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

描述（由申请人提供）：该项目的目标是开发一种新的先进成像系统，以基于两种类型的组织对比的组合来实现小癌性肿瘤的原位可视化：(1)与侵袭性恶性肿瘤功能相关的脱氧血红蛋白分子对比，以发展血管生成和消耗氧气；(2)基于肿瘤相对于正常组织密度增加的结构对比。功能对比将由激光光声成像系统（LOIS）提供，结构对比将由超声成像提供。在之前NCI资助的两个项目（R33CA095883, R44CA089959）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。临床结果使我们获得了超过300万美元的私人资金，用于开发商业临床系统。另一方面，我们的临床研究表明，3D光声成像和LOIS与超声的相关性，目前fda批准的x射线乳房x线摄影辅助，将允许实现光声成像的全部诊断潜力，并加快放射科医生接受LOIS作为乳腺癌的临床诊断成像方式。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（偏铌酸铅）制成的超宽带超声换能器的技术问题，结合LOIS和USI系统的新型硬件，固件和软件，最后，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，并在沿着激光束和正交于切片的轴线执行平移扫描时显示最终的3D图像。操作者可以选择光声模式、B超模式或结合两种组织对比（解剖和功能）的组合模式。目前的医学成像方法在区分癌性和正常乳腺肿瘤方面只取得了很小的成功。基于肿瘤微血管对血液的吸收，光声成像利用了癌组织相对于正常或良性组织的最高已知物理或化学对比度，并提供了典型超宽带超声成像0.5 mm的优异分辨率。正在开发的新型PET/CT、3D CT和MRI系统不能提供实时图像，价格高达数百万美元。我们将利用在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放在开发、制造和测试单一换能器元件上，该换能器元件能够进行超宽带超声检测，并发射无振铃的超声脉冲。二期项目将开发一种新型换能器的弧形线性阵列及其模拟二维阵列的机械平移，修改现有系统的固件和软件，使两种类型的图像能够双模态操作和相关，并在12名乳腺癌患者中对系统进行幻影测试，随后进行临床评估。计划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.