SPECT and PET in Neurodegenerative Diseases · SPECT and PET in Neurodegenerative Diseases Isabel Roca, MD HU VALL HEBRON Barcelona, Spain

SPECT and PET in SPECT and PET in Neurodegenerative DiseasesNeurodegenerative Diseases

Isabel Roca, MDHU VALL HEBRONBarcelona, Spain

Global Global prevalenceprevalence ofof dementiadementia

Ferri et al 2005

Number of people with dementia in developing and developed countriesNumber of people with dementia in developing and developed countries

1. SPECT: perfusion and metabolism2. DATSCAN: dopamine transporters3. IBZM: D2 receptors

Neurodegenerativediseases

othermovement disorders

Parkinsonismand

SPECTperfusionmetabolism PET

FDGother

SPECTDATSCAN

IBZMother

SPECT Type of Image/Information PET

99mTc-HMPAOPERFUSION

15O-H2O

99mTC-ECD

99mTC-ECD METABOLISM 18F-FDG

123I-ioflupane DOPAMINETRANSPORTERS 18F-DOPA

123I-IBZM DOPAMINERECEPTORS 11C-raclopride

201Thallium TUMOR VIABILITY 11C-metionine

IMAGING FUNDAMENTALSIMAGING FUNDAMENTALSBrainBrain PerfusionPerfusion SPECTSPECT

HMPAOECDFDG

DATSCANIBZM

FDG

HMPAO

ECD

HMPAOECDFDG

DATSCANIBZM

FDG

HMPAO

ECD


DATSCANIBZM

FDG

HMPAO

ECD

HMPAOECDFDG


HMPAOECDFDG

DATSCANIBZM

FDG

HMPAO

ECD

IMAGING FUNDAMENTALSIMAGING FUNDAMENTALSDatscanDatscan oror IBZM SPECTIBZM SPECT

DIFFERENCES SPECT PET

RADIOPHARMACEUTICALS

ECD FDGHMPAO DOPAMINE

DATSCAN H2O

IBZM METHIONINECUANTIFICATION relative relative and absolute

SPATIAL RESOLUTION 6-7 mm 3-4 mm

PET: PositronEmission

Tomography

PerfusionPerfusionBrain SPEBrain SPECCTT

‘FROZEN’IMAGE

METABOLISM – BRAIN PERFUSIONAT TRACER INJECTION

99mTc-HMPAO / ECD

SYMMETRIC / ASSYMETRIC

Left / Right

DIFFERENTIAL DIAGNOSIS OF PARKINSONISM DIFFERENTIAL DIAGNOSIS OF PARKINSONISM

OrganicParkinsonism

Non-OrganicParkinsonism

NORMAL PATHOLOGIC

SPECT 123I-FP-CITDATSCAN

PATHOLOGY PERFUSIONSPECT

IOFLUPANESPECT

IBZMSPECT

PRE-POSTSYNAPTIC

Alzheimer’sdisease Beta-Amyloid Temporo-

parietal bilateral Normal Normal No

Lewy-bodies’dementia

Diffuse Lewy bodies +/- occipital

Diminishedsimilar to PD Normal Pre

Fronto-temporaldegeneration

Diffuse corticalbilateral

. Pick’s Thaupathy 3R Frontal bilateral Normal Normal ?

. DCB Thaupathy 4R Assymetric Diminished Pre & Post

. PSP Thaupathy 4R Symmetric Pre & PostA. Multi-systemicAMS-C AMS-P

Astrocytic glyosis Diffuse hypoperfusion+ cerebellum

Pre & Post

Parkinson’sdiseaseLewy bodies

(substantia nigra) Normal Normal Pre

Vascular Multiple Infarcts Multiple perfusiondefects Normal(often)

Abnormal (often) Post

(often)

DiminishedDiminishedDiminished

DiminishedDiminished

Diminished

CONDITION

Temporo-parietal bilateral

DIFFERENTIAL DIAGNOSISof dementia

133Xe-CBF• From 10 years old, regional cerebral blood flow (cortical traceruptake) progressively decreases

• From birth to 2 years old, the brain MATURES

• From 2 to 10 years old, the brain keeps a high metabolic rate

Newborn

6 months

1 y

2 ys

8 ys40 ys

50 ys

60 ys

70 ys

80 ys

MATURINGAGEING

DIMINISHING ACTIVITY:• FRONTAL• POSTERIOR TEMPORALINCREASING ACTIVITY:• OCCIPITAL

40 a

50 a

60 a

70 a

80 a

AGEING BRAIN

FRONTALANTERIOR

FRONTALPOSTERIOR

TEMPORALPOSTERIOR

OCCIPITAL

DEMENTIA DEMENTIA –– UTILITY of SPECT and PETUTILITY of SPECT and PET• Early detection• Differential diagnosis• Follow-up

Natural Natural HistoryHistory ofof thethe NeurodegenerativeNeurodegenerative ProcessProcessSymptoms

NORMAL MCI DEMENTIA

Amyloiddeposits

COGNITIONGLUCOSE METAB.NEURONAL FUNC.


NORMAL MCI DEMENTIA

Amyloiddeposits


DiagnosisCognition Tests


NORMAL MCI DEMENTIA

Amyloiddeposits



DiagnosisPET-SPECT


NORMAL MCI DEMENTIA

Amyloiddeposits



DiagnosisPET-SPECT

DiagnosisPIB

VoxelVoxel--byby--voxelvoxel quantitativequantitative analysisanalysisisis superior superior toto visual visual evaluationevaluation

Tatsch, K

QuantitativeQuantitative methodsmethods::3D3D--SSPSSP

Voxel-by-voxel quantitative analysis is superior to visual evaluationVoxel-by-voxel quantitative analysis is superior to visual evaluationTatsch, K

• SPM determines the voxel differences between groups based on the level of significance. It is necessary to transform original space to MNI space (proportional to Talairach space) by registering to a template.

REFREF

Group 1

REFREF

Group 2

QuantitativeQuantitative methodsmethods::SPMSPM-- StatisticalStatistical ParametricParametric MappingMapping

• Neurogam allows the individual comparison with a normal database, very useful when analyzing patients individually and correlating to clinical data.

• Neurogam determines abnormal voxels between the patient and the normal or reference database. It is necessary to transform original space to Talairach space by adjusting the limits of the brain.

Hiperactivity

HipoactivityHipoactivity

QuantitativeQuantitative methodsmethods::NeurogamNeurogam

Differential diagnosisDifferential diagnosisMultiMulti--infarct dementiainfarct dementia

� Characterized by: • Slowly progressing memory loss.• Cortical degeneration with:

� amyloid plaques (fibers of beta-amyloid peptide).� neurofibrillar tangles (hyperphosphoriled tau protein).

� It is considered the most prevalent (60%) of cortical dementias.

Dementia of AlzheimerDementia of Alzheimer’’s types type

Progression pattern of Progression pattern of AlzheimerAlzheimer’’s diseases disease

NIA Alzheimer’s Disease: Unraveling the Mystery

Beta-amyloid plaquesNeuronal damage by vecinity Tau protein tangles

Axonal damage

Causes ofCauses ofAlzheimerAlzheimer’’s diseases disease

Amyloid plaque

Tau proteinNeurofibrillar tangle

AlzheimerAlzheimer’’s diseases diseaseNeuropathologic changes Metabolic changes

Tatsch, K

AlzheimerAlzheimer’’s diseases disease

Progression pattern of Progression pattern of AlzheimerAlzheimer’’s diseases disease

Brain SPECT→ Initial stage

• hipoactivity - parietal and/or posterior temporal cortex• unilateral or bilateral

→ Intermediate stage• hipoactivity - extensive, parietal and temporal, bilateral• hipoactivity – posterior frontal

→ Advanced stage• diffuse cortical hipoactivity• less/not affected: motor areas, occip[ital, BG, cerebellum

DementiaDementia of of AlzheimerAlzheimer’’ss typetype

SPMStatistical Parametric Mapping


Normal DB > DAT

P=0.001

Significant differences in severalBrodmann areas localized in:

• Cingulate• Temporal lobe• Parietal lobe• Frontal lobe• Especially in right hemisphere

DementiaDementia of of AlzheimerAlzheimer’’ss typetypeResultsResults -- SPMSPM

Normal DB > DATSignificant differences(hypoactivity ≤ 2SD):

• Cingulate 100%• Parietal 80%• Anterior temporal 60%• Anterior frontal 60%• Posterior temporal 50%

DementiaDementia of of AlzheimerAlzheimer’’ss typetypeResultsResults -- NeurogamNeurogam

concordant Brodmann areas

SPM - NEUROGAMCINGULATE 24, 32FRONTAL 10, 46

TEMPORAL 21PARIETAL 7, 37, 39, 40

PARIETAL-OCCIPITAL 19

DementiaDementia of of AlzheimerAlzheimer’’ss typetypeComparisonComparison SPM SPM -- NeurogamNeurogam

Tatsch, K


Diagnosis of AD (n=54)

Sensitivity 89.5%Specificity 81.5%

Positive Predictive Value 93.2%Negative Predictive Value 73.3%

Bonte FJ, Weiner MF, Bigio EH, White CL III. Brain blood flow in the dementias: SPECT with histopathologic correlation in 54 patients.

Radiology 1997;202:793–7.

Brain SPECT in the Evaluation of Dementia

The OPTIMA Study

Sensitivity Specificity PPV NPVSPECT 68 98 78 86Clincial Dx (Probable) 59 95 84 86

Conversion from Mild Cognitive Impairment (MCI) to Alzheimer’s disease

99mTc-ECD

Basal 3 years

Conversion: 52/76 patients with MCI in 3 yearsHirao et al. Neuroimage 2005;28:1014-21

Normal cognition Alzheimer’s (necropsy diagnosis)

Normal cognition Alzheimer’s (necropsy diagnosis)

Pittsburgh compound B

Klunk et al. Ann Neurol 2004

PIB

RM

PETglucose

Normal volunteer70 y.o.Mini-Mental 29

AD patient75 y.o.Mini-Mental 26

11C-PIBDifferential diagnosis

- DAT - FLD

Alzheimer’s DiseaseAmyloid and hypometabolism

Increased PIB

Alzheimer’s Diseaseβ-Amyloid deposits

Alzheimer’s DiseaseIn vivo and post- mortem amyloid correlates

β-Amyloid deposit and memoryin non-demented individuasls

11C-PIB uptake(Pittsburgh Compound-B)

Edison et al. Neurology 2007;68:501-8

� generic denomination proposed at the First International Workshop on Lewy Body Dementia (Newcastle upon Tyne, 1995).

• diffuse Lewy body disease• senile dementia of Lewy body type• Lewy body variant of Alzheimer's disease

� it is considered second in prevalence of cortical dementiasafter AD:

15 - 20% of all dementias

Lewy body dementiaLewy body dementia

McKeith et al. Neurology 2005;65

1. ↓ dopamine transporters uptake2. ↓ diffuse cortical uptake, ↓ occipital3. ↓ MIBG myocardial uptake

123I-FP-CIT SPECT allows differential diagnosis between dementia of Alzheimer’s type (DAT)

and diffuse Lewy body disease (LBD)LBD DAT

Brain perfusion scintigraphy with 99mTc-HMPAO or 99mTc-ECD and 123I-β-CIT single-photonemission tomography in dementia of the Alzheimer-type and diffuse Lewy body disease.

Eur J Nucl Med, March 1997

Decreased uptake Normal uptake


Kaufer DI et al. Rev Neurol 2003;37:127-30

LBD DAT

Occipital hypoperfusion in brain SPECT


A comparison of 99mTc-HMPAO SPET changes in dementia with Lewy bodiesand Alzheimer’s disease using statistical parametric mapping.

Eur J Nucl Med Mol Imaging 2002;29:615–22

LBD DAT↓ MIBG myocardial uptake


58 patients - Brain SPECT - MIBG myocardial scintigraphy

Comparative value of brain perfusion SPECT and [123I]MIBG myocardial scintigraphy in distinguishing between dementia with Lewy bodies and Alzheimer‘s disease

Eur J Nucl Med Mol Imaging, Nov 2005

patient with DLB 73-year-old man MMSE score 22

patient with AD74-year-old woman MMSE score 21


Brain SPECTMedial occipital lobe

Myocardial MIBGH/M ratio

Comparative value…(cont.)Eur J Nucl Med Mol Imaging, Nov 2005


Differential diagnosisDifferential diagnosisDAT vs. FTDDAT vs. FTD

Prefrontal Cortex

FrontoFronto--temporal temporal degeneration (FTD)degeneration (FTD)

Josephs et al. Neurology 2006;66:41-8


PickPick’’s disease (PiD)s disease (PiD)


CorticoCortico--basal basal degeneration (CBD)degeneration (CBD)


Progressive supranuclear Progressive supranuclear palsy (PSP)palsy (PSP)

� SPECT:Severe bilateral cortical hypoactivity

PSP: symmetric CBD: assymetric

Differentiating between progressive supranuclear palsy and corticobasaldegeneration by brain perfusion SPET

Nucl Med Comm 2001

PSP and CBDPSP and CBD


FrontoFronto--temporal temporal degeneration (FTD)degeneration (FTD)

D

OlivoOlivo--pontoponto--cerebellar cerebellar atrophy (AMSatrophy (AMS--C)C)

PATHOLOGY PERFUSIONSPECT

IOFLUPANESPECT

IBZMSPECT

PRE-POSTSYNAPTIC

Alzheimer’sdisease Beta-Amyloid Temporo-

parietal bilateral Normal Normal No

Lewy-bodies’dementia

Diffuse Lewy bodies +/- occipital

Diminishedsimilar to PD Normal Pre

Fronto-temporaldegeneration

Diffuse corticalbilateral

. Pick’s Thaupathy 3R Frontal bilateral Normal Normal ?

. DCB Thaupathy 4R Assymetric Diminished Pre & Post

. PSP Thaupathy 4R Symmetric Pre & PostA. Multi-systemicAMS-C AMS-P

Astrocytic glyosis Diffuse hypoperfusion+ cerebellum

Pre & Post

Parkinson’sdiseaseLewy bodies

(substantia nigra) Normal Normal Pre

Vascular Multiple Infarcts Multiple perfusiondefects Normal(often)

Abnormal (often) Post

(often)

DIFFERENTIAL DIAGNOSIS

DiminishedDiminishedDiminished

DiminishedDiminished

Diminished

CONDITION

Temporo-parietal bilateral

The End

SPECT and PET in SPECT and PET in Neurodegenerative DiseasesNeurodegenerative Diseases

SPECT and PET in Neurodegenerative Diseases · SPECT and PET in Neurodegenerative Diseases Isabel Roca, MD HU VALL HEBRON Barcelona, Spain

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