Transcript Magnetic Resonance Imaging

Neuro-imaging applications in
Psychiatry
Professor David Wyper
Institute of Neurological Sciences
Glasgow
[email protected]
X-ray Computed Tomography
X-ray Computed Tomography
Transmission tomography
Developed at EMI laboratories in 1972 by Godfrey Houndsfield
CT in psychiatry
Dementia
Control
Hippocampal atrophy
Alzheimer’s
Magnetic Resonance Imaging
Magnetic resonance imaging
• MRI
imaging
• MRA
angiography
• MRS
spectroscopy
• fMRI
functional
• DTI
diffusion tensor
Absorbing RF energy
Emitting RF energy
Tissue contrast
MRI ‘pulse sequences’ control the transmission of radio signals and
the timing of detection of signals emitted from the body.
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 invivo research
MR in psychiatry
Alzheimer’s disease - progression
Normal ageing
Early onset AD
difference at 12m
difference at 12m
CSF volume in Schizophrenia
Control
Schizophrenia
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;56:544-552
MR in psychiatry
• Schizophrenia - activation; Diffusion imaging
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
functional MRI of motor function
Paradigm:
* stimulus every 12 seconds
* if ‘2’ press; if ‘5’ don’t press
Anterior cinulate
Inferior frontal cortx
Anticipation
Goalmouth vs open play
Hedonia
Goal vs Miss
Inferior putamen & amygdala
Lateral temporal cortex
Diffusion imaging
A Einstein. Investigation of the theory of Brownian motion:
Dover; New York, 1956
MRI: diffusion imaging
Isotropic diffusion
Anisotropic diffusion
Examples: Glass of water;
cerebral grey matter
Examples: textile
fibres, nerve fibres
MRI diffusion imaging
Emission tomography
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
In emission tomography a tracer in injected intravenously and
delivered by blood-flow to the organ of interest
The patient’s view
Gamma ray
detectors
Intravenus
injection of radiopharmaceutical
Duration
30-40 minutes
Positron emission tomography
For more info on PET see: http://www.crump.ucla.edu/software/lpp/lpphome.html
SPECT Cameras
PET / SPECT
PET
SPECT
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
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
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
A typical SPECT perfusion scan
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 temporoparietal defects was 82%
Frontal lobe dementia
• Frontal hypo-perfusion sometimes including temporal lobes
Alzheimer’s disease
Bi-lateral temporo-parietal
deficits
Frontal lobe dementia
Bi-lateral frontal lobe
deficits
Vascular dementia
• Multiple regions of focally reduced perfusion
Molecular imaging:
Receptors & transporters
The dopamine neurotransmitter system
Tyrosine
Dopamine
synthesis
L-DOPA
DA
Vesicles
Pre-synaptic terminal
Glial cell
Dopamine
Transporters
MAO-B
COMT
D2 Receptors
Post-synaptic cell
Dopamine neurotransmitter tracers
Tyrosine
L-DOPA
F18-Dopa
DA
Glial cell
Vesicles
Pre-synaptic terminal
MAO-B
COMT
I123 IBZM
or epidepride
I123 FPCIT
or ß-CIT
Post-synaptic cell
Dopamine transporter imaging
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&Y1
PD: H&Y2
PD: H&Y3
Measuring the biological effect of drug action
Molecular Imaging of drug action
SPECT images of
SERT binding
Measurement of drug action
Modern antidepressant drugs (SSRIs) block the serotonin transporter (SERT)
Pre-synaptic terminal
Serotonin transporters
(SERT)
Synapse
Serotonin
Serotonin reuptake
inhibitor (SSRI)
SPECT tracer
Post-synaptic cell
Image available
binding sites
Measurement of drug action
before antidepressant
after antidepressant