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THE UNIVERSITY OF NEW MEXICO COLLEGE OF PHARMACY ALBUQUERQUE, NEW MEXICO The University of New Mexico Correspondence Continuing Education Courses for Nuclear Pharmacists and Nuclear Medicine Professionals VOLUME 111, NUMBER 1 Radiopharmaceuticals for the Diagnosis of Psychiatric Illness by; Margo J. Muniz, R. Ph. Co-sponsored by: mpi phormcicy services inc an Amer$ham company H The University 01 Ncw Mexico College {)( Phtirnlfic y is approved hy !hc Alncrican Council on Pharmaceutical E[l(!c;itinn as a pr(>vider of c(~nlin(ling pharn~aceulical cdtlcation. Progrti[n No. 180-039-93-006. 2.5 Conlact Hollrs (Jr .25 CEU’S @

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Page 1: Correspondence Continuing Education Courses for Nuclear …pharmacyce.unm.edu/nuclear_program/freelessonfiles/Vol3... · 2018-12-03 · brain. The tight junctions and the plasma membrane

THE UNIVERSITY OF NEW MEXICOCOLLEGE OF PHARMACY

ALBUQUERQUE, NEW MEXICO

The University of New Mexico

Correspondence Continuing Education Coursesfor

Nuclear Pharmacists and Nuclear Medicine Professionals

VOLUME 111, NUMBER 1

Radiopharmaceuticals for the Diagnosisof

Psychiatric Illness

by;

Margo J. Muniz, R. Ph.

Co-sponsored by: mpiphormcicy services incan Amer$ham company

●H

The University 01 Ncw Mexico College {)( Phtirnlfic y is approved hy !hc Alncrican Council on Pharmaceutical

E[l(!c;itinn as a pr(>vider of c(~nlin(ling pharn~aceulical cdtlcation. Progrti[n No. 180-039-93-006. 2.5 ConlactHollrs (Jr .25 CEU’S

@

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Editor

Director of Phamcy Continuing Education

William B. Hla(lik 111,M.S., R.Ph.College of Pharmacy

University of New Mexico

Associate Editor

and

Production Specialist

Sharon 1. Ramirez, Staff AssistantCollege of Pharmacy

University of New Mexico

While the advice find information in this pLlhli~SLtiOntire believed to be true tind ficcurfite at press lime, neither the tiuthor(s) northe editor nor the publisher can accepl tiny legal responsibility for tiny errors or omissions thtit may bc m~dc. The publishermakes no wtirranty, express or implied, with respect to [he material contained herein.

Copyright 1994University (If New Mexico

Phartnacy Ct]ntinuing EducationAlbuquerque, New Mexico

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RADIOPHARMACEUTICALS FOR THE DIAGNOSIS OF PSYCHIATRIC ILLNESS

STATEMENT OF OBJECTIVES

The goal of this correspondence course is to increase the reader’s knowledge of currentresearch in the assessment of psychiatric disorders using nuclear medicine techniques.

applications andThis continuing

education lesson is intended for nuclear pharmacists and nuclar medicine professionals who have an interestin the relationship between brain physiology and psychiatric disorders.

Upon successful completion of this matetial the reader should be able to;

1, Discuss general aspects of brain anatomy.

2. Compare and contrast structural imaging modalities and functional imaging modalities,

3. Develop a familiarity with radionuclides utilized in positron emission tomography (PET) brainimaging.

● 4. Develop a familiarity with single photon emission computed tomography (SPECT) brain imagingradiopharmaceuticals currently being used in the assessment of psychiatric illness.

5. Discuss the current status of nuclear medicine brain imaging.

6. Cite new developments in nuclear medicine brain imaging.

7. Identify current and potential roles of nuclear medicine brain

Alzheimer’s Disease:: Depression and Affective Disorders

Obsessive-Compulsive Disorder;: Schizophrenia

imaging in the following disase states:

1

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COURSE OUTLINE RAD1OPHARMACEUTICALS FOR THEDIAGNOSIS OF PSYCHIATRIC ILLNESS

J. INTRODUCTION

IL ANATOMY OF THE HUMAN BRAIN

111. BLOOD BRAIN BARRIER

IV, STRUCTURAL IMAGING MODALITIES

v. FUNCTIONAL IMAGING MODALITIES

A. Physiological Imaging with PETi. Procedure Discussion

ii. PET Radiopharmaceuticals...111. PET Procedures: Assets and

Liabilities

B. Physiological Imaging with SPECTi. Procedure Discussion

ii. SPECT Radiopharmaceuticals...111. SPECT Procedure: Assets and

Liabilities

VI. CURRENT APPLICATIONS INPSYCHIATRY

A.

B.

c.

D

Alzheimer’s Disease and the Dementiasi. Disease Overview

ii. Diagnostic Accuracy...111. Structural Imagingiv. Functional Imaging

Depressioni. Disease Overvitiw

ii. PET Imaging...111. SPECT Imaging

Obsessive-Compulsive Disorder (OCD)i. Disease Overview

ii. PET Imaging...111. SPECT Imaging

Schizophreniai. Disease Overview

ii. PET Imaging...111. SPECT Imaging

v. CONCLUSION

by:

Margo Muniz, R.Ph.Honors Program

Problem Based Learning CurriculumSouthern Illinois University Mtiical School

Carbondale, Illinois

INTRODUCTION

Functional brain imaging and its application inevaluating brain physiology, as it relates to psychiatricdisorders, is advancing at a rapid pace. Over the lasttwo decades, there has been a drive toward developingmethods that provide better structural and functionalassessments of the brain that are less invasive and moreaccurate. Current technologies for brain assessmentare classitled as either structural as in x-ray computdtomography (CT) and magnetic resonance imaging(MRI) or functional as in single photon emissioncomputed tomography (SPECT) and positron emissiontomograph y (PET) (1,2). The primary differencebetween an anatomic (structural) modality and aphysiologic (functional) modality is that the anatomicscan can appear the same whether the patient is dead oralive (Fig 1, see Center Spread). Functional imaging,on thti other hand, allows the psychiatrist toimmediately view cerebral blood flow and metabolism(l). This emphasis on brain functioning provides amore objective measure of hypothesized brainabnormalities in psychiatric illness. Thus, nuclearmedicine applications promise exciting and progressiveadvances for the tleld of psychiatry,

In this lesson, current brain imaging modalities willbe examined along with some of their current andpotential applications in psychiatric assessment. Tohelp prepare for the following discussions, a review ofbrain anatomy, various imaging modalities, and somepotential applications of these to clinical psychiatry,will be provided.

ANATOMY OF THE HUMAN BRAIN

The two components of the central nervous systemare the Brain and the Spinal Cord. The brain

possesses two symmetric hemispheres (left and right),which together make up the cerebrum. Each of thetwo hemispheres can be divided into the followinglobes--frontal, parietal, temporal. occipital, insular andlimbic. The cerebrum comprises the greater portion of

2

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the brain mass and occupies the majority of the skullcavity. The cerebrum has an outer layer of grayWter which is composed of unmyelinated neurons.This layer is referred to as the cerebral cortex.Beneath the cortex lies tracts of fibers comprising thewhite mtiter, which are myelinated nerve fibers. Deepto the nerve fibers there are additional aggregates ofneuronal cell bodies. These aggregates, known asbasal ganglia, are involved in somatic (inhibitory)motor functions. Locatd in the posterior fossa. whichis found dorsal and inferior to the cerebralhemispheres, is the smaller cerebellum. Thecerebellum also contains two hemispheres and isprimarily responsible for motor coordination andspatial orientation of the body. Medial to the cerebralhemispheres Andextending towards the inferior, is thepart of the brain referred to as the brainstem.

The superior-most structures of the hrainstem arethe thalamus and the closely positioned hypothalamus.Thti thalamus finctions in the integration of sensoryexperiences result ing in proper motor responses. Italso integrates sensory input with correspond ingemotional responses and regulates the state ofawareness (consciousness). The hypothalamus islocated directly inferior to the thalamus and lies in thefloor of the fourth ventricle. The hypotha]amusmaintains neuronal connections with the frontal andtemporal cortices, thalamus, and hrainstem. Thehypothalamus also is responsible for emotionalbehaviors, and regulation of the autonomic visceralnervous system. Finally, it integrates descendingimpulses related to both retlexive and skilledmovements. Postero-inferior to the thalamus is themidbrain portion of the brainstem, then the pens. andlastly the medulla. The midbrain possesses severalimportant control functions including autonomicreflexes associated with visual and auditory systemsand movement patterns. The pens is located ventrtillyto the cerebellum and inferior to the midbrain andtherefore forms a bridge whose primary function is toconnect the cerebellum with th~ hrainstem and thecerebrum. The medulla oblongata is a passagewaycomposed of nerve tiher tracts that extend between thespinal cord and the higher regions of the brain, Itcontains reflex centers and the cranitil nerve nucleilocated throughout the brainstem.

The ventricles of the brain form Aci~ntinuous fluid-fdled system of spaces within the brain. The choroidplexus are networks of capillaries associated with thelinings of the ventricles and are responsible for theproduction of cerebral spinal fluid (CSF). The CSF isa watery fluid with a composition similar to that ofplasma. The CSF serves as a cushion for the entirecentral nervous system, protecting the delic~te tissuesfrom impact and damage (3-5).

BLOOD BRAIN BARRIER (BBB)

The blood brain barrier (BBB) is the principalgoverning mechanism of any sort of physiologicimaging, The BBB is an anatomic barrier, which isformed by endothelial cells of the capillary beds in thebrain. The tight junctions and the plasma membraneof these endothel ial cells combine to form thiscontinuous physical barrier to intercellular diffusion ofsubstances. This harrier is selective and is the primarydeterminant of what substances will enter the brainfrom the blood supply. There are many substanceswhich, as a result, are restricted from entering thebrain. Thus, some radiopharmaceuticals will beprohibited from entering the brain if the BBB is intact.However in many disease states, the BBB iscompromised and, therefore, there is a significantdisplay of radiotracer (3-7). In the case of psychiatricpatients, without concomitant anatomic pathology, theradiotracer must he able to traverse the intact BBB inorder to obtain useful images. Newer brain-imagingradiotracers, therefore. are usually iipophilic and of asmall enough molecular weight to allow passivediffusion across the intact BBB.

STRUCTURAL IMAGING MODALITIES

X-ray computed tomography (CT) and magneticrmonancfi imtiging (MRJ) evaluate structure and notfunction, and thus are not generally utilized bythemselves in the assessment of psychiatric disorders.However, when used in conjunction with SPECT orPET, they do possess a certain diagnostic utility (8).Structural imaging techniques can he combined withnuclear medicine evaluations to determine whetherthere are any variations between functional andanatomical aspects of the brain. In other words, theCT or MRI study can he utilized along with the nuclearmedicine study to elucidate any structural changestheir corresponding or related functional deficits.

FUNCTIONAL IMAGING MODALITIES

Physiologiwl Imaging with PET

and

Procedure Discussion. PET offers a method ofstudying the dynamics of cerebral glucose utilizationand cerebral blood flow in the intact functioning humanbrain. The PET technique involves the merging of twovery complex technologies. First, there is thegeneration of a positron emitting nuclide by an on-sitecyclotron, which is then tagged to a suitablebiologically active tracer and introduced into thecerebral circulation. Secondly. the distribution of theradiotrdcers in the various regions of the brain isassessed via computerized tomographic construction.

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This data can then he used to determine the cerebralblood flow, metabolic activity, and other physiologicparameters of the functioning human brain.

The decay of a positron-emitting nuclide results inthe release of apostiron--a particle with a sirtgle excesspositive charge. This particle will then travel throughthe tissue for only a few millimeters, before beingcaptured by an electron with a single negative charge.This collision of oppositely charged particles results inthe production of two gamma rays of equal energy(511 keV), which are released in opposite directions(2,9). (Fig 2, see Center Spread) The PET scannerdetects the presence of the twin gamma rays when theyhit the crystal in the detector to release fluorescentflashes of light. The scanner possesses paired detectorheads which recognize and record any gammaemissions which occur on a coincideti line (180degrees). The computer assesses the time it takes forthese two gamma rays, traveling in their 180 degreeopposite trajectories, to simultaneously hit the detector,and determines where the gamma rays originated fromin the tissue. These coincident events are measured onvarious tomographic planes, since paired detectors willonly detect events occurring in the narrow slice oftissue between them. By utilizing a circular array ofdetector heads positioned around the organ of interest,a detailed tomographic representation of the pattern ofradiotracer distribution can be determined. Thus PETis capable of producing a regional map of functionalactivity in a manner similar to the reconstruction of astructural brain image as performed by an x-ray CTscanner (9).

PET Radiophrmaceuticals. At present, there areseveral positron-emitting radiopharmaceuticals beingutilized clinically. The most common clinical studiesutilize F-1 8 labeled flurodeoxyglucose (FDG). Sincethe brain derives almost all of its energy from glucose,this technique is well suited to image alterations inregional cerebral metabolism. Radiolaheled FDGproduces metabolizes that are retained in the braintissue for a prolongd period of time, which gives thiscompound a distinct advantage over radiolabeledglucose. Thus, FDG allows for an extend~ imagingtime. Measurements can be made in the fasting patientwithin 40-120 minutes post-injection with F-18 FDG.

Another common PET radiopharmaceutical is waterIabeld with a positron-emitting isotope of oxygen (O-15). This radiotracer can he used to assess perfusionand blood volumes. Oxygen-15 is also used toradiolabel carbon monoxide and oxygen gas. Otherradionuclides can be used to evaluate brain blood flowor the location, density, and activity level of a varietyof receptors. The nuclides C-1 1, 0-15, N-13, and F-18, are often incorporated into biological tracers usedin PET imaging (2, 10-12). Further discussions of PET

radipharmaceuticals may be found in Volume II, No 5of this continuing education series (“Radiopharmaceuti-cals for Clinical PET: Formulation and QualityControl, Regulatory Issues, and Professional Responsi-bilities, ” Morlein SM, Welch MJ, Seigel, BA, 1993).

PET Procedures: Assets ad Liabilities. There areseveral assets and liabilities related to the use of PETin the clinical setting. The first advantage is that PETis capable of attaining high resolution (down to 5mm).This is because the attenuating effect of the tissues canbe regionally measurd, thus allowing for appropriatecorrections to be made (9). Secondly, PET canevaluate a very important metabolic process in thebrain--that of glucose utilization. Much of the workdone with PET allows the acquired information to beinterpreted both qualitatively and quantitatively (2).

Ttihle 1. Ahbrevitited list of c(>umpounds labeledPET radionuclides*

PRIMARY APPLICATIONS I,AftE1.Ell COMPOUNIIS

Cerebral Rlmd k’low H2150, C1502, IlC.a]coho]S,

ethanol

Transwrt and Metaklism

Oxygen

Glucose and Metabolitcs

lsN_lab~l~d Amino Acids

llc.labcl~d Amino Acids

Rweptnrs

Dopamine

Benxodi~zepinc

Cholinergic

Opiate

Adrenergic

1507

(18F)2-dcoxy-2.flouro-D-glucose,

with

18F.

Ilc.

D-glucose, 2-(1lC)-deoxy-D-glucose

L(’3N)-glutamate and l-glutaminealanine, aspartate, Ieucine, isoleucine,mcthioninc

L(’’C)-aspartate, leucine, glutamate,valinc, D,L(’ ‘C)-alanine, lcucinc,tryptophtin, oxalacetate.

InF_ “C-spiperone, ‘sF-haloperidol,“C-’L-DOPA

“C-ftunitrazepam, Diazepam,’*F-v~lium

l’C-imipr~minc

llc.ctowhinc ~-methyl-’’ moqhincnc

1Ic.norcpincphrinc, pr~PanolO1

* adapted from Phelps ME, et al. (13)

Unfortunately, PET also has a number of liabilities.The radionuclides utilized in PET studies all have shorthalf-lives. This fact necessitates the close proximity of

4

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cyclotron to the imaging site. Due to the prohibitivecosts of a cyclotron, PET studies are currentlypredominately performed at large academic centerswhich are able to shoulder this substantial expense.Cyclotron costs can vary from $1,000,000 to$2,000,000 (2). Because of the complex nature ofcyclotron maintainence and operation, PET studies alsorequire a large expenditure in terms of time and thecost related to training specialized technicians. Thesecombined factors can result in a high cost per injection,ranging from $2000 to $10,000 (2, 10). Therefore, theneed for highly specialized technical support combinedwith the cost of fldcilities currently negates the use ofPET imaging in routine clinical applications.

Physiologic Imtiging with SPECT

Procedure Discussion. The term single-photonemitting radionuclides refers to all commercially avait-able photon-emitting nuclides that emit only one photonper disintegration. Examples used in brain imaging in-clude iodine-123, technetium-99m, and xenon-133. Theterm differentiates these rad ionucl ides from the dualphoton-emitting nuclides used in PET. As previouslydiscussed, the technology used in PET is cumbersomeand costly. For these reasons. there is great interest indeveloping the more widely-available and lessexpensive SPECT brain imaging techniques (14).

Tal)le 2. Comparison of PE’I Hnd SPKCT Brain lmilging*

Variat)lr

Sensitivity

Resolution ofCommcrcifil Devices

Commonly usedIsotof)cs

Tl,2 uf Nuclides

Prrsduction ofRtidionuclidcs

Cost per Scan

Very High< ~o-12M

5-6mm

0-15C-IIF.18

q ‘O, 110 mill-,-

On-siteCyclntrun

$1,500-10,000

s[,l~’r

H igll< ~O-llM

8-l Qmm

1-123,Tc-99m,XC-133

l]ours 613, , 127

Commercialsupplier or simple

on-silt generator

$?5-400

* Adti\~tcd from Innis Rt3 (10) and Scl~uckit MA (2)

The scanner used in SPECT detects light producedwhen gamma rays collide with a sodium iodide crystal,The energy of the gamma ray and the trajectory of the

incoming rays will he assessd by a computer whichwill then format the information into data regarding theoriginal position of the scintillation. This data will beaccumulated and used in forming tomographic imageslices of the tissue in question.

A single head camera may he used which rotatesaround the patient’s hwdd. This approach enables theutilization of methods currently available in manyhospital nuclear mdicine departments. The singlecamera head is the least expensive SPECT imagingsystem, and can also be utilized for both SPECTapplications and planar imaging techniques of otherareas of the body (15,16).

Newer techniques involve the use of multiplecamera heads in which two or more detectors arebrought into close proximity of the patient’s head.This approach results in greater resolution of imagesand decreases the scan time necessary for imageacquisition. Multidetector SPECT cameras incorporatemultiple detectors into a ring. As a result, there are nodetector heads which revolve around the patient.Instead the patient is placed in a ring-shaped scannerfor imaging. The array of detectors may either rotateor be in a stationary position as the information isgathered. These systems are very expensive, hut havethe advantage of excellent image resolution. Since theanatomic structures can be visualized with highaccuracy, ring systems are particularly suitd tocomparisons with conc(}mminent CT or MRI images(15-17).

Both single detectors and multidetector SPECTsystems allow the development of image reconstructionin multiple orthogonal planes. For diagnostic clarity,current protocols require the acquisition of at leastthree orthogona[ image planes (i .e., transaxial, coronal,and sagittal) (14, 15, 18).

SPECT Radiophumaceuticals. The SPECTapproach takes advantage of’ many commercially-available radiopharmaceut icals. The majority ofSPECT brain imaging radiopharmaceuticals arecerebral blood flow (CBF) or perfusion agents (15).The first, Xe-133, has a long history of use as a two-dirnensional CBF imaging agent (9,14). Radioactivexenon, a gas which has been soluhilized in normalsaline, is administered by intracarotid injection. Thisstudy is correlated with cerebral angiography for thepurpose of identifying the blood vessels under study,Because of the ability of the lungs to rapidly removethe gas, a relatively large quantity can be injectedwithout an excessive radiation dose, even when serialinjections are performed [5 mCi every 10-15 min(maximum of five injections)]. Since the gas isadministered via the carotid, the activity will localizein one hemisphere, allowing for a very high count ratefor the two-dimensional (side view) technique. This

I

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technique is traumatic to the patient, however, and hasbeen largely abandoned, favoring newer noninvasivetechniques. With the advent of cornputd tomographytechniques and rotating camera heads, intraarterialinjections have given way to inhalation techniques.Tomographic images are obtained using a four-camerasystem and Xc-l 33 which is admixed to air. Theadmixture should result in an alveolar concentration ofabout 10 mCi/liter per 1.5 minute inhalation. Duringthe inhalation and for three one-minute periodsthereafter, a series of tour tomc]graphic images isacquired. The entire procedure lasts less than fiveminutes and is completely atraumatiu. CBF is obtainedin three slices of brain tissue with corresponding bloodtlow calculations. Xenon. however, is not the idealCBF SPECT agent. The gas has the disadvantages ofa short shelf life (3-5 days) and poor image rtisolutiondue to its low enery gamma ray (81 keV), which iseasily scattered in the brain tissue. (2,13, 14,19).

A second frequently-used radiopharmaceutical is I-123 iodoamphetamine (iofetamine) (currently unavail-able in the U.S.). This radiopharmaceutical has theadvantage of a high energy gamma ray (159 keV),which results in a higher resolution image than thatobtained with xenon. 1-123 iofetamine is marketed ina prepared unit-dose vial, which allows for conven-ience in that the dose is already buffered and hasundergone quality control testing by the manufacturer.1-123 iofetarnine, however, is costly. In addition, thisproduct has a physical half-life ot’ 13 hours. which mayserve as a potential disadvantage in that it must heordered within 24 hours of its use. This agent isinjected intravenously; it exhibits a high tirst passextraction (approximate y 90 YO ) and brain uptake isreasonably constant between 20-60 minutes postinjection, The distribution of 1-123 iofetamine bestcorrelates with rCBF at 13-27 minutes post injection(79) and, thus, imaging should be performed within 30minutes following injection. The accessibility of 1-123iofetamine to areas of the brain affected hy alteredbrain anatomy or changes in function are currentlyunder further investigation (2, 13,15, 19,20).

The third frequently used brain imaging agent ishexarnethylpropy leneamine oxime (HMPAO), a tech-netium-99m labeled chelate, which readily crosses theBBB, The compound is a neutral, lipophilic complexwhich is used in rCBF assessment with SPECT. Thegeneric name of this radiopharmaceutical is exameta-zime and it carries the trade name Ceretec@ (Medi-Physics--an Amersham Company). It is currently theonly lipophilic technetium brain imaging agentapproved by the FDA (15).

Following intravenous injection, brain activity willpeak within one minute, and will plateau at twominutes at about 88% of peak activity. Brain activity

mains relatively constant for several hours. Imagingwith Tc-99m exametazime results in good differenti-ation between cerebral grey tier and cerebral whtie@ter, with higher uptake in grey titer. Retentionof the chelate is directly relatd to the glutathione ●concentrations in brain tissue.

This radiopharmaceutical has several advantages.The first of which is its long shelf life. Unlabeledexametazime can be stored for months and can beeasily compounded with eluate from a small on-sitecommercial Mo-99/Tc-99m generator. Secondly, theradiolabeled product can he injected in much higherdoses than Xe-133 or 1-123 iofetamine. In addition,imaging may begin as early as 15 minutes post-injection. Ceretec@ has a high extraction efficiency,resulting in good image quality. However, much aswith I-123-iofetamine, further research is needed toallow for greater understanding of this drug’s dis-tribution within the brain of patients with variousdisease states (2,21,78).

Neuroreceptor imaging shows great promise inSPECT psychiatric scintillation studies. Brainreceptors are prohahl y more closely Iinked to the actualpathology of psychiatric disease than is glucosemetabolism or blood tlow. Neuroreceptor imaging isalsu significant since brain receptors are the mediatorsof the actions of most psychotropic drugs. Thus,neuroreceptor imaging may provide insight intopsychiatric drug efficacy and pharmacokinetics. In thepast, receptor studies have been principal] y performedusing PET, but the advent of newer drugs such as I-123 iomazenil (Ro16-O154), a radioiodinated version oftlumazenil (Romazicon@--Hoffman-LaRoche), a henzo-diazepine receptor antagonist, will make receptorimaging more accessible to the clinical setting viaSPECT (10,22).

SPECT Procedures: Assets and Liabilities. SPECTimaging (]ffers many advantages for brain imagingrelative to PET. The use of longer-lived radionuclidescircumvents the requirement for an on-site cyclotron,SPECT is more affordable and less technicallycumbersome. Newer drugs, improved equipment,availability for routine clinical use, and better imagingtechniques are Iikely to give SPECT the advantage overPET in psychiatric applications.

CURRENT APPLICATIONS IN PSYCHIATRY

Alzheimer’s Distise and the DementiasDisease Overview. Dementia is det~nti as a

deterioration from a previous level of intellectualfunctioning due to organic brain pathology. Symptomsinclude personality changes and deficits in short termmemory, abstract thinking, judgement, and impulsecontr[~l. Deficits in memory are often one of the first

6

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symptoms to appear, with recent memory being worsethan long-term memory. The dementia patient hasdifficulty learning new material and will minimize ordeny these deficits. The disease may he chronic witha slow insidious onset as found with Alzheimer’s or beacute as found in brain injury due to trauma or disease(77).

Alzheimer’s disease is the most common of thedementias, accounting for at least 50 percent of allcases of hospital-reported dementia and 80 percent ofcommunity reports (23), According to current figuresfrom the National Institute of Aging, Alzheimer’sdisease is the fourth leading cause of death in theUnited States. Alzheimer’s disease, therefore, followsheart disease, cancers, and stroke in terms of yearlydeaths attributable to disease. The costs associatedwith Alzheimer’s disease is formidable. The currentestimates for care and treatment are a staggering $88billion. In terms of health care cost, the figures makesAlzheimer’s one of the most costly diseases in thecountry (24).

The progressive degenerative dementias (such asAlzheimer’s disease), frontal lobe degeneration, andvascular dementia are often initially presented in theclinical setting as psychiatric changes. However, thepatients develop the psychiatric symptoms as a result ofbrain degeneration that involves anatomic pathologiesdue to injury and/or degeneration of tissues in specificregions of the brain (24,25). Although CT and MRIhave certain utility in the evaluation of progressivedegenerative dementias, these modalities illustratestructural, not functional, changes in the brain. Forexample, CT scans in advanced cases of Alzheimer’smay show marked sulcal widening, insular atrophy,and ventricular enlargement that are common findingsin cases of brain atrophy (23.26). Physiologicalimaging techniques can then he used to evaluate theregional fictional activity of the disease state. Forinstance, regional cerebral blood tlow is c~~upledtochanges in metabolic demand, and th~refore anychange in blood flow patterns may indicate variationsin neuronal metabolism (27). By augmenting structuralevaluations with functional brain imaging, there is asignificant improvement in the accuracy of differentialdiagnosis of the dementias. Initial clinical studies haveshown that patients with Alzheimer’s disease andpatients with multi-infdrct dementia can he diagnosedwith a high degree of accuracy (28-31).

Alzheimer’s disease and Pick’s disease are the twomajor degenerative diseases with a large corticalcomponent. Their principal clinical expression isdementia. [t is important to note that there are manyother causes of dementia, such as cerehrovasculardisease. encephalitis, hydrocephtilus, and variousmetabolic diseases. For reasons discussed below. it is

important to make the proper diagnosis (24,30).There are two common features that the

degenerative diseases share: I) They are diseases ofneurons which selectively impact one or more systemsof neurons and at the same time leave others intact.For example, in Alzheimer’s disease there is aprogressive devolution of the temporoparietal cortex,yet the visual cortex and motor sensory strip are almostentirely exempted. 2) Degeneration of the centralnervous system structures is bilateral, symmetric andtemporally progressive (26).

tignostic Accuracy. Approximately one-half ofthe patients presenting with the early c1inical symptomsof dementia cannot be assessed in an accurate mannerby current clinical criteria (28). Of these dementias,statistics show that the best institutions correctlydiagnose only 80% to 90% of the Alzheimer’s casescorrectly. Of misdiagnosed patients, 1% to 2 % havereversible diseases that could be treated (24). Thus,accurate diagnosis is extremely important becausedementia-like symptoms may, in fdct, be masking acondition that is treatable or even reversible.Examples include depression, which is a reversibledisorder, and vascular dementia, which has a treatablecomponent, Thus, proper and accurate diagnosis isextremely important in order to properly assess thepatient in terms of both prognosis and treatmentregimens.

Structural Imaging. The CT study can providevaluable information in the evaluation of progressivedementias. Although the CT scan is not capable ofproviding detlnitive diagnosis of Alzheimer’s disease,it does exhibit utility in the ruling out of tumors,strokes, and hydrocephalus--which may be responsiblefor an inaccurate diagnosis of dementia or Alzheimer’sdisease. CT studies are not capable of illustrating thepathology which occurs in the temporoparietal cortex(24), While MRI and CT provide accurate informationon cortical atrophy and periventricular white matterchanges, nuclear medicine studies demonstrate regionalcerebral blood flow changes not evidenced hy thesestructural studies (32).

Functio~l Imaging. Alzheimer’s disease is a focalillness in that it primarily attacks very specific regionsof the brain. This disease tends to exhibit posteriorhemisphere abnormalities, and studies reflect thispathology with a corresponding change in brainfunction (28,33). This fact is important, in that non-Alzheimer’s dementia, frontal lobe dementia, andprogressive supranuclear palsy show selective anteriorabnormalities in SPECT studies as opposti to theposterior deficiencies exhihited in Alzheimer’s disease(21,34,35). Specifically, Alzheimer’s disease attacksthe hippocampus and the neocortex (24), Hippocampaldamage manifests itself by alteration in memory

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functions. The nmcortical damage usually manifestsitself as the inability or change of a patient’s ability toperform visual spatial skills, to perform certainlanguage skill tasks, and to calculate and manipulatenew information (33,36).

Functional imaging with modalities such as SPECTand PET enable the clinician to see focalhypometabolisms and perfusion deficits which, whencoupled with the case history and physical exam, willlead to greatly improved diagnostic capabilities (33).PET studies done by Miller at UCLA have shownexpectti patterns in cerebral glucose metabolism.Namely, there is marked hypometaholisrn in thetemporoparietal cortex and normal metabolism in theareas spared by the disease, principally the visualcortex and motorsensory strip (24). In patients withAlzheimer’s, PET imaging has shown a significantdecrease in glucose metabolism in the frontal,temporal, parietal, sensory-motor and striatal regions(37). In advanced cases, PET shows a reduction inmetabolism that is uniformly dispersed throughout thecortex, sparing only the above-mentioned primaryvisual and sensory-motor cortices. This correspondswell with the neuropsychological tlnd ings in thesepatients (27).

Due to the high expense and limited availability ofPET scanning, there has been an increased interest inthe use of SPECT to assess regional blood flow.Studies utilizing 1-123 labeled iofetamine have beenperformed to determine the diagnostic accuracy of thisradiopharmaceutical in the assessment of Alzheimer’sdisease as compared with normal healthy patients.Results have been promising, yielding a sensitivity andspecificity of 88% and 87%, respectively (30). Studieswith this radiotracer, as with the PET studies, indicatewhole-brain functional activity is reduced inAlzheimer’s when compared to age-matched healthycontrol subjects, and that the temporoparietal andoccipital regions were the most functionally impaired(30,38). Other research groups have been able toachieve similar results using SPECT and Tc-99mexametazime (38-43). This research also has beensuccessful at illustrating a reduction in uptake in theposterior hemisphere of Alzheimer’s-positive patients.Selective anterior deficits in other dementia types haveillustrated the potential value of SPECT in thedifferential diagnosis of primary cerebral atrophies(29,34).

SPECT studies are rapidly becoming important inthe diagnostic evaluation of patients showing memoryand cognitive abnormalities (30). There are severalclinical studies which indicate a high degree ofaccuracy in the assessment of patients with Alzheimer’sin comparison with both normal subjects and patientswith multi-infidrct dementias (30,38). For severe cases

of Alzheimer’s, the sensitivity of SPECT is very high,and in patients with mild impairment, sensitivityapproaches 80% (30).

Experts state, “The predominant finding of bilateralposterior temporal and parietal perfusion defects inthese patients is highly predictive of Alzheimer’sdisease (28). ” The reduced radiotracer uptake maybedue to several factors, such as, a reduced regionalcerebral blood flow, decreased thickness of corticaltissue in the affected neocortex, and a reduced numberof neurons in the affected areas. The combined effectof decreased cerebral blood flow and atrophy increasethe diagnostic sensitivity of functional imagingmodalities (28,39-47).

DtiprtissionDisease Ovemiew. Major depression is a common

illness, with an annual incidence of 0.4-2.7 per 1000people experiencing clinical depression. Close toseven percent of the population will experience a majordepressive episode in their lifetime. The mostsignificant risk factors for depression are geneticloading and progressing age. Depression usuallypresents as a mood disorder. but also may have othercomponents associated with it, such as psychomotordisturbances and cognitive impairment, so calltipseudodementia. This latter presentation can lead tomisdiagnosis as primary degenerative dementia (48).

Major depression may also be referred to as aunipofar disorder, in that the patient experiences onlydepressive episodes without any episodes of mania.The depressive episodes are characterized bydysphoria, loss of interest in usually pleasurableactivities, feelings of guilt, and psychomotorretardation or agitation. The major affective disordersmay be further classified by whether the patient has ahistory of a manic episode. The manic patient maydisplay groundless or excessive states of euphoria,hyperactivity, and aggression. The presence of currentor past manic episodes justifies the diagnosis of abipolar disorder. The patient may oscillate betweenperiods of euphoria, dysphoria, and normal moodlevels (46,77).

Researchers speculate that depression and its subsetsare due to a functional disturbance in one or more ofthe cerebral monoamine pathways (13,48). Cell bodiesof the monoamine systems are, in general, localized tothe brainstem and send out protuberances to thesubcort ical and cortical structures. Whether thedisturbance is linkti to specitic structures or whetherit is more globally distributed has not been determined,although the Iimhic system has been frequentlyimplicated (48-52).

As previously cited, physiological imaging has beenshown to have certain clinical utility in diagnosing

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L

‘f

dementia. However, SPECT and PET currently cannotbe used in the primary diagnosis of depression.Further investigations are required to establish imagingdifferences between different subtypes of depression.Whether imaging modalities contain diagnostic orprognostic significance is the focus of ongoing research(5,13). There have been several studies over the lastten years which have discovered variations inmetabolism or cerebral perfusion in depressed patientscompared with controls (8, 13,45). There arepromising patterns in glucose metabolism and bloodflow which are hccoming apparent as more studies arecompleted. Thus, SPECT and PET studies do holdgreat promise in the future assessment of depressiveillness.

PET Imaging. PET studies have shown regionaldecreases in glucose metabolism in both bipolar andunipolar depression (48,53,54). Whole brainhypometabo] ism is evidenced in bipolar patients,whereas subsets of unipolar patients show a morespecit~c Iefi frontal hypometabolism (54). Reductionsin glucose metabolism in the left dorsal antero]ateralprefrontal cortex have been consistently found byseveral researchers in patients with unipolar depression(48,54,55). The left to right relative asymmetry of theprefrontal cortex found in depressed patients htis shownnormalization of activity upon pharmacothtrapy andelectrouonvuls.ive therapy (ECT), and correlates wellwith clinical improvement (48,54).

PET, when combined with statistical parametricmapping, has been utilized to study regional blood flowin depressed patients. The research identifieddissociations between focal abnormalities in cerebralfunction due to mood disorders tind related cognitiveimptiirment. The depressed group tis d whole showeddecreased regional cerebral blood flow (rCBF) in theleft anterior cingulate and the left dorsolateralprefrontal cortex. The patients that exhihited cognitiveimpairment showed additional signifiutint decreases inregional blood flow in the left me~iialfrontdl gyrus andan increased rCBF in the cerebella vermis (48). Thisis significant, in that it indic~tes tin anatomicaldissociation between the rCBF in the depressed stateand depression-related cognitive impairment. Thus,PET has the potential to identify and differentiatebetween these two subtypes of depression.

SPECT Imaging. SPECT studies have paralleledmany of the results found in PET. Detailedcomparisons of depressed patients and controls showdecreased perfusion in the anterior cingulatc. temporaland frontal cortices, and in the caudate nuclei andthalami of men only (50,58). Unipolar major dcpres-sivti patients, when imaged with Tc-99m exametazime,show a lower whole brain blood flow and reducedrcgiona] flow to the frontal, temporal, and parietal

lobes (51,56). Right inferior flow deficits are notuncommon in unipolar depression. The flow deficit inthe right frontal lobe has been shown to be a result ofcircumferential hypoperfusion (8,57). This type ofimage is also found in bipolar disease, although it isnot as common (8,13) (see Fig 3, Center Spread).

Bipolar depressives show higher flow values thannormal in the left parietal and temporal lobes. Patientswith rapidly cycling bipolar disorder have been shownto have dramatically increased activity in the righttemporal lobe during periods of depression. Thisasymmetry was noted to normalize during periods ofeuthymia and after pharrnacotherapy (36). Thus,current research has important applications in leadingto a possible method of differentitil diagnosis betweenbipo]tir and unipolar disorders.

Some researchers are investigating the hypothesisthat there is a “mood system, ” such as the prefrontaland limhic areas, which may constitute an anatomicalnetwork that may be functionally abnormal in patientsexhibiting major depressive disorder (8,48). Majordepression is associated with findings of functionalchanges in the left anterior cingulate and the leftdorsolateral prefrontal cortex (48).

While not currently diagnostic for depression, PETand SPECT studies hold promise for assessing regionalbrain fllnction in patients with depressive illness.Current research is investigating the usefulness ofSPECT to differentiate depression with pseudodementiafrom primary dementia with secondary depression.SPECT is also being used to attempt differentiation oftreatment resistant patients from those who respondwell to pharmacotherapy (8,36) (see Figs 4a and 4b,Center Spread). Research along these lines may leadto a major role for SPECT in patient diagnosis,prognosis and treatment.

Ohstissive-Compulsive Disorder.Disease Ovemiew. Obsessive compulsive disorder

(OCD) is a classic psychoneurosis, which frequentlyhtis a secondary component of depression. Thisdisorder is estimated to affect some five millionAmericans. Obsessive-compulsive disorder is general-ly considered as an anxiety disorder, and includes afidmily of psychological problems such as generalanxiety, phobias, and repetitive, cornpulsivti behaviors.Obsessions are repetitive and intrusive thoughts orimpulses that are unwanted and distressing to thepatient. The obsessions arise involuntarily despiteattempts by the patient to suppress or ignore them.The most frequent topics of obsessions includeviolence. doubts shout having performed routine tasksproperly, and fear of cont~mination. The compulsivecomponent of OCD is comprised of repetitive

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Figure 1. A normal corrlputed ro~?)ogrfrphy (CT) study (left) and a normal single-phototl ertlissiotl computed tomogra)(SPECT) study following the administration of the radiopharmaceutical technetium-99m ~xametazime (ri~l

[courtesyof Dr. R.A. O’Connell (l)]

?hyIt) ,

ANNIHllATl~

COINCIDENCE-”DETECTION

Figure 2. A schematic illustration of the detection of paird photons which have arisen from a positron-el~tron annihilationreaction. The coincidence counting records only those events that occur within the plane of tissue situatedbetwwn the two detectors. preprinted with permission from Powell MP, Gibbs JM. Brain: positron emissiontonlography--’~~Xenon blood flow. In: Davis ER, Thomas EG, (ds). Nuclear Medicine: Applications toSurgery. New York: Sheridan House. 1988 :254-269.]

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Figure 3. A thr= dimensional rCBF SPECT study in a patient with major depressive disorder (patient was medication-frw). The study demonstrates right inferior frontal hypoperfusion and circumferential (mtiial worse than lateral)right temporal lobe hypoperfusion.

●Figure 4a. Male patient with depression exhibiting signiti~ant clinival improvement upon treatment with elwtroconvulsive

therapy as seen in this SPECT study obtainti following the administration of twhnetium-99m exametazime(transaxial view). [courttisy of Dr. Lukasz Konopka, V. A. }Iines hospital and Loyo]a University Mdical School,Maywood, IL]

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Figure 4b. Coronal view of same patient as in Figurti 4a. [courtesy of Dr. Lukasz Konopka, V.A. Hines Hospital and

Loyola University Medical School, Maywood, IL]

●Figure 5. These SPECT studies show examples of increased and decreased perfusion in the frontal lobes of different

medication-free patients. [courttisyof Dr. R.A. O’Comell (l) I

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stereotypical acts which are performed reluctantly bythe patient in an effort to alleviate intrusive thoughts.Some examples include hand-washing, touching,counting, and checking, Attempts are usually made bythe individual to resist the ritual, as the frequency andduration of the repetitions make them inconvenient andeven incapacitating. If the ritual is successfullyprevented, obsessive-compulsive individuals becomeanxious (77).

The anatomic and biochemical basis of this diseasehas not been elucidated and is currently under intensiveresearch. Many theories suggest a biological basis forthe disorder (59-61). Current research suggests thatOCD may involve dysfunction of serotonin neurotrans-mission and anatomical deficits in the orbital gyri (theleft more than the right) and also in the caudate nuclei(59-62,77).

Recent imaging modalities (principally PET) haveimplicated brain malfunctions involving certain brainstructures, principal 1y the orbital prefrontal cortex andthe striatum. The anterolateral prefrontal cortex, asprevious] y discussed, has been implicated in themediation of depression, This undoubtedly accountsfor the imaging abnormalities identified in these areasduring the investigation of OCD (60-62).

Results of research indicate that certain brain areasmediate the behaviors commonly expressed inobsessive compulsive patients (60,6 1). The orbitalcortex is associated with the manifestation of anxiety,with impulse control, and conscientious attention tohygiene. Evidence also indicates that this region of thebrain is involved in behavioral inhibition and extinctionand perseverative behaviors. Abnormalities of orbitalcortex function account for compulsive behaviors foundin OCD patients (61).

The striatum is also thought to he involved inperseverative behavior. The caudate nucleus is a partof the striatum which receives pr~]jections from theinferior prefrontal cortex. This region of the striatumis associated with adventitious movement. and theresulting motor activities are mediated thr(}ugh thebasal ganglia. Deficiencies in function in the caudate,along with the orbital areas, also produce similarperseverative difficulties in animal studies. This mayaccount for the diftlculty of OCD patients in ceasingtheir repetitivti, compulsive behaviors, Pfithologywhich is distributed throughout the striatum results inOCD symptoms, such as simple tics (lesions in theputamen), simple obsessive disorders (ventral medialpart of the caudate), or complex thought disturbanctis(the more dorsal arwds of the striaturn). Thecompulsions that an OCD patient rntinifests arise in aneffort to eliminate troublesome thoughts, Thesecompulsions are mediated thr{~ughmotor activity viathe cortex (61,62).

PET /mging. PET with F-18 tluorodeox yglucoseis currently the most commonly employd imagingprocedure being used to investigate OCD. Imagingyields elevations of relative glucose metabolism infrontal areas such as the orbital and anterior cingulategyri, the basal ganglia, and the frontal orbital cortex(63). Reductions in radiotracer uptake have been seenin certain parietal regions. As previously noted, theheads of the caudate nuclei have been implicated.Interestingly, as with depression, glucose metabolismtends to normalize afier pharmacotherapy (60,64-66).

SPECT Imaging. SPECT studies have yieldedsimilar results (64,66). The striatum and the prefrontalcortex both utilize serotonin as a neurotransrnitter.This correlates with the success OCD patients exper-ience during treatment with serotonin uptake blockerssuch as fluoxitine (Prozacm, Dista).

In the future, PET imaging, along with receptor-specific ligands, could be used to investigate receptorlevel dysfunctions. Since the cortex-striatumintegration is complex and involves many differenttransmitters, serotonin may not be the primary effecter(61). 1-123 iomazenil, a radioiodinatd version of abenzodiazapine antagonist, allows SPECT evaluation ofhenzodiazepine receptors (1O). The dopamine D2receptor can be evaluated with radiolabeldiodobenzarnide (IBZM), a close analog of Raclopride(67-69). Yohimhine, when administered with Tc-99mexametazime, can be used to evaluate the alpha-2vascular receptor by antagonizing it (69). Otherreceptor-based SPECT agents are currently underdevelopment and promise insight into the neuropharm-acology of OCD and other disease states (64).

The use of SPECT or PET imaging, in OCD,currently has several obstacles which ned to beovercome before physiological imaging with thesemodalities can become a routine clinical practice. Thisis due to the subtlety of the disease state process whichrequires further investigateion. The consistent abnorm-alities, however, in the anterior cingulate gyrus, basalganglia, and orbital-frontal cortex do indicate a highpotential for application ot’nuclear medicine techniquesin the evaluation of OCD (15). Further investigationsinto this disease state will help to elucidate thedifferences between this disorder and the affectivedisorders. The future holds promise as there is newand progressive research occurring in this area.

SchizophrcniuDisease Oveniew. Schizophrenia is not a single

disorder but is a heterogeneous group of mentaldisorders, that result in severe and prolonged mentaldisturbance. Schizophrenia includes a wide gamut ofseverely disordered behavior. The clinical presentationinvariably shows thought disturbances, hallucinations,

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and delusions. The patient may also exhibit aberrantbehavior and deterioration in the general level offunctioning. In the United States, hospitalization dueto schizophrenia occurs with a frequency of 1 in 100persons and an estimated two million new cases ofschizophrenia occur yearly throughout the world (77).

Schizophrenic symptornatology maybe precipitatedby social and psychological circumstances. Currently,there is evidence to suggest that regardless of theprecipitating event, schizophrenia has an organic base.Evidence from twin studies indicate a geneticcomponent to the disease. Investigations done withMRI and CT scanning show minor abnormalities in thebrains of people with schizophrenia, primarily a sizeincrease in the frontal and temporal horns of thecerebral ventricles. SPECT and PET studies are alsoeffective in the investigation of the neurobiology of thisserious illness (64).

The frontal lobes, basal ganglia, and temporal lobeshave all been implicated in the pathology ofschizophrenia as an organic disease. Evidence frombrain imaging, postmortem studies, rcueptor studies,and psychopharmacologic studies support thesesuppositions. The frontal lobes are the sites forexecutive function and abstrtict thinking.Abnormalities in the function ot’ this section of thebrain coincide with the integrative and evaluativedeficits encountered in schizophrenic patients. Thebasal ganglia are dopamine-rich, which accounts forthe success of pharmacologic treatment withneurolept ic drugs that block doparnine receptors. Theleft temporal lobe is crucial in linguistic function. Thedisordered speech patterns and asymmetries in cerebralfunction implicate this particular region of the brain.Assessment of these speciftc regions of the brain cannow be made via physiological imaging (64,69).

PET lwging. The frontal lobes, as previouslystated, are frequently the focus in schizophrenicphysiological studies (Fig 5, see Center Spread). PETstudies have addressed this area because decreasedperfision of the frontal lobes is theoretically expecteddue to the loss of function associated with theprefrontal cortex that is exhibited by these patients.Decreased perfusion in this area has been confirmed bymany studies using a variety of imaging techniques(64,70,71). “Hypofrontality” htis been reported byinvestigators using the Xc-l 33 two dimensionalnontornographic blood tlow method as well as SPECTand PET techniques (72-74).

SPECT Imaging. SPECT imaging of CBF usingXe-133 demonstrates hypofrontality in the left lobe andis found especially in patients of the paranoid type(72). A decrease in rCBF does not necessarily.,correlate with aevidenced by the

decrease in glucose metabolism aSnegative “hypofrontatity” findings of

several laboratories. However, the majority of PETand rCBF studies utilizing F18 FDG agree on thefindings of low function in the frontal regions ofpatien~s with schizophrenia. SPECT studies with 1-123iofetamine have corroborated the findings of many PET @studies (72,75,76).

The hypofrontality found in schizophrenia is notonly something that is reported from imaging studies inpatients. It is predicted on thmretical basis, as thefrontal lobe controls attention, motivation, and organi-zational behaviors--and these behaviors are founddetlcient in patients with schizophrenia. Hypofrontalitymay be readily demonstratti via the use of a cognitivetask utilized to stimulate the frontal cortex (72).

The basal ganglia and their specific role in basalganglia-thalamus-cortex loops have also beenimp]icated in schizophrenia, Dopamine and glutamateimbalance is proposed as the primary mechanism. Thethalamus’ role in the loop corr~lates with the inabilityof schizophrenia patients to filter incoming sensorystimuli and the resulting perceptual diftlculties theyexperience. Autopsy stud ies reveal changes in receptordensity and the effects noted with the use ofneurol eptics are consistent with changes in themetabolic rate of the caudate and putamen (69,71).

In general, the data on perfusion or metabolismabnormalities of the basal ganglia in these patienw areconflicting. Some of the reports indiudte reducedmetaholisrn in the basal gdnglia of schizophrcticpatients. However, other studies report normal hdsalganglia and still others suggest enhanced perfusion(64,71). The bulk of the information indicates thatenhanced metabolism or perfusion in the basal ganglia is,in fdct, due to neuroleptic medication effecw (64,73).

The left temporal lobe is the third region of interestin the evaluation of schizophrenia. Although widemethodologies have been used, most studies show lowermetabolic rates in the left temporal lobe (71). Temporallobe abnormalities are still inconclusive and requiremore res~arch ddta befc~reactual clinical correlations canbe drawn.

The clinical assessment of schizophrenia with SPECTand PET has a number of potential applicatiomq.Nucldar medicine findings, such as that of hypofront-ality, will allow psychiatrists and the nuclear medicinecommunity to identify applications for these imagingtechnologies. For example, assessment of hypofront-ality may he used to predict the success of tredtmentwith neuroleptics. It may also he used to predict properdosagti and drug regimens. The perfusion hypofrontalityobserved with SPECT and PET imaging (especiallywhen performed during psychological tasks to stress theprefrontal cortex) are rapidly approaching the stagewhere findings are consistent enough to warrant attemptsat clinical application (64).

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CONCLUS1ON

The unique information obtained from both PET

●and SPECT studies promise an exciting new additionto the psychiatric field. Functional imaging allowsphysicians to use diagnostic capabilities in moreclinical]y relevant ways. These modalities have alsoprovided an insight into a more detailed understandingof the intricate relationships between brain structure,function, and various psychiatric disease states. Thedevelopment of PET has increas~ current

understanding of the actual physiological functioning ofthe human brain, As with all new technologies, theapplication of dynamic imaging modalities such asPET, require the development of less expensive andless complicated technology (2). As a result, researchwith SPECT has been intense. SPECT is currentlymore accessible and much less costly than PET. Betterracliopharmaceuticals and improved imaging technologyhave already improved the resolution of SPECT,drawing its capabilities closer to that of PET. Furtheradvances in SPECT will allow regular clinicalapplication in diagnosis of psychiatric illness.

The unique information provided by functionalimaging modalities can certainly help to minimize costsincurred by prolonged diagnostic evaluations, incorrectdiagnoses, and therapeutic mismanagement. These

●procedures also promise applications ii the tailoring oftreatment regimens on the basis of neurochemical andbrain function characteristics of the patient (67). Inconclusion, as the use of nuclear medicine inpsychiatry progresses, more potential clinicalapplications will continue to evolve.

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QUESTIONS

Nuclear medicine brain

a. shows function

imaging

(physiology), asopposed to structure (anatomy),

b. shows structure (anatomy), asopposed to function (physiology).

c. shows both anatomy and function,d. does not show either function or

anatomy.

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2.

3.

4.

5.

The basal ganglia, structures which areimplicated in the manifestation ofobsessive-compulsive disorder

a. integrate sensory information andcoordinate the resulting motorresponses.

b. connect the cerebell urn to the brainstem and the cerebrum.

c, are aggregates of neuronal cellbodies which are involved insomatic (inhibitory) motorfunctions.

d. are passageways composed of nervefiber tracts extending between thespinal cord and the higher brainregions.

During the decay of a positron-emittingnuclide, the nucleus will release

a. a particle withnegative charge.

b. a particle withcharge.

c. two positively

a single excess

a single positive

charged particlestraveling in 180 degree oppositetrajectories.

d. both a and c

PET and SPECT brain imaging techniquesare similiar in that they both

a. utilize radioactive deoxyglucose inscanning procedures.

b. utilize radionuclides which emitonly one photon per disintegration.

c. can be used in routine clinicalpractice.

d. can produce tomographic images.

Advantages of PET imaging include:

a. PET is capable of attainingimage resolution.

high

b. PET is capable of evaluatingimportant metabolic processes ofthe brain (i.e. ,glucose metabolism).

c. PET imaging is readily accessibleand inexpensive.

d. a and b

6. SPECT imaging can be used to show

neuroreceptor density;: regional cerebral blood

oxygen consumption:: a and b

flow

7. Advantages of SPECT brain imaging overthat of PET include which of thefollowing?

a. SPECT is capable of attainingconsistently higher imageresolution.

b. SPECT utilizes methods andequipment currently found in manyhospital nuclear medicinedepartments.

c, SPECT imaging is less expensiveand less technically cumbersome.

d. b and c

8. Which of the following statements are mof SPECT brain imaging?

a. The SPECT approach utilizesaccelerator-produced radionuclideswhich necessitate the presence of anon-site cyclotron.

b, The majority of SPECT radio-pharmaceuticals measurebenzodiazapine receptor density.

c. The majority of SPECT radio-

pharmaceuticals are brain perfusionor cerebral blood flow agents.

d. a and c

9. In patients with symptoms of Alzheimer’sdisease, SPECT brain imaging can help

a. increase diagnostic accuracyespecially when combined withpatient history and structuralevaluations.

b. clearly illustrate the marked sulcalwidening common in the brainatrophy found in this disease.

c. assist in the differential diagnosis ofbrain tumor and Alzheimer’sdisease.

d. a and c

19

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10, In patients with Alzheimer’s disease,SPECT brain studies

a. demonstrate decreased blood flowin the temporoparietal cortex.

b. demonstrate increase cerebral bloodflow to the temporoparietal cortex.

c, demonstrate marked deoxyglucoseglypometabolism in the temporo-parietal cortex.

d, demonstrate insular atrophycommon in this disease.

11. When performing PET brain imaging on apatient with Alzheimer’s disease, one mightexpect to see which of the following?

a. normal glucose metabolism in thevisual cortex

b. normal glucose metabolism in themotor sensory strip

c. decreased glucose metabolism in theparietal region

d. all of the above

12. In patients with symptoms of depression,SPECT scanning can

a. provide a definitive diagnosis.b. augment treatment of depression.c. assist in the differentiation of

unipolar depression and bipolardepression.

d. show regional decreases in leftfrontal glucose metabolism.

13. PET studies performed on depressedpatients have shown which of thefollowing?

a. whole brain hypometabolisrn inbipolar depression patients

b. left frontal hypometabolism inunipolar depression patients

c. normalization of profrontal cortexasymmetries in depressed patients,

upon pharmaceutical and

electroconvulsive therapiesd. all of the above

14. Which of the following statementspertaining to imaging in depression can beregarded as ~?

a, The prefrontal and limbic areas are o

thought by researchers to constitutea “mood system” which may befunctionally abnormal in depressedpatients.

b. The temporal, parietal and motor-sensory areas are thought byresearchers to constitute a “moodsystem” which may be functional yabnormal in depressed patients.

c. Both PET and SPECT studies haveshown decreased perfusion in theanterior cingulate and frontalcortices of depressed patients.

d. a and c

15. Examples of PET brain imaging agentsinclude the following:

a. (“C)d-glucoseb. (lxF)2-deoxy-2 flouro-d-glucose

c. (’921r)-deoxyglucosed. a and b

16. Which of the following common behaviors,expressed in obsessive-compulsive patients,correctly corresponds with its associatedbrain region?

a. orbital cortex--compulsions andanxiety

b. putamen--simplec. dorsal striatum

disturbancesd. all of the above

ticscomplex thought

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17. Which of the following statementsregarding obsessive-compulsivebehavior?

is ~(oCD)

● a. Obsessive-compulsive patientsfrequent] y experience anxiety,compulsions, and hallucinations.

b. Positron Emission Tomograph ywith L(l ‘C)-aspartate is the mostcommonly employed imagingprocedure to investigate OCD.

c. a and bd. none of the above

18, Schizophrenic patients exhibit which of thefollowing abnormalities?

a, size increases in the frontal andtemporal horns of the cerebralventricles as seen by MRI and CTstudies

b. decreased frontal lobe blood flowdemonstrated by Xenon-133 andSPECT

c. cortical atrophy and sulcal widening

ademonstrated by Tc-99m labeledexametazime and SPECT

d. a and b

19. Which of the following have beenimplicated in the pathology ofschizophrenia?

a. frontal lobesb. basal gangliac. temporal lobesd. all of the above

20. Which of the following is a commonly-employed SPECT brain imaging agent forpsychiatric applications’?

Tc-99m labeled exametazi me:: Tc-99m labeled DTPAc. Tc-99m labeled deoxyglucosed. none of the above

21. “Hypofrontality” is a common finding inpatients with

depression;: Alzheimer’s diseasec. obsessive-compulsive disorderd. Schizophrenia

22. Enhanced metabolism or perfusion in thebasal ganglia of schizophrenic patients uponPET or SPECT imaging is most likely dueto

a. exceptional y large basal gang] iafound in schizophrenic patients

b. neurolep tic medicationadministration

c. back scatter from surrounding brainstructures

d. idiopathic inflammatory lesions

23. SPECT brain scanning may be useful inclinical psychiatry for:

differential diagnosis:: monitoring treatment regimensc. measuring receptor densitiesd. all of the above

24. Imaging of rCBF with 1-123 iofetamine isprobably best performed at what time periodpost injection?

within the first 20 minutes:: after 1 hourc. after 3 hoursd. after 6 hours

25. What imaging modality and correspondingradiolabeled compound are currently themost frequently utilized in the assessment ofobsessive-compulsive disorder?

a. positron emission tomography andlxF-fluoro-deoxygl ucose

b. positron emission tomography and2.(1 lC)-deoxy-D-glucose

c. single photon emission computedtomography and Tc-99m labeledexametazime

d. single photon emission computedtomography and 1-123 iofetamine

21

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