PET CT

1. Physics of PET-CT David S. Graff PhD

2. The Short, Rich Life of Positronium What is PET In this instance, the celebration is of discoveries about antimatter that enable contemporary scientists, engineers, and physicians to make everyday use of antimatter in ways that would have been Radiation regarded as impossibly exotic only a few decades ago. The sculpture, built in the Michigan shops by ,quot;$-+.#$&. Jens Zorn, has an abstract quality for the risks 23 general viewer; however people familiar with the ens Zorn relevant science will recognize it as a bronze, now lo- stylized expression of the creation and Randall destruction of the simplest atom of antimatter. West Hall. Positrons and electrons are antiparticles that pril 5, 1999. are strongly attracted to one another. Electrons are common constituents of ordinary matter, while positrons are created only under special circumstances of atomic and PET Tracers nuclear interactions. Once created, the positron inevitably finds itself in the company of electrons, and a typical fate for the positron is to couple with one of those electrons in a mutually encircling, ever-decreasing orbit. This two-body system T he sculpture “The Short, Rich Life of Positronium” commemorates the is called “positronium” and resembles an ordinary atom in many ways. During its How a fundamental research on antimatter done at short lifetime (only a few millionths of a the University of Michigan by Arthur Rich second), positronium emits light as its orbit (1937-1990), his students and colleagues. shrinks. Finally, the positron and electron Its creation was made possible by the annihilate one another as they convert into scanner works Physics Department, by the University’s a pair of high-energy gamma-rays in the Administration, and by the friends and fam- purest-known example of Einstein’s famous ily of Arthur Rich. It provides a permanent, relationship of mass to energy: E=mc2. visual reminder to the University Michigan physicists, (notably Arthur Rich, community and visitors that scientists at later with David Gidley, and their students Michigan have made (and continue to make) and collaborators) have studied the important discoveries. formation and annihilation of positronium 17 News of Michigan Physics Corrections

3. The Short, Rich Life of Positronium What is PET In this instance, the celebration is of discoveries about antimatter that enable contemporary scientists, engineers, and Radiation physicians to make everyday use of antimatter in ways that would have been risks regarded as impossibly exotic only a few decades ago. The sculpture, built in the Michigan shops by . Jens Zorn, has an abstract quality for the general viewer; however people familiar with the PET Tracers relevant science will recognize it as a n , - stylized expression of the creation and ll destruction of the simplest atom of antimatter. l. Positrons and electrons are antiparticles that 9. are strongly attracted to one another. Electrons are common constituents of ordi- How a nary matter, while positrons are created only scanner works under special circumstances of atomic and nuclear interactions. Once created, the positron inevitably finds itself in the company of electrons, and a typical fate for the positron is to couple with one of those electrons in a mutually encircling, ever-decreasing orbit. This two-body system Corrections T he sculpture “The Short, Rich Life of Positronium” commemorates the fundamental research on antimatter done at is called “positronium” and resembles an ordinary atom in many ways. During its short lifetime (only a few millionths of a the University of Michigan by Arthur Rich second), positronium emits light as its orbit (1937-1990), his students and colleagues. shrinks. Finally, the positron and electron Its creation was made possible by the annihilate one another as they convert into Physics Department, by the University’s a pair of high-energy gamma-rays in the Administration, and by the friends and fam- purest-known example of Einstein’s famous ily of Arthur Rich. It provides a permanent, relationship of mass to energy: E=mc2.

4. What is PET P E T

5. What is PET? Positron Emission Tomography

7. Tomography From CT: tomography requires lines of sight over all angles Lines of sight 360º coverage

8. Tomography From CT: reconstruct with Filtered Back Projection

9. Tomography requires sampling along known lines of sight through patients Emission Positron

11. In Transmission tomography, we know the location of the source and the detector, so we can reconstruct a line of sight Line of Sight

12. In Emission Tomography, source is diffused through patient. How to construct a line of sight?

13. Tomography requires sampling along known lines of sight through patients Emission tomography is challenging because source position (and hence line of sight) is difﬁcult to ﬁnd Positron

15. A Positron is the antimatter partner of an electron Mass: 511 keV Mass: 511 keV Charge: –1.6 10-19C Charge: +1.6 10-19C

16. Positron decay makes back-to-back photons 1 keV = 51 11 hν 5 eV y: 0 =+ 51 1k – rg : e ge En ar m: h/λ : hν = 511 h entu gy : 0 er ge λ= - + C m Mo n r E a : h/ Ch men tum Mo TOTAL Energy: 2mc2 = 1022 keV Charge: 0 Momentum: 0

17. Professor Arthur Rich holds a special place in the hearts o community. His untimely death in 1990 prompted the The short, rich life of positronium remember his contributions with sculpture. Jens Zorn PhD, University of Michigan of Positroniu The Short, Rich Life In this instan discoveries abou contemporary sc physicians to m antimatter in wa regarded as imp decades ago. The sculpture, bu !quot;#$%quot;&'()$*+,quot;$-+.#$&. Jens Zorn, has a /&0+('&1+23 general viewer; how sculpture by Jens Zorn relevant science 1998, welded bronze, 64”x38quot;x20quot; is now lo- stylized express cated between Randall destruction of the s Laboratory and West Hall. Positrons and elec It was installed April 5, 1999. are strongly att Electrons are com nary matter, while under special circ nuclear interact positron inevita company of electr the positron is to electrons in a ever-decreasing o T he sculpture “The Short, Rich Life of Positronium” commemorates the fundamental research on antimatter done at is called “positro ordinary atom in short lifetime (on the University of Michigan by Arthur Rich second), positroni (1937-1990), his students and colleagues. shrinks. Finally, Its creation was made possible by the

18. Coincidence detection determines line of sight

19. Coincidence detection determines line of sight

20. Tomography requires sampling along known lines of sight through patients Emission tomography is challenging because source position (and hence line of sight) is difﬁcult to ﬁnd Positron annihilates into back-to-back photons. Line of sight is between two detectors. Allows Tomography

21. physicians to make everyday use of antimatter in ways that would have been regarded as impossibly exotic only a few $&. Positron annihilates into back-to-back photons decades ago. The sculpture, built in the Michigan shops by Jens Zorn, has an abstract quality for the Simultaneous detection yields line of sight general viewer; however people familiar with the orn relevant science will recognize it as a ze, lo- stylized expression of the creation and dall destruction of the simplest atom of antimatter. Enables efﬁcient emission tomography Hall. Positrons and electrons are antiparticles that 999. are strongly attracted to one another. Electrons are common constituents of ordinary matter, while positrons are created only under special circumstances of atomic and nuclear interactions. Once created, the positron inevitably finds itself in the company of electrons, and a typical fate for the positron is to couple with one of those electrons in a mutually encircling, ever-decreasing orbit. This two-body system T he sculpture “The Short, Rich Life of Positronium” commemorates the fundamental research on antimatter done at is called “positronium” and resembles an ordinary atom in many ways. During its short lifetime (only a few millionths of a the University of Michigan by Arthur Rich second), positronium emits light as its orbit (1937-1990), his students and colleagues. shrinks. Finally, the positron and electron Its creation was made possible by the annihilate one another as they convert into Physics Department, by the University’s a pair of high-energy gamma-rays in the Administration, and by the friends and fam- purest-known example of Einstein’s famous ily of Arthur Rich. It provides a permanent, relationship of mass to energy: E=mc2. visual reminder to the University Michigan physicists, (notably Arthur Rich, community and visitors that scientists at later with David Gidley, and their students Michigan have made (and continue to make) and collaborators) have studied the important discoveries. formation and annihilation of positronium 17 News of Michigan Physics

22. What is PET Radiation risks PET Tracers How a scanner works Corrections

23. 300× more lead needed to block PET photons Typical diagnostic scan 511 keV

24. d PET/CT Shielding 6 only used 511 keV Lead dose q How much protection would be afforded by a lead vest? se rate similar ositron- FIG. 1. Plot of lead broad beam transmission factors as a function of lead e high- thickness.

25. Staff doses from PET can be high 33 mSv/hr 30 µSv/hr 4 mSv/hr Typical dose 1.5 mSv/scan Typical dose 0.2 mSv/scan 2 lbs ALARA<50 mSv/yr ALARA<5 mSv/yr

26. PET materials are more risky Ci for Ci 6 Exposure rate constant 4 R/Ci/hr/cm2 2 Thallium 201 0 Technetium 99m Fluorine 18

27. The majority of the patient dose comes from the CT scan PET 0.7 rem / scan CT 1.8 rem / scan Ref: Beyer T, Mueller SP, Brix G et al. Radiation exposure during combined whole-body FGD-PET/CT imaging. 51st Annual Meeting, Society of Nuclear Medicine, June 22, 2004. Abstract 1331.

28. Positron annihilates into back-to-back photons Simultaneous detection yields line of sight Enables efﬁcient emission tomography PET uses penetrating photons (TVL 16 mm Pb) Potential serious dose from injection and patient positioning

29. What is PET Radiation risks PET Tracers How a scanner works Corrections

30. Type of decay depends on isotope Too Big Number of Protons to ns y pro m an ns Too ut ro e n yn o ma To Number of Neutrons

31. Positrons are created with β+ radioactive decay n+ p0 +

32. Isotopes used in PET Number of Protons Number of Neutrons

33. PET Isotopes have to be manufactured in a cyclotroron

34. Production of 18F Number of Protons Number of Neutrons

35. Nearly all PET scans use FDG as a tracer Shows Glucose use and hence general metabolic activity

36. FDG traces glucose usage. • Actively brought • Actively brought into active cell into active cell • Phosphorilized • Phosphorilized • Metabolized • Decay • Metabolized

37. Normal PET scan

38. These PET scan images superimposed on MRI scan images shows a healthy medical student's brain function when performing arithmetical tasks at the same time as being exposed to irrelevant speech. Some brain areas are found significantly modulated: (A) Shows bilateral decreases in the auditory cortex. (B) Shows an increased activity in the left posterior parietal cortex. Courtesy and © Karolinska Institute and Hospital, PET Cognitive Neurophysiology, Sweden.

39. NonHodgkin’s Lymphoma

40. 41 year old female with a history of breast cancer, status post lumpectomy and axillary node dissection, and radiation treatment was referred for a restaging PET/CT examination. Metastatic breast cancer with ovarian metastases

41. Lymphoma - 56-year-old male

42. Positron annihilates into back-to-back photons Simultaneous detection yields line of sight Enables efﬁcient emission tomography PET uses penetrating photons (TVL 16 mm Pb) Potential serious dose from injection and patient positioning Most scans use FDG as a tracer Produced offsite in a cyclotron Traces glucose uptake

43. What is PET Radiation risks How a PET Tracers scanner works Corrections

44. How PET works A tracer isotope decays and emits back-to-back photons Two detectors light up at the same time We infer the position of the tracer somewhere along the line of sight More lines of sight localize the tracer

45. New OSEM reconstruction algorithm handles noise better

46. &!()*+/! 1 iter!quot;#$ 0!()*+/! 2 iters '!()*+/! 5 iters #78! /! ,)*F!F,),!,?-.:!H()C!>+-I(?*/!)C+-1:C! !()*+/! 6#78! &9!()*+/! &'!()*+/! 10 iters 15 iters /!

47. /J !F ) + ,.F!D-+-.,?!G(*HA!,?-.:!H()C!>+-I(?*/!)C+-1:C!(=,:*/;!@2A!#>C*+*!>C,.)-=! ,), ,./ !, ,E &/ !quot;#$ &/ !) ( ?-. (,?!, : !) ()* + <)* -?+,)(- < -?F ,: !H( .F! ) C! /, ,)(- .! F ! /> . !/ cold contrast >-) ()), >?- :()), ) !-I! ?!G( -)!!B ! !-I! ?!G H I(:1 (*quot;3!4 A I(:1 *HA!I 6N! +0/ !/ !I+-= # *&!-1 56 +*/!-I +-= !()* = I!2/* !.- &!() 7 !=* !.-( +/! *) ( 8 * ( +(); /*!I+* +/)!; /*!!I+* +/! *!:* 1 iter * . *+, 0 !quot; !:* #$ .*+,)* !quot;# $ 0! ()*+ ) *F! !()*+ F / F quot;#$ 2 !F,) 0 ! ! ,),! /! ,!,? & 4 3,DM:+-1.F!B6N%!&9!>?,.*/! , ?-.: -.:! !/12 56 /*)/ #78 '!() ! H() '!() H ()C! ! ! *+/! C !>+- *+/! > +-I I(?* ( ?*/! & / !)C+ &9! ) C+- 1 5 9!() *+/ - 1:C ()*+/! :C! ! ! noise &'! & '!( () 10 *+/ )*+/ ! ! 15 <-?F!/>C*+*!B6N%!O!>?,.*/! < < -?F -?F ! !/

48. • Given two competing PET systems, which would you recommend? • The one with better contrast. • The one with less noise.

49. Positron annihilates into back-to-back photons Simultaneous detection yields line of sight Enables efﬁcient emission tomography PET uses penetrating photons (TVL 16 mm Pb) Potential serious dose from injection and patient positioning Most scans use FDG as a tracer Produced offsite in a cyclotron Traces glucose uptake Pixelated scintillator absorbs photon and emits light Light detected by photomultiplier tube Computer model of patient iteratively modiﬁed until statistically matches scanner data (OSEM)

50. What is PET Radiation risks PET Tracers How a Corrections scanner works

51. Photons from deep tissue may attenuate

52. CT measures attenuation Measure PET and CT at the same time

53. Including attenuation

54. Scatter can add noise. One of the two photons scatters in the patient A “wrong” detector lights up The wrong line of sight is inferred Incorrect information adds noise to image

55. Too much activity can add noise. Randoms Two decays occur at almost the same time The wrong detectors light up at the same time The wrong line of sight is inferred Incorrect information adds noise to image

56. Time of ﬂight PET can decrease noise It takes more time for the photon to travel to the far detector. (Speed of light: 1 ft/0.0000000001 sec) Measure the time difference between detectors Deduce where along line of Δt = 1.2 ± 0.3 ns sight event came from. More information reduces noise

57. 34567.%8(97:%((;.-4<(=4:>?(@:;.4%; '()$ !#$%& !quot;#$%&%!quot;# '()*1 '()*/ !quot;#$%&%!quot;# '()*+ A/(?4:B(&C5( D4-:C4( B474%;C?( 5.:8%&945( E.;=(FGH 20-.%(%&%!quot;# 20-.%(!quot;# )0-.%(!quot;# ),-.%(!quot;# 20+(CI9J( '()$ A,*/(KLM ),(-N. #OPJ( )(=B(@&9;Q .%R47;.&% !quot;

58. Positron annihilates into back-to-back photons Simultaneous detection yields line of sight Enables efficient emission tomography PET uses penetrating photons (TVL 16 mm Pb) Potential serious dose from injection and patient positioning Most scans use FDG as a tracer Produced offsite in a cyclotron Traces glucose uptake Pixelated scintillator absorbs photon and emits light Light detected by photomultiplier tube Computer model of patient iteratively modified until statistically matches scanner data (OSEM) Noise from Scatter, Randoms Randoms can increase noise with high activity Time of flight can reduce noise for large patients

59. physicians to make everyday use of antimatter in ways that would have been regarded as impossibly exotic only a few $&. Positron annihilates into back-to-back photons decades ago. The sculpture, built in the Michigan shops by Jens Zorn, has an abstract quality for the Simultaneous detection yields line of sight general viewer; however people familiar with the orn relevant science will recognize it as a ze, lo- stylized expression of the creation and dall destruction of the simplest atom of antimatter. Enables efficient emission tomography Hall. Positrons and electrons are antiparticles that 999. are strongly attracted to one another. Electrons are common constituents of ordinary matter, while positrons are created only under special circumstances of atomic and nuclear interactions. Once created, the positron inevitably finds itself in the PET uses penetrating photons (TVL 16 mm Pb) company of electrons, and a typical fate for the positron is to couple with one of those electrons in a mutually encircling, Potential serious dose from injection and patient ever-decreasing orbit. This two-body system T he sculpture “The Short, Rich Life of Positronium” commemorates the fundamental research on antimatter done at is called “positronium” and resembles an ordinary atom in many ways. During its short lifetime (only a few millionths of a positioning the University of Michigan by Arthur Rich second), positronium emits light as its orbit (1937-1990), his students and colleagues. shrinks. Finally, the positron and electron Its creation was made possible by the annihilate one another as they convert into Physics Department, by the University’s a pair of high-energy gamma-rays in the Administration, and by the friends and fam- purest-known example of Einstein’s famous Most scans use FDG as a tracer ily of Arthur Rich. It provides a permanent, relationship of mass to energy: E=mc2. visual reminder to the University Michigan physicists, (notably Arthur Rich, community and visitors that scientists at later with David Gidley, and their students Michigan have made (and continue to make) and collaborators) have studied the important discoveries. Produced offsite in a cyclotron formation and annihilation of positronium Traces glucose uptake 17 News of Michigan Physics Pixelated scintillator absorbs photon and emits light Light detected by photomultiplier tube Computer model of patient iteratively modified until statistically matches scanner data (OSEM) Noise from Scatter, Randoms Randoms can increase noise with high activity Time of flight can reduce noise for large patients

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