The functional diffusion map: An imaging biomarker for the early prediction of cancer treatment outcome
The functional diffusion map: An imaging biomarker for the early prediction of cancer treatment outcome
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DOI：
10.1593/neo.05844
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发表时间：
2006-04-01
期刊：
影响因子：
4.8
通讯作者：
Ross, Brian D.
中科院分区：
文献类型：
--
作者：
Moffat, Bradford A.;Chenevert, Thomas L.;Ross, Brian D.
功能性弥散图（functional diffusion map，fDM）是脑肿瘤临床治疗结果的早期和定量生物标志物。这种MRI方法在空间上映射并量化了由细胞密度/细胞膜功能和微环境改变引起的肿瘤水扩散值的治疗诱导变化。本研究旨在评价FDM用于剂量递增研究临床前评价的能力，并确定这些变化是否与结局指标（细胞杀伤和总生存期）相关。对接受三种剂量的1，3-双（2-氯乙基）-1-亚硝基脲（6.65、13.3和26.6 mg/kg，i. p.）的原位植入9 L脑肿瘤的啮齿动物进行系列T-2加权和扩散MRI。所有图像均与基线T-2加权图像配准以进行FDM分析。治疗后第4天的肿瘤FDM数据分析检测到肿瘤扩散值的剂量依赖性变化，也发现其具有空间依赖性。经治疗的肿瘤的组织学分析证实了FDM观察到的细胞结构的空间变化。发现肿瘤扩散值的早期变化与药物剂量和独立的生物学结局指标（细胞杀伤和存活）高度相关。因此，用于早期预测治疗疗效的FDM成像生物标志物可用于药物开发过程。
Functional diffusion map (fDM) has been recently reported as an early and quantitative biomarker of clinical brain tumor treatment outcome. This MRI approach spatially maps and quantifies treatment-induced changes in tumor water diffusion values resulting from alterations in cell density/cell membrane function and microenvironment. This current study was designed to evaluate the capability of fDM for preclinical evaluation of dose escalation studies and to determine if these changes were correlated with outcome measures (cell kill and overall survival). Serial T-2-weighted and diffusion MRI were carried out on rodents with orthotopically implanted 9L brain tumors receiving three doses of 1,3-bis(2-chloroethyl)-1-nitrosourea (6.65, 13.3, and 26.6 mg/kg, i.p.). All images were coregistered to baseline T-2-weighted images for fDM analysis. Analysis of tumor fDM data on day 4 posttreatment detected dose-dependent changes in tumor diffusion values, which were also found to be spatially dependent. Histologic analysis of treated tumors confirmed spatial changes in cellularity as observed by fDM. Early changes in tumor diffusion values were found to be highly correlative with drug dose and independent biologic outcome measures (cell kill and survival). Therefore, the fDM imaging biomarker for early prediction of treatment efficacy can be used in the drug development process.