This work is supported by the Research Grants Program of the Epilepsy Foundation &amp; American Epilepsy Society and the Faculty Career Development Fellowship of Harvard Medical School, Office for Faculty Development.

作者什么都没有透露。

从动物和人类研究会聚证据表明，氢氟烯烃是癫痫组织一个新的潜在生物标志物。尽管有这方面的证据，氢氟烯烃具有诊断或癫痫的监测，在临床实践中使用非常有限，主要是因为:（i）在对氢氟烯烃没有正式的和全球性的定义; （ⅱ）不同的研究小组使用用于记录和分析数据不同方法; （三）氟烯烃的无创检测与神经成​​像技术是具有挑战性的;及（iv）氟烯烃的审查过程是费时和不切实际的，尤其是对多通道EEG或MEG记录了大量的传感器。在努力提供全球标准化的方法，促进在临床实践中系统地使用氢氟烯烃，即随后在波士顿儿童医院的无创记录，检测的方法，并从小儿癫痫患者发作氢氟烯烃的定位提出。代表Source从两个孩子难治性癫痫与头皮同时EEG和MEG检测氢氟烯烃电子结果也呈现。 该协议中的关键步骤拟议的方法包括以下关键步骤:（i）高信号噪声比（SNR）从儿科病人发作间活动的EEG和MEG同步录音的性能与难治性癫痫（步骤2.1.1和2.1.2 ）; （ii）与发作放电数据（步骤3.1和3.2）的精心预处理和选择; （三）以高特异性识别的氢氟烯烃的事件的视觉审查（步骤4.3.1，4.3.2和4.3.3）;和（iv）用合适的定位方法（步骤5.2）的氢氟烯烃的可靠定位。 在这个协议中最关键的步骤是通过自动检测器确定的HFO事件的视觉审查。自动检测到的氢氟烯烃的严格审查为Crucial丢弃非脑起源氢氟烯烃。然而，疲劳或人评的分心多信道脑电图和MEG数据的视觉检查过程中可能导致错误，减少在检测过程中的特异性。 修改和故障排除我们避免为了使用该信号空间投影（SSP）和信号空间分离（SSS）的方法72,73，以确保没有从他们的应用的HFO活性失真。这些方法通常使用的大多数的特定的MEG供应商的用户的抑制外部干扰和来校正头部运动72。进一步的研究中，以确保这些方法的应用不会影响或扭曲的HFO活性或不产生可能类似于人类氢氟烯烃的寄生效应是必要的。信号包络（步骤4.1.1.3）的Z值的最低门槛的小的修改和交流的门槛可能需要释放等的值（步骤5.2.6），以提高在检测氢氟烯烃的算法的灵敏度和限制在一个更焦点区域中的氢氟烯烃区域的定位。 该技术的局限性所描述的方法提出了应在今后的研究中进一步解决的限制。首先，它不会只考虑在MEG和EEG信号中发生的氢氟烯烃，它不包括氢氟烯烃在MEG信号的自动检测，这意味着一些实际的低信噪比MEG氢氟烯烃可能逃脱目测74。此外，所提出的方法来检测氢氟烯烃和它的高精度本地化能力，他们的敏感性和特异性应与头皮脑电图，脑磁图和iEEG 75的同时进行的录像进行验证。我们的数据表明，单一的ECD表示延长刺激性区域相比，焦氢氟烯烃区。然而，当的ECD的平均值，那么偶极location为相当接近两个病人HFO区。我们的数据指示的2种方法示出了用于致痫（特别是对于患者2为谁HFO区是与SOZ重叠）相比，刺激性区HFO区的可能的更高的特异性的特异性的，虽然安全结论不能被绘制从病人这么小的队列。更重要的是，由HFO源的定位不直接意味着本地化的EZ是负责癫痫发作。我们的调查结果应与癫痫手术，我们计划在今后的研究中做的结果进行验证。最后，以记录脑电图数据，使用一个70信道系统。然而，在大多数的中心的标准临床脑电图设置用于根据本10，从19电极记录数据置于 - 20系统。高得多的信道数目（多达256个）的更先进的儿科脑电图系统目前在市场上买到。使用这些系统可以进一步提高吨头皮脑电图检测到的氢氟烯烃区，他的定位精度。 相对于现有的/替代方法的技术意义据我们所知，这是报告发作的氢氟烯烃具有同时EEG和MEG的非侵入性的定位，同时也考察了国产化结果与颅内记录的一致性的第一项研究。无创记录，检测和氢氟烯烃的定位是具有挑战性的。这是因为，氢氟烯烃是由小的大脑区域立方毫米16,76和还通过噪声和脑后台活动受阻的顺序上产生非常弱的信号。最近的一项研究提出，氢氟烯烃记录的非侵入头皮脑电图代表多个空间分布的焦点和连贯来源60活动的总和。迄今为止，很少有研究28,29,37,38,60设法表明氢氟烯烃可以非侵入方式使用SCA来检测LP EEG和MEG;甚至更少通过求解逆问题37-38本地化这一活动。 这里，发作间氢氟烯烃的证据都被已同时头皮脑电图和MEG从两个小儿患者癫痫检测。氢氟烯烃通过使用先前描述框架38本地化。代表的数据表明，发作氢氟烯烃的非侵入性的定位是通过使用在任头皮脑电图或MEG录音进行源的成像技术，假定适当的定位技术使用是可行的。这与先前的研究所使用的假想结构类似于氢氟烯烃的发电机，这表明氢氟烯烃可以无创检测并与MEG 32准确局部线。 检测和发作氢氟烯烃的标签是传统上通过从人脑的专家数据的视觉检查进行。虽然这种方法是经常伦瑞格DED作为金标准，它提出了严格的限制，因为它有差，评论家间的可靠性77,78，并不适用于大MEG和脑电图数据集有大量的传感器。至关重要在临床实践中氢氟烯烃的应用是从头皮录音减少人工输入的需要自动检测氢氟烯烃算法的开发。头皮氢氟烯烃的视觉识别，其实是相当具有挑战性，因为:（一）关于头皮的氢氟烯烃低信噪比; （二）在头皮记录相比，氢氟烯烃颅内的人，这意味着更长的记录时间分析的低利率; （三）高通道数来分析，特别是在高密度EEG或MEG。对于氢氟烯烃的自动和半自动检测几种算法已在过去十年54被提出。依靠在时域的阈值，以便查明事件早些时候探测器可以从正在进行的背景活动4区分开来9,80。最近的进展建议也掺入从频域信息，假设一个HFO必须显示为与在一个不同的频率50,56,81的分离的光谱峰的短命事件。半自动化的方法似乎是氢氟烯烃的在临床实践中应用最合适的方法。由专家，它具有高特异性（ⅰ）一种具有高灵敏度的事件的初始自动检测，和（ii）的事件的视觉审查:这些方法包括两个阶段。这种方法提供了相对于全自动化的方法更高的特异性，并确保最终审查事件是脑来源的实际氢氟烯烃。 这里，提出了一种半自动化方法，可实现从发作头皮脑电图和MEG录音氢氟烯烃的检测。该方法扩展了在认定标准结合两个导入前面所述的检测从头皮脑电图60氢氟烯烃技术蚂蚁的功能:（i）所述的HFO事件的自动时间 - 频率数据;及（ii）在这两个MEG和脑电图记录事件的氢氟烯烃的时间同意。 掌握这一技术后，未来的应用或指示氢氟烯烃与非侵入性神经成像方法，如头皮脑电图和MEG的可靠的定位，是至关重要的。掌握，改进和验证该协议将会为医生提供了EZ鉴定的可靠，无创记录的生物标志物。这样的生物标志物的发展有可能减少用于长期监测和侵入颅内录音导致在儿科患者的术前评估过程中的显著改善的要求的潜力。它不仅将有助于确定手术的癫痫组织，也将允许癫痫的最终鉴别诊断患有急性症状发作，需要一个完全迪菲租的治疗方法，并从非癫痫性发作不遗余力在一些患者长期监测的需要。此外，这可能使治疗性干预的功效的评估，而无需等待发生另一发作。

小儿癫痫是一种常见的神经系统疾病与4的患病率-每6 1000名儿童1。它可能对儿童的发展2产生重大影响，并可能影响显著他们长大成人。在儿童期发病的癫痫长期随访研究表明，癫痫患者约30％，成为难治3-6，而且通常需要resective癫痫手术治疗。在许多这些患者中，癫痫手术导致发作频率显著降低和常常发作自由。要取得成功，癫痫手术要达到以最小的或无功能障碍发作，自由状态。这要求痫区（EZ）7，&#39;皮质区域，是对于癫痫发作的产生不可缺少&#39;8的仔细描述。在EZ不能直接测量;它的位置是基于测试塔的大量数据一致估计ŧ确定其他皮层区域。侵入颅内脑电图（iEEG）作为金标准为发作起始区（SOZ），其中癫痫发作产生和发出的发作记录区域的定位。然而iEEG是昂贵，依赖于儿童的合作，进行感染和出血9一定的风险，并且在植入10期间可能诱发额外的神经损伤。此外，该记录可能导致错误的结论，因为大脑的大区域被留下未开发。从而，一个强大的术前生物标记，有助于在EZ的识别是需要外科治疗癫痫的成功。 病理氢氟烯烃（80 - 500赫兹）11,12都出现在过去十年中，作为可以改善患者的术前诊断及手术结果癫痫13致痫组织的鉴定的生物标志物。采用微型报告电极与深度电极脑电图表现相结合的氢氟烯烃癫痫患者的存在。氢氟烯烃是在发作期和发作间期期间使用标准macroelectrodes也有发现。最近的研究已经表明，氢氟烯烃鉴定具有更高的灵敏度和特异性的SOZ相比刺激性区14,15，生成该智能电子设备的区域，即手术切除的HFO-产生组织的以比除去的更好的结果相关联SOZ或刺激性区15。氢氟烯烃通常归类为波纹（80 - 250 Hz）或快速波纹（250 - 500赫兹）。快速涟漪已经更加紧密地联系在一起病理活动并向SOZ 16的定位，但是人脑的录音调查表明，这两个涟漪和快速涟漪致痫区17增加。 尽管这些有希望的结果，氢氟烯烃尚未适合的诊断或监测癫痫在临床实践中。主要障碍依然存在:（一）缺乏对氢氟烯烃正式的和全球性的定义; （ii）该方法的结果异质性办法用于他们的学习;和（iii）的实际困难，以检测并从头皮录音无创本地化它们。后者来源于这样的事实即电极是远离信号源，该信号可能是由背景噪音和肌肉活动模糊，并且信号可以由头皮或在颅骨的囟门和缝线被扭曲，特别是在婴幼儿患者。此外，它是困难的正常和异常氢氟烯烃18,19之间进行区分，因为这两个波纹和快速波动是即使在正常人类脑组织20本。早期的研究报告，头皮脑电图氢氟烯烃在只有一小-癫痫患者21-23（0.2 3.4％）部分。然而，最近的研究表明，氢氟烯烃可以非侵入与头皮脑电图来检测。 Ictally，HFO小号已经报道了在韦斯特综合症的儿童发作（50 - 100赫兹24，40 - 120赫兹25），以及在伦诺克斯-Gastaut综合征强直性发作的发病（50 - 100赫兹）26。发作间期氢氟烯烃（70 - 200赫兹）上的头皮脑电图首先观察孩子睡眠引起的电气性癫痫持续状态27。然后，发作间氢氟烯烃（80 - 200赫兹）中的患者与SOZ 28内更高的速率局灶性癫痫头皮脑电图进行鉴定。有趣的是，氢氟烯烃的患者高数量发作癫痫样放电（IED）的的更频繁，而且它们被认为是比的IED为SOZ 29更具体地，突出氢氟烯烃与致痫的关系。 MEG似乎相比头皮脑电图为氢氟烯烃的非侵入性检测和定位呈现显著优点:（ⅰ）在MEG高频活性比脑电图更不易从肌肉污染活动30-31，（ⅱ）MEG信号不会通过头骨传导和由颅骨的未熔融区域，如囟或缝合比脑电图较少失真，和（iii）的MEG传感器阵列具有较高的密度相比脑电图总是面临歪曲盐的问题，电极之间的桥梁时，头小，有孩子。从该模拟氢氟烯烃发电机幻象结构证据表明，氢氟烯烃可以被检测且高定位精度的局部（2 - 3毫米），用MEG 32。最近的几项研究报道在纹波频率波段33-38患者记录癫痫MEG信号氢氟烯烃。时间-频率分析表明的MEG数据包含有关在EZ 33-36高频分量。然而，只有少数的研究已经确定发作氢氟烯烃为可见事件在时域中站在出背景信号，因为通常与iEEG 37-38进行。凡克林克等。 37检测使用基于从智能电子装置获得空间信息波束形成技术构建的虚拟通道中的波纹带氢氟烯烃。冯Ellenrieder 等 。 38检测MEG信号氢氟烯烃从物理传感器独立的简易爆炸装置和使用的最大熵的平均值（MEM）方法来定位其来源，并探讨其与EZ关系。 Rampp 等 。 （2010）也发现癫痫高伽玛振荡与MEG，这是独立的穗穗锁定或和本地化本次活动最小范源分析39。他们发现，这些快速振荡的特性（ 例如 ，全频段平均振荡的最大振幅的明确，发病时间）是高度与SOZ有关。氢氟烯烃还用MEG在儿科患者发作活动癫痫痉挛40中检测到。然而，MEG提出了一些明显的局限性相比，头皮脑电图检查:（i）其是樱雪nsitive到具有相对于所述头部的中心的径向方向源，（ⅱ）它不允许长时间的录制能够提高检测和记录发作事件的可能性，以及（iii）其传感器不能符合头部形状每一个人，因为在头盔内的头盔和传感器阵列都是固定的形状。因此，最大化的可能性，以检测和定位的致癫痫活性提供了理想的设置是由来自头皮脑电图和MEG组合信息。 在这项研究中，我们的目标是通过头皮EEG和MEG的同时录音儿科治疗难治性癫痫来说明我们遵循发作氢氟烯烃的无创性检测的方法。我们目前的记录的设置和数据分析的使用，我们已经用于检测同步的MEG和脑电图数据HFO事件开发的半自动化方法的管道。最后，我们还存在的本地化底层头皮氢氟烯烃，通过求解逆问题得到的发电机，并且因为这是由癫痫病定义它与SOZ比较。

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			<td height="21" style="height:21px;width:216px;">VectorView MEG system</td>
			<td style="width:287px;">Elekta-Neuromag, Finland</td>
			<td style="width:119px;"></td>
			<td style="width:407px;">MEG System</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Magentically Shielded Room</td>
			<td style="width:287px;">Imedco, Hagendorf, Switzerland</td>
			<td style="width:119px;"></td>
			<td style="width:407px;">Three-layer MSR</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">EEG system</td>
			<td style="width:287px;">Elekta-Neuromag, Finland</td>
			<td style="width:119px;"></td>
			<td>70 Channel EEG system</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">3D digitizer</td>
			<td style="width:287px;">Polhemus, Colchester, VT</td>
			<td style="width:119px;"></td>
			<td></td>
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interictal high frequency oscillations detected with simultaneous magnetoencephalography and electroencephalography as biomarker of pediatric epilepsy

关键癫痫手术的成功是标识致痫灶（EZ）强大的生物标志物的可用性。高频振动（氢氟烯烃）已经成为了除了间痫样放电（IED）的发作期和活动标识EZ的潜在生物标志物术前。尽管它们是有希望的本地化的EZ，它们尚未适合在临床实践中诊断或癫痫的监视。主要的障碍仍然存在:缺乏对氢氟烯烃正式的和全球性的定义;的用于他们的学习方式方法随之而来的异质性;和实际困难来检测和从头皮录音无创本地化它们。在这里，我们提出了一个方法，用于记录，检测和儿科难治性癫痫患者发作氢氟烯烃的定位。我们报告氢氟烯烃的代表性数据从头皮发作间期脑电图和MEG从两个孩子无创检测接受手术。 氢氟烯烃的底层发电机通过求解逆问题的局部及其定位进行比较的发作起始区（SOZ），因为这是由癫痫病限定。对于这两个病人，发作间期痫放电（简易爆炸装置），并进行了氢氟烯烃与和谐的位置的来源成像本地化。对于一个病人，颅内脑电图（iEEG）的数据也可用。对于这个病人，我们发现，氢氟烯烃定位是无创性和侵入性的方法之间的和谐。 iEEG与头皮记录结果的比较有助于验证这些结果。据我们所知，这是从呈现脑电图同步和MEG记录比较有创记录的结果头皮氢氟烯烃的源定位的首次研究。这些结果表明，氢氟烯烃可以可靠地检测与头皮脑电图和MEG无创本地化。我们的结论是interic的无创本土化TAL氢氟烯烃可以显著改善小儿癫痫患者的术前评估。

小儿难治性癫痫患者是从波士顿儿童医院的癫痫诊所（美国波士顿）招募。在这里，从2例具有代表性的数据呈现:一个15岁的女孩，右侧大脑中动脉（MCA）区（患者1）的脑软化，和一个11岁的男孩，左顶叶/颞脑软化（病人2）。数据收集作为其术前手术后处理的一部分。同时MEG和脑电图记录均在Athinoula A.马蒂诺中心的生物医学成像执行。 （ - 150赫兹80）在这两个EEG和MEG和上覆简易爆炸装置发生对于两名患者，氢氟烯烃在纹波频率波段进行鉴定。 图4表示来自患者1 10秒的发作活动同时头皮脑电图和MEG数据（ 上图 ）的相同图中还报道了n扩展时间的信号，其示出在时域中（ 中间板 ）所检测的氢氟烯烃的比例部分（2秒），并在时间-频率平面（ 下图 ）。该患者表现出8.8氢氟烯烃/分钟的速率。因为观察到高于150赫兹的频率没有显着的活性150赫兹 - 为清晰起见，时间 - 频率平面的显示被从80限制。在患者1，自动检测识别记录的8.65分钟内248氢氟烯烃的事件。检测到的事件的视觉经过审查，76事件被留了被认为是真正的氢氟烯烃，获得8.8氢氟烯烃/ min的速率。 <img alt="图4" src="/files/ftp_upload/54883/54883fig4.jpg" /> 图4:覆盖在头皮脑电图和MEG检测IED的氢氟烯烃。 上图 :来自患者1的IED从头皮脑电图（左）和MEG（右）进行检测。数据的10秒1过滤 - 70赫兹。 中间面板 :脑电图和MEG数据的扩展时间标度显示（2秒）强调了与在上部面板灰色背景。 150赫兹 - 数据从80过滤。 下面板 :2代表脑电图和MEG频道时频平面。 <a href="http://ecsource.jove.com/files/ftp_upload/54883/54883fig4large.jpg" target="_blank">请点击此处查看该图的放大版本。</a> 图5给出了从头皮脑电图和MEG病人都在1本地化氢氟烯烃结果。这两种技术的局部的氟烯烃在靠近右颞顶骨结的位置病变的附近。的MEG和脑电图呈现略微不同的定位结果:MEG活性位于更前方相比EEG和靠近病变的后部边界。的两个最大值的MEG和脑电图wMEM活性之间的距离为15.0毫米。氢氟烯烃localizati上也是相邻的刺激区域，因为这是由MEG定义。平均的ECD和最大wMEM活动之间的欧氏距离为18.7毫米的MEG 28.0毫米头皮脑电图。对于患者2，我们确定与IED并且我们用于HFO分析最小工件慢波非REM睡眠中的数据的8分钟。 头皮氢氟烯烃的数量比在患者1表示0.4氢氟烯烃/分的速度显著低。 图6给出头皮氢氟烯烃为MEG和头皮脑电图，使用的ECD由MEG本地化的IED的源定位的结果，并且通过iEEG检测氢氟烯烃的位置。 2最大值为MEG和脑电图wMEM活性之间的距离为16.4毫米。平均的ECD和最大wMEM活性之间的距离为10.9毫米的MEG及24.1毫米的脑电图。头皮脑电图和MEG非侵入性确定的HFO区是在同一位置的氢氟烯烃是IDE与iEEG侵入ntified。与氢氟烯烃的最高编号的电极为LA51，LA52和LA53， 如图6中 ，其定位为一致与非侵入性地本地化的HFO活性。 <img alt="图5" src="/files/ftp_upload/54883/54883fig5.jpg" /> 图5:氢氟烯烃和简易爆炸装置的定位。氢氟烯烃区通过使用MEG和脑电图的wMEM从病人1覆盖在患者的MRI（ 左 ）本地化。的氢氟烯烃地图表示在最大活性的60％阈值化的归一化的激活值的平均值。由简易爆炸装置用的ECD MEG（ 右 ）本地化。所述的ECD的位置和方向在青色表示。紫色三角形表示平均的ECD（46的ECD）的位置，红色矩形从平均的IED（简易爆炸装置28）幼儿发展的位置。对于简易爆炸装置的平均，我们确定具有类似形态的尖峰。 <a href="http://ecsource.jove.com/files/ftp_upload/54883/54883fig5large.jpg" target="_blank">请点击此处查看该图的放大版本。</a> <img alt="图6" src="/files/ftp_upload/54883/54883fig6.jpg" /> 图6:HFO区本地化与非侵入性脑电图头皮和MEG的刺激性区和HFO区局部侵入性iEEG之间的空间一致性。 上图 :在患者的MRI从患者2头皮脑电图（左）和MEG（中），并与MEG简易爆炸装置的国产化氢氟烯烃的本地化（右）覆盖。的氢氟烯烃地图表示在最大活性的60％阈值化的归一化的激活值的平均值。青色圆圈和条表示的ECD的位置和方向。紫色三角形表示平均的ECD的位置（30的ECD），红色矩形Ť从平均的IED（简易爆炸装置21）的ECD他的位置。 较低的面板 :从最高HFO速率信道的iEEG（左）和2秒的录音氢氟烯烃的定位。植入电极显示在患者的MRI检查。电极位置由共同注册后植入计算机断层扫描（CT）和磁共振成像得到的。与氢氟烯烃的最高速率的电极突出植入在患者的皮质网格的地图上。 <a href="http://ecsource.jove.com/files/ftp_upload/54883/54883fig6large.jpg" target="_blank">请点击此处查看该图的放大版本。</a> 这里提出的代表性结果表明，儿童患者的术前评估与医学难治性癫痫在临床中的无创性鉴定和氢氟烯烃的本地化的潜在用途所描述的技术。对于这两个病人，氢氟烯烃均升ocalized一致为头皮脑电图和MEG（ 见图5）。的几个毫米本地化的差异可能归因于比起头皮脑电图70的高密度的MEG的优异定位能力，或者可以代表不同的底层发电机71。本地化也是一致的刺激区域，因为这是由MEG（参见图5 -右图 ）定义。在患者2，从iEEG数据也可用。头皮脑电图和MEG局部无创的氢氟烯烃区是一致的与iEEG侵入定义的氢氟烯烃区域（ 见图6）。该方法的成果能指导癫痫手术的EZ潜在识别期间电网的位置。

Watch this Scientific Journal Video about Interictal High Frequency Oscillations Detected with Simultaneous Magnetoencephalography and Electroencephalography as Biomarker of Pediatric Epilepsy at JoVE

Interictal High Frequency Oscillations Detected with Simultaneous Magnetoencephalography and Electroencephalography as Biomarker of Pediatric Epilepsy

高频振动（氢氟烯烃）已经成为了鉴别致痫灶的小儿患者的医学难治性癫痫术前的生物标志物。一种无创记录，检测，并同时头皮脑电图（EEG）和脑磁图（MEG）氟烯烃的定位方法介绍。

同时用脑磁图和脑电图为小儿癫痫的生物标志物检测发作间期高频振动

Crucial to the success of epilepsy surgery is the availability of a robust biomarker that identifies the Epileptogenic Zone (EZ). High Frequency ...

interictal-high-frequency-oscillations-detected-with-simultaneous

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Linear Time- Invariant Systems

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20.0K 次观看.  Boston Children's Hospital, Harvard Medical School. 高频振动（氢氟烯烃）已经成为了鉴别致痫灶的小儿患者的医学难治性癫痫术前的生物标志物。一种无创记录，检测，并同时头皮脑电图（EEG）和脑磁图（MEG）氟烯烃的定位方法介绍。 

视频: Interictal High Frequency Oscillations Detected with Simultaneous Magnetoencephalography and Electroencephalography as Biomarker of Pediatric Epilepsy

Surgical Management of Meatal Stenosis with Meatoplasty

Meatal stenosis is a common urologic complication after circumcision. Children present to their primary care physicians with complaints of deviated urinary stream, difficult-to-aim, painful urination, and urinary frequency. Clinical exam reveals a pinpoint meatus and if the child is asked to urinate, he will usually have an upward, thin, occasionally forceful urinary stream with incomplete bladder emptying. The mainstay of management is meatoplasty (reconstruction of the distal urethra /meatus). This educational video will demonstrate how this is performed.

Meatoplasty, surgical management of meatal stenosis.

管理与Meatoplasty尿道外口狭窄的外科治疗

Meatal stenosis is a common urologic complication after circumcision.  Children present to their primary care physicians with complaints of deviated ...

科研

医学

Guidelines for Elective Pediatric Fiberoptic Intubation

Fiberoptic intubation in pediatric patients is often required especially in difficult airways of syndromic patients i.e. Pierre Robin Syndrome. Small babies will desaturate very quickly if ventilation is interrupted mainly to high metabolic rate. We describe guidelines to perform a safe fiberoptic intubation while maintaining spontaneous breathing throughout the procedure. Steps requiring the use of propofol pump, fentanyl, glycopyrrolate, red rubber catheter, metal insuflation hook, afrin, lubricant and lidocaine spray are shown.

We describe guidelines to perform a safe and efficient elective fiberoptic intubation in pediatric patients while maintaining spontaneous ventilation.

选修儿科光纤插管指南

Fiberoptic intubation in pediatric patients is often required especially in difficult airways of syndromic patients i.e. Pierre Robin Syndrome. Small ...

High Throughput Sequential ELISA for Validation of Biomarkers of Acute Graft-Versus-Host Disease

Unbiased discovery proteomics strategies have the potential to identify large numbers of novel biomarkers that can improve diagnostic and prognostic testing in a clinical setting and may help guide therapeutic interventions. When large numbers of candidate proteins are identified, it may be difficult to validate candidate biomarkers in a timely and efficient fashion from patient plasma samples that are event-driven, of finite volume and irreplaceable, such as at the onset of acute graft-versus-host disease (GVHD), a potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT).
Here we describe the process of performing commercially available ELISAs for six validated GVHD proteins: IL-2R&alpha;5, TNFR16, HGF7, IL-88, elafin2, and REG3&alpha;3 (also known as PAP1) in a sequential fashion to minimize freeze-thaw cycles, thawed plasma time and plasma usage. For this procedure we perform the ELISAs in sequential order as determined by sample dilution factor as established in our laboratory using manufacturer ELISA kits and protocols with minor adjustments to facilitate optimal sequential ELISA performance. The resulting plasma biomarker concentrations can then be compiled and analyzed for significant findings within a patient cohort. While these biomarkers are currently for research purposes only, their incorporation into clinical care is currently being investigated in clinical trials.
This technique can be applied to perform ELISAs for multiple proteins/cytokines of interest on the same sample(s) provided the samples do not need to be mixed with other reagents. If ELISA kits do not come with pre-coated plates, 96-well half-well plates or 384-well plates can be used to further minimize use of samples/reagents.

High throughput validation of multiple candidate biomarkers can be performed by sequential ELISA in order to minimize freeze/thaw cycles and use of precious plasma samples. Here, we demonstrate how to sequentially perform ELISAs for six different validated plasma biomarkers1-3 of graft-versus-host disease (GVHD)4 on the same plasma sample.

高通量顺序酶联免疫吸附试验的急性移植物抗宿主病的生物标志物的验证

Unbiased discovery proteomics strategies have  the potential to identify large numbers of novel biomarkers that can improve  diagnostic and prognostic ...

Brain Source Imaging in Preclinical Rat Models of Focal Epilepsy using High-Resolution EEG Recordings

Electroencephalogram (EEG) has been traditionally used to determine which brain regions are the most likely candidates for resection in patients with focal epilepsy. This methodology relies on the assumption that seizures originate from the same regions of the brain from which interictal epileptiform discharges (IEDs) emerge. Preclinical models are very useful to find correlates between IED locations and the actual regions underlying seizure initiation in focal epilepsy. Rats have been commonly used in preclinical studies of epilepsy1; hence, there exist a large variety of models for focal epilepsy in this particular species. However, it is challenging to record multichannel EEG and to perform brain source imaging in such a small animal. To overcome this issue, we combine a patented-technology to obtain 32-channel EEG recordings from rodents2 and an MRI probabilistic atlas for brain anatomical structures in Wistar rats to perform brain source imaging. In this video, we introduce the procedures to acquire multichannel EEG from Wistar rats with focal cortical dysplasia, and describe the steps both to define the volume conductor model from the MRI atlas and to uniquely determine the IEDs. Finally, we validate the whole methodology by obtaining brain source images of IEDs and compare them with those obtained at different time frames during the seizure onset.

This video introduces the preparation, recording, and source analysis procedures of high-resolution EEG on sedated rats with a particular preclinical model of focal epilepsy under noninvasive conditions.

采用高分辨率脑电图记录脑源成像局灶性癫痫的临床前模型大鼠

Electroencephalogram (EEG) has been traditionally used to determine which brain regions are the most likely candidates for resection in patients with ...

High-frequency Ultrasound Imaging of Mouse Cervical Lymph Nodes

High-frequency ultrasound (HFUS) is widely employed as a non-invasive method for imaging internal anatomic structures in experimental small animal systems. HFUS has the ability to detect structures as small as 30 &#181;m, a property that has been utilized for visualizing superficial lymph nodes in rodents in brightness (B)-mode. Combining power Doppler with B-mode imaging allows for measuring circulatory blood flow within lymph nodes and other organs. While HFUS has been utilized for lymph node imaging in a number of mouse&#160; model systems, a detailed protocol describing HFUS imaging and characterization of the cervical lymph nodes in mice has not been reported. Here, we show that HFUS can be adapted to detect and characterize cervical lymph nodes in mice. Combined B-mode and power Doppler imaging can be used to detect increases in blood flow in immunologically-enlarged cervical nodes. We also describe the use of B-mode imaging to conduct fine needle biopsies of cervical lymph nodes to retrieve lymph tissue for histological&#160; analysis. Finally, software-aided steps are described to calculate changes in lymph node volume and to visualize changes in lymph node morphology following image reconstruction. The ability to visually monitor changes in cervical lymph node biology over time provides a simple and powerful technique for the non-invasive monitoring of cervical lymph node alterations in preclinical mouse models of oral cavity disease.

This protocol describes the application of high-frequency ultrasound (HFUS) for imaging mouse cervical lymph nodes. This technique optimizes visualization and quantification of cervical lymph node morphology, volume and blood flow. Image-guided biopsy of cervical lymph nodes and processing of lymph tissue for histological evaluation is also demonstrated.

鼠标颈淋巴结高频超声成像

High-frequency ultrasound (HFUS) is widely employed as a non-invasive method for imaging internal anatomic structures in experimental small animal ...

A Multimodal Imaging- and Stimulation-based Method of Evaluating Connectivity-related Brain Excitability in Patients with Epilepsy

Resting-state functional connectivity MRI (rs-fcMRI) is a technique that identifies connectivity between different brain regions based on correlations over time in the blood-oxygenation level dependent signal. rs-fcMRI has been applied extensively to identify abnormalities in brain connectivity in different neurologic and psychiatric diseases. However, the relationship among rs-fcMRI connectivity abnormalities, brain electrophysiology and disease state is unknown, in part because the causal significance of alterations in functional connectivity in disease pathophysiology has not been established. Transcranial Magnetic Stimulation (TMS) is a technique that uses electromagnetic induction to noninvasively produce focal changes in cortical activity. When combined with electroencephalography (EEG), TMS can be used to assess the brain's response to external perturbations. Here we provide a protocol for combining rs-fcMRI, TMS and EEG to assess the physiologic significance of alterations in functional connectivity in patients with neuropsychiatric disease. We provide representative results from a previously published study in which rs-fcMRI was used to identify regions with abnormal connectivity in patients with epilepsy due to a malformation of cortical development, periventricular nodular heterotopia (PNH). Stimulation in patients with epilepsy resulted in abnormal TMS-evoked EEG activity relative to stimulation of the same sites in matched healthy control patients, with an abnormal increase in the late component of the TMS-evoked potential, consistent with cortical hyperexcitability. This abnormality was specific to regions with abnormal resting-state functional connectivity. Electrical source analysis in a subject with previously recorded seizures demonstrated that the origin of the abnormal TMS-evoked activity co-localized with the seizure-onset zone, suggesting the presence of an epileptogenic circuit. These results demonstrate how rs-fcMRI, TMS and EEG can be utilized together to identify and understand the physiological significance of abnormal brain connectivity in human diseases.

Resting-state functional-connectivity MRI has identified abnormalities in patients with a wide range of neuropsychiatric disorders, including epilepsy due to malformations of cortical development. Transcranial Magnetic Stimulation in combination with EEG can demonstrate that patients with epilepsy have cortical hyperexcitability in regions with abnormal connectivity.

评价中的连接有关的大脑兴奋患者癫痫多式联运Imaging-和激励为基础的方法

Resting-state functional connectivity MRI (rs-fcMRI) is a technique that identifies connectivity between different brain regions based on correlations ...

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 ...

Topical Airway Anesthesia for Awake-endoscopic Intubation Using the Spray-as-you-go Technique with High Oxygen Flow

A patient&#39;s willingness to cooperate is an absolute precondition for successful awake intubation of the trachea. Whilst drug-sedation of patients can jeopardize their spontaneous breathing, topical anesthesia of the airway is a popular technique. The spray-as-you-go technique represents one of the simplest opportunities to anesthetize the airway mucosa. The application of local anesthetic through the working channel of the flexible endoscope is a widespread practice for anesthetists as well as pulmonologists. There is neither need for additional devices nor special training as a pre-requisite to perform this technique. However, a known clinical problem is the coughing and gagging reflex that may occur when the liquid anesthetic strikes the airway mucosa and other sensitive structures like the vocal cords. This can be avoided by the use of oxygen applied through the working channel with the aim of fogging the local anesthetic into finer particles. Furthermore, the oxygen flow provides a higher oxygen supply and contributes to a better view, dispersing mucus secretions and blood away from the lens. Using an atomizer with a high oxygen flow of 10 L/min we maximized these benefits, caused less coughing and had more satisfied and therefore cooperative patients. Possible, but very rare complications of using oxygen flow including gastric insufflation, organ rupture or barotrauma did not arise. We attribute the complication-free use of high oxygen flow to the design of the set, which permits flow and pressure release.

The topical anesthetic lidocaine was atomized using a high oxygen flow through the working channel of a flexible intubating endoscope to achieve topical airway anesthesia for awake endotracheal intubation. We prefer this modified spray-as-you-go technique for endoscopic intubation to classical bolus application because of higher patient satisfaction and better compliance.

气道局部麻醉清醒用于内镜插管使用喷雾为你去技术在高氧流量

A patient&#39;s willingness to cooperate is an absolute precondition for successful awake intubation of the trachea. Whilst drug-sedation of patients can ...

Vinyl Chloride and High-Fat Diet as a Model of Environment and Obesity Interaction

Vinyl chloride (VC), an abundant environmental contaminant, causes steatohepatitis at high levels, but is considered safe at lower levels. Although several studies have investigated the role of VC as a direct hepatotoxicant, the concept that VC modifies sensitivity of the liver to other factors, such as nonalcoholic fatty liver disease (NAFLD) caused by high-fat diet (HFD) is novel. This protocol describes an exposure paradigm to evaluate the effects of chronic, low-level exposure to VC. Mice are acclimated to low-fat or high-fat diet one week prior to the beginning of the inhalation exposure and remain on these diets throughout the experiment. Mice are exposed to VC (sub-OSHA level: &#60;1 ppm) or room air in inhalation chambers for 6 hours/day, 5 days/week, for up to 12 weeks. Animals are monitored weekly for body weight gain and food consumption. This model of VC exposure causes no overt liver injury with VC inhalation alone. However, the combination of VC and HFD significantly enhances liver disease. A technical advantage of this co-exposure model is the whole-body exposure, without restraint. Moreover, the conditions more closely resemble a very common human situation of a combined exposure to VC with underlying nonalcoholic fatty liver disease and therefore support the novel hypothesis that VC is an environmental risk factor for the development of liver damage as a complication of obesity (i.e., NAFLD). This work challenges the paradigm that the current exposure limits of VC (occupational and environmental) are safe. The use of this model can shed new light and concern on the risks of VC exposure. This model of toxicant-induced liver injury can be used for other volatile organic compounds and to study other interactions that may impact the liver and other organ systems.

The goal of this protocol was to develop a murine model of low-level toxicant exposure that does not cause overt liver injury but rather exacerbates pre-existing liver damage. This paradigm better recapitulates human exposure and the subtle changes that occur upon exposure to toxicant concentrations that are considered safe.

氯乙烯和高脂肪饮食作为环境与肥胖相互作用的典范

Vinyl chloride (VC), an abundant environmental contaminant, causes steatohepatitis at high levels, but is considered safe at lower levels. Although ...

Assessment of Static Graviceptive Perception in the Roll-Plane using the Subjective Visual Vertical Paradigm

Vestibular disorders are among the most common syndromes in medicine. In recent years, new vestibular diagnostic systems have been introduced that allow the examination of all semicircular canals in the clinical setting. Assessment methods of the otolithic system, which is responsible for the perception of linear acceleration and perception of gravity, are far less in clinical use. There are several experimental approaches for measuring the perception of gravity. The most frequently used method is the determination of the subjective visual vertical. This is usually measured with the head in an upright position. We present here an assessment method for testing otolith function in the roll plane. The subjective visual vertical is measured in the head upright position as well as with head inclination of &#177; 15&#176; and &#177; 30&#176; in the roll plane. This extended functional paradigm is an easy-to-perform clinical test of otolith function and ensures increased information content for the detection of impaired graviceptive perception.

The perception of gravity is commonly determined by the subjective visual vertical in the head upright position. The additional assessment at head tilts of &#177; 15&#176; and &#177; 30&#176; in the roll plane ensures increased information content for the detection of impaired graviceptive perception.

使用主观视觉垂直范式对卷平面中的静态视觉感知的评估

Vestibular disorders are among the most common syndromes in medicine. In recent years, new vestibular diagnostic systems have been introduced that allow ...

同时用脑磁图和脑电图为小儿癫痫的生物标志物检测发作间期高频振动

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