brachytherapy based micrort - american association … roti roti d. hallahan andrei laszlo buck...
Post on 09-May-2018
217 Views
Preview:
TRANSCRIPT
1
Preclinical Image Guided Microirradiators: Concepts, Design
and ImplementationE.W.E.W. Izaguirre, B.L. Kassebaum, J. Birch, I. Izaguirre, B.L. Kassebaum, J. Birch, I. Su, P. Su, P.
Grigsby, and D.Grigsby, and D. A. Low.A. Low.
This work is supported by NIH grant 5R01EB007705
Brachytherapy Based Brachytherapy Based MicroRTMicroRT
Instrument Diagram
BrachytherapyBrachytherapy Based Based MicroRTMicroRT
xyz positioning system
Pinhole aperturecylindrical support
Parametric beam simulation
Image Guided Image Guided MicroirradiatorsMicroirradiators
•• Anatomical ImagingAnatomical Imaging••microCTmicroCT••microMRImicroMRI
•• Functional Imaging Functional Imaging ••microSPECTmicroSPECT••microPETmicroPET••Optical Optical ••microMRImicroMRI
UCSF MicrocT-MicroSPECTM. Sun, E.W. Izaguirre, J. Carver
and B. Hasegawa
2
BackgroundBackground� Current commercial small animal imaging instrumentation : microCT, microMRI, microPET, microSPECT, and optical scanners.
� >50% of cancer patients receive radiation therapy.
� 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.
� New instrumentation should provide a state of the art platform and to perform experiments that cannot be performed with the current irradiator technology.
MicroCT + MicroRT = MicroIGRTMicroCT + MicroRT = MicroIGRT
MicroCT
MicroRT
MicroIGRTMicroIGRT Instrument Instrument OverviewOverview
The designed micro image guided radio therapy (microIGRT) systemshowing 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 submillimeterbeam penumbra to small animals.
MicroCT
MicroRT
MicroIGRTMicroIGRT Instrument Instrument OverviewOverview
3
MicroIGRTMicroIGRT : Design : Design •• Study the feasibility of using industrial Study the feasibility of using industrial orthovoltageorthovoltage sources to deliver sources to deliver
accurate dose distributions to radiobiological animal models.accurate dose distributions to radiobiological animal models.
•• Determine the best commercial Determine the best commercial orthovoltageorthovoltage source to achieve the source to achieve the following target values :following target values :
�� Dose Delivery Accuracy : 5 %Dose Delivery Accuracy : 5 %�� Dose Rate : 400Dose Rate : 400--4000 4000 cGycGy minmin--11�� Dose Homogeneity :5 %Dose Homogeneity :5 %�� Penumbra : 0.25 mm (90%Penumbra : 0.25 mm (90%--10%) 10%) �� Positioning Accuracy : 0.25 mm Positioning Accuracy : 0.25 mm �� Throughput :10 to 20 min/subjectThroughput :10 to 20 min/subject
•• Develop an accurate treatment planning system with a realistic mDevelop an accurate treatment planning system with a realistic model odel of the selected of the selected orthovoltageorthovoltage source.source.
OrthovoltageOrthovoltage Source Simulator Code Source Simulator Code Flow DiagramFlow Diagram
Anode Emission model
Source Filament model
Beam ModelOutputSpectrum
I(E), N(E), Itot
InputFilament Power Afil, ∆∆∆∆Vfil
Tube kVpTube mA
Tube msec
Animal Phantom model
OutputAnimal dose
The othtovoltagesource simulation program was developed using Visual C++.The code is fully compatible with DSP development tools forhardware/software optimization
Source Filament ModelSource Filament Model
Filament Input Power
Filament Electron Current
Anode Emission ModelAnode Emission Model
Photon EmissionDifferential Cross Section
BremsstrahlungIntensity
Emitted Photons per Interval of Energy
4
Anode Emission ModelAnode Emission Model
Anode Mass Stopping Power
Fraction of Photons Exiting the Anode
Electron Penetration Distance
Mass Attenuation Coefficient
Bremsstrahlung Coefficient
Anode Focal Spot AnalysisAnode Focal Spot Analysis
Anode Focal Spot Anode Focal Spot Contour Level Map
Anode Line Profile Anode Line Profile
Anode Focal Spot: SimulationAnode Focal Spot: Simulation
Simulated Anode Focal Spot The emission is modulated with the empirical intensity
parameterizationAnode Emission Parameterization
Othovoltage Source Spectrum
Measured anode focal spot
Energy (keV)
I(A
.U.)
Spectrum emitted from an arbitrary anode point
Simulated anode focal spot
5
Beam Penumbra Simulations Beam Penumbra Simulations
Average Penumbra0.25 mm
Beam Cross SectionBeam Width: 2x2 mm2
Beam Profile Collimator: 7 mm Tungsten
Source Collimator
FilteringFiltering
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.
OrthovoltageOrthovoltage Source Spectrum Source Spectrum
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).
Energy (keV)
Ener
gy f
luen
ce(a
.u.)
Total Body IrradiationTotal Body Irradiation
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.
Unfiltered Filtered
Unfiltered FilteredAbsorbed Dose Profile
6
The The MicroIGRTMicroIGRT
.The 3D diagram shows the instrument tandem architecture.
Each subsystem can be independently operated.
The The MicroRTMicroRT SubsystemSubsystem
The MicroRT gantry showing the orthovoltage source,the collimation system, and primary beam shielding cup.
The The MicroRTMicroRT SubsystemSubsystem
The microRT gantry linear translation stages to support the orthovoltage source
The The MicroRTMicroRT SubsystemSubsystem
The microRT gantry showing the 320 kVp orthovoltage source mounted on a rotating and a linear stages.
Source distance to axis 6” to 12”.
7
The The MicroRTMicroRT SubsystemSubsystem
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 The MicroRTMicroRT SubsystemSubsystem
The microRT bearing system for accurategantry rotation. Rotation precision: 2 arc min.
Design Implementation
The The MicroRTMicroRT SubsystemSubsystemThe The MicroRTMicroRT SubsystemSubsystem
Source rotation system
HV generator
Gantry rotation system
Beam stopper + Mouse bed
8
The The MicroIGRTMicroIGRT
Image of the Instrument - June 2008
Beam Diam. 4 mm
Beam profile
The Micro CT SubsystemThe Micro CT Subsystem
MicroCT gantry showing the flat panel detector and the microfocus x-ray source
The Micro CT SubsystemThe Micro CT Subsystem
The microCT bearing system for accurategantry rotation. Rot precision: 2 arc min.
The Micro CT SubsystemThe Micro CT Subsystem
The microCT gantry plate. The gantry is constructed using hollow beams for light weigh and high rigidity
9
The Micro CT SubsystemThe Micro CT Subsystem
The microCT gantry showing the four high precision linear stages for imaging instrumentation radial positioning
The MicroCT Micro Focus SourceThe 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 SourceThe 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 SourceThe 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
10
The MicroCT Micro Focus SourceThe 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 CTThe Micro CT
Design Implementation
The Micro CT SubsystemThe Micro CT Subsystem
Complete microCT subsystem with the animal bedThe combined circular motion of the gantry with the linear motion
of the couch allows circular and helical tomographic scanning
The Micro CT SubsystemThe Micro CT Subsystem
Rotation gear Cable collection belt
11
The MicroCT The MicroCT SubsystemSubsystem• micro-focus 80kVp x-ray source • Focal Spot 75x75 mm2 focal
spot • Flat panel amorphous silicon
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
mm • Dose less than 1cGy/scan.
MicroIGRTMicroIGRT
Design
Implementation
Instrumentation Software Instrumentation Software
Software Platform : Visual C++ (Microsoft) + National Instruments drivers + In house developed drivers
Treatment Planning Software Treatment Planning Software
Source model
Mouse Phantom
Pencil Beam
Monte Carlo
12
Mouse Bed and Animal HandlingMouse Bed and Animal Handling
•• Gas Anesthesia: Gas Anesthesia: IsofluraneIsoflurane•• Temperature control :Temperature control :
IR lamp heaterIR lamp heater•• Respiratory motion sensorsRespiratory motion sensors•• Gas flow sensorsGas flow sensors
Shielding ?Shielding ?
Al Al
Pb
Box frame
Shielding panels construction
Brachytherapy Based Brachytherapy Based MicroRTMicroRT
Instrument Diagram
Brachytherapy Brachytherapy MicroRTMicroRT
2 months 3 months 4 monthsTime
New pinhole
Previous pinhole
13
Sensitization of Orthotopic Glioblastomas to Radiotherapy by Transglutaminase 2
Inhibitors
Average Fold Change of Tumor Size in Individual Mice
0.9
0.95
1
1.05
1.1
1.15
1.2
1.25
Start Date
Jan
20
Jan 20
- Ja
n 23
Jan 20
- Ja
n 27
Jan 20
- Ja
n 30
Tu
mo
r S
ize
(Lo
g o
f A
vg C
han
ge i
n B
iolu
min
esce
nce
)
.
Control
Radiation Only
Radiation & Drug
Optical Imaging
Collaboration with Dr Keith Rich , Neurosurgery , WU
List of Collaborative ProjectsList 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
• PET tracers to optimize tumor treatment in xenograph models of breast cancer: K. Shoghi-Jadid
• Variations in cancer cell motility induced by ionizing irradiation. P. Grigsby, M. Taylor, A. Laszlo and E. Izaguirre
Multiple Beam Conformal IrradiationMultiple Beam Conformal Irradiation
Mouse phantom Mouse phantom
Mask generation using back propagationMask generation using back propagation
Liver phantom Liver phantom Collimator exchangeCollimator exchange
Multiple beam irradiationMultiple beam irradiation
Results and ConclusionsResults and Conclusions•• We are constructing a small animal imaged guided micro irradiatoWe are constructing a small animal imaged guided micro irradiator which consist in a r which consist in a
microRT subsystem integrated with an on board microCT subsystem.microRT subsystem integrated with an on board microCT subsystem.
•• Simulated microCT reconstructed tomographic data demonstrates thSimulated microCT reconstructed tomographic data demonstrates that a resolution of at a resolution of 120 120 µµm is achievable using 128 projections and a maximum radiation dom is achievable using 128 projections and a maximum radiation dose of 1cGy. se of 1cGy.
•• Automatic animal positioning and handling could be performed witAutomatic animal positioning and handling could be performed within a precision of hin a precision of 100 100 µµm. The treatment beam can be aimed at different latitude and lonm. The treatment beam can be aimed at different latitude and longitude angles gitude angles in steps of 2 arc min. and translated at 50in steps of 2 arc min. and translated at 50µµm steps (x,y,z). The beam cross section m steps (x,y,z). The beam cross section can be modulated with submillimeter precision using steps of 50 can be modulated with submillimeter precision using steps of 50 µµmm. .
•• We determined that a source of nominal maximum potential output We determined that a source of nominal maximum potential output of 320kVp and of 320kVp and focal spot of 0.4x0.4 mm2 outperformed other available sources. focal spot of 0.4x0.4 mm2 outperformed other available sources. We designed a We designed a ThoraeusThoraeus--like filter to obtain a like filter to obtain a bremsstrahlungbremsstrahlung spectrum energy greater than 4mm of spectrum energy greater than 4mm of Cu to increase skin spare and reduce bone dose. Cu to increase skin spare and reduce bone dose.
•• An average beam penumbra of 0.25mm and a dose rate of 16 An average beam penumbra of 0.25mm and a dose rate of 16 GyGy/min is possible /min is possible using this filtered beam.using this filtered beam. Higher energy sources would increase cost and shielding Higher energy sources would increase cost and shielding thickness. Lower energies sources showed limited intensities whethickness. Lower energies sources showed limited intensities when they were n they were aggressively filtered.aggressively filtered.
•• The construction of the device will be finished shortly. The comThe construction of the device will be finished shortly. The commissioning of the missioning of the complete system is expected by the end of this year complete system is expected by the end of this year
14
AcknowledgmentsAcknowledgmentsCollaboratorsCollaboratorsDaniel Low Daniel Low
Jeff MichalskiJeff MichalskiMarie Taylor Marie Taylor
Robert MyersonRobert MyersonSasa MuticSasa Mutic
ParaqParaq Parikh Parikh Perry GrigsbyPerry Grigsby
Keith RichKeith RichJoseph Deasy Joseph Deasy Joel Garbow Joel Garbow
Kooresh ShoghiKooresh ShoghiSreekrishna M GodduSreekrishna M GodduJose Garcia RamirezJose Garcia Ramirez
Dharanipathy RangarajDharanipathy RangarajJoseph Joseph RotiRoti RotiRoti
D. D. HallahanHallahanAndrei LaszloAndrei LaszloBuck RogersBuck Rogers
SuzanaSuzana GonzaloGonzaloIlonaIlona FleischerFleischer
Animal PhantomAnimal PhantomJohn Hopkins Univ.John Hopkins Univ.Paul Paul SegarsSegarsBenhaminBenhamin Tsui Tsui
Laboratory MembersBethany Kassebaum Xiumin DiaoJordan Birch I-Tan Su
Thank you ! Thank you !
We are looking for a postdoc !!!
High Resolution Low Dose MicroCTHigh Resolution Low Dose MicroCTCurrent Imaging of Tumor Current Imaging of Tumor
VasculatureVasculature
-- Techniques to image tumor Techniques to image tumor vasculature are based in multiple vasculature are based in multiple micro CT images (8 frames /view).micro CT images (8 frames /view).--Unnecessary high dose delivered Unnecessary high dose delivered to the animal to the animal KindlmannKindlmann et al.et al.
New technique: New technique: Low dose micro CTLow dose micro CT-- High efficiency detectors for small High efficiency detectors for small animal: 80kVpanimal: 80kVp--The only option is to change the The only option is to change the scintillatorscintillator--Dual energy microCT Dual energy microCT
Study of the Tumor Micro EnvironmentStudy of the Tumor Micro Environment
Goals of the project :
Imaging angiogenesis
Determine vascular renormalization induced
during treatment
Correlate tumor vascularity with
oxygen distribution
15
Dual Energy MicroCTDual Energy MicroCT
X-ray Source Spectrum Dual energy simulations
top related