Image-guided management of uncertainties in scanned particle therapy
1. Image-guided management of uncertainties
in scanned particle therapy
13 March 2014
Giovanni Fattori
Department of Electronics, Information and Bioengineering
Politecnico di Milano
-- PhD Thesis Defense --
2. Presentation outline
Image-guided particle therapy @ CNAO
Optical tracking and X-ray imaging
Development and clinical implementation
Geometrical accuracy
Dosimetrical aspects
Treatment of moving targets
Optical tracking for real time motion monitoring
4D dosimetry (experimental studies)
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3. Particle radiotherapy
1. PHYSICS
Favorable tissue depth-dose distribution
2. RELATIVE BIOLOGICAL EFFECTIVENESS
Microscopic spatial energy distribution
DOSE DELIVERY
Active scanning
Kramer et al. [2012 J. Phys]
Kramer et al. [2010 Eur. Phys. J. D ]
Durante et al. [2009 Nat Rev Clin Oncol]
3 / 35
RBE =
Dphoton
Dion iso
4. Uncertainties in therapy
Challenge
Development of technologies for therapy to manage treatment
uncertainties
Setup errors
Moving targets
Critical issues
Particle sensitivity to tissue density
variation
Organ motion
• Inter-fractional
• Intra-fractional
Treatment of moving targets
Questionable cost-benefit ratio
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5. IGRT: the case of CNAO
In-room imaging
6 DOF treatment couch (PPS)
Solutions for real time monitoring
OTS OPTICAL TRACKING SYSTEM
• Non-invasive
• Real time patient monitoring
PVS PATIENT VERIFICATION SYSTEM
• Schaer-engineering: isocentric double
projection
• Custom system for robotic imaging:
Radiograph and Cone Beam CT
TREATMENT ROOM 1-3 TREATMENT ROOM 2
TREATMENT
SETUP
PPS
OTS
PVS
NOMINAL
POSITION
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6. Optical tracking
Point-based patient registration and motion
monitoring
SMART, BTS Bioengineering
3 free-standing infrared TVC cameras
15 min calibration procedure
• Accuracy = 0.3 mm in 1 m3 volume
• Frequency: 70/100 Hz
PATIENT MODEL OPTICAL DATA
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What is needed: nominal point-based geometry from planning CT images
Sub millimeter scale accuracy (1-3 mm slice thickness in CT)
Manual segmentation
Low 3D accuracy
Inter-operator variability
Automatic fiducials localization in CT images
7. Automatic fiducials localization in CT images
SURFACE
EXTRACTION
SURFACE
PROCESSING
MARKER
RECOGNITION
Geometric filters
1. 10 mm < diag < 22 mm
2. Hausdorff < 20 mm2
3. n° triangles < 650
4. Side difference < 5 mm
CANDIDATE SURFACE
Geometrical prior knowledge: aluminum spheres. (1cm diameter, 1800 HU)
Fattori et al. [2012 IEEE TBME]
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8. Automatic fiducials localization in CT images
LOCALIZATION ACCURACY
3 mm 1 mm
I 0.1640 0.2113
II 0.2374 0.0322
II
I
0.1414 0.2054
LOCALIZATION ROBUSTNESS
Accuracy: 20 μm
N° patients CT resolution
Fiducials per
patient
N° of fiducials Fiducials found
10 head
25 thorax
1.27x1.27x3 mm
6/8 233 215
3 head 0 0 0
92.3%
LEICA LTD 500
** CLINICAL USE SINCE 2011 **
Fattori et al. [2012 IEEE TBME]
High true positive ratio
No false positive
High accuracy
3D error [mm]
8 / 35
9. In-room imaging system for CNAO central room
Specifications:
Limited operating space (Horizontal & Vertical beam lines)
X-ray radiographs and Cone Beam CT
Registration performance comparable with lateral rooms
Geometric residual error < 1mm / 1
Patient setup procedure < 2 min
Integration with existing technologies (PPS, PACS)
Project leader:
Image registration:
Robot & Safety:
Software:
G. Baroni
M. Riboldi
G. Fattori
M. Peroni
P. Cerveri
A. Pella
G. Fattori
G. Fattori
M. Riboldi
Treatment Isocenter
Imaging Isocenter
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2 YEARS PROJECT
1st year: 2D-3D
2nd year: 3D-3D
10. Hardware components 10 / 35
Custom C-arm
SID=1772.2 mm;
SAD=1272.2mm
Robotic arm
Kawasaki
ZX300S
Flat panel detector
Varian 4030D
(30 Hz, 2048x1536 pixels
193.8x194 um pitch)
X-ray source
Varian A277
Generator
Sedecal HF
series
Exposure controlGantry pendant Intrusion detection
11. X-ray Patient Positioning Verification software
Gantry control
Exposure settings
Automatic registration
PPS communication
PACS integration
ROI
Interactive
checkerboard
Images
overlay
Visualization
settings
Automatic
registration
Manual
registration
ROI
Load/Save
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12. Geometry calibration
Calibration phantom (Brandis
Medizintechnik Vertriebs GmbH,
Weinheim, Germany)
36 metal bearings
Optimization of on-plane
projection error
Free parameters:
• Image center
• Panel orientation
System geometric daily QA
SOURCE
(0,0)
Center of
rotation
(-cx,-cy)
Panel
rotations
Imaging Isocenter
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13. System installation in CNAO Room 2
CLINICAL WORKFLOW
PPS MOTION TO TREATMENT ISOCENTER
OTS Point-based registration at treatment isocenter
(≈1min)
PPS MOTION TO IMAGING ISOCENTER (≈3min)
Image-based registration at imaging isocenter
PPS MOTION TO TREATMENT ISOCENTER
(≈3min)
Treatment start
1. Images acquisition
2. Automatic registration
(≈1min)
3. PPS correction
4. Images acquisition
(verification)
5. Automatic registration
Image-based registration
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20. Dosimetric consequences of setup errors after IGRT
Nominal
Setup errors
D95
D105D05
HU-WE
Setup
CI =
Vol95%
VolCTV
IC =
(MaxDose - MinDose)
MinDose
Purpose
To provide clinicians with dosimetric information
about treatment setup besides the residual
geometric error
Range
Interpretation of results
Indexes clearly readable by clinicians
• Envelope DVH (ΔD95CTV, ΔD105CTV, ΔD05OAR)
• Conformity Index for CTV
• Inhomogeneity Coefficient for CTV
Materials and Methods
• Image processing & TRiP98 (M. Krämer)
• Comparison of treatment delivery in nominal
situation and in presence of uncertainty
(Optimum=1)
(Optimum =0)
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21. Simulation of setup errors
ERROR SPACE SAMPLING
Orthogonal sampling (64 simulations)
• 6 Dimensions (translations,
rotations)
Implementation of isocentric 6DOF Correction vector on patient CT
1. Image resampling T
2. Dose calculation
3. Dose cube resampling Tinv
Figure 2. Plan no 299. (Upper part) Convergence of the various algorithms as function of iteration
steps (left hand side) and computation time (right hand side). (Lower part) DVH (left hand side)
and dose distribution in a CT-slice (right hand side). Only results of CGFR optimization are shown.
The indicated isodoses are in percent of the prescribed dose.
For the sake of completeness we additionally present the Levenberg–Marquardt
minimization (LMM) which we also investigated. As far as the number of iterations are
concerned (see figure 1, upper left part) LMM looks quite promising but the computation
times are extremely large (see figure 1, upper right part). The disadvantage of LMM is that in
every iteration step a large system of linear equations has to be solved. Solving the system of
linear equations with the Cholesky decomposition requires about 60 times more computation
time compared with CGFR (figure 1). We investigated alternative equation solvers, for
example the iterative Krylov subspace methods. With the Krylov subspace methods the
computation times could be decreased by a factor of approximately 3 (Buschbacher 2009),
which is by far not enough to allow the usage of LMM in our context.
We further investigated the distribution of the resultant particle numbers on the raster
grid. This is important because large fluctuations of particle numbers between rasterspots
might require changing of the particle intensities by the ion accelerator system. This is time
consuming and could potentially decrease the number of patients treated per day. We examined
some treatment plans and independently from the chosen algorithm we did not observe large
fluctuations of particle numbers between neighbouring rasterspots.
20%
40%
60%
80%
95%
105%
> 105%Figure 2. Plan no 299. (Upper part) Convergence of the various algorithms as function of iteration
steps (left hand side) and computation time (right hand side). (Lower part) DVH (left hand side)
and dose distribution in a CT-slice (right hand side). Only results of CGFR optimization are shown.
The indicated isodoses are in percent of the prescribed dose.
For the sake of completeness we additionally present the Levenberg–Marquardt
minimization (LMM) which we also investigated. As far as the number of iterations are
concerned (see figure 1, upper left part) LMM looks quite promising but the computation
times are extremely large (see figure 1, upper right part). The disadvantage of LMM is that in
every iteration step a large system of linear equations has to be solved. Solving the system of
linear equations with the Cholesky decomposition requires about 60 times more computation
time compared with CGFR (figure 1). We investigated alternative equation solvers, for
example the iterative Krylov subspace methods. With the Krylov subspace methods the
computation times could be decreased by a factor of approximately 3 (Buschbacher 2009),
which is by far not enough to allow the usage of LMM in our context.
We further investigated the distribution of the resultant particle numbers on the raster
grid. This is important because large fluctuations of particle numbers between rasterspots
might require changing of the particle intensities by the ion accelerator system. This is time
consuming and could potentially decrease the number of patients treated per day. We examined
some treatment plans and independently from the chosen algorithm we did not observe large
fluctuations of particle numbers between neighbouring rasterspots.
6. Summary and conclusion
The task for the optimization of RBE-weighted dose is
depending nonlinearly on the particle numbers
20%
40%
60%
80%
95%
105%
> 105%
-30° Dos
+30° CT
1 mm 1 setup error
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23. Patient 1: worst case simulation for D95CTV
ce of the various algorithms as function of iteration
ght hand side). (Lower part) DVH (left hand side)
de). Only results of CGFR optimization are shown.
scribed dose.
20%
40%
60%
80%
95%
105%
> 105%
rgence of the various algorithms as function of iteration
me (right hand side). (Lower part) DVH (left hand side)
nd side). Only results of CGFR optimization are shown.
e prescribed dose.
ionally present the Levenberg–Marquardt
ed. As far as the number of iterations are
looks quite promising but the computation
ht part). The disadvantage of LMM is that in
20%
40%
60%
80%
95%
105%
> 105%
SETUP ERROR
SETUP AND RANGE ERROR
(Expected) Results:
Dose coverage remains acceptable
Conformity is reduced
Inhomogeneity is increased
Quantification of dosimetric deviations wrt nominal condition
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LL:
AP:
SI:
Pitch:
Rotate:
Roll:
-0.34mm
-0.87mm
-0.97mm
-0.19°
-0.97°
0.78°
Setup error
+
Rel WEL +2.6%
24. IGRT: Conclusion and Limitations
Tools for automated fiducials localization in treatment planning CT images
Development of a custom robotic in-room imaging system
Implementation at CNAO
Double projection: Clinical use since April 2013
CBCT: foreseen for April 2014
Overall residual setup error following CNAO IGRT strategy (OTS + in-
room imaging): Millimeter and degree scale.
Tool to provide valuable dosimetric information to clinicians
Not far from pre-treatment setup verification: about 10 mins (single
simulation)
Treatment plan robustness test: 2 hours
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25. From static to moving target with active scanning
X-RAY SOFT-TISSUE IMAGING
US MRI
PHASE1
4D IMAGING
(4D CT)
PHASEN
OPTICAL TRACKING +
CORRELATION MODELS
BASIC ASSUMPTION:
TARGET MOTION REPEATIBILTY
4D TREATMENT PLAN (TP)
TIME RESOLVED TREATMENT DELIVERY
ENERGY ADAPTATIONLATERAL DEFLECTION
MOTION MONITORING
DOSE DELIVERY (beam tracking)
MOTION MONITORING SYSTEMS
Real time feedback to TCS to drive
the treatment delivery
Verify consistency wrt TP
Trigger image acquisition
MOTION MITIGATION STRATEGIES
BEAM TRACKING
GATING
RESCANNING
Direct observation Surrogate signal
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26. Optical tracking for time resolved treatment
PURPOSE
To interface a commercial solution for optical tracking with a Therapy Control System
for particles: beam tracking and gating
WHAT IS REQUIRED
Real time monitoring of multiple surrogates
Compatibility with 4DCT acquisition protocols
Real time communication with TCS: delay compensation
Static
Residual
Interplay
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27. The tracking code package
Optical Tracking System Therapy Control System
Correction
vector
3D OTS DATA
BTU
Wedge
range shifter
Steering
magnets
Depth
compensation
Lateral
compensation100 Hz frame rate
LABELLER
TARGE
T
FRAMES
INTERPOLATION
POLYNOMIAL
COEFFICIENTS
TIMECRITICALTHREADOTSDRIVENTHREAD
BREATHING
SIGNAL
MOTION PHASE
DETECTION
CORRELATION MODELS [ x y z ]
[ MP ]
PATIENT
MODEL
MOTION
PHASE TABLE
RCS
TRANSFORM
MATRIX
SHARED RESOURCES
DIGITALCOMMUNICATION(UDPSOCKET)
Treatment
plan
Fattori et al. [2012 AAPM]
KEY FEATURES:
Phase/Amplitude 4DCT
Ethernet link (UDP)
Signal time prediction
Ready for Gating and Beam
tracking experiments
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28. Procedure for system latencies quantification
DEPTH
WE
compensation
Mean
Std.Dev
1 mm 27.43 7.51
9 mm 34.1 6.29
5measurements(0,
DEPTH
Calculatedbydiffere
TOTAL–LATERAL
Laser distantiometer
OTS marker
Fattori et al. [2013 TCRT Express]
LAT ERAL
OTSbenchmark with Laser distantiometer (1KHz frm.rate)
5 measurements(0,5,10,15,20 msec.advance prediction)
DEPT H
Calculated by difference
TOTAL– LATERAL
Motion OTS
LATERAL
OTSbenchmark with Laser distantiometer (1KHz frm.rate)
5 measurements(0,5,10,15,20 msec.advance prediction)
DEPTH
Calculated by difference
TOTAL– LATERAL
Motion OTS TCS
34
(mea
1
MAGNETS
WEDGEFILTER
LATERAL
14.6 msec
DEPT H
Calculated by difference
TOTAL– LATERAL
Motion OTS
28 / 35
29. Signal time prediction accuracy
Polynomial fitting: Ist order
5 samples history, 100 Hz data
Time compensated Vs. Reference
Fattori et al. [2013 TCRT Express]
REFERENCE
NON COMPENSATED
TIME COMPENSATED
• Reference = Non-compensated + δ (=14.6ms)
• 10 mins acquisition:
RMS = 0.05 mm
RMS = 0.1 mm
30. Beam tracking @ GSI: Setup
Purpose:
To evaluate the feasibility of
OTS driven 4D treatment
Steidl et al. [2012 PMB]
Breathing phantom
Correlated target/thorax motion
10x5x10 cm (x,y,depth)
Treatment plan
1 Gy homogeneous, 12C
35 mm side
4DCT: 8 MPh, phase
binned
Motion monitoring:
SMART-DX100, 2 TVC
Dose measurement
16 PTW Pinpoint ionization
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31. Beam tracking @ GSI: Results
Fattori et al. [2013 TCRT Express]
Note:
Pure translational target motion
No soft tissue material inside the thorax
Excellent target and thorax motion repeatibility
Median(IQR) 2.0 (25.9) % -0.3 (2.3) % -1.2 (9.3) %
Measured delta wrt static irradiation
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32. Lateral beam tracking @ CNAO
Phantom
- Planar target motion (2D)
- 25 mm (lat) 18 mm (vert) peak-to-peak
- Planarity: median 0.038 mm (IQR:0.09)
- Repeatibility: mean std 0.18 0.3 mm
‘Treatment plan’
- Squared PTV
- 6 cm side
Purpose
Proof the OTS/TCS integration
STATIC TRACKING INTERPLAY GATING
Average flatness 4 % 5.7 % 24 % 9.5 %
Average penumbra 9.2 mm 9 mm 19 mm 9.1 mm
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Pella, Fattori et al. [PTCOG52]
33. Moving targets: Conclusion and Limitations
General solution for OTS/TCS integration was described
Ethernet link, UDP protocol
Procedure for delays quantification
The tracking code package available for research (CNAO, GSI,… )
Development and benchmark of int-ext correlation model (M. Seregni)
Functional gating and beam tracking modules
GSI: 3D optical driven beam tracking
CNAO: 2D optical driven beam tracking and gating
BEAM TRACKING: how to deal with deviations from treatment plan?
1. Real time dose compensation with beam tracking [Lüchtenborg 2012, Med Phys]
2. Dose changes outside the VOIs (inverse interplay effect)
33 / 35
34. Final remarks
IGRT
1. Development and implementation of state-of-the art methods for IGRT
• Point based
• Anatomical information (bone anatomy + soft tissue imaging)
2. CNAO Room 2: Custom system for robotic imaging:
(!) 2D-3D available for clinical use
(!) CBCT almost available for clinical use
(!) Double projection & CBCT dataset: 2D-3D / 3D-3D Comparison
Treatment of moving targets
1. GSI: beam tracking, lateral and depth compensation
2. CNAO:
• lateral compensation
• ready for gated treatment:
(!) strategy to compensate for residual motion in the gating window
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35. Future directions
IGRT @ CNAO
1. ‘CT-of-the-day’ software module
• Pre-treatment dose simulation on the updated CT
• Anatomical information in perspective of PET in-room
2. 4D CBCT
Treatment of moving targets
Tailored treatment on patient specific basis:
• Motion reduction: gating + rescanning/overlapped pencil
beams
• Motion compensation: multiple points + tumor tracking
• Adequate strategy for margin definition
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