PET and SPECT Scanning: Functional Brain Imaging


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The Presentation for The Neuroscience and Addiction Conference 2009, presented by Dr. Mechtler.

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  • Diffusion Weighted Imaging The package based on contains: Diffusion SE - EPI sequences. Both multi-shot and single shot are available depending on the gradient configuration. This allows: high SNR high resolution high speed PhaseTrak uses a navigator echo to correct for the phase artifacts that occur due to patient motion. number of selectable b-values in one scan is 16. 3 diffusion sensitivity directions can be scanned within 1 scan - time saving Automatic calculation of the Isotropic diffusion weighted image (DWI_I) when the 3 directions are selected.
  • PET and SPECT Scanning: Functional Brain Imaging

    1. 1. PET & SPECT scanning: Functional Brain Imaging
    2. 2. Definition <ul><li>PET </li></ul><ul><ul><li>Positron emission tomography </li></ul></ul><ul><ul><li>Cyclotron or special generator </li></ul></ul><ul><ul><li>High resolution </li></ul></ul><ul><ul><li>$3000 </li></ul></ul><ul><li>SPECT </li></ul><ul><ul><li>Single photon emission computed tomogr. </li></ul></ul><ul><ul><li>Low resolution </li></ul></ul><ul><ul><li>$400 </li></ul></ul>
    3. 3. PET/CT In Oncology POSITRON EMISSION TOMOGRAPHY • Nuclear decay produces a positron • Positron travels short distance and annihilates with electron • Annihilation process produces two photons and conserves: - Energy so each photon is 511KeV - Momentum so photons are “ back - to - back ” • Simultaneous detection of the two 511KeV photons -- > event was along line between detector pair Positron Annihilation Detector Ring 511KeV 511KeV   ~1 - 3mm  
    4. 4. Neurologic applications <ul><li>Dementia </li></ul><ul><li>Movement disorders </li></ul><ul><li>Neuro-oncology </li></ul><ul><li>Inflammatory diseases </li></ul><ul><li>Epilepsy </li></ul><ul><li>Psychiatry </li></ul><ul><li>Cerebrovascular diseases </li></ul>
    5. 5. Positron Emission Tomography (PET) <ul><li>PET is used for in vivo assessment of brain physiology and biochemistry. </li></ul><ul><li>The basic principle behind PET is that blood supply and glucose metabolism within a brain region are largely coupled. </li></ul><ul><li>As neuronal activity increases, there is an associated increase in blood flow, which supports the oxygen and glucose consumption required. </li></ul><ul><li>It involves the peripheral injection of a radiotracer into a vein, which then travels to the brain and deposits into neurons and glia. </li></ul><ul><li>Compares regional cerebral blood flow (rCBF) between states. </li></ul><ul><li>radioactive isotopes emit positrons </li></ul><ul><li>positrons collide with electrons, emitting two photons (gamma rays) in opposite directions </li></ul><ul><li>detectors surrounding brain register simultaneous photons and compute likely source </li></ul>
    6. 6. PET (Contd…) <ul><li>Most studies measure the metabolism of FDG (Fluorodeoxyglucose) which reflects the rate of cerbral glucose metabolism. </li></ul><ul><li>Metabolism of 15 O 2 labeled water reflects cerbral blood flow. </li></ul><ul><li>Metabolism of 18 F labeled fluorodopa parallels dopamine metabolism. </li></ul>
    7. 7. Functional Brain Imaging <ul><li>PET & SPECT </li></ul>
    8. 8. Definition <ul><li>PET </li></ul><ul><ul><li>Positron emission tomography </li></ul></ul><ul><ul><li>Cyclotron or special generator </li></ul></ul><ul><ul><li>High resolution </li></ul></ul><ul><ul><li>$2000-3000 </li></ul></ul><ul><li>SPECT </li></ul><ul><ul><li>Single photon emission computed tomogr. </li></ul></ul><ul><ul><li>Low resolution </li></ul></ul><ul><ul><li>$400 </li></ul></ul>
    9. 9. Neurologic applications <ul><li>Dementia </li></ul><ul><li>Movement disorders </li></ul><ul><li>Neuro-oncology </li></ul><ul><li>Inflammatory diseases </li></ul><ul><li>Epilepsy </li></ul><ul><li>Psychiatry </li></ul><ul><li>Cerebrovascular diseases </li></ul>
    10. 10. 50 yr-old heroin abuser normal PET FDG coronal axial
    11. 11. Cocaine abuse Axial FDG-PET Normal FDG_PET nl
    12. 12. DA D2 Receptor Availability control addicted Cocaine Alcohol DA DA DA DA DA DA DA Reward Circuits DA DA DA DA DA Reward Circuits DA DA DA DA DA DA Drug Abuser Non-Drug Abuser Heroin Meth Dopamine D2 Receptors are Lower in Addiction
    13. 13. Single Photon Emission Computerized Tomography (SPECT) <ul><li>SPECT used in neuropsychiatry to determine the three-dimensional distribution of a radiotracer within the human brain. </li></ul><ul><li>t can map cerebral blood flow, and to a certain extent neurotransmitter receptor activity. </li></ul><ul><li>SPECT uses readily available, stable radioligands, such as radioactive xenon, that do not require a cyclotron for preparation and have a relatively long half-life </li></ul><ul><li>Uses neuroreceptor imaging and activation strategies. </li></ul><ul><li>Clinical Applications </li></ul><ul><li>Acute stroke </li></ul><ul><li>Transient ischemic attacks </li></ul><ul><li>Differentiation of recurrent tumor from radiation necrosis </li></ul><ul><li>Epilepsy </li></ul><ul><li>Dementias, especially Alzheimer,s disease </li></ul><ul><li>Suspected brain death </li></ul>
    14. 14. PET and SPECT Radionuclides <ul><li>Nuclide Half-life </li></ul><ul><li>PET (positron emitters) </li></ul><ul><li>15 O 2 min </li></ul><ul><li>13 N 10 min </li></ul><ul><li>11 C 20 min </li></ul><ul><li>16 F 110 min </li></ul><ul><li>SPECT (single photon emitters) </li></ul><ul><li>99 Tc 6 hr </li></ul><ul><li>123 I 13 hr </li></ul>
    15. 15. Comparison of PET and SPECT <ul><li>Consideration PET vs. SPECT </li></ul><ul><li>Cost PET>SPECT </li></ul><ul><li>Availability SPECT>PET </li></ul><ul><li>Spatial resolution PET>SPECT </li></ul><ul><li>Temporal resolution PET>SPECT </li></ul><ul><li>Sensitivity PET>SPECT </li></ul><ul><li>Signal: noise ratio PET>SPECT </li></ul><ul><li>Variety of ligands PET>SPECT </li></ul>
    16. 16. MRI vs. fMRI MRI studies brain anatomy . Functional MRI (fMRI) studies brain function .
    17. 17. Advanced MRI in Substance Abuse <ul><li>Functional MRI </li></ul><ul><li>MR spectroscopy </li></ul><ul><li>Perfusion MRI </li></ul><ul><li>DWI/ADC </li></ul><ul><li>Diffusion Tensor Imaging (DTI) </li></ul>
    18. 18. B. Functional Neuroimaging <ul><li>FMRI (Functional Magnetic Resonance Imaging) </li></ul><ul><li>PET and SPECT have shown promise in studying the neurochemical and physiological basis of a variety of neuropsychiatric disorders. </li></ul><ul><li>SPECT (Single Photon Emission Computed Tomography) </li></ul><ul><li>MRS (Magnetic Resonance Spectroscopy)-It is used to measure the concentration of the major neurotransmitters and metabolites. </li></ul>
    19. 19. What is Functional Magnetic Resonance Imaging (fMRI)? <ul><li>Different brain regions are specialized to perform different sensory, motor and cognitive functions </li></ul><ul><li>Brain regions become more active metabolically when they perform the activity for which they are specialized </li></ul><ul><li>The increased metabolic activity in “activated” brain regions causes local increases in cerebral blood flow </li></ul><ul><li>fMRI localizes the regions in which there is increased blood flow during performance of particular cognitive functions </li></ul><ul><li>The BOLD technique (blood oxygenation level dependent) </li></ul>
    20. 20. The Basics of Functional MRI the BOLD technique <ul><li>Functional MRI makes use of a technique discovered in the early 1900s- The BOLD technique (blood oxygenation level dependent) </li></ul><ul><li>the BOLD technique can generate data to create images because oxygenated and deoxygenated blood have different magnetic properties. </li></ul><ul><li>Hence, brain areas can be assessed temporally in relation to a specific task, to see what’s going on in a certain area in the brainthat is of interest. The signal in this technique is derived from the fact that loss of oxygen from hemoglobin causes it to become paramagnetic, hence influencing the magnetic field. T2-weighted images are used here, to take advantage of the differences between oxyhemoglobin and deoxyhemoglobin. </li></ul>
    21. 21. When neurons become active, their use of oxygen increases. This is followed within seconds by an increase in blood flow and volume, which results in a net decrease in the amount of deoxygenated hemoglobin present. This is detected with the BOLD technique. It is the basis for most studies using fMRI to generate activation maps.
    22. 22. How fMRI Experiments Are Done 􀀟 Alternate subject’s neural state between 2 (or more) conditions using sensory stimuli, tasks to perform, … 􀀟 Can only measure relative signals, so must look for changes 􀀟 Acquire MR images repeatedly during this process 􀀟 Search for voxels whose NMR signal time series matches the stimulus time series pattern 􀀟 Signal changes due to neural activity are small Need 50+ images in time series (each slice) ⇒ takes minutes Other small effects can corrupt the results ⇒ postprocess 􀀟 Lengthy computations for image recon and temporal pattern matching ⇒ data analysis usually done offline
    23. 23. Types of fMRI <ul><li>BOLD-fMRI -measures regional differences in oxygenated blood </li></ul><ul><li>Perfusion fMRI- measures regional cerebral blood flow </li></ul><ul><li>Diffusion-weighted fMRI -measures random movement of water molecules </li></ul><ul><li>MRI spectroscopy -measure certain cerebral metabolites noninvasively </li></ul>
    24. 25. 1.5T vs. 3.0T Motor Task Finger Apposition Spiral 2D single shot, 200 frames, TR 1000ms, TE 40ms 3T 60°; 1.5T 70° (T1› @ 3T: T1@1.5T~900ms; T1@3.0T~1400ms) 20cm FOV, 5mm/skip 0, 90x90, 6 slices 70° 60° G. Glover, Dept. of Radiology
    25. 26. MRI-PET Fusion (Surface Mapping)
    26. 27. Magnetic Resonance Spectroscopy (MRS) <ul><li>Form of MRI that provides information about tissue biochemistry and metabolic changes. </li></ul><ul><li>Useful and important as an additional evaluation tool for various neurodisorders, such as brain cancer, stroke, epilepsy, Alzheimer’s disease, multiple sclerosis, etc. </li></ul><ul><li>Proton MRS (1H-MRS) is the most commonly used method in psychiatric research. </li></ul><ul><li>Myoinositol has been suggested as a marker for Alzheimer’s disease, with increased myoinositol and decreased NAA seen in patients who have Alzheimer’r disease . </li></ul><ul><li>7Li-MR spectroscopy can provide a noninvasive measurement of brain lithium in patients. </li></ul><ul><li>19F-MR spectroscopy may be useful in providing an in vivo means of measuring flurorinated drugs and their metabolites in the brain </li></ul>
    27. 28.     Main compounds observed by 1H MRS Neurotransmitter GABA g -Amino butyric acid Final product of anaerobic glycolysis  Lac Lactate Energy source Glc Glucose Product of the  reaction between Glu and ammonia. Regulator of Glu and detoxification. Signals from Gln and Glu are indistinguishable and are noted Glx Gln Glutamine Excitation neurotransmitter Glu Glutamate Glial marker mI myo -Inositol Sum of signals from all derivatives of choline including  acetylcholine neurotransmitter, derivatives of membrane phosphatidylcholine and betaine Cho Choline Source of phosphate to convert ADP to ATP Cr Creatine/phosphocreatine Neuronal marker. Other compounds with N-acetyl groups contribute to the signal (NAAG). NAA N -Acetyl aspartate Biological role Abbreviation Compound
    28. 29. Normal MRS Myoinsitol - Choline - Creatine - Glutamine/glutamate - N-acetyl aspartate - Lipids/lactate
    29. 30. GBM, Tumor Extension Beyond Enhancement
    31. 32. Cho map shows tumor outside of enhancement in GBM
    32. 33. Diffusion Tensor Imaging <ul><li>Diffusion tensor imaging is a variation of MRI able to study brain tissue microstructure and examine white matter tracts. </li></ul><ul><li>It measures the molecular diffusion of the water particles in brain tissue. </li></ul><ul><li>It may improve the understanding of neural connectivity and how specific regions of the brain interconnect, with specific applications to neuropsychiatric disorders including dementia, schizophrenia, and addictions </li></ul><ul><li>Diffusion MRI is also being applied in stroke, preoperative planning for neurosurgery, autism, and aging . </li></ul><ul><li>Abnormal patterns have been suggested linking declarative-episodic verbal memory deficits to the left uncinate fasciculus and deficits in executive function to the left cingulate bundle in patients who have schizophrenia </li></ul>
    33. 34. Image Intensity to FA Maps ADC calculation b=800 Diffusion-Weighted images b=0 ADC images xy yz xz x-z -yz -xy <ul><ul><li>(Gx,Gy,Gz) = {(1,1,0), (0,1,1), (1,0,1), (-1,1,0), (0,-1,1), (1,0,-1)} </li></ul></ul>xy yz xz x-z -yz -xy Principle Eigenvalue maps Fractional Anisotropy maps
    34. 35. S. Mori, JHU FA “Atlas” of the Brain
    35. 36. DTI as a Connective Atlas
    37. 38. Drug abuse Smoking HIV/AIDS Child abuse Violence Stress Cancer Drunk driving Heart disease Alcohol abuse Americans’ Views of the Seriousness of Health Problems (Top Ten of Thirty-Six Problems) 65% 65% 68% 69% 71% 73% 74% 75% 78% 82% Stress Alcohol abuse Smoking Child abuse Violence HIV/AIDS Heart disease Drunk driving Cancer Drug abuse % saying “very serious problem” Harvard School of Public Health/Robert Wood Johnson Foundation/ICR, August 2000
    38. 39. Prevalence of Drug Disorders (other than nicotine) Conway et al., J Clin Psychiatry, February 2006. General public Any Mood Disorder Any Anxiety Disorder Depression Mania Panic w/ Agoraphobia Panic w/out Agoraphobia Social Phobia Generalized Anxiety Percent 0 5 10 15 20 25 30 35 40 Prevalence of Nicotine Addiction General public Schizophrenia Depression Percent 0 20 40 60 80 100
    39. 40. Biology/Genes Environment DRUG Addiction 3. ADDICTION INVOLVES MULTIPLE FACTORS Brain Mechanisms
    40. 41. Dopamine in Drug Abuse <ul><li>Reinforcing effects- </li></ul><ul><li>a. Increase in DA in straitum(nucleus accumbens) </li></ul><ul><li>b. rate of DA increase </li></ul><ul><li>Motivation - elevated DA in dorsal striatum </li></ul><ul><li>Long-term drug use- decreased DA function </li></ul><ul><li>Reduction in D2 DA receptors </li></ul><ul><li>Orbitofrontal Cortex –reduced activity (salient attribution) </li></ul><ul><li>Cingulate gyrus- reduced activity (inhibitory control) </li></ul>
    41. 42. Drug Addiction involves 4 circuits <ul><li>Reward – nucleus accumbens(NAc) </li></ul><ul><li>ventral pallidum </li></ul><ul><li>Motivation/drive- orbitalfrontal cortex (OFC) </li></ul><ul><li>subcallosal cortex </li></ul><ul><li>Memory and learning- amygdala </li></ul><ul><li>hippocampus </li></ul><ul><li>Control- prefrontal cortex </li></ul><ul><li>anterior cingulate gyrus </li></ul>
    42. 43. Brain structures and addiction 􀁺 The human brain has reward centers that mediate the experience of pleasure. 􀁺 The ventral tegmental area and the nucleus accumbens are the primary locations for core pleasure experiences. 􀁺 When a person experiences pleasure from chocolate, a ride in a fast car, a buzz off a drug, the nucleus accumbens has been activated.
    43. 44. VTA and NAc <ul><li>􀁺 Reward-seeking is facilitated by the </li></ul><ul><li>release of the neurotransmitter dopamine </li></ul><ul><li>in the nucleus accumbens (NAc), </li></ul><ul><li>􀁺 Subpopulations of NAc neurons even </li></ul><ul><li>respond to predictive cues to promote </li></ul><ul><li>reward-seeking behavior. Even cues about </li></ul><ul><li>a drug can mobilize brain centers to begin </li></ul><ul><li>pleasure expectations. </li></ul>
    44. 45. In addition to the internal structures that mediate reward experiences, the anterior cingulate cortex (ACC) along with the orbitofrontal cortex basically navigates among reward and consequences expectations. Among individuals with addictions, the ACC is hypoactive, suggesting diminished capacity to do the kind of sorting out among rewards and punishments that could be expected from using drugs.
    45. 46. Dopamine Pathways <ul><li>Functions </li></ul><ul><li>reward (motivation) </li></ul><ul><li>pleasure,euphoria </li></ul><ul><li>motor function </li></ul><ul><li>(fine tuning) </li></ul><ul><li>compulsion </li></ul><ul><li>perserveration </li></ul><ul><li>decision making </li></ul>Serotonin Pathways <ul><li>Functions </li></ul><ul><li>mood </li></ul><ul><li>memory </li></ul><ul><li>processing </li></ul><ul><li>sleep </li></ul><ul><li>cognition </li></ul>nucleus accumbens hippocampus striatum frontal cortex substantia nigra/VTA raphe
    46. 47. Anatomy DA DA DA DA DA DA DA signal Dopamine Cell DA Transporters DA Receptors Metabolism Brain Dopamine System
    47. 48. Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release Much greater Activity than any Other drug of abuse -causes neurotoxicity 0 100 200 300 400 500 600 700 800 900 1000 1100 0 1 2 3 4 5 hr Time After Amphetamine % of Basal Release DA DOPAC HVA Accumbens AMPHETAMINE 0 100 200 300 400 0 1 2 3 4 5 hr Time After Cocaine % of Basal Release DA DOPAC HVA Accumbens COCAINE 0 100 150 200 250 0 1 2 3 hr Time After Nicotine % of Basal Release Accumbens Caudate NICOTINE 100 150 200 250 0 1 2 3 4hr Time After Ethanol % of Basal Release 0.25 0.5 1 2.5 Accumbens 0 Dose (g/kg ip) ETHANOL
    48. 49. Di Chiara and Imperato Basilar release (%) Time after ingestion (hour) Effects of Drugs on Dopamine Levels Amphetamine Cocaine Nicotine Neurotoxic
    49. 50. Therapeutic Implications Suggested by Brain Imaging Studies <ul><li>Multiprong approach that includes pharmacological and behavioral interventions: </li></ul><ul><ul><li>(a) decrease the rewarding value of drugs, </li></ul></ul><ul><ul><li>(b) increase the value of non-drug reinforcers, </li></ul></ul><ul><ul><li>(c) weaken learned positive associations with drug and drug cues, </li></ul></ul><ul><ul><li>(d) strengthen frontal lobe function to provide self-control. </li></ul></ul><ul><li>These interventions can be divided into those that </li></ul><ul><ul><li>(a) interfere with the acute effects of the drug on DA, </li></ul></ul><ul><ul><li>(b) compensate for the chronic effects of long-term use of drugs. </li></ul></ul>
    50. 51. What have we learned from functional imaging? <ul><li>we can study human brain at a finer scale </li></ul><ul><li>we have generated more plausible models of brain function </li></ul><ul><li>we have a clearer understanding of uniquely human functions </li></ul><ul><li>we can study the correlation between brain and behavior </li></ul><ul><li>we can extract general organizational principles </li></ul><ul><li>effect of experience </li></ul>
    51. 52. DA transporter effectors D1 dopamine receptor agonists D3 dopamine receptor agonists DA autoreceptor antagonists Mu/kappa opioid agonists/partial agonists Glucocorticoid receptor antagonists Multi-system effector compounds Drug combinations/cocktails Cannabinoid receptor antagonists Corticotropin-releasing-factor (CRF) antagonists Molecular Targets and Strategies for Addiction Treatment Medications
    52. 53. Neuroimaging Studies-Pitfalls <ul><li>Very expensive ($500-$3000) </li></ul><ul><li>Few subjects, low statistical power, high risk for experimental errors </li></ul><ul><li>Extremely sensitive to head movement </li></ul><ul><li>Awkward environment for emotional paradigms </li></ul><ul><li>Contraindications: </li></ul><ul><li>-Irremovable magnetic devices </li></ul><ul><li>-extreme claustrophobia </li></ul>
    53. 54. Schizophrenia Brain Imaging Studies-I <ul><li>The majority of CT studies of patients with schizophrenia have reported enlarged lateral and third ventricles in 10-50% of patients cortical atrophy in 10-35% of patients (1). </li></ul><ul><li>MRI studies have shown evidence for enlarged lateral and third ventricles, decreased cortical gray matter, especially in the temporal cortex, decreased volume of limbic system structures (amygdala, hippocampus, and parahippocampus), and increased volume of basal ganglia nuclei (2, 3, 4, 5). </li></ul><ul><li>The thalamus may have reduced volume in schizophrenia, particularly the posterior portion (6). </li></ul><ul><li>In a 18F - FDG-PET study of glucose metabolism within specific thalamic subdivisions of schizophrenic patients, glucose metabolism in the mediodorsal nucleus and the centromedian nucleus was significantly lower and glucose metabolism in the pulvinar was significantly higher than in controls (7). </li></ul>
    54. 55. Schizophrenia Brain Imaging Studies-II <ul><li>Twofold to threefold increase in D2 receptors density in the striatum was reported in neuroleptic-naïve schizophrenic patients (8). This finding was not replicated in several subsequent studies in which normal densities of D2 receptors were found in schizophrenic patients (9, 10, 11). </li></ul><ul><li>One SPECT study using 123I IBZM found significant differences in D2 binding at low dose (5mg) or a high dose (20mg) of olanzapine, but no clinically significant differences in ratings, symptoms, or extrapyramidal symptoms (12). </li></ul><ul><li>Using 11C raclopride as a measure of D2 binding, quetiapine was found to cause transient blockade of the D2 receptor 2-3 hours after administration, at levels up to approximately 60%, that would then slowly decrease over time (13). </li></ul>
    55. 56. Schizophrenia Brain Imaging Studies-III <ul><li>Cognitive dysmetria posits that cerebellar dysfunction is involved in the schizophrenic patient’s uncordinated thought processes, similar to the uncoordinated motor deficits seen with lesions in motor-related portions of the cerebellum (14). </li></ul><ul><li>fMRI study using an injected contrast agent showed increased cerebellar blood flow in patients with schizophrenia, and lower than normal flow in patients with bipolar disorder (15). </li></ul><ul><li>The first functional cerebral abnormality reported in older schizophrenic patients was a reduction in frontal blood flow, or hypofrontality (16). </li></ul><ul><li>Hypofrontality is an inconsistent finding (17, 18,19,20, 21,22). </li></ul><ul><li>In fact, one study reported hyperfrontality in unmedicated schizophrenic patients (23) </li></ul><ul><li>In never-medicated patients scanned during a visual continous-performance task, lower metabolic rates in the lateral and medial prefrontal and cingulate cortices and basal ganglia were found (24). </li></ul><ul><li>In another FDG PET study patients with reality distortion and patients with negative symptoms had decreased activity in the anterior cingulum/mesial frontal area. Negative symptoms were associated with hyperfrontality (25). </li></ul>
    56. 57. Schizophrenia - References <ul><li>1. Ciompi L et al, Lebensweg und alter der schizophrenen. Eine katamnestische lonzeitstudies bis ins senium. Berlin, Springer-Verlag, 1976 </li></ul><ul><li>2. Barta PE et al: Am J Psychiatry 146: 1457-1462, 1990 </li></ul><ul><li>3. Bogerts B et al, Psychiatry Res 35:1-13, 1990 </li></ul><ul><li>4. Breier A et al , Arch Gen Psychiatry 49: 921-926, 1992 </li></ul><ul><li>5. Suddath RL et al, N Eng J Med 322 (12): 789-794, 1990 </li></ul><ul><li>6. Andreasan NC et al, Science 266: 294-298, 1994 </li></ul><ul><li>7. Hazlett E et al,. Am J Psychiatry 2004; 161: 305-14 </li></ul><ul><li>8. Wong DF et al, Science 234: 1558-1563, 1986 </li></ul><ul><li>9. Farde L et al,. Arch Gen Psychiatry 44: 671-672, 1987 </li></ul><ul><li>10. Farde L et al, Arch Gen Psychiatry 47: 213-219, 1990 </li></ul><ul><li>11. Nordstrom A-L et al, Psychiatry Res 61: 67-83, 1995a </li></ul><ul><li>12. Raedler TJ et al, Psychiatry Res 90: 81-90, 1999 </li></ul>
    57. 58. Schizophrenia References ( Contd…) <ul><li>13. Kapur S et al, Am J Psychiatry 157: 514-520, 2000b </li></ul><ul><li>14. Andreasan NC et al, Bio Psychiatry 46: 908-920, 1999 </li></ul><ul><li>15. Loebler RT et al, Schizphr Res 37: 81-89, 1999 </li></ul><ul><li>16. Ingvar DH et al,. Acta Psychiatr Scand 50: 425-462, 1974 </li></ul><ul><li>17. Berman KF et al, Functional brain imaging studies in schizophrenia, in neurobiology of Mental Illness. Edited by Charney DS, Nestler EJ, Bunney BS. New York, Oxford University Press, 1999, pp 2246-2257 </li></ul><ul><li>18. Cleghorn JM et al, Psychiatry Res 28: 119-133, 1989 </li></ul><ul><li>19. Early TS et al, Proc Natl Acad Sci USA 84: 561-563, 1987 </li></ul><ul><li>20. Gur RE et al,. Arch Gen Psychiatry 52: 657-667, 1995 </li></ul><ul><li>21. Paulman RG et al, Biol Psychiatry 27: 377-399, 1990 </li></ul><ul><li>22. Tamminga CA et al, Arch Gen Psychiatry 49: 522-530, 1992 </li></ul><ul><li>23. Ebmeier KP et al, Biol Psychiatry 33: 487-495, 1993 </li></ul>
    58. 59. Major Depressive Disorder <ul><li>Smaller volumes of the frontal lobe, the cerebellum, the caudate, and the putamen have been reported. </li></ul><ul><li>In patients with primary unipolar major depression, CT studies have shown nonspecific differences of enlarged ventricles and global atrophy. </li></ul><ul><li>MRI studies of focal hyper intensities have indicated that white matter lesions are most prevalent in territories associated with frontal cortex and the basal ganglia. </li></ul><ul><li>Morphometric MRI studies have shown specific volumetric abnormalities involving the frontal cortex in unipolar depression. </li></ul><ul><li>PET and SPECT studies have consistently shown evidence of decreased frontal lobe function (1-8). </li></ul><ul><li>Variable changes have been reported in other limbic-paralimbic (amygdala, anterior temporal, insula) and subcortical (basal ganglia, thalamus) abnormalities have been reported (9-15). </li></ul>
    59. 60. Major Depression <ul><li>1. Baxter LR et al, Arch Gen Psychiatry 46: 243-250, 1989 </li></ul><ul><li>2. Bench CJ et al, Psychol Med 22: 607-615, 1992 </li></ul><ul><li>3. Buchsbaum MS et al,. J Affect Disord 10: 137-152, 1986 </li></ul><ul><li>4. Drevets WC et al,. Nature 386: 824-827, 1997 </li></ul><ul><li>5. Ebert D et al, Biol Psychiatry 39: 747-755, 1996 </li></ul><ul><li>6. George MS et al, Depression 2: 59-72, 1994c </li></ul><ul><li>7. Ketter TA et al,. The Neuroscientist 2: 55-65, 1996 </li></ul><ul><li>8. Lesser I et al, Arch Gen Psychiatry 51: 677-686, 1994 </li></ul><ul><li>9. Mayberg HS et al, J Nucl Med 35: 929-934, 1994 </li></ul><ul><li>10. Mayberg HS et al,. Neuroreport 8: 1057-1061, 1997 </li></ul>
    60. 61. Mood D/o Brain Imaging Studies <ul><li>Brain imaging work on dopaminergic pathways in mood disorders is still in its infancy. Much of the work is preliminary and clearly needs replication. </li></ul><ul><li>The work thus far provides some evidence for decreased pre-synaptic dopamine function in depression but whether or not pre-synaptic dopamine function is increased in mania clearly requires further examination. </li></ul><ul><li>Dopamine transporter appears to be increased in depression but no studies to date have examined dopamine transporter in mania. </li></ul>
    61. 62. Bipolar Disorder <ul><li>The most commonly reported finding in patients with bipolar I disorder is the presence of an enlarged third ventricle. </li></ul><ul><li>Less commonly, reduced volumes of the cerebellum and temporal lobes have been reported. </li></ul><ul><li>Several studies have reported an increased incidence of white matter hyper intensities in patients with bipolar I disorder. </li></ul><ul><li>Decreased brain N-acetyl-aspartate (NAA) –marker of neuronal activity. </li></ul><ul><li>Cell loss in hippocampus-CA3 pyramidal neurons. </li></ul><ul><li>Decreased number and density of glial cells. </li></ul><ul><li>During a counting stroop interference task patients with euthymic bipolar disorder exhibited relatively greater activation in the medial occipital cortex. Healthy subjects exhibited relatively increased activation in temporal cortex, middle frontal gyrus, putamen, and midline cerebellum (1). </li></ul><ul><li>1. Stephen M. Strakowski et al, Am J Psychiatry 2005; 162: 1697-1705 </li></ul>
    62. 63. Obsessive-Compulsive Disorder <ul><li>Volumetric CT scans have shown decreased caudate volumes bilaterally in patients as compared with normal controls. </li></ul><ul><li>Morphometric MRI has revealed significantly more gray matter and less white matter than normal controls. </li></ul><ul><li>Using resting FDG PET scans, OCD were shown have increased metabolism in the caudate and frontal gyri (1, 2). </li></ul><ul><li>Treatment interventions alter the abnormal metabolic patterns. FDG PET during a continuous task was performed on OCD patients before and after treatment with clomipramine. With clomipramine, metabolism in the basal ganglia and orbital frontal cortex decreased to a level comparable to that seen in healthy volunteers; clinical improvement correlated with the normalized caudate and frontal metabolism (3). </li></ul><ul><li>In a resting SPECT study, OCD patients had increased mesial-frontal perfusion, which normalized with fluoxetine treatment (4). </li></ul><ul><li>In one of the earliest FMRI studies, abnormally increased activity was found in the orbit frontal cortex and in the anterior cingulate, anterior temporal, and insular regions (5). </li></ul>
    63. 64. OCD-Contd. <ul><li>1. Baxter LR Jr et al, Arch Gen Psychiatry 44: 211-218, 1987 </li></ul><ul><li>2. Baxter LR Jr et al, Am J Psychiatry 145: 1560-1563, 1988 </li></ul><ul><li>3. Benkelfat C et al, Arch Gen Psychiatry 47: 840-848, 1990 </li></ul><ul><li>4. Hoehn-Saric R et al, Am J Psychiatry 148: 1243-1245, 1991 </li></ul><ul><li>5. Breiter HC et al, Arch Gen Psychiatry 53: 595-606, 1996 </li></ul>
    64. 65. Posttraumatic Stress Disorder <ul><li>Significant positive correlation has been shown between severity of PTSD and the difference in amygdala responses between masked fearful and happy faces and a corresponding negative correlation for the difference between unmasked fearful and happy faces (1). </li></ul><ul><li>Increased activity have been in reported in the amygdala in patients with PTSD (2) in relation to healthy controls in response to pictures (3), trauma related scripts (4), and masked fearful faces (5). </li></ul><ul><li>1. Jorge L. Armony et al, Am J Psychiatry 2005; 162: 1961-1963 </li></ul><ul><li>2. LeDpoux JE et al: Annu Rev Neurosci 200; 23: 155-184 </li></ul><ul><li>3. Hendler T et al, Neuroimage 2003; 19: 587-600 </li></ul><ul><li>4. Shin LM et al, Arch Gen Psychiatry 2004; 61: 168-176 </li></ul><ul><li>5. Rauch SL et al, Bio Psychiatry 2000; 47: 769-776 </li></ul>
    65. 66. Conclusions <ul><li>Structural imaging studies such as CT and MRI , proved to be a powerful research tool for studying human brain structure in disease and health. </li></ul><ul><li>Functional MRI techniques hold considerable promise for unraveling the neurocircuitary and metabolic pathways of psychiatric disorders in the immediate future and in helping in psychiatric diagnosis and treatment planning down the road. </li></ul><ul><li>Once fMRI techniques are perfected, they will likely offer considerable advantage over PET and SPECT scanning in all aspects except receptor-ligand studies. </li></ul>
    66. 67. iMRI Systems <ul><li>0.12 to 3.0 Tesla </li></ul>
    67. 68. Latest Rush to Higher Fields? TESLA ENVY?????????