Hemodynamic Imaging for Brain Tumor Prognosis

描述(由申请人提供)： 如果能够在不同的治疗阶段对正在治疗的肿瘤进行功能监测和成像，这是至关重要的和有利的。在选择、指导和跟踪癌症治疗时，迫切需要一种非侵入性、便携、经济有效的体内成像工具。这一阶段性提案的总体目标是开发一种新的成像方式，通过利用近红外(NIR)断层成像结合血流动力学建模来从功能上获得动物脑肿瘤的血流动力学图像，这些肿瘤正在接受有或没有呼吸干预的放射手术。不同剂量的放射治疗和高氧干预可获得脑肿瘤在不同剂量下的血色素浓度、血流量和氧耗率的变化的断层图像。这样的血流动力学图像可以为临床放射外科实践提供关于肿瘤对治疗和干预的不均匀反应以及治疗效果的预后信息。R21阶段有三个具体目标：(1)设计和实现适用于大鼠脑内氧合血红蛋白浓度和总血红蛋白浓度(HBO，HBT)的八源、八探测器近红外光谱成像仪，(2)开发二维断层重建算法，并使用大鼠脑肿瘤模型获得不同氧气干预下血管氧合的二维动态断层扫描，(3)通过血流动力学模型实验，开发和验证数学模型，以定量地将肿瘤的血流量(BF)和氧耗率(O2CR)与其近红外光谱测量确定的HBO和HBT相关联。在最初的R21开发成功后，R33阶段的三个具体目标是：(1)使用动态肿瘤模型验证BF和O2CR的2D断层图像；(2)获得大鼠脑瘤(9L胶质肉瘤)在有和没有Carbogen介入放射治疗的情况下放射治疗前后HBO、HBT、BF和O2CR的动态图像；以及(3)研究脑瘤对介入治疗和放射手术的异质性反应，并检查血流动力学参数(Hb、HBO、BF、和O2CR)用于放射治疗，与相应肿瘤的组织学分析比较。

DESCRIPTION (provided by applicant): It is crucial and advantageous if tumors under therapy can be functionally monitored and imaged at different treatment stages. A non-invasive, portable, cost-effective, in vivo imaging tool is much needed to choose, guide and follow cancer therapy. The overall objective of this phased proposal is to develop such a novel imaging modality by utilizing Near Infrared (NIR) tomography in combination with hemodynamic modeling to functionally obtain hemodynamic images of animal brain tumors, which are under radio-surgery with and without respiratory interventions. The tomographic images of changes in hemoglobin concentrations, blood flow, and oxygen consumption rate of the brain tumor caused by different radiation doses in radio-surgery along with hyperoxic interventions can be obtained non-invasively and chronically. Such hemodynamic images may provide prognostic information, for clinical radio-surgery practice, on inhomogeneous responses of the tumor to the therapy and intervention as well as on the effectiveness of the therapy. There are three specific aims in the R21 phase: (1) to design and implement an 8-source, 8- detector, NIR spectroscopic imager suitable for dynamic rat brain imaging of oxygenated hemoglobin concentration and total hemoglobin concentration (HbO, HbT), (2) to develop a 2D tomographic reconstruction algorithm and to obtain 2D dynamic tomography of vascular oxygenation under different oxygen interventions using rat brain tumor phantoms, and (3) to develop and validate, through hemodynamic phantom experiments, mathematical models to quantitatively associates the blood flow (BF) and oxygen consumption rate (O2CR) of the tumor to its HbO and HbT determined by the NIR spectroscopic measurements. After success of the initial R21 development, three specific aims in the R33 phase are: (1) to validate 2D tomographic images of the BF and O2CR using dynamic tumor phantoms, (2) to obtain dynamic images of respiratory-induced changes in HbO, HbT, BF, and O2CR from rat brain tumors (9L Gliosarcoma) before and after radiation therapy with and without carbogen intervention during radiation, and (3) to investigate heterogeneous response of the brain tumors to the intervention and to the radio surgery and to examine the prognostic value of the hemodynamic parameters (Hb, HbO, BF, and O2CR) for the radiation therapy by comparing with the histological analysis of the corresponding tumors.