Thackeray James T, Bankstahl Jens P, Bengel Frank M
Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany.
Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany
J Nucl Med. 2015 Oct;56(10):1615-21. doi: 10.2967/jnumed.115.160820. Epub 2015 Aug 13.
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.
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).
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.
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.
小鼠血容量有限，无法进行重复采样，因此需要一个可靠的图像衍生输入函数（IDIF）来定量葡萄糖摄取。我们旨在比较不同的IDIF体积，并评估改变拟合时间间隔对健康小鼠心脏中Patlak摄取动力学的影响。
对27只C57BL/6小鼠在一系列代谢条件下进行研究：无干预（对照）、过夜禁食、异氟烷麻醉下注射胰岛素和葡萄糖（6 mU/g，1 mg/g），以及在氯胺酮-赛拉嗪麻醉下以抑制葡萄糖摄取。使用18F-FDG（7.7±0.9 MBq）进行动态PET成像。使用左心室腔、左心房腔或下腔静脉作为IDIF对图像进行分析。使用可变拟合时间间隔进行Patlak分析：自动拟合、10至60分钟拟合（晚期）、2至30分钟拟合（早期）或2至10分钟拟合（极早期）。
与下腔静脉相比，心室和心房腔在晚期帧中均显示出心肌的溢出（每克注射剂量百分比，对照：21.4±6.1对10.0±3.9对2.5±0.3，P<0.001）。下腔静脉中观察到更高且更快的峰值活性通过，但2分钟以上的曲线下面积相似。下腔静脉的Patlak斜率显著高于心房IDIF（mL/g/min，对照：0.11±0.02对0.07±0.01；禁食：0.09±0.03对0.06±0.02；胰岛素：0.52±0.09对0.23±0.12；氯胺酮-赛拉嗪：0.001±0.001对0.002±0.002；P<0.01）。根据IDIF，葡萄糖摄取率同样升高（P<0.01）。各种IDIF的Patlak值显著相关（r=0.867，P<0.001）。自动拟合在未治疗、禁食和氯胺酮-赛拉嗪治疗的小鼠中可靠进行，与晚期、早期或极早期拟合相比无统计学差异。急性胰岛素治疗后，自动拟合和晚期拟合显著低估了Patlak复合速率常数（Ki），反映了早期18F-FDG的快速摄取。
IDIF的选择对Patlak动力学和计算的18F-FDG摄取有深远影响。为了进行准确计算，可能需要调整拟合时间间隔，特别是在急性胰岛素治疗时。即使不进行部分容积校正，下腔静脉也为小鼠心肌葡萄糖摄取的Patlak分析提供了可靠且可重复的IDIF。
