NeuroGrid (and maybe even NeuroPsyGrid)

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NeuroGrid (and maybe even NeuroPsyGrid)

• Stephen Lawrie
• Edinburgh

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A collaboration between clinical, imaging and
e-scientists to create a Grid-based network of
neuroimaging centres and a neuroimaging tool-kit,
focused on three clinical exemplars dementia,
stroke and psychosis. Sharing data, experience
and expertise will facilitate the archiving,
curation, retrieval and analysis of imaging data
from multiple sites enable large clinical
studies.
 
 
 
 
 
 
 
 

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The main issues in (UK) clinical brain imaging
studies

• Potential
• - demonstrate effects of risk factors, including
  genes
• early diagnosis
• treatment response / prognosis prediction
• treatment effect monitoring
• biomarker for novel drug development
• Concerns
• lack of standardisation across scanners and even
  in basic approach to e.g. connectivity
• lack of normative data reference points for
  relevant age ranges
• safe data storage
• expense
• constantly developing technology

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Methodological issues in multi-centre brain
imaging

• Multiple influences on brain structure and
  function
• Scanner, servicing and session effects
• (see e.g. McGonigle 2000 Marshall 2004)
• Sequences for sfMRI and tasks for fMRI
• Signal and spatial inhomogeneities

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Single Subject, 33 sessions over 2 month period,
finger-tapping task
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Neurogrid psychosis exemplar

• Database and ontology, building on EHRS data set
  (0.5WTE)
• Scanner harmonisation issues, focussing on EHRS
  use of two machines (1WTE)
• Combined analysis of psychosis data sets from
  Oxford Edinburgh, focussing on sex / assymmetry
  (1 WTE)
• Registration and Partial Volume Metric for
  Multi-Center sMRI Scanner Harmonization Moorhead
  TWJ, Job DE, Gountouna V-E, Johnstone EC, Lawrie
  SM. HBM2005. NeuroImage 2005
• Signal-to-Noise (SNR) and Contrast-to-Noise (CNR)
  metrics in longitudinal and multicenter MRI
  studies Gountouna VE, Moorhead TWJ, Job DE,
  Johnstone EC, Lawrie SM. HBM2005 NeuroImage 2005
  
• Entropy as a measure of scanner and sequences
  change. Dominic E. Job, T. William J. Moorhead,
  Eve C. Johnstone, Stephen M. Lawrie. NeuroImage
  2006 Volume 31, Supplement 1 Annual Meeting
  Human Brain Mapping, June 11-15 Florence Italy
• Test-retest reliability of the Hayling sentence
  completion task assessment for multicenter fMRI
  using voxel-wise Intraclass Correlation
  Coefficients (ICCs). Viktoria-Eleni Gountouna,
  Heather Whalley, T.William Moorhead, Dominic Job,
  David McGonigle, Eve Johnstone, Stephen Lawrie.
  HBM2006 NeuroImage 2006 Volume 31,

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Methodological (part) solutionsHarmonisation
metrics (Gountouna 2005)
Grey Matter Signal to Noise Ratio for repeated
visits of 6 subjects.
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Methodological (part) solutionsHarmonisation
methods (Moorhead 2005)

• Registration

Amended pre-processing Stripped Brain Optimised
Metric_reg0.96
Default SPM99 pre-processing Metric_reg0.73
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Edinburgh High Risk Study

• A prospective study of 200 subjects at high risk
  (HR) of Schizophrenia for genetic reasons i.e.
  initially healthy subjects aged 16-25 who had two
  or more close relatives with schizophrenia.
  Compared to first-episode cases and healthy
  controls on...

• Baseline measures
• genetic liability
• dermatoglyphics
• obstetric complications
• minor physical anomalies / neurological soft
  signs
• CBCL
• SIS
• RISC
• Also took blood for genes at the end of the study

• Repeated measures
• substance use
• life events
• neuropsychology
• structural MRI
• functional MRI
• PSE
• PANSS

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Edinburgh High Risk Study (EHRS)Main Results
1995-2004

• Isolated and/or transient symptoms very common
• Baseline risk of psychosis 20 / 162 (12.5)
• Risk in HR i.e. those with symptoms 18 / 80
  (25)
• Most measures differed significantly between
  those at high risk and controls, typically with
  the sub-group pattern
• Con lt/gt HR- lt/gt HR ltlt/gtgt HRill
• Within high risk subjects, however, only AVLT,
  CBCL, RISC/SIS and some imaging indices predicted
  schizophrenia

(Johnstone et al 2005 Br J Psych)
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Neuro-psychology NART IQ, WAIS-R VRs, RBMT
story especially AVLT 1-5 total score
EHRS Baseline predictors
Neuro-anatomy AMYG-HIPP vol Gyrification Index
R PFC
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EHRS changes towards psychosis
Cannabis use and major life events are associated
with psychotic symptoms and (weakly) with
psychosis 2-4 yrs later. 0-2 yrs pre-diagnosis,
anxiety/depression fall, typical psychotic
symptoms supervene and GM density falls. But, no
apparent changes in neuropsychological test
scores over this time.
Mean scores on the six PSE principal components
on three occasions of 8 HR subjects who fell ill
(relative to NP chronics)
GM density Reduces In Right Uncus, Fusiform
Cerebellum 2.5 yrs on avge before Dx
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Neuregulin in the EHRS

• Law et al (2006) reported that the risk allele of
  SNP8NRG243177, part of the original
  disease-associated haplotype, alters the binding
  sites for three transcription factors in a
  promoter region of NRG1 increasing expression
  of the type IV transcript
• We found a highly significant effect of
  SNP8NRG243177 genotype on the development of
  psychotic symptoms in the EHRS cohort with 100
  of individuals homozygous for the risk allele
  (T/T) developing psychotic symptoms at some time
• Subjects with the risk (T/T) genotype showed
  significantly decreased activation of right
  medial PFC and right posterior medial temporal
  gyrus in the contrast of sentence completion
  versus rest
• Using the National Adult Reading Test (NART), a
  measure of pre-morbid IQ, we found a significant
  effect of genotype on IQ which derived from the
  T/T group having a significantly decreased IQ

Hall et al, 2006 Nature Neuroscience
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A health informatics project which builds on the DoH funded UK MHRN. Psygrid aims to develop the MHRN into a functioning e-community and build a secure electronic database to hold anonymised clinical data about people presenting to NHS services with first episode psychosis.
 
 
 
 
 
 
 
 

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Towards multi-centre clinical, genetic and brain
imaging studies of people at high risk of
psychosis
MRC Collaboration grant application NeuroPsyGrid
towards an ontology and multi-centre brain
imaging in early psychosis
 
 
 
 
 
 
 
 

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Multi-centre organisation

• Scotland
• - CaliBrain multicentre sfMRI pilot
• - SHEFC Pooling for Imaging Project
• UK
• - MRC funded NeuroGrid PsyGrid
• Europe
• US

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BIRN

• For harmonisation, BIRN have shown that an
  image/method for gradient non-linearity
  correction and possibly a phantom for other coil
  inhomogeneity corrections are very useful.

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Neuro/PsyGrid and BIRN

• Shared interests in scanner (clinical and
  genetic) harmonisation and shared database,
  metadata and ontology for psychosis
• During discussions about NPG we thought of
  looking at
• - a collaborative ontology
• - variations across sites in clinical and
  biological data acquisition
• - using BIRN Bio-Mediator
• - 4D spatio-temporal analyses of imaging (fMRI)
  and genetic data
• - joint work on NeuroFMA
• - a requirements analysis for NPG-BIRN
  harmonisation.

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Concluding remarks

• If brain imaging is to impact on clinical
  practice in psychiatry, as we know it could, we
  urgently require
• Multi-centre clinical studies of people in early
  stages of major psychiatric disorders
• Standardisation of scanners and imaging
  acquisition and processing techniques across
  mental health research networks
• Studies of normal neuro-development across age
  ranges of relevance to (adult) psychiatric
  disorders
• These would benefit, possibly even depend upon,
  on e-science approaches to collecting, storing
  and accessing data.