Table 1.
Demographics.
Table 2.
Average HC baseline [18F]AV45 kinetic rate constants and SUVR (at 50–60 min p.i.) used in the simulations.
Fig 1.
Simulation scheme based on the 2TCM describing the effect of a change in blood flow on SUVR for variable uptake periods.
(A) Heterogeneous blood flow change: K1prec (upper) or K1CB (lower) was varied between [0.46–1.08] or [0.40–0.93] (corresponding to [-40%–+40%] from average HC baseline) with K1/k2 constant and all other parameters fixed to baseline values, to determine the corresponding SUVRprec and SUVRCB, respectively. Remark that SUVRprec and SUVRCB are independent of the choice of the reference and target region, respectively. (B) Global blood flow change: K1prec and K1CB were simultaneously and in equal proportion varied to determine the corresponding . In this figure, precuneus was chosen as the target and CB as the reference; simulations using different target or reference regions are similar. Abbreviations: NS = non-specific; Cplasma = metabolite-corrected plasma input function; IRF = 2TCM impulse response function; Ctissue(t) = simulated time-activity curve in the tissue.
Fig 2.
Impact of simulated blood flow change on regional activity concentration and SUVR as a function of uptake time.
(left) Simulated TACs of the precuneus (A), CB (B), and WM (C) for various K1prec, K1CB, and K1WM, respectively. (right) Percentage change in SUVRprec (A), SUVRCB (B), and SUVRWM (C) as a function of time for various K1prec, K1CB, and K1WM, respectively. Simulated K1 changes corresponded to -40, -20, +20, and +40% relative to average HC baseline. Remark that % SUVRprec and % SUVRCB or WM change are independent of the choice of the reference and target region, respectively. Abbreviations: TAC = time-activity curve; K1 = tracer delivery rate; SUVR = standardised uptake value ratio; prec = precuneus; CB = cerebellar grey matter; WM = subcortical white matter.
Fig 3.
Regression curves of ΔSUVR (50–60 min p.i.) versus ΔK1 derived from simulations.
(A) Heterogeneous blood flow changes: ΔSUVRprec, ΔSUVRCB, or ΔSUVRWM versus ΔK1prec (black), ΔK1CB, (blue) or ΔK1WM (red), respectively. Remark that ΔSUVRprec and ΔSUVRCB or WM are independent of the choice of the reference and target region, respectively. (B) Homogeneous blood flow changes: or
versus ΔK1prec = ΔK1CB (light grey) or ΔK1prec = ΔK1WM (dark grey), respectively. Simulated K1 changes corresponded to -40, -20, -10, -5, +5, +10, +20, and +40% relative to average HC baseline. A third order polynomial function was fitted to the curves (r2 = 0.99). Abbreviations: K1 = tracer delivery rate; SUVR = standardised uptake value ratio; prec = precuneus; CB = cerebellar grey matter; WM = subcortical white matter.
Table 3.
ΔSUVRtarget in alternative target areas due to simulated ΔK1target.
Fig 4.
Regression curves for each diagnostic group based on subject-specific baseline and a heterogeneous blood flow change.
The subject-specific curves of ΔSUVRprec (A), ΔSUVRCB (B) or ΔSUVRWM (C) versus ΔK1prec, ΔK1CB, or ΔK1WM, respectively, were averaged per diagnostic group (average ± SD). There was a significant difference between HC and aMCI (p = 0.012, ANOVA) and AD (p = 0.005) for the precuneus. Remark that ΔSUVRprec and ΔSUVRCB or WM are independent of the choice of the reference and target region, respectively. Abbreviations: K1 = tracer delivery rate; SUVR = standardised uptake value ratio; prec = precuneus; CB = cerebellar grey matter; WM = subcortical white matter.
Fig 5.
Regression curves for each diagnostic group based on subject-specific baseline and a global blood flow change.
The subject-specific curves of (A) or
(B) versus ΔK1prec = ΔK1CB or ΔK1prec = ΔK1WM, respectively, were averaged per diagnostic group (average ± SD). There was a significant difference between HC and aMCI (p = 0.024, ANOVA) and AD (p = 0.018) for the precuneus and reference WM. Remark that ΔSUVRprec and ΔSUVRCB or WM are independent of the choice of the reference and target region, respectively. Abbreviations: K1 = tracer delivery rate; SUVR = standardised uptake value ratio; prec = precuneus; CB = cerebellar grey matter; WM = subcortical white matter.