Chicago PET Development and R P i Di i l TOFPETRecent ...

Chicago PET Development and R P i Di i l TOFPETRecent Progress in Digital TOFPET1. Heejong Kim, Chien-Min Kao, Qingguo Xie, Yun Dong,

Ming-Chi Shih, Antonio Machado, and Chin-Tu Chen2 Octavia Biris Jialin Lin Fukun Tang Lin Zhou and2. Octavia Biris, Jialin Lin, Fukun Tang, Lin Zhou, and

Henry Frisch3. Robert Wagner, Karen Byrum, and Gary Drake4. Woon-Seng Choong and William Moses

1 Department of Radiology & Committee on Medical• 1. Department of Radiology & Committee on Medical Physics, University of Chicago, IL

• 2. Enrico Fermi Institute & Department of Physics, p y ,University of Chicago, IL

• 3. High Energy Physics Division, Argonne National Laboratory Argonne ILLaboratory, Argonne, IL

• 4. Lawrence Berkeley National Laboratory, Berkeley, CA

PET Imaging Chain and UC PET R&DCyclotron/

Radiotracer Detector &

System Clinical Outcomes

& Biological[Multi-Modality

Probes][Panel-PET &

SiPM]Discoveries

[Cancer, Cardiac, Brain Drug etc ]

Subject (Human/Animal)Performance Electronics

Brain, Drug, etc.]

(Human/Animal)Performance Evaluation

[Task-Based [Digital PET]

Integration with Medicine & Biology

Image Assessment] Medicine & Biology

Quantitative Image Analysis

[MM QIA & Li t M d

Reconstruction [MM-IR & ROI-IR]

[MM QIA & List-Mode Dynamic 4D/5D QIA]

Q tit ti I iQuantitative ImagingMulti-Modality IntegrationMulti Modality Integration

High-PerformanceLow-Cost

Broad-AccessBroad-Access





Probes][Panel-PET &

SiPM]Discoveries



Brain, Drug, etc.]






[MM QIA & Li t M d



Imaging of Life andg gLife Processes

Patient 1 Patient 2Live Brain Dead BrainPatient 1 Patient 2

MR PET MR PET

Task-Based Image Quality AssessmentTasks Detection and EstimationTasks – Detection and Estimation

2008 IEEE NSS/MIC/RTSD2008 IEEE NSS/MIC/RTSDMIC Short Course

" Image Quality in Adaptive and Multimodality Imaging"Multimodality Imaging

20 October 2008Dresden, Germany

Organizer: Harrison Barrett,Organizer: Harrison Barrett, Matthew A. Kupinski,

Lars R FurenlidLars R. Furenlid


RadiotracerDetector &



Probes][Panel-PET &

SiPM]Discoveries



Brain, Drug, etc.]






[MM QIA & Li t M d



Key Characteristics of Key Characteristics of

Biomarker GeneratorBiomarker Generator

•• Lower cost & much smaller to be Lower cost & much smaller to be located at scannerlocated at scannerTo be an approved FDA medicalTo be an approved FDA medical•• To be an approved FDA medical To be an approved FDA medical devicedevice

•• Produce dose of FProduce dose of F--18 or C18 or C--11 11 bi k i 20 ibi k i 20 ibiomarker in 20 minutesbiomarker in 20 minutes

•• Base chemistry system for drug Base chemistry system for drug discoverydiscovery

Micro AcceleratorMicro Accelerator

Mi h i t & Mi fl idi

•• Handling of micro to millicuries, not Handling of micro to millicuries, not curiescuries

Microchemistry & Microfluidics

Courtesy ofNanotek & ABT

Multi-Modality Targeting Molecular Imaging & Therapeutic Probes p

(Phage and Micelle Nanosystem)

Ultrasound, MRI, SPECT, PET, X-Ray/CT Fluorescence & TherapeuticsX-Ray/CT, Fluorescence & Therapeutics





Probes][Panel-PET &

SiPM]Discoveries



Brain, Drug, etc.]






[MM QIA & Li t M d



Image Co-Registration & IntegrationFusion of PET, SPECT, MRI, CT,MRI, CT,

EPRI, Histology

Halpern,Halpern, Pelizzari KarczmarWeichselbaum





Probes][Panel-PET &

SiPM]Discoveries



Brain, Drug, etc.]






[MM QIA & Li t M d

Reconstruction[MM-IR & ROI-IR]


600 ps

2 ns



SystemClinical Outcomes


Probes][Panel-PET &

SiPM]Discoveries



Brain, Drug, etc.]






[MM QIA & Li t M d



Silicon PM CharacterizationF tFront

MPPC: 1x1mm2

25-μm, 50-μm, or 100-μm

Back

Source:F 18

LYSO:1x1x10mm3 2x2x10mm3F-18 1x1x10mm3, 2x2x10mm3

F-18/LYSO Sample PulsesF 18/LYSO Sample Pulses

PMT 25-μm MPPC

50-μm MPPC 100-μm MPPC

A Table-Top PrototypeA Table Top PrototypeThe prototype consists of two HRRT Detector HeadsHRRT (High Resolution Research Tomograph) detector heads. The spacing between detectors shown is ~6 cm, which is adequate for imaging rodents.

A single double-layered, 8 x 8 LSO crystalA single double layered, 8 x 8 LSO crystal block affixes onto 4 photomultiplier tubes in the quadrant-sharing configuration.

CNMF, September 26, 2008

Central SensitivityCentral Sensitivity(GATE Simulation, 20% ER, 3ns TR)

25

30 2ns6nsS

e

15

2010ns

ensitiv

10

15ity (%)

0

5

0200 250 300 350 400 450

LLD (keV)

Noise-Equivalent Count RateNoise Equivalent Count RateComparison with reported NECR peaks

Mouse RatMouse

Reported NECR peaksReported NECR peaks

FDG Resolution phantomFDG Resolution phantomreal data

1 00.75

2.4

1.0 mm

1 35

mm

mm

2 0

1.35mm

1 7 2.0 mm

1.7 mm

Modeling the Ideal line integralModeling the responses by MC simulation

Ideal line integral

Sample ImageSample Imagereal FDG-Rat data

Ideal line integral Modeling responseIdeal line integral Modeling response

22

Initial FDG-Rat ImagesInitial FDG Rat Images1020

Transaxial

10

20

30

40

20

40

60 40

50

60

70

80

100

20 40 60 80 100

70

80120

140

160

180

200

20

40

20 40 60 80 100

220

50 100 150 200 250

60

CoronalSagittalSagittal





Probes][Panel-PET &

SiPM]Discoveries



Brain, Drug, etc.]






[MM QIA & Li t M d



Digital PET Data AcquisitionDigital PET Data AcquisitionA Multi-Threshold Approach

d

TDCPMT IN

V1

discriminators

TDC

C

V2

TDC

TDC

V3

TDCV4

Multi-Threshold Approachpp

•Sampling pulse at pre-defined voltagep g p p glevels.

•Output : only digitized timings.

•Pulse reconstruction using digitized timings.

•Remove analog blocks.(Pre-Amp, ADC, CFD)

Di it l Si l P i (DSP) t h l•Digital Signal Processing (DSP) technology can be utilized.

(event time, energy)PMT waveform by 20GS/s oscilloscopey psuperimposed with timing readouts by the multi-threshold board + HPTDC

Multi Threshold Board + HPTDCMulti-Threshold Board + HPTDCMulti threshold discriminator boardMulti-threshold discriminator board•2 boards with 4channels in each.

•0-700mV of adjustable threshold levelHPTDC (CERN) •0-700mV of adjustable threshold level.

•Used ADCMP582 comparators.4 chs output

•Timings at leading and falling edges.

M lti th h ld b d (l ft)

InputThreshold SetHigh Performance TDC (HPTDC)

8/32 channels.25 ps/bitMulti-threshold board (left)

connected to HPTDC module (right).25 ps/bit.developed at CERN.

Experimental Setupp p•Two Hamamatsu R9800 photomultiplier tubes

(HV 1 300V)(HV = -1,300V)•Coupled with LSO crystals

( 6.25x6.25x25mm3).S t d 5 t•Separated 5cm apart.

•Na-22 used for positron source locatedat the center.

•Multi threshold discriminator board setup:•Multi-threshold discriminator board setup:Inputs from 2 PMT signals

Thresholds : 50, 100, 200, 300mV•Timing Readout :•Timing Readout :

TDS6154 oscilloscope20GS/s.(Tektronix)

HPTDC.A Block diagram of the setup HPTDC.( 8chs, 25 ps/bit, developed at CERN)

A Block diagram of the setup.

Time Resolution of DiscriminatorTime Resolution of Discriminator

Time(ns)0.14 0.16 0.18 0.2 0.22 0.24 0.26 0.28 0.30

50

100

150

200

250

/ ndf 2χ 49.31 / 21

Constant 7.4± 270.4

Mean 0.0002± 0.1949

Sigma 0.000111± 0.007144

/ ndf 2χ 49.31 / 21


Mean 0.0002± 0.1949

Sigma 0.000111± 0.007144

Time(ns)0.14 0.16 0.18 0.2 0.22 0.24 0.26 0.28 0.30

50

100

150

200

250

/ ndf 2χ 49.31 / 21


Mean 0.0002± 0.1949

Sigma 0.000111± 0.007144

•Sent pulse generator signals to two channels.

Time(ns)0.14 0.16 0.18 0.2 0.22 0.24 0.26 0.28 0.30

50

100

150

200

250

/ ndf 2χ 49.31 / 21


Mean 0.0002± 0.1949

Sigma 0.000111± 0.007144

/ ndf 2χ 49.31 / 21


Mean 0.0002± 0.1949

Sigma 0.000111± 0.007144

Time(ns)0.14 0.16 0.18 0.2 0.22 0.24 0.26 0.28 0.30

50

100

150

200

250

/ ndf 2χ 49.31 / 21


Mean 0.0002± 0.1949

Sigma 0.000111± 0.007144

•Measured time difference with the TDS6154 oscilloscope.

Time(ns)0.14 0.16 0.18 0.2 0.22 0.24 0.26 0.28 0.30

50

100

150

200

250

/ ndf 2χ 49.31 / 21


Mean 0.0002± 0.1949

Sigma 0.000111± 0.007144

/ ndf 2χ 49.31 / 21


Mean 0.0002± 0.1949

Sigma 0.000111± 0.007144

Time(ns)0.14 0.16 0.18 0.2 0.22 0.24 0.26 0.28 0.30

50

100

150

200

250

/ ndf 2χ 49.31 / 21


Mean 0.0002± 0.1949

Sigma 0.000111± 0.007144

•Time resolution of single channel : ~13.3ps(FWHM)

Time(ns)0.14 0.16 0.18 0.2 0.22 0.24 0.26 0.28 0.30

50

100

150

200

250

/ ndf 2χ 49.31 / 21


Mean 0.0002± 0.1949

Sigma 0.000111± 0.007144

/ ndf 2χ 49.31 / 21


Mean 0.0002± 0.1949

Sigma 0.000111± 0.007144

Time(ns)0.14 0.16 0.18 0.2 0.22 0.24 0.26 0.28 0.30

50

100

150

200

250

/ ndf 2χ 49.31 / 21


Mean 0.0002± 0.1949

Sigma 0.000111± 0.007144

Time offset between two channelsof the Multi-threshold discriminator.

Pulse Reconstruction (HPTDC)Pulse Reconstruction (HPTDC)

Charge(pC)0 100 200 300 400 500 600 700 8000

20

40

60

80

100

120

/ ndf 2χ 83.05 / 31


Mean 0.6± 369.6

Sigma 0.48± 20.76

/ ndf 2χ 88.29 / 33


Mean 0.8± 357.5

Sigma 0.78± 27.02

PMT Signal

Reconstructed

•Select the gamma coincidence events.events with 2, 3 and 4 hits from each b d

Charge(pC)0 100 200 300 400 500 600 700 8000

20

40

60

80

100

120

/ ndf 2χ 83.05 / 31


Mean 0.6± 369.6

Sigma 0.48± 20.76

/ ndf 2χ 88.29 / 33


Mean 0.8± 357.5

Sigma 0.78± 27.02

PMT Signal

Reconstructed

board.

•Reconstructed pulse shape.

Charge(pC)0 100 200 300 400 500 600 700 8000

20

40

60

80

100

120

/ ndf 2χ 83.05 / 31


Mean 0.6± 369.6

Sigma 0.48± 20.76

/ ndf 2χ 88.29 / 33


Mean 0.8± 357.5

Sigma 0.78± 27.02

PMT Signal

Reconstructed •Linear fit on the leading edge. (event time).

Charge(pC)0 100 200 300 400 500 600 700 8000

20

40

60

80

100

120

/ ndf 2χ 83.05 / 31


Mean 0.6± 369.6

Sigma 0.48± 20.76

/ ndf 2χ 88.29 / 33


Mean 0.8± 357.5

Sigma 0.78± 27.02

PMT Signal

Reconstructed

•Exponential fit on the falling edge. (energy, decay constant)

Energy distribution of 511keV gamma.

Pulse Recontstruction 2Pulse Recontstruction - 2

Time(ns)0 10 20 30 40 50 60 70 80 90 1000

50

100

150

200

250

300

350 / ndf 2χ 2.673 / 10


Mean 0.04± 44.82

Sigma 0.032± 1.709

/ ndf 2χ 25 / 20

Constant 4.9± 150

Mean 0.11± 43.89

Sigma 0.078± 3.903

PMT Signal

Reconstructed

Time(ns)0 10 20 30 40 50 60 70 80 90 1000

50

100

150

200

250

300

350 / ndf 2χ 2.673 / 10


Mean 0.04± 44.82

Sigma 0.032± 1.709

/ ndf 2χ 25 / 20

Constant 4.9± 150

Mean 0.11± 43.89

Sigma 0.078± 3.903

PMT Signal

Reconstructed

20GS waveform Multi-threshold

Energy resolution 13%(FWHM)

Time(ns)0 10 20 30 40 50 60 70 80 90 1000

50

100

150

200

250

300

350 / ndf 2χ 2.673 / 10


Mean 0.04± 44.82

Sigma 0.032± 1.709

/ ndf 2χ 25 / 20

Constant 4.9± 150

Mean 0.11± 43.89

Sigma 0.078± 3.903

PMT Signal

Reconstructed

resolution 13%(FWHM) 18%

Decay constant

45ns (4ns width)

44ns (9ns width)

Time(ns)0 10 20 30 40 50 60 70 80 90 1000

50

100

150

200

250

300

350 / ndf 2χ 2.673 / 10


Mean 0.04± 44.82

Sigma 0.032± 1.709

/ ndf 2χ 25 / 20

Constant 4.9± 150

Mean 0.11± 43.89

Sigma 0.078± 3.903

PMT Signal

Reconstructed

( ) ( )

The decay time constant.

Coincidence Timing ResolutionCoincidence Timing Resolution

Time(ns)-1.5 -1 -0.5 0 0.5 1 1.50

20

40

60

80

100

120

140

/ ndf 2χ 58.95 / 53


Mean 0.0032± -0.1597

Sigma 0.0023± 0.1399

•Select the coincidence events.

L t fit t th l di d

Time(ns)-1.5 -1 -0.5 0 0.5 1 1.50

20

40

60

80

100

120

140

/ ndf 2χ 58.95 / 53


Mean 0.0032± -0.1597

Sigma 0.0023± 0.1399

•Least square fit to the leading edge timings.

Use two leading edges

Time(ns)-1.5 -1 -0.5 0 0.5 1 1.50

20

40

60

80

100

120

140

/ ndf 2χ 58.95 / 53


Mean 0.0032± -0.1597

Sigma 0.0023± 0.1399

•Use two leading edgeswith100, 200mV thresholds.

•Extrapolated at 0mV

Time(ns)-1.5 -1 -0.5 0 0.5 1 1.50

20

40

60

80

100

120

140

/ ndf 2χ 58.95 / 53


Mean 0.0032± -0.1597

Sigma 0.0023± 0.1399

•Extrapolated at 0mV.

•The time difference, t1-t2. (FWHM)Oscilloscope : 330ps

Time difference of 511keV gammacoincidence events

Oscilloscope : 330psHPTDC : 350ps





Probes][Panel-PET &

SiPM]Discoveries



Brain, Drug, etc.]






[MM QIA & Li t M d



Motor Activity Study (Stroke)Motor Activity Study (Stroke)

Motor Activity StudiesMotor Activity Studies

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