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

通过回波去相关实时预测热消融诱导的细胞死亡

基本信息

批准号：
8676729
负责人：
T Douglas Mast
金额：
$ 42.17万
依托单位：
UNIVERSITY OF CINCINNATI
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-10 至 2016-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8676729
关键词：
Ablation Accounting Adherence Apoptosis Archives Cancer Patient Carcinoma Categories Cattle Cell Death Cell Survival Cells Cessation of life Clinic Clinical Coagulation Process Coagulative necrosis Custom Data Development Devices Elements Ensure Evaluation Excision Feedback Focused Ultrasound Therapy Future Goals Heating Hematoxylin and Eosin Staining Method Histologic Histology Image Image Analysis Implant In Vitro Link Liver Location Malignant Neoplasms Malignant neoplasm of liver Maps Measures Methods Monitor Morphology Nuclear Oryctolagus cuniculus Outcome Patients Physiologic pulse Plant Roots Procedures Public Health Publishing Radiofrequency Interstitial Ablation Receiver Operating Characteristics Recurrence Research Research Personnel Resolution Safety Series Soft Tissue Neoplasms Staining method Stains TdT-Mediated dUTP Nick End Labeling Assay Testing Thermal Ablation Therapy Time Tissue Viability Tissues Translations Transplantation Treatment Efficacy Tumor Tissue Ultrasonography base cancer therapy improved in vivo in vivo imaging indexing interest microwave ablation millisecond minimally invasive mortality novel novel strategies prospective radiofrequency research clinical testing research study success time use treatment planning tumor

项目摘要

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.

描述（由申请人提供）：该项目的主要目标是使用超声回波去相关成像实时预测热消融引起的细胞死亡，超声回波去相关成像是一种在毫秒时间尺度上绘制组织中快速、消融引起的变化的方法。初步研究表明局部回声去相关与热组织凝固之间存在很强的相关性。然而，局部回声去相关与所需的临床最终效果（即恶性肿瘤组织死亡）之间的直接联系尚未确定。我们假设超声回波去相关成像可以直接实时预测热消融引起的细胞死亡。我们的假设将使用一种新颖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巨大优势。图像引导治疗将使用图像处理超声阵列进行，该阵列能够使用相同的压电阵列元件进行热消融和高质量脉冲回波成像。因此，所有成像和治疗都在同一平面上进行，并且可以高精度评估基于图像的局部消融诱导的细胞死亡的预测。定制的图像治疗超声阵列将在一系列体内试验中对植入 VX2 癌的兔肝脏进行消融和成像。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比）和高强度聚焦超声消融（与目前正在开发和使用的无创聚焦超声消融设备相比）。癌症治疗的临床测试）。实验将首先测试累积回波去相关图像预测消融引起的细胞死亡的能力，通过活体和组织学染色进行评估，并根据逐像素接收者操作特征曲线分析判断预测准确性。将统计评估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。回波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来绘制。进一步的实验将评估实时消融控制的程序，其中继续治疗，直到空间平均回声去相关超过目标感兴趣区域内的预先指定的阈值。将评估回声去相关成像控制的准确性，以准确预测目标 ROI 中的细胞死亡以及与目标消融边缘的对应性。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，以在热消融过程中实时预测热消融引起的细胞死亡。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上重要的微创和无创癌症治疗的功效和安全性。