Fujiyoshi Kanehiro, Hikishima Keigo, Nakahara Jin, Tsuji Osahiko, Hata Junichi, Konomi Tsunehiko, Nagai Toshihiro, Shibata Shinsuke, Kaneko Shinjiro, Iwanami Akio, Momoshima Suketaka, Takahashi Shinichi, Jinzaki Masahiro, Suzuki Norihiro, Toyama Yoshiaki, Nakamura Masaya, Okano Hideyuki
Departments of Orthopedic Surgery, Physiology, Department of Orthopedic Surgery, National Hospital Organization Murayama Medical Center, Tokyo 208-0011, Japan.
Physiology, Central Institute for Experimental Animals, Kanagawa 210-0821, Japan, and.
J Neurosci. 2016 Mar 2;36(9):2796-808. doi: 10.1523/JNEUROSCI.1770-15.2016.
White matter abnormalities in the CNS have been reported recently in various neurological and psychiatric disorders. Quantitation of non-Gaussianity for water diffusion by q-space diffusional MRI (QSI) renders biological diffusion barriers such as myelin sheaths; however, the time-consuming nature of this method hinders its clinical application. In the current study, we aimed to refine QSI protocols to enable their clinical application and to visualize myelin signals in a clinical setting. For this purpose, animal studies were first performed to optimize the acquisition protocol of a non-Gaussian QSI metric. The heat map of standardized kurtosis values derived from optimal QSI (myelin map) was then created. Histological validation of the myelin map was performed in myelin-deficient mice and in a nonhuman primate by monitoring its variation during demyelination and remyelination after chemical spinal cord injury. The results demonstrated that it was sensitive enough to depict dysmyelination, demyelination, and remyelination in animal models. Finally, its utility in clinical practice was assessed by a pilot clinical study in a selected group of patients with multiple sclerosis (MS). The human myelin map could be obtained within 10 min with a 3 T MR scanner. Use of the myelin map was practical for visualizing white matter and it sensitively detected reappearance of myelin signals after demyelination, possibly reflecting remyelination in MS patients. Our results together suggest that the myelin map, a kurtosis-related heat map obtainable with time-saving QSI, may be a novel and clinically useful means of visualizing myelin in the human CNS.
Myelin abnormalities in the CNS have been gaining increasing attention in various neurological and psychiatric diseases. However, appropriate methods with which to monitor CNS myelin in daily clinical practice have been lacking. In the current study, we introduced a novel MRI modality that produces the "myelin map." The myelin map accurately depicted myelin status in mice and nonhuman primates and in a pilot clinical study of multiple sclerosis patients, suggesting that it is useful in detecting possibly remyelinated lesions. A myelin map of the human brain could be obtained in <10 min using a 3 T scanner and it therefore promises to be a powerful tool for researchers and clinicians examining myelin-related diseases.
中枢神经系统白质异常最近在各种神经和精神疾病中都有报道。通过q空间扩散磁共振成像（QSI）对水扩散的非高斯性进行定量分析，可以呈现生物扩散屏障，如髓鞘；然而，这种方法耗时的特性阻碍了其临床应用。在当前研究中，我们旨在优化QSI方案以使其能够应用于临床，并在临床环境中可视化髓鞘信号。为此，首先进行动物研究以优化非高斯QSI指标的采集方案。然后创建了源自最佳QSI（髓鞘图）的标准化峰度值热图。通过监测化学性脊髓损伤后脱髓鞘和再髓鞘化过程中髓鞘图的变化，在髓鞘缺陷小鼠和非人类灵长类动物中对髓鞘图进行了组织学验证。结果表明，它足够敏感，能够描绘动物模型中的髓鞘发育异常、脱髓鞘和再髓鞘化情况。最后，通过对一组选定的多发性硬化症（MS）患者进行的初步临床研究评估了其在临床实践中的实用性。使用3T磁共振扫描仪可在10分钟内获得人脑髓鞘图。髓鞘图对于可视化白质很实用，并且它能灵敏地检测到脱髓鞘后髓鞘信号的重新出现，这可能反映了MS患者的再髓鞘化情况。我们的结果共同表明，髓鞘图是一种与峰度相关的热图，可通过省时的QSI获得，可能是一种在人类中枢神经系统中可视化髓鞘的新颖且具有临床实用性的方法。
中枢神经系统的髓鞘异常在各种神经和精神疾病中越来越受到关注。然而，在日常临床实践中缺乏监测中枢神经系统髓鞘的合适方法。在当前研究中，我们引入了一种新型磁共振成像模式，可生成“髓鞘图”。髓鞘图准确描绘了小鼠、非人类灵长类动物以及多发性硬化症患者初步临床研究中的髓鞘状态，表明它在检测可能的再髓鞘化病变方面很有用。使用3T扫描仪可在不到10分钟的时间内获得人脑髓鞘图，因此它有望成为研究人员和临床医生检查髓鞘相关疾病的有力工具。
