The authors wish to thank Aisha Dar, Vanathy Niranjan, and Dr. Umar Dar for technical assistance with rTMS delivery and data collection. The authors also wish to acknowledge the generous support of the Toronto General and Western Hospital Foundation, the Buchan Family Foundation, and the Ontario Brain Institute in funding this work.

这项研究是在大学健康网络经研究伦理委员会。 1.选题<ol><li>在一个准病人进行初步评估。纳入标准包括一个当前抑郁发作是抗至少1适当药物的试验的情况下，和一个精神障碍诊断和统计手册，第五版，（DSM-5）诊断的MDD作为由评估精神科医生建立。明确诊断与标准化简易精神状态检查（MINI）。 </li><li>确保患者在一个稳定的药物或之前将其第一磁刺激治疗会话洗出他们的药物治疗例程的至少4周。不要改变整个治疗的rTMS这种药物团，以帮助消除歧义的任何临床上观察到的改善或恶化的原因。 </li><li>谁排除可能有一个潜在的禁忌rTMS治疗或MRI检查的患者，我ncluding发作史，心律失常，植入或外来设备/金属的颗粒，不稳定的医疗条件，或妊娠。患者合并症创伤后应激障碍，强迫症，其它焦虑障碍，注意缺陷多动障碍，神经性贪食症或暴食症，或中度集B个性特征也适用于这种处理，不需要被排除在外。双相障碍患者，而不是MDD也可以是适于这种待遇。患者的精神障碍，活性物质的使用，边缘型或反社会型人格障碍，性或持续性抑郁障碍（精神抑郁症）的主要诊断可能不太适合于治疗和可能需要排除。 </li></ol> 2.采集磁共振图像<ol><li>获得患者的核磁共振成像，在治疗前的任何时间。在这里，使用3特斯拉的扫描仪具有8通道相控阵头线圈（见表垫的erials），或能够产生一个病人的大脑的3D表示任何扫描仪。 </li><li>秉承本地站点协议，收购T1加权快速梯度回波扫描解剖。使用下面的参数：TE = 12毫秒，TI = 300毫秒，翻转角= 20°，116矢状切片，厚度= 1.5毫米，没有间隙，256×256矩阵，FOV 240毫米以下在电机阈值和疗程这种扫描将用于实时的rTMS神经导航。 </li></ol> 3.预处理解剖扫描的实时神经导航<ol><li>准备利用神经导航系统指导MRI。 注意：下面的步骤使用遮阳2.0神经导航系统（参考表材料），但是其它的导航系统，如Brainsight TMS导航，StealthStation，Aimnav，和NBS系统4使用类似的程序。 </li><li>段解剖核磁共振到其头皮和大脑的组件。注册两段成标准stereotactic空隙，如塔莱拉什和Tournoux空间19。 </li><li>地方目标标记通过选择MRI以下几点：鼻根;左耳和右耳，针对耳屏;前连合;后连合;纵裂点（两半球之间的点）;前最点的大脑;后最点的大脑;上级最点的大脑;和左，右最点的大脑。 </li><li>重建患者的头皮和大脑中的标准空间创建一个三维表面的基于头部模型的表面 - 该图像将被用于识别立体头皮坐标覆dmPFC（塔莱拉什和Tournoux坐标X0，Y + 60，Z + 60），用于在治疗过程中的最佳线圈顶点放置。 注意：此方法使用人口坐标来确定目标的刺激。其他的方法来确定一个目标的刺激，在讨论中概述，包括单科解剖或FMR我激活的地图。 </li><li>注册的大脑和立体空间坐标头皮为个性化的线圈放置病人的空间。 </li></ol> 4.运动阈值评估<ol><li>座椅病人在治疗椅，调节摄像机为病人一览无遗。 </li><li>放置与连接到它绕患者的头部的标记片段的​​头带。标记的剪辑应该坐下上面鼻梁。 </li><li>预处理对于在步骤3中描述上面的病人的解剖扫描。 </li><li>加载预处理解剖扫描到神经导航程序并打开相机。 </li><li>使用神经导航笔，突出对患者头皮各目标点。与神经导航笔所完成的动作将被投影的红色线条的形式在电视屏幕上。 </li><li>评估患者的运动阈值，需要在全球范围内的最小强度激发运动通路，之前的rTMS treatm耳鼻喉科。对于此步骤，通过使患者的下肢延伸并从下方支撑，使用粪便或装有一个可扩展的腿支承椅子开始。 </li><li>对于运动阈值测定，神经导航下，目标内侧初级运动皮层。将线圈顶点在矢状裂，0.5-1.0厘米前方中央沟。使用有角度或锥双线圈脉冲更深渗透到内侧区域。使用刺激搭载了流体冷却盘管，其绕组角度为120°，以允许脉冲更深地穿透（参见表材料）。 </li><li>分别执行电动机阈值用于左和右半球。定向线圈横向引导磁刺激诱 ​​发的电流流动到所需的半球20。例如，刺激左半球，定位线圈与把手指向向右和电流流向左半球的方向。观察对侧（右）下肢对于此过程中的运动。 </li><li>视觉的大脚趾的halluces长肌确定的阈值和诱发的电机运动。 注：不同于传统的运动阈值检测为目标的手部肌肉，刺激管壁内侧运动皮层的将目标锁定在脚趾的肌肉。运动诱发电位（MEPS）也可以用作更精确地确定的运动阈值，但它是一个更冗长的方法。 <ol><li>通过刺激在最大强度的机器55％开始，然后向上或向下调整的〜5％的增量取决于是否反应观察​​。稳步减小增量大小至〜1％作为电动机阈逼近，如前所述21。刺激不超过0.2赫兹（每秒5秒）更频繁，以免随着时间的推移抑制或兴奋作用。 </li><li>一旦运动阈值被确定，移动顶点1-2厘米向前向后，并在2-3毫米探索增量，以阻止矿井是否有替代的网站提供了一个较低的运动阈值。使用沿此弧形每侧达到的最低阈值。 </li></ol></li></ol> 5.治疗颅磁刺激适应性和滴定<ol><li>执行neuronavigated dmPFC-rTMS治疗一个疗程，共使用20-30日常会话超过4-6周。对于治疗，使用120°角度的，流体冷却盘管和下面dmPFC刺激在每一次治疗（参考表材料 ）中列出的参数。 </li><li>座椅病人在治疗椅，调节摄像机为病人一览无遗。 </li><li>放置与连接到它围绕病人的头部的标记剪辑头带（置于横向以免挡住磁刺激线圈放置在内侧目标部位），如上所述。使用照相机中，神经导航系统，将检测标记片段和将允许预处理和神经导航。 </li><li>加载预处理ANAtomical扫描到神经导航程序，并打开相机。 </li><li>使用神经导航笔，突出对患者头皮各目标点。与神经导航笔所完成的动作将被投影的红色线条的形式在电视屏幕上。 </li><li>放置在线圈采用神经导航系统MRI指导下dmPFC目标。为了进行校验，这点应位于接近距离的25％，从鼻根到INION。横向。定向线圈横向，与把手指向远离半球被刺激。刺激左半球，然后重新定向线圈180°，以刺激右半球，保持在同一位置过dmPFC头皮位点的顶点。 </li><li>确保头皮的网站dmFPC保持与线圈本身在整个治疗紧密接触。确保患者和操作人员在治疗期间佩戴耳塞或其它听力保护。 </li><li>对于10 Hz的刺激，使用5秒的上10秒关，总共每会话半球60列车（3000脉冲）的占空比。通过横向定向线圈执行左然后右半球的这个协议，如前所述20。 注：所描述的协议，用于10赫兹rTMS治疗是以外的国际安全准则（Rossi 等 ，2009）。有证据表明它的安全性18,22。 </li><li>为TBS刺激，使用2秒时，8秒关的占空比为总共600个脉冲每半球每个会话。通过横向定向线圈执行左然后右半球的这个协议，如前所述20。 </li><li>自适应从20％最大刺激强度的初始值滴定颅磁刺激刺激强度向上，以允许患者使其习惯到在初始会话期间23与磁刺激相关的疼痛和头皮不适。由2-5％增加刺激强度的刺激每列车，作为容忍。 <ol><li>为了评估耐受性，对从0口头模拟评分（VAS）病人率痛到10（0 =无疼痛，10 =极限耐受性无情绪困扰）刺激每列车交付后。 </li></ol></li><li>首先每个会话更高的刺激强度，使用与前一交易日中度耐受性（VAS 5-6）相关联的水平，直到患者开始在休息运动阈值的每个半球120％的目标强度。在此滴定过程保持低于9整个处理口头模拟量表。滴定通常在完成2-5天。 </li><li>监测患者在治疗期间的其他不利影响。 注意：最常见的治疗中断的不利影响是一个晕厥发作，治疗的患者〜1％的第一或第二会话期间所产生的。患者可追述感到头晕，淡淡的，或迷失方向，并可能短暂（约10秒）LOSE意识。经常，反复抽搐或运动后发作混淆超过几秒钟持久的更多的应该是不存在的，但是。在晕厥发作的情况下，降低在椅子上，如果可能的头枕和鼓励病人保持静止不动，直到痊愈。如果患者被回收并愿意几分钟后，以继续该会话可以继续。 </li><li>监测患者的治疗过程中全身强直 - 阵挛性发作。 注意：这些事件是罕见的，我们还没有观察到扣押dmPFC-rTMS治疗的〜8000届跨&gt; 200个别病人的日期。正规，有节奏的，充满活力的运动抽搐持续10-40秒，最初约3赫兹和逐渐变得不那么快，并伴有反应迟钝，均提示癫痫发作，而不是晕厥。然而，这两种可能难以区分对于未经训练的观察者。 <ol><li>在所有的治疗使用视频监控，这样的情节可以由neurologis进行审查T对于以后的评估，如果有必要的。在这样的情节的情况下，应用标准的发作急救措施，包括清除对象的面积与可能造成的伤害，将病人在地面上，如果可能的或降低治疗椅到水平位置，如果不是，铺设患者在左侧如果可能的话，确保清理呼吸道，并确保人仍然与病人直至发作终止和该人恢复全部的警觉。 </li><li>呼叫紧急服务，如果扣押不〜60秒后自行终止。 </li></ol></li></ol> 6.临床数据采集<ol><li>收集标准化自我报告问卷在基线，每周在整个治疗和随访（ 例如 ，2，4，6，12，和26周治疗后）。收集以下自我报告的数据：贝克抑郁量表（BDI-II）24，和贝克焦虑量 ​​表25在整个TR每天eatment。 </li><li>通过临床医生额定17项汉密尔顿量表收集抑郁严重程度评分为抑郁评分26（HAMD 17）在基线，每周治疗期间，并在2，4，6，12和26周治疗后的随访。 </li></ol>

Authors Ms. Dunlop and Ms. Gapriellian have no disclosures to report.

这里，MRI引导dmPFC-磁刺激涂敷了用于治​​疗难治性抑郁症。在一般情况下，的rTMS在这个网站的耐受性良好，轻度头皮不适和疼痛刺激时的网站使用自适应滴定充分的管理。在开放性试验和图审查，既10赫兹和theta爆裂刺激导致抑郁症的严重程度显著的改善为由HAMD 17和BDI-II测量。 有两个值得注意的rTMS治疗过程中进行优化dmPFC刺激的关键步骤。首先，有角度的，双锥形...

重复经颅磁刺激（rTMS治疗）是间接的局灶性皮质刺激的一种形式。颅磁刺激员工短暂，焦电磁场脉冲穿透颅骨刺激目标的大脑区域。磁刺激被认为是啮合的突触长期增强，长期抑郁的机制，从而增加或减少区域的皮层的兴奋性刺激的1。一般地，磁刺激脉冲的频率决定其效应：较高频率刺激趋向于兴奋性，而较低的频率是抑制性的。非侵入性的刺激程序也被广泛使用作为因果探针以诱导临时“皮质性病变”，并且通过暂时禁用期望皮层区2的功能建立神经行为关系或功能区域- 4。 颅磁刺激治疗涉及多个刺激会话，通常施一次ðaily在几个星期，治疗各种疾病，包括重度抑郁症（MDD）5，进食障碍6，和强迫症7。磁刺激MDD的是难治的患者潜在的选择，并且允许临床医生能够无创靶向并改变直接参与与抑郁病因或病理生理学皮质区的兴奋性。对于MDD-rTMS治疗常规皮质目标是背外侧前额叶皮层（DLPFC）8。然而，从神经影像学，病变组织，刺激研究的证据，确定背内侧前额皮层（dmPFC）作为MDD 9潜在的重要治疗靶标和各种在自我调节的思想，行为特征在于赤字其它精神障碍和情感规定10。该dmPFC是一致的活化在情绪调节11，行为监管12,13的区域。该dmPFC也与神经化学相关的14，15的结构和功能异常16在MDD 此处所描述的程序是用于磁共振成像（MRI）引导的磁刺激的dmPFC双边的20届（4周），作为用于抑郁症的治疗。除了 ​​施加在30分钟的常规10赫兹协议，间歇THETA突发刺激方案（TBS）进行了讨论，其在6分钟会话17施加50赫兹三峰脉冲串在5赫兹。这两个协议都被认为是兴奋性的，与具有实现使用短得多的会话18可比效 ​​应的可能性的TBS协议。在这两个协议，解剖核磁共振成像以及临床评估之前将磁刺激获得的。神经导航使用解剖扫描占dmPFC的解剖变化和优化磁刺激的位置。一个相对较新的120°-angled流体冷却磁刺激线圈也是我们ED为了刺激更深中线皮质结构。最后，磁刺激强度滴定，使用过的rTMS会话的第一个星期，以确保病人能，观察者与dmPFC刺激相关的更高的疼痛水平相对于传统DLPFC刺激。

<table border="0" cellpadding="0" cellspacing="0">
	<tbody>
		<tr>
			<td>3T GE Signa HDx Scanner</td>
			<td>GE</td>
			<td>n/a</td>
			<td></td>
		</tr>
		<tr>
			<td>Visor 2.0 Neuronavigation System</td>
			<td>ANT Neuro</td>
			<td>n/a</td>
			<td></td>
		</tr>
		<tr>
			<td>MagPro R30 Stimulator</td>
			<td>MagVenture</td>
			<td>n/a</td>
			<td></td>
		</tr>
		<tr>
			<td>Cool-DB80 Coil</td>
			<td>MagVenture</td>
			<td>n/a</td>
			<td></td>
		</tr>
	</tbody>
</table>

mri-guided dmpfc-rtms as a treatment for treatment-resistant major depressive disorder

Here we outline the protocol for magnetic resonance imaging (MRI) guided repetitive transcranial magnetic stimulation (rTMS) to the dorsal medial prefrontal cortex (dmPFC) in patients with major depressive disorder (MDD). Technicians used a neuronavigation system to process patient MRIs to generate a 3-dimensional head model. The head model was subsequently used to identify patient-specific stimulatory targets. The dmPFC was stimulated daily for 20 sessions. Stimulation intensity was titrated to address scalp pain associated with rTMS. Weekly assessments were conducted on the patients using the Hamilton Rating Scale for Depression (HamD17) and Beck Depression Index II (BDI-II). Treatment-resistant MDD patients achieved significant improvements on both HAMD and BDI-II. Of note, angled, double-cone coil rTMS at 120% resting motor threshold allows for optimal stimulation of deeper midline prefrontal regions, which results in a possible therapeutic application for MDD. One major limitation of the rTMS field is the heterogeneity of treatment parameters across studies, including duty cycle, number of pulses per session and intensity. Further work should be done to clarify the effect of stimulation parameters on outcome. Future dmPFC-rTMS work should include sham-controlled studies to confirm its clinical efficacy in MDD.

在先前的工作中，HAMD 17被用来作为10赫兹dmPFC-磁刺激。 表1显示了前和后处理HAMD 17的分数，在预先公布的情况下，一系列的27治疗反应的量度。在所有科目，治疗前HAMD 17得分21.66.9由4331％的显著下降到12.58.2后颅磁刺激（T 22 = 6.54，P &lt;0.0001），27。使用HAMD 17≤7，一个缓解准则23例8汇至如下处理。 表2显示，在相同?...

Watch this Scientific Journal Video about MRI-guided dmPFC-rTMS as a Treatment for Treatment-resistant Major Depressive Disorder at JoVE.com

MRI-guided dmPFC-rTMS as a Treatment for Treatment-resistant Major Depressive Disorder

Here we outline the procedure for MRI-guided repetitive transcranial magnetic stimulation to the dorsomedial prefrontal cortex as an experimental treatment for major depressive disorder.

MRI引导dmPFC-rTMS治疗作为治疗难治性抑郁症

Here we outline the protocol for magnetic resonance imaging (MRI) guided repetitive transcranial magnetic stimulation (rTMS) to the dorsal medial ...

mri-guided-dmpfc-rtms-as-treatment-for-treatment-resistant-major

Research

JoVE Journal

Medicine

13.7K 次观看.  University of Toronto. Here we outline the procedure for MRI-guided repetitive transcranial magnetic stimulation to the dorsomedial prefrontal cortex as an experimental treatment for major depressive disorder.

视频: MRI-guided dmPFC-rTMS as a Treatment for Treatment-resistant Major Depressive Disorder

MRI-guided Disruption of the Blood-brain Barrier using Transcranial Focused Ultrasound in a Rat Model

Focused ultrasound (FUS) disruption of the blood-brain barrier (BBB) is an increasingly investigated technique for circumventing the BBB1-5. The BBB is a significant obstacle to pharmaceutical treatments of brain disorders as it limits the passage of molecules from the vasculature into the brain tissue to molecules less than approximately 500 Da in size6. FUS induced BBB disruption (BBBD) is temporary and reversible4 and has an advantage over chemical means of inducing BBBD by being highly localized. FUS induced BBBD provides a means for investigating the effects of a wide range of therapeutic agents on the brain, which would not otherwise be deliverable to the tissue in sufficient concentration. While a wide range of ultrasound parameters have proven successful at disrupting the BBB2,5,7, there are several critical steps in the experimental procedure to ensure successful disruption with accurate targeting. This protocol outlines how to achieve MRI-guided FUS induced BBBD in a rat model, with a focus on the critical animal preparation and microbubble handling steps of the experiment.

Microbubble-mediated focused ultrasound disruption of the blood-brain barrier (BBB) is a promising technique for non-invasive targeted drug delivery in the brain1-3. This protocol outlines the experimental procedure for MRI-guided transcranial BBB disruption in a rat model.

MRI引导下的破坏血脑屏障在大鼠模型经颅聚焦超声

Focused ultrasound (FUS) disruption of the blood-brain barrier (BBB) is an increasingly investigated technique for circumventing the BBB1-5. The BBB is a ...

科研

医学

Osteopathic Manipulative Treatment as a Useful Adjunctive Tool for Pneumonia

Pneumonia, the inflammatory state of lung tissue primarily due to microbial infection, claimed 52,306 lives in the United States in 20071 and resulted in the hospitalization of 1.1 million patients2. With an average length of in-patient hospital stay of five days2, pneumonia and influenza comprise significant financial burden costing the United States $40.2 billion in 20053. Under the current Infectious Disease Society of America/American Thoracic Society guidelines, standard-of-care recommendations include the rapid administration of an appropriate antibiotic regiment, fluid replacement, and ventilation (if necessary). Non-standard therapies include the use of corticosteroids and statins; however, these therapies lack conclusive supporting evidence4. (Figure 1)

Osteopathic Manipulative Treatment (OMT) is a cost-effective adjunctive treatment of pneumonia that has been shown to reduce patients&#8217; length of hospital stay, duration of intravenous antibiotics, and incidence of respiratory failure or death when compared to subjects who received conventional care alone5. The use of manual manipulation techniques for pneumonia was first recorded as early as the Spanish influenza pandemic of 1918, when patients treated with standard medical care had an estimated mortality rate of 33%, compared to a 10% mortality rate in patients treated by osteopathic physicians6. When applied to the management of pneumonia, manual manipulation techniques bolster lymphatic flow, respiratory function, and immunological defense by targeting anatomical structures involved in the these systems7,8, 9, 10.

The objective of this review video-article is three-fold: a) summarize the findings of randomized controlled studies on the efficacy of OMT in adult patients with diagnosed pneumonia, b) demonstrate established protocols utilized by osteopathic physicians treating pneumonia, c) elucidate the physiological mechanisms behind manual manipulation of the respiratory and lymphatic systems. Specifically, we will discuss and demonstrate four routine techniques that address autonomics, lymph drainage, and rib cage mobility: 1) Rib Raising, 2) Thoracic Pump, 3) Doming of the Thoracic Diaphragm, and 4) Muscle Energy for Rib 1.5,11

Pneumonia is one of the top ten leading causes of death in the U.S. Osteopathic manipulative techniques (OMT) may be utilized as an adjunctive therapy in the treatment of pneumonia to enhance biomechanical and immune function; and ultimately, to reduce hospital stay, duration of antibiotics, incidence of respiratory failure, and mortality. In this video-article, we will review randomized controlled studies on the use of OMT in pneumonia patients, as well as demonstrate specific hands-on techniques that are routinely practiced by osteopathic physicians when treating pulmonary infections.

整骨手法治疗为肺炎是非常好的辅助工具

Pneumonia, the inflammatory state of lung tissue primarily due to microbial infection, claimed 52,306 lives in the United States in 20071 and resulted in ...

Isolated Hepatic Perfusion as a Treatment for Liver Metastases of Uveal Melanoma

Isolated hepatic perfusion (IHP) is a procedure where the liver is surgically isolated and perfused with a high concentration of the chemotherapeutic agent melphalan. Briefly, the procedure starts with the setup of a percutaneous veno-venous bypass from the femoral vein to the external jugular vein. Via a laparotomy, catheters are then inserted into the proper hepatic artery and the caval vein. The portal vein and the caval vein, both supra- and infrahepatically, are then clamped. The arterial and venous catheters are connected to a heart lung machine and the liver is perfused with melphalan (1 mg/kg body weight) for 60 min. This way it is possible to locally perfuse the liver with a high dose of a chemotherapeutic agent, without leakage to the systemic circulation.
In previous studies including patients with isolated liver metastases of uveal melanoma, an overall response rate of 33-100% and a median survival between 9 and 13 months, have been reported. The aim of this protocol is to give a clear description of how to perform the procedure and to discuss IHP as a treatment option for liver metastases of uveal melanoma.

Here, we present a protocol how to perform an isolated liver perfusion (IHP) with melphalan and we also discuss IHP as a treatment option for liver metastases of uveal melanoma.

隔离肝脏灌注作为治疗葡萄膜黑色素瘤肝转移

Isolated hepatic perfusion (IHP) is a procedure where the liver is surgically isolated and perfused with a high concentration of the chemotherapeutic ...

Evaluation of the Efficacy of the H. pylori Protein HP-NAP as a Therapeutic Tool for Treatment of Bladder Cancer in an Orthotopic Murine Model

Bladder cancer is one of the most common malignancies of the urogenital tract. Intravesical injection of Bacillus Calmette-Gu&#233;rin (BCG) is the gold standard treatment for the high-grade non-muscle invasive bladder cancer (NMIBC). However, since the treatment-related side effects are relevant, newer biological response modifiers with a better benefit/side effects ratio are needed.
The tumour microenvironment can influence both tumour development and therapy efficacy. In order to obtain a good model, it is desirable to implant tumour cells in the organ from which the cancer originates.
In this protocol, we describe a method for establishing a tumour in the bladder cavity of female mice and subsequent delivery of therapeutic agents; the latter are exemplified by our use of Helicobacter pylori neutrophil activating protein (HP-NAP). A preliminary chemical burn of the mucosa, followed by the injection of mouse urothelial carcinoma cell line MB49 via urethral catheterization, enables the cells to attach to the bladder mucosa. After a period, required to allow an initial proliferation of the cells, mice are treated with HP-NAP, administrated again via catheterization. The anti-tumour activity of HP-NAP is evaluated comparing the tumour volume, the extent of necrosis and the degree of vascularization between vehicle- and HP-NAP-treated animals.

Evaluation of the Efficacy of the H. pylori Protein HP-NAP as a Therapeutic Tool for Treatment of Bladder Cancer in an Orthotopic Murine Model

Here the method to establish a syngeneic mouse model of orthotopic bladder tumour to evaluate the anti-tumour efficacy of the bacterial protein HP-NAP is described.

评价疗效<em&gt;小时。幽门螺杆菌</em&gt;蛋白HP-NAP为膀胱癌的治疗在原位小鼠模型的治疗工具

Bladder cancer is one of the most common malignancies of the urogenital tract. Intravesical injection of Bacillus Calmette-Gu&#233;rin (BCG) is the gold ...

Percutaneous Hepatic Perfusion (PHP) with Melphalan as a Treatment for Unresectable Metastases Confined to the Liver

Unresectable liver metastases of colorectal cancer can be treated with systemic chemotherapy, aiming to limit the disease, extend survival or turn unresectable metastases into resectable ones. Some patients however, suffer from side effects or progression under systemic treatment. For patients with metastasized uveal melanoma there are no standard systemic therapy options. For patients without extrahepatic disease, isolated liver perfusion (IHP) may enable local disease control with limited systemic side effects. Previously, this was performed during open surgery with satisfying results, but morbidity and mortality related to the open procedure, prohibited a widespread application. Therefore, percutaneous hepatic perfusion (PHP) with simultaneous chemofiltration was developed. Besides decreasing morbidity and mortality, this procedure can be repeated, hopefully leading to a higher response rate and improved survival (by local control of disease). During PHP, catheters are placed in the proper hepatic artery, to infuse the chemotherapeutic agent, and in the inferior caval vein to aspirate the chemosaturated blood returning through the hepatic veins. The caval vein catheter is a double balloon catheter that prohibits leakage into the systemic circulation. The blood returning from the hepatic veins is aspirated through the catheter fenestrations and then perfused through an extra-corporeal filtration system. After filtration, the blood is returned to the patient by a third catheter in the right internal jugular vein. During PHP a high dose of melphalan is infused into the liver, which is toxic and would lead to life threatening complications when administered systemically. Because of the significant hemodynamic instability resulting from the combination of caval vein occlusion and chemofiltration, hemodynamic monitoring and hemodynamic support is of paramount importance during this complex procedure.

Percutaneous Hepatic Perfusion PHP with Melphalan as a Treatment for Unresectable Metastases Confined to the Liver

In this manuscript, we describe percutaneous isolated hepatic perfusion with simultaneous chemofiltration as treatment for unresectable liver metastases. This procedure is performed under general anaesthesia in the angiosuite by an experienced team, consisting of an interventional radiologist, a clinical perfusionist and anaesthesiologist.

经皮肝脏灌注（PHP）与美法仑作为囿于肝脏不能手术切除转移的治疗

Unresectable liver metastases of colorectal cancer can be treated with systemic chemotherapy, aiming to limit the disease, extend survival or turn ...

Network Analysis of Foramen Ovale Electrode Recordings in Drug-resistant Temporal Lobe Epilepsy Patients

Approximately 30% of epilepsy patients are refractory to antiepileptic drugs. In these cases, surgery is the only alternative to eliminate/control seizures. However, a significant minority of patients continues to exhibit post-operative seizures, even in those cases in which the suspected source of seizures has been correctly localized and resected. The protocol presented here combines a clinical procedure routinely employed during the pre-operative evaluation of temporal lobe epilepsy (TLE) patients with a novel technique for network analysis. The method allows for the evaluation of the temporal evolution of mesial network parameters. The bilateral insertion of foramen ovale electrodes (FOE) into the ambient cistern simultaneously records electrocortical activity at several mesial areas in the temporal lobe. Furthermore, network methodology applied to the recorded time series tracks the temporal evolution of the mesial networks both interictally and during the seizures. In this way, the presented protocol offers a unique way to visualize and quantify measures that considers the relationships between several mesial areas instead of a single area.

This protocol describes a procedure to track the evolution of mesial network measures in temporal lobe epilepsy (TLE) patients. It is based on the combination of intracranial recordings with a novel numerical technique for data analysis. Specifically, we present a protocol for network analyses of foramen ovale recordings.

在耐药性颞叶癫痫患者卵圆孔电极记录的网络分析

Approximately 30% of epilepsy patients are refractory to antiepileptic drugs. In these cases, surgery is the only alternative to eliminate/control ...

MRI-guided Focused Ultrasound Thalamotomy for Patients with Medically-refractory Essential Tremor

Essential tremor (ET) is the most common type of tremor in adults. While ET does not result in decreased life expectancy, the disabilities associated with ET can have a significant impact on quality of life, mood, functional activities, and socialization. Patients suffering from ET not sufficiently treated with first line medications may be eligible for alternative strategies such as deep brain stimulation, radiofrequency ablation, and MRI guided focused ultrasound (MRgFUS). High-intensity MRgFUS is an emerging modality to treat ET, its attraction for patients being that it is noninvasive and associated with short recovery time, as patients are home the day after treatment. While MRgFUS centers are still limited, it will become important for clinicians to consider MRgFUS as a treatment alternative, particularly in the case of a patient for whom open surgery is contraindicated. This article outlines the steps of patient selection, equipment setup, sonication, and post-treatment follow-up, as well as critical steps to be aware of when performing a MRgFUS procedure.

High-intensity MRI guided focused ultrasound is an emerging noninvasive technique to precisely ablate brain tissue. It has been shown to be safe and effective in treating medically-refractory essential tremor. This article describes the protocol for thalamotomy from patient selection to equipment setup to post-treatment follow-up.

MRI 引导下聚焦超声丘脑治疗难治性原发性震颤

Essential tremor (ET) is the most common type of tremor in adults. While ET does not result in decreased life expectancy, the disabilities associated with ...

Vagus Nerve Stimulation As an Adjunctive Neurostimulation Tool in Treatment-resistant Depression

Vagus nerve stimulation (VNS) is an approved neurostimulation therapy. The purpose of the method is to treat patients with therapy-resistant depression (TRD). VNS exhibits antidepressive and stabilizing effects. This method is particularly useful as a long-term treatment, in which up to two-thirds of patients respond. The vagus nerve stimulator is positioned on the left vagus nerve during a surgical procedure and is activated telemetrically by a wand connected to a handheld computerized device. The treating physician can perform various adjustments of the vagus nerve stimulator during in-office visits (e.g., by modifying stimulation intensity or stimulation frequency) to achieve maximum therapeutic effects with low side effects. Set-up of the device usually takes several months. Typical side effects include wound infection, temporary salivation, coughing, paralysis of the vocal cords, bradycardia, or even asystole. The patient can stop the VNS by placing a magnet over the generator. The current protocol describes delivery of the specific stimulation tool and methods for adjusting the tuning parameters to achieve the best remission rates in patients with TRD.

Vagus nerve stimulation (VNS) has been shown to be effective as an adjunct treatment for treatment-resistant depression (TRD). VNS leads to antidepressive and antisuicidal effects and quality of life improvements. This protocol offers a step-by-step guide to managing and adjusting a vagus nerve stimulator for efficient treatment of TRD.

迷走神经刺激作为抗抑郁抑郁症的辅助神经刺激工具

Vagus nerve stimulation (VNS) is an approved neurostimulation therapy. The purpose of the method is to treat patients with therapy-resistant depression ...

Involving Individuals with Developmental Language Disorder and Their Parents/Carers in Research Priority Setting

A protocol for involving individuals presenting with developmental language disorder (DLD) (iDLD) and their parents/carers (iDLDPC) in a research priority setting exercise is presented.
iDLD have difficulties with communication skills, such as understanding language, word-finding and discourse. Such difficulties mean existing research priority setting protocols are difficult for iDLD to access, since they require sophisticated communication skills. Thus, a novel protocol for involving iDLD in these exercises is warranted. The same protocol is recommended for use with iDLDPC, to ensure accessibility.
The protocol is presented in 4 steps. Step 1 describes a program of activities delivered by trained, specialist DLD speech and language therapists (SLTs) that prepares iDLD/iDLDPC for involvement. Step 2 outlines an approach to elicit iDLD/iDLDPC&#8217;s opinions on research priorities. Steps 3 and 4 describe methods to analyze and integrate this data at multiple stages of the research priority setting process.
9 trained specialist DLD SLTs delivered steps 1 and 2. 17 iDLDs and 25 iDLDPCs consented to involvement. Opinions from all participants were elicited, and this data was used to influence the process and output of the exercise.
An advantage of this protocol is its accommodation of the heterogeneity in support needs of iDLD/iDLDPC, through a menu of options, whilst also providing a structured framework. Due to the novelty of the protocol, the methods for data integration were developed by the research group. These are potential limitations of the protocol, and may bring the reliability and validity under scrutiny, which are yet to be tested.
This protocol enables meaningful involvement of iDLD/iDLDPC in&#160;research priority setting and could be utilized for people with other kinds of speech, language or communication needs. Further research should evaluate the effectiveness of the protocol and whether it can be adapted for involvement of such populations in other research studies.

A protocol to enable individuals with developmental language disorder (DLD) and their parents/carers to meaningfully participate in a research priority setting exercise is established. The protocol includes a defined program of activities for data collection, and methods to incorporate this data into the broader research priority setting process.

让发育性语言障碍患者及其父母/照顾者参与研究重点设定

A protocol for involving individuals presenting with developmental language disorder (DLD) (iDLD) and their parents/carers (iDLDPC) in a research priority ...

The Miniature Pig: A Large Animal Model for Cochlear Implant Research

Cochlear implants (CI) are the most effective method to treat people with severe-to-profound sensorineural hearing loss. Although CIs are used worldwide, no standard model exists for investigating the electrophysiology and histopathology in patients or animal models with a CI or for evaluating new models of electrode arrays. A large animal model with cochlea characteristics similar to those of humans may provide a research and evaluation platform for advanced and modified arrays before their use in humans. 
To this end, we established standard CI methods with Bama mini-pigs, whose inner ear anatomy is highly similar to that of humans. Arrays designed for human use were implanted into the mini pig cochlea through a round window membrane, and a surgical approach followed that was similar to that used for human CI recipients. Array insertion was followed by evoked compound action potential (ECAP) measurements to evaluate the function of the auditory nerve. This study describes the preparation of the animal, surgical steps, array insertion, and intraoperative electrophysiological measurements. 
The results indicated that the same CI used for humans could be easily implanted in mini-pigs via a standardized surgical approach and yielded similar electrophysiological outcomes as measured in human CI recipients. Mini-pigs could be a valuable animal model to provide initial evidence of the safety and potential performance of novel electrode arrays and surgical approaches before applying them to human beings.

Miniature pigs (mini-pigs) are an ideal large animal model for research into cochlear implants. Cochlear implantation surgery in mini-pigs can be utilized to provide initial evidence of the safety and potential performance of novel electrode arrays and surgical approaches in a living system similar to human beings.

微型猪：人工耳蜗研究的大型动物模型

Cochlear implants (CI) are the most effective method to treat people with severe-to-profound sensorineural hearing loss. Although CIs are used worldwide, ...