Neuro-imaging applications in Psychiatry Professor David Wyper Institute of Neurological Sciences Glasgow d.wyper@udcf.gla.ac.uk 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