DETECTORS FOR MEDICAL PHYSICS

Maria Giuseppina BisogniMaria Giuseppina BisogniUniversita’ di Pisa, Dipartimento di Fisica “E. Fermi”INFN Sezione di Pisa

Corso CLXXV - "Radiation and particle detectors“, Varenna, 20 - 25 Luglio 2009

Lectures Contents

� Radiation detectors for morphological imaging.

�Digital mammography

2

� Radiation detectors for functional imaging

�Multimodality Imaging: advantages and technological challenges.

Contents

� Foreword

� Digital Radiology

3

� Digital Radiology

� Digital Mammography

� Clinical CT

� Micro CT

The beginning

� 1895 Prof. Wilhelm Conrad Roentgen discovers X-rays

� Phosphor screens introduced early 20th century

� In the ‘70 years routine use of fluoroscopy with image intensifiers coupled to TV cameras

� In the ‘80 years 'the radiography becomes digital (imaging plates, CCDs, flat-panels, semiconductor detectors both

4

plates, CCDs, flat-panels, semiconductor detectors both amorphous and crystalline) M. Hoheisel, NIM A563 (2006) 215–224

Digital Radiographic Imaging

�Film-screen systems cons:� detection and display on the same medium

�Digital radiography features: �transmitted intensity pattern sampling (pixels)�transmitted intensity pattern sampling (pixels)

� spatial sampling (del, pixel)

3D reconstruction techniques

6

Alessandra Retico - SPIE Medical Imaging 2009

Computer Aided Detection

CAD input

CADI for internal nodule detection

CADJP for juxtapleural nodule detection

Alessandra Retico - SPIE Medical Imaging 2009 7

CAD output

Several imaging modalities …

� General radiography

� Angiography

� Digital Subtraction Angiography (DSA)

� Mammography

8

� Mammography

� Stereotactic biopsy

� Computed

Tomography (CT)

…with different requirements 9

Radio-graphy

Angio-graphy

Mammo-graphy

Stereo-Tactic biopsy

CT

Detector size (cm2)

43 x 43 30 x40 18 x 2424 x 30

5 x 9 4 x 70 size (cm ) 24 x 30

Pixel (µm) 125–165 150–400 50–100 <50 500

Resolution 12 bits 12 bits 12 bit 16 bit 20 bit

Frame rate Single shot < 1 s

< 60 f/s Single shot < 1s

Single shot < 1 s

1000 MB/s

Best Detector for ?

� Wrong approach: Detector driven

“I have the best detector for… what??”

10

� Right approach: Experiment driven

“I have this biological, medical, clinical experiment to

make with these requirements: � which is the best

detector to be used, built or developed ?”

Classification of Digital Radiology

� Computed Radiography (CR)� photostimulable phosphor Imaging plates

� Digital Radiography(DR)

11

� Digital Radiography(DR)� Indirect

� e.g. a-Si flat panel detector, CCD or CMOS based detectors

� Direct � a-Se flat panel detector

� single photon counting (e.g. hybrid detectors, MWPCs)

Charge Coupled Devices (CCD)

� Tecnology Metal Oxide Semiconductor (MOS)

� The charge produced is stored in a potential well

� Potential changes to make the charges shift from one pixel to the next in a given column

� Serial read-out with a clock con un clock

� Coupled to scintillators CsI(Tl) to improve efficiency

OPDIMA® Siemens

Read-out architectures for CCD14

CCD linear array

CCD camera system- Light loss- Demagnification

Reduced DQE→

a-Si Flat Panels for DR

� a-Si:H photodiodes (low dark current, high sensitivity to green light)

� Coupled to CsI phosphors to improve efficiency

15

from J. A. Seibert, UC Davis Medical Center, CA, USA

Scintillator: CsI:Tl needle crystals

� Thickness 550µm

� good X-ray absorption

� Needles act as light-guides

16

� Needles act as light-guides

� sharp MTF

� CsI:Tl emits green light

Scintillator

Read-Out Architecture

AddressingReadout

ADC

X-ray film: dynamic range18

Over-exposedUnder-exposed

8 mAs0.5 mAs 2 mAs 4 mAs 16 mAs 32 mAs 63 mAs

M. Overdick, Philips Research Labs – Aachen, IWORID 2002

Flat panel detector: dynamic range19

typical usage

M. Overdick, Philips Research Labs – Aachen, IWORID 2002

a-Se Flat Panels Direct DR

� alloyed a-Se with % As and with ppm Cl

20

from J. A. Seibert, UC Davis Medical Center, CA, USA

from J. A. Seibert, UC Davis Medical Center, CA, USA

alloyed a-Sewith % As (stabilizer, ↓ holes lifetime, ↑ e- lifetime) with ppm Cl (↑ holes lifetime, ↓ e- lifetime)

DIGITAL MAMMOGRAPHY

22

DIGITAL MAMMOGRAPHY

Mammography

� Tumour masses� Healthy tissue degeneration

� X-ray Attenuation properties

similar to healthy tissue

� Size > 5 mm

Microcalcifications� Microcalcifications

� Submillimetric calcium deposits

� Denser than gland and adipose tissues

� Cluster of microcalcificatons are tumour markers

nn

X rays

µ1µ1

µ2µ2tt

xx

Quantic Image

Detector Signal-Transfer properties

(depend on the object size!)

Detector Signal-Transfer properties

(depend on the object size!)

Physical Parameters

l2l1

n2n1Quantic Image

DigitalDetector

Detected Image

Image line profileImage histogram

Signal to Noise Ratio

n2n1

1 2

2 21 2

n nSNR

σ σ−=+

Only statistics fluctuations

25

n1

n2

x

( )( ) 1

11

ts NAe

SNR eR

µµ ε−

− ∆= −+

If SNR = k and (∆µ)s << 1 small 2

12 4

(1 )exp( )( )

( )

k R tN k

s

µε µ+≈

∆

ε= detection efficiency

Mammography

26

Tumour masses� Healthy tissue degeneration

� X-ray Attenuation properties

similar to healthy tissue

� Size > 5 mm

Microcalcifications• Submillimetric calcium deposits• Denser than gland and adipose tissues• Cluster of microcalcificatons are tumour markers

First Digital Mammography System27

� GE Senographe 2000D

� Revolution™ Flat Panel Digital Detector a-Si +CsI(Tl)

� 18x 24 cm2

Pixel: 100 x 100 µm2� Pixel: 100 x 100 µm2

� 12 bit resolution

� 11 years R&D

and 130 M$ investment

� First digital mammographic

system approved by FDA (2000)

Direct Digital Mammography28

� A-Se based flat panels

� SeleniaTM, LORAD-Hologic

� Mammomat NovationDR Siemens

� Active area 24 x 29 cm2� Active area 24 x 29 cm

� 70 µm pixel size

� Dual target X-ray tube: Mo/Mo, Mo/Rh, W/Rh for dose reduction

� Giotto Image MD Internazionale Medico Scientifica Srl (I.M.S. Bologna, Italy)

� active area 23.9 x 30.5 cm2

� pixel size of 85 µm

� Mo and Rh filter

Single Photon Counting (SPC) Systems29

� Noise suppression� Higher SNR or lower dose

� Low event rate applications

� Linear and wider dynamic range� Limited by counter saturation� Limited by counter saturation

� Energy discrimination� Compton events rejection

� X-ray fluorescence rejection

� “Energy weighting” suppression� Low energy photons weight less than high

energy ones in integrating systems

� In SPC systems all photons have same weight

First SPC commercial mammographic system30

Sectra MicroDoseTM

� Si strip detectors, 768 strips, 50 µm pitch

slight fan-out (to � slight fan-out (to compensate beam divergency), 2 cm long

� 500 µm thick

� “quasi” edge-on

(4º- 4.5º tilt angle)

� ~90% efficiency @ 30 keV

� ASIC:

� 128 channels

� counting rate/pixel: >1 MHz

Photon Counting in X-ray MammographyCourtesy of Mats Danielsson, Sectra Mamea AB ,Sweden (2009)

32

� M. Lundqvist et al., “Evaluation of a Photon-Counting X-Ray Imaging System”, IEEE Trans.Nucl.Sci. 48 (4), August 2001

SYRMEP Project (INFN GV, early ‘90)33

(ELETTRA Synchrotron, Trieste) Combined use of syncrotron light, new detectors and non-conventional imaging techniques aimed at the improvement of the image quality in mammography

Erik Vallazza – INFN Trieste – VCI 2007

Edge-on Si strip detector

� A silicon microstrip detector is used in the so called “edge-on” geometry matching the laminar geometry of the beam

� The absorption length seen by the impinging radiation is given by the strip length (~100% in 1 cm of silicon for 20 keV photons)

� Almost complete scattering rejection

� The pixel size is determined by the strip pitch (H) times the detector thickness (V)

� Drawback: the dead volume in front of the strip34

Phase contrast nylon wires

Contrast –detail phantom17 keV

35

� Phase contrast nylon wires

Integrated Mammographic Imaging Project� Technology Transfer project funded by the Italian Ministry for

Reseach (under law 46/82 article 10)

� Technologies originally developed for High Energy Physics experiments applied to mammographic and functional breast

36

experiments applied to mammographic and functional breast imaging

� Collaboration between national Universities, INFN and Industry

� Research lines� Gamma camera for scintimammography

� GaAs pixel detectors and bump bonding techniques

� Mammography system demonstrator based on GaAs pixel detectors

� High intensity Quasi-monochromatic X-rays source

Why GaAs ?

Photoelectric interaction probability ≈ 100% in the mammographic energy range (10 - 30 keV) for a 200µm thick GaAs crystal

The Medipix-1/PCC detection unit

38 GaAs Detector

Indium Bump -bonding

Detectors by AMS ItalyGaAs: 200 µm thickpixel 170 x 170 µm2

Schottky 150x150 µm2

channels 64 x 64total area 1.2 cm2

Electronic chip

Indium Bump -bondingBy AMS Italy

Input Preamp

LatchedComparator

Pulseshaper

ThresholdAdjust(3 bits)

TestInput

Cfb

Test(1 bit)

Ctest

Rst

AnalogReset

Mask(1 bit)

Shutter

Data

Clk

Clkout

1

0

01

Sel

Sel

Mux

Mux

ShiftReg

To lowerpixel

From upperpixel

Photon Counting Chip (PCC)MIC CERN SACMOS 1 µmFASELEC ZurigoPixel 170 x 170 µm2

Channels 64 x 64Area 1.7cm2 (active area =1.2cm2)Threshold adjust 3-bitPseudo-random counter 15-bit

httphttp:://medipix//medipix..webweb..cerncern..ch/MEDIPIXch/MEDIPIXhttphttp:://medipix//medipix..webweb..cerncern..ch/MEDIPIXch/MEDIPIX

Mammographic Demonstrator39

X ray tube

Pb collimatorMammographic

Head

Mammographic Head40

� The Detection Unit

� The assemblies have been produced and bump bonded by Alenia Marconi Systems (Roma)

� Each detection unit has been mounted in a protective case.

Aluminum nitride (AlN) substrate,LEXAN cover on top (not shown)

GaAs MPXI/PCCassembly

Step and Shoot41

� 18 x 24 cm2 exposure field

� 1D scanning

� 9 x 2 assemblies

� 26 exposures� 26 exposures

� “off-line” image reconstruction

1 cm

Some radiographs

Al disk 15 micron thickAl disk 15 micron thick

42

Radiograph of Al disks embedded in wax

In a lucite matrix (5 cm thick, 10 cm in diameter)

Dose 2 mGy

Radiograph of Al disks embedded in wax

In a lucite matrix (5 cm thick, 10 cm in diameter)

Dose 2 mGy

Al disk 15 micron thick

Contrast 0.8 %

Al disk 15 micron thick

Contrast 0.8 %

Tulip Radiograph

Image size 14 x 20 cm^2

Dose 2 mGy

Tulip Radiograph

Image size 14 x 20 cm^2

Dose 2 mGy

Image Quality Assessment

�Transfer Function Analysis

Protocol IEC 62220-1-2: "Medical electrical equipment -Characteristics of digital X-ray imaging devices - Part 1-2: Determination of the detective quantum efficiency -Detectors used in mammography"

� MTF, NNPS, DQE

�Contrast Threshold Analysis

Protocol EUREF: Perry N et al. L (eds), “ European Guidelines for

quality assurance in breast cancer screening and diagnosis –Fourth Edition”, Luxembourg (2006)

�Contrast-detail curves

SystemSystemPSF(x) = Point Spread Function

input = q(x)input = q(x) output = d(x)output = d(x)Space Invariant Linear Systems Theory Space Invariant Linear Systems Theory Space Domain

Modulation Transfer FunctionsModulation Transfer Functions

Space-Frequency Domain

T(u) = Characteristic Function

Modulation Transfer Function

∫∞

∞−

⋅= dxexLSFMTFxiνπν 2)()(

45

� It measures how much an imaging system affects

the amplitude of an input sinusoidal signal

� It is function of the spatial frequency

� Fourier transform of the Line Spread Function LSF(x)

C(x) = autocorrelation function of the signal variations ∆d(x) around the mean signal <d(x)>

Ergodic Wide-Sense Stationary process

Noise Power SpectrumNoise Power Spectrum

for Digital Imaging Systems...

flood imageflood imageflood imageflood image

Detective Quantum EfficiencyDetective Quantum Efficiency

)(

)()(

2

2

uSNR

uSNRuDQE

in

out=)(

)()(

2

uNNPSq

uMTFuDQE =

Fraction of Poisson-distributed quanta contributing to form the image

Degradation of information in the signal in the detector system.

Detective Quantum Efficiency

DQE( f ) = SNRout2

SNRin2

• DQE describes how the Signal to Noise Ratio varies

48

• DQE describes how the Signal to Noise Ratio varies

across the imaging system stages.

• It depends on the frequency through the MTF and the

NNPS, both frequency functions.

• At zero frequency, DQE(0) depends on the detection

efficiency and on the image variance

Mammographic Systems Comparison

49 System IMI Prototype Giotto IMS Fuji FCR 5000MA

GE Senographe 2000D

Detector Crystalline GaAs, a-Se Imaging plates Caesium Iodide. Detector Crystalline GaAs, Si

a-Se Imaging plates Caesium Iodide. TFT array

Electronic mode Single Photon Counting

TFT. Charge integration

Laser scanner TFT. Charge integration

Pixel pitch 170 micron 85 micron 50 micron 100 micron

Image matrix (pix) 1152 x 1536 2048x2816 3600 x 4800 1914 x 2294

Image size (cm) 18 x 24 17.4 x23.9 18 x 24 19 x 23

Beam (Target/Filter)

Mo/Mo Mo/Mo, Mo/Rh Mo/Mo Mo,Mo/Mo,Rh,Rh/Rh

Note Slot scanning Full field Full Field Full Field

CDMAM 3.4 Phantomresult of the project: "Quality Assurance in Mammography, Department of Radiology, University Medical Centre

Threshold Contrast Visibility

EUREF protocol Medical Centre Nijmegen, the Netherlands." By M.A.O. Thijssen, Ph.D., K.R. Bijkerk, M.Sc. and J.M. Lindeyer, B.Sc.Technical specifications

aluminum base containing gold discs of various thicknesses and diameters which are arranged in a matrix of 16 rows and 16 columns. Each square contains two identical discs (same diameter and thickness), one in the center and one in a corner.

Diameters from 0.06 mm to 2 mm.

Thickness: from 0.03 to 2 µm.

Phantom ImageParticular MGD 2 mGyImaged with 4 cmthick lucite layer

� EUREF protocol � Three experienced observers

determine the minimum contrast visible on two images

� Every observer must score two different images

� The results of the three observers must be averaged

Contrast detail CurvesDisk

Diameter(mm)

EUREF Acceptable value (micron)

EUREF Achievable value (micron)

IMI Thickness Threshold (µm) 1.58 mGy

IMI Thickness Threshold (µm) 2.21 mGy

2 mm 0.069 0.038 0.0375 0.0362

1 mm 0.091 0.056 0.0588 0.0475

0.50 mm 0.15 0.103 0.1537 0.1312

0.25 mm 0.352 0.244 0.3833 0.3417

Senographe200D data from:“EVALUATION AND CLINICAL ASSESSMENT OF DIGITAL MAMMOGRAPHY SCREENING USING THE GE SENOGRAPHE 2000D SYSTEM”, NHSBSP Equipment Report 0602, May 2006, Published by NHS Cancer Screening Programmes

0.1 mm 1.68 1.10 - -

Image QualityConfronto Senographe 2000D e dimostratore IMI in progress..

Disk Diameter(mm)

EUREF Acceptable value (contrast %)* [thickness (micron)]

EUREF Achievable value (contrast %)* [thickness (micron)]

IMI Th. Contrasts( %)* [thickness (µm)]

36 mAs

IMI Th. Contrast (%)*[thickness (µm)]

50 mAs

Senodgraphe 2000D Threshold Contrast

2 mm 1.05% [0.069] 0.55% [0.038 ] 0.53% 0.51% 0.65%

1 mm 1.4% [0.091] 0.85% [0.056] 0.82% 0.67% 1.00%

0.50 mm 2.35% [0.15] 1.6% [0.103] 2.14% 1.83% 1.84%

0.25 mm 5.45% [0.352] 3.8% [0.244] - - 4.15%

0.1 mm 23% [1.68] 15.8% [1.10 ] - - 16%0.1 mm 23% [1.68] 15.8% [1.10 ] - - 16%

Senographe200D data from:“EVALUATION AND CLINICAL ASSESSMENT OF DIGITAL MAMMOGRAPHY SCREENING USING THE GE SENOGRAPHE 2000D SYSTEM”, NHSBSP Equipment Report 0602, May 2006, Published by NHS Cancer Screening Programmes

MTF comparison53

Nyquist frequency MTF

Giotto Image MD 5.88 lp/mm 46 %

1.0

GE Senographe 2000DMedipix I 170 um pitch Fuji FCR 5000MA Giotto Image MD Medipix II 55 um pitch

Medipix II 9.1 lp/mm 60 %

GE Senographe 2000 D 5 lp/mm 20 %

FCR 5000MA 10 lp/mm 1 %0 5 10 150.0

0.5MT

F

lp/mm

Detective Quantum Efficiency

54

S.R. Amendolia et al., "Characterization of a mammographic system based on single photon counting pixel arrays coupled to GaAs x-ray detectors" Med. Phys. Volume 36, Issue 4, pp. 1330-1339 (April 2009)

Measurement of Detector DQE

0.7

0.6

0.5

0.4

Kodak CR 850 EHR-M Konica Regius 190 Fuji CR Profect GE Senographe DS Lorad Selenia Sectra MDM

0.3

0.2

0.1

0.0

DQ

E

109876543210Spatial frequency [mm-1]

* Monnin et al. Medical Physics, March 2007, Volume 34, Issue 3, pp. 906-914 S.R. Amendolia et al., "Characterization of a mammographic system based on single photon counting pixel arrays coupled to GaAs x-ray detectors" Med. Phys. Volume 36, Issue 4, pp. 1330-1339 (April 2009)

DQE for the system

Courtesy of Mats Danielsson, Sectra Mamea AB ,Sweden (2009)

Sectra 3D photon counting (Tomosynthesis)

Courtesy of Mats Danielsson, Sectra Mamea AB ,Sweden (2009)

Dual energy with photon counting technique

If one measures the pulse height in Photon Counting one can estimate the energy of each x-ray (color) and potentially enhance structures of clinical interest such as structures of clinical interest such as microcalcifications, e.g. using the so-called dual-energy technique

Photon Counting Enables Electronic Spectrum Splitting

6

8

10

12

14

16

18

Spectrum after breast

Flu

ence

(10

6 ph.

/cm

2 )

4

6

8

10

12

14Spectra after breast

Flu

ence

(10

6 pho

t/cm

2 )

10 15 20 25 30 35 40 450

2

4

6

Energy (keV)

Flu

ence

(10

0 10 20 30 400

2

4

Flu

ence

(10

Energy (keV)

Advantage 1: No high- and low-energy spectra overlapAdvantage 2: Single exposure

Fantom bilderLow energy image High energy image

Total image Dual energy subtraction

Bornefalk H, Lewin JM, Danielsson M, Lundqvist M. Single-shot dual-energy subtraction mammography with electronic spectrum splitting: Feasibility. Eur J Radiol 2006;60:275-278.

COMPUTED TOMOGRAPHY ( Clinical CT)

61

Originally called:

Computerized Axial Tomography (CAT)

Rotation givesmultiple projections

X-raytube

Thin fan beamof x-rays

Patient

Computed Tomography (CT)

Array of detectors(rare-earth doped ceramics

with photodiodes)

Patient(stationary)

Use 1D projectionas a template

Back projectionof pixel

brightness

PROJECTIONRECONSTRUCTION

http://www.colorado.edu/physics/2000/index.pl

Spiral CT: Scanning Principle63 Start of

spiral scanPath of continuouslyrotating x-ray tubeand detector

Kalender WA et al. Radiology 1989; 173(P):414 and 1990; 176:181-183

Direction of continuouspatient transport 0

0 t, s

z, mm

64

2424--row 16r ow 16--slice slice ‘adaptive / hybrid’ ‘adaptive / hybrid’

Array Detector’Array Detector’

1.5 mm 0.75 mm4 x 1.5

mm4 x 1.5

mm16 x 0.75

mm

16 x 0.75 mm@ 0.5 s

16 x 1.5 mm@ 0.5 s

12 x 0.75 mm@ 0.42 s

Courtesy of W. Kalender, ECR-2003

Axial Geometry evolution (z-direction)65

zz

MPR

1998: M=4 2002: M=16<1998: M=1

z

(drawn in an exaggerated way)

Courtesy of W. Kalender, ECR-2003

NOW 256 slices

MSCT

66

3D Isotropic Resolution in Spiral CT3D Isotropic Resolution in Spiral CTx/y-plane

0.1 mm0.2 mm0.3 mm

0.4 mm 0.5 mm 0.6 mm 0.7 mm

x

y

z-direction (MPR)

0.1 mm0.2 mm0.3 mm

0.4 mm 0.5 mm 0.6 mm 0.7 mm

z

y

1.1 mm 1.0 mm 0.9 mm 0.8 mm

1.2 mm 1.3 mm 1.4 mm 1.5 mm

y

1.1 mm 1.0 mm 0.9 mm 0.8 mm

1.2 mm 1.3 mm 1.4 mm 1.5 mm

Scans in UHR mode with 2 Scans in UHR mode with 2 ×××××××× 0.5 mm collimation, 0.5 mm collimation, Seff = 0.5 mm

y

Fuchs T, Krause J, Kalender WA. Physica Medica 2001; 17(3):129Fuchs T, Krause J, Kalender WA. Physica Medica 2001; 17(3):129--134134

68

Tube

Area detector CT – the future of CT

aSi Detector

C-Arm CT Flat Panel Detector CT

Cone beam CT

COMPUTED TOMOGRAPHY

69

COMPUTED TOMOGRAPHY ( MicroCT)

MicroMicro ComputedComputed TomographyTomography

((MicroMicro--CT, µCT)CT, µCT)

There is no unique definition for µCT!

Most used, but arbitrary�

Spatial resolution of better than 100 µm

� Rotating gantry or rotating object

70

� Rotating gantry or rotating object

� Circular or spiral data acquisition

� Fan- and cone-beam data acquisition

� X-ray tube or synchrotron radiation

� Developed medical

[and for industrial] applications

Micro Computed TomographyMicro Computed Tomography

(Micro(Micro--CT, µCT)CT, µCT)

Technical details and constraints

� As expensive as “economy class” CT used in clinical scanning

71

used in clinical scanning

� Small fields of measurement (typically. 5-50 mm)

� Very low power x-ray sources (typically 5-50 W)

� Long scan times (typically 5-30 minutes)

Medical Applications of MicroMedical Applications of Micro--CTCT

Organ / Disease

� Bone

� Teeth

72

Sample / Animal• Biopsies • Excised materials

� Teeth

� Vessels

� Cancer

• Excised materials • Small animals

(rats / mice)���� in vivo

ex-vivoin vitro

CCD Micro-tomographer

X-ray source ................ 20-100kV,10W, <5µm spot size or 20-80kV, 8W, <8µm spot size

X-ray detector ............. 10Mp or 1.3Mp cooled CCD fiber-optically coupled to scintillator

Detail detectability ...... <1µm with 10Megapixel camera, <2µm with 1.3 Megapixel camera

Maximum object size... 68mm in diameter with 10 Mp camera, 37mm - with 1.3Mp camera 1.3Mp camera

Reconstruction ............ single PC or cluster volumetric reconstruction (Feldkamp algorithm)

http://www.skyscan.be/products/1172.htm

3D Images

Object: mouseScanner: SkyScan1076 Image: full body mouse scan using

contrast agent, 35um isotropic voxel size35um isotropic voxel size

Object: mouse lung sampleScanner: SkyScan1172/100kV/10Mpusing contrast agent + CTan processing softwareImage: pseudo3D visualization (MIP) of lungs vascular structure, 5.7um pixel size

Benchtop Micro-CT75

cone beam

x-ray tube CCD detectorsample

axis of

high voltage

Benchtop MicroBenchtop Micro--CTCT76

Trabecular Structure

� 3D morphology� thickness

� separation

� structure model index

� anisotropy

77

30 years30 years30 years30 years� anisotropy

� Euler number

(ETH Zürich, Aarhus)

� 3D density(ESRF, Grenoble)

30 years30 years30 years30 years

70 years70 years70 years70 years

Courtesy of W. Kalender, ECR-2003

High-Resolution Micro-CT78

0.6

0.8

1.0

0 20 40 60 80 100

0.6

0.8

1.0

System MTF of transaxial slice

MTF

5 µm resolution @ 2 % MTF

0 20 40 60 80 1000.0

0.2

0.4

0.0

0.2

0.4

MTF

LP/mm10 µm tungsten wire7 µm voxel size

Courtesy of W. Kalender, ECR-2003

CMOS Flat Panels

� CMOS Monolithic Active Pixel Sensors (MAPS), developed for visible light imaging in visible light imaging in early ’90s, look very promising for application in medical imaging

G.Rizzo – IWORID-8 – Pisa, July 2-6 2006

79

Principle of Operation80

Signal generated by a particle is collected by a diode (n-well/p-epitaxial layer), then readout by CMOS electronics integrated in the same substrate… BUT :

Charge generated by the incident particle moves by thermal diffusion in the thin (~ 10 µm) p-

P-epitaxial layer ~ 10 mm

G.Rizzo – IWORID-8 – Pisa, July 2-6 2006

thermal diffusion in the thin (~ 10 µm) p-epitaxial layer

P-epi layer doping ~1015 cm-3

� not depleted

� carrier lifetime O(10 ms), small diffusion distance

P++ substrate gives a small contribution to the collected charge (very low carrier lifetime)

Typical collection time: ≤ 100 ns for small diode, faster with larger diodes.

Charge-to-voltage conversion provided by sensor capacitance -> small collecting electrode

(Monolithic active pixel sensor)MAPS CMOS Detector (detector and readout incorporated in the same layer)

• no bias voltages• charge diffusion• 100% fill factor

- charged particles

Epilayer

7/20/2009 LMB, CambridgeTurchetta et alNIM A458 (2001) 677-689

Substrate

CMOS: Single Pixel Readout

T1,T2, T3 are all transistors

7/20/2009 LMB, Cambridge

Comparison of CCD and CMOS Readout

7/20/2009 LMB, Cambridge

Single (or few) node readout, slower

Charge shifted along columns/row

Parallel readout, fasterCharge converted to voltage In pixel

Commercial CMOS Flat Panels

A small animal CT prototype:FasTac (Pisa)

85

X-ray source

• Fixed tungsten anode• Maximum voltage: 60 kV• Maximum power: 10 W• Measured focus size: 7 µm FWHM• Beam aperture: 32°

X-ray detector

• 1024 x 2048 pixels (48 µm each)• 5 cm x 10 cm active area• Maximum frame rate 2.7 fps• 10lp/mm resolution

MEDIPIX286

� 0.25 um IBM technology 33M transistors

� 256x256 pixels, 55 x 55 µm2 (65536 pixel/chip)

� Positive and negative input signals

� Preamplifier equipped with leakage current compensation circuit at pixel level

Max count rate/pixel: 1 MHz� Max count rate/pixel: 1 MHz

� Two leading edge discriminators, threshold adjustable at pixel level (3 bits resolution)

� “energy window” logic

� 13 bits Counter / shift register

� Read-out

� Serial: 100 MHz 9 ms/frame LVDS drivers, Fast Shift Register

� Parallel: 100 MHz 266 µs/frame bus 32 bit

� Dead area 55 µm on three sides

MPX2 designed by M. Campbell and X. Llopart (2000) of the microelectronics group CERN, in the framework of the international collaboration MEDIPIX2

http://medipix.web.cern.ch/MEDIPIX/

14111 µµm

16120

87

16120 µµm

MPX2 Bone studies on small animals

Transaxial Sagittal

1 mm

Panetta, D.: 8th International Workshop on Radiation Imaging Detectors – July 2-6 2006, Pisa – ITALY

Coronal

60 µµµµm

Conclusions

� Radiological Imaging � Morphological Imaging but not only !!

� CT is still a hot topic!

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� CT is still a hot topic!

� There is Room for improvement :

� � Dose Reduction at the same image quality

� Better Image quality at the same dose

SINGLE PHOTON COUNTING � the FUTURE

THE END

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THE END

Abstract #1

The development of radiation detectors in the field of nuclear and particle physics hashad a terrific impact in medical imaging since this latter discipline took off in late ’70with the invention of the CT scanners. The massive use in High Energy Physics of positionsensitive gas detectors, of high Z and high density scintillators coupled to Photomultiplier(PMT) and Position Sensitive Photomultipliers (PSPMT), and of solid state detectors hastriggered during the last 30 years a series of novel applications in Medical Imagingwith ionizing radiation. The accelerated scientific progression in genetics and molecular

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with ionizing radiation. The accelerated scientific progression in genetics and molecular

biology has finally generated what it is now called Molecular Imaging. This field

of research presents additional challenges not only in the technology of radiationdetector, but more and more in the ASIC electronics, fast digital readout and parallel

software. In this series of three lectures I will try to present how High Energy

Physics and Medical Imaging development have both benefited by the cross-

fertilization of research activities between the two fields and how much they will takeadvantage in the future.

Abstract #2

With particular evidence to Medical Imaging I will address and discuss:

1 - The use of gas, scintillator and solid state detectors in digital radiology and digital mammography, clinical CT and small animal CT.

2 - The use of scintillators and PMT/PSPMTs in functional imaging and in particular:

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2 - The use of scintillators and PMT/PSPMTs in functional imaging and in particular:

- For Molecular Imaging with PET and SPECT (clinical and preclinical);

- For Breast Cancer Imaging (PEM and SPEM, PEMT and SPEMT);

- For on line PET dosimetry in hadrontherapy .

3 - The impact of the novel solid state photomultipliers in Medical Imaging and the advent of multimodality imaging such as PET/CT and SPECT/CT, PET/MRI and SPECT/MRI.

Detector and Front-End� The Si Detector

� 256 to 1024 strips

� Strip length 2 cm

� 100 or 50 µm strip pitch

� Detector thickness: 300 µm

� Dead entrance window ~200 - 400 µm

� Detection efficiency: 80% (20 keV)

� The Mythen-II ASIC

� Evolution of the Mythen-I

� 0.25 µm UMC technology

� Upgrades:

� 24 bit counter

� re-design of the digital part

� 6-bit threshold trim DAC for each channel

� with proper optimization usable up to 3 MHz (work in progress)

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MHz (work in progress)

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ConeCone--beambeamSpiral CTSpiral CT(CSCT)(CSCT)

here:here:MM = 16= 16

• 0.5 s rotation• 0.5 s rotation• 16××××0.75 mm• 70 cm in 28 s• 1.4 GB rawdata• 1400 images

Whole body rat imaging95

Vessels� in vitro scans

� casting of vessels with Microfil (compound with lead chromate)

� applications

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BrainBrain

KidneyKidneyapplications � heart

� kidney

� liver

� lung

MPRMPR MIPMIP Vol RendVol RendHoldsworth et al.: Trends Biotech. 2002 Holdsworth et al.: Trends Biotech. 2002 Wan et al: Comp Biol Med. 2002Wan et al: Comp Biol Med. 2002Ortey et al: Kidney Int. 2000Ortey et al: Kidney Int. 2000

KidneyKidney

TumorTumorHeartHeart

Muscle and Fat97

rat heart musclerat heart muscleorientation of fibersorientation of fibersJorgensen et al.: Jorgensen et al.: Am J Physiol 1998Am J Physiol 1998

Mouse in vivo scansMouse in vivo scansfat content and distribution changesfat content and distribution changesHildebrandt et al.: Hildebrandt et al.: J Pharmacol Toxicol Meth 2002J Pharmacol Toxicol Meth 2002

Cancer Research

Monitoring of Lung cancer growthby micro-CT

Resolution 150 µm

98DayDay

00

1010

tumor cell tumor cell injectioninjection

treatm. treatm. startstart

Resolution 150 µm

Scan time 5-7 min

here: no change intumor size

Kennel et al.: Med Phys. 2000

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