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
Rodent visual pathway
Retina
52%
48%
Optic Nerve
Optic Chiasm
>90%
<10%
Optic Tract
Lateral Geniculate Nucleus/
Superior Colliculus
Optic Radiation
Visual Cortex
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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
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INTBP2100 Biology of Vision - Imaging of the Visual System with MRI
Advantages of MRI:
•
•
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•
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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
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Basic Principles
INTBP2100 Biology of Vision - Imaging of the Visual System with MRI
1D NMR
Physics
Physics
2D MRI 3D & Fast MRI
Physics Chemistry Chemistry Physiology & Medicine
5
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
ωo
Larmor Equation:
Precession (Larmor) frequency
Bo
  B
Gyromagnetic ratio
Magnetic
field strength
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Basic Principles
INTBP2100 Biology of Vision - Imaging of the Visual System with MRI
(RF Coil)
Magnetic Resonance Imaging (MRI)
Precession frequency
  B
Gyromagnetic ratio
Magnet (B0) only
Magnetic
field strength
Excitation (Energy Gained)
Relaxation
(RF Energy Released)
Magnet (B0) + RF pulse (B1) at ω
Magnet (B0) only
Bo
Bo
Bo
B1 at ω
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Basic Principles
INTBP2100 Biology of Vision - Imaging of the Visual System with MRI
(Gradient Coil)
Magnetic Resonance Imaging (MRI)
Excitation (Energy Gained)
Gradient X
Gradient X
  B
Magnet (B0) + Gradient (ΔB)
+ RF pulse (B1) at ωo
ωo -Δω
ωo
ωo +Δω
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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
  B
Higher static magnetic field (B0)
Gyromagnetic ratio
-> Better SNR.
Magnetic
field strength
Human MRI
1.5T (64MHz)
3T (128MHz)
7T (300MHz)
3T Siemens MR brain scanner 7T Siemens MR whole body scanner
•
•
•
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•
Animal MRI
4.7T (200MHz)
7T (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
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•
T1 Relaxation Time
T2 or T2* Relaxation Time
Proton Density
Diffusion
Spectroscopy
Contrast enhancement
Perfusion
Magnetization Transfer, etc.
Multimodal MRI
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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
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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
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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
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 mm3)
Intraorbital Optic Nerve (~3mm behind globe)
Optic
Nerve
Early
Adv.
Advanced
Glaucoma
Optic
Chiasm
Early
Glaucoma
Optic Chiasm
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
axon
Axon
Anisotropic diffusion
Fasciculus
λ//
Nerve fiber
λ┴
White matter fiber bundles
Fractional Anisotropy
λ//: Axial Diffusivity
λ┴: Radial Diffusivity
andofClinical
of Diffusion
Tensorwith
Imaging
INTBP2100Basic
Biology
Vision Applications
- Imaging of the
Visual System
MRI
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
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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//
Lower Fractional Anisotropy (FA) in
Advanced Glaucoma < Early Glaucoma
-> Transneuronal degeneration?
λ┴
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
(N-acetyl-aspartate)
Cho reduction
(Creatine)
(Choline)
Coronal
Visual
Cortex
(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
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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
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INTBP2100 Biology of Vision - Imaging of the Visual System with MRI
Animal Glaucoma fMRI
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 Mn2+ transport
Chan et al, NeuroImage, 2008
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INTBP2100 Biology of Vision - Imaging of the Visual System with MRI
Human
Glaucoma fMRI
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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
Lower Visual
Field Stimulation
Visual
Cortex
Advanced Glaucoma
Early Glaucoma
Upper Visual
Field Stimulation
Weaker brain functional responses in more advanced glaucoma patients
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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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Ocular MRI
INTBP2100 Biology of Vision - Imaging of the Visual System with MRI
Typical OCT
Mn-MRI, rat,
25x25x800 μm3
Duong, et al, NMR
Biomed 2008
Gd-MRI, rat,
10x10x14 μm3
Duong, et al, ISMRM
2011
Cr-MRI, rat, 50x50x50 μm3
[Chan KC, et al MRM 2012)]
Ocular MRI
andofClinical
of Diffusion
Tensorwith
Imaging
INTBP2100Basic
Biology
Vision Applications
- Imaging of the
Visual System
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
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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)
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References/Further Readings
http://www.imaios.com/en/e-Courses/e-MRI