NeuroGrid
(and maybe even NeuroPsyGrid)
Stephen Lawrie
Edinburgh
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.
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
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 s&fMRI and
tasks for fMRI
• Signal and spatial
inhomogeneities
M1
Single Subject, 33 sessions over 2 month period, finger-tapping task
1
2
3
33
...
M1
SMA
Neurogrid – psychosis exemplar
1.
2.
3.
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,
Methodological (part) solutions
‘Harmonisation’ metrics (Gountouna 2005)
Grey Matter
Signal to Noise
Ratio for
repeated visits
of 6 subjects.
Methodological (part) solutions
‘Harmonisation’ methods (Moorhead 2005)
• Registration:
Amended pre-processing
Stripped Brain Optimised
Metric_reg=0.96
Default SPM99 pre-processing
Metric_reg=0.73
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
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 </> HR- </> HR+ <</>> HRill
Within high risk subjects, however, only AVLT, CBCL,
RISC/SIS and some imaging indices predicted
schizophrenia
(Johnstone et al 2005 Br J Psych)
Neuro-psychology: NART IQ, WAISR & VRs, RBMT story & especially
AVLT 1-5 total score
EHRS Baseline predictors
10
11
No. items recalled
9
8
7
6
FES
HR
CON
5
4
3
2
1
0
AHC - L AHC - R
3V
Thal - L Thal - R
Neuro-anatomy: AMYG-HIPP
vol & Gyrification Index R
PFC
10
9
8
7
CONTROL
HR-
HR+
ILL
fMRI – HSCT (parametric contrast): AHC/STG
* * *
4
2
3
a
1
4
* * *
1
3
b
2
4
2
1
d
c
3
a.) R ahc/stg; b.) R lingual gyrus; c.) L ahc/stg; d.) L cerebellum
*
4
3
1
2
*
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)
depression
1.5
1
hallucinations
and control
delusions
0.5
0
-0.5
-1
-1.5
-2
-2.5
On
entry
2nd
time
on
falling
ill
mania
oddness
anxiety
GM density
Reduces
In Right
Uncus,
Fusiform &
Cerebellum
2.5 yrs on
avge
before Dx
Neuregulin in the EHRS
•
•
•
•
Law et al (2006) reported that the risk allele
of SNP8NRG243177, part of the original
b
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 d
Subjects with the risk (T/T) genotype
0
showed significantly decreased
activation of right medial PFC and -10
right posterior medial temporal
-20
gyrus in the contrast of sentence
completion versus rest
Using the National Adult Reading
Test (NART), a measure of premorbid IQ, we found a significant
effect of genotype on IQ which
derived from the T/T group having a
significantly decreased IQ
c
e
0
-10
-20
C/C
C/T
T/T
C/C
C/T
Hall et al, 2006
Nature Neuroscience
T/T
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.
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
Multi-centre organisation
• Scotland
- CaliBrain: multicentre s&fMRI
pilot
- SHEFC Pooling for Imaging
Project
• UK
- MRC funded NeuroGrid &
PsyGrid
• Europe…
• US …
BIRN
• For harmonisation,
BIRN have shown
that an image/method
for gradient nonlinearity correction
and possibly a
phantom for other coil
inhomogeneity
corrections are very
useful.
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.
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 escience approaches to collecting, storing and accessing
data.