私たちは心からのビデオ制作や編集の支援のためにF. Bierryに感謝します。

動物を対象とするすべての手順は、大学病院制度動物ケア委員会によって承認されている。 1。関節内細菌接種<ol><li>注射前に、脊柱起立筋の筋肉内キシラジン（4 mg / kg体重）と混合ケタミンの筋肉内注射（30 mg / kg体重）を用いてウサギを麻酔。動物は、彼らは足のピンチに反応しないことをチェックすることによって、完全に麻酔であることを確認してください。このプロトコルは、膝関節の関節内注射のために十分な麻酔を提供します。麻酔時に酸素マスクの下に動物を配置します。 </li><li>動物の膝を剃る。ポビドンヨード溶液の塗布に続いポビドンヨードスクラブとアルコールの3交互ワイプによって無菌注射のために膝を準備します。 </li><li>手動で図のように滅菌針キャップまたは滅菌プローブを用いた膝の前方側面に弾性構造として膝蓋腱を識別します。 </li><lI&gt;ビジュアルコントロール付きと前方アプローチを使用することにより、膝蓋腱12〜ウサギのそれぞれの右膝に経皮的に25 G針を配置。 </li><li> 10 6の濃度UFC / mlで黄色ブドウ球菌の細菌懸濁液（ノイマン株）1mlでそれぞれ膝を注入。抵抗なく注入は、針の先端の関節位置を確認します。 </li><li>注射の手続きの後、熱損失を回避し、胸の動きを観察することによって、呼吸数を監視するために対流ソースの下に動物を保つ。いったん目を覚まし、食料と水への無料アクセスをケージに動物を飼う。 </li><li> 8時間毎に0.1 mg / kgをブプレノルフィンの筋肉内注射を投与することによって痛みを管理する。 </li><li>臨床的に食物および水、体重減少、温度、および一般的な挙動の消費量を監視して、毎日ウサギを観察する。 </li><li>画像への感染の急性期には、すぐに最初のMRイメージングセッションを行う動物としてかなりの体重減少（10％）を提示、一般的に、これは約2日後に発生します。 </li><li>静脈内薬物投与はMRI検査前に必要とされている場合は、耳介静脈アクセスが（参照以下）をインストールすることができます。 </li></ol> 2。 MRI検査イメージングは​​動物を生きているときは、慎重に動物のインストールでは、動物の快適性と最適な麻酔を確保するための重要な機能です。これは最高のイメージング結果を可能にし、縦断的研究のための生殖の画像取得が保証されます。動物の大きさに起因し、臨床サイズのMR部（1.5 T 3またはT）の使用が最も好適である。それは、ウサギの膝探査するのに適した解像度とコントラスト対ノイズ比を提供するように8チャンネル臨床膝コイルが使用される。 <ol><li>イメージング·システムにインストールする前に、耳介静脈を通じて末梢静脈アクセスをインストールしてください。このアクセ​​スは、造影剤を注入するのに役立つであろう。 <ol><li>剃ると耳を消毒。 </li><l私は&gt;リドカインを皮下注射することにより局所麻酔を行います。 </li><li>横耳介静脈の内側25 Gカテーテルを挿入します。 </li><li> 1ミリリットル滅菌生理血清を注射することにより浸透性を評価する。 </li><li>接着タッピングとカテーテルを維持。 </li></ol></li><li>キシラジン（4 mg / kg体重）と混合ケタミンの筋肉内注射（30 mg / kg体重）を用いて動物を麻酔。彼らは足のピンチへの応答に失敗した後の動物は完全に麻酔する。 200ml /分の流量でそれを酸素を与え、ウサギに顔のマスクを配置する。 </li><li>一度完全に麻酔、MRイメージング装置に動物を取る。膝がMRコイルの中心部に位置されるように動物を配置します。脛骨の長軸はMR撮像部テーブルと平行になるように、完全な拡張で動物の足を置く。最適な足の位置を維持するために、ベルクロファスナーや砂袋を使用してください。 </li><li>心肺動物のモニタリングは、次のようにする必要はありません麻酔プロトコルは、自発呼吸に深い麻酔を可能にしますが、動物は麻酔誘発性熱損失を避けるために、カバーされなければならない。 </li><li> MRプロトコルは、表1に詳述されている。最適なインストールを含む総取得のための平均時間は約20分です。 </li><li>異なる平面でMRイメージングを実行します。それはシーケンシャル縦検査用画像位置の解剖学的再現性を確保し、組織学的スライスを最適な相関が許す限りそれにもかかわらず、膝（脛骨に直交）の横断面は参考プランです。 </li><li>非造影シーケンスの完了時に、耳介静脈アクセスを介してUPSIO造影剤を注入する。ゆっくり150モルのFe / kgを単回用量で酸化鉄粒子を管理します。滅菌生理血清を1mlの注入によってカテーテルをすすぐ。 </li><li>注射後に強化されたGRE加重シーケンス24時間を繰り返します。この遅延は、粒子はで貪食することができるマクロファージ。 </li><li>薬物の効果（抗生物質、ステロイド、抗マクロファージ抗体等 ）を評価長手研究のために、上述したプロトコルを用いて順次MR検査を繰り返す。 </li></ol> 3。画像解析<ol><li>縦評価のために、同じ解剖学的レベルで測定を行い、容易に識別マークを定義します。例えば、膝蓋骨の最大直径が観測される軸平面を通じて買収は、再現性のある測定（ 図1）を得た信頼性の高い方法である。 </li><li> DICOMベースのソフトウェア（例えば、OsiriXのような）又は画像処理ソフト（ImageJの）を用いて画像解析を行う。 </li><li> ImageJのソフトウェアを使用して、 &quot;不規則なエリア&quot;描画ツールを使用してUSPIO強化GRE T2強調画像上の信号損失を示して滑膜領域のセグメンテーションを行う。暗信号と滑膜が概説されたら、/面積を得るために、 &quot;分析&quot;をクリック画素数（ 図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>

著者らは、開示することは何もありません。

非特異ガドリニウムベースの造影剤は、細胞外の空間の容積と血流に関する情報を提供しながら、USPIO強化MRによってマクロファージイメージングは、組織採取9を必要とせずに感染した滑膜内の正確な解剖学的局在とマクロファージ浸潤の定性的な評価を可能にします。その高感度のため、USPIOも微妙セルラー、感染の初期段階に存在する潜入発揮できる。病原体が徐々に削除される?...

磁気共鳴イメージング（MRI）は、その高い空間分解能及び軟組織コントラストに起因する感染性滑膜炎の実証のための選択の撮像モダリティであると考えられる。血管拡張と血管新生1に増加した血管のせいでの組織学的所見と一致して関節炎低いT1および細胞外の水分含量の増加存在を反映して高いT2信号、及びガドリニウムベース·造影剤投与後の顕著な増強をMRIで観察された信号の変化、。それにもかかわらず、MRIは拡大された細胞外空間（肉芽組織、線維性瘢痕）2の持続のために臨床的および生物学的に治癒した敗血症性関節炎患者の関節で観察することができ、多くの場合、永続的な拡張として抗生物質治療中に感染の分解能を発揮することができません。細胞外の変化に加えて、マクロファージの強烈な動員を含む炎症性細胞が大量に潜入滑液をフェクト。マクロファージは細菌感染3の急性および慢性期の両方で重要な役割を果たす。彼らは、病原微生物を根絶するために必要な炎症反応を誘発し、マクロファージ誘発性炎症が4を開始し修復を防止、壊死組織が ​​除去されない限り解消されないように、炎症の解像度を調整します。したがって、効率的な治療後に感染した滑液内のマクロファージ浸潤の減少は感染の分解能の信頼できる指標となることができます。細胞イメージングは​​、病理組織内の特定細胞浸潤を発揮することができます。標的造影剤を使用して、特定のマクロファージMRイメージングが広く検討されており、関節の炎症や感染5-7を実証する能力を実証した。静脈内注射、例えばUSPIO（超小型、超常磁性酸化鉄）粒子はマクロファージなどの食細胞によって取り込まれるような標的造影剤と、後その磁気特性のために、マクロファージ浸潤8を提示する組織における信号変化を誘導する。 生体侵襲マクロファージ浸潤の評価、及びUSPIOロードされ、マクロファージの削減関連信号変化における治療の成功を証明するであろうため、これらのMR信号の変化治療のフォローアップ縦が可能になります。この報告書の目的は、非侵襲的に滑膜内のマクロファージ浸潤の低減を示すことによって、敗血症性関節炎を監視するマクロファージMRイメージングを実行する方法を提示することである。

<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

マクロファージは、開始、開発、細菌感染に対する炎症反応の調節に重要な細胞である。マクロファージは、ますます集中感染の初期段階から敗血症関節で募集され、浸潤が病原体の効率的な除去が得られる一度退縮することになっている。治療の急性滑膜炎及び監視の早期発見：感染した関節インビボマクロファージ活性を識別する能力は、したがって、二つのアプリケーションを提供することができる。 インビボでマクロファージの非侵襲的検出は、例えば、超小型、超常磁性酸化鉄（USPIO）などの鉄ナノ粒子を用いた磁気共鳴イメージングを行うことができる。 USPIOが具体的に活性化マクロファージによる貪食、そして、それらの磁気特性に起因している血管内または関節内投与後、マクロファージ浸潤を提示組織における信号の変化を誘導する。 quantitativ粒子噴射が組織内の鉄の量と相関するので、USPIO負荷された細胞の数を反映した後、信号損失を有する領域（暗い画素数）は勾配エコーMR画像で観察されるように浸潤の電子評価は、実現可能である。 我々は、マクロファージの浸潤および治療 ​​作用の評価のインビボで非侵襲的評価の初期及び長手方向を可能にする、ここで敗血症性関節炎の動物モデルにおいてUSPIOが強化されたMRイメージングを用いたマクロファージ撮影を行うためのプロトコルを提示する。

非造影画像に、感染した膝の滑膜は、大腿骨と膝蓋骨が低信号構造（ 図1）のように表示されている間、軟部組織の周囲から区別ないです中間信号の拡散腫れを提示します。 USPIO-強調画像、造影剤投与の24時間後に、USPIO担持マクロファージを含む滑領域は、信号損失（ 図1および2）を実証する。 滑膜内のマク?...

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

我々は最初のと縦ができ、化膿性関節炎で超小型、超常磁性造影剤（USPIO）を使用してマクロファージMRイメージングを実行する方法を示し<em生体内で&gt;</emマクロファージの浸潤および治療効果の評価の&gt;非侵襲的評価。

敗血症性関節炎の経時的評価のためにMRターゲット造影剤を用いたin vivoイメージングのマクロファージ

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

9.2K ビュー.  University Hospital of Strasbourg. 我々は最初のと縦ができ、化膿性関節炎で超小型、超常磁性造影剤（USPIO）を使用してマクロファージMRイメージングを実行する方法を示し非侵襲的評価。

ビデオ: 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).

MicroCTを使用して造影血管イメージング

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

医学

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.

小説を使用して、脊髄損傷後のマウス後肢の骨の損失の経時的評価、 in vivoで、方法論

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.

縦用の眼の前房に移植、非侵襲<emインビボ&gt;</emリアルタイムでのシングルセル分解能&gt;イメージング

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.

低分子CLT1ペプチド標的造影剤を用いて前立腺がんの分子イメージングのMR

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.

蛍光SAPC-DOPSナノベシクルを用いて脳腫瘍、関節炎のin vivo光イメージング中

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.

縦<em&gt;インビボ</em&gt;脳血管系のイメージング：中枢神経系疾患との関連

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.

ラットの総頸動脈で位相コントラスト磁気共鳴イメージング

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.

顔面性腰痛患者における動的骨回転率の評価に関する定量的[18F]-Naf-PET-MRI分析

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.

造影剤としてのプロトン磁気共鳴イメージングと酸素を用いたヒト肺における特定の換気の定量的マッピング

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

Stabilized Longitudinal In Vivo Cellular-Level Visualization of the Pancreas in a Murine Model with a Pancreatic Intravital Imaging Window

Direct in vivo cellular-resolution imaging of the pancreas in a live small animal model has been technically challenging. A recent intravital imaging study, with an abdominal imaging window, enabled visualization of the cellular dynamics in abdominal organs in vivo. However, due to the soft sheet-like architecture of the mouse pancreas that can be easily influenced by physiologic movement (e.g., peristalsis and respiration), it was difficult to perform stabilized longitudinal in vivo imaging over several weeks at the cellular level to identify, track, and quantify islets or cancer cells in the mouse pancreas. Herein, we describe a method for implanting a novel supporting base, an integrated pancreatic intravital imaging window, that can spatially separate the pancreas from the bowel for longitudinal time-lapse intravital imaging of the pancreas microstructure. Longitudinal in vivo imaging with the imaging window enables stable visualization, allowing for the tracking of islets over a period of 3 weeks and high-resolution three-dimensional imaging of the microstructure, as evidenced here in an orthotopic pancreatic cancer model. With our method, further intravital imaging studies can elucidate the pathophysiology of various diseases involving the pancreas at the cellular level.

Stabilized Longitudinal In Vivo Cellular-Level Visualization of the Pancreas in a Murine Model with a Pancreatic Intravital Imaging Window

In vivo high-resolution imaging of the pancreas was facilitated with the pancreatic intravital imaging window.

膵臓内イメージングウィンドウを用いたマウスモデルにおける膵臓の細胞レベル可視化におけるビ ボ における縦方向の安定化

Direct in vivo cellular-resolution imaging of the pancreas in a live small animal model has been technically challenging. A recent intravital imaging ...