作者感谢所有的家庭为他们的参与在这项研究中，护士，医生，和工作人员的新生儿重症监护病房的特别护理幼儿园，小儿神经的生育单位在马萨诸塞州总医院，布里格姆与妇女医院和波士顿儿童医院他们的帮助和支持。我们特别感谢琳达·J.·Marter，罗伯特M. Insoft，乔纳森·H.克罗宁，朱丽安Mazzawi和史蒂芬A.振铃。作者还感谢，玛西娅 - 菲利普Kocienski，伊冯娜谢尔顿，Alpna Aggarwall，麦迪Artunguada和吉纳维夫殿在测量过程中的协助。该项目的支持，R21 NIH R01-HD042908，HD058725，P41-RR14075和R43 HD071761。玛西娅Kocienski菲利普和Yvonne谢尔登所支持的临床转化科学奖UL1RR025758哈佛大学和布里格姆与妇女医院从美国国家研究资源中心。内容是纯粹的a的责任uthors，并不一定代表美国国家研究资源中心或美国国立卫生研究院的官方意见。

1。准备床头办法的<ol><li>的FDNIRS和DCS系统结构紧凑，便于移动小推车的婴儿在医院的病床边（ 图1）。 </li><li>在移动推车与设备的床边，打开系统和连接的光学探针的FDNIRS和DCS设备。确保两个实验者是每个测量：一个管理的工具和计算机，和一个拿着探头。 </li><li>根据婴儿的胎龄（PMA）选择合适的探头。与FDNIRS源检测器1，1.5，2和2.5厘米的分离的光学探头用于婴儿&lt;37周PMA和探针与FDNIRS分离1.5，2，2.5和3 cm用于较大婴儿（图2-A中）。选择较短的源探测器分离早产儿的小尺寸和更大的头​​部曲率决定。当使用较大的探头，早产儿，1.902，坚果类，深色叶菜更小尺寸的婴儿的头部，其重要曲率妨碍婴儿的头部和所有的源和探测器之间的有效接触。出于这个原因，探头与FDNIRS源检测器1，1.5，2和2.5厘米的分离嵌合用于早产儿。我们的研究已证实，所选择的源检测器分离足以测量光学性能的大脑皮层的早产儿和足月14。 DCS源和检测器的纤维被布置在一排平行的FDNIRS纤维与源检测器的距离为1.5（一个检测器）和2厘米（三个检测器）在早产儿和足月儿探针。 </li><li>消毒消毒擦拭，将探头插入和纤维成单次使用的聚丙烯塑料套筒一个撒尼布的光学探针。 </li></ol> 2。 FDNIRS增益设置和校准<ol><li>打开的FDNIRS的图形用户界面（GUI）和选择程序的设置文件对应于该探测器和校准块被使用。 </li><li>调整探测器的收益，轻轻将探头面积为对象的头部没有头发（最好是左侧的额头），并保持在相同的位置，不施加任何压力。打开源和探测器和PMT电压调整，直到任何的源激光器的振幅达到20,000计数。 32000计数是最大的数字化​​的模拟 - 数字采集卡，及收益低于该阈值需要被设置的数据采集过程中，以避免饱和。的增益应该被设定在与前部面积，因为这个区域通常具有最低的激光光的吸收，因此，最容易出现饱和。 </li><li>关闭光源和检测器，将探头返回到校准块的。需要关闭移动探头时，对人眼安全的激光探测器需要关闭，因为光电倍增管是非常敏感和接触的强光我ncreases背景噪音，并可能会永久损坏。 </li><li>随着调查的深入，重新校准块，如果使用中性密度（ND）滤镜任何来源的探测器对饱和。由于优化收益的婴幼儿可以选择不同的ND过滤器将探头与不同肤色仍然为16秒，而运行校准程序。由于我们没有一个源物理移动到不同的距离，从一个单一的检测方案，实现了多距离，而是用四种组合的两个独立的来源和两个独立的探测器，我们需要两个来源不同功率的校准和的两个检测器的不同的增益。通过测量已知的光学性质的校准块，我们估计需要恢复的吸收和散射系数的校准块的振幅和相位校正因子。 </li><li>校准后，获得16秒的数据块上和视觉上评估是否有足够的日Ë校准内部MATLAB GUI。在所有波长的测量μA和微秒的符合实际的校准块的系数。重新校准如果配合差。 </li><li>如果检测器的增益需要被改变，或源和探测器纤维的需要，在测量过程中被断开，重复的校准程序的FDNIRS设备。 </li><li>的测量会议结束时，获得另一个16秒的数据校准块，以验证，校准是否维持在测量过程中的主体。如果校准并没有被保持，在测量结束的第二校准，并适用于所获取的数据。 </li></ol> 3。 DCS设置<ol><li>打开内部的DCS数据采集图形用户界面和加载相应的光学探头的设置文件。 </li><li>在开始测量之前，请验证的激光功率的DCS来源是适合皮肤接触测量T他用功率计和检查的IR的观看卡（激光发射波长为785 nm，这是不可见的）的光点尺寸与激光功率的DCS源。 DCS的激光功率是〜60毫瓦，而耦合到一个较小的直径的纤维（400-600微米）。为了满足皮肤接触的ANSI标准，必须在探头的光衰减，在一个大面积扩散。这是通过覆盖的纤维与一个3毫米直径的白色特氟隆片（ 图2-A）的前端。的Teflon高散射和广泛扩散的激光束。在床边，确保在探头的激光功率是小于25 mW和点的大小是大于3毫米直径。至于的FDNIRS，始终关闭光源和检测器移动时的光学探针。 </li><li> DCS检测是光子计数，并有需要为FDNIRS设备没有APD增益调整。采集软件中的一个标志，表示如果检测到太多的光，在这种情况下，光耦合到企业所得税她的源或检测器纤维通过转动上述光纤连接器的需要被减小。充足的光线检测的有200,000-4,000,000检测光子（-26〜0分贝的电脑上显示）的范围。室内光线要避免过度降低背景噪音。 </li><li> DCS不需要校准测量CBF 我 。血流量是失去相关所花费的时间成比例。没有足够的固体块，检查信号质量，因为没有运动的散射粒子引起的衰减。实验者的手臂，而不是衰减 - 血液流动的速度就越快，越陡的衰减。 </li></ol> 4。数据采集<ol><li> ，虽然FDNIRS和DCS测量可以很快完成的顺序，先测量一台设备的所有位置，然后重复同样的发展与其它设备，使用独立的采集软件，对应于每个。 </li><li>测量七个地点覆盖额叶，颞叶和pariet人领域，根据10-20系统（FPZ，FP1，FP2，C3，C4，P3，P4），在序列（ 图2-B）。部分的头发沿的源检测线，该区域的头把探头。 </li><li>打开FDNIRS激光器和探测器，并检查信号质量：振幅计数应该是在2000和20000之间，相移SNR &lt;2度。如果在这些范围之外，重新定位探头，确保头发分开和所有源和探测器是在与皮肤接触。 </li><li>采集数据时间为16秒。重复测量三次，在每个位置（ 图2-C），每个采集在一个稍微不同的点分开的头发和重新定位探头。这样做是为了最大限度地减少，如头发和浅表大血管的地方的不均匀性的影响，并提供代表的区域，而不是一个单一的点的值。 </li><li>打开DCS激光和探测器，采集数据，持续10秒。重新定位探头和rep吃的的收购（的FDNIRS措施）。 </li><li>关闭所有的激光器之间移动探头的位置。在所有7个位置的数据收集是不可能的。停止测量的主题体现遇险或运动的任何迹象。如果可能的话，请重试收购。脑电图电极或呼吸设备，在一些地方也排除测量。 </li></ol> 5。测量系统参数<ol><li>对于计算CMRO 2I，两个系统参数，动脉血氧（ 血氧饱和度），血红蛋白（HGB）的血液，必须获得。 HGB，也需要计算CBV值。传统的脉搏血氧仪提供的血氧饱和度的措施，，HGB传统测量血液测试。 Masimo公司开发的，是一个新的脉搏血氧仪，能够测量HGB使用多个波长的非侵入性的。该设备是FDA批准用于婴幼儿&gt; 3千克，并允许床边的快速测量茜的血氧饱和度和HGB。 </li><li>记录血氧饱和度和HGB使用MASIMO脉搏血氧饱和度仪（Pronto的突击检查脉冲合作血氧饱和度）。对于这些测量，粘合剂一次性使用的传感器的宝宝的脚的大脚趾。 HGB将被显示在监视器上，在几秒钟内。 </li><li>当它是无法使用的MASIMO测量脉搏碳氧血氧仪， 血氧饱和度与其他FDA批准的脉搏血氧仪。 HGB可以恢复患者的临床图表或估计使用规范值。 </li></ol> 6。数据分析<ol><li>打开一个内部数据分析后处理GUI使用MATLAB。该软件不仅所有的血流动力学参数估计的冗余数据，同时还采用了自动评估测量的质量和制约的结果。 </li><li>自动目标的质量控制标准包括丢弃数据的FDNIRS如果：R2模型拟合的实验数据，p值&lt;0.98&gt; 00.02 8测得的吸收系数之间的皮尔逊积差相关系数和血红蛋白配合（ 图3-A），p-值&gt; 0.02的线性拟合，可以减少散射系数随波长的变化（ 图3-B），15。如果超过33％的数据值得丢弃，整组将被丢弃。对于DCS，数据将被丢弃，如果：超过0.02的拟合曲线的尾部不同于1，3第一点的曲线之间的累积变化是大于0.1，或3第一点的平均值，更比1.6（ 图4）。如果超过50％的曲线被丢弃，或拟合值有一个系数的变化&gt; 15％，整个组被丢弃15。 </li><li>计算绝对HBO和HBr浓度的拟合系数在所有波长的吸收，利用文学血红蛋白值，消光系数16组织17中水的浓度为75％。获得总血红蛋白浓度（HBT = HBO + HBR）和HBO和HBR浓度SO 2（HBO / HBT）。 </li><li>估计脑血流量使用Ijichi 等[18]描述的等式。 CBV值=（HBT×分子量血红蛋白 ）/（HGB×D bt的 ），其中分子量血红蛋白 = 64500 [[g / mol的分子量的Hb，ðbt的 = 1.05克/毫升的脑组织密度。 </li><li>计算CBF i由拟合测得的时间自相关函数的扩散相关方程。详细的理论框架来计算CBF 我是博厄斯等。博厄斯和Yodh 10,11。在这些等式中，使用单独的测得的吸收系数从FDNIRS和一个平均的散射系数在整个人口。 </li><li>计算指数脑氧消耗通过使用FDNIRS衡量SO的<sub&gt; 2，利用下面的方程：CMRO 2i的 “DCS衡量CBFi”=（HGB×CBFi×（血氧饱和2 - SO 2））/（4×分子量血红蛋白 ×β）15，其中的第4因子反映了四个O 2分子绑定到每个血红蛋白和β是静脉隔间的血红蛋白氧合测量19％的贡献。 </li></ol>

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R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Validation+of+diffuse+correlation+spectroscopy+measurements+of+rodent+cerebral+blood+flow+with+simultaneous+arterial+spin+labeling+MRI;+towards+MRI-optical+continuous+cerebral+metabolic+monitoring.">Validation of diffuse correlation spectroscopy measurements of rodent cerebral blood flow with simultaneous arterial spin labeling MRI; towards MRI-optical continuous cerebral metabolic monitoring.</a> Biomed. Opt. Exp. 1, 553-565 (2010).</li><li>Durduran, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Optical+measurement+of+cerebral+hemodynamics+and+oxygen+metabolism+in+neonates+with+congenital+heart+defects.">Optical measurement of cerebral hemodynamics and oxygen metabolism in neonates with congenital heart defects.</a> J. Biomed. Opt. 15, 037004 (2010).</li><li>Roche-Labarbe, N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Near+infrared+spectroscopy+assessment+of+cerebral+oxygen+metabolism+in+the+developing+premature+brain.">Near infrared spectroscopy assessment of cerebral oxygen metabolism in the developing premature brain.</a> J. Cereb. Blood Flow Metab. 32, 481-488 (2012).</li></ol>

玛丽亚·安吉拉·弗朗西，她的丈夫大卫·博厄斯，贝尼亚米诺，巴比（ISS公司）拥有这项技术的专利。

我们展示了定量测量脑血流动力学和代谢与FDNIRS和DCS在新生儿人口。探头配置优化的，用于测定新生儿大脑皮层14。 DCS测量血流量的变化，得到了广泛的验证，对其他技术在动物和人类研究22,23。通过使用直接DCS衡量的血流量，我们能够以减少在CMRO 2i的 24计算的方差。重复测量的方差比的大脑区域，并与20岁之间的变化也较小。 从我们以前的结果，CBFi和CMRO 2I表现出显着的变化与PMA在健康的早产儿。 CMRO 2i的的措施是能够更好地检测比的措施的SO 2的脑损伤。这表明，联合措施，血管和代谢参数服务，更健壮的biomarkers仅比氧饱和度新生儿大脑的健康和发展。技术的改进将集中在两个文书的整合，以减少采集时间35％至40％，每会话和执行数据质量的实时反馈，被丢弃的措施，以减少频率。在不久的将来，该系统可以作为一种新型的脑氧代谢的改变的床旁监护仪临床最终用户提供。通过测量轨迹CMRO 2随着时间的推移也可能会增加临床意义，并预测结果。此工具最终可能使新生儿脑损伤，改善管理的一个重大贡献。

FDNIRS的移动设备是一个定制的频域系统从ISS的公司与两个相同的套8的激光二极管，发射在八个波长范围从660至830nm，和两个光电倍增管（PMT）探测器。源和探测器被调制在110兆赫和110兆赫，加5千赫，分别实现第6外差探测。每个激光二极管的开启顺序为10毫秒，每个周期为160毫秒总采集时间。源和探测器被耦合到光纤，并布置在一排中的光学探针。在探头上的纤维的排列是这样的，它产生四个不同的源 - 检测器分离。通过测量透射光（振幅的衰减和相移），在多个距离，我们可以量化（微秒）（μA）的吸收和散射系数下的组织观察。从在多个波长的吸光系数，然后我们估计充氧（血红蛋白）的绝对值的和脱氧血红蛋白浓度（HBR）7，脑血容量（CBV）和血红蛋白的氧饱 ​​和度（SO 2）。 DCS设备是一个家庭-一个博士开发的内置系统类似。阿琼Yodh和图尔古特杜尔杜兰大学美国宾夕法尼亚8,9。在DCS系统，由一个固体-状态，长期连贯性激光在785 nm的，四光子计数雪崩光电二极管（APD）检测器（EG＆G珀金埃尔默SPCM-AQRH）低暗计数（&lt;50计数/秒）和一个高量子产率（&gt; 40％的波长为785 nm），和一个四信道，256-bin的多-tau的相关器，与200纳秒的分辨率。与DCS，我们测量微血管血流在大脑皮质通过量化的的乘法散射光产生的多普勒频移通过移动的红血细胞产生的时间上的强度波动。激光多普勒血流仪监测，类似的技术（ 即他们是傅立叶训练班ansform类似物），超过200纳秒的范围内 - 0.5秒的延迟时间计算出的数字相关器的每个检测器通道的强度波动测量的自相关函数。相关器计算的时间上的强度，从组织中的光的重新出现的自相关。然后，我们适合测量的自相关函数的扩散相关方程，获得顺序，大约每秒一次，以获得的血液流动指数（CBFⅰ）10,11。已被广泛验证的血流量变化的的DCS措施的12,13。 SO 2结合FDNIRS措施与的DCS措施的CBF 我 ，我们实现了脑氧的代谢（CMRO 2I）的估计。

<table border="1"><tbody><tr><td> 设备 </td><td> 公司 </td><td> 目录编号 </td><td> 评论（可选） </td></tr><tr><td> Imagent </td><td> ISS </td><td></td><td> FDNIRS </td></tr><tr><td> DCS激光纤维</td><td> Thorlabs公司</td><td> FT400 </td><td> DCS组件</td></tr><tr><td> DCS检测纤维</td><td> Thorlabs公司</td><td> 780HP </td><td> DCS组件</td></tr><tr><td> DCS激光</td><td> CrystaLaser </td><td> DL785-070-S </td><td> DCS组件</td></tr><tr><td> DCS探测器</td><td>步行者国际</td><td> SPCM-AQRH-14-FC </td><td> DCS组件</td></tr><tr><td> DCS相关器</td><td> Correlator.com </td><td> Flex05-8CH </td><td> DCS组件</td></tr><tr><td>弹指一挥间合作，血氧饱和度测定仪</td><td> MASIMO </td&gt; <td></td><td> HGB和血氧饱和度监测</td></tr><tr><td> NOVA </td><td> OPHIR </td><td> 7Z01500 </td><td>激光功率计</td></tr><tr><td>感应卡</td><td>新港</td><td> F-IRC1-S </td><td> IR观众</td></tr><tr><td>中性密度​​滤镜</td><td>柯达</td><td> NT54-453 </td><td></td></tr></tbody></table>

non-invasive optical measurement of cerebral metabolism and hemodynamics in infants

围产期脑损伤的婴儿死亡率和发病率仍然是一个重要的原因，但目前还没有一个有效的的床边的工具，可以准确地筛选脑损伤，显示器损伤演化，或评估对治疗的反应。能源使用的神经元大多来自组织氧化代谢，神经活动过度和细胞死亡的脑氧代谢的（CMRO 2）通过相应的变化反映。因此，神经元的可行性措施是经过深思熟虑的CMRO 2，提供重要的诊断信息，使CMRO 2床边测量脑部健康的理想目标。 脑成像技术，如正电子发射断层扫描（PET），单光子发射计算机断层扫描（SPECT）产量措施的的脑葡萄糖和氧代谢，但这些技术都需要管理的放射性核苷酸，它们被用在最严重的情况下，。 连续波近红外光谱仪（CWNIRS）提供非侵入性和非电离辐射，脑耗氧量作为替代措施，血氧饱和度（SO 2）。然而，SO 2是不到理想的替代品，因为它是影响脑氧代谢的氧输送和消费。此外，SO 2的测量不敏感，可以探测到脑损伤的侮辱1,2小时后，由于氧的消耗和交付达到平衡后急性瞬变3。我们使用更先进的近红外光学方法来量化脑氧代谢的健康和脑损伤的新生儿床旁调查的可能性。更具体地说，我们相结合的频域NIRS（FDNIRS）的与漫反射相关光谱法（DCS）测量的血液流动指数（CBF）的SO 2的措施yielð指数CMRO 2（CMRO 2I）4,5。 随着的合并FDNIRS / DCS系统，我们能够量化脑代谢和血流动力学的影响。这代表CWNIRS用于检测大脑健康，大脑发育，治疗新生儿的改进。此外，这种方法坚持所有新生儿重症监护病房（NICU）的感染控制政策和体制政策的激光安全。未来的工作将寻求整合两个仪器，以减少采集时间在床边，并实现实时的反馈数据的质量，以减少数据的拒绝率。

在过去五年中，我们已经证明了所提出的方法的可行性和临床应用价值。特别是我们已经表明CMRO的2比SO 2是比较有代表性的大脑的健康和发展。 的横截面超过50名健康婴儿的研究，我们发现，虽然CBV是在生命的第一年的两倍多，SO 2保持不变（ 图5）。在对70名健康新生儿的研究中，我们还发现，SO 2的大脑区域是恒定的，而CMRO 2I，CBV和CBF较高的时间和顶叶区域在额区（ 图6），这是符合PET葡萄糖的摄取调查结果21。在我们的研究中，不断的SO 2，在60-70％的范围内，氧气的输送密切与当地消费相匹配，而CBV，CBF和CMRO的2个月重新紧密结合神经系统的发育。 要验证CMRO，2i是一个更好的SO 2在检测新生儿脑损伤的筛查工具，而不是，我们测量了脑损伤的婴儿，在急性期5，在几个婴儿在伤后数个月的慢性期。 图7的结果表明，SO 2是不显着改变，脑损伤早期（1-15天之后的侮辱），慢性（月伤后）阶段，，而CMRO 2i是比正常情况显着不同的急性和慢性阶段。具体中，CMRO 2i的升高，在颅脑损伤后急性期，因为癫痫发作活动，并低于正常值在慢性期由于神经元的损失。 目前，婴儿缺氧缺血性损伤的治疗与治疗性低温（TH），以降低脑代谢，减少损伤后缺氧插件ULT。治疗性降低体温维持了三天，我们已经能够监测11例在治疗过程中（ 图8）。我们发现，CMRO 2I显着下降到正常水平以下TH期间，这种下降似乎与反应的治疗和发展的结果。这些初步的研究结果表明，FDNIRS-DCS方法也许能够引导，优化低温治疗。 <img alt="图1" src="/files/ftp_upload/4379/4379fig1.jpg" /> 图1。和DCS设备FDNIRS购物车的图片。这两部仪器是紧凑，足以容纳一个可移动的小车上，小车的婴儿在新生儿重症监护病房的床头。 <img alt="图2" src="/files/ftp_upload/4379/4379fig2.jpg" /> 图2（A）光学探头配置。 <strong（B）的测量位置的计划。（C）A对婴儿照片的一个的典型FDNIRS-DCS测量。 <img alt="图3" fo:content-width="5in" fo:src="/files/ftp_upload/4379/4379fig3highres.jpg" src="/files/ftp_upload/4379/4379fig3.jpg" /> 图3。好的和坏的合适的测量（A）的吸光系数和血红蛋白配合（B）的散射系数和的线性拟合的代表性例子。 P-值&gt; 0.02，是指一个不适合的。 <a href="http://www.jove.com/files/ftp_upload/4379/4379fig3large.jpg" target="_blank">点击这里查看大图</a> 。 <img alt="图4" src="/files/ftp_upload/4379/4379fig4.jpg" /> 图4计算的强度波动的自相关函数拟合好的和坏的一个典型的例子。由超过200纳秒 - 0.5秒的延迟时间范围的一个相关。在不适合人物的拟合曲线的尾部超过0.02与1和3点的变化超过0.1。 <a href="http://www.jove.com/files/ftp_upload/4379/4379fig4large.jpg" target="_blank">点击这里查看大图</a> 。 <img alt="图5" fo:content-width="4in" fo:src="/files/ftp_upload/4379/4379fig5highres.jpg" src="/files/ftp_upload/4379/4379fig5.jpg" /> 图5。 CBV和SO 2的额叶，颞叶和顶叶皮质地区的婴儿从出生到一岁之间的变化。 <img alt="图6" fo:content-width="4in" fo:src="/files/ftp_upload/4379/4379fig6highres.jpg" src="/files/ftp_upload/4379/4379fig6.jpg" /> 图6。 CBF，SO 2，CBV和CMRO的2I的正面，德在70名健康新生儿的mporal和顶叶区域。 <img alt="图7" src="/files/ftp_upload/4379/4379fig7.jpg" /> 图7。婴幼儿脑损伤后的耗氧量的异常和正常的SO 2的例子。脑损伤被标记的变化与正常CMRO 2，SO 2是不显着异于常人。请注意，在这两个数字，CMRO 2计算使用格拉布关系，由于DCS的措施是不提供在这些测量的时间。 <img alt="图8" src="/files/ftp_upload/4379/4379fig8.jpg" /> 图8。 rCMRO低温治疗的过程中与年龄相匹配的健康对照组的11名婴儿。在所有婴幼儿低温治疗，大大减少氧代谢。

Watch this Scientific Journal Video about Non-invasive Optical Measurement of Cerebral Metabolism and Hemodynamics in Infants at JoVE.com

Non-invasive Optical Measurement of Cerebral Metabolism and Hemodynamics in Infants

我们结合频域近红外光谱技术措施的脑弥漫性相关光谱技术措施的脑血流指数估算索引的氧代谢血红素氧合。我们测试了这项措施的效用作为一种的床边筛查工具，以评估新生儿大脑的健康和发展的。

婴幼儿的脑代谢和血流动力学的非侵入式光学测量

Perinatal brain injury remains a significant cause of infant mortality  and morbidity, but there is not yet an effective bedside tool that can  accurately ...

non-invasive-optical-measurement-cerebral-metabolism-hemodynamics

Research

JoVE Journal

Medicine

19.9K 次观看.  Massachusetts General Hospital, Harvard Medical School. 我们结合频域近红外光谱技术措施的脑弥漫性相关光谱技术措施的脑血流指数估算索引的氧代谢血红素氧合。我们测试了这项措施的效用作为一种的床边筛查工具，以评估新生儿大脑的健康和发展的。

视频: Non-invasive Optical Measurement of Cerebral Metabolism and Hemodynamics in Infants

Corneal Confocal Microscopy: A Novel Non-invasive Technique to Quantify Small Fibre Pathology in Peripheral Neuropathies

The accurate quantification of peripheral neuropathy is important to define at risk patients, anticipate deterioration, and assess new therapies. Conventional methods assess neurological deficits and electrophysiology and quantitative sensory testing quantifies functional alterations to detect neuropathy. However, the earliest damage appears to be to the small fibres and yet these tests primarily assess large fibre dysfunction and have a limited ability to demonstrate regeneration and repair. The only techniques which allow a direct examination of unmyelinated nerve fibre damage and repair are sural nerve biopsy with electron microscopy and skin-punch biopsy. However, both are invasive procedures and require lengthy laboratory procedures and considerable expertise. Corneal Confocal microscopy is a non-invasive clinical technique which provides in-vivo imaging of corneal nerve fibres. We have demonstrated early nerve damage, which precedes loss of intraepidermal nerve fibres in skin biopsies together with stratification of neuropathic severity and repair following pancreas transplantation in diabetic patients. We have also demonstrated nerve damage in idiopathic small fibre neuropathy and Fabry's disease.

Corneal Confocal microscopy is a non-invasive clinical technique which may be used to quantify C fibre damage to diagnose and stratify patients with increasing neuropathic severity.

角膜共聚焦显微镜：一种新型的非侵入性技术来量化小纤维病变周围神经病变

The accurate quantification of peripheral neuropathy is important to define at risk patients, anticipate deterioration, and assess new therapies. ...

科研

医学

An in vivo Rodent Model of Contraction-induced Injury and Non-invasive Monitoring of Recovery

Muscle strains are one of the most common complaints treated by physicians. A muscle injury is typically diagnosed from the patient history and physical exam alone, however the clinical presentation can vary greatly depending on the extent of injury, the patient's pain tolerance, etc. In patients with muscle injury or muscle disease, assessment of muscle damage is typically limited to clinical signs, such as tenderness, strength, range of motion, and more recently, imaging studies. Biological markers, such as serum creatine kinase levels, are typically elevated with muscle injury, but their levels do not always correlate with the loss of force production. This is even true of histological findings from animals, which provide a "direct measure" of damage, but do not account for all the loss of function. Some have argued that the most comprehensive measure of the overall health of the muscle in contractile force. Because muscle injury is a random event that occurs under a variety of biomechanical conditions, it is difficult to study. Here, we describe an in vivo animal model to measure torque and to produce a reliable muscle injury. We also describe our model for measurement of force from an isolated muscle in situ. Furthermore, we describe our small animal MRI procedure.

An in vivo Rodent Model of Contraction-induced Injury and Non-invasive Monitoring of Recovery

An in vivo animal model of injury is described. The method takes advantage of the subcutaneous position of the fibular nerve. Velocity, timing of muscle activation, and arc of motion are all pre-determined and synchronized using commercial software. Post injury changes are monitored in vivo using MR imaging/spectroscopy.

一个在体内收缩引起的损伤，非侵入性的监测恢复啮齿动物模型

Muscle strains are one of the most  common complaints treated by physicians. A muscle injury is typically diagnosed from the patient history and  physical ...

Non-invasive Assessment of Microvascular and Endothelial Function

The authors have utilized capillaroscopy and forearm blood flow techniques to investigate the role of microvascular dysfunction in pathogenesis of cardiovascular disease. Capillaroscopy is a non-invasive, relatively inexpensive methodology for directly visualizing the microcirculation. Percent capillary recruitment is assessed by dividing the increase in capillary density induced by postocclusive reactive hyperemia (postocclusive reactive hyperemia capillary density minus baseline capillary density), by the maximal capillary density (observed during passive venous occlusion). Percent perfused capillaries represents the proportion of all capillaries present that are perfused (functionally active), and is calculated by dividing postocclusive reactive hyperemia capillary density by the maximal capillary density. Both percent capillary recruitment and percent perfused capillaries reflect the number of functional capillaries. The forearm blood flow (FBF) technique provides accepted non-invasive measures of endothelial function: The ratio FBFmax/FBFbase is computed as an estimate of vasodilation, by dividing the mean of the four FBFmax values by the mean of the four FBFbase values. Forearm vascular resistance at maximal vasodilation (FVRmax) is calculated as the mean arterial pressure (MAP) divided by FBFmax. Both the capillaroscopy and forearm techniques are readily acceptable to patients and can be learned quickly.
The microvascular and endothelial function measures obtained using the methodologies described in this paper may have future utility in clinical patient cardiovascular risk-reduction strategies. As we have published reports demonstrating that microvascular and endothelial dysfunction are found in initial stages of hypertension including prehypertension, microvascular and endothelial function measures may eventually aid in early identification, risk-stratification and prevention of end-stage vascular pathology, with its potentially fatal consequences.

Capillaroscopy is a non-invasive, relatively inexpensive methodology for directly visualizing the microcirculation. The forearm blood flow technique provides accepted non-invasive measures of endothelial function.

非侵入性的评估微血管和内皮功能

The authors have utilized capillaroscopy and forearm blood flow techniques to investigate the role of microvascular dysfunction in pathogenesis of ...

Non-invasive Imaging and Analysis of Cerebral Ischemia in Living Rats Using Positron Emission Tomography with 18F-FDG

Stroke is the third leading cause of death among Americans 65 years of age or older1. The quality of life for patients who suffer from a stroke fails to return to normal in a large majority of patients2, which is mainly due to current lack of clinical treatment for acute stroke. This necessitates understanding the physiological effects of cerebral ischemia on brain tissue over time and is a major area of active research. Towards this end, experimental progress has been made using rats as a preclinical model for stroke, particularly, using non-invasive methods such as 18F-fluorodeoxyglucose (FDG) coupled with Positron Emission Tomography (PET) imaging3,10,17. Here we present a strategy for inducing cerebral ischemia in rats by middle cerebral artery occlusion (MCAO) that mimics focal cerebral ischemia in humans, and imaging its effects over 24 hr using FDG-PET coupled with X-ray computed tomography (CT) with an Albira PET-CT instrument. A VOI template atlas was subsequently fused to the cerebral rat data to enable a unbiased analysis of the brain and its sub-regions4. In addition, a method for 3D visualization of the FDG-PET-CT time course is presented. In summary, we present a detailed protocol for initiating, quantifying, and visualizing an induced ischemic stroke event in a living Sprague-Dawley rat in three dimensions using FDG-PET.

Non-invasive Imaging and Analysis of Cerebral Ischemia in Living Rats Using Positron Emission Tomography with 18F-FDG

Brain damage resulting from cerebral ischemia may be non-invasively imaged and studied in rats using pre-clinical positron emission tomography coupled with the injectable radioactive probe, 18F-fluorodeoxyglucose. Further, the use of modern software tools that include volume of interest (VOI) brain templates dramatically increase the quantitative information gleaned from these studies.

无创成像和脑缺血分析生活中的大鼠使用正电子发射断层扫描<sup&gt; 18</sup&gt; F-FDG

Stroke is the third leading cause of death among Americans 65 years of age or older1. The quality of life for patients who suffer from a stroke fails to ...

Murine Model for Non-invasive Imaging to Detect and Monitor Ovarian Cancer Recurrence

Epithelial ovarian cancer is the most lethal gynecologic malignancy in the United States. Although patients initially respond to the current standard of care consisting of surgical debulking and combination chemotherapy consisting of platinum and taxane compounds, almost 90% of patients recur within a few years. In these patients the development of chemoresistant disease limits the efficacy of currently available chemotherapy agents and therefore contributes to the high mortality. To discover novel therapy options that can target recurrent disease, appropriate animal models that closely mimic the clinical profile of patients with recurrent ovarian cancer are required. The challenge in monitoring intra-peritoneal (i.p.) disease limits the use of i.p. models and thus most xenografts are established subcutaneously. We have developed a sensitive optical imaging platform that allows the detection and anatomical location of i.p. tumor mass. The platform includes the use of optical reporters that extend from the visible light range to near infrared, which in combination with 2-dimensional X-ray co-registration can provide anatomical location of molecular signals. Detection is significantly improved by the use of a rotation system that drives the animal to multiple angular positions for 360 degree imaging, allowing the identification of tumors that are not visible in single orientation. This platform provides a unique model to non-invasively monitor tumor growth and evaluate the efficacy of new therapies for the prevention or treatment of recurrent ovarian cancer.

We describe a non-invasive animal imaging platform that allows the detection, quantification, and monitoring of ovarian cancer growth and recurrence. This intra-peritoneal xenograft model mimics the clinical profile of patients with ovarian cancer.

小鼠模型的非侵入性成像检测和监测卵巢癌复发

Epithelial ovarian cancer is the most lethal gynecologic malignancy in the United States. Although patients initially respond to the current standard of ...

A Methodological Approach to Non-invasive Assessments of Vascular Function and Morphology

The endothelium is the innermost lining of the vasculature and is involved in the maintenance of vascular homeostasis. Damage to the endothelium may predispose the vessel to atherosclerosis and increase the risk for cardiovascular disease. Assessments of peripheral endothelial function are good indicators of early abnormalities in the vascular wall and correlate well with assessments of coronary endothelial function. The present manuscript details the important methodological steps necessary for the assessment of microvascular endothelial function using laser Doppler imaging with iontophoresis, large vessel endothelial function using flow-mediated dilatation, and carotid atherosclerosis using carotid artery ultrasound. A discussion on the methodological considerations for each of the techniques is also presented, and recommendations are made for future research.

The present article describes the methodological considerations for several non-invasive assessments of vascular function and morphology that are commonly used in medical research to assess different stages of atherosclerosis.

方法论方法血管功能和形态的非侵入性评估

The endothelium is the innermost lining of the vasculature and is involved in the maintenance of vascular homeostasis.  Damage to the endothelium may ...

Non-invasive Assessments of Subjective and Objective Recovery Characteristics Following an Exhaustive Jump Protocol

Fast recovery after strenuous exercise is important in sports and is often studied via cryotherapy applications. Cryotherapy has a significant vasoconstrictive effect, which seems to be the leading factor in its effectiveness. The resulting enhanced recovery can be measured by using both objective and subjective parameters. Two commonly measured subjective characteristics of recovery are delayed-onset muscle soreness (DOMS) and ratings of perceived exertion (RPE). Two important objective recovery characteristics are countermovement jump (CMJ) performance and peak power output (PPO). Here, we provide a detailed protocol to induce muscular exhaustion of the frontal thighs with a self-paced, 3 x 30 countermovement jump protocol (30-s rest between each set). This randomized controlled trial protocol explains how to perform local cryotherapy cuff application (+ 8 &#176;C for 20 min) and thermoneutral cuff application (+ 32 &#176;C for 20 min) on both thighs as two possible post-exercise recovery modalities. Finally, we provide a non-invasive protocol to measure the effects of these two recovery modalities on subjective (i.e., DOMS of both frontal thighs and RPE) and objective recovery (i.e., CMJ and PPO) characteristics 24, 48, and 72 h post-application. The advantage of this method is that it provides a tool for researchers or coaches to induce muscular exhaustion, without using any expensive devices; to implement local cooling strategies; and to measure both subjective and objective recovery, without using invasive methods. Limitations of this protocol are that the 30 s rest period between sets is very short, and the cardiovascular demand is very high. Future studies may find the assessment of maximum voluntary contractions to be a more sensitive assessment of muscular exhaustion compared to CMJs.

This protocol describes the procedure for non-invasive recovery assessments during a 72 h recovery period. This protocol induces muscular exhaustion of the frontal thighs using countermovement jumps and uses either local cold-cuff or thermoneutral-cuff application as a recovery modality.

根据彻底的跳跃协议进行的主观和客观恢复特征的非侵入性评估

Fast recovery after strenuous exercise is important in sports and is often studied via cryotherapy applications. Cryotherapy has a significant ...

Non-invasive Assessment of Dorsiflexor Muscle Function in Mice

Assessment of skeletal muscle contractile function is an important measurement for both clinical and research purposes. Numerous conditions can negatively affect skeletal muscle. This can result in a loss of muscle mass (atrophy) and/or loss of muscle quality (reduced force per unit of muscle mass), both of which are prevalent in chronic disease, muscle-specific disease, immobilization, and aging (sarcopenia). Skeletal muscle function in animals can be evaluated by a range of different tests. All tests have limitations related to the physiological testing environment, and the selection of a specific test often depends on the nature of the experiments. Here, we describe an in vivo, non-invasive technique involving a helpful and easy assessment of force frequency-curve (FFC) in mice that can be performed on the same animal over time. This permits monitoring of disease progression and/or efficacy&#160;of a potential therapeutic treatment.

Measurement of rodent skeletal muscle contractile function is a useful tool that can be used to track disease progression as well as efficacy of therapeutic intervention. We describe here the non-invasive, in vivo assessment of the dorsiflexor muscles that can be repeated over time in the same mouse.

小鼠肌功能的无创评价

Assessment of skeletal muscle contractile function is an important measurement for both clinical and research purposes. Numerous conditions can negatively ...

Coronary Progenitor Cells and Soluble Biomarkers in Cardiovascular Prognosis after Coronary Angioplasty

Major adverse cardiovascular events (MACEs) negatively impact the cardiovascular prognosis of patients undergoing coronary angioplasty due to coronary ischemic injury. The extent of coronary damage and the mechanisms of vascular repair are factors influencing the future development of MACEs. Intrinsic vascular features like the plaque characteristics and coronary artery complexity have demonstrated prognostic information for MACEs. However, the use of intracoronary circulating biomarkers has been postulated as a convenient method for the early identification and prognosis of MACEs, as they more closely reflect dynamic mechanisms involving coronary damage and repair. Determination of coronary circulating biomarkers during angioplasty, such as the number of subpopulations of mononuclear progenitor cells (MPCs) as well as the concentration of soluble molecules reflecting inflammation, cell adhesion, and repair, allows for assessment of future developments and the prognosis of MACEs 6 months post coronary angioplasty. This method is highlighted by its translational nature and better performance than peripheral blood circulating biomarkers regarding prediction of MACEs and its effect on the cardiovascular prognosis, which may be applied for risk stratification of patients with coronary artery disease undergoing angioplasty.

Development of major adverse cardiovascular events, which impact cardiovascular prognosis after coronary angioplasty, are influenced by the extent of coronary damage and vascular repair. The use of novel coronary cellular and soluble biomarkers, reactive to vascular damage and repair, are useful to predict the development of MACEs and prognosis.

冠状血管化后心血管预后冠状动脉祖细胞和可溶性生物标志物

Major adverse cardiovascular events (MACEs) negatively impact the cardiovascular prognosis of patients undergoing coronary angioplasty due to coronary ...

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.