Histological correlation of diffusional kurtosis and white matter modeling metrics in cuprizone-induced corpus callosum demyelination.
Histological correlation of diffusional kurtosis and white matter modeling metrics in cuprizone-induced corpus callosum demyelination.
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DOI：
10.1002/nbm.3140
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发表时间：
2014-08
影响因子：
2.9
通讯作者：
Helpern JA
中科院分区：
文献类型：
--
作者：
Falangola MF;Guilfoyle DN;Tabesh A;Hui ES;Nie X;Jensen JH;Gerum SV;Hu C;LaFrancois J;Collins HR;Helpern JA
cuprizone小鼠模型已建立，可用于研究胼胝体脱髓鞘和再髓鞘形成过程，并与弥散张量成像（DTI）一起用于研究髓鞘和轴突病理。虽然已经确定了一些导致扩散张量（DT）指标变化的潜在形态学机制，但对组织学和扩散测量之间特定关联的理解仍然有限。扩散峰度成像（DKI）是DTI的扩展，它提供了扩散非高斯性的度量，为此开发了一种相关的白质建模（WMM）方法。本研究的主要目的是定量评估铜酮诱导的小鼠胼胝体脱髓鞘模型中扩散指标与组织学指标之间的关系。发现弥漫性峰度（DK）和WMM指标提供了额外的信息，增强了检测胼胝体吻侧段疾病过程慢性期形态学异质性的敏感性。具体而言，在吻侧节段轴突水分含量（d = 2.6, p<0.0001）、径向峰度（d = 2.0, p=0.001）和平均峰度（d = 1.5, p=0.005）组间敏感性最高，p值具有统计学意义，且Cohen’s d值较高。这些结果表明，DK和WMM指标能够检测与铜酮诱导的脱髓鞘相关的白质变化和炎症过程。它们也在一定程度上验证了这些新的WMM指标在研究神经系统疾病中的应用，并有助于阐明它们的生物物理意义。
The cuprizone mouse model is well-established for studying the processes of both demyelination and remyelination in the corpus callosum, and it has been utilized together with diffusion tensor imaging (DTI) to investigate myelin and axonal pathology. Although some underlying morphological mechanisms contributing to the changes in diffusion tensor (DT) metrics have been identified, the understanding of specific associations between histology and diffusion measures remains limited. Diffusional kurtosis imaging (DKI) is an extension of DTI that provides metrics of diffusional non-Gaussianity, for which an associated white matter modeling (WMM) method has been developed. The main goal of the present study was to quantitatively assess the relationships between diffusion measures and histological measures in the mouse model of cuprizone-induced corpus callosum demyelination. The diffusional kurtosis (DK) and WMM metrics were found to provide additional information that enhances the sensitivity to detect the morphological heterogeneity in the chronic phase of the disease process in the rostral segment of the corpus callosum. Specifically, in the rostral segment axonal water fraction (d = 2.6; p<0.0001), radial kurtosis (d = 2.0; p=0.001) and mean kurtosis (d = 1.5; p=0.005) showed the most sensitivity between groups with respect to yielding statistically significant p-values and high Cohen’s d values. These results demonstrate the ability of DK and WMM metrics to detect white mater changes and inflammatory processes associated with cuprizone-induced demyelination. They also validate, in part, the application of these new WMM metrics for studying neurological diseases, as well as help to elucidate their biophysical meaning.