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Show Journal of Neuro- Ophthalmology 20( 4): 285- 287, 2000. © 2000 Lippincott Williams & Wilkins, Inc., Philadelphia Functional Magnetic Resonance Imaging of Lateral Geniculate Nucleus at 1.5 Tesla Atsushi Miki, MD, PhD, Jonathan Raz, PhD, John C. Haselgrove, PhD, Theo G. M. van Erp, MA, Chia- Shang J. Liu, B A, and Grant T. Liu, MD Although activation of the lateral geniculate nucleus has been detected by functional magnetic resonance imaging with magnetic field strengths higher than 2.0 Tesla, there have been no reports of functional magnetic resonance imaging of the lateral geniculate nucleus with the more widely available 1.5 Tesla scanner. The authors used functional magnetic resonance imaging techniques at 1.5 Tesla to detect lateral geniculate nucleus activation in five of seven healthy subjects. This study shows that visual activation of the lateral geniculate nucleus can be obtained with functional magnetic resonance imaging using conventional 1.5 Tesla scanners. Key Words: Functional magnetic resonance imaging- Lateral geniculate nucleus- Visual cortex- 1.5 Tesla. The lateral geniculate nucleus ( LGN), a deep subcortical structure of the thalamus, is the location of the first synapse in the afferent visual pathway. Most of the fibers from retinal ganglion cells terminate there, and postsynaptic neurons of the LGN project to the primary visual cortex. Although there are many reports of activation of visual cortex using functional magnetic resonance imaging ( fMRI) techniques ( 1,2), there have been only a few reports of fMRI of the LGN. Although the signal increase was small relative to that of the visual cortex, Supported by Post- Doctoral Research Fellowship PD98017 ( AM) and Grant- in- Aid GA98015 ( GTL), Prevent Blindness America, Schaumburg, Illinois; Brain Science Foundation ( AM), Tokyo, Japan; Uehara Memorial Foundation ( AM), Tokyo, Japan; NIH grant R29MH51310 ( JR), Bethesda, Maryland; and Knights Templar Eye Foundation ( GTL), Chicago, Illinois. Manuscript received September 27, 1999; accepted June 7, 2000. From the Division of Neuro- ophthalmology, the Departments of Neurology and Ophthalmology ( AM, GTL), Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania; the Department of Bio-statistics ( JR), University of Michigan, Ann Arbor, Michigan; the Department of Radiology ( JCH), Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; the Department of Psychology ( TVE), University of Pennsylvania, Philadelphia, Pennsylvania; and the University of Pennsylvania School of Medicine ( AM, JR, JCH, TVE, CJL, GTL), Philadelphia, Pennsylvania. Address correspondence and reprint requests to Atsushi Miki, MD, PhD, Division of Neuro- ophthalmology, Department of Neurology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104. LGN activation has been found by fMRI using magnets at 2.0 Tesla ( T) or higher ( 3- 7). However, these MRI systems are not widely accessible, and most are experimental. To our knowledge, there have been no reports of LGN activation detection using fMRI with the more widely available 1.5T MRI scanners. We investigated whether it was possible to detect activation of the LGN by fMRI with a conventional 1.5T MR scanner. METHODS Seven healthy volunteers ( four men and three women; mean age, 23.7 years; range, 22- 27) gave informed consent before participating in this study. The consent form was approved by the Institutional Review Board of the Children's Hospital of Philadelphia. All subjects had normal visual acuity, confrontational visual fields, and stereopsis. All subjects were examined twice and underwent the second session 2 to 7 days ( mean, 4.5) later. Imaging was performed with a clinical 1.5- T MRI system ( Vision; Siemens, Erlangen, Germany). The subjects' heads were padded with foam padding within the quadrature head coil to restrict motion. Subjects were instructed to hold their heads still. Sixteen oblique axial images that were positioned parallel to the calcarine fissure were collected for anatomic images using a Tl-weighted spin echo sequence. Thereafter, 16 functional images were acquired on the identical and parallel slices of the anatomic images using a T2*- weighted echo-planar image sequence ( time to recovery/ time to echo = 1.68/ 64 ms [ 3 second interscan interval]; flip angle = 90°; matrix = 64 x 64; field of view = 240 mm; in-plane resolution = 3.75 x 3.75mm2) with the slice thickness of 5 mm without interslice gap. One hundred twenty image sets of 16 images were acquired for functional imaging. Light- proof binocular goggles with 6 x 5 light-emitting diodes ( modified S10VSB; Grass Instruments, Quincy, MA) flashing at the frequency of 8 Hz were placed over subjects' eyes to provide binocular full- field visual stimulation. The subjects were instructed to keep their eyes open during the visual stimulation. The visual stimuli were turned on and off with the use of a trigger from the magnet. Ten scans of visual stimulation of both 285 286 A. MIKIETAL. TABLE 1. Location of lateral geniculate nucleus ( LGN) activation in Talairach coordinates Left LGN Right LGN Subject 1 2 3* V 5* 5* 1* V * first Location - 22, - 30, 5 - 22, - 34, 5 - 22, - 30, 0 - 22, - 30, 0 - 26, - 30, 5 - 22, 30,5 - 22, - 26, 0 - 26, - 26, 5 study; tsecond study. Z- score 4.74 4.50 5.83 6.78 5.38 4.84 6.42 6.01 Location 26, - 26, 0 22, - 26, 5 26, - 26,5 22, - 26, 0 - 26, - 22, 5 26, - 30, 5 30, - 26, 5 Z- score 6.27 5.39 5.39 7.01 - 5.27 5.28 5.35 eyes ( epochs 1, 3, 5, 7, 9, and 11) a lternated with ten scans of darkness ( epochs 2, 4, 6, 8, 10, and 12). DATA ANALYSIS Data analysis was performed on UNIX workstations with IDL ( Interactive Data Language) and SPM96 ( Wellcome Department of Cognitive Neurology, London, UK) packages. The first five scans of echo- planar images were discarded to eliminate magnetic saturation effects. The average signal intensity of each image in the functional image set was normalized to compensate for baseline drift of the magnetic resonance signal. Functional images of each subject were realigned using a six- parameter ( three translations and three rotations) FIG. 1. Z- maps superimposed on the SPM96 T1- template of a subject who showed LGN activation in the first ( A) and second ( B) study ( in transverse view, Z = 0 [ A] and Z = 5 [ B] level in Talairach coordinates). The subject's left is on the left. In addition to the activation of the visual cortex, isolated bilateral activation of LGN can be seen in these images. Z- maps from another subject also show a bilateral LGN activation in the first ( C) and second ( D) study ( Z = 0 [ C] and Z = 0 [ D] level). FIG. 2. Z- maps superimposed on the T1 - template in coronal view for three subjects ( y = - 26.25 [ A], y = - 26.25 [ B], y = - 30 [ C], y = - 26.25 [ D] level in Talairach coordinates). A and B are from the same subject as in Figure 1A and 1B. C is from the same subject as in Figure 1C and 1D. rigid body transformation to the first volume. After this, the images were transformed into the anatomic space of Talairach and Tournoux ( 8). This spatial normalization routine was performed by minimizing the sum of squares difference between the functional images and the echo-planar images template, using an 8- parameter affine transformation. Data were smoothed with a Gaussian filter ( full width at half maximum = 8.0 x 8.0 x 10.0 mm). A box- car delayed by 6 seconds and temporal smoothing were used. T- statistics were calculated for each voxel and then transformed into z- values ( SPM [ Z]). In all subjects, Z > 4.5 approximately corresponded with P < 0.05 after the correction for multiple comparisons in the entire image. RESULTS Statistically significant ( P < 0.05 after the correction for multiple comparisons) activation was observed in the bilateral LGN in five subjects ( Table 1), in addition to the activation of the visual cortex in all subjects. Two subjects showed bilateral LGN activation in both studies, and the activated areas in the LGN were consistent across the studies, separated by several days ( Figs. 1 and 2). The other two subjects showed bilateral LGN activation in only one study. Another subject had bilateral LGN activation in one study and unilateral LGN activation in the other study. DISCUSSION The position of LGN activation was consistent with the known anatomic locations ( 9) and also with the previous fMRI reports at higher magnetic field strengths ( 3- 7). Also, the three- dimensional location of LGN ac- / Neuro- Ophthalmol, Vol. 20, No. 4, 2000 FUNCTIONAL MRI OF LGN AT 1.5 TESLA 287 livation in the standard space was almost constant for all subjects. Activation of LGN has been identified using flash goggles ( 6), checkerboard ( 3,5,7), and a visual motion cask ( 4). Although the optimal visual stimulus for detecting this nucleus using fMRI remains to be investigated, our study shows functional mapping of LGN can be performed by fMRI at 1.5T, even with standard flash goggles. The activation of LGN could not be found in two subjects and was not reproducible in some subjects. This is probably because of our relatively large voxel size, the use of spatial filter in our study, and the relatively small size of the LGN ( partial volume effects) ( 10). In addition, visual activation using fMRI can vary substantially within and between subjects, in part because of changes in head position, the subjects' attention to the stimulus and level of arousal, or the state of the MR scanner ( e. g., temperature) ( 11). We have shown that functional mapping of the LGN can be performed with a conventional, widely available 1.5T MR scanner. Although the LGN has been imaged using anatomic MR images ( 9), fMRI may provide an adjunctive localization method of this small nucleus in living human subjects. This should allow more neuro-ophthalmologists and other clinical investigators the opportunity to study the LGN in healthy subjects and in subjects with visual deficits, for example, by permitting precise clinico- pathologic comparisons. Future investigations with fMRI at 1.5T may also include a detailed retinotopic mapping of the LGN and a study of patients with retrogeniculate lesions and retrograde degeneration. REFERENCES 1. 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