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A framework for designing dynamic lp-ntPET studies to maximize the sensitivity to transient neurotransmitter responses to drugs: application to dopamine and smoking

机译：设计动态lp-ntPET研究的框架以最大程度地提高药物对瞬时神经递质反应的敏感性：在多巴胺和吸烟中的应用

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The “linear parametric neurotransmitter PET” (lp-ntPET) model was introduced to capture the time course of transient endogenous neurotransmitter response to drug stimulus from dynamic PET data. We previously used this novel analysis tool to probe the short-lived dopamine (DA) response induced by cigarette smoking in the PET scanner. It allowed us to find a sex difference in the DA signature of cigarette smoking. To make best use of this tool to characterize neurotransmitter response to drug stimulus, the sensitivity of lp-ntPET to detect such responses must be maximized. We designed a series of simulation studies to examine the impact of the following factors on the sensitivity of lp-ntPET using smoking-induced DA release as an example application: tracer delivery protocol, pre-processing for image denoising, timing of the smoking task, duration of the PET scan, and dose of the radiotracer. Our results suggest that a Bolus paradigm could replace a more difficult B/I paradigm without sacrificing the sensitivity of the method. Pre-processing the PET data with the de-noising algorithm HYPR could improve the sensitivity. The optimal timing to start the smoking task is 45min in a 90min scan and 35min in a 75min scan. A mild shortening of the scan time from 90mCi to 75min should be acceptable without loss of sensitivity. We suggest a lower dose limit of a bolus injection at 16mCi to limit underestimation of DA activation. This study established the framework to optimize the experimental design for reaching the full potential of lp-ntPET to detect neurotransmitter responses to drugs or even behavioral tasks.
机译：引入“线性参数神经递质PET”（lp-ntPET）模型以从动态PET数据中捕获瞬时内源性神经递质对药物刺激的反应的时间过程。我们以前使用这种新颖的分析工具来探测在PET扫描仪中吸烟引起的短暂多巴胺（DA）反应。它使我们能够在吸烟的DA签名中发现性别差异。为了充分利用此工具来表征神经递质对药物刺激的反应，必须最大化lp-ntPET检测此类反应的敏感性。我们设计了一系列模拟研究，以吸烟引起的DA释放为例，研究了以下因素对lp-ntPET敏感性的影响：示踪剂传输协议，图像去噪的预处理，吸烟任务的时间安排， PET扫描的持续时间以及放射性示踪剂的剂量。我们的结果表明，Bolus范例可以替代更困难的B / I范例，而不会牺牲该方法的灵敏度。使用降噪算法HYPR对PET数据进行预处理可以提高灵敏度。开始吸烟任务的最佳时机是90分钟扫描45分钟和75分钟扫描35分钟。将扫描时间从90mCi略微缩短到75min应该是可以接受的，同时又不降低灵敏度。我们建议在16mCi下推注剂量的剂量下限，以限制对DA激活的低估。这项研究建立了优化实验设计的框架，以充分发挥lp-ntPET的潜力来检测对药物甚至行为任务的神经递质反应。

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