nuclear physics in medicine chapter: medical imaging nupecc liaisons 1 alexander murphy and 2...
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Nuclear Physics in MedicineChapter: Medical Imaging
NuPECC liaisons1Alexander Murphy and 2Faiçal Azaiez
1 The University of Edinburgh, UK2 IPN Orsay, IN2P3-CNRS, France
Conveners3Jose Manuel Udias and 4David Brasse
3 Universidad Complutense Madrid, Spain4 IPHC Strasbourg, IN2P3-CNRS, France
Piergiorgio Cerello, INFN Torino, ItalyChristophe de La Taille, Omega/IN2P3/CNRS, FranceAlberto Del Guerra, University of Pisa, ItalyNicola Belcari, University of Pisa, ItalyPeter Dendooven, University of Groningen, The NetherlandsWolfgang Enghardt, University Hospital TU Dresden, GermanyFine Fiedler, Helmholtz-Zentrum Dresden-Rossendorf, GermanyIan Lazarus, STFC, Daresbury Laboratory, Warrington, United KingdomGuillaume Montemont, CEA/LETI, FranceChristian Morel, CPPM/IN2P3/CNRS, Aix-Marseille University, FranceJosep F. Oliver, IFIC, Valencia University, SpainKatia Parodi, Ludwig Maximilians University Munich, GermanyMarlen Priegnitz, Helmholtz-Zentrum Dresden-Rossendorf, GermanyMagdalena Rafecas, IFIC, Valencia University, SpainChristoph Scheidenberger, Justus-Liebig-University Giessen and GSI-Darmstadt, GermanyPaola Solevi, IFIC,Valencia University, SpainPeter .G. Thirolf, Faculty of Physics at LMU Munich, GermanyIrene Torres-Espallardo, IFIC, Valencia University, Spain
List of Contributors
~ 10 years ago…
PET/CT is a technical evolution that has led to a medical revolution(Johannes Czernin, UCLA, 2003)
Invention of the Year
SNM Image of the Year
Anthony Stevens, Medical Options
From IMV
PET Clinical Procedures in US
…in Europe… (data from Anthony Stevens, Medical Options, EANM 2011)
In 2011,
Number of patient studies using PET or PET/CT: - between 2005 and 2010: 21 % increase - 2011: > 900 000 exams
FDG availability, scanner technology, … - 2010: 506 providers of PET or PET/CT in western Europe
64 %: public facilities
Average patient per scanner 2002 : 651 2010: 1559
PET Time Of Flight ImprovementFrom 400 ps to ….
From David Townsend (2008 AAPM Summer school)PET/MRI is a medical evolution based on a technical revolution (Thomas Beyer)
Nowadays…Few highlights
Spectral CT, K-edge imaging
Courtesy of C Morel et al, CPPM, France
Outline
• From Nuclear to Molecular Imaging– Small animal imaging system
• New Challenges– Detector design– Photon counting: towards spectral CT– -PET imaging– Simulation and reconstruction
• Interfaces– Quality Control in Hadrontherapy– Mass Spectrometry
From Nuclear to Molecular Imaging
The necessity of understanding biochemical processes at the molecular level
Advance in technological instrumentation
Preclinical Imaging
PET:the merging of biology and imaging
into molecular imaging(M Phelps)
University of Pittsburgh
Major efforts are devoted towards obtaining higherSensitivity
Spatial resolutionCheaper and easier to handle
15 MBq to target platelet,IPHC, Strasbourg
SPECT/CT PET/CT
SPECT/MR PET/MR
From Mediso Judenhofer et al, Nat. Med 14, 459-465, 2008
Courtesy of Dr. Piero A., Salvadori and Dr. Daniele Panetta, IFC-CNR Pisa
New Challenges…in Detector Design
• PET/CT Hybrid Imaging virtually available anywhere– Clinical routine in cancer staging, therapy assessment
• PET/MRI Hybrid Imaging… on its way
• Excellent performance
Can the performances be improved? Why?
• Better image quality and/or Lower dose• Better sensitivity & specificity in disease detection• Quantitative PET analysis
– that also requires protocol standardization
• Shorter Exam Time / Lower Cost
How to improve?
• 4D detectors with new design– Depth of Interaction, Time Of Flight– MR compatibility– Compactness– Cost & Scalability
How to Improve the Design ?
• Scintillators• Photon Detectors• Front-End Electronics• System Design & Integration
Dorenbos et col., IEEE TNS, 57, 2010 pp1162-1167
Y (ph/keV): 9Decay (ns): 300R (%): 10
Y (ph/keV): 30Decay (ns): 40R (%): 10
Y (ph/keV): 60Decay (ns): 16R (%): 3
How to Improve the Design ?
• Scintillators• Photon Detectors• Front-End Electronics• System Design & Integration
How to Improve the Design ?
• Scintillators• Photon Detectors• Front-End Electronics• System Design & Integration
• “Catch the first de-excitation photon”– Speed– Low Noise– Low (double) threshold– Low power consumption
Courtesy of Christophe De La Taille, Omega
How to Improve the Design ?
• Scintillators• Photon Detectors• Front-End Electronics• System Design & Integration
• Segmented / Continuous crystal• Radial/ axial orientation• Block structure / 1:1 coupling
System Performances - Spatial & timing resolutions - Count rate capability - Overall sensitivityCost/compactness/scalability
A lot of projects going on…Focus on the AX-PET collaboration
It consists only of two camera modules•48 LONG LYSO crystals (6 layers x 8 crystals)•156 plastic WLS strips (6 layers x 26 strips)
7
3.5
• Crystals are staggered by 2 mm. • Crystals and WLS strips are read out on alternate
sides to allow maximum packing density. • The other side is Al-coated, i.e. mirrored.
The layers are optically separated from each other.
Hamamatsu MPPC3×3 mm2
Hamamatsu MPPC3.22×1.19 mm2
3×3×100 mm3
3×0.9×40 mm3
Courtesy of the AXPET Collaboration
<RE>511 = 11.7 % (FWHM)1.48 mm FWHM in the axial direction
Photon Counting…towards spectral CT
Originally developed for vertex detectors in high energy physicsHybrid pixel arrays could replace conventional « charge integration »
Advantages: - absence of dark noise, - a high dynamic range - photon energy discrimination
-> Can provide spectral information
Pixelized sensorSi, CdTe, CZT
Readout ElectronicsStandard CMOS process
Technical specification of some hybrid pixel detector circuits
Photon Counting…towards spectral CT
Photon Counting…towards spectral CT
K-edge imaging of iodine
XPAD3 cameraXPAD-S ASIC500um thick silicon sensors500 kpixels130x130 um2 pixel pitch
Courtesy ofF Cassol Brunner and C Morel, CPPM, France
Medical Imaging using + Coincidences
whole class of potential PET isotopes excluded from medical application:
44mSc, 86Y, 94Tc, 94mTc, 152Tb, or 34mCl
3rd, higher-energy ray emitted from excited state in daughter nucleus:
- resulting extra dose delivered to the patient - expected increase of background from Compton scattering or pair creation
Perspective:
turn alleged disadvantage into promising benefit:
provided the availability of customized gamma cameras higher sensitivity for reconstruction of radioactivity distribution in PET examinations
PET imaging: so far (exclusive) + emitters: 18F, 11C
All present approaches towards ‘triple- imaging’ or ‘-PET’ :
based on Compton Camera:
Medical Imaging using + Coincidences
XEMIS: Xenon Medical Imaging System (since 2004 by Subatech, Univ. Nantes)
- cryogenic Time Projection Chamber (TPC) filled with liquid xenon (LXe) acting simultaneously as scatter, absorption and scintillation medium for the additional 3rd photon
E/E ~ 5.7% (511 keV 4.3% (1.157 MeV)
~ 1.25o
x = 2.3 mm (10 cm distance)
TPC
C. Grignon et al., Nucl. Instr. Meth. A 571 (2007) 142.T. Oger et al., Nucl. Instr. Meth. A 695 (2012) 125.J. Donnard et al., Nucl. Med. Rev. 15 (2012), C64–C67
Example: PET + TPC
New Challenges…in Simulation & Reconstruction
Both tomographic reconstruction and Monte-Carlo methods became feasible thanks to the advances in computer technology
The development of novel prototypes for emission tomography is usually supported by dedicated Monte-Carlo simulations and image reconstruction algorithms.
Monte-Carlo simulations are useful to optimize the system design and understand the observed phenomenaImage reconstruction is needed to determine the (expected) prototype performance at image level
Common Challenge
Model accuracy / Image qualityLow High
Simple modelsSimple simulated phantomsFew iterations of the recon
Complex modelsComplex simulated scenarii
Computational burdenShorter Longer
Efforts required to optimize balance between accuracy & computing time
Main Challenges…in Simulation (Emission Tomography)
To increase simulation speed without jeopardizing model accuracyParallel ImplementationImplementation in GPUsImplementation in FPGAs
To keeping pace with novel technologies and research scenariiFurther experiments and validation studies might be needed
Example of Model complexity
Which phenomena should be included?Light transport / Electron tracking / Voxelized phantomsTime-dependent phenomena:
Radioisotope decay / Phantom motionScanner rotation / Accidental coincidenceElectronic chain: pile-up, dead-time... Moving phantoms
Radiationtherapy + Imaging Scenarios
Main Challenges…in Reconstruction
From Scanner to Image
+ =
Instrumentation Image Reconstruction
PhysicsTowards improving
image quality
Main Challenges…in Reconstruction
Originally:A 2D image representing radioisotope distribution within one section of the body
Nowadays:Reconstruction of 3D images (volume)Dynamic reconstruction (4D): time sequences
Recent advances: 5D and 6D reconstructionTime evolutionHeart/respiratory motionsKinetic parameters
Some examples…
D. Wiant et al. Med. Phys. 37. 2010
Modeling of the PSF
Clinical PET
Analytic vs iterative
Small animal PET
Interfaces…Quality Control in HadrontherapyMotivation: range uncertainties
Source: HZDR, DKFZ
A monitoring of the dose delivery is requiredIn order to fully profit from the advantages of ion beams
The range of the particlesthen the maximum dose deliveryis very sensitive to modifications:
tissue density,inaccuracies in patient positioning
Deviations in dose distribution
Interfaces…Quality Control in Hadrontherapy« Several methods of medical imaging in particle ion beam therapy are under investigation in order to measure the range of the particles in the tissue or even directly measure the applied dose in vivo »
Positron Emission Tomography
Prompt gamma ray imaging
Charged particles imaging
Ion radiography and tomography
Three implementations are investigatedIn-beam PET (GSI, NIRS, Catana)In-room PET (MGH, Kashiwa)Offline PET (HIT, Hyogo)
Different detector conceptsCollimated gamma cameraMulti slit cameraCompton cameraPrompt gamma timing
Recent proof-of-principle simulation and experimental studies reported from research group in France, Italy and Germany
Direct measurement of the residual range of high-energy low-intensity ions traversing the patient. Prototypes are under development for both protons and carbon ion beams
Interfaces…Quality Control in HadrontherapyFocus on PET: « the only clinically investigated method »
PET activation (right) measured after delivery of the planned carbon ion treatment dose (left) at HIT, in comparison to the corresponding PET MC prediction (middle). The arrow marks an example of good range agreement (adapted from [Bauer 2013] with permission).
On going developments: - TOF PET with T<200ps - Characterization of nuclear reaction cross sections - Feasibility of PET verification for moving targets - Extension to others ions - Solution for automated PET range evaluation in clinical routine - Application of high energy photon therapy
Interfaces…Mass Spectrometry
« Imaging Mass Spectrometry, where high spatial resolution is combined with mass spectrometric analysis of the sample material, is a versatile and almost universal method to analyze the spatial distribution of analytes in tissue sections”
Some examples:Tissue recognitionDrug developmentMultimodal imaging
Left: single-pixel mass spectrum of the outer stripe outer medulla; The green label indicates the mass peak that is characteristic for imatinib. Right: imaging mass spectrometry yields the distribution of different substances in the mouse kidney (figures reprinted from ref. [Röm13]).
IMS spectra of a mouse kidney after treatment with the anti-cancer drug imatinib.
OutlookMedical imaging in general, and nuclear medicine in particular, has experienced and continues to exhibit evolution at exponential speeds.
The work performed in nuclear physics groups such as radiation detection, simulations, electronics, and data processing, find application in nuclear medicine.
This chapter provided a glimpse of how nuclear physics research has been involved in the advance of medical imaging and, more interestingly, how our current efforts are paving the way for the imaging technologies of tomorrow.
This chapter reflects the fact that inside the nuclear physics community, research and development activities in medical imaging detector development coexist, at times even within the same research group.
It is our duty to help and promote the translation of developments from our nuclear physics laboratories and basic nuclear science experiments into practical tools for the clinical and preclinical environments.
Piergiorgio Cerello, INFN Torino, ItalyChristophe de La Taille, Omega/IN2P3/CNRS, FranceAlberto Del Guerra, University of Pisa, ItalyNicola Belcari, University of Pisa, ItalyPeter Dendooven, University of Groningen, The NetherlandsWolfgang Enghardt, University Hospital TU Dresden, GermanyFine Fiedler, Helmholtz-Zentrum Dresden-Rossendorf, GermanyIan Lazarus, STFC, Daresbury Laboratory, Warrington, United KingdomGuillaume Montemont, CEA/LETI, FranceChristian Morel, CPPM/IN2P3/CNRS, Aix-Marseille University, FranceJosep F. Oliver, IFIC, Valencia University, SpainKatia Parodi, Ludwig Maximilians University Munich, GermanyMarlen Priegnitz, Helmholtz-Zentrum Dresden-Rossendorf, GermanyMagdalena Rafecas, IFIC, Valencia University, SpainChristoph Scheidenberger, Justus-Liebig-University Giessen and GSI-Darmstadt, GermanyPaola Solevi, IFIC,Valencia University, SpainPeter .G. Thirolf, Faculty of Physics at LMU Munich, GermanyIrene Torres-Espallardo, IFIC, Valencia University, Spain
List of Contributors
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