Transcript Magnetic Resonance Imaging
Neuro-imaging applications in Psychiatry
Professor David Wyper Institute of Neurological Sciences Glasgow
X-ray Computed Tomography
X-ray Computed Tomography Transmission tomography Developed at EMI laboratories in 1972 by Godfrey Houndsfield
Dementia
CT in psychiatry Control Hippocampal atrophy Alzheimer’s
Magnetic Resonance Imaging
Magnetic resonance imaging
• MRI • MRA • MRS • fMRI • DTI imaging angiography spectroscopy functional 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
in vivo research
MR in psychiatry
Alzheimer’s disease - progression Normal ageing difference at 12m Early onset AD 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
Hedonia Goal vs Miss Inferior putamen & amygdala Lateral temporal cortex Anterior cinulate Inferior frontal cortx Anticipation Goalmouth vs open play
Diffusion imaging
A Einstein. Investigation of the theory of Brownian motion: Dover; New York, 1956
MRI: diffusion imaging
Isotropic diffusion Examples: Glass of water; cerebral grey matter Anisotropic diffusion 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
Gamma ray detectors
The patient’s view
Intravenus injection of radio pharmaceutical 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
PET / SPECT
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 99m Tc -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 temporo parietal defects was 82%
Frontal lobe dementia • Frontal hypo-perfusion sometimes including temporal lobes Alzheimer’s disease Frontal lobe dementia Bi-lateral temporo-parietal deficits Bi-lateral frontal lobe deficits
Vascular dementia • Multiple regions of focally reduced perfusion
Molecular imaging: Receptors & transporters
The dopamine neurotransmitter system Dopamine synthesis
Glial cell
MAO-B COMT
Tyrosine L-DOPA DA Vesicles Post-synaptic cell Pre-synaptic terminal
Dopamine Transporters D2 Receptors
Dopamine neurotransmitter tracers I123 IBZM or epidepride F18-Dopa
Vesicles Tyrosine L-DOPA DA Pre-synaptic terminal Glial cell
MAO-B COMT I123 FPCIT or ß-CIT
Post-synaptic cell
Dopamine transporter imaging
Diagnosis and staging of PD and LBD
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 Imaging diagnosis 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 Synapse Serotonin Serotonin transporters (SERT) Serotonin reuptake inhibitor (SSRI)
SPECT tracer
Post-synaptic cell
Image available binding sites
Measurement of drug action before antidepressant after antidepressant