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INTBP2100 Biology of Vision - Imaging of the Visual System with MRI Kevin C. Chan, PhD Assistant Professor Neuroimaging Laboratory, Departments of Ophthalmology.

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Presentation on theme: "INTBP2100 Biology of Vision - Imaging of the Visual System with MRI Kevin C. Chan, PhD Assistant Professor Neuroimaging Laboratory, Departments of Ophthalmology."— Presentation transcript:

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 1

2 INTBP2100 Biology of Vision - Imaging of the Visual System with MRI 2 Human visual pathway Rodent visual pathway Retina Optic Nerve Optic Chiasm Optic Tract Lateral Geniculate Nucleus/ Superior Colliculus Optic Radiation Visual Cortex 52% 48% >90% <10% Basic Anatomy of Human and Rodent Visual Systems:

3 INTBP2100 Biology of Vision - Imaging of the Visual System with MRI 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 National Eye Institute Cataract: Vision recovery may be possible (e.g. artificial lens) Glaucoma: Irreversible vision loss

4 INTBP2100 Biology of Vision - Imaging of the Visual System with MRI 4 Advantages of MRI: Disadvantages 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.) 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 INTBP2100 Biology of Vision - Imaging of the Visual System with MRI 5 Physics Chemistry Physiology & Medicine 1D NMR 2D MRI 3D & Fast MRI Basic Principles

6 INTBP2100 Biology of Vision - Imaging of the Visual System with MRI 6 Magnetic Resonance Imaging (MRI) Gyromagnetic ratio Magnetic field strength Precession (Larmor) frequency No Applied Field Applied Field (Bo) Magnet Larmor Equation: Bo ωoωo 3 Major Components (Magnet) Basic Principles

7 INTBP2100 Biology of Vision - Imaging of the Visual System with MRI 7 Magnetic Resonance Imaging (MRI) Gyromagnetic ratio Magnetic field strength Precession frequency Magnet (B 0 ) only Magnet (B 0 ) + RF pulse (B 1 ) at ω Bo B 1 at ω Excitation (Energy Gained) Relaxation (RF Energy Released) Magnet (B 0 ) only Bo (RF Coil) Basic Principles

8 INTBP2100 Biology of Vision - Imaging of the Visual System with MRI 8 Magnetic Resonance Imaging (MRI) Magnet (B 0 ) + Gradient (ΔB) + RF pulse (B 1 ) at ω o Excitation (Energy Gained) ωoωo ω o +Δωω o -Δω Gradient X (Gradient Coil) Basic Principles

9 INTBP2100 Biology of Vision - Imaging of the Visual System with MRI MRI scanners Human MRI 1.5T (64MHz) 3T (128MHz) 7T (300MHz) Animal MRI 4.7T (200MHz) 7T (300MHz) 9.4T (400MHz) 11.7T (500MHz) 9 Earth’s magnetic field = 0.5 Gauss 1 Tesla (T) = 10,000 Gauss 3T Siemens MR brain scanner7T Siemens MR whole body scanner 9.4T Agilent animal MR scanner 7T Bruker animal MR scanner Gyromagnetic ratio Magnetic field strength Precession frequency Higher static magnetic field (B 0 ) -> Better SNR.

10 INTBP2100 Biology of Vision - Imaging of the Visual System with MRI 10 Multimodal MRIMRI Contrasts/Parameters 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 INTBP2100 Biology of Vision - Imaging of the Visual System with MRI 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 11

12 INTBP2100 Biology of Vision - Imaging of the Visual System with MRI 12 Human Glaucoma MRI: 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 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

13 INTBP2100 Biology of Vision - Imaging of the Visual System with MRI 1. Structural MRI 13 2. Metabolic MR Spectroscopy 3. Functional MRI A. Imaging Glaucoma in the Brain’s Visual System B. Structural-Metabolic-Functional Relationships within the Brain’s Visual System in Glaucoma and relationships with structural and functional clinical ophthalmic measurements Glaucoma as a Brain Disease?

14 INTBP2100 Biology of Vision - Imaging of the Visual System with MRI 1. Structural MRI 14 2. Metabolic MR Spectroscopy 3. Functional MRI A. Imaging Glaucoma in the Brain’s Visual System B. Structural-Metabolic-Functional Relationships within the Brain’s Visual System in Glaucoma and relationships with structural and functional clinical ophthalmic measurements Glaucoma as a Brain Disease?

15 INTBP2100 Biology of Vision - Imaging of the Visual System with MRI Intraorbital Optic Nerve (~3mm behind globe) Anatomical T1-weighted MRI (1x1x1 mm 3 ) Optic Chiasm Human Glaucoma MRI Early Adv. Optic Nerve LR Advanced Glaucoma Early Glaucoma Optic Chiasm

16 INTBP2100 Biology of Vision - Imaging of the Visual System with MRI axon Nerve fiberWhite matter fiber bundles Microstructural Diffusion Tensor MR imaging (DTI): Fasciculus Axon λ // λ┴λ┴ Fractional Anisotropy Water diffusion probes microscopic structures in the brain Free diffusion Anisotropic diffusion λ //: Axial Diffusivity λ ┴: Radial Diffusivity

17 INTBP2100 Biology of Vision - Imaging of the Visual System with MRI Basic and Clinical Applications of Diffusion Tensor Imaging http://schneiderlab.lrdc.pitt.edu/ High-definition fiber tracking

18 INTBP2100 Biology of Vision - Imaging of the Visual System with MRI 18 λ //: Axial Diffusivity;λ ┴: Radial Diffusivity

19 INTBP2100 Biology of Vision - Imaging of the Visual System with MRI Diffusion Tensor MRI detects loss of microstructural integrity in the glaucomatous optic nerve Hui, Ho, Chan et al. ISMRM 2007; ISMRM 2014 LR Week 1 Week 4 Toluidine blue stain Fractional Anisotropy Map Injured (R) Control (L) Animal Glaucoma MRI Optic Nerve λ // λ┴λ┴ Fractional Anisotropy

20 INTBP2100 Biology of Vision - Imaging of the Visual System with MRI Microstructural diffusion tensor MRI (DTI) of Optic Radiation λ // λ┴λ┴ Fractional Anisotropy (FA) Lower Fractional Anisotropy (FA) in Advanced Glaucoma < Early Glaucoma -> Transneuronal degeneration? Human Glaucoma MRI Optic Radiation

21 INTBP2100 Biology of Vision - Imaging of the Visual System with MRI 1. Structural MRI 21 2. Metabolic MR Spectroscopy 3. Functional MRI A. Imaging Glaucoma in the Brain’s Visual System B. Structural-Metabolic-Functional Relationships within the Brain’s Visual System in Glaucoma and relationships with structural and functional clinical ophthalmic measurements Glaucoma as a Brain Disease?

22 INTBP2100 Biology of Vision - Imaging of the Visual System with MRI Visual Cortex Metabolic MR Spectroscopy of Neurochemistry in Visual Cortex in Glaucoma Chan et al. Exp Eye Res, 2009 22 Coronal Cho reduction Underlying pathophysiological mechanisms of glaucoma might be associated with the dysfunction of the cholinergic nervous system in the visual pathway. Animal Glaucoma MRS (N-acetyl-aspartate) (Creatine) (Choline) (Glutamate) L R

23 INTBP2100 Biology of Vision - Imaging of the Visual System with MRI Metabolic MR Spectroscopy (MRS) of Visual Cortex Humphrey Visual Field Function Report Clinical OCT Retinal Thickness reports Human Glaucoma MRS Visual Cortex

24 INTBP2100 Biology of Vision - Imaging of the Visual System with MRI 1. Structural MRI 24 2. Metabolic MR Spectroscopy 3. Functional MRI A. Imaging Glaucoma in the Brain’s Visual System B. Structural-Metabolic-Functional Relationships within the Brain’s Visual System in Glaucoma and relationships with structural and functional clinical ophthalmic measurements Glaucoma as a Brain Disease?

25 INTBP2100 Biology of Vision - Imaging of the Visual System with MRI Manganese-enhanced functional MRI of anterograde axonal transport 25 L R b Chan et al, NeuroImage, 2011 Partial Transection of superior optic nerve Animal Glaucoma fMRI

26 INTBP2100 Biology of Vision - Imaging of the Visual System with MRI 26 Reduced anterograde axonal transport of manganese ions in the glaucomatous optic nerve at Week 6 but not Week 2 after ocular hypertension induction. Reduced Mn 2+ transport Chan et al, NeuroImage, 2008 Coronal view Axial view Sagittal view Animal Glaucoma fMRI Optic Nerve

27 INTBP2100 Biology of Vision - Imaging of the Visual System with MRI 27 Human Glaucoma fMRI

28 INTBP2100 Biology of Vision - Imaging of the Visual System with MRI 28 Blood-oxygenation-level-dependent (BOLD) functional MRI of Visual Cortex Early Glaucoma Advanced Glaucoma Upper Visual Field Stimulation Lower Visual Field Stimulation Human Glaucoma fMRI Weaker brain functional responses in more advanced glaucoma patients Visual Cortex

29 INTBP2100 Biology of Vision - Imaging of the Visual System with MRI 1. Structural MRI 29 2. Metabolic MR Spectroscopy 3. Functional MRI A. Imaging Glaucoma in the Brain’s Visual System B. Structural-Metabolic-Functional Relationships within the Brain’s Visual System in Glaucoma and relationships with structural and functional clinical ophthalmic measurements Glaucoma as a Brain Disease?

30 INTBP2100 Biology of Vision - Imaging of the Visual System with MRI Typical OCT Mn-MRI, rat, 25x25x800 μm 3 Duong, et al, NMR Biomed 2008 Gd-MRI, rat, 10x10x14 μm 3 Duong, et al, ISMRM 2011 Cr-MRI, rat, 50x50x50 μm 3 [Chan KC, et al MRM 2012)] Ocular MRI

31 INTBP2100 Biology of Vision - Imaging of the Visual System with MRI MNTP 2012 Basic and Clinical Applications of Diffusion Tensor Imaging 27 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 Ocular MRI

32 INTBP2100 Biology of Vision - Imaging of the Visual System with MRI 32 Ocular MRI in Glaucoma

33 INTBP2100 Biology of Vision - Imaging of the Visual System with MRI 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) 33

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


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