Pmod software version 3

Each participant underwent PET scans with ¹¹C-PiB and ¹⁸F-florzolotau to quantify Aβ and tau accumulations, respectively.
Radiosynthesis of these PET ligands was carried out as described elsewhere.^{32 (link),33 (link)} Injected radioactivities of ¹¹C-PiB and ¹⁸F-florzolotau are shown in Table 1. For details of PET acquisition, see Supplementary Methods 1.
All PET images were corrected for scatter using a single-scatter simulation method. A head fixation device was used to minimize the subject’s head movement during the PET measurements. Motion-corrected PET images were co-registered to the corresponding individual T₁-weighted MR images using PMOD^® software version 3.8 (PMOD Technologies Ltd., Zurich, Switzerland). Parametric PET images were generated by voxel-based calculation of the standardized uptake value ratio (SUVR) to the cerebellar GM (excluding the vermis) at 50–70 and 90–110 min for ¹¹C-PiB and ¹⁸F-florzolotau, respectively.

In pharmacokinetic modeling, tracer kinetics are assumed to be separable into compartments with a flux of the tracer from one compartment to another. The flux between compartments can be physical (transport across a membrane) or notional (between bound and unbound receptor or chemical transformation in the same physical space). In the current study, the reversible single-tissue compartment model (1T2k+VB) (with K1 = Rate constant from blood to tissue, k2 = rate constant from the tissue compartment to the arterial blood, distribution volume (DV) = K1/k2 and VB = blood volume parameter), the irreversible (2T3k+VB) and reversible (2T4k+VB) two-tissue compartment model (adding a tissue compartment representing the FDOPA pool of the tumor, with k3 = inward and k4 = outward) were tested (PMOD software version 3.8; PMOD Technologies; Zürich, Switzerland). These three compartmental models are the most commonly used for full kinetic analysis of PET tracers in oncology. The model providing the best fits (Levenberg-Marquadt algorithm) to the tumoral TAC with the 5 different time samplings was selected on the basis of the Akaike information criterion (AIC) for small sample sizes [17 (link)].

PET images were analysed using the PMOD software version 3.7 (PMOD Technologies Ltd, Zürich, Switzerland). Using combined PET/CT images, a volume-of-interest (VOI) was drawn in liver tissue, excluding large blood vessels and visible intrahepatic bile ducts. The VOIs were used to generate the time courses of liver tissue concentration of [¹¹C]CSar and [¹⁸F]FDGal, C_liver(t) (kBq/cm³ liver tissue), for kinetic analysis of PET data. Mean VOI volumes for [¹¹C]CSar and [¹⁸F]FDGal PET were 21.5 mL (range 11.5–52.6) and 29.8 mL (range 24.4–34.4) liver tissue, respectively.

The acquisition and processing protocols for 18F-FDG and 11C-PIB PET imaging have been described in our previous study (Zhang et al., 2017 (link); Wang et al., 2019 (link)). Briefly, PET images were acquired in the three-dimensional scanning mode on a GE Discovery LS PET/CT 710 scanner. 11C-PIB was administered intravenously at a dose of 370-555MBq, and a 90-min dynamic PET scan was performed according to a predetermined protocol. One hour after the 11C-PiB PET scan, 185-259 MBq of 18F-FDG was then injected intravenously, A 10-min static PET emission scan was performed 40 min after FDG injection with the same scanning mode. FDG PET and PiB PET images were preprocessed using MRI data for partial volume effect correction and spatial normalization. PiB PET imaging analysis was performed using Statistical Parameter Mapping 8 (SPM8) software on MATLAB 2010b for Windows (Mathworks, Natick, MA, USA) or PMOD software (version 3.7, PMOD Technologies Ltd., Zurich, Switzerland), as described in our previous study. The average of all specific regions was calculated from the PiB integral image. FDG frames for each subject were summed and normalized to mean pons activity. It is then displayed on the NIH color scale and can be windowed and viewed on three planes according to the rater’s discretion.

A subset of 20 participants (10 ICB+ and 10 ICB−) completed a PET scan with [¹⁸F]Fallypride as described in refs. ^{47 (link),48} . D2-like receptor levels were estimated using the simplified reference tissue model (SRTM) performed in PMOD software version 3.7 (PMOD Technologies, Zurich Switzerland) to measure [¹⁸F]fallypride binding potential (BP_ND; the ratio of specifically bound [¹⁸F]fallypride to its nondisplaceable concentration as defined under equilibrium conditions)^{47 (link),48} . BP_ND images were co-registered to the T1-weighted image using FSL FLIRT (FSL v5.0.2.1, FMRIB, Oxford, UK). FSL FIRST was used to obtain the thalamic mask and the mean BP_ND values were recorded (Fig. 3).

PET/CT imaging and data analysis were performed according to previous works of our group [21 (link),26 (link),27 (link)] using PMOD software (version 3.7; PMOD Technologies LLC, Zürich, Switzerland). The processed PET images were subsequently co-registered with the mouse brain volume-of-interest (VOI) template (Mouse Mirrione atlas), and the PMOD software and tracer uptake values were extracted for each delineated VOI. Due to the fact that mice differed in body weight, the injected dose percentage per gram (ID%/g) was chosen as unit of measurement and acquired for each VOI.