Brachytherapy Based MicroRT
Preclinical Image Guided
Microirradiators: Concepts, Design
and Implementation
E.W. Izaguirre, B.L. Kassebaum, J. Birch, I. Su, P.
Grigsby, and D. A. Low.
Instrument Diagram
This work is supported by NIH grant
5R01EB007705
Brachytherapy Based MicroRT
Image Guided Microirradiators
• Anatomical Imaging
• microCT
• microMRI
• Functional Imaging
Pinhole aperture
cylindrical support
xyz positioning system
Parametric beam
simulation
• microSPECT
• microPET
• Optical
• microMRI
UCSF MicrocT-MicroSPECT
M. Sun, E.W. Izaguirre, J. Carver
and B. Hasegawa
1
Background
Current commercial small animal imaging instrumentation :
microCT, microMRI, microPET, microSPECT, and optical
scanners.
>50% of cancer patients receive radiation therapy.
MicroCT + MicroRT = MicroIGRT
MicroCT
The development of small animal micro irradiation technology
has not reached the sophistication of small animal imaging
instrumentation.
Highly conformal microirradiators with an on board
anatomical imaging subsystem should be developed to foster
preclinical radiobiology research.
MicroRT
New instrumentation should provide a state of the art platform
and to perform experiments that cannot be performed with the
current irradiator technology.
MicroIGRT Instrument Overview
MicroIGRT Instrument Overview
MicroCT
MicroRT
The designed micro image guided radio therapy (microIGRT) system
showing the primary components. The instrument is designed in a
tandem configuration where the animal bed is located in the microCT
field of view for anatomical imaging and is then shifted to the micro
irradiator subsystem for conformal irradiation.
The Washington University Image guided Micro Irradiator (MicroIGRT)
The microirradiator subsystem consists of a high power orthovoltage source
with a high dissipation anode to achieve a small focal spot source capable
of delivering high dose rates, percentage depth dose, and submillimeter
beam penumbra to small animals.
2
MicroIGRT : Design
• Study the feasibility of using industrial orthovoltage sources to deliver
accurate dose distributions to radiobiological animal models.
• Determine the best commercial orthovoltage source to achieve the
following target values :
Dose Delivery Accuracy : 5 %
Dose Rate : 400400-4000 cGy minmin-1
Dose Homogeneity :5 %
Penumbra : 0.25 mm (90%(90%-10%)
Positioning Accuracy : 0.25 mm
Throughput :10 to 20 min/subject
• Develop an accurate treatment planning system with a realistic model
model
of the selected orthovoltage source.
Source Filament Model
Filament Input
Power
Filament Electron
Current
Orthovoltage Source Simulator Code
Flow Diagram
Input
Filament Power Afil, ∆Vfil
Tube kVp
Tube mA
Tube msec
The othtovoltage
source simulation
program was
developed using
Visual C++.
The code is fully
compatible with DSP
development tools for
hardware/software
optimization
Source Filament model
Anode Emission model
Output
Beam Model
Spectrum
I(E), N(E), Itot
Animal Phantom model
Output
Animal dose
Anode Emission Model
Photon Emission
Differential Cross Section
Bremsstrahlung
Intensity
Emitted Photons per Interval of Energy
3
Anode Emission Model
Anode Focal Spot Analysis
Fraction of Photons
Exiting the Anode
Electron Penetration Distance
Anode Focal Spot
Anode Mass Stopping Power
Anode Focal Spot
Contour Level Map
Mass Attenuation Coefficient
Bremsstrahlung Coefficient
Anode Line Profile
Othovoltage Source Spectrum
I(A.U.)
Anode Focal Spot: Simulation
Anode Line Profile
Measured anode focal spot
Energy (keV)
Anode Emission Parameterization
Simulated Anode Focal Spot
The emission is modulated
with the empirical intensity
parameterization
Spectrum emitted from
an arbitrary anode point
Simulated anode focal spot
4
Beam Penumbra Simulations
Filtering
Source Collimator
Beam Cross Section
Beam Width: 2x2 mm2
Average Penumbra
0.25 mm
Beam Profile
Collimator: 7 mm Tungsten
In order to reduce bone dose we propose to filter the radiation
beam. Solid line (blue) unfiltered output, doted line (red) filtered
output and dash line (black) bone f-factor. In our proposed filter
most of the filtered beam spectrum lies above 150 keV, where the
bone f-factor is within 10% of the muscle f-factor.
Energy fluence (a.u.)
Orthovoltage Source Spectrum
Total Body Irradiation
Unfiltered
Filtered
Energy (keV)
Simulation of the 320kVp x-ray source without additional filtration and
with a filter composed of 1.5 mm Lead, 5 mm Tin, 1 mm Copper, and 4
mm Aluminum. This filter removes the low energy x-ray components to
raise the average bremsstrahlung energy to 4.6 mm of Cu. Unfiltered dose
profile (red line) and filtered dose profile (green line).
Unfiltered
Filtered
Absorbed Dose Profile
Dose rates of 16 Gy/min (filtered) and 40
Gy/min (unfiltered) can be delivered to an
animal phantom if the source is operated
at 1.5 mA.
The maximum source current is 5 mA at the
maximum voltage bias, so even greater dose
rates will be possible.
Animal Phantom: Modified MOBY, John Hopkins Univ.
5
The MicroIGRT
.
The 3D diagram shows the instrument tandem architecture.
Each subsystem can be independently operated.
The MicroRT Subsystem
The microRT gantry linear translation stages
to support the orthovoltage source
The MicroRT Subsystem
The MicroRT gantry showing the orthovoltage source,
the collimation system, and primary beam shielding cup.
The MicroRT Subsystem
The microRT gantry showing the 320 kVp orthovoltage source
mounted on a rotating and a linear stages.
Source distance to axis 6” to 12”.
6
The MicroRT Subsystem
The microRT primary beam shielding. The lead shield is located
on the opposite side of the gantry to compensate the
high torque produced by the orthovoltage source weight.
The MicroRT Subsystem
The MicroRT Subsystem
The microRT bearing system for accurate
gantry rotation. Rotation precision: 2 arc min.
The MicroRT Subsystem
Source rotation system
Design
Gantry rotation system
Implementation
HV generator
Beam stopper + Mouse bed
7
The Micro CT Subsystem
The MicroIGRT
Beam Diam. 4 mm
Image of the Instrument - June 2008
Beam profile
The Micro CT Subsystem
The microCT bearing system for accurate
gantry rotation. Rot precision: 2 arc min.
MicroCT gantry showing the
flat panel detector and the
microfocus x-ray source
The Micro CT Subsystem
The microCT gantry plate. The gantry is constructed using
hollow beams for light weigh and high rigidity
8
The Micro CT Subsystem
The microCT gantry showing the four high precision
linear stages for imaging instrumentation radial positioning
The MicroCT Micro Focus Source
The micro focus source collimator. The source is
collimated to limit the beam scattering and unnecessary
irradiation to non-imaged portions of the animal body
The MicroCT Micro Focus Source
The micro focus source of the microCT subsystem.
Source characteristics: tube potential 80 kVp, tube current
0.5mA, focal spot 75x75um2, and beam divergence 30o.
The MicroCT Micro Focus Source
The micro focus source shutter. A high speed rotary
solenoid is used to shut on and off the beam between exposures
9
The MicroCT Micro Focus Source
The micro focus source multiple filter system.
The microCT is optimized to acquire high contrast
low dose tomographic images of small rodents.
The Micro CT Subsystem
Complete microCT subsystem with the animal bed
The combined circular motion of the gantry with the linear motion
of the couch allows circular and helical tomographic scanning
The Micro CT
Design
Implementation
The Micro CT Subsystem
Rotation gear
Cable collection belt
10
The MicroCT
Subsystem
MicroIGRT
• micro-focus 80kVp x-ray source
• Focal Spot 75x75 mm2 focal
spot
• Flat panel amorphous silicon
Design
detector with 1024x1024 pixels.
• High efficiency CsI(Tl)
scintillator.
• High precision gantry rotation
( 1/60 deg, 0.0001 axis tilt)
• Micrometric source and detector
positioning (50 mm)
• microCT spatial resolution ~ 120
•
Implementation
mm
Dose less than 1cGy/scan.
Instrumentation Software
Treatment Planning Software
Source model
Mouse Phantom
Pencil Beam
Monte Carlo
Software Platform : Visual C++ (Microsoft) + National
Instruments drivers + In house developed drivers
11
Mouse Bed and Animal Handling
Shielding ?
• Gas Anesthesia: Isoflurane
• Temperature control :
IR lamp heater
• Respiratory motion sensors
• Gas flow sensors
Shielding panels construction
Al
Box frame
Al
Pb
Brachytherapy Based MicroRT
Instrument Diagram
Brachytherapy
MicroRT
Previous pinhole
New pinhole
2 months
Time
3 months
4 months
12
Sensitization of Orthotopic Glioblastomas to
Radiotherapy by Transglutaminase 2
Inhibitors
List of Collaborative Projects
• MRI imaging of necrosis induced by ionizing
radiation J. Garbow
• Extracellular matrix and Sensitization of
orthotopic glioblastomas to radiotherapy by
Transglutaminase 2 inhibitors K. Rich
1.25
1.2
• PET tracers to optimize tumor treatment in
1.15
xenograph models of breast cancer: K. Shoghi-
1.1
1.05
1
Radiation Only
0.95
Radiation & Drug
30
20
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ionizing irradiation. P. Grigsby, M. Taylor, A.
Ja
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• Variations in cancer cell motility induced by
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rt
D
ate
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23
20
0.9
Sta
Optical Imaging
Jadid
Control
Ja
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Tumor Size
(Log of Avg Change in Bioluminescence)
.
Average Fold Change of Tumor Size in Individual Mice
Laszlo and E. Izaguirre
Collaboration with Dr Keith Rich , Neurosurgery , WU
Multiple Beam Conformal Irradiation
Results and Conclusions
•
We are constructing a small animal imaged guided micro irradiator
irradiator which consist in a
microRT subsystem integrated with an on board microCT subsystem.
•
Simulated microCT reconstructed tomographic data demonstrates that
that a resolution of
120 µm is achievable using 128 projections and a maximum radiation dose
dose of 1cGy.
•
Automatic animal positioning and handling could be performed within
within a precision of
100 µm. The treatment beam can be aimed at different latitude and longitude
longitude angles
in steps of 2 arc min. and translated at 50µ
50µm steps (x,y,z). The beam cross section
can be modulated with submillimeter precision using steps of 50 µm .
• We determined that a source of nominal maximum potential output of 320kVp and
Mouse phantom
Liver phantom
Mask generation using back propagation
focal spot of 0.4x0.4 mm2 outperformed other available sources. We designed a
ThoraeusThoraeus-like filter to obtain a bremsstrahlung spectrum energy greater than 4mm of
Cu to increase skin spare and reduce bone dose.
Collimator exchange
•
An average beam penumbra of 0.25mm and a dose rate of 16 Gy/min
Gy/min is possible
using this filtered beam. Higher energy sources would increase cost and shielding
thickness. Lower energies sources showed limited intensities when
when they were
aggressively filtered.
•
The construction of the device will be finished shortly. The commissioning
commissioning of the
complete system is expected by the end of this year
Multiple beam irradiation
13
Collaborators
Daniel Low
Jeff Michalski
Marie Taylor
Robert Myerson
Sasa Mutic
Paraq Parikh
Perry Grigsby
Keith Rich
Joseph Deasy
Joel Garbow
Kooresh Shoghi
Sreekrishna M Goddu
Jose Garcia Ramirez
Dharanipathy Rangaraj
Joseph Roti Roti
D. Hallahan
Andrei Laszlo
Buck Rogers
Suzana Gonzalo
Ilona Fleischer
Acknowledgments
Laboratory Members
Bethany Kassebaum
Xiumin Diao
Jordan Birch
I-Tan Su
Animal Phantom
John Hopkins Univ.
Paul Segars
Thank you !
We are looking for a postdoc !!!
Benhamin Tsui
High Resolution Low Dose MicroCT
Current Imaging of Tumor
Vasculature
- Techniques to image tumor
vasculature are based in multiple
micro CT images (8 frames /view).
-Unnecessary high dose delivered
to the animal Kindlmann et al.
New technique:
Low dose micro CT
- High efficiency detectors for small
animal: 80kVp
-The only option is to change the
scintillator
-Dual energy microCT
Study of the Tumor Micro Environment
Goals of the project :
Imaging angiogenesis
Determine vascular
renormalization induced
during treatment
Correlate tumor
vascularity with
oxygen distribution
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Dual Energy MicroCT
X-ray Source Spectrum
Dual energy simulations
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