186 Chapter 8 Definitions of biomarkers Several chapters in this thesis include [18F]florbetapir PET data. PET scans can be performed using static or dynamic scanning protocols, which both have advantages and disadvantages. Static scanning protocols are relatively short with a lower patient burden, and provide semi-quantitative standardized uptake value ratio (SUVr) images. Dynamic scanning protocols take substantially longer with a higher patient burden and costs, yet can be used to calculate binding potential (BPND) images which provide a quantitative measurement of amyloid burden. SUVr is the measure that is used most often in literature. Although SUVr is shown to be more prone to bias than BPND (21), its use is probably sufficient for many purposes, such as cross-sectional associations between amyloid burden and clinical correlates, or for the binary classification of individuals into amyloid positive or negative. Indeed, in chapter 3, we found that thresholds, based on either SUVr or BPND, were associated with memory decline and all corresponded well with visual assessment. However, in longitudinal PET research it is especially important to eliminate sources of noise and bias, making BPND a more preferable method over SUVr (21, 22), which is the method we used in chapter 6 and 7. BPND is less affected by underlying pathophysiological mechanisms such as decreased perfusion compared to SUVr, and SUVr is therefore more prone to overestimation of [18F]florbetapir uptake (23). Another advantage of dynamic scanning protocols, is that it enables the additional calculation of R1 images. R1 represents the ratio between K1 (the rate constant for ligand transfer from plasma to tissue) in the target region and the reference region, which can be used as proxy for rCBF (24-26). Literature suggests rCBF is closely associated with vascular damage, or that a low rCBF could reflect decreases in metabolism and synaptic failure (27-30). In chapter 6, we found amyloid accumulation and rCBF were longitudinally associated and both independently related to cognitive decline. This means that with a single [18F] florbetapir PET scan, information about two relevant biomarkers can be obtained.
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