part i physicists do it in hospital tong xu dept. of physics carleton university
TRANSCRIPT
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Part I
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Physicists do it in Hospital
Tong Xu
Dept. of PhysicsCarleton University
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Why there are physicists in the hospital?
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Medical Physicists
Where in the hospital can you find them? Diagnosis imaging departments:
• Radiology and Nuclear Medicine (CT, MRI, PET…) Cancer centre
• Medical Physics department (Radiotherapy)
What is their job? Make sure the equipments are working
according to their physics specifications Perform radiotherapy treatment planning
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Why we need physicists to perform these tasks?
Let’s to go back to the history of some of the medical technologies.
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Related Medical Technologies
X-ray CT
Magnetic Resonance Imaging
Radiation Therapy
Three examples …
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Discovery of X-ray
First discovered by German Physicist Wilhelm C. Röntgen in 1895
On a New Kind of Rays Nature 53, 274-276 (23 January 1896)
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Discovery of X-ray Independently
discovered by Nikola Tesla in 1896
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Discovery of x-ray 1. Crookes Tube
Invented by Sir William Crookes, chemist and physicist, around 1860s.
A demonstration of the cathode ray – accelerated electron beam.
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Discovery of x-ray2. Cathode ray
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Cathode ray is a beam of electrons
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Discovery of x-ray3. Rontgen’s experiment
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A mystery radiation was coming out from the tube
Röntgen called it
X-ray
In fact, x-ray is just a ray of light photons with much higher energy than
ordinary light
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Typical x-ray spectrum
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Medical Application of x-ray
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Röntgen received the First Physics Nobel price in 1901
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X-ray radiograph
It’s a shadow image of human
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What do we need to see through a human?
X-ray
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X-ray Computer tomography
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X-ray projections of heart
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CT Image reconstruction
Projections at different angle 3D structure
http://rpop.iaea.org/
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Inventers
Theory proposed by a physicist Allan MacLeod Cormack in1956 two papers in the Journal of Applied Physics
in 1963 and 1964
First Prototype by electrical engineer Godfrey Hounsfield in 1969
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The first CT prototype
First Prototype by Godfrey Hounsfield in 1969
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Cormack and Hounsfield shared the Medical Nobel prize in 1979
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Magnet Resonance Imaging1. Stern molecule beam (1922)
Individual gas molecules fly through a pair of magnets
developed by German Physicist Otto Stern and Walther Gerlach in 1922
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Magnet Resonance Imaging2. Some nucleus are like tiny
magnets
S
N
S
N
Detector
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Magnet Resonance Imaging2. Some nucleus are like tiny
magnets
N
S
S
N
Detector
S
N
S
N
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Otto Stern received Physics Nobel prize in 1943
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Magnet Resonance Imaging3. Precession of magnetic dipoles
Some nuclear has magnetic momentum
They are like magnetic dipoles
They precess around the external magnetic field Just like a Gyroscope
Check out this animationhttp://www.simplyphysics.com/MRI_shockwave.html
B
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Magnet Resonance Imaging3. Precession of magnetic dipoles
The precession frequency
ω is in the radio frequency range is the Gyromagnetic ratio
BB
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Magnet Resonance Imaging3. Precession of Magnetic dipoles
BAligned against the external
Magnetic field B
Higher energy state
Aligned with the external Magnetic field B
Lower energy state
The nucleus feel more comfortable to stay in lower energy state
N
S
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Magnet Resonance Imaging4. Nuclear Magnetic Resonance
What if I send nucleurs a Radio wave that has the same frequency as the
precession?
American physicist Isador I. Rabi had an great idea!
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Magnet Resonance Imaging4. Nuclear Magnetic Resonance
Detector
S
N
S
N
Radio frequency signal ~
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Magnet Resonance Imaging4. Nuclear Magnetic Resonance
The nucleus will resonance with the RF wave
They absorb RF energy
And flip to higher energy state
Can measure the nuclear magnetic montemtum precisely
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Isador I. Rabi received Physics Nobel prize in 1944
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Magnet Resonance Imaging5. NMR with solids and liquids
In 1946, two other Americans, Edward M. Purcell and the Swiss-born Felix Bloch, separately apply this nuclear magnetic resonance (NMR) method to solids and liquids.
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Purcell and Bloch received Physics Nobel prize in 1952
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Principle of NMR
Since the gyromagnetic ratio γ is unique for nucleus of each elementsNuclear Magnetic Resonance is a powerful tool for chemical analysis
B
Resonance frequency
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Until 1970s….
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Magnet Resonance Imaging5. Apply NMR to imaging
Paul Lauterbur & Peter Mansfield applied NMR to image body in 1970s
Introduced gradients to the magnetic field
Thus, frequency the radio wave emitted by the nucleus tell us where they are.
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MRI scanner
Source: sfu.ca
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MRI
A technique for imaging soft tissues
source: lecture slides from Prof. I. Cameron
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Lauterbur and Mansfield received Medical Nobel prize in 2003
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Cancer diagnosis
http://www.dcmsonline.org/
Ch
est
X-
ray
x-ra
y C
T
Nu
cle
ar
Med
icin
e
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Physics in Cancer treatment
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Radiation Therapy
Uses ionizing radiation
Kills tumour by damaging tumour cells
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Radiation therapy
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External beam radiation therapy
Use x-ray generated from linear accelerator.
Max energy: 4~20 (MeV, 106 eV)
Mega-Electron-Volt Compare to visible light: 2-3 eV Compare to UV light: 3-5 eV 1000,000 times higher than UV light
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Linear accelerator (Linac)
Source:www.cerebromente.org.br
Accelerated high energy electron beam hit aTungsten target
Produce high energy x-ray beam
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Treatment planning
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It’s also a job for physicists !
X-ray , electrons, photons, scatter radiation dose …
Only a medical physicist were trained to deal with them !
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Summary
Many medical technologies are originated from physics discovery.
Then, developed by physicists.
Medical physicists are The “customer service” team Improve the techniques Develop new techniques
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Ionizing radiation damages the cell
Ionizing radiation
DNA
x-ray photons
Electron
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Ionizing radiation
DNA
X-ray photon
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Excited by physics discoveries
Passionate about People’s well being
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Positron Emission Tomography (PET)
http://www.mni.mcgill.ca/cog/paus/techniques.htm
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PET image
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How is x-ray been generated?1. Bremsstrahlung radiation
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How is x-ray been generated2. Characteristic x-ray radiation
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Part II
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Positron Emission Tracking (PeTrack): the prototype and its evaluations
Tong Xu, Marc Chamberland, Benjamin Spencer, Simon Massad
Carleton University, Ottawa, Canada
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Outline
Introduction
Concept of PeTrack
Simulation study and results
The prototype the evaluation
Conclusion
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External beam Radiation therapy
http//www.stfranciscare.org
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Radiation delivery requirement
Deliver high radiation dose to tumour
Minimize radiation to healthy tissue around the tumour
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Accurate delivery of x-ray beam
3 Tricks...
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Trick #1:Focusing multiple beams
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Trick #2:Collimate the beam to the shape of tumour
This method is called3D-conformal radiation therapy (3D-CRT)
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3D conformal Radiation therapy (3D-CRT)
Shape the field following the outline of tumor
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Trick #3:Intensity modulation inside the field
This is one step forward of 3D-CRT, with the addition of intensity modulation inside the field.Intensity modulated radiation therapy (IMRT)
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Tumour
Spinal cord3D
-CRT
Intensity is uniform inside the field
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IMRT
Intensity is not uniform inside the field
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Accuracy of radiation therapy Significant development has been
done in diagnose and delivery techniques (PET, SPECT, IMRT…)
The tumor motion remains a limiting factor.
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The moving target
Tumour moves due to:RespirationCardiac beatingOther visceral motions
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The tumor can move by more than 3 cm !
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Three level of motion management
None Breath holding orRespiratory gating
Real-timetumor tracking
Radiation field
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Motion management
Breath holding
Respiratory gating
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Breath holding
Methods:– Self breath holding – Active breathing control device
Limitations– Reproducibility (up to 6 mm residual
motion)– Difficult for Lung cancer patient to
tolerate
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Respiratory gating
Breath normally!
Uses: External markers Implanted internal markers Others
– Spirometry– Temperature sensor– Strain gauge…
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Respiratory gating
LinacBeam
On
Off
Gating Thresholds
Berbeco et al. 2005
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External markersTang et al. 2004
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Correlation between external and internal motion Koch et al 2004
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Unstable breathing Ozhasoglu et al. 2002
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Phase shift Ozhasoglu et al. 2002
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Internal markers
Implanted in or close to tumor
Invasive
Provide exact location of tumor
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Internal marker tracked by x-ray Shirato et al. 2000
X-ray tube
Image detector
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Radiation dose from the x-ray fluoroscopy Shirato et al. 2004
Up to 1.2 Gy skin dose per hour of treatment time
Not feasible for intensity modulated radiation therapy – 20 – 30 minutes /fraction– large volume of normal tissue 25-30% of
tumor dose!
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Calypso® 4D LocalizationSystem (EM marker)
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MRI artifacts of EM transponders X Zhu et al, 2009
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RealEye tracking system Shchor et al 2010
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RealEye tracking system Can only track one marker
Can not be used for 10MV beam or higher due to induced radioactivity
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Tracking with Positron emission marker
Miniature markers ( 0.8 mm)
Labeled with positron emission isotopes (0.1 mCi)
Track markers by detecting annihilation gamma
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PeTrack
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PeTrack is NOT PET
(Clinical Whole body PET)
Can PET system locates an object with <1 mm accuracy?
Over-all image resolution of PET : 4 - 8 mm
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Yes, if the geometry of the source is known
Find a point in 3D with the minimum summed distance to the coincident lines
It is NOT image reconstruction !
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Localize PeTrack marker
Patient
Detector Detector
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PeTrack system for tumor tracking
Linac
PeTrack detectors
PositronemissionMarker
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PeTrack Detector modules
Detector module
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PeTrack marker and isotopes
I-124 As-74 Rb-84
T1/2
(days)
4.2 18 32
β+
Fraction23% 29% 23%
Can be implanted with biopsy needle of size 18 Gauge (1.27 mm)
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The challenge
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The algorithm
Classify the coincident lines using Mixture-of-Gaussians clustering technique
Determine the position of each markers from its coincident line cluster
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Find the true location with iteration
Initial estimation
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Computer simulation results
Based on a Monte Carlo simulation package: GEANT4.Four markers were simulated
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Localization precision
0 50 100 150 200 2500.0
0.5
1.0
1.5
Loca
lizat
ion
erro
r (m
m)
Coincidient Lines per marker
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Dynamic Thorax Phantom
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Phantom rod
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MarkerDirection of motion
RMSE (mm)
3D RMSE (mm)
R2
1
AP 0.30
0.39
0.844
LR 0.20 0.954
IS 0.14 0.997
2
AP 0.42
0.53
0.636
LR 0.26 0.812
IS 0.17 0.997
3
AP 0.29
0.40
0.969
LR 0.25 0.986
IS 0.13 0.998
Average 0.24 0.44 -
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The PeTrack Prototype
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BGO crystal and Position Sensitive PMT
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Single Marker
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Adj. R2
Measured amplitude
(mm)
Expected value(mm)
Error(mm)
x 0.99 9.63 ± 0.05 10.00 -0.37
y 0.99 5.16 ± 0.04 5.34 -0.18
z 0.81 0.65 ± 0.02 0.67 -0.02
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3D track of two markers
-5
0
5
10
15
-20
-15
-10
-50
510
-15
-10
-5
0
5
10
15
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Positions of one of the marker
0 10 20 30 40 50 60
-5
0
5
10
15
positio
n (
mm
)
Time(s)
X Y Z
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Two markers precision
Standard deviation of the distance between the two marks during the motion tracking: 0.73 mm
Estimated precision: 0.52mm
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Conclusion
PeTrack can perform tracking of multiple fiducial markers with sub-mm precision
It is a potential technique for achieve hyperfractionation treatment for moving tumors.
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Acknowledgement
Dr. Richard Wassenaar Nathan Churchill, University of
Toronto
Supported by Natural Sciences and Engineering Research Council of Canada
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Thank you!
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Tracking of a single Line marker
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Life time dose (0.1 mCi marker)
Isotope 124I 74As 84Rb
Half life (days) 4.2 18 32
dose (Gy) @ 5 mm (volume: 0.5cc) 2.6 9.0 18.6
dose (Gy) @ 10mm (volume: 4.2cc) 0.7 2.46 4.96
dose (Gy) @ 15mm (volume: 14 cc) 0.32 1.09 2.24
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As compared with x-ray fluoroscopy dose Higher maximum dose
Very small volume effected (~ 10 cc vs 1000 cc
Can be implanted inside the tumor
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Precision
5.0 mm PET spatial resolution provides 0.5 mm localization precision
With only about 100 events!
lines coincident ofNumber
resolution spatial PETPrecision
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Motion trace of marker #3 and
predicted motion trace
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Distribution of the1D prediction error
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95th percentile (100 ms) = 2.3 mm
95th percentile (200 ms) = 2.7 mm
Distribution of the3D prediction error
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Latency(s)
1D pred. error(mm)
3D pred. error(mm)
0.1 0.0 ± 0.8 1.3 ± 0.6
0.2 0.0 ± 0.9 1.4 ± 0.7
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Life time doseActivity = 0.1 mCi
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Sensitivity within the Field of view
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Frame based stereotactic neurosurgery
http://www.elekta.com/healthcare_international_stereotactic_neurosurgery.php
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Fiducial-less trackingSchweikard et. al. 2004
Synthetic a serial of CT at different time points by deforming two CT scans : Inhale and exhale
Registration of real-time x-ray projections with digitally reconstructed images from Synthetic CT scans
Registration computing time: 5 -10 sec Accuracy depends on the deforming
model of lung
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Physical Requirement of tumor tracked radiation therapy
Track the tumor in real-time Predict the tumor position to
account for the lag of delivery system
Fast reaction of delivery system
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Current internal tracking techniques
X-ray marker EM marker
Sampling rate 30 sec-1 10 sec-1
Precision 0.5 mm 0.2 mm
Marker size Φ0.8~1.6mm
Φ1.8mm x 8. mm cylinder
Radiation dose Upto 1.2 G/h Zero
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Correlation between external and internal motionOzhasoglu et al. 2002
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Complex tumor trajectory Ozhasoglu et al. 2002
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Correlation coefficient (R)Koch et al. 2004
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SpirometryHoisak et al. 2004
Higher correlation (R= 0.51 - 0.99) than that of skin marker (R= 0.39 – 0.98)
Difficult to tolerate
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Radiation dose from the x-ray fluoroscopy Shirato et al. 2004
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External markers -1
Passive or active infrared skin markers
Marker position tracked by camera in real time
Linac gated by the position of external markers
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Linear accelerator generate pulsed x-ray
Pulse frequency– 100 – 400 Hz
Pulse width – 1 – 10 μs
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Blanking of PeTrack detector
Expected data acquisition duty cycle > 80%
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PMT HV gating
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Expectation-Maximization -1 Expectation step. Compute the
probabilities for all trajectories, n=1,…N, belonging to each cluster, k=1,…K
K
j
ij
ijn
ij
ik
ikn
iki
kn
mTdGa
mTdGap
1
)()()(
)()()(
)(,
,),(
,),(
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Expectation-Maximization -2 Maximization step. Update
parameters
N
pa
N
n
ikn
ik
1
)(,
)1(k
ik
ik Vmm
)()1(
N
n
ikn
N
n
ikn
ikn
ik
p
mTdp
1
)(,
1
2)()(
,)1(
),(
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Previous worksGundogdu, 2005
Intended for industrial application Two particle was tracked Resolution 20 -30 mm
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The challenge
Simultaneously tracking of three or more markers
Distance between markers: a couple centimeters
The existing algorithm for single particle tracking dose not apply
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Scatter rejection
R=2σ
Patient
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Expectation-Maximization iterations
1. Initial estimation
2. Expectation Clustering by the probability of each trajectory
3. Maximization Update the position of markers
4. Repeat step 2 and 3 until converge.
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Speed of the algorithm
Four markers 400 coincident events 2.8GHz P4
20 ms/run Tumor position can be updated at
a rate > 10 Hz
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Lift time dose for different treatment duration
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Required activity at the time of implanting
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Breath holding
Methods:– Self breath holding – Active breathing control device
Limitations– Reproducibility (up to 6 mm residual
motion)– Difficult for Lung cancer patient to
tolerate
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Respiratory gating
Breath normally!
Uses: External markers Implanted internal markers Others
– Spirometry– Temperature sensor– Strain gauge…
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Respiratory gating
LinacBeam
On
Off
Gating Thresholds
Berbeco et al. 2005
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External markersTang et al. 2004
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Correlation between external and internal motion Koch et al 2004
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Unstable breathing Ozhasoglu et al. 2002
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Phase shift Ozhasoglu et al. 2002
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Identify failed markers
A failed marker should be identified automatically from the output of the algorithm
ka
k
Relative activity of marker # kRoot mean square distance form marker # k to its trajectories
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Identify failed markers
> 3 mm
< 0.02ka
k
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Identify failed markers with criteria
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The source of tumor motion Respiration
Cardiac beating
Other visceral motions
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Lung tumor motions trajectoriesSeppenwoolde et al. 2002
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Internal marker tracked by x-ray Shirato et al. 2000
X-ray tube
Image detector
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Internal marker tracked by x-ray Shirato et al. 2000
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Positron emission and annihilation
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Positron Emission Tomography (PET)
http://www.mni.mcgill.ca/cog/paus/techniques.htm
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PET image
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Physical limits on PET resolution
Humm et al, 2003
Over-all resolution: 4 - 8 mm(Whole body PET)
http://www.raytest.de/pet/clearPET/clearPET.html
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Three 22Na Markers
Activity of 22Na: ~425 kBq/marker
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PET Image reconstruction
http://depts.washington.edu/nucmed/IRL/pet_intro/intro_src/section4.html
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Yes! A single point source can be tracked with < 1 mm accuracy
Park et al. 1993, Park et al. 2002
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The algorithm
Assuming the distance from a marker to its annihilation coincident lines follows a Gaussian distribution
k Standard deviation ~ system spatial resolution
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Methods
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PeTrack simulation model Based on a Monte Carlo simulation
package: GEANT4 Patient: Φ 30cm x 60 cm water
phantom Distance from isocenter to detectors:
50 cm Detector: 40x40 array of 4x4x30 mm3
BGO crystals Energy resolution: 25% Spatial resolution ~ 4 mm
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PeTrack simulation model Marker: active 0.4 mm spherical
core with a 0.2 mm thick gold shell
Single marker simulation:– Sensitivity, scatter fraction, dose
Four markers with I-124 were placed around isocenter: (0,0,0), (15,0,0), (0, 20,0), (0,0,20) (in mm)– Evaluate the algorithm
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Definition of a valid event (trajectory)
Detected energies fall in the energy window (420-600 keV)
Coincidence has to be between detector A1 and A2, or between B1 and B2
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Simulate the initial estimation error Error on the initial estimation
– patient setup– respiration– marker migration
Initial estimation is generated randomly around the true position– ± 5, ± 10 , ± 15 mm
1000 runs of the algorithm
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Definition of success marker and run Localized by the algorithm within 1.5
mm from its true position
A successful run:– All four markers was allocated successfully
Precision:– Mean error among 1000 runs from the true
positions
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Run success rate
0 200 400 600 800 1000
20
30
40
50
60
70
80
90
100R
un s
ucce
ss r
ate
(%)
Coincident lines per marker
± 5 mm initial error ±10mm initial error ±15mm initial error
Total coincident lines per run
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Marker success rate
0 50 100 150 200 25065
70
75
80
85
90
95
100M
arek
er s
ucce
ss r
ate
(%)
Coincident lines per marker
± 5 mm initial error ±10mm initial error ±15mm initial error
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Number of runs with different number of Successful markers
Initial error range (mm)
± 5 ± 10 ± 15
All 4 markers are successful 997 985 777
3 markers are successful 3 15 144
2 markers are successful 0 0 75
1 marker is successful 0 0 4
All 4 markers failed 0 0 0
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Cardiac BeatingShirato et al. 2004
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Yes! A single point source can be tracked with < 1 mm accuracy
Park et al. 1993, Park et al. 2002, Sarah E. Palmer et al, 2006