Name: measurement of tumor t2* relaxation times after iron oxide nanoparticle administration
Uploaded: 2023-05-19T13:10:00
Description: Watch this Scientific Journal Video about Measurement of Tumor T2* Relaxation Times after Iron Oxide Nanoparticle Administration at JoVE.com

这项工作部分得到了国家癌症研究所的资助，拨款号为U24CA264298。我们感谢PET / MRI代谢服务中心的Dawn Holley，Kim Halbert和Mehdi Khalighi在斯坦福大学卢卡斯研究中心获得PET / MRI扫描的帮助。我们感谢Daldrup-Link实验室的成员对这个项目的宝贵意见和讨论。

该协议已生成用于前瞻性临床试验和联合临床研究。该研究符合《健康保险流通与责任法案》（HIPAA），并得到了斯坦福大学机构审查委员会（IRB）的批准。所有患者或其法定授权代表都签署了书面知情同意书，所有7至18岁的儿童都签署了同意书。
1. 安装并启动 T2 拟合图插件
<ol><li>启动 Osirix 软件。从插件管理器安装 T2 Fit Map 插件并重新启动软件。<ol><li>在菜单...

<ol>
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我们的协议允许我们根据多回波梯度回波序列、外部软件和用于创建 T2* 图的插件来测量肿瘤 T2* 弛豫时间。协议中的关键步骤是将具有非常短TE的多回波梯度回波序列包含在扫描协议中，以及使用外部软件对多回波梯度回波图像进行单指数拟合。根据采集时间排列输入多回波梯度回波图像非常重要。这可以通过在外部软件的首选项：数据库下拉菜单下按采集时间对成像数据系列进行排序来实现。<...

用磁共振成像（MRI）广泛建立了对身体各组织中肿瘤T2*弛豫时间的无创定量1。本文的基本原理是提供一种用于测量肿瘤T2*弛豫时间的协议，该协议独立于Osirix2等扫描仪软件。这将允许对来自不同中心、不同扫描仪和不同供应商的成像数据进行统一分析。事实上，成千上万的用户可能会使用相同的方法，从而提高肿瘤T2*测量的标准化。T2* 测量被神经放射科医生、心脏成像专家和腹部成像专家等用于不同的目的。用于测量组织 T2* 弛豫时间的 MRI 脉冲序列已被应用并优化，用于评估颅内出血3、肝铁含量 1,4 和心脏铁含量 5,6 等。其他研究人员使用T2*测量来生成恶性肿瘤中氧化铁纳米颗粒积累的定量估计7,8。然而，以前的许多方法都使用机构软件或特定的扫描仪软件，这些软件仅限于在特定机构使用或用于处理在特定扫描仪上获得的数据。在这里，我们描述了一种普遍适用的方法，该方法基于来自任何可以生成多回波梯度回波图像的扫描仪的临床前或临床MRI数据生成肿瘤T2*图和肿瘤T2*弛豫时间。所需的梯度回波序列应具有非常短的首次回波时间和紧密的回波间隔9,10。然后将多回波梯度回波图像输入外部软件，计算肿瘤T2*图，并测量肿瘤T2*弛豫时间。外部模型的 T2* 衰减曲线中的 T2 拟合图插件作为 S（t） = So e-t/T2* 11 的单指数拟合，其中 S（t） 表示给定时间 t 的信号或过程值;S 0 是 t =0 时信号或过程的初始值;t 表示时间;T2*，也称为表观横向弛豫时间，表征信号或过程的衰减速率;e 是自然对数的底数（大约等于 2.71828）。该方程描述了指数衰减，其中信号或过程随时间减小，是衰减速率T2*的函数。T2*的值越大，衰减速率越慢，反之亦然。同一软件还可用于输入多回波自旋回波图像，并通过将 T2 衰减曲线拟合为 S（t） = So e-t/T2 来生成肿瘤 T2 值。曲线拟合是使用外部软件执行的，没有包含恒定的偏移。两条衰减曲线都表现出单一的指数行为，与T2相比，T2*的持续时间更短。
在含铁血黄素沉着症和血色素沉着症患者中，通过组织活检定量肝铁含量是金标准，而无创MR成像是建立基线值和无创监测随时间变化的护理点12,13。虽然生成用于肝铁定量的T2*图谱已经建立4，但没有标准化的方案来测量肿瘤T2*弛豫时间。虽然 T2* 地图也可以由扫描仪软件生成，但它仅限于特定的扫描仪和供应商。在肿瘤学领域，给定患者的连续成像研究通常发生在不同的扫描仪上，并且多中心MRI数据是基于来自不同扫描仪和不同供应商的成像研究获得的。此外，共临床成像研究正在越来越多地实施，并且需要比较患者的MRI数据和模拟其肿瘤的小鼠模型。该协议的目的是提供独立于扫描仪软件的肿瘤T2 *弛豫时间测量协议。这将允许对来自不同中心和不同扫描仪的成像数据进行统一分析。事实上，成千上万的用户可能会使用相同的方法，从而提高肿瘤T2*测量的标准化和可重复性。我们的协议使用外部软件，可以从互联网上下载。多回波梯度回波图像被输入软件并拟合到单指数衰减公式中以生成 T2* 图，在该图谱上，可以使用操作员定义的感兴趣区域 （ROI） 测量肿瘤 T2* 弛豫时间5。氧化铁纳米颗粒可以以不同的剂量输注14，在我们的研究中，患者接受了Ferumoxytol注射液（30mg / mL），其中含有510mg元素铁，体积为17mL，剂量为每公斤体重5mg元素铁。随后使用设定的序列参数获得多回波梯度回波序列15进行数据采集。

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>OsiriX</td>
			<td>Pixmeo SARL</td>
			<td></td>
			<td>https://www.osirix-viewer.com/</td>
		</tr>
		<tr>
			<td>3T GE MR 750</td>
			<td>GE Healthcare, Chicago, IL</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>FERAHEME (ferumoxytol injection)</td>
			<td>AMAG Pharmaceuticals, Inc. 1100 Winter Street Waltham, MA 02451</td>
			<td></td>
			<td></td>
		</tr>
	</tbody>
</table>

measurement of tumor t2* relaxation times after iron oxide nanoparticle administration

T2*弛豫法是用磁共振成像（MRI）测量超顺磁性氧化铁纳米颗粒对肿瘤组织影响的既定方法之一。氧化铁纳米颗粒缩短肿瘤的T1，T2和T2*弛豫时间。虽然 T1 效应根据纳米颗粒的大小和组成而变化，但 T2 和 T2* 效应通常占主导地位，T2* 测量在临床环境中最省时。在这里，我们介绍了我们测量肿瘤T2*弛豫时间的方法，使用多回波梯度回波序列，外部软件和标准化协议，用于使用扫描仪独立软件创建T2 *图谱。这有助于比较来自不同临床扫描仪、不同供应商和联合临床研究工作的成像数据（即在小鼠模型和患者中获得的肿瘤T2*数据）。安装软件后，需要从插件管理器安装 T2 Fit Map 插件。该协议提供了分步程序细节，从将多回波梯度回波序列导入软件，到创建颜色编码的T2 *图和测量肿瘤T2*弛豫时间。该方案可应用于任何身体部位的实体瘤，并已根据临床前成像数据和患者的临床数据进行了验证。这可以促进多中心临床试验的肿瘤T2*测量，并提高肿瘤T2*测量在共临床和多中心数据分析中的标准化和可重复性。

<img alt="Figure 10" class="xfigimg" src="/files/ftp_upload/64773/64773fig10.jpg"> 图 10：T2* 图，ROI 叠加在转移性骨肉瘤病变上，显示平均值和标准偏差 T2* 值。 <a href="https://www.jove.com/files/ftp_upload/64773/64773fig10large.jpg" target="_blank">请点击此处查看此图的大图。</a>
<img alt="Figure 11" class="xfigimg" src=...

Watch this Scientific Journal Video about Measurement of Tumor T2* Relaxation Times after Iron Oxide Nanoparticle Administration at JoVE.com

Measurement of Tumor T2* Relaxation Times after Iron Oxide Nanoparticle Administration

我们提出了一种标准化的方案，用于使用外部软件量化肿瘤的T2 *弛豫时间。采集多回波梯度回波图像并将其输入软件，以创建肿瘤T2*图并测量肿瘤T2*弛豫时间。

氧化铁纳米颗粒给药后肿瘤T2*弛豫时间的测量

T2* relaxometry is one of the established methods to measure the effect of superparamagnetic iron oxide nanoparticles on tumor tissues with magnetic ...

我们的协议可在各种扫描仪、制造商和机构中进行标准化的肿瘤 T2*测量。该协议无需编程语言即可提高质量保证和广泛的临床能力。该技术的主要优点是能够在各种MRI扫描仪上促进可靠和一致的肿瘤T2 *测量。此外，它提供了一种可访问且用户友好的方法，降低了采用的障碍。NOI 可能会在正确的序列设置和 ROI 选择方面遇到困难。建议遵循协议步骤，确保正确的T排列并练习ROI绘图，以实现准确的T2 *地图生成和拟合。首先启动OsiriX软件以安装T2 Fit Map插件。单击菜单栏上的插件按钮，然后从下拉菜单中选择插件管理器。加载插件管理器后，从可用插件中选择 T2 拟合贴图。单击下载安装。然后关闭插件管理器。重新启动软件后，将多回波渐变装饰序列图像作为DICOM文件加载到软件中。更改鼠标按钮功能以绘制感兴趣区域或 ROI。然后从下拉菜单中，选择椭圆形或封闭多边形或所需的形状，并在具有不同回声时间的所需图像中绘制ROI。从需要T2*映射的不同回波时间的图像中选择ROI。从下拉菜单中，单击插件按钮，选择图像过滤器，然后选择 T2 拟合贴图。单击 T2 拟合地图后，将打开一个对话框。然后点击生成地图。要在数据外部的图像序列上定义遮罩 ROI，请打开所需的序列并选择切片。从 ROI 下拉菜单中，选择增长区域和 3D 增长区域单选按钮。在算法下拉菜单中，选择阈值将下限阈值和上限分别设置为对侧肌肉信号的 0% 和 X %。根据需要命名投资回报率。然后单击图像以放置ROI增长的种子，然后单击“计算”。在“ROI”菜单中，选择“保存此系列的所有 ROI”。接下来，在 4D 查看器中打开数据集。确保 ROI 位于第一个 3D 体积中后，从 ROI 菜单中选择“导入 ROI”应用蒙版“以通过选择”将像素值设置为“来映射数据。然后选择”应用于具有相同名称的 ROI”。选中传播到 4D 系列框，将 ROI 内的像素设置为零，并将“到此新值”设置为零。这项研究显示了转移性骨肉瘤患者的T2*弛豫时间的量化。生成拟合曲线，其中包含所选ROI的最小，平均值和最大T2*值，以及该患者的不同回波时间。将颜色编码的T2*图与对比度增强的T1加权梯度装饰图像合并以进行解剖学定位。根据采集时间排列输入的多回波渐变装饰图像非常重要。这可以通过在首选项数据库下拉菜单下的外部软件中按采集时间对成像数据系列进行排序来实现。我们的方案显著提高了可重复性和可重复性，在各种癌症研究中提供了一致的T2*弛豫时间。

Research

JoVE Journal

Medicine

Mesenteric Artery Contraction and Relaxation Studies Using Automated Wire Myography

肠系膜动脉收缩和舒张的研究，使用自动线Myography

Proximal resistance vessels, such as the mesenteric arteries, contribute substantially to the peripheral resistance. These small vessels of between ...

科研

医学

Labeling Stem Cells with Ferumoxytol, an FDA-Approved Iron Oxide Nanoparticle

Ferumoxytol，一个FDA批准的氧化铁纳米粒子标记干细胞

Stem cell based therapies offer significant potential for the field of regenerative medicine. However, much remains to be understood regarding the in vivo ...

Analytical Techniques for Assaying Nitric Oxide Bioactivity

为含量测定一氧化氮生物活性分析技术

Nitric oxide (NO) is a diatomic free radical that is extremely short lived in biological systems (less than 1 second in circulating blood)1. NO may be ...

Intranasal Administration of CNS Therapeutics to Awake Mice

清醒小鼠滴鼻的CNS药物治疗管理

Intranasal administration is a method of delivering  therapeutic agents to the central nervous system (CNS). It is  non-invasive and allows large ...

Synthesis, Characterization, and Application of Superparamagnetic Iron Oxide Nanoprobes for Extrapulmonary Tuberculosis Detection

超超磁氧化铁纳米探针在肺外结核检测的合成、表征及应用

A molecular imaging probe comprising superparamagnetic iron oxide (SPIO) nanoparticles and Mycobacterium tuberculosis surface antibody (MtbsAb) was ...

Polyethyleneimine-coated Iron Oxide Nanoparticles as a Vehicle for the Delivery of Small Interfering RNA to Macrophages In Vitro and In Vivo

Polyethyleneimine-coated Iron Oxide Nanoparticles as a Vehicle for the Delivery of Small Interfering RNA to Macrophages In Vitro and In Vivo

聚乙胺包覆氧化铁纳米粒子作为载体, 在体外和体内向巨噬细胞输送小干扰 rna

Because of their critical role in regulating immune responses, macrophages have continuously been the subject of intensive research and represent a ...

Tracking Superparamagnetic Iron Oxide-labeled Mesenchymal Stem Cells using MRI after Intranasal Delivery in a Traumatic Brain Injury Murine Model

跟踪超副磁性氧化铁标记的美感血干细胞使用MRI后，创伤性脑损伤Murine模型内伤分娩

Stem cell-based therapies for brain injuries, such as traumatic brain injury (TBI), are a promising approach for clinical trials. However, technical ...

Measurement of Natural Killer Cell-Mediated Cytotoxicity and Migration in the Context of Hepatic Tumor Cells

肝肿瘤细胞背景下自然杀伤细胞介导细胞毒性和迁移的测量

Natural killer (NK) cells are a subset of the cytotoxic lymphocyte population of the innate immune system and participate as a first line of defense by ...

Intratracheal Administration of Dry Powder Formulation in Mice

小鼠干粉配方的内经管理

In the development of inhalable dry powder formulations, it is essential to evaluate their biological activities in preclinical animal models. This paper ...

Acetylcholine Re-Challenge After Intracoronary Nitroglycerine Administration

冠状动脉内给药硝酸甘油后乙酰胆碱再挑战

Coronary artery spasm (CAS) can be diagnosed in a large proportion of patients with recurrent angina with non-obstructive coronary artery disease (ANOCA) ...