1. PET Positron Emission Tomography Jan Axelsson Umeå University Umeå University Hospital 2016-FEB-16

2. Why PET MRPET Anatomical imaging + + + Resolution + + ++ Sensitivity + + + Molecular imaging ++ + +

3. Mediso Nanoscan PET CT upplösning 30um

4. Animal bed

5. Andnings och hjärt-gating

6. PET Anti-materia i bilder P ositron(anti-materia) E missions (radioaktivt sönderfall) T omografi (mät i skikt) IsotopHalveringstid 11 C (kol-11)20 min 15 O (syre-15)2 min 18 F (flour-18)110 min www.hamamatsu.com/ Jan Axelsson

7. PET – i korta drag Human dose: 4 MBq/kg Amount measured in decays per second (Bq) Mouse dose: 10 MBq

8. Acquisition

9. Bild av molekyls funktion Samtida signal i två detektorer Då vet vi att molekylen låg någonstans på en linje mellan de två detektorer som gav signal Då kan vi göra tomografi! Alla fotoner kommer inte ut – vi kan korrigera för ”attenuering” med hjälp av CT Tomografisk rekonstruktion & Samtida signal i två detektorer (koincidens) = vårt data http://www.nature.com/ PET mäter: Bq/cm 3 ( Becquerel/cm 3 ) SUV ( Standariserat Upptags-Värde )

10. Image creation

11. Filtered Back-Projection (FBP) Post filter Reconstructing data to imagesPositrons  Detection  Corrections  Images Using a drawing program ….

12. Iterative methods Reconstructing data to imagesPositrons  Detection  Corrections  Images Simulate raw data if image looks as guessed image Compare with raw data, and correct guessed image Initially, guess image

13. OSEM Ordered Subset Expectation Maximum Most commonly used Less noise compared to FBP Known to overestimate low uptakes http://web.uchile.cl/vignette/borrar2/AlasbimnImages/aj18-bhb-fig03.gif

14. Quantitative imaging

15. BUT – Attenuation corrupts Constant activity gives higher activity at borders Can we use CT information for correction Collected data Positrons  Detection  Corrections  Images

16. Attenuation – how it works a b attenuation factor = exp (-  a) attenuation factor = exp (-  b) combined attenuation factor = exp (-  a+b]) - independent of source position coincidence unit combined attenuation factor = exp (-ma)* exp (-mb) = exp (-  a+b] ) AttenuationPositrons  Detection  Corrections  Images Can we use CT information for correction ?

17. One continuous spectrum is used to measure attenuation This is used to map attenuation of a mono-chromatic higher-energy photon source. Attenuation from CT Differences x-rays from brehmsstralung and annihilation photons Intensity Energy 511 keV Positron (  + ) 511 keV  

18. Attenuation from CT Some problems with the translation C. Burger, G. Goerres, S. Schoenes, A. Buck, A.H.R. Lonn, G.K. von Schulthess, Eur J Nucl Med, 29 (2002) 922-927 Teflon Metalic implant Carbon fiber (table) Triangles (from low to high attenuation value) : lungs, adipose, breast, liver, muscle, trabecular and cortical bond Metal is BAD!

19. Attenuation Homogenous activity after attenuation correction Insamlat dataKorrigerat data Positrons  Detection  Corrections  Images

20. Decay correction IsotopHalveringstid 11 C (kol-11)20 min 15 O (syre-15)2 min 18 F (flour-18)110 min t=0, scan start ALL images decay corrected to start of scan – You may forget the decay!

21. SUV Tomogoraphic reconstruktion PET measures: Bq/cm 3 ( Becquerel/cm 3 ) Standardized Uptake value (SUV)

22. S illy U seless V alue ? tumör blod tumör blod ”normal” SUV body weight SUV lean body mass Sugawara et al, Radiology 213 (1999) 521-525

23. Silly Useless? Nej – fungerar bra: –skalar om olika injicerad aktivitet –relativt robust –bra tumregel om malignt för många tumörtyper Bra nog med homogen population Troligen bättre med –SUV lbm (but many methods in literature)

24. Image protocols

25. PET scan modes

26. STATIC STATIC scan: Easy to scan Easy to analyze Pipe-line many subjects/day BUT: important to start at exactly right time No kinetic information

27. DYNAMIC DYNAMIC scan: Long scan time More information to analyze Fewer subjects per day BUT: Pharmaco-kinetic model can extract different tissue characteristics Summing of frames allows also static information

28. Tracer biology

29. Cancer och PET Andra molekyler: FLT mäter celldelning Acetat lipid-bildning för bl.a. prostatacancer Vatten mäter genomblödning FDG fastnar i cellen FDG = fluoro-deoxy-glucose

30. Today, the following tracers may be delivered: MoleculeFunction 11C-SCH23390D1 receptor 11C-RacloprideD2 receptor 11C-AcetateAcetyl-CoA, metabolism, lipid creation 18F-PE2IDAT transport 18F-FDGGlucose metabolism 18F-FLTproliferation 18F-NAFvascular microcalcifikation, osteoblast activity 68Ga-DOTATOCSomatostatin receptors 68Ga-PSMAprostate specific membrane antigene FDG is the work horse of PET imaging, and is readily available on a day-to-day basis. The delivery of tracer has to be agreed between the hospital and the researcher, where the facility may act as a mediator. Tracers

31. FDG tidsberoende S. Sanz-Viedma et al, Rev Esp Med Nucl. 2009;28(3):159-166

32. Analysis

33. Resolution MR / CTPETIdealt Region-of-Interest (ROI)

34. Size dependent recovery http://cdn.iopscience.com/images/0031-9155/60/1/137/Full/pmb504808f05_online.jpg

35. Thresholding Assumption: everything above background is tumour Problem: spill-out due to partial volume effects PET SUV=2.5 PET SUV=40% CT PET visual DA Schinaglet al, Int J Radiat Oncol Biol Phys 2007;69:1282–9.

36. SUV-max, an alternative SUVmax on smaller lesions (clinical use) SUV mean is dependent on region selection Noise makes SUV- max unreliable

37. Kombinerad PET - CT info Typically, PET and CT/MR does not display same regions EANM publication. PET/CT Radiotherapy planning, Part 3, A technologists Guide, ISBN: 978-3-902785-05-3 Often PET uptake is more regional than CT and MRI – biologically active region

38. Pharmaco-kinetic modeling The kinetic uptake curve describes something biological Compartmental models: Rate constants may be determined by fitting comparmental models to measured data

39. ”Graphical methods”

40. Patlak – irreversible binding Irreversible binding (k4=0) Patlak, gives influx rate Ki = slope

41. Logan - Receptor studies Logan analysis: Binding Potential (BP) BP is a combined measure of affinity and receptor availability BP = slope -1

42. Parametric images Patlak on all pixels

43. Summary MRI gives soft tissue contrast PET measures actual molecular biology FDG (sugar analog) common Any molecule may be labelled PET static images (fast) PET dynamic images (lots of information) Pharmaco-kinetic modeling