| Objective:1. To explore the value of2D-1H MRS in thalamus of patients with chronic hepatic cirrhosis (CHC);3. To explore the neuropsychological disfunction of CHC patients,and by correlating it with2D-1H MRS, to study the pathogenesis of these changes.Material and Method:1. SubjectsConventional1.5T MRI scan and1H-MRS examinations were performed in all28cases of CHC patients (hepatic cirrhosis group, HC) and23volunteers (control group) during April of2011to November of2011in the same period.The24males and4females of the HC group, aged27～61years, were infected by hepatitis B virus(HBV), and the course of disease ranges from9month to31years. According to a compatible liver biopsy or clear evidence of liver failure and complications associated with portal hypertension documented, all patietients were considered as cirrhosis and classified into Child A(n=11),B(n=11) or C(n=6) in accordance with clinical materials.The control group was strictly selected in line with the CHC group, which recruited healthy individuals with an equivalent education level,the same gender and near age that the gap was less than3years. Exclusion criteria for all participants included hypertention, other potential causes of neuropsychiatric abnormalities, for example, concomitant neurological disorders such as subdural haematoma, cerebral infartion, severe leukoaraiosis and Wernicke’s syndrome, other metabolic abnormalities such as electrolyte imbalance, diabetes mellitus and intoxication with alcohol or drugs.2.Neuropsychological ExaminationsCommissioned by the Organisation Mondiale de Gastroente’ rologie, the Working Party reached a consensus in the definition of HE and presented it at the11th World Congress of Gastroenterology (WCOG) in Vienna,1998. In2002,the Working Party presented their final report, suggesting a modification of nomenclature for clinical diagnosis of HE,,which contains the result of4neuropsychological tests: Number Connection Tests A and B(NCT A,B),Digit-Symbol(DST), and Block-Design Test (BDT). They suggested that patients performing abnormally in2or more tests, after excluding other potential causes of neuropsychiatric abnormalities, should be considered MHE. In this research, before MR scan, all subjects underwent a combination of psychometric tests including NCT A and DST, the most popular2tests. In NCT A, randomly dispersed numbers are to be connected with each other in serial order as quickly as possible, and the time comsumed were the result of the test (including the time of correcting mistakes). For DST, givened a sheet of paper on which each digit from1to9is assigned a symbol, subjects wrote down the corresponding symbol under each digit a timed manner over90s. The number of correctly transcribed symbols indicated performance. That means, for example, a low score means poor performance. In the SDT, subjects placed a dot exactly in the center of large circles arranged in8rows, beginning each row on the left side and working towards the right.3.Main instruments and equipmentsUsing a1.5T MR imager (Achieva Nova-Dual Philips, Best, the Netherlands), MR imaging data were obtained in the Department of Medical Imaging, Guangdong No.2Provincial People’s Hospital. Adopt the sixteen-channel phased array head coil for conventional MRI scan and MRS dedicated single-channel quadrature head coil for MRS scan. Image post-processing using the accompnying software provided by manufacturer.4. MR examination methodsEach subjects lay supine, with the head snugly fixed by a belt and foam pads in order to make the chin lowing slightly, which will make sure the AC-PC line nearly at axial plane. Subjects were introduced to keep as still as possible.Conventional MR imaging included TiWL T2WI FSE、T2Flair and DWI respectively for the whole brain. Scan Parameters:T1WI(TR/TE=487.6/15.0ms,320×256, FOV=79.68mm2, NEX=2); T2WI (TR/TE=3979/110ms,512×288FOV=90.625mm2, NEX=2), T2Flair (TR/TE=9600/110ms,288×224,78.85mm2, NEX=1), DWI (TR/TE=6000/120ms; b:1000s/mm2); section thickness,10mm, intersection gap,0mm; all for axial plane, some add coronal or sagittal plane.For2D-1H MRS scan:1H-MRS imaging using two-dimensional multi-voxel spectroscopic imaging acquisition mode, the pulse sequences using point resolved spectroscopy (PRESS), TR/TE:2000/35ms, voxel thickness10mm, spacing10mm, NEX=2. FOV18x18mm. VOI (50x30mm) was Located in the layer of the interverntricular foramen, in which the thalamus show the maximun area. Scan positioning was achieved in T1weighted anatomy axial section. Put four VSS around the VOI to minimized the partial volume effect of cerebrospinal fluid (CSF) and surrounding tissues on the quality of MRS. MRS scan started when the FWHM≤10, with the best water suppression。The total scan time was13mins.5. Image post-processing and data measurementImage post-processing and data measurement for1H-MRS:using the accompanying software. Choose three fixed-voxels in the bilateral thalamus respectively, which should be of higher signal noise ratio(SNR), and their MR spectroscopy curve should have straight baseline and significantly narrow spectroscopy peaks, their average value will be the final outcome The four major metabolites including N-acetylaspartic acid (NAA), choline (Cho), creatine (Cr) and glutamine and glutamic acid(Glx) will be our interest. The relative ratio of NAA/Cr, Cho/Cr and Glx/Cr will be measured.6. Statistical analysisData analysis was performed by using SPSS13.0software in this study. The data obtained were represented as mean±standard. All data were subjected to1-Sample Kolmogorov-Smirnov Test for normality. Use Paired-Sample T Test to compare bilateral values of thalamus; merge the bilateral values if there was no difference and compare with the control group respectively if difference exit. The results of neuropsychological tests or1H-MRS difference between two groups was analyzed with Independent-Samples T Test. The1H-MRS difference among the Child A, B, C and the control group was analyzed with One-Way ANOVA, if differences between the groups were statistically significant, then underwent multiple comparisons, using LSD-t test if homogeneity of variance, DUNNETT’s T3if heterogeneity of variance. We made a Partial Correlation Analysis to find out the correlation between1H-MRS and neuropsychological tests results, controlled the effect of age, sex and the education. The statistical differences were considered as statistically significant when P values were less than0.05.Result(1). In this research most2D-1H-MRSI can be achieved at the first time, and can be used to have a diagnose. Except for the press、MV、VSS etc, we select the short TE35ms which can not only achieve NAA, Cho, Cr, but also Glx at2.2ppm-2.4ppm, for visual radiation, the NAA was the number one high peak, the second can be Cho or Cr; for visual center, the NAA was the first high peak, and the second was Cr; besides, we use the AC-PC line as the VOI positon which was proved to have ability to achieve better MRSI.(2). results of’H-MRS data and neuropsychological tests between HC and control groupThe difference of NAA/Cr, Cho/Cr, ml/Cr and Glx/Cr ratio betweenl left and right thalimus were significang in neither control group nor HC group(in control group:t=-1.220,-0.752,-1.281,-0.377,P=0.235,0.460,0.214,0.709; HC group: t=-1.808,-1.670,0.795,1.759,P=0.082,0.106,0.433,0.090). The difference of NAA/Cr between control group and HC group was no significant (t=1.826, P=0.074), while diferences of Cho/Cr, ml/Cr and Glx/Cr ratio were significant (t=4.733, P<0.001; t=7.176, P<0.001; t=-8.582, P<0.001)(3).’H-MRS data results among the four groupsResult of one-way ANOVA:Cho/C、Glx/Cr ratio among the4groups had statistical significance(F=8.205, P<0.001; F=67.200, P<0.001), but NAA/Cr radio didn’t (F=1.588, P=0.205)。Results of Welch:diferrence of ml/Cr was significant among the4groups(F=16.414, P<0.001)Multiple Comparision results:①Cho/Cr ratio:significant diferrence presented between Child-A、B、C scale and control group respectively (p=0.018; P=0.001, P <0.001), but between Child-A and B, A and C, B and C, there was no significant (P>0.05)。②mI/Cr ratio:there was significant difference between Child-A、B、C and control group (P=0.032; P=0.001, P<0.001), also the same as between Child A and C, B and C scale (P=0.001, P=0.045), but not between Child A and B (P=0.510)。③Glx/Cr ratio:Between Child-A、B、C scale and control group, there were significant difference(P<0.001; P<0.001, P<0.001) as well as between Child A and C, B and C (P<0.001, P<0.001), while between Child A and B,there was no difference (P=0.408)。(4). Correlation between neuropsychological tests and’H-MRS in HC groupThe difference of NCT-A, DST between control group and HC group was significant (F=7.158, P=0.010; F=4.758, P=0.034). Controling the effect of age, sex and education, we found that in HC, among metabolites, ml/Cr ratio was negatively correlated with Glx/Cr(P<0.001, r=0.729), Cho/Cr negative with Glx/Cr (P<0.001, r=-0.567) and positive with mI/Cr(P=0.002, r=0.435)。Cho/Cr ratio was negatively correlated with NCT-A, positive with DST (r=-0.477, P=0.001;0.478, P=0.001), So did the ml/Cr ratio (r=-0.695, P<0.001; r=0.632, P<0.001). Glx/Cr ratio had a positive correlation with NCT-A but negative one with DST (r=0.665, P< 0.001; r=-0.572, P<0.001).Conclusion1.2D-1H MRS Technology can get Spectrum signals from different areas at one scanning, and it can be used to check human thalamus so that it could not only save time, but also be easy for comparison of the involved area; with PRESS and MV technique, using short TE35ms, and positioning VOI on the AC-PC line, we may achieve qualified spectrum.2. Compared with conventional MRI,1H-MRS was more sensitive in detection the metabolic changes in vivo in normally appearing brain structures, which support the NH3-glutamin-low degree cerebral edema hypothesis, thus have potential to be a noninvasive marker for changes in CNS of HC patients3. Patients with CHC had neropsychological dystuction, and the results od tests were correlated with MRS results in thalamus, witch indicate that may be the chages of metabolites in thalamus account for the changed neuropsychological performance. |
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