Name: universal hand-held three-dimensional optoacoustic imaging probe for deep tissue human angiography and functional preclinical studies in real time
Uploaded: 2014-11-04T13:00:00.000+00:00
Duration: 9 min 56 s
Description: Watch this Scientific Journal Video about Universal Hand-held Three-dimensional Optoacoustic Imaging Probe for Deep Tissue Human Angiography and Functional Preclinical Studies in Real Time at JoVE.com

The research leading to these results has received funding from the European Research Council under grant agreement ERC-2010-StG-260991.

体積ハンドヘルド光音響プローブを動作させるための詳細な手順については後述する。この手順は、動物およびヒトの実験に関する承認された制度的規制に従って行われる。 1.システムの準備<ol><li>出力光ビームを安定化させるための操作前〜15分のウォームアップ期間のためのレーザーのスイッチを入れる。 </li><li>皮膚（ 図1）と接触している隔離膜で一部を囲む水を置きます。 NOTE：（皮膚接触）分離膜とトランスデューサ（球形プローブの中心）の最大感度を有する領域との間の距離は、有効撮像深さを確立する。 </li><li>ポンプを用いて脱イオン水を用いて単離した膜と変換器の表面との間に約100mlの全容積を満たす。 </li><li>水漏れでも気泡がpresaの複数形されていないことを確認NT。あるいは、水の循環を提供することにより、気泡を避ける。 </li><li>室温で実験を実施し、この温度に維持される結合媒体（水）を確保する。 </li></ol> 2.イメージングの準備<ol><li>人間の撮影準備。 </li><li>画像内の望ましくないバックグラウンドを避けるために、脱毛ローション付きツー·画像化することが部分から毛を削除します（このステップはオプションです）。 </li><li>効果的な音響結合を提供するために、画像化される領域の周りの皮膚に超音波ゲルを適用する。関心領域内の光音響プローブを配置します。気泡が超音波カップリングゲル中に存在しないことを確認してください。 </li><li>動物の撮影準備。 </li><li>動物とのケアと実験手順は、制度や政府の規則や規制と一致していることを確認してください。 </li><li>シェービングローションで画像化される領域での動物の毛皮を削除します。で動物の目を保護超短パルスレーザ放射への暴露から乾燥や損傷を防止獣医軟膏、。 </li><li> 0.9リットルでケタミン/キシラジン体積（100 mg / kgをkgのケタミン+ 5mg / kgのキシラジンKG）は、実験に先立って、または使用イソフルラン麻酔（2-3％（）の腹腔内注射（IP）を使用して動物を麻酔/実験中の最小ガス流量）。動物の後肢の反射をチェックすることにより、麻酔を確認します。 </li><li>効果的な音響結合を提供し、関心領域内の光音響プローブを配置するために画像化される領域の周りの皮膚に超音波ゲルを適用する。気泡が超音波カップリングゲル中に存在しないことを確認してください。 </li></ol> 3.プリビュー動作モード<ol><li> 690 nmおよび900 nmおよび10および50 Hzのパルス繰り返し率と撮像波長（複数可）を確立する。音響データ収集システムのためのパラメータを選択します - 1MΩ入力インピーダンス。第12ビットの垂直分解能あたり40メガサンプルのサンプリングレートで各レーザパルス2030のサンプルを取得する。レーザーのQスイッチ出力と取得をトリガーする。 </li><li>オペレータと患者の両方が光励起波長（群）に適合した保護メガネを使用していることを確認してください。人体実験19の安全曝露限界を満たすために及び動物における熱ひずみおよび皮膚損傷を防止するために、組織表面での光のフルエンスは、近赤外波長について、実験中は20mJ / cm 2程度以下に維持されるように、レーザパワーを設定する。 </li><li>レーザーのパルス繰り返しレートに対応するフレームレートで三次元画像を可視化できるようにする処理アルゴリズムのGPU実装とプリビューソフトウェアを起動します。 </li><li>プローブおよび/または可視化の性能を最適化し、目的の構造を局所化するために、撮像対象を移動させる。 </li></ol> 4.データ収集<ol><li> （ハンドヘルド）モードを走査するためのデータ収集。 </li><li>必要であれば、関心領域のコントラストを豊かにするための取得に先立って造影剤を注入する。 注：私たちの実験では、我々は造影人間イメージングを行っていない。しかし、様々な造影剤は、潜在的にこの目的に使用することができる。インドシアニングリーン（ICG）は、成人の体重を2mg / kgでの最大推奨用量でのコントラストの強調のために使用することができる臨床的に承認された光学造影剤の一例である。 </li><li>プレビューソフトウェアの実行を維持し3.1で説明したパラメータを持つデータ取得のためのハードウェアを起動します。静かに関心のある構造を追跡するために、画像化領域の周囲にプローブを移動させる。 注：複数のレーザ波長で画像を同時に取得されると、ハンドヘルドモードでのプローブの運動の速度は、（好ましくは2mm /秒未満に著しく減少されなければならないスペクトル的に混合されていない画像の動きに関連するアーチファクトを回避するために、50Hzのレーザパルス繰返し率）である。 </li><li>定常モードのためのデータ収集。 </li><li>ホルダーに、撮像対象（ 例えば 、動物）とハンドヘルドプローブをマウントし、プレビューソフトウェアの実行を維持し3.1で説明したパラメータを使用して取得を開始します。 </li><li>関心領域内の動的な生物学的事象を可視化するために、実験中の同じ位置における光音響プローブと撮像部を保持する。 </li><li>関心領域内の動的配布を追跡するために造影剤を注入する。 注：我々のマウス実験では、インドシアニングリーン（ICG）はコントラスト強調のために使用した。一般的なガイドラインとして、ICGの10ナノモル、または0.4〜10mg / kgの量は、in vivoでのマルチスペクトルoptoacousticsで検出可能なコントラストを作成するために、マウスの循環中に導入されなければならない。 注：造影剤は、でなければなりませんそれぞれの機関によって、ヒトおよび/または動物の使用のために承認した。 </li></ol> 5.実験ファイナライズ<ol><li>レーザーを停止します。 </li><li>撮像された領域から光音響プローブを除去。動物実験では、麻酔の供給を停止する。 </li><li>暖かいそれを維持し、それが完全に麻酔から回復するまで他の動物との接触を防ぐために、赤外線ヒーターの下に動物を配置します。麻酔からの回復中に無人の動物を放置しないでください。 </li></ol> 6.オフラインデータ処理<ol><li>データ処理に使用されるソフトウェアアプリケーションで取得した光音響信号を含むファイルを読み込む。 </li><li>各フレームおよび各波長に対する光吸収のボリュメトリック画像に対応する3次元マトリクス配列を得るために再構成アルゴリズムを使用する。 注：再構成のために、そのようなheterogeneなどの要因を歪ませるためのアルゴリズムのアカウンティングを使用することが好ましい吸収されたエネルギー分布のより定量的な表現を得るために、撮像対象でITIES減衰、最終的な帯域幅と検出素子と光フルエンス変動の幾何学的形状の影響。 </li><li>各多波長フレーム、試料中に存在する各吸収性物質の光吸収を表す3次元マトリックスアレイの新しいセットから、取得するアンミキシングアルゴリズムを使用する。 </li><li>必要に応じて、さらなる生物学的に関連するパラメータの可視化および読み取りを容易にするために、光吸収分布を表す行列アレイを処理する。 </li></ol>

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The authors have nothing to disclose.

小動物研究に光音響イメージング技術によって提供されるユニークな利点は、 例えば想定診断と治療モニタリングアプリケーションの数と、臨床の実践に技術を変換するための強力な動機を作成している。、乳癌および皮膚癌、炎症または末梢血管疾患で。しかし、効果的な断層像取得ジオメトリを作成するための照明源と検出素子の十分な数で囲むことができるマウス又は小さな動...

光音響（光音響）イメージング技術1-5が提供するユニークな利点を活用する新しいアプリケーションのさまざまな出版物を網羅増え続けることで明示されるよう、生物学および医学研究コミュニティからの関心の高まりを魅了しています。具体的には、はるかに光の拡散限界を超えた深さで高時空間解像度の画像スペクトル的に独特の光吸収剤の能力は、機能と分子イメージング6-10前例のない機能を開きます。 実際、臨床診療への光音響技術の翻訳は多くの疾患の診断および治療のモニタリングに有望な見通しが付属しています。しかし、光学的に散乱された光子を吸収組織や光音響現象に関連した一般的に弱い応答の限られた伝播は、この方法の適用可能な深さを制限。結果として、ハンドヘルドoptoa内視鏡システムは、自然のオリフィス13を介してそれらを挿入することによって、身体内から画像を提供するために使用されている間cousticプローブボディ11,12の外部からアクセス可能な画像部分に試みられてきた。そのような女性の胸のような人間の体の一部の低吸収部も、断層光音響スキャナ14,15でアクセスできます。それは同様に超音波検査を、大きな汎用性を可能にするので特に興味深いのは、手持ち式のアプローチである。ここでは、光音響イメージングのための一般的な超音波リニアアレイプローブの適応は、主に超音波およびoptoacoustics間の断層画像化要件の根本的な違いにより、依然として厳しい。標準的な超音波検査の高いフレームレートはkHzの範囲で高いパルス繰り返し周波数を用いた送受信シーケンシャル方式で有効にされているが、リアルタイムの三次元光音響イメージングは​​、単一のintから体積断層撮影データを同時に収集することにより達成されるレーザーパルスをerrogating。これにより、高品質の光音響イメージングは​​、撮像対象の周りに可能な限り大きな立体角から3次元データの取得を意味する。 最近、我々はリアルタイムで16を 3次元（体積）イメージングのための最初のハンドヘルド光音響プローブを導入しました。システムは、90°の角度をカバーする球面上に配置された圧電素子256（ 図1A中の青色のドット）の二次元配列に基づいている。約3×3mmの2の個々の要素の大きさ、ならびにそれらの配向および周波数帯域幅（約2-6メガヘルツ）は、 図中の球体の中心（黒立方体を囲むセンチメートルスケールのボリュームから有効な信号収集を保証する1A）。任意の波長SUSCように、撮像領域の光学的励起は、アレイの中央の円筒形キャビティを通って挿入繊維束を備えて​​いる繊維束を透過するのeptibleは、イメージングのために使用することができる。光ファイバ束と共にトランスデューサのアレイの実際の画像は、 図1Bに示されている。レーザーのパルス繰り返し周波数で決まるフレームレートでリアルタイムイメージングは​​さらに、グラフィックスを用いて有効にされるように、効率的な励起および信号の同時検出は、シングルショット励起（一方のレーザーパルス）と深部組織イメージングを可能にする処理ユニット（GPU）再建手続き17の実装。透明なポリエチレン膜（ 図1C）を有する円筒状ケーシングは、音響的に送信する液体媒体（水）を囲むように、トランスデューサアレイに接続されている。膜はさらに音響ゲルを用いて組織に結合されている。手持ち式の動作モードで使用されているような光音響プローブの画像が図1Dに示されている。 実証THR臨床診断および潜在的な用途の数の重要な利点が付属してリアルタイム機能イメージング能力と組み合わせるeeの次元ハンドヘルド光音響イメージングは​​、例えば、末梢血管疾患などの種々の適応症、リンパ系障害、乳癌、皮膚病変のために想定されている炎症または関節炎18。さらに、高速撮像能力は静止位置に配置されたプローブを用いた動的な生物学的事象の可視化を可能にします。高速波長同調光パラメトリック発振器（OPO）レーザー技術と組み合わせて、このアプローチは、光吸収剤の生体内分布のリアルタイムイメージングを可能にする。これにより、新たな可能性は等しく、例えば 、小動物イメージング用途に出現することができる。、組織血行動態を研究する、 インビボでの細胞追跡、薬物動態、臓器灌流の視覚化は、腫瘍及び心臓血管系、または神経画像の分子イメージング標的。

<table><tbody><tr><td>Optical parametric oscillator (OPO)-based laser</td><td>Innolas Laser GmbH, Krailling (Germany)</td><td>custom-made</td><td>The laser provides laser pulses with a duration around 10 nsec and an energy up to 80 mJ.&lt;br/&gt; The wavelength is tunable between 680-950 nm.</td></tr><tr><td>Spherical array of piezocomposite detectors</td><td>Imasonic SaS, Voray (France)</td><td>custom-made</td><td>The array consists of 256 piezoelectric sensors distributed on a spherical surface.&lt;br/&gt; Each element has dimensions 3 x 3 mm&lt;sup&gt;2&lt;/sup&gt;, a central frequency of 4 MHz and a bandwidth of 100%.&amp;nbsp;</td></tr><tr><td>Data acquisition system (DAQ)</td><td>Falkenstein Mikrosysteme GmbH, Taufkirchen (Germany)</td><td>custom-made</td><td>The DAQ simultaneously acquires 256 signals at 40 megasamples per second and 2,030 samples.&lt;br/&gt; The input impedance is 1 MW.</td></tr><tr><td>Fiber bundle</td><td>CeramOptec GmbH, Bonn (Germany)</td><td>custom-made</td><td>The bundle consists of 480 individual fibers randomly distributed in the input and output.&lt;br/&gt; The numerical aperture of each individual fiber is 0.22.</td></tr><tr><td>Athymic nude mouse</td><td>Harlan Laboratories (The Netherlands)</td><td>Athymic nude - Foxn1&lt;sup&gt;nu&lt;/sup&gt;</td><td>The mouse was 8 weeks old (adult) at the time of the experiment.&lt;br/&gt; The ethical protocol was approved by the Bavarian goverment (number 55.2.1.54-2632-102-11)</td></tr><tr><td>Bepanthen cream</td><td>Bayer AG (Germany)</td><td></td><td>Vet ointment to protect the eyes during anesthesia</td></tr><tr><td>Data processing software</td><td>Matlab (Mathworks, Natick, MA, USA)</td><td>custom-made</td><td>The data processing software was devoped at our institute.&lt;br/&gt; It allows reconstruction at each wavelength and multi-wavelength unmixing, as well as further data processing.</td></tr><tr><td>Water-enclosing part</td><td></td><td>custom-made</td><td>This part contains the water that acts as an acoustic coupling medium between skin and transducer elements</td></tr><tr><td>Indocyanine green (ICG)</td><td>PULSION Medical Systems SE</td><td></td><td>ICG-PULSION (active ingredient: indocyanine green dye) is a drug used in cardiac, circulatory and micro-circulatory diagnostics, liver function diagnostics and ophthalmic angiography diagnostics.</td></tr></tbody></table>

universal hand-held three-dimensional optoacoustic imaging probe for deep tissue human angiography and functional preclinical studies in real time

The exclusive combination of high optical contrast and excellent spatial resolution makes optoacoustics (photoacoustics) ideal for simultaneously attaining anatomical, functional and molecular contrast in deep optically opaque tissues. While enormous potential has been recently demonstrated in the application of optoacoustics for small animal research, vast efforts have also been undertaken in translating this imaging technology into clinical practice. We present here a newly developed optoacoustic tomography approach capable of delivering high resolution and spectrally enriched volumetric images of tissue morphology and function in real time. A detailed description of the experimental protocol for operating with the imaging system in both hand-held and stationary modes is provided and showcased for different potential scenarios involving functional and molecular studies in murine models and humans. The possibility for real time visualization in three dimensions along with the versatile handheld design of the imaging probe make the newly developed approach unique among the pantheon of imaging modalities used in today&#8217;s preclinical research and clinical practice.

代表的な結果は、説明した容積ハンドヘルド光音響プローブの能力を実証し、このセクションで紹介されています。全ての場合において、皮膚表面上の光のフルエンスを20mJ / cm 2と19の安全曝露限界以下に維持した。 ヒト末梢血管系の追跡リア ​​ルタイムでプローブの性能は、図2に紹介されている。この実験の過程で、プローブをゆっく?...

Watch this Scientific Journal Video about Universal Hand-held Three-dimensional Optoacoustic Imaging Probe for Deep Tissue Human Angiography and Functional Preclinical Studies in Real Time at JoVE.com

Universal Hand-held Three-dimensional Optoacoustic Imaging Probe for Deep Tissue Human Angiography and Functional Preclinical Studies in Real Time

We provide herein a detailed description of the experimental protocol for imaging with a newly developed hand-held optoacoustic (photoacoustic) system for three-dimensional functional and molecular imaging in real time. The demonstrated powerful performance and versatility may define new application areas of the optoacoustic technology in preclinical research and clinical practice.

ディープティシュ人間血管造影および機能前臨床研究のためのユニバーサルハンドヘルド三次元光音響イメージングプローブリアルタイムで

The exclusive combination of high optical contrast and excellent spatial resolution makes optoacoustics (photoacoustics) ideal for simultaneously ...

universal-hand-held-three-dimensional-optoacoustic-imaging-probe-for

Research

JoVE Journal

Bioengineering

10.7K ビュー.  Helmholtz Zentrum München. We provide herein a detailed description of the experimental protocol for imaging with a newly developed hand-held optoacoustic (photoacoustic) system for three-dimensional functional and molecular imaging in real time. The demonstrated powerful performance and versatility may define new application areas of the optoacoustic technology in preclinical research and clinical practice.

ビデオ: Universal Hand-held Three-dimensional Optoacoustic Imaging Probe for Deep Tissue Human Angiography and Functional Preclinical Studies in Real Time

Three-dimensional Optical-resolution Photoacoustic Microscopy

Optical microscopy, providing valuable insights at the cellular and organelle levels, has been widely recognized as an enabling biomedical technology. As the mainstays of in vivo three-dimensional (3-D) optical microscopy, single-/multi-photon fluorescence microscopy and optical coherence tomography (OCT) have demonstrated their extraordinary sensitivities to fluorescence and optical scattering contrasts, respectively. However, the optical absorption contrast of biological tissues, which encodes essential physiological/pathological information, has not yet been assessable. 
The emergence of biomedical photoacoustics has led to a new branch of optical microscopy optical-resolution photoacoustic microscopy (OR-PAM)1, where the optical irradiation is focused to the diffraction limit to achieve cellular1 or even subcellular2 level lateral resolution. As a valuable complement to existing optical microscopy technologies, OR-PAM brings in at least two novelties. First and most importantly, OR-PAM detects optical absorption contrasts with extraordinary sensitivity (i.e., 100%). Combining OR-PAM with fluorescence microscopy3 or with optical-scattering-based OCT4 (or with both) provides comprehensive optical properties of biological tissues. Second, OR-PAM encodes optical absorption into acoustic waves, in contrast to the pure optical processes in fluorescence microscopy and OCT, and provides background-free detection. The acoustic detection in OR-PAM mitigates the impacts of optical scattering on signal degradation and naturally eliminates possible interferences (i.e., crosstalks) between excitation and detection, which is a common problem in fluorescence microscopy due to the overlap between the excitation and fluorescence spectra. 
Unique for optical absorption imaging, OR-PAM has demonstrated broad biomedical applications since its invention, including, but not limited to, neurology5, 6, ophthalmology7, 8, vascular biology9, and dermatology10. In this video, we teach the system configuration and alignment of OR-PAM as well as the experimental procedures for in vivo functional microvascular imaging.

Optical-resolution photoacoustic microscopy (OR-PAM) is an emerging technology capable of imaging optical absorption contrasts in vivo with cellular resolution and sensitivity. Here, we provide a visualized instruction on the experimental protocols of OR-PAM, including system configuration, system alignment, typical in vivo experimental procedures, and functional imaging schemes.

三次元光学分解能光音響顕微鏡

Optical microscopy, providing valuable insights at the cellular and organelle levels, has been widely recognized as an enabling biomedical technology. As ...

生物工学

Three-Dimensional Ultrasonic Needle Tip Tracking with a Fiber-Optic Ultrasound Receiver

Ultrasound is frequently used for guiding minimally invasive procedures, but visualizing medical devices is often challenging with this imaging modality. When visualization is lost, the medical device can cause trauma to critical tissue structures. Here, a method to track the needle tip during ultrasound image-guided procedures is presented. This method involves the use of a fiber-optic ultrasound receiver that is affixed within the cannula of a medical needle to communicate ultrasonically with the external ultrasound probe. This custom probe comprises a central transducer element array and side element arrays. In addition to conventional two-dimensional (2D) B-mode ultrasound imaging provided by the central array, three-dimensional (3D) needle tip tracking is provided by the side arrays. For B-mode ultrasound imaging, a standard transmit-receive sequence with electronic beamforming is performed. For ultrasonic tracking, Golay-coded ultrasound transmissions from the 4 side arrays are received by the hydrophone sensor, and subsequently the received signals are decoded to identify the needle tip&#39;s spatial location with respect to the ultrasound imaging probe. As a preliminary validation of this method, insertions of the needle/hydrophone pair were performed in clinically realistic contexts. This novel ultrasound imaging/tracking method is compatible with current clinical workflow, and it provides reliable device tracking during in-plane and out-of-plane needle insertions.

Accurate and efficient visualization of invasive medical devices is extremely important in many ultrasound-guided minimally invasive procedures. Here, a method for localizing the spatial position of a needle tip relative to the ultrasound imaging probe is presented.

三次元超音波針の先端光ファイバー超音波受信機と追跡

Ultrasound is frequently used for guiding minimally invasive procedures, but visualizing medical devices is often challenging with this imaging modality. ...

工学

Generation and 3-Dimensional Quantitation of Arterial Lesions in Mice Using Optical Projection Tomography

The generation and analysis of vascular lesions in appropriate animal models is a cornerstone of research into cardiovascular disease, generating important information on the pathogenesis of lesion formation and the action of novel therapies. Use of atherosclerosis-prone mice, surgical methods of lesion induction, and dietary modification has dramatically improved understanding of the mechanisms that contribute to disease development and the potential of new treatments.
Classically, analysis of lesions is performed ex vivo using 2-dimensional histological techniques. This article describes application of optical projection tomography (OPT) to 3-dimensional quantitation of arterial lesions. As this technique is non-destructive, it can be used as an adjunct to standard histological and immunohistochemical analyses.
Neointimal lesions were induced by wire-insertion or ligation of the mouse femoral artery whilst atherosclerotic lesions were generated by administration of an atherogenic diet to apoE-deficient mice.
Lesions were examined using OPT imaging of autofluorescent emission followed by complementary histological and immunohistochemical analysis. OPT clearly distinguished lesions from the underlying vascular wall. Lesion size was calculated in 2-dimensional sections using planimetry, enabling calculation of lesion volume and maximal cross-sectional area. Data generated using OPT were consistent with measurements obtained using histology, confirming the accuracy of the technique and its potential as a complement (rather than alternative) to traditional methods of analysis.
This work demonstrates the potential of OPT for imaging atherosclerotic and neointimal lesions. It provides a rapid, much needed ex vivo technique for the routine 3-dimensional quantification of vascular remodelling.

Ex vivo analysis of arterial lesions from animal models of cardiovascular disease classically relies on histological and immunohistochemical techniques. These provide 2-dimensional measurements in 3-dimensional lesions. This manuscript describes the generation of arterial lesions for quantitative analysis in 3-dimensions using optical projection tomography.

発生と光学投影トモグラフィを用いたマウスにおける動脈病変の3次元定量

The generation and analysis of vascular lesions in appropriate animal models is a cornerstone of research into cardiovascular disease, generating ...

医学

Non-invasive Parenchymal, Vascular and Metabolic High-frequency Ultrasound and Photoacoustic Rat Deep Brain Imaging

Photoacoustics and high frequency ultrasound stands out as powerful tools for neurobiological applications enabling high-resolution imaging on the central nervous system of small animals. However, transdermal and transcranial neuroimaging is frequently affected by low sensitivity, image aberrations and loss of space resolution, requiring scalp or even skull removal before imaging. To overcome this challenge, a new protocol is presented to gain significant insights in brain hemodynamics by photoacoustic and high-frequency ultrasounds imaging with the animal skin and skull intact. The procedure relies on the passage of ultrasound (US) waves and laser directly through the fissures that are naturally present on the animal cranium. By juxtaposing the imaging transducer device exactly in correspondence to these selected areas where the skull has a reduced thickness or is totally absent, one can acquire high quality deep images and explore internal brain regions that are usually difficult to anatomically or functionally describe without an invasive approach. By applying this experimental procedure, significant data can be collected in both sonic and optoacoustic modalities, enabling to image the parenchymal and the vascular anatomy far below the head surface. Deep brain features such as parenchymal convolutions and fissures separating the lobes were clearly visible. Moreover, the configuration of large and small blood vessels was imaged at several millimeters of depth, and precise information were collected about blood fluxes, vascular stream velocities and the hemoglobin chemical state. This repertoire of data could be crucial in several research contests, ranging from brain vascular disease studies to experimental techniques involving the systemic administration of exogenous chemicals or other objects endowed with imaging contrast enhancement properties. In conclusion, thanks to the presented protocol, the US and PA techniques become an attractive noninvasive performance-competitive means for cortical and internal brain imaging, retaining a significant potential in many neurologic fields.

The present work describes a new protocol to perform non-invasive high-frequency ultrasound and photoacoustic based imaging on rat brain, to efficiently visualize deep subcortical regions and their vascular patterns by directing signals on skull foramina naturally present on animal cranium.

非侵襲的実質細胞、血管および代謝高周波超音波および光音響ラット脳深部イメージング

Photoacoustics and high frequency ultrasound stands out as powerful tools for neurobiological applications enabling high-resolution imaging on the central ...

神経科学

An Experimental Protocol for Assessing the Performance of New Ultrasound Probes Based on CMUT Technology in Application to Brain Imaging

The possibility to perform an early and repeatable assessment of imaging performance is fundamental in the design and development process of new ultrasound (US) probes. Particularly, a more realistic analysis with application-specific imaging targets can be extremely valuable to assess the expected performance of US probes in their potential clinical field of application.
The experimental protocol presented in this work was purposely designed to provide an application-specific assessment procedure for newly-developed US probe prototypes based on Capacitive Micromachined Ultrasonic Transducer (CMUT) technology in relation to brain imaging.
The protocol combines the use of a bovine brain fixed in formalin as the imaging target, which ensures both realism and repeatability of the described procedures, and of neuronavigation techniques borrowed from neurosurgery. The US probe is in fact connected to a motion tracking system which acquires position data and enables the superposition of US images to reference Magnetic Resonance (MR) images of the brain. This provides a means for human experts to perform a visual qualitative assessment of the US probe imaging performance and to compare acquisitions made with different probes. Moreover, the protocol relies on the use of a complete and open research and development system for US image acquisition, i.e. the Ultrasound Advanced Open Platform (ULA-OP) scanner.
The manuscript describes in detail the instruments and procedures involved in the protocol, in particular for&#160;the calibration, image acquisition and registration of US and MR images. The obtained results prove the effectiveness of the overall protocol presented, which is entirely open (within the limits of the instrumentation involved), repeatable, and covers the entire set of acquisition and processing activities for US images.

The development of new ultrasound (US) probes based on Capacitive Micromachined Ultrasonic Transducer (CMUT) technology requires an early realistic assessment of imaging capabilities. We describe a repeatable experimental protocol for US image acquisition and comparison with magnetic resonance images, using an ex vivo bovine brain as an imaging target.

脳イメージングへの応用による CMUT 技術に基づく新しい超音波プローブの性能を評価するための実験プロトコル

The possibility to perform an early and repeatable assessment of imaging performance is fundamental in the design and development process of new ...

Switchable Acoustic and Optical Resolution Photoacoustic Microscopy for In Vivo Small-animal Blood Vasculature Imaging

Photoacoustic microscopy (PAM) is a fast-growing invivo imaging modality that combines both optics and ultrasound, providing penetration beyond the optical mean free path (~1 mm in skin) with high resolution. By combining optical absorption contrast with the high spatial resolution of ultrasound in a single modality, this technique can penetrate deep tissues. Photoacoustic microscopy systems can have either a low acoustic resolution and probe deeply or a high optical resolution and probe shallowly. It is challenging to achieve high spatial resolution and large depth penetration with a single system. This work presents an AR-OR-PAM system capable of both high-resolution imaging at shallow depths and low-resolution deep-tissue imaging of the same sample in vivo. A lateral resolution of 4 &#181;m with 1.4 mm imaging depth using optical focusing and a lateral resolution of 45 &#181;m with 7.8 mm imaging depth using acoustic focusing were successfully demonstrated using the combined system. Here,&#160;in vivo&#160;small-animal blood vasculature imaging is performed to demonstrate its biological imaging capability.

Switchable Acoustic and Optical Resolution Photoacoustic Microscopy for In Vivo Small-animal Blood Vasculature Imaging

Here a switchable acoustic resolution (AR) and optical resolution (OR) photoacoustic microscopy (AR-OR-PAM) system capable of both high resolution imaging at shallow depth and low resolution deep tissue imaging on the same sample in vivo is demonstrated.

切り替え可能な音響光学分解能光音響顕微鏡<em&gt;インビボ</em&gt;小動物の血管系イメージング

Photoacoustic microscopy (PAM) is a fast-growing invivo imaging modality that combines both optics and ultrasound, providing penetration beyond the ...

A High-performance Compact Photoacoustic Tomography System for In Vivo Small-animal Brain Imaging

In vivo small-animal imaging has an important role to play in preclinical studies. Photoacoustic tomography (PAT) is an emerging hybrid imaging modality that shows great potential for both preclinical and clinical applications. Conventional optical parametric oscillator-based PAT (OPO-PAT) systems are bulky and expensive and cannot provide high-speed imaging. Recently, pulsed-laser diodes (PLDs) have been successfully demonstrated as an alternative excitation source for PAT. Pulsed-laser diode PAT (PLD-PAT) has been successfully demonstrated for high-speed imaging on photoacoustic phantoms and biological tissues. This work provides a visualized experimental protocol for in vivo brain imaging using PLD-PAT. The protocol includes the compact PLD-PAT system configuration and its description, animal preparation for brain imaging, and a typical experimental procedure for 2D cross-sectional rat brain imaging. The PLD-PAT system is compact and cost-effective and can provide high-speed, high-quality imaging. Brain images collected in vivo at various scan speeds are presented.

A High-performance Compact Photoacoustic Tomography System for In Vivo Small-animal Brain Imaging

A compact pulsed-laser diode-based photoacoustic tomography (PLD-PAT) system for high-speed in vivo brain imaging in small animals is demonstrated.

高性能小型光音響トモグラフィーシステム<em&gt;インビボ</em&gt;小動物脳イメージング

In vivo small-animal imaging has an important role to play in preclinical studies. Photoacoustic tomography (PAT) is an emerging hybrid imaging modality ...

Hand-held Clinical Photoacoustic Imaging System for Real-time Non-invasive Small Animal Imaging

Translation of photoacoustic imaging into the clinic is a major challenge. Handheld real-time clinical photoacoustic imaging systems are very rare. Here, we report a combined photoacoustic and clinical ultrasound imaging system by integrating an ultrasound probe with light delivery for small animal imaging. We demonstrate this by showing sentinel lymph node imaging in small animals along with minimally invasive real-time needle guidance. A clinical ultrasound platform with access to raw channel data allows the integration of photoacoustic imaging leading to a handheld real-time clinical photoacoustic imaging system. Methylene blue was used for sentinel lymph node imaging at 675 nm wavelength. Additionally, needle guidance with dual modal ultrasound and photoacoustic imaging was shown using the imaging system. Depth imaging of up to 1.5 cm was demonstrated with a 10 Hz laser at a photoacoustic imaging frame rate of 5 frames per second.

A clinical handheld photoacoustic imaging system will be demonstrated for real-time non-invasive small animal imaging.

手持ちの臨床音響小動物の非侵襲的な実時間イメージングによる画像計測

Translation of photoacoustic imaging into the clinic is a major challenge. Handheld real-time clinical photoacoustic imaging systems are very rare. Here, ...

Dual Raster-Scanning Photoacoustic Small-Animal Imager for Vascular Visualization

Imaging of vascular networks on small animals has played an important role in basic biomedical research. Photoacoustic imaging technology has great potential for application in the imageology of small animals. The wide-field photoacoustic imaging of small animals can provide images with high spatiotemporal resolution, deep penetration, and multiple contrasts. Also, the real-time photoacoustic imaging system is desirable to observe the hemodynamic activities of small-animal vasculature, which can be used to research the dynamic monitoring of small-animal physiological features. Here, a dual-raster-scanning photoacoustic imager is presented, featuring a switchable double-mode imaging function. The wide-field imaging is driven by a two-dimensional motorized translation stage, while the real-time imaging is realized with galvanometers. By setting different parameters and imaging modes, in vivo visualization of small-animal vascular network can be performed. The real-time imaging can be used to observe pulse change and blood flow change of drug-induced, etc. The wide-field imaging can be used to track the growth change of tumor vasculature. These are easy to be adopted in various areas of basic biomedicine research.

A dual raster-scanning photoacoustic imager was designed, which integrated wide-field imaging and real-time imaging.

血管可視化のための二重ラスター走査光音響小動物イメージャー

Imaging of vascular networks on small animals has played an important role in basic biomedical research. Photoacoustic imaging technology has great ...

Multispectral Optoacoustic Tomography for Functional Imaging in Vascular Research

Microcirculatory impairment has been recognized in various disease processes, underlying this growing theme within vascular research. In recent years, the development of live imaging systems has set the (analytical) pace in both basic and clinical research, with the objective of creating new instruments capable of providing real-time, quantifiable endpoints with clinical interest and application. Near-infrared spectroscopy (NIRS), positron emission tomography (PET), computed tomography (CT), and magnetic resonance imaging (MRI) are available, among other techniques, but cost, image resolution, and reduced contrast are recognized as common challenges. Optoacoustic tomography (OT) offers a new perspective on vascular functional imaging, combining state-of-the-art optical absorption and spatial resolution capacities (from micrometer optical to millimeter acoustic resolution) with tissue depth. In this study, we tested the applicability of multispectral optoacoustic tomography (MSOT) for functional imaging. The system uses a tunable optical parametric oscillator (OPO) pumped by an Nd: YAG laser, providing excitation pulses sensed by a 3D probe at wavelengths from 680 nm to 980 nm. Images obtained from the human forearm were reconstructed through a specific algorithm (supplied within the manufacturer&#39;s software) based on the response of specific chromophores. Maximal Oxygenated Hemoglobin (Max HbO2) and Deoxygenated Hemoglobin (Max Hb), Total Hemoglobin (HbT), and mean Oxygen Saturation (mSO2) to vascular density (&#181;Vu), inter-unit average distances (&#950;Ad), and capillary blood volume (mm3) may be measured using this system. The applicability potential found with this OT system is relevant. Ongoing software developments will surely improve the utility of this imaging system.

The present protocol describes the acquisition of multispectral optoacoustic images of in vivo human skin vasculature. These include the quantification of hemoglobin and melanin, regarded as chromophores of interest for functional analysis.

血管研究における機能イメージングのためのマルチスペクトル光音響断層撮影

Microcirculatory impairment has been recognized in various disease processes, underlying this growing theme within vascular research. In recent years, the ...

ディープティシュ人間血管造影および機能前臨床研究のためのユニバーサルハンドヘルド三次元光音響イメージングプローブリアルタイムで

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