High-Repetition Rate Laser for Real-Time and 3D Photoacoustic Imaging

光声成像（PA）是一种集光学成像和超声成像于一体的新型成像技术。在吸收高能激光脉冲后，组织经历快速和局部加热。组织经历热弹性膨胀，产生美国波。波向组织表面传播，在那里它们被美国传感器阵列检测到。PA成像可以成像到几厘米深的组织，比任何其他光学成像技术都要深得多。此外，PA成像可以检测血管，定量血氧饱和度和缺氧，这是高度特异性的癌症生物标志物。因此，PA成像可以通过增加癌症特异性吸收对比的功能成像来增强经典US。在此，我们建议发展实时和三维光声断层扫描（PAT）来检测前列腺癌和乳腺癌。******建立在我们以前的CHRP和CRD拨款，原型PAT系统已开发用于癌症成像。我们已经开发出一种光纤导管，可以通过尿道向前列腺输送高能量和均匀的激光照明。一种最佳的美国换能器扫描和检测几何已开发用于前列腺成像。在离体组织中，高达4厘米的成像深度已被证实。对于乳腺癌成像，使用自动乳腺超声扫描仪获取PAT图像。我们发现，通过将PAT添加到多参数US中，可以为乳腺癌的诊断和分期提供一套强有力的指标。然而，我们之前使用的激光只有10赫兹的重复频率，太慢了。这限制了PAT系统仅获得组织静态图像的能力。对于临床应用，为了监测动态变化和克服运动伪影，需要以数百赫兹的速度与US相媲美的实时PAT成像。对于三维PAT，需要数百次激光射击才能从三维体中获取PA信号。******在此应用中，需要具有快速100 Hz重复率的激光器。我们建议开发用于前列腺癌和乳腺癌检测的实时和三维PAT。我们还将开发定制的PAT/US成像探头，采用新颖的电容式微机械超声换能器（CMUT）阵列，该阵列具有独特的大，灵活和透明。我们还将把我们的图像分析方法从美国成像扩展到PAT。拟议的研究计划将通过提高美国的成像能力，在医学成像方面取得重大进展。通过将PAT的血液吸收和血氧饱和度对比与我们的多参数超声（包括b模式、弹性成像、时间序列和多普勒）相结合，有望大大提高癌症检测的特异性和敏感性。我们将开发和设计特定的PAT成像技术，并将这些技术转化为前列腺癌和乳腺癌成像的临床应用。PAT/US成像将有很大的潜力改善癌症的检测和治疗结果。

Photoacoustic (PA) imaging is a novel imaging technique that takes the advantages of both optical and ultrasound (US) imaging. Upon absorbing a high energy laser pulse, tissue experiences a rapid and localized heating. The tissue undergoes thermoelastic expansion which generates US waves. The waves propagate towards the tissue surface where they are detected by an US transducer array. PA imaging can image up to a few centimeters into tissue, much deeper than any other optical imaging techniques. Furthermore, PA imaging can detect blood vessels, and quantify blood oxygen saturation and hypoxia, which are highly specific biomarkers of cancer. Thus, PA imaging can augment classical US by adding functional imaging of cancer specific absorption contrasts. Here we propose to develop real-time and 3D photoacoustic tomography (PAT) for detecting prostate and breast cancers. ******Built upon our previous CHRP and CRD grants, a prototype PAT system has been developed for cancer imaging. We have developed an optical fiber catheter to deliver high energy and uniform laser illumination to the prostate through the urethra. An optimum US transducer scanning and detecting geometry has been developed for prostate imaging. Up to 4 cm imaging depth has been demonstrated in ex vivo tissues. For breast cancer imaging, an automated breast ultrasound scanner was used to acquire PAT images. We found that by adding PAT to multi-parametric US can offer a powerful set of metrics for the diagnosis and staging of breast cancer. However, the laser we used before only has 10 Hz repetition rate which is too slow. This has limited the capability of the PAT system to obtain only static images of tissue. For clinical applications, real-time PAT imaging at a speed comparable to US at hundreds of Hertz is needed in order to monitor dynamic changes and overcome motion artifacts. For 3D PAT, hundreds of laser shots are needed in order to acquire PA signals from a 3D volume.******In this application, a laser with fast 100 Hz repetition rate is requested. We propose to develop real-time and 3D PAT for detecting prostate and breast cancers. We will also develop custom PAT/US imagining probes by novel capacitive micromachined ultrasonic transducer (CMUT) arrays that are uniquely large, flexible, and transparent. We will also extend our image analysis approaches from US imaging to PAT. The proposed research program will make major advances in medical imaging by enhancing the capability of US based imaging. By adding the blood absorption and oxygen saturation contrasts from PAT to our multi-parametric US that includes B-mode, elastography, time series, and Doppler, it is expected to greatly enhance the specificity and sensitivity of cancer detection. We will produce and engineer specific techniques of PAT imaging and translate the techniques to clinical applications on prostate and breast cancer imaging. PAT/US imaging will have great potential to improve cancer detection and treatment outcome.