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首页> 外文期刊>NeuroImage >A framework for designing dynamic lp-ntPET studies to maximize the sensitivity to transient neurotransmitter responses to drugs: Application to dopamine and smoking
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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，以最大限度地提高对药物的瞬时神经递质反应的敏感性：对多巴胺和吸烟的应用

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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 1p-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 losg 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：“线性参数神经递质PET”（LP-ntPET）模型中引入捕获从动态PET数据瞬态内源性神经递质响应于药物刺激的时间过程。我们以前使用这种新的分析工具来探测在PET扫描仪诱导吸烟短命多巴胺（DA）响应。它使我们能够发现吸烟的DA签名性别差异。为了使这个工具来表征神经递质对药物刺激的最佳利用，1P-ntPET来检测这样的响应灵敏度必须最大化。我们设计了一系列模拟研究以检查使用吸烟诱导的DA释放作为一个例子应用在LP-ntPET的灵敏度以下因素的影响：示踪剂输送协议，预处理的图像去噪，发烟任务的定时， PET的持续时间扫描，和放射性示踪剂的剂量。我们的研究结果表明，大剂量模式可以代替一个更困难的B / I模式不牺牲方法的灵敏度。预处理与去噪算法HYPR PET数据可以提高灵敏度。的最佳时机，开始吸烟的任务是在75分钟扫描一个90分钟扫描35分钟和45分钟。从90mCi至75分钟的扫描时间的温和缩短应是可接受的，而不灵敏度losg。我们建议在16mCi弹丸注射到DA激活的限制低估的低剂量限值。本研究建立的框架，优化的实验设计，达到LP-ntPET的全部潜力，检测神经递质反应，药物，甚至行为的任务。

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