Monitoring of Breast Neoadjuvant Therapy by Thermo- and Photo- Acoustic Tomograph

描述(由申请人提供)：我们建议通过采用临床超声成像系统来开发高分辨率微波诱导热声断层扫描(TAT)和激光诱导光声断层扫描(PAT)。这三种兼容的成像方式共享相同的超声检测系统，并提供互补的对比。长期目标是为乳房新辅助治疗(化疗或激素治疗)的早期功能监测提供临床工具。许多乳腺癌患者接受新的辅助治疗，以缩小肿瘤大小，并实现保乳治疗，否则是不可能的。一种检测治疗反应的灵敏方法可能会使治疗更早调整，从而产生更好的结果。此外，如果药物选择没有产生反应，及时和及早改变药物方案将减轻患者在等待治疗反应期间在治疗期间遭受的一些不必要的发病率。TAT/PAT的基础是通过将短脉冲电磁能量安全地沉积到乳房中来产生热声/光声波。每一个微波/激光脉冲都会引起大约10毫度的快速升温。利用一组超声换能器检测由于热弹性膨胀而产生的超声波发射，然后用于重建图像。TAT和PAT旨在克服纯微波和纯光学成像的低空间分辨率，但仍不能保持高对比度。在空间分辨率方面，纯微波成像由于微波波长较长而受到强衍射的影响，而纯光学成像则受到组织中强烈的光学散射的影响。超声波可以以相对较低的散射在组织中传播，因此可以提供良好的空间分辨率。申请者展示了高分辨率(低至0.5 mm)的无斑点图像。我们假设，TAT和PAT的联合对比以及超声检查可以准确地预测乳房新辅助治疗的反应。TAT主要测量水/钠对比，而PAT测量血容量和血氧对比。具体目标如下：1.TAT/PAT乳腺成像系统的研制。2.飞利浦临床超声成像系统的改装。3.体模研究：用组织体模验证所提出的成像系统。4.活体研究：首先，对少量的人体乳房进行成像，以微调成像系统。其次，对人体乳房进行图像处理，并进行回溯统计分析。第三，对人体乳房进行成像，并对成像系统进行前瞻性验证。

DESCRIPTION (provided by applicant): We propose to develop high-resolution microwave-induced thermoacoustic tomography (TAT) and laser-induced photoacoustic tomography (PAT) by adapting a clinical ultrasound imaging system. These three compatible imaging modalities share the same ultrasound detection system and provide complementary contrasts. The long-term goal is to provide a clinical tool for the early functional monitoring of breast neoadjuvant therapy (chemo- or hormone therapy). Many breast cancer patients receive neoadjuvant treatment to reduce tumor size and enable breast conserving therapy that would otherwise have not been possible. A sensitive method of detecting response to therapy might allow earlier adjustments in treatment, and thus, result in better outcomes. Furthermore, if drug choices are not resulting in response, prompt and early changes in drug regimens will alleviate some of the unnecessary morbidity that patients suffer during treatment while awaiting response to therapy. TAT/PAT is based on the generation of thermoacoustic/photoacoustic waves by the safe deposition of short-pulsed electromagnetic energy into the breast. Each microwave/laser pulse causes a rapid temperature rise on the order of 10 millidegrees. The ultrasonic emission due to thermoelastic expansion is detected with an array of ultrasonic transducers and then used to reconstruct an image. TAT and PAT are designed to overcome the poor spatial resolution of pure microwave and pure optical imaging yet to retain the high contrasts. In terms of spatial resolution, pure microwave imaging suffers from strong diffraction due to long microwave wavelength, whereas pure optical imaging suffers from strong optical scattering in tissue. Ultrasonic waves can propagate in tissue with relatively low scattering and can therefore provide good spatial resolution. The applicants have demonstrated speckle-free images at high resolution (as low as 0.5 mm). We hypothesize that the combined contrasts from TAT and PAT as well as ultrasonography can accurately predict breast neoadjuvant therapeutic response. TAT measures dominantly water/sodium contrast, whereas PAT measures blood volume and blood oxygenation contrasts. The specific aims are as follows: 1. Development of the TAT/PAT breast imaging system. 2. Adaptation of a Philips clinical ultrasound imaging system. 3. Phantom study: Validate the proposed imaging system with tissue phantoms. 4. In vivo study: First, image a small number of human breasts to fine tune the imaging system. Second, image human breasts and perform statistical analysis retrospectively. Third, image human breasts and validate the imaging system prospectively.