Zhang R, Kanick S, Vinogradov S, Esipova T, Pogue B
Dartmouth College, Hanover, NH.
University of Pennsylvania.
Med Phys. 2012 Jun;39(6Part5):3646-3647. doi: 10.1118/1.4734811.
To show that Cherenkov emission is generated by external radiotherapy beam in tissue, and could serve as optical source to excite an oxygen sensitive phosphor, Oxyphor G4, within tissue. The intensity and lifetime of the phosphorescence was measured with a time-gated system and reveals the oxygenation levels in the tissue phantom.
A tissue phantom made with PBS, 1% v/v Intralipid-20% (Sigma Aldrich), 1% v/v whole blood and Oxyphor G4 in 1 μM concentration is irradiated by 18MeV external radiotherapy electron beam at a dose rate of 4 Gy/min generated by a medical linear accelerator (Varian LINAC 2100C, Varian Medical Systems). On one side of the phantom, a fiber bundle is used to conduct optical signal to a spectrometer connected to a fast gating ICCD (PI-MAX3, Princeton Instruments). For each oxygenation level, a series of spectrum of phosphorescence at different time points is measured by the time domain gating technique. Lifetime of phosphorescence is analyzed by exponential fitting and is validated by comparison to an independent analysis by frequency domain phosphorimetry. Monte Carlo simulations using GEANT4, of the fiber optic collection of Cerenkov light were performed to decide the sensitivity of the optical system for a range of specified geometries and beam types. Simulation results identify the effective depth within the phantom that is sampled by the optical collection of the Cerenkov signal.
Simulations show that we can detect the Cherenkov signals comes from an approximately 5 mm depth from within the tissue phantom. Lifetime of the phosphorescence and pO2 of the phantom could be measured and calculated correctly by the time domain gating system.
This work indicates time domain gating techniques combined with an oxygen sensitive phosphor are capable of accurately monitoring tissue oxygenation from a reasonable sampling depth in tissue in vivo during external beam radiotherapy. NIH grant R01CA109558.
证明切伦科夫辐射由组织中的外照射放疗束产生,并可作为光源激发组织内的氧敏磷光体Oxyphor G4。用时间门控系统测量磷光的强度和寿命,以揭示组织模型中的氧合水平。
用磷酸盐缓冲盐水(PBS)、1%(体积/体积)的20% Intralipid(西格玛奥德里奇公司)、1%(体积/体积)的全血和浓度为1 μM的Oxyphor G4制成组织模型,由医用直线加速器(瓦里安医疗系统公司的Varian LINAC 2100C)以4 Gy/分钟的剂量率产生的18 MeV外照射放疗电子束进行照射。在模型的一侧,使用光纤束将光信号传导至与快速门控ICCD(PI-MAX3,普林斯顿仪器公司)相连的光谱仪。对于每个氧合水平,通过时域门控技术测量不同时间点的一系列磷光光谱。通过指数拟合分析磷光寿命,并通过与频域磷光法的独立分析进行比较来验证。使用GEANT4对切伦科夫光的光纤收集进行蒙特卡罗模拟,以确定光学系统在一系列指定几何形状和束类型下的灵敏度。模拟结果确定了切伦科夫信号光学收集所采样的模型内有效深度。
模拟表明,我们可以检测到来自组织模型内约5 mm深度的切伦科夫信号。时域门控系统能够正确测量和计算模型的磷光寿命和pO2。
这项工作表明,时域门控技术与氧敏磷光体相结合,能够在体外束放疗期间从体内组织的合理采样深度准确监测组织氧合。美国国立卫生研究院资助项目R01CA109558。