PET-MRI in Parkinsonism

Nadya PYATIGORSKAYA

Pitié-Salpêtrière, Paris, France

Since October 2015, TOF 33T PET/MR (SIGNA system, GE Healthcare)

General workflow :

Half-time research

Half-time clinical (2.5 days/week)

Number of examinations (clinical)

Per month : 100-120

Main axes

Neurodegenerative disorders : 75%

Oncology : 23% including

7% brain tumor; 8% H&N cancer; 5% others cancers (pancreas, ovary, prostate)

Drug-resistant partial epilepsy : 2%

To provide at least as much information as both a sequential PET/CT and MR examinations

To achieve the highest diagnostic performance

To avoid the collection of redundant information by the two imaging modalities

Minimal scanner occupancy times to maximize clinical utilization

Examination duration : 25 to 45 min

Daily clinical workflow : 11-15 examinations

Imaging in the same space: special alignment

Advantages over coregistration

Movements and atrophy (problems with coregistration to standard space)

Attenuation and partial volume effects correction

Time saving : one examination, temporal synchronization

Functional and metabolic imaging : same timing

Common diagnosis

Timing of the examination : risks of movements

Cost : PET/MR system and tracers

Attenuation correction : challenges

Dixon : 5 classes of tissues based on fat/water tissue separation, each class: linear attenuation coefficient

Underestimation of the cortical bone attenuation effect

Atlas based bone correction or ZTE sequence

Limited access to coils

Daily clinical workflow : 11-15 examinations per day

Example 1:

4 H&N PET-MRI (H&N and whole body)

2 brain tumors or 2 Parkinson’s diseases, 7 dementia cases

Example 2:

8 dementia and epilepsy cases

4 body PET-MRI : pancreas, ovary, prostate

Dual interpretation : nuclear medicine physician and radiologist

Suspicion of early AD

Differentia diagnosis between AD, fronto-temporal dementia…

Suspicion of cortico-basal dementia…

all the complicated cases

Morphological and functional aspect of AD, confirmed bby CSF M

77 years’ old

Frontal stroke

Amnesia

Speech semantic dysfunction

Examen TEP-FDG / IRMAnalyse des petites structures Analyse des petites structures

Atrophie et hyposignal T2* cortical du gyrus précentral

Examen TEP-FDG / IRM

Parkinson’s syndromes:

Tauopathy : PSP, CBD

Synucleinopathy : Parkinson's disease, Lewy body dementia, MSA

Dopaminergic : PD, atypical parkinsonism

MRI:

Typical patterns : MSA ++, PSP

Atrophy, functional imaging, DTI, perfusion

PET:

Molecular information

F-DOPA:

Dopaminergic denervation

Differential diagnosis : essential tremor/Parkinson disease/secondarily parkinsonism

Differential diagnosis : AD/ LBD

FDG:

AD/FTD/CBD

Atypical parkinsonism

PET imaging:18F-DOPA:

Presynaptic tracer, decrease with disease progression

Aspecific, clinical practice

11C-Raclopride:

Postsynaptic D2 receptors, early increase in putamen and caudate (compensatory) in PD, decrease with time and treatment

Correlation with motor compensation

Stabilisation after DBS

Early decrease in PSP and MSA : differential

FDG : slight aspecific modifications ; differential diagnosis

Increase : globus pallidus, putamen, thalamus, cerebellum, pons, sensorimotor cortex,

Hypometabolism : lateral frontal and parieto- occipital areas

Clinical correlates

MRI imaging:

Imaging assessment in clinical practice:

Neuromelanin imaging: good correlation with DOPA lost, volume ++, >R2* (Isaias et al, 2016)

Dorsolateral nigral hyperintensity imaging: good concordance with DOPA (Yun Jung Bae et al, 2018)

R2*, DTI, fMRI assessment:

R2* increase in deep ganglia

Extranigral impairment DTI, volumetry, fMRI

Reduced activation in the posterior motor putamen, correlation with motor symptoms

ASL:

Parieto-occipital hypoperfusion : cognitive

Precuneus, posterior cingulum : motor impairment, cognitive

Better diagnostic confidence:

Biomarkers combination

Partial volume correction

Underlying abnormalities,

Differential diagnosis

Early disease detection : biomarker combination

Interest in preclinical forms (iRBD): NM vs 18F-DOPA

Perspectives : lesion extension and anatomical/functional correlations synuclein tracers

mmbination

Mostly differential diagnosis: normal imaging expected

PET imaging:Cerebellar metabolism increase

Other variations : thalamus, red nucleus, inferior olive, sensori-motor cortex

MRI imaging:

DTI/fMRI modifications

PET correlates

Pathophysiology, treatment follow-up

PET-FDG imaging :Frontal area, caudate nucleus, thalamus, brainstem

PET-DOPA imaging

Aspecific, presynaptic decrease

MRI imaging

Specific : midbrain atrophy (Hummingbird sign, Mickey Mouse sign)

Aspecific : dorsolateral nigral hyperintensity, NM signal decrease

PET/MRI interest:

Early forms, diagnostic doubt

Atypical forms: 70-80% of PSP are not PSP-RS, poorly known

Pathophysiology, treatment follow-up

PET-FDG imaging :Metabolism reduction in putamen, pons, cerebellum

More than corresponding atrophy

PET-DOPA imaging

Aspecific, presynaptic decrease

MRI imaging

Putaminal atrophy and marginally increased T2 signal

Hot cross bun sign, cerebellar atrophy, MCP atrophy

Neuromelanin and DNH lost, controversy

PET/MRI :

Good correlation between DTI (MD) and FGD uptake decrease in posterior putamen, improves DA (Baudrexel et al, 2013)

Pathophysiology, treatment follow-up

PET-FDG imaging :

Generalized decreased uptake (occipital ++)

Posterior cingulum preservation

PET-DOPA imaging:

Aspecific, presynaptic decrease

MRI imaging:

Aspecific : dorsolateral nigral hyperintensity, NM signal decrease, global atrophy

PET/MRI:

Diagnostic confidence, biomarker validation

PET-FDG imaging :

Asymmetric fronto-parietal metabolism : cingulate, sensorimotor, prefrontal

Thalamic and striatum decrease

PET-DOPA imaging

Aspecific, presynaptic decrease

MRI imaging

Fronto-parietal atrophy

PET-MRI imaging:

Early forms, subtle abnormalities

Complex forms investigation : PSP-CBS (Tau/MRI)

Diagnosis :

Atypical PSP

PSP-P vs PD

MSA-P vs PD

Secondarily parkinsonism and multiple pathologies

Early forms

Physiopathology :

Metabolism/functional/morphological translation

Better pathophysiological understanding

Who arrives first?

New biomarkers for new therapeutic trials

Biomarkers validation

New tracers :

PET-tau: first and second generation, problems of aspecificbinding, correction matrix

Synuclein?

New MRI developments

DNH and neuromelanin imaging in clinical practice

Advanced DTI sequences and models

R2* and QSM for iron load

Perfusion/ ASL/ IRMf

ii

Glucose metabolisme

pattern of regional brain metabolism

Resting state fMRI

spontaneous fluctuations in different brain regions which can be synchronized

ASL : brain perfusion

On HC : correlation in the default mode network, lower in other areas (limbic)

On AD :

correlation ASL/FGD, more limited areas in ASL

Correlation between hippocampus/precuneus disconnection and hippocampus metabolism

DA increase from 91 to 97% for biomarkers combination

Both DAT and NM correlates with disease duration and severity

No correlation with levodopa treatment

NM locus > PET DOPA uptake

NM SN: not tested

In-vivo staging of pathology in REM sleep behaviour disorder: a multimodality imaging case-control studyKaroline Knudsen*, Tatyana D Fedorova*, Allan K Hansen, Michael Sommerauer, Marit Otto, Kristina B Svendsen, Adjmal Nahimi, Morten G Stokholm, Nicola Pavese, Christoph P Beier, David J Brooks, Per Borghammer

DNH lost in unaffected side in DAT

Earlier damage?

Loss of substantia nigra hyperintensity on 7 Tesla MRI of Parkinson'sdisease, multiple system atrophy, and progressive supranuclear palsy

Jong-Min Kim a, Hye-Jin Jeong b, Yun Jung Bae c, Sung-Yeon Park b, Eunhee Kim c,Seo Young Kang d, Eung Seok Oh e, Kyeong Joon Kim a, Beomseok Jeon a, Sang Eun Kim d, f,Zang-Hee Cho b, Young-Bo Kim b, *

Contents lists available at ScienceDirect

Parkinsonism and Related Disorders

journal homepage: www.elsevier .com/locate/parkreldis

Subcortical 18F-AV-1451 Binding Patterns in ProgressiveSupranuclear Palsy

Hanna Cho, MD,1 Jae Yong Choi, PhD,2 Mi Song Hwang, BSN,1 Seung Ha Lee, MD,1 Young Hoon Ryu, MD, PhD,2

Myung Sik Lee, MD, PhD,1 and Chul Hyoung Lyoo, MD, PhD1*

MRI outperforms [18F]AV-1451 PET as a longitudinal biomarker in progressive supranuclear palsy

Jennifer L. Whitwell, PhD1, Nirubol Tosakulwong, BS4, Christopher G. Schwarz, PhD1, Hugo Botha, MD2, Matthew L. Senjem, MS1,3, Anthony J. Spychalla, BS1, J. Eric Ahlskog, PhD, MD2, David S. Knopman, MD2, Ronald C. Petersen, MD, PhD2, Jr Clifford R. Jack, MD1, Val J. Lowe, MD1, and Keith A. Josephs, MD, MST, MSc2

In vivo retention of 18F-AV-1451 incorticobasal syndrome

Ruben Smith, MD, PhD

Feasibility of PET/MR in movement disorder imaging

MRI + PET : accurate pathology description, attenuation correction

Combination of metabolic information with tissue contrast and high resolutionin MRI

The same space, complementarity in information, no reslicing issues,decrease of movement issues

Better confidence in pathology assessment, complex cases, vascular

Increasing of diagnostic accuracy, common interpretation

Better convenience : single examination

Perspectives : quantitative analysis, comparisons voxel/voxel, deep learning

Precise cartography of different markers

Better understanding of underlying pathophysiology: metabolism, perfusion, function

New sequences and new tracers: new diagnosis, early forms, follow-up?

Thank you for your attention