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OxyLiteTM光纤微探针验证非血流动力学响应函数分析的血氧水平依赖功能MRI检测大鼠C6胶质瘤组织氧含量变化的可靠性

Using OxyLiteTM fiber-optic microprobes to verify the reliability of detecting the oxygenation in rats C6 glioma by blood oxygenation level dependent functional MRI with non-hemodynamic response function analysis

摘要:

目的:利用兼容MRI的OxyLiteTM光纤传感器,验证非血流动力学响应函数(non-HRF)后处理算法的血氧水平依赖fMRI(BOLD fMRI)技术评价大鼠皮下C6胶质瘤组织氧含量变化的可靠性。方法构建20只雄性SD大鼠的皮下C6胶质瘤模型。采用1.5 T MRI系统、Micro-47显微线圈及单次激发梯度回波-平面回波(GRE-EPI)序列对瘤体行Carbogen气体(95%O2+5%CO2混合气体)呼吸激励的BOLD fMRI扫描,同时记录置于瘤体内OxyLiteTM微探针测得的肿瘤内局部氧分压(pO2)的动态读数。图像数据经non-HRF后处理算法分析后生成“氧合地图”和“氧合幅度图”。在MR图像上以探针尖端为中心定义边长为1.5 mm的正方形ROI,并将其复制到“氧合地图”和“氧合幅度图”上分别提取该区域的BOLD信号改变显著性参数(T值)和信号强度变化百分比(ΔPSC值)。提取微探针测得的Carbogen气体吸入前与吸入后pO2的均数并计算其差值(ΔpO2)。在Carbogen气体吸入前后的pO2差别采用Mann Whitney U检验,对测量点区域测得的ΔpO2值、T值及ΔPSC值之间的相关性采用Spearman相关性检验。结果共获得15只大鼠23个OxyLiteTM微探针有效测量点数据:23个测量点的pO2-Air为2.285(19.056)mmHg,pO2-Car为14.701(48.390)mmHg,ΔpO2为8.107(33.557)mmHg,ΔPSC值为0.402(2.192)%,T值为2.025(8.293)。(1)10个测量点明确位于肿瘤实质成分内。该区域pO2均值在吸入Carbogen气体时[59.904(56.710)mmHg]较吸入空气时[19.462(21.511)mmHg]显著增高(U=14.000, P=0.007);(2)5个测量点明确位于肿瘤坏死成分内,其pO2均值在吸入空气时[0.149(0.479)mmHg]与吸入Carbogen气体时[0.273(8.050)mmHg]相比差异无统计学意义(U=9.000,P=0.465);(3)8个测量点位于肿瘤实质成分与坏死成分的交界区。其中5个的pO2值变化类似于肿瘤坏死成分区,2个类似于肿瘤实质成分区,1个点的动态pO2值在吸入Carbogen气体后持续性减低。ΔpO2值与其相应区域测得的ΔPSC值、T值均呈正相关(r=0.660,0.576,P<0.01)。其中10个位于肿瘤实质区测量点处的ΔpO2值与PSC值存在正相关(r=0.717,P=0.020)。结论结合non-HRF后处理算法的BOLD fMRI功能成像技术得到的“氧合地图”及“氧合幅度图”能较可靠地反映肿瘤内部氧合变化发生的部位及程度。

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abstracts:

Objective Using MRI compatible OxyLiteTM fiber-optic microprobes to verify the reliability of detecting the oxygenation changes in rats C6 glioma by BOLD fMRI with non- hemodynamic response function (non-HRF) post-processing algorithm. Methods A total of 20 male SD rats were used to establish the subcutaneous C6 glioma model. GRE-EPI BOLD fMRI scans were performed in the tumor-bearing rats with Carbogen inhalation after anatomic scans using 1.5 T MR imaging system with <br> Micro-47 microscopic coil. Fiber-optic microprobes were implanted in tumor to acquire the dynamic pO2 indications during BOLD fMRI scan.“Oxy-localization map”and“oxy-amplitude map”were generated from BOLD functional image data by non-HRF post-processing algorithm analysis. A ROI about 1.5 mm on a side centered to the tip of microprobe was defined on the MRI morphological image, and then was copied onto the“oxy-localization map”and“oxy-amplitude map”to extract the values of significant re-oxygenation (T), percent BOLD signal change (ΔPSC). The mean difference of pO2(ΔpO2) measured by fiber-optic microprobes before(pO2-Air)and after (pO2-Car)Carbogen inhalation in the ROI areas was calculated. Correlation analysis was madebetween cov (T value, Δ pO2) and cov (ΔPSC value, Δ pO2). The difference between pO2-Air and pO2-Car were tested by Mann Whitney U test. Results pO2 was successfully measured and recorded from 23 points in tumor using fiber-optic microprobe during the BOLD fMRI scan. The analysis results both of physiological and functional imaging parameters were as follows: pO2-Air=2.285(19.056) mmHg,pO2-Car=14.701(48.390)mmHg,ΔpO2=8.107(33.557)mmHg,ΔPSC=0.402(2.192)%,T=2.025 (8.293). (1) 10 points were identified clearly in parenchyma area of tumor. The mean value of pO2 during air inhalation [19.462(21.511)mmHg] significantly increased after Carbogen inhalation [59.904(56.710)mmHg] (U=14.000,P=0.007). (2) 5 points were identified in tumor necrosis area. The mean value of pO2 during air inhalation [0.149(0.479)mmHg] showed no significant change comparing with Carbogen inhalation[0.273 (8.050)mmHg](U=9.000,P=0.465). (3) 8 points were identified in the boundary of tumor parenchyma and necrosis areas. Among which, 5 showed the similar pO2 change to that located in tumor necrosis area, 2 showed the similar to the tumor parenchyma. However, the pO2 showed continuously decrease after Carbogen inhalation in the last 1 point. TheΔpO2 measured from the total of 23 points correlated positively toΔPSC and T value extracted from the corresponding ROI (r=0.660,0.576,P<0.01). TheΔpO2 measured from 10 points in tumor parenchyma correlated positively to ΔPSC(r=0.717,P=0.020). Conclusion“Oxy-localization map”and“oxy-amplitude map”generated from BOLD fMRI combined with non-HRF post-processing algorithm could show reliably not only the location but also the extent where the re-oxygenation occurred within tumor.

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作者: 徐瑾 [1] 陈安 [1] 蒋震 [1] 张彩元 [1] 孙亚琼 [1] 张峻围 [1] 沈钧康 [1]
期刊: 《中华放射学杂志》2016年50卷7期 542-548页 MEDLINEISTICPKUCSCD
栏目名称: 实验研究
DOI: 10.3760/cma.j.issn.1005-1201.2016.07.013
发布时间: 2016-07-21
基金项目:
国家自然科学基金(81271554)Fund programNational Natural Science Foundation of China
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