Name: visualizing and quantifying pharmaceutical compounds within skin using coherent raman scattering imaging
Uploaded: 2021-11-24T13:00:00
Description: Watch this Scientific Journal Video about Visualizing and Quantifying Pharmaceutical Compounds within Skin using Coherent Raman Scattering Imaging at JoVE.com

作者要感谢埃文斯小组的Fotis Iliopoulos博士和Daniel Greenfield博士对本手稿的讨论和校对。此外，作者还希望得到LEO Pharma的支持。 图 2 是使用 BioRender.com 创建的。

裸鼠耳组织的使用得到了马萨诸塞州总医院机构动物护理和使用委员会（IACUC）的批准，而人体皮肤组织的使用则得到了马萨诸塞州总医院机构审查委员会（IRB）的批准。根据IACUC协议，新鲜安乐死的小鼠是从具有裸鼠菌落的合作者那里获得的。人体组织是通过批准的协议从马萨诸塞州总医院的选择性腹部整形手术中采购的。此外，腹部皮肤以外的特定组织类型是通过身体捐赠机构获得的，也是通...

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局部BA / BE的评估是一个研究领域，需要多方面的方法，因为没有一种方法可以完全表征 体内 cPK。该协议提出了一种基于相干拉曼成像的局部药物产品BA / BE评估方法。可能被忽视的第一点是皮肤样品必须有多薄，特别是对于定量传输SRS成像。如果皮肤太厚（即光 不能轻易通过），SRS检测器测量的信号很少甚至没有，因此它将提供较差的浓度数据。必须注意正确制备这些组织样本，?...

局部药物产品应用后评估cPK的方法已从经典的体外渗透试验（IVPT）研究1，2，3，4，5和胶带剥离6，7，8扩展到其他方法，如开流微灌注或真皮微透析9，10，11，12，13，14.根据感兴趣的疾病，可能存在各种治疗作用的局部部位。因此，可能有相应数量的方法来评估 API 到达预期本地操作站点的速率和程度。虽然上述每种方法都有其优点，但主要缺点是缺乏微尺度的cPK信息（即无法可视化API的去向及其渗透方式）。
一种用于估计局部BA和BE的非侵入性方法是CRI，它可以分为两种成像方式：CARS和SRS显微镜。这些相干拉曼方法能够通过非线性拉曼效应对分子进行化学特异性成像。在CRI中，两个激光脉冲序列在样品内聚焦和扫描;激光频率之间的能量差被设置为特定于目标化学结构的振动模式。由于CRI过程是非线性的，因此仅在显微镜焦点处产生信号，从而允许对组织进行三维药代动力学断层扫描成像。在cPK的背景下，CARS已被用于获取组织结构信息，例如富含脂质的皮肤结构的位置15。相比之下，SRS已被用于量化分子浓度，因为其信号与浓度呈线性关系。对于 离体 皮肤标本，在外延方向16 和SRS传输模式下进行CARS是有利的。因此，薄的组织样品将允许SRS信号检测和定量。
作为模型组织，裸鼠耳朵具有几个优点，但缺点很小。一个优点是组织厚度已经〜200-300μm，不需要进一步的样品制备。此外，通过一个视场轴向聚焦（例如角质层、皮脂腺 （SG）、脂肪细胞和皮下脂肪）可看到多个皮肤分层 16，18。这允许在移动到人体皮肤样本之前对皮肤渗透途径进行初步临床前估计和局部BA估计。然而，裸鼠模型存在局限性，例如由于皮肤结构19的差异而难以外推到体内场景。虽然裸鼠耳朵是获得初步结果的优秀模型，但人体皮肤模型是黄金标准。尽管关于冷冻人体皮肤对准确概括体内渗透动力学的适用性和适用性已有各种评论20，21，22，但使用冷冻人体皮肤是评估体外API渗透动力学的公认方法23，24，25.该协议可视化小鼠和人体皮肤中的各种皮肤层，同时量化富脂质和贫脂结构中的API浓度。
虽然CRI已被用于许多领域以特异性地可视化组织内的化合物，但研究局部应用药物产品的cPK的努力有限。为了使用CRI评估外用产品的局部BA / BE，有必要首先制定标准化方案以进行准确的比较。以前使用CRI将药物递送到皮肤的努力已经证明了数据中的可变性。由于这是CRI的相对较新的应用，因此建立协议对于获得可靠的结果至关重要18，26，27。这种方法仅针对拉曼光谱生物沉默区域中的一个特定波数。然而，大多数API和非活性成分在指纹区域内都有拉曼位移。由于指纹区域组织中产生的固有信号，这在以前已经提出了挑战。最近的激光和计算进步已经消除了这一障碍，这也可以与这里介绍的方法结合使用28。这里介绍的这种方法允许量化API，其在沉默区域（2，000-2，300 cm-1）具有拉曼位移。这不仅限于药物的物理化学性质，这可能是前面提到的一些cPK监测方法29的情况。
该协议必须减少各种制剂的皮肤厚度的样品间差异，因为由于厚样品的光散射，厚人皮样品在药物产品应用后会产生最小的信号。本手稿的目标是提出一种组织制备方法，以确保可重复的成像标准。此外，CRI系统的设置如前所述，以减少潜在的误差源，并最大限度地减少信噪比。但是，本文不会讨论CRI显微镜的指导原理和技术优点，因为之前已经介绍了30。最后，探索广泛的数据分析程序，以允许解释结果以确定实验的成功或失败。

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Tissue Preparation</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Autoclavable Biohazard Bags</td>
			<td>FisherBrand</td>
			<td>22-044562</td>
			<td>As refered to in text: biohazard bags 
			https://www.fishersci.com/shop/products/fisherbrand-polyethylene-biohazard-autoclave-bags-without-sterilization-indicator-8/22044562?searchHijack=true&#38;searchTerm= 22044562&#38;searchType=RAPID&#38; matchedCatNo=22044562</td>
		</tr>
		<tr>
			<td>Cell Culture Buffers: Dulbecco&#39;s Phosphate-Buffered Salt Solution 1x</td>
			<td>Corning</td>
			<td>MT21030CV</td>
			<td>As refered to in text: PBS 
			https://www.fishersci.com/shop/products/corning-cellgro-cell-culture-buffers-dulbecco-s-phosphate-buffered-salt-solution-1x-8/MT21030CV?searchHijack=true&#38;searchTerm= 21-030-cv&#38;searchType= RAPID&#38;matchedCatNo=21-030-cv</td>
		</tr>
		<tr>
			<td>Disposable Scalpels</td>
			<td>Exel International</td>
			<td>14-840-00</td>
			<td>As refered to in text: scalpel 
			https://www.fishersci.com/shop/products/exel-international-disposable-scalpels-3/1484000?keyword=true</td>
		</tr>
		<tr>
			<td>High Precision 45&#176; Angle Broad Point Tweezers/Forceps</td>
			<td>Fisherbrand</td>
			<td>12-000-132</td>
			<td>As refered to in text: forceps 
			https://www.fishersci.com/shop/products/high-precision-45-angle-broad-point-tweezers-forceps/12000132#?keyword=</td>
		</tr>
		<tr>
			<td>Kimwipes Delicate Task Wipers, 1-Ply</td>
			<td>Kimberly-Clark Professional Kimtech Science</td>
			<td>06-666</td>
			<td>As refered to in text: task wiper 
			https://www.fishersci.com/shop/products/kimberly-clark-kimtech-science-kimwipes-delicate-task-wipers-7/06666</td>
		</tr>
		<tr>
			<td>Parafilm M Laboratory Wrapping Film</td>
			<td>Bemis</td>
			<td>13-374-12</td>
			<td>As refered to in text: parafilm 
			https://www.fishersci.com/shop/products/curwood-parafilm-m-laboratory-wrapping-film-4/1337412</td>
		</tr>
		<tr>
			<td>Petri Dish (35 mm x 10 mm)</td>
			<td>Fisherbrand</td>
			<td>FB0875711YZ</td>
			<td>As refered to in text: small petri dish 
			https://www.fishersci.com/shop/products/fisherbrand-petri-dishes-specialty-6/FB0875711YZ?keyword=true</td>
		</tr>
		<tr>
			<td>Petri Dish (60 mm x 15 mm)</td>
			<td>Fisherbrand</td>
			<td>FB0875713A</td>
			<td>As refered to in text: large petri dish 
			https://www.fishersci.com/shop/products/fisherbrand-petri-dishes-clear-lid-12/FB0875713A?keyword=true</td>
		</tr>
		<tr>
			<td>Surgical Scissors</td>
			<td>Roboz</td>
			<td>NC9411473</td>
			<td>As refered to in text: scissors 
			https://www.fishersci.com/shop/products/scissors-327/NC9411473?searchHijack=true&#38;searchTerm= RS-5915SC&#38;searchType=RAPID&#38; matchedCatNo=RS-5915SC</td>
		</tr>
		<tr>
			<td>Laser/microscope</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>650/60 nm BrightLine single-band bandpass filter</td>
			<td>Semrock</td>
			<td></td>
			<td>As refered to in text: CARS filter - CH2 vibrations (645nm/60nm filter)</td>
		</tr>
		<tr>
			<td>Control box IX2-UCB</td>
			<td>Olympus</td>
			<td></td>
			<td>As refered to in text: Control Box</td>
		</tr>
		<tr>
			<td>D700/30m</td>
			<td>Chroma</td>
			<td></td>
			<td>As refered to in text: CARS filter - deuterated band 
			https://www.chroma.com/products/parts/d700-30m</td>
		</tr>
		<tr>
			<td>DeepSee Insight</td>
			<td>Spectra-Physics</td>
			<td></td>
			<td>As refered to in text: Laser 
			https://www.spectra-physics.com/f/insight-x3-tunable-laser</td>
		</tr>
		<tr>
			<td>Digital Handheld Optical Power and Energy Meter Console</td>
			<td>ThorLabs</td>
			<td>PM100D</td>
			<td>As refered to in text: power meter 
			https://www.thorlabs.com/newgrouppage9.cfm?objectgroup_id=3341</td>
		</tr>
		<tr>
			<td>Fluoview Software</td>
			<td>Olympus</td>
			<td></td>
			<td>As refered to in text: Microscope Control software</td>
		</tr>
		<tr>
			<td>Frosted Microscope Slides</td>
			<td>FisherBrand</td>
			<td></td>
			<td>As refered to in text: microscope slides 
			https://www.fishersci.com/shop/products/fisherbrand-frosted-microscope-slides-4/22265446</td>
		</tr>
		<tr>
			<td>FV1000</td>
			<td>Olympus</td>
			<td></td>
			<td>As refered to in text: Microscope</td>
		</tr>
		<tr>
			<td>Incubation Chamber</td>
			<td>Tokai Hit</td>
			<td>GM-800</td>
			<td>As refered to in text: incubation chamber</td>
		</tr>
		<tr>
			<td>Integrating Sphere Photodiode Power Sensor</td>
			<td>ThorLabs</td>
			<td>S142C</td>
			<td>As refered to in text: photodiode 
			https://www.thorlabs.com/newgrouppage9.cfm?objectgroup_id=3341</td>
		</tr>
		<tr>
			<td>Power supply FV31-PSU</td>
			<td>Olympus</td>
			<td></td>
			<td>As refered to in text: Power Supply</td>
		</tr>
		<tr>
			<td>Precision 4063, 80MHz Dual Channel Function Generator</td>
			<td>BK Precision</td>
			<td></td>
			<td>As refered to in text: function generator</td>
		</tr>
		<tr>
			<td>ProScan &#8211; Precision Microscope Automation</td>
			<td>Prior Scientific Instruments</td>
			<td></td>
			<td>As refered to in text: stage controller 
			https://www.prior.com/microscope-automation/inverted-microscope-systems/proscan-linear-stage-highest-precision-microscope-automation</td>
		</tr>
		<tr>
			<td>SecureSeal Imaging Spacers</td>
			<td>Grace Biolabs</td>
			<td>654004</td>
			<td>As refered to in text: spacer 
			https://gracebio.com/product/secureseal-imaging-spacers-654004/</td>
		</tr>
		<tr>
			<td>SRS Detection Kit</td>
			<td>APE</td>
			<td></td>
			<td>As refered to in text: SRS detector</td>
		</tr>
		<tr>
			<td>UPLSAPO 20X NA:0.75</td>
			<td>Olympus</td>
			<td></td>
			<td>As refered to in text: 20X Objective 
			https://www.olympus-lifescience.com/en/objectives/uplsapo/</td>
		</tr>
		<tr>
			<td>Lipid/Drug Imaging</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>&#160;35 mm Dish, No. 0 Uncoated Coverslip, 14 mm Glass Diameter</td>
			<td>MatTek Corporation</td>
			<td>NC9711297</td>
			<td>As refered to in text: Glass bottom dish 
			https://www.fishersci.com/shop/products/glass-bottom-mircrowell-dish/nc9711297</td>
		</tr>
		<tr>
			<td>Cotton-tipped applicators</td>
			<td>FisherBrand</td>
			<td></td>
			<td>As refered to in text: Cotton-tipped applicator</td>
		</tr>
		<tr>
			<td>Distriman Postive Displacement Pipette</td>
			<td>Gilson</td>
			<td></td>
			<td>As refered to in text: Postive Displacement Pipette 
			https://www.fishersci.com/shop/products/gilson-distriman-positive-displacement-repetitive-pipette/F164001G#?keyword=</td>
		</tr>
		<tr>
			<td>Distriman Postive Displacement Pipette Tips</td>
			<td>Gilson</td>
			<td></td>
			<td>As refered to in text: Tips for pipette 
			https://www.fishersci.com/shop/products/gilson-distritip-syringes-6/f164100g?keyword=true</td>
		</tr>
		<tr>
			<td>Data Analysis</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>FIJI</td>
			<td>Open-source</td>
			<td></td>
			<td>As refered to in text: FIJI/ImageJ 
			https://imagej.net/software/fiji/</td>
		</tr>
		<tr>
			<td>Jupyter-Lab</td>
			<td>open-source</td>
			<td></td>
			<td>As refered to in text: JupyterLab 
			https://jupyter.org/</td>
		</tr>
		<tr>
			<td>Rstudio</td>
			<td>Open-source</td>
			<td></td>
			<td>As refered to in text: Rstudio 
			https://www.rstudio.com/</td>
		</tr>
	</tbody>
</table>

visualizing and quantifying pharmaceutical compounds within skin using coherent raman scattering imaging

局部制剂应用后的皮肤药代动力学（cPK）一直是监管和药物开发科学家特别感兴趣的研究领域，以机械方式了解局部生物利用度（BA）。半侵入性技术，如胶带剥离、真皮微透析或真皮开流微灌注，均可量化大尺度 cPK。虽然这些技术提供了大量的cPK知识，但社区缺乏对细胞水平的活性药物成分（API）渗透和渗透的机制理解。 
解决微尺度cPK的一种非侵入性方法是相干拉曼散射成像（CRI），其选择性地靶向内在分子振动，而无需外在标记或化学修饰。CRI有两种主要方法 - 相干反斯托克斯拉曼散射（CARS）和刺激拉曼散射（SRS） - 能够对API或非活性成分进行灵敏和选择性定量。CARS通常用于获取结构皮肤信息或可视化化学对比度。相比之下，SRS信号与分子浓度呈线性关系，用于量化皮肤分层中的API或非活性成分。 
虽然小鼠组织通常用于CPK与CRI，但在监管批准之前，最终必须在人体组织中评估局部BA和生物等效性（BE）。本文提出了一种制备和成像 离体 皮肤的方法，用于定量药代动力学CRI研究，以评估局部BA和BE。随着时间的推移，该方法可在人类和小鼠皮肤内实现可靠且可重复的API定量。定量富脂区和贫脂区室内的浓度，以及随时间推移的总API浓度;这些用于估计微观和宏观尺度的BA，以及潜在的BE。

如果组织在实验完成后没有在轴向（<10μm）或横向方向上显着移动，则认为成像成功（图4）。如果目标 API 的 SRS 测量值不代表初始深度，则立即表明初始深度的定量是层特异性的。通过对每个感兴趣的 XY 位置进行 z 轴成像来缓解这种情况，权衡是时间分辨率。如果在这些研究中使用冷冻皮肤，则与新鲜皮肤相比，API的渗透和渗透速度很快，并且从配方应用到开始成像之间?...

Watch this Scientific Journal Video about Visualizing and Quantifying Pharmaceutical Compounds within Skin using Coherent Raman Scattering Imaging at JoVE.com

Visualizing and Quantifying Pharmaceutical Compounds within Skin using Coherent Raman Scattering Imaging

本文介绍了一种相干拉曼散射成像方法，用于可视化和量化皮肤内的药物化合物。本文介绍了皮肤组织制剂（人和小鼠）和局部制剂的应用，用于量化时空浓度曲线的图像采集，以及用于评估局部药物递送的初步药代动力学分析。

使用相干拉曼散射成像对皮肤内的药物化合物进行可视化和定量

Cutaneous pharmacokinetics (cPK) after topical formulation application has been a research area of particular interest for regulatory and drug development ...

这种方法的重要性在于，它允许使用相干拉曼成像来量化局部应用的药物产品的可重复性和准确性。其他方法提供笨重的皮肤药代动力学信息，而该方法可以提供体积和微量的皮肤药代动力学信息，例如药物的渗透途径。可视化，定量和渗透途径将允许开发具有特定途径的药物产品以到达目标位点。组织制备将被证明是这种方法中最具挑战性的部分。组织应该足够薄，以便人们能够通过皮肤阅读。要开始制备裸鼠耳朵皮肤组织，获取安乐死的裸鼠并使用镊子和显微外科剪刀去除小鼠的耳朵。然后将一只耳朵放在大小为60毫米×15毫米的大型培养皿中。接下来，用PBS冲洗鼠标耳朵两次，每次用任务刮水器将耳朵拍干。如果在24小时内使用，请将耳朵放在PBS中，放入35毫米×10毫米的小培养皿中，温度为2至8摄氏度。收获24小时后使用，将耳朵放在不含PBS的培养皿中，然后用parafilm覆盖培养皿以零下20摄氏度储存在冰箱中。在生物罩下工作时，将人体皮肤组织放在一个大培养皿中，角质层一侧朝下，以便皮下脂肪可及。然后使用镊子和显微外科剪刀去除皮下脂肪。一旦皮下脂肪不能再用剪刀去除，使用10刀片一次性手术刀与皮肤成45度角，以去除剩余的皮下脂肪，同时用镊子保持皮肤静止。当脂肪被去除时，将人体皮肤切成一厘米乘一厘米的碎片。对于脂质成像，将小鼠耳朵的前部朝向35毫米零号培养皿的玻璃底部放置。对于人体皮肤，将角质层朝下放置皮肤，以便从浅层到深层进行药物定量。一旦组织在玻璃底部居中，使用棉尖涂抹器以确保皮肤平坦，并与玻璃底部培养皿的盖玻片表面完全接触。为了防止成像时的任何移动，请将垫圈放在皮肤顶部，并确保通过垫圈的中心孔可以看到组织，以进行刺激拉曼散射或SRS传输检测。将预先确定剂量的制剂移液到皮肤上，然后用戴手套的手指顺时针摩擦制剂30秒。在分配的配方渗透时间过后，取出多余的配方，然后将皮肤与制剂面朝向玻璃底盘放置。接下来，通过打开显微镜控制或MC软件进行实验设置。透过目镜观察，使用调节旋钮调整轴向焦点，以确保组织在焦点范围内。完成后，打开泵和斯托克斯光束，并确认ALG1和ALG2通道已启用。确保SRS光电二极管位于聚光镜上方，然后单击MC软件上的Focus x2以可视化CARS和SRS通道中的皮肤。在“多区域延时摄影”或“MATL”模块中，转到“视图”选项卡，然后单击“注册点列表”以显示成像列表。一旦识别出角质层，滚动轴向焦点或Z焦点以识别特定的组织分层。可以在皮肤内添加特定的深度，例如角质层，皮脂腺，脂肪细胞或皮下脂肪，如在具有脂质调谐对比的实时成像中确定的那样。但是，如果要采用整个深度堆栈，则可以添加 XY 位置，并且可以忽略相对 Z 位置。如果对每个皮肤分层的特定深度进行成像，请选择“寄存点”以将其添加到 MATL 队列中。对于完整深度堆栈，请单击“采集参数”窗口中的“使用深度选择为每个 XY 位置注册点”。接下来，在 MATL 模块中将重复次数设置为 1 次，然后单击“就绪”。当“播放”箭头从灰色变为黑色时，按“播放”开始对初步脂质堆栈进行成像。成像周期完成后，阻挡泵浦和斯托克斯光束，并根据目标波数或拉曼振动将激光图形用户界面上的波长更改为所需波长。调整手动延时阶段，同时确保使用相同的功率对先验建立的脂质和活性药物成分或API进行成像。选择总循环重复次数后，使用光电二极管解锁泵束并检查功率是否与所需功率匹配，然后按“播放”开始对设定点进行自动成像。接下来，通过将皮脂腺脂质图像导入斐济并选中标记为“拆分通道”的框，将文件拆分为CARS和SRS通道，从而对每个皮肤分层进行数据分析。要打开感兴趣区域或 ROI 管理器，请单击“分析”、“工具”和“ROI 管理器”。使用 SRS 通道使 C 等于 1，对图像中的皮脂腺进行取消选取，并通过单击 ROI 管理器中的添加 T 将标记添加到 ROI 管理器中。对图像中的每个皮脂腺重复该过程。若要遮盖富含脂质的区域，请选择每个 ROI，然后单击“更多”、“或合并”和“添加选项卡”。要遮盖出脂质较差区域，请使用斐济菜单中的矩形工具，并在整个图像周围绘制一个正方形。将区域添加到 ROI 管理器。除了在 ROI 管理器中选择所有富含脂质区域的 ROI 之外，还可以单击新添加的方形 ROI。在“更多”下，选择“XOR”以生成脂质贫乏区域的蒙版，并将其添加到 ROI 管理器中。通过按顺序转到“图像”、“堆栈”、“工具”和“连接”选项卡，按数字顺序连接图像。或者，通过将图像加载到斐济，然后在设置页面上选择一个名为“组具有相似名称的文件”的选项来导入图像。在激活串联图像的同时，转到 ROI 管理器以选择富含脂质的区域，并在选择“多重测量”之前单击“更多”选项卡，然后等待“结果”窗口出现。在结果 窗口中，将数据导出到电子表格，并添加标题为“区域”的列，以将富含脂质的区域添加到每行数据中。将脂质贫乏添加到脂质以外的区域。若要可视化数据，请将电子表格保存并导入到 R 包 ggplot2 中。然后将数据绘制为图像数量与平均强度的函数，以估计浓度时间数据。在 RStudio 中对从电子表格导入的强度时间数据运行非区室分析或 NCA，并调用一个图层。完成后，绘制并直观地比较Jmax和AUCflux-all指标。此外，在实验条件下进行统计比较。代表性分析描绘了角质层，皮脂腺，脂肪细胞，裸鼠耳朵皮肤的皮下脂肪，以及来自人体皮肤的角质层，状真皮和皮脂腺。在裸鼠耳部皮肤中，在配施时和施用后120分钟，以相同的腺体组织深度观察到皮脂腺的有限组织运动。在施用药物120分钟后，皮肤中的大量组织运动显示出几乎看不见的皮脂腺，这表明原始方案的低效率。在几项研究中，强度与时间曲线显示高初始浓度，随后浓度降低，表明药物没有进一步吸收到组织中。另一方面，一些研究表明强度上升，后来在实验持续时间内下降，表明进入组织的通量在成像之前没有达到最大值。对同一API的两种制剂的浓度时间曲线的NCA分析表明，与凝胶制剂相比，无论皮肤层如何，乙氧基乙氧基乙醇都提供了延长的API渗透性。相同配方之间的总暴露分析在皮肤的深层显示出类似的观察结果。药物施用后人体皮肤的制备和玻璃底培养皿上的适当皮肤放置对于实验的成功至关重要。这里的明确解决方案表明了这种方法的适用性。进一步的研究将涉及上市配方，如面霜，以了解配方如何影响API渗透和渗透。

Research

JoVE Journal

Medicine

Accurate and Simple Measurement of the Pro-inflammatory Cytokine IL-1&beta; using a Whole Blood Stimulation Assay

Accurate and Simple Measurement of the Pro-inflammatory Cytokine IL-1ÃƒÅ½Ã‚Â² using a Whole Blood Stimulation Assay

使用全血刺激试验的促炎性细胞因子IL -1β的精确和简单的测量

Inflammatory processes resulting from the secretion of soluble mediators by immune cells, lead to various manifestations in skin, joints and other tissues ...

科研

医学

Quantitative Visualization and Detection of Skin Cancer Using Dynamic Thermal Imaging

定量可视化和皮肤癌症使用动态热成像检测

In 2010 approximately 68,720 melanomas will be diagnosed in the US alone, with around 8,650 resulting in death 1. To date, the only effective treatment ...

MALDI Imaging Mass Spectrometry of Neuropeptides in Parkinson's Disease

MALDI成像帕金森病的神经肽质谱

MALDI imaging mass spectrometry (IMS) is a powerful approach that facilitates the spatial analysis of molecular species in biological tissue samples2 ...

Cerenkov Luminescence Imaging of Interscapular Brown Adipose Tissue

肩胛间褐色脂肪组织的切伦科夫发光成像

Brown adipose tissue (BAT), widely known as a &#8220;good fat&#8221; plays pivotal roles for thermogenesis in mammals. This special tissue is closely ...

Povidone Iodine Rectal Preparation at Time of Prostate Needle Biopsy is a Simple and Reproducible Means to Reduce Risk of Procedural Infection

聚维酮碘直肠准备在前列腺穿刺活检的时间是一个简单的和可重复的手段，以减少程序感染的风险

Single institution and population-based studies highlight that infectious complications following transrectal ultrasound guided prostate needle biopsy ...

Combined Near-infrared Fluorescent Imaging and Micro-computed Tomography for Directly Visualizing Cerebral Thromboemboli

结合近红外荧光成像和微计算机断层扫描直接可视化脑血栓

Direct thrombus imaging visualizes the root cause of thromboembolic infarction. Being able to image thrombus directly allows far better investigation of ...

Using Multi-fluorinated Bile Acids and In Vivo Magnetic Resonance Imaging to Measure Bile Acid Transport

Using Multi-fluorinated Bile Acids and In Vivo Magnetic Resonance Imaging to Measure Bile Acid Transport

使用多氟化胆汁酸和<em&gt;在体内</em&gt;磁共振成像来衡量胆汁酸运输

Along with their traditional role as detergents that facilitate fat absorption, emerging literature indicates that bile acids are potent signaling ...

Inducing Ischemia-reperfusion Injury in the Mouse Ear Skin for Intravital Multiphoton Imaging of Immune Responses

在鼠耳皮肤的免疫反应的活体多光子成像诱导缺血再灌注损伤

Ischemia-reperfusion injury (IRI) occurs when there is transient hypoxia due to the obstruction of blood flow (ischemia) followed by a subsequent ...

Quantitative Visualization of Leukocyte Infiltrate in a Murine Model of Fulminant Myocarditis by Light Sheet Microscopy

通过轻型显微镜对小鼠急性心肌炎模型中白细胞浸润的定量可视化

Light-sheet fluorescence microscopy (LSFM), in combination with chemical clearing protocols, has become the gold standard for analyzing fluorescently ...

Rapid Evaluation of Toxicity of Chemical Compounds Using Zebrafish Embryos

利用斑马鱼胚胎对化合物毒性的快速评价

The zebrafish is a widely used vertebrate model organism for the disease and phenotype-based drug discovery. The zebrafish generates many offspring, has ...