neuroimaging in psychiatry

NEUROIMAGING IN PSYCHIATRY

Dr. Subrata NaskarEmail :

nsubrata09@gmail.com

PLAN OF PRESENTATION• INTRODUCTION• HISTORICAL MILESTONES• WHY NEUROIMAGING IN PSYCHIATRY ?• TYPES OF NEUROIMAGING• BASIC PRINCIPLES• NEUROIMAGING IN SOME SPECIFIC PSYCHIATRIC DISORDERS• CONCLUSION• BIBLIOGRAPHY

INTRODUCTION• RADIOIMAGING ARE METHODOLOGIES THAT ALLOW

MEASUREMENT OF THE STRUCTURE, FUNCTION, & CHEMISTRY OF THE LIVING HUMAN BRAIN

• IT HAS PROVIDED NEW INFORMATION ABOUT THE PATHOPHYSIOLOGY OF PSYCHIATRIC DISORDERS

• IT CAN BE USEFUL FOR DIAGNOSING ILLNESS, PREDICTING PROGNOSIS & FOR DEVELOPING NEW TREATMENTS

HISTORY• THE FIRST CHAPTER OF THE HISTORY OF NEUROIMAGING TRACES BACK TO THE ITALIAN NEUROSCIENTIST

ANGELO MOSSO WHO INVENTED THE 'HUMAN CIRCULATION BALANCE', WHICH COULD NON-INVASIVELY MEASURE THE REDISTRIBUTION OF BLOOD DURING EMOTIONAL AND INTELLECTUAL ACTIVITY.

• IN 1918 THE AMERICAN NEUROSURGEON WALTER DANDY INTRODUCED THE TECHNIQUE OF VENTRICULOGRAPHY. X-RAYIMAGES OF THE VENTRICULAR SYSTEM WITHIN THE BRAIN WERE OBTAINED BY INJECTION OF FILTERED AIR DIRECTLY INTO ONE OR BOTH LATERAL VENTRICLES OF THE BRAIN.

• IN 1927 EGAS MONIZ INTRODUCED CEREBRAL ANGIOGRAPHY, WHEREBY BOTH NORMAL AND ABNORMAL BLOOD VESSELS IN AND AROUND THE BRAIN COULD BE VISUALIZED WITH GREAT PRECISION.

ANGELO MOSSO WALTER DANDY EGAS MONIZ

HISTORY1946 – MR PHENOMENON EXPLAINED BY BLOCH & PURCELL [1952 – NOBEL PRIZE]1950 – 1970 – NMR DEVELOPED AS AN ANALYTICAL TOOL1963 – 1ST INSTANCE OF SPECT USING ANGER CAMERA – KUHN & EDWARDS1972 – COMPUTERIZED TOMOGRAPHY [GODFREY HOUNSFIELD, ALAN MCLEOD CORMACK, 1979 – NOBEL PRIZE]1973 – BACKPROJECTION MRI – LAUTERBUR1983 – COMPTON CAMERA FOR SPECT – MANBIR SINGH & DAVID DORIA1985 – DTI – LE BIHAN D & BRETON E1986 – GRADIENT ECHO IMAGING, NMR MICROSCOPE1987 – MR ANGIOGRAPHY – DUMOULIN1992 – FUNCTIONAL MRI BY RICHARD .R. ERNST

WHY NEUROIMAGING IN PSYCHIATRY ?

TO HELP US IDENTIFY NEURAL SYSTEM ABNORMALITIES THAT ARE MORE ACCURATE THAN TRADITIONAL CLINICAL MEASURES

FUNCTIONAL NEUROIMAGING TECHNIQUES CURRENTLY HAVE AN ADJUNCTIVE ROLE IN THE EVALUATION OF DEMENTIA AND SEIZURE DISORDERS

BETTER CLASSIFICATION SYSTEM OF PSYCHIATRIC ILLNESS

TYPES OF NEUROIMAGINGSTRUCTURAL FUNCTIONAL

CT SCAN FMRIMRI PET

PLAIN SKULL RADIOGRAPHY SPECTPNEUMO-ENCEPHALOGRAPHY MRS

DTIBRAIN ELECTRICAL ACTIVITY

MAPPING (BEAM)

COMPUTED TOMOGRAPHY

COMPUTED TOMOGRAPHY

CT SCANNERS TAKE A SERIES OF HEAD X-RAY PICTURES

FROM ALL VANTAGE POINTS360º AROUND A PATIENT'S

HEAD

THE AMOUNT OF RADIATION THAT PASSES THROUGH, OR IS NOT ABSORBED FROM, EACH

ANGLE IS DIGITIZED & ENTERED INTO A COMPUTER

THE COMPUTER USES MATRIX ALGEBRA CALCULATIONS TO

ASSIGN A SPECIFIC DENSITY TO EACH POINT WITHIN THE

HEAD & DISPLAYS THESE DATA AS A SET OF 2-D IMAGES

WHEN VIEWED IN SEQUENCE, THE IMAGES ALLOW MENTAL

RECONSTRUCTION OF THE STRUCTURE OF THE BRAIN

CT SCANTISSUE APPEARANCE

BONE WHITE

CALCIFIED TISSUE WHITE

CLOTTED BLOOD WHITE

GREY MATTER LIGHT GREY

WHITE MATTER MEDIUM GREY

CSF NEARLY BLACK

WATER NEARLY BLACK

AIR BLACK

• CT IMAGE IS DETERMINED ONLY BY DEGREE TO WHICH TISSUES ABSORB X-RAY

• BONY TISSUE ABSORB LARGE AMOUNT OF X-RAYS AND TEND TO OBSCURE THE DETAILS OF NEIGHBORING STRUCTURES POOR VISIBILITY IN BRAINSTEM.

• POOR DIFFERENTIATION OF GREY-WHITE PATTERN THAN COMPARED TO MRI.

• CERTAIN TUMORS MAY BE INVISIBLE ON CT BECAUSE THEY ABSORB AS MUCH IRRADIATION THAN THE SURROUNDING BRAIN VISIBLE ON CONTRAST CT.

• BONE, CLOTTED BLOOD, CALCIFIED TISSUE, CONTRAST MATERIAL ALL APPEAR WHITE & CSF BLACK

• THE ONLY COMPONENT OF BRAIN BETTER SEEN ON CT SCAN IS CALCIFICATION, WHICH MAY BE INVISIBLE ON MRI

NORMAL CT SCAN OF BRAIN

SOME IMPORTANT STRUCTURES THAT WE SHOULD KNOW

• CRITERIA FOR CONTRAST- – PATIENTS WITH H/O SEIZURE– PATIENTS WITH H/O CEREBRO-VASCULAR ACCIDENT– SUSPICION OF INTRACRANIAL SOLS INCLUDING GRANULOMAS, CNS

TUMOURS, METASTATIC LESIONS

• PLAIN CT– DIAGNOSTIC ACCURACY 82%

• CONTRAST CT – IV IODINATED CONTRAST MEDIUM– DIAGNOSTIC ACCURACY 92%

IMAGE SHOWING ENHANCEMENT AFTER CONTRAST ADMINISTRATION

• ADVANTAGES

– SIMPLER, CHEAPER, MORE ACCESSIBLE

– TOLERATED BY CLAUSTROPHOBICS

– NO ABSOLUTE CONTRAINDICATIONS

– BETTER THAN MR FOR BONE DETAIL & CALCIFICATION

• DISADVANTAGES

₋ IONIZING RADIATION

₋ IV CONTRAST COMPLICATIONS

₋ LIMITED RANGE OF TISSUE CONTRASTS

CLNICAL INDICATIONS OF CT BRAIN IN PSYCHIATRY

• CONFUSION &/OR DEMENTIAS OF UNKNOWN CAUSE• FIRST EPISODE OF PSYCHOSIS• FIRST EPISODE OF MAJOR AFFECTIVE DISORDER AFTER 50 YEARS OF

AGE• PERSONALITY CHANGES AFTER 50 YEARS OF AGE• PSYCHIATRIC SYMPTOMS FOLLOWING HEAD INJURY• TO RULE OUT COMPLICATIONS DUE TO POSSIBLE HEAD TRAUMA

CLNICAL INDICATIONS OF CT BRAIN IN PSYCHIATRY

• PROLONGED CATATONIA

• CO EXISTENCE OF SEIZURE WITH PSYCHIATRIC SYMPTOMS

• MOVEMENT DISORDERS OF UNKNOWN ETIOLOGY

• FOCAL NEUROLOGICAL SIGNS ACCOMPANYING PSYCHIATRIC SYMPTOMS

MAGNETIC RESONANCE IMAGING

MAGNETIC RESONANCE IMAGING

NUCLEI OF ALL ATOMS ARE THOUGHT TO SPIN ABOUT AN AXIS RANDOMLY ORIENTED IN

SPACE

PLACED IN MAGNETIC FIELD AXIS OF ALL ODD-NUMBERED NUCLEI (MAINLY HYDROGEN) ALIGN WITH THE MAGNETIC

FIELD

WHEN EXPOSED TO A PULSE OF RADIOFREQUENCY WAVES - AXIS OF NUCLEUS DEVIATES AWAY FROM THE MAGNETIC

FIELD

WHEN THE PULSE TERMINATES, THE AXIS OF THE SPINNING

NUCLEUS REALIGNS ITSELF WITH THE MAGNETIC FIELD

DURING THIS REALIGNMENT, IT EMITS ITS OWN

RADIOFREQUENCY SIGNAL

MRI SCANNERS COLLECT THE EMISSIONS OF INDIVIDUAL REALIGNING NUCLEI & USE

COMPUTER ANALYSIS TO GENERATE A SERIES OF 2-D

IMAGES THAT REPRESENT THE BRAIN

• RADIOFREQUENCY AND MAGNETIC FIELD PULSES MANIPULATED TO CREATE DIFFERENT PULSE SEQUENCES.

• BASED ON THE DURATION OF RF PULSE & THE LENGTH OF TIME - DIFFERENT PULSE SEQUENCES ARE OBTAINED.

• EXAMPLES: T1, T2, FLAIR, DWI ETC.

SOME IMPORTANT POINTS TO REMEMBER

• MAGNETIC FIELD STRENGH IS THE MEASURED INTENSITY OF MAGNETIC FIELD

• MAGNETIC FIELD STRENGTH IS MEASURED IN Tesla (T) OR Gauss (G)

• FDA APPROVED MRI SCANNER ≤ 3T• 3T = 50,000 EARTH’S MAGNETIC FIELD

SOME IMPORTANT POINTS TO REMEMBER

• AN MRI IMAGE IS A SLICE OF A PART OF HUMAN BODY• EACH SLICE HAS A THICKNESS• VOXELS ARE VOLUME ELEMENTS• SEVERAL VOLUME ELEMENTS IS PRESENT IN A SLICE• VOXEL = 3mm• PIXEL – PICTURE ELEMENTS OF AN MRI IMAGE

T1 WEIGHTED MRI• BEST FOR VISUALIZING NORMAL NEUROANATOMY• SHARP BOUNDARIES BETWEEN GREY MATTER, WHITE MATTER,

AND CSF• USEFUL IN EVALUATION OF CEREBRO-PONTINE ANGLE, CISTERN

& PITUITARY FOSSA• BONE WHITE• WHITE MATTER LIGHT GREY• GREY MATTER MEDIUM GREY• WATER/CSF/AIR BLACK

T1 WEIGHTED MRI

T1 IS THE ONLY SEQUENCE THAT ALLOWS CONTRAST ENHANCEMENT WITH GADOLINIUM.

CONTRAST ENHANCED STRUCTURES ON T1 APPEARS WHITE

T2 WEIGHTED MRI• LESS DISTINCT BOUNDARIES BETWEEN WHITE AND GREY

MATTER• BEST FOR DISPLAYING PATHOLOGY• USEFUL IN DEMYELINATION, EDEMA & TUMOUR INFILTRATION– GRAY MATTER MEDIUM GRAY– WHITE MATTER DARK GREY– CSF AND WATER WHITE

T1 WEIGHTED MRI T2 WEIGHTED MRI

FLUID ATTENUATED INVERSION RECOVERY(FLAIR)

• SPECIAL TYPE OF MRI SCAN• T1 IMAGE IS INVERTED & ADDED TO THE T2 IMAGE• CONTRAST BETWEEN GREY & WHITE MATTER IS DOUBLED &

THE NORMAL CSF SIGNAL IS SUPPRESSED.• SPECIAL INDICATIONS– TO DETECT SCLEROSIS OF HIPPOCAMPUS IN TEMPORAL LOBE

EPILEPSY.– TO LOCALIZE THE AREAS OF ABNORMAL METABOLISM IN

DEGENERATIVE NEUROLOGICAL DISEASES.

FLUID ATTENUATED INVERSION RECOVERY(FLAIR)

DIFFUSION WEIGHTED IMAGING (DWI)• SENSITIVE TO SPEED OF WATER DIFFUSION • VISUALIZES AREA OF ISCHEMIC STROKE IN 1ST FEW HOURS- EARLIEST TO DETECT

ISCHEMIA.• MRI TECHNIQUE THAT ENABLES THE MEASUREMENT OF THE RESTRICTED DIFFUSION OF

WATER IN TISSUE• PRINCIPLE APPLICATION IS IN THE IMAGING OF WHITE MATTERWHERE THE LOCATION,

ORIENTATION, AND ANISOTROPY OF THE TRACT S CAN BE MEASURED• THE ARCHITECHTURE OF THE AXONS IN PARALLEL BUNDLES, AND THEIR MYELIN

SHEATHS, FACILITATE THE DIFFUSION OF THE WATER MOLECULES PREFERENTIALLY ALONG THEIR MAIN DIRECTION. SUCH PREFERENTIALLY ORIENTED DIFFUSION IS CALLED ANISOTROPHIC DIFFUSION

THREE-DIMENSIONAL RECONSTRUCTION BASED ON DIFFUSION DATA

IMPORTANT POINTS• MRI MAGNETS USED IN CLINICAL PRACTICE RANGES FROM 0.3 TO 2.0 TESLA STRENGTH.• HIGHER FIELD-STRENGTH SCANNERS PRODUCE IMAGE OF HIGHER RESOLUTION.

INDICATION ADVANTAGES DISADVANTAGES

TO RULE OUT ORGANIC CAUSE OF PSYCHIATRIC ILLNESS

DOES NOT EXPOSE THE PATIENT TO IONIZING RADIATIONS

AVOIDED IN PATIENTS WEARING METALLIC DEVICES

ABRUPT CHANGE IN MENTAL STATE

DEMYELINATING DISEASE CAN BE ASSESSED RELIABLY

CLAUSTROPHOBIA

NEW ONSET MEMORY LOSS OR DEMENTIA

BETTER STUDY OF POSTERIOR FOSSA STRUCTURES

DOES NOT PICK UP BONY ABNORMALITIES

DIFFICULT IN UNCOOPERATIVE PATIENTS

IV CONTRAST IN NEURO-IMAGING• CT → IODINE BASED

– IODINE IS HIGHLY ATTENUATING OF X-RAY BEAM (BRIGHT ON CT)• MRI → GADOLINIUM BASED (GADOLINIUM DTPA)

– GADOLINIUM IS A PARAMAGNETIC METAL THAT HASTENS T1 RELAXATION OF NEARBY WATER PROTONS (BRIGHT ON T1-WEIGHTED IMAGES)

• TISSUE THAT GETS BRIGHTER WITH IV CONTRAST IS SAID TO BE “ENHANCED”• ENHANCEMENT REFLECTS THE VASCULARITY OF TISSUE,• THE BLOOD-BRAIN BARRIER KEEPS IV CONTRAST OUT OF THE BRAIN• ENHANCEMENT IMPLIES BBB IS ABSENT OR DYSFUNCTIONAL

LOCATION OF SOME IMPORTANT BRAIN STRUCTURES

AMYGDALA

HIPPOCAMPUS

CAUDATE HEAD

PUTAMEN

GLOBUS PALLIDUS

MAGNETIC RESONANCE SPECTROSCOPY(MRS)

• BASIC PRINCIPLE:BASIC PRINCIPLE SIMILAR TO MRI EXCEPT..

MRS CAN DETECT SEVERAL ODD-NUMBERED NUCLEI

PERMITS STUDY OF MANY METABOLIC PROCESSES

MAGNETIC RESONANCE SPECTROSCOPY(MRS)

• NUCLEI ALIGN THEMSELVES IN THE STRONG MAG. FIELD

• A RADIOFREQUENCY PULSE CAUSES THE NUCLEI OF INTEREST TO ABSORB & THEN EMIT ENERGY

• READOUT ON MRS IS IN THE FORM OF A SPECTRUM

• CAN BE CONVERTED INTO A PICTORIAL IMAGE OF THE BRAIN

NUCLEI USED IN MRS & THEIR USES IN PSYCHIATRYNUCLEI USES

H¹ DECREASED ASPARTATE (NAA) IN DEMENTIA & OTHER NEUROLOGICAL CONDITIONS

LI 7 PHARMACOKINETICS OF LITHIUM

C¹³ STUDY OF METABOLIC PATHWAY

F 19 PHARMACOKINETICS OF CERTAIN DRUGS LIKE SSRIS (FLUOXETINE, FLUOXAMINE) ANALYSIS OF GLUCOSE METABOLISM

P³¹ TISSUE METABOLISM (COMPOUND CONTAINING HIGH ENERGY PHOSPHATES LIKE ATP, ADP ETC.)

SIGNIFICANCE OF MRS IN PSYCHIATRY• MRS HAS REVEALED DECREASED NAA CONC. IN TEMPORAL

LOBES & INCREASED CONC. OF INOSITOL IN OCCIPITAL LOBES OF PTS WITH ALZHEIMER DEMENTIA.

• MRS HAS REVEALED DECREASED NAA CONC. IN TEMPORAL & FRONTAL LOBES OF PTS WITH SCHIZOPHRENIA.

• ALSO IT HAS SHOWN ELEVATED BRAIN LACTATE LEVELS DURING PANIC ATTACKS IN PTS WITH PANIC DISORDER.

FUNCTIONAL MAGNETIC RESONANCE IMAGING(fMRI)

PRINCIPLE• A SUB-TYPE OF MRI SCAN• USES THE NEW T2 OR THE BLOOD-OXYGEN LEVEL DEPENDENT (BOLD)

SEQUENCE • DETECTS LEVELS OF OXYGENATED HB IN THE BLOOD• MAPS BRAIN FUNCTION• DETECTS NOT THE BRAIN ACTIVITY PER SE, BUT THE BLOOD FLOW

NEURONAL ACTIVITY WITHIN

THE BRAIN

LOCAL INCREASE IN BLOOD FLOW

INCREASES THE LOCAL HB CONC

WHICH REFLECTS THE FUNC.

ACTIVITY OF BRAIN ON T2 SEQUENCE

ADVANTAGES• POSSIBLE TO STUDY BOTH CEREBRAL ANATOMY & FUNCTIONAL

NEUROPHYSIOLOGY USING A SINGLE TECHNIQUE (BULLMORE & FLETCHER 2003)

• NO RADIO ACTIVE EXPOSURE

• USED IN CRIMINAL PSYCHIATRY OR FEDERAL INVESTIGATIONS AS A LIE DETECTOR

LIMITATIONS OF fMRI• FMRI ASSESES NEURONAL ACTIVITY INDIRECTLY BY MEASURING BLOOD

FLOW (OR TISSUE PERFUSION). THIS LIMITS ITS RESOLUTION.• TWO TASKS THAT ACTIVATES CLUSTERS OF NEURONS 5 MM APART WILL

YIELD OVERLAPPING SIGNALS ON FMRI & THUS ARE INDISTINGUISHABLE BY THIS TECHNIQUE.

• SENSITIVITY & RESOLUTION CAN BE IMPROVED BY USING ULTRA-SMALL NON TOXIC IRON OXIDE PARTICLES.

• ACQUISITION OF SUFFICIENT IMAGES FOR STUDY CAN REQUIRE 20 MINUTES TO 3 HOURS, DURING WHICH THE SUBJECT’S HEAD MUST REMAIN IN EXACTLY THE SAME POSITION.

DEPRESSION

SCHIZOPHRENIA

SINGLE PHOTON EMISSION COMPUTERIZED TOMOGRAPHY (SPECT)

BASIC PRINCIPLE• A TYPE OF NUCLEAR IMAGING THAT SHOWS HOW BLOOD

FLOWS TO TISSUES & ORGANS

• INTEGRATES : CT + RADIOACTIVE MATERIAL (TRACER)

• SPECT USES COMPOUNDS LABELED WITH SINGLE PHOTON-EMITTING ISOTOPES: IODINE-123, TECHNETIUM-99M, AND XENON-133

PRINCIPLE

INJECT WITH RADIO-LABELLED

MATERIAL

GAMMA RAYS EMITTED

DETECTED BY SCANNER

TRANSLATED INTO 2-D IMAGE

THESE IMAGES ADDED

TOGETHER TO GET A 3-D IMAGE

WHERE USED ?• REGIONAL CEREBRAL BLOOD FLOW• TC99 IS MOST COMMONLY USED FOR DEEPER STRUCTURES OF BRAIN

• XE133 FOR SUPERFICIAL STRUCTURES OF BRAIN (RCBF TECHNIQUE)

• MUSCARINIC CHOLINERGIC SYSTEM USING I123

• DOPAMINERGIC SYSTEM• RADIOLABELLED RECEPTOR BINDING AGENTS I123, IBZM (IODOBENZAMIDE) FOR D2

RECEPTORS• ADRENERGIC SYSTEM• EARLY DIAGNOSIS OF ALZHEIMER'S DISEASE

*RCBF – REGIONAL CEREBRAL BLOOD FLOW

POSITRON EMISSION TOMOGRAPHY(PET)

• A RADIOACTIVE ISOTOPE IS INJECTED & DECAYS, EMITTING A Β + PARTICLE.

• WITHIN A SHORT DISTANCE, THE Β + PARTICLE BUMPS INTO AN ELECTRON & THE TWO ANNIHILATE, PRODUCING A PAIR OF G - RAYS.

• BY DETECTING & RECONSTRUCTING WHERE THE G - RAYS COME FROM, WE CAN MEASURE THE LOCATION & CONC OF RADIO-ISOTOPE.

POSITRON EMISSION TOMOGRAPHY• MOST COMMONLY USED ISOTOPES

– F 18– N 13– O 15

• APPLICATIONS:

• TO ESTIMATE REGIONAL CEREBRAL BLOOD FLOW

• TO ESTIMATE REGIONAL CEREBRAL GLUCOSE METABOLISM (REGIONAL CEREBRAL METABOLIC RATE FOR GLUCOSE - RCMRGLU)

• FOR RECEPTOR IMAGING

• TO STUDY NORMAL BRAIN DEVELOPMENT

SPECT PETSINGLE PHOTON POSITRON

99MTC OR I 123 11C OR 18F

SHORT HALF LIFE LONGER HALF LIFE

LESS SENSITIVE HIGHLY SENSITIVE (100 TIMES MORE THAN SPECT)

LOW SPATIAL RESOLUTION SUPERIOR SPATIAL RESOLUTION

CHEAPER AND EASILY AVAILABLE THAN PET COSTLY, NOT EASILY AVAILABLE

PET SCAN CHANGES IN DEPRESSION

PET CHANGES IN ADHD

SOME OTHER MODALITIES• BRAIN MAPPING

– CONNECTOGRAM

• FUNCTIONAL NEAR INFRARED SPECTROSCOPY (fNIRS)

• ALL NEUROIMAGING CAN BE CONSIDERED PART OF BRAIN MAPPING.

• BRAIN MAPPING CAN BE CONCEIVED AS A HIGHER FORM OF NEUROIMAGING, PRODUCING BRAIN IMAGES SUPPLEMENTED BY THE RESULT OF ADDITIONAL (IMAGING OR NON-IMAGING) DATA PROCESSING OR ANALYSIS, SUCH AS MAPS PROJECTING (MEASURES OF) BEHAVIOR ONTO BRAIN REGIONS (FMRI).

• ONE SUCH MAP, CALLED A CONNECTOGRAM, DEPICTS CORTICAL REGIONS AROUND A CIRCLE, ORGANIZED BY LOBES.

CONNECTOGRAMS• ON AN INDIVIDUAL LEVEL, CONNECTOGRAMS CAN BE USED TO

INFORM THE TREATMENT OF PATIENTS WITH NEUROANATOMICAL ABNORMALITIES.

• CONNECTOGRAMS HAVE BEEN USED TO MONITOR THE PROGRESSION OF NEUROLOGICAL RECOVERY OF PATIENTS WHO SUFFERED A TRAUMATIC BRAIN INJURY

FUNCTIONAL NEAR-INFRARED IMAGING• FUNCTIONAL NEAR-INFRARED SPECTROSCOPY (FNIR OR FNIRS), IS THE USE OF NIRS

(NEAR-INFRARED SPECTROSCOPY) FOR THE PURPOSE OF FUNCTIONAL NEUROIMAGING.

• USING FNIR, BRAIN ACTIVITY IS MEASURED THROUGH HEMODYNAMIC RESPONSES ASSOCIATED WITH NEURON BEHAVIOR.

• THE USE OF FNIR AS A FUNCTIONAL IMAGING METHOD RELIES ON THE PRINCIPLE OF NEURO-VASCULAR COUPLING ALSO KNOWN AS THE HAEMODYNAMIC RESPONSE OR BOLD (BLOOD-OXYGENATION-LEVEL-DEPENDENT) RESPONSE.

IMAGING IN SPECIFIC PSYCHIATRIC DISORDERS

DEMENTIA

• PURPOSE– DIAGNOSING THE CAUSE– MONITORING DISEASE PROGRESSION– STAGING OF DISEASE

ALZHEIMER’S DEMENTIA

STRUCTURING IMAGING FINDINGS

CT SCAN

CEREBRAL ATROPHY (TYPICAL DILATATION OF LATERAL VENTRICLES & WIDENING OF CORTICAL SULCI) PARTICULARLY IN POSTERIOR TEMPORAL & PARIETAL REGIONS

SPECIFIC BRAIN REGIONS LIKE HIPPOCAMPUS AND MEDIAL TEMPORAL LOBE.

MRIVOLUMETRIC MRI REVEALS SHRINKAGE IN VULNERABLE BRAIN REGIONS, PARTICULARLY THE MEDIAL TEMPORAL LOBE & HIPPOCAMPUS.

FUNCTIONAL IMAGING

• EARLY STUDIES USING PET OR SPECT REVEALED A CHARACTERISTIC PATTERN OF HYPOMETABOLISM IN THE POSTERIOR PARIETAL LOBES.

• MRS IN AD REVEALED- DECREASED CONC OF NAA IN THE TEMPORAL LOBES & INCREASED CONC OF INOSITOL IN THE OCCIPITAL LOBES

SPECT

HYPOMETABOLISM IN THE POSTERIOR PARIETAL LOBES.

PET OF GLUCOSE METABOLISM IN NORMAL VS. ALZHEIMER’S DISEASE

• MOST RECENT DEVELOPMENT IN BRAIN IMAGING IN AD IS THE DEVELOPMENT OF RADIO-LABELLED LIGANDS THAT CAN BIND WITH AMYLOID, AND THEN CAN BE VISUALISED WITH PET.

• THIS TECHNIQUE IS CURRENTLY UNDER INVESTIGATION.

FRONTO-TEMPORAL DEMENTIA• STRUCTURAL IMAGING REVEALS- – SEVERE SHARPLY LOCALISED ATROPHY – BILATERALLY SYMMETRIC

“KNIFE-BLADE ATROPHY”– HYPER-INTENSE SIGNAL IN THE CORTEX & UNDERLYING WHITE MATTER

OF THE AFFECTED AREAS• AREAS INVOLVED- DORSOLATERAL PREFRONTAL CORTEX & MEDIAL TEMPORAL

LOBES• AREAS SPARED- POSTERIOR PARIETAL AND OCCIPITAL CORTICES.

• FUNCTIONAL IMAGING REVEALS-– FRONTO-TEMPORAL HYPOMETABOLISM

SEVERE SHARPLY LOCALISED ATROPHY – BILATERALLY SYMMETRIC “KNIFE-BLADE ATROPHY”

KNIFE-BLADE ATROPHY

SEVERE SHARPLY LOCALISED ATROPHY – BILATERALLY SYMMETRIC “KNIFE-BLADE ATROPHY”

BI-LATERAL TEMPORO-PARIETAL DEFICITS

BI-LATERAL FRONTAL LOBE DEFICITS

ALZHEIMER’S DISEASE FRONTAL LOBE DEMENTIA

FRONTAL LOBE DEMENTIA

FRONTAL HYPO-PERFUSION SOMETIMES INCLUDING TEMPORAL LOBES

LEWY BODY DEMENTIA • TO DATE, NO MRI FEATURES HAVE BEEN IDENTIFIED TO

CHARACTERIZE LEWY BODY DEMENTIA.

• THE ABSENCE OF SIGNIFICANT MEDIAL TEMPORAL LOBE ATROPHY IN AN ELDERLY DEMENTED PATIENT SUGGESTS LEWY BODY DEMENTIA ETIOLOGY RATHER THAN AD.

• PET OR SPECT MAY REVEAL REDUCED OCCIPITAL FUNCTION WITH GENERALIZED REDUCTION OF CORTICAL ACTIVITY.

VASCULAR DEMENTIA• DEMENTIA DUE TO CHRONIC CEREBROVASCULAR DISEASE IS

2ND MOST COMMON CAUSE OF DEMENTIA IN ELDERLY

• 3 MAIN FORMS ARE RECOGNIZED– MULTI-INFARCT DEMENTIA– SUB CORTICAL VASCULAR DEMENTIA/ BINSWANGER’S DISEASE– CEREBRAL AMYLOID ANGIOPATHY

SPECT FINDINGS IN VASCULAR DEMENTIA

• 99MTC – HMPAO SPECT OF THE BRAIN IN VASCULAR DEMENTIA SHOWS MULTIPLE PATCHY PERFUSION DEFECTS

MULTIPLE REGIONS OF FOCALLY REDUCED PERFUSION

NORMAL PRESSURE HYDROCEPHALUS• TRIAD:– DEMENTIA– GAIT DISTURBANCES– URINARY INCONTINENCE

• AGE : USUALLY AFTER 60 YEARS• THEORIES:– IMPAIRED EXTRAVENTRICULAR CSF ABSORPTION, DUE TO PRIOR SUB-ARACHNOID

HEMORRHAGE/ MENINGITIS.– DECREASED WHITE MATTER TENSILE STRENGTH DUE TO DEEP WHITE MATTER

INFARCTION/ ISCHEMIC CHANGES

VENTRICULAR ENLARGEMENT OUT OF PROPORTION TO SULCAL ATROPHY.

• PRIMARY MRI FINDINGS IN NPH

– VENTRICULAR ENLARGEMENT OUT OF PROPORTION TO SULCAL ATROPHY.

– PROMINENT PERIVENTRICULAR HYPERINTENSITY (HALO).

– PROMINENT FLOW VOID IN THE AQUEDUCT AND THIRD VENTRICLE, THE SO-CALLED JET SIGN, (PRESENTS AS A DARK AQUEDUCT AND THIRD VENTRICLE ON A T2-WEIGHTED IMAGE WHERE REMAINDER OF CSF IS BRIGHT)

– THINNING AND ELEVATION OF CORPUS CALLOSUM ON SAGITTAL IMAGES

IMAGING IN OBCESSIVE COMPULSIVE DISORDER• STRUCTURAL FINDINGS: (MRI & CT)

– BILATERALLY SMALLER CAUDATE IN OCD PTS.

– SIGNIFICANTLY MORE CEREBRAL GREY MATTER & LESS WHITE MATTER VOLUME THAN NORMAL CONTROLS.

– DECREASED VOLUME OF LEFT ORBITAL FRONTAL CORTEX.

– ABNORMALITY IN LENGTH OF CORPUS CALLOSUM.

– ABNORMALITY IN PITUITARY VOLUME MAY ALSO BE NOTED.

– LARGER ANTERIOR CINGULATE VOLUMES (ACV) A/W INCREASED OCD SYMPTOMS SEVERITY BUT NOT DURATION OF ILLNESS

• MAIN INCREASED (A) AND DECREASED (B) GREY MATTER REGIONS IN INDIVIDUALS WITH OBSESSIVE–COMPULSIVE DISORDER COMPARED WITH HEALTHY CONTROLS

• (A) INCREASED GREY MATTER IN LENTICULAR NUCLEI

• (B) DECREASED GREY MATTER IN DORSAL MEDIOFRONTAL/ANTERIOR CINGULATE GYRI

MRS IN OCD• OCD PATIENTS WERE DIVIDED INTO THREE GROUPS

– RESPONDERS TO A SSRI– RESPONDERS TO A SSRI + AN ATYPICAL ANTIPSYCHOTIC– NON-RESPONDERS TO EITHER SSRI OR SSRI + AN ATYPICAL

ANTIPSYCHOTIC• MRS WAS USED TO MEASURE NAA CONCENTRATIONS

IN THE ANTERIOR CINGULATE, THE LEFT BASAL GANGLIA & THE LEFT PREFRONTAL LOBE OF THE SUBJECTS

• SIGNIFICANTLY LOWER NAA CONCENTRATIONS IN RESPONDERS TO SSRI + AAP IN ANTERIOR CINGULATE GYRUS

GREATER GLUTAMATERGIC CONC. IN CAUDATE, AS MEASURED BY ¹H-MRS IN COMPARISON TO CONTROLS

N-acetyl-aspartate (NAA)

SPECT & PET IN OCD• IN A RESTING SPECT STUDY, OCD PTS HAS INCREASED MESIAL FRONTAL PERFUSION,

WHICH NORMALISES WITH FLUOXETINE RX.• PET HAVE SHOWN

– INCREASED ACTIVITY (EG. METABOLISM & BLOOD FLOW) IN THE FRONTAL LOBES, BASAL GANGLIA (SP. CAUDATE), AND THE CINGULATE GYRUS IN OCD PTS. (FINDINGS CONSISTENT WITH THE MRI FINDINGS)

• HEAD OF THE CAUDATE – PET : GREATER ACTIVITY– SPECT : DECREASED ACTIVITY

• PHARMALCOLOGICAL AND BEHAVIORAL RX REPORTEDLY REVERSE THESE ABNORMALITIES.

IMAGING IN DEPRESSION & BIPOLAR DISORDER

CT & MRI IN DEPRESSION• SMALLER VOLUMES OF FRONTAL CORTEX, CEREBELLUM, CAUDATE & PUTAMEN.

• VENTRICULAR ENLARGEMENT, CORTICAL ATROPHY, AND SULCAL WIDENING ALSO HAVE BEEN REPORTED IN SOME STUDIES.

• THE MOST CONSISTENT ABNORMALITY OBSERVED IN DEPRESSION IS– INCREASED FREQUENCY OF ABNORMAL HYPERINTENSITIES IN SUBCORTICAL REGIONS INCLUDING

PERIVENTRICULAR REGIONS, BASAL GANGLIA, AND THALAMUS.

• THESE HYPERINTENSITIES MAY REFLECT THE DELETERIOUS EFFECTS OF RECURRENT AFFECTIVE EPISODES. (SPECIALLY IN BIPOLAR I DISORDER AND AMONG ELDERLY)

• SOME DEPRESSED PTS MAY ALSO HAVE SPECIFICALLY REDUCED HIPPOCAMPAL OR CAUDATE NUCLEUS VOLUMES, SUGGESTING PRESENCE OF MORE FOCAL DEFECTS.

• FOCAL AREAS OF ATROPHY HAVE BEEN ASSOCIATED WITH INCREASED ILLNESS SEVERITY, BIPOLARITY AND INCREASED CORTISOL LEVELS.

fMRI IN DEPRESSION• BILATERAL ANTERIOR CINGULATE CORTEX & RIGHT AMYGDALA

SIGNIFICANTLY SMALLER IN SIZE.

• INACTIVATION OF LEFT PREFRONTAL CORTEX IN DEPRESSED

INACTIVATION OF RIGHT PREFRONTAL CORTEX IN MANIA

fMRIINACTIVATION OF LEFT PREFRONTAL CORTEX IN DEPRESSED

SPECT IN DEPRESSION

• BASELINE CEREBRAL BLOOD FLOW (CBF) WAS LOWER IN DEPRESSED PATIENTS – IN FRONTAL CORTEX & SUBCORTICAL NUCLEI BILATERALLY

• MEDICATION RESPONSE – NORMALIZATION OF CBF DEFICIT.

PET IN DEPRESSION• THE MOST WIDELY REPLICATED PET FINDING IN

DEPRESSION IS

– DECREASED ANTERIOR BRAIN (FRONTAL / PREFRONTAL CORTEX) METABOLISM SPECIALLY ON DOMINANT HEMISPHERE (LEFT SIDE).

– REVERSAL OF THIS HYPOFRONTALITY OCCURS WHEN PT. SHIFTS FROM DEPRESSION INTO MANIA (I.E. DECREASE RIGHT FRONTAL LOBE FUNCTION SEEN IN MANIA)

– IT HAS BEEN SEEN THAT ANTIDEPRESSANTS AT LEAST PARTIALLY NORMALISES THESE CHANGES.

PET SCANS OF A 45 YEAR OLD WOMAN WITH RECURRENT DEPRESSION PRE AND POST TREATMENT

BIPOLAR DISORDER• PET STUDIES IN DEPRESSED BP-I, BIPOLAR II, AND MANIC

INDIVIDUALS HAVE SHOWN INCREASED AMYGDALA AND VENTRAL STRIATAL LIMBIC SUBCORTICAL ACTIVITY COMPARED WITH HEALTHY CONTROLS

• IN ADULTS, THERE ARE FINDINGS OF ENLARGED (OR SHRUNKEN) AMYGDALA, DECREASED DORSAL AND VENTRAL PREFRONTAL CORTICES, AND SMALLER OR NO CHANGE IN HIPPOCAMPUS.

BIPOLAR DISORDER EARLY ONSET. STUDIES SHOW • MARKEDLY INCREASED

PERFUSION IN BILATERAL FRONTAL AND POSTERIOR PARIETAL LOBES.

• THERE IS ALSO HYPOPERFUSION OF BOTH ORBITO-FRONTAL AREAS, ANTERIOR AND MESIAL TEMPORAL AREAS.

CT/MRI IN SCHIZOPHRENIA • ENLARGEMENT OF LATERAL & THIRD VENTRICLES MAY BE

STATIC OR PROGRESSIVE.• FRONTAL LOBE ABNORMALITIES, PARTICULARLY

PREFRONTAL GRAY MATTER AND ORBITOFRONTAL REGIONS.

• PARIETAL LOBE ABNORMALITIES, PARTICULARLY OF THE INFERIOR PARIETAL LOBULE WHICH INCLUDES BOTH SUPRAMARGINAL AND ANGULAR GYRI.

• SUBCORTICAL ABNORMALITIES I.E. CAVUM SEPTI PELLUCIDUM, BASAL GANGLIA, CORPUS CALLOSUM, AND THALAMUS.

• ALL THESE STRUCTURAL ABNORMALITIES MAY BE STATIC OR PROGRESSIVE.

• DECREASED SIZE OF MEDIAL TEMPORAL LOBE STRUCTURES (WHICH INCLUDE THE AMYGDALA, HIPPOCAMPUS, AND PARAHIPPOCAMPAL GYRUS), AND ABNORMALITIES OF NEOCORTICAL TEMPORAL LOBE REGIONS (SUPERIOR TEMPORAL GYRUS).

• HIPPOCAMPUS IS NOT ONLY SMALLER IN SIZE BUT ALSO FUNCTIONALLY ABNORMAL (DISTURBED GLUTAMATE TRANSMISSION IN FUNCTIONAL SCANS)

• REDUCED SYMMETRY IN VARIOUS BRAIN AREAS MAY BE INDICATIVE OF DISRUPTION OF BRAIN LATERALISATION DURING NEURODEVELOPMENT.

• ANATOMICAL & FUNCTIONAL DEFICITS IN PREFRONTAL CORTEX.

• VOLUME SHRINKAGE OR NEURONAL LOSS IN MEDIAL DORSAL NUCLEUS OF THALAMUS.

• POSITIVE SYMPTOMS - DECREASED VOLUME OF SUPERIOR TEMPORAL GYRUS

• NEGATIVE SYMPTOMS - ENLARGED LATERAL VENTRICLE & DECREASED VOLUME OF MEDIAL TEMPORAL LOBE STRUCTURES

• TYPICAL ANTI-PSYCHOTICS INCREASES THE SIZE OF THE BASAL GANGLIA

CORONAL MR SCANS FROM A CHRONIC SCHIZOPHRENIC (RIGHT) AND NORMAL COMPARISON SUBJECT (LEFT). NOTE INCREASE IN CSF IN LEFT AMYGDALA-HIPPOCAMPAL COMPLEX (SMALLER AMYGDALA ON LEFT)

NORMAL CHRONIC SCHIZOPHRENIA

FUNCTIONAL IMAGING• HYPOFRONTALITY

• FUNCTIONAL SCANS HAVE ALSO REVEALED LOWER LEVELS OF PHOSPHOMONOESTER & INORGANIC PHOSPHATE AND HIGHER LEVELS OF PHOPHODIESTER IN SCHIZ PTS.

• NAA LEVELS WERE ALSO LOWER IN HIPPOCAMPUS AND FRONTAL LOBES IN PTS WITH SCHIZOPHRENIA.

IMAGING IN ANXIETY DISORDERS

• STRUCTURAL IMAGING (CT & MRI)-– OCCASIONAL INCREASE IN SIZE OF VENTRICLES.– ABNORMALITIES IN RIGHT HEMISPHERE BUT NOT IN THE LEFT

HEMISPHERE.– THIS FINDING SUGGESTS THAT SOME TYPE OF CEREBRAL ASYMMETRY

MAY BE IMPORTANT IN THE DEVELOPMENT OF ANXIETY DISORDER.

• FUNCTIONAL IMAGING (FMRI, SPECT, PET)-– ABNORMALITIES IN FRONTAL CORTEX, OCCIPITAL & TEMPORAL AREAS

IN PTS. WITH ANXIETY DISORDER & ABNORMALITIES IN PARAHIPPOCAMPAL GYRUS IN PTS WITH PANIC DISORDER.

MRS

• IN PANIC D/O USED TO RECORD THE LEVELS OF LACTATE, WHOSE IV INFUSION CAN PPT. PANIC EPISODES IN ~ 3/4TH OF THE PTS. WITH EITHER PANIC D/O OR MAJOR DEPRESSION

• BRAIN LACTATE CONC. WERE FOUND TO BE ELEVATED DURING PANIC ATTACKS, EVEN WITHOUT PROVOCATIVE INFUSION IN PANIC DISORDER PTS.

IMAGING IN PTSD• STUDIES IN PTSD VIETNAM COMBAT

VETERANS REVEALED:– REDUCED LEFT AND RIGHT

HIPPOCAMPAL VOLUME– VOLUME REDUCTIONS WERE

ASSOCIATED WITH SEVERITY OF COMBAT EXPOSURE.

– A SIMILAR STUDY WAS UNDERTAKEN WITH GULF WAR VETERANS IN ISRAEL, AND THESE DATA ARE HAVE SHOWN SIMILAR FINDINGS

HIPPOCAMPUS (GREEN), FORNIX (BLUE) AND MAMMILARY BODIES (GRAY) ARE SHOWN IN 3D.

• SMALLER HIPPOCAMPAL VOLUME IS NOT A NECESSARY RISK FACTOR FOR DEVELOPING PTSD AND DOES NOT OCCUR WITHIN 6 MONTHS OF EXPRESSING THE DISORDER

• THIS BRAIN ABNORMALITY MIGHT OCCUR IN INDIVIDUALS WITH CHRONIC OR COMPLICATED PTSD.

TWIN STUDY IN PTSD• A STUDY REPORTED IN NATURE-NEUROSCIENCE EVALUATED MR BRAIN

MORPHOMETRY OF THE HIPPOCAMPUS IN MONOZYGOTIC TWINS DISCORDANT FOR PTSD. THE PTSD TWIN WAS DIAGNOSED WITH PTSD AS A RESULT OF COMBAT EXPOSURE IN THE VIETNAM WAR.

• THE TWIN ASPECT OF THIS STUDY WAS IMPORTANT AS IT SHOWED THAT INDIVIDUALS DISCORDANT FOR PTSD SHOWED REDUCED HIPPOCAMPAL VOLUME COMPARED WITH TWINS WHERE PTSD WAS PRESENT IN NEITHER TWIN.

• THIS FINDING SUGGESTS THAT THERE MAY BE A PREDISPOSITION OR VULNERABILITY FACTOR INVOLVED IN THE GENESIS OF PTSD

FUNCTIONAL IMAGING IN PTSD

• fMRI STUDIES HAVE FOUND INCREASED ACTIVITY IN AMYGDALA, A BRAIN REGION ASSOCIATED WITH FEAR.

IMAGING IN ADHD (CT & MRI)• SHOWS NO CONSISTENT FINDINGS.

• INCREASED CORTICAL GREY & WHITE MATTER VOLUMES FROM 5 YRS OF AGE WITH PEAK AT 12-15 YRS OF AGE.

• EARLY ONSET ADHD MAY BE ASSOCIATED WITH SMALLER TOTAL BRAIN VOLUME IN- 4% CASES.

• DECREASE IN THE VOLUME OF POSTERIOR INFERIOR CEREBELLAR VERMIS MAY BE NOTED.(REGION INVOLVED IN ATTENTION PROCESSING)

FUNCTIONAL IMAGING (fMRI, SPECT, PET)• PET HAS SHOWN THAT ADOLESCENT FEMALES WITH ADHD HAVE GLOBALLY LOWER

GLUCOSE METABOLISM THAT BOTH NORMAL CONTROLS & MALES WITH ADHD.

• PET SCAN HAS ALSO SHOWN LOWER CBF AND METABOLIC RATES IN THE FRONTAL LOBES OF CHILDREN WITH ADHD.

• THIS MAY BE BECAUSE FRONTAL LOBES IN CHILDREN WITH ADHD ARE NOT ADEQUATELY PERFORMING THEIR INHIBITORY MECHANISM ON LOWER STRUCTURES, LEADING TO DISINHIBITION.

• LESS STRIATAL ACTIVATION DURING COGNITION INHIBITION TASKS.

fMRI LOWER CBF AND METABOLIC RATES IN THE FRONTAL LOBES

PET SCAN IN ADHD VS NORMALWHITE, RED, ORANGE = HIGHER GLUCOSE METABOLISM

BLUE, GREEN, PURPLE = LOWER GLUCOSE METABOLISM

GLOBALLY LOWER GLUCOSE METABOLISM

IMAGING IN AUTISM• SIGNIFICANT DECREASE OF GREY MATTER CONCENTRATION IN SUPERIOR TEMPORAL

SULCUS BILATERALLY, AN AREA WHICH IS CRITICAL FOR PERCEPTION OF KEY SOCIAL STIMULI.

• ALSO A DECREASE OF WHITE MATTER CONCENTRATION IN THE RIGHT TEMPORAL POLE AND IN CEREBELLUM COMPARED TO NORMAL CHILDREN.

• INCREASE IN TOTAL CEREBRAL VOLUME, BOTH IN GREY AND WHITE MATTER, MOSTLY IN THE OCCIPITAL, TEMPORAL AND PARIETAL LOBES.

• BRAIN ENLARGEMENT HAS BEEN CONSIDERED AS A POSSIBLE BIOMARKER FOR AUTISTIC DISORDER.

BRAIN ENLARGEMENT IN AUTISM

FUNCTIONAL IMAGING• BILATERAL HYPOPERFUSION OF THE TEMPORAL LOBES IN

AUTISTIC CHILDREN.

• IN ADDITION, ACTIVATION ABNORMALITIES MAY BE OBSERVED IN THE TEMPORAL LOBES AND AMYGDALA, WHICH ARE INVOLVED IN LANGUAGE AND SOCIAL COGNITION.

• AN INCREASE IN VISUAL CORTEX ACTIVITY WAS ALSO REPORTED

BILATERAL HYPOPERFUSION OF THE TEMPORAL LOBES IN AUTISTIC CHILDREN

A - NORMAL CHILD

B - AUTISTIC CHILD

ALCOHOL DEPENDENCE• CT SCAN:

– ALCOHOLIC PATIENTS TEND TO HAVE LARGER VENTRICLES AND WIDER CEREBRAL SULCI AND FISSURES THAN CONTROL.

– CORTICAL ATROPHY IS ALSO REPORTED FREQUENTLY– ABSTINENT PATIENTS MAY SHOW A REDUCTION IN VENTRICULAR SIZE

• MRI– PRONOUNCED AND LASTING REDUCTION IN CORTICAL VOLUME –DISRUPTION OF

NEURODEVELOPMENTAL PROCESS

• DTI– DISRUPTION IN THE INTEGRITY OF WHITE MATTER TRACKS. THE VOLUMETRIC CHANGES ARE

PARTICULARLY SEVERE IN PATIENTS WITH WERNICKE-KORSAKOFF SYNDROME

• MRS– DURING ACUTE WITHDRAWAL CORTICAL GABA LEVELS APPEAR TO BE

NORMAL– WITH RECOVERY FROM ALCOHOL DEPENDENCE, CORTICAL GABA

LEVELS APPEAR TO DECLINE AND MAY BE SIGNIFICANTLY BELOW THE LEVEL SEEN IN NORMAL HEALTHY SUBJECTS

• fMRI– ABNORMAL ACTIVATION PATTERNS IN FRONTAL CORTEX, THALAMUS,

STRIATUM, CEREBELLUM AND HIPPOCAMPUS – INCREASED LIMBIC AND ORBITO-FRONTAL CORTEX ACTIVATION WHEN

EXPOSED TO ALCOHOL RELATED CUES THAT ELICIT CRAVING

• PET & SPECT IN ADS:

– DOPAMINE: IMAGING SHOWS DA SYNTHESIS IS REDUCED IN THE STRIATAL REWARD AREAS OF SOME ALCOHOL DEPENDENT SUBJECTS

– THE POST-SYNAPTIC DOPAMINE D2/D3 RECEPTORS, PREDOMINANTLY LOCALIZED ON GABA TERMINALS IN THE STRIATAL REWARD AREAS IS ALSO REDUCED IN LIMBIC STRIATUM AND SENSORIMOTOR STRIATUM IN ALCOHOL DEPENDENT SUBJECTS IN ACUTE AND PROLONGED ABSTINENCE.

– SEROTONIN: 5HT TRANSPORTER AVAILABILITY IS REDUCED IN THE BRAINSTEM OF ALCOHOL DEPENDENT SUBJECTS WITH IMPULSIVE AGGRESSION AND VIOLENCE, SUGGESTING THAT ALCOHOL AND AGGRESSION ARE ASSOCIATED WITH LOWER 5HT TRANSMISSION

– GABA: INITIAL IMAGING STUDIES EVALUATED GABA-A BZD RECEPTOR AVAILABILITY ---RECEPTOR LEVELS ARE FOUND TO BE LOWER IN FRONTAL, PARIETAL AND TEMPORAL CORTICES OF ADS PATIENTS

OTHERS SUBSTANCE RELATED DISORDERS• COCAINE DEPENDENCE:– PET SCANS OF BRAINS OF PATIENTS BEING TREATED FOR COCAINE ADDICTION

SHOW HIGH ACTIVATION OF THE MESOLIMBIC DA SYSTEM WHEN ADDICTS PROFOUNDLY CRAVE A DRUG

– PATIENTS DESCRIBE FEELINGS OF INTENSE CRAVING FOR THE DRUG WHILE PET SCAN SHOWED ACTIVATION IN AREA FROM THE AMYGDALA AND ANTERIOR CINGULATE TO THE TIP OF BOTH TEMPORAL LOBES

• OPIOID DEPENDENCE:– FEW STUDIES USING PET HAVE SUGGESTED THAT ONE EFFECT OF ALL OPIOIDS IS

DECREASED BLOOD FLOW IN SELECTED REGIONS OF BRAIN IN PERSONS WITH OPIOID DEPENDENCE

• TOBACCO SMOKING:– NICOTINE’S ACTIONS AT B2-N ACH RECEPTOR INITIATES A CASCADE OF

EFFECTS THROUGHOUT MOST MAJOR NEUROTRANSMITTER SYSTEMS IN THE BRAIN INCLUDING

– THE DOPAMINERGIC– GABAERGIC– GLUTAMINERGIC– NORADRENERGIC – SEROTONERGIC SYSTEMS

– SUGGESTING THAT THE ADDICTIVE PROPERTIES OF TOBACCO SMOKING ARE LIKELY MEDIATED BY MULTIPLE NEUROTRANSMITTER SYSTEMS

– SMOKERS HAVE LOWER LEVELS OF MAO ENZYMES AS DEMONSTRATED USING PET.

SUMMARY• NEUROIMAGING CAN BE STRUCTURAL / FUNCTIONAL• FUNCTIONAL IMAGING MORE USEFUL THAN STRUCTURAL IN

PSYCHIATRY• NEUROIMAGING IN PSYCHIATRY IS PRESENTLY USED MAINLY TO RULE

OUT NEUROLOGICAL CAUSES, AND IN EVALULATION OF DEMENTIA• SENSITIVIY & SPECIFITY OF IMAGING IN PSYCHIATRY IS NOT MUCH• STILL VARIOUS STUDIES AND THEIR FINDINGS AND NEWER

DEVELOPMENTS HOLDS A PROMISING FUTURE FOR NEUROIMAGING IN PSYCHIATRIC DIAGNOSIS & MANAGEMENTS.

THANK YOU