Parametric Imaging of [11C]Flumazenil Binding in the Rat Brain

Abstract

Purpose: This study evaluates the performance of several parametric methods for assessing [¹¹C]flumazenil binding distribution in the rat brain.

Procedures: Dynamic (60 min) positron emission tomography data with metabolite-corrected plasma input function were retrospectively analyzed (male Wistar rats, n = 10). Distribution volume (V _T) images were generated from basis function method (BFM), Logan graphical analysis (Logan), and spectral analysis (SA). Using the pons as pseudo-reference tissue, binding potential (BP _ND and DVR-1) images were obtained from receptor parametric imaging algorithms (RPM and SRTM2) and reference Logan (RLogan). Standardized uptake value images (SUV and SUVR) were also computed for different intervals post-injection. Next, regional averages were extracted from the parametric images, using pre-defined volumes of interest, which were also applied to the regional time-activity curves from the dynamic data. Parametric data were compared to their regional counterparts and to two-tissue compartment model (2TCM)-based values (previously defined as the model of choice for rats). Parameter agreement was assessed by linear regression analysis and Bland-Altman plots.

Results: All parametric methods strongly correlated to their regional counterparts (R ² > 0.97) and to the 2TCM values (R ² ≥ 0.95). SA and RLogan underestimated V _T and BP _ND (slope of 0.93 and 0.86, respectively), while SUVR-1 overestimated BP _ND (slope higher than 1.07 for all intervals). While BFM and SRTM2 had the smallest bias to 2TCM values (0.05 for both), ratio Bland-Altman plots showed Logan and RLogan displayed relative errors which were comparable between different regions, in contrast with the other methods. Although SUV consistently underestimated V _T, the bias in this method was also constant across regions.

Conclusions: All parametric methods performed well for the analysis of [¹¹C]flumazenil distribution and binding in the rat brain. However, Logan and RLogan slightly outperformed the other methods in terms of precision, providing robust parameter estimation and constant bias. Yet, other methods can be of interest, because they can provide tissue perfusion (i.e., K ₁ with BFM and SA), relative flow (i.e., R ₁ with RPM and SRTM2), and model order (SA) images.

Keywords: PET; Parametric imaging; Rat; Small-animal imaging; [11C]flumazenil.

Fig. 1

Representative (n = 1) parametric images of a V _T, b SUV_30–40, c BP _ND, d K ₁ images, and e R ₁ images.

Fig. 2

Regression analysis and Bland-Altman plots of V _T compared to 2TCM values. a Linear regression between parametric (BFM, Logan, and SA) and 2TCM V _T values determined by VOI analysis. The solid line is the identity line, and the dashed lines represent the regression lines. b Bland-Altman plot of the agreement in V _T estimation between the parametric methods and the reference values obtained from the 2TCM (VOI). The dashed line represents zero bias. c Ratio Bland-Altman plot between BFM, Logan, SA, and 2TCM V _T values. The dashed line represents a ratio of one, corresponding to full agreement between methods.

Fig. 3

Plot of differences in estimates between 2TCM reference values across regions and a distribution volume and b binding potential. Individual values are represented by circles, the mean is represented by the black line, and the bars represent the SD.

Fig. 4

Regression analysis and Bland-Altman plots of BP _ND. a Linear regression between parametric (RLogan, RPM, and SRTM2) and 2TCM DVR–1 (BP _ND) values determined by VOI analysis. The solid line represents the identity line, and the dashed lines correspond to each of the regression lines. b Bland-Altman plot of the agreement in BP _ND estimation between the parametric methods and the reference values obtained from the 2TCM (VOI). The dashed line corresponds to zero bias. c Ratio Bland-Altman plot between BP _ND of parametric methods and 2TCM BP _ND. The dashed line corresponds to a ratio of one, representing full agreement between methods. The y-axis is truncated at −1.0.

Fig. 5

Regression analysis and ratio Bland-Altman plot of SUV from different intervals. a Regression analysis between SUV (parametric) and 2TCM V _T (VOI) for three different intervals p.i. The dashed lines represent the regression lines. b Ratio Bland-Altman plot between V _T estimates from SUV and from 2TCM V _T (VOI) for the same intervals.

Fig. 6

Regression analysis and ratio Bland-Altman plot of SUVR from different intervals. a Regression analysis between SUVR–1 (parametric) and 2TCM BP _ND (VOI) for three different p.i. intervals. The solid line represents the identity line, and the dashed lines correspond to each of the regression lines. b Ratio Bland-Altman plot between binding potential estimates from SUVR–1 and from 2TCM BP _ND (VOI) for the same intervals. The dashed line corresponds to a ratio of one, representing full agreement between methods. The y-axis is truncated at −1.0.

Fig. 7

Representative image (n = 1) of model order obtained from the parametric SA method, displaying, in the different views, a difference between cortical and non-cortical regions.