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

3. 124 million (about 2%) had low vision
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. 1D NMR 2D MRI 3D & Fast MRI Basic Principles Physics Physics Physics
Chemistry
Chemistry
Physiology & Medicine

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

7. Magnetic Resonance Imaging (MRI)
Basic Principles
Magnetic Resonance Imaging (MRI)
(RF Coil)
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. Magnet (B0) + Gradient (ΔB)
Basic Principles
Magnetic Resonance Imaging (MRI)
(Gradient Coil)
Excitation (Energy Gained)
Gradient X
Gradient X
Magnet (B0) + Gradient (ΔB)
+ RF pulse (B1) at ωo
ωo -Δω ωo
ωo +Δω

9. MRI scanners Human MRI 1.5T (64MHz) 3T (128MHz) 7T (300MHz) Animal MRI
Precession frequency
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
Human MRI
1.5T (64MHz)
3T (128MHz)
7T (300MHz)
Animal MRI
4.7T (200MHz)
9.4T(400MHz)
11.7T (500MHz)
3T Siemens MR brain scanner
7T Siemens MR whole body scanner
7T Bruker animal MR scanner
9.4T Agilent animal MR scanner

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: Structural MRI: Diffusion tensor MR imaging
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?
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

14. 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

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

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

17. High-definition fiber tracking
Basic and Clinical Applications of Diffusion Tensor Imaging
High-definition fiber tracking

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

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

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

21. 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

22. Metabolic MR Spectroscopy of Neurochemistry in Visual Cortex in Glaucoma
Animal Glaucoma MRS
Visual
Cortex
(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. L R
Chan et al. Exp Eye Res, 2009

23. Metabolic MR Spectroscopy (MRS) Humphrey Visual Field Function Report
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?
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

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

26. Animal Glaucoma fMRI Coronal view Axial Sagittal
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
Sagittal
Reduced Mn2+ transport
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?
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

30. Cr-MRI, rat, 50x50x50 μm3 [Chan KC, et al MRM 2012)]
Ocular MRI
Multimodal Optical/MR imaging of Retinal Layer Properties
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)]

31. Ocular MRI 47x47x400 um at 11.7T Wild type mouse eye
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