Department of Medicine, University of Alberta Faculty of Medicine & Dentistry, Edmonton, Alberta, Canada.
National Cardiac PET Centre, Department of Medicine (Cardiology), University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
Eur J Nucl Med Mol Imaging. 2020 Jul;47(7):1722-1735. doi: 10.1007/s00259-019-04629-5. Epub 2019 Dec 9.
Cardiac sympathetic nervous system (SNS) dysfunction is associated with poor prognosis in chronic heart failure patients. This study characterized the reproducibility and repeatability of [C]meta-hydroxyephedrine (HED) positron emission tomography (PET) quantification of cardiac SNS innervation, regional denervation, and myocardial blood flow (MBF).
Dynamic HED PET-CT scans were performed 47 ± 22 days apart in 20 patients with stable heart failure and reduced ejection fraction. Three observers, blinded to clinical data, used FlowQuant® to evaluate the test-retest repeatability and inter- and intra-observer reproducibility of HED tracer uptake and clearance rates to measure global (LV-mean) retention index (RI), volume of distribution (V), and MBF. Values were also compared with and without regional partial-volume correction. Regional denervation was quantified as %LV defect size of values < 75% of the LV-maximum. Test-retest repeatability and observer reproducibility were evaluated using intra-class-correlation (ICC) and Bland-Altman coefficient of repeatability (NPC).
Intra- and inter-observer correlations of both V and RI were excellent (ICC = 0.93-0.99). Observer reproducibility (NPC = 3-13%) was lower than test-retest repeatability (NPC = 12-61%). Both regional (%LV defect size) and global (LV-mean) measures of sympathetic innervation were more repeatable using the simple RI model compared to V (NPC = 12% vs. 19% and 30% vs. 54%). Using either model, quantification of regional denervation (defect size) was consistently more reliable than the global LV-mean values of RI or V. Regional partial-volume correction degraded repeatability of both the global and regional V measures by 2-12%. Test-retest repeatability of MBF estimation was relatively poor (NPC = 30-61%) compared with the RI.
Quantitative measures of global and regional SNS innervation were most repeatable using the simple RI method of analysis compared with the more complex V. Observer variability was significantly lower than the test-retest repeatability using a highly automated analysis program. These results support the use of the simple RI method for reliable analysis of HED PET images in clinical research studies for future evaluation of new therapies and for risk stratification in patients with heart failure.
心脏交感神经系统（SNS）功能障碍与慢性心力衰竭患者预后不良有关。本研究旨在描述[C]间羟麻黄碱（HED）正电子发射断层扫描（PET）定量评估心脏 SNS 神经支配、区域性去神经支配和心肌血流（MBF）的可重复性和再现性。
20 例稳定型心力衰竭和射血分数降低的患者，两次动态 HED PET-CT 扫描间隔 47±22 天。三位观察者在不了解临床数据的情况下使用 FlowQuant®评估 HED 示踪剂摄取和清除率的测试-再测试重复性以及观察者内和观察者间的可重复性，以测量全局（LV-均值）保留指数（RI）、分布容积（V）和 MBF。还比较了有无局部部分容积校正。区域去神经支配程度用<75%的 LV-最大值的 LV 缺陷大小的百分比（%LV 缺陷大小）来定量。使用组内相关系数（ICC）和 Bland-Altman 可重复性系数（NPC）评估测试-再测试重复性和观察者可重复性。
V 和 RI 的观察者内和观察者间相关性均非常好（ICC=0.93-0.99）。观察者重复性（NPC=3-13%）低于测试-再测试重复性（NPC=12-61%）。与 V 相比，使用简单的 RI 模型时，无论是区域性（%LV 缺陷大小）还是全局（LV-均值）的交感神经支配测量结果都更具可重复性（NPC=12%比 19%和 30%比 54%）。无论使用哪种模型，区域去神经支配（缺陷大小）的定量评估均比 RI 或 V 的全局 LV-均值更可靠。局部部分容积校正使全局和区域性 V 测量的重复性降低了 2-12%。MBF 估计的测试-再测试重复性相对较差（NPC=30-61%），与 RI 相比。
与更复杂的 V 相比，使用简单的 RI 分析方法对全球和区域性 SNS 神经支配的定量测量最具可重复性。使用高度自动化的分析程序，观察者的变异性明显低于测试-再测试的可重复性。这些结果支持使用简单的 RI 方法对 HED PET 图像进行可靠分析，用于未来对新疗法的评估和心力衰竭患者的风险分层，用于临床研究。
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