我们衷心感谢楼Bierry为协助在视频编辑制作。

大学医院机构动物保健委员会已经批准了所有程序，涉及受试动物。 1。关节腔内的细菌接种<ol><li>在注射前，麻醉兔子通过肌内注射氯胺酮（30毫克/公斤体重）混合，用甲苯噻嗪（4毫克/千克）在竖脊肌肌肉之内。确保通过检查，他们无法应对爪子捏动物完全麻醉。此协议可提供足够的膝关节的关节内注射麻醉。在麻醉过程中，将氧气面罩下的动物。 </li><li>剃须动物的膝盖。准备膝盖无菌注射3碘伏擦洗和酒精，然后通过应用聚维酮碘溶液交替湿巾。 </li><li>手动识别作为弹性结构的髌腱的膝盖上面的前方，用无菌针帽，如图所示，或者无菌的探头。 </li><l我与视觉控制和使用方法前，放置25 G针经皮的12只在右膝髌腱通过。 </li><li>金黄色葡萄球菌的细菌悬浮液用1毫升（诺伊曼株）注入每个膝盖UFC /毫升的浓度为10 6。一种注射无阻力确认针尖的关节内的位置。 </li><li>注射后的程序，保持动物对流源下，通过观察胸部的运动，以避免热损失和监测呼吸频率。一旦醒来，让动物在笼子里免费获得食物和水。 </li><li>管理疼痛管理肌内注射丁丙诺啡0.1毫克/千克，每8小时。 </li><li>临床观察兔子的每一天，监控消耗大量的食物和水，减肥，温度，和一般的行为。 </li><li>为了形象感染的急性期，尽快执行第一MR成像会议作为动物带来了重大的减肥（10％），一般发生这种情况后，约2天。 </li><li> MRI检查之前，如果需要静脉给药的耳静脉通路可以安装（参见下文）。 </li></ol> 2。 MRI检查当成像活的动物，动物仔细安装是一个关键的功能，以确保动物的舒适度和最佳的麻醉。这将允许最佳的成像效果，并确保生殖图像采集纵向研究。由于动物的大小，使用的临床尺寸MR单元（1.5 T或3个T）是最适合的。 8通道临床膝关节线圈使用，因为它提供了合适的分辨率和对比度噪声比兔膝关节勘探。 <ol><li>成像系统安装前，安装外围通过耳静脉的静脉通路。这种访问将有助于注入造影剂。 <ol><li>刮脸和消毒的耳朵。 </li><lI&gt;皮下注射利多卡因进行局部麻醉下通过。 </li><li>插入一个25 G的侧向耳静脉导管内。 </li><li>评估渗透性注射1毫升无菌生理血清。 </li><li>保持导管用粘合剂攻丝。 </li></ol></li><li>麻醉动物通过肌内注射氯胺酮（30毫克/公斤体重）混合，用甲苯噻嗪（4毫克/千克）。动物是完全麻醉，一旦他们无法回应爪子捏。将兔子一个面膜，给它与流速为200毫升/分钟的氧气。 </li><li>一旦完全麻醉，采取动物磁共振成像单元。动物的地方，让膝盖位于MR线圈的中心。完整的分机号，以便将动物的腿的胫骨的长轴平行于MR成像单元表。使用尼龙搭扣或砂袋，以保持最佳的腿部位置。 </li><li>不是必需的，因为在心肺监测动物麻醉协议允许自主呼吸深麻醉，但动物进行覆盖，以避免麻醉引起的热损失。 </li><li>议员协议的详细内容见表1。总收购包括最佳的安装时间平均约20分钟。 </li><li>在不同的平面上，进行磁共振成像。然而，横向平面膝（胫骨正交）的参考计划，因为它可以确保重现性解剖的顺序纵向检查图像的位置，和允许最佳的组织学切片的相关性。 </li><li>在完成平扫序列，注入UPSIO的造影剂通过耳静脉通路。慢慢地管理氧化铁颗粒在单剂量为150微摩尔的Fe /公斤。冲洗导管注射1毫升无菌生理血清。 </li><li>重复增强的GRE加权序列24小时后注射。此延迟允许颗粒吞噬巨噬细胞。 </li><li>纵向研究评价药物的影响（抗生素，类固醇，抗巨噬细胞抗体等 ），重复使用上述协议的顺序MR检查。 </li></ol> 3。图像分析<ol><li>纵向评价相同的解剖水平进行测量，并定义一个容易辨认的标志。比如，收购通过观察髌骨的最大直径，轴向平面是一个可靠的方式来获得可重复的测量（ 图1）。 </li><li>使用基于DICOM软件（如Osirix）或图像处理软件（ImageJ的）进行图像分析。 </li><li>使用ImageJ软件，执行滑膜区域分割的USPIO增强GRE T2加权图像使用"不规则区域"的绘图工具，演示上的信号损失。概述与黑暗的信号一旦滑膜，点击"分析"获得区/像素数（ 图2）。 </li></ol>

<ol>
	<li>Madri, J., Kissane, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Inflammation+and+healing.">Inflammation and healing.</a> Anderson's Pathology. , 67-110 (1990).</li><li>Sephel, G., Woodward, S., Rubin, R., Strayer, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Repair,+regeneration,+and+fibrosis.">Repair, regeneration, and fibrosis.</a> Rubin's Pathology. , 71-98 (2008).</li><li>Verdrengh, M., Tarkowski, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Role+of+macrophages+in+Staphylococcus+aureus-induced+arthritis+and+sepsis.">Role of macrophages in Staphylococcus aureus-induced arthritis and sepsis.</a> Arthritis Rheum. 43 (10), 2276-2282 (2000).</li><li>Heale, J., Speert, D., Burke, B., Lewis, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Macrophages+in+bacterial+infection.">Macrophages in bacterial infection.</a> The Macrophage. , 210-252 (2008).</li><li>Bierry, G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Macrophage+activity+in+infected+areas+of+an+experimental+vertebral+osteomyelitis+model:+USPIO-enhanced+MR+imaging--feasibility+study.">Macrophage activity in infected areas of an experimental vertebral osteomyelitis model: USPIO-enhanced MR imaging--feasibility study.</a> Radiology. 248 (1), 114-123 (2008).</li><li>Bierry, G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=MRI+of+macrophages+in+infectious+knee+synovitis.">MRI of macrophages in infectious knee synovitis.</a> AJR Am. J. Roentgenol. 194 (6), W521-W526 (2010).</li><li>Lutz, A. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Detection+of+synovial+macrophages+in+an+experimental+rabbit+model+of+antigen-induced+arthritis:+ultrasmall+superparamagnetic+iron+oxide-enhanced+MR+imaging.">Detection of synovial macrophages in an experimental rabbit model of antigen-induced arthritis: ultrasmall superparamagnetic iron oxide-enhanced MR imaging.</a> Radiology. 233 (1), 149-1457 (2004).</li><li>Weissleder, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ultrasmall+superparamagnetic+iron+oxide:+an+intravenous+contrast+agent+for+assessing+lymph+nodes+with+MR+imaging.">Ultrasmall superparamagnetic iron oxide: an intravenous contrast agent for assessing lymph nodes with MR imaging.</a> Radiology. 175 (2), 494-498 (1990).</li><li>Lefevre, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Septic+arthritis:+monitoring+with+USPIO-enhanced+macrophage+MR+imaging.">Septic arthritis: monitoring with USPIO-enhanced macrophage MR imaging.</a> Radiology. 258 (3), 722-728 (2011).</li><li>Sigovan, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Rapid-clearance+iron+nanoparticles+for+inflammation+imaging+of+atherosclerotic+plaque:+initial+experience+in+animal+model.">Rapid-clearance iron nanoparticles for inflammation imaging of atherosclerotic plaque: initial experience in animal model.</a> Radiology. 252 (2), 401-409 (2009).</li></ol>

什么都没有透露。

虽然非特异性钆的造影剂提供的信息有关的细胞外空间的体积和灌注，巨噬细胞USPIO增强MR成像允许一个精确的解剖定位于受感染的滑膜组织的巨噬细胞浸润和定性评价，而不需要对组织取样9。由于其高灵敏度，USPIO可以证明哪怕是细微的细胞浸润在感染的早期阶段。根据成功的抗生素治疗，逐渐除去病原体，被认为是这种渗透减少，导致的滑膜内的USPIO摄取的减少。的面积的暗信号的相?...

磁共振成像（MRI）被认为是给出示范传染性滑膜炎，由于它的高空间分辨率和软组织对比度的成像模态。 MRI上的信号变化关节炎低T1和T2高信号反映细胞外液量增加存在，基于钆的造影剂管理显着增强后，符合组织的调查结果增加血管，由于血管扩张和血管生成1。然而，MRI往往是在抗生素治疗过程中无法显示分辨率感染持久性增强，可观察到患者的关节与临床和生物愈合化脓性关节炎，由于扩大的细胞外空间的持久性（肉芽组织，纤维化瘢痕）2。除了细胞外的变化，大量炎症细胞，包括巨噬细胞激烈的招聘渗透染病滑液。巨噬细胞的急性和慢性细菌感染3阶段发挥了重要作用。他们需要消除病原微生物引起的炎症反应，并协调炎症消退，如巨噬细胞诱发炎症仍然存在，只要坏死组织不会被删除，防止维修开始4。因此，高效的治疗后滑膜内感染的巨噬细胞浸润减少感染的分辨率可以是一个可靠的指标。细胞成像是能够证明的具体病理组织内细胞浸润。使用有针对性的具体的巨噬细胞MR成像造影剂已被广泛研究，并已经证明它有能力证明关节发炎或感染5-7。 USPIO（超小超顺磁性氧化铁）颗粒这种有针对性的造影剂，如静脉注射后，被吞噬细胞如巨噬细胞，由于其磁特性，诱导组织中的信号的变化，呈现巨噬细胞浸润8。那些MR信号的变化治疗的纵向跟进允许在体内的非侵入性的评价巨噬细胞浸润和USPIO加载的巨噬细胞相关的信号的变化减少了将证明治疗的成功。本报告的目的是介绍如何进行巨噬细胞MR成像，无创监测化脓性关节炎滑膜内通过论证减少巨噬细胞浸润。

<table border="1">
	<tbody>
		<tr>
			<td>Name of Reagent/Material</td>
			<td>Company</td>
			<td>Catalog Number</td>
			<td>Comments</td>
		</tr>
		<tr>
			<td>P904</td>
			<td>Guerbet</td>
			<td></td>
			<td>Dose: 150 &#956;mol Fe/kg</td>
		</tr>
		<tr>
			<td>Ketamine (500 mg/ml ketamine)</td>
			<td>Virbac</td>
			<td></td>
			<td>Dose: 30 mg/kg</td>
		</tr>
		<tr>
			<td>Rompun (20 mg/ml Xylazine)</td>
			<td>Axience</td>
			<td></td>
			<td>Dose: 4 mg/kg</td>
		</tr>
		<tr>
			<td>Buprenorphine</td>
			<td>Vetoquinol</td>
			<td></td>
			<td>Dose: 0.1 mg/kg/8 hr</td>
		</tr>
		<tr>
			<td>BD 22 G, 1 inch</td>
			<td>BD Biosciences</td>
			<td>381423</td>
			<td></td>
		</tr>
		<tr>
			<td>BD 25 G, 5/8 inch</td>
			<td>BD Biosciences</td>
			<td>305122</td>
			<td></td>
		</tr>
	</tbody>
</table>

in vivo macrophage imaging using mr targeted contrast agent for longitudinal evaluation of septic arthritis

巨噬细胞是关键细胞，在发起，发展和细菌感染的炎症反应的调节。巨噬细胞密集和日益招募关节化脓性感染的早期阶段，并获得高效去除病原体的渗透应该是一次倒退。识别能力， 在体内的巨噬细胞活性，在被感染的关节，因此可以提供两个主要应用:急性滑膜炎的早期发现和治疗监测。 在体内的巨噬细胞的非侵入性的检测可以进行磁共振成像使用铁纳米粒子，如超小超顺磁性氧化铁（USPIO）。血管内或关节内给药后，USPIO专门吞噬活化的巨噬细胞，并且，由于其磁特性，诱导呈现巨噬细胞浸润的组织中的信号的变化。 àquantitativ的渗透ë键评价是可行的，信号损失中的区域（暗像素数量）颗粒注射后在组织内的铁量密切相关，因此，该数字反映的USPIO加载细胞上观察到的梯度回波MR图像。 我们在座的协议来执行巨噬细胞成像使用USPIO增强MR成像化脓性关节炎动物模型中，让体内的巨噬细胞的浸润和评估治疗作用的非侵入性评估的初始和纵向。

在未增强的图像上，受感染的膝盖滑膜非区别于周围的软组织，而股骨和髌骨显示为低信号结构（ 图1）的中间信号提出了一种漫肿。 造影剂给药后24小时，滑膜区域，其中包含加载USPIO-巨噬细胞在USPIO增强图像上，将演示信号损失（ 图1和2）。 使用特定的免疫染色（ 图3），可以证明在滑膜组织中的巨?...

Watch this Scientific Journal Video about In vivo Macrophage Imaging Using MR Targeted Contrast Agent for Longitudinal Evaluation of Septic Arthritis at JoVE.com

In vivo Macrophage Imaging Using MR Targeted Contrast Agent for Longitudinal Evaluation of Septic Arthritis

我们演示了如何执行巨噬细胞MR成像使用超小超顺磁造影剂（USPIO）化脓性关节炎，让初次和​​纵向<em&gt;在体内</em&gt;非侵入性评价的巨噬细胞浸润和治疗疗效的评估。

在体内的巨噬细胞成像采用MR靶向造影剂化脓性关节炎的纵向评价

Macrophages are key-cells in the initiation, the development and the regulation of the inflammatory response to bacterial infection. Macrophages are ...

in-vivo-macrophage-imaging-using-mr-targeted-contrast-agent-for

Research

JoVE Journal

Medicine

In vivo Macrophage Imaging Using MR Targeted Contrast Agent for Longitudinal Evaluation of Septic Arthritis

9.3K 次观看.  University Hospital of Strasbourg. 我们演示了如何执行巨噬细胞MR成像使用超小超顺磁造影剂（USPIO）化脓性关节炎，让初次和​​纵向在体内非侵入性评价的巨噬细胞浸润和治疗疗效的评估。

视频: In vivo Macrophage Imaging Using MR Targeted Contrast Agent for Longitudinal Evaluation of Septic Arthritis

Contrast Enhanced Vessel Imaging using MicroCT

Microscopic computed tomography (microCT) offers high-resolution volumetric imaging of the anatomy of living small animals. However, the contrast between different soft tissues and body fluids is inherently poor in micro-CT images 1. Under these circumstances, visualization of blood vessels becomes a nearly impossible task. To overcome this and to improve the visualization of blood vessels exogenous contrast agents can be used. Herein, we present a methodology for visualizing the vascular network in a rodent model. By using a long-acting aqueous colloidal polydisperse iodinated blood-pool contrast agent, eXIA 160XL, we optimized image acquisition parameters and volume-rendering techniques for finding blood vessels in live animals. Our findings suggest that, to achieve a superior contrast between bone and soft tissue from vessel, multiple-frames (at least 5-8/ frames per view), and 360-720 views (for a full 360&deg; rotation) acquisitions were mandatory. We have also demonstrated the use of a two-dimensional transfer function (where voxel color and opacity was assigned in proportion to CT value and gradient magnitude), in visualizing the anatomy and highlighting the structure of interest, the blood vessel network. This promising work lays a foundation for the qualitative and quantitative assessment of anti-angiogenesis preclinical studies using transgenic or xenograft tumor-bearing mice.

Contrast enhanced small animal vessel imaging by microCT is a rapid, cost-effective and high-throughput technique for serial in situ examination for tumor development, for analyzing the network of blood vessels that nourish them, and for following the response of tumors to preclinical therapeutic intervention(s).

增强容器成像MicroCT

Microscopic computed tomography (microCT) offers high-resolution volumetric imaging of the anatomy of living small animals. However, the contrast between ...

科研

医学

Evaluation of Nanoparticle Uptake in Tumors in Real Time Using Intravital Imaging

Current technologies for tumor imaging, such as ultrasound, MRI, PET and CT, are unable to yield high-resolution images for the assessment of nanoparticle uptake in tumors at the microscopic level1,2,3, highlighting the utility of a suitable xenograft model in which to perform detailed uptake analyses. Here, we use high-resolution intravital imaging to evaluate nanoparticle uptake in human tumor xenografts in a modified, shell-less chicken embryo model. The chicken embryo model is particularly well-suited for these in vivo analyses because it supports the growth of human tumors, is relatively inexpensive and does not require anesthetization or surgery 4,5. Tumor cells form fully vascularized xenografts within 7 days when implanted into the chorioallantoic membrane (CAM) 6. The resulting tumors are visualized by non-invasive real-time, high-resolution imaging that can be maintained for up to 72 hours with little impact on either the host or tumor systems. Nanoparticles with a wide range of sizes and formulations administered distal to the tumor can be visualized and quantified as they flow through the bloodstream, extravasate from leaky tumor vasculature, and accumulate at the tumor site. We describe here the analysis of nanoparticles derived from Cowpea mosaic virus (CPMV) decorated with near-infrared fluorescent dyes and/or polyethylene glycol polymers (PEG) 7, 8, 9,10,11. Upon intravenous administration, these viral nanoparticles are rapidly internalized by endothelial cells, resulting in global labeling of the vasculature both outside and within the tumor7,12. PEGylation of the viral nanoparticles increases their plasma half-life, extends their time in the circulation, and ultimately enhances their accumulation in tumors via the enhanced permeability and retention (EPR) effect 7, 10,11. The rate and extent of accumulation of nanoparticles in a tumor is measured over time using image analysis software. This technique provides a method to both visualize and quantify nanoparticle dynamics in human tumors.

We present a novel approach to quantify nanoparticle localization in the vasculature of human xenografted tumors using dynamic, real-time intravital imaging in an avian embryo model.

使用实时活体成像在肿瘤纳米粒子吸收的评价

Current technologies for tumor imaging, such as ultrasound, MRI, PET and CT, are unable to yield high-resolution images for the assessment of nanoparticle ...

Longitudinal Evaluation of Mouse Hind Limb Bone Loss After Spinal Cord Injury using Novel, in vivo, Methodology

Spinal cord injury (SCI) is often accompanied by osteoporosis in the sublesional regions of the pelvis and lower extremities, leading to a higher frequency of fractures 1. As these fractures often occur in regions that have lost normal sensory function, the patient is at a greater risk of fracture-dependent pathologies, including death. SCI-dependent loss in both bone mineral density (BMD, grams/cm2) and bone mineral content (BMC, grams) has been attributed to mechanical disuse 2, aberrant neuronal signaling 3 and hormonal changes 4. The use of rodent models of SCI-induced osteoporosis can provide invaluable information regarding the mechanisms underlying the development of osteoporosis following SCI as well as a test environment for the generation of new therapies 5-7 (and reviewed in 8). Mouse models of SCI are of great interest as they permit a reductionist approach to mechanism-based assessment through the use of null and transgenic mice. While such models have provided important data, there is still a need for minimally-invasive, reliable, reproducible, and quantifiable methods in determining the extent of bone loss following SCI, particularly over time and within the same cohort of experimental animals, to improve diagnosis, treatment methods, and/or prevention of SCI-induced osteoporosis.
An ideal method for measuring bone density in rodents would allow multiple, sequential (over time) exposures to low-levels of X-ray radiation. This study describes the use of a new whole-animal scanner, the IVIS Lumina XR (Caliper Instruments) that can be used to provide low-energy (1-3 milligray (mGy)) high-resolution, high-magnification X-ray images of mouse hind limb bones over time following SCI. Significant bone density loss was seen in the tibiae of mice by 10 days post-spinal transection when compared to uninjured, age-matched control (na&iuml;ve) mice (13% decrease, p&lt;0.0005). Loss of bone density in the distal femur was also detectable by day 10 post-SCI, while a loss of density in the proximal femur was not detectable until 40 days post injury (7% decrease, p&lt;0.05). SCI-dependent loss of mouse femur density was confirmed post-mortem through the use of Dual-energy X-ray Absorptiometry (DXA), the current "gold standard" for bone density measurements. We detect a 12% loss of BMC in the femurs of mice at 40 days post-SCI using the IVIS Lumina XR. This compares favorably with a previously reported BMC loss of 13.5% by Picard and colleagues who used DXA analysis on mouse femurs post-mortem 30 days post-SCI 9. Our results suggest that the IVIS Lumina XR provides a novel, high-resolution/high-magnification method for performing long-term, longitudinal measurements of hind limb bone density in the mouse following SCI.

Longitudinal Evaluation of Mouse Hind Limb Bone Loss After Spinal Cord Injury using Novel, in vivo, Methodology

A longitudinal examination of bone loss in the femurs and tibiae of adult mice was performed following spinal cord injury using sequential low-dose X-ray scans. Tibia bone loss was detected throughout the study, while bone loss in the femur was not detected until 40 days post injury.

鼠标使用新型脊髓损伤的后肢骨质流失的纵向评价，在体内，方法论

Spinal cord injury (SCI) is often accompanied by osteoporosis in the sublesional regions of the pelvis and lower extremities, leading to a higher ...

Transplantation into the Anterior Chamber of the Eye for Longitudinal, Non-invasive In vivo Imaging with Single-cell Resolution in Real-time

Intravital imaging has emerged as an indispensable tool in biological research. In the process, many imaging techniques have been developed to study different biological processes in animals non-invasively. However, a major technical limitation in existing intravital imaging modalities is the inability to combine non-invasive, longitudinal imaging with single-cell resolution capabilities. We show here how transplantation into the anterior chamber of the eye circumvents such significant limitation offering a versatile experimental platform that enables non-invasive, longitudinal imaging with cellular resolution in vivo. We demonstrate the transplantation procedure in the mouse and provide representative results using a model with clinical relevance, namely pancreatic islet transplantation. In addition to enabling direct visualization in a variety of tissues transplanted into the anterior chamber of the eye, this approach provides a platform to screen drugs by performing long-term follow up and monitoring in target tissues. Because of its versatility, tissue/cell transplantation into the anterior chamber of the eye not only benefits transplantation therapies, it extends to other in vivo applications to study physiological and pathophysiological processes such as signal transduction and cancer or autoimmune disease development.

Transplantation into the Anterior Chamber of the Eye for Longitudinal, Non-invasive In vivo Imaging with Single-cell Resolution in Real-time

A new approach combining intraocular transplantation and confocal microscopy enables longitudinal, non-invasive real-time imaging with single-cell resolution within grafted tissues in vivo. We demonstrate how to transplant pancreatic islets into the anterior chamber of the mouse eye.

纵向，非侵入性的移植到眼睛的前房<em在体内</em&gt;单细胞分辨率的实时成像

Intravital imaging has emerged as an indispensable tool in biological research.  In the process, many imaging techniques have been developed to study ...

MR Molecular Imaging of Prostate Cancer with a Small Molecular CLT1 Peptide Targeted Contrast Agent

Tumor extracellular matrix has abundance of cancer related proteins that can be used as biomarkers for cancer molecular imaging. In this work, we demonstrated effective MR cancer molecular imaging with a small molecular peptide targeted Gd-DOTA monoamide complex as a targeted MRI contrast agent specific to clotted plasma proteins in tumor stroma. We performed the experiment of evaluating the effectiveness of the agent for non-invasive detection of prostate tumor with MRI in a mouse orthotopic PC-3 prostate cancer model. The targeted contrast agent was effective to produce significant tumor contrast enhancement at a low dose of 0.03 mmol Gd/kg. The peptide targeted MRI contrast agent is promising for MR molecular imaging of prostate tumor.

To demonstrate MR cancer molecular imaging with a small peptide targeted MRI contrast agent specific to clotted plasma proteins in tumor stroma in a mouse prostate cancer model.

前列腺癌与小分子肽CLT1靶向造影剂的磁共振分子成像

Tumor extracellular  matrix has abundance of cancer related proteins that can be used as biomarkers  for cancer molecular imaging. In this work,  we ...

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 ...

Longitudinal In Vivo Imaging of the Cerebrovasculature: Relevance to CNS Diseases

Remodeling of the brain vasculature is a common trait of brain pathologies. In vivo imaging techniques are fundamental to detect cerebrovascular plasticity or damage occurring overtime and in relation to neuronal activity or blood flow. In vivo two-photon microscopy allows the study of the structural and functional plasticity of large cellular units in the living brain. In particular, the thinned-skull window preparation allows the visualization of cortical regions of interest (ROI) without inducing significant brain inflammation. Repetitive imaging sessions of cortical ROI are feasible, providing the characterization of disease hallmarks over time during the progression of numerous CNS diseases. This technique accessing the pial structures within 250 &#956;m of the brain relies on the detection of fluorescent probes encoded by genetic cellular markers and/or vital dyes. The latter (e.g., fluorescent dextrans) are used to map the luminal compartment of cerebrovascular structures. Germane to the protocol described herein is the use of an in vivo marker of amyloid deposits, Methoxy-O4, to assess Alzheimer&#39;s disease (AD) progression. We also describe the post-acquisition image processing used to track vascular changes and amyloid depositions. While focusing presently on a model of AD, the described protocol is relevant to other CNS disorders where pathological cerebrovascular changes occur.

Longitudinal In Vivo Imaging of the Cerebrovasculature: Relevance to CNS Diseases

This manuscript describes a procedure to track the remodeling of the cerebrovasculature during amyloid plaque accumulation in vivo using longitudinal two-photon microscopy. A thinned-skull preparation enables the visualization of fluorescent dyes to assess the progression of cerebrovascular damage in a mouse model of Alzheimer&#39;s disease.

纵<em&gt;在体内</em&gt;的Cerebrovasculature影像:相关性疾病CNS

Remodeling of the brain vasculature is a common trait of brain pathologies. In vivo imaging techniques are fundamental to detect cerebrovascular ...

Phase Contrast Magnetic Resonance Imaging in the Rat Common Carotid Artery

Phase contrast magnetic resonance imaging (PC-MRI) is a noninvasive approach that can quantify flow-related parameters such as blood flow. Previous studies have shown that abnormal blood flow may be associated with systemic vascular risk. Thus, PC-MRI can facilitate the translation of data obtained from animal models of cardiovascular diseases to pertinent clinical investigations. In this report, we describe the procedure for measuring blood flow in the common carotid artery (CCA) of rats using cine-gated PC-MRI and discuss relevant analysis methods. This procedure can be performed in a live, anesthetized animal and does not require euthanasia after the procedure. The proposed scanning parameters yield repeatable measurements for blood flow, indicating excellent reproducibility of the results. The PC-MRI procedure described in this article can be used for pharmacological testing, pathophysiological assessment, and cerebral hemodynamics evaluation.

The overall goal of this procedure is to measure the blood flow in the rat common carotid artery by using noninvasive phase contrast magnetic resonance imaging.

大鼠颈总动脉的相位对比磁共振成像

Phase contrast magnetic resonance imaging (PC-MRI) is a noninvasive approach that can quantify flow-related parameters such as blood flow. Previous ...

Quantitative [18F]-Naf-PET-MRI Analysis for the Evaluation of Dynamic Bone Turnover in a Patient with Facetogenic Low Back Pain

Imaging techniques that reflect dynamic bone turnover may aid in characterizing a wide range of bone pathologies. Bone is a dynamic tissue undergoing continuous remodeling with the competing activity of osteoblasts, which produce the new bone matrix, and osteoclasts, whose function is to eliminate mineralized bone. [18F]-NaF is a positron emission tomography (PET) radiotracer that enables visualization of bone metabolism. [18F]-NaF is chemically absorbed into hydroxyapatite in the bone matrix by osteoblasts and can thus noninvasively detect osteoblastic activity, which is occult to conventional imaging techniques. Kinetic modeling of dynamic [18F]-NaF-PET data provides detailed quantitative measures of bone metabolism. Conventional semi-quantitative PET data, which utilizes standardized uptake values (SUVs) as a measure of radiotracer activity, is referred to as a static technique due to its snapshot of tracer uptake in time.&#160; Kinetic modeling, however, utilizes dynamic image data where tracer levels are continuously acquired providing tracer uptake temporal resolution. From the kinetic modeling of dynamic data, quantitative values like blood flow and metabolic rate (i.e., potentially informative metrics of tracer dynamics) can be extracted, all with respect to the measured activity in the image data. When combined with dual modality PET-MRI, region-specific kinetic data can be correlated with anatomically registered high-resolution structural and pathologic information afforded by MRI. The goal of this methodological manuscript is to outline detailed techniques for performing and analyzing dynamic [18F]-NaF-PET-MRI data. The lumbar facet joint is a common site of degenerative arthritis disease and a common cause for axial low back pain.&#160; Recent studies suggest [18F]-NaF-PET may serve as a useful biomarker of painful facetogenic disease.&#160; The human lumbar facet joint will, therefore, be used as a prototypical region of interest for dynamic [18F]-NaF-PET-MRI analysis in this manuscript.

Quantitative [18F]-Naf-PET-MRI Analysis for the Evaluation of Dynamic Bone Turnover in a Patient with Facetogenic Low Back Pain

Imaging techniques that reflect dynamic bone turnover may aid in characterizing a wide range of bone pathologies. We present detailed methodologies for performing and analyzing dynamic [18F]-NaF-PET-MRI data in a patient with facetogenic low back pain using the lumbar facet joints as a prototypical region of interest.

定量 =18F_-Naf-PET-MRI 分析,用于评估面部腰痛患者的动态骨质周转率

Imaging techniques that reflect dynamic bone turnover may aid in characterizing a wide range of bone pathologies. Bone is a dynamic tissue undergoing ...

Quantitative Mapping of Specific Ventilation in the Human Lung using Proton Magnetic Resonance Imaging and Oxygen as a Contrast Agent

Specific ventilation imaging (SVI) is a functional magnetic resonance imaging technique capable of quantifying specific ventilation &#8213; the ratio of the fresh gas entering a lung region divided by the region&#8217;s end-expiratory volume &#8213; in the human lung, using only inhaled oxygen as a contrast agent. Regional quantification of specific ventilation has the potential to help identify areas of pathologic lung function. Oxygen in solution in tissue shortens the tissue&#8217;s longitudinal relaxation time (T1), and thus a change in tissue oxygenation can be detected as a change in T1-weighted signal with an inversion recovery acquired image. Following an abrupt change between two concentrations of inspired oxygen, the rate at which lung tissue within a voxel equilibrates to a new steady-state reflects the rate at which resident gas is being replaced by inhaled gas. This rate is determined by specific ventilation. To elicit this sudden change in oxygenation, subjects alternately breathe 20-breath blocks of air (21% oxygen) and 100% oxygen while in the MRI scanner. A stepwise change in inspired oxygen fraction is achieved through use of a custom three-dimensional (3D)-printed flow bypass system with a manual switch during a short end-expiratory breath hold. To detect the corresponding change in T1, a global inversion pulse followed by a single shot fast spin echo sequence was used to acquire two-dimensional T1-weighted images in a 1.5&#160;T MRI scanner, using an eight-element torso coil. Both single slice and multi-slice imaging are possible, with slightly different imaging parameters. Quantification of specific ventilation is achieved by correlating the time-course of signal intensity for each lung voxel with a library of simulated responses to the air/oxygen stimulus. SVI estimations of specific ventilation heterogeneity have been validated against multiple breath washout and proved to accurately determine the heterogeneity of the specific ventilation distribution.

Specific ventilation imaging is a functional magnetic resonance imaging technique that allows for quantification of regional specific ventilation in the human lung, using inhaled oxygen as a contrast agent. Here, we present a protocol to collect and analyze specific ventilation imaging data.

以质子磁共振成像和氧为造影剂对人肺特异性通气进行定量定位

Specific ventilation imaging (SVI) is a functional magnetic resonance imaging technique capable of quantifying specific ventilation &#8213; the ratio of ...

在体内的巨噬细胞成像采用MR靶向造影剂化脓性关节炎的纵向评价

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