1

Pidikiti R, Stojadinovic S, Saha D, Speiser M, SeliounineS, Song K, Timmerman RD, Solberg TD

Department of Radiation OncologyUniversity of Texas Southwestern Medical Center

timothy.solberg@utsouthwestern.edu

PROGRESS TOWARDS AN IMAGE-GUIDED STEREOTACTIC SMALL ANIMAL IRRADIATOR

• High dose rate (up to 10 Gy/min)• Minimize anesthesia time• Mimic clinically-applicable dose rates

• Provide uniform tumor dose and minimal peripheral dose• Multi-directional delivery• Sharp penumbra

• Variable small field sizes (3 mm to 20 mm)

• Image guidance• Precise localization• Visualization of orthotopic tumors / normal structures

Essential Irradiator Characteristics

Stereotactic Irradiation of Small Animals

Historical Capabilities

GammaKnife – coordinate based

Commercial Linac –visual alignment and image guidance

Dedicated small animal irradiator –visual alignment and image guidance

Frame Experience

2

Linac Experience

Normalized Tumor Volume versus Time Following Irradiation

0.0

1.0

2.0

3.0

4.0

5.0

6.0

7.0

8.0

9.0

10.0

0 2 4 6 8 10 12 14 16 18 20 22

Days Following First Fraction

No

rma

lized

Tu

mo

r V

olu

me

Untreated 5 x 7 Gy 3 x 10 Gy 20 Gy Slow 20 Gy Fast

A549 Lung Cancer

Linac Experience

A498 Renal Cell Carcinoma

3 x 16 Gy

C4-2 Prostate Cancer

15, 22.5, 45 Gyin 3 fractions

Dedicated IGRT Device – Generation One (“The Box”)

SLR

Mirror

Initial Image Reference DRR Verification Image

Double Exposure

3

Generation Two

Ring gantry design with robotic positioning

2D and 3D (CBCT) Image Guidance

Sophisticated Field Shaping

Monte Carlo treatment planningSU-FF-J-157

Generation One B – Decouple collimators from localization device

Generation One B – Direct digital imaging capabilities and computer automated localization

Positioning stage

Digital panel

Animal support

Varian PaxScan 1313

Digital Imager

Positioning stages

Animal support

X-ray Tube Filter

Collimator

Generation One B – Direct digital imaging capabilities and computer automated localization

4

Lookup Table

Generation One B – add horizontal rotation stage

Dynamic positioning during treatment

Beam CharacteristicsPercent Depth Dose (250 kVp)

SSD 25 cm SSD 25 cm SSD 25 cm SSD 25 cm

0

10

20

30

40

50

60

70

80

90

100

0 20 40 60 80 100 120 140

Depth (mm)

PD

D(%

)

10 mm Diameter

5 mm Diameter

7.5 mm Diameter

3.5 mm Diameter

1 mm Diameter

Correlation with Monte CarloBeam Characteristics

Dose Rate versus Field Size (250 kVp)

20 cm SSD

5

Off Axis Ratios

1.330.7510.0 mm Collimator

1.160.67.5 mm collimator

1.100.735.0 mm Collimator

1.050.713.5 mm Collimator

0.910.791.0 mm Collimator

Penumbra (mm)Perpendicular - axis

Penumbra (mm)Transverse - axis Nominal Aperture Diameter

Pre-Tx 1 wk 2 wk

15 Gy

30 Gy

Pre-Tx 1 wk 2 wk

Orthotopic Lung Tumor in Mice Orthotopic Glioma Model

Initial Position

Localize and Verify

Irradiate

6

20 G

y10

Gy

08-28-08 09-09-08 09-23-08 10-01-08

x

08-28-08 09-09-08 09-23-08 10-06-08 10-13-08 10-17-08

Irradiation on 8-28-08

Orthotopic Lung Tumor in Rats

Orthotopic Prostate Tumor Model

Orthotopic Prostate Tumor Model

Micro CT Plan

Micro MR Plan

7

A B

C D

AP

Lat

Pre-localization Post-localization

Orthotopic Prostate Tumor Model

We are developing a number of tumor and normal tissue models to explore biology of large dose per fraction irradiation

New devices are needed to properly mimic stereotactic delivery in humans in small animal models

Summary

Thank you