Image-Derived Input Function from the Vena Cava for¹⁸F-FDG PET Studies in Rats and Mice

Abstract

Measurement of arterial input function is a restrictive aspect for quantitative 18 F-FDG PET studies in rodents because of their small total blood volume and the related difficulties in withdrawing blood. Methods: In the present study, we took advantage of the high spatial resolution of a recent dedicated small-animal scanner to extract the input function from the 18 F-FDG PET images in Sprague-Dawley rats (n 5 4) and C57BL/6 mice (n 5 5), using the vena cava. In the rat experiments, the validation of the image-derived input function (IDIF) method was made using an external microvolumetric blood counter as reference for the determination of the arterial input function, the measurement of which was confirmed by additional manually obtained blood samples. Correction for tracer bolus dispersion in blood between the vena cava and the arterial tree was applied. In addition, simulation studies were undertaken to probe the impact of the different IDIF extraction approaches on the determined cerebral metabolic rate of glucose (CMR Glc ). In the mice measurements, the IDIF was used to compute the CMR Glc , which was compared with previously reported values, using the Patlak approach. Results: The presented IDIF from the vena cava showed a robust determination of CMR Glc using either the compartmental modeling or the Patlak approach, even without bolus dispersion correction or blood sampling, with an underestimation of CMR Glc of 7% ± 16% as compared with the reference data. Using this approach in the mice experiments, we measured a cerebral metabolic rate in the cortex of 0.22 ± 0.10 μmol/g/min (mean ± SD), in good agreement with previous 18 F-FDG studies in the mouse brain. In the rat experiments, dispersion correction of the IDIF and additional scaling of the IDIF using a single manual blood sample enabled an optimized determination of CMR Glc , with an underestimation of 6% ± 7%. Conclusion: The vena cava time-activity curve is therefore a minimally invasive alternative for the measurement of the 18 F-FDG input function in rats and mice, without the complications associated with repetitive blood sampling. Gl ucose metabolism can be efficiently measured in vivo using PET and adequate radiotracers, such as the glucose analog 18 F-FDG, opening the way to a large range of metabolic studies in rodents (1). The quantification of the metabolic rate of glucose (MR Glc ) from 18 F-FDG PET experiments requires the knowledge of the arterial input function (AIF), which is typically measured by serial arterial blood sampling (2). However, in small animals, the total amount of blood is limited and continuous blood sampling over the entire experiment duration (on the order of 45 min) is technically challenging and might affect the physiology of the animal.Several methods have been developed in the last decade to overcome this difficulty. New microfluidic blood sampling devices were developed to minimize the amount of blood withdrawn (3). Another method minimizing blood losses is the use of an arteriovenous shunt, coupled with either...

2-18F-Fluoroethanol Is a PET Reporter of Solid Tumor Perfusion

“…2). These modeling data are somewhat limited by the use of an image-derived input function instead of direct blood draws to assess 2-18 F-FEtOH in the bloodstream, although image analysis methods have fared well when directly compared with blood collection methods (26). Future kinetic modeling of 2-18 F-FEtOH should include analysis of FEtOH metabolites and assessment of enzymes that will relate to enhanced metabolic trapping.…”

“…PET imaging was conducted as previously published (21). The rate of irreversible 2-18 F-FEtOH uptake was determined with the Patlak method (25) using image-derived input functions from the vena cava as previously published (26) and analysis conducted with MatLab software (The MathWorks).…”

Impact of Image-Derived Input Function and Fit Time Intervals on Patlak Quantification of Myocardial Glucose Uptake in Mice

“…The shorter early frames used in the present study (2 vs. 10 s) may allow sharper definition of the vena cava activity peak and clearance. A third study also evaluated the vena cava as IDIF, demonstrating a modest overestimation (;10%) of cerebral Patlak slope, compared with microvolumetric blood counting in rats (13). This discrepancy was somewhat mitigated by application of a dispersion correction, but limitations due to partial-volume errors in the small vena cava of mice remained problematic.…”

Performing Repeated Quantitative Small-Animal PET with an Arterial Input Function Is Routinely Feasible in Rats

“…For a while, we used externalized catheters for repeated studies on rats (7), but protection of the externalized catheter was difficult, and skin infections often occurred. Although an image-derived input function is a good alternative for repeated PET measurements, acquisition of a set of dynamic images requires that an animal be anesthetized (15). PET findings from an anesthetized animal may not represent the physiology of the conscious brain (16).…”