D evelopment of a small animal irradiation system

Stanford University

Molecular Imaging Program at Stanford

MIPSDepartment of Radiation Oncology and

BIO-X, School of Medicine

Development of a small animal Development of a small animal irradiation systemirradiation system

Magdalena BazalovaMagdalena BazalovaStanford University, CA, USAStanford University, CA, USA

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Small animal radiotherapy teamSmall animal radiotherapy team

• Edward Graves, PIEdward Graves, PI• Paul KeallPaul Keall• Hu ZhouHu Zhou• Manuel RodriguezManuel Rodriguez• Geoff NelsonGeoff Nelson• Rahil JoganiRahil Jogani• Amy MotomuraAmy Motomura

• Fred van den HaakFred van den Haak• Jiali XuJiali Xu• Xinzhi ZhuXinzhi Zhu• Yongjiang XianYongjiang Xian• Phuoc TranPhuoc Tran• Sanjeev DattaSanjeev Datta• and othersand others

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Why small animal radiotherapyWhy small animal radiotherapy

• Rotating radiation sources, conformal Rotating radiation sources, conformal collimators, image guidance and verification collimators, image guidance and verification are widely used in modern RT.are widely used in modern RT.

• Analogous systems for small animal RT lack Analogous systems for small animal RT lack most of these features.most of these features.

• Spatial and dosimetric accuracies achievable Spatial and dosimetric accuracies achievable with existing systems are limited.with existing systems are limited.

• 3D conformal animal RT systems are highly 3D conformal animal RT systems are highly desirable.desirable.

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Current small animal RT systemsCurrent small animal RT systems• Washington University: Washington University: 192192Ir with fixed Ir with fixed

collimatorscollimators• John Hopkins University: imaging with 120kVp, John Hopkins University: imaging with 120kVp,

treatment with 225kVp non-coplanar beamstreatment with 225kVp non-coplanar beams• Princess Margaret Hospital: a decomissioned Princess Margaret Hospital: a decomissioned

simulator tube for imaging and 225kVp beam simulator tube for imaging and 225kVp beam for treatmentfor treatment

• Stanford: modified microCT scanner with Stanford: modified microCT scanner with 120kVp beam for both imaging and treatment120kVp beam for both imaging and treatment

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Stanford small animal radiotherapyStanford small animal radiotherapy

• Based on an eXplore RS120 microCT scannerBased on an eXplore RS120 microCT scanner

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Turning an imaging device into a Turning an imaging device into a treatment machinetreatment machine

• The tumor has to be positioned to the The tumor has to be positioned to the isocenter of the microCT scanner for isocenter of the microCT scanner for treatment – treatment – two-dimensional translation two-dimensional translation stage.stage.

• The photon beam has to be conformal to the The photon beam has to be conformal to the shape of the tumor – shape of the tumor – two-stage variable two-stage variable aperture collimator.aperture collimator.

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Two-dimensional translation stageTwo-dimensional translation stage• Mounted on the microCT couch (Mounted on the microCT couch (zz axis), moves axis), moves

in in xx and and yy, controlled by a software (written , controlled by a software (written in?) from the microCT computer.in?) from the microCT computer.

The reproducibility is The reproducibility is better than 0.05mm in better than 0.05mm in both directions.both directions.

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CollimatorCollimator• A variable aperture collimator installed in the A variable aperture collimator installed in the

gantry between the x-ray source and the bore.gantry between the x-ray source and the bore.• 0 – 102 mm (fully open for imaging)0 – 102 mm (fully open for imaging)

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Calibration of the collimatorCalibration of the collimator

• Physical aperture vs machine unit calibrationPhysical aperture vs machine unit calibration– Using solid cylinders with diameters ranging from Using solid cylinders with diameters ranging from

6mm to 36mm with precision of 0.025mm.6mm to 36mm with precision of 0.025mm.– Readings of the position sensor fit with a linear Readings of the position sensor fit with a linear

function.function.• Collimator-beam axis alignmentCollimator-beam axis alignment– Displacement and tilting have to be minimizedDisplacement and tilting have to be minimized• Split field test.Split field test.• Imaging of a fixed object at 0° and 180°.Imaging of a fixed object at 0° and 180°.• Evaluation of the hexagonal beam profiles.Evaluation of the hexagonal beam profiles.

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Collimator beam-axis alignmentCollimator beam-axis alignmentox

0°

180°0° 180°

Displacement and tilting adjustments after Displacement and tilting adjustments after the calibration were less than 0.1 mm.the calibration were less than 0.1 mm.

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Collimator performanceCollimator performance

• Collimator motion times.Collimator motion times.

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Dosimetric characterization of the Dosimetric characterization of the systemsystem

• Performed with EBT Gafchromic films and an Performed with EBT Gafchromic films and an ion chamber (PTW N30006).ion chamber (PTW N30006).

• EBT films offer high spatial resolution, they are EBT films offer high spatial resolution, they are tissue equivalent and show little energy tissue equivalent and show little energy dependence.dependence.

• Films were read out at 508 dpi using a flatbed Films were read out at 508 dpi using a flatbed Epson Perfection V500 scanner in light Epson Perfection V500 scanner in light transmission mode.transmission mode.

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Dosimetric measurementsDosimetric measurements

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Dose rate as a function of beam sizeDose rate as a function of beam size

Tube current Dose rate (Gy/min)(mA) 6.0 cm 5.0 cm 4.0 cm

50 2.13 2.08 2.0440 1.72 1.68 1.6225 1.11 1.08 1.02

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PDD and beam profilesPDD and beam profiles• The dose rate is more than 1.5 Gy for beams The dose rate is more than 1.5 Gy for beams

as small as 2 mm.as small as 2 mm.• Beam penumbra and heel effect studied.Beam penumbra and heel effect studied.

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Plan deliveryPlan delivery• 8 beams with diameters of 2 mm.8 beams with diameters of 2 mm.• The measured and calculated dose at the The measured and calculated dose at the

isocenter are within 1.5%isocenter are within 1.5%

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Treatment planning systemTreatment planning system• Under developmentUnder development• GUI based on RT_ImageGUI based on RT_Image† † is linked to a MC system is linked to a MC system

based on the EGSnrc codes.based on the EGSnrc codes.• Inverse planning is being incorporated.Inverse planning is being incorporated.

• † † Graves EE, Quon A, Loo BW. RT_Image: An Open-Source Tool for Investigating PET in Graves EE, Quon A, Loo BW. RT_Image: An Open-Source Tool for Investigating PET in Radiation Oncology. Technology in Cancer Research and Treatment2007;6:111-121.Radiation Oncology. Technology in Cancer Research and Treatment2007;6:111-121.

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Monte Carlo treatment planning for Monte Carlo treatment planning for small animal radiotherapysmall animal radiotherapy

• For kilovoltage photon beams, the dose has to For kilovoltage photon beams, the dose has to be calculated by the Monte Carlo (MC) method.be calculated by the Monte Carlo (MC) method.

• We investigated We investigated – the efficiency of MC dose calculation for kV photon the efficiency of MC dose calculation for kV photon

beams in submillimeter voxels beams in submillimeter voxels – the importance of tissue segmentation for kV photon the importance of tissue segmentation for kV photon

beambeam• BEAMnrc and DOSXYZnrc EGSnrc codes are used.BEAMnrc and DOSXYZnrc EGSnrc codes are used.• Two methods for dose calculations are studied Two methods for dose calculations are studied

and optimized.and optimized.• Dual-energy microCT imaging is studied.Dual-energy microCT imaging is studied.

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MC dose calculationsMC dose calculations

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Two calculation approaches: Two calculation approaches: comparisoncomparison

For (0.2×0.2×0.2) mmFor (0.2×0.2×0.2) mm33, , 120 kVp beam 120 kVp beam

• beam < 30 mm beam < 30 mm phase-space filesphase-space files

• beam > 30 mmbeam > 30 mmBEAMnrc sourceBEAMnrc source

3.0 GHz machine

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Comparison of MC dose distributions Comparison of MC dose distributions to measurementsto measurements

• Using PDD curves and beam profiles parallel Using PDD curves and beam profiles parallel and perpendicular to heal effectand perpendicular to heal effect

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Beam profilesBeam profiles

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Tissue segmentationTissue segmentation• How important is it for MC dose calculations How important is it for MC dose calculations

using the microCT 120kVp beam?using the microCT 120kVp beam?a) b)

c)34 ICRU 34 ICRU tissuestissues

ICRU tissuesICRU tissues

0.3<0.3<ρρ<1.9<1.9(g/cm(g/cm33))

6.7<6.7<ZZ<14.0<14.0

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Tissue segmentation - ResultsTissue segmentation - Results

Need to know Z.

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Dual-energy microCT (DEmCT) imagingDual-energy microCT (DEmCT) imaging

• DEmCT is based on a DEmCT is based on a parameterization of the parameterization of the linear attenuation linear attenuation coefficient.coefficient.

• Results in Results in ρρ and and ZZ of each of each voxel.voxel.

• Tested on a mouse Tested on a mouse phantom and a calibration phantom and a calibration phantom with 70 and 120 phantom with 70 and 120 kVp beams.kVp beams.

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DEmCT phantom: ResultsDEmCT phantom: Results• ρρ and Z extracted and Z extracted

with a reasonable with a reasonable accuracyaccuracy

• beam hardening beam hardening does seem to play a does seem to play a role (will be role (will be investigated)investigated)

• noise is an noise is an important issue, important issue, image quality should image quality should be improved be improved

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DEmCT of a frozen mouseDEmCT of a frozen mouse• 11 organs of a mouse delineated and the 11 organs of a mouse delineated and the

mean HU of each organ used for DEmCTmean HU of each organ used for DEmCT

mouse extractedICRU human tissues

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RT_ImageRT_Image

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RT_Image and EGSnrcRT_Image and EGSnrc

• Interactive tissue and mass density segmentation.Interactive tissue and mass density segmentation.• EGSnrc input file is created, run on an 8-core Mac.EGSnrc input file is created, run on an 8-core Mac.

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RT_Image is coolRT_Image is cool

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Phantom irradiationPhantom irradiation

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Mouse irradiationMouse irradiation

• MYC-induced lung tumors of two mice MYC-induced lung tumors of two mice irradiated to a dose of 2 Gy.irradiated to a dose of 2 Gy.

• Anesthetized mice were imaged at 70 kV.Anesthetized mice were imaged at 70 kV.• The target was localized and an 8 equally The target was localized and an 8 equally

spaced beam plan was created.spaced beam plan was created.• After irradiation, the mice were sacrificed and After irradiation, the mice were sacrificed and

tissue were harvested. The lungs fixed in tissue were harvested. The lungs fixed in formalin and cut into 20 mm sections. formalin and cut into 20 mm sections.

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Mouse irradiation (cont.)Mouse irradiation (cont.)

• The section were stained with antibodies The section were stained with antibodies against against γγH2AX (double strand breaks) and H2AX (double strand breaks) and DAPI (to visualize cell nuclei).DAPI (to visualize cell nuclei).

• The immunohistochemical (fixed tissue) The immunohistochemical (fixed tissue) sections were visualized with fluorescence sections were visualized with fluorescence microscopy.microscopy.

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Mouse irradiation planMouse irradiation plan

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Fluorescence imagingFluorescence imaging

γH2AX

DAPI

~2 Gy ~0.3 Gy

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DiscussionDiscussion

• Increase in temperature of the x-ray tube Increase in temperature of the x-ray tube generator – reduce duty cycle and take breaks generator – reduce duty cycle and take breaks between irradiationsbetween irradiations

• Tissue segmentation using DEmCT imaging is Tissue segmentation using DEmCT imaging is limited by microCT image quality. Noise has to limited by microCT image quality. Noise has to be reduced.be reduced.

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ConclusionsConclusions

• A GE microCT scanner was successfully modified A GE microCT scanner was successfully modified for delivery of radiation to small animals.for delivery of radiation to small animals.

• MC treatment planning is close to its final MC treatment planning is close to its final version.version.

• Inverse treatment planning is being incorporated.Inverse treatment planning is being incorporated.• More than 20 mice have been irradiated.More than 20 mice have been irradiated.• Ready to irradiate more animals and study the Ready to irradiate more animals and study the

response of various tumors/tissues to radiation.response of various tumors/tissues to radiation.• For less than $25,000 (plus a microCT scanner).For less than $25,000 (plus a microCT scanner).

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Small animal irradiationSmall animal irradiation

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D evelopment of a small animal irradiation system