Rich Laurie J, Seshadri Mukund
From the Departments of Molecular and Cellular Biophysics (L.J.R., M.S.), Pharmacology and Therapeutics (M.S.) and Head and Neck Surgery (M.S.), Roswell Park Cancer Institute, CGP L4-314, Elm and Carlton Streets, Buffalo, NY 14263.
Radiology. 2015 Apr;275(1):110-8. doi: 10.1148/radiol.14140654. Epub 2014 Nov 20.
To noninvasively assess vascular hemodynamics with photoacoustic imaging (PAI) and blood oxygenation level-dependent (BOLD) magnetic resonance (MR) imaging in phantoms and in an animal model.
In vivo studies were performed with institutional animal care and use committee approval. In vitro experiments were performed by using a tissue-mimicking phantom in multiple oxygenation conditions (n = 6) to compare PAI measurements and BOLD MR imaging measurements. PAI and T2-weighted spin-echo-based BOLD MR imaging were performed to assess tumor response to carbogen (95% O2, 5% CO2) in mice with head and neck tumors before (n = 11) and after (n = 9) treatment with a vascular disrupting agent (VDA). Two-tailed Pearson correlation analysis was performed to determine the correlation between the parameters measured with PAI and BOLD MR imaging in vitro. Two-tailed paired t tests were used to compare change in tumor hemoglobin oxygen saturation (sO2) levels and BOLD signal in response to carbogen. Changes in PAI and BOLD signal intensity before and after VDA treatment were analyzed for significance by using analysis of variance with repeated measures.
Phantom measurements yielded good correlation between photoacoustically derived sO2 levels and BOLD signal intensity (r = 0.937, P = .005) and partial pressure of oxygen (r = 0.981, P = .005). In vivo hemodynamic response to carbogen was characterized by a significant increase in tumor sO2 levels (P = .003) and BOLD signal (P = .001). When compared with pretreatment estimates, treatment with VDA resulted in a significant reduction in the tumor hemodynamic response to carbogen at PAI (P = .030).
Carbogen-based functional imaging with PAI and BOLD MR imaging enables monitoring of early changes in tumor hemodynamics after vascular targeted therapy.
在体模和动物模型中,利用光声成像(PAI)和血氧水平依赖(BOLD)磁共振(MR)成像对血管血流动力学进行无创评估。
体内研究经机构动物护理和使用委员会批准后进行。体外实验使用在多种氧合条件下的组织模拟体模(n = 6),以比较PAI测量值和BOLD MR成像测量值。对患有头颈部肿瘤的小鼠在使用血管破坏剂(VDA)治疗前(n = 11)和治疗后(n = 9)进行PAI和基于T2加权自旋回波的BOLD MR成像,以评估肿瘤对卡波金(95% O₂,5% CO₂)的反应。进行双尾Pearson相关分析以确定体外PAI和BOLD MR成像测量参数之间的相关性。使用双尾配对t检验比较肿瘤血红蛋白氧饱和度(sO₂)水平和BOLD信号对卡波金的变化。使用重复测量方差分析分析VDA治疗前后PAI和BOLD信号强度的变化是否具有显著性。
体模测量结果显示,光声衍生的sO₂水平与BOLD信号强度(r = 0.937,P = 0.005)以及氧分压(r = 0.981,P = 0.005)之间具有良好的相关性。体内对卡波金的血流动力学反应表现为肿瘤sO₂水平(P = 0.003)和BOLD信号(P = 0.001)显著增加。与治疗前的估计值相比,VDA治疗导致PAI时肿瘤对卡波金的血流动力学反应显著降低(P = 0.030)。
基于卡波金的PAI和BOLD MR功能成像能够监测血管靶向治疗后肿瘤血流动力学的早期变化。