Diffusion kurtosis imaging probes cortical alterations and white matter pathology following cuprizone induced demyelination and spontaneous remyelination.
Diffusion kurtosis imaging probes cortical alterations and white matter pathology following cuprizone induced demyelination and spontaneous remyelination.
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DOI：
10.1016/j.neuroimage.2015.10.052
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发表时间：
2016-01-15
期刊：
影响因子：
5.7
通讯作者：
Verhoye M
中科院分区：
文献类型：
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作者：
Guglielmetti C;Veraart J;Roelant E;Mai Z;Daans J;Van Audekerke J;Naeyaert M;Vanhoutte G;Delgado Y Palacios R;Praet J;Fieremans E;Ponsaerts P;Sijbers J;Van der Linden A;Verhoye M
虽然MRI是诊断和监测多发性硬化症（MS）的金标准，但目前的常规MRI技术往往无法检测皮质改变，也无法提供病变区域胶质细胞形成、轴突损伤和髓磷脂状态的信息。弥散张量成像（DTI）和弥散峰度成像（DKI）提供了敏感和互补的神经组织微观结构测量方法。此外，最近还导出了模拟白质扩散的特定白质束完整性（WMTI）指标。在目前的研究中，我们使用表征良好的铜zone小鼠中枢神经系统脱髓鞘模型来评估急性炎症性脱髓鞘和自发性再脱髓鞘后弥散张量（DT）、弥散峰度张量（DK）和wmti衍生指标的时间演变。虽然dt衍生的指标无法检测到铜酮诱导的皮质改变，但与年龄匹配的对照组相比，在铜酮管理下，运动和体感觉皮质的平均峰度（MK）和径向峰度（RK）都有所下降。在恢复期结束时，运动皮层的MK仍然下降，反映了髓鞘形成的长期损害。在白质中，根据病变的分期和严重程度，DT、DK和wmti衍生指标能够检测到铜酮引起的不同变化。更具体地说，MK、RK和轴突水分数（AWF）对铜酮诱导的胼胝体膝区变化最敏感，而这一区域受铜酮的影响较小。此外，在急性炎症脱髓鞘期，小胶质瘤与MK和RK的增加有关。在发生严重脱髓鞘的区域，即胼胝体的体部和脾部，dt衍生的指标，特别是平均扩散（MD）和径向扩散（RD），是铜酮和对照组之间最好的鉴别器，因此突出了它们检测急性和长期变化的能力。有趣的是，wmti衍生的指标显示出区分疾病不同阶段的能力。结果表明，铜普利酮组大鼠轴突内弥散性（Da）和AWF均降低，其中Da在急性炎性脱髓鞘期明显降低，而AWF的降低与自发性脱髓鞘形成和恢复期有关。总之，我们的研究结果表明，DKI对皮质区域的改变很敏感，并与WMTI指标一起，为白质和灰质脱髓鞘特征以及随后与脱髓鞘事件相关的炎症过程提供了补充dt衍生指标的信息。
Although MRI is the gold standard for the diagnosis and monitoring of multiple sclerosis (MS), current conventional MRI techniques often fail to detect cortical alterations and provide little information about gliosis, axonal damage and myelin status of lesioned areas. Diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) provide sensitive and complementary measures of the neural tissue microstructure. Additionally, specific white matter tract integrity (WMTI) metrics modelling the diffusion in white matter were recently derived. In the current study we used the well-characterized cuprizone mouse model of central nervous system demyelination to assess the temporal evolution of diffusion tensor (DT), diffusion kurtosis tensor (DK) and WMTI-derived metrics following acute inflammatory demyelination and spontaneous remyelination. While DT-derived metrics were unable to detect cuprizone induced cortical alterations, the mean kurtosis (MK) and radial kurtosis (RK) were found decreased under cuprizone administration, as compared to age-matched controls, in both the motor and somatosensory cortices. The MK remained decreased in the motor cortices at the end of the recovery period, reflecting long lasting impairment of myelination. In white matter, DT, DK and WMTI-derived metrics enabled the detection of cuprizone induced changes differentially according to the stage and the severity of the lesion. More specifically, MK, RK and the axonal water fraction (AWF) were the most sensitive for the detection of cuprizone induced changes in the genu of the corpus callosum, a region less affected by cuprizone administration. Additionally, microgliosis was associated with an increase of MK and RK during the acute inflammatory demyelination phase. In regions undergoing severe demyelination, namely the body and splenium of the corpus callosum, DT-derived metrics, notably the mean diffusion (MD) and radial diffusion (RD), were among the best discriminators between cuprizone and control groups, hence highlighting their ability to detect both acute and long lasting changes. Interestingly, WMTI-derived metrics showed the aptitude to distinguish between the different stage of the disease. Both the intra-axonal diffusivity (Da) and the AWF were found to be decreased in the cuprizone treated group, Da specifically decreased during the acute inflammatory demyelinating phase whereas the AWF decrease was associated to the spontaneous remyelination and the recovery period. Altogether our results demonstrate that DKI is sensitive to alterations of cortical areas and provides, along with WMTI metrics, information that is complementary to DT-derived metrics for the characterization of demyelination in both white and grey matter and subsequent inflammatory processes associated with a demyelinating event.