LH由NPL的MedAccel计划资助，该计划由商业，能源和工业战略部的工业战略挑战基金资助。JMG在GR 5824/1项目下获得了德国研究基金会（DFG）的资助。JJ感谢医学科学院跳板（REF:SBF007\100007）奖的资助。SEB感谢英国癌症研究中心的支持，资助号为C9545 / A29580。AMI，BZ和SR得到了英国商业，能源和工业战略部通过国家测量系统的资助。图 1 和 图 2 是使用 BioRender 创建的。

表1:软组织中发现的声学和光学特性概述。 光学特性涵盖 600 至 900 nm 的光谱范围。应该注意的是，这些只是旨在提供一般指导的代表性值。精确值可能因实验条件（例如温度）和频率/波长而异。文献提供了更具体的价值观。*未找到具体参考资料。 <a href="https://www.jove.com/files/ftp_upload/65475/65475_Table%201_rev.xlsx" target="_blank">请按此下载此表格。</a>
给定的方案已被开发用于制造~120 mL的幻影材料。组件的质量可以缩放以制造不同体积的幻影材料。请注意，对于较大的体积（>500 mL），建议的设备可能无法充分均匀地加热虚拟混合物。为此，应适当调整加热设备。
注意:始终确保在整个制造过程中佩戴合适的个人防护装备（PPE）。这可能包括使用实验室外套、护目镜和安全手套;参考并遵守当地安全准则。该程序改编自 Hacker 等人 39; 步骤 1 显示了这些步骤的摘要。
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/65475/65475fig01.jpg"> 图1:油中共聚物材料的制造 。 （1）将用于光散射和吸收的材料添加到矿物油中，（2）在90°C超声处理直至溶解。（3）加入聚合物和稳定剂，（4）在低搅拌下在油浴中将混合物加热至160°C。（5）所有组分溶解后，将样品倒入合适的幻像模具中，（6）在室温下硬化。该图转载自Hacker等人39。 <a href="https://www.jove.com/files/ftp_upload/65475/65475fig01large.jpg" target="_blank">请点击此处查看此图的大图。</a>
1. 混合物的制备
<ol><li>通过将 0.4 g Nigrosin 加入 40 mL 矿物油来制备 Nigrosin 储备溶液。通过超声处理和彻底涡旋样品确保均匀混合。将储备溶液储存在室温下。 注意:储备溶液在重复使用前应始终彻底混合。如果首选没有光散射体（TiO 2）或吸收体（染料）的幻影材料，则可以跳过步骤1和2。继续执行步骤 3。</li>
	<li>在100 mL（83.8 g）矿物油中超声处理0.15 gTiO 2和1 mL染料储备溶液，直到所有组分完全溶解（~60分钟）（图1:步骤1和2）。如果设备允许，将超声仪设置为高温（90°C），因为这有利于混合过程。在超声处理时间内继续执行步骤3-5。 注意:如果首选具有更高吸收和散射特性的模型，则可能需要延长超声处理时间。</li>
	<li>称取所需浓度（例如，SEBS = 25.14 g;LDPE = 6.70 g）（图 1:步骤 3）。<ol><li>可选:可以添加抗氧化剂以增加稳定性，但如果加热温度不超过 180°C，则不是强制性的。 注意:如果在制造过程的后期阶段遇到溶解度或粘度问题，建议排除LDPE。加入LDPE以提高材料中的声速（表3）;但是，创建稳定的幻像不是必需的。通过省略LDPE，可以简化制造和成型过程，但会导致最终材料的后续声速降低（表3）。</li>
	</ol></li>
	<li>使用合适的玻璃器皿和硅油制作油浴;小心地将其固定在电炉上。确保热电偶保留在硅油浴中，并且在整个过程中不会接触玻璃器皿的边缘（图2）。 注:确保按照设备制造商的说明仔细安装温度调节附件。</li>
	<li>在油浴内放置足够长度的磁力搅拌棒，以确保热量均匀分布。</li>
	<li>打开加热板，将加热温度设置为160°C，并将搅拌器的每分钟转数（rpm）设置为50。</li>
	<li>将LDPE和SEBS转移到含有超声矿物油（含TiO2 和Nigrosin）的玻璃烧杯中。将足够长度的磁力搅拌棒引入玻璃烧杯中，并将其转移到油浴的中心以加热被测组件。确保浴液中的油位保持在烧杯内的矿物油液位以上（图1:步骤4）。</li>
</ol>2. 加热混合物
<ol><li>如果在任何阶段添加的聚合物似乎漂浮在矿物油上，请使用金属刮刀手动搅拌矿物油溶液，以便任何漂浮的聚合物分布在矿物油内。戴上耐热手套。</li>
	<li>将混合物保持在160°C，直到所有聚合物溶解并且溶液看起来均匀混合，具有光滑均匀的质地（~1.5小时）。</li>
</ol>3. 吸尘
注意:要去除气泡，请按照以下步骤操作，具体取决于可用的设备。
<ol><li>将热烧杯小心地放入真空室中，并在最高设置（最低真空）下将样品 真空 2-3分钟。使用金属刮刀小心地去除积聚在表面上的任何气泡。如果在此步骤后仍然存在气泡，请重新加热混合物并重复吸尘步骤，直到去除所有气泡。</li>
	<li>打开 真空烤箱 并将其加热至160°C。 达到所需温度后，将装有溶液的烧杯转移到真空烤箱中。 注意:始终戴上热防护手套处理烧杯。<ol><li>将真空打开到可用的最高设置（最低真空）。如果在溶液顶部产生了泡沫层，请关闭真空并使用刮刀从表面上去除气泡（重复此步骤，直到去除所有气泡）。</li>
		<li>将烧杯在真空炉中以最高真空设置放置1小时。 注意:为保持真空烤箱清洁，请用纸巾清洁烧杯的硅油外表面。 </li>
	</ol></li>
</ol>4. 将样品倒入模具中
<ol><li>在将样品倒入样品模具之前，如有必要，用刮刀去除混合物表面残留的气泡。</li>
	<li>小心地将溶液倒入合适的模具中，戴上耐热手套或使用足够的防护设备。确保从低高度平稳地倾倒，以减少形成任何气泡的机会（图1:步骤5）。对于形状复杂的模具，在浇注之前在模具上涂上一层薄薄的油（矿物油[例如蓖麻油或硅油]除外），以便于去除固化的样品。 注意:在烘箱中预热模具有助于实现更高的样品均匀性。</li>
	<li>倒入后，用金属刮刀快速去除样品顶部的任何气泡。如果混合物中积聚了许多气泡，请重复真空步骤，前提是模具的类型和形状允许。</li>
	<li>让溶液在室温下凝固。虽然较小的样品可以在不到2小时内固化，但将样品放置过夜以消除任何不完全固化的风险。将样品储存在室温下（图1:步骤6）。</li>
</ol>5. 图像采集
<ol><li>对于图像采集，请将模型放置在成像设备的视野中。</li>
	<li>对于PAI或超声系统，例如，使用超声凝胶或水对幻影表面与超声换能器进行声耦合。 注意:如果协议得到正确遵循，则不会有不均匀性干扰视野。定制的虚拟支架可以帮助在测量之间进行可重复的样品定位。</li>
	<li>如果采集温度与虚拟的存储温度不同，请让虚拟温度与周围环境保持稳定。</li>
	<li>获取图像。</li>
</ol>6. 材料表征测量
注意: 材料表征测量的目的是验证材料的光学和声学特性。应该注意的是，幻影制造方案已显示出高重现性39，因此，如果需要进一步的验证研究，则仅提供以下通用测量协议作为指导。测量的各个步骤将取决于所使用的表征设备。在这里，使用基于宽带通过传输替代方法41（英国国家物理实验室（NPL）提供）的系统进行声学表征，并使用内部双积分球（DIS）系统（基于42）进行光学表征。表征系统的设置显示在补充图1中。有关测量设置（声学43;光学42,44）和测量程序39的更多详细信息，请参见其他专题。测量程序应根据所使用的每个特定表征系统进行调整。
<ol><li>声学表征 注意:声学表征测量基于采用10 MHz中心频率超声换能器（有源晶片直径为10 mm）进行脉冲生成和宽带水听器（30 mm有源晶片直径bilaminar膜水听器）进行脉冲检测的系统（两者都放置在装满去离子水的水箱中;尺寸为112 cm x 38 cm x 30 cm3).传感器由脉冲发生器接收器驱动。波形是使用示波器采集的。有关设置和测量程序（包括系统特定的B型对测量的影响）的更多详细信息，请参见 43。<ol><li>准备适合测量设置的样品（例如，在这种情况下，直径为7-8厘米，厚度为6-9毫米的圆形样品）。确保样品成分均匀，没有任何杂质、气泡或表面不规则。</li>
		<li>使用游标卡尺测量测试样品的厚度，并使用校准的温度计记录水箱的温度。</li>
		<li>将样品放入系统中。确保样品与系统组件正确对齐。 注意:基于万向节支架43 的自动控制样品架可以帮助精确控制样品的旋转和倾斜。</li>
		<li>为每个测量集采集四个声脉冲:声路中没有样本的参考通水脉冲;通过样品传输;以及发射器从样品的正面和背面接收的声反射。</li>
		<li>从测量中得出样品的声学特性。使用等式 （1）43 计算声速 c（f）（单位为 m·s−1）。 <img alt="Equation 1" src="/files/ftp_upload/65475/65475eq01.jpg" style="margin: auto;">（1） CW表示水声的温度相关速度，θ1（f）、θ2（f）、θw（f） 和 θs（f） 分别是前反射、背反射、通过水和通过采样电压脉冲的相应未包裹相位谱。材料的频率相关衰减系数（α i（f））可以使用公式（2）43所示的双样品置换技术得出。 <img alt="Equation 2" src="/files/ftp_upload/65475/65475eq02v2.jpg" style="margin: auto;">（二） Uw（f）和Us（f）分别是通水和通样脉冲的电压幅度谱，αw（f）是纯水在特定水箱温度45下的超声衰减系数（单位为dB·cm-1），d 1和d 2（d2>d1）是两个样品厚度。 注:对于本协议，评估了界面损耗的衰减，发现其影响可以忽略不计。</li>
		<li>在测试样品的不同位置重复测量三次以上。计算测量值的平均值和标准偏差，以得出最终样本值。</li>
	</ol></li>
	<li>光学表征 注意:对于光学测试，使用了双积分球系统（基于 42），采用两个积分球（50毫米内径），通过两根光纤 连接到 两个光谱仪。反射球通过第三根光纤 连接到 光源。<ol><li>准备适合测量设置的样品（例如，在这种情况下，宽度为 5.9 cm、高度为 1.8 cm、厚度范围在 2 到 3 mm 之间的矩形样品）。确保样品成分均匀，没有任何杂质、气泡或表面不规则。</li>
		<li>打开光源，使其根据制造商的说明稳定下来（例如，15分钟）。</li>
		<li>使用游标卡尺确定样品的厚度。如果适用，请指定测量的波长范围和步长（例如，450-900 nm，步长为1 nm）。</li>
		<li>记录透射球和反射球的参考测量值。<ol><li>对于反射球，首先通过记录反射率值R0进行开口测量，去除透射球并打开光源。然后，用参考标准品记录反射率值 R1，将参考标准放在反射球（光源打开）前面。</li>
			<li>对于透射球，首先通过在关闭对齐的反射率和透射率球体和光源的情况下记录透射率值 T0来进行遮挡光束测量。然后，通过在对齐的反射率和透射率球体和光源打开的情况下记录透射率值 T1来进行入射光束测量。 注意:测量必须确保球体和参考标准品的清洁表面，因为灰尘或其他污染物的附着可能会影响组件的性能46.</li>
		</ol></li>
		<li>将样品放在球体之间。测量反射率 Rs 和透射率 Ts 值。确保样品未被压缩，因为这可能会影响测量精度。将一个球体放在电动载物台上可能有助于通过使其适应测量的样品厚度来精确控制球体之间的距离。</li>
		<li>使用公式 （3） 和 （4）42 计算归一化反射率 M R 和透射率 MT 值。 <img alt="Equation 3" src="/files/ftp_upload/65475/65475eq03.jpg" style="margin: auto;">（三） <img alt="Equation 4" src="/files/ftp_upload/65475/65475eq04.jpg" style="margin: auto;">（四） RSTD 描述了从99%反射率标准反射的强度。</li>
		<li>将测量值输入逆加倍（IAD）程序（源代码:http://omlc.org/software/iad/）44 ，以估计材料的光学特性。 注意:根据以前的报告，散射各向异性因子（g）可以取为g = 0.7，折射率为n = 1.4 30。</li>
		<li>在沿测试样品的不同位置重复测量至少三次。计算测量值的平均值和标准偏差，以得出最终样本值。</li>
	</ol></li>
</ol>

制造稳定的、具有生物相关性的体模材料

Sarah Bohndiek此前曾获得光声成像仪器供应商CYBERDYNE INC和iThera Medical GmbH的研究支持。其他作者与本手稿没有利益冲突需要披露。

在这里，提出了一个协议，旨在为稳定的生物相关材料提供通用配方，可用于创建用于多模态声学和光学生物医学成像应用的校准测量和标准化的模型。该材料先前已被证明在时间内稳定39，具有高批次间重现性，使用安全，并且由标准科学供应商提供的现成、具有成本效益的成分组成。材料属性在相关的声学和光学范围内独立可调。此外，它具有机械坚固性且不溶于水，因此可以承受粗暴处理，并且对用于超声波/光声研究的水基偶联剂呈惰性。有人强调，可以使用不同类型的夹杂物创建不同的模型设计，这些夹杂物由相同或不同的材料类型组成。鉴于这些特性，该材料满足上述理想生物光子模型的关键标准，并且与其他现有的组织模拟材料相比显示出关键优势3。通过详细说明确切的制造过程，我们希望最大限度地减少制造过程中出现的变化，从而优化其用于校准、验证和跟踪成像系统性能的使用。
已经确定了两个关键步骤对制造过程至关重要。首先，需要将成分充分混合并均匀加热，以形成均匀的材料。使用超声仪和磁力搅拌器进行混合，使用油浴进行加热，确保材料成分在基质内均匀分布。需要注意的是，油浴不要达到非常高的温度（>180°C），因为这会导致材料成分氧化，导致变黄。手动搅拌可以支持混合过程，并补偿材料-空气界面的热量不足。当使用较高浓度的TiO2 和/或聚合物以确保材料的均匀组成时，可能需要延长超声处理和混合的时间。其次，需要去除气泡以防止在基质内形成异质性。虽然这可以通过真空泵或烤箱来实现，但也应从低处小心倾倒，以尽量减少材料内的空气滞留。
该材料的一个显着优点是其热塑性特性（源自SEBS聚合物），允许其重新加热和重塑，而不会对其声学和光学性能产生任何显着影响39。然而，再加热需要逐渐小心地进行，因为如果再加热太快，材料很容易燃烧和氧化。当使用较高的LDPE浓度时，再加热也变得更加困难，因为LDPE不表现出与SEBS相同的热塑性行为。
该协议仍然存在一些限制。由于聚合物的高熔融温度（150°C），幻影模具需要由耐热材料制成，例如玻璃或不锈钢。此外，如果使用高聚合物浓度来调节声学特性，则材料在液态下相当粘稠，使得填充小成像目标变得困难。最后，声学特性的调谐到目前为止仅限于~1450-1,516 m·s-1的声速范围，该声速范围支持模拟组织，如乳房或脂肪（c = 1,450-1,480 m·s−1），但对于肌肉或肾脏等组织（c > 1,520 m·s−1）可能不足。还应考虑伴随的声学衰减变化。
在这里，我们重点介绍了该材料作为超声和光学成像应用的稳定模型的应用。然而，油中共聚物材料也显示出在弹性成像应用中的价值35，并且可能允许与磁共振成像等进一步的成像方式兼容。使用3D打印模具可以实现模型的解剖真实度，如类似研究29,47,48,49所示。早期的研究还证明了材料本身的3D可打印性，进一步扩展了其在加工和制造方面的灵活性。这些发展突显了该材料作为多模态成像应用中广泛使用的稳定幻影介质的令人兴奋的未来潜力。

通过技术验证1,2建立新型光学成像生物标志物的精密度和准确性对于确保其在临床实践中的成功实施至关重要。为了实现这一目标，技术验证研究经常采用耐用的物理模型，这有助于仪器间性能评估和常规质量控制。为了在研究和临床转化中广泛使用幻影材料，需要一种简单、高度可重复的制造方案。理想的生物光子模型材料应包括以下特性3:（1）在生物学相关范围内独立可调性质;（2）机械坚固性;（3）长期稳定;（4）几何形状和结构的灵活性;（5）安全处理;（6）可从标准科学供应商处购买的广泛可用的成分;（7）成本低。目前，生物光子应用缺乏一种被广泛接受的幻影材料的标准化协议，该协议满足概述的要求，并且还包括用于混合应用的可调谐声学特性，例如光声成像（PAI）。
针对光学和声学组合应用的生物相关虚拟材料包括水凝胶4,5，聚乙烯醇（PVA）6,7,8,9和聚氯乙烯塑料溶胶（PVCP）10,11,12,13,14,15,16 .然而，这些材料的特点是具有某些局限性，限制了它们作为稳定的幻影材料的应用。例如，水凝胶容易脱水、机械损伤和细菌向内生长，从而限制了它们的保质期17,18,19。添加化学品可以延长寿命，但常见的防腐剂，如甲醛20或苯扎氯铵21，是危险的，在处理过程中需要采取谨慎措施。此外，含有水溶性染料的靶材如果不封装，可能会在基材内扩散。PVA冷冻凝胶的特点是具有更高的寿命和结构坚固性，但其制备过程涉及较长的冻融循环22。这会限制声学和光学参数23的独立可调性，并且如果略有变化，则可能导致不均匀性6，从而损害再现性。此外，在1年后观察到夹杂物中染料的扩散13。PVCP具有复杂的制造工艺，包括高达180-220°C的高温13,14,24,25。PVCP还缺乏与科学供应商的供应链26，并且可能含有基于邻苯二甲酸酯的增塑剂，这可能会对生殖和发育造成伤害27，使其成为一些国家的受控物质。
油中共聚物组合物，例如凝胶蜡28,29,30,31或基于热塑性苯乙烯弹性体32,33,34,35,36的共混物，表现出良好的纵向稳定性并具有类似组织的声学和光学特性31,35,36,37，因此在多模式应用中作为耐用的幻影候选者具有很高的潜力。此外，这类材料具有成本效益、不吸水、无毒和生物惰性35,38。声速c（f）和声衰减系数α（f）可以通过聚合物浓度33,35,39的变化在生物学相关范围内调节（表1），而光吸收μ a（λ）和减少的散射μ s'（λ）系数可以通过添加油溶性染料或二氧化钛（TiO 2）39来改变， 分别。
在这里，提出了一种简单、易于遵循的协议，用于创建适用于光学、超声或光声设备校准的耐用油中共聚物模型。所有成分都有明确的化学文摘服务（CAS）编号，并且可从标准科学供应商处轻松获得。强调了制造过程中的潜在困难，并提出了克服这些困难的方法。虽然该协议允许制造具有一系列声学和光学特性的材料，但所提出的协议产生的材料声速为~1,481 m·s-1，与室温（20°C）下水的声速对齐40。该值被选为代表各种现有组织特性的中性标准品（表1），从而可以建立一致且可靠的参考点进行比较。通过提供这个详细的协议，我们的目标是扩大这种有前途的幻影材料类型的吸收和制造可重复性，从而促进生物光子、声学和光声验证研究，并支持临床前和临床成像应用中的常规质量控制。

<table><tbody><tr><td>Low-density Polyethylene (LDPE)</td><td>Alfa Aesar&amp;nbsp;</td><td>43949.30&lt;br/&gt; CAS: 9002-88-4</td><td>6.70 g&lt;br/&gt; 5.8% w/w</td></tr><tr><td>Mineral oil</td><td>Sigma Aldrich</td><td>330779-1L&lt;br/&gt; CAS: 8042-47-5</td><td>83.80 g&lt;br/&gt; 72.5% w/w</td></tr><tr><td>Nigrosin&amp;nbsp;</td><td>Sigma Aldrich&amp;nbsp;</td><td>211680-100G&lt;br/&gt; CAS: 11099-03-9</td><td>0.4 g&amp;nbsp;</td></tr><tr><td>Polystyrene-block-poly(ethylene-ran-butylene)-block-polystyrene (SEBS)</td><td>Sigma Aldrich&amp;nbsp;</td><td>200557-250G&lt;br/&gt; CAS: 66070-58-4</td><td>25.14 g&lt;br/&gt; 21.7% w/w</td></tr><tr><td>Silicone oil for oil bath</td><td>Sigma Aldrich&amp;nbsp;</td><td>85409-1L&lt;br/&gt; CAS: 63148-62-9&lt;br/&gt; ~1 L (depending on size of oil bath)</td><td></td></tr><tr><td>Titanium(IV) oxide, anatase (TiO&lt;sub&gt;2&lt;/sub&gt;)</td><td>Sigma Aldrich&amp;nbsp;</td><td>232033&lt;br/&gt; CAS: 1317-70-0</td><td>0.15 g</td></tr><tr><td>Antioxidant (optional; e.g., butylated hydroxytoluene)</td><td>Sigma Aldrich&amp;nbsp;</td><td>W218405-1KG-K&lt;br/&gt; CAS: 128-37-0</td><td>may be added to prevent discolouration if higher fabrication temperatures are used&amp;nbsp;</td></tr><tr><td>Oil-solule dyes for inclusions (optional)</td><td>e.g., Caligo safe wash relief inks, Cranfield Colours, Cwmbran, UK*</td><td></td><td>may be added depending on preferred absorption</td></tr><tr><td>Bath Sonicator&amp;nbsp;</td><td>Ultrawave Ltd, UK*</td><td>U500H Ultrasonic Cleaning Bath*</td><td>ideally with temperature control; recommended operating frequencies between 30-50 kHz)</td></tr><tr><td>Crystallising dish for silicone oil bath (up to +200 &amp;deg;C)</td><td>any suitable supplier</td><td></td><td>(ext. diameter ~140 mm for 250 mL glass beaker)</td></tr><tr><td>Glass beaker (~250 mL); glass sample dishes/phantom mould</td><td>any suitable supplier</td><td></td><td></td></tr><tr><td>Hot plate with magnetic stirrer and thermoregulator (external probe thermocouple) with maximum temperature of &gt; 200 &amp;deg;C</td><td>Thermo Fisher Scientific, UK*</td><td>Velp Scientifica AREC.X Digital Ceramic Hot Plate Stirrer*</td><td></td></tr><tr><td>Laboratory scales / scientific balances accurate to 0.01 g</td><td>any suitable supplier</td><td></td><td></td></tr><tr><td>Metallic spatula</td><td>any suitable supplier</td><td></td><td></td></tr><tr><td>Vaccuum oven or vaccum chamber</td><td>Memmert, Germany (Vacuum oven)*&lt;br/&gt; &lt;br/&gt; Cole-Parmer Instrument Company, UK (Vaccum chamber)*</td><td>VO29 (Vacuum oven)&lt;br/&gt; &lt;br/&gt; DWK Life Sciences (Kimble) Glass Vacuum Desiccator with Collar (Vaccum chamber)*</td><td></td></tr><tr><td>1. Acoustic characterization system*</td><td></td><td></td><td></td></tr><tr><td>Hydrophone</td><td>GEC Marconi</td><td>30 mm active element diameter bilaminar membrane hydrophone</td><td></td></tr><tr><td>Oscilloscope</td><td>Tektronix UK, Bracknell, UK</td><td>DPO 7254&amp;nbsp;</td><td></td></tr><tr><td>Pulser&amp;ndash;receiver&amp;nbsp;</td><td>Olympus NDT, Waltham, MA, USA</td><td>Olympus 5073PR</td><td></td></tr><tr><td>Sample holder</td><td>Newport Spectra-Physics, Didcot, UK</td><td>Newport 605-4 Series Low-Distortion Axial Clamping Gimbal Optic Mount</td><td>may require additional adaptor for sample holding</td></tr><tr><td>Thermometer</td><td>G. H. Zeal, London, UK</td><td>UKAS-calibrated IP 39C spirit-in-glass thermometer</td><td></td></tr><tr><td>Ultrasound transducer&amp;nbsp;</td><td>Force Technology, Brondby, Denmark</td><td>Transducer of active element diameter 10 mm&amp;nbsp;</td><td></td></tr><tr><td>Vernier callipers</td><td>any suitable supplier</td><td></td><td></td></tr><tr><td>Water tank filled with deionized water&amp;nbsp;</td><td>any suitable supplier</td><td></td><td>requires sufficent size (e.g., dimensions 112 &amp;times; 38 &amp;times; 30 cm&lt;sup&gt;3&lt;/sup&gt;)</td></tr><tr><td>2.Optical characterization system*</td><td></td><td></td><td></td></tr><tr><td>Integrating sphere (two)</td><td>Avantes, Apeldoorn, the Netherlands</td><td>AvaSphere-50, 50 cm internal diameter</td><td></td></tr><tr><td>Light source&amp;nbsp;</td><td>Avantes, Apeldoorn, the Netherlands</td><td>Avalight-HAL-s-mini</td><td></td></tr><tr><td>Motorized stage (optional)</td><td>Thorlabs,</td><td>Thorlabs MTS50</td><td></td></tr><tr><td>Optical fibres (three)</td><td>any suitable supplier</td><td></td><td></td></tr><tr><td>Reflectance standard</td><td>Labsphere, North Sutton, USA</td><td>99%, white, 1.25&quot; diameter, USRS-99-010, AS-01158-060</td><td></td></tr><tr><td>Spectrometer</td><td>Avantes, Apeldoorn, the Netherlands</td><td>Starline Avaspec-2048</td><td></td></tr><tr><td>Software</td><td></td><td></td><td></td></tr><tr><td>Data acqusition software (e.g., Labview)</td><td>National Instruments, Austin, TX, USA</td><td></td><td></td></tr><tr><td>Data analysis software (e.g., Matlab)</td><td>Mathworks, Natick, USA</td><td></td><td></td></tr><tr><td>Inverse adding doubling (IAD) program&amp;nbsp;</td><td></td><td></td><td>Source code: http://omlc.org/software/iad/</td></tr><tr><td>*Please note that similar equipment may also be used.</td><td></td><td></td><td></td></tr></tbody></table>

a stable phantom material for optical and acoustic imaging

建立提供长期稳定性的组织模拟生物光子模拟材料对于跨供应商和机构的生物医学成像设备的比较、支持国际公认标准的制定以及协助新技术的临床转化至关重要。这里介绍了一种制造工艺，该工艺产生了一种稳定、低成本、组织模拟油中共聚物的材料，用于光声、光学和超声标准化工作。
基础材料由矿物油和具有定义化学文摘服务（CAS）编号的共聚物组成。这里提出的协议产生了一种代表性材料，在5 MHz时声速c（f）= 1,481 ± 0.4 m·s-1（对应于水在20 °C时的声速），在5 MHz时声衰减α（f） = 6.1 ± 0.06 dB·cm-1，在800 nm处的光吸收μa（λ） = 0.05 ± 0.005 mm-1， 和800 nm 处的光散射μ s'（λ） = 1 ± 0.1 mm-1。该材料允许通过分别改变聚合物浓度或光散射（二氧化钛）和吸收剂（油溶性染料）来独立调整声学和光学特性。展示了不同模型设计的制造，并使用光声成像确认了所得测试对象的均匀性。
由于其简单、可重复的制造工艺和耐用性，以及其生物学相关特性，该材料配方在多模态声光学标准化计划中具有很高的前景。

按照这个方法，已经创建了三种具有代表性的光声成像模型设计，针对具有不同光学照明和声学检测几何形状的不同系统设计（图3A）。如果模型制备程序成功执行，则模型材料看起来光滑均匀，没有任何滞留的气泡或杂质，并且在生成的图像中看不到任何伪影（此处使用光声成像可视化;图3B，C）。该方案产生的代表性材料具有声速c（f）= 1481±0.4 m·s-1（对应于20 °C40时水的声速），声衰减α（f） = 6.1 ± 0.06 dB·cm-1（均在5 MHz时），光吸收μa（λ） = 0.05 ± 0.005 mm-1，光散射μs'（λ） = 1 ± 0.1 mm-1（均在 800 nm 处）（不确定度描述了不同操作员独立生产的n = 3个批次的标准偏差;所有测量均在室温[20°C]下进行）。
光散射系数可以通过TiO 2的变化来调节，而光吸收系数可以通过添加任何油溶性染料来调节，这里用Nigrosin演示（表2和图3D）。虽然表2中的值集中在较低的吸收和散射组织，如肌肉或乳房（表1），但我们在添加较高浓度的吸收体和散射体时没有遇到任何困难。然而，添加较高浓度的光散射体/吸收体可能需要更长的超声处理时间才能实现溶液的均匀混合。
声衰减和声速可以通过聚合物浓度的变化来调节（表3）。在这里，调谐到目前为止仅限于~1,450-1,516 m·s-1的声速范围。较低的聚合物浓度可能导致样品的物理稳定性较低，从而导致随时间推移的塑性变形34。较高的聚合物浓度会导致材料的脆性和不均匀的质地。声学特性的范围可能有助于模拟乳房或脂肪等组织（c = 1,450-1,480 m·s−1），但对于肌肉或肾脏等组织可能不足（c > 1,520 m·s−1;表 1）。
虚拟制备中的常见误差源包括气泡去除不足和基础组分混合不均匀（图 4）。这可以通过分别通过吸尘和小心倾倒以及搅拌/涡旋来最小化。
<img alt="Figure 2" class="xfigimg" src="/files/ftp_upload/65475/65475fig02.jpg"> 图 2:模型制造的实验设置。 使用夹子将装有幻影成分的玻璃烧杯放置在硅油浴中，以避免油浴表面与玻璃烧杯直接接触。热板上的温度反馈确保仔细的温度控制。磁力搅拌器可以混合硅油和幻影成分。 <a href="https://www.jove.com/files/ftp_upload/65475/65475fig02large.jpg" target="_blank">请点击此处查看此图的大图。</a>
<img alt="Figure 3" class="xfigimg" src="/files/ftp_upload/65475/65475fig03.jpg"> 图 3:模型制造过程的代表性结果。 （A）各种模型设计，显示出应用于不同光声成像系统的多功能性。左:小矩形模型，其绳子嵌入在不同深度（0.5、1.5和2.5毫米;目标间距离为1.25毫米），设计用于测试高分辨率成像系统;中间:带有两个夹杂物的圆柱形模型（夹杂物之间的距离为 12 毫米），使用绿色和紫色油溶性染料，设计用于测试断层扫描系统;右:大型矩形模型，通道嵌入在不同深度（6 mm、10 mm 和 14 mm;夹杂物之间的距离为 3.5 mm），设计用于测试手持式系统。（B）带有嵌入弦的矩形幻影的示例光声图像，使用商用光声成像系统在532 nm处获取。（C）圆柱形断层扫描模型的示例光声图像，用商业光声成像系统在800nm处获取。（D）通过增加黑素浓度（浓度以图像上矿物油总体积的重量百分比表示）而增加光吸收浓度的幻影。图3B，C转载自Hacker等人39。比例尺 = 10 mm。<a href="https://www.jove.com/files/ftp_upload/65475/65475fig03large.jpg" target="_blank">请点击此处查看此图的大图。</a>
<img alt="Figure 4" class="xfigimg" src="/files/ftp_upload/65475/65475fig04.jpg"> 图 4:常见的幻像故障 。 （A，B）显示被困在基质内的气泡的照片。（C）基础成分混合不足导致所得光声图像中的不均匀性（红色箭头）。比例尺 = 5 毫米 （A）。 <a href="https://www.jove.com/files/ftp_upload/65475/65475fig04large.jpg" target="_blank">请点击此处查看此图的大图。</a>
表2:光吸收（μa）和散射（μ s'）值调整的表格概述。百分比值以重量百分比表示基础溶液的总体积（矿物油，第1列）和虚拟材料的总重量（第2列）。尼格罗辛浓度表示绝对尼格罗辛（非储备溶液）的总量。所有样品均含有5%丁基化羟基甲苯作为抗氧化剂（可选）。n = 每个样品 3 次测量。该表的可视化表示可以在 Hacker et al.39 中找到。缩写:neg = 可忽略不计。<a href="https://www.jove.com/files/ftp_upload/65475/Table%202v3.xlsx" target="_blank">请按此下载此表格。</a>
表 3:声衰减 （α） 和声速 （c） 值调谐的表格概述。 由幂律描述 α 0 f n，具有从非线性最小二乘拟合获得的α 0和 n 参数（每个样本n = 4 个测量值）。 F表示以MHz为单位的频率。 百分比值以重量百分比表示基础溶液（矿物油）的总重量。所有样品均含有5%丁基化羟基甲苯作为抗氧化剂（可选）。该表的可视化表示可以在 Hacker et al.39 中找到。 <a href="https://www.jove.com/files/ftp_upload/65475/65475_Table%203_rev.xlsx" target="_blank">请按此下载此表格。</a>
补充图S1:用于验证的声学和光学表征系统的设置。 显示了用于确定声衰减系数和声速的声学表征系统的照片（A）和示意图（B）。各个系统组件在照片和原理图中用注释HP（水听器）、S（样品）和T（传感器）表示。显示了用于评估光吸收系数和降低散射系数的双积分球系统的照片（C）和示意图（D）。各个系统组件在照片和原理图中用注释 S（样本）、RS（反射球）、TS（传输球）、OF（光纤）和 MS（电动载物台）表示。该图转载自Hacker等人 39。 <a href="https://www.jove.com/files/ftp_upload/65475/Suppl.%20Fig%201.pdf" target="_blank">请点击此处下载此文件。</a>

Watch this Scientific Journal Video about A Stable Phantom Material for Optical and Acoustic Imaging at JoVE.com

作者聚焦:用于光学和声学成像的稳定 Phantom 材料  

该协议描述了用于光学和声学生物医学成像应用的稳定，生物学相关模型材料的制造，具有独立可调的声学和光学特性。

用于光学和声学成像的稳定幻影材料

Establishing tissue-mimicking biophotonic phantom materials that provide long-term stability are imperative to enable the comparison of biomedical imaging ...

我们的研究重点是开发用于早期癌症检测的新成像模式。特别是在这项研究中，我们专注于开发一个稳定的测试对象，也称为幻影，以验证基于光和/或声音的成像模式。已经提出了不同的资源来开发声学光学方案中的组织模拟材料。例如，PVA、水凝胶、聚氨酯或 PVCP。本研究重点研究了一种基于岩心Polyman油成分的有前途的新材料类型，该材料类型克服了许多可调性和稳定性挑战。生物医学光学领域涵盖了广泛的成像模式，可以应用于当今医学面临的一些关键挑战。许多光学成像模式的深度相对有限，但我们也可以通过光声效应将光与声音耦合，以利用超声波的一些深度穿透优势。光声成像在从炎症成像到癌症诊断的广泛临床试验中显示出前景。然而，由于缺乏能够准确模拟组织的光学和声学特性并随着时间的推移保持稳定的可用模型材料，定量性能评估仍然具有挑战性。许多新的光学和光声成像系统正在开发中，但我们缺乏标准化的参考模型来验证这些系统并比较它们的性能。我们的材料是填补这一空白并支持这些令人兴奋的新技术的进一步发展和转化为临床的有希望的候选者。将来，我们希望专注于创建更逼真的解剖学模型设计和架构，以适应评估不同系统配置的性能。例如，微观、介观和宏观系统，它们具有不同的几何形状和空间分辨率。

a-stable-phantom-material-for-optical-and-acoustic-imaging

Research

JoVE Journal

Medicine

A Stable Phantom Material for Optical and Acoustic Imaging

2.8K 次观看.  University of Cambridge. 我们的研究重点是开发用于早期癌症检测的新成像模式。特别是在这项研究中，我们专注于开发一个稳定的测试对象，也称为幻影，以验证基于光和/或声音的成像模式。已经提出了不同的资源来开发声学光学方案中的组织模拟材料。例如，PVA、水凝胶、聚氨酯或 PVCP。本研究重点研究了一种基于岩心Polyman油成分的有前途的新材料类型，该材料类型克服了许多可调性和稳...

视频: 作者聚焦:用于光学和声学成像的稳定 Phantom 材料  

Construction of a Preclinical Multimodality Phantom Using Tissue-mimicking Materials for Quality Assurance in Tumor Size Measurement

World Health Organization (WHO) and the Response Evaluation Criteria in Solid Tumors (RECIST) working groups advocated standardized criteria for radiologic assessment of solid tumors in response to anti-tumor drug therapy in the 1980s and 1990s, respectively. WHO criteria measure solid tumors in two-dimensions, whereas RECIST measurements use only one-dimension which is considered to be more reproducible 1, 2, 3,4,5. These criteria have been widely used as the only imaging biomarker approved by the United States Food and Drug Administration (FDA) 6. In order to measure tumor response to anti-tumor drugs on images with accuracy, therefore, a robust quality assurance (QA) procedures and corresponding QA phantom are needed.
To address this need, the authors constructed a preclinical multimodality (for ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI)) phantom using tissue-mimicking (TM) materials based on the limited number of target lesions required by RECIST by revising a Gammex US commercial phantom 7. The Appendix in Lee et al. demonstrates the procedures of phantom fabrication 7. In this article, all protocols are introduced in a step-by-step fashion beginning with procedures for preparing the silicone molds for casting tumor-simulating test objects in the phantom, followed by preparation of TM materials for multimodality imaging, and finally construction of the preclinical multimodality QA phantom. The primary purpose of this paper is to provide the protocols to allow anyone interested in independently constructing a phantom for their own projects. QA procedures for tumor size measurement, and RECIST, WHO and volume measurement results of test objects made at multiple institutions using this QA phantom are shown in detail in Lee et al. 8.

This paper describes in-house procedures of constructing a preclinical multimodality phantom made of tissue-mimicking (TM) materials for quality assurance (QA) of tumor size measurement in animal imaging modalities such as ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI).

幻影使用肿瘤尺寸测量的质量保证组织模仿材料的潜伏期多模工程

World Health Organization (WHO) and the Response Evaluation Criteria in Solid Tumors (RECIST) working groups advocated standardized criteria for ...

科研

生物工程

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

Perinatal brain injury remains a significant cause of infant mortality and morbidity, but there is not yet an effective bedside tool that can accurately screen for brain injury, monitor injury evolution, or assess response to therapy. The energy used by neurons is derived largely from tissue oxidative metabolism, and neural hyperactivity and cell death are reflected by corresponding changes in cerebral oxygen metabolism (CMRO2). Thus, measures of CMRO2 are reflective of neuronal viability and provide critical diagnostic information, making CMRO2 an ideal target for bedside measurement of brain health.
Brain-imaging techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) yield measures of cerebral glucose and oxygen metabolism, but these techniques require the administration of radionucleotides, so they are used in only the most acute cases.
Continuous-wave near-infrared spectroscopy (CWNIRS) provides non-invasive and non-ionizing radiation measures of hemoglobin oxygen saturation (SO2) as a surrogate for cerebral oxygen consumption. However, SO2 is less than ideal as a surrogate for cerebral oxygen metabolism as it is influenced by both oxygen delivery and consumption. Furthermore, measurements of SO2 are not sensitive enough to detect brain injury hours after the insult 1,2, because oxygen consumption and delivery reach equilibrium after acute transients 3. We investigated the possibility of using more sophisticated NIRS optical methods to quantify cerebral oxygen metabolism at the bedside in healthy and brain-injured newborns. More specifically, we combined the frequency-domain NIRS (FDNIRS) measure of SO2 with the diffuse correlation spectroscopy (DCS) measure of blood flow index (CBFi) to yield an index of CMRO2 (CMRO2i) 4,5.
With the combined FDNIRS/DCS system we are able to quantify cerebral metabolism and hemodynamics. This represents an improvement over CWNIRS for detecting brain health, brain development, and response to therapy in neonates. Moreover, this method adheres to all neonatal intensive care unit (NICU) policies on infection control and institutional policies on laser safety. Future work will seek to integrate the two instruments to reduce acquisition time at the bedside and to implement real-time feedback on data quality to reduce the rate of data rejection.

We combined frequency-domain near-infrared spectroscopy measures of cerebral hemoglobin oxygenation with diffuse correlation spectroscopy measures of cerebral blood flow index to estimate an index of oxygen metabolism. We tested the utility of this measure as a bedside screening tool to evaluate the health and development of the newborn brain.

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 ...

医学

In Vivo Optical Imaging of Brain Tumors and Arthritis Using Fluorescent SapC-DOPS Nanovesicles

We describe a multi-angle rotational optical imaging (MAROI) system for in vivo monitoring of physiopathological processes labeled with a fluorescent marker. Mouse models (brain tumor and arthritis) were used to evaluate the usefulness of this method. Saposin C (SapC)-dioleoylphosphatidylserine (DOPS) nanovesicles tagged with CellVue Maroon (CVM) fluorophore were administered intravenously. Animals were then placed in the rotational holder (MARS) of the in vivo imaging system. Images were acquired in 10&#176; steps over 380&#176;. A rectangular&#160;region of interest (ROI) was placed across the full image width at the model disease site. Within the ROI, and for every image, mean fluorescence intensity was computed after background subtraction. In the mouse models studied, the labeled nanovesicles were taken up in both the orthotopic and transgenic brain tumors, and in the arthritic sites (toes and ankles). Curve analysis of the multi angle image ROIs determined the angle with the highest signal. Thus, the optimal angle for imaging each disease site was characterized. The MAROI method applied to imaging of fluorescent compounds is a noninvasive, economical, and precise tool for in vivo quantitative analysis of the disease states in the described mouse models.

In Vivo Optical Imaging of Brain Tumors and Arthritis Using Fluorescent SapC-DOPS Nanovesicles

We describe a multi-angle rotational optical imaging (MAROI) system for in vivo quantitation of a fluorescent marker delivered by saposin C (SapC)-dioleoylphosphatidylserine (DOPS) nanovesicles. Employing mouse models of cancer and arthritis, we demonstrate how the MAROI signal curve analysis can be used for the precise mapping and biological characterization of disease processes.

在脑肿瘤和关节炎的用荧光SAPC-DOPS纳米囊泡体光学成像

We describe a multi-angle rotational optical imaging (MAROI) system for in vivo monitoring of physiopathological processes labeled with a fluorescent ...

Multimodal 3D Printing of Phantoms to Simulate Biological Tissue

Biomedical optical imaging is playing an important role in diagnosis and treatment of various diseases. However, the accuracy and the reproducibility of an optical imaging device are greatly affected by the performance characteristics of its components, the test environment, and the operations. Therefore, it is necessary to calibrate these devices by traceable phantom standards. However, most of the currently available phantoms are homogeneous phantoms that cannot simulate multimodal and dynamic characteristics of biological tissue. Here, we show the fabrication of heterogeneous tissue-simulating phantoms using a production line integrating a spin coating module, a polyjet module, a fused deposition modeling (FDM) module, and an automatic control framework. The structural information and the optical parameters of a &#34;digital optical phantom&#34; are defined in a prototype file, imported to the production line, and fabricated layer-by-layer with sequential switch between different printing modalities. Technical capability of such a production line is exemplified by the automatic printing of skin-simulating phantoms that comprise the epidermis, dermis, subcutaneous tissue, and an embedded tumor.

Spin coating, polyjet printing, and fused deposition modeling are integrated to produce multilayered heterogeneous phantoms that simulate structural and functional properties of biological tissue.

幻影的多模态3D打印模拟生物组织

Biomedical optical imaging is playing an important role in diagnosis and treatment of various diseases. However, the accuracy and the reproducibility of ...

工程学

Combined In vivo Optical and &#181;CT Imaging to Monitor Infection, Inflammation, and Bone Anatomy in an Orthopaedic Implant Infection in Mice

Multimodality imaging has emerged as a common technological approach used in both preclinical and clinical research. Advanced techniques that combine in vivo optical and &#956;CT imaging allow the visualization of biological phenomena in an anatomical context. These imaging modalities may be especially useful to study conditions that impact bone. In particular, orthopaedic implant infections are an important problem in clinical orthopaedic surgery. These infections are difficult to treat because bacterial biofilms form on the foreign surgically implanted materials, leading to persistent inflammation, osteomyelitis and eventual osteolysis of the bone surrounding the implant, which ultimately results in implant loosening and failure. Here, a mouse model of an infected orthopaedic prosthetic implant was used that involved the surgical placement of a Kirschner-wire implant into an intramedullary canal in the femur in such a way that the end of the implant extended into the knee joint. In this model, LysEGFP mice, a mouse strain that has EGFP-fluorescent neutrophils, were employed in conjunction with a bioluminescent Staphylococcus aureus strain, which naturally emits light. The bacteria were inoculated into the knee joints of the mice prior to closing the surgical site. In vivo bioluminescent and fluorescent imaging was used to quantify the bacterial burden and neutrophil inflammatory response, respectively. In addition, &#956;CT imaging was performed on the same mice so that the 3D location of the bioluminescent and fluorescent optical signals could be co-registered with the anatomical &#956;CT images. To quantify the changes in the bone over time, the outer bone volume of the distal femurs were measured at specific time points using a semi-automated contour based segmentation process. Taken together, the combination of in vivo bioluminescent/fluorescent imaging with &#956;CT imaging may be especially useful for the noninvasive monitoring of the infection, inflammatory response and anatomical changes in bone over time.

Combined In vivo Optical and  &#181;CT Imaging to Monitor Infection, Inflammation, and Bone Anatomy in an Orthopaedic Implant Infection in Mice

Combined optical and &#956;CT imaging in a mouse model of orthopaedic implant infection, utilizing a bioluminescent engineered strain of Staphylococcus aureus, provided the capability to noninvasively and longitudinally monitor the dynamics of the bacterial infection, as well as the corresponding inflammatory response and anatomical changes in the bone.

结合<em&gt;在体内</em&gt;光学及μCT成像监视感染，炎症和骨解剖在骨科植入物感染的小鼠

Multimodality imaging has emerged as a common technological approach used in both preclinical and clinical research. Advanced techniques that combine in ...

Cerenkov Luminescence Imaging of Interscapular Brown Adipose Tissue

Brown adipose tissue (BAT), widely known as a &#8220;good fat&#8221; plays pivotal roles for thermogenesis in mammals. This special tissue is closely related to metabolism and energy expenditure, and its dysfunction is one important contributor for obesity and diabetes. Contrary to previous belief, recent PET/CT imaging studies indicated the BAT depots are still present in human adults. PET imaging clearly shows that BAT has considerably high uptake of 18F-FDG under certain conditions. In this video report, we demonstrate that Cerenkov luminescence imaging (CLI) with 18F-FDG can be used to optically image BAT in small animals. BAT activation is observed after intraperitoneal injection of norepinephrine (NE) and cold treatment, and depression of BAT is induced by long anesthesia. Using multiple-filter Cerenkov luminescence imaging, spectral unmixing and 3D imaging reconstruction are demonstrated. Our results suggest that CLI with 18F-FDG is a practical technique for imaging BAT in small animals, and this technique can be used as a cheap, fast, and alternative imaging tool for BAT research.

In this video report, we show the application of Cerenkov Luminescence Imaging (CLI) for interscapular brown adipose tissue in mice under activated and depressed conditions.

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 ...

Fabrication and Characterization of Optical Tissue Phantoms Containing Macrostructure

The rapid development of new optical imaging techniques is dependent on the availability of low-cost, customizable, and easily reproducible standards. By replicating the imaging environment, costly animal experiments to validate a technique may be circumvented. Predicting and optimizing the performance of in vivo and ex vivo imaging techniques requires testing on samples that are optically similar to tissues of interest. Tissue-mimicking optical phantoms provide a standard for evaluation, characterization, or calibration of an optical system. Homogenous polymer optical tissue phantoms are widely used to mimic the optical properties of a specific tissue type within a narrow spectral range. Layered tissues, such as the epidermis and dermis, can be mimicked by simply stacking these homogenous slab phantoms. However, many in vivo imaging techniques are applied to more spatially complex tissue where three dimensional structures, such as blood vessels, airways, or tissue defects, can affect the performance of the imaging system. 
This protocol describes the fabrication of a tissue-mimicking phantom that incorporates three-dimensional structural complexity using material with optical properties of tissue. Look-up tables provide India ink and titanium dioxide recipes for optical absorption and scattering targets. Methods to characterize and tune the material optical properties are described. The phantom fabrication detailed in this article has an internal branching mock airway void; however, the technique can be broadly applied to other tissue or organ structures.

Optical tissue phantoms are essential tools for calibration and characterization of optical imaging systems and validation of theoretical models. This article details a method for phantom fabrication that includes replication of tissue optical properties and three-dimensional tissue structure.

含有宏观结构的光学组织幻影的制备与表征

The rapid development of new optical imaging techniques is dependent on the availability of low-cost, customizable, and easily reproducible standards. By ...

Agarose-based Tissue Mimicking Optical Phantoms for Diffuse Reflectance Spectroscopy

This protocol describes how to make agarose-based tissue-mimicking phantoms and demonstrates how to determine their optical properties using a conventional optical system with an integrating sphere. Measuring systems for the acquisition of the diffuse reflectance and total transmittance spectra are constructed with a broadband white light source, a light guide, an achromatic lens, an integrating sphere, a sample holder, an optical fiber probe, and a multi-channel spectrometer. An acrylic mold consisting of two rectangular acrylic pieces and a U-shaped acrylic piece is constructed to create an epidermal phantom and a dermal phantom with whole blood. The application of a sodium dithionite (Na2S2O4) solution to the dermal phantom enables the researcher to deoxygenate hemoglobin in red blood cells distributed in the dermal phantom. The inverse Monte Carlo simulation with the diffuse reflectance and total transmittance spectra measured by a spectrometer with an integrating sphere is performed to determine the absorption coefficient spectrum &#181;a(&#955;) and the reduced scattering coefficient spectrum &#181;s&#39;(&#955;) of each layer phantom. A two-layered phantom mimicking the diffuse reflectance of human skin tissue is also demonstrated by piling up the epidermal phantom on the dermal phantom.

Here, we demonstrate how agarose-based tissue-mimicking optical phantoms are made and how their optical properties are determined using a conventional optical system with an integrating sphere.

基于琼脂糖组织模拟光学幽灵的漫反射光谱研究

This protocol describes how to make agarose-based tissue-mimicking phantoms and demonstrates how to determine their optical properties using a ...

Patient-Specific Polyvinyl Alcohol Phantom Fabrication with Ultrasound and X-Ray Contrast for Brain Tumor Surgery Planning

Phantoms are essential tools for clinical training, surgical planning and the development of novel medical devices. However, it is challenging to create anatomically accurate head phantoms with realistic brain imaging properties because standard fabrication methods are not optimized to replicate any patient-specific anatomical detail and 3D printing materials are not optimized for imaging properties. In order to test and validate a novel navigation system for use during brain tumor surgery, an anatomically accurate phantom with realistic imaging and mechanical properties was required. Therefore, a phantom was developed using real patient data as input and 3D printing of molds to fabricate a patient-specific head phantom comprising the skull, brain and tumor with both ultrasound and X-ray contrast. The phantom also had mechanical properties that allowed the phantom tissue to be manipulated in a similar manner to how human brain tissue is handled during surgery. The phantom was successfully tested during a surgical simulation in a virtual operating room.
The phantom fabrication method uses commercially available materials and is easy to reproduce. The 3D printing files can be readily shared, and the technique can be adapted to encompass many different types of tumor.

This protocol describes the fabrication of a patient specific skull, brain and tumor phantom. It uses 3D printing to create molds, and polyvinyl alcohol (PVA-c) is used as the tissue mimicking material.

患者特异性聚乙烯酒精幻影制造与超声波和X射线对比脑肿瘤手术规划

Phantoms are essential tools for clinical training, surgical planning and the development of novel medical devices. However, it is challenging to create ...

Formulation and Acoustic Modulation of Optically Vaporized Perfluorocarbon Nanodroplets

Microbubbles are the most commonly used imaging contrast agent in ultrasound. However, due to their size, they are limited to vascular compartments. These microbubbles can be condensed or formulated as perfluorocarbon nanodroplets (PFCnDs) that are small enough to extravasate and then be triggered acoustically at the target site. These nanoparticles can be further enhanced by including an optical absorber such as near infrared organic dye or nanoparticles (e.g., copper sulfide nanoparticles or gold nanoparticles/nanorods). Optically tagged PFCnDs can be vaporized through laser irradiation in a process known as optical droplet vaporization (ODV). This process of activation enables the use of high boiling point perfluorocarbon cores, which cannot be vaporized acoustically under the maximum mechanical index threshold for diagnostic imaging. Higher boiling point cores result in droplets that will recondense after vaporization, resulting in "blinking" PFCnDs that briefly produce contrast after vaporization before condensing back into nanodroplet form. This process can be repeated to produce contrast on demand, allowing for the background free imaging, multiplexing, super-resolution, and contrast enhancement through both optical and acoustic modulation. This article will demonstrate how to synthesize optically-triggerable, lipid shell PFCnDs utilizing probe sonication, create polyacrylamide phantoms to characterize the nanodroplets, and acoustically modulate the PFCnDs after ODV to improve contrast.

Optically activated perfluorocarbon nanodroplets show promise in imaging applications outside of the vascular system. This article will demonstrate how to synthesize these particles, crosslink polyacrylamide phantoms, and modulate the droplets acoustically to enhance their signal.

光学汽化全氟化碳纳米液滴的配方和声学调制

Microbubbles are the most commonly used imaging contrast agent in ultrasound. However, due to their size, they are limited to vascular compartments. These ...

用于光学和声学成像的稳定幻影材料

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