Principles of PET Imaging. Positron Emission Tomography (PET) Fundamental Principles WHAT IS PET?

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1 Positron Emission Tomography (PET) Fundamental Principles Osama Mawlawi Ph.D Department of Imaging Physics MD Anderson Cancer Center Houston TX. WHAT IS PET? Functional imaging modality as compared to structural Functional images show: Blood flow Glucose metabolism Receptor density Principles of PET Imaging Injection of a radioactive tracer to image chemical/biological processes. Radioactive tracer decays by Positron Emission. When the tracer is introduced into the body, its site-specific uptake can be traced by means of the labeled atom. EMISSION IMAGING vs. TRANSMISSION IMAGING 1

2 The PET Process Detector ring photon electron Injection Nucleus positron photon Why Positron Emitters: Many of the positron emitters occur naturally in biological molecules (C, N, O, etc.) Many have small molecular weights relative to the biological molecules they may be used to label (e.g., F) even if they aren t found there naturally. Consequently, radioactive isotopes can be attached to biologically interesting molecules with no or minimal impact on the behavior of those molecules in the body. Adapted from Positron Decay p = n + β + + υ A nucleus with too low a neutron-to-proton ratio converts a proton to a neutron, emitting a positron (β + ) and a neutrino (υ) to carry off the excess energy. β + 2

3 Nuclide Production We need to lower the neutron-to-proton ratio in order to make positron emitters. Neither reactors nor fission will do it as we don t need more neutrons but Cyclotrons can. 14 N(p,α) 11 C 16 O(p,α) 13 N 13 C(p,n) 13 N 14 N(d,n) 15 O 15 N(p,n) 15 O 16 O(p,pn) 15 O 18 O(p,n) 18 F 20 Ne(d,α) 18 F Decay schemes 18-F 18 O(p,n) 18 F 18 9 F (109.77m) 18 8O (stable) + EC 1, β 1 ρ=0.967 Reproduced From MIRD: Radionuclide Data and Decay Schemes The PET Process Detector ring photon electron Injection Nucleus positron photon 3

4 Memory storage Axial Axial Image reconstruction after the application of several corrections From physics in Nuclear medicine Sorenson and phelps 4

5 Quantification: Power of PET Measured Data Random subtract Normalize Dead time Correct Geometry Calculate/subtract scatter Correct Attenuation FBP or IR reconstruction Ideal measured data Type of recorded events Scatter Random True Total events = Trues + Randoms + Scatter 5

6 SCATTER 8*8 Line source 2D in air Line source 2D in water Line source 3D in water The theory and practice of 3D PET by Bendriem and Townsend Normalization Detector responses are difficult to match exactly, so the equivalent of a uniformity correction is performed by scanning a uniformly distributed source and scaling each detector s or each detector pair s response to the average response. Norm = i M i= 1 Det i M Det i or N i= 1 Pair i N Pair i 6

7 Pre-Normalization Post_Normalization Normalization sinogram Courtesy of magnus dahlbom Dead-time Correction The singles rate affects the dead-time of each detector and thus the true coincidence rate that it measures for a given activity within the field of view. Dead-time corrections based on measured count rate are typically predetermined for each PET system and then applied as a correction factor. Decay Correction Decay Correction: λ*1 t ( *2) t e *( t2* /(1 e λ λ )) Where t1 = scan start time t2 = scan duration 7

8 Geometric Correction 2R D Non-uniform sampling ( ) 2 Δx = Δd 1 x / R r t r D xr Attenuation Correction μ tissue, 511keV = cm 2 /g HVL tissue, 511keV ~ 7.2 cm Since both photons must exit the body to make a coincidence event, the attenuation length is the total thickness along the path of the photons. μx μx ρ I0 ρ Imeasured = Ie 0 = e Imeasured Attenuation I t I e I e = I t e -μl 8

9 P L1 1 = e μ L2 P2 = e μ P P e L 1* 2 = μ Attenuation is dependant on the path length and not the depth of the source of activity Four ways to get an attenuation map 1) Measured (MAC) 2) Calculated (CAC) 3) Segmented (SAC) 4) CT based (CTAC) Nuclear Medicine: Diagnosis and therapy. Harbert J, Eckelman W., Neumann R. Attenuation correction using transmission scan Transmission rod source ( 68 Ge) Emission Transmission Final 9

10 Calibration Transforming counts per second to activity per cc or to SUV Require a calibration factor (ex. uci/cc/cps) SUV decay-corrected dose/ml of tumor SUV = injected dose/patient weight in grams SUV lean decay corrected dose/ml of tumor = injected dose/patient lean body mass in grams The standardized uptake value (SUV) is one means of making PET results more quantitative. Tracer kinetic modeling is used extensively in quantitative PET (may include blood samples and dynamic imaging). Regular PET Imaging Emission (2D mode) Transmission (scans are interleaved) 5 to 6 bed positions 8 min per position 5 EM, 3 Tx Total scan duration min 15.5 cm Tx rod sources 10

11 SUV = (Measured activity * Patient weight)/injected dose PET APPLICATIONS ONCOLOGY Lung Cancer Melanoma 11

12 Neurology Parkinson s Disease Cardiology NH3 FDG Mismatch 2D 3D 12

13 Line source 2D in air Line source 2D in water Line source 3D in water The theory and practice of 3D PET by Bendriem and Townsend Factors affecting image resolution Detector size Detector type (block/single) Penetration / spill over Positron Range Non collinearity Linear (interleaving/mashing) and angular sampling Image Matrix Filter used in image reconstruction 13

14 Detectors Intrinsic resolution (FWHM) ~ Detector size/2 Depth of Interaction Penetration & Spillover Nuclear Medicine: Diagnosis and therapy. Harbert J, Eckelman W., Neumann R. Positron Range Modified from 14

15 Positron Range Zanzonico et al. Sem. Nuc. Med. vol 34 No Non Collinearity Deviation from 180 by ± FWHM (mm) = * Ring Diameter (mm) Linear sampling Angular sampling From physics in Nuclear medicine Cherry, Sorenson and phelps 15

16 Reconstruction Filter From physics in Nuclear medicine cherry, Sorenson and phelps Image Resolution Decreasing counts or sensitivity Decreasing resolution or more smoothing Image Matrix: Pixel size = FOV / Matrix size < 1/3 FWHM detector Filter used in image reconstruction: Type of filter and its cutoff frequency affects image resolution decrease cutoff ===> Increase smoothing 16

17 Reconstruction Comparison Decreasing counts or sensitivity Filtered Back Projection Truth OSEM (1 iteration, 10 subsets) (No smoothing filter) Factors affecting the absolute quantification of PE Matching emission and transmission scans Patient motion Partial voluming Scatter from outside the FOV Modified from 17

18 Modified from Phantom Study Coronal Sagital Axial Mip Sphere (volume) Gated Static Error (%) 1 (16.5 cc) (8.4 cc) (4 cc) (2 cc) (1 cc) (0.5 cc) Partial Volume Nuclear Medicine: Diagnosis and therapy. Harbert J, Eckelman W., Neumann R 18

19 Recovery Coefficient From physics in Nuclear medicine Sorenson and phelps Scatter from outside the FOV Disadvantages of the current PET imaging techniques Transmission Noise due to low gamma ray flux from rod source Transmission is contaminated by emission data Scan duration Time consuming (emission & transmission ) Increased patient movement (image blurring) Efficiency Decreased patient throughput Difficulty in accurately correlating images to other diagnostic modalities 19

20 Short duration, low noise CT-based attenuation correction Regular PET Imaging Emission (2D mode) Transmission (scans are interleaved) 5 to 6 bed positions 8 min per position 5 EM, 3 Tx Total scan duration min 15.5 cm Tx rod sources Faster scanning could be achieved by: Higher sensitivity (Better scanner efficiency) Faster detectors (shorter light decay time => LSO vs BGO) Decreasing scan time (3D vs 2D with similar statistics) Decreasing the Transmission scan time (use CT scans for attenuation) 20

21 The PET/CT design Gantry dimensions: 240(W) x 275(D) x 200 (H) Weight: 7800 lb lb table Bore size: 70 cm for PET & CT CT: Litespeed Ultra (8 slices) PET: Det (6.3*6.3*30), 89 cm ring dia. 24 rings, 47 (3.3mm) slices, 6-8 mm resol. 153 cm 70 cm 200 cm CT PET 160 cm Dual-modality imaging range PET-CT Attenuation Correction Inherent Image Registration 53 year old man with lymphoma with increased FDG uptake in the spleen and multiple intra and extra-thoracic nodes consistent with Multi-focal malignancy. 21

22 Converting CT Numbers to Attenuation Values For CT values < 0, materials are assumed to have an energy dependence similar to water For CT values > 0, material is assumed to have an energy dependence similar to a mixture of bone and water The green line shows the effect of using water scaling for all materials Attenuation at 511keV Water/air Bone/Water CT number measured at 140kVp Quantitative PET Performance 3 Factors that may affect SUV measurements Patient Compliance Fasting Blood Glucose levels Scan Conditions Scan time post injection Patient anxiety/comfort during uptake (room temperature, etc.) Patient motion during acquisition Intrinsic System Parameters and Capability Calibration QA Maintenance of operating parameters Performance characteristics of scanners Partial Volume effects Image processing algorithms Improper Prep. Non fasting 22

23 Fast Track Insulin Scan mg/dl Ideal mg/dl - clinical decision > 200 mg/dl - cancel Quantitative PET Performance 3 Factors that may affect SUV measurements Patient Compliance Fasting Blood Glucose levels Scan Conditions Scan time post injection Patient anxiety/comfort during uptake (room temperature, etc.) Patient motion during acquisition Intrinsic System Parameters and Capability Calibration QA Maintenance of operating parameters Performance characteristics of scanners Partial Volume Effects Image processing algorithms Effect of Scan time post injection: Beast Cancer N=20 Beaulieu S et al JNM

24 PET-CT Normal Brown Fat Max SUV 15.7 Ax CT Ax PET Cor MIP Fused Muscle Uptake Crutch Utilized Left Side Phantom Study Coronal Sagital Axial Mip Sphere (volume) Gated Static Error (%) 1 (16.5 cc) (8.4 cc) (4 cc) (2 cc) (1 cc) (0.5 cc)

25 Quantitative PET Performance 3 Factors that may affect SUV measurements Patient Compliance Fasting Blood Glucose levels Scan Conditions Scan time post injection Patient anxiety/comfort during uptake (room temperature, etc.) Patient motion during acquisition Intrinsic System Operating Parameters Calibration QA Maintenance of operating parameters System performance characterization Partial Volume Effects Image processing algorithms Effect on Partial voluming All spheres contain the same activity concentration Profile (10 mm) Recovery (%) Standard 8 x 8 detector Sphere diameter Recovery coefficients HI-REZ 13 x 13 detector Courtesy of Siemens A 3D IR 2it 20sub B 3D FORE 2it 5sub C 3D FORE 5it 28sub D 3D FORE FBP Max SUVbw in different spheres A B C D

26 A 2D OSEM 2it 20sub B 2D OSEM 2it 28sub C 2D OSEM 4it 28sub Max SUVbw in different spheres A B C Effect of ROI type Courtesy of Kinahan UW 26

27 SUV Modifiers SUVbw (gm/ml) SUVBSA (m2/ml) SUVLBM (gm/ml) SUV Modifiers SUVig (gm/ml) Quantitative PET Performance 3 Factors that may affect SUV measurements Patient Compliance Fasting Blood Glucose levels Scan Conditions Scan time post injection Patient anxiety/comfort during uptake (room temperature, etc.) Patient motion during acquisition Intrinsic System Operating Parameters Calibration QA Maintenance of operating parameters System performance characterization Partial Volume Effects Image processing algorithms 27

28 Breathing Artifacts Caused by difference in respiratory motion between PET and CT scans. PET scan is acquired while patient is free breathing. The final image is an average of many breathing cycles. CT scan is acquired during a specific stage of the breathing cycle. Breathing Artifact- Curvilinear Cold Areas Photopenic Artifact CT PET FUSEDIMAGE NON AC Impact of Whole-body Respiratory Gated PET/CT Static wholebody Single respiratory phase (1 of 7, so noisier) 1 cc lesion on CT The max SUV of the lesion goes from 2 in the static image to 6 in the respiratory-gated image sequence Courtesy of P Kinahan, UW 28

29 Breathing Artifact Mismatch of lesion location between helical CT and PET Breathing Artifact Mismatch of lesion location between helical CT and PET Inaccurate attenuation correction inaccurate quantification Mismatch between PET and CT Cardiac Application Courtesy of J. Brunetti, Holly name 29

30 Courtesy of J. Brunetti, Holly name Blurring due to object motion during data acquisition Underestimation of Activity concentration Stationary Moving Possible solutions 30

31 % Average CT 4D CT X-ray on off 1st table position 2nd table position (0-2cm) (2-4 cm) EI 0% EI 0% 3rd table position (4-6 cm) Respiratory singal EE 50% EE 50% CT images 4D-CT images Helical CT Helical CT Combined helical and 4DCT averaging without thorax respiration-averaged CT 1 Image averaging Respiration-averaged CT 2 Courtesy of Tinsu Pan, MDACC Clinical Studies Mismatch 1: CT diaphragm position lower than PET +57% Mismatch 2: CT diaphragm position higher than PET Courtesy of Tinsu Pan, MDACC CT PET Fused RACT PET Fused No AC (A) (B) (C) (D) Courtesy of Tinsu Pan, MDACC 31

32 Improve the restaging after chemo Misregistration lead to a false positive response to chemo. A true negative response when misregistration is removed with ACT Courtesy of Tinsu Pan, MDACC Impact on treatment planning Old GTV New GTV Previous GTV was outlined based on CT and clinical PET without motion correction. New GTV was redefined based on the correct information from PET with ACT. Courtesy of Tinsu Pan, MDACC Gated PET (Used to image repetitively moving objects: cardiac, respiratory) Trigger Trigger time Bin 1 Bin 8 Prospective fixed forward time binning Ability to reject cycles (cardiac) that don t match Single 15 cm FOV Gated PET User defined number of bins and bin duration As number of bins increase, the duration and motion per bin decreases. However images will be noisy unless acquired for longer durations. 32

33 4D-Gated PET Phantom Study Coronal Sagital Axial Mip Sphere (volume) Gated Static Error (%) 1 (16.5 cc) (8.4 cc) (4 cc) (2 cc) (1 cc) (0.5 cc) New CT Application Advantage 4D CT Respiratory tracking with Varian RPM optical monitor CT images acquired over complete respiratory cycle Image acquired signal to RPM system X-ray on First couch position Second couch position Third couch position Respiratory motion defined retrospective gating 33

34 4D-PET/CT 4D PET/CT CT only PET-CT only 4D CT only 4D PET-CT only Courtesy of Dr. Heron, UPMC 34

35 GTV Determination From PET Images Thresholding Thresholding 35

36 Thresholding Original Max = % of Original Max Thresholding Original Max = % of Original Max Thresholding Original Max = % of Original Max 36

37 Thresholding Original Max = % of Original Max Thresholding Original Max = % of Original Max Thresholding Original Max = % of Original Max 37

38 Thank you Quantitative PET Performance 3 Factors that may affect SUV measurements Patient Compliance Fasting Blood Glucose levels Scan Conditions Scan time post injection Patient anxiety/comfort during uptake (room temperature, etc.) Patient motion during acquisition Intrinsic System Operating Parameters Calibration QA Maintenance of operating parameters System performance characterization Partial Volume Effects Image processing algorithms Effect on Partial voluming All spheres contain the same activity concentration Profile (10 mm) Recovery (%) Standard 8 x 8 detector Sphere diameter Recovery coefficients HI-REZ 13 x 13 detector Courtesy of Siemens 38

39 A 3D IR 2it 20sub B 3D FORE 2it 5sub C 3D FORE 5it 28sub D 3D FORE FBP Max SUVbw in different spheres A B C D A 2D OSEM 2it 20sub B 2D OSEM 2it 28sub C 2D OSEM 4it 28sub Max SUVbw in different spheres A B C Gated PET CT PET Fusion? Primary tumor PET MIP Trans. Coronal 4D PET MIP 4D PET Coronal Gated acq. statistics Single FOV Helical CTAC 10 minute scan duration 8 respiratory gated bins Impact Enhanced visualization Increased quantitative accuracy Motion assessment Images courtesy of Holy Name Hospital 39