手持式实时非侵入性小动物成像的临床光声成像系统
Summary
一个临床手持光声成像系统将证明 real-time 非侵入性小动物成像。
Abstract
光声成像在临床中的翻译是一项重大挑战。手持 real-time 临床光声成像系统是非常罕见的。在这里, 我们报告一个联合光声和临床超声成像系统集成了一个超声探头与轻分娩的小动物成像。我们通过在小动物身上显示前哨淋巴结成像以及微创 real-time 针引导来证明这一点。一个具有原始通道数据的临床超声平台允许将光声成像集成到手持 real-time 的临床光声成像系统中。亚甲蓝用于前哨淋巴结成像 675 nm 波长。此外, 使用成像系统显示了双模态超声和光声成像的针制导。高达1.5 厘米的深度成像演示了10赫兹激光器的光声成像帧速率为每秒5帧。
Introduction
对于癌症的检测和分期, 有不同的成像技术。一些广泛使用的成像模式是磁共振成像 (MRI), x 射线计算机断层扫描 (CT), x 射线, 超声 (美国), 正电子发射断层扫描 (PET), 荧光成像,等1,2,3,4. 但是, 现有的一些成像技术要么是侵入性的、有害的辐射, 要么是缓慢的、昂贵的、笨重的或对病人不友善的。因此, 有一个不断需要开发新的, 快速的, 和 cost-effective 成像技术的诊断和治疗5。
光声成像 (排) 是一种新兴的成像技术, 它结合了丰富的光学对比度和高超声分辨率在更深的成像深度5,6,7,8, 9。在排, 一个短的激光脉冲用于组织照射。光被组织吸收, 导致小的温度上升。由于热弹性膨胀, 压力波 (以声波的形式) 在组织内产生。产生的声波 (也称为光声 (PA) 波) 是获得了一个宽带超声换能器 (一) 外的组织边界。这些获得的 pa 信号可以用来重建 pa 图像, 揭示组织内部的结构和功能信息。排有广泛的应用, 包括: 血管成像, 前哨淋巴结成像, 脑血管成像, 肿瘤成像, 分子成像,等10,11,12, 13,14,15排有许多应用, 因为它的优点是: 更深的穿透深度, 良好的空间分辨率, 和高的软组织对比度。在排的对比可以是内生的血液, 黑色素,等。当内源对比度不够强时, 外源对比剂如有机染料、纳米粒子、量子点、等16、17、18、19、20,21可用于改善对比度。
尽管排便与其他成像技术相比有许多好处, 但临床翻译仍然是一个很大的挑战。主要的限制是使用的激光器笨重的性质, 大多数用于数据采集的 USTs 与临床美国系统不兼容, 而且没有提供可供使用的美国临床成像系统, 可以访问原始通道数据.直到最近, 具有访问原始数据的商用临床美国机器才成为可用的22。在这项工作中, 我们的目的是展示使用一个临床美国平台的手持式安装的可行性。我们的目的是通过在小动物模型中显示前哨淋巴结 (淋巴结) 的非侵入性成像来证明这一点。
侵袭性乳腺肿瘤是女性癌症死亡的主要原因之一。早期诊断和分期乳腺癌是决定治疗策略的关键, 对患者的预后起着重要作用。乳腺癌分期前哨淋巴结活检 (SLNB) 通常使用23,24。SLN 是主要的淋巴结, 可能发现癌细胞是最高的, 由于转移。SLNBs 涉及注射染料或放射性示踪剂, 其次是用小切口切开该区域, 然后在染料的情况下或在盖革计数器的帮助下以视觉方式定位 SLN, 以防放射性示踪剂。经过鉴定, 一些 SLN 被删除的病理学研究24,25。阳性 SLNB 表明, 肿瘤已转移到附近的淋巴结和其他器官可能。阴性 SLNB 表明, 转移的概率是微不足道的26。SLNB 有许多相关的并发症, 如手臂麻木, 淋巴水肿,等27为了消除 SLNB 相关的并发症, 需要一种非侵入性的成像技术。
对于小动物和人类的 SLN 映射, PA 成像在不同对比剂的帮助下得到了广泛的探索15,28,29,30,31,32. 但是, 目前所使用的系统不能用于临床情况, 正如前面所指出的那样。另一个需要解决的问题是 SLNB28中涉及的外科手术过程。为了减少患者的恢复时间和副作用, 需要对细针穿刺活检 (FNAB) 进行微创手术。在这项工作中, 一个临床美国系统被用来结合美国和 PA 成像是使用。为了便于临床安装, 设计了一种定制的用于住宅光纤和光的手持支架。亚甲蓝 (MB) 用于识别和测绘淋巴结. 此外, 为了消除与 SLNB 手术相关的并发症, 还演示了无创 real-time 针跟踪。
Protocol
所有动物实验都是根据新加坡南洋理工大学动物保育和使用委员会批准的指导方针和规定进行的 (动物协议号-SBS/NIE-A0263). 1. 手持式实时临床 PA 和美国成像系统 手持式临床排系统的示意图 33 显示在 图 1a 中。它由一个光学参量振荡器 (参量) 激光器泵浦的频率加倍的纳秒脉冲钕: YAG 激光器, 分岔光纤束 ( 图 …
Representative Results
图 1: 系统描述。(a)具有双模态临床美国系统的排系统的示意图表示。参量-光学参量振荡器, 光纤束, 跳频光纤支架, USM-临床美国机器。光纤支架集成了两个输出光纤束。在实验过程中, 使用异氟醚和氧的麻醉机来保持动物的麻醉。(b)分岔光纤的照片。i/o 表示光纤的输入端…
Discussion
目前癌症的筛查、诊断和治疗的费用非常高。有不同的成像方式, 正在用于癌症筛查和诊断。然而, 这些成像技术有很多限制, 包括笨重的机器大小, 侵入性诊断, 友好病人, 太昂贵, 要求电离辐射, 或使用放射性造影剂。因此, 需要有一个高效、成本效益高、real-time 的成像和引导系统。结合美国和 PA 成像是一种技术, 可用于有效的, 非侵入性的筛查, 诊断和分期的癌症。临床 PA 成像可以使更可行的 FDA…
Disclosures
The authors have nothing to disclose.
Acknowledgements
作者想感谢新加坡教育部资助的1级研究补助金 (RG48/16: M4011617) 和新加坡教育部资助的2级研究补助金 (ARC2/15: M4020238) 的财政支持。作者想承认 Dr. Rhonnie 奥地利 Dienzo 对动物处理的帮助。
Materials
| Q-switched Nd:YAG laser | Continuum | Surelite | Pump laser |
| Optical parametric oscillator | Continuum | OPO laser | |
| Clinical ultrasound imaging system | Alpinion | E-CUBE 12R | Dual modal ultrasound and photoacoustic imaging system |
| Linear array ultrasound transducer | Alpinion | L3-12 | 128 element linear array transducer with centre frequency of 8.5 MHz, fractional bandwidth of 95%, |
| Bifurcated optical fiber | CeramOptec | Custom made | To couple the light from the laser to the handheld fiber holder |
| Lens | Thorlabs | LB1869 | Focus light from the laser to the optical fiber |
| Ultrasound gel | Progress/parker acquasonic gel | PA-GEL-CLEA-5000 | Acoustic coupling |
| Image Processing software | Mathworks | Matlab | Home made program using Matlab |
| Anesthetic Machine | medical plus pte ltd | Non-Rebreathing Anaesthesia machine with oxygen concentrator. | Supplies oxygen and isoflurane to animal |
| Pulse Oxymeter portable | Medtronic | PM10N with veterinary sensor | Monitors the pulse oxymetry of the animal |
| Animal distributor | In Vivos Pte Ltd, Singapore | Animal distributor that supplies small animals for research purpose. | |
| Breathing mask | Custom made | Used along with animal holder to supply anesthesia mixture to the animal | |
| chicken breast tissue | Pasar | Used to add depth to mimic human imaging scenario | |
| 23G needle | BD Precisionglide | 23G,1 and half inch | Used for realtime needle guidance |
| Holder for the fiber optic cable | Custom made | To hold the input end of the bifurcated cable | |
| Handheld probe | Custom made 3D printed | With two slots for the two output ends of the optical fiber and one slot for the ultrasound transducer | |
| Methylene blue (10 mg/mL) | Sterop | Contrast agent for PA imaging | |
| Laser tuning software | Surelite OPO PLUS | SLOPO | Software to tune the wavelength of OPO laser |
| Photodiode | Thorlabs | SP05/M | To detect the laser pulse to trigger the ultrasound system |
| Photodiode bias module | Thorlabs | PBM42 | To amplify the photodiode signal to tigger ultrasound signal |
| Depilatory cream | Reckitt Benckiser | Veet | Used to remove hair from the imaging area |
| Laser power meter | Ophir | Starlite, p/n: 7Z01565 | Used to measure the laser power |
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Cite This Article
Sivasubramanian, K., Periyasamy, V., Pramanik, M. Hand-held Clinical Photoacoustic Imaging System for Real-time Non-invasive Small Animal Imaging. J. Vis. Exp. (128), e56649, doi:10.3791/56649 (2017).