Metabolic brain pattern recognition in patients with parkinsonian and dementing conditions K.L. Leenders University Medical Center Groningen (UMCG)

Metabolic brain pattern recognition in patients with parkinsonian and dementing conditions K.L. Leenders University Medical Center Groningen (UMCG) TARGET conference Groningen, 5 april 2013

Content lecture Introduction Glucose consumption of the brain Image analysis Principal Component analysis Selected cases GLIMPS-project Conclusion

Introduction Differential diagnosis neurodegenerative brain diseases difficult in early phases overlapping clinical signs and symptoms Early diagnosis important Prognosis and management differ Auxiliary imaging investigations F-DOPA-PET/FP-CIT SPECT scan MRI [18F]-fluoro deoxy glucose (FDG) PET

Introduction [18F]-fluoro deoxy glucose (FDG) PET Glucose-analog Regions with high FDG-uptake (red/yellow) associated with brain activity Various brain diseases: different altered glucose utilisation patterns

Image-analysis Visual assessment Simple measures. Z-values. SPM comparisons with healthy control subjects Co-variance methods SSM-PCA: per group and per individual subject. (Scaled Subprofile Model Principal Component Analysis) Available: profiles of IPD, MSA, PSP en AD Individual subject score Future: improved techniques? Machine learning, supervised and unsupervised

Visual assessment individual FDG-PET scan PD MSA High FDG uptake PSP CBD Low FDG uptake DLB

Co-variance methods (SSM-PCA ) Voxel wise Scaled subprofile modeling (SSM) Principal component analysis (PCA) PCA identifies relations between brain regions which can not be seen readily by ordinary visual inspection Determines the chance that different voxels with increased or decreased activity are related to each other Pattern: contribution of each individual through his subject score to the disease specific profile Moeller et al. 1987, 1999; Eidelberg et al. 1994, 2009; Spetsieris et al. 2007, 2009, 2010

PDRP and PDCP expression (SSM) in 15 early PD patiënts Huang e.a. 2007 (BRAIN)

Specificity and sensitivity between groups of patients by SSM-PCA

Selected cases

Z score Case (1) mr T, 62 yr Since 1 yr mask face, problems walking, balance problems and increased slowness Rigidity and bradykinesia left > right. UPDRS (III) 24 Suspicion M Parkinson Levodopa 3x 125 mg After some time concentration problems, depression, more balance disturbances, moderate response to levodopa D/ suspicion m. Parkinson, dd PSP controls PD Advice: FDG-PET scan

GLIMPS Case (1) mr T, 62 yr Subjectscore of 1 patient (mct scan) compared with the PD, AD, PSP and MSA covariance pattern 2.0 1.5 1.0 0.5 0.0-0.5-1.0-1.5-2.0-2.5 PD14 pt op PDRP pt op ADRP pt op PSPRP pt op MSARP PD14 controls PD

Case (2) mv S, 42 yr Second opinion suspicion m. Parkinson Since 2 yr fatigue, slowness, stiffness left > right UPDRS (III) 45 Suspicion PD Management: increasing levodopa After 4 yrs moderate effect of levodopa and apomorfine, accelerated progression, swallowing difficult, incontinence for urine, wheel chair Suspicion MSA Advice FDG-PET

Case (2) mv S, 42 yr MSA17 Subjectscore of 1 patient (HR+ scan) compared with the MSA, PSP, PD and AD covariance pattern 3 2 1 0-1 -2 pt op MSARP pt op PSPRP pt op PDRP pt op ADRP MSA17-3

GLIMPS Identification metabolic covariance pattern AD via SSM/PCA analysis (cohort 1) 4 3 2 1 0 * * z-score = 0,65 Sensitivity = 93,3% Specificity = 94,4% PPV = 93,3% NPV = 94,4% -1-2 leave-one-out z-scores healthy controls leave-one-out z-scores Alzheimer's Disease patients Submitted L.K. Teune, F. Strijkert, R.J. Renken, G.J. Izaks, J.J. de Vries, M. Segbers, J.B.T.M. Roerdink, R.A.J.O. Dierckx, K.L. Leenders.

GLIMPS Prospective individual patients tested on the AD pattern patients with memory complaints (cohort 2) 3 2.5 2 1.5 1 0.5 0-0.5-1 individual patients probable AD individual patients non probable AD Submitted L.K. Teune, F. Strijkert, R.J. Renken, G.J. Izaks, J.J. de Vries, M. Segbers, J.B.T.M. Roerdink, R.A.J.O. Dierckx, K.L. Leenders.

Case (4) mr K, 59 yr Since 4 yr calculation problems at work. Since 2 yr word finding and orientation problems. In unfamiliar environments loses his way Apraxia, disturbed orientation and fronto-executive dysfunction. No clear memory disturbances MMSE 28/29 FAB 12/18 DD/ AD, FTD, CBD Advice MRI, FDG-PET

Case (4) mr K, 59 yr Subjectscore of 1 patient (HR+ scan) comapred with the AD, PD, PSP en MSA covariance pattern 3 2.5 2 1.5 1 0.5 0-0.5 rswad07b.img pt op ADRP pt op PDRP pt op PSPRP pt op MSARP rswad07b.img -1

GLIMPS Improved classification using decision tree method Individual subject scores per component Classification 76 subjects at the same time Four groups Only 3 of 76 subjects wrongly classified In progress Johann Bernoulli Institute for Mathematics and Computer Science, RUG D. Mudali, L.K. Teune, R.J. Renken, K.L. Leenders, J.B.T.M. Roerdink

GLIMPS Glucose IMaging in Parkinsonian Syndromes National FDG-PET database project Website data entry Improved differential diagnosis for neurodegenerative brain diseases > 10 Dutch centers participate Start spring 2012

GLIMPS: clinical benefit and research Improved diagnosis in parkinsonian conditions Every patient who according to the practicing clinician might benefit from a FDG-PET scan. At short notice direct visual scan assessment Testing typical profiles Development of pattern recognition methods Supervised Unsupervised

GLIMPS Database

GLIMPS Feedback z-scores, patiënt Leeuwarden Klinische gegevens: Vrouw 53 jaar, bekend met M Parkinson sinds 4 jaar. Klachten: slikken verminderd, vallen, oogbewegingen niet afwijkend. Geen reactie op Levodopa. Vraagstelling: aanwijzingen voor PSP? FDG-PET visueel beeld:

GLIMPS Feedback z-scores, patiënt Leeuwarden Z-scores voor deze patiënt 4 3 2 1 Conclusie: PSP patroon geëxprimeerd, overeenkomstig klinische verdenking. 0-1 pt op PDRP pt op MSARP pt op PSPRP pt op ADRP -2-3

GLIMPS Feedback z-scores, patiënt Roermond Klinische gegevens: Man, 70 jaar, bekend met parkinsonisme. Vraagstelling: MSA, IPD? Visuele beoordeling FDG-PET scan door nucleair geneeskundige Roermond: Verminderde FDG-stapeling pariëto occipitaal rechts tov links. Verminderde uptake in nucleus caudatus bdz (re>li) en thalamus rechts. Conclusie: geen specifiek patroon. FDG-PET visueel beeld:

GLIMPS Feedback z-scores, patiënt Roermond Z-scores voor deze patiënt 3 09_002 Conclusie: IPD patroon meest geëxprimeerd. 2 1 09_002 0 pt op PDRP pt op MSARP pt op PSPRP pt op ADRP -1

Conclusions Network abnormalities in brain metabolism in neurodegenerative brain diseases proven Ready for practical application Better subgroups necessary to determine more profiles Elaboration into a system of functional and pathophysiological patterns instead of diseases?

Thank you