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Functional Alterations Of Primary Visual Cortex In POAG Using FMRI-retinotopic Mapping

Posted on:2011-08-11Degree:MasterType:Thesis
Country:ChinaCandidate:L P ShiFull Text:PDF
GTID:2154360308975196Subject:Medical imaging and nuclear medicine
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Background and objectiveGreat progresses have achieved in retinotopic mapping techniques in recent years, including functional magnetic resonance imaging (fMRI), electroencephalography (EEG), magnetoencephalography (MEG), etc. Among all these techniques, Bold-fMRI retinotopic mapping, characterized by high spatial resolution and non-invasion, perfectly suits for the investigations on human visual system in vivo. Traveling wave method is the most often adopted technique for fMRI retinotopic mapping study. But this technique is difficult to perform due to its sophisticated experimental designs and data processing, as a result, we adopted meridian stimulus in this study to reveal the retinotopic mapping distribution characteristics of visual areas in healthy subjects, and we also investigated the feasibilities of this technique and its applications in our studies.Methods4 right-handed healthy volunteers with normal visual acuity (3 males and 1 female, aged from 30 to 57 years) were enrolled in this study. Meridians with contrast-reversing checkerboard patterns (horizontally and vertically) was used as the stimuli (contrast=100%). Functional and anatomic image data were acquired on a super conductive 3.0 T full-body MRI scanner (Magnetom Trio Tim 3. 0 T, Siemens) with echo planar pulse sequences and in coronal view perpendicular to calcarine fissure. High-resolution anatomic data was obtained by a sagittal 3D MPRAGE sequence. Image processing and the functional data analysis were performed in BrainVoyager QX 2.0 software. The procedures included: grey-matter segmentations and reconstructions, unfolding, cutting and flattening of cortex. Analyzed with general linear model (GLM), the functional imaging data were overlaid on flattened cortex, and visual cortex areas were differentiated according to fundamental physiological features of retinotopic mapping. ResultsThe actual response curve of function images obtained from meridian stimulus, was well matched with the designed model curve, fitting correlation coefficient values of the vertical and horizontal meridian stimulus were 0.862, 0.816, 0.859, 0.883, 0.863, 0.792 and 0.765, 0.859 (subjects 1 to 4) which could delineate the dorsal V1d, V2d, V3 and V3a, and ventral V1v,V2v,Vp and V4 regions.ConclusionsFMRI-retinotopic mapping using meridian stimulus can noninvasively identify the boundaries among V1~V4 in detail. Distributions of these areas were generally in accordance with each other, but there were individual differences in size and functional anatomic sub-area. Accordingly, only if based on subareas can visual system be more accurately studied and analyzed. Background and objectiveGlaucoma is one of the severe ophthalmologic diseases. It is the world second leading cause of blindness and also the second common cause of blindness in China. Primary open-angle glaucoma (POAG), characterized by progressive retinal ganglion cells (RGCs) death and the optic atrophy, intraocular-pressure increase, and distinctive absence of visual field, is a very complicated ophthalmologic diseases or syndromes. The recent understandings of its pathogenesis and progression are limited. In recent years, it was suggested to be a neurodegenerative disease of whole visual pathways including the defects of cortical functions by studies on experimental animal models and autopsy of glaucoma patients. FMRI retinotopic mapping technology, with a great superiority in high spatial resolution and non-nvasion procedures, has been widely used in the studies of visual cortical functions and in the studies of neurodegenerative diseases, such as amblyopia. In this study, the fMRI-retinotopic mapping using meridian technique, functional area of V1 visual cortex were identified. The mechanism in central nervous system of POAG and clinical value of such measurements were evaluated based on individual V1 cortical signal and area of activation provoked by separate stimulations on each eye of subjects; and approach to the correlation between activation pattern and corresponding ophthalmologic test results.Methods20 right-handed POAG patients were recruited from ophthalmology department of Southwest hospital and glaucoma center of Daping hospital (15 males and 5 females, aged from 18 to 75 years, corrected visions of both eyes≥0.5); 20 age and gender matched right-handed healthy volunteers were included as well (15 males and 5 females, aged from 20 to 75 years, corrected visions of both eyes≥1.0). All the subjects were informed of experimental procedures in detail, and signed informed consents. All subjects underwent one-eyed stimulations with contrast-reversing checkerboard patterns stimulus and two-eyed stimulations with meridian mapping as the same as that in Part I (BLOCK design). Based on topological characteristics of retina'mapping on occipital cortex, the functional images stimulated by meridian mapping, were overlaid on the flattened cortex to delineate V1 as a region of interest (ROI). Then after calculation of the bilateral V1 areas (mm2), the ROI were applied on the functional images obtained with one-eyed circular checkerboard stimuli. BOLD signal from bilateral V1 areas was extracted and the value of all plateau signals (BOLD signal, %) in bilateral V1 at various time points were averaged to obtain the averaged response of one-eye-stimulated. The activation areas in V1 were manually drawn, saved as ROIs, and automatically calculated for areas of activation in V1. Data obtained was analyzed with SPSS 16.0 for Windows Software. Comparisons of stimulated cortical fMRI responses between left and right eyes in healthy subjects and those between glaucoma eyes and fellow eyes in the glaucoma patients were compared by (severer eye defined as glaucomatous eye, and the other as fellow eye) paired samples t-test; the glaucomatous eyes and fellow eyes were compared with corresponding eyes from matched controls by independent samples t-test, respectively; differences of two-eyed visual functions in the patients (contrast of PSD) and those of V1 cortical functions (contrast of BOLD signal) were analyzed by linear correlation analysis; the degree of activation of V1 in one side of cortex of the early and mid-late stage patients were compared with bilateral cortex by paired samples t-test; the degree of activation of V1 of the fellow eyes of patients were compared with corresponding result from age , gender and eye-side matched controls by independent samples t-test. A level of P<0.05 was adopted as statistical significance.Results1. After preprocessing, there were 2 patients whose head-motions of function images were over 2.5mm, 2 patients couldn't concentrate on watching visual stimuli, and 1 patient with excessive head-motion in structural images making grey matter segmentation impossible. After strict controlling of factors including head-motion, behavioral performance, and mechanical noises, etc., there were 15 POAG patients fulfilled experimental criteria, including 10 males and 4 females (7 in primary stage, 4 medium, and 4 late stage). 15 genders and ages matched healthy subjects (10 males and 5 females) were picked from the pool of normal volunteers. There were no significant differences in ages between the patients and the controls (paired samples t-test, t=-0.495,P=0.8628). In all subjects, the actual response curve of function images well matched with the designed model curve, and could clearly identify the boundaries of V1 and V2.2. V1 fMRI responses of individually stimulated glaucomatous eyes and fellow eyes of the POAG group were 1.24% and 2.18%, respectively, demonstrating a significantly decreased response in glaucomatous eyes (t=4.757,P<0.001). V1 fMRI responses of the left and right eyes of the controls were 1.99% and 1.96% without apparent difference (t=0.205,P=0.840). The glaucomatous and fellow eyes of the patients were compared with the age, gender and side matched controls, respectively: response average measurements of the individually stimulated glaucomatous and fellow eyes were 1.24% and 2.01%, respectively. The responses of the glaucomatous eyes were weaker than those of the fellow ones (t=-3.011, P=0.006); averaged measurements of V1 cortical response of the individually stimulated fellow eyes and matched eyes were 2.18% and 1.95%, respectively, indicating that V1 cortical response of the fellow eyes were higher than those of eyes of controls, however, no differences between fellow and matched eyes were found (t=0.742, P=0.465). The interocular difference of V1 cortical response in the POAG patients and PSD difference by visual field examination were analyzed in linear correlation analysis. The functional difference of V1 cortical response of individually stimulated glaucomatous and fellow eyes was negatively correlated with the visual difference (r=-0.887,P<0.001).3. The activated area indexes in left and right V1 cortexes of the individually eye-stimulated controls and patients in the early and mid-late stages, were compared with paired samples t-test: the activated area indexes in the left and right V1 cortexes of the individually left-eye-stimulated controls were 0.83 and 0.88, respectively, while the individually right-eye-stimulated controls were 0.81 and 0.86, respectively. The activated area indexes in the right V1 cortex of the individually eye-stimulated controls were obviously higher than that in the left V1 cortex (t=-2.384,P=0.032; t=-2.247,P=0.041). The activated area indexes in the left and right V1 cortexes of the individually left-eye-stimulated early staged patients were 0.66 and 0.85, respectively, while individually right-eye-stimulated early staged patients were 0.67 and 0.81, respectively. The activated area indexes in the right V1 cortex of the individually eye-stimulated early staged patient were apparently higher than that in the left V1 cortex (t=-2.606,P=0.040; t=2.949,P=0.026). The activated area indexes in the left and right V1 cortex of the individually left-eye-stimulated mid-late staged patients were 0.47 and 0.66, respectively, whereas individually right-eye-stimulated mid-late staged patients were 0.65 and 0.41, respectively. The activated area indexes in the right V1 cortex of the individually eye-stimulated mid-late staged patients were significantly higher than that in the left V1 cortex (t=2.621,P=0.034) .4. The activated area indexes in the V1 cortex of fellow eyes and of the age, gender and eye-side matched controls were compared by independent samples t-test, with results of 0.70 and 0.85, respectively. And the former was significantly lower than the later (t=-3.801,P=0.001).Conclusions1. The impairment of cortical function to glaucoma is in accordance with that of visual function.2. With the progression of POAG, the asymmetry of the activation between the left and right V1 cortexes will change. The left eye maintained superiority in right V1 while right eye was projected to left V1 in mid-lat staged patient; the change of cortical activation asymmetry was consistent with the impairment pattern of retinal nerve fibre layer (RNFL).3 Located and quantified measurement with fMRI-retinotopic mapping is a useful method for clinical follow-up and evaluation of functional alteration of glaucomatous visual cortex, and a potentially useful means of studying trans-synaptic degeneration of visual pathways of in vivo glaucoma. Background and objectiveThe volume change of the fourth ventricle could be produced by communicating hydrocephalus, intracranial hypertension, internal hemorrhage and expansion of the fourth ventricle, some mental illnesses, encephalatrophy, and occupied lesions of the fourth ventricle and its surrounding structure. The normal value of the fourth ventricle's volume is a crucial point for the clinical diagnosis and scientific researches of these diseases. However, its normal volumetric value in normal adults is limited to linear measurements of a small sample's CT or autopsy. Linear measurements may not fully reflect the shape and volume of the irregular fourth ventricle, causing the measurements incapable to demonstrate its actual volume, and autopsy cannot reflect result of in vivo morphological size. MRI, characterized by high spatial resolution, strong soft-tissue contrast and hardening artifacts, can display 3D anatomic structure of the fourth ventricle after reconstruction. Based on high-resolution 3D MR images of 1000 normal Chinese adults, 3D volumetric software with automatic tracking technique was utilized in our study to manually outline the ROI. The volumes of Chinese fourth ventricle were measured and the gender differences and the correlation with ages were also observed. The normal reference value of in vivo Chinese adults was provided for clinical applications and the studies of human brain development and relevant diseases, and give fundamental data for establishment of digitized standard brain of Chinese adults.MethodsFrom a multi-center clinical experiments in 16 general hospitals, 1000 Chinese healthy volunteers (age range=18 to 70) were divided into 5 groups, namely A (age range=18 to 30), B (age range=31 to 40), C (age range=41 to 50), D (age range=51 to 60), and E (age range=61 to 70). Each group contained 100 males or 100 females. The brain MRI scans of all volunteers were obtained with T1 weighted three-dimensional magnetization prepared rapid acquisition gradient echo sequences. At sagittal view, automatic trace with Midob1.2 software package and manual outlining techniques, the fourth ventricle border was outlined and volumes measured after Three Dimension Data Reconstruction. The differences of measurements between male and female were analyzed with independent samples t-test, and those among age groups were analyzed by ANOVA. Pearson's Correlation Coefficient was used in age and volume.ResultsThe fourth ventricle volumes of A, B, C, D and E male group were as follows: (2.06±0.91), (2.12±0.77), (2.15±0.79), (2.14±0.99), (2.42±0.84) ml; those of females'were as follows: (1.95±0.71), (1.89±0.59), (1.77±0.56), (1.93±0.67), (2.01±0.65) ml. The fourth ventricle volumes of males were larger than those of females, which had significant differences (t=5.573, P=0.000); there were no significant differences among the female groups (F=1.788, P=0.130); there were significant differences among the male groups (F=2.639, P=0.033), whose multiple comparison found that the 60 years old was the watershed with significant differences (P<0.05). Correlation between the change of males'volumes and the ages was not strong (r=0.119, P=0.008), and the females'volumes did not correlated with their ages (r=0.041, P=0.360).ConclusionsThere are gender differences in the fourth ventricle volumes of normal Chinese adults, males'volumes are larger than females'. The changes of the fourth ventricle volume with aging are different between males and females, males'volume increased after 60 years of age, and females'are not obvious.
Keywords/Search Tags:retina, receptive field, fMRI, visual cortex, meridian, visual field, glaucoma, Fourth ventricle, Volume, Magnetic resonance imaging, Organ Size
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