Machine learning-based approach reveals essential features for simplified TSPO PET quantification in ischemic stroke patients

Introduction: Neuroinflammation evaluation after acute ischemic stroke is a promising option for selecting an appropriate post -stroke treatment strategy. To assess neuroinflammation in vivo, translocator protein PET (TSPO PET) can be used. However, the gold standard TSPO PET quantification method includes a 90 min scan and continuous arterial blood sampling, which is challenging to perform on a routine basis. In this work, we determine what information is required for a simplified quantification approach using a machine learning algorithm. Materials and Methods: We analyzed data from 18 patients with ischemic stroke who received 0 - 90 min [ 18 F]GE-180 PET as well as T1-weigted (T1w), FLAIR, and arterial spin labeling (ASL) MRI scans. During PET scans, five manual venous blood samples at 5, 15, 30, 60, and 85 min post injection (p.i.) were drawn, and plasma activity concentration was measured. Total distribution volume (V T ) was calculated using Logan plot with the full dynamic PET and an imagederived input function (IDIF) from the carotid arteries. IDIF was scaled by a calibration factor derived from all the measured plasma activity concentrations. The calculated V T values were used for training a random forest regressor. As input features for the model, we used three late PET frames (60 - 70, 70 - 80, and 80 - 90 min p.i.), the ASL image reflecting perfusion, the voxel coordinates, the lesion mask, and the five plasma activity concentrations. The algorithm was validated with the leave -one -out approach. To estimate the impact of the individual features on the algorithm ' s performance, we used Shapley Additive Explanations (SHAP). Having determined that the three late PET frames and the plasma activity concentrations were the most important features, we tested a simplified quantification approach consisting of dividing a late PET frame by a plasma activity concentration. All the combinations of frames/samples were compared by means of concordance correlation coefficient and Bland -Altman plots. Results: When using all the input features, the algorithm predicted V T values with high accuracy (87.8 +/- 8.3%) for both lesion and non -lesion voxels. The SHAP values demonstrated high impact of the late PET frames (60 - 70, 70 - 80, and 80 - 90 min p.i.) and plasma activity concentrations on the V T prediction, while the influence of the ASL-derivedperfusion, voxel coordinates, and the lesion mask was low. Among all the combinations of the late PET frames and plasma activity concentrations, the 70 - 80 min p.i. frame divided by the 30 min p.i. plasma sample produced the closest V T estimate in the ischemic lesion. Conclusion: Reliable TSPO PET quantification is achievable by using a single late PET frame divided by a late blood sample activity concentration.