High resolution, quantitative MR neuroimaging at 7 Tesla: A

reliable measure of iron, myelin and volumetric changes?

Steffen Bollmann – Centre for Advanced Imaging

University of Queensland, Australia

What is Quantitative Imaging?

provides quantitative measures of specific MRI parameters

of brain tissue (Weiskopf et al. 2015, Current Opinion in Neurology)

For example:

volume / thickness of certain structures

relaxation Times T1, T2, T2*

Susceptibility

Steffen Bollmann - Centre for Advanced Imaging, University of Queensland, Australia 2

T1 map T2* map Susceptibility mapVolumetry

Why Quantitative Imaging?

theoretically free from bias such as the transmit and receive

profiles of radio-frequency coils (Weiskopf et al. 2015, Current Opinion in Neurology)

“true” biological tissue parameters high degree of

comparability across different scanners / imaging centres (Weiskopf et al. 2015, Current Opinion in Neurology)

enables tracking of longitudinal changes in microstructure and

identify subtle differences (Weiskopf et al. 2015, Current Opinion in Neurology)

Steffen Bollmann - Centre for Advanced Imaging, University of Queensland, Australia 3

T1

weighted

T1

map

Quantitative Imaging at ultra-high field

Will 7 Tesla MRI enable us to measure

iron, myelin and hippocampal subfield volumes?

Steffen Bollmann - Centre for Advanced Imaging, University of Queensland, Australia 4

T1 map T2* map Susceptibility mapVolumetry

Quantitative Imaging at ultra-high field

Will 7 Tesla MRI enable us to measure

iron, myelin and hippocampal subfield volumes?

Steffen Bollmann - Centre for Advanced Imaging, University of Queensland, Australia 5

T1 map T2* map Susceptibility mapVolumetry

The data is from a project in close collaboration with Lars Marstaller, where we

aim to segment the Hippocampus and the Amygdala in neurodegenerative diseases

Quantifying Volume

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3T – MP2RAGE - 1mm isotropic

Quantifying Volume

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7T – MP2RAGE - 0.5mm isotropic

Quantifying Volume

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7T – MP2RAGE - 0.5mm isotropic + fs v6 segm.

Quantifying Volume

Steffen Bollmann - Centre for Advanced Imaging, University of Queensland, Australia 9

7T – MP2RAGE - 0.5mm isotropic

Quantifying Volume

Steffen Bollmann - Centre for Advanced Imaging, University of Queensland, Australia 10

7T –TSE - 0.3mm in-plane

Quantifying Volume

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7T –TSE - 0.3mm in-plane + MP2RAGE fs6 segm.

Quantifying Volume

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7T –TSE - 0.3mm in-plane + Multispectral fs6 segm.

Quantifying Volume

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How stable are the segmentation results across 3 scans in a healthy individual?

0

100

200

300

400

500

600

700

1 2 3

Subfield

Volu

me in m

m3

Scan 1, 2, 3

left_subiculum

left_Hippocampal_tail

left_CA1

left_hippocampal-fissure

left_parasubiculum

left_presubiculum

left_HATA

left_fimbria

left_CA4

left_CA3

left_GC-ML-DG

left_molecular_layer_HP

~5% Test-retest variability

Quantitative Imaging at ultra-high field

Will 7 Tesla MRI enable us to measure

iron, myelin and hippocampal subfield volumes?

Steffen Bollmann - Centre for Advanced Imaging, University of Queensland, Australia 14

T1 map T2* map Susceptibility mapVolumetry

Myelin and iron

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How can quantitative imaging help us to get information about myelin and iron in the brain?

myelination: reduced T1(Schmierer et al. 2004, Ann Neurol), T2(Laule et al. 2006, Multiple Scler),

reduced T2*(Langkammer et al. 2012, NI)

reduced susceptibility(Langkammer et al. 2012, NI)

iron load: reduced T1(Gelman et al. 2001, MRM), T2

reduced T2*(Langkammer et al. 2010, Radiology)

increased susceptibility(Langkammer et al. 2010, Radiology)

A clever combination and modelling of different maps could allow us to disentangle the contributions of myelin and iron

Quantitative Imaging at ultra-high field

Will 7 Tesla MRI enable us to measure

iron, myelin and hippocampal subfield volumes?

Steffen Bollmann - Centre for Advanced Imaging, University of Queensland, Australia 16

T1 map T2* map Susceptibility mapVolumetry

T1 map using MP2RAGE

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Marques et al. 2010, NeuroImage

Marques et al. 2013, PLoS ONE

e.g. via lookup tables:

T1 map using MP2RAGE

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T1 maps show

highly myelinated

areas such as

sensory-motor

auditory and

visual cortex

Marques et al. 2013, PLoS ONE

Quantitative Imaging at ultra-high field

Will 7 Tesla MRI enable us to measure

iron, myelin and hippocampal subfield volumes?

Steffen Bollmann - Centre for Advanced Imaging, University of Queensland, Australia 19

T1 map T2* map Susceptibility mapVolumetry

Iron and T2* in V1/V2

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[Fukunaga et

al. 2010, NI]

T2* iron staining

T2* similar to

iron staining

myelin staining

But: Distribution of

intracortical iron

mimics that of myelin

Quantitative Imaging at ultra-high field

Will 7 Tesla MRI enable us to measure

iron, myelin and hippocampal subfield volumes?

Steffen Bollmann - Centre for Advanced Imaging, University of Queensland, Australia 21

T1 map T2* map Susceptibility mapVolumetry

(Quantitative) Susceptibility Map

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0.75 mm,

GRE, 7T

Acquiring QSM fast

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Daniel Stäb, Steffen Bollmann, Christian Langkammer, Kristian Bredies, Markus Barth -

Accelerated Mapping of Magnetic Susceptibility Using 3D Planes-on-a-

Paddlewheel (POP) EPI at Ultra-High Field Strength (in review)

Standard 2D EPI trajectory 3D POP trajectory Plane/projection order

… and with little distortion.

Steffen Bollmann - Centre for Advanced Imaging, University of Queensland, Australia 24

GRE

4min

EPI

16s

EPI

16s

GRE

4min

Acquiring QSM fast

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Acquiring QSM fast

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(Quantitative) Susceptibility Map

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Susceptibility is claimed to be a direct measure of

non-haem iron (Weiskopf et al. 2015, Current Opinion in Neurology)

oligodendrocytes and iron (Todorich et al. 2009, Glia)

oligodendrocytes produce myelin

oligodendrocytes require constant iron delivery (by

transferrin and H-ferritin)

but: continued iron accumulation with age oxidative stress

indicator of neurodegenerative processes and myelin breakdown in

Alzheimer's, Huntingdon's, and Parkinson's disease

QSM, T1map, T2* map

Steffen Bollmann - Centre for Advanced Imaging, University of Queensland, Australia 28

Quantitative Imaging at ultra-high field

Will 7 Tesla MRI enable us to measure

iron, myelin and hippocampal subfield volumes?

Steffen Bollmann - Centre for Advanced Imaging, University of Queensland, Australia 29

T1 map T2* map Susceptibility mapVolumetry

One Approach: R1, R2*, QSM + GLM

Steffen Bollmann - Centre for Advanced Imaging, University of Queensland, Australia 30

T1, T2* and χ are all linearly related to iron and myelin concentrations (Schaefer, ESMRMB 2014 & Stueber et al. 2014, NI)

Paramagnetic contribution eg. ions

of metals (iron, magnesium,

gadolinium)

-> unpaired electrons -> positive

magnetic susceptibility

𝑇1 = 𝑎𝑃𝑎𝑟𝑎 ∗ 𝑐𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛𝑃𝑎𝑟𝑎 + 𝑎𝑑𝑖𝑎 ∗ 𝑐𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛𝑑𝑖𝑎 + 𝑎𝑜𝑓𝑓

𝑇2∗ = 𝑏𝑃𝑎𝑟𝑎 ∗ 𝑐𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛𝑃𝑎𝑟𝑎 + 𝑏𝑑𝑖𝑎 ∗ 𝑐𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛𝑑𝑖𝑎 + 𝑏𝑜𝑓𝑓

𝜒 = 𝑐𝑃𝑎𝑟𝑎 ∗ 𝑐𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛𝑃𝑎𝑟𝑎 + 𝑐𝑑𝑖𝑎 ∗ 𝑐𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛𝑑𝑖𝑎 + 𝑐𝑜𝑓𝑓

Diamagnetic contribution eg.

water, copper, nitrogen, barium

sulfate

-> no intrinsic magnetic moment -

> negative magnetic susceptibility

One Approach: R1, R2*, QSM + GLM

Steffen Bollmann - Centre for Advanced Imaging, University of Queensland, Australia 31

“Groundtruth”

PIXE = particle induced

X-ray emission

(Stueber et al. 2014, NI)

GLM

Challenges

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reverse inference is complicated and not unique

e.g.: increased iron concentration can appear as an increase

in myelination in T1 maps (both shorten T1) (Weiskopf et al. 2015, Current Opinion in Neurology)

One way out: multiple measures can be combined to

solve non uniqueness

e.g.: Multiple regression / multivariate models

needed for this to work:

robust estimates of the individual measurements

Forward models linking tissue parameters to MRI parameters

Summary & ToDo List

Steffen Bollmann - Centre for Advanced Imaging, University of Queensland, Australia 33

Quantitative imaging at ultra-high field could offer:

highly reproducible and sensitive measurements to track subtle disease processes in single subjects affecting volume of structures, myelin and iron content in clinically feasible measurement times

For this to work robustly we need to improve on:

even higher resolution we need laminar information

More stable mapping and fitting procedures for T1, T2*, QSM

Models linking histology and MRI parameters e.g. what are the microstructural variations caused by amyloid

plaques?

Thank you: Kieran O’Brien, Lars Marstaller, Viktor Vegh, Hana Burianova, Andrew Janke, Alan Hockings, David Butler,

Rients Lootsma, Simon Robinson, Christian Langkammer, David Reutens, Jürgen Götz, Christine Guo, Vinh Nguyen

Contact: cai.uq.edu.au/bollmann Twitter: @stebo85 Funding: UQPRF, NIF