NEUROIMAGING IN PANS/PANDAS

Transcription

1 NEUROIMAGING IN PANS/PANDAS Harry T. Chugani, M.D. Chief, Pediatric Neurology Nemours A.I. dupont Hospital for Children Wilmington, Delaware, USA Professor of Pediatrics and Neurology Thomas Jefferson University School of Medicine Philadelphia, Pennsylvania, USA

2 MRI ADVANCES IN BRAIN IMAGING ALLOW AN UNPRECEDENTED OPPORTUNITY TO STUDY NEUROLOGICAL DISORDERS IN HUMANS STRUCTURAL MRI DIFFUSION/PERFUSION MRI FUNCTIONAL MRI (fmri) DIFFUSION TENSOR IMAGING (DTI) VOLUMETRIC MRI SPECT (cerebral blood flow) PET GLUCOSE METABOLISM GABA A (FLUMAZENIL) SEROTONIN SYNTHESIS PROTEIN SYNTHESIS BRAIN INFLAMMATION

3 POSITRON EMISSION AND ANNIHILATION P N P N N P P P N N P Unstable parent nucleus F-18, N-13 C-11, O O --> b N + n + energy P N P N N N N P P P N Proton decays to neutron in nucleus - positron and neutrino emitted g n e+ e- g Positron combines with electron and annihilates

4 PET DATA ACQUISITION AND ANALYSIS Proton acceleration Isotope production Labeling Modeling Imaging Acquisition

5 PARTIAL LIST OF PET RADIOTRACERS NEUROLOGY [ 18 F] Flurodeoxyglucose (FDG) [ 18 F] Altanserin [ 11 C] Carfentanil [ 11 C] DASB [ 11 C] DTBZ (or [ 18 F]Fluoropropyl-DTBZ) [ 11 C]Leucine [ 11 C] α-methyl-l-tryptophan (AMT) [ 18 F] Fallypride [ 18 F] Florbetapen [ 18 F] Florbetapir [ 18 F] or [ 11 C] Flumazenil [ 18 F]Fluorodopa [ 18 F] Desmethoxyfallypride [ 18 F] MPPF Pittsburgh compound B [ 11 C] PK [ 11 C] Raclopride [ 18 F] Setoperone [ 11 C] Verapamil ONCOLOGY FDG [ 11 C] Acetate [ 11 C] Methionine [ 11 C] α-methyl-l-tryptophan (AMT) [ 11 C] Choline [ 18 F] Fluorocholine [ 18 F] Fluorodopa [ 18 F]Fluoro-etyhl-tyrosine(FET) [ 18 F] FMISO 3'-[ 18 F] Fluorothymidine (FLT) CARDIOLOGY Oxygen-15 water Nitrogen-13 ammonia Rb-82 chloride [ 11 C] Acetate

6 TOURETTE SYNDROME CHILDHOOD ONSET NEUROPSYCHIATRIC DISORDER CHARACTERIZED BY MOTOR AND VOCAL TICS, OFTEN COMORBID WITH OCD AND ADHD ETIOLOGY AND PATHOPHYSIOLOGY OF TS ARE STILL POORLY UNDERSTOOD, BUT MANY STUDIES HAVE IMPLICATED THE CORTICAL-STRIATAL-THALAMIC- CORTICAL (CSTC) CIRCUIT AS BEING AFFECTED CONVENTIONAL NEUROIMAGING SUCH AS CT AND STANDARD MRI HAVE NOT BEEN PARTICULARLY USEFUL, BUT MORE ADVANCED NEUROIMAGING METHODS ARE BEGINNING TO REVEAL ABNORMALITIES IN THE CSTC CIRCUIT

7 NORMAL 18 FLUORO-DEOXYGLUCOSE PET SCAN

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9 TRACER PROPERTIES OF a[c-11]methyl-l-tryptophan is not incorporated into protein is converted to a[c-11]methyl-serotonin in brain a[c-11]methyl-serotonin is localized to serotonergic neurons and nerve terminals a-[c-11]methyl-serotonin is not a substrate for the degradative enzyme MAO

10 Patterns of abnormal serotonin synthesis in Tourette syndrome (Br) caudate + thalamus bilateral caudate/putamen increase (ca) (Fr) right frontal left frontal, temporal, and caudate (Di)

11 Serotonin Synthesis PET Study Fronto-striato-thalamic loop Some symptoms associated with pattern of serotonin synthesis Questions: -Can we predict symptom remission? Is remission associated with normalization of scan? -Do these patterns of serotonin synthesis assist in clinical treatment?

12 TOURETTE SYNDROME (ADD co-morbidity)

13 TOURETTE SYNDROME TIC SEVERITY ALSO CORRELATED SIGNIFICANTLY WITH ASYMMETRIC THALAMIC AMT UPTAKE

14 PK11195 PET NEUROINFLAMMATION IS MEDIATED BY ACTIVATED MICROGLIA WHICH ARE MESODERM-DERIVED BRAIN MACROPHAGES REPRESENTING THE RESIDENT IMMUNOCOMPETENT CELLS ACTIVATED MICROGLIA EXPRESS TRANSLOCATOR PROTEIN RECEPTORS (TSPO) AND ARE THE PRIMARY SOURCE OF TSPO EXPRESSION IN NEUROINFLAMMATION THE PET TRACER 11 C-[R]-PK11195 IS A SPECIFIC LIGAND WHICH BINDS TO TSPO PK11195 PET HAS BEEN SUCCESSFULLY APPLIED TO STUDY A WIDE VARIETY OF NEUROINFLAMMATORY DISORDERS CHARACTERIZED BY MICROGLIAL ACTIVATION

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16 [ 11 C] PK11195 Scans 11 yr old Viral encephalitis Normal (9yr old) Limbic Encephalitis After IVIG therapy

17 11 C-PK11195 PET Scan in a 13 year old boy with Rasmussen s Encephalitis

18 NIEMANN-PICK TYPE C 11 C-PK11195 PET SCAN Kumar & Chugani., 2011

19 Pediatric Autoimmune Neuropsychiatric Disorder Associated with Infection Kumar, A, et al, J Child Neurol. 2015

20 Serial 11 C-PK11195 (PK) PET Scans in a child (HR, M/8 yrs) with PANDAS PK PET-08/04/2010 PK PET-09/03/2010 PK PET-10/07/2010

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25 Giedd et al., 2000

26 THE FUTURE IS HERE! 3T whole-body PET/MR scanner allowing simultaneous acquisition of PET and MR data