Disclosures
Applications of Millimeter Precision
Small Animal Radiation
Eric Ford, PhD
• Commercialization agreement with Gulmay
Medical Ltd., Surrey, UK
• NCI funding: R01 CA108449
Department of Radiation Oncology and Molecular Radiation
Sciences
Johns Hopkins School of Medicine
AAPM 28 July 2009
Anaheim, CA
Outline
Small Animal Radiation Research Platform
TUBE
• Technology – brief overview & results
• Example applications
– Spine radiosurgery model
– Radiation & stem cells
– Radiation + vaccine trials
• New developments
Integrates imaging and treatment
• X-ray tube on gantry
50 – 225 kVp
0.4/3.0 mm focal spot
• Adjustable filtration
ROBOT
STAGE
FLAT PANEL
DETECTOR
• Flat panel detector
Portable system
• Fits through door
• Can be installed in animal
containment area
Operational since Nov 2006
3’ x 4’ x 6’
Adjustable collimation
Open (20x20 cm) … 0.5 mm
Gantry rotation
+
Animal rotation
Outputs:
(a)
Size
Gy/min
5 x 5 mm
2.28
3 x 3 mm
2.22
0.5 mm
1.02
d=1cm, 35 SAD, 0.16 mm Cu filter
225 kVp, 13 mA, 3 mm spot
0.5 mm
30 mm
3 mm
Gantry rotation
Gantry rotation
+
+
Animal rotation
Animal rotation
Gantry rotation
Gantry rotation
+
+
Animal rotation
Animal rotation
Gantry rotation
Gantry rotation
+
+
Animal rotation
Animal rotation
Non-coplanar
Beams possible
CT imaging
Remove Collimator
Rotate Animal
Collaboration with
Netherlands Cancer Institute
M. Van Herk, J.J. Sonke
• Animal exactly in treatment position
• “Point and click” robotic positioning
Example Experiment and Timeline: Single Isocenter
2 min
3
2
3
Beam Profiles
3x3 mm beam
Monte Carlo calculations (EGSnrc)
7 min
E. Tryggestad et al.
17 min
0.5 mm
beam
Note: low energy for sharp penumbra
Geometric Calibration
Rotation
Axis
AP
5 mm
Orthogonal images of a BB phantom, CT alignment
1/
1
Outline
• New developments
Z
Spine radiosurgery model
“port film”
5 mm beam
• Technology – brief overview & results
• Example applications
– Spine radiosurgery model
– Radiation & stem cells in brain
– Radiation + vaccine trials
Y
09
6/
09
FWHM: 2.0 mm
X
6/
EBT
films
•
Robotic
Calibration
fn (φ)
6/
1
Uncalibrated
LAT
∆ (mm)
1mm
beam
End-to-End Alignment QA
tumor
glue cap
Cone-beam
• Rat model
• Implanted tumor: metastatic breast cancer
• 20 Gy vs. 8 Gy x 5
• Radiosensitizers
Wes Hsu et al.
Brain : targeting validation with immunohistochemistry
Ventricle Targeting Validation: Immunohistochemistry
10 Gy
3 mm beam
γH2Ax Ser139
10 Gy strip
DNA strand
breaks
Ki67 proliferative stain
Effect of radiation on stem-cells
Unirradiated
Irradiated 10 Gy
B
Proliferating
Cells
Nestin:
stem cell
C
Ventricles
A
Unirradiated
10 Gy, 1 day post
P. Achanta et al.
Irradiated
DCx:
Migrating
neuroblast
Prostate: Local RT + GVAX prostate ca vaccine
Prostate: Local RT + GVAX prostate ca vaccine
5x9 mm Tx field
Pelvic Bone
RT
Delayed IR
T-GVAX
RT/T-GVAX
2
RT/T-GVAX
0
RT/T-GVAX -7
RT/T-GVAX -14
RT/T-GVAX -21
*
RT/T-GVAX -28
*
5
Spleen
(×
× 105)
Prostate
(×
× 104)
Prostate
Draining Lymph
Node (× 103)
3
No Treatment
*
30
(+T-GVAX)
4
RT
# HA specific CD8+ IFN-γ
γ+
T cells (×
× 104)××10 )
# HA spe cific CD8 IFN-γ
γ
γ T cells (×
A specific CD8+T cells
No Treatment
0
40
T-GVAX
RT/T-GVAX
*
2
+
20
+
*
10
*
1
0
#H
Immediate IR
*
10
cells
Bladder w/ contrast
# HA specific CD8+ IFN-γ
γ+ T
15
C
Spleen
(× 105)
Prostate Draining
Lymph Node (×10
× 3)
×
Prostate
(× 104)
0
0Gy
3Gy
6Gy
12Gy
24Gy
36Gy
Dose (Gy)
Wada, Tryggestad, Drake et al. 2009
Summary
Wada, Tryggestad, Drake et al. 2009
New Developments: µMLC
Technical issues
• Need for on-board CT
• Calibration is critical for < 1 mm accuracy
• Practical use: <30 min CT guided Tx
Variety of new radiobiological applications
• Simulating clinical Tx: e.g. SRS spine
• Cancer vaccines with intact immune response
• Stem cells in the brain
What’s next?
• More experiments
• Improved ease of use – automatic collimation system
• Improved targeting
• Two motors: 1 for each bank; electro-magnetic controlled
• Tungsten MLC (20mm x 30mm)
• Interlocking ends and sides
New developments: further on-board imaging
New developments: on-board imaging
45o mirror
• Better soft-tissue resolution
e.g. orthotopic models
• On-board optical imaging
e.g. fluoroescent reporter gene systems
Acknowledgments
SARRP design / Rad Onc
John Wong, PhD
Woody Armour, PhD
Erik Tryggestad, PhD
Todd McNutt, PhD
Eric Ford, PhD
Peter Kazanzides, PhD
Iulian Iordachita, PhD
Babak Matinfar
Mike Armour
Juvenal Reyes, MD
Kristin Redmond, MD
Robert Ivkov, PhD
Joseph Herman, MD
Theodore DeWeese, MD
Frank Verhaegen, PhD
MAASTRO
Marcel van Herk, PhD
Jan-Jakob Sonke, PhD
NKI, Amsterdam
Alfredo Quinones-Hinojosa, MD
Pragathi Achanta, PhD
Hugo Guerrero-Cazares, MD, PhD
Michael Lim, MD
Wes Hsu, MD
Chuck Drake, MD
Wenzhen Duan, PhD
US
Probe
On-board ultrasound
• imaging orthotopic tumors
Light tight,
x-ray
transparen
t housing
CCD
camer
a
On-board optical
• Imaging reporter gene systems