作者想感谢 Mahla 的卡梅隆. 布拉德利, 雷切尔. 安妮和乔安娜. 斯蒂芬。另外还要感谢 Dr. 史蒂文 Mcguigan 作为第二个麻醉师的支持。佩帕帕斯提供了宝贵的麻醉护士监督。马库斯. 斯通欣然地将他的时间和专长用于编辑和拍摄该协议。Dr. Muthukumaraswamy 给出了关于数据分析和结果解释的具体建议。最后, 杰拉德戈特了许多令人振奋的讨论, 帮助执行了一些试点实验, 并在泡沫头支撑设计的中心。
这项研究得到了詹姆斯. 麦克唐纳合作赠款 #220020419 "重建意识", 授予乔治 Mashour, 迈克尔阿维丹, 马克斯 Kelz 和大卫 Liley。

作者没有什么可透露的。

本文概述了一个全面的协议, 同时记录的 MEG 和脑电图在麻醉气体交付与 N2O 和氙。这样的一个协议将是有价值的研究的电磁神经相关的麻醉诱导减少意识。该议定书还预计将推广到其他麻醉气体, 如七氟醚或异氟醚的交付。这将有助于更好地理解的共同的, 具体的和独特的宏观机制, 基础麻醉诱导减少意识的一系列麻醉剂有相当不同的分子模式和行动目标。理解麻醉剂的功能是神经科学的?...

临床前神经证据表明, 人的意识现象依赖于显式神经回路的完整性。这种电路被系统的下降到无意识的影响的观察证实了需要在麻醉过程中使用的神经影像技术, 并使 ' 导航 ' 搜索的神经系统相关性意识.除了睡眠, 麻醉是唯一的方法, 通过它可以控制, 可逆和重现的时尚, 扰乱, 从而解剖, sub-serve 意识的机制, 特别是在宏观尺度全球脑动力学。临床上, 全身麻醉可以定义为催眠/无意识, 静止和镇痛的状态, 仍然是最广泛使用和最安全的医疗干预之一。尽管最终结果的清晰度和效率, 仍然有很大的不确定性有关的作用机制的各种类型的药物引起麻醉性昏迷1。
麻醉剂可以分为静脉注射剂, 特别是异丙酚和巴比妥酸盐, 或挥发性/气态剂, 如七氟醚, 氟烷, 一氧化二氮 (N2O) 和氙 (氙气)。麻醉药理学已经很好地建立了多个细胞靶点确定与麻醉作用。大多数研究对象的行为主要通过 agonism γ-氨基丁酸 (GABA) 受体介导的活动。相反, 氯胺酮, 氙和 n2O 被认为是发挥其作用的主要目标是 n-甲基-d-天门冬氨酸 (NMDA) 谷氨酸受体2,3。其他重要的药理靶点包括钾通道、乙酰胆碱受体和残留的谷氨酸受体、AMPA 和酸, 但是它们对麻醉作用的贡献程度仍然难以捉摸 (全面审查见4)。
在作用机制的变化程度和观察到的生理和神经效应的不同类型的代理人呈现得出的一般结论对其影响有意识加工困难。gaba 剂引起的意识丧失通常以大脑活动的全球变化为特征。这是明显的在高, 低频三角洲 (δ, 0.5-4 Hz) 波浪和减少在高频率, 伽玛 (γ, 35-45Hz) 活动在脑电图 (EEG), 类似慢波睡眠5,6以及脑血流和葡萄糖代谢的广泛减少5,67891011.Boveroux et al。13通过功能性磁共振成像 (fMRI) 显示异丙酚麻醉下的静止状态功能连通性显著下降, 从而增加了这种观察。相比之下, 游离麻醉药对大脑活动的影响却不那么清晰。在某些情况下, 它们与脑血流量和葡萄糖代谢的增加有关14,15,16,1718,19, 20,21当研究由 Rex 和同事22和 Laitio 和同事23,24查看氙气的效果提供了增加和减少大脑的证据活动.类似的不规则性在 EEG 信号的影响上可以看到25,26,27,28。约翰逊et al。29显示了低频带三角洲和θ的总功率的增加, 以及在高密度 EEG 中进行氙麻醉的高频段伽玛的研究, 而在三角洲、θ和alpha 频带30,31和更高频率的氙气32。氙对电头皮活动的影响的这种可变性在α和 beta 频率范围可以被观察, 同时增加33和减少34被报告。
尽管存在上述的差异, 当人们试图查看大脑区域之间功能连通性的变化时, 这幅图开始变得更加一致。然而, 这种措施主要限于在空间或时间分辨率方面必须作出让步的方式。虽然使用 EEG 的研究显示出清晰, 并在一定程度上一致, 在麻醉/镇静期间功能网络的拓扑结构的变化与异丙酚35, 七氟醚,36和 N2O37,广泛间隔的传感器电平 EEG 数据没有足够的空间分辨率来有意义地定义和描绘相应的功能网络的顶点。相反, 研究利用功能磁共振成像和正电子发射断层扫描 (PET) 的优越空间分辨率, 发现类似的拓扑改变在 large-scale 函数连接到 EEG13,38,39 、40、41, 但没有足够的时间分辨率来表征α (8-13 Hz) EEG 带中的相振幅耦合和其他正在出现的重要特征的动态现象麻醉动作12,42。此外, 这些措施并没有直接评估电磁神经活动43。
因此, 为了有意义地推进对与麻醉药作用相关的宏观过程的理解, 必须解决以前提到的调查的局限性;麻醉剂的限制性覆盖范围和非侵入性测量的时空分辨率不足。在此基础上, 作者概述了同时记录脑 (MEG) 和脑电图活动的健康志愿者的方法, 已开发为管理气体游离麻醉剂, 氙和 N2O。
MEG 被利用, 因为它是唯一的非侵入性的神经技术, 除了 EEG, 在毫秒范围内有一个时间分辨率。EEG 的问题是模糊的电磁场的头骨, 这是一个低通过滤器的外皮生成的活动, 而 MEG 是不太敏感的这个问题和问题的音量传导44。可以认为, MEG 具有更高的空间和源定位精度比脑电图45,46。EEG 不允许真正的无参考记录37,47, 但 MEG 确实如此。MEG 系统也通常记录的皮层活动比脑电图更广泛的频率范围, 包括高伽玛48(通常是 70-90 Hz), 这已经被建议参与麻醉剂的催眠作用, 包括氙29和 N2O28。meg 提供神经的活动, 由 eeg 转达的恭维, 因为 eeg 活动涉及细胞外电流, 而 meg 主要反映的磁场产生的细胞内流46,49. 此外, MEG 是特别敏感的电生理活动切向皮层, 而 EEG 主要记录细胞外活动径向到皮层49。因此, 结合 MEG 和 EEG 数据具有 super-additive 优势50。
气体分离剂氙和 N2o 已选择的原因如下: 它们是无嗅的 (氙) 或基本上无嗅 (N2o), 因此可以很容易地利用在控制条件的存在, 当受聘于亚浓度。此外, 它们很适合在实验室环境中进行远程管理和监测, 因为它们的心肺-呼吸抑制剂效果不佳61。氙和较小程度的 N2O, 保留相对较低的最小肺泡浓度-(MAC)-清醒, 其中50% 的病人变得没有反应的口头命令的值为32.6 ± 6.1%51和 63.3 +-7.1%52分别。尽管氙和 N2O 都是 NMDA 受体拮抗剂, 他们不同地调制 EEG-氙似乎表现得更像一个典型的 gaba 剂时, 使用双频谱指数33,53,54(用于 electroencephalographically 监测麻醉深度的几种方法之一)。相比之下, N2O 产生的脑电图效果要低得多, 因为如果使用双频索引26, 则它的监视很差。由于氙有不同的报告脑电图性质的其他游离剂, 但具有相似的特点, 以更普遍研究的 gaba 剂, 其电生理研究有潜力揭示重要与意识的神经相关和相应的功能网络变化有关的特点。由于 nmda 受体介导的活动在学习和记忆中所起的关键作用, 以及它在一系列领域中的牵连作用, 在 nmda 受体上作用的药物可能会更多地揭示依附正常和改变意识的脑网络。精神疾病, 包括精神分裂症和抑郁症80。
本文主要研究了在医院环境下, 同时记录 MEG 和脑电图的气体麻醉剂的要求和复杂的数据收集过程。基本数据分析在传感器水平概述和示例数据提供说明, 高保真录音可以获得最低的头部移动。对于随后的源成像和/或功能连接分析, 通常使用此类数据执行的许多潜在方法都没有描述, 因为这些方法在文献中得到了很好的描述, 并演示了各种选项分析55,56。

<table><tbody><tr><td>Neuromag TRIUX 306-channel MEG system</td><td>Elekta Oy, Stockholm, SWEDEN</td><td>N/A</td><td></td></tr><tr><td>Polhemus Fastrak 3D system</td><td>Polhemus, VT, USA</td><td>N/A</td><td></td></tr><tr><td>MEG compatible ER-1 insert headphones</td><td>Etymotic Research Inc., IL, USA</td><td>N/A</td><td></td></tr><tr><td>Low Density foam head cap, MEG compatible</td><td>N/A</td><td>N/A</td><td>Custom made by research team</td></tr><tr><td>Harness, MEG compatible</td><td>N/A</td><td></td><td>~3 m long, ~ 5 cm wide, cloth/jute strip to secure participant position on MEG chair</td></tr><tr><td>Ambu Neuroline 720 Single Patient Surface Electrodes</td><td>Ambu, Copenhagen, Denmark</td><td>72015-K10</td><td></td></tr><tr><td>3.0T TIM Trio MRI system</td><td>Siemens AB, Erlangen, GERMANY</td><td>N/A</td><td></td></tr><tr><td>Asalab amplifier system</td><td>ANT Neuro, Enschede, NETHERLANDS</td><td>N/A</td><td>this system is no longer manufactured and has been deprecated to 64 channel eego EEG amplifier</td></tr><tr><td>64-channel Waveguard EEG cap, MEG compatible</td><td>ANT Neuro, Enschede, NETHERLANDS</td><td>CA-138</td><td>size Medium</td></tr><tr><td>Magnetically shielded cordless battery box</td><td>ANT Neuro, Enschede, NETHERLANDS</td><td>N/A</td><td>Magnetic shielding not provided by manufacturer &amp;ndash; Modified by research team</td></tr><tr><td>OneStep ClearGel Electrode gel</td><td>H+H Medizinprodukte GbR, Munster, GERMANY</td><td>154547</td><td></td></tr><tr><td>Akzent Xe Color Anesthesia Machine</td><td>Stephan GmbH, Gackenbach, GERMANY</td><td>N/A</td><td></td></tr><tr><td>Omron M6-Comfort Blood Pressure Monitor</td><td>Omron Healthcare, Kyoto, JAPAN</td><td>N/A</td><td></td></tr><tr><td>Xenon gas (99.999% purity)</td><td>Coregas, Thomastown, VIC, AUSTRALIA</td><td>N/A</td><td>we estimate that we use approx 40 L (SATP) per participant</td></tr><tr><td>Medical Nitrous Oxide</td><td>Coregas, Thomastown, VIC, AUSTRALIA</td><td>N/A</td><td>x2 G size cylinders</td></tr><tr><td>Medical Oxygen</td><td>Coregas, Thomastown, VIC, AUSTRALIA</td><td>N/A</td><td>x2 G size cylinders</td></tr><tr><td>Medical Air</td><td>Coregas, Thomastown, VIC, AUSTRALIA</td><td>N/A</td><td>x2 G size cylinders</td></tr><tr><td>Filter Respiratory &amp;amp; HMES with Capno Port Hypnobag</td><td>Medtronic, MN, USA</td><td>352/5805</td><td></td></tr><tr><td>Yankauer High Adult</td><td>Medtronic, MN, USA</td><td>8888-502005</td><td></td></tr><tr><td>Quadralite EcoMask anaesthetic masks</td><td>Intersurgical Australia Pty Ltd</td><td>7093000/7094000</td><td>size 3 and size 4</td></tr><tr><td>Suction Canister Disp 1200 mL Medival Guardian</td><td>Cardinal Health, OH, USA</td><td>65651-212</td><td></td></tr><tr><td>Catheter Mount Ext 4-13 cm with&amp;nbsp; 90A elbow</td><td>Medtronic, MN, USA</td><td>330/5667</td><td></td></tr><tr><td>Catheter IV Optiva 24g x 19 mm Yellow St Su</td><td>Smiths Medical, MN, USA</td><td>5063-INT</td><td></td></tr><tr><td>Dexamethasone Mylan Injection Vials (4 mg/1 mL)</td><td>Alphapharm Pty Ltd, Sydney, AUSTRALIA</td><td>400528517</td><td></td></tr><tr><td>Ondasetron (4 mg/2 mL)</td><td>Alphapharm Pty Ltd, Sydney, AUSTRALIA</td><td>400008857</td><td></td></tr><tr><td>Medical resuscitation cart</td><td></td><td></td><td>The medical resuscitation cart is configured according to the suggested minimal requirements for Adult resuscitation recommended in the document &quot;Standards for Resuscitation: Clinical Practice and Education; June 2014) by the Australian and New Zealand Resuscitation councils and specifically endorsed by multiple professional health care organizations including the Australian and New Zealand College of Anaesthetists.&amp;nbsp; It includes all the necessary airway and circulatory equipment, as well as the associated pharmacuetical agents to enable full cardio-respiratory resuscitation and support in a non-clinical environment.&amp;nbsp; Full details can be found at https://resus.org.au/standards-for-resuscitation-clinical-practice-and-education/</td></tr><tr><td>Maxfilter Version 2.2</td><td>Elekta Oy, Stockholm, SWEDEN</td><td>N/A</td><td>Data analysis software provided with Elekta&#039;s Neuromag TRIUX MEG system</td></tr></tbody></table>

recording brain electromagnetic activity during the administration of the gaseous anesthetic agents xenon and nitrous oxide in healthy volunteers

麻醉可以说是研究全球意识/无意识的神经系统相关性的唯一系统方法之一。然而到目前为止, 大多数神经影像或神经的研究都局限在人类的γ-氨基丁酸 (GABA)-受体-agonist-based 麻醉剂, 而游离 n-甲基-d-天门冬氨酸 (NMDA) 的影响,受体 antagonist-based 麻醉剂氯胺酮, 一氧化二氮 (N2O) 和氙 (氙气) 大多是未知的。本文介绍了从健康男性吸入气体麻醉剂 N2O 和氙的同时记录图 (MEG) 和脑电图 (eeg) 的方法。结合 MEG 和脑电图数据, 可以评估在高时、中度的麻醉过程中的电磁脑活动。在这里, 我们描述了一个详细的协议, 在多个录音会议, 包括学科招聘, 麻醉设备设置在 MEG 扫描仪室, 数据收集和基本数据分析。在本协议中, 每个参与者在重复的测量交叉设计中暴露于不同级别的氙和 N2O。在相关的基线记录之后, 参与者将会接触到逐步增加的氙和 N2O 的8、16、24和 42%, 以及16、32和47% 分别, 在这期间, 它们的响应程度是通过听觉连续性能任务 (aCPT)。给出了许多记录的结果, 以强调原始数据的传感器级特性、频谱形貌、头部运动的最小化以及对听觉诱发反应的明确水平依赖性效应。这一范式描述了一个一般的方法来记录的电磁信号与行动的不同类型的气体麻醉剂, 这可以很容易地适应用于挥发性和静脉麻醉剂。预计该方法可以帮助理解的宏观规模的机制, 麻醉通过启用方法扩展涉及源空间成像和功能网络分析。

本节利用从一个主题获得的数据, 以证明同时录制的典型特征和这些信息的潜力有助于更好地了解麻醉引起的意识改变状态。为了简化博览会, 结果显示为 i) post-anti-催吐剂管理基线 (基线 3), ii) 0.75 等 MAC 清醒峰值气体浓度 (3 级), N2O (47%) 和氙 (24%) 和 iii) 氙峰值气体浓度 42% (4级)。选择级别3和 4, 因为它们分别为 N2O 和氙的最高稳态级别。此外, 4 级氙涉及明?...

Watch this Scientific Journal Video about Recording Brain Electromagnetic Activity During the Administration of the Gaseous Anesthetic Agents Xenon and Nitrous Oxide in Healthy Volunteers at JoVE.com

Recording Brain Electromagnetic Activity During the Administration of the Gaseous Anesthetic Agents Xenon and Nitrous Oxide in Healthy Volunteers

同时图和脑电图提供了一个有用的工具, 以寻找共同和独特的宏观规模的机制, 减少意识的不同麻醉剂诱导。本文阐述了在吸入一氧化二氮和氙时, 从健康人的 n-甲基-d-天门冬氨酸 (NMDA) 受体 antagonist-based 麻醉中记录这些数据的经验方法。

在健康志愿者的气体麻醉剂氙和一氧化二氮的管理中记录大脑电磁活动

Anesthesia arguably provides one of the only systematic ways to study the neural correlates of global consciousness/unconsciousness. However to date most ...

recording-brain-electromagnetic-activity-during-administration

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10.9K 次观看.  Swinburne University of Technology. 同时图和脑电图提供了一个有用的工具, 以寻找共同和独特的宏观规模的机制, 减少意识的不同麻醉剂诱导。本文阐述了在吸入一氧化二氮和氙时, 从健康人的 n-甲基-d-天门冬氨酸 (NMDA) 受体 antagonist-based 麻醉中记录这些数据的经验方法。

视频: Recording Brain Electromagnetic Activity During the Administration of the Gaseous Anesthetic Agents Xenon and Nitrous Oxide in Healthy Volunteers

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 ...

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医学

Assessing Changes in Volatile General Anesthetic Sensitivity of Mice after Local or Systemic Pharmacological Intervention

One desirable endpoint of general anesthesia is the state of unconsciousness, also known as hypnosis. Defining the hypnotic state in animals is less straightforward than it is in human patients. A widely used behavioral surrogate for hypnosis in rodents is the loss of righting reflex (LORR), or the point at which the animal no longer responds to their innate instinct to avoid the vulnerability of dorsal recumbency. We have developed a system to assess LORR in 24 mice simultaneously while carefully controlling for potential confounds, including temperature fluctuations and varying gas flows. These chambers permit reliable assessment of anesthetic sensitivity as measured by latency to return of the righting reflex (RORR) following a fixed anesthetic exposure. Alternatively, using stepwise increases (or decreases) in anesthetic concentration, the chambers also enable determination of a population's sensitivity to induction (or emergence) as measured by EC50 and Hill slope. Finally, the controlled environmental chambers described here can be adapted for a variety of alternative uses, including inhaled delivery of other drugs, toxicology studies, and simultaneous real-time monitoring of vital signs.

Loss of the righting reflex has long served as a standard behavioral surrogate for unconsciousness, also called hypnosis, in laboratory animals. Alterations in volatile anesthetic sensitivity caused by pharmacological interventions can be detected with a carefully controlled high-throughput assessment system, which may be adapted for delivery of any inhaled therapeutic.

局部或全身药物干预后评估的变化小鼠中挥发性全身麻醉药敏感性

One desirable endpoint of general anesthesia is  the state of unconsciousness, also known as hypnosis. Defining the hypnotic state in animals is  less ...

MRI Mapping of Cerebrovascular Reactivity via Gas Inhalation Challenges

The brain is a spatially heterogeneous and temporally dynamic organ, with different regions requiring different amount of blood supply at different time. Therefore, the ability of the blood vessels to dilate or constrict, known as Cerebral-Vascular-Reactivity (CVR), represents an important domain of vascular function. An imaging marker representing this dynamic property will provide new information of cerebral vessels under normal and diseased conditions such as stroke, dementia, atherosclerosis, small vessel diseases, brain tumor, traumatic brain injury, and multiple sclerosis. In order to perform this type of measurement in humans, it is necessary to deliver a vasoactive stimulus such as CO2 and/or O2 gas mixture while quantitative brain magnetic resonance images (MRI) are being collected. In this work, we presented a MR compatible gas-delivery system and the associated protocol that allow the delivery of special gas mixtures (e.g., O2, CO2, N2, and their combinations) while the subject is lying inside the MRI scanner. This system is relatively simple, economical, and easy to use, and the experimental protocol allows accurate mapping of CVR in both healthy volunteers and patients with neurological disorders. This approach has the potential to be used in broad clinical applications and in better understanding of brain vascular pathophysiology. In the video, we demonstrate how to set up the system inside an MRI suite and how to perform a complete experiment on a human participant.

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. ...

Intra-Operative Neural Monitoring of Thyroid Surgery in a Porcine Model

Intraoperative injury to the recurrent laryngeal nerve (RLN) can cause vocal cord paralysis, which interferes with speech and can potentially interfere with breathing. In recent years, intraoperative neural monitoring (IONM) has been widely adapted as an adjunct technique to localize the RLN, detect RLN injury, and predict vocal cord function during the operations. Many studies have also used animal models to investigate new applications of IONM technology and to develop reliable strategies for preventing intraoperative RLN injury. The aim of this article is to introduce a standard protocol for using a porcine model in IONM research. The article demonstrates the procedures for inducing general anesthesia, performing tracheal intubation, and experimental design to investigate the electrophysiological characteristics of RLN injuries. Applications of this protocol can improve overall efficacy in implementing the 3R principle (replacement, reduction and refinement) in porcine IONM studies.

This study aims to develop a standard protocol of intra-operative neural monitoring of thyroid surgery in a porcine model. Here, we present a protocol to demonstrate general anesthesia, to compare different types of electrodes, and to investigate the electrophysiological characteristics of the normal and injured recurrent laryngeal nerves.

猪手术模型对甲状腺手术的手术内神经监测

Intraoperative injury to the recurrent laryngeal nerve (RLN) can cause vocal cord paralysis, which interferes with speech and can potentially interfere ...

Optogenetic Activation of Afferent Pathways in Brain Slices and Modulation of Responses by Volatile Anesthetics

Anesthetics influence consciousness in part via their actions on thalamocortical circuits. However, the extent to which volatile anesthetics affect distinct cellular and network components of these circuits remains unclear. Ex vivo brain slices provide a means by which investigators may probe discrete components of complex networks and disentangle potential mechanisms underlying the effects of volatile anesthetics on evoked responses. To isolate potential cell type- and pathway-specific drug effects in brain slices, investigators must be able to independently activate afferent fiber pathways, identify non-overlapping populations of cells, and apply volatile anesthetics to the tissue in aqueous solution. In this protocol, methods to measure optogenetically-evoked responses to two independent afferent pathways to neocortex in ex vivo brain slices are described. Extracellular responses are recorded to assay network activity and targeted whole-cell patch clamp recordings are conducted in somatostatin- and parvalbumin-positive interneurons. Delivery of physiologically relevant concentrations of isoflurane via artificial cerebral spinal fluid to modulate cellular and network responses is described.

Ex vivo brain slices can be used to study the effects of volatile anesthetics on evoked responses to afferent inputs. Optogenetics are employed to independently activate thalamocortical and corticocortical afferents to non-primary neocortex, and synaptic and network responses are modulated with isoflurane.

脑切片中传入通路的光遗传学激活和挥发性麻醉剂对反应的调节

Anesthetics influence consciousness in part via their actions on thalamocortical circuits. However, the extent to which volatile anesthetics affect ...

神经科学

Real-Time fMRI Brain Mapping in Animals

Dynamic fMRI responses vary largely according to the physiological conditions of animals either under anesthesia or in awake states. We developed a real-time fMRI platform to guide experimenters to monitor fMRI responses instantaneously during acquisition, which can be used to modify the physiology of animals to achieve desired hemodynamic responses in animal brains. The real-time fMRI set-up is based on a 14.1T preclinical MRI system, enabling the real-time mapping of dynamic fMRI responses in the primary forepaw somatosensory cortex (FP-S1) of anesthetized rats. Instead of a retrospective analysis to investigate confounding sources leading to the variability of fMRI signals, the real-time fMRI platform provides a more effective scheme to identify dynamic fMRI responses using customized macro-functions and a common neuroimage analysis software in the MRI system. Also, it provides immediate troubleshooting feasibility and a real-time biofeedback stimulation paradigm for brain functional studies in animals.

Animal brain functional mapping can benefit from the real-time functional magnetic resonance imaging (fMRI) experimental set-up. Using the latest software implemented in the animal MRI system, we established a real-time monitoring platform for small animal fMRI.

动物实时功能磁共振成像大脑映射

Dynamic fMRI responses vary largely according to the physiological conditions of animals either under anesthesia or in awake states. We developed a ...

Hyperpolarized 129Xe Lung MRI and Spectroscopy in Mechanically Ventilated Mice

Hyperpolarized (HP) xenon-129 (129Xe) is an inhaled magnetic resonance imaging (MRI) contrast agent with unique spectral and physical properties that can be exploited to quantify pulmonary physiology, including ventilation, restricted diffusion (alveolar-airspace size), and gas exchange. In humans, it has been used to evaluate disease severity and progression in a variety of pulmonary disorders and is approved for clinical use in the United States and United Kingdom. Beyond its clinical applications, the ability of 129Xe MRI to noninvasively assess pulmonary pathophysiology and provide spatially resolved information is valuable for preclinical research. Among animal models, mice are the most widely used due to the accessibility of genetically modified disease models. Here, 129Xe MRI is promising as a minimally invasive, radiation-free, and sensitive technique to longitudinally monitor lung disease progression and therapy response (e.g., in drug discovery). This technique can extend to preclinical applications by incorporating an MRI-triggered, free-breathing apparatus or mechanical ventilator to deliver gas. Here, we describe the steps and provide checklists to ensure robust data collection and analysis, including creating a thermally polarized xenon gas phantom for quality control, optimizing polarization, animal handling (sedation, intubation, ventilation, and care for mice), and protocols for ventilation, restricted diffusion, and gas exchange data. While preclinical 129Xe MRI can be applied in various animal models (e.g., rats, pigs, sheep), this protocol focuses on mice due to the challenges posed by their small anatomy, which are balanced by their affordability and the availability of many disease models.

Hyperpolarized xenon MRI can quantify regional lung microstructure (air-space dimensions) and physiology (ventilation and gas exchange) in translational research and clinical care. Although challenging, it can provide comparable pulmonary insights in preclinical studies. This protocol describes the infrastructure and procedures needed to perform routine xenon lung MRI in mice.

Hyperpolarized (HP) xenon-129 (129Xe) is an inhaled magnetic resonance imaging (MRI) contrast agent with unique spectral and physical properties that can ...

生物工程

A Novel Inhalation Mask System to Deliver High Concentrations of Nitric Oxide Gas in Spontaneously Breathing Subjects

Nitric Oxide (NO) is administered as gas for inhalation to induce selective pulmonary vasodilation. It is a safe therapy, with few potential risks even if administered at high concentration. Inhaled NO gas is routinely used to increase systemic oxygenation in different disease conditions. The administration of high concentrations of NO also exerts a virucidal effect in vitro. Owing to its favorable pharmacodynamic and safety profiles, the familiarity in its use by critical care providers, and the potential for a direct virucidal effect, NO is clinically used in patients with coronavirus disease-2019 (COVID-19). Nevertheless, no device is currently available to easily administer inhaled NO at concentrations higher than 80 parts per million (ppm) at various inspired oxygen fractions, without the need for dedicated, heavy, and costly equipment. The development of a reliable, safe, inexpensive, lightweight, and ventilator-free solution is crucial, particularly for the early treatment of non-intubated patients outside of the intensive care unit (ICU) and in a limited-resource scenario. To overcome such a barrier, a simple system for the non-invasive NO gas administration up to 250 ppm was developed using standard consumables and a scavenging chamber. The method has been proven safe and reliable in delivering a specified NO concentration while limiting nitrogen dioxide levels. This paper aims to provide clinicians and researchers with the necessary information on how to assemble or adapt such a system for research purposes or clinical use in COVID-19 or other diseases in which NO administration might be beneficial.

This simple and highly adaptable system device for the inhalation of high-concentration nitric oxide (NO) gas does not require mechanical ventilators, positive pressure, or high gas flows. Standard medical consumables and a snug-fitting mask are used to safely deliver NO gas to spontaneously breathing subjects.

一种新型吸入面膜系统，可在自发呼吸受试者中提供高浓度的一氧化氮气体

Nitric Oxide (NO) is administered as gas for inhalation to induce selective pulmonary vasodilation. It is a safe therapy, with few potential risks even if ...

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 ...

使用超极化氙 129 MRI 评估肺功能

Quantitative Measure of Lung Structure and Function Obtained from Hyperpolarized Xenon Spectroscopy

Hyperpolarized Xenon-129 (HXe) magnetic resonance imaging (MRI) provides tools for obtaining 2- or 3-dimensional maps of lung ventilation patterns, gas diffusion, Xenon uptake by lung parenchyma, and other lung function metrics. However, by trading spatial for temporal resolution, it also enables tracing of pulmonary Xenon gas exchange on a ms timescale. This article describes one such technique, chemical shift saturation recovery (CSSR) MR spectroscopy. It illustrates how it can be used to assess capillary blood volume, septal wall thickness, and the surface-to-volume ratio in the alveoli. The flip angle of the applied radiofrequency pulses (RF) was carefully calibrated. Single-dose breath-hold and multi-dose free-breathing protocols were employed for administering the gas to the subject. Once the inhaled Xenon gas reached the alveoli, a series of 90&#176; RF pulses was applied to ensure maximum saturation of the accumulated Xenon magnetization in the lung parenchyma. Following a variable delay time, spectra were acquired to quantify the regrowth of the Xenon signal due to gas exchange between the alveolar gas volume and the tissue compartments of the lung. These spectra were then analyzed by fitting complex pseudo-Voigt functions to the three dominant peaks. Finally, the delay time-dependent peak amplitudes were fitted to a one-dimensional analytical gas-exchange model to extract physiological parameters.

作者聚焦:利用自由呼吸超极化氙 129 MRI 推进肺病研究

The manuscript presents a detailed protocol for using hyperpolarized Xenon-129 chemical shift saturation recovery (CSSR) to trace pulmonary gas exchange, assess the apparent alveolar septal wall thickness, and measure the surface-to-volume ratio. The method has the potential to diagnose and monitor lung diseases.

通过超偏振氙光谱法获得的肺结构和功能的定量测量

Hyperpolarized Xenon-129 (HXe) magnetic resonance imaging (MRI) provides tools for obtaining 2- or 3-dimensional maps of lung ventilation patterns, gas ...

在健康志愿者的气体麻醉剂氙和一氧化二氮的管理中记录大脑电磁活动

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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