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Neuroimaging by dr k k sharma

basic neuroimaging for psychiatry students

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Neuroimaging by dr k k sharma

  1. 1.  Introduction  Milestones in Neuroimaging  Types of Neuroimaging  Indications for Neuroimaging  Basic Principles  Neuroimaging in Psychiatric condition  Conclusion  Bibliography
  2. 2. Milestones
  3. 3. 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
  4. 4. 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.
  5. 5. TYPES OF 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.
  6. 6. Various techniques • Electrical imaging: EEG, Evoked potentials, brain electrical activity mapping. • Radiological techniques: x-ray skull, angiography, cranial CT. • MRI ,MRS • Radio-isotopes imaging: SPECT, PET, Cerebral blood flow studies. • Blood flow studies: Doppler and Xenon
  7. 7. 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.
  8. 8. 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
  10. 10. A conventional X-ray image is basically a shadow. Shadows give you an incomplete picture of an object's shape. 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. Comparison of CT withConventional Radiography
  11. 11. HISTORY • Sir Godfrey hounsfield-1972 • Nobel prize in 1979 • Original scanners took approximately 6 minutes to perform a rotation (one slice) and 20 minutes to reconstruct. Despite many technological advances since then, the principles remain the same.
  12. 12. PARTS OF CT SCAN 1) Gantry- which houses X ray apparatus 2) X ray tube-akin to that in a X ray machine. 3) Detectors 4) Patient couch 5) Viewing console
  13. 13. PRINCIPLE • Uses X rays applied in sequence of slices across the organ • Images reconstructed from X ray absorption data • X ray beam moves around the patient in a circular path
  14. 14. …Contd CT Scanners take a series of head X-ray pictures from all vantage points 360º around a patient's head The amount of radiation that passes through, or is not absorbed from, each angle is digitized & entered into a computer The computer uses matrix algebra calculations to assign a specific density to each point within the head & displays these data as a set of 2-D images When viewed in sequence, the images allow mental reconstruction of the structure of the brain
  15. 15. BASICS…. • X-RAYS ARE ABSORBED TO DIFFERENT DEGREES BY DIFFERENT TISSUES • Always describe CT findings as densities- isodense/hypodense/hyperdense. • Higher the density = whiter is the appearance • Lower the density = darker the appearance • Brain is the reference density • Anything of the density as brain= isodense • Higher density than brain= hyperdense ( skull is the best example) • Anything darker (lower density) than brain= hypodense( CSF and air are classical examples)
  16. 16. HOUNSFIELD UNITS • Related to composition & nature of tissue • Represent the density of tissue • Also called as CT NUMBER
  17. 17. air --- 1000 fat ---70 Pure water 0 Csf +8 White matter +30 Gray matter +45 blood +70 Bone/calcification +1000
  18. 18. • Criteria for Contrast- – Patients with H/O seizure – Patients with H/O cerebro-vascular accident – Suspicion of intracranial SOLs including granulomas, CNS tumours, metastatic lesions ¤ Plain CT • Diagnostic accuracy 82% ¤ Contrast CT • IV iodinated contrast medium • Diagnostic accuracy 92%
  19. 19. • Confusion &/or dementias of unknown cause • First episode of psychosis • First episode of major affective disorder after 50 years of age • Personality changes after 50 years of age • Psychiatric symptoms following head injury • To rule out complications due to possible head trauma • Prolonged catatonia • Co existence of seizure with psychiatric symptoms • Movement disorders of unknown etiology • Focal neurological signs accompanying psychiatric symptoms CLNICAL INDICATIONS OF CT BRAIN IN PSYCHIATRY Weinberg 1984; Beresford et al 1986
  20. 20. TECHNIQUE….. Slice thickness may vary, but in general, it is between 5 and 10 mm for a routine Head CT
  21. 21. Densities on ct scan…….
  23. 23. Lateral View of Brain
  25. 25. NORMAL ANATOMY……. A=Frontal Lobe, B= Frontal Bone (Superior Surface of Orbital Part), C= Dorsum Sellae, D=Basilar Artery E= Temporal Lobe F= Mastoid Air Cells G=Cerebellar Hemisphere
  32. 32. Physiological calcifications
  33. 33. • Simpler, cheaper, more accessible • Tolerated by claustrophobics • No absolute contraindications • Better than MR for bone detail & Calcification ADVANTAGES OF CT SCAN
  34. 34. LIMITATION OF CT SCAN  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.  Certain tumors may be invisible on CT because they absorb as much irradiation than the surrounding brain visible on Contrast CT.
  35. 35.  Ionizing radiation  The bony structures absorb high amounts of irradiation and tend to obscure details of neighboring structures, an especially troublesome problem in the brainstem, which is surrounded by a thick skull base.  There is relatively little difference in the attenuation between gray matter and white matter in X-ray images.  Details of the gyral pattern may be difficult to appreciate in CT scans.
  36. 36. Magnetic Resonance (MR) • MR Angiography/Venography (MRA/MRV) • Diffusion and Diffusion Tensor MR • Perfusion MR • MR Spectroscopy (MRS) • Functional MR (fMRI)
  37. 37. 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.
  38. 38. MRI Liquid Helium Cooled 1.5 Tesla Solenoid Magnet Patient Platform Radiofrequency Transmitter/Reciever Coil
  39. 39. 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.
  40. 40. 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.
  41. 41. 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.
  42. 42. 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.
  43. 43. T1 Weighted MRI • Best for visualizing normal neuroanatomy  Sharp boundaries between grey matter, white matter, and CSF  Useful in evaluation of cerebro- pontine angle cistern & pituitary fossa •T1 is the only sequence that allows contrast enhancement with Gadolinium. •Contrast enhanced structures on T1 appears white.
  44. 44. T2 Weighted MRI • Less distinct boundaries between white and grey matter • Best for displaying pathology  Useful in demyelination, edema & tumour infiltration
  46. 46. Fluid Attenuated Inversion Recovery (FLAIR) • Special type of MRI scan • T1 image is inverted & added to the T2 image • Contrast between grey & white matter is doubled & the normal CSF signal is suppressed. • Special indications 1. To detect Sclerosis of hippocampus in Temporal lobe epilepsy. 2. To Localize the areas of abnormal metabolism in degenerative neurological diseases.
  47. 47. Contd.  MRI magnant are rated in Teslas Unit (T).  In clinical practice rang use from 0.3 to 2.0 Teslas.(max 9.4 T)  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.
  48. 48. 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
  49. 49. ADVANTAGES OF MRI • Does not expose the patient to ionizing radiations • Demyelinating disease can be assessed reliably • better study of posterior fossa structures
  50. 50. 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.
  52. 52. Amygdala
  53. 53. Hippocampus
  54. 54. Caudate Head
  55. 55. Putamen
  56. 56. Globus Pallidus
  57. 57. 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.
  58. 58. 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.  No radioactive isotopes are administered in fMRI, a great advantage over PET and SPECT.
  59. 59. Mechanism of BOLD Functional MRI Brain activityBrain activity Oxygen consumption Cerebral blood flow Oxyhemoglobin Deoxyhemoglobin Magnetic susceptibility T2* MRI signal intesityMRI signal intensity
  60. 60. 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.
  61. 61. 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
  62. 62. 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
  63. 63. • What fMRI detects is not brain activity per se, but blood flow. The volume of brain in which blood flow increases exceeds the volume of activated neurons by about 1 to 2 cm and limits the resolution of the technique. • Thus, two tasks that activate clusters of neurons 5 mm apart, such as recognizing two different faces, yield overlapping signals on Fmri • The method detects tissue perfusion, not neuronal metabolism. In contrast, PET scanning may give information specifically about neuronal metabolism.
  64. 64. MRS(magnetic resonance 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
  65. 65. MRS(magnetic resonance 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.
  66. 66. CONTD. • The multiple peaks for each nucleus reflect that the same nucleus is exposed to different electron environments (electron clouds) in different molecules. • The hydrogen nuclei in a molecule of creatine, therefore, have a different chemical shift (position in the spectrum) than the hydrogen nuclei in a choline molecule, for example. • Thus, the position in the spectrum (the chemical shift) indicates the identity of the molecule in which the nuclei are present.
  67. 67. CONTD. • The height of the peak with respect to a reference standard of the molecule indicates the amount of the molecule present. • The MRS of the hydrogen-1 nuclei is best at measuring N-acetylaspartate (NAA), creatine, and choline-containing molecules; but MRS can also detect glutamate, glutamine, lactate, and myo-inositol.
  68. 68. Contd.  Measure the concentration of Antipsychotic drugs in the brain particularly lithium in BPAD.  Although glutamate and GABA, the major amino acid neurotransmitters, can be detected by MRS, the biogenic amine neurotransmitters (e.g., dopamine) are present in concentrations too low to be detected with the technique
  69. 69. 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
  70. 70. DTI (Diffusion Tensor 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.
  71. 71. 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.
  72. 72. SPECT (Single Photon Emission Computed Tomography)  The word tomography means delineation of slides or sections. when single gamma emitting method is used it is called single photon emission computed tomography.  Image obtained by a gamma camera image is a 2D view of 3D distribution of a radio-nuclide.
  73. 73.  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.
  74. 74. Equipment required in SPECT  A rotating gamma camera and attached scan view computer system  Reconstruction software  Radioactive component used in SPECT to study regional differences in cerebral blood flow within the brain.
  75. 75.  Gamma camera is rotated around the patient head.  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  Xenon quickly enters brain and is distributed to areas of brain as a result of regional blood flow, Xenon- SPECT is thus used in the regional cerebral blood flow (rCBF) technique
  76. 76. 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.
  77. 77. 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.
  78. 78. Regional cerebral blood flow  Tc 99 is most commonly used for deeper structures of brain  Xe 133 for superficial structures of brain (rCBF Technique) Muscarinic cholinergic system & Dopaminergic system BY I123 Adrenergic system Alzheimer's disease USES OF SPECT
  79. 79. 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.
  80. 80.  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.
  81. 81.  Thus, the brain regions with the highest metabolic rate and the highest blood flow take up the most FDG but cannot metabolize and excrete the usual metabolic products. The concentration of 18F builds up in these neurons and is detected by the PET camera.  [18F]-labeled 3,4-dihydroxyphenylalanine (DOPA), the fluorinated precursor to dopamine, has been used to localize dopaminergic neurons.
  82. 82.  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.
  83. 83. 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.
  84. 84. SPECT v/s PET SPECT PET Single photon Positron 99mTc or I 123 11C or 18F Short half life Longer half life Less sensitive Highly sensitive (100 times more than SPECT) Can buy isotopes Local cyclotron Low spatial resolution Superior spatial resolution Cheaper and easily available than PET Costly, not easily available
  85. 85. Increased loss of gray matter in adolescence between the ages of 12-16 compared to healthy adolescence. Red—Gray Matter Gain Blue—Gray Matter Loss PET scan
  86. 86. PET scans of a 45 year old woman with recurrent depression pre and post treatment.
  87. 87. PET Scan ADHD vs. Normal White, Red, Orange = higher glucose metabolism Blue, Green, Purple = lower glucose metabolism NORMAL ADHD
  89. 89. Neuroimaging in certainpsychiatric condition
  90. 90. DEMENTIA • The most common cause of dementia is Alzheimer's disease, which does not have a characteristic appearance on routine neuroimaging but, rather, is associated with diffuse loss of brain volume. • ventricular size increases with age even in healthy persons and particularly so in the later decades of life. • With regard to dementia,in elderly subjects, cortical atrophy is a rather better discriminator than the ventricular size.
  91. 91. CONTD. • MRI is particularly valuable in the diagnosis of dementing illnesses and has more sensitivity than CT. • The volumetric measures of particular anatomical structures such as amygdala, hippocampus and entorhinal cortex rather than the brain as a whole, have a good positive predictive value in the diagnosis of Alzheimer’s disease.
  92. 92. CONTD. • In addition to major strokes, extensive atherosclerosis in brain capillaries can cause countless tiny infarctions of brain tissue; patients with this phenomenon may develop dementia as fewer and fewer neural pathways participate in cognition. • This state, called vascular dementia, is characterized on MRI scans by patches of increased signal in the white matter.
  94. 94. 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
  95. 95. Few conditions that can have symptoms like dementia • Infarction of the cortical or subcortical areas, or stroke, can produce focal neurological deficits, including cognitive and emotional changes. Strokes are easily seen on MRI scans. • Depression is common among stroke patients, either because of direct damage to the emotional centers of the brain or because of the patient's reaction to the disability. Depression, in turn, can cause pseudodementia .
  96. 96. CONTD. • Huntington's disease typically produces atrophy of the caudate nucleus; thalamic degeneration can interrupt the neural links to the cortex. • Space-occupying lesions can cause dementia. • Chronic infections, including neurosyphilis, cryptococcosis, tuberculosis, and Lyme disease, can cause symptoms of dementia and may produce a characteristic enhancement of the meninges, especially at the base of the brain.
  97. 97. CONTD. • Human immunodeficiency virus (HIV) infection can cause dementia directly, in which case is seen a diffuse loss of brain volume. • Creutzfeldt-Jakob virus : progressive multifocal leukoencephalopathy, which affects white matter tracts and appears as increased white matter signal on MRI scans.
  98. 98. CONTD. • Chronic demyelinating diseases, such as multiple sclerosis, can affect cognition because of white matter disruption. Multiple sclerosis plaques are easily seen on MRI scans as periventricular patches of increased signal intensity.
  99. 99. MRI in Dementia –  Atrophy of whole brain along with enlargement of the ventricles and sulci and CSF spaces.  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.
  100. 100. CT Scan Dementia  Differentiate vascular dementia from other type of dementia.  Shows cerebral Atrophy and ventricular enlargement.
  101. 101. measurements of hippocampus Normal ALZHEIMER’S DISEASE
  102. 102. 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
  103. 103. PET of Glucose Metabolism in normal vs. Alzheimer’s Disease
  104. 104. 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.
  105. 105. 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
  106. 106. SPECT of rCBF in AD (Cummings and Mega, 2003)
  107. 107. Neuroimaging in ocd
  108. 108. • Bilaterally smaller caudate in OCD pts. • Decreased volume of Left orbital frontal cortex. • Abnormality in Pituitary volume may also be noted. • Larger anterior cingulate volumes (ACV)  a/w increased OCD symptoms severity but not duration of illness • Abnormality in length of Corpus callosum. CT & MRI IN OCD
  109. 109. • Greater Glutamatergic conc. in caudate, as measured by ¹H-MRS in comparison to controls • OCD patients were divided into three groups – Responders to a SSRI – Responders to a SSRI + an Atypical Antipsychotic – Non-Responders to either SSRI or SSRI + an Atypical Antipsychotic • MRS was used to measure NAA concentrations in the anterior cingulate, the left basal ganglia & the left prefrontal lobe of the subjects • Significantly lower NAA concentrations in responders to SSRI + Atypical Antipsychotic in anterior cingulate gyrus MRS IN OCD
  110. 110. SPECT in OCD  In a resting SPECT study, OCD pts has increased mesial frontal perfusion, which normalised with fluoxetine Rx.  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.  Pharmalcological and behavioral Rx reportedly reverse these abnormalities.
  111. 111. PET have shown- Increased activity (eg. Metabolism & blood flow) in  the frontal lobes, basal ganglia(sp. caudate), and the cingulate gyrus in OCD pts. (findings consistent with the MRI findings) PET in OCD
  112. 112. Neuroimaging in Schizophrenia
  113. 113. CT Scan in Schizophrenia  Evidence of dilated cerebral sulci.  Cerebellar Atrophy.  Enlarged 3rd ventricles as a consistent finding in schizophrenic patients.  Decreased size of medial temporal lobe structures which include the amygdala, hippocampus, and parahippocampal gyrus ,superior temporal gyrus.  Hippocampus is not only smaller in size but also functionally abnormal (disturbed glutamate transmission in functional scans)
  114. 114.  Parietal lobe abnormalities, particularly of the inferior parietal lobule which includes both supramarginal and angular gyri.  Subcortical abnormalities ( cavum septi pellucidum, basal ganglia, corpus callosum, and thalamus)  Abnormal ventricular size tend to have worst psychometric performance & a predominance of (-) ve symptoms and responds poor to neuroleptic medication.
  115. 115. • Reduced symmetry in various brain areas may be indicative of disruption of brain lateralisation during neurodevelopment. • Anatomical & functional deficits in prefrontal cortex. • Volume shrinkage or neuronal loss in medial dorsal nucleus of thalamus.
  116. 116. MRI in Schizophrenia  Childhood onset schizophrenia – smaller brain volume.  (As mentioned in earlier slides ) Disproportionally large volume losses commonly seen in medial temporal lobe structures such as amygdale, hippocampus parahippocampal gyrus and superior-temporal gyrus.  In adolescents and young adults who manifest symptoms of the schizophrenia prodrome, or who are in their first episode of schizophrenia, many of the changes associated with chronic schizophrenia are already present.
  117. 117. Contd.  Typical antipsychotic increases the size of basal ganglia.  Positive Syndrome – -Decreased volume of superior temporal gyrus.  Negative Syndrome – -Enlarged lateral ventricles.  Family members of individuals with schizophrenia show a pattern of reductions in cortical gray and white matter volume that resembles, but is milder than, that associated with schizophrenia.
  118. 118. CONTD.  It is interesting to note that some data suggest the possibility that treatment with some “second generation” or “atypical” antipsychotic medications may reduce the short-term, i.e., 1 to 2 years, progression of cortical volume reductions  the typical antipsychotic treatment-related increase in basal ganglia volume in patients with schizophrenia.  There is hope that these types of studies might reveal neuroprotective effects of future pharmacotherapies for schizophrenia.
  119. 119. Ventriculomegaly in sch
  120. 120. Ventriculomegaly in discordant monozygotic twins seen on T2-weighted MRI scans HEALTHY TWIN TWIN WITH SCHIZOPHRENIA
  121. 121. 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.
  122. 122. MRS in Schizophrenia • Decreased NAA concentration in the temporal and frontal lobe.
  123. 123. SPECT in Schizophrenia  By study regional cerebral blood flows a patient of cerebral hypoperfusion in schizophrenic patient never treated with antipsychotic drugs.
  124. 124. PET study in Schizophrenia  Hypofrontality in Schizophrenia patient.  Reduced glucose intake in left frontal region.  Lower glucose utilization in central gray matters.
  125. 125. Scan showing Increased loss of gray matter in adolescence between the ages of 12-16 compared to healthy adolescence. Red—Gray Matter Gain ; Blue—Gray Matter Loss
  126. 126. Neuroimaging in mood disorder
  127. 127. DISORDERS OF MOOD AND AFFECT • Disorders of mood and affect can also be associated with loss of brain volume and decreased metabolic activity in the frontal lobes. • Inactivation of the left prefrontal cortex appears to depress mood; inactivation of the right prefrontal cortex elevates it.
  128. 128. • The most consistent abnormality observed in the depressive disorders is increased frequency of abnormal hyperintensities in subcortical regions, such as periventricular regions, the basal ganglia, and the thalamus. • More common in bipolar I disorder and among the elderly, these hyperintensities appear to reflect the deleterious neurodegenerative effects of recurrent affective episodes.
  129. 129. CONTD. • Ventricular enlargement, cortical atrophy, and sulcal widening also have been reported in some studies. • Some depressed patients also may have reduced hippocampal or caudate nucleus volumes, or both, suggesting more focal defects in relevant neurobehavioral systems.
  130. 130. CONTD. • Diffuse and focal areas of atrophy have been associated with increased illness severity, bipolarity, and increased cortisol levels. • The most widely replicated positron emission tomography (PET) finding in depression is decreased anterior brain metabolism, which is generally more pronounced on the left side.
  131. 131. • Increased glucose metabolism has been observed in several limbic regions, particularly among patients with relatively severe recurrent depression and a family history of mood disorder. • During episodes of depression, increased glucose metabolism is correlated with intrusive ruminations.
  132. 132. 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.
  133. 133. 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.
  134. 134. 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.
  135. 135. Long-term prognosis of geriatric major depression in relation to cognition and white matter integrity
  136. 136. PET in Depression  Decreased anterior brain metabolism more pronounced in left side.  Relative increases activity in nondomaint hemisphere.  Reduce cerebral blood flow.  Severity correlates negativity with 5 HTT in the thalamus in MDD subject.
  138. 138. ADHD • Functional neuroimaging studies of persons with attention-deficit/hyperactivity disorder (ADHD) either have shown no abnormalities or have shown decreased volume of the right prefrontal cortex and the right globus pallidus. • In addition, whereas normally the right caudate nucleus is larger than the left caudate nucleus, persons with ADHD may have caudate nuclei of equal size. • These findings suggest dysfunction of the right prefrontal-striatal pathway for control of attention.
  139. 139. Structural imaging (CT & MRI) • Shows no consistent findings. • Increased cortical grey & white matter volumes from 5 yrs of age with peak at 12-15 yrs of age. • Decrease in the volume of posterior inferior cerebellar vermis may be noted.(region involved in attention processing)
  140. 140. Functional imaging (fMRI, SPECT, PET) • PET has shown that adolescent females with ADHD have globally lower glucose metabolism that both normal controls & males with ADHD. • PET scan has also shown lower CBF and metabolic rates in the frontal lobes of children with ADHD. • This may be because frontal lobes in children with ADHD are not adequately performing their inhibitory mechanism on lower structures, leading to disinhibition. • Less striatal activation during cognition inhibition tasks.
  141. 141. PET Scan ADHD vs. Normal White, Red, Orange = higher glucose metabolism Blue, Green, Purple = lower glucose metabolism
  143. 143. Structural imaging • Significant DECREASE of grey matter concentration in superior temporal sulcus bilaterally, an area which is critical for perception of key social stimuli. • Also a decrease of white matter concentration in the right temporal lobe and in cerebellum compared to normal children. • INCREASE in total cerebral volume, both in grey and white matter, mostly in the occipital, temporal and parietal lobes. • Brain enlargement has been considered as a possible biomarker for autistic disorder.
  144. 144. Functional imaging • Bilateral hypoperfusion of the temporal lobes in autistic children. • In addition, activation abnormalities may be observed in the temporal lobes and amygdala, which are involved in language and social cognition. • An increase in visual cortex activity was also reported
  145. 145. PET- Autism • Increase in diffuse cortical metabolism noted.
  146. 146. MRI in Anxiety  Occasionally shows increase size of ventricles.  Specific defect (smaller) in right temporal lobe nucleus in Panic Disorder.  Asymmetrical cerebral hemisphere.  Smaller left hippocampal volume in adult women with childhood sexual abuse and women with PTSD.
  147. 147. fMRI in Anxiety Disorder • Increased activity of Amygdala in PTSD associated with fear.( Lt and rt part )
  148. 148. MRS in panic disorder • To record the level of lactate • Brain lactate concentrations were found To be elevated during panic attacks.
  149. 149. HEAD INJURY
  150. 150. Suggested systematic approach to interpretation • Check patient information • Check the scout image. • A quick ‘first pass’ is recommend, noting gross pathology, followed by a more detailed analysis of the images. Use the mnemonic ‘ABBCS’ to remember important structures.
  151. 151. ABBCS • ‘A’ – Asymmetry • ‘B’ – Blood – Acute haemorrhage appears hyperdense in relation to brain, due to clot retraction and water loss. Haemorrhage typically has a CT number in the range of 50– 100 HU. ( Review the sulci and fissures for subtle evidence of a SAH).
  152. 152. ‘B’ – Brain • Abnormal density Hyperdensity – acute blood (free and within vessels), tumour, bone, contrast and artefact/foreign body. Hypodensity – oedema/infarct, air and tumour. • Displacement Look for midline shift ,Examine midline structures such as the falx cerebri, pituitary and pineal glands.
  153. 153. • ‘C’ – CSF spaces – Cisterns, sulci and ventricles. • ‘S’ – Skull and scalp – Assess the scalp for soft tissue injury.
  154. 154. Ischaemic stroke Hyperacute infarct (< 12 hours): Acute infarction (24 hr) Subacute/chronic infarction (>7 days – months)
  155. 155. Haemorrhagic stroke • Haemorrhagic and ischaemic strokes are difficult to distinguish clinically. • Patients with haemorrhagic strokes are generally sicker, with abrupt onset and rapid deterioration. • Common symptoms are headache, decreased conscious level, seizures, nausea and vomiting. Hypertension is characteristic. • ECG changes may include myocardial ischaemia or dysrhythmias.
  156. 156. Radiological features • Acute haemorrhage is hyperdense. • Surrounding oedema will result in loss of the grey/white matter differentiation. • Mass effect will result in compression of overlying sulci, ventricular compression, midline shift and reduction in the size of the basal cisterns. • Site and size of the haemorrhage are important, and will influence future treatment options.
  157. 157. Subdural haematoma (SDH) • Subdural haemorrhage arises between the inner layer of dura and arachnoid membrane of the brain. • Bleeding results from torn bridging veins that cross the potential space between the cerebral cortex and dural venous sinuses. • Subdural haematomas are more common in elderly and alcoholic patients, where the subdural spaces are larger due to age related involution and/or atrophy.
  158. 158. • Patients generally have a decreased level of consciousness with focal neurological defects or seizures. There may be signs of raised intracranial pressure. • Patients with a primary or secondary coagulopathy (e.g. alcoholics) may develop an acute SDH after only minor head trauma. • A small acute SDH may be asymptomatic.
  159. 159. Chronic SDH • Chronic SDH often presents in the elderly with vague symptoms of – gradual depression, – personality changes, – fluctuations of consciousness, – unexplained headaches – evolving hemiplegia.
  160. 160. CT features • Acute SDH Peripheral high density crescentic fluid collection between the skull and cerebral hemisphere usually with: • A concave inner margin. A small haematoma may only minimallypress into brain substance. • Convex outer margin following normal contour of cranial vault. • Signs of mass effect with compression of overlying sulci, ventricular compression, midline shift and reduction in the size of the basal cisterns.
  161. 161. • Chronic SDH After approximately 2 weeks, chronic SDH’s are often hypodense crescentic collections, with or without mass effect. • Acute-on-chronic - SDHs can further complicate the images, with hyperdense fresh haemorrhage intermixed, or layering posteriorly, within the chronic collection.
  162. 162. extradural haemorrhage • An extradural haemorrhage arises within the potential space between the skull and dura. • The young are more frequently affected as the dura is more easily stripped away from the skull. The dura becomes more adherent with age. • Most commonly bleeding is from a lacerated (middle) meningeal artery/vein, adjacent to the inner table, from a fracture of the adjacent calvarium.
  163. 163. • Patients often present with a history of head trauma. Associated with a variable level of consciousness. 20% to 50% have a brief loss of consciousness at the time of impact. • As the haematoma continues to expand, they suffer a rapid deterioration. This lucid interval is referred to as the ‘talk and die’ presentation. • Neurological examination may reveal lateralising signs with a unilateral up-going plantar response. • A sensitive sign in the conscious patient is pronator drift of the upper limb, when asked to hold both arms outstretched with the palms upwards.
  164. 164. • Biconvex hyperdense elliptical collection with a sharply defined edge. • Mixed density suggests active bleeding. • Haematoma does not cross suture lines unless a diastatic suture fracture is present. extradural haemorrhage
  165. 165. SAH • Blood enters the subarachnoid space onto the surface of the brain, between the pia and arachnoid, and may lead to raised intracranial pressure by obstructing the ventricular outflow of CSF. • Meningeal irritation generates symptoms of neck stiffness, photophobia and low back pain, with a positive Kernig’s sign. • SAH classically presents with a sudden onset of a severe ‘thunderclap’ occipital headache, often described as the ‘worst headache in their life’.
  166. 166. Neurocysticercosis
  167. 167. 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.
  168. 168. 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.
  169. 169. 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  

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