N 6 -Methyladenosine (m 6 A) is a dynamic mRNA modification which regulates protein expression in various posttranscriptional levels. Functional studies of m 6 A in nervous system have focused on its writers and erasers so far, whether and how m 6 A readers mediate m 6 A functions through recognizing and binding their target mRNA remains poorly understood. Here, we find that the expression of axon guidance receptor Robo3.1 which plays important roles in midline crossing of spinal commissural axons is regulated precisely at translational level. The m 6 A reader YTHDF1 binds to and positively regulates translation of m 6 A-modified Robo3.1 mRNA. Either mutation of m 6 A sites in Robo3.1 mRNA or YTHDF1 knockdown or knockout leads to dramatic reduction of Robo3.1 protein without affecting Robo3.1 mRNA level. Specific ablation of Ythdf1 in spinal commissural neurons results in pre-crossing axon guidance defects. Our findings identify a mechanism that YTHDF1-mediated translation of m 6 A-modified Robo3.1 mRNA controls pre-crossing axon guidance in spinal cord.

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Background and purposeNeurite orientation dispersion and density imaging (NODDI) is a new diffusion MRI technique that has rarely been applied for glioma grading. The purpose of this study was to quantitatively evaluate the diagnostic efficiency of NODDI in tumour parenchyma (TP) and peritumoural area (PT) for grading gliomas and detecting isocitrate dehydrogenase-1 (IDH-1) mutation status.MethodsForty-two patients (male: 23, female: 19, mean age: 44.5 y) were recruited and underwent whole brain NODDI examination. Intracellular volume fraction (icvf) and orientation dispersion index (ODI) maps were derived. Three ROIs were manually placed on TP and PT regions for each case. The corresponding average values of icvf and ODI were calculated, and their diagnostic efficiency was assessed.ResultsTumours with high icvfTP (≥0.306) and low icvfPT (≤0.331) were more likely to be high-grade gliomas (HGGs), while lesions with low icvfTP (<0.306) and high icvfPT (>0.331) were prone to be low-grade gliomas (LGGs) (P < 0.001). A multivariate logistic regression model including patient age and icvf values in TP and PT regions most accurately predicted glioma grade (AUC = 0.92, P < 0.001), with a sensitivity and specificity of 92% and 89%, respectively. However, no significant differences were found in NODDI metrics for differentiating IDH-1 mutation status.ConclusionsThe quantitative NODDI metrics in the TP and PT regions are highly valuable for glioma grading. A multivariate logistic regression model using the patient age and the icvf values in TP and PT regions showed very high predictive power. However, the utility of NODDI metrics for detecting IDH-1 mutation status has not been fully explored, as a larger sample size may be necessary to uncover benefits.

2 Technical Efficacy Stage 2 J. MAGN. RESON. IMAGING 2018;48:423-430.

ObjectiveTo investigate the cause of the motor asymmetry in Wilson's disease (WD) patients using functional MRI.MethodsFifty patients with WD and 20 age‐matched healthy controls were enrolled. Neurological symptoms were scored using the modified Young Scale. All study subjects underwent diffusion tensor imaging (DTI), susceptibility‐weighted imaging (SWI), and resting‐state functional MRI (rs‐fMRI) of the brain. Six regions of interest (ROI) were chosen. Fiber volumes between ROIs on DTI, corrected phase (CP) values on SWI, amplitude of low‐frequency fluctuation (ALFF), and regional homogeneity (REHO) values on rs‐fMRI were determined. Asymmetry index (right or left value/left or right value) was evaluated.ResultsAsymmetry of rigidity, tremor, choreic movement, and gait abnormality (asymmetry index = 1.33, 1.39, 1.36, 1.40), fiber tracts between the GP and substantia nigra (SN), GP and PU, SN and thalamus (TH), SN and cerebellum, head of the caudate nucleus (CA) and SN, PU and CA, CA and TH, TH and cerebellum (asymmetry index = 1.233, 1.260, 1.269, 1.437, 1.503, 1.138, 1.145, 1.279), CP values in the TH, SN (asymmetry index = 1.327, 1.166), ALFF values, and REHO values of the TH (asymmetry index = 1.192, 1.233) were found. Positive correlation between asymmetry index of rigidity and fiber volumes between the GP and SN, SN and TH (r = .221, .133, p = .043, .036), and tremor and fiber volumes between the CA and TH (r = .045, p = .040) was found.ConclusionsThe neurological symptoms of patients with WD were asymmetry. The asymmetry of fiber projections may be the main cause of motor asymmetry in patients with WD.