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

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

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

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

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 3

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

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 4

Basic Principles

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

1D NMR 2D MRI 3D & Fast MRI

Physics Physics Physics Chemistry Chemistry Physiology & Medicine

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Basic Principles

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

(Magnet)

Magnetic Resonance Imaging

(MRI)

3 Major Components No Applied Field Applied Field (Bo) Magnet

Bo

ω o

Larmor Equation: Precession (Larmor) frequency

  

B

Magnetic field strength Gyromagnetic ratio 6

Basic Principles

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

Magnetic

(RF Coil)

Resonance Imaging

(MRI)

Precession frequency

 Gyromagnetic ratio  

B

Magnetic field strength Magnet (B 0 ) only

Bo Excitation

(Energy

Gained

) Magnet (B 0 ) + RF pulse (B 1 ) at ω

Bo B 1 at

ω

Relaxation

(RF Energy

Released

) Magnet (B 0 ) only

Bo

7

Basic Principles

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

Magnetic Resonance

(Gradient Coil)

Imaging

(MRI)

Gradient X Gradient X

  

B

Excitation

(Energy

Gained

) Magnet (B 0 ) +

Gradient ( ΔB)

+ RF pulse (B 1 ) at ω o ω o Δω ω o ω o + Δω 8

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

MRI scanners

Earth’s magnetic field = 0.5 Gauss 1 Tesla (T) = 10,000 Gauss Precession frequency Higher static magnetic field (B 0 ) -> Better SNR.

  Gyromagnetic ratio 

B

Magnetic field strength • • • • Human MRI 1.5T

( 64MHz ) 3T 7T ( 128MHz ) ( 300MHz )

3T Siemens MR brain scanner 7T Siemens MR whole body scanner

• • • • • Animal MRI 4.7T

7T ( 200MHz ) ( 300MHz ) 9.4T

( 400MHz ) 11.7T

(

500MHz

)

7T Bruker animal MR scanner 9.4T Agilent animal MR scanner

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

MRI Contrasts/Parameters • T1 Relaxation Time • T2 or T2* Relaxation Time • Proton Density • Diffusion • Spectroscopy • Contrast enhancement • Perfusion • Magnetization Transfer, etc.

Multimodal MRI • Structural • Metabolic • Physiological • Functional • Cellular • Molecular, etc.

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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

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

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 12

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

Glaucoma as a Brain Disease?

A. Imaging Glaucoma in the Brain’s Visual System

1. Structural MRI 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

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

Glaucoma as a Brain Disease?

A. Imaging Glaucoma in the Brain’s Visual System 1. Structural MRI

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

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

Human Glaucoma MRI

Anatomical T1-weighted MRI (1x1x1 mm 3 )

Intraorbital Optic Nerve (~3mm behind globe)

Optic Nerve Early

Optic Chiasm

Optic Chiasm Adv.

L R

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

• Microstructural Diffusion Tensor MR imaging (DTI): Water diffusion probes microscopic structures in the brain

Free diffusion Anisotropic diffusion Fasciculus Nerve fiber White matter fiber bundles

Fractional Anisotropy λ ┴ λ //: Axial Diffusivity λ ┴: Radial Diffusivity λ //

High-definition fiber tracking

http://schneiderlab.lrdc.pitt.edu/

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

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

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

Animal Glaucoma MRI Diffusion Tensor MRI detects loss of microstructural integrity in the glaucomatous optic nerve

Fractional Anisotropy Map

Week 1 Week 4 Optic Nerve

L R Toluidine blue stain

Control (L) Injured (R) λ // λ ┴ Fractional Anisotropy Hui, Ho, Chan et al. ISMRM 2007; ISMRM 2014

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

Human Glaucoma MRI

Microstructural diffusion tensor MRI (DTI) of Optic Radiation

Optic Radiation

Fractional Anisotropy (FA)

λ // λ ┴ Lower Fractional Anisotropy (FA) in Advanced Glaucoma < Early Glaucoma

-> Transneuronal degeneration?

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

Glaucoma as a Brain Disease?

A. Imaging Glaucoma in the Brain’s Visual System

1. Structural MRI

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

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

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

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

Human Glaucoma MRS

Metabolic MR Spectroscopy (MRS) of Visual Cortex Clinical OCT Retinal Thickness reports

Visual Cortex

Humphrey Visual Field Function Report

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

Glaucoma as a Brain Disease?

A. Imaging Glaucoma in the Brain’s Visual System

1. Structural MRI 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

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

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

Animal Glaucoma fMRI

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

Optic Nerve 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 Sagittal view

Reduced Mn 2+ transport

Chan et al, NeuroImage, 2008 26

Human Glaucoma fMRI

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

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

Human Glaucoma fMRI

Blood-oxygenation-level-dependent (BOLD) functional MRI of Visual Cortex

Upper Visual Field Stimulation Lower Visual Field Stimulation Visual Cortex Weaker brain functional responses in more advanced glaucoma patients 28

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

Glaucoma as a Brain Disease?

A. Imaging Glaucoma in the Brain’s Visual System

1. Structural MRI 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

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Ocular 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

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

Cr-MRI, rat, 50x50x50 μm 3

[Chan KC, et al MRM 2012)]

Ocular MRI Retinal degeneration 1 (rd1) mouse eye Note loss of photoreceptor layer MNTP 2012 47x47x400 um at 11.7T

Wild type mouse eye (Red: photoreceptor layer parallel to optic nerve; Blue: lens cortex // neural retina ) 27

Ocular MRI in Glaucoma

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

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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

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