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

• 批准号: 8857112
• 负责人: T Douglas Mast
• 金额: $ 36.72万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-10 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8857112
• 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; 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; image guided; improved; in vivo; in vivo imaging; indexing; interest; microwave ablation; millisecond; minimally invasive; mortality; novel; novel strategies; prospective; quantitative imaging; radiofrequency; research clinical testing; research study; success; temporal measurement; time use; treatment planning; tumor

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诱导的细胞死亡，这是一种在毫秒时间尺度上绘制快速消融诱导的组织变化的方法。初步研究表明，局部回声去相关与热组织凝固有很强的相关性。然而，局部回声去相关与期望的临床最终效果（即恶性肿瘤组织死亡）之间的直接联系尚未建立。我们假设超声回波去相关成像可以直接实时预测热烧蚀诱导的细胞死亡。我们的假设将使用一种新的消融和成像配置进行验证，该配置具有精确、定量比较治疗方案、超声图像和消融组织组织学的巨大优势。图像引导治疗将使用具有热消融和高质量脉冲回波成像能力的图像处理超声阵列进行，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上进行，基于图像的局部消融诱导细胞死亡预测可以进行高精度评估。在一系列体内试验中，一种定制的图像处理超声阵列将对植入VX2癌的兔肝脏进行消融和成像。超声暴露条件将包括体热消融（相当于射频和微波消融，目前用于临床微创癌症治疗）和高强度聚焦超声消融（相当于目前正在开发和临床测试的用于癌症治疗的无创聚焦超声消融设备）。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，通过生命和组织学染色来评估，并通过逐像素的接收器工作特性曲线分析来判断预测准确性。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将进行统计评估。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来绘制。进一步的实验将评估一种实时消融控制程序，在该程序中，治疗将继续进行，直到空间平均回波去相关超过目标区域内预定的阈值。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关系。如果成功，该项目将为临床医生提供一种实时的、基于超声的成像方法，以实时预测热消融过程中热消融诱导的细胞死亡。这种实时监测和控制热消融过程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。