Jorge Cabello PET, SPECT, Animal PET · Jorge Cabello. Technische Universität München...

Technische Universität München

Nuklearmedizinische Klinik und Poliklinik

Klinikum rechts der Isar Technische Universität München


Klinikum rechts der Isar Technische Universität MünchenTechnische Universität München

PET, SPECT, Animal PET

Jorge Cabello





Klinikum rechts der Isar

• Basic Nuclear Medicine

• Detectors

• Gamma Camera, SPECT

• Positron Emission Tomography

• Multimodal Imaging

• Biokinetic Modelling






Aims of Nuclear Medicine

• Diagnostics

Visualisation and quantification of biochemical

processes in vivo

• Therapy:

Treatment of pathologic processes based on selective

accumulation in body tissues






Principles of Nuclear Medical Diagnostics

• Tracer principle

Radiopharmaceuticals are distributed, metabolized or excreted in

the organism according to their structure

• Representation of body functions by:

– Images

– Numerical data

– Graphs






Positron Emission Tomography (PET)

Most sensitive method for

quantitative measurement of

physiologic processes

in vivo

13.06.2016 5






Coincidence circuit

PET Measuring Principle

Electronic Collimation

(511 keV)

(511 keV)

Nucleus

e+

e-

180±0.25°

13.06.2016 6






PET Nuclides

NuclideHalf life

(min)

EMax

(MeV)

Rmax

(mm H2O)

Ravg

(mm H2O)

11C 20.40 0.97 5.0 0.3

13N 9.90 1.19 5.4 1.4

15O 2.05 1.72 8.2 1.5

18F 109.70 0.64 2.4 0.2

68Ga 4086 1.88 - -

13.06.2016 7E: Energy, R: Range






Typical radioligands

Radioligand Target18F-FDG Glucose consumption (cancer, dementia…)

68Ga-PSMA Prostate cancer

18F-FET Aminoacid transporter (glioma grading)

18F-DOPA Dopamine transporters (Schizophrenia, Parkinson)

18F-FMISO Hypoxia (cancer cells resistance)

11C-PIB Fibrillar amyloid-beta (Aβ) plaques (Alzheimer)

13N-NH3 Myocardial perfusion

15O-H2O Brain oxygenation






Detector

Element

PET

Coincidence

lines

Field

of view

13.06.2016 9






Positron Emission Tomography – 3D

Scattered within FOV

Random Coincidences

True Coincidences

Scattered outside FOV

CrystalShielding

Short Coincidence Window

Good Energy Resolution

High Crystal Efficiency

Crystal

13.06.2016 10






PET Block Detector

13.06.2016 11






PET Block Detector

X

y

A

C D

B X =

y =

(B+D) - (A+C)

(A+B+C+D)

(A+B) - (C+D)

(A+B+C+D)

Crystal Identification

13.06.2016 12

Anger logic:






PET Block Detector BGO Crystals, 20 or 30 mm long

13.06.2016 13






0.0 5 10 15

1.0

0.5

0.0

Resolution

10 mm

4 mm

Object Size (mm)

Re

co

ve

ry C

oe

ffic

ien

t

~0.8

~0.4

Effect of Spatial Resolution

13.06.2016 14






Characteristics PET – Determining Factors

• Detector material

decay time time resolution coincidence window

light yield energy resolution scattering fraction

atomic number attenuation length sensitivity

• Tomograph

detector concept spatial resolution

diameter sensitivity

scattering fraction

shielding randoms

13.06.2016 15






Scintillation Crystals

PropertyNaI BGO LSO GSO

NaI:Tl Bi4Ge3O12 Lu2SiO5:Ce Gd2SiO5:Ce

Density (g/cm3) 3,67 7,1 7,4 6,7

Effective Z 51 73 65 59

Attenuation length at

511keV (mm)

29,1 10,4 11,4 14,1

Light yield (photons/MeV) 41000 9000 26000 8000

Decay time (ns) 230 300 40 60

Emission (nm) 410 480 420 440

13.06.2016 16

Lu-176 (2,6%): + >350 keV: ~100/sec per cm3






PET Systems: Characteristics, Limitations

• Spatial resolution

• Sensitivity

• Scattering

• Random coincidences

• Dead time of system

Measurement in realistic situation

Values can differ depending on the object

13.06.2016 17






Clinical PET

Crystals BGO, LSO,LYSO, GSO

Spatial resolution (mm) 4.5 - 5.0

Energy resolution (%) 12 - 23

Scatter fraction 2D (%) 10 - 15

Scatter fraction 3D (%) 35 - 42

Sensitivity 2D (cps/Bq/ml) 6 - 9

Sensitivity 3D (cps/Bq/ml) 35 - 55

max. NEC 2D 50 - 100

max. NEC 3D 70 - 180

13.06.2016 18






New Ce-doped Scintillators

PropertyRbGd2

Br7

LaCl3 LaBr3

Light yield

(photons/MeV)

56000 50000 56000

Energy resolution

(662 keV)

4.5% 3.2% 2.9%

Decay time (ns) 45 20 25

Density (g/cm3) 4.7 3.9 5.3

13.06.2016 19

*Image courtesy of M. Balcerzyk, Soltan Institute

1˝ LaCl3:Ce






500 ps timing resolution 7.5 cm localization

DMid 1980s: BaF2

Now: LaBr3, LSO

13.06.2016 20

Time-of-Flight PET






Time-of-Flight PET

Δ𝑥 =𝑐

2Δ𝑡

The real gain is in noise:

Type equation here.

N𝐸𝐶𝑅(𝑇𝑂𝐹) = 𝑁𝐸𝐶𝑅(𝑛𝑜𝑛 − 𝑇𝑂𝐹)𝐷

Δ𝑥D: Diameter of the object

Spatial resolution gain:






System time resolution: 460 ps System energy resolution: 7.5%

LaBr3 (5% Ce) 4 x 4 x 30 mm3

LaBr TOF PET Scanner

Joel Karp et al. MIC 2005

13.06.2016 22






13.06.2016 23

TOF

No TOF

LaBr TOF PET Scanner

Number of counts (9-54 M)

Daube-Witherspoon et al PMB 2009






13.06.2016 24

Vereos PET/CT (Philips Healthcare)

Digital SiPM technology

LYSO crystals

Time resolution < 316 ps






Time-of-Flight PET






PET - Quantification

Goal: Physiologic parameter

Standardized uptake values (SUV)

Requirement: Absolute activity concentration

Necessary: Corrections for

• detector differences (sensitivity)

randoms

scatter

attenuation

dead time

13.06.2016 26






AttenuationLosses due to Compton and photo effect

13.06.2016 27






13.06.2016 28

Attenuation

Real Reconstructed






Coincidence method

Ge-68 rod source

Single photon method

Cs-137 point sourceshielded

(662 keV)high rate

PET – Transmission Measurement

13.06.2016 29






Attenuation: State of the art

• Rotating source

• CT is used for AC in PET/CT

• MR sequences are used for AC in PET/MR

Active area of research!

• TOF is used for AC in PET scanners with TOF

capabilities

Still recent and under evaluation for clinical prattice






Scatter correction

Scatter fraction: 40—60 %

Single scatter 90%

Multiple scatter 10%






Scatter correction

With scatter correction Without scatter correction

Projection space

(sinograms)

Image space

Scatter correction methods:

• Single scatter simulation

• Multiple energy windows

• Monte Carlo simulations






Standardized Uptake Value (SUV)

at a specific time point

SUV = Activity concentration in image (kBq/ml)

Injected activity (kBq) / body weight (kg)

Uptake concentration depends on each patient physiognomy

Lean body weight (Body weight-Body fat weight)

Body surface area (0.007184xW0.425xH0.725)





Klinikum rechts der Isar Technische Universität MünchenTechnische Universität München

Small animal research






~90% of all laboratory animals are mice

worldwide > 25 Mio. (Science 04/2000)

Animal Models

• Brain sciences: rat

• Oncology: rat, mouse

• Genetic research: mouse (“knock-out”)

13.06.2016 35






• C-11, F-18, H-13, P-32 tracers

• Measurement of time course in one animal (no follow-

up studies)

• Repeat measurements in the same animal

Size spatial resolution: 1-2 mm

Specific activity sensitivity: high (>2%)

Small Animal PET

in vivo autoradiography

13.06.2016 36






8 x 8 array of

LSO crystals (2 x 2 x 10 mm)

Optical fibersPosition sensitivePMT

Densely packed crystals

Cherry, 1997

UCLA microPET

13.06.2016 37






18F-FDG Rat Heart

13.06.2016 38

microPET

Crump Institute for Molecular Imaging

74 MBq, 45 min acquisition time






Crump Institute for Molecular Imaging

MicroPET P4

• 26 cm ring diameter

• 20 cm transverse FOV

• 7.8 cm axial FOV

• 168 detector modules (8x8)

• 4 rings of 42 detectors

• 10,752 individual detectors

• Transmission source

• Resolution 2.2 mm (10 ml)

• Sensitivity ~ 2%

13.06.2016 39






18F- FDG

Whole-Body

Biodistribution

in the Mouse

Crump Institute for

Molecular Imaging

13.06.2016

0

5

10

15

20

25

30

0 10 20 30 40 50 60

liverkidney

bladdertumor

Time (min.)






microPET II17,640 LSO elements (0.95x0.95x12.5 mm)

8 cm transaxial field of view

4.8 cm axial field of view

Reconstructed resolution ~ 1.2 mm

(filtered backprojection)

Sensitivity: ~2.3% at center of FOV

(250-750 keV)

13.06.2016 41

DEPARTMENT OF BIOMEDICAL ENGINEERING






APDs and SiPMs versus PMTs

• PRO:

– very compact (one-to-one coupling)

– high quantum efficiency

– low bias voltage

– work in magnetic fields

• CON:

– noise

– lower gain

– timing performance

13.06.2016 42






Resolution 1.75 mm (intrinsic)2.1 2.1 3.1 mm3 or 14 µl

Efficiency 200 cps/µCi ( 0.51% )

Sensitivity 2 kcps/µCi/ml/cm

Peak NEC 61 kcps (11 cm)

Lecomte et al, IEEE TNS 43 (1996) 1952-7

APD Detector Module

BGO

Scintillator

Avalanche

Photodiode

Sherbrooke Animal PET Scanner

13.06.2016 43






0

20

40

60

80

100

120

140

160

180

0 4 8 12 16 20 24 28 32

LV V

olu

me

(µl)

Gate Number

Normal Rat, 250 g

ECG-Gating

1 cm

FDG-PET Study of Cardiac Function in Rat

13.06.2016 44






Hamamatsu

Photonics1 cm

Photomultiplier

Avalanche photodiodes

APD Matrices

13.06.2016 45






APD matrix

LSO crystals(3.7 x 3.7 x 12 mm3)

- Energy resolution: 15%

- Spatial resolution: 2.3 mm

- Sensitivity: 0.04 %

4 mm

Munich Avalanche Diode PET Prototype

13.06.2016 46

MPI






0 100%

MADPET – In Vivo Study

FDG in the myocardium of a rat

1 mCi, 45 min p.i.,

18 min acquisition time

Realigned images

MPI

13.06.2016 47






Depth-of-Interaction

(DOI)

Coincidence Response FunctionDepends on ring diameter, crystal length

13.06.2016 48






crystal

light sensor

light sensor

ratio of signals

DOI

LSO

GSO crystal

light sensor

light sensor

crystal

signal shape

DOI

individual layers

DOI

Depth Of Interaction (DOI) Measurement

13.06.2016 49






• Custom 64 element PD array identifies hit crystal

• PD/(PD+PMT) determines depth of interaction

• Photomultiplier tube provides timing pulse

LSO Array

64

Element

PD Array

1” Square PMT1" Square Photomultiplier Tube

20mm

Array of 64 Photodiodes

64 LSO Crystals 3 mm square

1"

1"

B. Moses, Lawrence Berkeley Laboratory

LBL PET Detector Concept

13.06.2016 50






LGSO/LYSO

GSO

Phoswich Detector – DOI

13.06.2016 51

Block detector

with pulse shape

discriminator

PMT PMT

HRRT: MPI Köln, CTI 1998

ATLAS: NIH, 2001

Light guide






Individual read-out of

2 radial crystal layers

1.6 mm x 1.6 mm

70 mm diameter

monolithic APD Matrix

MADPET II Dual Layer Tomograph

MPI

13.06.2016 52






• Energy resolution:

~ 15% @ 511 keV

• Time resolution: 2,5 ns

APD-Matrix

LSO Crystals(2x2x8 mm3)

APD-MatrixLSO Crystals(2x2x6 mm3)

LSO-APD-Detector Module for 2 Radial Layers

13.06.2016 53






MADPET IV Dual Layer Tomograph

Designed to be compatible with a 7T MRI scanner

Stand alone

PET insert

PET insert integrated

in volume coil

Compact uniform

crystal distribution

Crystal structure

with SiPMs

Densely packed

cabling

150 mm 88 mm

20 mm

• High resolution– 1.5x1.5 mm2 LYSO crystals.

• High count rate – one-to-one coupling.

• Uniform spatial resolution– dual layer: 6/14 mm long crystals.

• No shielding in MR bore– No magnetic-sensitive

components

• Temperature stable SiPMs– No cooling






Small Animal PET – Systems System Res.(mm) Sens. D(mm) LZ(mm) Detector Type

RAT –PET 2.4 4.3% 115 50 BGO PMT

Sherbrooke 2.1 0.51% 310 10.5 BGO APD

TierPET 2.1 0.32% 160 – 500 40 YAP PSPMT

MicroPET P4# 2.0 1.35% 260 80 LSO PSPMT

Brussels 3.0 3.5% 200 52 BaF2 Drift Ch.

YAP-PET 2.0 1.7% 100 – 250 40 YAP PSPMT

HIDAC# 1 0.9% 100 – 200 210 MWPC

ATLAS 1.9 1.8% 118 20 phoswich§ PSPMT

Massachusetts 1.3 0.08% 120 4.5 LSO PMT

MADPET 2.30 0.035% 86 3.6 LSO APD

MADPET II 1.0 2% 71 18.1 LSO APD m.

13.06.2016 55

Sensitivity at different energy thresholds #commercial; §GSO + LGSO






• Anesthesia

• Preparation of animals

• Fixation of animal

• Triggering (respiration, ECG)

• Morphologic Imaging

Animal PET – Other Issues

13.06.2016 56

Jorge Cabello PET, SPECT, Animal PET · Jorge Cabello. Technische Universität München...

Documents

Transcript of Jorge Cabello PET, SPECT, Animal PET · Jorge Cabello. Technische Universität München...