Endoskeletal nanodrops for x-ray acoustic dosimetry

项目摘要 在美国，超过一半的癌症患者接受放射治疗（RT）作为其治疗的一部分。 癌症治疗（每年> 500，000名患者）。癌症患者通常接受高度靶向剂量的 放射性治疗持续数天或数周。每名患者通常每天接受25-40次治疗。 治疗结果取决于放射线的准确输送。所有RT患者治疗计划均基于 在治疗开始前几天或几周进行计划性“模拟”CT扫描。然而，由于体重 在模拟和治疗之间的时间损失或肿瘤缩小，解剖学变化可能导致健康的 被照射的组织。辐射健康组织的副作用可能很严重。自适应 优化 具有 机会然而，抗逆转录病毒疗法的实施受到严重限制， 能够准确测量患者体内输送的辐射分布的实时设备。目前 不存在能够测量患者体内的辐射剂量分布的系统。 RT（ART）- re- 基于患者日常解剖结构的辐射分布，以保持计划质量- 已经被提出作为一种手段，以提供更多的辐射，减少正常组织的损伤;增加 副作用更少的治疗方法 该项目将通过开发第一种用于成像放射治疗的造影剂来满足这一需求。我们 这种方法将采用X射线声学（XA）效应，其类似于“光声效应”，即物理声学效应。 通过吸收来自脉冲光子的热能而产生声波的现象 梁在XA计算机断层扫描（XACT）中，光子束是由光子束产生的高能X射线辐射。 医用直线加速器（LINAC）用于临床放射治疗。需要新型XA造影剂 以改善XACT成像，并对我们的XACT剂量学概念至关重要。为此，我们 最近发明的可蒸发内骨架液滴（VEDs）包括液体氟碳化合物液滴和固体 碳氢化合物“骨架”。我们发现液态碳氟化合物液滴在加热和熔化时蒸发 的碳氢化合物固体。从液滴到气泡的膨胀会发出声波， XACT，并且所得的微泡对于超声成像是回声的。该项目将开发VED 通过1）配制包含高Z值的VED， 烃骨架相中的金属离子，以吸收X射线并刺激蒸发;以及2） 测量高z值VED的XA效应。完成这些目标将使未来的商业化， 体内临床前试验和临床翻译。

PROJECT SUMMARY More than half of all cancer patients in the United States receive Radiation Therapy (RT) as a part of their cancer treatment (>500,000 patients per year). Cancer patients typically receive a highly targeted dose of radiation over the course of days or weeks. Each patient will typically receive 25-40 daily treatments. Treatment outcome is dependent on accurate delivery of radiation. All RT patient treatment plans are based on a planning `simulation' CT scan, acquired days or weeks before the start of treatment. However, due to weight loss or tumor shrinkage in the time between simulation and treatment, anatomical changes may lead to healthy tissues being irradiated. Side effects of irradiating healthy tissue can be severe. Adaptive optimizing has chance . However, the implementation of ART is severely limited by the lack of a real-time device that can accurately measure the delivered radiation distribution within the patient. Currently no system exists which is capable of measuring the radiation dose distribution within the patient. RT (ART) – re- the radiation distribution based on the patient's daily anatomy in order to maintain the plan quality – been proposed as a means to deliver more radiation with reduced normal tissue damage; increasing the of a cure, with fewer side effects This project will address this need by developing the first contrast agent for imaging radiation therapy. Our approach will employ the x-ray acoustic (XA) effect, which is analogous to the “photoacoustic effect”, a physical phenomenon whereby acoustic waves are generated by the absorption of heat energy from a pulsed photon beam. In XA Computed Tomography (XACT), the photon beam is high-energy x-ray radiation generated by a medical linear accelerator (LINAC) used in clinical radiation therapy. Novel XA contrast agents are needed to improve XACT imaging and are essential to our concept of XACT dosimetry. Toward this end, we recently invented vaporizable endoskeletal drops (VEDs) comprising a liquid fluorocarbon droplet with a solid hydrocarbon “skeleton”. We discovered that the liquid fluorocarbon droplet vaporizes upon heating and melting of the hydrocarbon solid. The drop-to-bubble expansion emits an acoustic wave that can be imaged with XACT, and the resulting microbubble is echogenic for ultrasound imaging. This project will develop the VED technology into a novel radiation therapy contrast agent for XACT by 1) Formulation of VEDs comprising high-z metal ions within the hydrocarbon skeletal phase to absorb x-rays and stimulate vaporization; and 2) Measurement of the XA effect of high-z VEDs. Completing these aims will enable future commercialization, in vivo preclinical testing, and clinical translation.