This work was partly supported by grants from the National Institutes of Health (NIH), under grant numbers R01 MH084021, R01 NS067015, R01 AG042753, NS076588, NS029029-20S1, R21 NS078656; and from National Multiple Sclerosis Society, under grant number of RG4707A2.

注:该协议被批准由得克萨斯大学西南医学中心的伦理审查委员会的大学。 图1.实验前的气体输送系统和准备的步骤<ol style="margin-left: 40px;"><li>审查的气体输送系统（ 图1）的图。填一个200升道格拉斯袋（项目＃1）用含有5％的CO 2，21％O 2，和74％的N 2的医用级的气体混合物。 </li><li>放置两个隔膜（项目＃4），在双向的非再呼吸阀（项目＃3），以确保单向气流。把这个组装双向阀和气体填充的道格拉斯袋（项目＃1）到磁体室。 </li><li>气体输送管（项目＃7）连接到双向阀（项目＃3）的输入端。附气体输送管（项目＃7）的头部线圈的侧配重支承。燃气输送管（编号7）的另一端连接到气体填充道格拉斯包（编号1）。 </li><li>连接喉舌（编号5）通过弯头连接的U形管（编号12）（编号13气体采样口密封）。 </li><li>连接气体取样管（编号:9）到U形管（编号12）通过其他弯头连接器（编号13）。 </li><li>连接一个小型空气过滤器（编号11）气体采样管（编号:9）的另一端。连接空气过滤器（编号:11）到CO 2（编号14）的另一端监控。 </li><li>在MRI套件的控制室，打开CO 2（编号14）和脉搏血氧饱和度（编号15）显示器。为CO 2的显示器进行自动校准。 </li><li>将显示器连接到使用USB接口的笔记本电脑。打开超级终端软件，与显示器进行通信。该显示器的次定时器写下定时器时间和相应的监视器的时间同步。的定时器时间和监视器的时间的差异将占到数据亲处理（对于步4.4）。 </li><li>插入信令杆的一端插入一个波导，使得棒的一端是所述磁铁的房间内，而另一端是在控制室。 注:信令栏用于三通阀的切换时，通知磁铁室内的研究者在扫描期间（项目＃2）是必要的。 </li></ol>在实验过程中2.程序<ol style="margin-left: 40px;"><li>让拍摄对象趴在桌子MRI但不要把他/她到磁铁孔呢。指示须按护士呼叫按钮，如果他们在扫描过程中感到不适。让拍摄对象擦拭他/她的鼻子用一块清洁湿巾，以消除任何油脂。 </li><li>指示需经口呼吸，并建立和维护一个呼吸节奏。然后应用鼻夹（编号6）关于这个问题。 </li><li>在U形管（编号12）的开口端连接的双向阀（编号3）通过EL中间口弓连接器（编号13）。 </li><li>轻轻将喉舌入主题的嘴里，这样的题目可以通过喉舌呼吸。轻轻附加的脉搏血氧饱和度（项目＃15）向受试者的指尖的手指传感器。 </li><li>确保被检体的头部是在头部线圈的异中心。操作MRI表将他磁铁孔内/她。 </li><li>确保一位研究人员住宿磁铁室内监控对象，并准备在道格拉斯袋（编号1）切换的三通阀。确保研究员戴耳塞和耳机，以阻止MRI噪音。 </li><li>关闭磁铁房间门，中控室，检查ETCO 2和动脉血氧饱和度分数（SO 2）对CO 2（编号14）和脉搏血氧饱和度（编号15）显示器显示的参数。开始在笔记本电脑上的参数的记录。 </li><li>指示MRI操作使用开始扫描血液氧合水平依赖（BOLD）序列。为3T MRI扫描器中，BOLD成像参数是:TR / TE = 1500/30毫秒，翻转角= 60°，视场= 220 X220毫米2，矩阵= 64×64，29片，厚度= 5毫米，片，361卷之间没有间隙。回顾在其上阀切换的定时列出一个预先准备片和当需要一个开关轻轻摆动的信令栏。狠抓主体的生理，包括心脏率，SO 2和ETCO 2。 </li><li>现在，在磁铁室内，关于道格拉斯袋切换基于所述信令杆，其控制气体受试者激发的类型的运动（项目＃1）。 </li><li>继续此过程为研究的长度。在9分钟拍摄期间，确保阀切换发生大约每分钟一次。需要注意的是开关的定时不必是完全精确的，只要所述的EtCO2时间过程被记录下来。&lt;BR /&gt;注:如果主体在扫描过程中按下护士呼叫按钮，扫描将中止与主体将立即搬出磁铁孔。研究者将移除口件和鼻夹从受试者。 </li><li>使用对讲机以通知扫描完成的课题。拉MRI表出来。从主题，同时提供清洁纸巾的主题擦拭任何口水轻轻取下鼻夹和喉舌。轻轻地取出从主题的脉搏血氧饱和度的手指传感器。那么这个问题可以坐起来，下车MRI表。 </li></ol>实验后3.清理程序<ol style="margin-left: 40px;"><li>丢弃气体采样管（编号9），空气过滤器（编号11），喉舌（项目5＃）和鼻夹（编号:6）。 </li><li>清洁可重用的组件。断开其他组件的双向阀（项目＃3）和（4项目＃）从阀移除隔膜。浸泡双向阀（项目＃3），隔膜（项目＃4）和U形管（项目＃12）中的浓缩无磷消毒剂，含有表面活性剂如在一容器中20分钟Bacdown洗涤剂消毒剂。洗涤剂消毒剂和蒸馏水的稀释比为1:64。 </li><li>冲洗在3.2用蒸馏水彻底描述的项​​目。 </li><li>干燥的U形管（编号12）用压缩空气。将二通阀（编号3）和隔膜（编号4）明确台面，让他们自然风干，彻底。 </li><li>清空道格拉斯袋。收起信令酒吧和灰色管。 </li></ol> 4.数据分析来计算CVR地图<ol style="margin-left: 40px;"><li>保存DICOM文件格式或任何其他供应商特定的格式MRI的数据。将数据传送到一个实验室计算机和数据转换成体积由卷文件系列，其中每个文件包含一个三维体积（ 例如，粗体图像）相对应的一个时间点。 </li><li>处理前的图像数据。执行图像的预处理步骤，包括重组，归一化，并使用该调用由软件统计参数映射（SPM）提供的库函数的脚本平滑。见补充代码文件1 Matlab的脚本的一个例子。 </li><li>使用脚本来读取的CO 2记录，通过由预先校准量移位的时间过程纠正采样管延迟（ 例如，12秒在此设置中被确定为一个呼吸之间的时间差来嘴件和外观上的CO 2记录该呼吸）的，并提取的EtCO2这是原始的时间序列的包络线（正峰）。见补充代码文件2 Matlab的脚本。 </li><li>基于该同步定时器，该段ETCO 2数据只保留记录从25秒的最后图像采集之后的第一个图像采集到100秒之前。在ETCO 2次课程输入功能的脉管，并用作在后述的线性回归分析的独立变量。 </li><li>通过计算这两个时间过程之间的交叉相关系数（CC）在不同的时间偏移确定ETCO 2（肺测量）和MRI信号（在大脑中测量）之间的生理时滞。能产生较高的CC移位值被认为是最佳时间。 </li><li>所述ETCO 2时间过程是由最佳延迟移位并且只有时间点匹配那些磁共振信号被保留，导致在一个时间序列是相同长度的磁共振信号。 </li><li>进行使用的SPM体素逐体素的线性回归，其中错开的EtCO2时间过程是自变量和核磁共振信号的时间过程是因变量。 </li><li>计算体素逐体素CVR的地图 <img alt="式（1）" fo:content-width="2in" src="/files/ftp_upload/52306/52306eq1.jpg" /> 其中，（I，J，K）是叔他体素索引，β1是与的EtCO2和β0相关的回归系数与常数项相关的回归系数。 分钟（ETCO 2）ETCO 2中的时间过程的最小值。 </li></ol>

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HL and PL are inventors of a provisional patent, owned by UT Southwestern Medical Center, that describes part of the gas delivery system.

本报告中提出的MR兼容的气体输送系统和一个综合实验协议，允许血管反应性的人脑的映射。气体输送系统的示意图示于图1。MRI扫描仪的房间内所有零件都是塑料，以确保他们的MRI兼容性。该系统可在概念上划分为三个子系统，包括一个进气子系统（袋，输送管，双向阀），一个呼吸接口子系统（鼻夹，嘴件，U形管），和监测子系统（CO 2浓度，氧饱和度，心脏速率，呼吸速率）。气进气子系统允许气体被吸入到达阀双向。仅吸入空气，但不能呼出的空气，将流过此子系统。呼吸接口子系统允许受呼吸进出预定气体。无论吸入和呼出的气体会流过该子系统。该monitorin因此克子系统应采样气体在沿着呼吸接口子系统的一个点。 这种技术的临床应用可以包括在神经系统的疾病，如中风，动脉粥样硬化，烟雾病，血管性痴呆，多发性硬化症，脑肿瘤脑血管储备的评价。该技术也可用于在功能性磁共振成像研究，以正常化或校准的fMRI信号为更好地量化神经活动23,24。 所提出的系统和实验方案的一个重要特征是，该气体混合物可被递送给受试者同时引起最少的运动或不适。因此，关键是要放置在U形管（项目＃12），使得它（以及连接到它的端部的吹口）自然落入向下进入被检者的口腔。这样一来，这个问题并不需要使用自己的面部肌肉以保持或支持的喉舌。它也是进口蚂蚁要知道，这个问题将无法说话，而喉舌，是在口里。因此，研究人员应该避免谈论同一个问题基调的主题。相反，只有清晰的，明确的说明，应该放在首位。此外，研究人员应该在实验的整个过程中密切关注生理参数（ 例如，ETCO 2，SO 2，心脏率，呼吸率），当一个或多个生理参数的偏差之外的典型范围及时回复。 而其他气体输送系统的详尽调查，在文献中使用已经超出了本文的范围，它在当前的系统比较了几个常用的17,18是有用的。一个主要的不同之处在于我们的系统使用一个吹口，提供预定的气体，而大多数其他系统已经使用在设计的掩模。使用掩模的潜在并发症是2倍。首先，口罩Øccupies的空间相当量，并且它可能不总是可行的，以适应所述掩模到头部线圈内的狭小空间，考虑的是，对于许多受试者，他们的鼻子几乎触碰磁头线圈，即使没有掩模。这是特别适用于旨在实现高灵敏度磁头线圈，其通常被设计以牢固地镶嵌到被检者的头部的情况。用的掩模设计相关联的第二个复杂的是，有导致吸入和呼出气体的实质性混合掩模内部大的空间。因此，它可能会影响ETCO 2，其中理想地，应仅基于呼出气体测定的准确性。准确ETCO 2当然是对CVR地图的可靠性很重要的。我们的系统相比，许多其它的系统的另一个主要区别是，我们的系统从一个袋，而不是一个气体罐提供燃气。因此，不需要在扫描仪领域的坦克，节省了宝贵的空间，在续<html> ROL房间的MRI套房。在我们的设计中，我们把包包扫描开始前，扫描之后，袋子被清空，折叠放好。最后，相比其它几个系统18,21，电流气体输送系统是简单，需要更少的训练时间，并且它的消耗品成本更低。 应当指出的是，虽然在本报告中提出的协议主要集中在CO 2的吸入，所提出的气体输送系统允许其它气体混合物（交付如任何分数的 O 2，CO 2的任何部分，任何的N 2，和它们的组合）分数，以人类为他们而他/她是躺在核磁共振成像扫描仪内呼吸。一还可以使用气体输送系统的MRI的上下文之外，例如结合脑电图（EEG），脑磁图（MEG），正电子发射断层扫描（PET），或最佳成像。 _content"&gt;当提供的摄像参数的建议，我们已主要集中在BOLD序列。可在CVR映射来潜在地使用的另一种序列是动脉自旋标记（ASL）的磁共振成像，它提供了脑血流量的定量测量（CBF）在生理单位（毫升每分钟100克组织血），因此，ASL基CVR映射的优点是，其结果是容易解释，不像BOLD信号反映血流量，血液量的组合效果，以及脑代谢改变的过程中的CO 2的挑战25-27可能作出的贡献，但是，在ASL技术的一个限制是，它的灵敏度比BOLD 28的下部数倍。其结果是，我们的经验是，目前，它是极具挑战性，以获得个人层面，素逐体素使用ASL。因此，对于CVR的应用研究中，我们主要使用了BOLD序列CVR的地图，因此也集中在这一技术中的OUR建议。 本方法的一个限制是，通过与鼻堵塞（由一鼻夹）吹嘴的呼吸是不完全的自然和一些受试者（尤其是人）可能会认为这是不舒服的来源。与吹嘴和鼻夹呼吸也可能加剧幽闭恐惧的感觉。此外，主题可能会遇到口干，由于只张口呼吸。因此，建议研究人员极力向完成实验迅速。最后，要注意的是，根据作者的经验，上述潜在的不适是短暂的，将尽快在实验结束后消失是很重要的。

大脑表示约2％的总体重，但消耗约20％的总能量1。不足为奇的是，足够的，并仔细调节的血液供应是至关重要满足这种高能量需求，并且为大脑才能正常工作。此外，大脑是一个空间异构和时间上的动态器官，具有不同区域需要不同量的血液供应的不同时间。因此，动态血液供应的调制代表在人脑循环的重要要求。幸运的是，这是已知的血管不只是刚性管和血管的一个重要功能是扩张并基于大脑和需求生理条件2收缩。 容器中，被称为脑血管-反应器（CVR）的此功能特性，被认为是血管健康的有用指示器，并且可以发现在几个神经conditio应用纳秒如中风3，痴呆4，动脉粥样硬化5，小血管疾病6，脑瘤7，烟雾病8，和药物成瘾9。在生理学和麻醉文献，已知的是，因为二氧化碳气体是一种强效血管扩张剂，CVR可以评估通过改变动脉的 CO 2水平（ 例如，吸入少量的CO 2），同时监测血管反应10-13 。在成像和放射领域，利用MRI CVR映射正在迅速成为了许多基本的科学家和临床医生8,14-19利益的新标志。它通常是通过检查多血管反应是如何引起的一个挑战血管活性估计。然而，有必要在气体输送系统的技术进步和实验方案的标准化。提供特殊的气体混合物的MRI扫描仪内部主体是不平凡的，并特别注意事项都需要一个MRI兼容的设计。特别注意事项，需要在设计MRI兼容的气体输送系统。这些特殊的考虑因素包括:1）中的所有组件必须是非金属（金属不能里面的MRI使用）; 2）系统应该工作在一个小空间，该MRI系统和它的头部线圈允许; 3）系统应以卧向下的位置工作（如MRI扫描仪需要），而不是坐起来，没有不适; 4）相关的生理参数，如潮气末CO 2（的EtCO2，在动脉血二氧化碳含量）和动脉血氧饱和度的近似，应准确记录的定时精度秒并存储在计算机用于分析用途上。这些问题可能​​会限制CVR映射的应用范围。 在这份报告中，我们提出了一个使用全面的气体输送系统，以调节启发气体的内容，而主题是躺在核磁共振成像扫描仪内的实验方案。我们荷兰国际集团这种方法，研究人员可以非侵入性地应用一个血管活性刺激物以最小的不适或整体运动的参与者。在约9分钟的整个时期，其中包括了室内空气和高二氧化碳气体呼吸交替块（每块1分钟），记录生理参数和MRI影像。代表性的结果。潜在的应用和局限性进行了讨论。

<table><tbody><tr><td>Douglas bag&amp;nbsp;</td><td>Harvard Apparatus</td><td>500942</td><td>200 L capacity</td></tr><tr><td>Three-way valve</td><td>Hans Rudolph</td><td>CR1207</td><td>100% plastic</td></tr><tr><td>Two-way non-rebreathing valve</td><td>Hans Rudolph</td><td>CR1480</td><td>22 mm/15 mm ID</td></tr><tr><td>Diaphragm</td><td>Hans Rudolph</td><td>602021-2608</td><td>Size: medium, Type: spiral</td></tr><tr><td>Mouth piece</td><td>Hans Rudolph</td><td>602076</td><td>Silicone, Model #&amp;nbsp;9061</td></tr><tr><td>Nose clip</td><td>Hans Rudolph</td><td>201413</td><td>Plastic foam, Model #9014</td></tr><tr><td>Gas delivery tube</td><td>Vacumed</td><td>1011-108</td><td></td></tr><tr><td>Blue cuff</td><td>Vacumed</td><td>22254</td><td></td></tr><tr><td>Gas sampling tube</td><td>QoSINA</td><td>T4305</td><td>Thin</td></tr><tr><td>Male luer</td><td>QoSINA</td><td>11547</td><td></td></tr><tr><td>Hydrophobic filter</td><td>Philips Medical Systems</td><td>9906-00</td><td>Disposable</td></tr><tr><td>U-shape tube</td><td>Made in-house</td><td></td><td></td></tr><tr><td>Elbow connector</td><td>QoSINA</td><td>51033</td><td></td></tr><tr><td>EtCO&lt;sub&gt;2&lt;/sub&gt; monitor</td><td>Philips Medical Systems</td><td>Model 1265</td><td></td></tr><tr><td>Pulse oximetry&amp;nbsp;</td><td>Invivo</td><td>Expression</td><td>MRI Monitoring Systems</td></tr><tr><td>MRI scanner&amp;nbsp;</td><td>Philips</td><td>Achieva 3.0T TX</td><td></td></tr><tr><td>Disinfectant</td><td>Fisher Scientific</td><td>04-355-13</td><td>Decon BDD Bacdown Detergent Disinfectant</td></tr></tbody></table>

mri mapping of cerebrovascular reactivity via gas inhalation challenges

大脑是一个异类空间和时间上的动态的器官，不同的地区需要不同量的血液供应，在不同的时间。因此，对血管扩张或收缩的能力，被称为脑血管-反应器（CVR），表示血管功能的一个重要领域。成像标记物表示此动态属性将提供正常和病变情况，如中风，痴呆，动脉粥样硬化，小血管疾病，脑肿瘤，脑外伤，多发性硬化下脑血管的新的信息。为了在人类中执行这种类型的测量中，有必要提供一个血管活性刺激物如CO 2和/或O 2的气体混合物的同时定量脑磁共振图像（MRI）被收集。在这项工作中，我们提出了一个MR兼容的气体输送系统和相关的协议，该协议允许的特殊气体混合物的输送（ 例如， </EM&gt; 的 O 2，CO 2，N 2，以及它们的组合），而受试者躺在MRI扫描仪的内部。该系统是相对简单的，经济的，并易于使用，并且在实验协议允许CVR在两个健康志愿者和患有神经障碍精确测绘的。这种方法具有在广泛的临床应用和更好地理解脑血管的病理生理学中使用的潜力。在视频中，我们演示了如何建立系统的MRI套件内，如何在人类参与者执行一个完整的实验。

两种类型的数据收集与所提出的协议，生理录音和MR图像; 图生理参数2和3显示从记录有代表性的受试者。 如图黑色迹2显示的 CO 2时程记录通过CO 2的显示器，其表示在空气采样附近的吹嘴的CO 2的含量。请注意，此跟踪快速波动与时间的函数。这是因为，在呼吸循环的吸入阶段，该记录反映了吸入空气中的CO 2的含量，并在呼气阶段，这种记录反映在呼出的空气中的 CO 2含量。这样，每个呼吸周期的上限峰值，被称为潮气末CO 2或ETCO 2，表示在肺，其可近似用作CO 2浓度在动脉血中的 CO 2含量。注日在CO 2浓度的动脉血是驱动力， 即输入功能，血管扩张反应。 CO 2的迹线（红色曲线于图2）的峰值分别划定一个检测算法，其中每个呼吸期间搜索峰值，与人工检验和校正的组合。其次的中值滤波，以除去由于部分呼吸突然峰和从肺血管脑血管的流动的过程中，考虑到血液混合。最后ETCO 2时间过程示出由绿色曲线在图2中，它是用来在CVR的计算。 图3示出了呼吸率，动脉血氧饱和度分数（SO 2），和心脏速率的时间进程。呼吸率从CO 2的显示器，同时获得SO 2和心脏率从脉搏血氧饱和度获得。由于可以为sEEN，这些参数不显示的高碳酸血症的挑战系统性的变化。注意，高碳酸血症不会引起过度通气中的主体，从而在肺中的O 2的分压会增加适度。然而，其对SO 2的影响是微乎其微的血红蛋白已经基本饱和，在室内空气呼吸和氧解离曲线是该范围内的相当平坦。 图4显示了在不同的实验时间代表BOLD MR图像。平均信号强度（任意MR单位）也被示出。由此可以看出，在大脑中的BOLD信号显示增加用CO 2吸入。需要注意的是房间空气和CO 2周期之间的信号差为1-3％的幅度的量级。 组合来自生理录音和MR图像数据，体素逐体素CVR地图可以计算。 图5示出了代表CVR图（以每毫米汞柱的CO 2的变化％的信号变化的单位）上扫描五个不同天健康受试者，展示结果的极好的再现性。所提出的技术迄今已在老化20，阿尔茨海默氏病4，多发性硬化症21，和运动训练22的研究中得到了应用。 <img alt="图1" src="/files/ftp_upload/52306/52306fig1highres.jpg" /> 图1.气体输送系统的示意图。 <a href="https://www.jove.com/files/ftp_upload/52306/52306fig1large.jpg" target="_blank">请点击此处查看该图的放大版本。</a> <img alt="图2" src="/files/ftp_upload/52306/52306fig2highres.jpg" /> 图2. CO 2的时间从代表主体杜课程响的实验。呼吸-呼吸的CO 2含量迹所记录的CO 2的显示器示出为室内空气呼吸周期（左下）和5％的CO 2的吸入期间（右下）段。提取ETCO 2时的课程都显示在彩色曲线。 <a href="https://www.jove.com/files/ftp_upload/52306/52306fig2large.jpg" target="_blank">请点击此处查看该图的放大版本。</a> <img alt="图3" src="/files/ftp_upload/52306/52306fig3highres.jpg" /> 图3.记录生理参数从在实验过程中有代表性的问题。（A）的呼吸率（BPM，每分钟呼吸）的主题的时间过程。（B）中 ，以便被检体2（％）时间过程。（C）的心脏率（BPM，每分钟节拍）的主题时程。主题是<html>同样的一个作为在图1。 <a href="https://www.jove.com/files/ftp_upload/52306/52306fig3large.jpg" target="_blank">请点击此处查看该图的放大版本。</a> <img alt="图4" src="/files/ftp_upload/52306/52306fig4highres.jpg" /> 图在不同的实验时间4。代表BOLD MR图像。显示的脑片的平均信号强度（以MNI空间轴向层面＃54）显示在最 ​​后一行。 <a href="https://www.jove.com/files/ftp_upload/52306/52306fig4large.jpg" target="_blank">请点击此处查看该图的放大版本。</a> <img alt="图5" src="/files/ftp_upload/52306/52306fig5highres.jpg" /> 图由代表主体代表性的CVR地图。.jove.com /文件/ ftp_upload / 52306 / 52306fig5large.jpg"目标="_空白"&gt;点击此处查看该图的放大版本。

Watch this Scientific Journal Video about MRI Mapping of Cerebrovascular Reactivity via Gas Inhalation Challenges at JoVE.com

MRI Mapping of Cerebrovascular Reactivity via Gas Inhalation Challenges

Non-invasive imaging of the brain vasculature&#8217;s ability to dilate or constrict may allow a better understanding of cerebrovascular pathophysiology in various neurological diseases. The present report describes a reproducible and patient-comfortable protocol to perform vascular reactivity imaging in humans using magnetic resonance imaging (MRI).

脑血管反应性通过气体吸入挑战MRI映射

The brain is a spatially heterogeneous and temporally dynamic organ, with different regions requiring different amount of blood supply at different time. ...

mri-mapping-cerebrovascular-reactivity-via-gas-inhalation

Research

JoVE Journal

Medicine

13.9K 次观看.  University of Texas Southwestern Medical Center. Non-invasive imaging of the brain vasculature’s ability to dilate or constrict may allow a better understanding of cerebrovascular pathophysiology in various neurological diseases. The present report describes a reproducible and patient-comfortable protocol to perform vascular reactivity imaging in humans using magnetic resonance imaging (MRI).

视频: MRI Mapping of Cerebrovascular Reactivity via Gas Inhalation Challenges

Magnetic Resonance Imaging Quantification of Pulmonary Perfusion using Calibrated Arterial Spin Labeling

This demonstrates a MR imaging method to measure the spatial distribution of pulmonary blood flow in healthy subjects 
during normoxia (inspired O2, fraction (FIO2) = 0.21) hypoxia (FIO2 = 0.125), and hyperoxia 
(FIO2 = 1.00). In addition, the physiological responses of the subject are monitored in the MR scan environment. MR images 
were obtained on a 1.5 T GE MRI scanner during a breath hold from a sagittal slice in the right lung at functional residual capacity. An arterial 
spin labeling sequence (ASL-FAIRER) was used to measure the spatial distribution of pulmonary blood flow 1,2 and a multi-echo fast 
gradient echo (mGRE) sequence 3 was used to quantify the regional proton (i.e. H2O) density, allowing the quantification 
of density-normalized perfusion for each voxel (milliliters blood per minute per gram lung tissue). 
With a pneumatic switching valve and facemask equipped with a 2-way non-rebreathing valve, different oxygen concentrations 
were introduced to the subject in the MR scanner through the inspired gas tubing. A metabolic cart collected expiratory gas via expiratory tubing. Mixed expiratory O2 and CO2 concentrations, oxygen consumption, carbon dioxide production, respiratory exchange ratio, 
respiratory frequency and tidal volume were measured. Heart rate and oxygen saturation were monitored using pulse-oximetry. 
Data obtained from a normal subject showed that, as expected, heart rate was higher in hypoxia (60 bpm) than during normoxia (51) or hyperoxia (50) and the arterial oxygen saturation (SpO2) was reduced during hypoxia to 86%. Mean ventilation was 8.31 L/min BTPS during hypoxia, 7.04 L/min during normoxia, and 6.64 L/min during hyperoxia. Tidal volume was 0.76 L during hypoxia, 0.69 L during normoxia, and 0.67 L during hyperoxia. 
Representative quantified ASL data showed that the mean density normalized perfusion was 8.86 ml/min/g during hypoxia, 8.26 ml/min/g during normoxia and 8.46 ml/min/g during hyperoxia, respectively. In this subject, the relative dispersion4, an index of global heterogeneity, was increased in hypoxia (1.07 during hypoxia, 0.85 during normoxia, and 0.87 during hyperoxia) while the fractal dimension (Ds), another index of heterogeneity reflecting vascular branching structure, was unchanged (1.24 during hypoxia, 1.26 during normoxia, and 1.26 during hyperoxia). 
Overview. This protocol will demonstrate the acquisition of data to measure the distribution of pulmonary perfusion noninvasively under conditions of normoxia, hypoxia, and hyperoxia using a magnetic resonance imaging technique known as arterial spin labeling (ASL). 
Rationale: Measurement of pulmonary blood flow and lung proton density using MR technique offers high spatial resolution images which can be quantified and the ability to perform repeated measurements under several different physiological conditions. In human studies, PET, SPECT, and CT are commonly used as the alternative techniques. However, these techniques involve exposure to ionizing radiation, and thus are not suitable for repeated measurements in human subjects.

A MR imaging method to study the distribution of pulmonary blood flow under a variety of physiological conditions, in this case exposure to three different inspired oxygen concentrations: hypoxia, normoxia, and hyperoxia, is described. This technique utilizes human pulmonary physiology research techniques in an MR scanning environment.

使用校准动脉自旋标记磁共振肺灌注显像定量

This demonstrates a MR imaging method to measure the spatial distribution of pulmonary blood flow in healthy subjects 
during normoxia (inspired O2, ...

科研

医学

The Use of Pharmacological-challenge fMRI in Pre-clinical Research: Application to the 5-HT System

Pharmacological MRI (phMRI) is a new and promising method to study the effects of substances on brain function that can ultimately be used to unravel underlying neurobiological mechanisms behind drug action and neurotransmitter-related disorders, such as depression and ADHD. Like most of the imaging methods (PET, SPECT, CT) it represents a progress in the investigation of brain disorders and the related function of neurotransmitter pathways in a non-invasive way with respect of the overall neuronal connectivity. Moreover it also provides the ideal tool for translation to clinical investigations. MRI, while still behind in molecular imaging strategies compared to PET and SPECT, has the great advantage to have a high spatial resolution and no need for the injection of a contrast-agent or radio-labeled molecules, thereby avoiding the repetitive exposure to ionizing radiations. Functional MRI (fMRI) is extensively used in research and clinical setting, where it is generally combined with a psycho-motor task. phMRI is an adaptation of fMRI enabling the investigation of a specific neurotransmitter system, such as serotonin (5-HT), under physiological or pathological conditions following activation via administration of a specific challenging drug.
The aim of the method described here is to assess brain 5-HT function in free-breathing animals. By challenging the 5-HT system while simultaneously acquiring functional MR images over time, the response of the brain to this challenge can be visualized. Several studies in animals have already demonstrated that drug-induced increases in extracellular levels of e.g. 5-HT (releasing agents, selective re-uptake blockers, etc) evoke region-specific changes in blood oxygenation level dependent (BOLD) MRI signals (signal due to a change of the oxygenated/deoxygenated hemoglobin levels occurring during brain activation through an increase of the blood supply to supply the oxygen and glucose to the demanding neurons) providing an index of neurotransmitter function. It has also been shown that these effects can be reversed by treatments that decrease 5-HT availability16,13,18,7. In adult rats, BOLD signal changes following acute SSRI administration have been described in several 5-HT related brain regions, i.e. cortical areas, hippocampus, hypothalamus and thalamus9,16,15. Stimulation of the 5-HT system and its response to this challenge can be thus used as a measure of its function in both animals and humans2,11.

The goal of this technique is to assess serotonin (5-HT) neurotransmitter function in the live and free-breathing animal with pharmacological magnetic resonance imaging (phMRI) and an intravenous challenge with a selective serotonin reuptake inhibitor (SSRI), fluoxetine.

挑战的药理功能磁共振成像：在临床前研究使用的5  - 羟色胺系统中的应用

Pharmacological MRI (phMRI) is a new and promising method to study the effects of substances on brain function that can ultimately be used to unravel ...

Functional Imaging with Reinforcement, Eyetracking, and Physiological Monitoring

We use functional brain imaging (fMRI) to study neural circuits that underlie decision-making.  To understand how outcomes affect decision processes, simple perceptual tasks are combined with appetitive and aversive reinforcement.  However, the use of reinforcers such as juice and airpuffs can create challenges for fMRI.  Reinforcer delivery can cause head movement, which creates artifacts in the fMRI signal.  Reinforcement can also lead to changes in heart rate and respiration that are mediated by autonomic pathways.  Changes in heart rate and respiration can directly affect the fMRI (BOLD) signal in the brain and can be confounded with signal changes that are due to neural activity.  In this presentation, we demonstrate methods for administering reinforcers in a controlled manner, for stabilizing the head, and for measuring pulse and respiration.

This presentation demonstrates the use of fMRI to study neural circuits that underlie decision-making. Simple perceptual tasks are combined with appetitive and aversive reinforcements to investigate how outcomes affect decision processes.

加固，Eyetracking，生理监测的功能成像

We use functional brain imaging (fMRI) to study neural circuits that underlie decision-making.  To understand how outcomes affect decision processes, ...

生物学

Simultaneous PET/MRI Imaging During Mouse Cerebral Hypoxia-ischemia

Dynamic changes in tissue water diffusion and glucose metabolism occur during and after hypoxia in cerebral hypoxia-ischemia reflecting a bioenergetics disturbance in affected cells. Diffusion weighted magnetic resonance imaging (MRI) identifies regions that are damaged, potentially irreversibly, by hypoxia-ischemia. Alterations in glucose utilization in the affected tissue may be detectable by positron emission tomography (PET) imaging of 2-deoxy-2-(18F)fluoro-&#7429;-glucose ([18F]FDG) uptake. Due to the rapid and variable nature of injury in this animal model, acquisition of both modes of data must be performed simultaneously in order to meaningfully correlate PET and MRI data. In addition, inter-animal variability in the hypoxic-ischemic injury due to vascular differences limits the ability to analyze multi-modal data and observe changes to a group-wise approach if data is not acquired simultaneously in individual subjects. The method presented here allows one to acquire both diffusion-weighted MRI and [18F]FDG uptake data in the same animal before, during, and after the hypoxic challenge in order to interrogate immediate physiological changes.

The method presented here uses simultaneous positron emission tomography and magnetic resonance imaging. In the cerebral hypoxia-ischemia model, dynamic changes in diffusion and glucose metabolism occur during and after injury. The evolving and irreproducible damage in this model necessitates simultaneous acquisition if meaningful multi-modal imaging data are to be acquired.

同时PET / MRI成像在小鼠脑缺氧缺血

Dynamic changes in tissue water diffusion and glucose metabolism occur during and after hypoxia in cerebral hypoxia-ischemia reflecting a bioenergetics ...

Retinal Vascular Reactivity as Assessed by Optical Coherence Tomography Angiography

The vascular supply to the retina has been shown to dynamically adapt through vasoconstriction and vasodilation to accommodate the metabolic demands of the retina. This process, referred to as retinal vascular reactivity (RVR), is mediated by neurovascular coupling, which is impaired very early in retinal vascular diseases such as diabetic retinopathy. Therefore, a clinically feasible method of assessing vascular function may be of significant interest in both research and clinical settings. Recently, in vivo imaging of the retinal vasculature at the capillary level has been made possible by the FDA approval of optical coherence tomography angiography (OCTA), a noninvasive, minimal risk and dyeless angiography method with capillary level resolution. Concurrently, physiological and pathological changes in RVR have been shown by several investigators. The method shown in this manuscript is designed to investigate RVR using OCTA with no need for alterations to the clinical imaging procedures or device. It demonstrates real time imaging of the retina and retinal vasculature during exposure to hypercapnic or hyperoxic conditions. The exam is easily performed with two personnel in under 30 min with minimal subject discomfort or risk. This method is adaptable to other ophthalmic imaging devices and the applications may vary based on the composition of the gas mixture and patient population. A strength of this method is that it allows for an investigation of retinal vascular function at the capillary level in human subjects in vivo. Limitations of this method are largely those of OCTA and other retinal imaging methods including imaging artifacts and a restricted dynamic range. The results obtained from the method are OCT and OCTA images of the retina. These images are amenable to any analysis that is possible on commercially available OCT or OCTA devices. The general method, however, can be adapted to any form of ophthalmic imaging.

This article describes a method for measuring retinal vasculature reactivity in vivo with human subjects using a gas breathing provocation technique to deliver vasoactive stimuli while acquiring retinal images.

光相一致性断层扫描血管造影评估的视网膜血管反应

The vascular supply to the retina has been shown to dynamically adapt through vasoconstriction and vasodilation to accommodate the metabolic demands of ...

神经科学

Cerebrovascular Reactivity Measurement with Functional Near Infrared Spectroscopy

Cerebrovascular reactivity (CVR) is the capacity of blood vessels in the brain to alter cerebral blood flow (either with dilation or constriction) in response to chemical or physical stimuli. The amount of reactivity in the cerebral microvasculature depends on the integrity of the capacitance vasculature and is the primary function of endothelial cells. CVR is, therefore, an indicator of the microvasculature&#8217;s physiology and overall health. Imaging methods that can measure CVR are available but can be costly, and require magnetic resonance imaging centers and technical expertise. In this study, we used fNIRS technology to monitor changes of oxyhemoglobin (HbO) and deoxyhemoglobin (HbR) in the cerebral microvasculature to assess the CVR of 15 healthy controls (HC) in response to a vasoactive stimulus (inhaled 5% carbon dioxide or CO2). Our results suggest that this is a promising imaging technology that offers a non-invasive, accurate, portable, and cost-effective method of mapping cortical CVR and associated microvasculature function, resulting from a traumatic brain injury or other conditions associated with cerebral microvasculopathy.

Presented here is a protocol for imaging and measurement of cerebrovascular reactivity in humans with functional Near Infrared Spectroscopy (fNIRS). fNIRS is a novel imaging modality that captures the concentration changes of hemoglobin species in the brain&#8217;s outermost cortex under specific stimuli.

Cerebrovascular reactivity (CVR) is the capacity of blood vessels in the brain to alter cerebral blood flow (either with dilation or constriction) in ...

Quantitative Mapping of Specific Ventilation in the Human Lung using Proton Magnetic Resonance Imaging and Oxygen as a Contrast Agent

Specific ventilation imaging (SVI) is a functional magnetic resonance imaging technique capable of quantifying specific ventilation &#8213; the ratio of the fresh gas entering a lung region divided by the region&#8217;s end-expiratory volume &#8213; in the human lung, using only inhaled oxygen as a contrast agent. Regional quantification of specific ventilation has the potential to help identify areas of pathologic lung function. Oxygen in solution in tissue shortens the tissue&#8217;s longitudinal relaxation time (T1), and thus a change in tissue oxygenation can be detected as a change in T1-weighted signal with an inversion recovery acquired image. Following an abrupt change between two concentrations of inspired oxygen, the rate at which lung tissue within a voxel equilibrates to a new steady-state reflects the rate at which resident gas is being replaced by inhaled gas. This rate is determined by specific ventilation. To elicit this sudden change in oxygenation, subjects alternately breathe 20-breath blocks of air (21% oxygen) and 100% oxygen while in the MRI scanner. A stepwise change in inspired oxygen fraction is achieved through use of a custom three-dimensional (3D)-printed flow bypass system with a manual switch during a short end-expiratory breath hold. To detect the corresponding change in T1, a global inversion pulse followed by a single shot fast spin echo sequence was used to acquire two-dimensional T1-weighted images in a 1.5&#160;T MRI scanner, using an eight-element torso coil. Both single slice and multi-slice imaging are possible, with slightly different imaging parameters. Quantification of specific ventilation is achieved by correlating the time-course of signal intensity for each lung voxel with a library of simulated responses to the air/oxygen stimulus. SVI estimations of specific ventilation heterogeneity have been validated against multiple breath washout and proved to accurately determine the heterogeneity of the specific ventilation distribution.

Specific ventilation imaging is a functional magnetic resonance imaging technique that allows for quantification of regional specific ventilation in the human lung, using inhaled oxygen as a contrast agent. Here, we present a protocol to collect and analyze specific ventilation imaging data.

以质子磁共振成像和氧为造影剂对人肺特异性通气进行定量定位

Specific ventilation imaging (SVI) is a functional magnetic resonance imaging technique capable of quantifying specific ventilation &#8213; the ratio of ...

Oxygenation-sensitive Cardiac MRI with Vasoactive Breathing Maneuvers for the Non-invasive Assessment of Coronary Microvascular Dysfunction

Oxygenation-sensitive cardiac magnetic resonance imaging (OS-CMR) is a diagnostic technique that uses the inherent paramagnetic properties of deoxyhemoglobin as an endogenous source of tissue contrast. Used in combination with standardized vasoactive breathing maneuvers (hyperventilation and apnea) as a potent non-pharmacologic vasomotor stimulus, OS-CMR can monitor changes in myocardial oxygenation. Quantifying such changes during the cardiac cycle and throughout vasoactive maneuvers can provide markers for coronary macro- and microvascular function and thereby circumvent the need for any extrinsic, intravenous contrast or pharmacologic stress agents.
OS-CMR uses the well-known sensitivity of T2*-weighted images to blood oxygenation. Oxygenation-sensitive images can be acquired on any cardiac MRI scanner using a modified standard clinical steady-state free precession (SSFP) cine sequence, making this technique vendor-agnostic and easily implemented. As a vasoactive breathing maneuver, we apply a 4-min breathing protocol of 120 s of free breathing, 60 s of paced hyperventilation, followed by an expiratory breath-hold of at least 30 s. The regional and global response of myocardial tissue oxygenation to this maneuver can be assessed by tracking the signal intensity change. The change over the initial 30 s of the post-hyperventilation breath-hold, referred to as the breathing-induced myocardial oxygenation reserve (B-MORE) has been studied in healthy people and various pathologies. A detailed protocol for performing oxygen-sensitive CMR scans with vasoactive maneuvers is provided.
As demonstrated in patients with microvascular dysfunction in yet incompletely understood conditions, such as inducible ischemia with no obstructive coronary artery stenosis (INOCA), heart failure with preserved ejection fraction (HFpEF), or microvascular dysfunction after heart transplantation, this approach provides unique, clinically important, and complementary information on coronary vascular function.

The assessment of microvascular function by oxygenation-sensitive cardiac magnetic resonance imaging in combination with vasoactive breathing maneuvers is unique in its ability to assess rapid dynamic changes in myocardial oxygenation in vivo and, thus, may serve as a critically important diagnostic technique for coronary vascular function.

氧合敏感性心脏 MRI 联合血管主动呼吸操作用于冠状动脉微血管功能障碍的无创评估

Oxygenation-sensitive cardiac magnetic resonance imaging (OS-CMR) is a diagnostic technique that uses the inherent paramagnetic properties of ...

PET-CT Scanning for Multi-Tracer Study of Cerebral Oxygen and Glucose Metabolism

Multi-Tracer Studies of Brain Oxygen and Glucose Metabolism Using a Time-of-Flight Positron Emission Tomography-Computed Tomography Scanner

The authors have developed a paradigm using positron emission tomography (PET) with multiple radiopharmaceutical tracers that combines measurements of cerebral metabolic rate of glucose (CMRGlc), cerebral metabolic rate of oxygen (CMRO2), cerebral blood flow (CBF), and cerebral blood volume (CBV), culminating in estimates of brain aerobic glycolysis (AG). These in vivo estimates of oxidative and non-oxidative glucose metabolism are pertinent to the study of the human brain in health and disease. The latest positron emission tomography-computed tomography (PET-CT) scanners provide time-of-flight (TOF) imaging and critical improvements in spatial resolution and reduction of artifacts. This has led to significantly improved imaging with lower radiotracer doses.
Optimized methods for the latest PET-CT scanners involve administering a sequence of inhaled 15O-labeled carbon monoxide (CO) and oxygen (O2), intravenous 15O-labeled water (H2O), and 18F-deoxyglucose (FDG)-all within 2-h or 3-h scan sessions that yield high-resolution, quantitative measurements of CMRGlc, CMRO2, CBF, CBV, and AG. This methods paper describes practical aspects of scanning designed for quantifying brain metabolism with tracer kinetic models and arterial blood samples and provides examples of imaging measurements of human brain metabolism.

Quantitative measurements of oxygen and glucose metabolism by PET are established technologies, but details of practical protocols are sparsely described in the literature. This paper presents a practical protocol successfully implemented on a state-of-the-art positron emission tomography-computed tomography scanner.

The authors have developed a paradigm using positron emission tomography (PET) with multiple radiopharmaceutical tracers that combines measurements of ...

MRI-动脉自旋标记集成以检测和监测脑血流 

Construction and Application of Cerebral Functional Region-Based Cerebral Blood Flow Atlas Using Magnetic Resonance Imaging-Arterial Spin Labeling

Cerebral conditions often require precise diagnosis and monitoring, necessitating advanced imaging techniques. Current modalities may not adequately detect early signs of reversible tissue damage, underlining the need for innovative diagnostic tools that can quantify changes in cerebral blood flow (CBF) with high specificity and sensitivity.&#160;This study integrates three-dimensional arterial spin labeling (3D-ASL) with structural MRI to develop comprehensive CBF atlases that cover all main functional regions of the brain. This innovative magnetic resonance imaging- arterial spin labeling (MRI-ASL) methodology provides a rapid and noninvasive means of quantifying region-specific CBF, offering a detailed view of CBF levels across different functional regions.The comparison between chronic cerebral ischemia (CCI) patients and healthy subjects revealed significantly diminished CBF across the cerebral functional regions in the constructed CBF atlases for the former. This approach not only allows for the efficient identification of CCI by analyzing concurrent decreases in CBF across critical areas relative to healthy distributions but also enables the tracking of treatment responses and rehabilitation progress through longitudinal CBF atlases.The CBF atlas developed using the MRI-ASL technique represents a novel advancement in the field of cerebral diagnostics and patient care. By comparing regional CBF levels against normative standards, this method enhances diagnostic capabilities, enabling clinicians to provide personalized care to patients with cerebral conditions.

作者聚焦:用于诊断神经系统疾病的人类功能脑区无创脑血流测定

This study integrated magnetic resonance imaging- arterial spin labeling images to derive cerebral blood flow (CBF) atlas for cerebral functional regions. Comparing typical healthy and chronic cerebral ischemia CBF atlases revealed significant differences in regional CBF distributions, enabling rapid, noninvasive assessments of functional CBF to assist in diagnosis and evaluate therapeutics.

基于磁共振成像-动脉自旋标记的基于脑功能区的脑血流图谱的构建与应用

Cerebral conditions often require precise diagnosis and monitoring, necessitating advanced imaging techniques. Current modalities may not adequately ...