Noninvasive Quantification of Cerebral Metabolic Rate for Glucose in Rats Using ¹⁸F-FDG PET and Standard Input Function

Abstract

Measurement of arterial input function (AIF) for quantitative positron emission tomography (PET) studies is technically challenging. The present study aimed to develop a method based on a standard arterial input function (SIF) to estimate input function without blood sampling. We performed 18F-fluolodeoxyglucose studies accompanied by continuous blood sampling for measurement of AIF in 11 rats. Standard arterial input function was calculated by averaging AIFs from eight anesthetized rats, after normalization with body mass (BM) and injected dose (ID). Then, the individual input function was estimated using two types of SIF: (1) SIF calibrated by the individual's BM and ID (estimated individual input function, EIFNS) and (2) SIF calibrated by a single blood sampling as proposed previously (EIF1S). No significant differences in area under the curve (AUC) or cerebral metabolic rate for glucose (CMRGlc) were found across the AIF-, EIFNS-, and EIF1S-based methods using repeated measures analysis of variance. In the correlation analysis, AUC or CMRGlc derived from EIFNS was highly correlated with those derived from AIF and EIF1S. Preliminary comparison between AIF and EIFNS in three awake rats supported an idea that the method might be applicable to behaving animals. The present study suggests that EIFNS method might serve as a noninvasive substitute for individual AIF measurement.

Pharmacokinetic Characterization of [18F]UCB-H PET Radiopharmaceutical in the Rat Brain

“…The significant drawbacks of such a method are the degree of complexity introduced and its invasiveness, making it nonsuitable for longitudinal studies. Standard input functions appear to be a noninvasive substitute for individual input function measurement . Therefore, we decided to use a PBIF, derived from measurements previously obtained with the β-microprobe system, and to implement it in the kinetic modeling of the individual rats scanned with [ 18 F]­UCB-H. We validated the use of the biexponential parent fraction curve described in our previous work by comparing the metabolism data.…”

“…Standard input functions appear to be a noninvasive substitute for individual input function measurement. 27 Therefore, we decided to use a PBIF, derived from measurements previously obtained with the βmicroprobe system, and to implement it in the kinetic modeling of the individual rats scanned with [ 18 F]UCB-H. We validated the use of the biexponential parent fraction curve described in our previous work by comparing the metabolism data. In this study, the measured parent fraction (64.3 ± 8.2%, 43.3 ± 6.6%, and 20 ± 3.5% at 5, 10, and 20 min, respectively) matched the biexponential parent fraction curve fitted by Warnock and colleagues, where the values at the same time points were 62.1%, 41.2%, and 23%, respectively, ensuring us the possibility to use it for the correction of the whole-blood radioactivity (measured by the β-microprobe).…”

Reproducibility of compartmental modelling of 18F-FDG PET/CT to evaluate lung inflammation

“…The TAC extracted from the blood pool ROI is then modelled as a continuous curve to reduce noise: models based on an initial linear rise followed by a sum of exponentials have been proposed in tumour kinetics [16]. In the brain, extensive effort has been made to improve input function modelling including those based on reference regions [17] and methods using carotid or other blood vessels with one or more manual samples [18–20] with voxel-based approaches also feasible [21]. In the lung, there remains a need for optimisation of input function modelling.…”