Toward real-time prediction and validation of ultrasonic hyperthermia profiles

超声热疗曲线的实时预测和验证

• 批准号: 7640069
• 负责人: Katherine W Ferrara
• 金额: $ 22.5万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7640069
• 关键词: 3-Dimensional; Acoustics; Address; Algorithms; Benign; Binding; Breast; Cardiotoxicity; Cessation of life; Cisplatin; Clinic; Clinical; Clinical Treatment; Computer software; Data; Deposition; Diffusion; Disease; Dose; Doxorubicin; Drug Delivery Systems; Encapsulated; Face; Fever; Goals; Head and neck structure; Heating; Hour; Human; Image; Implant; Knowledge; Label; Lesion; Liposomes; Location; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of liver; Maps; Methodology; Methods; Modeling; Molecular; Monitor; Nanotechnology; Neoplasm Metastasis; Pharmaceutical Preparations; Pharmacotherapy; Positron-Emission Tomography; Protocols documentation; Radiation; Recurrence; Research Infrastructure; Scanning; Site; Solid Neoplasm; Standardization; System; Technology; Temperature; Testing; Therapeutic; Time; Tissues; Toxic effect; Transducers; Translating; Treatment Protocols; Ultrasonic Transducer; Ultrasonics; Ultrasonography; United States; Validation; Work; base; cancer cell; drug efficacy; hyperthermia treatment; image guided therapy; imaging probe; interest; killings; nanoparticle; neoplastic cell; optical imaging; particle; pharmacokinetic model; public health relevance; treatment planning; tumor

DESCRIPTION (provided by applicant): We have demonstrated that ultrasonic drug release using mild hyperthermia is feasible. Here, our goal is to develop fast methods to predict and validate the region that is heated with mild ultrasound hyperthermia, developing methods that will be used in clinical treatment planning. In this treatment methodology, temperature sensitive drug delivery particles are injected and allowed to accumulate within a region of interest, typically over 6-24 hours. Ultrasound is then scanned through the volume of interest to locally increase the temperature by 2-40C for a short period, releasing a drug and greatly increasing its local concentration. In order to accomplish this goal, the following components have been developed in preliminary work: activatable drug delivery vehicles with enhanced stability, advanced ultrasound transducers integrated within a clinical ultrasound system, positron emission tomography (PET) and optical imaging probes to monitor the vehicle shell and core, methods to track particles and the encapsulated drug, a pharmacokinetic model using imaging data as the inputs, and lipoPEGpeptides targeted to tumor cells and tumor vasculature. Applying our new infrastructure, we have demonstrated that we can: target a significant fraction of drug-carrying particles to tumors (~up to 23% of the injected dose per gram following systemic administration), obtain a high (up to 33 dB) target to background ratio image of the vehicles, release model drugs within the region of interest while imaging the release optically, and enhance drug efficacy with ultrasound. In order to translate this technology into the clinic, algorithms and software for treatment planning and validation must be generated. Here, our specific aims are: first, develop fast methods to calculate the effective field and temperature distribution for varied beam geometries and scanning protocols; second, validate the field and temperature profiles in phantom; third, demonstrate rapid and effective drug release in implanted tumor models. Radiation force estimates of displacement and thermal strain are used to estimate the beam location. PUBLIC HEALTH RELEVANCE: Currently, one in 4 deaths in the United States is due to cancer. Available options for preemption and treatment are limited by the toxicity profiles of various drugs. As a result, substantial efforts have been directed to develop nanotechnology-based methods for increasing the efficacy and decreasing the toxicity of drug therapies. Ultrasound can be used to release a drug from a nanoparticle remotely and selectively, even within deep within tissues. In order to translate ultrasonic drug delivery into the clinic, here we develop methods to predict and validate ultrasound intensity and temperature profiles over an entire volume.

描述（由申请人提供）：我们已经证明了使用轻度高温的超声药物释放是可行的。在这里，我们的目标是开发快速的方法来预测和验证被轻度超声热疗加热的区域，开发将用于临床治疗计划的方法。在这种治疗方法中，注射温度敏感的药物递送颗粒，并使其在感兴趣的区域内积累，通常超过6-24小时。然后通过感兴趣的体积进行超声扫描，以在短时间内将温度局部升高2- 40 ℃，释放药物并大大增加其局部浓度。为了实现这一目标，在初步工作中开发了以下组成部分：具有增强的稳定性的可活化的药物递送载体，集成在临床超声系统内的先进超声换能器，监测载体壳和核的正电子发射断层扫描（PET）和光学成像探针，跟踪颗粒和包封的药物的方法，使用成像数据作为输入的药代动力学模型，和靶向肿瘤细胞和肿瘤脉管系统的脂PEG肽。应用我们的新基础设施，我们已经证明，我们可以：将大部分载药颗粒靶向肿瘤（全身给药后每克注射剂量的约23%），获得高（高达33 dB）的载体靶向背景比图像，在感兴趣的区域内释放模型药物，同时光学成像释放，并用超声增强药物疗效。为了将这项技术转化为临床，必须生成用于治疗计划和验证的算法和软件。在这里，我们的具体目标是：首先，开发快速方法来计算不同光束几何形状和扫描协议的有效场和温度分布;第二，验证体模中的场和温度分布;第三，证明植入肿瘤模型中快速有效的药物释放。辐射力的位移和热应变的估计被用来估计梁的位置。公共卫生相关性：目前，在美国，四分之一的死亡是由于癌症。各种药物的毒性特征限制了可供选择的预防和治疗方法。因此，大量的努力已经指向开发基于纳米技术的方法，用于增加药物治疗的功效和降低毒性。超声波可用于远程和选择性地从纳米颗粒中释放药物，甚至在组织深处。为了将超声药物输送转化为临床，在这里，我们开发了预测和验证整个体积内超声强度和温度分布的方法。