感谢耶鲁PET中心化学示踪合成，成像示踪剂注入和图像采集和希拉女士黄专家流程图设计团队团队成员。 大部分的的ntPET技术的发展是得到R21 AA15077 E.莫里斯。 K.科斯格罗夫K02 DA031750支持。

整个过程的概要的，如下所述的制造多片层电影多巴胺概述在图1的流程图中。 <ol><li>前PET MR扫描在一个单独的一天从PET扫描获得一个结构性的MR扫描。该MR扫描将提供为PET图像的解剖参考。典型的采集参数结构MRI:3D MPRAGE MR脉冲序列TE = 3.3毫秒，翻转角= 7度;层厚1.0毫米，0.98 x 0.98 mm像素。 <ol><li>实践PET /吸烟会安排的主题实践吸烟运动在PET扫描仪扫描前，理想的情况下，较早访问的PET中心。这将避免在实际PET扫描的混乱或不适。这也可以消除在扫描仪中的第一次的新颖性。因为西门子HRRT的是一个高分辨率的大脑扫描仪，隧道很窄到他/她的嘴香烟的吸烟者的最小间隙。虽然我们有一个复杂的系统来解决头部运动，它仍然是最好有吸烟者实践吸烟，同时尽量不将他/她的头。 </li><li>病人准备<ol><li>四号线必须插入静脉，由注册护士，并准备以后提供示踪剂泵附件。示踪将被注入患者通过静脉线。 </li><li>头部运动监视器粘贴反光球头的主体的顶部。的Vicra头部跟踪系统的激光反射球的位置在20赫兹的速率轮询。球体连接到刚性，十字型的"工具"，该工具连接到由被摄体穿莱卡泳帽。研究人员监测头部运动，以确保该激光系统，应使用工具的位置的实时显示<html>米有一个通畅的工具和记录头的位置不断图像重建中供以后使用。 </li></ol></li><li>准备注射泵<ol><li>编程适当的输液泵范式雷氯必利的，为了最大限度地提高灵敏度的PET图像多巴胺整个扫描周期的波动，管理示踪剂，11 C-雷氯必利，作为初始剂量，然后由一个恒定输注。要确定正确的相对量的示踪交付与输液初始剂量，我们遵循的方法卡森等人 22来计算的比例丸剂量输注率（以分钟为单位的的"Kbol" ）给定的知识，在人类的11 C-雷氯必利的脉冲响应函数。根据给定的协议示踪剂的发送是由一个内部的计算机程序，它驱动一个可编程的输液泵控制。 </li></ol></li><li>启动空气滤清器T"要消除从PET套房二手烟雾​​在吸烟，位置摄入的空气，过滤器（Movex的公司，北安普顿，PA）扫描仪前端和主体的头部上方。发表主题空间带来的他/她的嘴香烟在吸烟过程中，该过滤器是在研究之前打开，并在各种条件下使用，如果执行多个扫描。 </li><li>传输扫描收购9分钟传输示踪剂​​注入和收购的PET扫描前扫描。获取的传输创建一个三维地图整个大脑的线性衰减系数。衰减图用于发射（PET）图像的重建。 </li></ol></li><li> PET扫描。 <ol><li>开始注射和PET扫描核医学技师必须经过认证的管理示踪剂。一般来说，一队的两个技术人员启动示踪管理和PET数据采集同步<html> LY。 </li><li>在吸烟时的评定量表管理简单的问卷调查，口头，紧接及以下吸烟的主题。吸烟者必须评估他/她的渴望，渴求，尼古丁高，厌恶的感觉满意的规模为1-100。 </li><li>抽烟为了捕捉自然吸烟体验的多巴胺反应，指导吸烟者，他自己的速度抽烟，抽他的自有品牌的香烟，最重要的是，执行自己的吸烟，而不是尼古丁或香烟管理研究人才。吸烟者 - 谁一直禁欲，因为前一天午夜12点 - 浓烟连续两个香烟。他们一般需要约10分钟才能完成这两个香烟。 </li><li>吸烟后评定量表（如上所述）。 </li></ol></li><li>后PET扫描<ol><li>完成扫描，发送通过国土资源部使用Vicra数据重建ontent"&gt;在收购完成后，重建的列表模式数据（时间和地点的记录，每一个人的衰变）到排放的图像。在我们中心的重建算法是一种迭代算法（卡森，Barker 等21），纠正使用高频Vicra录音事件级别的议案。更正为散射衰减，死区时间，正常化，扫描仪几何，点扩散函数中还包括重建算法。三维PET图像产生一个动态的系列，在预先选定的时间框架。 </li><li>陈前处理和MR-PET注册使用标准算法，以消除头骨从主体的MR图像23。 MR必须去科头颅的前对准PET，因为大多数示踪剂不采取头骨。 </li></ol></li><li>过滤动态PET数据HYPR 应用的一个变种空间滤波方法，高度约束反投影（，HYPR-LR），所有的PET图像一帧一帧的方式工作，基督教等。8,24。 HYPR-LR的吸引力是它降低空间噪声，而不会降低在每个体素的时间信息，我们将使用它来创建我们的多巴胺电影。 </li><li> PET数据对齐MR模板对齐的PET主体的MR数据产生变换矩阵1。 （这一般是与从早在PET扫描的图像）。寄存器MR数据的一个标准的MR模板，得到变换矩阵2。结合注册HYPR过滤PET的数据的标准模板空间变换1和2。这些数据是在一个标准的解剖空间各向同性体素（2毫米x 2毫米x 2毫米）。 </li><li>应用纹状体面膜雷氯必利具有足够的信号的背景的对比度，可以使用仅在纹状体。这是的脑部区域毒瘾牵连。继马丁内斯等25前连合纹状体（腹侧纹状体，背尾，背壳）的面具在模板空间中的所有PET数据。 </li><li>基于体素的配合两款车型<ol><li>选择多巴胺为LP-ntPET的响应函数选择响应函数可能多巴胺的刺激的反应是一致的。 ，人们可以通过选择特定的一组响应函数的估计多巴胺反应为我们的特定的刺激预期的曲线的形状和定时约束。吸烟，我们预​​计单峰多巴胺浓度的上升和下降（"γ-变量"形曲线）。在吸烟的情况下，在45分钟到扫描，家庭响应函数"起飞40分钟（允许一些预期），后来被列入"时代。 </li><li>套用LP-ntPET的模型适合LP-ntPET的模埃尔根据诺曼丁等7的方法，在每个单独的体素中的掩模区的PET捕量。在图3a所示的业务模型的方程。的商品的PET TAC与每个响应函数的积分变成非线性基函数的一组模型（见最后项的运算公式）。 ，因为LP-ntPET的是直链，基函数拟合动态PET数据为基础的方法，它可以迅速地估计上述（a）的动力学参数示踪剂的作用，及（b）的时间相对多巴胺的档案扫描会话期间的浓度变化，在每个像素。 <ol><li>创建WSSR地图记录加权残差平方和契合LP-ntPET到每个体素（WSSR LP-ntPET）的，使用的数据（WSSR），地图的下面。拟合模型在每个像素生成图像示踪参数:R 1，K 2 &lt;/ sub&gt;的，K 2a中 ，和γ。 R 1是相对流量值，K 2是在基准区域的流出速率，K 2a的在目标区域是明显的流出速率，和γ是多巴胺信号幅度。可以被认为是作为一个图像，以及在每个像素的残差平方的加权和。 </li></ol></li><li>应用（常规）多线性参考组织模型（MRTM） 适合MRTM的模型9的每一个人像素蒙面地区PET时间活动数据。 MRTM是一个线性模型-通常应用于动态PET数据-是传递到lp ntPET相同的， 但它缺乏一个随时间变化的多巴胺术语 。配件MRTM逐体素的数据产量估计只有三个参数图像:R 1，K 2，K 2A。记录的平方的加权和在每个像素的数据，以及适合的MRTM（WSSR MRTM）的地图。 </li></ol></li> &lt;LI&gt;计算的F-地图创建地图的总和的平方映射的F-F统计量，通过计算在每个像素中的掩模。 F统计量进行比较WSSR的线对ntPET到WSSR MRTM，修正自由在各自的配合程度的差异。 </li><li>阈值的F地图在一个值，该值转换为概率阈值的F-地图P &lt;0.05（基于模型拟合的自由度）。该阈值是相同的，在每个体素。二值化的地图，使一个新的"意义面膜"，只保留那些像素在纹状体的PET总可捕量是合适的（统计）更好地与LP-ntPET的与MRTM比。 </li><li>筛选的意义面膜执行形态的"开放"（其次是扩张侵蚀）的意义面膜消除微小的，孤立的体素群，我们假设是由于噪声。的各向同性的2×2×2像素内核是用于重新移动隔离体素组2体素或更小的直径。我们现在有末期意义面膜。 </li><li>创建4D多巴胺在色彩的电影存储的价值归为k 2A估计多巴胺曲线的，在每个像素中的最后重大意义面膜。这些数据构成"归多巴胺图像"，并将于4维。它们是有效的，为每个像素在每个时间点的相对值多巴胺发现有显着的的多巴胺响应的刺激。通过施加一个颜色查找表的归一化的多巴胺图像创建颜色编码的图像序列。相应的MR模板图像上叠加的颜色编码多巴胺图像。保存该系列颜色编码的图像为*。png文件。这是单一片"多巴胺电影"。安排成一个电影每片含腹侧纹状体的多巴胺电影。这样的安排是一个多片层多巴胺电影。 </li><li>分析吸烟数据和控制数据卡ilarly 每一个实验条件进行审查的数据进行同样的分析。对于这个项目，我们采集和分析数据各科在两个独立的条件:吸烟和控制（禁止吸烟）。 </li><li>比较吸烟，控制通过构建复合多巴胺电影同一主题的电影在不同的条件下， 如基线或假的任务与吸烟产生多巴胺。生产"合成多巴胺的电影"一个科目为基线和吸烟纹状体所有切片。 </li><li>运行电影玩"多片多巴胺电影"（显示结果）透露，包括大脑的吸烟独特的多巴胺反应的空间和时间模式。 </li></ol>

<ol>
	<li>Constantinescu, C. C., Bouman, C., Morris, E. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Nonparametric+extraction+of+transient+changes+in+neurotransmitter+concentration+from+dynamic+PET+data.">Nonparametric extraction of transient changes in neurotransmitter concentration from dynamic PET data.</a> IEEE Trans. Med. Imaging. 26, 359-373 (2007).</li><li>Constantinescu, C. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Estimation+from+PET+data+of+transient+changes+in+dopamine+concentration+induced+by+alcohol:+support+for+a+non-parametric+signal+estimation+method.">Estimation from PET data of transient changes in dopamine concentration induced by alcohol: support for a non-parametric signal estimation method.</a> Phys. Med Biol. 53, 1353-1367 (2008).</li><li>Morris, E. D., Constantinescu, C. C., Sullivan, J. M., Normandin, M. D., Christopher, L. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Noninvasive+visualization+of+human+dopamine+dynamics+from+PET+images.">Noninvasive visualization of human dopamine dynamics from PET images.</a> NeuroImage. 51, 135-144 (2010).</li><li>Morris, E. D., Normandin, M. D., Schiffer, W. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Initial+comparison+of+ntPET+with+microdialysis+measurements+of+methamphetamine-induced+dopamine+release+in+rats:+support+for+estimation+of+dopamine+curves+from+PET+data.">Initial comparison of ntPET with microdialysis measurements of methamphetamine-induced dopamine release in rats: support for estimation of dopamine curves from PET data.</a> Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging. 10, 67-73 (2008).</li><li>Morris, E. D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=ntPET:+a+new+application+of+PET+imaging+for+characterizing+the+kinetics+of+endogenous+neurotransmitter+release.">ntPET: a new application of PET imaging for characterizing the kinetics of endogenous neurotransmitter release.</a> Molecular Imaging. 4, 473-489 (2005).</li><li>Normandin, M. D., Morris, E. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Estimating+neurotransmitter+kinetics+with+ntPET:+A+simulation+study+of+temporal+precision+and+effects+of+biased+data.">Estimating neurotransmitter kinetics with ntPET: A simulation study of temporal precision and effects of biased data.</a> NeuroImage. 39, 1162-1179 (2008).</li><li>Normandin, M. D., Schiffer, W. K., Morris, E. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+linear+model+for+estimation+of+neurotransmitter+response+profiles+from+dynamic+PET+data.">A linear model for estimation of neurotransmitter response profiles from dynamic PET data.</a> NeuroImage. 59, 2689-2699 (2012).</li><li>Christian, B. T., Vandehey, N. T., Floberg, J. M., Mistretta, C. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dynamic+PET+denoising+with+HYPR+processing.">Dynamic PET denoising with HYPR processing.</a> Journal of Nuclear Medicine: Official publication, Society of Nuclear Medicine. 51, 1147-1154 (2010).</li><li>Ichise, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Linearized+reference+tissue+parametric+imaging+methods:+application+to+[11C]DASB+positron+emission+tomography+studies+of+the+serotonin+transporter+in+human+brain.">Linearized reference tissue parametric imaging methods: application to [11C]DASB positron emission tomography studies of the serotonin transporter in human brain.</a> Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 23, 1096-1112 (2003).</li><li>Benowitz, N. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pharmacology+of+nicotine:+addiction,+smoking-induced+disease,+and+therapeutics.">Pharmacology of nicotine: addiction, smoking-induced disease, and therapeutics.</a> Annual review of pharmacology and toxicology. 49, 57-71 (2009).</li><li>Volkow, N. D., Swanson, J. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Variables+that+affect+the+clinical+use+and+abuse+of+methylphenidate+in+the+treatment+of+ADHD.">Variables that affect the clinical use and abuse of methylphenidate in the treatment of ADHD.</a> The American journal of psychiatry. , 160-1918 (2003).</li><li>Di Chiara, G., Imperato, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Drugs+abused+by+humans+preferentially+increase+synaptic+dopamine+concentrations+in+the+mesolimbic+system+of+freely+moving+rats.">Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats.</a> Proc. Natl. Acad. Sci. U.S.A. 85, 5274-5278 (1988).</li><li>Barrett, S. P., Boileau, I., Okker, J., Pihl, R. O., Dagher, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+hedonic+response+to+cigarette+smoking+is+proportional+to+dopamine+release+in+the+human+striatum+as+measured+by+positron+emission+tomography+and+[11C]raclopride.">The hedonic response to cigarette smoking is proportional to dopamine release in the human striatum as measured by positron emission tomography and [11C]raclopride.</a> Synapse. 54, 65-71 (2004).</li><li>Brody, A. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Gene+variants+of+brain+dopamine+pathways+and+smoking-induced+dopamine+release+in+the+ventral+caudate/nucleus+accumbens.">Gene variants of brain dopamine pathways and smoking-induced dopamine release in the ventral caudate/nucleus accumbens.</a> Arch. Gen. Psychiatry. 63, 808-816 (2006).</li><li>Brody, A. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Smoking-induced+ventral+striatum+dopamine+release.">Smoking-induced ventral striatum dopamine release.</a> The American journal of psychiatry. 161, 1211-1218 (2004).</li><li>Montgomery, A. J., Lingford-Hughes, A. R., Egerton, A., Nutt, D. J., Grasby, P. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+effect+of+nicotine+on+striatal+dopamine+release+in+man:+A+[11C]raclopride+PET+study.">The effect of nicotine on striatal dopamine release in man: A [11C]raclopride PET study.</a> Synapse. 61, 637-645 (2007).</li><li>Scott, D. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Smoking+modulation+of+mu-opioid+and+dopamine+D2+receptor-mediated+neurotransmission+in+humans.">Smoking modulation of mu-opioid and dopamine D2 receptor-mediated neurotransmission in humans.</a> Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology. 32, 450-457 (2007).</li><li>Takahashi, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Enhanced+dopamine+release+by+nicotine+in+cigarette+smokers:+a+double-blind,+randomized,+placebo-controlled+pilot+study.">Enhanced dopamine release by nicotine in cigarette smokers: a double-blind, randomized, placebo-controlled pilot study.</a> Int. J. Neuropsychopharmacol. 11, 413-417 (2008).</li><li>Morris, E. D., Fisher, R. E., Alpert, N. M., Rauch, S. L., Fischman, A. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=In+vivo+imaging+of+neuromodulation+using+positron+emission+tomography:+Optimal+ligand+characteristics+and+task+length+for+detection+of+activation.">In vivo imaging of neuromodulation using positron emission tomography: Optimal ligand characteristics and task length for detection of activation.</a> Human Brain Mapping. 3, 35-55 (1995).</li><li>Alpert, N. M., Badgaiyan, R. D., Livni, E., Fischman, A. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+novel+method+for+noninvasive+detection+of+neuromodulatory+changes+in+specific+neurotransmitter+systems.">A novel method for noninvasive detection of neuromodulatory changes in specific neurotransmitter systems.</a> NeuroImage. 19, 1049-1060 (2003).</li><li>Carson, R. E., Barker, W. C., Jeih-San, L., Johnson, C. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Nuclear+Science+Symposium+Conference+Record.">Nuclear Science Symposium Conference Record.</a> 2003 IEEE. 3285, 3281-3285 (2003).</li><li>Carson, R. E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comparison+of+bolus+and+infusion+methods+for+receptor+quantitation:+application+to+[18F]cyclofoxy+and+positron+emission+tomography.">Comparison of bolus and infusion methods for receptor quantitation: application to [18F]cyclofoxy and positron emission tomography.</a> Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 13, 24-42 (1993).</li><li>Smith, S. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fast+robust+automated+brain+extraction.">Fast robust automated brain extraction.</a> Human brain mapping. 17, 143-155 (2002).</li><li>Floberg, J. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Improved+kinetic+analysis+of+dynamic+PET+data+with+optimized+HYPR-LR.">Improved kinetic analysis of dynamic PET data with optimized HYPR-LR.</a> Medical physics. 39, 3319-3331 (2012).</li><li>Martinez, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Imaging+human+mesolimbic+dopamine+transmission+with+positron+emission+tomography.+Part+II:+amphetamine-induced+dopamine+release+in+the+functional+subdivisions+of+the+striatum.">Imaging human mesolimbic dopamine transmission with positron emission tomography. Part II: amphetamine-induced dopamine release in the functional subdivisions of the striatum.</a> Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 23, 285-300 (2003).</li><li>Montgomery, A. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Correction+of+head+movement+on+PET+studies:+comparison+of+methods.">Correction of head movement on PET studies: comparison of methods.</a> Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 47, 1936-1944 (2006).</li><li>Yoder, K. K., Wang, C., Morris, E. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Change+in+binding+potential+as+a+quantitative+index+of+neurotransmitter+release+is+highly+sensitive+to+relative+timing+and+kinetics+of+the+tracer+and+the+endogenous+ligand.">Change in binding potential as a quantitative index of neurotransmitter release is highly sensitive to relative timing and kinetics of the tracer and the endogenous ligand.</a> Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 45, 903-911 (2004).</li><li>Wang, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> , (2012).</li><li>Ginovart, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Imaging+the+dopamine+system+with+in+vivo+[11C]raclopride+displacement+studies:+understanding+the+true+mechanism.">Imaging the dopamine system with in vivo [11C]raclopride displacement studies: understanding the true mechanism.</a> Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging. 7, 45-52 (2005).</li><li>Sullivan, J. M., Kim, S. J., Cosgrove, K. P., Morris, E. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> , (2012).</li><li>Miller, R. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Simultaneous Statistical Inference. , (1981).</li><li>Paterson, L. M., Tyacke, R. J., Nutt, D. J., Knudsen, G. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Measuring+endogenous+5-HT+release+by+emission+tomography:+promises+and+pitfalls.">Measuring endogenous 5-HT release by emission tomography: promises and pitfalls.</a> Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 30, 1682-1706 (2010).</li><li>Ridler, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Characterization+of+in+vivo+pharmacological+properties+and+sensitivity+to+endogenous+serotonin+of+[11C]+P943:+a+positron+emission+tomography+study+in+Papio+anubis.">Characterization of in vivo pharmacological properties and sensitivity to endogenous serotonin of [11C] P943: a positron emission tomography study in Papio anubis.</a> Synapse. 65, 1119-1127 (2011).</li><li>Cosgrove, K. P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Assessing+the+sensitivity+of+[(1)(1)C]p943,+a+novel+5-HT1B+radioligand,+to+endogenous+serotonin+release.">Assessing the sensitivity of [(1)(1)C]p943, a novel 5-HT1B radioligand, to endogenous serotonin release.</a> Synapse. 65 (1), 1113-1117 (2011).</li><li>Finnema, S. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fenfluramine-induced+serotonin+release+decreases+[11C]AZ10419369+binding+to+5-HT1B-receptors+in+the+primate+brain.">Fenfluramine-induced serotonin release decreases [11C]AZ10419369 binding to 5-HT1B-receptors in the primate brain.</a> Synapse. 64, 573-577 (2010).</li><li>Finnema, S. J., Varrone, A., Hwang, T. J., Halldin, C., Farde, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Confirmation+of+fenfluramine+effect+on+5-HT(1B)+receptor+binding+of+[(11)C]AZ10419369+using+an+equilibrium+approach.">Confirmation of fenfluramine effect on 5-HT(1B) receptor binding of [(11)C]AZ10419369 using an equilibrium approach.</a> Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 32 (11), 685-695 (2012).</li><li>Morris, E. D., Yoder, K. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Positron+emission+tomography+displacement+sensitivity:+predicting+binding+potential+change+for+positron+emission+tomography+tracers+based+on+their+kinetic+characteristics.">Positron emission tomography displacement sensitivity: predicting binding potential change for positron emission tomography tracers based on their kinetic characteristics.</a> Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 27, 606-617 (2007).</li><li>Gunn, R. N., Lammertsma, A. A., Hume, S. P., Cunningham, V. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Parametric+imaging+of+ligand-receptor+binding+in+PET+using+a+simplified+reference+region+model.">Parametric imaging of ligand-receptor binding in PET using a simplified reference region model.</a> NeuroImage. 6, 279-287 (1997).</li><li>Lammertsma, A. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comparison+of+methods+for+analysis+of+clinical+[11C]raclopride+studies.">Comparison of methods for analysis of clinical [11C]raclopride studies.</a> Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 16, 42-52 (1996).</li></ol>

作者指出，他们什么都没有透露。

吸烟的多巴胺反应在PET文献的研究结果是不一致13-18。有可能是多方面原因造成的。各种方法上的困难出现的任何企图图像吸烟。最起码，必须与可能的运动伪影的数据，研究人员的二手烟暴露，多巴胺温和而短暂的变化，只有细微的改变导致了示踪剂的摄取和滞留，11 C-雷氯必利。 人工诱导多巴胺一个庞大而持续的反应可能会对未能通过施用静脉注射大剂量的尼古丁。然而，这将是我们的基本目标相反，在建立多巴胺电影吸烟。我们的目的是尽可能仔细检查整个的吸烟行为的多巴胺反应。在网瘾的研究，一个重要的区分被动管理药物的主体和自我管理。我们的目标是形象的自我管理 - 吸烟者吸烟他/她自己的首选品牌香烟 - 为了捕捉和描述吸烟简短的多巴胺反应。 PET分析通常假设的影响扫描时间相对长寿命的药物或其他挑战。因此，成像吸烟需要创新建模和实验PET。 在我们的协议中的关键步骤在扫描仪促进吸烟<ol><li>为了形象的自我管理（ 如吸烟），我们必须消除二手烟的环境，健康和安全部门的满意。这是通过拉周围的空气通过HEPA过滤器的主题，以除去颗粒物的便携式空气过滤系统，该系统的使用。本机配备有明显的圆顶形进气罩，可降低超过吨他拍摄对象的脸部，但不妨碍他/她吸烟。 </li><li>吸烟引起头部运动 - ，即使吸烟者指示将他们的手，并保持他们的头部仍然。在一个单一的时间帧的运动降低了扫描仪的点扩散函数。也就是说，它有助于在图像模糊。在扫描过程中的头部运动也意味着，头是在发射和传输过程中在不同的位置。这种不匹配可能会导致文物当传输扫描纠正衰减。的Vicra头跟踪系统解决了这两个问题，通常被认为是代表国家的最先进的解决方案的问题26。 </li></ol> 11 C-雷氯必利吸收多巴胺水平的微小变化的敏感性最大化<ol start="3"><li>以前的模拟我们小组的工作已表明，多巴胺水平的变化的敏感度是整个扫描时间，如果没有统一的示踪剂是admin通过大剂量注射27一起注册。另一方面，示踪剂了初始剂量随后出现大大的灵敏度相等的PET数据，在扫描过程中在任何时间吸烟缓慢输注。 </li><li>吸烟诱发多巴胺的变化是在PET数据本身的噪音相对较小。高度约束反投影重建（HYPR）8,24平滑fMRI的数据，最近被应用到PET的常用方法。这种空间平滑技术降低了噪音没有磨灭我们感兴趣的数据。也就是说，变形时间活动曲线代表示踪剂与内源性多巴胺的竞争时空特征。我们的前期工作，28表示有HYPR过滤器，最大限度地提高阈值F-映射（ 即保留体素数），差异吸烟基线康迪特之间的差异是一个最佳的选择离子。的最佳的过滤器（选择所给出的数据）可能取决于激活区域（参见图2）的近似大小上的的HYPR内核的大小适当的匹配。 </li><li>吸烟诱发多巴胺的变化是短暂的。传统PET分析方法都不能很好地适合于捕获瞬态的神经递质事件25,29。我们有特点的缺点，使用各种常规分析仿真实验和人体数据30。出于这些原因，我们的实验室中已开发和验证了一些在PET数据1-7的多巴胺瞬变的影响进行建模的数学技术。 7由诺曼丁等。最近的一项创新是线性我们原来ntPET模式，所以它可以适用于体素水平。这样做的结果是一种多巴胺本文提出类似的电影。我们的方法主要方面为估计多巴胺瞬变，在PET数据已验证的前情Y:在老鼠同时接受PET和微透析4和人类执行一个手指敲击任务3,4。 </li><li>统计测试的某种需要隔离多巴胺诚实的变化不同于偶然事件。我们选择使用F统计量（又名"F比率"）确定的地区（ 即体素）的图像是最有可能含有检测和量化多巴胺的反应。 F统计量是用来比较两个嵌套模型的拟合平方的总和，同时活动数据。在这种情况下，我们比较适合传统的模型没有一个随时间变化的多巴胺，长期我们最近推出的的LP-ntPET模型包含一个随时间变化的长期多巴胺波动。只有那些F比率超过一个给定的统计阈值的体素被保留在最后的多巴胺电影。 </li></ol>呈现的结果的解释的限制 &lt;醇&gt; <li>这里介绍的是样品的结果，当然不是一个完整的研究。深入研究吸烟会涉及基线条件，吸烟状况和假吸烟情况来控制运动诱发多巴胺的释放 - 不同的运动伪影（见上文）。在我们的实验室，这些研究正在进行。 应该指出的是，构造合适的假吸烟条件远非如此简单。对于吸烟者，他们的嘴将熄灭香烟单纯的行为可能是有益的，因此释放多巴胺。因此，但不期望的运动的控制很可能是可比较的努力和频率以在香烟的抽吸的定向电机运动，但不是运动，可能不以任何方式按钮或手动对象的操作，如与吸烟相关的。 </li><li>清楚地认识到，如果有足够多的比较，将有超过一个给定的统计阈值的机会发现<html>老31。我们所采取的比较之间的配合常规模式和所有体素在纹状体LP-ntPET的模型的拟合。目前，我们没有正式纠正多比较（ 例如 ，"Bonferroni校正"）。相反，我们已向的多巴胺电影分析基线条件除了有吸烟状况。如果我们多巴胺电影吸烟只是偶然的结果，我们希望激活区域（超阈值的体素数）在基准相同的密度，在吸烟的数据。这显然不是这种情况（ 见图7）。 </li><li>当然，我们的技术的可再现性是一个重要的相关问题。人们预计，吸烟者的大脑应对同样抽着烟今天或明天或下周。目前，我们正在从事评估重测重现性多巴胺电影。 </li></ol>未来jove_content"&gt; PET示踪剂摄取中存在的内源性神经递质水平的短期波动，我们已经开发了一种新的模式，由于模型是线性的参数，它可以快速，轻松地计算在许多体素配件等的终点体素，由-体素的基础上的PET数据的一个模型是"电影"。研究的D2受体示踪剂，11 C-雷氯必利，端点是多巴胺电影。多巴胺是关键神经递质参与大脑的处理奖励刺激，导致成瘾。由于某些刺激（最显着的香烟和酒精）产生只有轻微的，可能是短命的多巴胺变化，可能有电影研究这两个刺激的滥用潜力最大的，如果我们可以用我们的多巴胺电影多巴胺的释放指示的依赖或滥用的风险识别空间和时间模式，这些模式可以作为标记的疾病，疾病的风险，- 假设模式是可逆的 - 指标（药物或认知）疗效。 关于我们的电影有什么，限制他们的多巴胺系统。所需要的是一个感兴趣的目标，是在相同的目标（ 即 ，很容易由位移）的内源性配体的波动敏感的PET示踪剂。日期，已停止进展情况以查明可靠敏感的内源性神经递质多巴胺以外的PET示踪剂。在2010年的5 -羟色胺文学的审查，例如，画令人警醒的画面，目前我们的能力有限，检测5 -羟色胺的释放与PET 32。最近，已经有一些令人鼓舞的发展。一些出版物曾报道的5 -羟色胺的敏感性示踪剂海拔内源性的5 -羟色胺在非人类灵长类动物33-36，但在人类的领域等待着类似的示威。正如我们已经讨论别处&lt;支持&gt; 37，内源性神经递质浓度的变化的敏感性似乎是由一个最佳的速率从受体结合的示踪剂从组织血液流出的易于使用的的位移。一旦5 - 羟色胺配位体已被验证，并显示出具有这样的属性，然后5 - 羟色胺的电影也将是可能的。 目前，大部分PET与受体示踪剂的研究导致的参数图像的生成。参数化的形象是一个给定的示踪动力学模型参数评估在每一个像素在对象（ 即大脑）的地图。 SRTM 38,39或产生一个或两个组织二室模型参数的图像里，区域流动参数，或BP，区域约束力的潜在价值，如传统机型的应用。这些参数都代表处于稳定状态的过程，被认为是生理常数。然而，有时，系统和/或过程的诠释erested是不稳定的。也就是说，它们是短暂的。就是这样短命多巴胺吸烟的情况。在这样的情况下，这是不可能用一个单一的参数图像表征多巴胺瞬态。它也不是适当的数据建模与模型是严格的时间参数不变。有必要与随时间变化的术语来描述的模型的纹状体中的多巴胺浓度的变化响应吸烟。使用这种模式时的自然输出与多巴胺示踪剂，是一部电影的多巴胺。这是一种新形式的图像输出功能，可能会刺激，需要新形式的分析，以最大限度地发挥其效用。

尽管有压倒性的证据的医疗风险，吸烟仍然是一个主要的健康问题。这简直是​​很难戒烟。超过20％的美国成人人口继续吸烟，大多数吸烟者试图戒烟的第一个月内复发10。不幸的是，有几个可用的治疗方法，以帮助戒烟和/或减少对尼古丁的依赖。在我们的实验室，我们感兴趣的是使用PET显像了解，为了帮助开发新药物戒烟和其他吸毒成瘾和依赖。 纹状体内多巴胺的迅速崛起被认为可能与撤离和随后的药物寻求编码的药物上瘾的责任和行为，11和多巴胺基线快速回笼。对于一些上瘾的物质，吸烟等行为，海拔纹状体多巴胺是非常短暂的时间（分钟）;ë键的上升幅度并不大（1-2X基线），这些响应可能是有限的空间范围小的子区域的纹状体。 动物实验清楚地表明，尼古丁会导致大鼠12伏隔核的多巴胺释放。但早期的尝试中使用传统的分析-估计在人类的多巴胺变化尼古丁或吸烟期间或之后，已经取得了不可靠的，矛盾的结果13-18。一些这些研究允许烟民吸烟外扫描器。其他仅交付尼古丁的主题。为了更好地研究香烟成瘾，我们开发出更好的的成像协议和补充他们与先进的分析，这将使我们能够捕捉大脑的反应的准自然的吸烟行为。 正电子发射断层扫描（PET）是唯一的大脑扫描技术，它能够探测人类大脑的神经化学&lt;<html>时间&gt;的体内。存在许多PET示踪剂跟踪多巴胺受体，许多人很容易受到内源性多巴胺的竞争。不幸的是，传统的PET图像分析方法估计绑定免费示踪剂，被称为束缚势（类似于体外方法），从动态PET图像的稳态比率。一个明显的变化的比率（ 例如 ，从基线到吸烟条件）在稳定状态下被表示多巴胺的变化。但成瘾有关的多巴胺变化本质上是短暂的，所以一个稳定的状态量的估计是有缺陷的。此外，典型区域的平均利率分析示踪剂浓度过大解剖学定义的地区，并有可能错过高度本地化的的大脑反应 - 如我们期望从吸烟。上一页PET研究吸烟可能也遭受运动吸烟者的头，期间吸烟扫描仪。 jove_content"功能磁共振成像（fMRI）技术提供了必要的时间和空间分辨率，将需要捕捉事件发生在子区域纹状体分钟的时间比例，但fMRI的缺乏分子特异性PET BOLD信号来自血流量的变化，因此，神经和分子非特异性的，因此，我们利用PET -而是一种新的方式。此协议的目的是短暂和局部的多巴胺反应估计吸烟，因为他们被认为是背后的神经化学表现渴求和觅药行为。 要估计多巴胺瞬变，动态PET图像与多巴胺受体配体捕获，我们之前推出了一系列统称为"ntPET"的神经递质PET 1,5,6,19，基于动力学模型，传统的两组织二室模型，但时间变化增强DOP胺和多巴胺和示踪（ 即竞争）之间的相互作用。已通过验证这些模型对金标准。具体地说，我们已经表明，我们的模型预测，随着时间的推移PET数据大鼠在良好的协议，同时收购微透析测量4,7多巴胺浓度优点 :最近我们的模型一直是线性和非参数（NP ntPET）1线性和参数（LP-ntPET）7。后者的模型源于较早的线性模型中引入阿尔珀特等。20。线性化是一个重要的发展，因为它保证了在体素水平的动态数据，运用模型计算简单。在最近的一个概念证明型的纸张，我们能够创造出一个人类主体多巴胺电影执行机动任务3，电影电机任务的时间将有望敏感。博Movi上课表示的在图像中的每个体素的多巴胺水平的时间过程。体素体素的方法，在PET普遍遭受低信号的信噪比，所以要尽量减少噪声固有的基于体素的活性曲线（TACS），我们采用一个创新的空间滤波器，&#39;HYPR&#39;，8作为预处理步骤。这一步保留关键的时空特征响应像素，同时降低噪音。 吸烟是超过尼古丁发送。香烟中含有4000多种化学物质，除了尼古丁。虽然尼古丁被认为是主要负责初始上瘾的效果，所有其他的线索和感官元件成为增强一个习惯性吸烟者吸烟。我们选择研究整个吸烟的行为，这意味着，我们需要能够对图像吸烟者吸烟，而里面的PET扫描仪。不幸的是，吸烟谈到头部运动。为了消除头部运动伪影图像中，我们使用Vicra的动议正跟踪系统（NDI系统，滑铁卢，加拿大）和事件事件运动校正作为一个迭代的，分辨率恢复重建算法21的一部分。 我们新的扫描和分析方法，旨在引起捕捉短暂和局部的瞬态多巴胺是大脑的反应，成瘾性药物和行为的独特签名。我们的模型进行体素体素，产生一组动态的的纹状体多巴胺波动图像- 即多巴胺电影"。这些电影代表了一种新的时空网瘾的生物标志物，可以作为一个直接的，多维的风险指标成瘾性和/或疗效指标。

<table><tbody><tr><td>Vicra</td><td>NDI Systems, Waterloo, Canada</td><td></td><td></td></tr><tr><td>HRRT</td><td>Siemens</td><td></td><td></td></tr><tr><td>Air Filter</td><td>Movex, Inc, Northampton, PA</td><td>LFK 175</td><td>With extractor and clear hood</td></tr><tr><td>&lt;sup&gt;11&lt;/sup&gt;C-raclopride</td><td></td><td></td><td>prepared at Yale PET Center from &lt;em&gt;O&lt;/em&gt;-Desmethyl precursor</td></tr><tr><td>O-Desmethylraclopride</td><td>ABX advanced biochemical compounds, Radeberg, Germany</td><td>Product #1510</td><td>Precursor of &lt;sup&gt;11&lt;/sup&gt;C-raclopride</td></tr><tr><td colspan="4">&lt;strong&gt;Table 1.&lt;/strong&gt; Materials used.</td></tr></tbody></table>

creating dynamic images of short-lived dopamine fluctuations with lp-ntpet:  dopamine movies of cigarette smoking

我们描述的实验和统计的步骤创建从动态PET数据的大脑多巴胺电影。电影代表多巴胺诱导抽着烟分钟到分钟的波动。吸烟者成像在自然吸烟经验，而其他可能的混杂影响最小化（如头部运动，期望，求新，或反复吸烟的厌恶）。 我们提出了我们独特的分析。 PET分析估计时间不变的动力学模型参数，它们不能捕捉短期波动的神经递质释放的常规方法。基于时变参数1-7动力学模型及其它分解技术，使我们的工作与我们的分析- ，产生多巴胺电影- 。这方面的分析 - 时空变化 - 是对我们工作的关键。因为我们的模型也是线性的参数，它是实用，计算，适用于日É体素水平。包括五个主要步骤:前处理，建模，统计比较，掩蔽和可视化分析技术。预处理PET独特的"HYPR过滤器8的空间，空间噪声降低，但保留关键的时间信息的数据被施加到。建模标识随时间变化的函数，最能说明11 C-雷氯必利吸收多巴胺的效果。统计一步比较适合我国的（LP-ntPET）模型7传统型号9。屏蔽限制治疗最好地描述了新的模型的体素。可视化地图上的每个像素的颜色规模的多巴胺功能和产生多巴胺电影。吸烟的中期业绩和样品多巴胺电影。

图2。两个不同的HYPR空间滤波器的平滑性在一个单一的纹状体的体素数据的时间 - 活性的影响。上面一排:11 C-雷氯必利PET排放集中在46.5分钟（不过滤，过滤用一个3×3×3像素内核，一个5×5×5像素内核过滤）3分钟帧的图像。中间行:11 C-雷氯必利的PET发射中心在61.5分钟（不过滤，过滤，用3×3×3像素内核，过滤得到的5×5×5像素内核）从3分钟的帧的图像。底行:相应的时间活动曲线相同的单体素位置在左背尾。请注意，虽然更大的过滤器的大小减少噪声，在11 C-雷氯必利的吸收（由于多巴胺释放），在吸烟时会保留视倾角。 图3。代表性的多巴胺反应功能的选择预COMputed到诺曼丁等7适合的lp ntPET模型PET的时间在每个像素的活动数据。在我们的无烟范式的情况下，吸烟开始后45分钟开始注射示踪剂。即使纹状体多巴胺反应编码预期吸烟- 例如 ，由于处理的香烟或其他线索，预示着吸烟-我们的理由可以安全地被限制的响应函数曲线起飞，从基线不早于5分钟前吸烟（一）。同样，曲线仅限于起飞时间不迟于 15分钟后开始吸烟。起飞时间在40分钟曲线代表可能的多巴胺反应由于期望。（二）代表响应函数从基线起飞45分钟的时候开始吸烟。产生500个不同的合理的响应函数。举例来说，地块&lt;&gt;（a）和（b）显示的采样曲线的形状和起飞时间。 图4（a）本业务为使用lp-ntPET的模型方程。该模型是线性的参数（γ，R 1，K 2，K 2a的 ），它允许在每个像素内的纹状体掩模参数估计值的快速计算。（二）:参数的图像（R 1，K 2，K 2a的 γ ）为一个单一的冠状脑片为一个单一的主题。虽然γ单独的参数，该参数编码多巴胺响应的幅度，同时估计所有4示踪参数是必要的，以适应模型在每个像素的数据的时间 - 活性。 图5。的的常规（MRTM）和新的（线对ntPET）模型的拟合，从左侧尾状核中的体素数据的时间 - 活性。是蓝色MRTM适合。 LP-ntPET适合为红色。 <p类=的"jove_content"&gt; 图6（a）表示加权的残差平方和（WSSR）从MRTM的，及（b）从LP-ntPET适合在每个纹状体的体素数据。两个WSSR从同一数据生成的图像进行比较，以产生在每个像素（ 即一个F-图），（c）中所示的F比在地图上，（d）在F-映射的阈值当p &lt;0.05并产生一个二进制的意义地图（见步骤2.10协议）。对于n时限，4个参数的LP-ntPET模型，F统计量对应的概率水平的门槛，P &lt;0.05（90分钟，3分钟帧的数据分级，阈值是4.23）（E ）的意义映射过滤形态滤波器（"开放"），以消除微小的像素，是最有可能代表噪声集群。最终意义面膜只保留那些体素的总可捕量，更好地适应在纹状体（统计istically）由使用lp-ntPET的模型，而不是到常规MRTM模型，并因此被认为包含多巴胺能响应吸烟。这个门槛不纠正多重比较。相反，谨防假阳性结果，我们创建了控制条件以及最终意义面具（ 见图7和"议定书"的步骤1.8 - 1.10）。 图7（a）显示冠状切片吸烟状况的最终意义面膜在一个单一的主题之一。图（b）给出了相应的主题和切片在基准条件下的最终意义面膜。 近集群的面具（见下文）多巴胺电影并不是单纯的偶然事件或事件中的噪声控制支持争完全没有保留体素在吸烟的面具，而不是集群的存在的数据。 （注:注入的活动 -因此，ð噪比的信号 - 在基线和吸烟条件是可比较的。） 图8。显示一个单一的方向在冠状脑切片的多巴胺的电影帧接一帧的多巴胺水平相对基底（静止）的多巴胺水平。（a）表示的基线条件的电影，和（b）示出的电影吸烟情况。颜色编码的多巴胺水平。具体而言，颜色 - 所示的色条与相应的数字值 - 表示多巴胺作为基底的百分比高于基础水平的变化。同样，多巴胺水平只显示像素在最终意义​​面膜超过P &lt;0.05的显着性水平。 图9所示 。多片，多条件多巴胺电影就相同主题的腹侧纹状体图8中的所有切片同时显示f<html>或基线和吸烟状况。 <img alt="图1" fo:content-width="6in" fo:src="/files/ftp_upload/50358/50358fig1highres.jpg" src="/files/ftp_upload/50358/50358fig1.jpg" /> 图1。实验流程图和图像分析程序（AC） <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/50358/50358fig1large.jpg" target="_blank">点击此处查看大图</a> 。 <img alt="图2" src="/files/ftp_upload/50358/50358fig2.jpg" /> 图2。 HYPR过滤不同的内核大小的图像（顶部和中间）和时间活动曲线（底部）在一个单一的体素的影响。 <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/50358/50358fig2large.jpg" target="_blank">点击这里查看大图</a> 。 <html> / files/ftp_upload/50358/50358fig3.jpg的"/&gt; 图3。多巴胺响应函数的例子，起飞（一）40分钟或（b）45分钟后注射示踪剂。 <img alt="图4" src="/files/ftp_upload/50358/50358fig4.jpg" /> 图4。产生的PET数据合身使用lp-ntPET的的操作（a）式的参数图像（二）的4个参数的模型中，R 1，K 2，K 2a中，γ，相对应的图像进行评估纹状体所示覆盖在相应的MR片。 <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/50358/50358fig4large.jpg" target="_blank">点击这里查看大图</a> 。 iles/ftp_upload/50358/50358fig5.jpg"/&gt; 图5。适合的活动数据从一个单一的体素MRTM（蓝色）和LP-ntPET的模型（红色）。 <img alt="图6" src="/files/ftp_upload/50358/50358fig6.jpg" /> 图6。的的WSSR为（一）MRTM及（b），LP-ntPET。各WSSR地图进行比较，以创建的F -图（c）所示 ，阈值而这又是一个二进制掩码（四），然后过滤，以参数的图像生产的最终意义面膜。 <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/50358/50358fig6large.jpg" target="_blank">点击这里查看大图</a> 。 <img alt="图7" src="/files/ftp_upload/50358/50358fig7.jpg" /> 图7。 （a）和控制吸烟的比较的最后重大意义面具 <stroNG&gt;（二）同一主题。 图8.Single片多巴胺电影为单一主体的控制权（"休息"）和吸烟情况。 <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/50358/50358fig8.swf" target="_blank">点击此处查看图8</a> 。 图9，多片多巴胺电影（顶部）吸烟和控制（下）（"休息"）的条件下的单一主体。 <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/50358/50358fig9.avi" target="_blank">点击此处查看图9</a> 。

Watch this Scientific Journal Video about Creating Dynamic Images of Short-lived Dopamine Fluctuations with lp-ntPET:  Dopamine Movies of Cigarette Smoking at JoVE.com

Creating Dynamic Images of Short-lived Dopamine Fluctuations with lp-ntPET:  Dopamine Movies of Cigarette Smoking

我们提出了一个新颖的PET成像的方法捕获由吸烟引起的多巴胺波动。在PET扫描仪的主题抽烟。动态PET图像的体素的体素的建模时间由LP-ntPET，其中包括一个随时间变化的多巴胺内。结果是&#39;电影&#39;在纹状体多巴胺波动的过程中吸烟。

创建动态图像的短命多巴胺波动与LP-ntPET:多巴胺电影吸烟

We describe experimental and statistical steps for creating dopamine movies of the brain from dynamic PET data. The movies represent minute-to-minute ...

creating-dynamic-images-short-lived-dopamine-fluctuations-with-lp

Nanyang Technological University

Research

JoVE Journal

Behavior

18.2K 次观看.  Yale University. 我们提出了一个新颖的PET成像的方法捕获由吸烟引起的多巴胺波动。在PET扫描仪的主题抽烟。动态PET图像的体素的体素的建模时间由LP-ntPET，其中包括一个随时间变化的多巴胺内。结果是'电影'在纹状体多巴胺波动的过程中吸烟。

视频: Creating Dynamic Images of Short-lived Dopamine Fluctuations with lp-ntPET:  Dopamine Movies of Cigarette Smoking

Examination of Rapid Dopamine Dynamics with Fast Scan Cyclic Voltammetry During Intra-oral Tastant Administration in Awake Rats

Rapid, phasic dopamine (DA) release in the mammalian brain plays a critical role in reward processing, reinforcement learning, and motivational control. Fast scan cyclic voltammetry (FSCV) is an electrochemical technique with high spatial and temporal (sub-second) resolution that has been utilized to examine phasic DA release in several types of preparations. In vitro experiments in single-cells and brain slices and in vivo experiments in anesthetized rodents have been used to identify mechanisms that mediate dopamine release and uptake under normal conditions and in disease models. Over the last 20 years, in vivo FSCV experiments in awake, freely moving rodents have also provided insight of dopaminergic mechanisms in reward processing and reward learning. One major advantage of the awake, freely moving preparation is the ability to examine rapid DA fluctuations that are time-locked to specific behavioral events or to reward or cue presentation. However, one limitation of combined behavior and voltammetry experiments is the difficulty of dissociating DA effects that are specific to primary rewarding or aversive stimuli from co-occurring DA fluctuations that mediate reward-directed or other motor behaviors. Here, we describe a combined method using in vivo FSCV and intra-oral infusion in an awake rat to directly investigate DA responses to oral tastants. In these experiments, oral tastants are infused directly to the palate of the rat &#8211; bypassing reward-directed behavior and voluntary drinking behavior &#8211; allowing for direct examination of DA responses to tastant stimuli.

Rapid fluctuations in extracellular dopamine (DA) mediate both reward processing and motivated behavior in mammals. This manuscript describes the combined use of fast scan cyclic voltammetry (FSCV) and intra-oral tastant administration to determine how tastants alter rapid dopamine release in awake, freely moving rats.

考试多巴胺快速与动态快速扫描循环伏安法在口内呈味物质管理清醒大鼠

Rapid, phasic dopamine (DA) release in the mammalian brain plays a critical role in reward processing, reinforcement learning, and motivational control. ...

科研

行为学

Presynaptic Dopamine Dynamics in Striatal Brain Slices with Fast-scan Cyclic Voltammetry

Extensive research has focused on the neurotransmitter dopamine because of its importance in the mechanism of action of drugs of abuse (e.g. cocaine and amphetamine), the role it plays in psychiatric illnesses (e.g. schizophrenia and Attention Deficit Hyperactivity Disorder), and its involvement in degenerative disorders like Parkinson's and Huntington's disease. Under normal physiological conditions, dopamine is known to regulate locomotor activity, cognition, learning, emotional affect, and neuroendocrine hormone secretion. One of the largest densities of dopamine neurons is within the striatum, which can be divided in two distinct neuroanatomical regions known as the nucleus accumbens and the caudate-putamen. The objective is to illustrate a general protocol for slice fast-scan cyclic voltammetry (FSCV) within the mouse striatum. FSCV is a well-defined electrochemical technique providing the opportunity to measure dopamine release and uptake in real time in discrete brain regions. Carbon fiber microelectrodes (diameter of ~ 7 &mu;m) are used in FSCV to detect dopamine oxidation. The analytical advantage of using FSCV to detect dopamine is its enhanced temporal resolution of 100 milliseconds and spatial resolution of less than ten microns, providing complementary information to in vivo microdialysis.

Using fast-scan cyclic voltammetry to measure electrically evoked presynaptic dopamine dynamics in striatal brain slices.

突触前多巴胺纹状体脑片的快速扫描循环伏安动态

Extensive research has focused on the neurotransmitter dopamine because of its importance in the mechanism of action of drugs of abuse (e.g. cocaine and ...

神经科学

Spectral Confocal Imaging of Fluorescently tagged Nicotinic Receptors in Knock-in Mice with Chronic Nicotine Administration

Ligand-gated ion channels in the central nervous system (CNS) are implicated in numerous conditions with serious medical and social consequences. For instance, addiction to nicotine via tobacco smoking is a leading cause of premature death worldwide (World Health Organization) and is likely caused by an alteration of ion channel distribution in the brain1. Chronic nicotine exposure in both rodents and humans results in increased numbers of nicotinic acetylcholine receptors (nAChRs) in brain tissue1-3. Similarly, alterations in the glutamatergic GluN1 or GluA1 channels have been implicated in triggering sensitization to other addictive drugs such as cocaine, amphetamines and opiates4-6.

Consequently, the ability to map and quantify distribution and expression patterns of specific ion channels is critically important to understanding the mechanisms of addiction. The study of brain region-specific effects of individual drugs was advanced by the advent of techniques such as radioactive ligands. However, the low spatial resolution of radioactive ligand binding prevents the ability to quantify ligand-gated ion channels in specific subtypes of neurons. 

Genetically encoded fluorescent reporters, such as green fluorescent protein (GFP) and its many color variants, have revolutionized the field of biology7.By genetically tagging a fluorescent reporter to an endogenous protein one can visualize proteins in vivo7-10. One advantage of fluorescently tagging proteins with a probe is the elimination of antibody use, which have issues of nonspecificity and accessibility to the target protein. We have used this strategy to fluorescently label nAChRs, which enabled the study of receptor assembly using F&ouml;rster Resonance Energy Transfer (FRET) in transfected cultured cells11.More recently, we have used the knock-in approach to engineer mice with yellow fluorescent protein tagged &alpha;4 nAChR subunits (&alpha;4YFP), enabling precise quantification of the receptor ex vivo at submicrometer resolution in CNS neurons via spectral confocal microscopy12. The targeted fluorescent knock-in mutation is incorporated in the endogenous locus and under control of its native promoter, producing normal levels of expression and regulation of the receptor when compared to untagged receptors in wildtype mice. This knock-in approach can be extended to fluorescently tag other ion channels and offers a powerful approach of visualizing and quantifying receptors in the CNS.

In this paper we describe a methodology to quantify changes in nAChR expression in specific CNS neurons after exposure to chronic nicotine. Our methods include mini-osmotic pump implantation, intracardiac perfusion fixation, imaging and analysis of fluorescently tagged nicotinic receptor subunits from &alpha;4YFP knock-in mice (Fig. 1). We have optimized the fixation technique to minimize autofluorescence from fixed brain tissue.We describe in detail our imaging methodology using a spectral confocal microscope in conjunction with a linear spectral unmixing algorithm to subtract autofluoresent signal in order to accurately obtain &alpha;4YFP fluorescence signal. Finally, we show results of chronic nicotine-induced upregulation of &alpha;4YFP receptors in the medial perforant path of the hippocampus.

We have developed a novel technique of quantifying nicotinic acetylcholine receptor changes within subcellular regions of specific subtypes of CNS neurons to better understand the mechanisms of nicotine addiction by using a combination of approaches including fluorescent protein tagging of the receptor using the knock-in approach and spectral confocal imaging.

光谱共焦成像的荧光标记的尼古丁受体敲在慢性尼古丁政府小鼠

Ligand-gated ion channels in the central nervous system (CNS) are implicated in numerous conditions with serious medical and social consequences.  For ...

Local Application of Drugs to Study Nicotinic Acetylcholine Receptor Function in Mouse Brain Slices

Tobacco use leads to numerous health problems, including cancer, heart disease, emphysema, and stroke. Addiction to cigarette smoking is a prevalent neuropsychiatric disorder that stems from the biophysical and cellular actions of nicotine on nicotinic acetylcholine receptors (nAChRs) throughout the central nervous system. Understanding the various nAChR subtypes that exist in brain areas relevant to nicotine addiction is a major priority.
Experiments that employ electrophysiology techniques such as whole-cell patch clamp or two-electrode voltage clamp recordings are useful for pharmacological characterization of nAChRs of interest. Cells expressing nAChRs, such as mammalian tissue culture cells or Xenopus laevis oocytes, are physically isolated and are therefore easily studied using the tools of modern pharmacology. Much progress has been made using these techniques, particularly when the target receptor was already known and ectopic expression was easily achieved. Often, however, it is necessary to study nAChRs in their native environment: in neurons within brain slices acutely harvested from laboratory mice or rats. For example, mice expressing "hypersensitive" nAChR subunits such as &alpha;4 L9&prime;A mice 1 and &alpha;6 L9&prime;S mice 2, allow for unambiguous identification of neurons based on their functional expression of a specific nAChR subunit. Although whole-cell patch clamp recordings from neurons in brain slices is routinely done by the skilled electrophysiologist, it is challenging to locally apply drugs such as acetylcholine or nicotine to the recorded cell within a brain slice. Dilution of drugs into the superfusate (bath application) is not rapidly reversible, and U-tube systems are not easily adapted to work with brain slices.
In this paper, we describe a method for rapidly applying nAChR-activating drugs to neurons recorded in adult mouse brain slices. Standard whole-cell recordings are made from neurons in slices, and a second micropipette filled with a drug of interest is maneuvered into position near the recorded cell. An injection of pressurized air or inert nitrogen into the drug-filled pipette causes a small amount of drug solution to be ejected from the pipette onto the recorded cell. Using this method, nAChR-mediated currents are able to be resolved with millisecond accuracy. Drug application times can easily be varied, and the drug-filled pipette can be retracted and replaced with a new pipette, allowing for concentration-response curves to be created for a single neuron. Although described in the context of nAChR neurobiology, this technique should be useful for studying many types of ligand-gated ion channels or receptors in neurons from brain slices.

In this paper, we describe a useful method to study ligand-gated ion channel function in neurons of acutely isolated brain slices. This method involves the use of a drug-filled micropipette for local application of drugs to neurons recorded using standard patch clamp techniques.

局部应用药物研究烟碱型乙酰胆碱受体功能的小鼠脑片

Tobacco use leads to numerous health problems, including cancer, heart disease, emphysema, and stroke. Addiction to cigarette smoking is a prevalent ...

Radiotracer Administration for High Temporal Resolution Positron Emission Tomography of the Human Brain: Application to FDG-fPET

Functional positron emission tomography (fPET) provides a method to track molecular targets in the human brain. With a radioactively-labelled glucose analogue, 18F-fluordeoxyglucose (FDG-fPET), it is now possible to measure the dynamics of glucose metabolism with temporal resolutions approaching those of functional magnetic resonance imaging (fMRI). This direct measure of glucose uptake has enormous potential for understanding normal and abnormal brain function and probing the effects of metabolic and neurodegenerative diseases. Further, new advances in hybrid MR-PET hardware make it possible to capture fluctuations in glucose and blood oxygenation simultaneously using fMRI and FDG-fPET.
The temporal resolution and signal-to-noise of the FDG-fPET images is critically dependent upon the administration of the radiotracer. This work presents two alternative continuous infusion protocols and compares them to a traditional bolus approach. It presents a method for acquiring blood samples, time-locking PET, MRI, experimental stimulus, and administering the non-traditional tracer delivery. Using a visual stimulus, the protocol results show cortical maps of the glucose-response to external stimuli on an individual level with a temporal resolution of 16 s.

This manuscript describes two radiotracer administration protocols for FDG-PET (constant infusion and bolus plus infusion) and compares them to bolus administration. Temporal resolutions of 16 s are achievable using these protocols.

人脑高时态分辨率正态发射断层扫描的放射跟踪器管理:在FDG-fPET中的应用

Functional positron emission tomography (fPET) provides a method to track molecular targets in the human brain. With a radioactively-labelled glucose ...

Live Imaging of Nicotine Induced Calcium Signaling and Neurotransmitter Release Along Ventral Hippocampal Axons

Sustained enhancement of axonal signaling and increased neurotransmitter release by the activation of pre-synaptic nicotinic acetylcholine receptors (nAChRs) is an important mechanism for neuromodulation by acetylcholine (ACh). The difficulty with access to probing the signaling mechanisms within intact axons and at nerve terminals both in vitro and in vivo has limited progress in the study of the pre-synaptic components of synaptic plasticity. Here we introduce a gene-chimeric preparation of ventral hippocampal (vHipp)&#8211;accumbens (nAcc) circuit in vitro that allows direct live imaging to analyze both the pre- and post-synaptic components of transmission while selectively varying the genetic profile of the pre- vs post-synaptic neurons. We demonstrate that projections from vHipp microslices, as pre-synaptic axonal input, form multiple, reliable glutamatergic synapses with post-synaptic targets, the dispersed neurons from nAcc. The pre-synaptic localization of various subtypes of nAChRs are detected and the pre-synaptic nicotinic signaling mediated synaptic transmission are monitored by concurrent electrophysiological recording and live cell imaging. This preparation also provides an informative approach to study the pre- and post-synaptic mechanisms of glutamatergic synaptic plasticity in vitro.

We developed a gene-chimeric preparation of ventral hippocampal &#8211; accumbens circuit in vitro that allows direct live imaging to analyze presynaptic mechanisms of nicotinic acetylcholine receptors (nAChRs) mediated synaptic transmission. This preparation also provides an informative approach to study the pre- and post-synaptic mechanisms of synaptic plasticity.

尼古丁诱导的钙信号和神经递质的释放了沿着腹侧海马轴突实时成像

Sustained enhancement of axonal signaling and increased neurotransmitter release by the activation of pre-synaptic nicotinic acetylcholine receptors ...

Modeling Fast-scan Cyclic Voltammetry Data from Electrically Stimulated Dopamine Neurotransmission Data Using QNsim1.0

Central dopaminergic (DAergic) pathways have an important role in a wide range of functions, such as attention, motivation, and movement. Dopamine (DA) is implicated in diseases and disorders including attention deficit hyperactivity disorder, Parkinson's disease, and traumatic brain injury. Thus, DA neurotransmission and the methods to study it are of intense scientific interest. In vivo fast-scan cyclic voltammetry (FSCV) is a method that allows for selectively monitoring DA concentration changes with fine temporal and spatial resolution. This technique is commonly used in conjunction with electrical stimulations of ascending DAergic pathways to control the impulse flow of dopamine neurotransmission. Although the stimulated DA neurotransmission paradigm can produce robust DA responses with clear morphologies, making them amenable for kinetic analysis, there is still much debate on how to interpret the responses in terms of their DA release and clearance components. To address this concern, a quantitative neurobiological (QN) framework of stimulated DA neurotransmission was recently developed to realistically model the dynamics of DA release and reuptake over the course of a stimulated DA response. The foundations of this model are based on experimental data from stimulated DA neurotransmission and on principles of neurotransmission adopted from various lines of research. The QN model implements 12 parameters related to stimulated DA release and reuptake dynamics to model DA responses. This work describes how to simulate DA responses using QNsim1.0 and also details principles that have been implemented to systematically discern alterations in the stimulated dopamine release and reuptake dynamics.

Fast-scan cyclic voltammetry can monitor in vivo dopamine neurotransmission in the context of drugs, disease, and other experimental manipulations. This work describes the implementation of QNsim1.0, a software to model electrically stimulated dopamine responses according to the quantitative neurobiological model to quantify estimates of dopamine release and reuptake dynamics.

使用QNsim1.0从电刺激多巴胺神经传递数据建模快速扫描循环伏安数据

Central dopaminergic (DAergic) pathways have an important role in a wide range of functions, such as attention, motivation, and movement. Dopamine (DA) is ...

Assessment of Dopaminergic Homeostasis in Mice by Use of High-performance Liquid Chromatography Analysis and Synaptosomal Dopamine Uptake

Dopamine (DA) is a modulatory neurotransmitter controlling motor activity, reward processes and cognitive function. Impairment of dopaminergic (DAergic) neurotransmission is strongly associated with several central nervous system-associated diseases such as Parkinson&#39;s disease, attention-deficit-hyperactivity disorder and drug addiction1,2,3,4. Delineating disease mechanisms involving DA imbalance is critically dependent on animal models to mimic aspects of the diseases, and thus protocols that assess specific parts of the DA homeostasis are important to provide novel insights and possible therapeutic targets for these diseases.
Here, we present two useful experimental protocols that when combined provide a functional read-out of the DAergic system in mice. Biochemical and functional parameters on DA homeostasis are obtained through assessment of DA levels and dopamine transporter (DAT) functionality5. When investigating the DA system, the ability to reliably measure endogenous levels of DA from adult brain is essential. Therefore, we present how to perform high-performance liquid chromatography (HPLC) on brain tissue from mice to determine levels of DA. We perform the experiment on tissue from dorsal striatum (dStr) and nucleus accumbens (NAc), but the method is also suitable for other DA-innervated brain areas.
DAT is essential for reuptake of DA into the presynaptic terminal, thereby controlling the temporal and spatial activity of released DA. Knowing the levels and functionality of DAT in the striatum is of major importance when assessing DA homeostasis. Here, we provide a protocol that allows to simultaneously deduce information on surface levels and function using a synaptosomal6 DA uptake assay.
Current methods combined with standard immunoblotting protocols provide the researcher with relevant tools to characterize the DAergic system.

Synaptosomal dopamine uptake and high-performance liquid chromatography analysis represent experimental tools to investigate dopamine homeostasis in mice by assessing the function of the dopamine transporter and levels of dopamine in striatal tissue, respectively. Here we present protocols to measure dopamine tissue content and assess the functionality of the dopamine transporter.

高效液相色谱分析和触多巴胺摄取对小鼠多巴胺能稳态的评价

Dopamine (DA) is a modulatory neurotransmitter controlling motor activity, reward processes and cognitive function. Impairment of dopaminergic (DAergic) ...

Probing Nicotinic Acetylcholine Receptor Function in Mouse Brain Slices via Laser Flash Photolysis of Photoactivatable Nicotine

Acetylcholine (ACh) acts through receptors to modulate a variety of neuronal processes, but it has been challenging to link ACh receptor function with subcellular location within cells where this function is carried out. To study the subcellular location of nicotinic ACh receptors (nAChRs) in native brain tissue, an optical method was developed for precise release of nicotine at discrete locations near neuronal membranes during electrophysiological recordings. Patch-clamped neurons in brain slices are filled with dye to visualize their morphology during 2-photon laser scanning microscopy, and nicotine uncaging is executed with a light flash by focusing a 405 nm laser beam near one or more cellular membranes. Cellular current deflections are measured, and a high-resolution three-dimensional (3D) image of the recorded neuron is made to allow reconciliation of nAChR responses with cellular morphology. This method allows for detailed analysis of nAChR functional distribution in complex tissue preparations, promising to enhance the understanding of cholinergic neurotransmission.

This article presents a method for studying nicotinic acetylcholine receptors (nAChRs) in mouse brain slices by nicotine uncaging. When coupled with simultaneous patch clamp recording and 2-photon laser scanning microscopy, nicotine uncaging connects nicotinic receptor function with cellular morphology, providing a deeper understanding of cholinergic neurobiology.

利用可活性可选位的激光光致发光体研究小鼠脑片中的烟碱乙酰胆碱受体功能

Acetylcholine (ACh) acts through receptors to modulate a variety of neuronal processes, but it has been challenging to link ACh receptor function with ...

Studying Metabolic Brain Connectivity Using 2-Deoxy-2-[18F]Fluoro-D-Glucose Dynamic Positron Emission Tomography at the Single-subject Level

To this day, metabolic brain connectivity is mostly studied on a group level through the acquisition of static positron emission tomography (PET) data of multiple subjects. Our research groups are currently studying changes in metabolic connectivity across multiple time points following an intracerebral hemorrhage on an intrasubject level in rats. To investigate intrasubject metabolic brain connectivity, temporal information of the tracer uptake in different brain regions is required, which can be achieved through dynamic PET. In this publication, we give a detailed description of our data acquisition and analysis protocol.
Dynamic PET data of the rat brain are acquired on a dedicated preclinical PET system using 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) as tracer. The tracer is injected intravenously as a bolus at the start of the PET scan. During the 60 min acquisition, animals are sedated with medetomidine.
After acquisition, the PET data are reconstructed into thirty 2 min time frames using an iterative reconstruction algorithm (Maximum-Likelihood Expectation-Maximization). A parcellated atlas consisting of multiple volumes of interest (VOIs) is used to extract time-activity curves of each VOI, which are then used to calculate the Pearson correlation coefficient between each pair of VOIs.
This dynamic PET protocol enables the assessment of metabolic connectivity differences between two single scans, rather than between groups of scans. This approach allows for the study of changes in metabolic connectivity within a single subject across different time points, or for the comparison of an individual&#39;s metabolic connectivity to a normal database. Such comparisons could be useful for tracking disease progression or aiding in the diagnosis of neurological disorders characterized by disrupted communication between brain regions, such as epilepsy or dementia.

The acquisition of dynamic positron emission tomography (PET) data and reconstruction into time frames allows for metabolic brain connectivity analysis at the single-subject level. We describe a method to acquire [18F]FDG dynamic PET data of the rat brain and obtain a connectivity matrix through the extraction of time-activity curves of volumes of interest.

在单受试者水平使用 2-脱氧-2-[18F] 氟-D-葡萄糖动态正电子发射断层扫描研究代谢脑连接

To this day, metabolic brain connectivity is mostly studied on a group level through the acquisition of static positron emission tomography (PET) data of ...