Nuclear Physics in Medicine
Chapter: Medical Imaging
NuPECC liaisons
1Alexander Murphy and 2Faiçal Azaiez
1
The University of Edinburgh, UK
2 IPN Orsay, IN2P3-CNRS, France
Conveners
3Jose Manuel Udias and 4David Brasse
3
Universidad Complutense Madrid, Spain
4 IPHC Strasbourg, IN2P3-CNRS, France
List of Contributors
Piergiorgio Cerello,
Christophe de La Taille,
Alberto Del Guerra,
Nicola Belcari,
Peter Dendooven,
Wolfgang Enghardt,
Fine Fiedler,
Ian Lazarus,
Guillaume Montemont,
Christian Morel,
Josep F. Oliver,
Katia Parodi,
Marlen Priegnitz,
Magdalena Rafecas,
Christoph Scheidenberger,
Paola Solevi,
Peter .G. Thirolf,
Irene Torres-Espallardo,
INFN Torino, Italy
Omega/IN2P3/CNRS, France
University of Pisa, Italy
University of Pisa, Italy
University of Groningen, The Netherlands
University Hospital TU Dresden, Germany
Helmholtz-Zentrum Dresden-Rossendorf, Germany
STFC, Daresbury Laboratory, Warrington, United Kingdom
CEA/LETI, France
CPPM/IN2P3/CNRS, Aix-Marseille University, France
IFIC, Valencia University, Spain
Ludwig Maximilians University Munich, Germany
Helmholtz-Zentrum Dresden-Rossendorf, Germany
IFIC, Valencia University, Spain
Justus-Liebig-University Giessen and GSI-Darmstadt, Germany
IFIC,Valencia University, Spain
Faculty of Physics at LMU Munich, Germany
IFIC, Valencia University, Spain
~ 10 years ago…
SNM Image of the Year
Invention of the Year
PET/CT is a technical evolution that has led to a medical revolution
(Johannes Czernin, UCLA, 2003)
Anthony Stevens, Medical Options
PET Clinical Procedures in US (Million)
PET Clinical Procedures in US
2
1.8
1.6
1.4
1.2
1
0.8
0.6
0.4
0.2
0
2000
From IMV
2002
2004
2006
2008
2010
2012
2014
…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
25%
20%
15%
10%
5%
0%
Germany
Italy
France
Iberia
UK
Others
Average patient per scanner
2002 : 651
2010: 1559
Nowadays…
Few highlights
PET/MRI is a medical evolution based on a
technical revolution (Thomas Beyer)
PET Time Of Flight Improvement
From 400 ps to ….
From David Townsend (2008 AAPM Summer school)
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
g-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)
Major efforts are devoted towards obtaining higher
Sensitivity
Spatial resolution
Cheaper and easier to handle
University of Pittsburgh
SPECT/CT
PET/CT
15 MBq to target platelet,
IPHC, Strasbourg
Courtesy of Dr. Piero A., Salvadori and
Dr. Daniele Panetta, IFC-CNR Pisa
SPECT/MR
From Mediso
PET/MR
Judenhofer et al, Nat. Med 14, 459-465, 2008
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
Y (ph/keV):
Decay (ns):
R (%):
Y (ph/keV):
Decay (ns):
R (%):
Y (ph/keV):
Decay (ns):
R (%):
60
16
3
30
40
10
9
300
10
Dorenbos et col., IEEE TNS, 57, 2010 pp1162-1167
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 sensitivity
Cost/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
Hamamatsu MPPC
3×3 mm2
The layers are
optically
separated
from each
other.
3.5
•
•
•
Hamamatsu MPPC
3.22×1.19 mm2
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.
<RE>511 = 11.7 % (FWHM)
1.48 mm FWHM in the axial direction
Courtesy of the AXPET Collaboration
Photon Counting…towards spectral CT
Originally developed for vertex detectors in high energy physics
Hybrid pixel arrays could replace conventional « charge integration »
Advantages:
- absence of dark noise,
- a high dynamic range
- photon energy discrimination
-> Can provide spectral information
Pixelized sensor
Si, CdTe, CZT
Readout Electronics
Standard CMOS process
Photon Counting…towards spectral CT
Technical specification of some hybrid pixel detector circuits
Photon Counting…towards spectral CT
XPAD3 camera
XPAD-S ASIC
500um thick silicon sensors
500 kpixels
130x130 um2 pixel pitch
K-edge imaging of iodine
Courtesy of
F Cassol Brunner and C Morel, CPPM, France
Medical Imaging using b+g Coincidences
 PET imaging:
so far (exclusive) b+ emitters: 18F, 11C
 whole class of potential PET isotopes excluded
from medical application:
44mSc, 86Y, 94Tc, 94mTc, 152Tb,
or 34mCl
 3rd, higher-energy g 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
 All present approaches towards ‘triple-g imaging’ or ‘g-PET’ :
based on Compton Camera:
Medical Imaging using b+g Coincidences
Example: PET + TPC
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
 DE/E ~ 5.7% (511 keV
4.3% (1.157 MeV)
 sq ~ 1.25o
 Dx = 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
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
phenomena
Image reconstruction is needed to determine the (expected) prototype performance at image level
Common Challenge
Low
Model accuracy / Image quality
Simple models
Simple simulated phantoms
Few iterations of the recon
Shorter
High
Complex models
Complex simulated scenarii
Computational burden
Longer
Efforts required to optimize balance between accuracy & computing time
Main Challenges…in Simulation (Emission Tomography)
To increase simulation speed without jeopardizing model accuracy
Parallel Implementation
Implementation in GPUs
Implementation in FPGAs
To keeping pace with novel technologies and research scenarii
Further experiments and validation studies might be needed
Example of Model complexity
Which phenomena should be included?
Light transport / Electron tracking / Voxelized phantoms
Time-dependent phenomena:
Radioisotope decay / Phantom motion
Scanner rotation / Accidental coincidence
Electronic chain: pile-up, dead-time...
Moving phantoms
Radiationtherapy + Imaging Scenarios
Main Challenges…in Reconstruction
From Scanner to Image
+
Instrumentation
=
Image Reconstruction
Physics
Towards 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 reconstruction
Time evolution
Heart/respiratory motions
Kinetic parameters
Some examples…
Modeling of the PSF
D. Wiant et al. Med. Phys. 37. 2010
Analytic vs iterative
Clinical PET
Small animal PET
Interfaces…Quality Control in Hadrontherapy
Motivation: range uncertainties
A monitoring of the dose delivery is required
In order to fully profit from the advantages of ion
beams
The range of the particles
then the maximum dose delivery
is very sensitive to modifications:
tissue density,
inaccuracies in patient positioning
Deviations in dose distribution
Source: HZDR, DKFZ
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
Three implementations are investigated
In-beam PET (GSI, NIRS, Catana)
In-room PET (MGH, Kashiwa)
Offline PET (HIT, Hyogo)
Prompt gamma ray imaging
Different detector concepts
Charged particles imaging
Collimated gamma camera
Multi slit camera
Compton camera
Prompt gamma timing
Recent proof-of-principle simulation and experimental studies reported from
research group in France, Italy and Germany
Ion radiography and tomography
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 Hadrontherapy
Focus on PET: « the only clinically investigated method »
On going developments:
- TOF PET with DT<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
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).
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 recognition
Drug development
Multimodal imaging
IMS spectra of a mouse kidney after
treatment with the anti-cancer drug imatinib.
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]).
Outlook
Medical 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.
List of Contributors
Piergiorgio Cerello,
Christophe de La Taille,
Alberto Del Guerra,
Nicola Belcari,
Peter Dendooven,
Wolfgang Enghardt,
Fine Fiedler,
Ian Lazarus,
Guillaume Montemont,
Christian Morel,
Josep F. Oliver,
Katia Parodi,
Marlen Priegnitz,
Magdalena Rafecas,
Christoph Scheidenberger,
Paola Solevi,
Peter .G. Thirolf,
Irene Torres-Espallardo,
INFN Torino, Italy
Omega/IN2P3/CNRS, France
University of Pisa, Italy
University of Pisa, Italy
University of Groningen, The Netherlands
University Hospital TU Dresden, Germany
Helmholtz-Zentrum Dresden-Rossendorf, Germany
STFC, Daresbury Laboratory, Warrington, United Kingdom
CEA/LETI, France
CPPM/IN2P3/CNRS, Aix-Marseille University, France
IFIC, Valencia University, Spain
Ludwig Maximilians University Munich, Germany
Helmholtz-Zentrum Dresden-Rossendorf, Germany
IFIC, Valencia University, Spain
Justus-Liebig-University Giessen and GSI-Darmstadt, Germany
IFIC,Valencia University, Spain
Faculty of Physics at LMU Munich, Germany
IFIC, Valencia University, Spain