Retrieving the accurate time-tracer activity concentration curve of the blood (arterial inputfunction) is mandatory for performing bio kinetic model analysis of dynamic PET data. Especially in small rodents, gathering the input function remains an active area of research äs no generally applicable solution was found so far. While surgically catheterizing biood vessels of rodents is possible, it is labour intensive and time resolution of blood sampling is restricted due to the limited amount of overall blood and the procedure of blood withdrawal itself. Obtaining the input function from the PET images themselves seems thus to be favourable, but suffers from several factors, one of them being spill-in of adjacent tissues. Particularly in mice and for [18F]FDG, the spill-in complicates using the time-activity curve (TAG) from a region of interest (ROI) over the left ventricle (LV) because the Signal of the ROI contains contributions from both, myocardial uptake äs well äs arterial blood activity. We propose non-negative matrix factorization (NMF) äs an image based algorithm for separating myocardial tracer concentration from the blood input function. The aim of this study was to evaluate the potential of NMF äs an image based algorithm for retrieving the input function by comparison with blood sampling and Factor Analysis (FA).
Method
The femoral arteries of eight mice were surgically catheterized. With the injection of [1SF]FDG, a 60 minute PET scan was started during which arterial blood samples were manually drawn from the catheter. For analysis, NMF and FA were performed in a ROI placed over the LV. The NMF algorithm shares similarities with principal component analysis and FA, the advantage over the later two being its non-negativity constraint. For normalization of the NMF extracted curve, the peak value of tracer activity in an early irnage of the LV and a late blood sample was used. The normalized NMF curve was visually compared to the TAG retrieved from the blood samples and to the FA retrieved TAG. For a quantitative comparison of performance, Pearson correlation and square-root of sum of squares (RSS) between NMF/FA and blood sampling curves was calculated.
Results
TAG based on NMF, FAand arterial blood samples were obtained and compared in all 8 mice. The NMF derived curves described the blood sampling based curves visually significantly better than FA. Pearson correlation between NMF and blood sampling curves ranged from 0.21 to 0.92 with an average of 0.69. Pearson correlation for FA ranged from 0.46 to 0.81 with an average of 0.65. Mean RSS was 2.70E + 006 for NMF and 3.40E + 006 for FA.
Conclusion
In the examined Parameters, visua! accordance, Pearson correlation and RSS, NMF performs superior to FA and seems to be a promising method for the extraction of the input function from PET images of small rodents without the need for arterial blood sampling.