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Neruoimaging final


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Neruoimaging final

  1. 1. Contents Basic fundamentals about       CT scan MRI MRS fMRI SPECT PET Imaging in some specific psychiatric disorders      Imaging in Dementia Imaging in OCD Imaging in Depression & Bipolar disorders Imaging in Schizophrenia Imaging in Anxiety disorders & PTSD Imaging in ADHD & Autism
  2. 2. NEUROIMAGING  Can allow measurement of the structure, function, & chemistry of the living human brain  Has provided new information about the pathophysiology of psychiatric disorders  Can be useful for diagnosing illness, predicting prognosis & for developing new treatments
  3. 3. USES OF NEUROIMAGING Indications in Clinical Practice  Neurological Deficits  To rule out neurological causes of psychiatric illnesses  Dementia Indications in Clinical Research  Analysis of Clinically Defined Groups of Patients  Analysis of Brain Activity during Performance of Specific Tasks
  4. 4. NEURO-IMAGING TECHNIQUES 1. Structural     2. Plain Skull Radiography Pneumo-encephalography CT scan Structural MRI Functional       Magnetic resonance spectroscopy (MRS) Functional MRI (fMRI) Positron emission tomography (PET) Single photon emission computed tomography (SPECT) Brain electrical activity mapping (BEAM) Evoked Potential
  6. 6. …Contd CT Scanners take a series of head X-ray pictures from all vantage points The amount of radiation that passes through, or is not absorbed from, each angle is digitized & entered into a computer When viewed in sequence, the images allow mental reconstruction of the structure of the brain BASICS 360º around a patient's head 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
  7. 7. Grey-scale Appearance on CT Tissue Appearance Bone White Calcified Tissue White Clotted Blood White Grey Matter Light Gray White Matter Medium Grey CSF Near Black Water Near Black Air Black
  8. 8. Points to remember  CT image is determined only by degree to which tissues absorb X-ray  Bony str. Absorb large amount of x-rays and tend to obscure the details of neighboring structures poor visibility in brainstem.  Poor differentiation of grey-white pattern than compared to MRI.  Certain tumors may be invisible on CT because they absorb as much irradiation than the surrounding brain visible on Contrast CT.  Bone, clotted blood, calcified tissue, contrast material all appear white & CSF black  The only component of brain better seen on CT scan is Calcification, which may be invisible on MRI
  9. 9. Normal CT Brain
  10. 10.  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%
  11. 11. Image showing enhancement after contrast administration
  12. 12. …Contd ADVANTAGES v/s DISADVANTAGES of CT ADVANTAGES  Simpler, cheaper, more accessible  Tolerated by claustrophobics  No absolute contraindications  Better than MR for bone detail & Calcification DISADVANTAGES  Ionizing radiation  IV contrast complications  Limited range of tissue contrasts
  13. 13. CLNICAL INDICATIONS OF CT BRAIN IN PSYCHIATRY           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 Weinberg 1984; Beresford et al 1986
  14. 14. MRI Liquid Helium Cooled 1.5 Tesla Solenoid Magnet Radiofrequency Transmitter/Reciever Coil Patient Platform
  15. 15. …Contd Nuclei of all atoms are thought to spin about an axis randomly oriented in space When the pulse terminates, the axis of the spinning nucleus realigns itself with the magnetic field During this realignment, it emits its own radiofrequency signal Placed in magnetic Field  axis of all odd-numbered nuclei (mainly Hydrogen) align with the magnetic field When exposed to a pulse of radiofrequency waves Axis of nucleus deviates away from the magnetic field MRI scanners collect the emissions of individual, realigning nuclei & use computer analysis to generate a series of 2-D images that represent the brain
  16. 16.  Radiofrequency and magnetic field pulses manipulated to create different pulse sequences.  Based on the duration of RF pulse & the length of time - different pulse sequences are obtained.  Examples: T1, T2, FLAIR, DWI etc.
  17. 17. 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  Bone white white matter light grey grey matter medium grey water/CSF/air- Black    •T1 is the only sequence that allows contrast enhancement with Gadolinium. •Contrast enhanced structures on T1 appears white.
  18. 18. T2 Weighted MRI  Less distinct boundaries between white and grey matter  Best for displaying pathology  Useful in demyelination, edema & tumour infiltration  Gray matter medium gray  white matter dark grey  CSF and water White
  20. 20. 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.
  21. 21. Diffusion-Weighted Imaging (DWI)  Sensitive to speed of water diffusion  Visualizes area of ischemic stroke in 1st few hours- earliest to detect ischemia.
  22. 22. IMPORTANT POINTS •MRI magnets used in clinical practice ranges from 0.3 to 2.0 Tesla strength. •Higher field-strength scanners produce image of higher resolution. INDICATIONS    To rule out organic cause of psychiatric illness Abrupt change in mental state DISADVANTAGES ADVANTAGES  Does not expose the patient to ionizing radiations  Demyelinating disease can be assessed reliably New onset memory loss or dementia  better study of posterior fossa structures  Avoided in patients wearing metallic devices  Claustrophobia  Does not pick up bony abnormalities  Difficult in uncooperative patients
  23. 23. IV CONTRAST IN NEURO-IMAGING  CT  Iodine based  Iodine is highly attenuating of X-ray beam (bright on CT)  MRI  Gadolinium based (Gadolinium DTPA)  Gadolinium is a paramagnetic metal that hastens T1 relaxation of nearby water protons (bright on T1-weighted images)  Tissue that gets brighter with IV contrast is said to be ―enhanced‖  Enhancement reflects the vascularity of tissue,  The blood-brain barrier keeps IV contrast out of the brain  Enhancement implies BBB is absent or dysfunctional
  24. 24. Amygdala
  25. 25. Hippocampus
  26. 26. Caudate Head
  27. 27. Putamen
  28. 28. Globus Pallidus
  29. 29. Magnetic Resonance Spectroscopy (MRS)
  30. 30. PRINCIPLE Basic principle similar to MRI MRS can detect several odd-numbered nuclei Permits study of many metabolic processes φ Nuclei align themselves in the strong mag. field φ A radiofrequency pulse causes the nuclei of interest to absorb & then emit energy φ Readout on MRS  in the form of a spectrum  Can be converted into a pictorial image of the brain
  31. 31. NUCLEI USED IN MRS & Their uses in Psychiatry NUCLEI USES H¹ Decreased aspartate (NAA) in dementia & other neurological conditions Li 7 Pharmacokinetics of Lithium C¹³ Study of metabolic pathway F 19 • • P³¹ Pharmacokinetics of certain drugs like SSRIs (Fluoxetine, Fluoxamine) Analysis of glucose metabolism Tissue metabolism (compound containing high energy phosphates like ATP, ADP etc.)
  32. 32. Significance of MRS in psychiatry  MRS has revealed decreased NAA conc. in temporal lobes & increased conc. of Inositol in occipital lobes of pts with Alzheimer dementia.  MRS has revealed decreased NAA conc. In temporal & frontal lobes of pts with Schizophrenia.  Also it has shown elevated brain Lactate levels during panic attacks in pts with panic disorder.
  33. 33. Functional Magnetic Resonance Imaging (fMRI)
  34. 34.  ADVANTAGES A sub-type of MRI scan  Uses the New T2 or the Blood-Oxygen Level Dependent (BOLD) sequence Detects levels of oxygenated Hb in the blood  Maps brain function  Detects not the brain activity per se, but the blood flow Neuronal activity within the brain Local increase in blood flow Increases the local Hb conc. • Possible to study both cerebral anatomy & functional neurophysiology using a single technique (Bullmore & Fletcher 2003) • No radio active exposure Which reflects the func. activity of brain on T2 sequence
  35. 35. Limitations of fMRI  fMRI asseses neuronal activity indirectly by measuring blood flow (or tissue perfusion)  this limits its resolution.  Two tasks that activates clusters of neurons 5 mm apart will yield overlapping signals on fMRI & thus are indistinguishable by this technique.  Sensitivity & resolution can be improved by using ultrasmall non toxic iron oxide particles.  Acquisition of sufficient images for study can require 20 minutes to 3 hours, during which the subject’s head must remain in exactly the same position.
  36. 36. fMRI Healthy Controls Depression group
  37. 37. Healthy Controls fMRI Schizophrenia group
  39. 39. …Contd BASICS A type of Nuclear Imaging that shows how blood flows to tissues & organs  Integrates : CT + Radioactive Material (Tracer)  SPECT uses compounds labeled with single photon-emitting isotopes: iodine123, technetium-99m, and xenon-133  Inject with radiolabelled material Gamma rays emitted detected by scanner Translated into 2-D image These images added together to get a 3-D image
  40. 40. USES  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  I 123  Dopaminergic system  Radiolabelled receptor binding agents I123, IBZM (Iodobenzamide) for D2 receptors  Adrenergic system  Early diagnosis of Alzheimer's disease
  41. 41. What SPECT can measure  Regional brain function: perfusion  Dopamine D2 receptor availability  Dopamine transporter function  M1 muscarinic receptors  Nicotinic receptors Same scanner: different radiopharmaceuticals
  42. 42. PET
  43. 43. …Contd BASIC PRINCIPLE -ray detector + Radioactive nucleus • • Most Commonly Used Isotopes • F 18 • N 13 • O 15 A radioactive isotope is injected & decays, emitting a β + particle. Within a short distance, the β + particle bumps into an electron & the two annihilate, producing a pair of - rays. • By detecting & reconstructing where the rays come from, we can measure the location & conc of radio-isotope.
  44. 44. …Contd APPLICATIONS  To estimate regional cerebral blood flow  To estimate regional cerebral glucose metabolism (regional cerebral metabolic rate for glucose - rCMRglu)  For receptor imaging  To study normal brain development
  45. 45. 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
  46. 46. PET scan 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
  47. 47. PET Scan Not Depressed vs. Depressed
  48. 48. PET scans of a 45 year old woman with recurrent depression pre and post treatment.
  49. 49. PET Scan ADHD vs. Normal NORMAL ADHD White, Red, Orange = higher glucose metabolism Blue, Green, Purple = lower glucose metabolism
  53. 53. Structural imaging  Cerebral atrophy (typical dilatation of lateral ventricles & widening of cortical sulci) particularly in posterior temporal & parietal regions &  specific brain regions like hippocampus and medial temporal lobe.  Volumetric MRI reveals shrinkage in vulnerable brain regions, particularly the medial temporal lobe & Hippocampus.
  54. 54. Measurements of hippocampus is the most sensitive marker of pathology of AD early in disease
  55. 55. Functional imaging  Early studies using PET or SPECT revealed a characteristic pattern of hypometabolism in the posterior parietal lobes.  MRS in AD revealed- Decreased conc of NAA in the temporal lobes & increased conc of inositol in the occipital lobes
  56. 56. SPECT of rCBF in AD (Cummings and Mega, 2003)
  57. 57. PET of Glucose Metabolism in normal vs. Alzheimer’s Disease
  58. 58. Recent..  Most recent development in brain imaging in AD is the development of radio-labelled ligands that can bind with amyloid, and then can be visualised with PET.  This technique is currently under investigation.
  60. 60. Structural imaging reveals Severe sharply localised atrophy – bilaterally symmetric ―KNIFE-BLADE ATROPHY‖  Hyper-intense signal in the cortex & underlying white matter of the affected areas  Areas involved- dorsolateral prefrontal cortex & medial temporal lobes Areas spared- posterior parietal and occipital cortices.  Functional imaging reveals Fronto-temporal hypometabolism
  61. 61. 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
  63. 63.  To date, no MRI features have been identified to characterize DLB.  The absence of significant Medial Temporal lobe atrophy in an elderly demented patient suggests DLB etiology rather than AD.  PET or SPECT may reveal reduced occipital function with generalized reduction of cortical activity.
  65. 65. Vascular dementia  Multiple regions of focally reduced perfusion
  67. 67. MRI findings include Ventricular enlargement out of proportion to sulcal atrophy.  Prominent periventricular hyperintensity (halo).  Prominent flow void in the aqueduct and third ventricle, the so-called jet sign, (presents as a dark aqueduct and third ventricle on a T2-weighted image where remainder of CSF is bright)  Thinning and elevation of corpus callosum on sagittal images
  68. 68. IMAGING IN OCD -Frontal lobe -Caudate -Cingulate gyrus
  69. 69. CT & MRI IN OCD  Bilaterally smaller caudate in OCD pts.  Significantly more Cerebral Grey matter & Less white matter volume than normal controls.  Decreased volume of Left orbital frontal cortex.  Abnormality in length of Corpus callosum.  Abnormality in Pituitary volume may also be noted.  Larger anterior cingulate volumes (ACV)  a/w increased OCD symptoms severity but not duration of illness
  70. 70. MRS IN OCD  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 Greater Glutamatergic conc. in caudate, as measured by ¹H-MRS in comparison to controls  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 + AAP in Sumitani S et al (2007) Psychiatry Res; 154: 85-92 anterior cingulate gyrus
  71. 71. SPECT & PET in OCD  In a resting SPECT study, OCD pts has increased mesial frontal perfusion, which normalised with fluoxetine Rx. 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)  Head of the caudate    PET : Greater activity  SPECT : Decreased activity  Pharmalcological and behavioral Rx reportedly reverse these abnormalities.
  72. 72. IMAGING IN DEPRESSION & BIPOLAR DISORDER -Left Prefrontal cortex -Subcortical nuclei
  73. 73. CT & MRI in Depression  Smaller volumes of frontal cortex, cerebellum, caudate & putamen.  Ventricular enlargement, cortical atrophy, and sulcal widening also have been reported in some studies.  The most consistent abnormality observed in depression isIncreased frequency of abnormal hyperintensities in subcortical regions including periventricular regions, basal ganglia, and thalamus.  These hyperintensities may reflect the deleterious effects of recurrent affective episodes. (specially in bipolar I disorder and among elderly)
  74. 74.  Some depressed pts may also have specifically reduced hippocampal or caudate nucleus volumes, suggesting presence of more focal defects.  Focal areas of atrophy have been associated with increased illness severity, bipolarity and increased cortisol levels.
  75. 75. fMRI IN DEPRESSION  Bilateral anterior cingulate cortex & Right amygdala significantly smaller in size. Tang Y et al (2007) Psychiatry Res.  Inactivation of Left prefrontal cortex in Depressed Inactivation of Right prefrontal cortex in Mania
  76. 76. fMRI Healthy Controls Depression group
  77. 77. SPECT in Depression  Baseline cerebral blood flow (CBF) was lower in depressed patients – in frontal cortex & subcortical nuclei bilaterally  Medication response – normalization of CBF deficit. Joensuu M et al (2007) Psychiatry Res. 154(2): 125-31
  78. 78. PET in Depression  The most widely replicated PET finding in depression is- Decreased anterior brain (frontal / prefrontal cortex) metabolism specially on dominant hemisphere (LEFT side).  Reversal of this hypofrontality occurs when pt. shifts from depression into mania (i.e. decrease RIGHT frontal lobe function seen in mania)  It has been seen that antidepressants at least partially NORMALISES these changes.
  79. 79. PET scans of a 45 year old woman with recurrent depression pre and post treatment.
  80. 80. Bipolar disorder  PET studies in depressed BPI, bipolar II, and manic individuals have shown increased amygdala and ventral striatal limbic subcortical activity compared with healthy controls  In adults, there are findings of enlarged (or shrunken) amygdalae, decreased dorsal and ventral prefrontal cortices, and smaller or no change in hippocampi. Altshuler LL, Bartzokis G, Grieder T, et al. An MRI study of temporal lobe structures in men with bipolar disorder or schizophrenia. Biol Psychiatry. 2000;48:147–162. Blumberg et al. 2003 "Amygdala and hippocampal volumes in adolescents and adults with bipolar disorder". Arch Gen Psychiatry 60 (12): 1201–8.
  82. 82. Structural imaging  Enlargement of lateral & third ventricles may be static or progressive.  Frontal lobe abnormalities, particularly prefrontal gray matter and orbitofrontal regions.  Parietal lobe abnormalities, particularly of the inferior parietal lobule which includes both supramarginal and angular gyri.  Subcortical abnormalities i.e. cavum septi pellucidum, basal ganglia, corpus callosum, and thalamus.  All these structural abnormalities may be static or progressive.
  83. 83.  Decreased size of medial temporal lobe structures (which include the amygdala, hippocampus, and parahippocampal gyrus), and abnormalities of neocortical temporal lobe regions (superior temporal gyrus).  Hippocampus is not only smaller in size but also functionally abnormal (disturbed glutamate transmission in functional scans)  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.
  84. 84.  Positive symptoms  Decreased volume of Superior temporal gyrus  Negative symptoms  Enlarged lateral ventricle & decreased volume of medial temporal lobe structures  Typical Anti-psychotics  increases the size of the basal ganglia
  85. 85. Ventriculomegaly in discordant monozygotic twins seen on T2-weighted MRI scans. Woolley J , and McGuire P APT 2005;11:195-202 ©2005 by The Royal College of Psychiatrists
  86. 86. Functional imaging  Hypofrontality  Functional scans have also revealed lower levels of phosphomonoester & inorganic phosphate and higher levels of phophodiester in schiz pts.  NAA levels were also lower in hippocampus and frontal lobes in pts with schiz.
  87. 87. 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
  89. 89.  Structural imaging (CT & MRI) Occasional increase in size of ventricles.  Abnormalities in RIGHT hemisphere but not in the left hemisphere. ○ This finding suggests that some type of cerebral asymmetry may be important in the development of anxiety disorder.  Functional imaging (fMRI, SPECT, PET) Abnormalities in frontal cortex, occipital & temporal areas in pts. with anxiety disorder & Abnormalities in parahippocampal gyrus in pts with panic disorder.
  90. 90.  MRS –  In panic d/o  used to record the levels of lactate, whose IV infusion can ppt. panic episodes in ~ 3/4th of the pts. with either Panic D/o or Major Depression  Brain lactate conc. were found to be elevated during panic attacks, even without provocative infusion in panic disorder pts.
  92. 92. Structural imaging in PTSD Studies in PTSD Vietnam combat veterans revealed:  Reduced left and right hippocampal volume  Volume reductions were associated with severity of combat exposure.  A similar study was undertaken with Gulf war veterans in Israel, and these data are have shown similar findings  Hippocampus (green), Fornix (blue) and Mammilary Bodies (gray) are shown in 3D. Boone, Omar et al. Longitudinal MRI Study of Hippocampal Volume in Trauma Survivors With PTSD. Am J Psychiatry 2001; 158:1248–1251
  93. 93.  Smaller hippocampal volume is not a necessary risk factor for developing PTSD and does not occur within 6 months of expressing the disorder  This brain abnormality might occur in individuals with chronic or complicated PTSD. Boone, Omar et al. Longitudinal MRI Study of Hippocampal Volume in Trauma Survivors With PTSD. Am J Psychiatry 2001; 158:1248–1251
  94. 94. Twin studies in PTSD  A study reported in Nature-Neuroscience evaluated MR brain morphometry of the hippocampus in monozygotic twins discordant for PTSD. The PTSD twin was diagnosed with PTSD as a result of combat exposure in the Vietnam War.  The twin aspect of this study was important as it showed that individuals discordant for PTSD showed reduced hippocampal volume compared with twins where PTSD was present in neither twin.  This finding suggests that there may be a predisposition or vulnerability factor involved in the genesis of PTSD Gilberson, MW et al. Smaller hippocampal volume predicts pathologic vulnerability to psychological trauma. Nature-Neuroscience, October 2002
  95. 95. Functional imaging in PTSD  fMRI studies have found increased activity in Amygdala, a brain region associated with fear.
  97. 97. 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.  Early onset ADHD may be associated with smaller total brain volume in- 4% cases.  Decrease in the volume of posterior inferior cerebellar vermis may be noted.(region involved in attention processing)
  98. 98. 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.
  99. 99. PET Scan ADHD vs. Normal White, Red, Orange = higher glucose metabolism Blue, Green, Purple = lower glucose metabolism
  101. 101. 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 pole 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.
  102. 102. 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
  103. 103. Message…  Neuroimaging can be structural / functional  Functional imaging more useful than structural in psychiatry  Neuroimaging in psychiatry is presently used mainly to rule out neurological causes, and in evalulation of dementia  Sensitiviy & specifity of imaging in psychiatry is not much  Still various studies and their findings and newer developments holds a promising future for neuroimaging in psychiatric diagnosis & managements.
  104. 104. Presented and Made by- Dr.Swapnil Agrawal Resident- Psychiatry Govt. Medical College, Kota (Raj)