Minier, A. | Search bioRxiv

bioRxiv2020

3-Dimensional Magnetic Resonance Imaging of the Freely Moving Human Eye

Abstract Eye motion is a major confound for magnetic resonance imaging (MRI) in neuroscience or ophthalmology. Currently, solutions toward eye stabilisation include participants fixating or administration of paralytics/anaesthetics. We developed a novel MRI protocol for acquiring 3-dimensional images while the eye freely moves. Eye motion serves as the basis for image reconstruction, rather than an impediment. We fully reconstruct videos of the moving eye and head. We quantitatively validate data quality with millimetre resolution in two ways for individual participants. First, eye position based on reconstructed images correlated with simultaneous eye-tracking. Second, the reconstructed images preserve anatomical properties; the eye’s axial length measured from MRI images matched that obtained with ocular biometry. The technique operates on a standard clinical setup, without necessitating specialized hardware, facilitating wide deployment. In clinical practice, we anticipate that this may help reduce burden on both patients and infrastructure, by integrating multiple varieties of assessments into a single comprehensive session. More generally, our protocol is a harbinger for removing the necessity of fixation, thereby opening new opportunities for ethologically-valid, naturalistic paradigms, the inclusion of populations typically unable to stably fixate, and increased translational research such as in awake animals whose eye movements constitute an accessible behavioural readout.Author contributions B.F., L.D.S., M.S., and M.M.M. conceptualised the problem. B.F. and L.D.S. developed, implemented, and tested the protocol. A.M. provided optometry assessments and assisted with eye movement analysis. S.I., D.Z., and M.P.N. assisted with installation of the eye-tracking system within the MRI scanner. J.A.M.B., J.J. and J.Y. contributed with the MRI sequences and compressed sensing framework. B.F., L.D.S. and M.M.M. drafted the manuscript, and all authors contributed to internal review.Competing interests B.F., L.D.S., J.A.M.B., J.Y., M.S., and M.M.M. declare the following competing financial interest: a patent application for the protocol described in this manuscript has been filed (patent application: EP19160832). A.M., S.I., D.Z., M.P.N. and J.J. declare no competing financial interests.Competing Interest StatementB.F., L.D.S., J.A.M.B., J.Y., M.S., and M.M.M. declare the following competing financial interest: a patent application for the protocol described in this manuscript has been filed (patent application: EP19160832). A.M., S.I., D.Z., M.P.N. and J.J. declare no competing financial interests.View Full Text

bioengineering↗

bioRxiv2018

Functional repair after ischemic injury through high efficiency in situ astrocyte-to-neuron conversion

Mammalian brains have largely lost internal neural regeneration capability except for a few discrete neurogenic niches. After brain injury, the cerebral cortex is especially difficult to repair due to its extremely low rate of adult neurogenesis. Previous studies have converted glial cells into neurons, but the total number of neurons generated is rather limited, casting doubt about its therapeutic potential. Here, we demonstrate that high-efficiency neuroregeneration can be achieved in adult mammalian brains by making use of an engineered AAV Cre-FLEX system to convert a large number of reactive astrocytes into functional neurons. Specifically, using a combination of GFAP::Cre and FLEX-NeuroD1 AAV system, we were able to regenerate enough new neurons from astrocytes to cover about 40% of the neurons lost from an ischemic injury (400 NeuN+ new neurons/mm2), compared to previously reported an average of <1% of cortical neurons (2-8 NeuN+ neurons/mm2) in an ischemic-injured adult mammalian cortex. Importantly, this in situ astrocyte-to-neuron conversion process also improved survival of injured pre-existing neurons, (additional 400 neurons/mm2), leading to a repaired motor cortex with layered cortical structures. Moreover, NeuroD1-converted neurons not only form functional neural circuits but also rescue motor and memory deficits after ischemic injury. Our results establish the proof-of-principle that a highly efficient in situ astrocyte-to-neuron conversion approach provides a novel treatment for neurological disorders that are in need of new neurons.

neuroscience↗