Comparison of Apparent Diffusion Coefficient and Intravoxel Incoherent Motion for Differentiating among Glioblastoma, Metastasis, and Lymphoma Focusing on Diffusion-Related Parameter

Background and Purpose
Brain tumor cellularity has been assessed by using apparent diffusion coefficient (ADC). However, the ADC value might be influenced by both perfusion and true molecular diffusion, and the perfusion effect on ADC can limit the reliability of ADC in the characterization of tumor cellularity, especially, in hypervascular brain tumors. In contrast, the IVIM technique estimates parameter values for diffusion and perfusion effects separately. The purpose of our study was to compare ADC and IVIM for differentiating among glioblastoma, metastatic tumor, and primary CNS lymphoma (PCNSL) focusing on diffusion-related parameter.
Materials and Methods
We retrospectively reviewed the data of 128 patients with pathologically confirmed glioblastoma (n = 55), metastasis (n = 31), and PCNSL (n = 42) prior to any treatment. Two neuroradiologists independently calculated the maximum IVIM-f (fmax) and minimum IVIM-D (Dmin) by using 16 different b-values with a bi-exponential fitting of diffusion signal decay, minimum ADC (ADCmin) by using 0 and 1000 b-values with a mono-exponential fitting and maximum normalized cerebral blood volume (nCBVmax). The differences in fmax, Dmin, nCBVmax, and ADCmin among the three tumor pathologies were determined by one-way ANOVA with multiple comparisons. The fmax and Dmin were correlated to the corresponding nCBV and ADC using partial correlation analysis, respectively.
Results
Using a mono-exponential fitting of diffusion signal decay, the mean ADCmin was significantly lower in PCNSL than in glioblastoma and metastasis. However, using a bi-exponential fitting, the mean Dmin did not significantly differ in the three groups. The mean fmax significantly increased in the glioblastomas (reader 1, 0.103; reader 2, 0.109) and the metastasis (reader 1, 0.105; reader 2, 0.107), compared to the primary CNS lymphomas (reader 1, 0.025; reader 2, 0.023) (P < .001 for each). The correlation between fmax and the corresponding nCBV was highest in glioblastoma group, and the correlation between Dmin and the corresponding ADC was highest in primary CNS lymphomas group.
Conclusion
Unlike ADC value derived from a mono-exponential fitting of diffusion signal, diffusion-related parametric value derived from a bi-exponential fitting with separation of perfusion effect doesn’t differ among glioblastoma, metastasis, and PCNSL.

背景与研究目的
既往多采用表观扩散系数（apparent diffusion coefficient, ADC）评估脑肿瘤细胞密度，但ADC值同时受灌注效应与真实分子扩散的双重影响，其中灌注效应会限制ADC在肿瘤细胞密度表征中的可靠性，在高血管性脑肿瘤中这一局限尤为显著。与之相对，体素内不相干运动（intravoxel incoherent motion, IVIM）技术可分别估算扩散与灌注效应对应的参数值。本研究旨在对比ADC与IVIM技术在鉴别胶质母细胞瘤、转移瘤及原发性中枢神经系统淋巴瘤（primary CNS lymphoma, PCNSL）中的效能，重点关注扩散相关参数。

材料与方法
本研究回顾性分析了128例经病理证实且未接受任何前期治疗的脑肿瘤患者数据，其中胶质母细胞瘤55例、转移瘤31例、原发性中枢神经系统淋巴瘤42例。两名神经放射医师独立采用16种不同b值，通过扩散信号衰减双指数拟合计算最大IVIM-f值（fmax）与最小IVIM-D值（Dmin）；同时采用b值为0与1000的单指数拟合计算最小表观扩散系数（ADCmin），并测量最大标准化脑血容量（normalized cerebral blood volume, nCBVmax）。采用单因素方差分析结合多重比较，分析三种肿瘤病理类型间fmax、Dmin、nCBVmax及ADCmin的差异；分别采用偏相关分析，探究fmax与对应nCBV、Dmin与对应ADC的相关性。

结果
采用扩散信号衰减单指数拟合时，原发性中枢神经系统淋巴瘤组的平均ADCmin显著低于胶质母细胞瘤组与转移瘤组。但采用双指数拟合时，三组的平均Dmin无显著差异。与原发性中枢神经系统淋巴瘤组（阅读者1：0.025；阅读者2：0.023）相比，胶质母细胞瘤组（阅读者1：0.103；阅读者2：0.109）与转移瘤组（阅读者1：0.105；阅读者2：0.107）的平均fmax显著升高（各组P均<0.001）。fmax与对应nCBV的相关性在胶质母细胞瘤组中最高，而Dmin与对应ADC的相关性在原发性中枢神经系统淋巴瘤组中最高。

结论
与基于扩散信号衰减单指数拟合得到的ADC值不同，通过分离灌注效应的双指数拟合得到的扩散相关参数值，在胶质母细胞瘤、转移瘤与原发性中枢神经系统淋巴瘤之间无显著差异。