Volume-of-interest-based supervised cluster analysis for pseudo-reference region selection in [¹⁸F]DPA-714 PET imaging of the rat brain

Aim of this study was to automatically select a suitable pseudo-reference brain region for the accurate, non-invasive quantification of neuroinflammation in a rat brain using dynamic [¹⁸F]DPA-714 PET imaging.

A supervised clustering analysis approach considering three kinetic classes (SVCA3) was used to select an appropriate pseudo-reference brain region. This pseudo-reference region was determined by selecting only brain regions with low specific tracer uptake (SVCA3_low) or by taking into account all brain regions and weighting each brain region with the corresponding fraction of low specific binding (SVCA3_wlow). Both SVCA3 approaches were evaluated in an animal model of neuro-inflammation induced by lipopolysaccharide injection in the right striatum of female Wistar rats. For this study setup, a population of 25 female Wistar rats received a dynamic PET scan after injection of ~ 60 MBq [¹⁸F]DPA-714. Animals were scanned at baseline (n = 3) and at different time points after inducing neuroinflammation: 1 day (n = 3), 3 days (n = 12), 7 days (n = 4), and 30 days (n = 3). Binding potential (BP) values using a simplified reference tissue model (SRTM) and the contralateral striatum as pseudo-reference region were considered as a reference method (BP_{L STR}) and compared with SRTM BP values using a pseudo-reference region obtained by either the SVCA3_low or SVCA3_wlow approach for both a 90- and 120-min acquisition time interval.

For the right striatum, SRTM BP values using a SVCA3_low- or SVCA3_wlow-based pseudo-reference region demonstrated a strong and highly significant correlation with SRTM BP_{L STR} values (Spearman r ≥ 0.89, p < 0.001). For the SVCA3_low approach, Friedman tests revealed no significant difference with SRTM BP_{L STR} values for a 120-min acquisition time while small but signification differences were found for a 90-min acquisition time (p < 0.05). For the SVCA3_wlow approach, highly signification differences (p < 0.001) were found with SRTM BP_{L STR} values for both a 90- and 120-min acquisition time interval.

A SVCA3 approach using three kinetic classes allowed the automatic selection of pseudo-reference brain regions with low specific tracer binding for accurate and non-invasive quantification of rat brain PET imaging using [¹⁸F]DPA-714. A shorter acquisition time interval of 90 min can be considered with only limited impact on the SVCA3-based selection of the pseudo-reference brain regions.