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Functional neuroimaging in psychiatry
- 1. Functional Neuro-Imaging in Psychiatry 1 Presenter:Dr. Amit Chail, Resident (Psychiatry) Moderator: Dr. K Chatterjee, Professor (Psychiatry)
- 2. Overview • Aim • Introduction •History • Functional Imaging Techniques • Physics and principles • Applications in Psychiatry • Future trends • Take home message • References 2
- 3. Aim • Familiarisation tofunctional Neuro-imaging modalities • fMRI / MRS / DTI/ SPECT / PET •Physics & Techniques •Interpretation • Relevance to psychiatry • Current • Future 3
- 4. Introduction • Prospective method •Structural & Functional correlates of – Psychiatric disorders – Psychopathology (Perception/ thought/ Behavior) – Diagnosis / Prognosis / Taxonomy – Where do I hit ?? – Do I cure? Can I? – Organicity in Functional disorders 4
- 5. Classification of Neuro-imagingTechniques X Ray Skull radiography, CT Scan NMR MRI, fMRI, MRS, DWI, MRA Emission PET , SPECT 5 Structural Plain skull XRay, PEG, CT Scan, MRI Functional fMRI MRS SPECT PET DWI/DTI
- 6. Structural Neuro-Imaging- Background Alzheimer’s Dementia MTLatrophy -marker - MCI Whole-brain and hippocampal atrophy rates - markers of progression of neurodegeneration Schizophrenia •Total Brain Vol, GM loss > WM •Increased ventricular size/ CSF Vol, •30% lower reductions in antipsychotic-naïve compared with the medicated patients •Progressive volume decreases for frontal, temporal, and parietal white matter Depression Decrease in right hippocampal volume- poorer treatment response 6 P. Fusar-Poli, A meta-analysis of longitudinal MRI studies, Neuroscience and Biobehavioral Reviews (2013)
- 7. Structural Neuro-Imaging- Background ADHDReduced right globus pallidus and putamen volumes as well as decreased bilateral caudate volumes Adults - ADHD symptoms - (ACC) volume reduction OCD Reduced GM volume - inferior and medial frontal gyrus, cingulate gyrus, superior temporal gyrus, and insula and caudate nucleus PTSD Reduced Hippocampal (B/L), ACC and Left Amygdala BPAD •Reduced volume- OFC, DLPFC, left precentral gyrus Hippocampal GM & amygdala •Increase –B/L amygdala, left hippocampus and bilateral thalamus in lithium-treated 7 Carlos López-Jaramillo, Increased hippocampal, thalamus and amygdala volume in long-term lithium-treated bipolar I disorder patients compared with unmedicated patients and healthy subjects, Bipolar Disorders 2017
- 8. History of Neuro-imaging 8 MRIHandbook: MR Physics, Patient Positioning, and Protocols, M. Elmaoğlu, First Edn, 2012 Springer Science+Business Media Wilhelm K Roentgen, Discovery of X Ray, 1895 Nobel Prize, Physics, 1901 Godfrey Hounsfield, CT Scanner, 1972 Nobel Prize, Medicine, 1979
- 9. History of Neuro-imaging 9 MRIHandbook: MR Physics, Patient Positioning, and Protocols, M. Elmaoğlu and A. Çelik, Springer Science+Business Media, LLC 2012 Discovery of NMR,1946 Nobel Prize, Physics, 1952 Richard Ernst Fourier transformation, 1964 Nobel Prize, Chemistry, 1991 Human MR images, 1970s Nobel Prize, Medicine 2003
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- 11. 11 1975 – PETscanner Seiji Ogawa & Kenneth Kwong
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- 13. Liquid Helium Cooled SolenoidMagnet Patient Platform Radiofrequency Transmitter/ Receiver Coil 13
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- 15. Basic Concepts/ Physicsof MR • NMR: – MRI & MRS • Spin of certain (odd) nuclei can be detected after magnetisation – Species of nucleus – Strength of Magnetic Field • Detection of net magnetisation 10 MRI Handbook: MR Physics, Patient Positioning, and Protocols, M. Elmaoğlu and A. Çelik, Springer Science+Business Media, LLC 2012
- 16. 16 RF pulse External MagneticFd MRI Handbook: MR Physics, Patient Positioning, and Protocols, M. Elmaoğlu and A. Çelik, Springer Science+Business Media, LLC 2012
- 17. The Magnetization Vector 17 Kaplanand Saddock’s Comprehensive Textbook of psychiatry, 9th edn, 2009 LWW
- 18. Image Convention 19 Neuroradiology- ThePrerequisites – 3rd edn, Grossman, 2010
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- 20. MR Spectroscopy (MRS) •Non invasive in-vivo chemical assay • Information in form of a spectrum • Biochemical information contained within a selected voxel of tissue • Nuclei used in psychiatric research- – 1H, 31 P 21 Ai-qin Lin, Metabolic changes in acute cerebral infarction: Findings from proton Magnetic Resonance Spectroscopic imaging, Experimental And Therapeutic Medicine, 2013
- 21. 22 Baló's concentric sclerosispresenting as a stroke-like syndrome, Ellen M Mowry, John H Woo and Beau M Ances, Nature Clinical Practice Neurology (2007) 3, 349- 354doi:10.1038/ncpneuro0522
- 22. Nuclei Uses inMRS H¹ Amino acid neurotransmitters and neuronal and glial compounds; imaging of water and lipids C¹³ Study of metabolic pathways P³¹ High energy phosphate levels, intracellular pH, phospholipid head groups Li 7 Pharmacokinetics of lithium O 15 Cerebral O2 consumption F 19 Cerebral pharmacokinetics of fluorinated drugs like fluoxetine and fluvoxamine 23 Maddock R, MR Spectroscopic Studies of the Brain in Psychiatric Disorders, Curr Topics Behav Neurosci, Springer-Verlag Berlin Heidelberg 2012
- 23. H¹ 2 ppm– NAA Neuronal Health, viability and mitochondrial function 3.2 ppm - Cho peak Reflect membrane turnover In pathological process like gliosis Cho peak -elevated 1.3 ppm – Lactate Cerebral Lactate is elevated in ischemia, hypoxia or in tumors 3.5 ppm – Inositol metabolites Intracellular msg transduction Serves as glial cell marker and indicator of neurotoxicity 24 Lin A, Metabolic changes in acute cerebral infarction: Findings from proton magnetic resonance spectroscopic imaging, Experimental And Therapeutic Medicine, 2013 Maddock R, MR Spectroscopic Studies of the Brain in Psychiatric Disorders, Curr Topics Behav Neurosci, Springer-Verlag Berlin Heidelberg 2012
- 24. Dementia NAA &MI Neuronal loss & Gliosis MRS & Psychiatry Mood disorders Li-7 & F-19 Pk & Brain conc of drugs H-1 NAA Hippocampus (depressed/anxious) Frontal (Bipolar) H-1 choline Basal Ganglia H-1 GLX Reversible GABA & glutamate/ glutamine level abnormalities P-31 PME BPAD; dys-regulated signal transduction and membrane metabolism. 25 Maddock R, MR Spectroscopic Studies of the Brain in Psychiatric Disorders, Curr Topics Behav Neurosci, Springer-Verlag Berlin Heidelberg 2012
- 25. NAA Cortical andlimbic areas MRS & Psychiatry- Schizophrenia 26 MRS finding Meaning PM correlate Other Evidence NAA – medication naïve. Impaired neuronal integrity (structural) neuronal size and dendritic arborization DTI – disturbed integrity of long fiber pathways metabolic disturbances Mitochondrial dysfunction PET Glutamate I Glutamine Over activity of Glu transmission Maddock R, MR Spectroscopic Studies of the Brain in Psychiatric Disorders, Curr Topics Behav Neurosci, Springer-Verlag Berlin Heidelberg 2012
- 26. MRS & Psychiatry ADSH-1 NAA Alcohol related neuro-toxicity H-1 choline H-1 GABA N- acute withdrawal - Recovery/ Abstinence 27 Maddock R, MR Spectroscopic Studies of the Brain in Psychiatric Disorders, Curr Topics Behav Neurosci, Springer-Verlag Berlin Heidelberg 2012
- 27. Current Trends MRS •Correlation of metabolites (Glx) with symptoms and role of intervention – Elevated Glx in certain brain areas in Schizophrenia – H1 MRS – Anti-psychotic treatment lowers Glx – Corresponds with symptoms reduction in some of the studies • BPRS • PANSS SANS 28 Egerton A, Effects of Antipsychotic Administration on Brain Glutamate in Schizophrenia A Systematic Review of Longitudinal 1H-MRS Studies. Front. Psychiatry, (May 2017)
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- 29. Functional MRI (fMRI) •Principle: differential magnetic susceptibilities of O2-Hb and deoxygenated Hb • Differential r CBF & r CMR • DeOxy-Hb is para-magnetic • Oxy Hb is diamagnetic • Lower the de-oxy Hb better the signal from the adjacent tissue. i.e images are BOLD • Detect tissue perfusion not the neuronal metabolism 30 Clinical Applications of Functional MRI, Neuroimaging Clinics of North America, Nov 2014
- 30. Mechanism of BOLDfMRI Brain activity Oxygen consumption Cerebral blood flow Oxyhemoglobin Deoxyhemoglobin Magnetic susceptibility T2* MR signal intensity 31 Clinical Applications of Functional MRI, Neuroimaging Clinics of North America, Nov 2014
- 31. Functional MRI (fMRI) 32 SilviaFrancesca Storti, Automatic selection of resting-state networks with functional magnetic resonance imaging , Front. Neurosci., 20 May 2013
- 32. 33 Kaplan and Saddock’sComprehensive Textbook of psychiatry, 9th edn, 2009 LWW
- 33. fMRI • Indications • Rolein seizure localisation • Study of neurodevelopmental disorders • Post-stroke recovery • Limitations – Vascular pathology reducing regional blood flow will impede signal acquisition by BOLD imaging – Psychotropic drugs • BZD agonist , antipsychotics – reduce CBF 34 Clinical Applications of Functional MRI, Neuroimaging Clinics of North America, Nov 2014
- 34. fMRI & Psychiatry 35 Guret al , FMRI in schizophrenia , Dialogues in Clinical Neuroscience - Vol 12 . 2010
- 35. fMRI & Psychiatry 36 IwabuchiaSJ, Localized connectivity in depression: A meta-analysis of resting state functional imaging studies , Neuroscience and Biobehavioral Reviews 51 (2015)
- 36. fMRI & Psychiatry 37 DementiaSchizophrenia Mood Disorders Serial fMRI- differential rate of volume changes Alterations in fn connectivity LTC LCSPTC Reduced activation of MTL Activation of PFC rCBF & rCMR in OFC & VLPFC No diagnostic criteria rCBF & rCMR in DLPFC ReHo in MPFC Iwabuchia SJ, Localized connectivity in depression: A meta-analysis of resting state functional imaging studies, Neuroscience and Biobehavioral Reviews 51 (2015) 77–86
- 37. fMRI in SubstanceAbuse • GM volume reduction in ADS - frontal and temporal lobes • Heavy drinking is associated with greater volume loss • Abstinent demonstrated greater tissue gain than LD or relapse. • Recovery in GM > WM. 38 Valerie A. Cardenas, Deformation-based morphometry of brain changes in alcohol dependence and abstinence, NeuroImage 34 (2007) 879–887
- 38. fMRI in SubstanceAbuse- Stimulant – Compromised white matter integrity – leading to functional impairments in decision making. 39 Karen D Ersche, Meta-analysis of structural brain abnormalities associated with stimulant drug dependence and neuroimaging of addiction vulnerability and resilience, Current Opinion in Neurobiology 2013,
- 39. fMRI Impact 40 Cognitive neuroscience Affect/ emotion Rewardpathways- neuro-economics Memory Default mode network Plasticity and brain development Legal Minimum age for capital punishment Lie detector Neuro-imaging before capital punishment Social: Parity Insurance Social cognition & meta-cognition (MFC) Therapeutic Reversibility of rCBF changes in depression Compliance Efficacy of treatments like DBS
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- 41. Diffusion MRI • Principle:diffusion of water molecules provides contrast • Information about the integrity and orientation of white matter tracts in the brain. • Assessing the tract disruption in disease states 42 Mori S, Principles of Diffusion Tensor Imaging and Its Applications to Basic Neuroscience Research, Neuron, Volume 51, Issue 5, 7 September 2006
- 42. Diffusion MRI • Clinicalutility: • Early identification of ischemic stroke • Differentiation of acute from chronic stroke • Assessment of the extent of diffuse axonal injury • Assessment of active demyelination 43 Mori S, Principles of Diffusion Tensor Imaging and Its Applications to Basic Neuroscience Research, Neuron, Volume 51, Issue 5, 7 September 2006
- 43. • Diffusion Tensor Imaging(DTI) –Type of DWI –several sets of diffusion weighted images are acquired with the diffusion gradients applied in different directions. –Enables the detection of diffusion anisotropy in various mediums such as brain white matter. 44 Mori S, Principles of Diffusion Tensor Imaging and Its Applications to Basic Neuroscience Research, Neuron, Volume 51, Issue 5, 7 September 2006 Han-Cheng Wang , Diffusion Tensor Imaging of Vascular Parkinsonism, Arch neurol/vol 69
- 44. 45 Shizukuishu T, DiffusionTensor Imaging Analysis for Psychiatric Disorders; Systematic Review, Magn Reson Med Sci, Vol 12, 2013
- 45. 46 DTI & Alzheimer'sDisease
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- 47. Radio tracer Imaging •Radio – unstable atom that decay • Tracer – administered in trace amounts • Typical tracer methods – PET – SPECT • PET – positron emitter – collides with electron - two photons released • SPECT – decays – single high energy photon 48
- 48. Radio tracer Imaging(Contd.) • Process of interest – – incorporate radionuclide in to a molecule of known physiological significance. • RADIOTRACER – Inhalation – Ingestion – Intravenous • Tracer uptake measured over time PET 49
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- 50. PET SPECT Radiotracer 18F-FDG C-13 or O-15 Xe-133, Tc-99 Physics Annihilation Gamma emission Direct Gamma photon emission Principle Co-incidence detection Back Projection Spatial resolution 2-5 mm 7-10 mm Measures rCBF & rCMR rCBF & rCMR 51
- 51. 52 Kaplan and Saddock’sComprehensive Textbook of psychiatry, 9th edn, 2009 LWW
- 52. PET IN COGNITIVEIMPAIRMENT 53
- 53. Mood Disorders • PET –Hypofrontality on frontal lobe in MDD but reversal occurs in Mania. – Less 5HT Tpt (SERT) availability in MDD – More 5HT 1A predict poor response. – High DAT availability in Rt caudate in MDD – Increased ACC and OFC activity - positive response to treatment – Activation in the right amygdala, striatum and insula -poor response 54 Cynthia H.Y. Fu, Predictive neural biomarkers of clinical response in depression: A meta-analysis of functional and structural neuroimaging studies of pharmacological and psychological therapies, Neurobiology of Disease 52 (2013) 75–83
- 54. PET in Depression 56 CynthiaH.Y. Fu, Predictive neural biomarkers of clinical response in depression: A meta-analysis of functional and structural neuroimaging studies of pharmacological and psychological therapies, Neurobiology of Disease 52 (2013) 75–83
- 55. Substance Abuse • PET& SPECT- – Deficit DA in mesolimbic system – Low 5HT in Type B & reverse in Type A – GABA receptor levels are low in frontal, temporal and parietal cortices in dependent cases. – HMPAO SPECT – poor rCBF in WKS – In Cocaine dependent -hypodopaminergic state & high DAT levels. 57 Kaplan and Saddock’s Comprehensive Textbook of psychiatry, 9th edn, 2009 LWW
- 56. Future Directions • SimultaneousPET/MRI – Biomarkers for psychiatric disorders • DTI – Tracts for identification of various pathologies. • Genetic-Imaging studies- predicting vulnerabilities • The future of fMRI lies in understanding the pathophysiology, diagnosis and prognosis of Psychiatric disorders (Thomas Insel) 58
- 57. Magnetoencephalography 59 Sanjay P. Singh,Magnetoencephalography: Basic principles, Ann Indian Acad Neurol. 2014 Mar;
- 58. Take Home Message 60 •Neuro-imaging provides a valuable and reliable tool in delineating organicity • Functional neuro-imaging can demonstrate subtle physiological changes before the actual structural changes become evident • Concept of organic and functional disorders • Physiological correlates of Psychiatric disorders have been shown • ? Causal / Vulnerability • Cost and availability- restrict their use as universal diagnostic biomarkers
- 59. References • Kaplan andSaddock’s Comprehensive Textbook of psychiatry, 9th edn, 2009 LWW. • New Oxford Textbook of Psychiatry, 2nd edn, 2012, OUP • Kaplan and Sadock's Synopsis of Psychiatry 11th Edition, 2014, LWW • Neuroradiology- The Prerequisites – 3rd edn, Grossman, 2010 • Clinical Applications of Functional MRI, Neuroimaging Clinics of North America, Nov 2014 61
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