| Objective:1. To explore the feasibility and method of 2D-1H MRS in glaucomatous optic radiations and visual center.2. To explore the value of 2D-1H MRS in glaucomatous optic radiations and visual center, and correlate it with conventional MR sequences.3. To study the pathogenesis of glaucomatous injury in visual pathway according to this research and relevant documents.Material and Method:1. Study populationConventional 3T MRI scan and 1H-MRS examinations were performed in 20 cases of primary glaucoma patients (glaucoma group) and 20 volunteers (control group) during July of 2010 to March of 2011 in the same period. All the patients were clinically assessed in ophthalmologic department of NanFang Hospital and ZhongShan ophthalmologic hospital. The glaucoma group consisted of 12 males and 8 females, aged 19～76 years (mean age,45years), both eyes were involved, referring to the intraocular pressure (IOP), the glaucoma group was classified into two groups: one was high IOP group(14 cases), the other was normal IOP group(6cases). The control group was strictly selected according to the glaucoma group, which need healthy individuals with the same gender and near age that the gap was less than 3 years. Exclusion criteria for the glaucoma and control groups included conditions other than glaucoma that could cause high IOP(ie, iridocyclitis, eye trauma) or optic neuropathy (eg, infection, inflammation, ischemic disease, compressive lesions), history of intraocular surgery, other intraocular eye diseases, other diseases that affected the visual field (eg, pituitary lesions, demyelinating diseases, diabetic retinopathy, age-related macular degeneration), and use of systemic medication that affected the visual field or the systemic blood pressure. Besides, the bare or corrected visual acuity of the control group should be normal, and the visual acuity was more than 0.8.2. Main instruments and equipmentsThe Signa EXCITE 3.0T superconducting magnetic resonance scanner of U.S. General Electric (GE) Company was adopted, Adopt the eight-channel phased array head coil for conventional MRI scan and MRS dedicated single -channel quadrature head coil for MRS scan. Image post-processing using software in ancillary ADW 4.3 workstation.3. MR examination methodsPosture and Fixation:taking supine position, examiner's head will be placed on the coil, and three plastic sponge will be placed in the occipital and each temporal side of the head in order to make the chin arising slightly and fix the CH-PC line at axial plane, located the positioning line in the eyes level. Conventional MRI scan:achieve T1 Flair,T2WI FSE,T2 Flair and DWI respectively for the whole brain, Scan Parameters:T1 FLAIR (TR/TE,2580/24ms),T2WI (TR/TE,5100/138ms),T2 Flair (TR/TE,9600/110ms),DWI (TR/TE6200/87.1ms; b:1000 s/mm2), Thickness 10mm, Pitch 0mm, all for axial plane, some add coronal or sagittal plane.2D-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 thickness 10mm, spacing 10mm, NEX 1. FOV 18x18mm. VOI was Located in the layer of the Optic Chiasm-Commissura Posterior. Scan positioning was achieved in T2WI image of complete Axial, Choose the best layer of optic radiation and visual cortex to scan, and VOI size was mobilized according to specific circumstances, including bilateral optic radiation and visual cortex, but to avoid skull, fat, air sinus and so on. Put six VSS around the VOI in order to reduce the partial volume effect of surrounding tissues on the quality of MRS. MRS scan started when the FWHM≤10, the water suppression(WS)≥98%. The total scan time was 8 min 6 s.4. Image post-processing and data measurementConventional MRI data measurement:select identical ROI in each side of optic radiation and visual cortex for three times both on T1 Flair and T2WI image to acquire the T1 intensity and T2 intensity, the average value will be the final intensity.Image post-processing and data measurement for 1H-MRS:using the software "FuncTool" to open the multi-voxel 1H-MRS signal data and T2WI position image simultaneously, we can get four kinds of pictures:chemical shift image(CSI), spectral map, metabolism, and metabolic and anatomical diagram integration map, then choose four fixed-voxels in the bilateral optic radiations, 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; select one ROI on each side of visual cortex which consists of 6 fixed-voxels, their average value will be the final value of visual cortex. 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.5. Statistical analysisData analysis was performed by using SPSS 13.0 software in this study. The data obtained were represented as mean±standard. All data were subjected to 1-Sample Kolmogorov-Smirnov Test for normality. Use Paired-Sample T Test to compare bilateral values of optic radiation and visual cortex; merge the bilateral values if there was no difference and compare with the control group respectively if difference exit. The T1 or T2 intensity difference between two groups was analyzed with Independent-Samples T Test. The 1H-MRS difference between two groups was analyzed with Independent-Samples T Test; the 1H-MRS difference among the high IP group, normal IP group 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 T3 if heterogeneity of variance. The statistical differences were considered as statistically significant when P values were less than 0.05.Result1. In this research most 2D-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 TE 35ms which can not only achieve NAA,Cho,Cr, but also Glx at 2.2ppm-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 CH-PC line as the VOI positon which was proved to have ability to achieve better MRSI.2. The glaucoma group's T1 intensity of optic radiation was 1788±213.7, control group 1785±213; the glaucoma group's T2 intensity of optic radiation was 1232±126, control group 1224±126; the difference between them was no significant(t=0.051, p=0.959; t=0.190, p=0.850); The glaucoma's T1 intensity of visual cortex was 1479±198, control group 1469±184; the glaucoma group's T2 intensity of visual cortex was 1447±158, control group 1433±161; the difference between them was no significant(t=0.164, p=0.870; t=0.277, p=0.783).3.1H-MRS data results:(1) The difference of NAA/Cr and Cho/Cr ratio in bilateral optic radiation and visual cortex was statistically significant, then both of them need to be compared respectively; for both the glaucoma and control group, the right side NAA/Cr ratio were all greater than that of left side, and the right side Cho/Cr ratio were all smaller than that of left side. The bilateral Glx/Cr ratio difference were no significant, then merge them to compare.(2) 1H-MRS data results of optic radiation of glaucoma and control groupNAA/Cr ratio:the control group's left and right side NAA/Cr ratio respectively were 1.724±0.169,1.835±0.141, the glaucoma group 1.482±0.202,1.669±0.270, the NAA/Cr difference between left and right side in the two groups were statistically significant(t=4.120, p<0.001; t=2.448, p=0.021). NAA/Cr-L of high IP group and normal IP group were respectively 1.533±0.183,1.363±0.209, NAA/Cr-R 1.608±0.264,1.811±0.246, compared with the control group with one-way ANOVA, there was statistically significant between groups(F=10.985, P<0.001; F=5.250, P=0.01),3 groups' LSD-t test show, the difference between control group and high IP group were all significant, but the difference between normal IP group and both the other two groups were no significant.Cho/Cr ratio:the control group's left and right side Cho/Cr ratio respectively were 0.984±0.193,0.896±0.173, the glaucoma group 1.482±0.202,1.669±0.270, the Cho/Cr difference between left and right side in the two groups were statistically significant(t=2.267, p=0.029; t=2.045, p=0.048). Cho/Cr-L of high IP group and normal IP group were respectively 0.981±0.189,0.989±0.225, NAA/Cr-R 0.858±0.162,0.986±0.179, compared with the control group with one-way ANOVA, the left side was no statistically significant between groups(F=2.507, P=0.095); the right side was statistically significant (F=3.894, P=0.029),3 groups' LSD-t test showed, the difference of right side's Cho/Cr between control group and high IP group were all significant, but the difference between normal IP group and both the other two groups were no significant.Glx/Cr ratio:the control group's Glx/Cr was 1.506±0.178, the glaucoma group was 1.669±0.332, the difference of Glx/Cr between the two groups was no significant(t=1.926, p=0.064). high IP group and normal IP group's Glx/Cr were respectively 1.573±0.290,1.892±0.341, compared with the control group with one-way ANOVA, there was statistically significant between groups(F=5.606, p=0.007); due to heterogeneity of variance(p=0.021), adopting Dunnett's T3 for multiple comparison, there were no statistically significant within groups of them.(3) 1H-MRS data results of visual cortex of glaucoma and control groupNAA/Cr ratio:the control group's left and right side NAA/Cr ratio respectively were 1.802±0.152,1.903±0.116, the glaucoma group 1.668±0.126,1.731±0.114, the NAA/Cr difference between left and right side in the two groups were statistically significant t=3.047, p=0.004; t=4.745, p<0.001).NAA/Cr-L of high IP group and normal IP group were respectively 1.673±0.132,1.654±0.120, NAA/Cr-R 1.742±0.117,1.705±0.112, compared with the control group with one-way ANOVA, there were statistically significant between groups(F=4.569, P=0.017; F=11.309, P <0.001),3 groups' LSD-t test show, the difference between control group and both high IP group and normal IP group were all statistically significant, but the difference between high IP group and normal IP group was no significant.Cho/Cr ratio:the control group's left and right side Cho/Cr ratio respectively were 0.745±0.065,0.700±0.083, the glaucoma group 0.645±0.065,0.610±0.076, the Cho/Cr difference between left and right side in the two groups were statistically significant(t=4.858, p<0.001; t=3.555, p=0.001). Cho/Cr-L of high IP group and normal IP group were respectively 0.648±0.064,0.637±0.073, NAA/Cr-R 0.617±0.085,0.594±0.051, compared with the control group with one-way ANOVA, there were statistically significant between groups (F=11.582, P<0.001; F=6.394, P=0.004),3 groups' LSD-t test showed, the difference of Cho/Cr between control group and both high IP group and normal IP group were all statistically significant, but the difference between high IP group and normal IP group was no significant.Glx/Cr ratio:the control group's Glx/Cr was 1.611±0.127, the glaucoma group was 1.707±0.201, the difference of Glx/Cr between the two groups was no significant(t=1.799, p=0.081). high IP group and normal IP group's Glx/Cr were respectively 1.701±0.148,1.720±0.310, compared with the control group with one-way ANOVA, there was no statistically significant between groups(F=1.605, P=0.214).Conclusion1.2D-1H MRS Technology can get Spectrum signals from different areas at one scanning, and it can be used to check human glaucomatous visual radiation and visual center 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 TE 35ms, and positioning VOI on the CH-PC line, we may achieve qualified spectrum.2. Compared with conventional MRI,1H-MRS was more sensitive in detection of glaucomatous injury in optic radiation and visual cortex.1H-MRS is a potential tool for studying the metabolic changes in glaucoma in vivo in normally appearing brain structures, and may be a noninvasive marker for this disease.3. for both the glaucoma and control group and for both the optic radiation and visual cortex,we found that the right side NAA/Cr ratio were all greater than that of left side, and the right side Cho/Cr ratio were all smaller than that of left side. No such changes was detected in bilateral Glx/Cr ratio. The reason was unclear. Generally speaking, the right hemisphere has much better imagery thinking than the left, and people have better eyes; besides the eyes often suffered differently.4. Different from the former research, we detected a greatly decrease in NAA/Cr and Cho/Cr in glaucoma group, for NAA/Cr,we presume that the glaucoma patients we chose were all at the period of onset that the condition was progressing quickly, so that the changes of NAA come to the degree that can be detected. For Cho/Cr, the decrease was associated with cell apoptosis, the damage of never cell signal transduction system and slow down of the cell renewing.5. Except for oxidative injury, glutamate excitotoxicity was the other component in transsynaptic degeneration, The marginally significant increase in Glu/Cr in the glaucoma group appeared to associate with the fact that less stimulations caused less Glu uptake and conversion.6. Compared with the control group, high IP group showed greatly decreased NAA/Cr and Cho/Cr both in optic radiation and visual cortex; the difference of the there ratios between high IOP group and normal IOP group were not apparent. As the major and most stable risk factor, the role that elevated intraocular pressure played in the glaucomatous injury still need further research.7. Our study agreed that glaucoma was a neurodegenerative disease of the visual system, but we still have no idea whether it is the RGC death that influence the whole visual way, or some part of the brain changes affect the optic nerve, or both exist. |
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