Accurate image derived input function in [18F]SynVesT-1 mouse studies using isoflurane and ketamine/xylazine anesthesia

Abstract Background Kinetic modeling in positron emission tomography (PET) requires measurement of the tracer plasma activity in the absence of a suitable reference region. To avoid invasive blood sampling, the use of an image derived input function has been proposed. However, an accurate delineation of the blood pool region in the PET image is necessary to obtain unbiased blood activity. Here, to perform brain kinetic modeling in [18F]SynVesT-1 dynamic scans, we make use of non-negative matrix factorization (NMF) to unmix the activity signal from the different tissues that can contribute to the heart region activity, and extract only the left ventricle activity in an unbiased way. This method was implemented in dynamic [18F]SynVesT-1 scans of mice anesthetized with either isoflurane or ketamine–xylazine, two anesthestics that we showed to affect differently radiotracer kinetics. The left ventricle activity (NMF-IDIF) and a manually delineated cardiac activity (IDIF) were compared with arterial blood samples (ABS), and for isoflurane anesthetized mice, arteriovenous (AV) shunt blood data were compared as well. Finally, brain regional 2 tissue compartment modeling was performed using IDIF and NMF-IDIF, and the model fit accuracy (weighted symmetrical mean absolute percentage error, wsMAPE) as well as the total volume of distribution (V T) were compared. Results In isoflurane anesthetized mice, the difference between ABS and NMF-IDIF activity (+ 12.8 $$\pm$$ ± 11%, p = 0.0023) was smaller than with IDIF (+ 16.4 $$\pm$$ ± 9.8%, p = 0.0008). For ketamine–xylazine anesthetized mice the reduction in difference was larger (NMF-IDIF: 16.9 $$\pm$$ ± 10%, p = 0.0057, IDIF: 56.3 $$\pm$$ ± 14%, p