9. brain imaging in psychiatry

8/12/2019 9. Brain Imaging in Psychiatry

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9. BRAIN IMAGING IN PSYCHIATRYRussell G Vasik, M . D

1. Which brain imaging techniques commonly are employed in the clinical practiceof adultpsychiatry?Comp uted axial tomography (CT) and magnetic resonance imaging (M RI) are used to assessbrain structure. Single photon em ission comp uted tomography (SPECT) and positron emission to-mography (PE T) are used to assess brainfunction. SPE CT scans provide a measure of regional cere-bral blood f l o w in the brain, while PE T scans indicate localized metabolic activity by measuringregional gluco se utilization. Sin ce metab olic rates and loca lized regional blood flow are closelylinked in the brain in most circumstances, the results of S PE CT and PE T often are comparable.Another technique to assess brain function is afforded by electroencephalography (EEG), wh ichprovides an instantaneous, localized measure of electrophysiologic activity of the brain. Recently,computer-assisted techniques have been developed to summ arize and present EEG data in a topo-graphic format; this technique is termed quantitative EEG, or brain electrical activity mapping(BEAM).2. What is the clinical rolefor brain imaging in the assessmentof psychiatric patients?The primary pu rpose of brain imaging studies is to detect or exclude organic factors that couldbe contributing to psy chiatric symptomatology. Sym ptom s such as cogn itive dysfunction, mooddisturbance, and psychotic m anifestations may b e cause d by occult organic disorders influencingbrain function. These studies play a complementary role in the overall clinical assessment of psy-

chiatric patients.Brain Disorders Presenting with Psychiatric Symptoms and Imaging TechniquesThat M a y Assist in DiagnosisDementiaMRI (structural assessment of atrophy)SPECT (blood flow patterns may identify Alzheimers disease)EEG (character istic ncrease in slow wave activity in dem entia)

MRI (anatomic assessment)SPECT (useful to assess tumor vascularization)EEG (may reveal focal slowing)MRI and CT (useful after infarction)SPECT (may identify early ischemic changes before CT and M RI)EEG (identifies extent of func tional disruption of electrophysiologic activity)MRI (identifies characteristic defects in neui-oanatomy)EEG (characteristicabnormal spikes a key to diagnosis)SPECT (hyperperfusion of seizure focus during seizure, hypoperfusion interictally)MRI (can reveal subtle neuroanatomic defects)

Tumor

Stroke

Parkinsons diseaseTemporal lobe epilepsy

Multiple sclerosisable continued o ollowing p a g e

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Brain im aging in Psychiatry 45Brain Disorders P resenting with Psychiatric Symptoms* and Imaging TechniquesThat May Assist in Diagnosis Continued )

Huntingtons diseaseAIDSToxic metabolic conditions and deliriumHead trauma

MRI (subtle neuroanatomic defects dem onstrable)SPECT (emerging reports suggest SPECT abnormalities characterized by diffuse focal hypoperfusion)EEG (disruption in usual EEG coherence, excessive for fast wave activity)CT (excellent to assess bone fracture, possible subarachnoid bleeds, other hem orrhagic events)MRI (superior resolution of subtle anatomic defects, but CT studies may be easier to obtain in urgentsituations)

Including depressive symptoms, cognitive dysfunction, and psychosis3. Which disorders are detected by imaging?The structural imaging techniques, CT and MRI, assess conditions that manifest tangibleanatomic defects. They play an important role in the differential diagnosis of dementia and the detec-tion of space-occupy ing lesions such as tumors, subdural hemato mas, and brain tissue defects sec-ondary to stroke. SPE CT scann ing identifies characteristic patterns of regional cerebral blood flow inmu lti-infarct and Alzheimers dem entia, and is contributory in the early assessmen t of strokes andcerebrovascular defects, providing evidence of d efects in cerebrovascular perfusion before they arediscernible by MR I or C T scanning. PET scans are far more expensive to obtain than SPE CT studies,and are less readily available to clinicians. PET studies do not, as yet, have significant clinical applic-

ability, but sho w great prom ise as a research tool.EEG and quantitative EEG, which measure the amount and location of different brain waveforms, can detect seizure disorders and also can contribute to the assessment of dementia. Both ofthese conditions exhibit characteristic patterns on E EG. To xic states including drug intoxication andmetabolic encephalopathies also exhibit characteristic patterns on EEG.4. What are the most important indicationsfor CT and MRI scanning in psychiatry?Consider the evaluation of brain structures in psychiatric practice:

To confirm or ru le out the presence of structural lesions that may b e contributing to psychiatricsymptoms. Such lesions require specific management and m ay be reversible. Examples include sub-dural hematoma, tumor, and multiple sclerosis.To assess psychiatric symptoms that could have, in part, a defined neuropatholog ical basis. Forexample, confusion in an elderly depressed patient might be related to multi-infarct dementia thatcould be demo nstrated by a brain imag ing study.To rule out or confirm o ther diagno stic possibilities that could be contributing to a patients psy-chiatric symptoms. For ex ample, to exclude organic pathology in a patient suffering from a conver-sion disorder.

5. CompareMRI and CT.M RI has largely su pplanted C T scanning in the assessment of brain structures. MRI is a tech-nique based on the phenomena of nuclear m agnetic resonance and com puter-based image reconstruc-tion techniques. CT studies reflect the attenuation of x-rays through tissue, while MRI providesinformation about the interaction of protons with their environm ent (T1 images) and interaction withother protons (T2 images).The superior spatial resolution of MRI allows detection of small obstructions in th e aqueductalsystem, which couId allow d iscrimination between com municating and noncomm unicating hydro-cephalus. MRI with gadolinium contrast affords detailed assessment of breakdown in the integrity ofthe blood brain barrier, which m ight result from stroke, inflammation, or tumor.


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6 Brain Im agin g in Psychiatryomvarison of T and MRI

MRI CTSuperior tissue resolutionVisualization in coronal, sagittal, transverse planesN o radiation risk; multiple studies feasibleSuperior spatial resolutionDiscrimination between gray and white matterReveals more anatomic detailCan detect small lesions e.g., glioblastoma)Posterior fossa, temporal lobes, cerebellum, andSuperior study of demyelinating diseases e.g.,

Superior bone imagingTransverse plane onlyRadiation risk presentDifferentiates acute parenchymal hemorrhage fromReveals calcifications, meningeal abnormalities,Areas are inaccessible due to bony artifactsSuperior detection of subarachnoid hemorrhageEvaluation relatively simple, quickPatients with mental implants can be scanned with

edemaand certain hemorrhagic events

brainstem accessiblemultiple sclerosis, basal ganglia, and periven-tricular areas) CTSuperior assessment of brain injury 48-72 hoursafter trauma*Evaluation logistically complex and slow**Patients with metal implants cannot be subjectedto MRIEspecially nonhemorrhagic intracranial injuriesreaction by patient In addition to time expenditure, possible claustrophobic

6. What is functional MRI?This technique uses MRI to evaluate measures such as changes in regional cerebral bloodvolume and can be used in experiments involving activation paradigms that measure changes inblood volume in resting and activated states. Functional MRI is the focus of increasing research in-terest and likely will play a role in clinical practice in the future.7. Are there any MRI or CT findings that specifically characterize depression mania orschizophrenia?CT and MRI investigations have been directed toward the assessment of patients with primaryaffective disorders. CT scanning has proven of limited value, due to low resolution in the brain andbony artifact obscuring potentially important structures. Some, but not all, studies found larger ven-tricles in patients with affective disorders compared to controls. Increased ventricular size was asso-ciated with psychotic symptoms, psychomotor retardation, and elevated urinary freecortisol levels

in the depressed patient populations studied.MRI studies of patients with primary affective disorder, such as major depressive illness ormania, have not yielded consistent results. Hyperintensities-bright white areas on MRI images-have been described in the periventricular white matter of young bipolar and elderly depressed pa-tients. Hyperintensities located deep in left frontal white matter and left putaminal regions have beencorrelated with geriatric depression. Subcortical hyperintensities also have been described in de-mented patients and have been associated with hypertension and vascular disease. Their pathophysi-ologic significance, if any, remains uncertain.The MRI research on schizophrenic patients has generated much data on subtle neuroanatomicabnormalities, particularly in ventricular and temporolimbic structures, but no consistent pathogno-monic neuroanatomic abnormality has been demonstrated. Structural changes in the brains of schiz-ophrenics appear to be located primarily in frontal and temporal lobes more than posterior brainregions. Increased lateral ventricular and third ventricle size, and abnormalities involving alterationof the circuitry of the limbic system, have been described. Hypofrontality has been observed repeat-edly in schizophrenia in response to various cognitive tasks.In summary, neither MRI nor CT scanning demonstrates characteristic neuroanatomical abnor-malities diagnostic of schizophrenia or affective illness, but accumulating evidence points to brainabnormalities in both conditions.


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Brain Im aging in Psychiatry 478. What are the most significant indicationsfor SPECT scanning in psychiatry?Differential diagnosis of dementia: Alzheimer's disease versus multi-infarct dementiaCerebrovascular disease: assessment of infarction versus ischemiaFocal epilepsy: identification of seizure focus

Brain tum or: assessment of blood supply of tumo r tissue; necrosis of tumor tissue versus re-SPE CT is particularly usefu l in the acute assess me nt of blood flow to the brain and is com-monly used in neurologic settings to assess stroke patterns. Of note, acute changes in cerebral bloodflow m ay not result in structural defects for several hours; hence, structural changes following strokemay be evident only over time.Recent studies have suggested that Alzheimer's disease can be differentiated from multi-infarctdem entia on the basis of the pattern of regional cerebral blood flow in these conditions. The perfu-sion defects in Alzheimer's disease are almost alw ays bilateral, involve the association cortex, andare most severe in the posterior tempo roparietal lobes. The hypoperfusion exhibited in these lobesoften is present in the early phases of the disease, with frontal lobe hypoperfusion being a later man-ifestation. Multi-infarct dem entia has a more p atchy, diffuse pattern o f hypoperfusion, with widelyscattered, focal perfusion defects.SP EC T also may play a role in the localization and assessm ent of epileptic seizure foci in pa-tients with focal epilepsy. Post-ictal SPECT has been used to identify unilateral temporal foci as re-gions of increased activity (e.g., increased regional cerebral blood flow) and can be used to confirmthe presence of the epileptic focus in those patients who have reduced uptake in the sam e location oninterictal SPECT.In focal seizure disorders, SPE CT images reveal a sh arp increase in regional cerebral blood flowduring the acute seizure; by contrast, interictally, the seizure focus is commonly hypoperfused rela-tive to normal non initable tissue. This has been of value in assessing temporal lobe disorders and

focal lesions giving rise to com plex partial seizures. This use of SPE CT provides an alternative tomo re invasive techniques, such as depth EE G.

currence

9. Describe the mechanismsof PET and SPECT.Both PET and SPEC T scanning use comp uter-assisted techniques for the reconstruct ion ofcross-sectional ima ges of radiotracer distributions. A ty pical reconstruction resolution value forPET is 4-6 mm, and for SPECT 6-8 mm . The commonly used PE T radionuclides are I5O 13N,C, '*F, which have short half-lives, ranging fr om 2 minutes to 2 hours. The SPE CT imaging ra-diotracers technetium 99 m and 1231ave half-lives of 6 hours and 13 hours, respectively. SPECTstudies can be performed several hours after injection of the radiotracer. The half-life of the par-ticular radionuclide emp loyed in a stud y is of importance in that i t imp acts flexibility in studydesign. A longer half-life radionuclide facilitates studies of longer duration, affording more timefor data acq uisition as, for examp le, when utilizing a cognitive activation p aradigm such a s theWisconsin Card Sort.10. Which is the more practical tool: SPECT or PET?SPECT. The cost of a PE T system, which requires a cyclotron for radioisotope production, is1-3 million dollars, while that of a SPEC T system is 0.3-0.6 million dollars. Th e cost per study fo ra SPECT ranges from 50&1000, while PET studies cost 1500-2000.Du e to the extraordinary expense associated with developing and m aintaining a PE T scanningfacility, PET imaging has remained primarily a technique of major research interest, not widely em -ployed in clinical practice. SPE CT scans, by com parison far less expensive, are increasingly avail-able to clinicians.11. Are there any SPECT or PET findings that specifically characterize depression maniaschizophrenia or anxiety disorders?SPE CT scans cannot be considered diagnostic of depressive disorders or mania at this time.Several noteworthy SPECT studies demonstrate specific regions of hypoperfusion in depressed


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48 Brain Imaging in Psychiatrypatients that resolve upon successful treatment of depression. The fron tal and temporal brain regionshave been implicated, but other brain regio ns, such as the caud ate nucleus, have been implicated aswell; the literature d oes not reveal a co nsensus gold standard finding as yet.Studies of schizophrenic patients have implicated the fro ntal lobes as regions of hypoperfusion,specifically in relation to activating tasks such as the Wisconsin Card Sort.Increased frontal lobe blood flow has been shown in obsessive-compulsive disorder, and a fewstudies have demonstrated a return to normal levels following treatment with serotonergic antide-pressant agents.PE T studies of schizophrenia generally have reported lo wer m etabolic rates in the frontal re-gions, particularly in response to cognitive tasks design ed for frontal lobe activation. Hypofrontalityappears to be associated with the negative symptom s of schizophrenia. Tem poral lobe abnormalitiesalso have been reported. PE T research on obsessive-compulsive diso rder has indicated an increase infrontal lobe and basal ganglia metabolism. Several PET studies of major depressive disorder haveobserved reduction in metabolic rate, particularly in the frontal lobes; this hypofrontality appears tobe more m arked in bipolar as compared to unipolar patients, and in som e studies appears to be mostprominent in the left lateral frontal region.

Future Application of PET and SPECT ImagingNeuroreceptor mappingIdentification of pathways of normal cerebral function

Identify neuroreceptor patterns in primary psychiatric disorders such as depression and schizophreniaAssess pathways of sensory function , including visual and auditoryIdentify neuroanatomical sites of affective and cognitive functionAnalyze subtypes of affective illness, bipolar versus unipolar depressionObsessive compulsive disorderPanic disorder

Quantification of metabolism in specific brain regions in primary psychiatric disorders

Further understanding of medical disorders that contribute to psychiatric symptomatologyAIDS dementiaChronic fatigue syndromeSubstance abuse (cocaine)

12. Describe the mechanism of EEG.EEG affords a continuous m easure of brain electrical activity w ith a chronological resolution inmilliseconds. Recen t advances in comp uter softw are technology have given rise to quantitative EEGtechniques that provide color-coded topographic displays of EEG data. Quantitative EEG employsconventional, stan dard EEG , but organizes and presents th e data in a fashion that facilitates visuo-spatial interpretation.EE G data provides information about the amoun t and spatial location of various EEG frequen -cies, ranging from fast activity (alpha) to slow wave activity (delta). Additionally, EEG assesses dis-continuities in electrical activity, characterized by spike an d wave formations consistent withseizures. Finally, evoked responses to auditory and visual stimulation can be assessed in relation toestablished norms.Patterns of the amo unt and location of the various EE G frequencies can be of diagnostic value.For exam ple, an increased am ount of topographically diffuse delta activity is comm only e ncou n-tered in dementia. D rug-induced toxic states are associated with increased alpha activity. The d iag-nosis of seizure disorder may be established by the characteristic spike and wave formationdemonstrated on the EEG .EE G provides instantaneous data, and 24-hour E EG studie s now can be obtained on an ambu-latory basis to facilitate the docum entation of seizure activity and its correlation to beh avioralphenomena.


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Brain Imaging in Psychiatry 4913. What is the role of EEG and quantitativeEEG in psychiatry?EEG has been used to assess brain function in a range of settings, including dem entia, in whichslow wave activity is prom inent; toxic states, typically characterized by fast activity; and seizure dis-orders, notew orthy fo r spike and wave patterns characteristic of seizure activity. EEG is consistentlyabnormal in patients with delirium and often is employed in m onitoring the co urse of that condition.EE G is particularly helpful in the assessment and differential diagnosis of cognitive dysfunction. Dem entia often is characterized by increased slow wave activity. Th e evaluation of unusua l be-havioral presentations, which may reflect an occult underlying seizure disorder, is another potentialrole for EEG . For example, a patient with marked obsession and quasi-philosophical preoccupationsmay be exhibiting behaviors consistent with the interictal personality features of patients with tem-poral lob e dysfunction.Currently, active research efforts are underway to describe patterns of E EG activity that m ightdistinguish depression from the early stages of dementia. As yet, there are no definitive EE G charac-teristics that consistently discriminate these disorders.14. How might brain imaging be useful in assessing the patient with cognitive dysfunction?Brain imaging studies can identify reversible causes of cognitive dysfunction, such as subduralhematoma or meningioma. E EG cou ld be helpful in discriminating between toxic-metabolic states,which could contribute to cognitive dysfunction, and incipient dementia. SP EC T scanning reveals atypical pattern of blood flow in Alzheimers dementia, an d a different pattern in other dem entiassuch as m ulti-infarct dem entia. Transient ischemic d isorders and cerebrovascular insufficiency alsocan be assessed by the SPE CT modality.15. How might brain imaging studies be useful in assessing a patient with depression?A variety of conditions that cause apathy, lethargy, trouble concentrating, and sad mood can beconfused with primary depression. Indeed, the concept of secondary depression, o r depressionsecondary to a discrete medical cause, is well established. Examples include certain post-stroke de-pressions and depression secondary to Parkinsons disease, multiple sclerosis, or other neurologicconditions. Post-stroke depression is particularly common following left anterior frontal lobe infarc-tions, wh ether they a re cortical or subcortical lesions. Additionally, differentiating dem entia and de-pression may be difficult without the data available through brain imaging.MRI and CT reveal structural defects in certain conditions such as stroke; EEG shows typicalpatterns in de mentia and seizu re activity, and also may show asym metries following strokes. SPECTscans can con firm the diagnosis of stroke, dementia, or underlying seizure foci.Imaging stud ies may be of particular value in the treatment of the refractory depressed patient orthe depressed patient with atypical features. The possibility of an occult neuropathologic conditioncontributing to the depressive disorder should be seriously considered in these patients.16. Are brain imaging studies indicatedfor assessing a patient with psychosis?Yes. Several organic conditions, including subdural hematoma and stroke, may result in psy-chotic sympto ms that could be confused with schizophrenia. Occult frontal or temporal lobe tumor,unusual seizure disorders, or drug-induced psychosis may need to be ruled ou t in the assessment ofpsychotic conditions. MRI or CT can assess organic states and determine the cause of unusual be-havior. EEG can help exclude toxic-metabolic con ditions that could be contributing to psychoticsymp toms. SPE CT sc anning could assess the possibility of cerebro vascular insufficiency as a con-tributory factor in altered m ental status.17. What are the main currents in brain imaging research that could prove clinically relevantin the near future?The m ajor advances in brain imaging research involve the development of new ligands for spe-cific receptor sites. These new ligands enab le researchers to m ore precisely assess neuroreceptorfunction in specific psychiatric cond itions, and to evaluate ch ange in receptor fun ction followingpsychotropic medication treatment. Ligands currently are available for use with P ET and SPE CT to


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50 Brain Im aging in Psychiatryas se s s cho li ne rg i c , benzod i azep i ne , and dopam i ne r g ic r ecep t o rs . M app i n g r ecep t o r d i s tr ibu t ion a ndassess ing in te rac t ion wi th pharm acologica l probes are beco m i ng i nc r ea si ng l y f ea s ib l e .

O n g o i n g d e v e l o p m e n t s in s o f t w a r e t e c h n o l o g y will f ac i l i t a t e t h e i n t eg r a t ion of a n a t o m i c a n dp h y s i o lo g i c t e c h n i q u e s t h r o u g h t h e c o r e g is t r at i o n o f MRI and SPECT i m a g e s . T h e p r e c is e neu-r o a n a t o m i c s u p e r i m p o s i ti o n of t h e s e d i f f e r e n t m o d a l i t i e s w i ll a l lo w m o r e e x a c t l o c a l iz a t io n ofpathophys io logic dysfunct ion in bra in d i sorders.

Phys io logic func t iona l MRI t e chn i ques a r e now con t r i bu t ing heav i l y t o s t ud i e s of bra in ac t iva-t ion in hea l th and d i sease , an d c l in ica l appl ica t ion may be found f o r the se t oo l s i n the near fu ture .

BIBLIOGRAPHYI Ames D , Chiu E (eds): Neuroimaging and the Psychiatry of Late Life. Cambridge, United Kingdom,2. Krishnan KR , Doraiswamy PM (eds): Brain Imaging in Clinical Psychiatry. NewYork M. D efier , 1997.3. Vasile RG: Single-pho ton emission com puted tom ography in psychiatry: Clinical perspectives. Harv Rev4. Lewis S: Structural brain imag ing in biological psychiatry. Br M ed Bull 52 (3) :46 54 73 , 1996.5. Wright DC , Bigler ED: Neu roima ging in psychiatry. Psychiatr Clin North Am 21(4):725-759, 1998.6. Buckley PF: Structu ral brain imag ing in schizophrenia. Psychiatr Clin North Am 21(1):77-92, 1998.7. Krausz Y Bonne 0 Marciano R, et al: Brain SPEC T imaging of neuropsychiatric disorders. Eur J Radio121(3): 183-1 8 7, 1996.8. Waldemar G ugh P, Paulson O B: Functional brain imaging with single-photon em ission com puted tomog-raphy in the dia gno sis of Alzheimers disease. Int Psycholgeriatr 9 Suppl 1:223-227, 1997.9. Levin JM, Ross MH, Renshaw PF: Clinical applications of functional MRI in neuropsychiatry. J NeuropsychClin Neurosci 7(4):511-522, 199 5.10 Dougherty D, Rauch SL: Neuroimaging and neurobiological models of depression. Harv Rev Psychiatry5:138-159, 1997.1 Saxema S Brody AL, Sch wartz JM, B axter LR: Neuroimaging and frontal-subcortical circuitry in obses-sive-compulsive disorder. Br J Psychiatry Suppl(3 5):26-3 7, 199 8.12. Keshaven MS , Krishana RR: New fro ntiers in psychiatric neuroimaging. Prog Neuropsychopharmacol B iolPsychiatry 2l(8):1181-11X3, 199 7.13. Gur RE, Chin S: Laterality in functional brain imaging studies of schizophrenia. Schizophr B ull 25(1):141-156, 1999.14. Kegeles LS Mann JJ: In vivo imaging of neurotransmitter systems using radiolabeled receptor ligands.Neuropsychopharmacology 17(5);293-307, 1997.15. Schmitz EB, M oriarty J, Costa DC e t al: Psychiatric profiles and patterns of cerebral blood flow in focalepilepsy: Interactions betwee n depression, obsessionality, and perfusion related to the laterality of theepilepsy. J Neurol Neurosurg Psychiatry 62(5):458-463, 1997.

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9. brain imaging in psychiatry

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