1. in the frame of the ERC Advanced Grant Agreement N°338953–TICAL
A Flagship project for Europe? Towards 10ps Time-of-Flight PET for a 10-fold sensitivity increase and equivalent dose reduction
Paul Lecoq
CERN, Geneva
This work is performed
in the frame of the ERC Advanced Grant Agreement N°338953–TICAL
and the COST Action TD1401

2. Physics is at the forefront of major advances in Medical Imaging
Wilhelm Röntgen
X-Ray discovery - NP1895
Felix Bloch
Edward M. Purcell
Magnetic resonance - NP1952
Allan MacLeod Cormack
Sir Godfrey N. Hounsfield
Tomographic principle - NP1979
In spite of these cultural differences and organizational difficulties physics has always been at the forefront of major advances in medical imaging
Sir Peter Mansfield
Paul C. Lauterbur
MRI – NP2003 2

3. Invention of the PET/CT
PET/CT Combine anatomic and functional information
Geneva University
Invention of the PET/CT

4. Low dose digital X-Ray Imaging
Physics Nobel Price 1992
Georges Charpak
CERN Physicist

5. “already transferred” technologies
Some illustrative
“already transferred” technologies
High Density Avalanche Chambers for pre-clinical PET
Scintillating crystals for PET/SPECT (BGO)
Photodetectors (PMT, SiPM)
Fast, low noise, highly integrated front end electronics
Intelligent multi-layered DAQ systems
Simulation tools (Geant 4, GATE platform)
And a number of technologies, on which our community spends a large amount of efforts and resources (with public money) , which constitutes a fertile breeding ground for innovation in the industrial domain
Large scale highly distributed data management
. . .

6. Arbitrary scale to not offend anybody
Impact of our action
What are the reasons?
- 0
- 100
Arbitrary scale to not offend anybody
Too high fragmentation of our action
Organization of our projects
Funding schemes
Too loose connections with the medical world
Oportunistic
Serendipity
Cultural gap between physics and medicine
Different appreciation scales for the performance of a system as seen by a physicist and by a MD
Too few incentives to bridge this gap
Potential impact
Real impact
Perceived impact
Recognition

7. How to improve the Physics-Medicine synergy?
ERAMMIT project: EU INFRA IA2 call
Enabling Research Access to Multiparametric Molecular Imaging Technologies
Open Access set of translational infrastructures with in 4 pillars
Isotopes production & radiochemistry for theranostics
Hardware development and characterization
Software development and characterization
Preclinical & Clinical validation platform
A very ambitious and federating project involving all the stakeholders: academy, industry, funding agencies
10ps TOFPET is one ERAMMIT JRA aiming at this goal
Can be seen as a EU challenge, similar as the US EXPLORER
Opens the way for EU-US collaboration, as the objectives are similar as EXPLORER but with a different technical approach
Impossible , no
Challenging? Certainly yes
12 septembre 1962: Kennedy said: we choose to go to the moon.

8. Why fast timing in PET?
TOF state-of-the-art commercial scanners: ps
≈ 9cm on the LOR
TOF for rejecting background events (event collimation)
Requires 200ps TOF resolution for a few cm ROI (EndoTOFPET-US FP7 project)
TOF for improving image S/N
Requires 100ps TOF resolution for x5 S/N improvement, which brings a potential sensitivity gain (dose reduction)
TOF for direct 3D information
Requires 10ps TOF resolution for 1.5mm resolution along LOR
TOF for restoring image quality for limited angle tomography

9. * SNR gain for 40 cm phantom
Time of Flight PET
Dt = tA – tB = [(d+d1) – (d-d1)]/c
Detector B
d1 = c Dt/2 tB d d1
Patient
10ps TOF resolution
SNRTOF/SNRCONV= 16!
dx = 1.5mm e+ e- tA
dt (ps)
100
300
500
1200
dx (cm)
SNR*
1.5
4.5
7.5
18.0
5.2
3.0
2.3
* SNR gain for 40 cm phantom
SNRTOF = √(2D/cDt) · SNRconv
Detector A

10. How to extract the best time extimator
The detection chain
Crystal
SiPM
electronics q2 g Dt
Random deletion 1
Absorption
Self-absorption
Random deletion 2
SiPM PDE
Unwanted pulses 2
DCR
Unwanted pulses 1
DCR, cross talk
Afterpulses
How to extract the best time extimator
from this complex series of hits?
tkth pe = Dt
Conversion depth
+ tk’ ph
Scintillation
process
+ ttransit
Transit time
jitter
+ tSPTR
Single photon
time spread
+ tTDC
TDC
conversion time

11. Parameters of interest to improve timing resolution
Parameters for LSO: Ce, Ca and Hamamatsu S P MPPC
CTR improves like
SQRT (photon time density)
Rise time influence limited
by SPTR (66ps)
S. Gundacker, CERN-THESIS p.

12. Factors influencing scintillator time resolution
P. Lecoq et al, IEEE Trans. Nucl. Sci. 57 (2010)
Besides all factors related to photodetection and readout electronics the scintillator contributes to the time resolution through:
The light production mechanism
Light yield,
Rise time,
Decay time
The light transport in the crystal
Time spread related to different light propagation modes
The light extraction efficiency (LYLO)
Impact on photostatistics
Weights the distribution of light propagation modes

13. Best timing results at CERN
LSO:Ce, 0.4%Ca, melmount coupled to 3x3mm2 NUV SiPM from FBK, 55%PDE
2x2mm2 section
511 KeV
150GeV muons
5MeV deposited
S. Gundacker et al., CERN

14. Fast sintillation timing: the way to reconstructionless TOFPET
P Lecoq et al. Nucl. Instrum. Meth. A 718 (2013) 569
No TOF
Ultrafast
Nano-crystals
ZnO:Ga
700 ps
Photonic crystals
ZnO:Ga 20 fold increase in photon density as compared to LSO:Ce, Ca. 500ps compared to 30ns, light yiled 1/3 of LSO:Ce, Ca
500 ps
Digital 3D SiPM
300 ps

15. Avalanche development in a 50mm diameter SPAD
Two factors determine the timing resolution of a SiPM.
the time jitter of the avalnche development within a SPAD
The time transit spread of the signals from different SPADs to the collecting anode.
On the first point the group of Cova and Rech in Milano are studying the influence of the SPAD geometry on the avanche development.
This is a measurement, not a simulation! This is slow motion move showing in 30sec the 1.2ns development of the avalanche in a 50microns circular SPAD
***
photon-triggered secondary avalanches start to develop
(The image is the level of the current, but the emitted light is proportional to the current so to end is the same- the emission is centered around 1um and reach 4-500nm in the blue and in the IR-Yes the point is the assisted mechanism- the rim is more intense because it is less quenched by the space charge resistor.)
Ivan Rech, Politecnico di Milano

16. Quantum dots stimulated emission
In nano-structured systems the delta like density of electronic states predicts a low, temperature-independant lasing threshold
Core/shell quantum dots systems (CdSe/CdS) suppress non radiative recombinations in colloïdal quantum dot structures
Consequence is to lower the population inversion threshold to a few mJ/cm2
time
photon energy
Spontanous emission 100ps
Stimulated emission <1ps
J.Grim, I.Moreels, ITT, Italy

17. Nanoplates-Preliminary tests results
J.Grim, ITT, Italy
LSO plate 1mm thick
+ CdSe nanoplate film 100mm thick
372 nm laser
Streak
Camera
Focal spot
LSO
1 mm
100mm CdSe film
deposition
optical
table
R. Martinez Turtos, CERN
Focus in CdSe film
540nm
420nm
Focus in LSO crystal
540nm
420nm
Left: Streak focussed on CdSe: Fast peak from laser excitation of CdSe. Long tail CdSe excitation by LSO scintillation light. Emission >540nm = LSO emissionnot absorbed by CdSe
Right: Streak focussed on LSO

18. Metamaterials: Towards a self-triggered lasing g-ray detector
Ionization density per dE/dx event can reach > 1020 eV/ cm3 ≈ 10J/cm3
Ultrafast X-ray or g-ray self-triggered stimulated emission is within reach τR
τSE CB VB
detectable SE
Courtesy J.Grim, I.Moreels, ITT, Italy
Geant 4 simulation
J. Grim, ITT, Italy

19. The dream of the ”fast timing imager”
Implies ≈ mm resolution along PET LOR
Thank you
Requires ≈ 10ps timing resolution
1mSv PET exposure ≈ 1 flight Paris-SF

20. Acknowledgements Joel Grim, Iwan Moreels, IIT, Genova, It
V. Nagirnyi, S. Omelkov, Univ. Tartu
M. Korzhik, INP, Minsk
A. Vasiliev, Lomonosov State University, Moscow
CERN collaborators (E. Auffray, S. Gundacker, R. Martinez Turtos et al.)
PICOSEC Marie Curie TN
ERC Advanced Grant
FAST COST Action
TURBOPET Eurostars