Opportunities and Technological Challenges
Ewald Roessl, Bernhard Brendel, Gerhard Martens, Roland Proksa,
Friedericke Schmidt, Axel Thran, Jens-Peter Schlomka
Philips Research Europe - Hamburg, Aachen
AAPM 51 st Annual Meeting, Anaheim, California July 27, 2009

Overview
• Motivation
• Physics of Photon-Counting Detectors
• Application Examples
• Technological Challenges
AAPM 51 st Annual Meeting, July 26-30, Anaheim California 2009, E. Roessl 2

Overview
• Motivation
• Physics of Photon-Counting Detectors
• Application Examples
• Technological Challenges
AAPM 51 st Annual Meeting, July 26-30, Anaheim California 2009, E. Roessl 3

Motivation for photon-counting CT
• Improved SNR with respect to integrating detectors [1], [2]
• Dose reduction (reduced electronic noise)
• Improved tissue differentiation / material labeling
• Improved quantitative imaging with CT
• Enabling novel imaging techniques, e.g., K-edge imaging [3],[4],[5]
• Reduction of beam hardening artifacts
[1] Tapiovaara, Wagner, Phys. Med. Biol., 30 (6), 1985.
[2] Shikaliev, Phys. Med. Biol., 53 (20), 2008
[3] S.J. Riederer, C.A. Mistretta, Med.Phys. 4 (6) (1977)
[4] Roessl, Proksa, Phys. Med. Biol., 52 (15), 2007.
[5] Schlomka et al., Phys. Med. Biol., 53 (15), 2008.
AAPM 51 st Annual Meeting, July 26-30, Anaheim California 2009, E. Roessl 4

Overview
• Motivation
• Physics of Photon-Counting Detectors
• Application Examples
• Technological Challenges
AAPM 51 st Annual Meeting, July 26-30, Anaheim California 2009, E. Roessl 5

Conventional Scintillator X-ray Detector
(schematic)
X-Ray Photon
Optical Photons Scintillator
Photo Diode charge collection
Integrator
A/D Converter
AAPM 51 st Annual Meeting, July 26-30, Anaheim California 2009, E. Roessl 6

T
1
T
2
T
3
T
4 u
Photon Counting X-ray Detector (schematic)
Direct Conversion
X-Ray Photon
Semiconductor electron/hole cloud holes electrons charge package
T
1
T
2 t
T n
AAPM 51 st Annual Meeting, July 26-30, Anaheim California 2009, E. Roessl
.
.
.
Bias digital counter digital counter digital counter
7

Simulation: Signal Generation in CZT or CdTe
Weighting Potential
• K-fluorescence
• (X-ray Compton scattering)
• Charge diffusion analytical: Kozorezov et al, J. Appl. Phys. 97, 074502 (2005)
• “Charge collection”: Induced currents low hole mobility and hole trapping, Ramo’s theorem, Small pixel effect
AAPM 51 st Annual Meeting, July 26-30, Anaheim California 2009, E. Roessl 8

Low-energy tail (241Am, 59.5 keV)
Measurement with oscilloscope Simulation
Energy loss due to K-fluorescence
K-fluorescence photons from neighbouring pixels
„background“ due to charge diffusion
• Histogram of single pixel, all pixels illluminated (<10keV was excluded)
• eVproducts CZT (produced before
2006), 3mm thick, 0.25 x 0.5 mm 2 pixel pitch
–
–
Confined weighting potential
Considerable charge diffusion
• Hole-induced low energy tailing:
Relevant for energies > 100 keV, almost negligible for 241 Am peak
Similar results (CdTe, 330µm pitch, 1 mm thickness):
Franchi et al, Photon counting X-ray imaging with
CdTe pixel detectors based on XPAD2 circuit, NIM A
563 (2006) 249–253
AAPM 51 st Annual Meeting, July 26-30, Anaheim California 2009, E. Roessl 9

Photon Counting Detector Modeling
• Forward model: M i
( A
1
,..., A
M
)
=
S i
( E )
Φ
( E ) e
−
α
M ∑
=
1 f α ( E ) A α dE , i
• Bin sensitivity S i
(E) & Spectrum
Φ
(E)
=
1 ,..., N
– Deduce phenomenological response function from series of monochromatic response measurements (K-escape, charge sharing, incomplete charge collection, etc.)
– Use measured tube spectrum
Φ
(E)
2.50E+03
2.00E+03
1.50E+03
1.00E+03
5.00E+02
0.00E+00
0 20 40 60 80 100
-5.00E+02
Detector response to monochromatic X-ray photons (Hasylab, Hamburg, Germany)
Schlomka et al., Phys Med Biol . 2008, 53 (15):4031-47
AAPM 51 st Annual Meeting, July 26-30, Anaheim California 2009, E. Roessl photon energy / keV
Bin sensitivities * spectrum
(6 energy bins, 90 kVp spectrum)
10

Overview
• Motivation
• Physics of Photon-Counting Detectors
• Application Examples
• Technological Challenges
AAPM 51 st Annual Meeting, July 26-30, Anaheim California 2009, E. Roessl 11

Applications Overview
Improve existing applications of CD and dual-energy CT and enable novel applications in x-ray computed tomography by energy-sensitive photon detection
• CT-Angiography
• Quantitative plaque analysis
• Easy separation of bones and vessels
• Separation of calcifications
• Tissue perfusion
• Higher sensitivity and accuracy for blood flow and blood volume measurements
• Detection of angiogenesis (Oncology)
• Myocardial Perfusion (infarct)
• Brain Perfusion (stroke)
• Novel Applications enabled by dedicated (targeted) contrast agents in combination with K-edge imaging
• CVD and Oncology
• …
AAPM 51 st Annual Meeting, July 26-30, Anaheim California 2009, E. Roessl 12

Beam hardening suppression
Bone phantom (
∅
5, 10, 20, 28.5mm) in water
Images of the 25-34 keV bin
• Decompose all bins to photo and Compton attenuation base
(Alvarez-Macovski)
• Calculate mono-energetic image
Mono-energetic Images at 40 keV
AAPM 51 st Annual Meeting, July 26-30, Anaheim California 2009, E. Roessl 13

Beam hardening suppression
Bone phantom (
∅
5, 10, 20, 28.5mm) in water
Cross-sections through object centre show no beam-hardening
Cut through the centre of reconstructed images of energy bin 25 – 34 keV
Cut through the centre of calculated monochromatic images at 40 keV
AAPM 51 st Annual Meeting, July 26-30, Anaheim California 2009, E. Roessl 14

K-edge Imaging in Computed Tomography 1),2),3)
• Selective imaging and quantification of (high Z) contrast agent elements: e.g., I, Gd, Au, Bi.
• Particularly interesting in combination with targeted contrast agents: “hot spot imaging”
Mass attenuation coefficient of Gadolinium
Hubbell, J.H. and Seltzer, S.M. (2004), Tables of X-Ray Mass
Attenuation Coefficients and Mass Energy-Absorption Coefficients
(version 1.4). [Online] Available: http://physics.nist.gov/xaamdi [2009,
July 24]. National Institute of Standards and Technology, Gaithersburg,
MD.
1) S.J. Riederer, C.A. Mistretta, Med.Phys. 4 (6) (1977)
2) E. Roessl, R. Proksa. Phys.Med.Biol. 52 (2007)
3) J.-P. Schlomka et al. Phys Med Biol. 53 (2008)
AAPM 51 st Annual Meeting, July 26-30, Anaheim California 2009, E. Roessl 15

X-Ray Tube Spectrum
Patient Attenuation
Compton Scatter
K-Edge Material
Photo-electric
E
Post Patient Spectrum
3E+11
3E+11
2E+11
2E+11
1E+11
5E+10
0
0 20 40 120 140 60 80
E / k e V
100
Energy Resolving Detector
160
E
AAPM 51 st Annual Meeting, July 26-30, Anaheim California 2009, E. Roessl 16

K-edge Sensitivity in CT
Detector type: measured resp. Tube voltage: 130kV
50
1e2
100
3e1
150
1e1
200
3e0
250
1e0
300
3e-1
350
1e-1
400
3e-2
450
1e-2
500
45 50 55 60 65 70 75 80 85
Z
Tube voltage: 130kV Object diameter: 400mm
10
1 10
2
Roessl et al. “ Sensitivity of Photon-Couting K-Edge
Imaging: Dependence on Atomic Number and Object
Size ,” in NSS Conf. Record, IEEE (2008).
Tissue
Tissue with CA d
Detector type: measured resp. Tube voltage: 130kV
D iodine (Z=53) barium (Z=56) gadolinium (Z=64) gold (Z=79) bismuth (Z=83)
10
0
10
1
10
0
10
-1 ideal resp.
gaussian resp.
shift inv. resp.
measured resp.
10
-2
45 50 55 60 65
Z
70 75 80 85
Gd (Z=64) particularly favourable
AAPM 51 st
10
-1
10
-2
50 100 150 200 250 300 350 400 450 500
D [mm]
Annual Meeting, July 26-30, Anaheim California 2009, E. Roessl 17

K-edge Imaging - projection based
Acquisition of energy-resolved attenuation measurements
(at least 3 independent)
Photo effect
25 35 45 55 65 75 85 95
E [keV]
Maximum likelihood processing
Decomposition to base materials attenuation
Compton effect Gadolinium Iodine
Conventional
FBP-based reconstruction
Material-specific images
Material-specific sinograms
AAPM 51 st Annual Meeting, July 26-30, Anaheim California 2009, E. Roessl
Schlomka et al. , Phys Med Biol. 53 (2008)
18

Roberts Prize Winner 2008
Best article published in PMB during 2008
Physics in Medicine & Biology (PMB), in association with the
Institute of Physics and Engineering in Medicine (IPEM)
AAPM 51 st Annual Meeting, July 26-30, Anaheim California 2009, E. Roessl 19

• Gantry with rotation speed up to 1/3 s per turn
•
μ
-Focus X-ray tube
– 40 kVp - 130 kVp
– max. 65W
•
•
• CdTe-based Photon-Counting detector
– single slice, 1024 pixel detector
– 6 energy bins per pixel
• Magnification: 2 - 6
Field-of-view:
Spatial Resolution:
6 cm - 23 cm
100
μ m - 250
μ m
First scanner: Philips Research Hamburg
Scanner copy: Washington University, St. Louis
AAPM 51 st
G. Lanza, S. Wickline
Annual Meeting, July 26-30, Anaheim California 2009, E. Roessl 20

Quantification of iodine blood-pool CA
White Swiss mouse images (Ex vivo)
Tail cross section
In collaboration with Anke de Vries 1), 2)
1) and Holger Gruell
Eindhoven University of Technology, The Netherlands
1), 2)
2) Philips Research Europe – Eindhoven, The Netherlands
AAPM 51 st Annual Meeting, July 26-30, Anaheim California 2009, E. Roessl
Quantification by spectral CT
21

Volume Rendering Iodine Image
Iodine data-set
From HPGe Detector
(no deconvolution)
Iodine Image Overlay with
Photo-Effect Image
In collaboration with Anke de Vries 1), 2)
1) and Holger Gruell
Eindhoven University of Technology, The Netherlands
1), 2)
2) Philips Research Europe – Eindhoven, The Netherlands
AAPM 51 st Annual Meeting, July 26-30, Anaheim California 2009, E. Roessl 22

S. Feuerlein et al., Radiology, 2008
Simulated calcified plaque inside a stent
Virtual native image
(no contrast agent)
Stent
Lumen
Calcification
4mm
Conventional
CT image
Gd - Image shows contrast agent only
(90 kV, 20 mAs)
In collaboration with Sebastian Feuerlein and Martin Hoffmann, Ulm University Hospital, Germany
AAPM 51 st Annual Meeting, July 26-30, Anaheim California 2009, E. Roessl 23

High-density lipoprotein (HDL)-coated gold nano-particles: Au- HDL
• Nanoparticle interacts extensively with macrophages
• High risk atherosclerotic plaque has increased macrophage density
• Au-HDL is ~10 nm in diameter
Lowest energy bin (25-34 keV) with Au-overlay
In collaboration with David Cormode, Willem Mulder and Zahi Fayad, Mount Sinai Medical School NY
AAPM 51 st Annual Meeting, July 26-30, Anaheim California 2009, E. Roessl 24

High-density lipoprotein (HDL)-coated gold nanoparticles
2 µm
Lowest energy bin (25-34 keV)
0.5 µm 0.1 µm with Au-overlay
Top: TEM image of a macrophage in the plaque of an apoE KO mouse that had been injected with
AuHDL 24 hours prior to sacrifice Bottom: Higher magnification images of the areas indicated.
(From sections taken of the aorta.)
In collaboration with David Cormode, Willem Mulder and Zahi Fayad, Mount Sinai Medical School NY
AAPM 51 st Annual Meeting, July 26-30, Anaheim California 2009, E. Roessl 25

High-density lipoprotein (HDL)-coated gold nanoparticles
Gold NP were found almost exclusively in the macrophages
200 nm
In collaboration with David Cormode, Willem Mulder and Zahi Fayad, Mount Sinai Medical School NY
AAPM 51 st Annual Meeting, July 26-30, Anaheim California 2009, E. Roessl 26

In collaboration with David Cormode, Willem Mulder and Zahi Fayad, Mount Sinai Medical School NY
AAPM 51 st Annual Meeting, July 26-30, Anaheim California 2009, E. Roessl 27

Targeted CA with Gd, Au or Bi payload
+ conventional CA (I) for coronary imaging
Vessel wall
Vessel lumen
Soft plaque
Calcified plaque
Gd (Au, Bi)-Image shows soft-plaque
(targeted CA angiogenesis, fibrin or macrophages)
I-Image shows
Coronary lumen
P,C images show anatomy allows Ca scoring
AAPM 51 st Annual Meeting, July 26-30, Anaheim California 2009, E. Roessl 28

:2
:2
:2
:2
Gadolinium dilution
:2 :2 :2 :2
Quantification of two contrast agents in a single scan
Gadolinium Iodine
:2
Maximum concentration:
• Iodine 240
μ mol/ml
• Gadolinium 60
μ mol/ml
Photo
AAPM 51 st Annual Meeting, July 26-30, Anaheim California 2009, E. Roessl
Compton
29

Washington University, St. Louis
In collaboration with Dipanjan Pan and Greg Lanza, Washington University St. Louis, School of Medicine,
St. Louis, MO
AAPM 51 st Annual Meeting, July 26-30, Anaheim California 2009, E. Roessl 30

In collaboration with Dipanjan Pan and Greg Lanza, Washington University St. Louis, School of Medicine,
St. Louis, MO
AAPM 51 st Annual Meeting, July 26-30, Anaheim California 2009, E. Roessl 31

Serially Diluted BiNC (40 v/v%) for Spectral CT
Bi
1
1050 HU
60keV
Bi
2
505
Bi
3
220
Bi
4
80
Bi
5
102
Ca
1060
“Virtual” conventional CT image With spectral overlays
Calcium
Bismuth
In collaboration with Dipanjan Pan and Greg Lanza, Washington University St. Louis, School of Medicine,
St. Louis, MO
AAPM 51 st Annual Meeting, July 26-30, Anaheim California 2009, E. Roessl 32

Polymeric Spectral CT Contrast Agent
In collaboration with Dipanjan Pan and Greg Lanza, Washington University St. Louis, School of Medicine,
St. Louis, MO
AAPM 51 st Annual Meeting, July 26-30, Anaheim California 2009, E. Roessl 33

Bi-Ca Separation on coronary phantom
Fibrin Targeting with BiNCs
“ Coronary Ruptured plaque imaging would change cardiovascular medicine.
”,
Prof. G. Lanza, Washington University, St. Louis
In collaboration with Dipanjan Pan and Greg Lanza, Washington University St. Louis, School of Medicine,
St. Louis, MO
AAPM 51 st Annual Meeting, July 26-30, Anaheim California 2009, E. Roessl 34

Bi-Ca Separation on coronary phantom
Green: Bi Brown: Calcium (from thresholded “conv.” image)
In frame 0 of movie: Bi/Ca sample (left), control with Ca only (right)
Measured Bi Concentration in the clot: highest : 0.13 M, typical: 0.05-0.10 M
In collaboration with Dipanjan Pan and Greg Lanza, Washington University St. Louis, School of Medicine,
St. Louis, MO
AAPM 51 st Annual Meeting, July 26-30, Anaheim California 2009, E. Roessl 35

Overview
• Motivation
• Physics of Photon-Counting Detectors
• Application Examples
• Technological Challenges
AAPM 51 st Annual Meeting, July 26-30, Anaheim California 2009, E. Roessl 36

Mammography, Radiography and Computed Tomography
Event rate/area
(photons/mm²
⋅ s)
Equivalent current/pixel for CZT (nA)
Pixel size (µm)
Mammography * General X-ray
Radiography **
5
⋅
10 7 10 6 to 5
⋅
10 8
0.2
typ. 85
0.03 – 20 typ. 150
Detector area (m 2 ) 0.072
0.12
Highest energy (keV) 28 - 40 70 - 120
Computed
Tomography ca. 10
2000
9
*** typ. 1000
0.14 (128 slices)
80 - 140
Count rate calculated from direct beam conditions:
*
**
***
28kVp, 144 mA, 0.65 m source-detector-distance (SDD)
70-120 kVp, 2-300 mA, 1.5 m SDD
140 kVp, 400 mA, 1.04 m with filtration of 1 mm AI, 2.5 mm Be,1 mm Oil,
1.2 mm Ti and 2 mm Teflon
Overdick et al., Nuc. Sci. Symp. Conf. Rec., 2008. NSS '08. IEEE , pp.1527-1535, 19-25 Oct. 2008
AAPM 51 st Annual Meeting, July 26-30, Anaheim California 2009, E. Roessl
37

Interposer
Direct converter
• Thin material to reduce the count rate per layer or slab
Horizontal Vertical; “edge-on“
Possible slab design:
• Special anode geometries needed: e.g. steering grid
• Advanced processing approaches dealing with the count rate problem.
High-rate photon-counting detection module
Overdick et al., Nuc. Sci. Symp. Conf. Rec., 2008. NSS '08. IEEE , pp.1527-1535, 19-25 Oct. 2008
AAPM 51 st Annual Meeting, July 26-30, Anaheim California 2009, E. Roessl
38

Roessl et al., Nuclear Science
Symposium Conference Record,
IEEE, 2008
Rate distribution in “first 100
μ m” of CZT
X-rays
0.1 mm (L
1
)
0.2 mm (L
2
)
Air
0.2-0.3 mm
0.45 mm (L
3
)
CZT
0.2-0.3 mm
2.25 mm (L
4
)
Count rates in primary beam (90kVp)
Mcps
L
1
L
2
L
3
L
4
L
T
0.2x0.2mm
12.5
7.5
3.3
0.9
24.2
2
AAPM 51 st Annual Meeting, July 26-30, Anaheim California 2009, E. Roessl
0.25x0.25mm
2
19.6
11.7
5.1
1.4
37.8
0.3x0.3mm
2
28.2
16.8
7.4
2.1
54.5
39

1),2)
Discard data measured above a certain pre-defined count rate limit per active readout cell (readout layer).
Assure that at least one readout cell (readout layer) per “detector column” is always active under primary beam conditions.
Combine data from unsaturated layers (data-rate limitations).
Further pre-processing and reconstruction
Physical and technological challenges
• Semi-conductor slicing (slabs of 200 - 300 µm)
• Material homogeneity, impurities
• Packaging , Wiring
• Data rates
→ combining data after counting (transverse & longitudinal )
• Charge sharing at smallest electrodes
• Layer dependent energy response
• Inter-layer X-ray Crosstalk
• Pulse pile-up and dead-time
1) Hoffman et al. , 2006. US Patent No. 2006 / 0056581 (A1).
2) Tkaczik et al. , 2007. US Patent No. 2007/0206721 (A1).
AAPM 51 st Annual Meeting, July 26-30, Anaheim California 2009, E. Roessl
40

Pulse Pile-Up at high count rates
Degradation of spectral quality
Response to mono-energetic input
AAPM 51 st Annual Meeting, July 26-30, Anaheim California 2009, E. Roessl
[cps]
41

Pulse Pile-Up at high count rates
Simple correction scheme
– Measurements using different beam currents
– Fitting of dead-time parameter using non-paralyzable model
12000000
10000000
8000000
6000000
4000000 bin 1 bin 2 bin 3 bin 4 bin 5 bin 6 bin-corrected 1 bin-corrected 2 bin-corrected 3 bin-corrected 4 bin-corrected 5 bin-corrected 6 bin-calc 1 bin-calc 2 bin-calc 3 bin-calc 4 bin-calc 5 bin-calc 6
Lowest energy bin
2000000
0
0 50 100 150 200 250 300 350 400 450 500 x-ray tube current / µA
Highest energy bin
AAPM 51 st Annual Meeting, July 26-30, Anaheim California 2009, E. Roessl
42

AAPM 51 st Annual Meeting, July 26-30, Anaheim California 2009, E. Roessl
43

• Expanding vessel (catheter)
• Forming a thrombus
• Targeting through catheter
• Flushing (by opening the vessel)
• Spectral CT Imaging of Bi particles
Gradient rendering of Bi image
In collaboration with Dipanjan Pan and Greg Lanza, Washington University St. Louis, School of Medicine,
St. Louis, MO
AAPM 51 st Annual Meeting, July 26-30, Anaheim California 2009, E. Roessl
44

Bismuth and Bones overlay on “Conventional
CT Image” after smoothing of Bi-data set.
ROI of same data set
Volume rendering of same dataset
In collaboration with Dipanjan Pan and Greg Lanza, Washington University St. Louis, School of Medicine,
St. Louis, MO
AAPM 51 st Annual Meeting, July 26-30, Anaheim California 2009, E. Roessl
45

Acknowledgement
Washington University St. Louis, School of Medicine, St. Louis, MO, USA
• Shelton Caruthers, PhD
• Greg Lanza, PhD, MD
• Dipanjan Pan, PhD
• Sam Wickline, MD
• Mike Scott
• Mike Hueghes, PhD
University of Technology Eindhoven, Eindhoven, The Netherlands
• Holger Gruell, PhD
• Anke de Vries, PhD
Mount Sinai School of Medicine, New York, NY, USA
• David Cormode, PhD
• Zahi Fayad, PhD
• Willem Mulder, PhD
Ulm University Hospital, Ulm, Germany
• Sebastian Feuerlein, MD
• Martin Hoffmann, MD
Philips Research Europe - Aachen, Germany
• Klaus-Jürgen Engel, PhD
• Christoph Herrmann, PhD
• Roger Steadman, PhD
• Gereon Vogtmeier, PhD
• Jens Wiegert, PhD
Philips Research Europe - Hamburg, Germany
• Peter Forthmann, PhD
• Thomas Istel
• Thomas Koehler, PhD
Philips Healthcare, CT, Haifa, Israel
• Ami Altman, PhD
• Raz Carmi, PhD
• Amir Livne, PhD
• Naor Wainer, PhD
Gamma Medica Ideas
• Bjørn Sundal, PhD
• Gunnar E. Maehlum, PhD
AAPM 51 st Annual Meeting, July 26-30, Anaheim California 2009, E. Roessl

AAPM 51 st Annual Meeting, July 26-30, Anaheim California 2009, E. Roessl