Area under the curve (AUC) of the metabolite-corrected AIF was calculated using numerical trapezoidal integration. Imaging data were analyzed using each approach: 1TCM, 2TCM, 2TCM-1k, MA-1, SIME, SUV, and SUVR. Plasma uptake delay (τ) was estimated using a 1TCM from the first 10 min of data and was fixed for 2TCM and 2TCM-1k analyses. Compartment modeling analyses were performed with the Compartment Model Kinetic Analysis Tool (COMKAT [
13]) in the MATLAB environment. 1TCM poorly described ROI TACs; therefore, results are not reported. In the 2TCM model, four rate constants were estimated:
K1,
k2,
k3, and
k4 [
14]. The 2TCM-1k model includes a fifth parameter (
kb) that models purported irreversible uptake in endothelial cells [
8]. The corrected Akaike Information Criterion (AICc [
15]) indicated model preference for a fixed blood volume fraction (
Vb = 5%) for 2TCM and 2TCM-1k. For MA-1 [
9],
VT was estimated using
t* = 30, consistent with prior work [
11]. Simultaneous estimation (SIME) simultaneously fits TACs across all ROIs to estimate whole-brain
VND which, in combination with regional
VT values, can estimate ROI binding potentials specific to total plasma concentration (BP
P) [
10]. Due to the low free fraction (~ 2%) resulting in poor
fP precision [
16], analyses incorporating ƒ
p in
VT estimates are only included for completeness as Additional file
1. Finally, SUV was calculated as mean tissue activity concentration for each ROI during specified timeframes (60–90 min, 90–120 min) normalized by subject body weight and injected [
11C]PBR28 dose. SUVR was estimated by dividing ROI SUV by whole-brain SUV. AICc was used to compare model parsimony for 2TCM vs. 2TCM-1k [
15].
Repeated measures analyses of variance (rmANOVA) were used to evaluate LPS effects on each calculated endpoint (statistical transformations applied as needed to normalize distributions) across ROIs (within-subject factor) with rs6971 genotype (HAB vs. MAB) as a between-subject factor (significance threshold: p < .05). Partial eta-squared (η2) effect sizes were estimated from rmANOVAs.