#Qspace quality testing freeMyelin is a lipid-enriched structure that hinders the free diffusion of water molecules. For example, although T2 hyperintensity is often interpreted as a hallmark of demyelination, a postmortem MRI study showed that remyelinated MS lesions were also T2 hyperintense ( Barkhof et al., 2003) and T2 lesion loads did not necessary correlate with physical disability measures in MS ( Barkhof, 1999). Conversely, visualization of myelin by conventional MRI has technical limitations. There have been attempts to detect myelin-specific signals by nonconventional magnetic resonance methods such as magnetization transfer ratio analysis ( Gass et al., 1994) and T2 relaxation study ( Laule et al., 2004) or positron emission tomography ( Stankoff et al., 2011), although the application of these methods in daily clinical practice has been hindered by their time-consuming nature (e.g., hours of acquisition time), relatively poor resolution, or the need to use radioactive tracers. Collectively, myelin pathology is attracting significant attention, not only in the context of demyelinating diseases such as multiple sclerosis (MS), but also in the setting of various neurological diseases. Myelin failure preceding neurodegeneration was reported in amyotrophic lateral sclerosis ( Kang et al., 2013). Myelin in the CNS not only enables saltatory conduction, but also plays an essential role in supporting neural survival ( Lee et al., 2012). 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. 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. However, appropriate methods with which to monitor CNS myelin in daily clinical practice have been lacking. SIGNIFICANCE STATEMENT Myelin abnormalities in the CNS have been gaining increasing attention in various neurological and psychiatric diseases. 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. 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. The human myelin map could be obtained within 10 min with a 3 T MR scanner. Finally, its utility in clinical practice was assessed by a pilot clinical study in a selected group of patients with multiple sclerosis (MS). The results demonstrated that it was sensitive enough to depict dysmyelination, demyelination, and remyelination in animal models. 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 heat map of standardized kurtosis values derived from optimal QSI (myelin map) was then created. For this purpose, animal studies were first performed to optimize the acquisition protocol of a non-Gaussian QSI metric. In the current study, we aimed to refine QSI protocols to enable their clinical application and to visualize myelin signals in a clinical setting. 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. White matter abnormalities in the CNS have been reported recently in various neurological and psychiatric disorders.
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