Laser System for Clinical Photoacoustic Imaging Applications

描述(申请人提供)：光声断层成像(PAT)的最新进展已经证明了其在穿透深度为许多厘米的软组织的3D无创高分辨率成像的潜力。此外，也许更重要的是，可以实现组织结构的成像，同时还可以提供关于组织成分和功能的关键信息。这些结果代表着软组织成像技术的重大突破。虽然这项技术有许多应用，但用于癌症筛查和诊断的乳房成像是相当重要的，它影响到全国和全球的医疗保健成本和质量。17 PAT使用特定波长的短持续时间(纳秒)强激光脉冲。靶组织对这些波长的选择性吸收产生了初级声信号。高分辨率的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设备和软件实现的。组织识别是从多个(深红色和近红外)波长的差异图像中获得的。对于需要深入组织穿透和肿瘤定位的乳房成像，感兴趣的关键波长位于紫翠宝石激光(或紫翠宝石和Nd：YAG激光(700-1100 nm))的调谐范围内。因此，满足乳房光声成像特殊要求的紫翠宝石激光器的开发对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涉及所使用的波长、脉冲时间序列、脉冲持续时间、脉冲能量以及由激光系统产生的光束的空间均匀性。Light Age Inc.是紫翠宝石和其他固态激光系统的发明者、设计者和主要开发商。在过去的十年里，它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。这些激光系统已成功开发用于各种应用，包括乳房软组织成像，最近取得了一些引人注目的成果(参见研究战略部分)。这里提出的努力是专门为这一应用开发一个原型PAT系统，并在动物和人类受试者身上进行初步测试。由于已知激光波长是无致突变的，而且这里使用的剂量水平远低于目前用于治疗成熟和FDA批准的紫翠宝石激光医疗设备中的色素和血管病变的剂量水平，因此研究对象不存在可想象的风险。这一第一阶段和后续第二阶段计划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。原型临床系统将满足乳房成像在性能、系统封装和易用性方面的所有基本要求。此外，它还可以提供先进的乳房肿瘤识别能力，超出当今最先进的水平。在第一阶段计划中，我们将为PAT开发和演示一种改进的激光光源。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。这可以改善通过对由于氧合和脱氧血红蛋白浓度引起的血管组织进行差示成像而实现的组织分辨能力。我们还将进行研究，以确定更高的重复率和更高的脉冲能量等操作因素将如何影响系统规模和成本。这些研究将有助于指导未来临床激光系统的规范。在第二阶段计划中，我们将向光电子公司(北卡罗来纳州的一家PAT系统开发商)交付一套包含快速波长切换功能的激光系统，以进行测试和临床鉴定。在第二阶段，我们还将对激光和PAT控制系统进行改进，以满足临床操作的需要。为了确保我们的技术工作仍然专注于PAT的关键性能领域，在整个第一阶段计划中，我们将咨询Optosonics的合作者。

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.