罗伯特 Gürkov 接受了拨款从德国研究和教育部 BMBF, 格兰特01号0901。

所有程序均经当地道德委员会批准 (慕尼黑大学/LMU 慕尼黑093-09 号议定书机构审查委员会)。所有患者都对所执行的程序给予知情同意。
1. 临床检查
<ol><li>识别患有疑似 MD 的患者, 与该部门合作进行耳鼻喉部的治疗。<ol>
<li>进行临床评估;眩晕, 耳鸣/耳铃, 听力损失 (可能波动) 需要评估。检查相关的恶心和呕吐。检查症状的持续时间。</li>
		<li>将临床和功能测试结果考虑到对 MD 的诊断: 检查听力、热量视频 oculography、前庭诱发肌电电位 (VEMP) 和 electrocochleography (ECoG) 在医院文件中的结果或电子病历系统。</li>
		<li>检查 MD 的典型发现: 测听可能显示纯音平均 (PTA) 听力水平受损, 热量灌溉可以揭示水平半圆麻痹, SP/AP 比可能在 ECoG 病理上高, VEMP 耳间振幅比可能是在 MD 患者中明显降低。</li>
	</ol>
</li>
</ol>2. MD 和健康控制患者的 MRI 图像采集
<ol><li>在患者组 MRI 扫描前应用鼓室钆注射液24小时。注射0.4 毫升的钆造影剂 intratympanically, (例如, Magnograf 稀释8倍的生理盐水), 24 小时之前的计划 MRI 扫描。</li>
	<li>为 MRI 检查准备病人: 检查金属植入物 (如果采取适当的预防措施, 则可以使用起搏器进行测试; 牙科植入通常是可行的), 幽闭恐惧症,等等使用降噪装置, 如减少噪音用于保护患者听觉的耳机。</li>
	<li>将病人充分定位到扫描仪中。将病人的头部伸直, 并合上并关闭 MR 头线圈。将病人的头部/颞骨放置在 MR 扫描仪的 isocenter。</li>
	<li>根据研究协议进行 MRI 扫描, 包括 3 d 型和3维-真实红外序列检测患者组淋巴积液和强 T2-weighted 3 d-连对患者组颅神经形态分析及健康的控制。</li>
	<li>为形态学扫描3维连设置序列参数, 如下所示: 重复时间 (TR) 5.79 毫秒, 回声时间 (TE) 2.58 毫秒, 翻转角度 34°, 视场 (FoV) 160 x 160 毫米2, 矩阵大小 320 x 320, 平均值 1, 切片厚度0.5 毫米 (表1).用9000毫秒的 TR 进行3维的扫描 TE 128 毫秒, 反转时间2500毫秒, 翻转角度的 180°, 基体尺寸 384 x 384, 切片厚度2毫米. 将3维 d 实际 IR 的参数设置为: TR 6000 毫秒, TE 155 毫秒, 反转时间1500毫秒, 翻转角度 180°, 基体尺寸 320 x 320, 片厚0.5 毫米。</li>
</ol>3. mri 对淋巴积液的 mri 质量检查和鉴定
<ol><li>检查 MRI 图像质量方面的工件, 如折叠工件, 脉动工件, 金属工件, 并采取特别帐户的评估目标, 在这种情况下, 脑神经七和八在整个过程中。</li>
	<li>评价患者组 MRI 扫描的淋巴积液。检查所获得的 3 d-天赋和3维-真实 IR 序列 (图 1) 检测到的耳蜗和迷宫淋巴积水的程度。</li>
</ol>4. 基于图像的颅神经测量
<ol><li>一般准备工作
	<ol>
<li>在评估工作站 (例如、OsiriX 或 Horos) 上安装图像评估和测量选择的 DICOM 查看器。</li>
		<li>通过双击应用程序的图标来运行 DICOM 查看器;将显示 "数据库" 窗口。</li>
		<li>通过鼠标左键单击上拉菜单上的 "文件" 导入患者图像数据, 然后选择 "导入" → "导入文件"。在文件选择器中, 选择患者图像数据;成功导入后, 患者姓名和数据将显示在 "数据库" 窗口中。 注意: 在上述 dicom 查看器中, 输入压缩文件 (例如、. zip) 或未压缩的 dicom 文件目录是可行的。</li>
		<li>在 "数据库" 窗口中, 通过左键单击患者姓名左侧的三角形符号, 展开 "病人图像" 文件夹。从这个文件夹选择序列 (这里连序列) 和双击它打开相应的图像数据。将显示患者图像数据。</li>
	</ol></li>
	<li>颅神经重建 注: 由于从脑干的神经通过桥小脑角 (CPA) 进入声道和进一步到内听觉管的眼底的时间长而不总是在平面过程中, 重建和评价神经的直径和在不同级别的 csa 是必要的。<ol>
<li>在颅神经整个过程中, 准备重建以下位置的横断面, 以避免在整个神经过程中从斜片中产生测量误差, 在 "3D 查看器" 下拉菜单中选择 "3D 平面"。在屏幕的顶部;将显示 "多平面" 窗口。</li>
		<li>调整缩放级别, 以适应要重建的结构 (这里脑神经 VII 和 VIII) 通过选择缩放工具 (放大镜) 从 "改变鼠标按钮功能" 区域在工具栏上左上半部分的多平面窗口。然后将鼠标光标移动到 "平面" 窗口中的3个平面中的每一个, 并通过向左单击并拖动鼠标来调整缩放级别 (鼠标光标将转换为放大镜)。</li>
		<li>重建中心 VIII 神经, 并将重建平面正交到神经过程中的 CPA。检查和适应所有3个平面/窗口中重建平面的方向 (应将其与神经交叉方向进行正交重建, 以避免在以下测量中产生局部体积效应)。<ol>
<li>检查是否有平面外遍历神经, 并分别校正平面方向。<ol>
<li>要纠正平面方向, 请将鼠标光标移动到多平面窗口中每面的轴十字线的中心 (当定位正确时, 鼠标光标将转换为手形符号)。</li>
				<li>用手形图标所指示的抓取工具单独抓取3个平面/窗口中的轴十字线, 并将轴近似地移动到3个平面中每一个内部的声波道。</li>
				<li>通过将鼠标移动到每个轴的侧面, 将3轴的方向调整到神经的路线上 (通过将鼠标光标更改为曲线图标, 可以描述正确的旋转函数)。然后按住鼠标左键按下并拖动鼠标调整平面方向。</li>
				<li>调整平面方向在所有3窗口的多平面化窗口。为了重建一个平面横向到八神经路线在中央的注册会计师, 转到左下窗在平面化窗口, 并移动鼠标到中间的轴十字线, 使鼠标光标将再次转换成一个手势符号。然后左键单击并拖动平面 (橙色线) 到所需位置 (这里, 到注册会计师中间)。</li>
				<li>如果需要缩放工具 (鼠标将通过左击和拖动将其图标更改为放大镜), 请调整缩放级别。</li>
				<li>左键单击到 "平面化" 窗口的右上窗, 选择此平面。选择 "文件" → "导出" → "导出到 DICOM 文件"。在 "DICOM 导出"-窗口选择 "序列:" → "仅当前图片" 由左击入毗邻圈子选择器。</li>
				<li>适当地重命名系列, 这里 "八注册会计师"。然后左键单击 DICOM 导出窗口右下半部分的 "确定" 按钮。 注: 这将关闭 DICOM 导出窗口, 将重建后的图像保存到患者数据库中, 并返回到 "平面图" 窗口。</li>
			</ol>
</li>
		</ol>
</li>
		<li>重建八神经分支的正交视图: 耳蜗神经 (CN), 前庭神经 (SVN) 和下前庭神经 (IVN) 在该科的道的水平, 其中代表性可视化通常是很可行的。检查是否有平面外遍历神经, 并分别校正平面方向。<ol>
<li>抓住3个平面/窗口中的轴十字线, 用手形图标表示的抓取工具, 将 axis 分别移动到 CN、SVN 和 IVN, 并将其方向调整为神经的航向, 使用旋转函数可在曲线图标所描述的每个轴的侧面进行, 如步骤 4.2. 3.1. 1-4.2. 3.1. 5。</li>
			<li>导出和重命名重建的飞机, 步骤 4.2. 3.1. 6-4.2. 3.1. 7。</li>
		</ol>
</li>
		<li>重建面神经 (颅神经 VII) 的正交视图, 在注册会计师的水平, 4.2.3 的道, 以及在《步骤》下所述的综合理事会的眼底。在每一级重建时, 检查神经的平面外遍历, 并分别校正平面方向。</li>
	</ol></li>
	<li>测量 注: 执行以下测量: 在重建的横向图像中, 测量 CSA, 长直径 (LD) 和垂直短直径 (SD) 面神经 (颅神经 VII) 和前庭蜗神经 (颅神经 VIII) (图4和图 5)。注意在扫描之间保持一致的窗口化水平, 以避免局部体积效应以非系统性方式影响定量测量。<ol>
<li>通过在 DICOM 查看器的 "数据库" 窗口中, 通过左键单击相应的图像文件 (以前命名为 "VIII 注册会计师"), 选择先前重建的颅神经八级图像。通过双击文件名打开它。重建后的图像将在一个窗口中打开。</li>
		<li>如有必要, 请按步骤4.2.2 中的指示放大图像结构。在屏幕顶部的工具栏上的 "更改鼠标按钮函数" 旁边的三角形符号上, 选择 "长度", 左键单击鼠标。左键单击并按住鼠标左键按下, 绘制一条线, 测量颅神经的最长直径八;这个测量是 LD。</li>
		<li>对 SD 测量进行垂直于 LD 的测量。 注意: 如果使用 OsiriX 或 Horos 作为 DCIOM 查看器, 测量将自动存储。<ol>
<li>重复这些测量的 LD 和 SD 也在重建的八神经在耳道的水平, 通过测量图像文件从图像数据库名为 "八道", 并在其眼底水平, 文件名为 "VIII。</li>
		</ol>
</li>
		<li>评估 CSA 最好使用封闭的多边形区域的兴趣 (ROI), 以考虑可能的不均匀性在颅神经的横断面轮廓。在屏幕上部的工具栏上, 按 "鼠标按钮函数" 区域右侧的三角形符号, 然后选择 "闭合多边形" (先前选定的线条符号将变为多边形)。</li>
		<li>通过左键在神经的边界上多次显示颅神经 VIII 的轮廓。在所需的点上关闭多边形双左键;将显示完整的轮廓。 注: 如果需要, 通过左键和移动来纠正多边形点的位置。</li>
		<li>打开先前在注册会计师级别上进行的面部神经重建 (图像文件名 "VII 注册会计师"), 并执行 4.3.1 4.3.5 后的颅神经 vii 的 LD、SD 和 CSA 的测量。</li>
		<li>在 IVN 的道上打开重建, 并对 CN、SVN、和颅神经七级的 LD、SD 和 CSA 进行测量, 步骤 4.3.1 4.3.5。</li>
		<li>在 IVN 的眼底层打开重建, 并对 CN、SVN、和颅神经七级的 LD、SD 和 CSA 进行测量, 步骤 4.3.1 4.3.5。</li>
	</ol></li>
</ol>

<ol>
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作者没有什么可透露的。

我们已经展示了一种可行的和可接近的方法评估颅神经的形态学变化, 因为它们可能发生在几个病理生理学的情况下, 这里在 MD 与正常听力控制。
修改和疑难解答:
对在这里报告的 7th和 8th颅神经的类似测量可以使用对不同级别的所有其他颅神经进行的3维连序列扫描, 只要它们仍然被脑液包围,否则, 与上述 MR 扫描序列技术可能...

磁共振成像 (MRI) 在人体解剖学和生理病理过程的可视化和分析中起着重要的作用。由于 Menière 疾病 (MD) 的临床和电生理诊断可能具有挑战性, 因此, 使用来自 MRI 的附加信息比帮助1、2、3、4更有用。采用体内方法, 通过 MRI 对 MD 淋巴积液和颅神经形态变化进行分析。采用这种联合方法, 对确定 MD 的诊断进行了验证, 并在整个神经过程中对颅神经的形态学变化进行了不同程度的研究。MD 的病因仍然不清楚5,6,7。有人建议, 神经细胞丧失可能涉及 MD, 但这还有待证实。
本研究分析了在 MD 中, 适合的颅神经用于形态学分析的7个th和8个th神经及其分支。只有少数研究可以被发现分析这些神经的形态学方面使用 MRI8,9,10。Henneberger et . 的研究分析了 7th和 8th脑神经在 MD 耳中的形态学变化, 与正常的听觉耳朵11相比。
这里提出的方法使在体内可视化和形态学分析的 7th和 8th脑神经在整个过程中从大脑到颞骨。使用这种方法, 我们发现 MD 患者组与健康耳有显著差异。我们建议在几种情况下使用的描述方法, 只要潜在的形态学变化的颅神经感兴趣。这种方法是否将建立在临床诊断资料仍有待评估的未来研究。实际的替代方法为在体内评估颅骨神经形态学变化, 而计算机断层扫描 (CT) 有它的优势, 如广泛的可用性, 速度和骨骼变化的描述, 它也表现出太低的组织对比, 以想象在脑颅和颞骨的颅神经微妙的变化。尸检后对 MD 患者颅神经变化的分析有待研究。以特殊的影像和评价技术为例, 可以分析 MD 患者颅神经的形态学变化和健康控制的 MRI。常规 MRI 检查的大脑往往不包括高分辨率, 强烈 T2-weighted 成像技术, 这是强制性的评估形态学变化的颅神经7和8。
所开发的方法可能进一步诊断的影响, 以评估不同程度的严重性在 MD, 以及发挥作用, 评估眩晕, 听力缺损, 和耳鸣。眩晕诊断和治疗检查专门中心在今天的医疗保健系统中起着重要作用, 我们的方法可以为专家提供诊断检查的可能工具12,13,14.眩晕是一种复杂的症状发生在一些疾病, 需要一个彻底的跨学科合作, 不同的专业, 如在诊断和治疗眩晕的专门中心显示12,13,14。
根据我们的知识, 在文献中没有任何方法可用于在医学和健康控制中对颅神经进行体内形态学分析。

<table border="0" cellpadding="0" cellspacing="0" style="width:572px;" width="573">
	<colgroup>
		<col />
		<col />
		<col />
		<col />
	</colgroup>
	<tbody>
		<tr height="189">
			<td height="189" style="height:189px;width:216px;">MR-scanner, e.g. Siemens Magnetom Verio, or appropriate MR-scans in DICOM format, e.g. 3D-CISS</td>
			<td style="width:71px;">Siemens Healthcare GmbH, Erlangen, Germany, or MR scans by any other vendor</td>
			<td align="right" style="width:119px;">1</td>
			<td style="width:167px;">Instead of the MR scanner, appropriately acquired MR-scans can be used for morphometric analysis</td>
		</tr>
		<tr height="105">
			<td height="105" style="height:105px;width:216px;">Osirix or any other DICOM-Viewer with appropriate evaluation tools</td>
			<td style="width:71px;">Pixmeo SARL, Geneva, Switzerland</td>
			<td align="right" style="width:119px;">2</td>
			<td>Software for viewing and evaluating DICOM images</td>
		</tr>
		<tr height="105">
			<td height="105" style="height:105px;width:216px;">MedCalc or any other statistical analysis software, e.g. SPSS&#160;</td>
			<td style="width:71px;">MedCalc Software bvba, Ostend, Belgium</td>
			<td align="right" style="width:119px;">3</td>
			<td>Software for statistical analysis</td>
		</tr>
		<tr height="105">
			<td height="105" style="height:105px;width:216px;">Computer running Windows or MacOSX/macOS</td>
			<td style="width:71px;">e.g. Lenovo, Apple or anything selfmade</td>
			<td align="right" style="width:119px;">4</td>
			<td>Hardware on which the above software can be employed</td>
		</tr>
	</tbody>
</table>

in vivo morphometric analysis of human cranial nerves using magnetic resonance imaging in meni&#232;re's disease ears and normal hearing ears

Menière 病 (MD) 的神经结构分析是非常重要的, 因为这种结构的损失以前已经提出给这个病人组, 但尚未证实。本协议描述了一种在体内评估神经变化的方法, 特别适用于磁共振成像 (MRI) 颅神经分析。使用扫描协议 (包括强 T2-weighted 3D 梯度-回声序列 (3 连), 在3吨 MR 扫描仪中检查 MD 患者和正常听力者。在患者组中, 通过 MRI 对淋巴积液的评估, 进一步证实了 MD。形态学分析是使用免费的 DICOM 查看器进行的。颅神经的评估包括测量不同级别神经的横截面积 (csa) 以及正交直径测量。

采用统计分析软件进行统计分析, 应用双侧独立样本t测试。图像评价由两个读者进行。患者组平均值 (n = 21) 和健康对照组 (n = 39) 之间的显著差异可用于测量面神经、CN、SVN 和 IVN (表 2) 的 CSA。csa 在患者组中的测量显示了显著较大的 csa 值 (图 2和图 3)。对 ld 和 sd 的测量结果进行了不同的评估, 根据测量地点?...

Watch this Scientific Journal Video about In Vivo Morphometric Analysis of Human Cranial Nerves Using Magnetic Resonance Imaging in MeniÃ¨re's Disease Ears and Normal Hearing Ears at JoVE.com

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

目的评价颅神经的形态学变化, 如神经结构丧失或颅神经肿胀 (MD) 或健康人在体内, 采用磁共振成像 (MRI) 建立了 Menière 的评价协议。.另外还对 MD 进行了 MRI 诊断。

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 ...

in-vivo-morphometric-analysis-human-cranial-nerves-using-magnetic

Research

JoVE Journal

Medicine

10.4K 次观看.  LMU Munich. 目的评价颅神经的形态学变化, 如神经结构丧失或颅神经肿胀 (MD) 或健康人在体内, 采用磁共振成像 (MRI) 建立了 Menière 的评价协议。.另外还对 MD 进行了 MRI 诊断。

视频: In Vivo Morphometric Analysis of Human Cranial Nerves Using Magnetic Resonance Imaging in Menière's Disease Ears and Normal Hearing Ears

Making Sense of Listening: The IMAP Test Battery

The ability to hear is only the first step towards making sense of the range of information contained in an auditory signal. Of equal importance are the abilities to extract and use the information encoded in the auditory signal. We refer to these as listening skills (or auditory processing AP). Deficits in these skills are associated with delayed language and literacy development, though the nature of the relevant deficits and their causal connection with these delays is hotly debated.
When a child is referred to a health professional with normal hearing and unexplained difficulties in listening, or associated delays in language or literacy development, they should ideally be assessed with a combination of psychoacoustic (AP) tests, suitable for children and for use in a clinic, together with cognitive tests to measure attention, working memory, IQ, and language skills. Such a detailed examination needs to be relatively short and within the technical capability of any suitably qualified professional. Current tests for the presence of AP deficits tend to be poorly constructed and inadequately validated within the normal population. They have little or no reference to the presenting symptoms of the child, and typically include a linguistic component. Poor performance may thus reflect problems with language rather than with AP. To assist in the assessment of children with listening difficulties, pediatric audiologists need a single, standardized child-appropriate test battery based on the use of language-free stimuli.
We present the IMAP test battery which was developed at the MRC Institute of Hearing Research to supplement tests currently used to investigate cases of suspected AP deficits. IMAP assesses a range of relevant auditory and cognitive skills and takes about one hour to complete. It has been standardized in 1500 normally-hearing children from across the UK, aged 6-11 years. Since its development, it has been successfully used in a number of large scale studies both in the UK and the USA. IMAP provides measures for separating out sensory from cognitive contributions to hearing. It further limits confounds due to procedural effects by presenting tests in a child-friendly game-format. Stimulus-generation, management of test protocols and control of test presentation is mediated by the IHR-STAR software platform. This provides a standardized methodology for a range of applications and ensures replicable procedures across testers. IHR-STAR provides a flexible, user-programmable environment that currently has additional applications for hearing screening, mapping cochlear implant electrodes, and academic research or teaching.

A test battery (IMAP) for performing an in-depth assessment of auditory and cognitive abilities contributing to listening skills is described. It is quick to administer, child-friendly and free from linguistic confounds. Stimulus generation and protocol management are controlled via a software platform (IHR-STAR) to ensure replicable procedures.

听力:IMAP测试电池的决策意识

The ability to hear is only the first step towards making sense of the range of information contained in an auditory signal. Of equal importance are the ...

科研

医学

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 ...

Isolation of Soluble and Insoluble PrP Oligomers in the Normal Human Brain

The central event in the pathogenesis of prion diseases involves a conversion of the host-encoded cellular prion protein PrPC into its pathogenic isoform PrPSc 1. PrPC is detergent-soluble and sensitive to proteinase K (PK)-digestion, whereas PrPSc forms detergent-insoluble aggregates and is partially resistant to PK2-6. The conversion of PrPC to PrPSc is known to involve a conformational transition of &alpha;-helical to &beta;-sheet structures of the protein. However, the in vivo pathway is still poorly understood. A tentative endogenous PrPSc, intermediate PrP* or "silent prion", has yet to be identified in the uninfected brain7.
Using a combination of biophysical and biochemical approaches, we identified insoluble PrPC aggregates (designated iPrPC) from uninfected mammalian brains and cultured neuronal cells8, 9. Here, we describe detailed procedures of these methods, including ultracentrifugation in detergent buffer, sucrose step gradient sedimentation, size exclusion chromatography, iPrP enrichment by gene 5 protein (g5p) that specifically bind to structurally altered PrP forms10, and PK-treatment. The combination of these approaches isolates not only insoluble PrPSc and PrPC aggregates but also soluble PrPC oligomers from the normal human brain. Since the protocols described here have been used to isolate both PrPSc from infected brains and iPrPC from uninfected brains, they provide us with an opportunity to compare differences in physicochemical features, neurotoxicity, and infectivity between the two isoforms. Such a study will greatly improve our understanding of the infectious proteinaceous pathogens. The physiology and pathophysiology of iPrPC are unclear at present. Notably, in a newly-identified human prion disease termed variably protease-sensitive prionopathy, we found a new PrPSc that shares the immunoreactive behavior and fragmentation with iPrPC 11, 12. Moreover, we recently demonstrated that iPrPC is the main species that interacts with amyloid-&beta; protein in Alzheimer disease13. In the same study, these methods were used to isolate Abeta aggregates and oligomers in Alzheimer's disease13, suggesting their application to non-prion protein aggregates involved in other neurodegenerative disorders.

A new species of cellular prion protein (PrPC) has recently been identified in uninfected human brains using the methods described here. These methods can be used to isolate various PrP species, while some of them are also useful in isolating other misfolded protein aggregates from human brains.

在正常人脑分离的可溶性和不溶性朊蛋白低聚物

The central event in the pathogenesis of prion diseases involves a conversion of the host-encoded cellular prion protein PrPC into its pathogenic isoform ...

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 ...

Diffusion Tensor Magnetic Resonance Imaging in the Analysis of Neurodegenerative Diseases

Diffusion tensor imaging (DTI) techniques provide information on the microstructural processes of the cerebral white matter (WM) in vivo. The present applications are designed to investigate differences of WM involvement patterns in different brain diseases, especially neurodegenerative disorders, by use of different DTI analyses in comparison with matched controls. 	
DTI data analysis is performed in a variate fashion, i.e. voxelwise comparison of regional diffusion direction-based metrics such as fractional anisotropy (FA), together with fiber tracking (FT) accompanied by tractwise fractional anisotropy statistics (TFAS) at the group level in order to identify differences in FA along WM structures, aiming at the definition of regional patterns of WM alterations at the group level. Transformation into a stereotaxic standard space is a prerequisite for group studies and requires thorough data processing to preserve directional inter-dependencies. The present applications show optimized technical approaches for this preservation of quantitative and directional information during spatial normalization in data analyses at the group level. On this basis, FT techniques can be applied to group averaged data in order to quantify metrics information as defined by FT. Additionally, application of DTI methods, i.e. differences in FA-maps after stereotaxic alignment, in a longitudinal analysis at an individual subject basis reveal information about the progression of neurological disorders. Further quality improvement of DTI based results can be obtained during preprocessing by application of a controlled elimination of gradient directions with high noise levels.	
In summary, DTI is used to define a distinct WM pathoanatomy of different brain diseases by the combination of whole brain-based and tract-based DTI analysis.

Diffusion tensor imaging (DTI) basically serves as an MRI-based tool to identify in vivo the microstructure of the brain and pathological processes due to neurological disorders within the cerebral white matter. DTI-based analyses allow for application to brain diseases both at the group level and in single subject data.

磁共振扩散张量成像在神经退行性疾病的分析

Diffusion tensor imaging (DTI) techniques provide information on the microstructural processes of the cerebral white matter (WM) in vivo. The present ...

Quantitative Magnetic Resonance Imaging of Skeletal Muscle Disease

Quantitative magnetic resonance imaging (qMRI) describes the development and use of MRI to quantify physical, chemical, and/or biological properties of living systems. Neuromuscular diseases often exhibit a temporally varying, spatially heterogeneous, and multi-faceted pathology. The goal of this protocol is to characterize this pathology using qMRI methods. The MRI acquisition protocol begins with localizer images (used to locate the position of the body and tissue of interest within the MRI system), quality control measurements of relevant magnetic field distributions, and structural imaging for general anatomical characterization. The qMRI portion of the protocol includes measurements of the longitudinal and transverse relaxation time constants (T1 and T2, respectively). Also acquired are diffusion-tensor MRI data, in which water diffusivity is measured and used to infer pathological processes such as edema. Quantitative magnetization transfer imaging is used to characterize the relative tissue content of macromolecular and free water protons. Lastly, fat-water MRI methods are used to characterize fibro-adipose tissue replacement of muscle. In addition to describing the data acquisition and analysis procedures, this paper also discusses the potential problems associated with these methods, the analysis and interpretation of the data, MRI safety, and strategies for artifact reduction and protocol optimization.

Neuromuscular diseases often exhibit a temporally varying, spatially heterogeneous, and multi-faceted pathology. The goal of this protocol is to characterize this pathology using non-invasive magnetic resonance imaging methods.

骨骼肌疾病的定量磁共振成像

Quantitative magnetic resonance imaging (qMRI) describes the development and use of MRI to quantify physical, chemical, and/or biological properties of ...

Depletion of Mouse Cells from Human Tumor Xenografts Significantly Improves Downstream Analysis of Target Cells

The use of in vitro cell line models for cancer research has been a useful tool. However, it has been shown that these models fail to reliably mimic patient tumors in different assays1. Human tumor xenografts represent the gold standard with respect to tumor biology, drug discovery, and metastasis research 2-4. Tumor xenografts can be derived from different types of material like tumor cell lines, tumor tissue from primary patient tumors4 or serially transplanted tumors. When propagated in vivo, xenografted tissue is infiltrated and vascularized by cells of mouse origin. Multiple factors such as the tumor entity, the origin of xenografted material, growth rate and region of transplantation influence the composition and the amount of mouse cells present in tumor xenografts. However, even when these factors are kept constant, the degree of mouse cell contamination is highly variable.
Contaminating mouse cells significantly impair downstream analyses of human tumor xenografts. As mouse fibroblasts show high plating efficacies and proliferation rates, they tend to overgrow cultures of human tumor cells, especially slowly proliferating subpopulations. Mouse cell derived DNA, mRNA, and protein components can bias downstream gene expression analysis, next-generation sequencing, as well as proteome analysis 5. To overcome these limitations, we have developed a fast and easy method to isolate untouched human tumor cells from xenografted tumor tissue. This procedure is based on the comprehensive depletion of cells of mouse origin by combining automated tissue dissociation with the benchtop tissue dissociator and magnetic cell sorting. Here, we demonstrate that human target cells can be can be obtained with purities higher than 96% within less than 20 min independent of the tumor type.

Human tumor xenografts are vascularized and infiltrated by cells of mouse origin during the growth phase in vivo. To circumvent the bias caused by these contaminating cells during downstream analysis, we developed a method allowing for comprehensive depletion of all mouse cells by magnetic cell sorting.

从人类肿瘤异种移植的小鼠细胞的消耗显着改善靶细胞下游分析

The use of in vitro cell line models for cancer research has been a useful tool. However, it has been shown that these models fail to reliably mimic ...

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 ...

Phosphorus-31 Magnetic Resonance Spectroscopy: A Tool for Measuring In Vivo Mitochondrial Oxidative Phosphorylation Capacity in Human Skeletal Muscle

Skeletal muscle mitochondrial oxidative phosphorylation (OXPHOS) capacity, which is critically important in health and disease, can be measured in vivo and noninvasively in humans via phosphorus-31 magnetic resonance spectroscopy (31PMRS). However, the approach has not been widely adopted in translational and clinical research, with variations in methodology and limited guidance from the literature. Increased optimization, standardization, and dissemination of methods for in vivo 31PMRS would facilitate the development of targeted therapies to improve OXPHOS capacity and could ultimately favorably impact cardiovascular health. 31PMRS produces a noninvasive, in vivo measure of OXPHOS capacity in human skeletal muscle, as opposed to alternative measures obtained from explanted and potentially altered mitochondria via muscle biopsy. It relies upon only modest additional instrumentation beyond what is already in place on magnetic resonance scanners available for clinical and translational research at most institutions. In this work, we outline a method to measure in vivo skeletal muscle OXPHOS. The technique is demonstrated using a 1.5 Tesla whole-body MR scanner equipped with the suitable hardware and software for 31PMRS, and we explain a simple and robust protocol for in-magnet resistive exercise to rapidly fatigue the quadriceps muscle. Reproducibility and feasibility are demonstrated in volunteers as well as subjects over a wide range of functional capacities.

Phosphorus-31 Magnetic Resonance Spectroscopy: A Tool for Measuring In Vivo Mitochondrial Oxidative Phosphorylation Capacity in Human Skeletal Muscle

This work demonstrates the feasibility of an in vivo phosphorus-31 magnetic resonance spectroscopy (31PMRS) technique to quantify mitochondrial oxidative phosphorylation (OXPHOS) capacity in human skeletal muscle.

磷31磁共振波谱分析:一种测量工具<em&gt;在体内</em&gt;线粒体氧化磷酸化能力人骨骼肌

Skeletal muscle mitochondrial oxidative phosphorylation (OXPHOS) capacity, which is critically important in health and disease, can be measured in vivo ...

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.

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 ...

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

摘要

探索更多视频

此视频中的章节

听力:IMAP测试电池的决策意识

磁共振衍生的心肌劳损评估使用特征跟踪

在正常人脑分离的可溶性和不溶性朊蛋白低聚物

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

磁共振扩散张量成像在神经退行性疾病的分析

骨骼肌疾病的定量磁共振成像

从人类肿瘤异种移植的小鼠细胞的消耗显着改善靶细胞下游分析

使用多氟化胆汁酸和

磷31磁共振波谱分析:一种测量工具

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

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

摘要

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听力:IMAP测试电池的决策意识

磁共振衍生的心肌劳损评估使用特征跟踪

在正常人脑分离的可溶性和不溶性朊蛋白低聚物

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

磁共振扩散张量成像在神经退行性疾病的分析

骨骼肌疾病的定量磁共振成像

从人类肿瘤异种移植的小鼠细胞的消耗显着改善靶细胞下游分析

使用多氟化胆汁酸和

磷31磁共振波谱分析:一种测量工具

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