Thermochemical Ablation in Image-Guided Interventions: Initial Assessment

描述（由申请人提供）：本实验室的长期研究目标是开发和实施新的、低成本的、微创的、图像引导的人类疾病干预措施，特别是改善适合这种方法的实体恶性肿瘤的预后，如乳腺癌或前列腺癌、转移性结直肠癌、肺癌和肝细胞癌（HCC），这是本申请的重点。目前的方法，如射频消融术，在可治疗的病变大小、肿瘤复发、生存获益、手术风险和成本方面是不够的。在这个应用程序的目的是建立在体内可行性的一种新的消融方法，最近发现的称为热化学消融。狭义上讲，这种技术通过利用在酸碱反应中形成水时释放的大量热能来克服这些缺点。该应用的中心假设是，热化学消融可以在肝组织中产生均匀分布的凝血区，而不会产生全身毒性。为了建立可行性并验证这一假设，概述了以下两个目标：目标1：量化急性热化学凝血区的大小、形状、可重复性和温度历史，基于已知的关键变量体积和浓度，在注射酸和碱速率恒定的情况下，通过多种相关模式测量。最终的目标是治疗人类，因为大多数患者的组织切除和病理相关性是不可行的。为了解决这个问题，将测量处理过的外植猪肝的CT扫描上看到的灌注缺陷，并将其与三个体积数据集相关联：大体病理学、活力染色和显微病理学。这将为使用该方法创建的凝血区提供可靠的成像生物标志物的初始数据。目的2：在组织和系统水平上表征热化学消融的急性效应。组织效应将在处理标本的选定切片上可视化，使用组织学方法成像坏死和细胞死亡。显微形态的消融将被表征，过渡区到正常组织将被评估。由于使用酸和碱的浓缩溶液，可能会改变整个动物的生理机能，因此可能产生全身效应。因此，将监测血清渗透压，动脉血气测量（pO2, pCO2, pH）和电解质，并在注射后连续取样以检测变化。

DESCRIPTION (provided by applicant): The long-term research goal of this laboratory is to develop and implement new, low-cost, minimally invasive, image-guided interventions for human diseases, in particular to improve outcomes in solid malignancies amenable to this approach such as breast or prostate cancer, metastatic colorectal cancer, lung cancer, and hepatocellular carcinoma (HCC), which is the focus of this application. Current methods such as radiofrequency ablation are inadequate with regard to treatable lesion size, tumor recurrence, survival benefit, procedural risk, and cost. The objective in this application is to establish in vivo feasibility of a new ablation method recently discovered called thermochemical ablation. This technique, when narrowly defined, overcomes these shortcomings by exploiting the considerable heat energy released as water is formed in acid-base reactions. The central hypothesis of this application is that thermochemical ablation can create an evenly distributed zone of coagulation in liver tissue without systemic toxicity. To establish feasibility and test this hypothesis two aims are outlined below: Aim 1: Quantify the size, shape, reproducibility, and temperature history of acute thermochemical coagulation zones measured by multiple correlated modalities based upon the known key variables of volume and concentration, with injection rates of acid and base constant. The eventual goal is treatment in humans where excision and pathologic correlation of tissues in most patients is not feasible. To address this, perfusion defects seen on CT scans of treated, explanted pig livers will be measured and correlated with three volume data sets: gross pathology, viability staining, and microscopic pathology. This will provide initial data for a robust imaging biomarker of the zone of coagulation created using the method. Aim 2: Characterize acute effects of thermochemical ablation at both tissue and systemic levels. Tissue effects will be visualized in selected sections from treated specimens using histologic methods to image necrosis and cell death. The microscopic appearance of the ablations will be characterized and the transition zone to normal tissue will be evaluated. Systemic effects are possible due to the use of concentrated solutions of acid and base that could potentially alter the whole animal physiology. Therefore serum osmolality, arterial blood gas measurements (pO2, pCO2, pH), and electrolytes will be monitored, with serial sampling after injection to detect changes.