 5 mo) were obtained for 7 Alzheimer disease (AD) patients, 11 patients with mild cognitive impairment (MCI), and 11 healthy controls. Parametric images were generated using reference parametric mapping (RPM2), reference Logan values, and standardized uptake value volume ratios (SUVr), the latter for intervals between 60 and 90 (SUVr 60-90 ) and 40 and 60 (SUVr 40-60 ) minutes after injection. In all analyses, cerebellar gray matter was used as a reference region. A global cortical volume of interest was defined using a probability map-based template. Percentage change between baseline and follow-up was derived for all analytic methods. Results: SUVr 60-90 and SUVr 40-60 overestimated binding with 13% and 10%, respectively, compared with RPM2. Reference Logan values were on average 6% lower than RPM2. Both SUVr measures showed high intersubject variability. Over time, R 1 , the delivery of tracer to the cortex relative to that to the cerebellum, decreased in AD patients (P , 0.05) but not in MCI patients and controls. Simulations showed that SUVr, but not RPM2 and reference Logan values, was highly dependent on uptake period and that changes in SUVr over time were sensitive to changes in flow. Conclusion: To reliably assess amyloid binding over time-for example, in drug intervention studies-it is essential to use fully quantitative methods for data acquisition and analysis.

An exploratory clinical study of p38α kinase inhibition in Alzheimer's disease

“…However, there were apparent reductions in amyloid plaque load in a subset of patients with lower baseline amyloid plaque load. In particular, as within subject variability in BP ND is less than 3% between two PET scans,21, 22 the three responder subjects in the 40 mg dose group are highly likely to have had significant reductions in brain amyloid plaque load during the study. We believe these reduction in brain amyloid plaque load are consistent with the scientific reports published during and after the conduct of the study that indicates neuronal p38 α through modulating autophagy‐lysosome protein degradation appears to play a “critical role” in amyloid beta generation and plaque production 28, 29.…”

“…The dynamic amyloid PET scanning method of van Berckel and colleagues at the VU Medical Center was followed 21. In this method, dynamic emission scanning consists of 23 frames with progressive increases in frame duration (1 × 15 #bib3 × 5, 3 × 10, 2 × 30, 3 × 60, 2 × 150, 2 × 300, and 7 × 600 sec) for a total scan duration of 90 min followed by a full quantitative data analysis of the images.…”

Quantification of Blood Flow-Dependent Component in Estimates of Beta-Amyloid Load Obtained Using Quasi-Steady-State Standardized Uptake Value Ratio

“…In contrast, changes in rCBF do not appear to have a significant effect on DVR values estimated using nonlinear modeling or graphical analysis. 28 In summary, quasi-steady-state SUVR can be understood as a composite value consisting of an amyloid load-(specific binding) dependent component and a rCBF-dependent component. Though the rCBF-dependent component may be small it may anyhow influence longitudinal amyloid imaging by confounding estimates of the potential increase in amyloid plaque load when gradual changes in rCBF occur such as after clinical AD diagnosis.…”

PET Amyloid Analyses

“…Again, investigators have reported more robust and apparently less variable results from longitudinal analyses of distribution volume ratio than of SUVRs (5).…”