3D Hybrid Optoacoustic-Ultrasonic System for Diagnostic Imaging of Breast Cancer

描述(申请人提供)：这个项目的目标是开发一种新的先进的成像系统，以基于两种类型的组织对比的组合来实现对小癌症肿瘤的原位可视化：(1)与侵袭性恶性肿瘤相关的脱氧血红蛋白的分子对比，以发展血管生成和消耗氧气的功能；以及(2)基于肿瘤密度相对于正常组织的增加的结构对比。功能对比度由激光光声成像系统(LOIS)提供，结构对比度由超声成像提供。在NCI(R33CA095883，R44CA089959)的前两个项目中，我们开发了二维LOIS的临床原型，并在36例乳腺癌患者中进行了可行性测试。临床结果使该公司获得了300多万美元的私人资金，用于开发商业临床系统。另一方面，我们的临床研究表明，LOIS的3D光声成像及其与超声的相关性，将使光声成像的全部诊断潜力得以实现，并加速放射科医生将LOIS作为乳腺癌临床诊断成像手段的接受。因此，我们提出了一个快速通道SBIR项目，以解决由新型压电陶瓷(偏碘酸铅)制成的超宽带超声换能器、结合LOIS和USI系统的新型硬件、固件和软件的相关技术问题，并最终对新系统进行试点临床测试。所提出的3D系统将实时显示乳房切片的2D图像，并在沿激光束并垂直于切片的轴向执行平移扫描时显示最终的3D图像。操作员将可以选择光声模式、B超模式或将两种类型的组织对比(解剖和功能)相关联的组合模式进行成像。目前的医学成像方法在区分乳腺癌和正常乳腺肿瘤方面只取得了轻微的成功。光声成像利用已知的相对于正常或良性组织的最高物理或化学对比度，基于肿瘤微血管对血液的吸收，并提供具有超宽带超声成像典型的0.5 mm优秀分辨率的图像。正在开发的新型PET/CT和3D CT和MRI系统不提供实时图像，将有数百万美元的价格标签。我们将利用以前和正在进行的研发项目中开发的电子硬件和软件来开发更先进的乳腺癌系统。第一阶段项目的重点将是开发、制造和测试能够进行超宽带超声检测和发射无振铃超声脉冲的单一换能器元件。第二阶段项目将开发一种新型换能器的弧形线性阵列及其机械平移，模拟2D阵列，修改现有系统的固件和软件，以实现两种类型图像的双模式操作和关联，并在12名乳腺癌患者的体模中测试该系统，然后进行临床评估。拟议项目的成功完成将激励我们的投资者参与商业开发和FDA批准的过程。

DESCRIPTION (provided by applicant): The objective of this project is to develop a new advanced imaging system to allow visualization of small cancerous tumors in situ based on combination of two types of tissue contrast: (1) molecular contrast of deoxygenated hemoglobin associated with the function of aggressive malignancy to develop angiogenesis and consume oxygen and (2) structural contrast based on increased density of tumors relative to normal tissue. The functional contrast will be provided by the Laser Optoacoustic Imaging System (LOIS) and the structural contrast will be provided by ultrasound imaging. In the course of the two previous projects sponsored by NCI (R33CA095883, R44CA089959) we developed a clinical prototype of two-dimensional LOIS and performed feasibility testing in 36 breast cancer patients. The clinical results enabled the receipt of over $3 million in private funding for development of the commercial clinical system. On the other hand, our clinical studies showed that 3D optoacoustic imaging and correlation of LOIS with ultrasound, current FDA-approved adjuvant to X-ray mammography, will permit realization of the full diagnostic potential of the optoacoustic imaging and expedite radiologist's acceptance of LOIS as a clinical diagnostic imaging modality for breast cancer. Therefore, we propose a fast-track SBIR project to resolve technical issues associated with ultrawide-band ultrasonic transducers made of a novel piezoelectric ceramics (lead metaniobate), novel hardware, firmware and software that combines LOIS and USI systems, and finally, pilot clinical testing of the new system. The proposed 3D system will display 2D images of breast slices in real time and display the final 3D image upon execution of the translation scan along the axis along the laser beam and orthogonal to the slices. The operator will have an option of imaging in the optoacoustic mode, the ultrasound B mode or the combined mode correlating two types of tissue contrast, anatomical and functional. The present methods of medical imaging are only marginally successful in differentiating between cancerous and normal breast tumors. Optoacoustic imaging utilizes the highest known physical or chemical contrast of cancerous tissues relative to normal or benign tissue based on absorption of blood in the tumor microvessels and provides images with excellent resolution of 0.5 mm typical of ultrawide-band ultrasonic imaging. Novel PET/CT and 3D CT and MRI systems being developed do not provide real-time images and will have multimillion dollar price tags. We will utilize electronic hardware and software developed in the course of previous and ongoing R&D projects for development of a more advanced system for breast cancer. The focus of the Phase-I project will be on development, fabrication and testing of a single transducer elements capable of ultrawide-band ultrasound detection and emission of ultrasound pulses with no ringing. The Phase- II project will develop an arc-shaped linear array of novel transducers and its mechanical translation that simulates 2D array, modify firmware and software of the present system to enable dual modality operation and correlation of the two types of images, and test the system in phantoms followed by clinical evaluation in 12 patients with breast cancer. Successful accomplishment of the proposed project will motivate our investors to engage in the commercial development and the process of FDA approval.