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Imaging the Human and Rodent Visual Systems with MRI

Explore the basic anatomy and function of the human and rodent visual systems using MRI. Understand the advantages and disadvantages of MRI in visual system imaging and learn about the various contrasts and parameters used in multimodal MRI. Discover the applications of MRI in glaucoma research and how it can help identify structural, metabolic, and functional changes in the brain's visual system.

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Imaging the Human and Rodent Visual Systems with MRI

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  1. INTBP2100 Biology of Vision - Imaging of the Visual System with MRI Kevin C. Chan, PhD Assistant Professor Neuroimaging Laboratory, Departments of Ophthalmology and Bioengineering, Center for the Neural Basis of Cognition, McGowan Institute for Regenerative Medicine Louis J. Fox Center for Vision Restoration, University of Pittsburgh, Pittsburgh, PA, USA

  2. Basic Anatomy of Human and Rodent Visual Systems: Human visual pathway Rodentvisual pathway Retina >90% Optic Nerve <10% 52% Optic Chiasm 48% Optic Tract Lateral Geniculate Nucleus/ Superior Colliculus Optic Radiation Visual Cortex

  3. WHO: 161 million visually impaired people in the world (~2.6% of the total population) • 124 million (about 2%) had low vision • 37 million (about 0.6%) were blind Cataract: Vision recovery may be possible (e.g. artificial lens) Glaucoma: Irreversible vision loss National Eye Institute

  4. Advantages of MRI: • Non-invasive; • No in-depth limitation (allows whole brain/eye imaging); • Does not rely on light (cataract OK); • Longitudinal monitoring; • Quantitative/semi-quantitative • Multimodality (structure, metabolism, functional, etc.) Disadvantages of MRI: • Ferromagnetic implants X (projectile effect) • Long scan time • Sensitive to Motions (motion artifact) • Claustrophobia X (anaesthesia might be needed) • Pregnancy not preferred; kids require short scan time • High cost

  5. Basic Principles 3D & Fast MRI 2D MRI Chemistry Physics Physics Physics Chemistry Physiology & Medicine 1D NMR

  6. Basic Principles MagneticResonanceImaging (MRI) (Magnet) 3 Major Components No Applied Field Applied Field (Bo) Magnet Larmor Equation: ωo Precession (Larmor) frequency Bo Magnetic field strength Gyromagnetic ratio

  7. Basic Principles (RF Coil) MagneticResonanceImaging (MRI) Precession frequency Magnetic field strength Gyromagnetic ratio Relaxation (RF Energy Released) Excitation (Energy Gained) Magnet (B0) only Magnet (B0) + RF pulse (B1) at ω Magnet (B0) only Bo Bo Bo B1 at ω

  8. Basic Principles MagneticResonanceImaging (MRI) (Gradient Coil) Excitation (Energy Gained) Gradient X Gradient X Magnet (B0) + Gradient (ΔB) + RF pulse (B1) at ωo ωo ωo -Δω ωo +Δω

  9. Precession frequency MRI scanners Magnetic field strength Earth’s magnetic field = 0.5 Gauss 1 Tesla (T) = 10,000 Gauss Higher static magnetic field (B0) -> Better SNR.  Gyromagnetic ratio 3T Siemens MR brain scanner 7T Siemens MR whole body scanner 7T Bruker animal MR scanner 9.4T Agilent animal MR scanner Human MRI 1.5T(64MHz) 3T(128MHz) 7T(300MHz) Animal MRI 4.7T(200MHz) 7T(300MHz) 9.4T(400MHz) 11.7T(500MHz)

  10. MRI Contrasts/Parameters Multimodal MRI • T1 Relaxation Time • T2 or T2* Relaxation Time • Proton Density • Diffusion • Spectroscopy • Contrast enhancement • Perfusion • Magnetization Transfer, etc. • Structural • Metabolic • Physiological • Functional • Cellular • Molecular, etc.

  11. Animal Glaucoma MRI: Rat/mouse models of chronic ocular hypertension Blockade of aqueous humour outflow Mimic chronic glaucoma in humans Structural MRI:Diffusion tensor MR imaging Metabolic MR spectroscopy:Proton MR spectroscopy Functional MRI:Manganese-enhanced fMRI

  12. Human Glaucoma MRI: American Glaucoma Society Coding System Early Glaucoma – Visual field defect in one hemifield and not involving central 10 deg Advanced Glaucoma – Visual field defect in 2 hemifields or involving central 10 deg Healthy Controls MRI 1. Anatomical MRI: 3D High-resolution T1-weighted MR imaging 2. Micro-Structural MRI: Diffusion tensor MR imaging 3. Metabolic MR Spectroscopy: Proton MRS of neurochemistry 4. Functional MRI: Blood-oxygen-level-dependent fMRI

  13. Glaucoma as a Brain Disease? 1. Structural MRI A. Imaging Glaucoma in the Brain’s Visual System 2. Metabolic MR Spectroscopy 3. Functional MRI and relationships with structural and functional clinical ophthalmic measurements B. Structural-Metabolic-Functional Relationships within the Brain’s Visual System in Glaucoma

  14. Glaucoma as a Brain Disease? 1. Structural MRI A. Imaging Glaucoma in the Brain’s Visual System 2. Metabolic MR Spectroscopy 3. Functional MRI and relationships with structural and functional clinical ophthalmic measurements B. Structural-Metabolic-Functional Relationships within the Brain’s Visual System in Glaucoma

  15. Human Glaucoma MRI Anatomical T1-weighted MRI (1x1x1 mm3) Intraorbital Optic Nerve (~3mm behind globe) Optic Nerve Early Adv. Optic Chiasm L R Optic Chiasm Early Glaucoma Advanced Glaucoma

  16. Water diffusion probes microscopic structures in the brain Anisotropic diffusion Free diffusion Fasciculus Axon λ// axon λ┴ Fractional Anisotropy λ┴: Radial Diffusivity λ//: Axial Diffusivity Microstructural Diffusion Tensor MR imaging (DTI): Nerve fiber White matter fiber bundles

  17. Basic and Clinical Applications of Diffusion Tensor Imaging High-definition fiber tracking http://schneiderlab.lrdc.pitt.edu/

  18. λ//: Axial Diffusivity; λ┴: Radial Diffusivity

  19. Diffusion Tensor MRI detects loss of microstructural integrity in the glaucomatous optic nerve Animal Glaucoma MRI Fractional Anisotropy Map Week 1 Week 4 L R Toluidine blue stain Control (L) Injured (R) λ// Optic Nerve λ┴ Fractional Anisotropy Hui, Ho, Chan et al. ISMRM 2007; ISMRM 2014

  20. Human Glaucoma MRI Microstructural diffusion tensor MRI (DTI) of Optic Radiation λ// λ┴ Optic Radiation Fractional Anisotropy (FA) Lower Fractional Anisotropy (FA) in Advanced Glaucoma < Early Glaucoma -> Transneuronal degeneration?

  21. Glaucoma as a Brain Disease? 1. Structural MRI A. Imaging Glaucoma in the Brain’s Visual System 2. Metabolic MR Spectroscopy 3. Functional MRI and relationships with structural and functional clinical ophthalmic measurements B. Structural-Metabolic-Functional Relationships within the Brain’s Visual System in Glaucoma

  22. Metabolic MR Spectroscopy of Neurochemistry in Visual Cortex in Glaucoma Animal Glaucoma MRS (N-acetyl-aspartate) Cho reduction (Creatine) (Choline) (Glutamate) Coronal • Underlying pathophysiological mechanisms of glaucoma might be associated with the dysfunction of the cholinergic nervous system in the visual pathway. R L Visual Cortex Chan et al. Exp Eye Res, 2009

  23. Human Glaucoma MRS Clinical OCT Retinal Thickness reports Metabolic MR Spectroscopy (MRS) of Visual Cortex Visual Cortex Humphrey Visual Field Function Report

  24. Glaucoma as a Brain Disease? 1. Structural MRI A. Imaging Glaucoma in the Brain’s Visual System 2. Metabolic MR Spectroscopy 3. Functional MRI and relationships with structural and functional clinical ophthalmic measurements B. Structural-Metabolic-Functional Relationships within the Brain’s Visual System in Glaucoma

  25. Animal Glaucoma fMRI L R Partial Transection of superior optic nerve b Manganese-enhanced functional MRI of anterograde axonal transport Chan et al, NeuroImage, 2011

  26. Animal Glaucoma fMRI Reduced anterograde axonal transport of manganese ions in the glaucomatous optic nerve at Week 6 but not Week 2 after ocular hypertension induction. Coronal view Axial view Reduced Mn2+ transport Optic Nerve Sagittal view Chan et al, NeuroImage, 2008

  27. Human Glaucoma fMRI

  28. Human Glaucoma fMRI Blood-oxygenation-level-dependent (BOLD) functional MRI of Visual Cortex Upper Visual Field Stimulation Lower Visual Field Stimulation Early Glaucoma Visual Cortex Advanced Glaucoma Weaker brain functional responses in more advanced glaucoma patients

  29. Glaucoma as a Brain Disease? 1. Structural MRI A. Imaging Glaucoma in the Brain’s Visual System 2. Metabolic MR Spectroscopy 3. Functional MRI and relationships with structural and functional clinical ophthalmic measurements B. Structural-Metabolic-Functional Relationships within the Brain’s Visual System in Glaucoma

  30. Ocular MRI Multimodal Optical/MR imaging of Retinal Layer Properties Typical OCT Mn-MRI, rat, 25x25x800 μm3 Duong, et al, NMR Biomed 2008 Cr-MRI, rat, 50x50x50 μm3 [Chan KC, et al MRM 2012)] Gd-MRI, rat, 10x10x14 μm3 Duong, et al, ISMRM 2011

  31. Basic and Clinical Applications of Diffusion Tensor Imaging Ocular MRI MNTP 2012 47x47x400 um at 11.7T Wild type mouse eye (Red: photoreceptor layer parallel to optic nerve; Blue: lens cortex // neural retina ) Retinal degeneration 1 (rd1) mouse eye Note loss of photoreceptor layer 27

  32. Ocular MRI in Glaucoma

  33. Conclusion / Take Home Messages Neuroimaging techniques (e.g. MRI/MRS) may offer biomarkers for non-invasive assessments of the structural, metabolic and functional properties of the eye and brain’s visual system complementary to current ophthalmic clinical diagnosis. Glaucoma is a neurodegenerative disease of the visual system (involving the brain apart from the eye) From bench to bedside and back again (animal glaucoma MRI <-> human glaucoma MRI)

  34. References/Further Readings http://www.imaios.com/en/e-Courses/e-MRI

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