Image Quantification for TSPO PET with a Novel Image-Derived Input Function Method

There is a growing interest in using (18)F-DPA-714 PET to study neuroinflammation and microglial activation through imaging the 18-kDa translocator protein (TSPO). Although quantification of (18)F-DPA-714 binding can be achieved through kinetic modeling analysis with an arterial input function (AIF) measured with blood sampling procedures, the invasiveness of such procedures has been an obstacle for wide application. To address these challenges, we developed an image-derived input function (IDIF) that noninvasively estimates the arterial input function from the images acquired for (18)F-DPA-714 quantification. Methods: The method entails three fully automatic steps to extract the IDIF, including a segmentation of voxels with highest likelihood of being the arterial blood over the carotid artery, a model-based matrix factorization to extract the arterial blood signal, and a scaling optimization procedure to scale the extracted arterial blood signal into the activity concentration unit. Two cohorts of human subjects were used to evaluate the extracted IDIF. In the first cohort of five subjects, arterial blood sampling was performed, and the calculated IDIF was validated against the measured AIF through the comparison of distribution volumes from AIF (V(T,AIF)) and IDIF (V(T,IDIF)). In the second cohort, PET studies from twenty-eight healthy controls without arterial blood sampling were used to compare V(T,IDIF) with V(T,REF) measured using a reference region-based analysis to evaluate whether it can distinguish high-affinity (HAB) and mixed-affinity (MAB) binders. Results: In the arterial blood-sampling cohort, V(T) derived from IDIF was found to be an accurate surrogate of the V(T) from AIF. The bias of V(T, IDIF) was −5.8 ± 7.8% when compared to V(T,AIF), and the linear mixed effect model showed a high correlation between V(T,AIF) and V(T, IDIF) (p < 0.001). In the nonblood-sampling cohort, V(T, IDIF) showed a significance difference between the HAB and MAB healthy controls. V(T, IDIF) and standard uptake values (SUV) showed superior results in distinguishing HAB from MAB subjects than V(T,REF). Conclusions: A novel IDIF method for (18)F-DPA-714 PET quantification was developed and evaluated in this study. This IDIF provides a noninvasive alternative measurement of V(T) to quantify the TSPO binding of (18)F-DPA-714 in the human brain through dynamic PET scans.