Real-time prediction of thermal ablation-induced cell death by echo decorrelation

描述（由申请人提供）：本项目的主要目标是使用超声回波去相关成像（一种用于在毫秒时间尺度上绘制组织中快速消融诱导变化的方法）在真实的时间内预测热消融诱导的细胞死亡。初步研究表明，局部回声去相关和热组织凝固之间有很强的相关性。然而，局部回波去相关和期望的临床最终效果之间的直接联系，即，死亡的恶性肿瘤组织，尚未建立。我们假设超声回波去相关成像可以直接预测热消融诱导的细胞死亡在真实的时间。我们的假设将使用一种新型的消融和成像配置进行测试，该配置在精确、定量比较治疗计划、超声图像和消融组织组织学方面具有很大优势。将使用能够进行热消融和高质量脉冲回波成像的图像治疗超声阵列进行图像引导治疗，使用相同的压电阵列元件。因此，所有成像和治疗都在同一平面内进行，并且可以高精度地评估局部消融诱导的细胞死亡的基于图像的预测。定制的图像治疗超声阵列将在一系列体内试验中对植入VX 2癌的兔肝进行消融和成像。超声暴露条件将包括整体热消融（与目前临床上用于微创癌症治疗的射频和微波消融相当）和高强度聚焦超声消融（与目前正在开发和临床测试的非侵入性聚焦超声消融器械相当）。实验将首先测试累积回波去相关图像预测消融诱导的细胞死亡的能力，通过活体和组织学染色进行评估，预测准确性由逐像素接收器操作特征曲线分析判断。将对回声去相关成像预测凝固性坏死、部分组织活力和热诱导细胞凋亡的能力进行统计学评估。回声去相关将与局部细胞活力相关，通过细胞核形态的定量图像分析绘制。进一步的实验将评估用于实时消融控制的程序，其中继续治疗直到空间平均回波去相关超过目标感兴趣区域内的预定阈值。将评估回波去相关成像控制的准确性，以准确预测靶向ROI中的细胞死亡以及与靶向消融边缘的对应性。如果成功，该项目将为临床医生提供一种基于超声的实时成像方法，以预测热消融过程中热消融诱导的细胞死亡的真实的时间。这种实时监测和控制热消融手术的新机会最终将大大提高这些临床重要的微创和非侵入性癌症治疗的疗效和安全性。

DESCRIPTION (provided by applicant):The major goal of this project is to predict thermal ablation-induced cell death in real time using ultrasound echo decorrelation imaging, a method for mapping rapid, ablation-induced changes in tissue over millisecond time scales. Preliminary research has shown a strong correlation between local echo decorrelation and thermal tissue coagulation. However, a direct link between local echo decorrelation and the desired clinical end effect, i.e., death of malignant tumor tissue, has not been established. We hypothesize that ultrasound echo decorrelation imaging can directly predict thermal ablation-induced cell death in real time. Our hypothesis will be tested using a novel ablation and imaging configuration with great advantages for precise, quantitative comparison of treatment plans, ultrasound images, and ablated tissue histology. Image- guided treatments will be performed using an image-treat ultrasound array capable of both thermal ablation and high-quality pulse-echo imaging, using the same piezoelectric array elements. As a result, all imaging and treatment takes place in the same plane, and image-based predictions of local ablation-induced cell death can be evaluated with high accuracy. A custom image-treat ultrasound array will perform ablation and imaging of rabbit liver with implanted VX2 carcinoma in a series of in vivo trials. Ultrasound exposure conditions will include both bulk thermal ablation (comparable to radiofrequency and microwave ablation, as currently used in the clinic for minimally-invasive cancer treatment), and high-intensity focused ultrasound ablation (comparable to noninvasive focused ultrasound ablation devices currently under development and clinical testing for cancer treatment). Experiments will initially test the capability of cumulative echo decorrelation images to predict ablation-induced cell death, as evaluated by vital and histologic staining, with prediction accuracy judged from pixel-by-pixel receiver-operating-characteristic curve analysis. The ability of echo decorrelation imaging to predict coagulative necrosis, partial tissue viability, and heat-induced apoptosis will be statistically assessed. Echo decorrelation will be correlated with local cell viability, mapped by quantitative image analysis of cell nuclear morphology. Further experiments will evaluate a procedure for real-time ablation control, in which treatments are continued until the spatially averaged echo decorrelation exceeds a prespecified threshold within a targeted region of interest. Accuracy of echo decorrelation imaging-controlled will be assessed, both for accurate prediction of cell death in the targeted ROI and for correspondence to the targeted ablation margins. If successful, this project will provide clinicians with a real-time, ultrasound-based imaging approach to predict thermal ablation-induced cell death in real time during thermal ablation. This new opportunity for real-time monitoring and control of thermal ablation procedures will ultimately result in greatly improved efficacy and safety for these clinically important, minimally invasive and noninvasive cancer treatments.