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L. S. Snebold, D. A. Poggel, J. C. Brookman, L. J. Toth, K. Hallock, D. S. Kim, J. F. Rizzo; Evolution of a Paradigm to Study the Visual Cortex of Normally-Sighted and Blind Beagles Using Functional MRI. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3022. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
This work is related to the efforts of the Boston Retinal Implant Project to develop a sub-retinal prosthesis to restore vision to the blind. The specific purpose of this presentation is to develop methods for conducting functional MRI on beagles to: 1) locate the visual cortex and 2) topographically differentiate cortical activity between beagles with normal vision and beagles blind from retinal degeneration.
Three normally-sighted beagles and 4 beagles with cone-rod dystrophy (crd1) underwent fMRI scans of the brain using a 3T Philips Intera scanner. Pilot testing for delivering anesthesia, preventing motion artifacts, and eliciting cortical activity evolved with the first two normal animals. Established methods were implemented for beagle #3 and all 4 blind animals. T1-weighted MR-imaging was used to acquire high-resolution anatomical images. Blood-Oxygen-Level Dependent (BOLD) fMRI (T2* weighted) was used to define the visual cortex. Full-field, black-and-white checkerboard patterns (8Hz) were presented alternating with a uniform gray background. In addition, separate series of vertical and horizontal bars provided more detailed mapping. Data were pre-processed and analyzed with Brain Voyager software (QX Version 1.8, Brain Innovation). BOLD activation maps were computed with General Linear Model (GLM) and linear correlation approaches.
Full-field stimulation activated the dorsal posterior parts of the cortex in beagles #1, #2, and #3. Horizontal and vertical mapping produced phase-related activation patterns in all visual cortices. Most notably, BOLD signal was found as early as 9 weeks in beagle #3, and in both beagles #2 and #3, BOLD signal showed increasing signal amplitude and clearer retinotopic organization up to 47 weeks. Signal patterns in crd1 beagles between 9 and 16 weeks were comparable in quality to normally-sighted beagles; but at 28 weeks decreased signal indicated onset of blindness.
This study yielded improved methods for detecting fMRI signals in dogs allowing localization of the visual cortex, showed signals can be detected in very young dogs, and demonstrated retinotopic (right vs. left; superior vs. inferior) activation in dog visual cortex using a novel stimulation technique.
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