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Previous studies have indicated that neurite orientation dispersion and density imaging (NODDI) could be used as a biomarker for detecting microstructural changes of brain.To quantitatively evaluate the changes in basal ganglia (BG) and thalamus in Wilson's disease (WD) by NODDI and assess the correlation between parameters and disease severity.Prospective case-control study.In total, 24 WD patients and 25 age- and sex-matched normal controls were involved in this study.EPI diffusion-weighted MR images (b-values = 0, 1000, and 2000 with 30 diffusion gradient directions) were acquired on a 3T scanner.Diffusion data were analyzed using voxel-based analysis. NODDI indices including intracellular volume fraction (Vic), orientation dispersion index (ODI), and isotropic volume fraction (Viso) were estimated from the BG and thalamus. The disease severity was assessed by two experienced neurologists based on the Global Assessment Scale (GAS). The relative importance of NODDI indices in diagnosing WD and predictive accuracy were also analyzed.The Shapiro-Wilk test, Student's t-test, χ2 test, Mann-Whitney-Wilcoxon test, Spearman rank correlation coefficient analysis and random-forest analysis were used for statistical analyses.The Vic and ODI in the BG and thalamus were significantly lower in WD patients than normal controls, while the Viso in the BG and thalamus were significantly higher (P0.01). The Vic in the putamen and ODI in the globus pallidus were negatively correlated with clinical severity (rvic = -0.727, P 0.001; rodi = -0.705, P 0.001). The Vic in the putamen was the most valuable predictor for diagnosing WD and the prediction accuracy of NODDI was 95.92%.NODDI can effectively evaluate the changes of microstructure and metabolism during copper deposition in WD, and thus, it is likely to be useful in detecting the changes in the brain of this disease and assessing its progression.2 Technical Efficacy Stage 2 J. MAGN. RESON. IMAGING 2018;48:423-430.

AIMS: To detect specific oculomotor deficits in preclinical stage of spinocerebellar ataxia type 3 (SCA3) and evaluate whether these abnormalities prove useful as potential biomarkers of disease progression. METHODS: A Chinese cohort of 56 patients with SCA3, including 12 preclinical carriers of SCA3 (pre‐SCA3) and 44 manifest SCA3, and 26 healthy control individuals were recruited. We performed a detailed investigation on central oculomotor performance including fixation, gaze, smooth pursuit, prosaccade, and antisaccade using video‐oculography. RESULTS: Common oculomotor features of pre‐SCA3 included square‐wave jerk during central fixation and gaze holding, impaired vertical smooth pursuit, slow upward saccade, and increased antisaccade error rate. In our SCA3 cohort, all oculomotor parameters were correlated with the score of the Scale for the Assessment and Rating of Ataxia, whilst some of them were correlated with disease duration. CONCLUSION: This study showed that a series of neuropathological changes reflected by oculomotor abnormalities appeared preferentially in preclinical stage of SCA3. Accordingly, objective oculomotor preclinical signs may be useful to detect the optimum time‐point for therapeutic interventions in future clinical trials of SCA3. Larger and longitudinal data are warranted to confirm our results.

Objective To evaluate damage to the extracorticospinal tract in Wilson disease (WD) patients using diffusion tensor imaging (DTI). Methods 70 patients with WD, including 50 with cerebral type and 20 with hepatic type, and 20 age-matched healthy controls were enrolled. Neurological symptoms were scored using the modified Young Scale. Patients with cerebral type WD were divided into four subgroups: those with (1) hypokinesia, (2) parkinsonism, (3) mouth and throat dystonia, and (4) psychiatric symptoms. All study subjects underwent DTI of the brain. Five regions of interest (ROIs) were chosen. Fractional anisotropy (FA) and fiber volumes between ROIs were determined, and the relationships between DTI metrics and clinical status were evaluated. Results FA values and fiber volumes between subcortical nuclei were lower in WD patients. Fiber volumes between the putamen (PU) and the globus pallidus (GP), substantia nigra (SN), and thalamus (TH); between the head of the caudate nucleus (CA) and the GP and TH; and between the TH and cerebellum were lower in group 1 than in the other groups of WD patients. Fiber volumes between the GP and the SN and TH were lower in group 2, and fiber volumes between the SN and TH were lower in group 3. DTI metrics differed between patients with the cerebral and hepatic types of WD. Conclusions DTI can reconstruct the network of the extracorticospinal tract. Fiber projection between subcortical nuclei was abnormal in WD patients. Damage to fiber connections may correlate with neurological symptoms in WD patients.

Aims: The aim of this study was to evaluate the feasibility of characterizing the brain-mineral deposition in patients with Wilson disease (WD) using susceptibility-weighted imaging (SWI). Materials and Methods: The study enrolled 30 WD patients and 20 age-matched healthy controls. Neurological symptoms were scored using the modified Young Scale. The hepatic function indices, serum and urinary copper content, and serum iron content were determined. All study objects received the magnetic resonance imaging (MRI) and SWI test of the brain. The values of corrected phase (CP) were calculated on SWI. The relationship between CP values and the clinical status were evaluated. Results: The serum iron content of WD patients was higher than the normal. The CP values of substantia nigra, caudate nucleus, and globus pallidus of WD were lower than the normal values, while the CP value of substantia nigra was the lowest. No correlations were determined between the CP values and the iron and copper parameters. There was negative correlation between the scores of dysarthria and the CP values of the globus pallidus. There was negative correlation between the scores of tremor and the CP values of caudate nucleus. Some regions, which had high signals on T2-weighted image, had low signals on SWI. Conclusions: There might be abnormal iron metabolism in patients with WD. The decreased CP values might reflect a deposition of both copper and iron. SWI may be more sensitive than the ordinary MRI. The mineral deposition may contribute to the neural symptoms.

To assess diffusion changes of the thalamus in Wilson's disease using diffusion tensor imaging (DTI).Fifteen patients with Wilson's disease and an abnormal signal in the thalamus (designated as group 1) and 18 patients with Wilson's disease with a normal-appearing thalamus (designated as group 2) at conventional magnetic resonance imaging (MRI) were recruited. Fifteen age-matched and sex-matched healthy volunteers were also enrolled as the control group (designated as group 3). The fractional anisotropy (FA), primary eigenvalue (λ1), second eigenvalue (λ2), and third eigenvalue (λ3) of the thalamus were measured and the differences were compared.The FA values of the thalamus were different in the three groups (group 1: 0.36 ± 0.02; group 2: 0.38 ± 0.02; group 3: 0.43 ± 0.02; F = 54.51, p0.001). A statistically significant difference was observed between group 1 and group 2 (p = 0.003), group 1 and group 3 (p = 0.001), and group 2 and group 3 (p0.001). The λ1, λ2, and λ3 values of the thalamus were different in the three groups (1.11 ± 0.06 mm(2)/s, 1.11 ± 0.06 mm(2)/s, and 1.10 ± 0.04 mm(2)/s of λ1 in group 1, group 2, and group 3, respectively; 0.82 ± 0.08 mm(2)/s, 0.78 ± 0.05 mm(2)/s, and 0.72 ± 0.02 mm(2)/s of λ2 in group 1, group 2, and group 3, respectively; 0.52 ± 0.05 mm(2)/s, 0.49 ± 0.06 mm(2)/s, and 0.42 ± 0.06 mm(2)/s of λ3 in group 1, group 2, and group 3, respectively; F = 1.65, p = 0.203 of λ1; F = 10.55, p0.001 of λ2; F = 4.21, p = 0.021 of λ3; respectively). A statistically significant difference in the λ2 value was observed between group 1 and group 3 (p0.001) and group 2 and group 3 (p = 0.005). A statistically significant difference in the λ3 value was also observed between group 1 and group 3 (p = 0.007). No significant difference in the λ1 value was noted between each of the two groups.Damage of the thalamus in Wilson's disease patients can be detected using DTI. DTI may provide information regarding thalamus damage in patients with Wilson's disease before abnormal signals on conventional MRI.

To explore the effects of gene transfer of insulin like growth factor-1 (IGF-1) on the penis of senile rats and the altered levels of mRNA and protein of endothelial nitric oxide synthase (eNOS).Ten young (4 months) and 20 senile (24 months) Sprague-Dawley male rats were selected. The senile rats were divided into 2 groups: phosphate buffer solution (PBS)-only (n = 10) and 100 µg IGF-1 plasmid treatment group (n = 10). After a 4-week injection of IGF-1, the responses of intracavernous pressure (ICP) with electrical stimulation to the cavernous nerve and systemic mean arterial pressure (MAP) were evaluated. In the control and transfected senile rats, the levels of eNOS mRNA and protein were examined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot respectively.The ICP/MAP and total ICP were significantly higher in the young control group versus the PBS-only group at Week 4 (P0.05). The ICP/MAP and total ICP were significantly higher in the young control group and the 100 µg IGF-1 treatment group versus the PBS-only group at Week 4 (P0.05). The levels of mRNA and protein of eNOS were higher in the 100 µg IGF-1 treatment group versus the PBS-only group at Week 4 (0.62 ± 0.16 vs 0.25 ± 0.08, 0.71 ± 0.19 vs 0.27 ± 0.09, both P0.05, respectively).The gene therapy of IGF-1 can ameliorate erectile functions and improve the levels of mRNA and protein of eNOS in senile rats.

To explore the values of serum copper and serum free copper in the diagnosis of Wilson's disease (WD), its carrier and viral hepatitis and explore the guiding significance of monitoring serum copper in the treatment of WD.A total of 80 WD patients (hepatic type, n = 60; encephalic type, n = 20), 30 carriers, 20 patients with viral hepatitis were enrolled and their levels of serum copper were determined. The neural symptoms were scored by modified Young grade. Hemogram, hepatic functions, blood clotting functions, serum copper and urinary copper were tested throughout all 8 courses of treatment with sodium dimercaptopropane sulfonate (DMPS). The patients were treated with zinc after discharging. All data were analyzed.The free serum copper increased in the patients with WD (0.17 mg/L ± 0.04 mg/L), carriers (0.13 mg/L ± 0.03 mg/L) and severe viral hepatitis (0.12 mg/L). A slight increase was also observed in the WD carriers. The level of serum copper was correlated with hepatic functions but not with the severity of neural symptoms. The serum copper increased in the patients with no improvement of neural symptoms. However, the serum copper decreased in the WD patients with the improvement of neural symptoms. The serum copper was stabilized at approximately 0.2 mg/L during the long-term treatment period.There is auxiliary diagnosis significance of serum copper in the determination of WD. Hepatic functions in hepatic type WD affect the level of serum copper. The serum copper of encephalic type WD can not indicate the severity of neural symptoms. The elevated level of serum copper indicates a poor prognosis. The serum copper is an effective marker in monitoring the development and therapeutic efficacy of the disease.

Previous studies have confirmed the gene transfer of insulin-like growth factor-1 (IGF-1) and the IGF-1 protein can improve the erectile function in aging rats. IGF binding protein (BP)-3 can regulates the availability of IGF-I. The higher expression of IGFBP-3 may play an important role in erectile dysfunction (ED).The study aimed to investigate the mRNA and protein expression of IGFBP-3 in young and old rat penile tissues and assess the alteration of the penile structure and the NO-guanosine 3',5'-cyclic-monophosphate (cGMP) signaling pathways-related marker in ED associated with aging.The main outcome measures for this study were the expression of IGFBP-3, morphological changes, NO-cGMP signaling pathways-related marker, erectile responses were determined.Traditional reverse transcriptase polymerase chain reaction (RT-PCR) and real-time PCR were performed to examine the mRNA expression of the IGFBP-3. The Western blot was used to confirm the protein expression. Immunohistochemistry was also performed to identify the cellular localization of the encoded protein. The percentage of smooth muscle in corpus cavernosum tissue, the activity of nitric oxide synthase (NOS), and concentration of cGMP in penile tissue were also analyzed.The expression levels of IGFBP-3 of mRNA and protein were greatly increased in aging rats compared with young control rats, which is confirmed by traditional RT-PCR, real-time PCR, and Western blot (P0.01, respectively). Increased IGFBP-3 protein was localized to the epithelium of the urethra, penile endothelium, and smooth muscle in the corpus cavernosum. Significant depletion of the smooth muscle density relative to the connective tissue was also observed in the penis of the aged rats, and the lower activity of NOS and lower concentration of cGMP was also demonstrated accompanied with a significant reduction in the intracavernous pressure.Our data suggest that the increased mRNA and protein expression of IGFBP-3 in old rats may play a role in ED.

The incidence of erectile dysfunction (ED) rises with the increase of age, for which gene therapy is a new option in the recent years. Different target genes, vehicles and therapeutic strategies have been tried and yielded good results. This paper offers an overview of the current advances in gene therapy for aging-related ED.