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Neuroimaging in psychiatry


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Neuroimaging in psychiatry

  1. 1. NEUROIMAGING IN PSYCHIATRY Presenter: Dr.P.J.Chakma Pgt,Psychiatry Moderator: Dr. S.Ghosh Assoc. Prof. Deptt. Of psychiatry Assammedical college5/11/2013
  2. 2. Plan of presentation  Introduction  Milestonesin Neuroimaging  Types of Neuroimaging  Indicationsfor Neuroimaging  Basic Principles  Neuroimaging in Psychiatric condition  Conclusion  Bibliography
  3. 3. Introduction The factors determining human behavior have fascinated man from times immemorial. There has been constant endeavor to localize areas of the brain responsible for various aspects of behavior & especially to map out changes responsible for abnormal behavior.
  4. 4. Contd. Neuroimaging methodologies allow measurement of the structure, function and chemistry of the living human brain. Studies using these methods have provided new information about the pathophysiology of various psychiatry disorders and developing new treatment.
  5. 5. Milestones
  6. 6. Why neuroimaging? The research agenda for DSM-V emphasizes a need to translate basic and clinical neuroscience research findings into a new classification system for all psychiatric disorders based upon pathophysiologic and etiological processes
  7. 7. Contd. Although structural imaging techniques are most useful for ruling out medical etiologies of mental status disturbances, functional neuroimaging techniques currently have an adjunctive role in the evaluation of dementia and seizure disorders and show promise for the evaluation of primary psychiatric disorders in the future.
  8. 8. TYPESOF NEUROIMAGING Neuroimaging types are mainly two domains – 1) Structural study - provides noninvasive visualization of the morphology of the brain. 2) Functional study - provides a visualization of the spatial distribution of specific bio- chemical processes.
  9. 9. Various techniques • Electrical imaging: EEG, Evoked potentials, brain electrical activity mapping. • Radiological techniques: x-ray skull, angiography, cranial CT,PEG • MRI • Radio-isotopes imaging: SPECT, PET, Cerebral blood flow studies. • Blood flow studies: Doppler and Xenon
  10. 10. Contd. • Plain skull Radiography: plain films of the skull are of little value in studying psychiatric disorders, as it gives very little information. • Angiography: water soluble iodinated contrast medium is selectively injected intra-arterialy & opacification is filmed by conventional radiography.
  11. 11. Contd. • Pneumo-encephalography: PEG is a process in which air is introduced in the ventricular cavities to visualize any changes. Results of PEG in psychiatric patients have been reviewed by Weinberger and Wyatt. Cerebral atrophy found in psychiatric patients.
  12. 12. Uses of Neuroimaging A. Indications for ordering Neurimaging in clinical practice: Neurological deficits Dementia, NPH Infarction or stroke, SOL, Head trauma Brain tumor, Chronic infection(neurosyphilis, TB,NCC) Chronic demyelinating disease B. Neuroimaging in clinical research: 1.Analysis of clinically defined groups of patients: Psychiatric research 2. Analysis of brain activity during performance of specific task
  13. 13. CT Scan  CT became the preferred method for brain imaging after 1973.  It is a simple as passing X-ray through the patient and obtaining information with a detector on the other side.  A fan beam of X-ray emitted from a single source.  X-ray source and detectors are interconnected and rotated around the patient during scanning period
  14. 14. Contd.  Digital computer then assembles the data that is obtained and integrated it to provide a cross sectional image and displayed on a computer scan.  The image can be photographed and store from later retrieval.  The CT image is determined only by the degree to which tissue absorb X-irradiation.  Bony structure absorbed high amount of irradiation and appear white.  Soft tissue absorbed less irradiation and appear gray. Soft tissue and cavities with air and water appear black.
  15. 15. Contd.  In the CT scan there is little difference between white and gray matter. Gray-white matters borders usually indistinguishable. Details gyral pattern may be difficult to appreciate.  The component of brain matter better seen in CT scan is calcification which is not visible on MRI.  Appreciation of tumor and area of inflammation can be increased by I/V infusion of iodine containing contrast agent.
  16. 16. CT Axial section above foramen magnum Frontal sinus Sphenoid sinus Temporal lobe Basilar A. Mastoid cells Cerebellar hemisphere Cisterna magna Medulla Optic nerve Pituitary Sphenoid bone Temporal bone Cerebellar tonsils
  17. 17. CT Axial section at 4th ventricle Frontal sinus Frontal bone Mid.cerebral A Basilar A. Pons 4th vent cerebellum Mid cerebellar peduncle Petro us bone Temporal horn Ant.cerebral a Sella turcica Vermis
  18. 18. CT Axial section at 3rd ventricle Genu of corpus callosum Caudate nucleus Int.capsule 3rd ventricle Pineal gland vermisOccipital lobe Choroid plexus Thalamus Lentiform nucleus Frontal horn Pericallosal A
  19. 19. This is the basic idea of computer aided tomography. In a CT scan machine, the X- ray beam moves all around the patient, scanning from hundreds of different angles. A conventional X-ray image is basically a shadow. Shadows give you an incomplete picture of an object's shape. Comparison of CT withConventional Radiography
  20. 20. Magnetic Resonance (MR) • MR Angiography/Venography (MRA/MRV) • Diffusion and Diffusion Tensor MR • Perfusion MR • MR Spectroscopy (MRS) • Functional MR (fMRI)
  21. 21. Basic of MRI  MRI technique is based on Nuclear Magnetic Resonance (NMR).  Nucleus of certain atoms behave like small magnet.  When atoms are placed in magnetic field the axis of odd numbers nucleus align with the magnetic field.  Axis of the nucleus is deviates away from the magnetic field when exposed to a pulse of radio- frequency electro-magnetic radiation oriented at 90o or 180o to the magnetic field.
  22. 22. Contd.  When pulse of radio-magnetic frequency is terminated the axis of the spinning nucleus is re- align itself with the magnetic field. During re- alignment it emits its own radio-frequency signal.  MRI scans collect the emission of each individual re-aligning nuclei and use computer analysis to generate a series of three dimensional images.  The images can be in the axial, coronal and sagital plans.
  23. 23. Contd.  Most abundant odd numbers nuclei in the brain are belongs to hydrogen.  The rate of hydrogen axis re-alignment is determined by its immediate environment.  Hydrogen nucleus within the fat re-aligned rapidly, within water re-aligned slowly and in protein and carbohydrate re-aligned intermediately.
  24. 24. Contd.  There are different types of radio-frequency pulse or sequence used in routine MRI.  T1 pulse is brief and data collection is brief.  Fat appear bright on T1 pulse.  CSF appear dark in T1 pulse.
  25. 25. Contd.  T1 is the only sequence that allows contrast enhancement. Contrast used in Gadolinium-DTPA. On T1 images, gadolinium-enhanced structures appear white.  T2 pulse is long and data collection is also long.  Brain tissue appear dark in T2 pulse.  CSF appear white in T2 pulse.  Area in the brain having abnormally high water content such as tumor, inflammation or stroke appear bright on T2.
  26. 26. Contd.  MRI magnant are rated in Teslas Unit (T).  In clinical practice rang use from 0.3 to 2.0 Teslas.  MRI is free from hazard of X-ray irradiation.  Electro-magnetic field of the strength use in MRI is not shown to damage the biological tissue.
  27. 27. Contd. • MRI-images of a slice through the human body • Each slice has a thickness (Thk) • Voxels - Volume elements (several volume elements that compose a slice) • Voxel - approx 3 mm3 • Pixels- Picture elements that constitute an MRI image
  28. 28. Disadvantages of MRI  MRI cannot be used for patient with pacemakers or implanted of Ferro-magnetic metals.  Some patient cannot tolerate the claustrophobic condition of routine MRI.  Radio-frequency pulse creates a loud banging noise.  Patient must remain motionless for minimum 20 minutes.
  29. 29. Functional MRI (fMRI)  fMRI is the indirect measurement of neural activity measuring the changes in local blood Oxygenation – blood oxygen level dependent.  Increased neuronal activity within the brain causes the local increase in blood flow and causes increased heamoglobin concentration.  Causes a change of Oxy and deoxy-heamoglobin concentration in local vasculature.
  30. 30. Contd.  Oxygenated blood is magnetically transparent (diamagnetic) deoxygenated blood is paramagnetic.  fMRI is useful localize neuronal activity to a particular lobe or sub-cortical nucleus and localize the activity to a single gyrus.  fMRI detect tissue perfusion not the neuronal metabolism.  No radio-isotope is use in fMRI.
  31. 31. Mechanismof BOLD Functional MRI Brain activityBrain activity Oxygen consumption Cerebral blood flow Oxyhemoglobin Deoxyhemoglobin Magnetic susceptibility T2* MRI signal intesityMRI signal intensity
  32. 32. Contd. fMRI revealed about the organization of language within the brain.  Rhyming produced different pattern of activation in men and women.  Rhyming activated the inferior frontal gyrus bilaterally in women but only on the left in men.  fMRI is widely used to study brain abnormality related to cognitive dysfunction.
  33. 33. INDICATIONS • Neurosurgical uses • Role in seizure localisation • Neuropsychiatry • fMRI is the study of neurodevelopment and disorders • Watching the brain heal itself-stroke recovery • fMRI in lie detection • future role in pain management
  34. 34. LIMITATIONS • Fast imaging reduces the spatial resolution to a few millimeters • The reliability is reduced when there are significant subject motions or physiologically related variations. • The origins and influence of various sources of such variance are not yet completely understood. • Aging and impaired cerebrovascular supply are also likely to affect the magnitude of the BOLD response. • Expensive
  35. 35. MRS(magneticresonance spectroscopy) • MRS is a diagnostic technique that distinguishes various metabolites on the basis of their slightly different chemical shift or resonance frequency. • MRS can be performed using a range of nuclei [ H-1,P- 31,C-13,FL-19,etc]. • Quantitative noninvasive assay of metabolites • Indispensable for State of Art Neurodiagnosis
  36. 36. MRS(magneticresonance spectroscopy)  Whereas MRI detects Hydrogen nuclei to determine anatomical structure of brain.  MRS can detect several odd numbers nuclei to detect metabolic process in the brain.  The readout of a MRS device is usually formed of spectrum which can be converted to pictorial images of brain.
  37. 37. Contd.  MRS signal from proteins to determine the concentration of brain metabolites such as N- acetylaspartate (NAA), cholin , creatine and lactate in the tissue.  Also detect myo-inositol , glutamate, GABA biogenic amines.  Measure the concentration of Antipsychotic drugs in the brain particularly lithium in BPAD.
  38. 38. Comparison of CT and MRI images (A) CT scan and (B) MRI showing the increased sensitivity that MRI adds in visualizing brain lesions, such as those in MS (arrows).
  39. 39. MRI Vs MRS • Digitizes signal & generates images. • Frequencies used to encode space. • H2O & Fat predominates • All field strengths • Digitizes signal & generates a spectrum • Frequencies used to encode chemistry • Metabolites predominate • Field strength equal or greater than 1.5 T
  40. 40. DTI (DiffusionTensor Imaging)  MRI technique that enable the measurement of the restricted diffusion of water in tissue.  Principal application of is in the imaging of white matter. Where the location, orientation and anisotropy of the tract can be measured.  The architecture of the axons in parallel boundless, and their myelin sheath facilitates the diffusion of water molecule preferentially along their main direction.
  41. 41. Contd.  DTI is mainly study the white matter integrity in Schizophrenia.  1986 diffusion MR is introduced.  1994 Peter Basser and Colleagues developed DTI.  First DTI study of Schizophrenia was by Monte S. Buchsbaum and co-workers in 1998.
  42. 42. SPECT (Single Photon Emission Computed Tomography)  Nuclear medicine tomographic imaging using gamma ray.  Image obtained by a gamma camera image is a 2D view of 3D distribution of a radio-nuclide.  SPECT gamma camera to acquire multiple 2D images from multiple angles.  A computer is then used to apply a tomographic reconstruction algorithm to the multiple projections giving 3D data set.
  43. 43. Contd.  Gamma camera is rotated around the patient head.  Projection acquired at defined points during the rotation typically every 3-6 degree.  Full 360 degree rotation is used to obtain an optical reconstruction.  Gamma ray emitting tracer isotope used in SPECT is technetium – 99m hexamethylpropyleneamine oxime (TC 99m HMPAO) ,xenon 133 and Iodine 123
  44. 44. Contd.  Reconstructed images typically have resolution of 64x64 or 128x128 pixel with the pixel sizes ranging from 3-6 mm.  SPECT is more widely available.  Radioisotope generation technology is long lasting and far less expensive.
  45. 45. Contd.  Gamma scanning equipment is less expensive.  The word tomography means delineation of slides or sections. When it is done with the help of computers it is called computed tomography and when single gamma emitting is used it is called single photon emission computed tomography.
  46. 46. Equipment required in SPECT  A rotating gamma camera and attached scan view computer system.  Computers  Computer Tomography enter phase.  Reconstruction software  Appropriate radio-pharmaceutical.  Radioactive component used in SPECT to study regional differences in cerebral blood flow within the brain.
  47. 47. Contd.  The injected gamma emitters isotopes are attached to molecules that are highly lipophillic and rapidly cross blood brain barrier and enter cells. Inside the cell the ligands are enzymatically converted to charged ions which remain trapped inside the cells.  Over time the tracers are concentrated in the area relatively higher blood flow.  Iodine 123 (123I) labeled ligands are used to study muscarinic, dopaminirgic and serotonergic receptor to study these receptor with SPECT technology.
  48. 48. PET (Positron Emission Tomography)  Nuclear medicine medical imaging technique which produces a three dimensional image of functional processes in the brain.  Injection of radioactive tracer isotope which decays by emitting a positron, which also has been chemically incorporated into a metabolically active molecule.  Waiting period of time while metabolically active molecules become concentrated.
  49. 49. CONTD  Patient is placed in the imaging scanner.  Modern PET system can provide 3D images of brain with resolution of the order of 4-6 mm.  The most commonly used molecules or ligands for the purpose of PET scan is Fluorodeoxyglucose (FDG) an analogue of glucose that the brain cannot metabolized. The waiting period of FDG is about typically an hour.
  50. 50. Contd.  Other commonly used isotopes are Carbon-11 about 20 min (waiting period) Nitrogen-13 (10 min) Oxygen-15 (2 min) and Fluorine -18(110 min).  Limitation to the use of PET arises from the high cost of CYCLOTRONS needed to produce the isotope of biological substance.  Need for specially adapted on-site chemical synthesis apparatus to produce the radio- pharmaceuticals.
  51. 51. Contd.  Depending upon the isotope used PET scanning can give information of cerebral blood flow, cerebral blood volume, and cerebral metabolism.  Also study normal brain development and function.  It can study the different receptor site also.
  52. 52. Neuroimaging in certainpsychiatric condition
  53. 53. MRI in Dementia –  Atrophy of whole brain along with enlargement of the ventricles and sulci and CSF spaces.  Focal atrophy in frontal temporal and parietal lobe.  Selective atrophy of frontal and temporal lobe in Fronto- temporal dementia.  Atrophy of putamen and caudate nucleus in Huntington’s disease.  Early onset Alzheimer’s disease has decrease in white matter in addiction to reduction in gray matter.
  54. 54. Normal Dementia
  55. 55. Alzheimer’s Disease  Reduction in Hippocampus volume seen in 19-40% cases.  15-20% reduction in parahippocampal gyrus.  30-40% smaller volumes of Amygdala  Reduction in the volume of corpus callosum
  56. 56. measurements of hippocampus Normal ALZHEIMER’S DISEASE
  57. 57. MRS in Dementia  NAA (N–acetyl-aspertate) concentration is decreased in temporal lobe in Alzheimer’s Disease.  NAA concentration also decreased in Parkinson ’s disease and Huntington’s Disease.  Increased concentration of Inositol in the occipital lobe seen in Alzheimer ’s disease. CINGULATE GYRUS
  58. 58. PET in Dementia  Parietal lobe involved symmetrical fusion often extension to the adjacent temporal and occipital lobe.  Huntington’s Disease chemical abnormality detected by PET.
  59. 59. CT Scan Dementia  Differentiate vascular dementia from other type of dementia.  Shows cerebral Atrophy and ventricular enlargement.
  60. 60. SPECT in Dementia  Perfusion defect in patients with Alzheimer’s disease almost bilateral asymmetrical in intensity most severe in the posterior temporal parietal lobe.  Muscarinic acetylcholine receptor has been imaged in Alzheimer’s Disease and normal subject using high affinity isotope. vascular dementia shows multiple patchy perfusion defects
  61. 61. DTI in Alzheimer’s Disease  Significant frontal, temporal and parietal white matter diffusion tensor changes in Alzheimer’s and mild cognitive impairment.
  62. 62. MRI in OCD  Decreased total cerebral white matter volume.  Left orbital frontal cortical volume is smaller in OCD.  Smaller volume of basal ganglia segment.  Corpus callosum length is abnormal.  Pituitary volume is abnormal.
  63. 63. SPECT in OCD  Serotonergic input into the fronto-subcortical circuit is reduced in OCD.  Reduced midbrain pons serotonin transporters binding in OCD.  Right basal ganglia hypoperfusion in OCD. PET in OCD  5 HTT availability was significantly reduced in the thalamus and midbrain.  Increase activity (metabolism) in frontal lobe, basal ganglia and cingulum.
  64. 64. MRS in OCD  MRS is used to measure NAA concentration in the anterior cingulate , the left basal ganglia and left prefrontal lobe of patient.  Significant lower NAA concentration in respond to SSRI with Anti-Anxiety Medicine in anterior cingulated gyrus.
  65. 65. DTI in OCD  Drug naive OCD patients showed significant increase in fractional anisotropic (FA) in the Corpus callosum.  Internal capsules white matter in the area superolated to the right caudate.
  66. 66. CT Scan in Schizophrenia  Enlarged ventricles (lateral ventricle)  Evidence of dilated cerebral sulci.  Cerebellar Atrophy.  Enlarged 3rd ventricles as a consistent finding in some schizophrenic patients.  Patients having larger ventricles responds least to neuroleptic medication.  Abnormal ventricular size tend to have worst psychometric performance & a predominance of (-) ve symptoms.
  67. 67. MRI in Schizophrenia  Childhood onset schizophrenia – smaller brain volume.  Disproportionally large volume losses commonly seen in medial temporal lobe structures such as amygdale, hippocampus parahippocampal gyrus and superior-temporal gyrus.  Few studies also report tissue deficit in frontal and parietal cortexes and corpus callosum.
  68. 68. Contd.  Typical antipsychotic increases the size of basal ganglia.  Positive Syndrome – -Decreased volume of superior temporal gyrus.  Negative Syndrome – -Enlarged lateral ventricles.
  69. 69. DTI in Schizophrenia  Fronto-temporal connection – uncinate fasciculus decrease left to right fractional anisotrophy in chronic patient.  Cingulus bundle which is involved in pain perception and emotion, self monitoring orientation and memory shows reduced anisotrophy in chronic schizophrenic patient.
  70. 70. MRS in Schizophrenia • Decreased NAA concentration in the temporal and frontal lobe.
  71. 71. SPECT in Schizophrenia  By study regional cerebral blood flows a patient of cerebral hypoperfusion in schizophrenic patient never treated with antipsychotic drugs.
  72. 72. PET study in Schizophrenia  Hypofrontality in Schizophrenia patient.  Reduced glucose intake in left frontal region.  Lower glucose utilization in central gray matters.
  73. 73. fMRI in Depression  Bilateral anterior cingulated cortex, right Amygdala. Significantly smaller in MDD.  Greater activation in frontal and anterior temporal areas during inhibiting task in MDD.  Successful inhibition – Bilateral inferior frontal gyrus and lateral amygdala insula.
  74. 74. SPECT in Depression  Baseline cerebral blood flow is lower in depressive patient in frontal cortex and sub-cortical nuclei bilaterally.  Medication response – normalization of cerebral blood flow deficit.  ECT – additional cerebral blood flow deficit decrease in the parieto-temporal and cerebeller region bilaterally.
  75. 75. MRI in Depression  Abnormal hyperintensities in periventricular area, basal ganglia and thalamus.  Ventricular enlargement.  Cortical Atrophy, widening of sulci.  Reduced hippocampus and caudate nucleus volume.  Diffuse and focal area of atrophy.
  76. 76. PET in Depression  Decreased anterior brain metabolism more pronounced in left side.  Relative increases activity in nondomaint hemisphere.  Reduce cerebral blood flow.  BPD reduced 5 HTT in MDD patient in the vicinity of the pontine raphe nuclei.  Severity correlates negativity with 5 HTT in the thalamus in MDD subject.
  77. 77. MRI in Anxiety  Occasionally shows increase size of ventricles.  Specific defect in right temporal lobe nucleus in Panic Disorder.  A symmetrical cerebral hemisphere.  Smaller left hippocampal volume in adult women with childhood sexual abuse and women with PTSD.  Panic disorders smaller temporal lobe.
  78. 78. fMRI in Anxiety Disorder • Increased activity of Amygdala in PTSD associated with fear.
  79. 79. MRS in panic disorder • To record the level of lactate • Brain lactate concentrations were found To be elevated during panic attacks.
  80. 80. MRI in ADHD  Early onset ADHD is associated with smaller total brain volume – 4% cases.  Decrease in the volume of the posterior inferior cerebeller vermis.  Person with ADHD may have equal size caudate nucleus.
  81. 81. MRI- Autism • In the cerebrum, volume loss of the parietal lobe cortex ,white matter, as well as the posterior corpus callosum has been reported • Another group reported that the midbrain and medulla were significantly smaller. • The brainstem and cerebellar vermis (lobules VIII to X) were significantly smaller in autistics than in controls .
  82. 82. PET- Autism • Increase in diffuse cortical metabolism noted.
  83. 83. HEAD INJURY
  84. 84. Neurocysticercosis
  85. 85. NORMAL PRESSURE HYDROCEPHALUS Three primary MR findings have been described in NPH: enlargement of the ventricular system out of proportion to the subarachnoid space a prominent periventricular halo and a prominent CSF flow void in the cerebral aqueduct.
  86. 86. Tuberous sclerosis
  87. 87. conclusion Just as in other medical fields, the application of latest technology in psychiatry has resulted in opening up of new vistas for the understanding of the various disorders. However, the technological progress is so fast that in next decade much information will be available regarding the underlying causes of psychiatric illness with the help of brain imaging techniques.
  88. 88. References  Comprehensive Text Book of Psychiatry – Kaplan & Sadock, 9th Edition page 201-221.  Synopsis of Psychiatry, Kaplan & Sadock, 10th Edition, page 110-117.  Saxena GN, Brain imaging in psychiatry ,Text book of Post Graduate Psychiatry, Ahuja & Vyas, Second edition 2003,vol 2,chap 48,681-690  