We have developed techniques for mapping the visual cortex function utilizing more of the visual field than is commonly used. This approach has the potential to enhance the evaluation of vision disorders and eye diseases.
High-resolution retinotopic blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) with a wide-view presentation can be used to functionally map the peripheral and central visual cortex. This method for measuring functional changes of the visual brain allows for functional mapping of the occipital lobe, stimulating >100° (±50°) or more of the visual field, compared to standard fMRI visual presentation setups which usually cover <30° of the visual field. A simple wide-view stimulation system for BOLD fMRI can be set up using common MR-compatible projectors by placing a large mirror or screen close to the subject’s face and using only the posterior half of a standard head coil to provide a wide-viewing angle without obstructing their vision. The wide-view retinotopic fMRI map can then be imaged using various retinotopic stimulation paradigms, and the data can be analyzed to determine the functional activity of visual cortical regions corresponding to central and peripheral vision. This method provides a practical, easy-to-implement visual presentation system that can be used to evaluate changes in the peripheral and central visual cortex due to eye diseases such as glaucoma and the vision loss that may accompany them.
Functional magnetic resonance imaging (fMRI) is a valuable method to assess changes in regional neurovascular function within the visual cortex in response to stimuli, as changes in regional blood flow correlate to the activation of brain regions1,2. High-resolution retinotopic blood oxygenation level-dependent (BOLD) signal measurements represent changes in deoxyhemoglobin, which are driven by localized changes in blood flow and blood oxygenation within the brain1,2. BOLD activity patterns collected from fMRI data can be used to functionally map the peripheral and central visual cortex, as well as detect changes in the retinotopic map in response to visual impairment and neurodegeneration3.
Most previous fMRI studies made use of narrow-view (around ±12° of the central visual field) non-retinotopic stimuli or simple retinotopic stimuli with narrow-view visual stimuli, which provided limited functional parcellation of the retinotopic representation in the visual cortex and limited assessment to only the central visual field, excluding the periphery3. Consequently, narrow-view fMRI data has reported inconsistent BOLD percent changes in glaucoma patients4,5,6. There is therefore a need for improved fMRI approaches to assessing the peripheral and central visual field, particularly in the evaluation of diseases such as glaucoma.
Glaucoma is the leading cause of irreversible blindness, affecting 10% of people by the age of 807. Glaucoma is caused by the progressive, irreversible neurodegeneration of retinal ganglion cells, which are responsible for transmitting visual stimuli to the brain through the optic nerve. In primary open-angle glaucoma (POAG), the most common form of glaucoma, increased intraocular pressure causes thinning of the retinal nerve fiber layer (RNFL), leading to the loss of peripheral vision followed by peripheral and central blindess8,9,10,11. Histological evidence from animal studies suggests that glaucoma additionally results in progressive neurodegeneration of the optic nerve, optic tract, lateral geniculate nucleus, optic radiation, and visual cortex12,13. MRI technology offers a minimally invasive method of assessing both blood oxygenation and neurodegeneration in the visual cortex. In patients with glaucoma, MRI has found evidence of gray-matter atrophy in the visual pathway13,14,15,16 and abnormal white matter in the optic chiasm, optic tract, and optic radiation1,17,18.
To further explore the effects on visual processing, fMRI can be used to detect brain function in response to visual cues. The protocol herein describes a novel method to obtain a low-cost, wide-view retinotopic map using high-resolution retinotopy fMRI with wide-field (>100°) stimuli, as described by Zhou et al3. Visual stimuli of expanding rings and rotating wedges were used to elicit retinotopic mapping of the eccentricity and polar angle for fMRI. BOLD fMRI percent changes were analyzed as a function of eccentricity to evaluate brain function, corresponding to both central and peripheral vision. The BOLD fMRI percent change may be used to visualize activation throughout the visual cortex. These fMRI measures provide a reliable new method to evaluate neurodegenerative changes and their functional effects on the visual cortex found in eye diseases involving visual field defects, such as glaucoma.
Research with human participants was performed in compliance with institutional guidelines at the University of Texas Health Science Center and Stony Brook University, with informed consent obtained from participants for these studies and use of their data.
1. Setup of MRI scanner and imaging protocols
2. Participant preparation
3. fMRI scanning of participant
4. Analysis of retinotopic fMRI data
Nine participants diagnosed with POAG (four males, 36-74 years old) and nine age-matched healthy volunteers (six males, 53-65) were evaluated using the aforementioned wide-view fMRI protocol, as previously described by Zhou et al3. POAG was confirmed clinically in patients with an open angle by assessment of the presentation of visual field defects consistent with glaucoma, optic disc cupping, and/or an intraocular pressure (IOP) greater than 21 mmHg3. A wide-view visual presentation (±55°) was used to evaluate central and peripheral vision in each group3.
Figure 3 depicts the retinotopic fMRI maps for polar (wedge) and eccentricity (ring) stimuli from a POAG and healthy control participant. The polar maps (Figure 3A) revealed no obvious differences between the POAG and healthy participants. The eccentricity maps (Figure 3B) showed that the central region of the parafovea that was activated by the smaller ring stimuli appeared larger in the POAG patient compared to the healthy participant. The enlarged parafoveal region in the visual cortex of POAG participants suggests cortical changes in response to peripheral vision disturbances.
BOLD percent changes for central (<24°) and peripheral (>24°) visual fields between POAG subgroups and the healthy control group were compared (Figure 4). BOLD percent changes at different eccentricities were reduced in POAG patients compared to healthy control participants, primarily at more peripheral eccentricities (Figure 4A). The BOLD percent changes were significantly reduced between the two groups, more so at larger eccentricities (p < 0.05, two-way ANOVA with Bonferroni post hoc test). The BOLD percent changes averaged for central vision (all stimuli <24°) were only slightly and not significantly reduced in POAG patients, while the BOLD response for peripheral vision (all stimuli >24°) was significantly reduced (Figure 4B). These results indicate this protocol's potential utility to assess changes in visual cortex function localized to peripheral or central vision, which is relevant to visual disorders such as glaucoma.
Figure 1: Experimental setup. (A) The 25 cm wide by 15 cm tall mirror held in place with a frame constructed from PVC pipe. (B) Setup of the presentation system on an MRI scanner, showing the posterior portion of a head array coil, the mirror and frame, and the back-projection screen (arrows) in the bore directly behind the head coil. Please click here to view a larger version of this figure.
Figure 2: Visual stimulation paradigms. (A) Three frames from the polar retinotopic visual stimulation paradigm, which consist of clockwise and counterclockwise spinning wedges with a contrast-alternating checkerboard pattern. (B) Three frames from the eccentricity paradigm, which consist of expanding and contracting rings with a contrast-alternating checkerboard pattern. Please click here to view a larger version of this figure.
Figure 3: Retinotopic polar and eccentricity maps. Representative (A) polar map using a rotating wedge from a normal control and (B) eccentricity maps using expanding/contracting rings from a normal control and a POAG participant. Both the left and right hemispheres (LH and RH) are shown with defined visual cortical boundaries (V1, V2, and V3). One frame from each paradigm is shown in the central inset. The color scales map to the corresponding regions of the visual field, as indicated by the color wheels, with A) mapping to the polar angle of the wedge stimuli, and B) mapping to the eccentricity of the ring stimuli. Please click here to view a larger version of this figure.
Figure 4: BOLD percent changes as a function of eccentricity and central or peripheral visual fields. (A) Group-averaged BOLD percent changes from the ring stimuli in healthy controls and POAG patients as a function of eccentricity. The BOLD percent change for each size of the ring stimuli were calculated to give the data at each eccentricity. (B) BOLD percent changes between healthy control and POAG patients of central (< ±12°) and peripheral (> ±12°) of the visual field, by binning data from all the eccentricities. Data are mean ± standard error of the mean. *p < 0.05, two-factor ANOVA with post hoc correlation. This figure has been modified from Zhou et al.3 with permission. Please click here to view a larger version of this figure.
The above protocol for utilization of wide-view retinotopic fMRI is an innovative method to evaluate the effects of vision loss and eye diseases on the brain. Through wide-field retinotopic mapping of the visual cortex with the use of a wider-view screen, this approach allows for a more comprehensive understanding of the visual system’s functional organization. This could lead to a better understanding of abnormalities in the brain’s visual processing system, which occurs in neurodegeneration, such as in glaucoma24,25. This technology can also be used to detect and analyze brain degeneration and reorganization in other conditions that cause blindness, such as age-related macular degeneration26,27.
A single human eye has about a 100° visual angle. Previous techniques used in most visual fMRI studies used a FOV of less than 30°, limiting the portion of the visual cortex that could be activated and analyzed by the fMRI28. Consequently, peripheral vision could not be visualized, forcing all analyses to be focused solely on the central visual field. Clinically, this prevented clinicians from accurately performing preoperative cortical mapping, crucial for avoiding vital locations when performing brain surgeries29. With the wide-view retinotopic fMRI technique described in this protocol, the visual angle has been increased to up to 100° (±50°)3,30,31. To allow for a wide-view image and decrease visual obstruction caused by the head coil, only the posterior half of the head coil is used. Head coils usually have a relatively small window, with bars across that impede the ability to fully see the wide-view retinotopic stimuli. However, using only the posterior portion of the head coil causes large signal inhomogeneity across the brain and reduces the SNR in the anterior and central regions. The image quality and SNR of the posterior occipital lobe should not be heavily impacted32. However, the exact effects of using only the posterior portion of the coil likely depend on a specific coil design (number and size of arrayed coils), so testing the SNR or signal-to-noise fluctuation ratio in a few subjects with and without the anterior portion can be done if there is a concern of significant SNR loss with a given coil32.
Proper setup of the T1-weighted MP-RAGE sequence is essential to properly register functional images to high-resolution brain structural images and for anatomical registration to templates or for group studies. As such, we acquire the T1-weighted image using the entire head coil, which may result in slight movement of the participant relative to the fMRI scan. Alignment of the fMRI to the anatomical scan is a routine analysis step, so this should not be an issue. Alternatively, the acquisition of the T1-weighted image without the anterior coil could be done, but the image inhomogeneity may impact the quality of registration to a reference template. To avoid motion artifacts, it is crucial to properly immobilize the participant’s head within the head coil. Motion artifacts can naturally occur without proper stabilization, which will negatively affect the quality of the fMRI data collected, leading to poorer results from the analysis. While post-processing motion correction is routine for fMRI analysis, large movements can still impact the results, so it is important to check functional scans for data quality and discard studies with major artifacts. In this protocol, participants were instructed to focus on a white cross for 10 s, both before and after each visual stimulation paradigm, to obtain baseline BOLD data. This helped reduce the variability of the fMRI at baseline, and also allowed the subject’s brain to adjust to the scanner sounds and background screen brightness before the actual visual data tests began.
There are a variety of alternative approaches that could be considered for wide-view fMRI. The approach described herein, using a large screen/mirror with only the posterior half of the head coil, can provide a moderate wide-view up to around a 100° FOV3,30. The cost to make the mirror/screen is very low (potentially <US $100), assuming a standard projector is already available. Greco et al. used a slightly different approach, with the screen placed after the mirror in the optical path, directly in front of the subject’s face (7.5 cm away), providing an 80° visual angle28. MR-compatible glasses were needed for the participant to be able to focus on the screen. Ellis et al. also used a similar approach, but with the projector tilted down onto a mirror on the bottom of the bore, which reflected the stimuli directly onto the top of the bore above the subject’s face, providing a 115° visual angle32. The view is distorted by the curved bore, which requires the images for the stimuli to be warped to correct. An extension of this approach was recently reported with a custom curved screen at the top of the scanner bore and two mirrors that were able to provide an ultra-wide FOV of 175°34. Some of these reported methods used the anterior portion of the head coil and others did not; however, any of these methods could be used either way, with potentially a slightly higher SNR using the anterior coil, but with the tradeoff of reduced visual angle and portions of the visual field being blocked. A potential limitation with all methods using a projector is that, for a screen with custom size and location, the projector has to be adjusted for the focus and size of the projected image by adjusting the projector/lens, moving the projector, or getting custom lenses if the previous methods are not sufficient.
Another approach used a transparent plastic rod with a curved end as the screen, with a projector to provide a slightly larger visual angle of 120°, which is compatible with using the anterior head coil without limiting the FOV. However, only monocular stimulation can be performed. A special lens for the projector is needed, which increases the cost, and contact lenses must be worn for the participant to be able to focus on the screen, which complicates the setup31. A similar approach used fiber-optic bundles to directly transmit and present images from a screen to a participant’s eye, which provided a visual angle of up to 120°33. Contact lenses must also be worn, and only a single eye could be stimulated at a time. This method requires a long and high-density fiber optic bundle, which can have relatively low resolution for the presentation and may be moderately expensive33.
Visual impairment and eye disease can affect the structure and function of the visual cortex. BOLD fMRI can be used to visualize retinotopic cortical function, but most visual presentation systems used for fMRI only stimulate the central visual field. This protocol describes the implementation of a wide-view presentation system for fMRI that can be used to functionally map the peripheral and central visual cortex. This system can be set up easily and at a low cost utilizing common MR-compatible projectors. Although with some limitations, the protocol described has the potential to analyze functions of the visual cortex corresponding to central and peripheral vision at a level that balances cost and precision. The data collected through this method can be analyzed to determine selective activation based on different types of visual stimuli and brain communication amongst different areas for visual processing. This method could be used to evaluate changes in the function of peripheral and central visual cortex due to vision loss and eye diseases such as glaucoma. This technology therefore has applications in the diagnosis, management, and treatment of eye diseases.
The authors have nothing to disclose.
This work was supported by the National Institutes of Health [R01EY030996].
1/4"-20 nylon machine screws, knurled head thumb screw | to attach rod to PVC frame | ||
1-1/4 inch PVC pipe | length of ~5-10 ft is needed | ||
3T MRI scanner | Siemens | ||
6-32 nylon machine screws, rounded head | to attach mirror/screen to rod | ||
8-channel head array coil | Siemens | ||
90 degree PVC elbow, 1-1/4 inch fitting | |||
Acrylic mirror | Width and length of 25-30cm | ||
Acrylic rod | 1 inch width, ~ 2 ft long depening on size of scanner bore and head coil | ||
E-Prime | Psychology Software Tools | to prepare and present visual stimuli paradigms | |
Plywood sheet, 1/2 inch thick | Size should be at least as large as the scanner bore. Cut as bore-sized frame for the projection screen | ||
Rear projection screen | Size should be at least as large as the scanner bore |