New techniques in MRI of epilepsy Dec 2013

Graeme Jackson,

Neurologist Florey Institute of Neuroscience and Mental Health,

Melbourne, Australia

American Epilepsy Society | Annual Meeting

Disclosure

None

American Epilepsy Society | 2013 Annual Meeting

Learning Objectives

• To provide an overview of the range of advanced MRI techniques that can be applied to patients with epilepsy.

•To be able to demand an ‘epilepsy protocol’ MRI

•To understand the concept of epileptic networks and the techniques available to define these

•To be aware of the range of near-future techniques provided by MRI

American Epilepsy Society | 2013 Annual Meeting

Outline

• Acquisition - the epilepsy protocol

• Analysis - individual v. group findings

• Finding lesions - make ‘obvious’ the unnoticed

• The hippocampus - diagnosis and aetiology

• Epilepsy networks - structural and functional

• ‘connectomics’ - connectome and connectivity

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Neuroscience is the science frontier and genetics and imaging are the primary tools of discovery

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Issues in acquisition are essential

Acquisition of images: issues

• Epilepsy protocol essential (T1, T2, FLAIR, SWI)

• MRI and EEG are the primary investigations

• Think of MRI like the EEG – Basic study

– Further effort eg sleep deprived, photic, hyperventilation (additional sequences, fMRI)

– Intensive eg video EEG monitoring (advanced structural analysis)

– Specialist eg intracranial monitoring (EEF fMRI, connectivity measures)

Wellmer et al Epilepsia 2013

Interpretation of MRI

• A large amount of data is generated

• A lesion is only ‘obvious’ once it has been found

• Finding subtle lesions may require the context of other imaging e.g. PET, SPECT

• Techniques for visualisation of data can be crucial

• A focal lesion on MRI is the most important finding for predicting surgical success

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Jackson GD, Badawy RAB. Epilepsy & Behavior. 2011

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Individual patient v. the group

• MRI now has a remarkable range of techniques that can help understand epilepsy

• Some apply directly to individual patient care, and some apply to understanding the disease in a group of patients

Kuzniecky and Jackson; Magnetic Resonance in Epilepsy

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Parahippocampal epilepsy with subtle dysplasia:

Pillay et al Epilepsia 2009

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Annals of Neurology 2003 Epilepsia 2006

Structural MRI – the focal lesions

• Hippocampus

• ‘obvious’ structural lesions (cavernoma, hypothalamic hamartoma, nodular heterotopia, major lesions etc)

• Malformations of cortical development

• Small focal abnormalities (BOSD, 2b dysplasia temporal pole encephalocele)

• Subtle changes in cortical parameters (eg cortical thickness in GGE)

HS - diagnosis

• HS is important accurately diagnose in life

• Features are atrophy, abnormal signal and altered micro architecture (CA1, CA4, dentate)

• Subtle abnormalities are seen with quantitative measures.

• Abnormalities exist at disease onset (both large and small), and in first degree relatives of HS patients (small).

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Jackson et al AJNR 1993

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Neurology 2013

The hippocampus

• ILAE consensus classification of HS in TLE Blümke et al Epilepsia 2013 (Pathology based)

• Type 1, CA1 and CA4 predominant

• Type 2, CA1 predominant

• Type 3, CA4 predominant

• Relevant to outcome prediction

• Challenges imaging to match this.

IFRD and SFRD, which are measures of encoding/early retrieval, were associated with CA3&DG, and DRD, which measures consolidation/late retrieval, with CA1.

…involvement of brain areas larger than the hippocampus - i.e. networks

Bernhardt et al 2010, 2012, 2013. Kim et al 2008. Worsley et al 2009

Subtle abnormalities of the cortex

• curvilinear reformatting of 3D MRI

• texture analysis

• quantitative voxel-based intensity analysis

• cortical thickness analysis

• sulcal morphometric analysis

• quantification of gray and white matter distribution by voxel-

based morphometry

• other voxel based techniques such as

T2 signal morphometry,

fixel based morphometry,

deformation based, diffusion based whole brain morphometry.

All depend on high quality acquisition of structural

data

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Bottom of Sulcus Dysplasia and Temporal Encephalocele

• Major lesions that need to be detected

• Often only found after suggested focal abnormality from another technique eg PET SPECT

• Distinctive lesions, highly epileptogenic, excellent outcome from very focal surgery

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Hoffmann et al AJR 2011

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Epilepsia, 51(10):2199–2202, 2010

Bottom of sulcus dysplasia

T1

FLAIR

Hoffman AJR 2011;10:4423

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Bernasconi et al 2005

Cortical thickness

• With improvements in acquisition appears to be sensitive

• 32 channel head coils help

• Occasional clear individual uses - can include in ‘feature mapping’

• Providing insights into brain development, drug effects

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PLOS one 2011

Single subject

Group data

Normalisation? Early onset of

thinning?

Neurodevelopmental processes are not normal in BECTS

Pardoe et al

2012 Overvliet et al

2013

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White matter

• The power of imaging white matter

• The problem with the Diffusion Tensor (DTI)

• The ‘connectome' and ‘connectomics’

• Epilepsy as a driven network disorder

• Superresolution imaging (TDI)

• Tract weighted imaging (TWI)

• Fixel-based imaging

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Diffusion in white matter

Farquharson et al J Neurosurg, 2013

MRTrix www.brain.org.au/software

Super-resolution imaging 200 micron isotropic from a 10 minute scan

Uncoupling of MRI from the signal to noise constraint

SuperresolutionTrack Density Imaging (TDI) superresolution of human white matter 200 micron resolution at 3T (10

mins)

Calamante et al Neuroimage 2008

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2010

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Completely automated tract extraction

R.E.Smith et al, ISMRM 2011, 673

White matter

fibre connections fMRI

language

organisation of the arcuate fasciculus

‘Fixel’ based studies

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• fibre orientation within a voxel

• allows quantitative assessment of fibre tracts

• fixel - based morrphometry

D.Raffelt et al, NeuroImage 2012, 59, 3976-3994

D.Raffelt et al, ISMRM 2013, 841."Tractographic Threshold-Free Cluster Enhancement”

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Quantitative comparison of tracts Fixel-Based Analysis

Vaughan Poster #3.184, Dec 9th

Structural and Functional Brain Networks

• The Connectome is basted on structural connections based on tractography

• Connectomics explores functional activity in those networks.

• Epilepsy is increasingly seen as a network disorder so the connectome and connectomics is important

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Adolescent Adult

connectivity - degree centrality: ILAE 2010 Functional

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Structural

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Archer Epilepsia 2013

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1. Find abnormalities that are important for individual patients and their care.

2. Be able to understand and explain their disease, its causes and explain the patients experiences.

Impact on Clinical Care and Practice

• Finding a lesion, particularly a subtle focal lesion on MRI changes the management of the patient, and raises the possibility of epilepsy surgery.

• Having an ‘epilepsy protocol’ for MRI acquisition is essential for finding the lesions that are important for optimal patient management

• Powerful new MRI techniques can help with individual diagnosis, while other emerging techniques help with understanding disease aetiology and mechanisms at a group level.

•Technology is developing rapidly, clinical translation is fast.