Laser System for Clinical Photoacoustic Imaging Applications

描述（由申请人提供）：光声断层扫描（PAT）的最新进展已经证明了其在穿透深度数厘米的软组织三维无创高分辨率成像方面的潜力。此外，也许更重要的是，组织结构的成像可以在提供关于组织组成和功能的关键信息的同时实现。这些结果代表了软组织成像技术的重大突破。虽然这项技术有许多应用，但以癌症筛查和诊断为目的的乳房成像是相当重要的应用之一，影响着国内和全球医疗保健的成本和质量PAT利用特定波长的强、短持续时间（纳秒）激光脉冲。目标组织对这些波长的选择性吸收产生了初级声信号。高分辨率声学成像是通过先进的声学探测器阵列和相关的信号处理电子和软件来实现的。组织识别是由多个（深红色和近红外）波长的差分图像获得的。对于需要穿透深层组织和肿瘤定位的乳腺成像，感兴趣的关键波长位于亚历山大变石激光器(或亚历山大变石和Nd:YAG激光器（700 - 1100 nm）的调谐范围内。因此，开发符合乳腺光声成像特定要求的翠绿宝石激光器对于肿瘤诊断和成像系统的发展至关重要。这些特定的激光要求主要与所使用的波长、脉冲时间序列、脉冲持续时间、脉冲能量和激光系统产生的光束的空间均匀性有关。光时代公司是亚历山大变石和其他固态激光系统的发明者、设计者和主要开发者。在过去的十年中，它已经开发并向研究人员交付了满足PAT某些关键要求的激光系统。这些激光系统已经成功地开发用于各种应用，包括乳房软组织成像，并且最近提供了一些戏剧性的结果（见研究策略部分）。这里提出的努力是开发一个原型PAT系统，专门为这个应用程序，并执行动物和人类受试者的初步测试。由于已知激光波长是非诱变的，并且在这里使用的影响水平远低于目前在公认的和fda批准的基于翠绿宝石的激光医疗设备中用于治疗色素和血管病变的常规水平，因此对研究对象没有可想象的风险。第一阶段和后续的第二阶段项目的目标是开发一种适合临床成像技术人员使用的基于激光的PAT系统。该原型临床系统将在性能、系统包装和易用性方面满足乳腺成像的所有基本要求。此外，它可以提供先进的乳房肿瘤识别能力，超越当今最先进的技术。在第一阶段计划中，我们将开发和演示用于PAT的改进激光源。在其性能特性的其他改进中，它将提供一种具有快速（脉冲到脉冲）波长切换的新型激光操作模式。这可能使组织识别的改进，可以实现通过血管组织的鉴别成像，由于氧和脱氧血红蛋白浓度。我们亦会进行研究，以确定操作因素，例如更高的重复频率和更高的脉冲能量，会如何影响系统的大小和成本。这些研究将有助于指导未来临床激光系统的规格。在二期项目中，我们将向optosonic， Inc.（一家位于北卡罗来纳州的PAT系统开发商）提供一种包含快速波长切换功能的激光系统，用于测试和临床鉴定。在第二阶段，我们还将对激光和PAT控制系统进行改进，以满足临床手术的需要。为了确保我们的技术工作始终专注于PAT性能的关键领域，在整个第一阶段项目中，我们将与Optosonics的合作者进行磋商。

DESCRIPTION (provided by applicant): Recent advances in photoacoustic tomography (PAT) have demonstrated its potential for 3D noninvasive high resolution imaging of soft tissues at penetration depths of many centimeters. Further, and perhaps even more importantly, imaging of tissue structure can be achieved while also providing crucial information regarding tissue composition and functionality. These results represent a dramatic breakthrough in soft tissue imaging technology. While there are a host of applications for this technology, breast imaging for the purpose of cancer screening and diagnosis is one of considerable import, affecting both cost and quality of healthcare nationally and globally.17 PAT makes use of intense, short-duration (nanosecond) laser pulses at specific wavelengths. The selective absorption of these wavelengths by targeted tissues gives rise to a primary acoustic signal. High resolution acoustic imaging is achieved by means of an advanced array of acoustic detectors and associated signal processing electronics and software. Tissue discrimination is obtained from differential images at multiple (deep red and near infrared) wavelengths. For breast imaging, requiring deep tissue penetration and tumor localization, the key wavelengths of interest lie within the tuning range of alexandrite lasers (or of alexandrite and Nd:YAG lasers (700 - 1100 nm). Consequently, the development of alexandrite lasers that meet the specific requirements for photoacoustic imaging of the breast is critical for the development of tumor diagnostic and imaging systems. These specific laser requirements relate primarily to the wavelengths used, pulse sequence in time, the pulse duration, the pulse energy, and the spatial uniformity of the beam produced by the laser system. Light Age Inc., is the inventor, designer, and principal developer of alexandrite and other solid-state laser systems. Over the past decade it has developed and delivered laser systems to researchers that meet certain key requirements for PAT These laser systems have been successfully developed for a variety of applications, including soft tissue imaging of the breast, and have recently provided some dramatic results (see Research Strategy section). The effort proposed here is to develop a prototype PAT system specifically for this application and to perform initial testing on animals and human subjects. Because the laser wavelengths are known to be non-mutagenic and the fluence levels used here are well-below those now routinely used to treat pigmented and vascular lesions in well-established and FDA-approved alexandrite laser-based medical devices, there is no conceivable risk to study subjects. The goal of this Phase I and follow-on Phase II program is to develop a laser-based PAT system suitable for use by a clinical imaging technician. The prototype clinical system will meet all of the basic requirements for breast imaging with respect to performance, system packaging, and ease of use. Additionally, it can provide advanced breast tumor discrimination capabilities beyond the present-day state-of-the-art. In the Phase I program, we will develop and demonstrate an improved laser source for PAT. Among other improvements in its performance properties it will provide a novel laser operating mode having rapid (pulse-to-pulse) wavelength switching. This may enable improvements in the tissue discrimination that can be achieved by means of differential imaging of vascular tissues due to oxy- and deoxy- hemoglobin concentrations. We will also conduct studies to determine how operating factors such as greater repetition rate and higher pulse energy will affect system size and cost. These studies will help guide the specifications for future clinical laser systems. In the Phase II program we will deliver a laser system that incorporates the rapid wavelength switching feature, to Optosonics, Inc. (a PAT system developer based in N. Carolina) for testing and clinical qualification. In Phase II we will also develop refinements to the laser and PAT control systems that are additionally desirable for clinical operation. To ensure that our technical work remains focused on the key areas of performance for PAT, throughout the Phase I program we will consult with collaborators at Optosonics.