1. Neuro-imaging applications in Psychiatry
Professor David Wyper
Institute of Neurological Sciences
Glasgow

2. X-ray Computed Tomography

3. X-ray Computed Tomography
Transmission tomography
Developed at EMI laboratories in 1972 by Godfrey Houndsfield

4. CT in psychiatry
Dementia
Control
Alzheimer’s
Hippocampal atrophy

5. Magnetic Resonance Imaging

6. Magnetic resonance imaging
MRI imaging
MRA angiography
MRS spectroscopy
fMRI functional
DTI diffusion tensor

8. Absorbing RF energy

9. Emitting RF energy

10. Tissue contrast
MRI ‘pulse sequences’ control the transmission of radio signals and the timing of detection of signals emitted from the body.

11. Magnetic Resonance Imaging
MRI can image structures with detail of 0.1mm.
MRI can be repeated without limit.
MRI has an enormous impact on clinical in-vivo research

12. MR in psychiatry Alzheimer’s disease - progression Normal ageing
difference at 12m
Early onset AD
difference at 12m

13. CSF volume in Schizophrenia
Control
Schizophrenia

14. Reduction in gray matter in schizophrenia
McIntosh AM….Lawrie SM and Johnstone EC Voxel-based Morphometry of Patients with Schizophrenia or Bipolar Disorder and their Unaffected Relatives, Biol Psychiatry 2004;56:

15. MR in psychiatry
Schizophrenia - activation; Diffusion imaging

16. Functional MRI
In response to a local increase in neuronal firing there is an increase in oxyhaemoglobin - HbO2 [red]
HbO2 is diamagnetic
If HbO2 increases then T2 relaxation gets longer and the MRI signal increases
fMRI uses a BOLD [Blood Oxygen Level Dependent] MRI pulse sequence

17. functional MRI of motor function
Paradigm: * stimulus every 12 seconds
* if ‘2’ press; if ‘5’ don’t press

18. Anticipation Hedonia Goalmouth vs open play Goal vs Miss
Anterior cinulate
Inferior frontal cortx
Anticipation
Goalmouth vs open play
Hedonia
Goal vs Miss
Inferior putamen & amygdala
Lateral temporal cortex

19. Diffusion imaging
A Einstein. Investigation of the theory of Brownian motion: Dover; New York, 1956

20. MRI: diffusion imaging
Isotropic diffusion
Examples: Glass of water; cerebral grey matter
Anisotropic diffusion
Examples: textile fibres, nerve fibres

21. MRI diffusion imaging

22. Emission tomography

23. 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.
The technologies range from experimental optical fluorescence imaging to clinical PET and SPECT
SPECT
SPECT
PET

24. In emission tomography a tracer in injected intravenously and delivered by blood-flow to the organ of interest

25. Intravenus injection of radio-pharmaceutical
The patient’s view
Gamma ray detectors
Intravenus injection of radio-pharmaceutical
Duration
30-40 minutes

26. Positron emission tomography
For more info on PET see:

27. SPECT Cameras

28. PET / SPECT
PET
SPECT

29. Emission Tomography
Both techniques are based on detection of gamma rays emitted from the body after injection of a tracer.
Positron Emission Tomography
[PET]
11C or 18F
Short half life
Local cyclotron
Good for study of drug delivery
Single Photon Emission Tomography [SPECT]
99mTc or 123I
Longer half life
Can buy isotopes
Good for study of drug action

30. Same scanner: different radio-pharmaceuticals
What SPECT can measure
Regional brain function: perfusion
Dopamine D2 receptor availability
Dopamine transporter function
M1 muscarinic receptors
Nicotinic receptors
Same scanner: different radio-pharmaceuticals

31. SPECT imaging of blood supply in the brain
The tracer 99mTc -HMPAO can measure the amount of blood that goes to each part of the brain.
It is extracted from blood passing through the brain and trapped in brain cells.
Uptake in neurones
High flow
Low flow
Time
injection
60 seconds

32. A typical SPECT perfusion scan

33. The AD perfusion pattern
The probability that patients with memory loss and normal perfusion had Alzheimer's disease was 19 %.
The probability of Alzheimer's disease with bilateral temporo-parietal defects was 82%

34. Frontal lobe dementia
Frontal hypo-perfusion sometimes including temporal lobes
Frontal lobe dementia
Alzheimer’s disease
Bi-lateral temporo-parietal deficits
Bi-lateral frontal lobe deficits

35. Vascular dementia
Multiple regions of focally reduced perfusion

36. Molecular imaging: Receptors & transporters

37. The dopamine neurotransmitter system
Tyrosine
Dopamine
synthesis
L-DOPA DA
Pre-synaptic terminal
Vesicles
Glial cell
Dopamine
MAO-B
Transporters
COMT
D2 Receptors
Post-synaptic cell

38. Dopamine neurotransmitter tracers
Tyrosine
L-DOPA
F18-Dopa DA
Pre-synaptic terminal
Glial cell
Vesicles
MAO-B
COMT
I123 IBZM or epidepride
I123 FPCIT or ß-CIT
Post-synaptic cell

39. Dopamine transporter imaging

40. Diagnosis and staging of PD and LBD
Imaging diagnosis
Clinical diagnosis
Accuracy of Diagnosis in Presumed PD Meara J et al Age and Ageing 1999;28:99-102 .
26% of patients receiving inappropriate treatment
Post-mortem data suggests figure may even be higher
Even on first presentation SPECT shows loss of 50% of neurones
Objective measurement of progression in assessment of therapy
Normal PD: H&Y PD: H&Y PD: H&Y3

41. Measuring the biological effect of drug action

42. Molecular Imaging of drug action
SPECT images of SERT binding

43. Measurement of drug action
Modern antidepressant drugs (SSRIs) block the serotonin transporter (SERT)
Pre-synaptic terminal
Serotonin transporters
(SERT)
Serotonin reuptake
inhibitor (SSRI)
SPECT tracer
Image available
binding sites
Synapse
Serotonin
Post-synaptic cell 43

44. Measurement of drug action
before antidepressant
after antidepressant