ČERENKOV IMAGING OF RADIATION THERAPY
DOSE AND TISSUE OXYGENATION
Brian W. Pogue1,2, Rongxiao Zhang2, Adam Glaser1, Scott Davis1
Sergey Vinogradov3, Colleen Fox4, David Gladstone4, Lesley Jarvis4
1Engineering, 2Physics
4Department
& Astronomy, Dartmouth College, 3University of Pennsylvania
of Medicine, Radiation Oncology, Geisel School of Medicine
Applications
1. Radiation beam dosimetry
2. Surface Dose Imaging in vivo
3. Molecular Imaging (oxygen)
1
MONTE CARLO MODELING – GEANT4 & TISSUE OPTICS PLUG-IN
Highenergy
photon
transport
Interaction
Compton
scattering
(photon, e-)
Pair
Photoelectric
Production
effect
(e+, e-)
(e-)
Charged
particle
generation
Charged
particle
transport
Interaction
X-ray
production
(e-/e+,
photon)
e-/e+
Annihilation
(photon,
photon)
e-/e+
e+
e-/e+
Cerenkov
Electron
effect
scattering
(e-/e+, optical (e-/e+, e-)
photon)
Optical
photon
generation
Glaser et al, Biomed. Opt. Express (2013)
Čerenkov emission, energy & dose
Cerenkov Emission in Tissue
6
∝
4
10
PET
Radionuclides
Photons per Electron
10
2
10
1
Radiation
Therapy
Energies
Total
energy
Dose
Cerenkov energy
0
10
0
5
10
15
Energy (MeV)
20
2
Radiation Therapy Technologies
Linear Accelerator (LINAC)
6 MeV-24 MeV
Intensity Modulated RT (IMRT)
Multi-leaf
collimators
at beam output
Dose Treatment Plan
Image Guided Radiation Therapy (IGRT)
Radiation induced Čerenkov Emission
Galvin JCO 2007
eeee-
Photograph of emission ring below water tank
Axelsson et al, Med. Phys. (2011)
3
FLUORESCENCE RANDOMIZES
THE EMISSION DIRECTION
Quinine sulphate
(fluorophore)
Galvin JCO 2007
Galvin JCO 2007
e-
e-
e-
e-
e-
e-
e-
e-
Glaser et al, Phys Med Biol (2013)
LINAC Beam Profiling Hardware
LINAC
Water
Tank
Patient
Bed
ICCD
ICCD
Water tank
Rotating arm
4
Multiple Angle Beam Imaging
Images at different angles
15O
0O
30O
45O
ROTATE
Reconstructed 3D volume
with filtered backprojection
position
Sinogram
0O
90O
Angle
180O
3D ČERENKOGRAPHY OF LINAC BEAMS
Square beam
Complex shaped beam
MedOp Inc., Hanover NH
5
IMPROVEMENTS IN SNR
TO ALLOW ČERENKOV IMAGING
W/cm2
1
Sunlight
10-1
10-2
10-3
10-4
Room light
(3 sec pulses @ 200 Hz)
dimmed
lights
10-5
GATED
TO LINAC
PULSING
10-6
10-7
10-8
Gated Acquisition - 105x gain
Čerenkov
10-9
Glaser et al, Optics Lett. 2012
What about Čerenkov emission from tissue?
1. Image Skin Dose
2. Avoidance of Dose Errors
3. Measure Molecular Signals In Vivo
6
Previous observations of Cerenkov in vivo
Nature, 1970
Surface Entrance Dose
Beam Size
Beam Angle
H=35cm
D=70cm
Zhang et al, Med Phys (in press, 2013)
7
Breast phantom treatment planning
Whole breast irradiation following surgery
Breast phantom
Standard two field treatment plan
Cerenkov dose imaging
tracking skin dose
Room lights off
Room lights on
8
Whole breast irradiation following
lumpectomy  tracking skin dose
Whole breast irradiation following surgery
Skin damage from irradiation
Čerenkoscopy of dog oral tumor Radiation Treatment
Upper palate
Lower jaw
Cerenkov video
Treatment area
Cerenkov video (room lights on)
9
Clinical trial
1
0.8
0.6
0.4
0.2
0
Breast Clinical trial awaiting final IRB approval
PI: Lesley Jarvis, MD PhD
Outcomes planned:
• Image 12 subjects during 10 fractions of breast irradiation
• Test for variability in emission between fractions
• Test for correlation to breast skin reaction
Čerenkov blood SO2 spectroscopy of tissue during RT ?
.
spectrum
theoretical
Absorption – SO2
oxygenated
De-oxygenated
blood in intralipid
phantoms
250
Spectrum
reports
tissue
blood conc.
Optical
Phantom
Spectra
0 M
3.4 M
6.7 M
10.1 M
13.4 M
Intensity(arb. u.)
200
150
100
50
0
550
600
650
700
 (nm)
750
800
850
Axelsson et al, Medical Physics, 2011
10
Oxygen imaging with luminescence lifetime tomography
PdG4 Oxyphor
(pO2 sensitive phosphor)
lifetime
with Sergei Vinogradov, UPenn
pO2
Zhang et al, J. Biomed Optics. 2013
SUMMARY:
1. Fast Beam Profiling
2. Surface Dosimetry
3. Molecular Sensing during RT
(Oxygen, Protoporphyrin IX, molecular tracers)
11
Čerenkography & Čerenkoscopy Team
Adam
Glaser
Rongxiao
Zhang
Sergei
Vinogradov, PhD
Chad
Kanick, PhD
David
Gladstone, DSc
Scott
Davis, PhD
Colleen
Fox, PhD
A. Phantom, PhD
Lesley
Jarvis, MD PhD
www.dartmouth.edu/optmed
www.nirfast.org
R01CA109558
Audrey Proudy
Development Fund
QUESTIONS?
12
LINAC Beam commissioning & Quality Assurance
Depth vs. dose of beam
Lateral profile of beam
Acquisition takes several hours for multiple 1-D scans
Takes over 24 hours for a full beam 3D scan.
LINAC Beam commissioning & Quality Assurance
Treatment plan
Targeted
dose map
Beam
delivery
Quality assurance plays a fundamental role in
radiation treatment of cancer: while modern
techniques offer the ability to deliver precise doses of
radiation to tumour tissue, this advantage is lost if the
equipment is not stable and accurate. Regular and
precise calibration of radiotherapy apparatus is thus an
essential procedure for hospitals.
Treatment plan: lung nodule
Beam
delivery
physicsworld.com “New accelerator enhances radiotherapy
accuracy”, Nov. 19, 2008
13
Classical theory of Cerenkov radiation in dielectric
Maxwell’s equations
⋅
stationary charged particle
4
⋅
0
1
1
4
(B)charged particle
fast
0
exp
1
⋅
0
4
4
̂
̂
̂
2
exp
̂
exp
4
Čerenkov radiation and its
applications, J. V. Jelley
̂
Classical theory of Cerenkov radiation and basic properties
Maxwell’s equations
⋅
1
4
⋅
0
1
1
1
4
2
exp
1
0
2
0
lim
→
lim
→
0
0
2
exp
2
1
⋅
exp
3
4
0
4
Emitted power per unit path per wavelength
4
d 2W
1
 3
dld 

̂
̂
d 2N
1
 2
dld 

̂
2
4
exp
exp
̂
̂
Čerenkov radiation and its
applications, J. V. Jelley
14
Cerenkov emission discovered from
Positron Emission Tomography (PET) agents
Beattie et al, PloS One 2012
Robertson et al, Phys. Med. Biol. 2009
15