Imaging Medico-Nucleare nelle demenze: indicazioni consolidate e novità

Transcript

1 Imaging Medico-Nucleare nelle demenze: indicazioni consolidate e novità Flavio Nobili Neurofisiologia Clinica DINOGMI, Università di Genova DNS, IRCCS AOU San Martino-IST, Genova

2 18 F-FDG SOMMARIO Radiofarmaci per la sostanza amiloide Radiofarmaci indicatori della funzione dopaminergica pre e post sinaptica Radiofarmaci indicatori della funzione colinergica: acetilcolinesterasi e recettori colinergici

3

4 Alzheimer s disease: a disconnection pathology Smith PNAS 2002;99:4135 Braak and Braak, Neurobiol Aging 1995;16:271

5 Which the phenomena leading to focal hypometabolism in AD? 1. Atrophy ( partial volume effect ) 2. Reduced metabolic consumption due to reduced number of synapses, as a consequence of neuronal loss in cortico-cortical neurons 3. Reduced metabolic consumption due to neuronal loss of distant neurons (deafferentation-diaschisis)

6 Normal elderly Mild AD Moderate AD Severe AD off pain FDG-PET

7 A patient with mild AD: SSP results of 18 FDG-PET Bartenstein, et al. J Nucl Med 1997

8 FDG-PET in Frontotemporal dementia Surface projections right lateral above left lateral Comparison to normal database

9 Questionable and mild AD vs. non-ad: ROC analysis X-axis: 1 - Specificity, Y-axis: Sensitivity 1.00 Slice Presentation 3D-SSP Presentation EXPERT EXPERT BEGINNER Burdette, et al. Radiology 1996 BEGINNER

10 SPM: use in an individual AD case vs. Controls: 99m Tc- HMPAO SPECT A mild Alzheimer patient vs. 31 controls; MMSE: 28 Selective Reminding Test : 43 (Grober-Buschke) Attentional and linguistic tests: more severe decreased performances

11 FDG-PET: prodromal AD ( MCI due to AD ) Surface projections right mesial Comparison to normal data base left mesial

12 Topographic mismatch between MRI and FDG-PET in MCI MRI: MCI converters (i.e., prodromal AD) Versus Controls Morbelli et al., EJNMMI 2010 FDG-PET: MCI converters (i.e., prodromal AD) Versus Controls

13 Medial Temporal Lobe (MTL) hypometabolism needs manual or automatic segmentation to be highlighted. Normalization and smoothing in softwares for voxelbased analysis may obscure MTL hypometabolism! Mosconi et al., EJNMMI 2006

14 18 FDG-PET. The posterior cingulate and precuneus as the early core of metabolic deficit, already affected in Apo E ε4 positive NORMAL middle-age subjects AD patients Normal Subjects Apo E ε4 +

15 Accuracy in predicting conversion to AD-dementia in patients with MCI Sensitivity Specificity FDG-PET 88.8% 84.9% Perfusion 83.8% 70.4% SPECT MRI 72.8% 81.0% Yuan et al., AJNR 2009;30:404

16 Amyloid tracers: Radiochemical strategies β-amyloid stains β-amyloid PET tracers [ 11 C]PIB [ 18 F]FDDNP Flutemetamol Florbetaben, Florbetapir

17 In-vitro and in-vivo imaging of amyloid plaques 11 C-PIB PET Control AD Control post-mortem AD 11 C-PIB PET and 18 FDG PET

18

19

20

21 18 F-FDDNP

22 β-amyloid brain PET with 18 F-Florbetaben - Standardized Uptake Value Ratios SUVR 1.0 AD patient H. Barthel, et al. Lancet Neurology 2011 Healthy control PET images: min p.i. added SUVR: Reference = Cerebellar cortex

23 18F-Flutemetamol AD control ANN NEUROL 2010;68:

24 18 F-Florbetapir PET In vivo Post-mortem Mean:3 months Later Clark et al. JAMA. 2011;305:

25 18 F-Florbetapir

26

27

28

29 Imaging dopaminergic metabolism

30 rcbf and dopamine transporter SPECT AD versus LBD Brain perfusion with 99m Tc-HMPAO or 99m Tc- ECD 123 I-beta-CIT single photon emission tomography Donnemiller et al. Eur J Nucl Med 1997; 24: DLB DLB AD Control

31 Multi-centre European study of FP-CIT Grade 0 Normal Grade 1 Abnormal Grade 2 Abnormal Grade 3 Abnormal Consensus diagnosis Sensitivity Specificity Visual rating by 3 blinded readers 78% 90% McKeith, O Brien, Walker et al Lancet Neurology 2007

32 Results (October 2009) 23 autopsy cases Sensitivity Specificity Initial clinical diagnosis 80% 46% Scan quantitative analysis (worse affected putamen) 100% 92% Walker, Jaros, Walker et al JNNP Walker & Walker 2009 Mov. Disorders

33 11 C-PE2I 11 C- -CFT 11 C- -CIT 11 C- -CIT-FE 18 F?

34 IPD and non-ipd

35

36 AchE PET imaging [ 11 C] MP4A in Lewy body pathology Shimada et al., Neurology 2009 brain cholinergic dysfunction occurs at a very early stage of PD and may precede the manifestation of motor symptoms in PD.

37 Decrease of nicotinic receptors (nachrs) in the nigrostriatal system in PD: evidence from 2-[18F]fluoro-A PET Kas et al., JCBFM 2009

38 Grazie per l attenzione Medicina Nucleare e Centro PET -Silvia Morbelli -Mattia Riondato -Gianmario Sambuceti e tutti gli specializzandi che sono bravissimi!!!! Neurofisiologia Clinica -Dario Arnaldi -Nicola Girtler -Paola Barbieri e tutti gli specializzandi che sono bravissimi!!!! Fisica INFN -Andrea Chincarini -Fabrizio De Carli