Introduction to [11C]PIB
Pittsburgh Compound B (PIB, PiB, or 6-OH-BTA-1) is a derivative of thioflavin T, and both bind to amyloid-β; [11C]PIB has been successfully used as a PET ligand to in vivo visualization and quantification of amyloid-β deposits.
Analysis of [11C]PIB PET studies
[11C]PIB binding to amyloid-β in the grey brain matter is specific and reversible. [11C]PIB binding in white matter is non-specific and non-saturable (Fodero-Tavoletti et al., 2009), but due to slower kinetics the uptake is prominent at later time points, which may impede the quantification of amyloid-β deposits in the grey matter in case of considerable partial volume effect.
The recommended analysis methods for quantification of amyloid load in the brain are
- MTGA analysis for reversible uptake (Logan plot) with reference tissue input
- Late-scan tissue-to-reference tissue ratio
Logan plot with PIB
Distribution volume ratio (DVR), or binding potential (BPND = DVR-1), can be calculated with Logan plot without arterial plasma data sampling, using cerebellar cortex as input (Mintun et al. 2006; Li et al. 2008). Reference region k2 was set to 0.2 min-1, but this value had only minimal impact on the results (Mintun et al. 2006). However, it may advance the time when Logan plot reaches linearity, thus reducing the required total scan length.
Regional analysis
Estimate the regional DVR using
logan
with option -k2=0.2
and set fit time from 20 minutes to a
common end time.
Pixel-by-pixel analysis
To produce DVR images use
imgdv
with option -k2=0.2
and set fit start time to 20.
BPND images (Mikhno et al., 2008) can be achieved by subtracting 1
from DVR images.
Tissue-to-cerebellum ratio
Amyloid load can be quantified by computing region-to-cerebellum ratio over 60 to 90 minutes (Lopresti et al., 2005; Kemppainen et al. 2006), either regionally withdftratio or pixel-by-pixel withimgratio. Optimal time range was thoroughly studied by McNamee et al. (2009); their suggestion was to use 40-60-min period in studies limited by low injected dose, but otherwise the 50-70-min period because of greater measurement stability, especially for longitudinal multisite studies.
Advantages of the ratio approach are 1) large effect sizes for Alzheimer's Disease (AD) and control group differences (Lopresti et al., 2005), and 2) possibility to obtain the required data from a single relatively short scan.
AD patients may have also cerebellar plaques, which may render cerebellum
vulnerable as a reference area. Therefore, it may be necessary to calculated
results also by using pons as a reference area (Koivunen et al., 2008).