Disrupted white matter structural connectivity in heroin abusers.

Neurocognitive impairment is one of the factors that put heroin abusers at greater risk for relapse, and deficits in related functional brain connections have been found. However, the alterations in structural brain connections that may underlie these functional and neurocognitive impairments remain largely unknown. In the present study, we investigated topological organization alterations in the structural network of white matter in heroin abusers and examined the relationships between the network changes and clinical measures. We acquired diffusion tensor imaging datasets from 76 heroin abusers and 78 healthy controls. Network-based statistic was applied to identify alterations in interregional white matter connectivity, and graph theory methods were used to analyze the properties of global networks. The participants also completed a battery of neurocognitive measures. One increased subnetwork characterizing widespread abnormalities in structural connectivity was present in heroin users, which mainly composed of default-mode, attentional and visual systems. The connection strength was positively correlated with increases in fractional anisotropy in heroin abusers. Intriguingly, the changes in within-frontal and within-temporal connections in heroin abusers were significantly correlated with daily heroin dosage and impulsivity scores, respectively. These findings suggest that heroin abusers have extensive abnormal white matter connectivity, which may mediate the relationship between heroin dependence and clinical measures. The increase in white matter connectivity may be attributable to the inefficient microstructure integrity of white matter. The present findings extend our understanding of cerebral structural disruptions that underlie neurocognitive and functional deficits in heroin addiction and provide circuit-level markers for this chronic disorder.

Ability of Mn(2+) to Permeate the Eye and Availability of Manganese-enhanced Magnetic Resonance Imaging for Visual Pathway Imaging via Topical Administration.

BACKGROUND: Manganese-enhanced magnetic resonance imaging (MEMRI) for visual pathway imaging via topical administration requires further research. This study investigated the permeability of the corneal epithelium and corneal toxicity after topical administration of Mn2+ to understand the applicability of MEMRI. METHODS: Forty New Zealand rabbits were divided into 0.05 mol/L, 0.10 mol/L, and 0.20 mol/L groups as well as a control group (n = 10 in each group). Each group was further subdivided into epithelium-removed and epithelium-intact subgroups (n = 5 in each subgroup). Rabbits were given 8 drops of MnCl2in 5 min intervals. The Mn2+ concentrations in the aqueous and vitreous humors were analyzed using inductively coupled plasma-mass spectrometry at different time points. MEMRI scanning was carried out to image the visual pathway after 24 h. The corneal toxicity of Mn2+ was evaluated with corneal imaging and pathology slices. RESULTS: Between the aqueous and vitreous humors, there was a 10 h lag for the peak Mn2+ concentration times. The intraocular Mn2+ concentration increased with the concentration gradients of Mn2+ and was higher in the epithelium-removed subgroup than that in the epithelium-intact subgroup. The enhancement of the visual pathway was achieved in the 0.10 mol/L and 0.20 mol/L epithelium-removed subgroups. The corresponding peak concentrations of Mn2+ were 5087 ± 666 ng/ml, 22920 ± 1188 ng/ml in the aqueous humor and 884 ± 78 ng/ml, 2556 ± 492 ng/ml in the vitreous body, respectively. Corneal injury was evident in the epithelium-removed and 0.20 mol/L epithelium-intact subgroups. CONCLUSIONS: The corneal epithelium is a barrier to Mn2+, and the iris and lens septum might be another intraocular barrier to the permeation of Mn2+. An elevated Mn2+ concentration contributes to the increased permeation of Mn2+, higher MEMRI signal, and corneal toxicity. The enhancement of the visual pathway requires an effective Mn2+ concentration in the vitreous body.

ZNF804A variants confer risk for heroin addiction and affect decision making and gray matter volume in heroin abusers.

Drug addiction shares common neurobiological pathways and risk genes with other psychiatric diseases, including psychosis. One of the commonly identified risk genes associated with broad psychosis has been ZNF804A. We sought to test whether psychosis risk variants in ZNF804A increase the risk of heroin addiction by modulating neurocognitive performance and gray matter volume (GMV) in heroin addiction. Using case-control genetic analysis, we compared the distribution of ZNF804A variants (genotype and haplotype) in 1035 heroin abusers and 2887 healthy subjects. We also compared neurocognitive performance (impulsivity, global cognitive ability and decision-making ability) in 224 subjects and GMV in 154 subjects based on the ZNF804A variants. We found significant differences in the distribution of ZNF804A intronic variants (rs1344706 and rs7597593) allele and haplotype frequencies between the heroin and control groups. Decision-making impairment was worse in heroin abusers who carried the ZNF804A risk allele and haplotype. Subjects who carried more risk alleles and haplotypes of ZNF804A had greater GMV in the bilateral insular cortex, right temporal cortex and superior parietal cortex. The interaction between heroin addiction and ZNF804A variants affected GMV in the left sensorimotor cortex. Our findings revealed several ZNF804A variants that were significantly associated with the risk of heroin addiction, and these variants affected decision making and GMV in heroin abusers compared with controls. The precise neural mechanisms that underlie these associations are unknown, which requires future investigations of the effects of ZNF804A on both dopamine neurotransmission and the relative increases in the volume of various brain areas.

Super-resolution dipole orientation mapping via polarization demodulation.

Fluorescence polarization microscopy (FPM) aims to detect the dipole orientation of fluorophores and to resolve structural information for labeled organelles via wide-field or confocal microscopy. Conventional FPM often suffers from the presence of a large number of molecules within the diffraction-limited volume, with averaged fluorescence polarization collected from a group of dipoles with different orientations. Here, we apply sparse deconvolution and least-squares estimation to fluorescence polarization modulation data and demonstrate a super-resolution dipole orientation mapping (SDOM) method that resolves the effective dipole orientation from a much smaller number of fluorescent molecules within a sub-diffraction focal area. We further apply this method to resolve structural details in both fixed and live cells. For the first time, we show that different borders of a dendritic spine neck exhibit a heterogeneous distribution of dipole orientation. Furthermore, we illustrate that the dipole is always perpendicular to the direction of actin filaments in mammalian kidney cells and radially distributed in the hourglass structure of the septin protein under specific labelling. The accuracy of the dipole orientation can be further mapped using the orientation uniform factor, which shows the superiority of SDOM compared with its wide-field counterpart as the number of molecules is decreased within the smaller focal area. Using the inherent feature of the orientation dipole, the SDOM technique, with its fast imaging speed (at sub-second scale), can be applied to a broad range of fluorescently labeled biological systems to simultaneously resolve the valuable dipole orientation information with super-resolution imaging.

Effects of seasonal changes on the ovulation rate and embryo quality in superovulated Black Suffolk ewes.

OBJECTIVE: The objective of this study was to investigate the effects of seasonal changes on the superovulation in Black Suffolk ewes, particularly the ovulation rate and embryo quality. DESIGN: Black Suffolk ewes were superovulated either in May (n=22) or in September (n=21), 2013. After estrus synchronization with CIDR, the donor ewes were superovulated with PMSG and seven decreasing doses of FSH (twice daily at 07:00 and 19:00 for four consecutive days. Then, they were subjected to laparoscopic intrauterine artificial insemination. The viable morula and blastocysts were recovered and immediately transferred to recipients. RESULTS: Ewes that were superovulated in May had a much higher ovulation rate than those were superovulated in September (16.8 ± 3.23vs. 10.2 ± 2.94, p<0.01); however, the viability rate of the embryo was lower than that of September (56.0 ± 1.92% vs. 92.5 ± 3.26%, p<0.01). There was no significant difference in the survival rate of the transferred viable embryos (33.9 ± 1.00% vs. 36.7 ± 1.64%, p>0.05) and the number of offspring per donor ewe (3.1 ± 0.54 vs. 2.9 ± 0.72, p>0.05) between May and September. In contrast, the offspring/ova ratio of the donor ewes superovulated in May was lower than that of September (18.5 ± 1.64% vs. 32.8 ± 2.14%, p<0.01). CONCLUSIONS: The superovulation of Black Suffolk ewes may be affected by the seasonal changes. Generallly, The ewe's ovulation rate was higher in May, whereas the viability rate of embryo was higher in September.

[Diffusion of fluorescent and magnetic molecular probes in brain interstitial space].

OBJECTIVE: To compare the diffusion properties of fluorescent probes dextran-tetramethylrhodamine (DT) and lucifer yellow CH (LY) and magnetic probe gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) in porous media and to screen out a suitable fluorescent probe for optical imaging of brain interstitial space (ISS). METHODS: Agarose gels sample were divided into DT group, LY group and Gd-DTPA group, and the corresponding molecular probes were imported in each group. The dynamic diffusions of DT and LY in agarose gels at different time points (15, 30, 45, 60, 90, and 120 min) were scanned with laser scanning confocal microscope, the dynamic diffusion of Gd-DTPA was imaged with magnetic resonance imaging. The average diffusion speed of LY were demonstrated to be consistent with those of Gd-DTPA. The LY was introduced into caudate putamen of 18 rats, respectively, the diffusion of LY in the sequential slices of rat brain at different time points (0.5, 1, 2, 3, 7, 11 h) were scanned, and the results were compared with those of rats' brain with Gd-DTPA imported and imaged in vivo with magnetic resonance imaging. RESULTS: The diffusions of the three probes were isotropic in the agarose gels, and the average diffusion speeds of DT, LY and Gd-DTPA were: (0.07±0.02)×10(-2) mm2/s, (1.54±0.47)×10(-2) mm2/s, (1.45±0.50)×10(-2) mm2/s, respectively. The speed of DT was more slower than both LY and Gd-DTPA (ANOVA, F=367.15, P<0.001; Post-Hoc LSD, P<0.001), and there was no significant difference between the speeds of LY and Gd-DTPA (Post-Hoc LSD, P=0.091). The variation tendency of diffusion area of DT was different with both that of LY and that of Gd-DTPA (Bonferroni correction, α=0.0125, P<0.001), and there was no significant difference between LY and Gd-DTPA (Bonferroni correction, α=0.0125, P=0.203), in analysis by repeated measures data of ANOVA. The diffusions of LY and Gd-DTPA were anisotropy in rat caudate putamen,and the average diffusion speeds of LY and Gd-DTPA were: (1.03±0.29)×10(-3) mm2/s, (0.81±0.27)×10(-3) mm2/s, respectively, no significant difference was demonstrated (t=0.759, P=0.490); half-time of single intensity of LY and Gd-DTPA was (2.58±0.04) h, (2.46±0.10) h, respectively, no significant difference was found (t=2.025, P=0.113). The diffusion area ratios between LY and Gd-DTPA in rat caudate putamen was not statistically different at hours 0.5, 1, 2, 3 and 7 (t=2.249, P=0.088; t=2.582, P=0.061; t=1.966, P=0.121; t=0.132, P=0.674; t=0.032, P=0.976), while, a slightly difference was found at 11 h (t=2.917, P=0.043,in analysis by t test). CONCLUSION: LY present the same diffusion property with Gd-DTPA in porous media witch including agarose gels and live rat brain tissue, indicates that LY is a suitable fluorescent probe for optical imaging of brain ISS, and it can be used for microscopic, macro and in vitro measure of brain ISS.

[Quantitative calculation of drugs distribution parameter in the brain extracellular space by using MRI tracer].

OBJECTIVE: To build a mathematical model to simulate the drug distribution accompanying with diffusion, distribution and clearance in the brain extracellular space (ECS). METHODS: Magnetic resonance imaging (MRI) technology was used to monitor changes in the signal-intensity-related tracer gadolinium-diethylene triamine pentaacetic acidm(Gd-DTPA), as an external drug which was injected into the rat brain, and then the mathematical model was built by using the data to establish the diffusion, distribution and clearance process of Gd-DTPA in the brain ECS. The model equation was resolved by Laplace transform. In the sphere coordinates, the linear regressive model was adopted to obtain the estimation method of diffusion coefficient, clearance rate of drugs distribution in the brain ECS. RESULTS: The diffusion coefficient D and the clearance rate k were obtained as (2.73±0.364)×10(-4) mm(2)/s and (1.40±0.206)×10(-5) /s, respectively. CONCLUSION: The proposed method can accurately reflect the isotropic drug distribution in the brain ECS, and can serve as the foundation to further solve problems about the orthotropic distribution in the brain ECS.

Protective effects of urinary trypsin inhibitor on vascular permeability following subarachnoid hemorrhage in a rat model.

AIMS: Inflammation and apoptosis play important roles in increasing vascular permeability following subarachnoid hemorrhage (SAH). The objective of this study was to evaluate whether urinary trypsin inhibitor (UTI), a serine protease inhibitor, attenuates vascular permeability by its antiinflammatory and antiapoptotic effects after experimental SAH. METHODS: Subarachnoid hemorrhage models were established in adult male Sprague-Dawley rats by endovascular perforation. UTI was administered by intraperitoneal injection immediately following SAH. Brain edema was assessed by magnetic resonance imaging (MRI) at 24 h after SAH. Neurological deficits, brain water content, vascular permeability, malondialdehyde (MDA) concentration, and myeloperoxidase (MPO) activity were evaluated. Immunohistochemical staining and Western blot were used to explore the underlying protective mechanism of UTI. RESULTS: Urinary trypsin inhibitor 50,000 U/kg significantly attenuated brain edema and neurological deficits and reduced vascular permeability at 24 h after SAH. MDA concentration and MPO activity in hippocampus were significantly decreased with UTI treatment. Furthermore, the levels of phosphorylated JNK, NF-κB (p65), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and proapoptotic protein p53, caspase-3 were elevated in the microvascular endothelial cells of the hippocampus after SAH, which were alleviated with UTI treatment. CONCLUSION: Urinary trypsin inhibitor reduced vascular permeability after SAH through its antiinflammatory and antiapptotic effects via blocking the activity of JNK, NF-κB, and p53.

[In vivo quantitative measurement of diffusion parameters in brain extracellular space of rat by using magnetic resonance imaging].

OBJECTIVE: To develop a novel method of quantitatively measuring the diffusion parameters of brain extracellular space (ECS) by using gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) as the tracer. METHODS: Six Sprague Dawley male adult rats were subjected to magnetic resonance (MR) imaging before and after the introduction of 2 µL Gd-DTPA into caudate nucleus (Cn). The enhancement on MR subtracted images was converted to the concentration of Gd-DTPA and an average diffusion rate was calculated pixel by pixel based on the traditional diffusion model. RESULTS: After the injection, the tracer diffused frontally and laterally with an average diffusion rate of (3.38±1.07)×10(-4) mm(2)/s. It reached at the margin of cortex 2 hours later, and drained into the subarachnoid space 3 hours later. The tortuosity [Λ(Cn (agar))] was 1.31±0.31 with the reference of free diffusion measured in agar gel, which was consistent with the result using real-time iontophoresis-tetramethylammonium method. A more feasible reference was acquired by using a routine MR diffusion weighed imaging and [Λ(Cn (MRI))] was calculated as 3.12±0.73. The tracer was finally clearly out at the end of 12 hours on MR images with a clearance rate constant in Cn of (7.60±4.18)×10(-5)/s. CONCLUSION: The biophysical properties of brain ECS can be quantitatively characterized by this newly developed method in living brain, which will enhance our understanding of the micro-environment of neuron and provide a new way to understand cognition and encephalopathy.

Application of T2 measurement on gradient echo T2-weighted imaging in differential diagnosis of intracranial hemorrhage and calcification.

BACKGROUND: Differential diagnosis of intracranial hemorrhage and calcification is a common problem encountered in clinical imaging diagnosis. The purpose of this study was to investigate the feasibility of T2 measurement on gradient echo (GRE) T2-weighted imaging (T2WI) in differential diagnosis of intracranial hemorrhage and calcification. METHODS: Thirty-eight hemorrhagic foci in 18 patients and 11 calcification foci in seven patients were included in this study. The diagnosis of hemorrhage and calcification was confirmed in all cases with enhanced T2 weighted angiography (ESWAN) magnetic resonance imaging (MRI) and CT respectively. The significance for the difference of T2 value between the central and peripheral areas of hemorrhage and calcification lesions was tested with univariate analysis of variance. RESULTS: The detection rate of GRE T2 WI on intracranial hemorrhage was 1.9-fold higher than that of CT, especially for the hemorrhage in the brainstem and cerebellum. However, GRE T2WI was far less sensitive to calcification than CT. There was a significant difference in the T2 value between the central area of hemorrhage and calcification (P < 0.001), though no difference in the T2 value was obtained between the peripheral area of hemorrhage and calcification (P > 0.05). CONCLUSIONS: Quantitative measurement of T2 value on GRE T2 WI with a single MRI examination provides a fast, convenient, and effective means in differential diagnosis between intracranial hemorrhage and calcification, which may thus reduce the medical cost and save precious time for clinical management.

[A study of motor unit number estimation by multiple point stimulation in patients with Hirayama disease].

OBJECTIVE: To explore the significance of motor unit number estimation (MUNE) by using multiple point stimulating technique to evaluate patients with Hirayama disease (HD). METHODS: Multiple point stimulating technique was used to estimate the motor unit number of abductor pollicis brevis and abductor digiti minimi in 35 normal subjects [14 - 33 years old, mean (20.9 ± 4.0) years old, 33 men and 2 women] without nerve and muscle disease and 69 patients definitely diagnosed as HD [16 - 35 years old, mean (21.46 ± 6.61) years old, 67 men and 2 women]. The differences between the two groups were examined by Fisher's exact test and t test. RESULTS: There were 42 patients with atrophy and 27 patients with normal clinical manifestation of left hand. For right hand there were 54 patients with atrophy and 15 normal. For controls, the MUNE value of left abductor pollicis brevis was 226.97 ± 30.59, while that of right side was 228.31 ± 25.35. The MUNE value of left abductor digiti minimi was 237.43 ± 30.78, while that of right side was 240.20 ± 37.73. For HD patients, the MUNE of left abductor pollicis brevis and abductor digiti minimi was 145.66 ± 126.10 (t = 5.07, P < 0.01) and 102.20 ± 112.67 (t = 9.31, P < 0.01) respectively, while those of right hand was 149.72 ± 117.80 (t = 5.31, P < 0.01) and 64.23 ± 69.27 (t = 16.76, P < 0.01) respectively. MUNE of left abductor digiti minimi in 17 patients that was below 200 among 27 patients with normal clinical manifestation (χ(2) = 9.57, P = 0.002). MUNE of right abductor digiti minimi in 12 patients that was below 200 among 15 patients with normal clinical manifestation (χ(2) = 4.64, P = 0.03). CONCLUSIONS: The differences of MUNE values by multiple point stimulating technique between the normal subjects and the HD patients is significant, which suggests this method is very useful to evaluate HD in the early state.

p53-induced uncoupling expression of aquaporin-4 and inwardly rectifying K+ 4.1 channels in cytotoxic edema after subarachnoid hemorrhage.

AIMS: To investigate the mechanism behind cytotoxic edema formation following subarachnoid hemorrhage (SAH). METHODS: We explored the role of aquaporin-4 (AQP4), inwardly rectifying K(+) 4.1 (Kir4.1) channels and their upstream orchestrators p53 and p38MAPK in this process. A p53 inhibitor, pifithrin-α (PFT-α) was administered intraperitoneally to rats undergoing SAH by endovascular perforation. Totally, 98 male SD rats were categorized into sham, SAH, SAH+ dimethyl sulfoxide (DMSO), SAH+ 0.2 or 2.0 mg/kg PFT-α groups. At 24 h after SAH, MRI (diffusion-weighted imaging [DWI]), immunohistochemistry, and Western blot were used. RESULTS: MRI (DWI) showed a significant cytotoxic edema in the brain following SAH with PFT-α therapy reducing it. Immunohistochemistry and Western blot showed an increased level of p53, phosphorylated-p38MAPK and AQP4 and a reduced level of Kir4.1; all of which could be reversed following PFT-α treatment. Treble labeling staining revealed colocalization of p53 with phosphorylated-p38MAPK and unmatched expression of AQP4 and Kir4.1 within astrocyte cells. CONCLUSION: These results indicated p53 mediates the formation of cytotoxic edema in the brain following SAH; an uncoupling expression of AQP4 and Kir4.1 on astrocytic end feet orchestrated by p38MAPK was partly responsible.

No association between ACE polymorphism and risk of nasopharyngeal carcinoma.

Emerging evidence has shown that angiotensin I-converting enzyme (ACE) plays pivotal roles not only in the regulation of cardiovascular homeostasis but also in the process of tumorigenesis. A common ACE I/D polymorphism has been found to be functional, with the D allele displaying a higher plasma ACE level and ACE activity. The purpose of this study was to investigate whether the ACE I/D polymorphism was related to the risk of nasopharyngeal carcinoma (NPC). The study included 175 patients with NPC and 279 age- and sex-matched control subjects. The ACE I/D polymorphism was identified by a polymerase chain reaction analysis. No association was found between the ACE I/D polymorphism and risk of NPC (ID vs. II: odds ratio [OR] = 0.77, 95% confidence interval [CI] 0.51-1.17; DD vs. II: OR = 0.98, 95%CI 0.56-1.72, respectively). This finding indicates that the ACE I/D polymorphism may not play a role in susceptibility to NPC. Further studies are warranted to confirm this finding, especially in ethnically disparate populations.

[Study of association between hyperIgEaemia and Hirayama disease].

OBJECTIVE: To investigate whether hyperIgEaemia is associated with Hirayama disease in China. METHODS: Serum total IgE were examined in 123 patients and 82 control subjects from 2006 to 2009 at this hospital and their correlations with clinical profiles investigated. The data were analyzed by t, Chi-square and nonparametric tests. RESULTS: Past or present history of allergy/atopy was found in 14 (11.4%) patients and 11(13.4%)controls. The median value of serum total IgE were 87.97, 59.21 and 51.39 IU/ml in patients, controls and health controls respectively. There were no significant difference between the patient and control groups (Z = -0.947, P = 0.344) and the health control groups (Z = -0.914, P = 0.361). Serum IgE was elevated in 57 (43.6%) patients and 30 (36.6%) controls. HyperIgEaemia was present in 29 (23.6%) patients and 13 (15.9%) controls. There was no significant difference in the frequency of history of allergy/atopy, IgE elevation or hyperIgEaemia (P > 0.05) between cases and controls. Even after analyzing the length of duration or the severity of clinical disabilities, there was no difference neither (P > 0.05). CONCLUSION: Whether the length of duration or the severity of clinical disabilities, the serum total IgE level has no significant difference between all groups. HyperIgEaemia is not associated with Hirayama disease.

[Imaging and quantitative measurement of brain extracellular space using MRI Gd-DTPA tracer method].

OBJECTIVE: To observe the diffusion of Gd-DTPA in brain extracellular space (ECS) by magnetic resonance imaging(MRI) and investigate the feasibility of ECS measurement by using MRI tracer method in vivo. METHODS: 2 microL Gd-DTPA was introduced into ECS by caudate nucleus according to stereotaxic atlas in 8 Sprague Dawley(SD) rats (male, 280-320 g). The MRI scans were performed at 1 h, 3 h, 6 h, 9 h and 12 h respectively after administration. MRI appearances of Gd-DTPA diffusion and distribution was observed and compared. The MRI signal enhancement was measured at each time point. The neuroethology assessment was performed after MRI scanning at 12 h. RESULTS: The injection was accurate at the center of the caudate nucleus in 6 rats, while, at the capsula externa in other 2 rats. Gd-DTPA diffused isotropically after it was introduced into caudate nucleus, which spread into lateral cortex at 3 h. The MRI signal enhancement distributed mainly in the middle cerebral artery territory. A significant difference was found between the signal enhancement ratio at 1 h and that at 3 h in the original point of caudate nucleus (t=95.63, P<0.01), and the signal enhancement attenuated following the exponential power function y=1.7886x(-0.1776) (R2=0.94). In 2 rats with the injection point at capsula externa, Gd-DTPA diffused anisotropically along the fiber track of white matter during 1 h to 3 h, and spread into the lateral cortex at 6 h. CONCLUSION: The diffusion and clearance of Gd-DTPA in brain ECS could be monitored and measured quantitatively in vivo by MRI tracer method.

[Measurement of brain extracellular space and its physiological and pathophysiological significance].

The extracellular space (ECS) of brain is defined as an irregular channel which is located in the interstitial tissue outside the plasma membranes of neurons, and occupied by interstitial fluid (ISF). Diffusion in ECS is described by a modified diffusion equation from which several parameters can be calculated, such as the diffusion coefficient (D), the tortuosity (Lambda), the volume fraction (alpha) and the clearance of molecules. Radiolabeled tracers were used for early diffusion measurements. Presently, the real-time iontophoresis (RTI) method is employed for small ions, whereas the integrative optical imaging (IOI) and the magnetic resonance diffusion weighted imaging (DWI) are developed for macromolecules tracers. Extensive experimental studies with such methods show that in normal brain tissue, the volume fraction of ECS typically is about 20% and the tortuosity is 1.6, although there are regional variations. These parameters change with the brain development and in various pathophysiological states. Knowledge of ECS diffusion properties help us to understand extrasynaptic volume transmission to the development of paradigms for drug delivery in brain.

[Impact of magnetic attachment keepers on magnetic resonance imaging examination].

OBJECTIVE: To evaluate the effects of magnetic attachment keepers on MRI images. METHODS: In in vitro part, keepers of MAGFIT EX 400, MAGFIT EX 600 and MAGNEDISC 800 magnetic attachment systems were cast into standard root-caps with different alloy respectively, including nickel-chromium alloy and gold-palladium alloy, or not be cast for contrast. In in vivo part, volunteers with keepers in different position and amount were included. All the specimens and volunteers were imaged by a Siemens SONATA 1.5-T MRI scanner. Extent of the artifacts in every slice was measured. The magnitude of the artifacts and the distortion of the anatomic structures were compared. RESULTS: All kinds of keepers being studied produced obvious MRI artifacts. The extent of MRI artifacts induced by MAGFIT EX 400 keepers, MAGFIT EX 600 keepers and MAGNEDISC 800 keepers are 158.94 mm, 168.52 mm and 173.00 mm, respectively. The images of mental region, tongue, palate, jawbone and sinus were evidently obscured by artifacts in all cases. When keeper was put in the molar region, the keeper-related MRI artifact may obscure the imaging of brain, spinal cord. SE sequence with right-left frequency-encoding direction was more desirable in MRI for the patients with magnetic attachment keepers. CONCLUSION: Keepers of magnetic attachment system did induce obvious artifacts in MRI examination.

[Investigation in vivo of effect of ultrasound-mediated microbubble destruction on entrance of feridex into the aortal wall].

OBJECTIVE: To explore feasibility for entrance of the contrast agent Sonovue and Feridex into the aortal wall. METHODS: 17 male Japanese giant ears rabbits (common grade), including 11 atherosclerosis (AS) animal models fed with food containing high-content lipid and normal animals fed with common food as control. Respectively, 10 animals in the AS group and 6 animals in the normal group were selected in a random way to undergo ultrasound-mediated microbubble destruction (UMMD) and no ultrasound-mediated microbubble destruction (-UMMD) half and half. One animal was administrated with double doses of Feridex. After general anesthesia, MR plain scan and intravenous injection of Feridex 100 micromol Fe/kg, immediately ultrasound focused on the front wall of the aortic arch, which underwent UMMD at the pressure of 3.5 Mpa with MI1.2 while 10 ml solution (Sonovue + normal saline)was injected intravenously at the speed of 0.5 ml/min FOR 20 min. 3T magnetic resonance (MR) was performed with a moderately T2* weighted gradient sequence. Enhanced scan were performed for 1 h, 24 h, 48 h, 72 h and after killing the animal. then the specimen were delivered to conduct optical and electronic microscope examination. Variance test for the re-measured data was adopted to verify the data obtained in every group. RESULTS: The effect of UMMD group on SPIO particles entrance into the aortal wall is of marked significance (P = 0.0004) statistically. The effect of UMMD on distribution in the vessel wall is of statistical significance (P = 0.01), more particles in the dventitia. Gas or microbubbles were found to enter into the intima, media of the aorta, and verified by Oil Red O staining. After staining the findings of iron particle in the cell and out of the cell are different. CONCLUSIONS: UMMD may facilitate entrance of those SPIO particles with a bigger diameter and microbubbles into the aortal wall. This discovery may provide a new solution for penetration of complex macromolecule probes and gene-carried drug through the tunica intima of the aorta.

[Clinical features and dynamics of cervical magnetic resonance imaging in Hirayama disease].

OBJECTIVE: to investigate the clinical feature and dynamic changes of the cervical dural sac and spinal cord during neck flexion in Hirayama disease (juvenile muscular atrophy of distal upper extremity). METHODS: Clinical data were taken and MRI in neutral neck position and a fully flexed neck position were performed on 27 cases of Hirayama disease. RESULTS: (1) All patients were consistent with the diagnostic criteria of Hirayama disease who had asymmetric muscular atrophy and weakness of the hand and forearm. All patients were young males and right handed of whom 77.8% had initial symptoms before they were 19 years old. More patients(20 cases,74%é had muscular atrophy in the right hand than in the left at onset. The duration after disease onset was from 2-72 months[(26.48+/-15.57) months]. (2) In neutral neck position by MIR examination, 16 patients showed abnormal cervical curvature, 14 showed atrophy of the lower cervical cord and 2 patients had intramedullary abnormal high signal. (3) In a fully flexed position of the neck, all patients showed forward displacement and flattening of the lower cervical cord, and a crescent-shaped high signal area behind the cord. (4) The crescent shaped area was enhanced on T1-weighed imaging and disappeared after the patient returned to a neural position in one case. CONCLUSION: Hirayama disease occurs mainly in young males. There are obviously dynamic changes of the cervical cord during neck flexion in Hirayama disease by MRI examination, which can help the doctor make diagnosis in the early stage.

Cerebrospinal fluid dynamics in Chiari malformation associated with syringomyelia.

BACKGROUND: About 50% - 70% of patients with Chiari malformation I (CMI) presented with syringomyelia (SM), which is supposed to be related to abnormal cerebrospinal fluid (CSF) flow around the foramen magnum. The aim of this study was to investigate the cerebrospinal fluid dynamics at levels of the aqueduct and upper cervical spine in patients with CMI associated with SM, and to discuss the possible mechanism of formation of SM. METHODS: From January to April 2004, we examined 10 adult patients with symptomatic CMI associated with SM and 10 healthy volunteers by phase-contrast MRI. CSF flow patterns were evaluated at seven regions of interest (ROI): the aqueduct and ventral and dorsal subarachnoid spaces of the spine at levels of the cerebellar tonsil, C2 - 3, and C5 - 6. The CSF flow waveforms were analyzed by measuring CSF circulation time, durations and maximum velocities of cranial- and caudal-directed flows, and the ratio between the two maximum velocities. Data were analyzed by t test using SPSS 11.5. RESULTS: We found no definite communication between the fourth ventricle and syringomyelia by MRI in the 10 patients. In both the groups, we observed cranial-directed flow of CSF in the early cardiac systolic phase, which changed the direction from cranial to caudal from the middle systolic phase to the early diastolic phase, and then turned back in cranial direction in the late diastolic phase. The CSF flow disappeared at the dorsal ROI at the level of C2 - 3 in 3 patients and 1 volunteer, and at the level of C5 - 6 in 6 patients and 3 volunteers. The durations of CSF circulation at all the ROIs were significantly shorter in the patients than those in the healthy volunteers (P = 0.014 at the midbrain aqueduct, P = 0.019 at the inferior margin of the cerebellar tonsil, P = 0.014 at the level of C2 - 3, and P = 0.022 at the level of C5 - 6). No significant difference existed between the two groups in the initial point and duration of the caudal-directed CSF flow during a cardiac cycle at all the ROIs. The maximum velocities of both cranial- and caudal-directed CSF flows were significantly higher in the patients than those in the volunteers at the aqueduct (P = 0.018 and P = 0.007) and ventral ROI at the inferior margin of the cerebellar tonsil (P < 0.001 and P = 0.002), as so did the maximum velocities of the caudal-directed flow in the ventral and dorsal ROIs at the level of C2 - 3 (P = 0.004; P = 0.007). CONCLUSIONS: The direction of CSF flow changes in accordance with cardiac cycle. The syringomyelia in patients with CMI may be due to the decreased circulation time and abnormal dynamics of the CSF in the upper cervical segment. The decompression of the foramen magnum with dural plasty is an alternative for patients with CMI associated with SM.