Imaging
Why is psychosis tractable now?
• Late 1990’s
– epidemiological discontinuities emerging
– new environmental risk factors identified
• 2000-3
– extended phenotype characterised
• 2002-5
– first susceptibility genes identified
• 2004-5
– first gene-environment interactions shown at
population and individual level
What questions can a big cohort address?
• Role of small risk factors
• Specificity of prodromes
• Rare subtypes:
– early onset
– ethnic subgroups
• Adverse outcomes:
–
–
–
–
recovery versus chronicity
suicide
Forensic
treatment complications
i.e. prevention and personalised prevention
What is PsyGrid?
• e-Science project funded by the MRC, and the Department of
Health
• Aim 1 (Technological): Develop applications and middleware
to support studies, clinical trials and diagnosis in mental health
(Team of 5 software developers)
• Aim 2 (Clinical): Use outputs of ‘Aim 1’ to perform longitudinal
study of schizophrenics from First Episode Psychosis over 2
years and study epidemiology of schizophrenia (Team of 8
research nurses)
Initiation:
May 2005
PsyGrid so far…
Electronic Data
collection starts
Mental Health Research Network
adopts PsyGrid as core technology
platform
April ‘06
May ‘06
Mental Health Clinical Trials
(Manchester) adopts PsyGrid platform
July ‘06
SCAG approval given to
link NHS Mental Health
Minimum Data Set
Sept ‘06
Project end:
May 2008
National EDEN early
intervention study
uses PsyGrid
Nov ‘06
EDIE 2:
clinical trial starts
on PsyGrid
Incremental development from
the core
E-Epidemiology
Workbench
Diagnosis and
prognosis
Data
Collection
Core
Clinical Trials
Platform
Y-BAR: young brains at risk
Left-sided
change
over 12
months
with new
onsets
in association with SANE
ales
Establish Grid-based image
analysis methodology
Females
0.3
Thalamo-cortical topography
– for normative database of
brain development during at
risk years for psychosis
– merge Grid-based clinical,
genetic and risk factor data
average asymmetry in grey matter
Volumetric slice profiles of average asymmetry in white matter
Volumetric slice profiles of a
onto
brain
development
to
for peak height
corrected for peak
corrected
9.24 height
identify signatures of onset
and chronicity
0.2
0.1
241.00
225.00
209.00
193.00
177.00
161.00
-0.1
145.00
129.00
113.00
0
-0.2
-0.3
-0.4
Planum temporale
-0.5
-10
-15
Talairach y coordinate (m m )
0.12
0.1
-37.50
0.02
-50.00
0.04
-62.50
0.06
-75.00
-6.45
0.08
-87.50
t-statistic
75.00
62.50
50.00
37.50
Leftward planum
asymmetry
6.45
-100.00
-8.09
25.00
-9.24
-5
12.50
0.00
-12.50
-25.00
-37.50
-50.00
-62.50
-75.00
-87.50
-100.00
Bullmore,
Roberts, Smith, Taylor, Crow, Deakin
-10
-10
-15
-15
y
coordinate
(m m
m ))
y coordinate (m
8.09
0
-112.50
t-statistic
75.00
75.00
62.50
62.50
-5
-5
50.00
50.00
0
0
37.50
37.50
5
25.00
25.00
5
5
12.50
12.50
10
0.00
0.00
10
10
-12.50
-12.50
15
-25.00
-25.00
y coordinate (m m )
15
15
Asymmetry (cm^3)
-112.50
0.14
0
-0.02
Talairach
Early Detection Workflow
Patient referred
by clinician
Retrieve
baseline scans
Submit scans for
morphometric
analysis to
PsyGrid analysis
If longitudinal
changes
detected
Baseline
Structural MRI
Scan
Store on
PsyGrid
12 Month followup structural
MRI Scan
Store on
PsyGrid
Retrieve
demographically
matched non-psychotic
patient data
Retrieve demographically
matched psychotic patient
data with medium term
outcome data
Compare with patient diagnostic indicator
Compare with patient
- prognosis indicator
and treatment guide
Feedback diagnostic
and prognosis
indicators to clinician
Infrastructure Needed
• Large scale distributed image storage with fast
access
• 3 data sets
– Active patient data
– Non-psychotic normative data
– Psychotic normative data
• High throughput image analysis capability
• Computationally intensive longitudinal morphometric analysis
• Security (clinical patient data)
• The MRI and ancillary data on individual patients, and the
diagnostic and prognostic reports issued as a result of their
analysis, will be highly sensitive and mandate the enhanced
data security enabled by the grid.
Infrastructure objectives
• Design and implement Grid infrastructure to support
submission of images and retrieval of results from
Manchester, Oxford, Edinburgh and London
• Design and implementation of a modular image
processing pipeline for optimal, standardized analysis of
longitudinal brain changes in structural MRI data.
• Design and implementation of databases that can i) hold
large quantities of MRI data derived morphometric
variables and ancillary (e.g. clinical, cognitive and
genetic) data; and ii) support interactive interrogation of
MRI databases as a basis for probabilistic diagnosis and
prognosis of index patient data.
Neuroscience objectives
• Standard MR image acquisition and quality
control protocols
• Reliability study to achieve harmonisation
between scanners at the four participating
centres
• Acquire longitudinal data on a cohort of 20
patients with a first episode of psychosis, each
scanned twice on a 12 month interval