Prospects for achieving < 100 ps FWHM coincidence resolving time - PowerPoint PPT Presentation

Prospects for achieving < 100 ps FWHM coincidence resolving time in time-of-flight PET Dennis R. Schaart, 28-Feb-2012, ICTR-PHE, Geneva, Switzerland Dennis R. Schaart 1 Delft University of Technology

Time-of-flight PET 114 kg; BMI = 32.2 13.4 mCi; 2 hr post-inj Colon cancer, left upper quadrant peritoneal node Non-TOF TOF (CRT ~650 ps) State-of-the-art clinical PET: coincidence resolving time (CRT) ≈ 500 ps Images: J. Karp, University of Pennsylvania 2

Silicon Photomultiplier (SiPM) 1 mm - 3 mm • Array of many self-quenched Geiger-mode APDs (microcells) connected in parallel • Increasingly interesting as replacement for PMTs: • high gain (~10 6 ) • high PDE • compact and rugged • transparent to γ -photons • fast response (ns) • insensitive to magnetic fields 20 µ m – 100 µ m Dennis R. Schaart 3 Delft University of Technology

In lab, 100 ps barrier has been broken Made possible by the combination of: • Small LaBr 3 :Ce(5%) crystals (3 mm x 3 mm x 5 mm) • Silicon Photomultipliers (Hamamatsu MPPC-S10362-33-050C) • Digital Signal Processing (DSP) 100 ps FWHM = > 15 mm FWHM D.R. Schaart et al, Phys Med Biol 55, N179-N189, 2010 4

Recent measurements with LSO:Ce,Ca FWHM = 125 ps • 3 mm x 3 mm x 5 mm LSO:Ce,Ca (U Tennessee) • 3 mm x 3 mm SiPM (MPPC-S10362-33-050C) S. Seifert et al, NDIP 2011 5

Digital SiPMs SPADs, TDC and digital readout circuitry integrated on a single chip 120 ps FWHM Photograph of Ca-codoped Time difference spectrum measured with LSO:Ce crystal mounted on a a Na-22 point source. dSiPM Measured CRT = 120 ps FWHM (for two detectors in coincidence). D.R. Schaart et al, IEEE NSS-MIC 2011 6

What is the best possible timing resolution achievable with a given scintillation detector?

Scintillation photon counting statistics γ emission γ absorption at t = Θ Emission of N sc optical T e = {t e,1 , t e,2 , …, t e ,Nsc } photons Detection of N optical T d = {t d,1 , t d,2 , …, t d ,N } photons N = η N sc , where η is the Ξ (= estimate of Θ ) photodetection efficiency (PDE) Dennis R. Schaart 8 Delft University of Technology

Fisher information and the Cramér–Rao lower bound 1 Ξ ≥ var( ) ( ) Θ I T d ( ) = ⋅ Ξ ≥ Θ CRT 2.35 2 var( ) 2.35 2 / I LB T d • The Cramér–Rao inequality defines the lower bound on the CRT of a pair of scintillation detectors • To calculate this lower bound (CRT LB ) we need the Fisher information I Td in the set T d Dennis R. Schaart 9 Delft University of Technology

Calculation of CRT LB τ τ d Parameters included in the calculation: r • Scintillation light yield Y Photodetection efficiency η • • Scintillation pulse shape, → For example, bi-exponential pulse with rise time constant τ r and decay time constant τ d • Probability density function describing the single-photon timing uncertainty → comprises optical path length variations in crystal, transit time spread (TTS) of sensor, trigger jitter, etc. → for a very small crystal and near-perfect detector readout, this contribution is dominated by the photosensor TTS → here represented by a Gaussian with standard deviation σ The math involves order statistics, it can be found in: S. Seifert, H.T. van Dam, and D.R. Schaart, “The lower bound on the timing resolution of scintillation detectors,” Phys Med Biol 57, 1797-1814, 2012 Dennis R. Schaart 10 Delft University of Technology

What are the physical limits on the timing resolution of PET scintillation detectors?

Lower bound on the CRT of LSO:Ce,Ca Measured: ~125 ps CRT LB : ~110 ps Transit Time Spread, σ (ps) 1 ( ) Ξ ≥ var ( ) Θ I T d N = 7500, σ = 50 ps CRT < 100 ps seems feasible with further SiPM improvements (PDE and TTS) Photodetection efficiency (PDE) Lower bound on the CRT of LSO:Ce,Ca + MPPC as a function of PDE and TTS Dennis R. Schaart 12 Delft University of Technology

PET scintillators τ ∝ From our CR model: d CRT LB N sc NaI:Tl BGO LSO:Ce LSO:Ce,Ca LaBr 3 :Ce Density (g/cm 3 ) 7.13 7.4 3.67 7.4 5.1 Effective Z 75 66 66 47 51 Atten. l. 511 keV (mm) 11.4 29.1 10.4 11.4 21.3 Decay time (ns) 300 40-45 30-35 16 230 30,000 # photons /MeV 40,000 8,500 30,000 70,000 Emission max. (nm) 480 420 420 410 380 Hygroscopic no no no yes yes Dennis R. Schaart 13 Delft University of Technology

Faster scintillator: LaBr 3 :Ce(>10%) 1 ( ) Transit Time Spread, σ (ps) Ξ ≥ var ( ) Θ I T d τ r = 150 ps, σ = 50 ps, PDE = 0.5 o < 50 ps feasible ? Rise Time Constant (ps) In principle, a CRT of ~50 ps might be feasible using LaBr 3 :Ce with high Ce concentration and by increasing SIPM PDE to ~50% and TTS to ~50 ps Dennis R. Schaart 14 Delft University of Technology

The holy grail: “10-picosecond PET” With a CRT less than ~20 ps events an be localized directly: • image reconstruction no longer necessary! • only attenuation correction • real-time image formation t 1 detector 1 position x along LOR t 1 - t 2 ∆ = ⋅ x c CRT / 2 ∆ ≤ Aim: x d t 2 ⇒ ≤ detector Tube or Line of CRT 2 / d c 2 Response (LOR) Clinical PET: ≤ ≤ 2 mm d 4 mm ⇒ ≤ CRT 20 ps d Dennis R. Schaart 15 Delft University of Technology

Ultrafast scintillators: example CRT < 20 ps in Transit Time Spread, σ (ps) principle feasible 1 ( ) Ξ ≥ var ( ) Θ I Example: τ d and τ r equal to ZnO:Ga T d Light Yield (photons/MeV) If a sub-ns scintillator emitting at least several thousand photons per MeV around ~400 nm can be made, sub-20 ps PET may come within reach Dennis R. Schaart 16 Delft University of Technology

We have reported experimental CRTs close to CRT LB in small crystals. But how about larger ones?

DOI-dependent signal delay in crystal Depth-of-interaction (DOI) variations deteriorate timing resolution γ 2 γ 1 gamma photon speed: scintillation photon speed: WW Moses and SE Derenzo IEEE Trans. Nucl. Sci. 46, 474-478 (1999) Dennis R. Schaart 18 Delft University of Technology

Depth-of-interaction determination Methods to determine DOI: (a) layered design, (b) single crystals with dual- sided readout, (c) phoswich design, (d) monolithic scintillator, (e) dual layer with offset, (f) dual layer with mixed shapes From: Peng & Levin, Current Pharmaceutical Biotechnology 11, 555-571, 2010 19

Digital PET system • Local position decoding and time-stamping → no limit on no. of channels, no loss of (Fisher) information • Real-time DOI correction of timing and spatial information • Fast, accurate & repeatable system calibration and time alignment Real-time signal processing Immediate digitization Detector Module System Images courtesy of Philips 20

1 ( ) Conclusion Ξ ≥ var ( ) Θ I T d With existing scintillators and photosensors, CRT’s of ~100 ps FWHM are close to the lower bound imposed by photon counting statistics ⇒ further improvement only possible by decreasing the lower bound! CRT < 20 ps in principle feasible Key enablers required: Bright (>> 10 3 ph/MeV), ultrafast • (~ 1 ns) scintillation materials Transit Time Spread (ps) • Ultraprecise (<< 100 ps TTS), highly efficient (PDE → 1) photon counters • Detector design mitigating optical transit time spread (<< 100 ps) while maintaining high gamma detection efficiency ( → 1) ⇒ None of these are available yet, but none are physically impossible Light Yield (photons/MeV) Dennis R. Schaart 21 Delft University of Technology

Thank You Dennis R. Schaart 22 Delft University of Technology

Backup slides Dennis R. Schaart 23 Delft University of Technology

Dennis R. Schaart 24 Delft University of Technology

Time-of-flight PET The accuracy of source position localization along line of response depends on the coincidence resolving time (CRT) ∆ x = uncertainty in position along LOR = c . CRT/2, where c is the speed of light. ∆ x The TOF benefit is proportional to ∆ x/D, where D is the effective patient diameter. => The smaller the CRT, the better. D State-of-the-art: CRT ≈ 500 ps ⇒ ∆ x ≈ 7.5 cm. Dennis R. Schaart 25 Delft University of Technology

Some essential findings Lower bound on the FWHM coincidence resolving time (CRT LB ) for 2 detectors, assuming Gaussian time difference spectra: ( ) = ⋅ Ξ = Θ CRT 2.35 2 var ( ) 2.35 2 / I LB LB T d 1 ∝ CRT LB N 1 τ << τ ∧ σ << τ ⇒ ∝ CRT r d d LB τ d τ ↓ ⇒ ↓ RT C r LB The latter 2 properties are due to the fact that most of the timing information is carried by the first detected photons, i.e. in the rising part of the pulse. S. Seifert et al, “The lower bound on the timing resolution of scintillation detectors,” 26 Phys Med Biol 57, 1797-1814, 2012

Order Statistics Timestamp for the n th detected scintillation photon n = 1 n = 5 n = 10 n = 15 n = 20 Exemplary probability density functions for the n th order statistic for LYSO:Ce on MPPC-S10362-33-050C Dennis R. Schaart 27 Delft University of Technology