Impact of Image-Derived Input Function and Fit Time Intervals on Patlak Quantification of Myocardial Glucose Uptake in Mice.
Limited blood volume in mice precludes repeated sampling, rendering a reliable image-derived input function (IDIF) desirable for quantification of glucose uptake. We aimed to compare different IDIF volumes and to evaluate the effects of changing fit time interval on Patlak uptake kinetics in hearts of healthy mice.


METHODS
C57BL/6 mice (n=27) were studied under a range of metabolic conditions: no intervention (ctl), overnight fasting, insulin and glucose (6 mU/g, 1 mg/g) under isoflurane, and under ketamine-xylazine anesthesia to suppress glucose uptake. Dynamic PET imaging with 18F-FDG (7.7±0.9 MBq) was conducted. Images were analyzed using left ventricle cavity, left atrial cavity, or inferior vena cava as the IDIF. Patlak analysis was conducted using variable fit time intervals: automated fit, fit from 10 to 60 min (late), fit from 2 to 30 min (early), or fit from 2 to 10 min (very early).


RESULTS
Both the ventricle and the atrial cavities displayed spill-in from the myocardium in late frames as compared with the vena cava (percentage injected dose per gram, ctl: 21.4±6.1 vs. 10.0±3.9 vs. 2.5±0.3, P<0.001). Higher and more rapid passage of peak activity was observed in the vena cava, but the area under the curve over 2 min was similar. The Patlak slope was significantly higher for the vena cava than atrial IDIF (mL/g/min, ctl: 0.11±0.02 vs. 0.07±0.01; fasting: 0.09±0.03 vs. 0.06±0.02; insulin: 0.52±0.09 vs. 0.23±0.12; ketamine-xylazine: 0.001±0.001 vs. 0.002±0.002; P<0.01). The rate of glucose uptake was similarly elevated depending on the IDIF (P<0.01). The various IDIF Patlak values were significantly correlated (r=0.867, P<0.001). Automated fit performed reliably in untreated, fasted, and ketamine-xylazine-treated mice, with no statistical difference compared with late, early, or very early fits. The Patlak composite rate constant (Ki) was markedly underestimated with automated and late fit after acute insulin treatment, reflecting the rapid early 18F-FDG uptake.


CONCLUSIONS
The choice of IDIF has a profound effect on Patlak kinetics and calculated 18F-FDG uptake. Adjustment of the time interval for fit may be necessary for accurate calculations, particularly with acute insulin treatment. Even without partial-volume correction, the inferior vena cava provides a reliable and reproducible IDIF for Patlak analysis of myocardial glucose uptake in mice.
Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany.
James T
JT
Thackeray
Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany.
Jens P
JP
Bankstahl
Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany bengel.frank@mh-hannover.de.
Frank M
FM
Bengel
D000465:Algorithms; D000758:Anesthesia; D000778:Anesthetics, Dissociative; D000818:Animals; D001786:Blood Glucose / Q000032:analysis / Q000378:metabolism; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted; D007649:Ketamine; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D015233:Models, Statistical; D009206:Myocardium / Q000378:metabolism*; D019275:Radiopharmaceuticals; D014684:Venae Cavae / Q000378:metabolism
D000778:Anesthetics, Dissociative; D001786:Blood Glucose; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D007649:Ketamine; D005947:Glucose
fluoro-deoxyglucose; myocardial metabolism; positron emission tomography; quantitative image analysis; small animal imaging