Nuclear Medical Imaging Basics

Transkript

1 Jorge Cabello Nuclear Medical Imaging Basics

2 Basic Nuclear Medicine Detectors Gamma Camera, SPECT Positron Emission Tomography Multimodal Imaging Biokinetic Modelling 6/6/2016 2

3 Basic Nuclear Medicine Detectors Gamma Camera, SPECT Positron Emission Tomography Multimodal Imaging Biokinetic Modelling 6/6/2016 3

4 Aims of Nuclear Medicine Diagnostics Visualisation and quantification of biochemical processes (metabolism, receptor binding ) in vivo Therapy: Treatment of pathologic processes based on selective accumulation in body tissues

5 Principles of Nuclear Medical Diagnostics Tracer principle Radiopharmaceuticals are distributed, metabolized or excreted in the organism according to their structure Representation of body functions by: Images Numerical data Graphs

6 Radiology vs. Diagnostic Nuclear Medicine Radiation Source Radiology Detector Contrast between tissues with different densities for x-rays, e.g. lung vs. bone. 6/6/2016 6

7 Radiology vs. Diagnostic Nuclear Medicine Detector 6/6/ Nuclear Medicine

8 Radiology vs. Diagnostic Nuclear Medicine Detector Activity distribution equivalent to distribution of the injected substance. 6/6/ Nuclear Medicine

9 Radiology vs. Diagnostic Nuclear Medicine Radiation Source Detector Radiology (Transmission imaging) Nuclear Medicine (Emission imaging) 6/6/2016 9

10 Radiopharmaceuticals Selection of the pharmaceutical according to the organspecific question Labelling of pharmaceuticals with radioactive isotopes External detection possible Radiopharmaceuticals must not affect the metabolism [ 18 F]Fludeoxyglucose Glucose analog Developed in 1976 Used in PET in /6/

11 Types of Radiation Range in Tissue Energy Range α some MeV < 1mm β 100 kev 1MeV ~ some mm γ 100 kev 500 kev < some cm 6/6/

12 Isotopes for Nuclear Medical Imaging Nuclide Half Life Type Energy [kev] 99m Tc 6 h γ Tl 73 h γ I 13 h γ I 8 d γ F 110 min e +, γγ 511 6/6/

13 Typical radioligands Radioligand Target 18 F-FDG Glucose consumption (cancer, dementia ) 68 Ga-PSMA Prostate cancer 18 F-FET Aminoacid transporter (glioma grading) 18 F-DOPA Dopamine transporters (Schizophrenia, Parkinson) 18 F-FMISO Hypoxia (cancer cells resistance) 11 C-PIB Fibrillar amyloid-beta (Aβ) plaques (Alzheimer) 99m Tc-HMPAO Cerebral blood flow 99m Tc-Sestamibi Myocardial perfusion 123 I/ 131 I-MIBG Neuroendocrine or neurological tumors

14 Target Structure Locked metabolism [ 18 F]FDG Immune response Internalization MAb, Fragmente Receptors Hormone Drugs Peptide Catecholamine Transport Transport Red. DNA-S HED Anti-Gen Strategie, DNA - Synthese PS AST AS Transport Protein synthesis Extracellular structure

15 Underlying physics Physical interactions of radiation Photoelectric absorption Compton scattering Nuclear detector Scintillators Photodetectors

16 Interaction of Gamma Quanta with Matter Gamma energy in nuclear medicine: Compton scattering and photoelectric effect Interaction depends on: Energy E hν of gamma quantum Density ρ of material Atomic number Z of material Thickness D of material 6/6/

17 Gamma Radiation Photoelectric Effect e e e e e e e e e Energy of gamma quantum gets absorbed 6/6/

18 Photoelectric Effect Z A 4 3 E h τ: probability of absorption ρ: Material density Z: Atomic number (number of protons) E hν : Photon energy A: Atomic weight 6/6/

19 Gamma Radiation Compton Scattering e e Parts of -energy are transferred to the electron -quantum changes energy and direction 6/6/

20 Compton Scattering Z A f E h 6/6/

21 Compton Scattering - Angular Distribution Klein-Nishina formula 6/6/

22 Impact of Photoelectric and Compton events on image resolution Stickel PMB 2004

23 Atomic Number Z Nuklearmedizinische Klinik und Poliklinik Probability of γ Interaction with Matter Lead NaI Diagnostic Photo effect Tissue Compton effect Gamma Energy [kev] 6/6/

24 Attenuation Coefficient Attenuation coefficient photo effect: Attenuation coefficient Compton effect: µ m = + Cherry, Sorenson, Phelps: Physics in Nuclear Medicine /6/

25 Scintillation Crystals Inorganic Crystals conduction band activator level (doping) Gap (Eg>5eV) phe- Light photons e- activator ground level valence band Electron ionizes electron hole pair hole ionizes activator, electron drops into activator activator deactivates by emission of a photon (10-7 sec) 6/6/

26 Scintillation Crystals Property NaI BGO LSO GSO NaI:Tl Bi 4 Ge 3 O 12 Lu 2 SiO 5 :Ce Gd 2 SiO 5 :Ce Density (g/cm 3 ) 3,67 7,1 7,4 6,7 Effective Z Attenuation length at 511keV (mm) 29,1 10,4 11,4 14,1 Light yield (photons/mev) Decay time (ns) Emission (nm) Lu-176 (2,6%): + >350 kev: ~100/sec per cm 3 6/6/

27 Photomultiplier light sensitive cathode HV anode 1 cm 6/6/

28 Quantum Efficiency Photomultiplier LSO BGO QE # photo electrons # light quanta Hamamatsu Photonics 6/6/

29 Scintillation Detector crystal Tl doped sodium iodide (NaI) photomultiplier γ Kristall light electrons electrical signal energy ~ light quantity ~ signal height 6/6/

30 Gamma Camera Anger Principle Scintillation light γ NaI-Crystal (40 cm x 40 cm) Light guide Photomultiplier Position, Energy 6/6/

31 SPECT Detector Requirements At 140keV ( 99m Tc): Photomultiplier *Image courtesy of L. Shao, Philips Medical Systems Scintillation Crystals (NaI:Tl) High efficiency (>85%) Good energy resol. (<15 kev fwhm) High spatial resol. (<4 mm) Small costs (< 15/cm 2 ) Short deadtime (<2000 s cm 2 ) 6/6/

32 Gamma Camera Linearity photomultiplier PMT Signal* intrinsic light guide crystal ideal Source position 6/6/

33 99m Tc Point Source (about pulses per second) Without homogeneity correction matrix UFOV Integral 6,17% CFOV Integral 5,25% UFOV Differential 4,46% CFOV Differential 4,46% 6/6/

34 99m Tc Point Source (about pulses per second) With homogeneity correction matrix UFOV Integral 2,49% CFOV Integral 2,44% UFOV Differential 1,99% CFOV Differential 1,99% 6/6/

35 X Y integration time, X-Y, linearity correction, energy discrimination digital pulse processing A D C A D C A D C A D C A D C A D C A D C A D C photomultiplier with preamplifier light guide NaI crystal collimator 6/6/

36 Scintillation Detector Deposited Energy γ γ γ γ γ Crystal Light quantity 6/6/

37 Scintillation Detector Ideal Spectrum Cherry, Sorenson, Phelps: Physics in Nuclear Medicine /6/

38 Abundance Nuklearmedizinische Klinik und Poliklinik Gamma Camera Energy Spectrum primary scattered all 6/6/

39 Energy Window 99m Tc Sphere Phantom 140 kev (15%) Events: 100% Matrix: 128x128 Pixel size: 3,8mm 104 kev (20%) Events: 35% 6/6/

40 Gamma Camera H. Anger 1964 Crystal Position Energy Collimator Photomultiplier 6/6/

41 Collimator Limiting Component Septum thickness depends on energy and attenuation coefficient Principle γ γ Lead collimator, several hundreds holes Crystal Septa 6/6/

42 Collimator Resolution Sensitivity crystal crystal crystal e.g.: length 35 mm, distance 1.5 mm, thickness 0.2 mm more events or higher resolution signal to noise 6/6/

43 Planar Scintigraphy Detector size ca. 50 cm x 60 cm ca. 60 photomultiplier tubes per detector Energy resolution: < kev Intrinsic spatial resolution: mm Extrinsic spatial resolution (Collimator): 8-20 mm 6/6/

44 Planar Scintigraphy bone scintigraphy shows increased metabolism in bone, e.g. due to - bone fractures - inflammatory processes - degenerative processes - bone metastasis 99m Tc-Bisphosphonat ventral dorsal 6/6/

45 Planar Scintigraphy bone metastasis rib fracture knee arthrosis 6/6/

46 Planar Scintigraphy Cameras for special use, e.g. thyroidal gland 6/6/

47 Planar Scintigraphy thyroidal scintigraphy normal thyroids uptake unifocal autonomy Hyperthyroidism 6/6/

48 Planar Scintigraphy Acquisition over time, e.g. renal scintigraphy 99m Tc-MAG3 (Mercaptoacetyltriglzcin) 6/6/

49 Planar Scintigraphy Visual and quantitative analysis 99m Tc-MAG3 (Mercaptoacetyltriglzcin) 6/6/

50 Tomography SPECT Recording Gamma Camera Gamma Camera measures projections of activity distribution Spatial Resolution clinical: ~8 20 mm 6/6/

51 Images of Different Directions

52 Single Photon Emission CT SPECT

53 Emission Tomography Measurement of many projections, many angles Mathematical reconstruction Tomographic images / slices through body

54 Projection, Discrete Sampling

55 SPECT Imaging Projection 6/6/

56 Reconstruction Back Projection Back projection of two projections Back projection of three projections

57 Filtration of Line Profile Unfiltered without noise with noise Filter hamming cutoff = 0.2 Filtered 6/6/

58 Filtered Back Projection Without Filter 6/6/

59 Statistical Iterative Reconstruction Correction Object Space Estimate Error- Estimate Error- Estimate Projection Comparison Back-projection Projection Space Estimated Projection Measured Projection Error - Projection Acceleration: OSEM, Cluster 6/6/

60 Statistical Iterative Reconstruction Forward projection Λ Image space System response A Projection space Y Backward projection System response: Probability of an event is emitted in voxel i and detected in detector j. i j FP: BP: N i=0 P j=0 A ij λ i A ij y j SR (A) can be estimated: Analytical Monte Carlo Simulated Experimental

61 Statistical Iterative Reconstruction Maximum Likelihood Expectation Maximization (Shepp and Vardi) FP: BP: N i=0 P j=0 A ij λ i A ij y j λ i k+1 = λ i k P P j=0 A ij j=0 A ij i=0 N y j A ij λ i k Size of A: Number of voxels x Number of detectors 172x172x172 x x10 11 elements x 4 bytes (unsigned) 570 Gb Acceleration methods, compression methods, computational methods

62 Quality Control Daily Background Energy window Tilt angle Weekly Efficiency Inhomogeneity Flood correction Rotation Centre Half-yearly Geometric scale Linearity Spatial resolution Tomographic inhomogeneity 6/6/

63 New Developments Single Photon Detection

64 Gamma Camera Anger Principle Collimator system resolution Intrinsic resolution ~ 4 mm dependent on energy, crystal thickness Reduction by: narrower distribution of light smaller photomultipliers more photomultipliers Consequence: higher percentage of inactive area worse spatial and energy resolution 6/6/

65 High Resolution Gamma Camera Imaging close to the object: Requirements: thyroid mammography small animals Compact High intrinsic resolution Good energy resolution 6/6/

66 Detectors Crystal Photomultiplier Photodiodes Semiconductor detector 6/6/

67 Position Sensitive Photomultiplier PSPMT scintillation light light sensitive cathode anode wires (X-Y) signal distribution X 6/6/

68 High Resolution Gamma Camera PSPMT 164mm collimator FZ Jülich PSPMT Hamamatsu 250mm NaI(Tl) slice ( 13 cm, thickness 3 mm) 28 X and 28 Y Anode wires + center of mass determination Intrinsic: < 2 mm E/E(140 kev): 9,6% 6/6/

69 Matrix of Compact PSPMT NaI(Tl) pixel: 2 x 2 x 6 mm 2,8 x 2,8 cm 2 x 2,7 cm 4 X and 4 Y wires (Hamamatsu) Intrinsic: < 2 mm; E/E(140 kev): 18% Patt et al., Majewski et al., LumaGEM, Dilon 6/6/

70 Matrix of PSPMT and NaI pixel compact detector head Dilon 6/6/

71 One-to-one coupling crystal sensor pixel size Scintillation Read-Out with Semiconductor Detectors intrinsic resolution Silicon photo diodes (PD) versus PMT: high quantum efficiency very compact MR-compatible require pre-amplification relatively high noise, electronic necessary 6/6/

72 Semiconductor detectors PMT PS-PMT APD array SiPM array SiPM pixel Digital SiPM array

73 Luminous Scintillators Properties NaI(Tl) CsI(Tl) Density Effective Z Attenuation length at 140 kev (mm) Light yield (%) Wavelength (nm) Decay time (ns) Hygroscopic ++ (+) Yield PMT / yield PD (at 550nm) = 1 : 3 6/6/

74 Individual Read-Out with PD-Matrix Electronics UCLA, LBL, Digirad 5 cm 4096 CsI(Tl) Crystals Collimator Digirad Crystal pixel size: 1.5 mm to 3 mm 6/6/

75 Gamma Camera with CsI-PD Detector Detector Head (21 cm x 21 cm) Digirad 6/6/

76 Semiconductor Detector Direct detection of gamma quanta Low noise Excellent energy resolution Cadmium-Zinc-Telluride CZT: High atomic number 7 mm CZT = 1 cm NaI (at 140keV) Room temperature Energy resolution 6% Individual pixels, size: 330µm... 5mm 6/6/

77 Cadmium Zinc Telluride Camera Detector Element top view Siemens, Hoffman Estates 1999 bottom view 6/6/

78 Cardiac Imaging Semiconductor Detector Erlandsson PMB 2009 Spectrum Dynamics D-SPECT Camera Based on CZT detectors Pinhole collimators focus on heart Er 5.5% Isr 2.46 mm Rse 12.5 mm 6/6/