衷心感谢Miriam Reinig的专家技术援助。 AH由海德堡大学医学院的博士后补助金资助。 MP由Else-Kröner-Fresenius基金会的纪念津贴支持。 AKM是德国感染研究中心（DZIF）DZIF学院的产假津贴的获得者。 JP是海德堡分子医学研究中心（HRCMM）职业发展奖学金的获得者。我们进一步感谢Julia M. Sattler和Friedrich Frischknecht提供了子孢子运动的典型电影。

本文中报道的所有动物实验均根据实验动物科学协会联合会（FELASA）B类和实验动物科学学会（GV-SOLAS）标准指南进行，并得到当地德国当局在卡尔斯鲁厄（卡尔斯鲁厄大学（RegierungspräsidiumKarlsruhe） ，德国）。请注意，生物安全级别2适用于蚊子和Bermhei疟原虫ANKA子孢子工作。 感染<ol><li>通过在拜访模式鼠标上喂养15分钟来感染按摩皂甙Stephensi蚊子与Berghei ANKA 疟原虫 。将感染的蚊子保持在80％湿度和21°C。 </li><li>在血餐后17天至22天，从笼子里收集女性蚊子。将它们放在冰上麻醉它们。 </li><li>使用镊子，将三至四只蚊子放在载有一滴冷RPMI培养基的玻片上。将幻灯片放在显微镜下。 </li> &lt;li&gt;使用镊子，小心翼翼地伸展头部和身体之间的蚊子。使用注射器和针头分离唾液腺。用剩余的蚊子重复这个步骤。 </li><li>通过用玻璃移液管吸取玻璃移液管，从玻片上收集唾液腺，并将其收集在1.5 mL离心管中。 注意:根据感染率，每唾液腺通常可以获得8,000至15,000个感染性子孢子。 </li><li>约3分钟，用小的塑料棒粉碎离心管内的分离的唾液腺，以将子孢子与唾液腺组织分离。 </li><li>在1,000×g和4℃下离心3分钟以净化剩余组织中的子孢子。 </li><li>将含有子孢子（SPZ）的上清液吸移到新的离心管中，并计数Neubauer血细胞计数器中的纯化子孢子。 </li><li>通过添加ph将浓缩的子孢子浓度调整为10,000 / mL盐酸缓冲盐水。 </li><li>将总共​​1000个子孢子（0.1mL）注入近交C57BL / 6小鼠的尾静脉中以引发感染。为了方便注射，将C57BL / 6小鼠置于限制器中，并将尾巴放入温热（约37℃）的水中以帮助尾静脉的可视化; 注意:注射本身是一个简短的过程，可以在几秒钟内完成。 </li><li>每天一次，在SPZ感染后，从第3天开始，检查血液涂片上的血液寄生虫血症。 注意:监测寄生虫血症以前在Mueller 等人的JoVE文章中可视化。 8 </li><li>从子孢子注射后的第5天开始，用Rapid Murine Coma and Behavior Scale（RMCBS）评分每日一次。 注意:Caroll 等人已经发表了此程序的详细描述，包括视频演示。 6 </li><li>评估根据RMCBS评分的MRI成像小鼠和研究问题需要解决。 6 </li></ol>磁共振成像设置<ol><li>使用用于射频传输的音量谐振器和4通道相控阵表面接收器线圈在9.4T小型动物扫描仪上进行MRI。将温度控制的水浴打开至42°C，以保持鼠标的体温。 </li><li>在室内使用2％异氟烷和压缩空气诱导麻醉，直到鼠标不再对脚趾反应。维持麻醉1-1.5％。 </li><li>将尾静脉导管放入小鼠的尾静脉。将鼠标放置在MRI上，并将其放置在装有头锁和牙杆的动物床上，以尽量减少头部运动。注意不要拉直老鼠的颈椎。 </li><li>将造影剂注射系统连接到尾静脉导管。使用填充有Gd-DTPA（0.3 mmol / kg）注射器的定制注射系统，或使用连接到Gd-DTPA（0.3 mmol / kg）注射器的PE管。 </li><li>将双酚茴香眼膏用于双眼。将4通道相控阵表面接收头线圈放置在鼠标头上。将呼吸垫放在鼠标背面并将其连接到呼吸监测装置上。 </li></ol>成像协议注意:根据要解决的研究问题，从下面列出的协议中选择成像序列。所有列出的参数对MRI软件有效，但如果使用其他软件程序，则可能需要进行调整。 <ol><li>首先进行本地化扫描，以确保鼠标的大脑位于磁铁的等中心。 </li><li> 为了定性评估血管性水肿，通过​​选择多切片RARE序列，使用3D T2加权成像。 <ol><li>输入以下pa参考MRI软件:重复时间= 2.000 ms，回波时间= 22 ms，各向同性分辨率= 0.1mm，视场= 20 x 10 x 12 mm 3 ;矩阵= 200×100×120，翻转角= 90〜180°; （自旋回波），稀有因子= 8.启动序列，等待10分48秒获取原始图像。 </li></ol></li><li> 定量评估血管性水肿，通过​​选择多切片多自旋回波序列来进行T2松弛度测定。 <ol><li>使用以下参数:重复时间= 3.100 ms，回波时间= 8-136 ms，增量为8 ms，切片数为17，切片厚度= 0.7 mm，平面分辨率= 0.116 mm x 0.116 mm，视场20 x 20 mm 2 ，矩阵= 172 x 172，翻转角= 90-180度; （自旋回波）。启动序列，等待8分53秒获取原始图像。 </li></ol></li><li> 为了定量评估血管性水肿和细胞毒性水肿，进行扩散加权成像/表观扩散系统通过选择自旋回波EPI扩散序列来实现（ADC）映射。 <ol><li>使用以下参数:重复时间= 3.400ms，回波时间= 20ms，切片厚度= 0.7mm，切片数= 17，扩散敏化方向数= 30，b值= 1.500s / mm 2 ，δ= 3ms ，Δ= 9ms，部分傅里叶编码加速因子= 1.51，视场= 12×15mm 2 ，矩阵= 96×128，平面内分辨率= 0.125mm×0.117mm，翻转角= 90-180度，以及饱和片数（矢状）= 1.启动序列，等待7分56秒，直到获取原始图像。 </li></ol></li><li> 评估微血肿，使用3D T2 *加权成像。选择流量补偿FLASH序列。 <ol><li>在MRI软件中输入以下参数:重复时间= 2.000 ms，回波时间= 22 ms，各向同性分辨率0.08 mm，视场= 32 x 15 x 8 mm 3 ，矩阵大小= 400 x 188 x 100，f唇角= 12度。启动序列，等待15分40秒获取原始图像。 </li></ol></li><li> 为了评估动脉通畅，通过选择3D FLASH序列来使用飞行时间血管造影。 <ol><li>在MRI软件中使用以下参数:重复时间= 16 ms，回波时间= 3.5 ms，切片厚度= 0.07 mm，平面内分辨率= 0.104 x 0.104 mm，视场= 20 x 20 x 10 mm 3 ，矩阵= 192×192×142，翻转角= 15度。启动序列并等待7分钟16秒直到获取图像。 </li></ol></li><li> 为了评估血脑屏障破坏，在造影剂注射0.3 mmol / kg之前和之后使用3D T1加权成像。选择具有全球射频激励的射频损坏FLASH序列。 <ol><li>在MRI软件中使用以下序列参数:重复时间= 5 ms，回波时间= 1.9 ms，各向同性分辨率= 0.156 mm，视场20 x 18.7×18.7mm 3 ，矩阵128×120×120，翻转角= 8.5°。启动序列并等待1分14秒，直到获取图像。 </li></ol></li></ol>图像处理与分析<ol><li>为了分析血脑屏障破坏，使用ImageJ中的算术工具或图像计算器工具从增强型T1加权图像中减去3D非增强T1加权图像。评估减法图像以增加信号，这对应于血脑屏障破坏。 9 </li><li>要分析大脑体积，请使用本机3D T1-或3D T2加权数据集。使用分割编辑器将大脑从嗅球描绘成小脑。 10 </li><li> 血管性水肿 <ol><li>用MRI软件处理T2松弛度数据或使用非线性最小二乘法拟合程序。 11使用MRI sof处理扩散加权数据以获得ADC图tware或FDT工具箱（请参阅材料表 ）。 </li><li>将感兴趣区域手动放置到不同的解剖区域。 注意:感兴趣区域的自动放置可能由于显着的大脑肿胀而不正确地注册。以这种方式获得所选解剖区域的T2时间和ADC值。 </li></ol></li><li>为了分析微出血体积，使用分割编辑器描绘在T2 *加权数据集上显示为卵形，黑色焦点的微出血。 </li></ol>

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The authors declare that they have no conflicts of interest.

在本文中，我们描述了一个全脑MRI方案来描绘实验性脑疟疾的变化。我们认为迄今为止，疟疾研究中MRI尚未得到充分利用，希望我们的方案能够帮助其他调查人员。我们想描述一些可能有帮助的附加要点。 如果严重恶心的小鼠成像，定位至关重要。由于颅内压升高，小鼠易死亡，因此颈椎不应伸展。麻醉也应保持在最低限度。如果轻度疾病的小鼠成像，MRI的最佳时间点是在预期首次出现临床症状前12-24小时。嗅球中的轻度血管性水肿在不显示ECM的临床体征的小鼠中是可见的（RMCBS评分为20）。 MRI协议本身的长度可以根据具体的研究问题进行调整。最小的原型col应包括T2加权序列或T2松弛度和T2 *加权序列，以判断血管性水肿和微血管负荷/微血管损伤的存在。为了获得优质图像，运动文物应保持在最低限度。运动将通过鼠标的适当定位并通过将呼吸速率保持在每分钟约60-80次呼吸来减少。 其他体内成像方法，如活体显微术，显示出在细胞水平上可视化ECM中的病理改变的希望。 14，15，16，17与MRI相比，活体显微镜可以提供高空间分辨率，但只能覆盖有限的皮层区域。相比之下，MRI能够以高达80μm的分辨率覆盖整个大脑。因此，MRI可以通过识别来指导进一步的细胞调查偏好地点 - 疾病的开始以及疾病的阶段，然后可以使用进一步的方法来评估疾病。可以将ECM中的MRI发现与在人脑疟疾中用MRI检测到的病理学改变进行比较。人类和实验性脑疟疾都在神经发生区域显示血管性水肿，以及微血管病变，如流域​​区域的继发性脑梗塞。 7，18白色和灰色物质以类似的方式受到影响，人和实验性脑疟疾中的脑肿胀都涉及严重疾病中的脑干，从而解释昏迷状态。 2，7 我们希望体内成像有助于揭开目前仍然难以捉摸的脑疟疾的潜在病理机制。由于水肿和脑肿胀几乎看不到体内，我在体内可视化这种病理学的方法是关键，将有助于改善新型疗法和疫苗接种的评估。

疟疾是一个重大的全球健康问题。 1严重疟疾的特征部分是脑受累，往往是不良预后因素。疟疾传播高的地区，五岁以下儿童的脑梗死是常见的，并且是该年龄组疟疾相关死亡的主要原因。 1虽然积极的治疗可以挽救生命，但是特别是早期阶段的脑疟疾检测可能很困难。涉及脑疟疾的病理过程包括微血管破裂和脑水肿，可导致严重的脑肿胀。在本文中，我们提出了磁共振成像（MRI）协议，允许全脑脑实验性脑疟疾（ECM） 体内成像。全脑高分辨率成像方法在这种疾病中已经广泛利用不足，尽管对ECM如何在中枢起搏方面知之甚少神经系统或什么具体机制导致疾病。涵盖全脑的体内 MRI代表了一种重要的研究工具，可以更好地了解ECM病理学。 MRI能够评估全球大脑脑肿胀，最近已经被认为是ECM的重要预测因子，也是人脑疟疾的重要预测因素。 2，3严重的脑肿胀发生在致命疾病中，代表了ECM模型与人类疾病之间的几种病理特征之一，其特征是炎症和微血管改变。 4 可以通过感染致死的疟原虫疟原虫ANKA在CBA或C57BL小鼠中诱导ECM 。 ECM的发病通常发生在感染后6天和10天之间，并且导致拟合，共济失调，呼吸窘迫和昏迷，这导致说唱id死亡。 4快速鼠类昏迷和行为量表（RMCBS）是评估ECM临床症状的有益成绩。它由10个参数组成，每个评分从0到2，最大可能得分为20. 6最近，我们在ECM小鼠中RMCBS评分的严重程度和MRI证实的病理变化之间表现出良好的一致性。 7在本协议中，我们描述了小鼠的ECM诱导和ECM小鼠的体内磁共振成像。

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Isoflurane</td>
			<td>Baxter</td>
			<td>1001747</td>
			<td>for anesthesia</td>
		</tr>
		<tr>
			<td>Dotarem</td>
			<td>Guebert</td>
			<td>1086923</td>
			<td>Gd-DTPA contrast agent; 0.5mmol/ml</td>
		</tr>
		<tr>
			<td>Amira (Image Processing Program)</td>
			<td>FEI Group</td>
			<td></td>
			<td>Version Amira 5.3.2</td>
		</tr>
		<tr>
			<td>MATLAB&#160;</td>
			<td>The MathWorks, Inc.,</td>
			<td></td>
			<td>Release 2012b</td>
		</tr>
		<tr>
			<td>FDT toolbox&#160;</td>
			<td colspan="2">FMRIB&#39;s Software Library</td>
			<td><a href="http://www.fmrib.ox.ac.uk/fsl/fdt/index.html">http://www.fmrib.ox.ac.uk/fsl/fdt/index.html</a></td>
		</tr>
	</tbody>
</table>

in vivo tracking of edema development and microvascular pathology in a model of experimental cerebral malaria using magnetic resonance imaging

Cerebral malaria is a sign of severe malarial disease and is often a harbinger of death. While aggressive management can be life-saving, the detection of cerebral malaria can be difficult. We present an experimental mouse model of cerebral malaria that shares multiple features of the human disease, including edema and microvascular pathology. Using magnetic resonance imaging (MRI), we can detect and track the blood-brain barrier disruption, edema development, and subsequent brain swelling. We describe multiple MRI techniques that can visualize these pertinent pathological changes. Thus, we show that MRI represents a valuable tool to visualize and track pathological changes, such as edema, brain swelling, and microvascular pathology, in vivo.

在C57BL / 6小鼠中，可以观察到ECM的第一临床症状，在用Berghei ANKA子孢子感染后的第 6天和第10天之间。 ECM在60-80％的感染小鼠中发展，并在24至48小时内迅速进入昏迷和死亡。相比之下，不会发展ECM的小鼠在感染后第二周因死于高血糖症严重贫血而死亡。 12 在MRI成像中，ECM的最早的迹象在嗅球中是可见的，嗅球属于小鼠的嗅觉系统，位于脑的脊髓部分。 7，13血脑屏障破裂的增加（在对比度增强的T1加权图像上看到）和流体增加（T2加权图像上的T2信号增加，T2弛豫测量和扩散加权成像）表明早期血管性水肿在已经存在轻度疾病（RMCBS评分20-16）的嗅球中，随着疾病的严重程度的增加而开始扩散。相对的T1信号图像有助于检测微小的血脑屏障中断（ 图1 ）。血脑屏障破坏和血管性水肿以特定的方式进展。这些病理变化沿着非常严重的疾病（RMCBS疮9-0）达到的脑干移植物流，成为神经母细胞的迁移途径。在T2图上， 如图2所示 ，通过将感兴趣的区域绘制到特定解剖区域可以量化血管性水肿的严重程度。对于每个区域，可以获得随着水肿增加而增加的T2弛豫时间。随着血管性水肿和血脑屏障破坏，脑肿胀开始于ECM严重程度增加。脑水肿指示水肿开始显着增加中度病态小鼠com与严重病态小鼠相比基线和进一步增加（ 图3 ）。 如血脑屏障破裂和血管性水肿的首次征象发生在微血管出血和血管易感性对比（对应于缓慢流量）的证据表明的微血管病理学，并且可以用T2 *加权成像显现。微出血主要发生在嗅球（ 图4 ）。随着进行性疾病，微出血数量增加。伴有进行性疾病，大脑皮质，基底神经节，小脑，白质和脑干中也出现微血管出血。 通过飞行时间血管造影术可以看出动脉通畅减少是与微血管变化平行的大血管损伤的征兆。脑梗塞不是ECM中的关键发现。然而，在非常严重的疾病，重点领域可以鉴定ADC减少，表明脑梗死。 <img alt="图1" src="/files/ftp_upload/55334/55334fig1.jpg" /> 图1:血脑屏障中断。 （ A ）代表冠状3D T1加权图像。在嗅球的中心区域中T1信号的增加是可见的。 （ B ）在相应的T1相对信号图像（T1对比度图像中减去T1对比度图像）后，造影剂外渗更易于描绘。造影剂外渗可见于额叶皮层区域（白色箭头）。 <a href="https://ecsource-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/55334/55334fig1large.jpg" target="_blank">请点击此处查看此图的较大版本。</a> <img alt="图2" src="/files/ftp_upload/55334/55334fig2.jpg" /> 图2:T2放松ometry。以不同高度的样本T2映射，其中RMCBS评分为5（ A ）的RMCBS评分和基线扫描（ B ）的不同高度以颜色标度显示，以灰度显示，灰度显示为ROI作为彩色重叠。深蓝色= RMS，绿色=皮质，绿松石=外胶囊，黄色=基底神经节，浅蓝色= DMS，橙色=丘脑，红色=脑干<a href="https://ecsource-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/55334/55334fig2large.jpg" target="_blank">请点击此处查看此图的较大版本。</a> <img alt="图3" src="/files/ftp_upload/55334/55334fig3.jpg" /> 图3:脑体积测量。中度病态小鼠的脑体积显着增加（RMCBS 15-10）。显示了10只小鼠的代表性值。数据表示为平均标准差。配对的学生t检验用于分析胸罩的差异在组之间膨胀。在中度/重度病态的小鼠中，与基线相比，脑体积显着增加（p = 0.021 / 0.001）。 <a href="https://ecsource-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/55334/55334fig3large.jpg" target="_blank">请点击此处查看此图的较大版本。</a> <img alt="图4" src="/files/ftp_upload/55334/55334fig4.jpg" /> 图4:微出血。显示在血液感染发生前（ A ）和感染RMCBS评分为14（ B和C ）的第8天之后的小鼠的代表性T2 *加权图像。在第一个图像中，没有明显的出血（ A ），而在第二和第三图像中，几个微出血是可见的，在嗅球中占优势（B:平面冠状图像; C:具有分段微出血的3D投影）。

Watch this Scientific Journal Video about In Vivo Tracking of Edema Development and Microvascular Pathology in a Model of Experimental Cerebral Malaria Using Magnetic Resonance Imaging at JoVE.com

In Vivo Tracking of Edema Development and Microvascular Pathology in a Model of Experimental Cerebral Malaria Using Magnetic Resonance Imaging

We describe a mouse model of experimental cerebral malaria and show how inflammatory and microvascular pathology can be tracked in vivo using magnetic resonance imaging.

使用磁共振成像实验性脑疟疾模型中的水肿发育​​和微血管病理学的体内追踪

Cerebral malaria is a sign of severe malarial disease and is often a harbinger of death. While aggressive management can be life-saving, the detection of ...

in-vivo-tracking-edema-development-microvascular-pathology-model

Nanyang Technological University

Research

JoVE Journal

Medicine

In Vivo Tracking of Edema Development and Microvascular Pathology in a Model of Experimental Cerebral Malaria Using Magnetic Resonance Imaging

6.4K 次观看.  Heidelberg University Hospital. We describe a mouse model of experimental cerebral malaria and show how inflammatory and microvascular pathology can be tracked in vivo using magnetic resonance imaging. 

视频: In Vivo Tracking of Edema Development and Microvascular Pathology in a Model of Experimental Cerebral Malaria Using Magnetic Resonance Imaging

Magnetic Resonance Derived Myocardial Strain Assessment Using Feature Tracking

Purpose: An accurate and practical method to measure parameters like strain in myocardial tissue is of great clinical value, since it has been shown, that strain is a more sensitive and earlier marker for contractile dysfunction than the frequently used parameter EF. Current technologies for CMR are time consuming and difficult to implement in clinical practice. Feature tracking is a technology that can lead to more automization and robustness of quantitative analysis of medical images with less time consumption than comparable methods.
Methods: An automatic or manual input in a single phase serves as an initialization from which the system starts to track the displacement of individual patterns representing anatomical structures over time. The specialty of this method is that the images do not need to be manipulated in any way beforehand like e.g. tagging of CMR images.
Results: The method is very well suited for tracking muscular tissue and with this allowing quantitative elaboration of myocardium and also blood flow.
Conclusions: This new method offers a robust and time saving procedure to quantify myocardial tissue and blood with displacement, velocity and deformation parameters on regular sequences of CMR imaging. It therefore can be implemented in clinical practice.

An accurate and practical method to measure parameters like strain in myocardial tissue is of great clinical value, since it has been shown, that strain is a more sensitive and earlier marker for contractile dysfunction than the frequently used parameter EF.

磁共振衍生的心肌劳损评估使用特征跟踪

Purpose: An accurate and practical method to measure parameters like strain in myocardial tissue is of great clinical value, since it has been shown, that ...

科研

医学

Magnetic Resonance Imaging Quantification of Pulmonary Perfusion using Calibrated Arterial Spin Labeling

This demonstrates a MR imaging method to measure the spatial distribution of pulmonary blood flow in healthy subjects 
during normoxia (inspired O2, fraction (FIO2) = 0.21) hypoxia (FIO2 = 0.125), and hyperoxia 
(FIO2 = 1.00). In addition, the physiological responses of the subject are monitored in the MR scan environment. MR images 
were obtained on a 1.5 T GE MRI scanner during a breath hold from a sagittal slice in the right lung at functional residual capacity. An arterial 
spin labeling sequence (ASL-FAIRER) was used to measure the spatial distribution of pulmonary blood flow 1,2 and a multi-echo fast 
gradient echo (mGRE) sequence 3 was used to quantify the regional proton (i.e. H2O) density, allowing the quantification 
of density-normalized perfusion for each voxel (milliliters blood per minute per gram lung tissue). 
With a pneumatic switching valve and facemask equipped with a 2-way non-rebreathing valve, different oxygen concentrations 
were introduced to the subject in the MR scanner through the inspired gas tubing. A metabolic cart collected expiratory gas via expiratory tubing. Mixed expiratory O2 and CO2 concentrations, oxygen consumption, carbon dioxide production, respiratory exchange ratio, 
respiratory frequency and tidal volume were measured. Heart rate and oxygen saturation were monitored using pulse-oximetry. 
Data obtained from a normal subject showed that, as expected, heart rate was higher in hypoxia (60 bpm) than during normoxia (51) or hyperoxia (50) and the arterial oxygen saturation (SpO2) was reduced during hypoxia to 86%. Mean ventilation was 8.31 L/min BTPS during hypoxia, 7.04 L/min during normoxia, and 6.64 L/min during hyperoxia. Tidal volume was 0.76 L during hypoxia, 0.69 L during normoxia, and 0.67 L during hyperoxia. 
Representative quantified ASL data showed that the mean density normalized perfusion was 8.86 ml/min/g during hypoxia, 8.26 ml/min/g during normoxia and 8.46 ml/min/g during hyperoxia, respectively. In this subject, the relative dispersion4, an index of global heterogeneity, was increased in hypoxia (1.07 during hypoxia, 0.85 during normoxia, and 0.87 during hyperoxia) while the fractal dimension (Ds), another index of heterogeneity reflecting vascular branching structure, was unchanged (1.24 during hypoxia, 1.26 during normoxia, and 1.26 during hyperoxia). 
Overview. This protocol will demonstrate the acquisition of data to measure the distribution of pulmonary perfusion noninvasively under conditions of normoxia, hypoxia, and hyperoxia using a magnetic resonance imaging technique known as arterial spin labeling (ASL). 
Rationale: Measurement of pulmonary blood flow and lung proton density using MR technique offers high spatial resolution images which can be quantified and the ability to perform repeated measurements under several different physiological conditions. In human studies, PET, SPECT, and CT are commonly used as the alternative techniques. However, these techniques involve exposure to ionizing radiation, and thus are not suitable for repeated measurements in human subjects.

A MR imaging method to study the distribution of pulmonary blood flow under a variety of physiological conditions, in this case exposure to three different inspired oxygen concentrations: hypoxia, normoxia, and hyperoxia, is described. This technique utilizes human pulmonary physiology research techniques in an MR scanning environment.

使用校准动脉自旋标记磁共振肺灌注显像定量

This demonstrates a MR imaging method to measure the spatial distribution of pulmonary blood flow in healthy subjects 
during normoxia (inspired O2, ...

Multi-modal Imaging of Angiogenesis in a Nude Rat Model of Breast Cancer Bone Metastasis Using Magnetic Resonance Imaging, Volumetric Computed Tomography and Ultrasound

Angiogenesis is an essential feature of cancer growth and metastasis formation. In bone metastasis, angiogenic factors are pivotal for tumor cell proliferation in the bone marrow cavity as well as for interaction of tumor and bone cells resulting in local bone destruction. Our aim was to develop a model of experimental bone metastasis that allows in vivo assessment of angiogenesis in skeletal lesions using non-invasive imaging techniques.
For this purpose, we injected 105 MDA-MB-231 human breast cancer cells into the superficial epigastric artery, which precludes the growth of metastases in body areas other than the respective hind leg1. Following 25-30 days after tumor cell inoculation, site-specific bone metastases develop, restricted to the distal femur, proximal tibia and proximal fibula1. Morphological and functional aspects of angiogenesis can be investigated longitudinally in bone metastases using magnetic resonance imaging (MRI), volumetric computed tomography (VCT) and ultrasound (US).
MRI displays morphologic information on the soft tissue part of bone metastases that is initially confined to the bone marrow cavity and subsequently exceeds cortical bone while progressing. Using dynamic contrast-enhanced MRI (DCE-MRI) functional data including regional blood volume, perfusion and vessel permeability can be obtained and quantified2-4. Bone destruction is captured in high resolution using morphological VCT imaging. Complementary to MRI findings, osteolytic lesions can be located adjacent to sites of intramedullary tumor growth. After contrast agent application, VCT angiography reveals the macrovessel architecture in bone metastases in high resolution, and DCE-VCT enables insight in the microcirculation of these lesions5,6. US is applicable to assess morphological and functional features from skeletal lesions due to local osteolysis of cortical bone. Using B-mode and Doppler techniques, structure and perfusion of the soft tissue metastases can be evaluated, respectively. DCE-US allows for real-time imaging of vascularization in bone metastases after injection of microbubbles7.
In conclusion, in a model of site-specific breast cancer bone metastases multi-modal imaging techniques including MRI, VCT and US offer complementary information on morphology and functional parameters of angiogenesis in these skeletal lesions.

In the pathogenesis of bone metastasis, angiogenesis is a crucial process and therefore represents a target for imaging and therapy. Here, we present a rat model of site-specific breast cancer bone metastasis and describe strategies to non-invasively image angiogenesis in vivo using magnetic resonance imaging, volumetric computed tomography and ultrasound.

利用磁共振成像，容积电脑断层扫描及超音波的裸鼠乳腺癌骨转移大鼠模型血管生成的多模态成像

Angiogenesis is an essential feature of cancer growth and metastasis formation. In bone metastasis, angiogenic factors are pivotal for tumor cell ...

In vivo 19F MRI for Cell Tracking

In vivo 19F MRI allows quantitative cell tracking without the use of ionizing radiation. It is a noninvasive technique that can be applied to humans. Here, we describe a general protocol for cell labeling, imaging, and image processing. The technique is applicable to various cell types and animal models, although here we focus on a typical mouse model for tracking murine immune cells. The most important issues for cell labeling are described, as these are relevant to all models. Similarly, key imaging parameters are listed, although the details will vary depending on the MRI system and the individual setup. Finally, we include an image processing protocol for quantification. Variations for this, and other parts of the protocol, are assessed in the Discussion section. Based on the detailed procedure described here, the user will need to adapt the protocol for each specific cell type, cell label, animal model, and imaging setup. Note that the protocol can also be adapted for human use, as long as clinical restrictions are met.

In vivo 19F MRI for Cell Tracking

We describe a general protocol for in vivo cell tracking using MRI in a mouse model with ex vivo labeled cells. A typical protocol for cell labeling, image acquisition processing and quantification is included.

在体内 19女性 MRI对细胞跟踪

In vivo 19F MRI allows quantitative cell tracking without the use of ionizing radiation. It is a noninvasive technique that can be applied to humans. ...

Noninvasive Assessment of Cardiac Abnormalities in Experimental Autoimmune Myocarditis by Magnetic Resonance Microscopy Imaging in the Mouse

Myocarditis is an inflammation of the myocardium, but only ~10% of those affected show clinical manifestations of the disease. To study the immune events of myocardial injuries, various mouse models of myocarditis have been widely used. This study involved experimental autoimmune myocarditis (EAM) induced with cardiac myosin heavy chain (Myhc)-&#945; 334-352 in A/J mice; the affected animals develop lymphocytic myocarditis but with no apparent clinical signs. In this model, the utility of magnetic resonance microscopy (MRM) as a non-invasive modality to determine the cardiac structural and functional changes in animals immunized with Myhc-&#945; 334-352 is shown. EAM and healthy mice were imaged using a 9.4 T (400 MHz) 89 mm vertical core bore scanner equipped with a 4 cm millipede radio-frequency imaging probe and 100 G/cm triple axis gradients. Cardiac images were acquired from anesthetized animals using a gradient-echo-based cine pulse sequence, and the animals were monitored by respiration and pulse oximetry. The analysis revealed an increase in the thickness of the ventricular wall in EAM mice, with a corresponding decrease in the interior diameter of ventricles, when compared with healthy mice. The data suggest that morphological and functional changes in the inflamed hearts can be non-invasively monitored by MRM in live animals. In conclusion, MRM offers an advantage of assessing the progression and regression of myocardial injuries in diseases caused by infectious agents, as well as response to therapies.

This study demonstrates the successful establishment of magnetic resonance microscopy imaging as a non-invasive tool to assess the cardiac abnormalities in mice affected with autoimmune myocarditis. The data indicate that the technique can be used to monitor the disease-progression in live animals.

心脏异常的实验性自身免疫性心肌炎的无创性评估磁共振成像显微镜在鼠标

Myocarditis is an inflammation of the myocardium, but only ~10% of those affected show clinical manifestations of the disease. To study the immune events ...

Tracking the Mammary Architectural Features and Detecting Breast Cancer with Magnetic Resonance Diffusion Tensor Imaging

Breast cancer is the most common cause of cancer among women worldwide. Early detection of breast cancer has a critical role in improving the quality of life and survival of breast cancer patients. In this paper a new approach for the detection of breast cancer is described, based on tracking the mammary architectural elements using diffusion tensor imaging (DTI). 
The paper focuses on the scanning protocols and image processing algorithms and software that were designed to fit the diffusion properties of the mammary fibroglandular tissue and its changes during malignant transformation. The final output yields pixel by pixel vector maps that track the architecture of the entire mammary ductal glandular trees and parametric maps of the diffusion tensor coefficients and anisotropy indices. 
The efficiency of the method to detect breast cancer was tested by scanning women volunteers including 68 patients with breast cancer confirmed by histopathology findings. Regions with cancer cells exhibited a marked reduction in the diffusion coefficients and in the maximal anisotropy index as compared to the normal breast tissue, providing an intrinsic contrast for delineating the boundaries of malignant growth. Overall, the sensitivity of the DTI parameters to detect breast cancer was found to be high, particularly in dense breasts, and comparable to the current standard breast MRI method that requires injection of a contrast agent. Thus, this method offers a completely non-invasive, safe and sensitive tool for breast cancer detection.

We describe how to obtain parametric and vector maps of the diffusion tensor of the breast using magnetic resonance imaging. The protocol and final output following imaging processing are tailored for tracking breast architectural features and detecting breast malignancy.

跟踪乳腺建筑特色与检测乳腺癌的磁共振扩散张量成像

Breast cancer is the most common cause of cancer among women worldwide. Early detection of breast cancer has a critical role in improving the quality of ...

Simultaneous PET/MRI Imaging During Mouse Cerebral Hypoxia-ischemia

Dynamic changes in tissue water diffusion and glucose metabolism occur during and after hypoxia in cerebral hypoxia-ischemia reflecting a bioenergetics disturbance in affected cells. Diffusion weighted magnetic resonance imaging (MRI) identifies regions that are damaged, potentially irreversibly, by hypoxia-ischemia. Alterations in glucose utilization in the affected tissue may be detectable by positron emission tomography (PET) imaging of 2-deoxy-2-(18F)fluoro-&#7429;-glucose ([18F]FDG) uptake. Due to the rapid and variable nature of injury in this animal model, acquisition of both modes of data must be performed simultaneously in order to meaningfully correlate PET and MRI data. In addition, inter-animal variability in the hypoxic-ischemic injury due to vascular differences limits the ability to analyze multi-modal data and observe changes to a group-wise approach if data is not acquired simultaneously in individual subjects. The method presented here allows one to acquire both diffusion-weighted MRI and [18F]FDG uptake data in the same animal before, during, and after the hypoxic challenge in order to interrogate immediate physiological changes.

The method presented here uses simultaneous positron emission tomography and magnetic resonance imaging. In the cerebral hypoxia-ischemia model, dynamic changes in diffusion and glucose metabolism occur during and after injury. The evolving and irreproducible damage in this model necessitates simultaneous acquisition if meaningful multi-modal imaging data are to be acquired.

同时PET / MRI成像在小鼠脑缺氧缺血

Dynamic changes in tissue water diffusion and glucose metabolism occur during and after hypoxia in cerebral hypoxia-ischemia reflecting a bioenergetics ...

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

Along with their traditional role as detergents that facilitate fat absorption, emerging literature indicates that bile acids are potent signaling molecules that affect multiple organs; they modulate gut motility and hormone production, and alter vascular tone, glucose metabolism, lipid metabolism, and energy utilization. Changes in fecal bile acids may alter the gut microbiome and promote colon pathology including cholerrheic diarrhea and colon cancer. Key regulators of fecal bile acid composition are the small intestinal Apical Sodium-dependent Bile Acid Transporter (ASBT) and fibroblast growth factor-19 (FGF19). Reduced expression and function of ASBT decreases intestinal bile acid up-take. Moreover, in vitro data suggest that some FDA-approved drugs inhibit ASBT function. Deficient FGF19 release increases hepatic bile acid synthesis and release into the intestines to levels that overwhelm ASBT. Either ASBT dysfunction or FGF19 deficiency increases fecal bile acids and may cause chronic diarrhea and promote colon neoplasia. Regrettably, tools to measure bile acid malabsorption and the actions of drugs on bile acid transport in vivo are limited. To understand the complex actions of bile acids, techniques are required that permit simultaneous monitoring of bile acids in the gut and metabolic tissues. This led us to conceive an innovative method to measure bile acid transport in live animals using a combination of proton (1H) and fluorine (19F) magnetic resonance imaging (MRI). Novel tracers for fluorine (19F)-based live animal MRI were created and tested, both in vitro and in vivo. Strengths of this approach include the lack of exposure to ionizing radiation and translational potential for clinical research and practice.

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

Tools to diagnose bile acid malabsorption and measure bile acid transport in vivo are limited. An innovative approach in live animals is described that utilizes combined proton (1H) plus fluorine (19F) magnetic resonance imaging; this novel methodology has translational potential to screen for bile acid malabsorption in clinical practice.

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 ...

Cardiac Magnetic Resonance Imaging at 7 Tesla

CMR at an ultra-high field (magnetic field strength B0&#160;&#8805; 7 Tesla) benefits from the signal-to-noise ratio (SNR) advantage inherent at higher magnetic field strengths and potentially provides improved signal contrast and spatial resolution. While promising results have been achieved, ultra-high field CMR is challenging due to energy deposition constraints and physical phenomena such as transmission field non-uniformities and magnetic field inhomogeneities. In addition, the magneto-hydrodynamic effect renders the synchronization of the data acquisition with the cardiac motion difficult. The challenges are currently addressed by explorations into novel magnetic resonance technology. If all impediments can be overcome, ultra-high field CMR may generate new opportunities for functional CMR, myocardial tissue characterization, microstructure imaging or metabolic imaging. Recognizing this potential, we show that multi-channel radio frequency (RF) coil technology tailored for CMR at 7 Tesla together with higher order B0 shimming and a backup signal for cardiac triggering facilitates high fidelity functional CMR. With the proposed setup, cardiac chamber quantification can be accomplished in examination times similar to those achieved at lower field strengths. To share this experience and to support the dissemination of this expertise, this work describes our setup and protocol tailored for functional CMR at 7 Tesla.

The sensitivity gain inherent to ultrahigh field magnetic resonance holds promise for high spatial resolution imaging of the heart. Here, we describe a protocol customized for functional cardiovascular magnetic resonance (CMR) at 7 Tesla using an advanced multi-channel radio-frequency coil, magnetic field shimming and a triggering concept.

7号特斯拉的心脏磁共振成像

CMR at an ultra-high field (magnetic field strength B0&#160;&#8805; 7 Tesla) benefits from the signal-to-noise ratio (SNR) advantage inherent at higher ...

In Vivo Morphometric Analysis of Human Cranial Nerves Using Magnetic Resonance Imaging in Meni&#232;re's Disease Ears and Normal Hearing Ears

Analysis of neural structures in Meni&#232;re's Disease (MD) is of importance, since a loss of such structures has previously been proposed for this patient group but has yet to be confirmed. This protocol describes a method of in vivo evaluation of neural changes especially well suitable for cranial nerve analysis using magnetic resonance imaging (MRI). MD-patients and normal hearing persons were examined in a 3-T MR-scanner using a scan protocol including strongly T2-weighted 3D gradient-echo-sequence (3D-CISS). In the patient group, MD was additionally confirmed using MRI-based assessment of endolymphatic hydrops. Morphometric analysis was performed using a freeware DICOM viewer. Evaluation of cranial nerves included measurements of cross-sectional areas (CSAs) of the nerves at different levels as well as orthogonal diametric measurements.

To evaluate morphological changes of cranial nerves such as loss of neural structures or swelling of cranial nerves in Meni&#232;re&#39;s Disease (MD) or in healthy persons in vivo, a protocol of evaluation has been developed using magnetic resonance imaging (MRI). Additional MRI-based confirmation of MD was performed.

体内Menière 病耳和正常听觉的磁共振成像对人颅神经的形态学分析

Analysis of neural structures in Meni&#232;re's Disease (MD) is of importance, since a loss of such structures has previously been proposed for this ...

使用磁共振成像实验性脑疟疾模型中的水肿发育​​和微血管病理学的体内追踪

使用磁共振成像实验性脑疟疾模型中的水肿发育和微血管病理学的体内追踪