The Sackler Institute in Scotland Glasgow Site

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The Sackler Institute in ScotlandGlasgow Site
Dave Wyper Jonathan Cavanagh Jennifer Chisholm
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Overview

• The setting in Glasgow
• Examples of completed studies
• Planned studies feedback from Sackler colleagues

Clinical depression Post traumatic stress
Sleep Learning Visual cognition
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Overview Setting Technologies Themes
Conclusion - D Wyper
Treatment of depression - J Cavanagh
Quality assurance in fMRI A learning study
Eccentric viewing - J Chisholm
Pleasure -D Wyper
Bubble, bubble toil and trouble - J Canvanagh
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The Sackler Institute in Glasgow
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The Sackler Institute in Glasgow
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Neuro-imaging programmes
The core Clinical Physics Neuroradiology
Neuroscience Dave Wyper Donald Hadley Barrie
Condon Jim Patterson Jennifer Chisholm Dave
Brennan Mary Dempsey Mhairi Macrae Debbie Dewar
Out with the Old Graham Teasdale David
Graham Jim McCulloch
In with the New Jonathan Cavanagh Tom
McMillan Philippe Schyns Tom Cullen Sackler Fellow
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Imaging facilities for mental health research in
Glasgow
Pre-Sackler
Post-Sackler

• Clinical
• NeuroSPECT Neurofocus
• Radiopharmacy
• 1.5T MRI but with no research time

• Clinical
• 3 MRI with guaranteed research time through
  Sackler funding

• Experimental
• microSPECT GU funded

• Experimental
• 7T small bore MRI

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Scotlands Brain Imaging Backbone Universities
Pooling bid

• Aberdeen
• PET
• 1.5T MRI
• Imaging Science

• Dundee
• 1.5T MRI

• Glasgow
• 3T 1.5T MRI
• Brain SPECT
• 7T small bore MRI
• microSPECT
• Imaging Science

• Edinburgh
• National Research 1.5T MRI
• Brain SPECT
• Imaging science

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Diagnostic Molecular Imaging Europe
The goal of the North Europe "Diagnostic
Molecular Imaging" (DiMI) programme is to
integrate multidisciplinary research for the
development of new probes and multimodal
non-invasive imaging technology for early
diagnosis, assessment of disease progression and
treatment evaluation.
http//www.mpifnf.de/dimix
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Molecular Imaging Single Photon Emission
Computed Tomography
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In-vivo molecular imaging
The purpose of molecular imaging is to improve
understanding of biology and medicine through
non-invasive in vivo investigation of cellular
molecular events involved in normal and
pathologic processes Society of Molecular
Imaging
Currently clinical molecular imaging is mainly
PET and SPECT
A critical and rate limiting factor is the
development of imaging tracers probes
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Molecular imaging tracer development

• Eight SPECT tracers have been taken from the
  laboratory to clinical application.
• Cholinergic dopaminergic serotonergic
  glutaminergic cell proliferation tK gene
  expression
• Working on norepinephrine transporter ligand

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SPECT or PET can measure the global pattern of
functional loss by mapping blood flow or glucose
metabolic rate
Non-selective molecular imaging
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By use of novel ligands that bind to specific
molecular targets PET and SPECT can probe more
selective abnormalities in patients with AD.
Selective molecular imagingRadiochemistry
R,R-123I-QNB is a selective ligand that binds
with high affinity and selectivity to
acetylcholine muscarinic receptors
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Imaging (a2-b4) nicotinic receptors with
5-I125-A-85380
Chemistry to develop precursor
Radio-labelling
In-vitro binding and displacement studies
Toxicology
GMP production
Clinical application
Neuropsychopharmacology. 2004 Jan29(1)108-16.
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Imaging nicotinic receptors with 123I-5IA
Control
AD
Early marker?
Image courtesy Prof K Ebmeier, University of
Edinburgh
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Nicotinic receptors and smoking
Sagittal views of brain showing nicotinic
receptor availability in thalamus, cortex and
cerebellum.
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Data analysis Compartment modelling
dC1/dt k21C2 - k12C1 dC2/dt k12C1 k32C3 -
(k21 k23)C2 dC3/dt k23C2 - k32C3
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SPECT data analysis

• Allow time for non-specific washout
• Use reference region comparison

Background
Selected region
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Measuring drug occupancy
DRUG FREE
ON DRUG

The reduced tracer uptake is due to drug occupancy
Selected region
A
Reference region
B

Reduction in A/B enables occupancy to be measured
A/B gives binding index
Better described as residual availability
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microSPECT
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Experimental molecular imaging microPET or SPECT
PET is not always better than SPECT

• Yang and Cherry Soc Mol Imaging 2004
• Limits of microPET.
• Sources of error
• Gammas are 1/4 degree off 180
• Range of positron depends on energy
• Size of detectors
• Scatter
• Limit with 18F is 0.5 mm.

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microSPECT Design team
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Magnetic Resonance Imaging
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The Sackler Institute in Glasgow
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3T MRI installation
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MRI hippocampal volume in depression
Histology 3Tesla MRI
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DTI diffusion tensor imaging value in
depression?
A Einstein. Investigation of the theory of
Brownian motion Dover New York, 1956
Alexopoulos et al Am J Psychiat (2003) Geriatric
Depression Association between Fractional
Anisotropy in frontal white matter 10mm and 15mm
above the AC-PC line and Response to citalopram
Dupont et al Arch Gen Psychiat (1990) Increased
incidence of subcortical hyperintensities on MRI
in bipolar disorder
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fMRI
Language training pleasure facial recognition

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7 Tesla small bore MRI
T1 and T2 images resolutions of about 100 microns
can be obtained in a few minutes Resolution down
to 50 microns can be obtained in an hour
Cucumber
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Validation of MRI
Is T2 relaxation influenced by?
Do drugs produce local tissue volume change?
What do volume change mean?
How accurate is MR perfusion measurement?
Do drugs produce local tissue perfusion change?
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Small bore MRI validation of arterial spin
labelling ASL

• Depression is characterised by changes in mood
  state that can be influenced by therapies.
• PET and SPECT have been used for imaging the
  global distribution of perfusion or glucose
  metabolic rate - but not often
• Perfusion MRI could enable multiple studies to be
  performed at times determined by mood state
• The limits of accuracy need to be determined

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Overview Setting Technologies Themes
Conclusion - D Wyper
Treatment of depression - J Cavanagh
Quality assurance in fMRI A learning study
Eccentric viewing - J Chisholm
Pleasure -D Wyper
Bubble, bubble toil and trouble - J Canvanagh